Gender-specific microbial signatures in saliva: Unveiling the association between the oral microbiome and the pathogenesis of glioma.

The intricate interplay between the human oral microbiome and systemic health is increasingly being recognized, particularly in the context of central nervous system pathologies such as glioblastoma. In this study, we aimed to elucidate gender-specific differences in the salivary microbiome of glioma patients by utilizing 16S rRNA sequencing data from publicly available salivary microbiome datasets. We conducted comprehensive bioinformatics analysis, encompassing quality control, noise reduction, species classification, and microbial community composition analysis at various taxonomic levels. Machine learning algorithms were employed to identify microbial signatures associated with glioma. When compared to healthy controls, our analysis revealed distinct differences in the salivary microbiota of glioma patients. Notably, the genera Leptotrichia and Atopobium exhibited significant variations in abundance between genders. Leptotrichia was prevalent in healthy females but exhibited a reduced abundance in female glioma patients. In contrast, Atopobium was more abundant in male glioma patients. These findings suggest that hormonal influences might play a role in shaping the salivary microbiome and its association with glioma. We utilized a combination of LASSO-logistic regression and random forest models for feature selection, and identified key microbial features that differentiated glioma patients from healthy controls. We developed a diagnostic model with high predictive accuracy and area under the curve and principal component analysis metrics confirmed its robustness. The analysis of microbial markers, including Atopobium and Leptotrichia, highlighted the potential of the salivary microbiota as a non-invasive biomarker for the diagnosis and prognosis of glioma. Our findings highlight significant gender-specific disparities in the salivary microbiome of patients with glioma, offering new insights into the pathogenesis of glioma and paving the way for innovative diagnostic and therapeutic strategies. The use of saliva as a diagnostic fluid, given its ease of collection and non-invasive nature, holds immense promise for monitoring systemic health and the trajectory of disease. Future research should focus on investigating the underlying mechanisms by which the salivary microbiome influences the development of glioma and identifying potential microbiome-targeted therapies to enhance the management of glioma.

No effect of surgery on kidney and cardiovascular risk factors in mild primary hyperparathyroidism: secondary analyses from a 10-year randomized controlled trial.

OBJECTIVE: Renal function and the skeleton are classic target organs in primary hyperparathyroidism (PHPT), affected by the chronic course of the disease. Most patients diagnosed today exhibit mild PHPT, characterized by slight hypercalcemia and no or unspecific symptoms. Concerns have been raised that PHPT could promote deteriorating kidney function and increase cardiovascular risk directly. To examine the effect of parathyroidectomy (PTX) on mild PHPT on renal function and markers for bone turnover, cardiovascular disease (CVD), and vascular inflammation. DESIGN: Prospective randomized controlled trial. ClinicalTrials.gov: NCT00522028. SETTING: Eight Scandinavian referral centers. PARTICIPANTS: From 1998 to 2005, 191 patients with mild PHPT were included in Sweden, Norway, and Denmark. Of these 150 were included in the present analyses. INTERVENTION: Seventy patients were randomized to PTX and 80 to observation without intervention (OBS). MEASURES: e-GFR was calculated based on creatinine and cystatin C. Markers of CVD and systemic inflammation: osteoprotegerin, vascular cell adhesion molecule 1, soluble CD40 ligand, interleukin-1 receptor antagonist, von Willebrand factor. Bone turnover markers: C-terminal telopeptide of type 1 collagen (CTX-1) and serum Procollagen type 1 N-terminal propeptide. RESULTS: No differences in the development of renal function or vascular and systemic inflammation were detected. CTX-1 was lower in PTX after 10 years. LIMITATIONS: Secondary analyses of a randomized controlled trial. CONCLUSION: PTX does not appear to affect renal function or markers of CVD and vascular inflammation in mild PHPT in a ten-year perspective.

Bioinformatics and systems biology approaches to identify potential common pathogeneses for sarcopenia and osteoarthritis.

Sarcopenia, a geriatric syndrome characterized by progressive loss of muscle mass and strength, and osteoarthritis, a common degenerative joint disease, are both prevalent in elderly individuals. However, the relationship and molecular mechanisms underlying these two diseases have not been fully elucidated. In this study, we screened microarray data from the Gene Expression Omnibus to identify associations between sarcopenia and osteoarthritis. We employed multiple statistical methods and bioinformatics tools to analyze the shared DEGs (differentially expressed genes). Additionally, we identified 8 hub genes through functional enrichment analysis, protein-protein interaction analysis, transcription factor-gene interaction network analysis, and TF-miRNA coregulatory network analysis. We also discovered potential shared pathways between the two diseases, such as transcriptional misregulation in cancer, the FOXO signalling pathway, and endometrial cancer. Furthermore, based on common DEGs, we found that strophanthidin may be an optimal drug for treating sarcopenia and osteoarthritis, as indicated by the Drug Signatures database. Immune infiltration analysis was also performed on the sarcopenia and osteoarthritis datasets. Finally, receiver operating characteristic (ROC) curves were plotted to verify the reliability of our results. Our findings provide a theoretical foundation for future research on the potential common pathogenesis and molecular mechanisms of sarcopenia and osteoarthritis.

