20 April 2019, Volume 33 Issue 2
    

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  • Editorial
    L. Franza, V. Carusi, S. Altamura, A. Gasbarrini, A. Caraffa, S.K. Kritas, G. Ronconi, C.E. Gallenga, F.Di. Virgilio, F. Pandolfi
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 315-319.
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  • Article
    L.Q. Wang, A.C. Deng, L. Zhao, Q. Li, M. Wang, Y. Zhang
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 321-330.
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    Nasopharyngeal carcinoma (NPC) is a malignant tumor with high invasive and metastatic properties. Dysregulation of miRNAs may contribute to disease progression by targeting disease-related genes. In this study we aimed to elucidate the role and function of aberrantly expressed miRNA in NPC tumorigenesis. We found that miR-1178-3p was highly expressed in NPC tissues. Overexpression of miR-1178-3p promoted the proliferation, migration and invasion of NPC cells in vitro. In contrast, knocking down endogenous miR-1178-3p by miRNA-specific inhibitor significantly suppressed the above phenotypes. Moreover, miR- 1178-3p was shown to negatively regulate serine/threonine-protein kinase 4 (STK4), an NPC-related tumor suppressor gene, in the post-transcriptional level. Furthermore, STK4 overexpression abolished miR-1178- 3p-induced cell proliferation, migration and invasion through STK4-mediated dephosphorylation of AKT. Our results indicate that miR-1178-3p acts as an oncomiRNA in NPC by suppressing STK4 expression, and inhibition of miR-1178-3p may become a therapeutic potential for NPC.

  • Article
    JJ. Xie, WH. Li, X. Li, W. Ye, CF. Shao
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 331-343.
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    LncRNA MALAT1 is reported to play a potential role in human cancers. Hence, we investigated the effects of MALAT1 on colorectal cancer in vitro and in vivo, and further validated whether MALAT1 affected colorectal cancer development and EZH2 expression via regulating miR-363-3p. The fresh colorectal cancer tissues, adjacent non-tumor tissues, FHC, LOVO, SW620, CL40 and HCT116 cells were analyzed in this study. MALAT1, miR-363-3p and EZH2 expression levels were assessed using qRT-PCR and Western blot. Cell proliferation, migration and invasion were also measured. Binding effects between MALAT1 and miR-363-3p, or miR-363-3p and EZH2 3'UTR were detected by dual luciferase assay. We observed that MALAT1 was highly expressed in colorectal cancer tissues and cells, and MALAT1 knockdown inhibited cell proliferation as well as expression levels of EZH2 by upregulated miR-363-3p in cell models and in vivo. Moreover, miR-363-3p functions as a downstream target of MALAT1, meanwhile EZH2 was a target of miR-363-3p, suggesting MALAT1 might regulate miR-363-3p and/or EZH2 expression. Collectively, we concluded that MALAT1 functioned as a ceRNA to promote colorectal cancer development and EZH2 expression through sponging miR-363-3p in vitro and in vivo.

  • Article
    Y M. Xue, H C. Cheng, J H. Wang, W. Wang, L. Miao
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 345-353.
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    5-methyl cytosine (5mC) can be oxidized to 5-hydroxymethyl cytosine (5hmC) under the action of TET protein family, and 5hmC plays important roles in the pathogenesis of various tumors including acute myeloid leukemia (AML). In this study, we evaluated the role of 5mC and 5hmC levels in HL60 AML cells and bone marrow samples from AML patients for KIT gene expression to analyze 5hmC level in AML pathogenesis. Results showed that the expression and 5hmC level increased significantly of the KIT gene but the change of its 5mC level was not obvious after being treated by decitabine (DAC) in HL60 cells. IDH1 and IDH2 expression increased followed by increased KIT 5hmC level. In AML patients with IDH1 or IDH2 mutation, KIT expression and 5hmC were much lower than in those without mutation. The study indicated that the expression of KIT gene was regulated by 5hmC level in HL60 cells, and the 5hmC level was regulated by IDH1 and IDH2.

  • Article
    R. Gao, T T. Sun
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 355-364.
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    This study aimed to investigate the effect of CD133 on the proliferation and migration of glioma cells and expressions of genes related to cancer stem cells/tumor stem cells (CSC/TSC) as well as their in-vivo oncogenicity. CD133-overexpressing U251-CD133 and U251-mock glioma cells were constructed. The effect of CD133 on in-vitro proliferation and the neurosphere-forming ability of glioma cells was determined by cell count and neurosphere formation assay. Real-Time PCR was performed to detect the expressions of CSC/TSC-related genes in the CD133-transfected cells. Nude mouse subcutaneous tumor formation assay was used to determine the effect of CD133 on the in-vivo oncogenicity of glioma cells. In serum-containing medium, human CD133 had no impact on the proliferation of U251 glioma cells, but the neural stem cells placed in serum-free medium promoted neurosphere formation. In the presence of CD133, the expressions of CSC/TSC-related genes were upregulated to varying degrees in glioma cells; CD133 greatly enhanced the in-vivo oncogenicity. In conclusion, CD133 promoted the upregulation of CSC/TSC-related genes in glioma cells, while enhancing the neurosphere-forming ability and in-vivo oncogenicity.

  • Article
    R R. Wang, Z M. LV, Y P. Dan, K Y. Chen, C. Zhang
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 365-374.
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    The effects of acarbose and sitagliptin on blood glucose fluctuation and islet β-cell function in patients with type 2 diabetes mellitus (T2DM) were studied. One hundred and three patients with poorly controlled T2DM with insulin aspart 30 were selected and randomly divided into three groups: group A [continuous subcutaneous insulin infusion (CSII) treatment group], group B (CSII combined with acarbose treatment), group C (CSII combined with sitagliptin treatment). The treatment lasted for two weeks and the clinical indicators in the three groups were measured. The insulin dosage was adjusted according to the blood glucose statuses of the three groups of patients. In the final three days, 72 h of continuous glucose monitoring (CGM) were carried out, and the OGTT test was performed again. The results showed that the MODD (absolute means of daily difference), intra-day blood glucose fluctuation indices [(24 h MBG (mean blood glucose), LAGE (largest amplitude of glycemic excursions) and MAGE (average blood glucose fluctuation)] and postprandial blood glucose fluctuation indices [PGS (postprandial glucose spike), △t, PPGE (postprandial glucose excursion) and T (time) total] in group C and group B were significantly lower than those in group A. Compared with group B, the difference in blood glucose fluctuation indices in group C was not statistically significant (P>0.05). The HOMA-islet (homeostasis model assessment of islet) (CP-DM) index and FC-P (Fasting c-peptide) levels in group C and group B were significantly higher than those in group A (P less than 0.01). The HOMA-IR (CP) index of groups B and C was significantly lower than that of group A (P less than 0.01), and there was no statistically significant difference between groups B and C (P less than 0.05). Sitagliptin combined with intensive insulin pump therapy can reduce blood glucose fluctuation throughout the day, reduce insulin dosage, improve islet B cell function and reduce hypoglycemia better than intensive insulin pump therapy alone.

  • Article
    X. Sui
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 375-384.
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    This study was aimed to investigate whether interferon (IFN)-induced protein 35 (IFI35) affects the signaling pathway of nuclear factor-kappa B (NF-κB) and to observe the effect of different expressions of IFI35 on the proliferation of endothelial cells and angiogenesis in rats with acute cerebral infarction. A suture method was adopted to prepare a mouse model of permanent middle cerebral artery occlusion (PMCAO). After the treatment of cerebral artery occlusion in 200 healthy male mice (weighting 20g-40g), 47 mice were selected and the double luciferase assay was used to identify different structural domains of IFI35; for the remaining 153 mice, RT-PCR and immunohistochemical assays were used to detect the mRNA expression of glioma-associated oncogene homolog 1 (Gli1), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and CD105 (endoglin). The results showed that IFI35 could reduce the level of p65 protein (REL-A) in the nucleus while affecting the production of p-p65 in the cytoplasm. At the same time, IFI35 could be used in combination with a NID1 protein domain + Nmi protein to inhibit the signaling pathway of NF-κB. Expressions of Gli1, VEGF, bFGF, and CD105 in the IFI35 treatment group were all significantly reduced (P less than0.05). In conclusion, IFI35 could suppress the activation of the NF-κB signaling pathway, reduce the proliferating potential of vascular endothelial cells, and lower the expression of vascular growth factors, thereby inhibiting angiogenesis in mice with acute cerebral infarction.

