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Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. Although the global incidence has been increasing in the recent years, the targeted treatment drugs remain unavailable. Recent studies have shown that vitamin D3 participates in fat metabolism, reduces insulin resistance, and has certain anti-oxidative, anti-apoptotic, anti-inflammatory, and anti-fibrotic properties. 25(OH)D is the active form of VD3. In the recent epidemiological studies, we observed lower serum 25(OH)D levels in patients with non-alcoholic fatty liver disease. Vitamin D3 supplementation can have some preventive effect on NAFLD occurrence and development. This article reviews the research progress and mechanisms of vitamin D3 action in NAFLD.
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Background: Previous studies have shown that the outcome of coronavirus disease 2019 (COVID-19) in patients with rheumatoid arthritis is influenced by certain comorbidities, diseases, and specific therapeutic modalities.
Aim: This study aimed to analyze the impact of disease-modifying antirheumatic drugs, vaccination status, and clinical and demographic characteristics on the hospitalization rate of COVID-19 patients with rheumatoid arthritis.
Patients and Methods: Retrospective analysis was obtained by completing a web-based survey, according to the European COVID-19 register. The data included demographic patient characteristics, comorbidities, immunosuppressive and other drugs, and 112 COVID-19 patients with rheumatoid arthritis. These patients were infected with severe acute respiratory syndrome coronavirus 2 from July 16 to November 22, 2021.
Results: In patients with rheumatoid arthritis, 21 (18.75%) were hospitalized due to COVID-19 infection. In the group of hospitalized patients, 19 (90.5%) patients required oxygen support therapy, while 6 (28.6%) patients died during hospitalization. The participants were predominantly female (78.6%), with a mean age of 54. Age was associated with a higher hospitalization rate in the univariate analysis. After multiple adjustments, the final regression model showed that hypertension (OR (odd ratio) = 5.994, 95% CI (confidence interval) 1.443–24.901, p = 0.014) and rituximab therapy (OR = 23.969, 95% CI 5.129–112.008, p < 0.001) were the risk factors associated with hospitalization. Vaccination status did not affect the outcome of COVID-19 infection.
Conclusions: In rheumatoid arthritis patients with COVID-19 infection, treatment with disease-modifying antirheumatic drugs, except for rituximab, did not increase the risk of hospitalization, while the use of tocilizumab proved to be protective. Independent factors associated with the hospitalization of rheumatoid arthritis patients were age, hypertension, and rituximab therapy. The strongest predictors for hospitalization due to severe acute respiratory syndrome coronavirus 2 infection were the use of rituximab and hypertension. Therapy with rituximab increases the risk of a severe course of infection. Therefore, it should be given with particular caution. Hypertension is a significant risk factor that further increases these patients’ hospitalization risk.
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Background: Conservative treatment of De Quervain’s syndrome includes corticosteroid infiltration and physical therapies.
Methods: In this prospective randomized clinical trial, 30 patients affected by De Quervain’s syndrome were assigned to either cortisone infiltrative treatment (steroidal group) or extracorporeal shock waves therapy (ESWT group). Therapy efficacy was estimated by monitoring pain (with VAS (visual analogue scale)), disability (with DASH (disability of the arm, shoulder and hand)) and quality of life (with SF-36) compared between recruitment (T0) and after three (T1) and six months (T2).
Results: Both groups demonstrated statistically significant improvement after treatment. Evaluating the comparison between times, a statistically significant difference was found for VAS, DASH and 6 scales of SF-36 (p < 0.05). No significant interaction was found in the comparison between groups and in the comparison between time and group.
Conclusions: ESWT could be a non-invasive option for treatment of De Quervain’s syndrome, particularly for those patients who prefer to avoid corticosteroid infiltration.
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Background: The crucial role of Long non-coding RNAs (lncRNAs) in the progression of diverse tumors has been reported, including esophageal squamous cell carcinoma (ESCC). Nonetheless, the mechanism of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in ESCC is rarely reported.
Methods: KCNQ1OT1, miR-125a-5p and Signal transduction and transcriptional activator 3 (STAT3) expression levels in ESCC tissues and cells were examined by qRT-PCR (quantitative real-time polymerase chain reaction). Additionally, Western blot was employed to examine STAT3 protein expression in ESCC cells. The biological functions of KCNQ1OT1, miR-125a-5p and STAT3 in ESCC cells were examined by Cell Counting Kit-8 (CCK-8), EdU (5-ethynyl-2’-deoxyuridine), and Transwell assays. Bioinformatics and dual-luciferase reporter experiments were applied to explore the regulatory mechanisms among KCNQ1OT1, miR-125a-5p and STAT3.
Results: KCNQ1OT1 and STAT3 were abnormally up-regulated in ESCC tissues, while miR-125a-5p was abnormally down-regulated. Silencing of KCNQ1OT1 remarkably suppressed the proliferation, migration, and invasion of ESCC cells. MiR-326 inhibition markedly counteracted the tumor-suppressive effect of KCNQ1OT1 silencing on ESCC cells. Moreover, KCNQ1OT1 competitively bound with miR-125a-5p to repress the degradation of STAT3.
Conclusions: The findings of this work imply that KCNQ1OT1 is implicated in ESCC progression through modulating miR-125a-5p/STAT3 axis and indicate that KCNQ1OT1 may be a promising biomarker and therapeutic target for ESCC.
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Background: TMEM45A is a hypoxia-related gene encoding a transmembrane protein, which plays a role in forming the extracellular matrix. Despite recent data demonstrating the role of TMEM45A in tumor development and prognosis in several cancer types, there is no pan-cancer study of its involvement in tumorigenesis. We assessed the predictive significance and possible participation of TMEM45A for diverse types of human cancers and also evaluated its impact on the immune response against stomach adenocarcinoma (STAD).
Methods: We collected data from public big data repositories including cBioPortal, GEPIA2, GSCA, Kaplan–Meier, LinkedOmics, TIMER2, TISCH, and others analyzed them via multiple bioinformatics methods to explore the potential role of TMEM45A as an oncogene.
Results: Our results demonstrated higher levels of TMEM45A mRNA expression in 13 cancer types, which was negatively associated with the prognosis of 12 cancer types. We further observed a positive correlation of TMEM45A with the immune, stromal, and ESTIMATE scores in STAD cells and many other tumor types.
Conclusions: TMEM45A is expressed in a variety of different types of tumors and may serve as a prognostic marker and may be implicated in new targeted therapy in the future.
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Background: According to many studies, the development of several tumors is significantly influenced by hypoxia-related indicators. However, the biochemical link between hypoxia markers and tumors, and their potential clinical implications, remain obscure.
Methods: We obtained sequencing data and clinical information on osteosarcoma (OS) from the TARGET database and screened for hypoxia-associated genes linked with its poor prognosis. We then identified PFKFB3 as a potential biomarker using pan-cancer analysis. The expression pattern of PFKFB3 and its immunological role were comprehensively investigated using pan-cancer analysis. The PFKFB3 protein was then systematically correlated with tumor progression-related features such as TMB, MSI, CNV, hypoxia score, and metabolic pathways. We also analyzed the role of PFKFB3 in predicting OS molecular subtypes and identified potential PFKFB3 target drugs.
Results: A total of 10 hypoxia-associated poor prognosis genes were screened from the OS dataset. By pan-cancer analysis, we found that PFKFB3 expression was positively associated with HIF1A in almost all tumor types. The overall survival was unfavorable in pan-cancer patients with high levels of PFKFB3 in ACC, KIRP, LIHC, and UVM. Additionally, we found that PFKFB3 positively correlated with chemokines, chemokine receptors, and immune suppressive signatures in most cancers. Furthermore, a high percentage of activation of the EMT pathway was observed in pan-cancer cells possibly affected by PFKFB3. The expression of PFKFB3 at the single-cell level was associated with hypoxia, metastasis, inflammation, and EMT in most tumors. Three distinct OS subtypes were identified using gene sets derived from genes positively related to PFKFB3 in the glycolytic, oxidative phosphorylation, and inflammatory signaling pathways. Drug sensitivity analysis showed that CH5424802 had the highest negative correlation with PFKFB3.