Recombinant human protein TCFL5-activated NRSN2-AS1 promotes esophageal cancer progression via the microRNA-874-5p/RELT regulatory axis.

The incidence of esophageal cancer continues to increase worldwide. Current therapeutic approaches have limited efficacy, so in order to search for better markers of the disease, it is necessary to further elucidate its molecular pathogenesis. Regulation of gene expression by long non-coding Rnas plays a role in many diseases, however the role in esophageal cancer is unclear. The aim of this study was to elucidate the role and regulatory mechanism of long non-coding RNA NRSN2-AS1 in the progression of esophageal cancer. By real-time quantitative PCR, immunohistochemistry, RNA interference, western blotting, and double luciferase reporter gene analysis, we found that NRSN2-AS1 was up-regulated in esophageal cancer tissues and cell lines, and was closely related to disease stage and prognosis. Functional studies have shown that the silencing of NRSN2-AS1 inhibits the proliferation of esophageal cancer cells, induces apoptosis, and prevents cell migration and invasion. In mouse models, NRSN2-AS1 also promoted tumor growth. The transcription factor TCFL5 upregulates the transcription of NRSN2-AS1, which acts as a sponge for microRNA(miR)-874-5p, thereby upregulating the expression of the oncogene RELT. Activation of the NRSN2-AS1/miR-874-5p/RELT regulatory axis was validated in vivo.

Evaluating the impact of exercise on intermediate disease markers in overweight and obese individuals through a network meta-analysis of randomized controlled trials.

The aim of this study is to investigate the impact of exercise on intermediate disease markers in populations with overweight and obesity, providing evidence-based recommendations for clinicians to utilize these markers in developing exercise prescriptions for this group. The study was conducted by retrieving data from PubMed, Embase, Cochrane Library, Web of Science, and CNKI and only including Randomized Controlled Trials (RCTs) to examine the effect of different exercise interventions on intermediate disease markers in overweight and obese people. The quality of the included studies was evaluated using the Cochrane Bias Risk Assessment tool and the data was analyzed using Stata 15.1 data analysis software. The RCTs were collected from January 2017 to March 2024. A total of 56 RCTs were included and the results of 10 outcomes were analyzed using random effects meta-analysis. The total sample size used in the study was 3193 The results showed that resistance training significantly reduced total cholesterol (SUCRA: 99.9%), triglycerides (SUCRA: 100.0%), low-density lipoprotein (SUCRA: 100.0%), systolic pressure (SUCRA: 92.5%), and increased high-density lipoprotein (SUCRA: 100.0%). Aerobic exercise significantly reduced insulin (SUCRA: 89.1%) and HbA1c (SUCRA: 95.3%). Concurrent training significantly reduced HOMA-IR (SUCRA: 93.8%), diastolic blood pressure (SUCRA: 71.2%) and Glucose (SUCRA: 87.6%). Exercise has a significant impact on intermediate disease markers in populations with overweight and obese. Compared with no exercise, exercise lowers total cholesterol, triglycerides, LDL, systolic blood pressure, diastolic blood pressure, HOMA-IR, insulin, and HbA1c, and increases HDL in people with overweight and obese. These findings provide evidence-based recommendations for exercise interventions aimed at weight reduction and the prevention of chronic diseases in individuals with overweight and obese.

Fatigue after spontaneous intracerebral haemorrhage: prevalence and associated factors.

BACKGROUND: Fatigue is a major complaint in stroke survivors, but data focusing on intracerebral haemorrhage (ICH) survivors are scarce. In a cohort of spontaneous ICH survivors, we assessed the long-term prevalence of fatigue and its associated factors. METHODS: We included consecutive 1-year ICH survivors from the prospective, observational, single-centre Prognosis of Intracerebral Haemorrhage (PITCH) study. We evaluated fatigue (defined as a score ≥ 4 in Chalder Fatigue Scale); the severity of neurological, depressive, and anxiety symptoms; and functional disability 1, 3, and 6 years after ICH. We performed univariable and multivariable models to evaluate clinical factors and brain magnetic resonance imaging (MRI) small vessel disease (SVD) markers associated with fatigue. RESULTS: Of 255 1-year ICH survivors, 153 (60%) underwent fatigue screening and were included in this study. Seventy-eight patients (51%) reported fatigue at 1-year, 56/110 (51%) at 3-year, and 27/67 (40%) at 6-year follow-up. Patients with fatigue exhibited more severe concomitant depressive/anxiety symptoms, but the severity of depressive symptoms was the only clinical factor significantly associated with 1-year fatigue in multivariable analysis (adjusted odds ratio 1.4 for one-point increase; 95% confidence interval 1.2-1.6). Patients with severe cortical atrophy at baseline had increased risk of fatigue at 1-year follow-up compared to patients with mild/no cortical atrophy (adjusted odds ratio 2.5; 95% confidence interval 1.1-5.8). CONCLUSIONS: Fatigue after ICH is frequent and long-lasting, and it is associated with cortical atrophy (but not with other MRI markers of cerebral SVD). The link between fatigue and depressive symptoms may represent a potential therapeutic target.