  • Letter
    L. Zhao, Y. Cao, Y. Liu
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 385-389.
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    The present study aims to investigate changes in serum fibroblast growth factor 19 (FGF19) levelstwo hours after oral use of 75 g of glucose in newly diagnosed type-2 diabetic patients, and explore itsinfluence factors. Fifty newly diagnosed type-2 diabetic patients, admitted to our hospital from January2015 to December 2015, were randomly enrolled in the present study (T group), while 50 age- and gendermatchedsubjects, who presented with normal physical examination results were enrolled in the controlgroup. All subjects underwent oral glucose tolerance test (OGTT). Serum FGF19 levels at two hoursafter sugar use were compared, and the related influence factors of serum FGF19 were determined.The difference between the two groups was not statistically significant (P>0.05). The comparison ofrelated indexes after OGTT revealed that serum FGF19 levels were lower in the T group (198.06 pg/ml, range: 120.03-346.46 pg/ml) than in the control group (222.27 pg/ml, range: 126.92-382.62 pg/ml),but the difference was not statistically significant (P>0.05). Among these influence factors, postprandialserum FGF19 level was positively correlated with LDL-C and postprandial blood glucose in the T group,while postprandial serum FGF19 level was positively correlated with HbA1c in the control group. Therewas no significant difference in postprandial serum FGF19 level between patients with type-2 diabetesmellitus and healthy subjects. LDL-C and postprandial blood glucose may be independent factors forserum FGF19 levels in type-2 diabetic patients, and there is a positive correlation among these.

  • Letter
    E S. Jin, J Y. Kim, J K. Min, S R. Jeon, K H. Choi, M S. Lee, J H. Jeong
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 391-396.
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    Rabbit models have been proposed for the study of postmenopausal osteoporosis by bilateralovariectomy with reduced dietary calcium intake or glucocorticoid administration. However, restrictingdietary calcium intake or administering a glucocorticoid can cause secondary osteoporosis and is notrepresentative of a pure postmenopausal osteoporosis model. The aim of this study was to establish anexperimental rabbit model of osteoporosis induced by ovario-hysterectomy alone. Fourteen female NewZealand rabbits were separated into two groups of a sham (control) group and an ovario-hysterectomyinducedosteoporosis group. Tibiae were extracted 24 weeks after ovario-hysterectomy and were scannedby micro-computed tomography. The evaluation parameters were bone mineral density (BMD), trabecularbone volume (BV/TV), trabecular number (Tb.N), trabecular thickness, and trabecular separation (Tb.Sp). The tibial samples were evaluated after hematoxylin and eosin and Masson’s trichrome staining. Thesham group had significantly higher BMD, BV/TV, and Tb.N values and the lowest Tb.Sp value comparedto the ovario-hysterectomy group. The histological analyses revealed a loss of the bony trabeculae andan increase in osteoporotic changes in the bone of the ovario-hysterectomy-induced osteoporosis groupcompared to the control group. Our results indicate that an ovario-hysterectomy-induced rabbit modelwould be a safe, reproducible model for postmenopausal osteoporosis studies.

  • Letter
    A. Bryja, M. Popis, B. Borowiec, M. Dyszkiewicz-Konwińska, I. Kocherova, A. Angelova-Volponi, K. Mehr, M. Bruska, M. Nowicki, B. Kempisty
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 397-401.
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    The culture of primary cells in vitro has enabled to gain knowledge in the field of cell biology, diseasemechanisms and to offer great potential in drug testing. To date, two main techniques of isolatingand culturing oral mucosal cells, the direct explant method and the enzymatic method, dominate theliterature and practice. In the present study, both techniques are discussed in detail, comparing theadvantages and disadvantages of the two approaches in setting up a primary culture of oral mucosalcell. The direct explant technique is well-established and has been commonly used for the past 20-30years. Although the method of setting up the cultures did not show much variations in the methodologydescribed by authors, the culturing conditions varied according to the aims of the projects. The enzymaticmethods showed many prominent variations as different enzymes, concentrations and other conditionswere introduced. Both methods of setting up the primary cell cultures of oral mucosal cells proceedto culturing conditions adapted to the purpose of the study. The variations of the methods aimed atmaintaining the purity (free from microbial contamination), identity and stability through maintenanceof the genotype and phenotype during growth and passage.

  • Letter
    WW. Cai, J. Hu, H. Wang, GJ. Zhu, S. Chen, XP. Chen
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 403-408.
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    Coronary artery bypass grafting (CABG) is an effective scheme for treatment of myocardial ischemia.Hypoxemia is a common complication of CABG, which can affect surgical effect and prognosis and eveninduce multiple organ failure. To explore the clinical efficacy of bi-level positive airway pressure ventilationin the treatment of CABG-associated hypoxemia, 216 patients who were admitted to our hospital betweenAugust 2015 and April 2017 and developed CABG-associated hypoxemia were selected and randomlydivided into 2 groups, an observation group (n=108) and a control group (n=108). Patients in the controlgroup were given conventional treatment including continuous oxygen inhalation through nasal tube, antiinfection,bronchodilation, phlegm resolving, nutrition support, analgesia, cardiac function maintenance,coronary dilatation, anticoagulation and maintenance of stable internal environment, while patients inthe observation group were given positive airway pressure ventilation via a breathing machine or nasalmask besides the conventional treatment. The arterial blood gas indexes and blood circulation indexes ofpatients in the two groups were detected before and after treatment, the number of cases of reintubationwas recorded, and the curative effects were analyzed. The results demonstrated that the arterial gasindexes and blood circulation indexes of patients in the observation group improved after treatment, andthe improvement of the observation group was significantly superior to that of the control group (P<0.05).The intensity of hypoxia of the observation group was higher, and the number of cases of reintubation ofthe observation group was lower than that of the control group (P<0.05). Thus bi-level positive airwaypressure ventilation is an effective non-invasive ventilation mode for treating CABG-associated hypoxemiabecause it can improve p(O2), reduce p(CO2) in a short time, relieve blood circulation, and reduce therate of reintubation. Patients who develop hypoxemia after removal of tracheal intubation are advised toundergo bi-level positive airway pressure in the early stage.

  • Letter
    LX. Liu, XJ. Zhang, FL. Wu, X. He
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 409-413.
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    Bronchiolitis is a widespread lower respiratory tract infection in infants and young children, and isclosely related to the incidence of asthma, and T regulatory cells (Tregs) play a role in its pathogenesis.Notch signaling pathways are closely related to T cells and play a role in respiratory syncytial virus(RSV) bronchiolitis. In this study, we observed the changes in Treg and the level of FoxP3 mRNA inPBMCs in children with RSV bronchiolitis after blocking Notch signaling pathway by γ-secretaseinhibitor MW167, which provides a new idea for RSV bronchiolitis immunotherapy. The study enrolled30 patients with RSV bronchiolitis and 25 normal controls. PBMC was separated and divided into anormal control group, an RSV group, and an MW167 group. The percentage of Tregs was detected byflow cytometry, and the level of FoxP3 mRNA was detected by real-time fluorescent quantitative PCR.Compared with the normal group, the percentage of Tregs in the RSV group was decreased, and thelevels of FoxP3 mRNA were significantly decreased. Compared with the RSV group, the percentage ofTregs in the MW167 group was increased, and the levels of FoxP3 mRNA were increased. There arechanges in the percentage of Tregs and the level of transcription factor FoxP3 in PBMCs of childrenwith RSV bronchiolitis, and γ-secretase inhibitor MW167 can reverse this change to a certain extent.

  • Letter
    D. Ostalska-Nowicka, K. Mackowiak-Lewandowicz, B. Perek, K. Zaorska, J. Zachwieja, M. Nowicki
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 415-420.
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    Obesity-related glomerulopathy (ORG) is an increasingly detected syndrome present in children withobesity. Megalin, a constitutive proximal tubule cell protein, when present in urine, can be consideredas a biomarker indicating renal injury in these children. The aim of the study was to analyze 24-hoururine megalin excretion in children with obesity and compare its clinical usefulness to both urine (u)and serum (s) concentrations of neutrophil gelatinase-associated lipocalin (NGAL) and angiotensinogen(AGT). The study group consisted of 112 patients with obesity; the control group was composed of 90age-matched healthy children. Daily urine megalin excretion, NGAL and AGT concentrations in serumand urine were estimated using ELISA assays. Obesity was defined by Body Mass Index (BMI) z score ≥2. GFR was calculated using Filler formula. An increased daily urine megalin excretion was detected innormo- and hypo-filtrating children with obesity (2.1±2.1 mg/kg b.w./24h and 12.4±3.6 mg/kg b.w./24h,respectively). In hyperfiltering children with obesity this excretion was found within control values(1.5±2.1 mg/kg b.w./24 h). sNGAL, uNGAL and uAGT concentrations were significantly increased inhyper- and hypo-filtering children with obesity. Normofiltering children with obesity (corresponding toindividuals with asymptomatic ORG), presented significantly increased uAGT concentration. ElevatedsNGAL and uNGAL concentrations are useful for characterization of both hyper- and hypo-filtrationstates in ORG. An increased daily urine megalin excretion in normofiltrating children with obesity,accompanied by elevated uAGT concentration, may indicate asymptomatic ORG in these children.

