Exploring the causal link between circulating cytokines and sarcopenia traits: A Mendelian randomization analysis.

BACKGROUND: Previous observational studies have linked circulating cytokines to sarcopenia, but their causal relationship remains unclear. This study employed Mendelian Randomization (MR) to investigate the causal links between circulating cytokines and sarcopenia-related traits using genetic data. METHODS: A two-sample bidirectional MR analysis was conducted using data from individuals of European ancestry, utilizing genome-wide association studies (GWAS) statistics. The study selected instrumental single nucleotide polymorphisms (SNPs) significantly associated with circulating cytokines and applied multiple MR methods, including inverse variance weighted (IVW), Weighted Median, MR-Egger, Weighted Mode, Simple Mode, and MR-PRESSO. The traits analyzed were appendicular lean mass (ALM) and grip strength. Heterogeneity, robustness, and consistency of results were assessed using Cochran's Q statistic, MR-Egger regression, and "leave-one-out" sensitivity analyses. RESULTS: The IVM-MR analysis showed a casual association between genetically predicted circulating levels of interleukin-16 and both ALM and grip strength (ALM: OR = 0.990, 95% CI: 0.980-1.000, p = .049; grip strength: OR = 0.971, 95% CI: 0.948-0.995, p = .020). Additionally, interferon-gamma-induced protein 10 (IP-10), interleukin-1-beta (IL-1ß), and hepatocyte growth factor (HGF) were correlated with ALM and vascular endothelial growth factor (VEGF), interleukin-12 (IL-12), and interleukin-5 (IL-5) with grip strength. Comparable results were confirmed via the MR-Egger, Weighted Median, Weighted Mode, and Simple Mode methods. Sensitivity analysis showed no horizontal pleiotropy to bias the causal estimates. CONCLUSION: The results suggest a significant causal effect of inflammatory cytokines on sarcopenia, offering new avenues for therapeutic target development. However, the study's focus on a European ancestry cohort limits its generalizability to other populations. Future research should aim to include diverse ethnic groups to validate and broaden these findings, thereby enhancing our understanding of sarcopenia's mechanisms in a global context.

Clinical characterization and immunosuppressive regulation of CD161 (KLRB1) in glioma through 916 samples.

BACKGROUND: Glioblastoma is a paradigm of cancer-associated immunosuppression, limiting the effects of immunotherapeutic strategies. Thus, identifying the molecular mechanisms underlying immune surveillance evasion is critical. Recently, the preferential expression of inhibitory natural killer (NK) cell receptor CD161 on glioma-infiltrating cytotoxic T cells was identified. Focusing on the molecularly annotated, large-scale clinical samples from different ethnic origins, the data presented here provide evidence of this immune modulator's essential roles in brain tumor biology. METHODS: Retrospective RNA-seq data analysis was conducted in a cohort of 313 patients with glioma in the Chinese Glioma Genome Atlas (CGGA) database and 603 patients in The Cancer Genome Atlas (TCGA) database. In addition, single-cell sequencing data from seven surgical specimens of glioblastoma patients and a model in which patient-derived glioma stem cells were cocultured with peripheral lymphocytes, were used to analyze the molecular evolution process during gliomagenesis. RESULTS: CD161 was enriched in high-grade gliomas and isocitrate dehydrogenase (IDH)-wildtype glioma. CD161 acted as a potential biomarker for the mesenchymal subtype of glioma and an independent prognostic factor for the overall survival (OS) of patients with glioma. In addition, CD161 played an essential role in inhibiting the cytotoxicity of T cells in glioma patients. During the process of gliomagenesis, the expression of CD161 on different lymphocytes dynamically evolved. CONCLUSION: The expression of CD161 was closely related to the pathology and molecular pathology of glioma. Meanwhile, CD161 promoted the progression and evolution of gliomas through its unique effect on T cell dysfunction. Thus, CD161 is a promising novel target for immunotherapeutic strategies in glioma treatment.

Study on the inversion of doped concentration induced by millisecond pulsed laser irradiation silicon-based avalanche photodiode.

In this paper, an experimental study of silicon-based avalanche photodiode (Si-APD) with millisecond pulse laser irradiation was carried out, and the C-V curve of Si-APD was obtained by using a semiconductor analyzer. Based on the single-side abrupt junction character of n+p, combined with the corresponding theoretical derivation, the doping concentration varying with the axial depth of damaged Si-APD was obtained by inverse computation. The lattice dislocation and junction reduction were the fundamental causes of the reduced doping concentration. The research results provide a new method for the study of the internal doping concentration for detectors with millisecond pulse laser damage.