Conclusions: We described the characterization of PFKFB3 and its potential utility as a prognostic indicator in OS and other cancers.
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Background: Filtering Facepiece Particle (FFP) masks are the most common Personal Protective Equipment used by healthcare workers, particularly in relation to COVID-19 pandemic. With the aim of improving compliance and decreasing the discomfort caused by prolonged use of facemasks, a new type of FFP2 and FFP3 facemasks, defined as “high breathability”, has been introduced to the market.
Methods: We compared the commonly used FFP2/N95 facemasks with these new “high breathability” facemasks in terms of discomfort caused by prolonged use of the facemasks and an assessment of nasal cavity and nasal respiratory symptoms in healthcare workers.
Results: We involved 36 healthcare workers employed in the operating room and outpatient activities at the Fondazione Policlinico Universitario Campus Bio-Medico of Rome. After seven days of wearing FFP2/BLS 502 facemasks, a statistically significant difference was found in the results to a discomfort questionnaire and the assessment of nasal cavity and the nasal respiratory symptoms, including nasal obstruction and rhinorrhea. Better results were obtained using the BLS 502 facemask in terms of the sneezing and nasal itchiness variables.
Conclusions: Thanks to its design and low breathing resistance, the FFP2/BLS 502 facemask appears to be more comfortable to wear than common FFP2/N95 facemasks.
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Background: To evaluate the effect of using a three-phase dual-flow contrast media (CM) injection scheme in low kilovolt (kV) head and neck computed tomography angiography (CTA) in rabbits to provide a theoretical basis for clinical practice.
Methods: Thirty rabbits were randomly divided into 3 groups of 10 rabbits each, depending on tube voltage and injection scheme. Group A: Two-phase injection with CM (1.5 mL/kg) at 100 kV. Group B: Two-phase injection with CM (1.5 mL/kg) at 80 kV. Group C: Three-phase injection with CM (1.5 mL/kg × 80%) at 80 kV. Hemodynamic testing on rabbits was performed using an ultrasound device to assess differences between groups. CTA scans were performed to observe the differences in CT (Computed Tomography) values, image quality, radiation dose, and CM dosage in three groups. Finally, laboratory tests and renal pathology were performed to observe the damage of CM.
Results: There was no significant difference in hemodynamics between the three groups. In the vessels, there was a decrease in group C versus group B at aortic arch (AA) (p < 0.05). Left superior vena cava (LSVC) was bigger in group C than in groups A and B (p < 0.05). There was no significant difference between three groups in image quality. Groups B and C showed 41% lower radiation dose than A (p < 0.05). For the CM dosage, Group C had CM dosage reduced by 20% compared to groups A and B (p < 0.05). For the laboratory tests result of group B and C, creatinine (Cre) was statistically different at 24 h and 48 h (p < 0.05), and blood urea nitrogen (BUN) showed a difference at the 48th (p < 0.05).
Conclusions: Contrast injection scheme with three phases of dual flow in the head and neck can be performed with low kV and significantly reduce intravenous CT values. At the same time, it can also reduce the radiation dose and CM dosage what reduces kidney damage while it ensures image quality.
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Background: Radiation enteritis (RE) is a frequent side effect of radiotherapy for abdominal and pelvic malignancies that could cause reduced treatment tolerance and quality of life of in patients. GGQL decoction is a widely used traditional Chinese medicine that is clinically used to inhibit inflammation in RE, however potential mechanism is unclear. In the research, we investigated the effects and potential molecular mechanism of GGQL decoction treatment in RE model rats.
Methods: RE model rats were established by exposing Sprague-Dawley (SD) rats to 9 Gy abdominal X-ray irradiation, with or without GGQL decoction administration. Enzyme-linked immunosorbent assay (ELISA) was employed to detect inflammatory cytokines, including IL-6, IL-1β, HMGB1 (high mobility group box 1) and TNF-α levels. Western blot was performed to detect inflammation-related signaling.
Results: GGQL decoction treatment decreased IL-1β, HMGB1, IL-6 and TNF-α levels. Western blot analysis showed that GGQL decoction treatment significantly increased HO-1 (haem oxygenase-1) levels and decreased the downstream targets Toll-like receptor (TLR)4 and HMGB1, which were upregulated by irradiation exposure. Further investigation demonstrated that GGQL decoction treatment protected the rat intestinal epithelial cell line IEC6 and human umbilical vein endothelial cells (HUVECs) from irradiation-induced apoptosis but did not affect cell proliferation. In both cell lines, GGQL decoction treatment decreased TLR4, HMGB1, cleaved caspase3, and cleaved PARP (poly (ADP-ribose) polymerase) levels and increased HO-1 levels, which were affected by irradiation. GGQL decoction treatment increased AKT (protein kinase B) phosphorylation, which is necessary for regulating HO-1 levels and exerting protective effects.
Conclusions: Therefore, these findings shed light on the pharmacologic mechanism of GGQL decoction as a treatment for radiation enteritis.
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Background: Diabetes mellitus has an adverse effect on human bones, which is a risk factor for osteoporosis. The aim of this study was to explore the mechanism of the effects of high glucose (HG) on the osteogenic differentiation of osteoblasts.
Methods: In this study, mouse MC3T3-E1 cells were cultured in high glucose level at 30 mM with 24.5 mM mannitol and 5.5 mM glucose as control. Plasmid circular deoxyribonucleic acids (pcDNAs) and small interference ribonucleic acids (RNAs) were transfected for functional analysis of RecQ helicase-like 4 (RECQL4) and sirtuin 1 (SIRT1). The viability, alkaline phosphatase (ALP) activity, and OCN (provide in full) concentration was measured via methyl thiazolyl tetrazolium (MTT), colorimetric, enzyme-linked immunosorbent assay (ELISA) assays. Mitochondrial functions were assessed by mitochondrial membrane potential (MMP) and the levels of adenosine triphosphate (ATP), glutathione (GSH), and malondialdehyde (MDA). Quantitative reverse-transcription polymerase chain reaction or western blot were conducted to detect the gene or protein expression. RECQL4 acetylation assay was performed and the interaction between RECQL4 and SIRT1 was detected via co-immunoprecipitation assay.
Results: The effects of HG on downregulating cell viability, the levels of osteogenic differentiation-related markers (ALP and OCN), p53 phosphorylation, ATP and GSH as well as RECQL4 and apoptosis-related factors (Cytochrome C and Cleaved caspase-3) upregulating MMP loss and MDA content were reversed following RECQL4 over expression (p < 0.01). Sirtuin 1 (SIRT1) over expression promoted the viability and the levels of ALP and OCN, while silencing RECQL4 did the opposite (p < 0.05) and caused a reversion in HG-treated osteoblasts (p < 0.01). Additionally, silencing SIRT1 inhibited the acetylation of RECQL4 (p < 0.01) and the interaction between SIRT1 and RECQL4.
Conclusions: HG repressed the osteogenic differentiation and downregulated MMP via SIRT1/RECQL4 axis in osteoblasts.
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Background and Purpose: Hepatic ischemia-reperfusion (I/R) injury has been considered a primary hindrance in liver operation. This study explored the efficiency of baicalin combined with bone marrow stromal cells (BMSCs) in treating rats’ liver I/R injury.
Methods: BMSCs hepatic differentiation was evaluated by determining the expression of hepatic markers, urea synthesis, and low-density lipoprotein (LDL) uptake after the identification of BMSCs. Hepatic injury was evaluated via Hematoxylin and Eosin (H&E) staining, LDH activity, and Reactive Oxygen Species (ROS) levels. Apoptosis in liver tissue was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and flow cytometry. The inflammatory cytokines levels were determined using enzyme-linked immunosorbent assay (ELISA). Oxidative stress damage was assessed using Superoxide Dismutase (SOD) activity. The target molecules expression was detected via Polymerase Chain Reaction (real-time PCR) and western blotting.