  • Letter
    YM. Li, YB. Zhang, HL. Yang
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 421-426.
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    Endometrial cancer which originates from the malignant proliferation and differentiation of endometrialepithelium cells, along with cervical cancer and ovarian cancer, are the three most malignant cancers inthereproductive system of females. The incidence of endometrial cancer ranked the second among themalignant cancers of reproductive system of females. Endometrial adenocarcinoma is the main pathologicalcategory, with an incidence of 20-30%. The current target treatment of endometrial adenocarcinoma isstill being explored. Therefore it is of great significance to study the expression of signal pathway and geneproteins in the cancerous development of endometrial epithelium cells and their invasion and metastasisprocess. To investigate the expression of gprotein-coupled estrogen receptor 30 (GPR30) and phosphorylatedextracellular signal-regulated kinase 1/2 (p-ERK1/2) in endometrial adenocarcinoma and its significance,the expressions of GPR30 and p-ERK1/2 in the tissues from 24 cases of endometrial adenocarcinoma, 24cases of endometrial atypical hyperplasia (EAH) and 24 cases of normal endometrium were detected usingstreptavidin-perosidase method. The results demonstrated that the positive expression rate of GPR30 in theEAH and endometrial adenocarcinoma group significantly increased, and the differences with the normalendometrium group had statistical significance (P<0.05). The positive expression rate of p-ERK1/2 was thehighest in the EAH group, and the difference with the normal endometrium group was statistically significant(P<0.05). The expression of GPR30 in endometrial cancer with different depth of myometrial invasion wassignificantly different; the deeper the myometrial invasion, the higher the positive expression rate (P<0.05).The expressions of GPR30 and p-ERK1/2 was in no correlation with the other clinicopathological parameters.There was no correlation between the expressions of GPR30 and p-ERK1/2 in the normal endometrium tissues(rs=0.032, P>0.05), but there was a positive correlation between the expressions of GPR30 and p-ERK1/2 inthe EAH and endometrial adenocarcinoma group (rs=0.601, 0.557, P<0.05). Thus, it can be concluded thatGPR30 may play its regulatory role in endometrial adenocarcinoma via p-ERK1/2 signal pathway.

  • Letter
    Y. Zhang, Y Y. Wang, R. Fu, X. Yan
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 427-432.
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    This study aimed to assess the distribution of pathotypes in primary nephrotic syndrome (PNS) and their relationship with glucocorticoid treatment efficacy. The study included 120 patients who were treated in the nephrology, internal medicine and pediatrics wards of The Second Affiliated Hospital of Qiqihar Medical University between March 2014 and October 2017 and who underwent renal biopsy to confirm PNS. The patients with PNS were divided into a child group (40 cases, aged 0~17 years) and an adult group (80 cases, aged over 18 years). We evaluated the correlation of the curative effect of glucocorticoid with age, pathological type, renal tubulointerstitial damage retinol binding protein and total urine protein. The main pathological types of PNS were glomerular minor lesion (GML) and mesangial proliferative nephritis (MPGN). The glucocorticoid treatment had an improved effect on children compared to adults, and also the effect decreased with age. The pathotypes of PNS were correlated with hormone resistance: tubulointerstitial lesions were associated with glucocorticoid resistance which was also associated with the degree of tubular damage. In both adults and children the retinol binding protein (RBP) urinary levels were positively associated with the degree of renal tubular injury. In conclusion, age, pathological type, renal tubulointerstitial damage, and RBP urinary level were related to the therapeutic effect of glucocorticoid treatment in adults and children with PNS.

  • Letter
    H. Wang, W. Chu, YH. Kou, SY. Zhang
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 433-438.
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    Cryptogenic ischemic stroke (CS) is an important risk factor for the death and disability of youngand middle-aged individuals. With the constant development of clinical medicine, it was found thatpatients with patent foramen ovale (PFO) have apparently higher risks of stroke than healthy people.Many scholars and some clinical scientists consider PFO as the main cause of stroke of unknown originoccurring in young and middle-aged. This study aimed to investigate the correlation between PFO andcryptogenic ischemic stroke and analyze the characteristics of cerebral Diffusion-weighted magneticresonance imaging (DW-MRI) of CS patients with PFO. One hundred and sixty-two young and middleagedpatients with CS who were admitted to our hospital between June 2014 and December 2016 wereselected. They were divided into a CS-PFO positive group (n = 106) and a CS-PFO negative group (n= 56) according to the results of contrast echocardiography of the right heart and transesophagealechocardiography. The results demonstrated that the percentage of CS patients with PFO wassignificantly higher than that without PFO, but the baseline data of the two groups had no significantdifference (P>0.05). The results of DWI suggested that infarct lesions of the CS-PFO negative groupwere mainly located in the cortex and sites which were more than 15 mm below the cortex compared tothe CS-PFO positive group, and the difference was statistically significant (P<0.05). Regarding vasculardistribution, infarct lesions of the two groups mainly located at the middle cerebral arteries (MCA),but the difference had no statistical significance (P>0.05). Thus, it is concluded that PFO may be animportant pathogenic factor for CS patients, infarct lesions of patients with CS and PFO mainly locateat the sites which were more than 15 mm below the cortex, and paradoxical embolism may be the mostprobable pathogenesis of PFO-induced cerebral infarction.

  • Letter
    Z. Sui, P. Qu
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 439-445.
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    In this study, phosphorylation levels of vasodilator stimulated phosphoprotein (VASP) were detectedby flow cytometry (FCM) to investigate the effects of ticagrelor and clopidogrel on platelet aggregationfunction (PAF) after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome(ACS). Eighty patients with ACS treated by PCI were enrolled in this study. They were randomly dividedinto a ticagrelor group (group A, 40 cases) and clopidogrel group (group B, 40 cases). The levels of VASPphosphorylation in platelets were measured with FCM before drug treatment and at 24 hours, 7 days and1 month after PCI treatment. In addition, the platelet reactivity index (PRI) was calculated and recorded,while the incidence of major adverse cardiovascular events (MACE) and bleeding events within 1 monthafter PCI intervention in the two groups was analyzed. The results showed that the PRI of group A wassignificantly lower than that of group B at 24 hours, 7 days and 1 month after PCI intervention (P<0.001).Significant difference was observed in the PRI of the two groups before drug treatment and at 24 hours,7 days and 1 month after PCI intervention (P<0.001). The overall mean values of PRI between the twogroups were also significantly different (P < 0.001). Furthermore, the percentage of PRI ≥ 50% in groupA at different time points was significantly lower than that of group B (P<0.01). Nevertheless, there wasno significant difference between the two groups in terms of the incidence of MACE and bleeding eventswithin 1 month after PCI (P>0.05). In conclusion, compared to clopidogrel, ticagrelor reduces PAF morestrongly and faster, which effectively reduced recurrence of post-PCI intervention ischemic cardiovascularevents without increasing the risk of bleeding during a short period.

