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Neurodegenerative diseases (NDDs) pose a significant public health challenge due to the rapid aging of the global population. Common features of NDDs include the abnormal aggregation of different proteins and disruption of normal function of organelles. Chaperone-mediated autophagy (CMA), one of the main pathways of lysosomal-mediated proteolysis, selectively delivers cytosolic proteins with an exposed KFERQ-like motif into the lysosomal lumen for degradation. CMA is essential for maintaining neuronal homeostasis, and its dysfunction has been implicated in aging and NDDs. Recent studies have revealed several mechanisms by which CMA is involved in the pathogenesis of NDDs. This review summarized the current understanding of the fundamental processes and regulatory mechanisms of CMA. Furthermore, we elucidate the links between CMA and NDDs, primarily focusing on how CMA regulates the function of cellular organelles in the pathological process underlying NDDs. Targeting impaired CMA represents an attractive and promising therapeutic strategy for the treatment of NDDs.
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Objective: This research was performed to analyze the diagnostic and prognostic value of thyroid function tests plus B-type natriuretic peptide (BNP) tests in patients with heart failure (HF).
Methods: This study matched 120 patients with HF (HF group) at a single institution from January 2019 and January 2021 with 120 healthy subjects (control group) (1:1 ratio) during the same period. All eligible participants received BNP and thyroid function tests.
Results: Patients with HF exhibited markedly higher BNP levels than healthy controls (p < 0.05). Patients with HF showed remarkably lower concentrations of free triiodothyronine (FT3) versus healthy controls (p < 0.05), while the concentrations of free thyroxine (FT4) and thyroid-stimulating hormone (TSH) showed no marked alterations (p > 0.05). The aggravation of HF causes a remarkable decrease in FT3 levels and an elevation in BNP levels (p < 0.05), while the alterations in the serum concentrations of FT4 and TSH levels were mild (p > 0.05). After treatment, markedly elevations of FT3 levels and a decline of BNP levels were found in the HF group (p < 0.05). Hybrid detection allows for a larger coverage of the detection area than the stand-alone test. The combined detection provided a larger area under the curve (AUC) and a higher 95% confidence interval and sensitivity versus single tests (p < 0.05), suggesting a superior diagnostic efficiency of the combined BNP and thyroid function tests.
Conclusion: The combination of BNP and thyroid function tests offers a viable diagnostic alternative for HF patients, with high diagnostic efficiency and prognostic assessment value.
Clinical Trial Registration: ChiCTR2200069567.
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Background: Gastric cancer is a globally prevalent malignancy characterized by dysregulated cellular processes including epigenetic modifications. However, the Polycomb Repressive Complex 2 (PRC2), a pivotal epigenetic regulator, modulates gene expression through trimethylation of histone H3 at lysine 27 (H3K27me3), thereby orchestrating cellular identity and function. Therefore, this study aimed to elucidate the impact of PRC2 and H3K27me3 on critical cellular behaviors, such as proliferation, migration, invasion, and apoptosis, which holds the potential to unveil novel insights into gastric cancer progression.
Methods: Human gastric cancer cells NCI-N87 were seeded in a 6-well plate and were divided into the normal, siRNA-negative control (siRNA-NC), siRNA-Enhancer of zeste homolog 2 (siRNA-EZH2), and siRNA-SUZ12 polycomb repressive complex 2 subunit (siRNA-SUZ12) groups. The cells were transfected to knock down the expression of PRC2 core subunits, siRNA-Enhancer of zeste homolog 2 (EZH2) and SUZ12 polycomb repressive complex 2 subunit (SUZ12). Moreover, Western Blot analysis and Quantitative real-time reverse-transcription PCR (qRT-PCR) were carried out to determine the expression levels of the EZH2 and SUZ12 in gastric cancer cells. Furthermore, the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to examine cell proliferation, the Transwell assay was employed to determine cell migration and invasion, and flow cytometry was used to evaluate cell apoptosis rate. Additionally, the confocal laser scanning technique was utilized to assess H3K27 methylation in gastric cancer cells. Finally, the interaction between PRC2 and H3K27 was evaluated using co-immunoprecipitation (Co-IP).