Key Results: Results showed that baicalin facilitated hepatic differentiation of BMSCs, as evidenced by enhancing expression of albumin (ALB), Cytokeratin-18 (CK-18), and alpha fetoprotein (AFP), urea production, and LDL uptake. As compared with BMSCs monotherapy, co-treatment with baicalin exhibited higher efficiency in attenuating liver injury. Moreover, combination with baicalin strengthened the inhibitory effect of BMSCs on apoptosis via reducing the expression of B-cell lymphoma-2 (Bcl-2) Associated X Protein (Bax) and cleaved caspase-3 but elevating the expression of Bcl-2. Additionally, oxidative stress and inflammatory response were restrained by combination with baicalin and BMSCs treatments. Finally, the promotion of Heme Oxygenase 1 (HO-1) expression and inactivation of the nuclear factor kappa-B (NF-κB) pathway were involved in the molecular mechanisms of this combined therapy.
Conclusions and Implications: In summary, combined therapy of baicalin and BMSCs showed higher efficiency in mitigating hepatic I/R injury than monotherapy, and this therapeutic action may depend on activating HO-1 and inhibiting the activation of NF-κB.
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Background: Pyroptosis is currently being explored for anti-tumor activity. However, few studies focus on the prognostic value of pyroptosis in hepatocellular carcinoma (HCC).
Objective: To develop and characterize an effective gene signature capable of anticipating the prognosis of HCC, based on pyroptosis.
Methods: Initially, the RNA (ribonucleic acid) sequencing data for HCC, along with its reciprocal clinical data, was taken from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Following this, pyroptosis-related genes (PRGs) were selected from the data of the TCGA cohort. Those PRGs having a differential expression between normal and HCC samples were selected and identified, using consensus clustering. Subsequently, differentially expressed genes (DEGs) in different clusters associated with pyroptosis were identified. At last, a gene signature was constructed, and its independent predicting power was illustrated using the Cox regression analysis, followed by functional analysis and single sample gene set enrichment analysis (ssGSEA). External validation of the gene signature was done using patient data obtained from the GEO dataset.
Results: Forty-two differentially expressed PRGs were identified and utilized to obtain two pyroptosis-related clusters from the patient data of the TCGA cohort. A total of 2667 DEGs were distinguished between two clusters (C1 and C2) (p < 0.05). Fourteen DEGs were utilized for constructing a prognostic gene signature capable of quantifying each patient. The median risk score (3.5) of the gene signature was used as a basis to classify the patients into two groups: high- (81 patients) and low-risk groups (81 patients). A comparison of survival rate between the two risk groups showed a significantly lower overall survival rate for the high-risk group (p < 0.001). The area under the ROC (receiver operating characteristic) curve values of the gene signature were 0.843, 0.798, and 0.752 over one, three, and five years, respectively. A functional study exhibited that the 14-DEGs presented diverse complement and coagulation cascades. The ssGSEA demonstrated that different risk groups presented diverse immunity conditions. All the above results have been externally verified.
Conclusions: A new gene signature based on pyroptosis can serve as an effective prognostic tool for predicting the survival of HCC patients. Pyroptosis may be related to both complement and immunity in HCC.
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Background: The aim of this study was to analyze the cephalometric effects of RME (rapid maxillary expander) and EGA (Eruption Guidance Therapy) therapy in Class II growing patients.
Methods: This retrospective study included patients with transversal maxillary contraction and skeletal Class II (ANB >4°). For all the patients, frontal and lateral teleradiographs were obtained at the beginning of therapy and at the end of the functional treatment. Cephalometric analysis was performed on each radiograph at the beginning of treatment (T0) and at the end of the functional therapy (T1) considering difference among the sagittal, vertical and transverse cephalometric values.
Results and Conclusions: The therapeutic protocol proposed in this study represents a simple and easy repeatable alternative for II class treatment and permits to obtain consistent and reliable results with important effects on the sagittal dimension, shown in the decrease of ANB and the increase of SNB angles, and vertical dimension. However, the lack of customization of functional therapy and the need for compliance by the patient are limitations that need to be addressed.
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Background: This research aims to analyze the potential of Coffea Robusta leaves in preventing post-exercise oxidative stress.
Methods: This research is a type of qualitative and quantitative research. Qualitative analysis is only presented in tabular form and quantitative analysis uses descriptive statistical analysis. The research analyzed the potential antioxidant content of Coffea Robusta leaves ingredients and antioxidant activity and the organoleptic preference test of Coffea Robusta in athletes. Total phenol content was analyzed using the Folin-ciocalteu method. Meanwhile, the caffeine content was analyzed using the Baily Andrew method, and antioxidant activity was analyzed based on its ability to scavenge free radicals using the DPPH (2,2-difenil-1-pikrilhidrazil) method.
Results: Coffea Robusta leaves qualitatively showed positive results for all phytochemicals tested, such as flavonoids, saponins, tannins, and steroids. In the quantitative analysis, the highest contents of flavonoids, saponins, and phenols were found in the traditional drying of Coffea Robusta leaves.
Conclusions: Based on the results and discussion it can be concluded that Coffea Robusta leaves have the potential to prevent post-exercise oxidative stress.
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Background: This study aimed to establish a high-performance liquid chromatography method for the detection of ganciclovir eye drops and to assess the stability and safety of 2% topical ganciclovir eye drops prepared in hospitals.
Methods: 2% ganciclovir solutions were prepared by dilution of a ganciclovir IV Infusion into saline and stored in a light-shielded container at 4, 25, or 37 °C for 4 weeks. The ganciclovir solution concentrations were determined by high-performance liquid chromatography on days 0, 1, 3, 7, 14, 21, and 28, respectively. Rabbits were used to assess ocular irritation following topical administration of ganciclovir solutions.
Results: The concentration and pH of 2% ganciclovir were maintained at the initial levels for 4 weeks. All the prepared 2%ganciclovir eye drops remained colorless and clear without precipitation for 4 weeks, except for one sample which showed white precipitation after 3 weeks at 4 °C. No ocular irritation was observed in the eyes of rabbits.
Conclusions: The drug in eye drop form was chemically stable for up to 4 weeks. The administration of 2% ganciclovir eye drops in rabbits did not show ocular irritation, suggesting safe dosage for use.
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Aim: To study the effect and mechanism of miR-218-5p on osteoblast differentiation and osteoclast formation.
Methods: TargetScan was employed to predict the target miRNA, which was tracked by luciferase reporter assays. MC3T3-E1 cells and receptor activator of nuclear factor-κB ligand (RANKL)-treated RAW 264.7 cells were co-transfected with miR-218-5p mimic, miR-218-5p inhibitor, and si-roundabout guidance receptor 1 (ROBO1). The expression of miR-218-5p was evaluated using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). MC3T3-E1 cells were stained with Alizarin red and alkaline phosphatase (ALP) kits, and ALP activity was assessed. Pit formation and F-actin ring immunofluorescence assays were conducted in RANKL-treated RAW 264.7 cells. Protein levels of ROBO1, Dickkopf-1 (DDK-1), ALP, runt-related transcription factor 2 (RUNX2), bone morphogenetic protein-2 (BMP-2), tartrate-resistant acid phosphatase (TRAP), and nuclear factor of activated T-cells 1 (NFATC1) were determined using western blot analyses.
Results: miR-218-5p targeted ROBO1 in the 3′-UTR. miR-218-5p and si-ROBO1 significantly decreased the levels of ROBO1 and DDK-1. miR-218-5p and si-ROBO1 increased calcified nodule formation, ALP activity, and levels of ALP, RUNX2, and BMP-2 but suppressed pit formation and F-actin ring formation and decreased levels of TRAP, F-actin, and NFATC1. In addition, miR-218-5p inhibitor weakened the effects of si-ROBO1 on osteoblast differentiation and osteoclast formation.
Conclusions: Collectively, miR-218-5p promotes osteoblast differentiation and inhibits osteoclast formation through the ROBO1/DKK-1 pathway, which provides a potential therapeutic strategy for bone remodeling.