  • Letter
    ZD. Shang, ZK. Tan, SZ. Liu, JK. Li, YZ. Qiang-Ba, P. Shang, HH. Wang
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 447-455.
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    The acute shortage of forage resources is a serious problem for Tibetan pigs in the Tibet region, andthe composition of feed can change the structure of the intestinal flora. This study first reported the effectof Alfalfa and Chenopodium glaucum feeding on the microbial diversity in Tibetan pigs, contributingto the forage exploitation of Tibetan pigs in the Tibet region. Results showed that the replacement ofconcentrate by green forage did not affect the feed intake of THE pigs. The daily weight gain of pigsfed with 45% green forage was significantly lower (p<0.05), whereas it remained unchanged for theother groups. A total of 483,570 high-quality sequences were obtained from 12 fecal samples. The alphadiversity index revealed no variation in the evenness of community, but a significant difference wasfound in the richness of community among the feeding groups. Principal component analysis showedan obvious alteration among the principal components of the microbial community structure in thedifferent feeding groups. At the phylum and genus levels, 6 phyla and 16 genera differed among thefour groups (p<0.05) but did not include the harmful bacteria. The intestinal microbiota of Tibetan pigsmainly involved 12 metabolic functions, among which, the mean proportion of amino acid metabolismand biosynthesis of other secondary metabolites were higher in the experimental groups. Although thestructure of intestinal microflora changed, harmful bacteria in the pigs did not increase when they werefed with Alfalfa and C. glaucum. These findings indicated that alfalfa and C. glaucum could be used asforage grass for Tibetan pigs.

  • Letter
    E. Loukovitis, E. Tsotridou, T. Vakalis, S. Asteriadis, T. Sousouras, Z. Zachariadis, P. Tranos, N. Kozeis, M. Balidis, G. Anogeianakis
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 457-460.
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    Keratoconus (KC) is a multifactorial, progressive, degenerative corneal disorder with an incidence ofapproximately 1 in 2,000 subjects. Although, the most frequent type of KC is sporadic, there are manycases of familial KC, mainly inherited through an autosomal dominant pattern. KC is characterized bygenetic heterogeneity as it has been associated with a plurality of genes. The present report focuses onsuperoxide dismutase 1 (SOD1) and zinc finger protein 469 (ZNF469) genes which are involved in manycases of KC and other corneal pathologies including the relation of the ZNF469 mutations with BrittleCornea Syndrome (BCS).

  • Letter
    M. Brązert, D. Iżycki, W. Kranc, B. BOROWIEC, M. Popis, K. Ożegowska, A. Bręborowicz, D. Rachoń, M. Nowicki, B. Kempisty
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 461-468.
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    Endocrinal interactions are one of the most crucial regulatory mechanisms that maintain the state of homeostasis in humans. Processes such as oogenesis, folliculogenesis, menstruation and pregnancy remain under hormonal control. A key role in folliculogenesis is played by granulosa cells. Moreover, granulosa cells take part in corpus luteum formation after ovulation. Because of that, it is important to understand the ways in which the granulosa cells, associated with those processes, respond to hormonal stimulus. In the present study, a transcriptomic analysis of human granulosa cells (GCs) was carried out with the use of expression microarrays. The results were validated by RT-qPCR. The total RNA was isolated after 1st, 7th, 15th and 30th days of long-term primary cultures. The main focus of this work was placed on the genes belonging to "Response to estradiol", "Response to follicle-stimulating-hormone", "Cellular response to hormone stimulus", "Cellular hormone metabolic process" and "Hormone biosynthetic process" gene ontology groups. These groups of genes have been associated with GC hormone metabolism and cellular response to hormones. Eighty genes belonging to these groups were identified. Those that were members of more than one of the analyzed gene ontology groups, or exhibited unique expression patterns, were selected for further analysis. All of the selected genes were described, with their expression patterns detailed. In this manuscript, two gene expression patterns have been described. The first one showed large downregulation of genes in the later stages of culture, with the second one presenting upregulation of expression after day 1 of IVC. The present research was focused on six genes found to be the most important for steroidogenesis: STAR, POR, CYP11A1, ADM, GCLC, IL1B, as well as three genes of higher expression at the later stages of long-term in vitro culture: NR2F2, BMP4, COL1A1. The main goal of the presented study was to select genes involved in response to hormonal stimulus and hormone metabolism in GC long-term in vitro culture.

  • Letter
    XJ. Mo, XZ. Ye, YP. Li
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 469-475.
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    In this study, effects of euphorbia kansui on serum levels of inflammatory factors in patients with severe acute pancreatitis were investigated, and the mechanisms underlying the role of Euphorbia kansui in the treatment of severe acute pancreatitis were discussed. 36 patients hospitalized in the Third Affiliated Hospital of Wenzhou Medical University from March 2017 to May 2018 due to severe acute pancreatitis were selected and divided into two groups using a randomized grouping method. ELISA (enzyme-linked immunosorbent assay) was used to detect expressions of various inflammatory cytokines, such as tumor necrosis factor α (TNF-α), soluble TNF receptors (sTNFR), nuclear factor-κB (NF-κB), interleukin-6 (IL-6), and interleukin-8 (IL-8), in the serum of patients at different time points. The results showed no significant difference between the two groups in terms of age, gender, predisposing factors, Balthaza CT scores, and APACHEII (Acute Physiology and Chronic Health Evaluation) scores. According to the experimental results, euphorbia kansui effectively reduced the expression of inflammation related cytokines, such as NF-κB, TNF-α, sTNFR, IL-6, and IL-8, in the serum of patients with severe acute pancreatitis. It was also proposed that euphorbia kansui hindered the release of inflammatory factors and treated SAP by inhibiting the activation of the NF-κB signaling pathway.

  • Letter
    S. Dziegielewska-Gesiak, E. Fatyga, G. Kasiarz, T. Wilczynski, M. Muc-Wierzgon, T. Kokot
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 477-483.
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    Vitamin and mineral disturbances may interfere with glucose metabolism. Elderly persons with diabetes type 2 (T2DM) are more prone to mineral disturbances and vitamin deficiencies. The aim of this study was to analyze concentrations of vitamins B12 and D and macro- and microelements among diabetic elderly patients. The study enrolled 347 patients with T2DM of whom 247 were elderly (median 76 years of age) (SenDM group) and 100 younger T2DM (median 59 years of age) (Y-DM group), and 320 patients aged 65 years and above without T2DM (mean 77 years of age) - Sen-nonDM - as a control group. Patient clinical and biochemical characteristics were recorded (drugs taken and glucose concentration, glycated hemoglobin level, complete blood count, concentration of Na, K, Ca, Fe and serum vitamins D and B12 levels). All elderly patients had insufficient/deficient vitamin D concentration. Vitamin B12 levels were below the reference limit for 15.6% of the SenDM group. No significant differences in Na, K, were observed among the investigated groups. 30.7% of the SenDM were Fe-deficient. In the SenDM group, vitamin B12-deficient patients did not develop macrocytic anaemia while Fe-deficient patients with T2DM tended to develop microcytic anaemia. The prevalence of vitamin deficiencies in elderly patients with T2DM is clinically relevant. Elderly patients with T2DM are clinically predisposed to Fe deficiencies. We suggest to monitor vitamin B12 and Fe concentration toward developing a full clinical picture as it may accelerate the treatment options and improve elderly patients' outcome.

  • Letter
    L. Han, JJ. Zhang, HF. Jing, L. Qin
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 485-490.
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    Acute ST-segment elevation myocardial infarction (STEMI) is one of the most common cardiovascularemergencies. With the improvement of living standards, the incidence and mortality rate of STEMI hasshown a significant growth trend. Percutaneous coronary intervention (PCI) is the preferred choice forthe treatment of STEMI, and the rational use of antiplatelet drugs is an important factor for its success.Therefore, the correct use of antiplatelet agglutination drugs has become a widespread concern. In orderto evaluate the clinical efficacy of emergency PCI for patients with acute STEMI, 120 patients whounderwent emergency PCT in our hospital between January 2016 and December 2017 were randomlyselected and grouped into a clopidogrel group (clopidogrel + aspirin) and a ticagrelor group (ticagrelor+ aspirin) 60 per group. The thrombolysis in myocardial infarction (TIMI) flow grade of infarct relatedarteries, platelet aggregation rate and P2Y12 response unit before and after PCI and the major adversecardiovascular events (MACE), bleeding events and cardiac function after 30 days were compared betweenthe two groups. The results suggested that the proportion of the TIMI flow grade 3 of the ticagrelor groupwas significantly higher than the clopidogrel group after PCI, but the platelet aggregation rate and P2Y12response unit were significantly lower, and the differences had statistical significance (P<0.05). After 30days of follow up, it was found that the incidence of re-infarction and cardiac death, left ventricular enddiastolic diameter (LVEED) and left ventricular end systolic diameter (LVESD) of the ticagrelor groupwere significantly lower than those of the clopidogrel group, but the left ventricular ejection fraction(LVEF) of the ticagrelor was obviously higher; the differences had statistical significance (P<0.05). Noneof the patients had severe bleeding events, and the difference of the incidence of mild bleeding between thetwo groups had no statistical significance. Therefore, in conclusion, ticagrelor has better performance ininhibiting platelet than clopidogrel and better blood perfusion effect for STEMI patients who undergo PCIand it will not increase bleeding risks while improving the short-term prognosis.