High Beclin-1 Expression in Human Alveolar Macrophage Significantly Correlate with the Bacteriologic Sterilization in Pulmonary Tuberculosis Patients.

BACKGROUND: Tuberculosis (TB) continues to be a major health problem, and there are few biomarkers for predicting TB progression and anti-TB outcome. Recently, studies suggested that autophagy may link the multistep process of intracellular MTB clearance. So we hypothesized that autophagy level might indicate anti-TB prognostic significance. METHODS: Sixty-five pulmonary tuberculosis (PTB) patients and 15 healthy controls were included in the study. Laboratory examinations were determined in all subjects. Beclin-1 level, which was highly related with autophagy process, was determined using RT-PCR and western blotting assay in human alveolar macrophages. We divided the patients into Beclin-1 high group and Beclin-1 low group and treated them with the same anti-TB regimens. The predictive ability of Beclin-1 on the treatment outcome was further studied. RESULTS: In this study, we found Beclin-1 was markedly increased in alveolar macrophages in PTB patients. Sterilization of the sputum culture was achieved faster in the Beclin-1 high group, as demonstrated either by the percentage of negative smear findings or by the colony-forming unit (CFU) assay. Furthermore, Beclin-1 high group demonstrated faster relief of respiratory symptoms. CONCLUSIONS: Our results suggested the expression of Beclin-1 could be a novel biomarker for predicting anti-TB outcomes.

Clinical pathologies of breast cancer in the elderly and youths and their prognosis.

OBJECTIVE: To explore the correlation between the clinical pathologies of breast cancer in the elderly and youths as well as their prognosis. METHODS: Two hundred and eighty breast cancer patients were divided into a youth group (<60, n=120) and an elderly group (≥60, n=160) according to the age. Their routine clinical pathological indices and immune indices were observed and determined, and the prognosis was observed after effective treatment. RESULTS: The positive expression rates of p63, CK5/6, CK14 and CK17 in the elderly group were significantly higher than those of the youth group (P<0.05). The tumor-free survival rate of the youth group (95.8%) was significantly higher than that of the elderly group (84.4%) (P<0.05). Multivariate Logistic regression analysis showed that the positive expressions of p63 and estrogen receptor, age, and postoperative chemotherapy were the independent risk factors of tumor-free survival rate (P<0.05). CONCLUSION: The immunohistochemical typing characteristics of the elderly and youths were different, and the prognosis of young patients was better, being correlated with the typing.

[Expression of thyroid stimulating hormone receptor in differentiated thyroid carcinoma and its clinical significance].

OBJECTIVE: To explore the expression of thyroid stimulating hormone (TSH) receptor in differentiated thyroid carcinoma and its clinical significance. METHODS: Seventy-four patients with differentiated thyroid carcinoma treated in our department from January 2009 to January 2011 were selected as the observation group, and 28 patients with nodular goiter were selected as the control group. Expression of TSH receptor in the two groups were detected by immunohistochemistry. RESULTS: The positive rate of TSH receptor expression in the observation group was 55.4 (41/74), significantly lower than that of the control group (89.3%, 25/28), with a significant difference between the two groups (χ(2) = 10.21, P < 0.05). In the observation group, the positive rate of TSH receptor expression was 75.9% (22/29) in the stage I patients, 47.8% (11/23) in the stage II patients, 38.9%6 (7/18) in the stage III patients, and 25.0% (1/4) in the stage IV patients. Along with the increase of TNM staging, the positive rate of TSH receptor expression was decreased gradually, with a significant difference between them (χ(2) = 8.93, P < 0.05). The positive rate of TSH receptor expression was 53.8% (14/26) in the lymph node metastasis positive group and 56.3% (27/48) in the lymph node metastasis negative groups, with a non-significant difference between them (χ(2) = 0.04, P > 0.05). CONCLUSIONS: Expression of TSH receptors in the patients with differentiated thyroid carcinoma is quite low, and along with the increase of TNM staging, its positive rate is decreasing gradually. Testing the expression of TSH receptor may provide a basis for TSH suppression therapy after thyroid cancer surgery. This TSH suppression therapy should be personalized in order to reduce the side effects and improve their quality of life.

[Identification and characterization of Aspergillus aculeatus JMUdb058 for naringinase production].