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Background: Currently, some patients with prostate cancer (PC) may develop resistance to docetaxel chemotherapy. Considering the reported regulatory effects of microRNA (miR)-195 and nuclear-enriched abundant transcript 1 (NEAT1) on the docetaxel resistance of PC cells, their interaction is discussed in this study.
Methods: Docetaxel-resistant prostate cancer cells were established by long-term docetaxel stimulation. The upstream and downstream targets of miR-195 in PC cells were predicted and verified by bioinformatics analysis and dual-luciferase reporter assay. PC cells transfected with miR-195 inhibitor, shNEAT1, miR-195 mimic, or ubiquitin-specific protease 22 (USP22) overexpression plasmid, were treated with docetaxel. MTT assay, Transwell assay, and flow cytometry were used to determine the malignant behavior of PC cells and the half maximal inhibitory concentration (IC50) of docetaxel. Real-time quantitative PCR and western blot were used to quantify the expressions of NEAT1/miR-195/USP22 axis-related and metastasis-related factors.
Results: MiR-195 was lowly expressed, while NEAT1 and USP22 were highly expressed in PC cells. Also, miR-195, while being sponged by NEAT1, could target USP22. MiR-195 mimic decreased the IC50 of docetaxel, migration, invasion, and the expressions of USP22, N-cadherin, and vimentin, while enhancing apoptosis and E-cadherin expression in docetaxel-resistant PC cells. USP22 overexpression increased the IC50 of docetaxel, migration and invasion, and reversed the regulatory effects of miR-195 mimic.
Conclusions: MiR-195, modulated by NEAT1, attenuates docetaxel resistance and metastasis of PC cells by downregulating USP22.
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Background: To evaluate the therapeutic effects of esmolol on rats with diffuse axonal injury (DAI).
Methods: DAI model rats were constructed by instantaneous high speed head rotation, and normal saline or esmolol hydrochloride was injected into the femoral vein after DAI induction. We scored the mNSS, observed the histology of brain tissues, evaluated blood-brain barrier (BBB) damage using Evans Blue (EB), and measured brain edema. We then detected the expressions of TNF-α, IL-6, IL-1β, MMP-9, cleaved-caspase-3, and cleaved-caspase-9 using western blots, quantified the contents of ROS, SOD, MDA, and CAT with related kits, measured the contents of Glu and Gln by HPLC, and calculated the Glu/Gln.
Results: The DAI rat model was successfully constructed, and the optimal administration duration of esmolol was 3 d. Compared with the preoperative or Sham group, the mNSS, EB permeability, cerebral water content, the expressions of RECA-1, CD31, inflammatory proteins and apoptosis proteins, and the contents of ROS, MDA, Glu, and Gln were significantly increased, while the SOD and CAT contents were decreased (p < 0.05). However, administration of esmolol for 3 d partially reversed these trends and improved the histology of brain tissue.
Conclusions: Esmolol partially ameliorated neurobehavioral abnormalities, BBB damage, and brain edema, inhibited inflammation, neuronal apoptosis and Glu accumulation, and repaired the ultrastructure of damaged neurons in DAI rats, thereby showing brain protection effects.
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Background: Limonin exhibits multiple biological functions, including anti-cancer, andanti-viral effects. This study aimed to explore the inhibitory effect and potential mechanism of limonin on colorectal cancer (CRC) cells.
Methods: In vivo experiments were performed on 30 male F344 rats: 24 rats were used to establish CRC models, and 6 rats were used as blank controls. MTT assay, Hoechst 33342 staining, flow cytometry, and Polymerase Chain Reaction (PCR) assay were performed in vitro to detect the viability of LoVo and SW480 cells affected by limonin. The change in the expression of the factors involved in the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway in CRC cells was assessed in vitro and in vivo by Western blot assay. Hematoxylin and eosin (H&E) staining and immunohistochemistry were used to assessed the changes in the morphology and protein expression of the cancer tissue, respectively. Survival curves were performed.
Results: Limonin group showed inhibition of the expression of Cyclin D1 and CDK4 mRNA, enhancement of the expression of p21 and p27 mRNA, blocked cell growth and proliferation leading to G0/G1 phase cell cycle arrestment and apoptosis and downregulation of the expression of ERK/MEK proteins in two CRC cell lines compared to the control group (p < 0.05). The establishment of the CRC model tool went through a total of 8 weeks and the in vivo results revealed that limonin treatment inhibited CRC progression and Ki67 expression, as well as downregulated the expression of ERK/MEK proteins. In addition, after 8 weeks, rats in the control group were heavier than those in the intervention groups, because of the treatment with azoxymethane (AOM) and dextran sulfate sodium (DSS). The survival curve showed that the limonin-treated CRC rats had a longer survival time (p < 0.05).
Conclusions: Limonin inhibits CRC by downregulating the expression of the factors involved in the ERK/MEK signaling pathway.
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Background: Neutrophils have both anti-tumor and pro-tumor effects. The aim of this study was to explore the predictive value of tumor neutrophil-related genes for breast cancer prognosis.
Methods: Data of BC (breast cancer) patients were obtained from the public database (TCGA (The Cancer Genome Atlas)) to build a multigene prognostic signature. The results of patients between high- and low-risk groups were compared. The immune cell infiltration score was evaluated.
Results: Eleven tumor neutrophil-related genes (RBFA, GOSR2, GPSM3, DHRS7, TSC22D4, RAC2, RBCK1, ATP6V0D1, TMEM14C, LCP1, UNC93B1) were obtained to construct the signature, which was named TAN1 (tumor-associated neutrophils)-11. This enabled dividing patients into two groups (high and low-risk groups). Patients with higher risk scores had poorer outcomes. The findings indicated that TANI-11 is an independent risk factor for prognosis. Higher risk score levels were positively associated with lymph node metastasis. In addition, TAN1-11 strongly was connected with immune infiltration like macrophage M0 & M2 (macrophages M0 and macrophages M2), resting natural killer cells, and neutrophils. This may affect the immunother-apeutic effect of the tumor.
Conclusions: A valid signature was first reported as associated with tumor neutrophils in breast cancer. The value of this signature in indicating the prognosis of breast cancer patients may make it of value in guiding breast cancer immunotherapy.
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Background: The current research was designed to clarify the molecular regulation mechanisms of traditional Chinese medicine Jianpi Bushen Qingchang Huashi Recipe (JBQHR) in ulcerative colitis (UC) rats.
Methods: Rat models of UC were established by administering 1 × 106 CFU Clostridium difficile spores. Then rats in each group were treated with the medicine of JBQHR (Z1), Jianpi Bushen (Z2), Bushen Qingchang (Z3), Jianpi Qingchang (Z4), Bushen (Z5), Jianpi (Z6), and Qingchang (Z7). The control rats were only treated with sterile water. The intestinal feces were collected for microbiota and bile acid determination using 16S rRNA sequencing and UPLC-MS.
Results: The Firmicutes abundance and the relative abundance between Firmicutes and Bacteroidetes increased markedly in Z1 compared to the model rats. Principal component analysis exhibited a significant difference between the Z1 and the control group, similar to the Z7. Quantitative analysis of 13 bile acids revealed that the expression of TUDCA in Z3 and Z7 groups was substantially increased compared with the model rats. The TCA contents of the control, Z1, Z2, Z3, Z4, and Z5 groups were markedly increased as compared to the model. The GCA levels of the Z5 group and GCDCA contents of Z2, Z3, Z4, and Z5 groups were greatly decreased versus the model. There was no evident difference in the expressions of HDCA, CA, DCA, UDCA, GDCA, and LCA between the treatment groups and the model group. Levels of CDCA in the control and Z1 groups, and THDCA levels in the control, Z1, Z4, and Z5 groups were notably higher versus the model group.
Conclusions: Our results demonstrated that the gut microbiota and partial bile acid contents of the UC rats were markedly changed after JBQHR treatment. This study indicates that JBQHR can mediate intestinal microecology and cause changes in bile acid contents in the intestinal lumen, thereby regulating intestinal immune inflammation and repairing the intestinal mucosa.