  • Letter
    KK. Hozyasz, J. Żółkowska
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 491-497.
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    Dietetic treatment of phenylketonuria (PKU) includes a low-phenylalanine (phe) diet that provides sufficient phe for maintenance and growth plus special phe-free formulas with amino acids to meet requirements for protein, energy and micronutrients.Dietetic treatment of phenylketonuria (PKU) includes a low-phenylalanine (phe) diet that providessufficient phe for maintenance and growth plus special phe-free formulas with amino acids to meetrequirements for protein, energy and micronutrients. Rules for predicting phenylalanine tolerancechanges during the course of pregnancy are not clear. The purpose of this report is to describe phetolerance in pregnant PKU patients with the PAH genotype p.R408W/p.R408W. Low-phe diet wasstarted before the pregnancies. The reviewed cases included three PKU women with two pregnanciesand four PKU women with one pregnancy. Phe restriction in a patient’s diet was determined upon theamount of this amino acid intake, which allows for stable blood phe concentrations within the targetrange of 120–360μmol/L. Daily phe tolerance increased from 344±85mg in the pre-conceptional periodup to 1348±466mg at the end of the third trimester. Before delivery, the lowest and highest phe toleranceexpressed per kg of the pregnant women’s body weight were 6.8 mg and 26.9 mg respectively. Phetolerance varies greatly even between pregnancies of patients with the same PKU genotype. Furtherresearch on pregnant PKU patients is essential to identify biological regulators of phe tolerance duringpregnancy and provide evidence-based guidelines to optimise the dietetic care.

  • Letter
    SX. Qian, JX. Gu, QB. Guan, XL. Zhang, YP. Wang
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 499-504.
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    The aim of this study was to investigate the correlation and clinical significance of oxidative stress and inflammatory response in vascular vertigo (VV). The subjects were divided into three groups: vascular vertigo (group A), non-vascular vertigo (group B) and controls (group C). The serum levels of IL-6 (interleukins-6), SOD (superoxide dismutase), MDA (malondialdehyde) and TNF-α (tumor necrosis factor-α) and CD62P (also called P-Selectin) activation rates were determined and compared among the three groups. The levels of IL-6, TNF-α, MDA and CD62P in group A were significantly higher than those of group B and group C (P less than 0.05). The SOD level of group A was lower than that of group B and group C (P less than 0.05). There was no significant difference between groups B and C in IL-6, TNF- αMDA, SOD and CD62P (P>0.05). In patients with vascular vertigo, TNF-α levels had a weak linear correlation with those of low-density lipoprotein (P = 0.025, r = 0.312). There was no linear correlation between TNF-α and SOD in patients with VV and non-VV. The occurrence of inflammatory reaction and oxidative stress may cause abnormal lipid metabolism in the body and promote the occurrence of VV, and platelet activation may be involved in its formation.

  • Letter
    X. Cheng, SL. Zhao, HM. Zhang
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 505-510.
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    The present study investigated two potential AF1q gene polymorphism proteomic markers in patientswith both leukemia and herpes zoster. A total of 40 individuals were randomly divided into two groups:Group A consisted of herpes zoster acute phase leukemia patients and Group B of healthy volunteers.Two polymorphisms, one in the promoter area and one in exon 1 of the AF1q gene were detected bypolymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP). BbvI and MseIdigestion of each AF1q gene polymorphism PCR amplicon revealed three distinct genotypes for eachpolymorphism. Proteomic results were extracted by iTraq. These results suggest that AF1q is involvedin the pathogenesis of leukemia combined with herpes zoster.

  • Letter
    X. Lian, CC. Shen, HJ. Sun, YJ. Zeng
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 511-516.
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    To explore the possible cytological mechanism underlying the role of Astragaloside IV in promotingthe repair of bone defects, osteoblasts were cultured in vitro and identified using inverted phase contrastmicroscopy, alkaline phosphatase (ALP) staining and alizarin red staining. Subsequently, cells were subculturedinto 24-well plates with different concentrations (0.1 μg/mL, 1 μg/mL, 10 μg/mL, 100 μg/mL,and 1000 μg/mL) of Astragaloside IV before the content of ALP in the culture medium was determined.Using a similar method, a proliferative assay of the cells was carried out to determine the proliferationability of cultured osteoblasts. The results showed that 1μg/mL, 10μg/mL and 100μg/mL AstragalosideIV solutions promoted proliferation of osteoblasts, while 10μg/mL and 100μg/mL promoted the secretionof ALP by osteoblasts. In conclusion, Astragaloside IV of concentrations in a certain range can promotethe proliferation and differentiation of osteoblasts, suggesting the presence of a cytological mechanismunderlying its role in promoting the repair of bone defects.

  • Letter
    JM. Wang, TY. Gong, ZJ. Zhao
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 517-523.
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    This study aimed to investigate the effect of different exercise loads on sex hormones and expressions of relevant genes in hypothalamus in obese mice. Sixty weaning male C57BL/6 mice were used as subjects. Among them, 15 mice were randomly classified into the normal diet group (CON group), and the remaining 45 mice into high-fat diet group (MOB group). The obesity was successfully achieved by high-fat diet 10 weeks later. Then the rats were randomly divided into three groups based on weight, namely, obesity control group (OBC group), obesity with moderate-intensity exercise group (MOBC group), and obesity with high-intensity exercise group (HOBC group), with 15 mice in each group. Mice in the MOBC group and HOBC group were offered 8 weeks of swimming training, and the exercise time increased incrementally until 2 h and 4 h per day. After the training was over, ELISA method was used to determine the serum levels of Adiponectin (Adipo), luteotropic hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T). Real-time PCR was implemented to detect the transcriptional levels of genes of Adipo and other relevant proteins in the hypothalamus. The result showed that compared with the CON group, there was a significant reduction in the serum levels of Adipo, LH, FSH and T in the OBC group (P<0.05). As compared with the OBC group, the serum levels of Adipo, LH, FSH and T increased significantly in the OBC group (P<0.05). There was a significant increase in the transcriptional levels of Adipo, Adipo receptor 1 (Adipo R1), and AMP-activated protein kinase (AMPK) in the OBC group (P<0.05) compared to in the CON group; meanwhile, the transcriptional levels of kisspeptin (Kiss) and gonadotropin-releasing hormone (GnRH) decreased significantly (P<0.05). In conclusion, long-term moderate-intensity exercise could improve the negative effect of obesity on sex development. Long-term high-intensity exercises could not improve the inhibitory effect of obesity on sex development.

  • Letter
    Y. Zhang, DR. Shao, ZP. He, XX. Ma, CJ. Shi
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 525-530.
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    Sepsis is a systemic inflammatory response that can further develop into severe sepsis (septic shock), which eventually leads to multiple organ dysfunction syndrome (MODS). This study aimed to assess the effects of continuous renal replacement therapy (CRRT) on acute renal injury caused by severe sepsis by monitoring biochemical parameters. A total of 60 patients with septic shock and acute kidney injury were included. The control group (30 cases) was treated with routine treatment and intermittent renal replacement therapy (IRRT). The experimental group (30 cases) was treated with routine treatment and continuous renal replacement therapy CRRT. The changes in inflammation and biochemical indexes and APACHE- II score were evaluated before the treatment and 1, 3, and 7days after the treatment. The inflammatory markers (neutrophil percentage, C-reactive protein (CRP) and procalcitonin (PCT) levels) in the experimental group decreased significantly after treatment. In the control group, the index of inflammation still increased one day after treatment and decreased on day 3 of treatment. After treatment, blood lactate, serum creatinine and urea nitrogen levels decreased, but the urine volume increased. After treatment, the vasoactive dose in the experimental group was significantly lower than that of the control group (P less than 0.05). CRRT is a good treatment for septic shock-related acute kidney injury, which improves biochemical indicators and protects kidney function.