OBJECTIVE: A new naringinase-producing strain, JMUdb058 was identified and characterized. METHODS: The strain was identified by morphological observation and 28S rDNA homogeneous analysis. Naringinase was identified by monitoring the hydrolysis of naringin to prunin and naringenin using a reversed phase High Performance Liquid Chromatography (HPLC). The regulation of naringinase expression was studied by measuring naringinase activity of 11 different carbon sources and 7 nitrogen sources in shaking cultivation. The naringinase-producing capacity was investigated in both solid-state fermentation and submerged fermentation. RESULTS: The macro-morphology and micro-morphology of JMUdb058 corresponded to the characteristics of Aspergillus section Nigri Gams, and the 28S rDNA sequences showed homogeneity at 100% to Aspergillus aculeatus. Crude enzymes prepared by both submerged fermentation and solid-state fermentation could hydrolyze naringin to prunin and naringenin. In addition, the enzyme could remove naringin from citrus juice effectively. Carbon resources, including hesperidin, naringin, rutin and rhamnose, and organic nitrogen resources, i. e., tryptone, soybean meal, yeast extract and corn syrup were shown to express the naringinase. The strain had an outstanding ability to yield naringinase in the solid-state fermentation, which showed an alpha-L-rhamnosidase activity of 5903 U/gds by HPLC, and the naringinase of 1939U/gds by HPLC and 72232 U/gds by Davis method. CONCLUSION: It is the first time to report a stain of Aspergillus aculeatus can produce naringinase, carbon source containing rhamnose groups are able to induce the enzyme expression. The stain JMUdb058 is a new microorganism source for high yield of naringinase, in particularly by the solid-state fermentation.

WITHDRAWN: Hidrosmin Attenuates Inflammatory Response Induced by IL1ß by Suppressing the Activation of NF-κB Involving Nrf2/HO1 Pathway in Human Osteoarthritis Chondrocytes

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Rat and mouse bone marrow mesenchymal stem cells can spontaneously express troponin T.

PURPOSE: This study aims to investigate whether the bone marrow mesenchymal stem cells (BMSCs) of rat and mice can spontaneously express troponin T (cTnT) in vitro. METHODS: The BMSCs of rats and mice were cultured in vitro. The expression of cTnT in the BMSCs of rats and mice was detected by immunofluorescence, immunohistochemistry, and Western blot. The detection of cTnT and α-sarcomeric actin coexpression on the surface of BMSCs was determined using immunofluorescence and qRT-PCR. RESULTS: In rats and mice, cTnT expression was detected in a portion of BMSCs. The positive rates of cTnT in rats and mice were approximately 10-52 % and 27-60 %, respectively. According to the results of the Western blot analysis, the gray values of cTnT in rats and mice were 0.64 ± 0.02 and 1.08 ± 0.03, respectively. Additionally, the surface of BMSCs can express cTnT and α-sarcomeric actin, which is a marker for striated muscle. CONCLUSION: The BMSCs of rats and mice can spontaneously express cTnT and automatically differentiate striated muscles in vitro.

Therapy of replenishing and regulating for manic episode in bipolar disorder: study protocol for a prospective, double-blind, randomized controlled trial.

Bipolar disorder (BD) is a chronic and recurrent disorder characterized by biphasic mood episodes of mania or hypomania and depression. It affects more than 1% of the global population and is a leading cause of disability in young people. Currently available treatments for BD are still fairly limited in terms of efficacy, with high rates of non-adherence, non-response, and undesirable side effects. Traditional Chinese medicine (TCM) has a long history and rich experience in stabilizing mania and improving quality of life. Aiming at rebalancing and in BD, therapy of replenishing and regulating (RYRY therapy) has been in clinical use for years in China. The present prospective, double-blind, randomized controlled trial is designed to investigate the efficacy and safety of RYRY therapy for bipolar mania and its possible mechanism from the point of regulating gut microbiota and anti-inflammation. A total of 60 eligible participants will be recruited from Beijing Anding Hospital. They will be randomized to either the study group or the control group in a ratio of 1∶1. Participants allocated to the study group will receive RYRY granule, while placebo granule will be applied in the control group. Participants in both groups will be prescribed conventional therapy for manic episode in BD. Four scheduled visits will be conducted over 4 weeks. Outcome measurements include Young Mania Rating Scale, TCM Symptom Pattern Rating Scale, Treatment Emergent Symptom Scale, levels of C-reactive protein, interleukin-6 and tumor necrosis factor-α and the gut microbial community profile of stool samples. Safety outcomes and adverse events will also be recorded. In this study, we set a number of scientific and objective assessments to evaluate the efficacy of RYRY therapy and study into its possible mechanism, hopefully offering clinicians an alternative approach to BD.