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Backgrounds: Esophageal carcinoma (EC), a type of malignant tumor originating from the esophageal mucosa, is frequently encountered in clinical practice. Fatty acids contribute to the polarization of tumor-associated macrophage to the immunosuppressive M2 phenotype. Fatty acid metabolism is an essential factor in tumor development and progression.
Methods: EC expression and clinical data were downloaded from the Cancer Genome Atlas database and GSE53625 dataset. Fatty acid metabolism gene sets were downloaded from the Msigdb database. Differentially expressed fatty acid-related genes (DFAGs) in tumor and normal samples were screened using a t-test, and their prognostic value was investigated. Optimal prognostic DFAGs were identified to establish the fatty-acid-risk score (FARS) model. A nomogram was then established based on the independent prognostic factors. Associations between the FARS and clinical features, immune infiltration, tumor mutation burden (TMB), drug sensitivity, and tumor immune dysfunction and exclusion (TIDE) were analyzed using the prophetic package.
Results: Six prognostic DFAGs were identified from 161 DFAGs and 13 prognostic genes. Three genes, PDHA1, PTGES3, and CPT2, were identified as optimal prognostic DFAGs to establish the FARS model. Patients with high FARS tended to present shorter survival times in the Cancer Genome Atlas (TCGA) database and GSE53625 cohorts. The tumor stage and FARS were identified as independent prognostic factors for establishing the nomogram. The nomogram showed high conformance with actual survival in predicting 1-, 3-, and 5-year survival rates. High-FARS groups had a high abundance of infiltrating M2 macrophages and higher TMB. Patients with high TMB tended to have low survival. High FARS also correlated with higher sensitivity to cisplatin, gemcitabine, and paclitaxel and a high TIDE score, indicating a poor response to immune checkpoint blockade (ICB) therapy.
Conclusions: Predicting model including DHA1, PTGES3 and CPT2 was established. These genes could predict overall EC survival, chemosensitivity, and immunotherapy response and were correlated with aggressive clinicopathologic features.
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Background: Peroxiredoxin 6 (Prdx6) affects intracellular reactive oxygen species (ROS) and phospholipid turnover to maintain cellular homeostasis and membrane integrity.
Methods: A rat model with lithium chloride-pilocarpine-induced epilepsy is employed to verify the effect and mechanism of Prdx6 on epilepsy in vivo experiments. Western blot analysis and immunofluorescence assay were used to determine the expression level of Prdx6. Furthermore, the expressions of cleaved caspase-3, Bal2 and Bax were also measured by western blot assay. The levels of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-px) were evaluated by kits. Cell apoptosis was measured through TUNEL assay. The time to onset of status epilepsy (SE), the duration of SE and the number of Racine IV or V in 28 days were recorded.
Results: The results demonstrated that pilocarpine induced oxidative stress and cell apoptosis in the hippocampus of the rat epilepsy model. The expression of Prdx6 decreased with the increasing length of pilocarpine treatment in the hippocampus of rats. Prdx6 overexpression decreased spontaneous seizures in pilocarpine-treated rats. Prdx6 overexpression detained oxidative stress by reducing MDA levels and enhancing SOD, CAT and GSH-px activities in the hippocampus of rats. Furthermore, Prdx6 overexpression repressed the cell apoptosis by inhibiting the expressions of Cleaved Caspase-3 and Bax/Bcl-2 in the hippocampus of pilocarpine-treated rats.
Conclusions: These findings suggest that Prdx6 can protect against oxidative stress and apoptosis in a rat model of pilocarpine-induced epilepsy, indicating that Prdx6 may be a helpful therapeutic target in treating epilepsy.
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Background: Shugan Sanjie Decoction (SGSJD), which includes various Chinese herbs, has a potential therapeutic effect on plasma cell mastitis (PCM). However, the specific mechanism of action is undefined, and will be expounded in this study.
Methods: A PCM rat model was established by subcutaneous injection of the water-in-oil emulsion of PCM tissues. Then low dose (0.018 mL/g) and high dose (0.036 mL/g) of SGSJD were administered to model rats. Hematoxylin and eosin staining was used to observe the rat mammary gland tissues. The expressions of CD138, interleukin-6 (IL-6) and epidermal growth factor receptor (EGFR) in rat mammary gland tissues were detected by immunohistochemistry. The mRNA expressions of four genes targeted by SGSJD (IL-6, EGFR, estrogen receptor 1, and nitric oxide synthase 3) were determined by quantitative real-time polymerase chain reaction. IL-6/signal transducer and activator of transcription 3 (STAT3) pathway-related protein expressions were measured by Western blot.
Results: SGSJD treatment could attenuate the inflammation, weaken the effect of modeling and reduce expressions of CD138, IL-6 and EGFR in mammary gland tissues of PCM model rats. Besides, SGSJD inhibited the activation of IL-6/STAT3 signaling pathway and EGFR in PCM model rats.
Conclusions: SGSJD suppresses the progression of PCM in rats, and the regulatory mechanism may be related to the regulation of IL-6/JAK2/STAT3 pathway and EGFR.
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Background and Objective: Diabetes mellitus (DM) might lead to dysfunctions in the kidney, retina, cardiovascular system, neurons and liver. Hence, identifying diagnostic biomarkers for diabetic complications is vital to improve the prognosis. The present study determines the association between RNA binding motif single stranded interacting protein 1 (RBMS1) and the prognosis of DM patients.
Methods: This prospective observational study enrolled 190 patients with type 2 diabetes (T2DM), who underwent bariatric surgery from June 2015 to December 2021. In addition, 100 healthy individuals were enrolled as control subjects. Then, the serum level of RBMS1, fibroblast growth factor 21 (FGF-21), glucagon-like peptide-1 (GLP-1), and omentin were measured using enzyme-linked immunosorbent assay (ELISA) at baseline (0 days) and at 14 days post-surgery. The demographic characteristics, risk factors for coronary heart disease (CHD), and biochemical indexes of all participants were included for the present study. The receiver operating characteristic (ROC) curve was drawn to determine the diagnostic value of RBMS1 for CHD in T2DM patients. Then, the correlations among RBMS1, FGF-21, GLP-1 and omentin were analyzed using Spearman’s correlation analysis.
Results: The serum level of RBMS1 was higher in T2DM patients, especially patients with CHD, when compared to control subjects. Furthermore, high RBMS1 level was associated with risk factors for CHD. The serum level of RBMS1 decreased after the surgery. A positive correlation was observed between RBMS1 and FGF-21, and a negative correlation was observed between RBMS1, and GLP-1 and omentin in T2DM patients. Therefore, high RBMS1 levels can predict the poor prognosis of T2DM patients.
Conclusions: RBMS1 is associated with the prognosis and incidence of CHD in DM patients.
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Background: This study aims to reveal the regulatory networks involving miR-223-3p in endometriosis.
Methods: The expression levels of miR-223-3p and FBXW7 and their correlations in ectopic, eutopic and normal endometrial tissues were determined by qRT-PCR and Pearson correlation test. We isolated and identified primary endometriosis ectopic endometrial stromal cells (ESCs) and normal endometrial cells. The prediction on downstream targets of miR-223-3p was performed by bioinformatic analysis. The association of miR-223-3p with its downstream gene FBXW7 was confirmed by adopting the dual-luciferase reporter experiment. After transfection, cell function experiments were undertaken to detect cell biological behaviors. Determining levels of miR-223-3p and FBXW7 in ESCs was conducted by utilising qRT-PCR and Western blot.
Results: MiR-223-3p was highly expressed, whilst FBXW7 was less expressed in eutopic and ectopic endometria. The ectopic ESCs and normal human endometrial cells were negative for CK19, but positive for Vimentin. FBXW7 levels were conversely related with miR-223-3p levels in normal, eutopic and ectopic endometria. MiR-223-3p mimic facilitated biological behaviors of human ESCs, whereas the opposite effect was seen with miR-223-3p inhibitor. Moreover, miR-223-3p inhibitor alleviated cell biological behaviors of human ESCs via elevating FBXW7 expression.