  • Letter
    W. Xie, J H. Su, J. Wang
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 531-536.
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    The aim of this study was to evaluate the effects of rehabilitative aerobic exercise on blood pressure, serum inflammatory factors, endothelin and quality of life in patients with hypertension. Ninety patients with mild hypertension visiting West China Hospital of Sichuan University from June 2017 to December 2017 were enrolled and randomly divided into an experimental group and a control group. Patients in both groups were given a low-salt diet, and the experimental group was given an extra three-month treadmill training. Systolic blood pressure (SBP), diastolic blood pressure (DBP), serum tumor necrosis factor α (TNF-α), serum interleukin-6 and endothelin-1, body mass index (BMI), triglyceride (TG) and other indicators were examined in both groups before and after exercise, SF-36 scale was used to evaluate the quality of life. The results showed that after 3 months of exercise, SBP and DBP in the experimental group were significantly lower than those in the control group (P less than 0.05). Compared with the control group, the concentrations of TNF-α, interleukin-6 and endothelin-1 in the experimental group were significantly decreased (P less than 0.05). Correlation analysis showed that IL-6 was positively correlated with SBP (P less than 0.05), and TNF-α and ET-1 were positively correlated with diastolic blood pressure (P less than 0.05). The general health status, energy, mental health, social function, emotional function and health changes of the experimental group were significantly improved compared with before exercise (P less than 0.05). In conclusion, rehabilitative aerobic exercise can lower blood pressure and improve the overall quality of life in mild hypertension patients by inhibiting vascular inflammation and lowering plasma endothelin-1.

  • Letter
    KN. Yang, W. Han, YJ. Qin, LN. Chen
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 537-542.
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    To investigate the effects of different doses of soluble PD-L1 (soluble form of Programmed death ligand 1, sPD-L1) protein on Lewis lung cancer cells, flow cytometry was used to detect the expression of PD-L1 (Programmed death ligand 1) on the surface of Lewis lung cancer cell lines and the expression of PD-1 on the surface of T lymphocytes in peripheral blood and spleen cells of C57BL/6 mice. A Lewis lung cancer animal model of C57BL/6 mice was established by transplanting Lewis lung cancer cells subcutaneously. The sPD-L1 protein was injected into the abdominal cavity of the mouse (sPD-L1 Ig) (working dose: 2.5, 5, 10 μg per mouse), while the sPD-L1 control protein was injected as a control. The growth of Lewis lung cancer xenografts was observed. On the 18th day after tumor cell inoculation, T lymphocyte subsets in mouse spleen were determined by flow cytometry. The PD-1 molecules on the surface of Lewis lung cancer cell line, C57BL/6 mouse spleen T lymphocytes and peripheral blood T lymphocytes were positively expressed. Compared with the control group, the volume of the transplanted tumor of Lewis lung cancer in C57BL/6 mice was larger with 10 μg sPD-L1 I g injection (P less than 0.05), and no significant difference was observed in tumor volume with 2.5 μg and 5 μg injection (P > 0.05). A certain level of soluble PD-L1 (10 μg/ mouse) could promote the growth of transplanted tumors of Lewis lung cancer in C57BL/6 mice.

  • Letter
    W. Jia, TZ. Wang
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 551-555.
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    This study aimed to evaluate the clinical efficacy of trastuzumab combined with lapatinib in thetreatment of human epidermal growth factor receptor 2 (HER2) positive breast cancer. One hundred andfifty-four patients with breast cancer were randomly divided into a trastuzumab group (group A, 52 cases),a lapatinib group (group B, 48 cases) and a combination group (group C, 54 cases). The patients fromgroup A received trastuzumab 4 mg/kg intravenously once a week in the first 9 weeks, and 2 mg/kg iv inthe second 9 weeks. The patients from group B took lapatinib 1.5 g orally once per day. The patients fromgroup C received the combination of 4 mg/kg intravenously once a week in the first 9 weeks, and 2 mg/kgiv trastuzumab (the same doses as in group A) in the second 9 weeks and 1.5 g lipatinib orally per day for18 weeks. After treatment, the clinical efficacy of the treatments in the three groups was observed, and theprogression free survival (PFS), overall survival (OS), central nervous system (CNS), overall response rate(ORR), clinical Benefit Response (CBP) and adverse reactions were compared before and after treatment.After treatment, PFS of group A, group B and group C were 44, 42 and 58 months, respectively. PFS ofgroup C was significantly higher compared with that of group A and group B (P<0.05). After treatment,during follow-up, OS in group A, group B and group C were 28, 20 and 22 months, respectively. Aftertreatment, the CNS metastasis rate in group C was significantly lower than that in group A and group B(P<0.05). ORR and CBR in group C were higher than those in group A and group B (P<0.05). The incidenceof adverse reactions in group C was significantly lower than that in group A and group B (P<0.05). Inconclusion, the potency of lapatinib combined with trastuzumab in the treatment of HER2 positive breastcancer patients is superior to treatment with lapatinib or trastuzumab only.

  • Letter
    Q. Zhang, L. Cao, XD. Miao, YP. Wu
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 557-562.
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    In order to investigate the diagnostic value of serum levels of tartrate-resistant acid phosphatase 5b (TRACP5b) in patients with bone tumors, enzyme linked immunosorbent assay (ELISA) was used to com¬pare serum levels of TRACP5b and alkaline phosphatase (ALP) in bone tumor patients (experimental group, 80 cases) and healthy controls (control group, 36 cases). It was found that the serum level of TRACP5b in the experimental group was significantly higher than that in the control group. In addition, the sensitivity and specificity of serum TRACP5b were higher than those of serum ALP in the diagnosis of bone tumors. Fur¬thermore, the serum level of TRACP5b was positively correlated with that of ALP. Therefore, it was conclud¬ed that the serum level of TRACP5b may be used as a sensitive indicator of bone tumors, and the sensitivity and specificity of TRACP5b are even higher than those of ALP in the diagnosis of bone tumors.

  • Letter
    S. Ma, F. An, LH. Li, YY. Lin, J. Wang
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 563-569.
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    This study aimed to detect the expression of Mucin 1 (MUC1) in acinic cell carcinoma (AciCC) of salivary gland and to explore the relationship between MUC1 and clinicopathological factors of AciCC of salivary gland. Patients with salivary gland tumors who were treated at our hospital were enrolled in this study. The pathological sections collected from all subjects were classified by histological examinations. In addition, 40 cases of primary salivary gland AciCC tissues were selected and classified into experimental group, whereas 40 cases of normal salivary gland (NSG) tissues were selected and classified into control group. MUC1 positive cells in both experimental and control groups were detected by immunohistochemistry assays, while all clinical data were analyzed statistically. The results showed that MUC1 was only expressed in the ductal epithelium of NSG and distributed at the apical side of the cell membrane. In primary salivary gland AciCC tissues, scattered expressions of MUC1 were found both on the cell membrane and in the cytoplasm of tumor cells, and sometimes even in the cell nuclei, thus completely eliminating the polarized distribution of MUC1 expressions. The percentage of MUC1 positive cells in experimental group was significantly higher than that in control group (P < 0.05). In addition, the expression of MUC1 in salivary gland AciCC was correlated with gender, age, histological type, lesion location, cervical lymph node metastasis, local recurrence, and distant metastasis. In conclusion, MUC1 is related to the occurrence and development of salivary gland AciCC. Therefore, MUC1 may be used as a novel tumor marker in the clinical diagnosis and treatment of salivary gland AciCC.

  • Letter
    Q. Sun, F. Fang, GC. Lu, HH. Mao, JH. Xu, SK. Zhou, XM. Tong, Y. Guo, JF. Wu, B. Jiang
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 571-579.
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    The aim of this study was to investigate the mechanism of hepatocyte apoptosis and regeneration after partial hepatectomy in obstructive jaundice (OJ) rats under different drainage methods of bile acid intervention. Forty male Sprague Dawley rats were randomly divided into five groups. An OJ rat model was established by the following protocols. Seven days after obstruction, an SD rats model with 70% partial hepatectomy was established by different drainage methods of OJ. Blood and liver tissue samples were collected from rats 72 h after surgery; 72 h after partial hepatectomy (PH), the liver regeneration rate, the expression of proliferating cell nuclear antigen (PCNA) and the level of mitotic index (MI) in the internal biliary drainage (IBD) group were higher than those in external biliary drainage (EBD) group (P less than 0.05). Those in the EBD group were higher compared to the OJ group (P less than 0.05). There was no significant difference among the IBD group, EBD+CA group and (SO) sham operation group (P>0.05). Bax expressions had the same trend as AI in the five groups. The expression of Bcl-2 was increased in the IBD group and EBD+CA group, which was statistically higher compared to the SO group (P less than 0.05). In conclusion, both internal and external drainage can relieve biliary obstruction. The difference in liver regeneration caused by external drainage and internal drainage may be attributed to the destruction of bile acid enterohepatic circulation, which increases hepatocyte apoptosis and affects liver regeneration.