Results: Compared to the siRNA-NC group, there was a significant decrease in the levels of EZH2 protein and mRNA in the cells of the siRNA-EZH2 group and SUZ12 protein and mRNA in the siRNA-SUZ12 group (p < 0.05). Furthermore, both the siRNA-EZH2 and siRNA-SUZ12 groups showed significantly reduced cell survival rates, and decreased count of migrating and invading cells, while exhibited significantly increased apoptosis rate compared to the siRNA-NC group. Moreover, the expression level of H3K27me3 significantly elevated in these cells (p < 0.05). Additionally, Co-IP results revealed a significant interaction of EZH2 and SUZ12 with H3K27me3.
Conclusion: This study delved into the impact of the PRC2 on gastric cancer cell behavior, focusing on the targeted regulation of histone H3K27me3. The findings suggest that PRC2 might modulate cellular proliferation, migration, invasion, and apoptosis within gastric cancer cells. Nevertheless, rigorous experimental validation is essential to establish causal relationship and gain deeper mechanistic insights into PRC2's role in gastric cancer.
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Objective: The current research aimed to explore the impact of higenamine on the hepatic stellate cells (HCC) activation Stimulated by transforming growth factor-β (TGF-β1) in vitro.
Methods: This is a prospective study, we investigated the impact of higenamine on the hepatic stellate cells (HSCs) activation stimulated by TGF-β1 in vitro and Liver fibrosis (LF) stimulated by tetrachloromethane (CCl4) in vivo. Cell Counting Kit-8 (CCK-8) was adopted for detecting the proliferation of LX-2 cells, HSC stain. Reactive Oxygen Species (ROS) production was determined using fluoroprobe 2′,7′-dichlorodihydrofluorescein diacetate (H2DCF-DA). The expression levels of ROS-producing enzymes (NOX2 and NOX4), as well as Smad2, p-Smad3, p-Smad2, and Smad3 were quantified via western blot (WB). The mRNA/protein expression of extracellular matrix (ECM) proteins (collagen I (Col I) and α-smooth muscle actin (α-SMA)) was detected via Quantitative Real-time Polymerase Chain Reaction (RT-qPCR) and WB. Haematoxylin and eosin (H&E) dyeing was conducted using liver tissues to examine histopathological damage and fibrosis. The serum levels of fibrosis biochemical markers including hyaluronic acid (HA), PC-III, as well as Col IV were tested by Enzyme-Linked Immunosorbent Assay (ELISA).
Results: Higenamine suppressed the proliferation and ROS production in TGF-β1-intervened LX-2 cells. The increased levels of NOX2/NOX4 and NOX activity in TGF-β1-intervened LX-2 cells were reduced by higenamine. Higenamine inhibited the mRNA/protein expression of α-SMA and Col I in TGF-β1-intervened LX-2 cells. Furthermore, the TGF-β1-intevened phosphorylation of Smad3 and Smad2 was attenuated by higenamine.
Conclusion: To sum up, these findings showed that higenamine prevented HSCs' activation via the TGF-β1/Smad pathway. Higenamine also attenuated CCl4-caused hepatic damage and fibrosis in vivo. Thus, higenamine is one possible therapeutic agent for LF prevention.
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Objective: Ulcerative colitis is an inflammatory disease that affects the lining of the colon and rectum. This study was to investigate the potential utility of Bletilla striata polysaccharide (BSP) for ulcerative colitis (UC) treatment and explore its immunoregulatory mechanisms.