Conclusions: miR-223-3p inhibitor restrains ESC progression via elevating FBXW7 expression.
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Purpose: Uterine microbial balance is an important factor affecting embryo implantation and pregnancy. Microbial balance can lead to diseases such as chronic endometritis, which can cause embryo implantation failure or miscarriage. This study aims to explore the composition of uterine microbiota and the potential role of microbiota in missed abortion.
Methods: We enrolled 17 patients diagnosed with missed abortion which chromosomal abnormalities were excluded by chromosomal testing and 12 healthy pregnant patients at 6–8 weeks gestation. Endometrial fluid samples were collected and amplified after DNA was extracted. Microbiota components of the uterine environment were identified using the 16S rRNA sequencing. We used the microbiota diversity data to reflect bacterial species richness and evenness within populations, while beta-diversity were performed to measure the shared diversity between populations of bacteria.
Results: Microbiomes were found in low abundance both in patients with missed abortion and those with normal pregnancies. There was a greater diversity of intrauterine microflora in patients who missed abortions compared to those who missed deliveries (p < 0.05). In terms of alpha diversity, no significant difference was observed between the two groups (p > 0.05), but there was a significant difference in terms of beta diversity. Moment array analysis by principal co-ordinates analysis (PCoA) did not show significant differences. The bacteria, Proteobacteria and Firmicutes, were significantly elevated in the patients with missed abortion than those in the normal pregnancy group.
Conclusions: This study revealed the specificity of uterine microorganisms in patients with embryo arrest, and found that Proteobacteria and Firmicutes play an important role in this process. They may serve as biomarkers of microorganismal diversity in the uterine cavity in embryonic loss of fetus.
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Background: Clinically, the paradox of survival between stage IIB/C and stage III colon cancer (CC) is so evident as to be overlooked, with the consideration that local spread into adjacent structures (T4 lesions) should be upgraded to a higher stage. In this study, we aimed to examine the prognostic accuracy of American Joint Committee on Cancer 8th edition (AJCC-8) in patients diagnosed as stage II or stage III CC with curable potential.
Methods: 49898 patients with CC, extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2021, were grouped into the training set, and 33161 patients from another SEER dataset between 2010 to 2015 grouped into the validation set. CC was staged by the 6th or 7th edition of the AJCC Cancer Staging system and then restaged by AJCC-8. Using a Cox proportional hazard regression model, the effects of other covariates were adjusted, and two revised Tumor-Node-Metastasis (TNM) staging systems were proposed according to the current Tumor and Node (TN) category based on cancer-specific survival (CSS).
Results: SEER CC analyses showed that the right colon was a protective factor for CSS in stage II CC, but this protective role is reverse in Stage III CC. T4 was a high-risk factor with the highest hazard ratio (HR) (HR, 5.129; 95% CI, 4.041–6.511; p < 0.01). Patients with T4N0M0 cancers had worse CSS than those with T3N0M0 cancers, similar to T2N2bM0 cancers. The CSS of T4bN1M0 was worse than that of T3N2bM0, but similar to that of T4N2M0. The CSS of T1-2N1M0 was similar to that of T3N0M0. The revised TNM staging showed distinctly better discrimination for T4 lesions.
Conclusions: This study supports the complexity of the significance of tumour location and calls for consideration of the shift of T1-2N1M0 disease from IIIA to IIA or II and T4 lesions to stage III.
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Background: Pancreatic cancer (PC) is one of the deadliest malignancies, with poor prognosis. Hypoxia is commonly detected in pancreatic tumors and considered a stimulating factor for their progression. Studies have showed that Cardamonin (Cad) acts as a tumor suppressor in PC. This study explored the effect of Cad on PC progression under hypoxic conditions and the mechanism of this effect.
Methods: Human PC cells (BxPC3 and PANC1) were treated with Cad, under hypoxic conditions. Pre-study bioinformatics analyses predicted that Cad targets aldo-keto reductase 1 member B1 (AKR1B1). The cytotoxicity of Cad at various concentrations on PC cells attacked by or not by hypoxic stress was determined with cell counting kit-8 assay. Cell invasion and apoptosis were measured with Transwell assay and flow cytometry, respectively. Expressions of N-Cadherin, E-Cadherin, matrix metalloproteinase (MMP)-9 and AKR1B1 in cells were analyzed with Western blot.
Results: Cad delivered cytotoxicity to PC cells and the effect was dose dependent. Cad counteracted all the hypoxia-induced effects and downregulated AKR1B1. AKR1B1 overexpression potentiated these effects in hypoxia-induced PC cells and abrogated the Cad-induced countering effects.
Conclusions: Cad downregulates AKR1B1 to counteract hypoxia-induced PC cell proliferation, epithelial-mesenchymal transition and apoptosis inhibition.
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Background: A asprosin and Meteorin-like (Metrnl) are related to diabetic. The aim of this study was to assess the impact of asprosin or Metrnl on the development of diabetes in pre-diabetics.
Methods: This is a prospective study. Subjects were divided into two groups: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) based on the results of an oral glucose tolerance test. Two years later, subjects were divided into three groups based on blood glucose outcome: Normal, pre-diabetic and diabetic groups. Biochemical methods were used to detect blood glucose, blood lipids, liver function, kidney function and thyroid function. Radioimmunoassay was used to detect tumor markers. The levels of Asprosin and Metrnl were detected by ELISA (enzyme-linked immunosorbent assay).
Results: A total of 403 subjects were enrolled in this study. At baseline, fasting blood glucose (FBG) and triglyceride (TG) were higher as well as 2-h postprandial blood glucose (PBG) and high-density lipoprotein (HDLC) were lower in IGT group than in IFG group (p < 0.05). Two years later, glycation hemoglobin (HbA1c), FBG, PBG, TG, kidney function related indexes creatinine (CREA) and Asprosin were lower while CHOL (total cholesterol) and HDLC were higher in prediabetic group than in diabetic group (p < 0.05). Asprosin and not Metrnl, positively correlated with HbA1c, PBG and CREA in diabetic patients (p < 0.001).
Conclusions: Asprosin is related to blood glucose levels and markers of renal function in patients with diabetes.
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Background: Calcific aortic stenosis’s pathology is associated with calcification of valvular interstitial cells (VICs). SOX2 (SRY (sex determining region Y)-box 2) has been reported to regulate osteogenic differentiation that leads to calcification and as a mediator of the methylation of NOTCH1 (The Notch homolog 1 translocation-associated). This study characterized the specific role of SOX2 in osteogenic differentiation of VICs.
Methods: VICs isolated from porcine hearts, identified by immunofluorescence assay, were induced into osteogenesis. SOX2 overexpression/knockdown plasmids and notch intracellular domain (NICD) overexpression plasmids were used to investigate the role of SOX2 and NOTCH1 on the osteogenic differentiation of VICs. Alkaline phosphatase activity, mineralized nodules, and calcium concentration were assessed by alkaline phosphatase staining, Alizarin Red S staining, and Arsenazo III dye assay, respectively. In these osteogenically differentiated VICs cells, the expressions of SOX2, NOTCH1, and osteogenesis-related markers (RUNX2 (Runt-related transcriptionfactor2), BMP2 (Bone morphogenetic protein 2) and OPN (Osteopontin)) were analyzed by western blot and/or quantitative reverse transcription-PCR (polymerase chain reaction). NOTCH1 promoter methylation was analyzed by bisulfite sequencing-PCR and methylated DNA (deoxyribonucleic acid) immunoprecipitation.
Results: In osteogenically differentiated isolated VICs, SOX2, and NOTCH1 expressions were decreased (p < 0.01; p < 0.001). SOX2 overexpression or NICD overexpression suppressed alkaline phosphatase activity, inhibited mineralized nodule formation, decreased calcium concentration (p < 0.001), osteogenesis-related markers (p < 0.05; p < 0.001), and NOTCH1 methylation (p < 0.001), and increased the expression of NOTCH1 (p < 0.05; p < 0.001). By contrast, SOX2 knockdown produced the opposite effect (p < 0.05). NICD overexpression reversed the SOX2 knockdown-induced effect (p < 0.001), which in turn abolished the NICD-induced effect.