  • Letter
    D.Beomonte Zobel, C. Dell'Atti, N. Magarelli, D. Coviello, G. Belmonte, M.F. Saccomanno, A. Paladini, G. Milano, A. Leone, C. Colosimo
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 581-586.
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    The aim of this study is to determine the diagnostic performance of Magnetic Resonance Arthrography(MRA) in evaluating lesions of the glenoid labrum, in young active patients with chronic unstableshoulder, compared to shoulder arthroscopy. We retrospectively considered 65 MRA examinations,performed between December 2011 and January 2018. Among them, thirty-five patients (31 men, 4women; mean age, 27.3 years; range, 16-53 years; 4 patients with a previous arthroscopy of the sameshoulder) underwent shoulder arthroscopy after MRA. Arthroscopic reports were collected andanalyzed for the correlation with MRA results. The inclusion criteria were: a) clinical symptoms ofchronic shoulder instability with at least 2 episodes and less than 5 episodes of shoulder dislocation; b)arthroscopy performed by surgeons in our institution; c) non-professional sportsmen, that is occasionalor amateur sport practice. MRA examinations, carried out with a 1.5 T superconductive magnet, wereevaluated by two radiologists. The authors observed complete agreement between MRA evaluation andarthroscopic findings in 31 patients, and disagreement in 4 patients. Sensitivity was 93%, specificity71%, positive predictive value 93%, negative predictive value 71% and the diagnostic accuracy for allglenoid lesions 88%. In patients with chronic shoulder instability, MRA confirmed its high sensitivityand positive predictive value for the diagnosis of labral lesions, providing useful information on the sizeand extent of the tears. The lower value of specificity and negative predictive value were probably dueto the small number of patients who underwent arthroscopy after an MRA negative for glenoid injuries.

  • Letter
    V. Monda, I. Villano, A. Messina, A. Valenzano, M. Salerno, S.Santo Signorelli, M. Monda, V. Russo, F. Sessa, G. Messina
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 587-592.
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    Aerobic exercise is associated with the sympathetic activation evoking adaptive responses to sustainmuscle engagement. Physical exercise can cause alterations in the cardiovascular activity and cellularstress may occur which could be marked by either heart rate (HR), or galvanic skin response (GSR).Moderate plasma levels of reactive oxygen species (ROS) are considered as health markers, absolving toimportant roles such as adaptive cellular responses to exercise. Orexin A, a hypothalamic peptide, causes awidespread stimulation of the sympathetic nervous system, playing a role in many physiological functions.The aim of this study was to analyze the effects of aerobic exercise on Orexin A plasma levels, evaluatingthe possible association with physical exercise and oxidative stress, both involved in the sympathetic andthermogenic reactivities. Three blood samples were collected at various periods of time from all participants(25 males with mean age of 23.4±2.1 years): resting time (0 min), exercise time (at the start and at endof exercise) and recovery time (30-45 min after training). At the same interval times, heart rate (HR),galvanic skin response (GSR), rectal temperature, and d-ROMs test were monitored. Exercise induceda significant increase in the following parameters: HR (p <0.01); GSR (p<0.05); rectal temperature(p<0.01); and plasma Orexin A (p < 0.01). No significant increase of the d-ROMs values were found.The results of this study confirmed that physical activity is associated with the sympathetic activation, asdemonstrated by HR and GSR increases after training. Changes in the Orexin A plasma levels reveal thepresence of hormonal adaptations in response to exercise, indicating that this peptide might be involved incardiovascular regulation. Further studies could confirm the multitasking role of this neuropeptide.

  • Letter
    M.Miraglia Del Giudice, C. Indolfi, G. Ciprandi, F. Decimo, G. Campana, G.R. Umano, E. Giannetti, M. Maglione
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 593-599.
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    Gastroesophageal reflux disease (GERD) may be frequently associated with asthma in childrenand may affect asthma control. Proton pump inhibitors (PPI) are commonly prescribed in asthmaticchildren, despite uncertain efficacy on respiratory symptoms and risk of relevant adverse effects. Weinvestigated whether Magnesium Alginate (MA), an alternative option to PPI in GERD management,improves symptom control in children with uncontrolled asthma. Children with uncontrolled asthmawere prospectively enrolled at two tertiary care pediatric respiratory centers over 4 years. The recruitedsubjects were randomly assigned to three groups, receiving, in addition to current asthma therapy,PPI, MA or no specific GERD treatment, respectively, for 8 weeks. Lung function, asthma control test(ACT), and asthma control questionnaire (ACQ) were assessed at baseline, at the end of the treatment,and at the follow-up. Both PPI and MA significantly improved ACT and ACQ in comparison withthe control group. ACQ improvement at follow-up resulted more relevant in the MA than in the PPIgroup (p=0.004). No difference between MA and PPI was detected with regard to ACT improvement. Inconclusion, added to standard asthma medications, MA may improve symptom control in children withuncontrolled asthma.

  • Letter
    F. Ameli, G. Ciprandi
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 601-607.
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    Recurrent respiratory infections (RRI) are an intriguing challenge for both otolaryngologists and paediatricians. Therefore, to prevent RRI is an ambitious target in clinical practice. In this regard, modulation of the immune system may have a critical role. Sinerga, a dietary supplement (containing: palmitoylethanolamide (PEA), Kluyveromyces marxianus B0399, bovine colostrum, and phenylalanine), was supplemented in 20 allergic children with RRI (20/30 days per 3 months) and treated with standard therapy (antihistamine plus intranasal corticosteroid). Other 20 allergic children with RRI were treated only with standard therapy. Sinerga significantly reduced the number of RI and the size of both inferior and middle turbinate consistently with the postulated mechanisms of action. In conclusion, the current study demonstrated that Sinerga supplementation in allergic children with RRI may significantly prevent RI and reduce events depending on allergic inflammation.

  • Letter
    G.F. Cupido, M. Gelardi, I. La Mantia, S.E. Aragona, G. Ciprandi, ITALIAN STUDY GROUP ON INFLAMMATORY OTORHINOLARYNGOLOGICAL DISORDERS
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 609-615.
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    Inflammation is a common pathogenic mechanism involved in many otorhinolaryngological (ORL)disorders. Broser® is an oral nutraceutical currently containing bromelain 100 mg, escin 30 mg, andselenium 42.5 mcg. It could exert a safe and effective anti-inflammatory activity by virtue of thesecomponents. Therefore, the aim of the current survey, conducted in clinical practice of 84 Italian ORLcenters, was to evaluate its safety and efficacy in the treatment of patients with: i) high-tract acute illness;ii) low-tract acute illness; iii) high-tract chronic illness; iv) low-tract chronic illness; or v) post-surgerycondition. The 3,203 (1,604 females and 1,599 males, mean age 44.9±8.9 years) patients were evaluatedat baseline (T0) and after a 2-week treatment (T1) with Broser® monotherapy (2 tablets/daily). Signs andsymptom severity were measured by visual analogue scale. Broser® significantly and safely diminishedthe clinical features in ORL disorders all sub-groups (p<0.001 for all). In conclusion, Broser® is an oralnutraceutical able to exert a safe and effective anti-inflammatory activity in patients with inflammation.

  • Letter
    GL. Marseglia, A. Licari, G. Ciprandi, ITALIAN STUDY GROUP ON PEDIATRIC ALLERGIC RHINOCONJUNCTIVITIS
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 617-622.
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    Allergic rhinoconjunctivitis (AR) treatment is usually pharmacological in children, but medications are merely symptomatic, may not be completely effective, and may have relevant side effects. Thus, doctors and parents look at complementary medicine, including nutraceuticals. Lertal®, an oral nutraceutical, contains extract of Perilla, quercetin, and Vitamin D3 It has been reported that adults with AR diminished allergic symptoms and medication use during Lertal® therapy. Therefore, the current polycentric, randomized, double blind, parallel-group, placebo-controlled study aimed to evaluate the efficacy and safety of Lertal® as an add-on treatment in children with AR. In this study, 146 children (94 males and 52 females, mean age 9.1±1.88) were randomly assigned to Lertal® + standard treatment or Placebo + standard treatment and were visited at baseline (W0), and after 2 (W2) and 4 weeks (W4). Standard treatment consisted of continuous antihistaminic schedule. The primary endpoint was the Total Symptom Score (TSS - last 12 hours) change from the baseline to the end of the 4-week treatment. Both groups significantly (p less 0.0001 for both) reduced TSS (last 12 hours) after 4 weeks (% change: - 63.6% in Lertal®-group and - 60.7% in Placebo-group; p= n.s. intergroup analysis). Notably, 24 children had symptom worsening between W2 and W4: 8 in the Lertal®-group and 16 in the Placebo-group, with significant intergroup difference (p less than 0.05). All of them were poly-allergic subjects exposed to multiple allergens. There was no relevant adverse event. The present study documented that Lertal®, as add-on treatment, was able to significantly prevent the occurrence of clinical worsening and was safe in AR poly-allergic children.