Methods: Male Wistar rats were assigned to four groups at a ratio of 1:1:1:1. The four groups of rats were treated with no intervention, 2,4,6-trinitrobenzenesulfonic acid (TNBS), high-performance liquid chromatography (HPLC)-purified BSP (60 mg/kg), sulfasalazine (100 mg/kg). Symptom severity was assessed. Flow cytometry and quantitative real-time polymerase Chain Reaction (qRT-PCR) were performed to assess T cell responses, including the proportions of cluster of differentiation 4+ (CD4+) T cells and particular cytokines. Autophagic markers microtubule-associated protein 1A/1B-light chain 3 (LC3) II and sequestosome 1 (p62), and granzyme (Grz)-related proteins, Granzyme M (GrzM), macrophage inflammatory protein 1 (MIP-1α) and macrophage migration inhibitory factor (MIF) were estimated by Western blot.
Results: Significant elevations of T helper 1 (Th1) and Th17 and declines of Th2 and regulatory T cells (Treg) were observed in the UC group versus the controls (p < 0.001). These alterations could be reversed significantly in UC rats treated with BSP, in contrast to UC group (p < 0.001). T cell percentage alterations were validated by mRNA expression of cytokines associated to distinct T cell subgroups. BSP therapy resulted in increased LC3 II and decreased p62, as well as an increase in GrzM and MIP-1 and a decrease in MIF. Except for LC3 II, significant differences were observed in these protein levels from those in the UC group (p < 0.001).
Conclusion: BSP demonstrates great potential for UC management via rebalancing of Th1/Th2 and T17/Treg subsets. The study provides a certain theoretical basis for the treatment of UC with traditional Chinese medicine, but the results might be biased due to the small sample size, and future studies are required to further explore.
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Background: Breast cancer, the most common cancer, is the leading cause of cancer-related deaths among women globally. To effectively reduce mortality, it has become a hot topic to find prognostic indicators that are highly correlated with poor prognosis of breast cancer in early stages. Therefore, this study aimed to explore the levels of serum cancer antigen 15-3 (CA15-3), cancer antigen 125 (CA125), and tissue polypeptide specific antigen (TPS) in individuals with breast cancer and to elucidate the relationship between these markers and clinicopathological factors, as well as their impact on disease prognosis.
Methods: This study included 140 subjects diagnosed with breast cancer (breast cancer subgroup), 120 subjects with breast cancer benign lesions (breast benign disease subgroup), and 120 healthy controls (control subgroup). The clinical data and blood samples were collected from all study subjects. Furthermore, the serum levels of CA15-3, CA125, and TPS were evaluated using corresponding enzyme linked immunosorbent assay (ELISA) kits. The correlation between serum indexes and clinicopathological factors was analyzed. Additionally, the 3-year survival rate of breast cancer patients was assessed using the Kaplan-Meier method.
Results: A statistically significant difference was observed in the serum CA15-3, CA125, and TPS levels across three subgroups: breast subgroup, benign breast disease subgroup, and control subgroup (p < 0.05), with higher levels observed in the breast subgroup followed by benign breast disease subgroup. Furthermore, their levels were correlated with pathological type, tumor node metastasis classification tumor node metastasis (TNM) stage, lymph node metastasis, and histological grade (p < 0.05, p < 0.001). Moreover, these markers were identified as independent risk factors for breast cancer using multivariate Logistic regression analysis (p < 0.05). The probability of survival of breast cancer subjects in high CA15-3 level subgroup, high CA125 level subgroup and high TPS level subgroup was notably lower than that in low level subgroup, which was shown by Kaplan-Meier analysis (p < 0.05).
Conclusion: The serum levels of CA15-3, CA125, and TPS are significantly elevated in subjects with breast cancer, and their expression levels are correlated with pathological type, TNM stage, lymph node metastasis, and histological grade. These tumor markers can be used as predictors of breast cancer prognosis.
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No abstract present.
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Correction of Journal of Biological Regulators and Homeostatic Agents 2023, 37 (8)
The authors wish to make the following correction to this paper [1]:
The corresponding author's email address longjpei_jpei@163.com should be changed to 5310015@zju.edu.cn.