Conclusions: SOX2 hinders VIC osteogenic differentiation by attenuating NOTCH1 promoter methylation via a NOTCH1-SOX2 positive-feedback loop.
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Background: Tumor-specific neoantigens are ideal targets for cancer immunotherapy, but few of these have been identified thus far. An analysis strategy was developed for neoantigen in non-coding regions by RNC (ribosome-nascent chain complex)-RNA-seq in mouse lung cancer.
Methods: In LLC (Lewis lung carcinoma) cell lines, RNC extraction, RNC-RNA extraction, RNC-RNA seq and bioinformatics analysis were carried out. The immunogenicity and specificity were determined by immunizing mice.
Results: Twenty neoantigens were identified from non-coding regions. Seventeen long peptides were synthesized successfully and 5/17 of these neoantigens were found to be immunogenic. In tumor transplant models, the non-coding neoantigen vaccines immunization achieved in vivo tumor control in protective and therapeutic settings.
Conclusions: In mice, the non-coding neoantigen vaccines can provoke anti-tumour effect against lung cancer. This can form the basis for future study of RNC-RNA-seq, as a method to identify non-coding neoantigens.
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Background: Cleaning the airway clear of mucus through clearance techniques seems essential for bronchiectasis treatment. The vibratory sputum drainage combined with nutritional intervention in patients with bronchiectasis may have profound clinical implications. Hence, we conducted a controlled clinical study of the nutritional condition and pulmonary function.
Methods: A total of 104 patients with bronchiectasis were recruited from August 2017 to October 2019 and were randomly divided into a control group (n = 52) and an observation group (n = 52). The patients in the control group were given routine nursing, while those in the observation group were given vibratory sputum drainage combined with nutritional intervention. A comparison in the volume of sputum drained per day, post-drainage blood oxygen saturation, respiratory rate, nutritional condition, pulmonary function, and the level of MMP (matrix metalloproteinase) and TNF-α (tumor necrosis factor-α) was conducted between the two groups.
Results: After one month of treatment, there was a significant improvement in the volume of sputum drained per day, post-drainage blood oxygen saturation, respiratory rate, forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC). The MMP and TNF-α were lowered in the observation compared to the control group (p < 0.05). After six months of treatment, the levels of prealbumin (PA), albumin (ALB), and body weight of the observation group were improved significantly compared to the control group (p < 0.05).
Conclusions: Vibratory sputum drainage combined with nutritional intervention significantly increases the volume of sputum drained per day, improves post-drainage blood oxygen saturation, reduces the respiratory rate and the level of MMP and TNF-α and improves the nutritional condition and pulmonary function of patients.
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Background: Chronic cough is common in postoperative patients with non-small cell lung cancer (NSCLC). But the mechanism of chronic cough is unclear.
Methods: Forty NSCLC patients with postoperative chronic cough (CC) after surgery were randomly divided into electroacupuncture (EA) and no therapy groups, each treated for 28 days. The quality of life (QOL) module in the European Organization for Research and Treatment of Cancer Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), the Dyspnea module in the EORTC QLQ-Lung Cancer Module 13 (EORTC QLQ-LC13) and the Mandarin Chinese version of the Leicester Cough Questionnaire (LCQ-MC) were completed before and after treatment. In vitro, thirty guinea pigs were randomly divided into sham operation group (sham group), simple modeling group (model group), electroacupuncture+model group (EA+M group) and treated for one week. After detecting cough frequency, samples were taken and the contents of markers in bronchoalveolar lavage fluid, blood and lung tissue were detected. Finally, immunofluorescence was used for verification.
Results: Compared to those before treatment, the scores of EORTC QLQ-C30 QOL model, the Dyspnea module in EORTC QLQ-LC13 and LCQ-MC physical dimension were significantly better (p < 0.01); The bradykinin (BK), Prostaglandin E2 (PGE-2), substance P (SP), calcitonin gene related peptide (CGRP) and transient receptor potential vanilloid 1 (TRPV1) levels were significantly lower (p < 0.01) significantly after treatment. In-vitro experiment revealed that compared to the Model group, the cough frequency of guinea pigs in either the EA+M group or the sham group was significantly lower (p < 0.01). Compared to those in the model group, the BK, PGE-2, SP and CGRP levels in bronchoalveolar lavage fluid, blood or lung tissues were also lower in the EA+M group (p < 0.01); Their levels were positively correlated with the cough frequency (p < 0.01). Finally, compared to the model group, p-TRPV1 immunofluorescence showed that it’s level in the EA+M and sham groups were significantly lower (p < 0.01).
Conclusions: The study suggests that EA could physiologically alleviate the symptoms of cough and dyspnea in patients with CC and improve their QOL. The mechanism might be linked to the decreased expression of TRPV1 provide in full on first mention in the abstract and neurogenic factors after electroacupuncture treatment.
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Objective: A close relationship between the structure of gut microbiota and the development of primary biliary cholangitis (PBC) has been revealed in previous studies. This study aims to reveal the components and metabolic pathways of gut microbiota associated with the non-response to ursodeoxycholic acid (UDCA) of PBC patients.
Methods: Fecal samples were collected from PBC patients before receiving UDCA (n = 8, PBC group), PBC patients with response to UDCA (n = 8, Resp group) and PBC patients with non-response to UDCA (n = 8, Non-Resp group). The 16S ribosomal RNA (rRNA) gene was sequenced to analyze the gut microbiota in feces. Subsequently, the relative abundance, alpha and beta diversity of gut microbiota, and the correlation between the abundance and clinical characteristics in the samples from the three groups were analyzed to construct a correlation network of gut microbiota.
Results: The diversity and richness of gut microbiota were significantly decreased in PBC patients in the Non-Resp group, which were significantly different from the PBC and Resp groups. The gut microbiota with the top 10 expressed abundances that exhibited differences and linear discriminant analysis (LDA) scored greater than 4. The abundance of Fusobacteria expression in the gut significantly increased in PBC patients in the Non-Resp group, while that of Ruminococcaceae and Verrucomicrobia expressions decreased.
Conclusions: The decrease of gut microbial diversity and richness in PBC patients with non-response to UDCA may be linked to the abnormal abundance and related metabolic pathways of gut microbiota such Fusobacteria, Ruminococcaceae, and Verrucomicrobia. Gut microbiota is a potential therapeutic target and diagnostic biomarker for PBC patients with non-response to UDCA.
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Objective: To evaluate the value of the blocker displacement amplification (BDA) technique combined with next generation sequencing (NGS) liquid biopsy in the diagnosis and treatment of anaplastic lymphoma kinase (ALK)-positive and repressor of silencing 1 (ROS1)-positive advanced non-small cell lung cancer. The hope is to provide new guidance for targeted treatment of advanced non-small cell lung cancer patients with ALK and ROS1 fusion gene positive, especially when tissue samples are not timely or IHC (immunohistochemistry) detection results are uncertain.
Methods: Analyze the background features of the study groups. BDA-NGS was used to detect ALK and ROS1 fusion genes in peripheral blood of 248 patients (include RNA extraction and reverse transcription of peripheral blood vesicles, amplification and enrichment of BDA target regions and product recovery, NGS detection). The expression of ALK and ROS1 was detected by immunohistochemistry (IHC) in tumor tissues from the same patients.
Results: In 248 paired samples of IHC and peripheral blood BDA-NGS test, the detection rate of positive ALK/ROS1 by IHC was significantly higher than that by peripheral blood BDA-NGS test (54.84% vs 36.29%, p < 0.001). The positive ALK/ROS1 results by two test methods exhibited moderate consistency (Kappa = 0.651, 0.738, p <0.001 and p < 0.001).