  • Letter
    E. Spinas, L. Generali, A. Mameli, C. Demontis, D. Martinelli, L. Giannetti
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 623-627.
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    Avulsion of one or more permanent teeth represents an emergency in dentistry. The main treatment isthe replantation of the tooth/teeth as soon as possible to decrease possible complications. However, this is notalways possible, and, in many cases, the patient undergoes a delayed replantation and subsequently prostheticand implant treatments. This becomes problematic when the traumatized patient is a child; in this case, thegoal is to maintain the space for the subsequent implant positioning and to give an adequate aesthetic resultuntil the bone growth has ceased. A review on the incidence of the inflammatory root resorption onset afterdelayed replantation was carried out to check the frequency and severity of these complications.

  • Letter
    L. Giannetti, E. Spinas, A.Murri Dello Diago
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 629-631.
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    The aim of this study is to assess what needs to be the priority in tooth avulsion: replantation asquickly as possible and deferred endodontic treatment, or replantation and elimination of every irritatingstimulus for the periodontal ligament. Twenty patients were selected and divided into 2 groups: in groupA attention was focused on the rapidity of replantation and postponed endodontic therapy, in group Bwe focused on the elimination of the necrotic pulp with extraoral endodontic therapy. Clinically, therewas no difference in stability, but there were 3 elements in infraocclusion in group A, and 4 in group B.Radiographically, a similar incidence of radicular resorption caould be observed in group B compared togroup A. In conclusion, as a result of dental avulsion, the speed of replanting always seems to be a priority.

  • Letter
    C. Bertoldi, M. Ferrari, L. Giannetti
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 633-636.
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    Periodontal tissue regeneration depends on several biological, homeostatic and regulative variables that directly induce the clinical features. The aim of this study is to compare the clinical results obtained using the enamel matrix derivative peptide (EMP) compared to the less manageable association of EMP and bovine bone xenographic (BPBM) in the treatment of deep intraosseous defects. Ten healthy patients, suffering from moderate or severe chronic periodontitis, having at least two deep and narrow intrabony defects in the same dental arch and needing surgical treatment, were selected. The same patient was treated with the two different materials: EMP -TG1 in one defect and the association-TG2 in the other. Immediately before surgery (T0) and 12-month after (T2) the probing depth (PD) and gingival recession (GR) were registered at the experimental sites. No statistically significant differences were shown between TG1 and TG2 at T0 nor at T1 in term of PD and GR, while a statistically significant PD decrease was found both in TG1 and TG2 between T0 and T1 (p less than 0.05). GR increase resulted statistically significant in TG1 (p less than 0.05) but not in TG2 between T0 and T1 (p≥0.05). In this split-mouth retrospective study, both the treatments achieve favourable clinical results but the TG1 shows a significant increase in GR probably because EMP is not able to support the gingiva covering the intrabony defect. Therefore, the choice of the type of periodontal defect to be treated with EMP will be a therapeutic key-point.

  • Letter
    M. Cabras, A. Gambino, R. Broccoletti, P.G. Arduino
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 637-642.
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    The occurrence of epithelial desquamation, erythema, and erosions on the gingival tissue could bedescribed in literature as “desquamative gingivitis” (DG), mostly due to a wide range of autoimmune/dermatological disorders. The objective of this systematic review was to assess the efficiency of thedifferent treatments for DG. The research was conducted using the following databases: PubMed, GoogleScholar, NIH (National Institute of Health), Up to Date, Scopus, Cochrane Library, Web of Science.The P.I.C.O. (Patient, Intervention, Control, Outcome) question was as follows: human patients withclinical-pathological diagnosis of DG (Patients); any topic, systemic medication, photobiomodulationor periodontal treatments (Intervention); no treatment, placebo or other drug (Comparison); andeffectiveness in terms of improvement of symptoms (primary Outcome) and signs (secondary Outcome).The PROSPERO record is number CRD42018084531. A total of 2,174 potential results were acquiredfrom the various databases, of which 998 were duplicates; the remaining 1,176 studies were submittedto a first reading of title and abstract: 1,137 articles had to be excluded, with 994 not being inherent tothe purposes of this review, and 143 being published in languages other than English. The remaining39 articles were subjected to full reading; 4 randomized controlled trials were considered eligible butonly 2 finally analysed. To date, 0.05% clobetasol propionate ointment compared with placebo, in themanagement of signs and symptoms of DG, showed no statistically significant differences. Differently, astructured plaque control appeared to be successful in reducing plaque and improving signs and relatedpain, with statistically significant differences regarding related symptoms, plaque index and mucosaldisease score. Regarding the clinical relevance based on our results, it is actually not possible to drawcertain and positive conclusions as to the best management modalities for DG. Future research shouldbe conducted in order to establish a proper therapy for this condition, primarily considering that it ismainly a characteristic clinical representation of dissimilar autoimmune bullous diseases. A promisingfield could be that of periodontal therapy, however, more data are needed.

  • Letter
    I. Vitali, O. Genovese, G. Conti, L. Raffaelli, A. D'Addona, A. Dell'Anna, L. Dassatti
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 643-647.
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    Ventilator Associated Pneumonia (VAP) is a serious complication in critically ill patients, and oralhygiene care may effectively reduce its incidence. The prevention of VAP is much more effective throughthe implementation of several interventions that together give rise to a potentially synergistic effect. FromJanuary 2018, according to the latest guidelines and the internal department protocol at the PaediatricIntensive Care Unit of A. Gemelli University Hospital, the measures for the management of the VAP havebeen implemented. Chlorhexidine 0.12% has been used, within the oral hygiene procedures establishedby the protocol, to evaluate its microbiological and clinical effectiveness on the development of ventilatorassociatedpneumonia in paediatric patients admitted to intensive care undergoing invasive mechanicalventilation. The main purpose of the present study was to verify the effectiveness of the prevention protocol,during its implementation, in reducing the incidence of pneumonia associated with invasive mechanicalventilation. The survey also aimed to evaluate the predictive power of the culture of the pharyngeal swabs,routinely performed according to the scientific evidence, in identifying the colonization of the trachea,in the patients admitted to our intensive care unit and subjected to mechanical ventilation for at least 48hours. Finally, the research has evaluated the conditions of the stomatognathic apparatus and of all thetissues and organs associated with it in the patients who use ventilators.

  • Letter
    S. Muraglie, G. Musumeci, C. Loreto, R.M. Leonardi
    Journal of Biological Regulators and Homeostatic Agents. 2019, 33(2): 649-655.
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    The aim of this study was to evaluate the expression of ADAMTS4 and ADAMTS5 in human gingivalcrevicular fluid (GCF) at different time-points following the application of an orthodontic force. Thirtytwohealthy patients (20 females, 12 males, mean age 13.8) who had undergone orthodontic treatmentand needed upper first premolar extractions were enrolled in this study. For each patient, one maxillarycanine was used as the test side and was subjected to a standardized orthodontic force while the contralateralcanine was used as a control and not subjected to any force. A GCF sample was taken on thecompression and test sides of the test tooth and on the control tooth at baseline, after 1, 4, 24 hoursand 7 and 21 days. Western blot analysis was performed to detect protein levels on controls and testteeth. Following the application of a force, the expression of ADAMTS4 increased significantly (p≤0.001)peaking at 4 hours in the tension side, while on the compression side it reached a peak, in a timedependentway, at 21 days (p≤0.001). ADAMTS5 levels peaked, on both tension and compression sides,at 1 hour following the application of force (p≤0.05), and on the compression side also at 24 hoursand 7 days. These results suggest that both ADAMTS4 and 5 are involved during the early stages oforthodontic tooth movement.