Conclusions: Blood samples can be used as substitutes for testing when tissue samples are not available. Moreover, peripheral blood BDA-NGS test can complement solid tumor tissue biopsy to guide the rational drug use in clinic.
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Background: G protein-coupled receptor kinase 2 (GRK2) is involved in G protein-coupled receptor (GPCRs) pathway and non-receptor signaling pathway, which is only the non-receptor signaling pathway or both the receptor and non-receptor signaling pathway closely related to the occurrence of neurological diseases. However, the regulatory mechanism of GRK2 in electrophysiological activity is still unclear.
Methods: In this study, GRK2 shRNA plasmid or GRK2 overexpression plasmid was transfected into human neuroblastoma cells SH-SY5Y. Transfection efficiency was detected using western blot and patch-clamp techniques were used to measure changes in electrophysiological activity in SH-SY5Y cells after overexpression or knockdown of GRK2.
Results: Western blot results showed successful transfection. Additionally, the measurement by patch-clamp technique demonstrated that GRK2 overexpression significantly decreased both action potential firing frequency and Na+ current, which inhibited neuronal excitability in SH-SY5Y cells (p < 0.05). However, knockdown of GRK2 had no significant effect on action potential firing frequency and Na+ current in SH-SY5Y cells (p > 0.05).
Conclusions: GRK2 overexpression may suppress the electrophysiological activity of SH-SY5Y cells by blocking the Na channel.
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Background: Diabetic kidney disease (DKD), a microvascular complication of type 2 diabetes mellitus (T2DM), contributes to chronic kidney disease and end-stage renal disease. Angiopoietin-like protein 2 (ANGPTL2) is a glycoprotein secreted by a variety of cells, especially visceral adipocytes. However, the relationship of ANGPTL2 and DKD remains unknown. The aim of this study was to explore the value of serum ANGPTL2 as a molecular biomarker for the prevention and management of DKD.
Methods: An age and gender matched cross-sectional study was carried out, looking at patients with T2DM and healthy population. The study looked for risk factors for DKD and assessed the diagnostic value of ANGPTL2 for DKD.
Results: A total of 140 cases and 140 control participants were included in the study. Serum ANGPTL2 level was significantly higher in T2DM patients than in healthy subjects, and significantly rose during DKD progression (p < 0.0001). Serum ANGPTL2, diabetic retinopathy (DR), and age over 65 years were independent predictors of DKD progression. In T2DM patients, ANGPTL2 level was positively correlated with age. The synergy of serum ANGPTL2 and DR was superior to a single index (ANGPTL2) in diagnosing DKD, especially for non-elderly T2DM patients (<65 years old) (p < 0.001).
Conclusions: ANGPTL2 has a close association with the occurrence and progression of DKD. Serum ANGPTL2 had higher diagnostic value for the younger T2DM patients (<65 years old), and might serve as a potential biomarker for diagnosing DKD.
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Background: The osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL) system is closely related to knee osteoarthritis (KOA) subchondral bone osteosclerosis. As a heat-sensitive therapy, Hui Medicine moxibustion (HMm) has a good therapeutic effect on KOA. This study focused on the OPG/RANKL/RANK signaling pathway in KOA subchondral bone reconstruction, and explored the mechanism of HMm action on the reconstruction of KOA subchondral bone.
Methods: KOA models were established via Hulth method, and treated with HMm and HMm together with OPG antagonist (anti-OPG antibody). Hematoxylin-eosin staining and toluidine blue staining were used to characterize the pathological features of tibia. The apoptosis of osteoclasts and osteoblasts were detected by double immunofluorescence. The expression of OPG, RANKL and RANK were detected by immunohistochemistry, Real-Time Polymerase Chain Reaction (RT-PCR) and western blotting. In addition, RT-PCR and western blotting were used to detect matalloproteinase 3 (MMP-3), matalloproteinase 9 (MMP-9), interleukin 1 (IL-1), type I collagen (COL I) and osteopontin (OPN). Hydroxyproline, hexosamine, aggrecan and calcium were detected by corresponding kit.
Results: After HMm treatment, the loss of cartilage and subchondral bone were significantly decreased. HMm treatment also increased the ratio of apoptotic osteoclasts to apoptotic osteoblasts. Compared with KOA group, HMm treatment promoted the protein level of OPG and decreased the protein level of RANKL. In addition, the expression levels of MMP-3, MMP-9 and IL-1 were markedly decreased and OPN was increased. The components of subchondral bone (hydroxyproline, hexosamine, aggrecan and calcium) were significantly promoted in the Hui/KOA group. However, OPG antagonist alleviated these effects of HMm treatment.
Conclusions: HMm treatment may improve subchondral bone in KOA by regulating the osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL) system. This study may provide a basis for KOA treatment.
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Objective: To compare the short-term efficacy and safety of lipiodol combined with drug-eluting beads transarterial chemoembolization (LD-TACE) with conventional transarterial chemoembolization (c-TACE) in patients with hepatocellular carcinoma (HCC).
Methods: The clinical data of 113 patients with HCC treated by transarterial chemoembolization (TACE) in two medical centers from January 2017 to June 2021 were retrospectively analyzed. Among them, 54 cases received LD-TACE, and 59 cases received c-TACE. For patients in the LD-TACE group, moderate lipiodol embolization was conducted first, followed by embolization with drug-eluting microspheres. For the patients in the c-TACE group, lipiodol was administered via chemotherapy drug emulsion embolization first; Then, gelatin sponge particles were used to strengthen the embolization. The objective response rate (ORR), disease control rate (DCR), serum alpha-fetoprotein (AFP), and postoperative adverse events (AEs) were analyzed and compared between the two groups of patients after the first TACE.
Results: At 6–8 weeks after the first TACE, the ORR of the LD-TACE and the c-TACE groups were 68.5% and 47.5%, respectively (p = 0.024), and the DCR of the groups were 94.4% and 88.1%, respectively (p = 0.238). The reduction rate in the serum AFP was 87% and 74.6%, respectively (p = 0.095). In terms of AEs, nausea and vomiting were experienced by 46 patients in the c-TACE group; However, they occurred in only 24 patients in the LD-TACE group (p < 0.001). In addition, 33 patients in the c-TACE group had elevated bilirubin (BIL) after surgery, while elevated BIL occurred in only 17 cases in the LD-TACE group (p = 0.007). There were no significant differences in the incidence of postoperative abdominal pain, fever, or elevated transaminase between the two groups (p > 0.05 in all).
Conclusions: Compared with the patients who received c-TACE, the patients who received LD-TACE had higher short-term ORRs and fewer postoperative gastrointestinal AEs in the treatment of selective unresectable HCC.
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Background: The dissecting aneurysm of M3 (the middle cerebral artery runs outwards from the top of the annular sulcus to the surface of the Sylvian fissure) portion of the middle cerebral artery caused by hypertensives intracerebral hemorrhage (HICH) drainage is very rare. Thus, it can be easily misdiagnosed and its treatment is challenging. Once occurred, it is able to develop into secondary cerebral artery infarction or rebleeding, leading to serious neurological damage.
Methods: This is a case study involving one patient that suffered HICH drill drainage. A follow-up Magnetic resonance imaging (MRI) in outpatient clinic after HICH drainage was performed9 months ago. The MRI results revealed an abnormal shadow in the left temporal lobe. The cerebral angiography confirmed that there was a dissecting aneurysm in the M3 segment of the middle cerebral artery with severe stenosis of the diseased vessel, along with slow distal blood flow. Aneurysm of M3 portion of the middle cerebral artery was dissected after drainage of hypertensives intracerebral hemorrhage. The patient underwent the dissection vessel isolation and vascular reconstruction.
Results: There was no neurological dysfunction after surgery, the diseased vessels were unobstructed and the contralateral limb muscle strength of the patient significantly improved in the followed up after 2 months postoperation.
Conclusions: MRI should be investigated as early as possible in patients with Intracranial arterial dissection (IAD) after intracranial surgery, especially when patient’s functional recovery differs from the preoperative prognostic determination.