Hepcidin Reduction during Testosterone Therapy in Men with Type 2 Diabetes: A Randomized, Double-Blinded, Placebo-Controlled Study.

High hepcidin is linked to low-grade inflammation and lower iron levels. The consequences of testosterone replacement therapy (TRT) on inflammation and the risk of cardiovascular disease (CVD) are undetermined. We investigate the effect of TRT on the inflammatory cardiovascular risk markers hepcidin-iron, fibroblast growth factor 23 (FGF23)-phosphate-klotho, and calprotectin pathways. METHODS: A randomized, placebo-controlled, double-blinded study at an academic tertiary-care medical center. Interventions were testosterone gel (TRT, n = 20) or placebo gel (n = 19) for 24 weeks. We included 39 men (50-70 years) with type 2 diabetes (T2D) on metformin monotherapy with bioavailable testosterone levels <7.3 nmol/L. Body composition was assessed with DXA- and MRI-scans; the main study outcomes were serum hepcidin-iron, FGF23, phosphate, klotho, and calprotectin. RESULTS: Hepcidin levels decreased during TRT (ß = -9.5 ng/mL, p < 0.001), lean body mass (ß = 1.9 kg, p = 0.001) increased, and total fat mass (ß = -1.3 kg, p = 0.009) decreased compared to placebo. Delta hepcidin was not associated with changes in lean body mass or fat mass. Iron and the pathways of FGF23-phosphate-klotho and calprotectin were unchanged during TRT. CONCLUSIONS: During TRT, the reduction in hepcidin was not associated with circulating iron levels, lean body mass, or fat mass; these findings suggested a direct anti-inflammatory effect of TRT and no indirect effect mediated through these factors.

Construction of diagnostic and prognostic models based on gene signatures of nasopharyngeal carcinoma by machine learning methods.

Background: Diagnostic models based on gene signatures of nasopharyngeal carcinoma (NPC) were constructed by random forest (RF) and artificial neural network (ANN) algorithms. Least absolute shrinkage and selection operator (Lasso)-Cox regression was used to select and build prognostic models based on gene signatures. This study contributes to the early diagnosis and treatment, prognosis, and molecular mechanisms associated with NPC. Methods: Two gene expression datasets were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) associated with NPC were identified by gene expression differential analysis. Subsequently, significant DEGs were identified by a RF algorithm. ANN were used to construct a diagnostic model for NPC. The performance of the diagnostic model was evaluated by area under the curve (AUC) values using a validation set. Lasso-Cox regression examined gene signatures associated with prognosis. Overall survival (OS) and disease-free survival (DFS) prediction models were constructed and validated from The Cancer Genome Atlas (TCGA) database and the International Cancer Genome Consortium (ICGC) database. Results: A total of 582 DEGs associated with NPC were identified, and 14 significant genes were identified by the RF algorithm. A diagnostic model for NPC was successfully constructed using ANN, and the validity of the model was confirmed on the training set AUC =0.947 [95% confidence interval (CI): 0.911-0.969] and the validation set AUC =0.864 (95% CI: 0.828-0.901). The 24-gene signatures associated with prognosis were identified by Lasso-Cox regression, and prediction models for OS and DFS of NPC were constructed on the training set. Finally, the ability of the model was validated on the validation set. Conclusions: Several potential gene signatures associated with NPC were identified, and a high-performance predictive model for early diagnosis of NPC and a prognostic prediction model with robust performance were successfully developed. The results of this study provide valuable references for early diagnosis, screening, treatment and molecular mechanism research of NPC in the future.

Moderate-intensity intermittent exercise prevents memory deficit, hippocampal neuron loss, and elevated level of Alzheimer's dementia markers in the hippocampus of trimethyltin-induced rats.

BACKGROUND: Moderate-intensity intermittent exercise (MIIE) has been proposed as an effective method for preventing Alzheimer's dementia (AD). AIM: This study aimed to investigate the effects of MIIE on the spatial memory and protein level of AD markers in the hippocampus of trimethyltin (TMT)-induced rat model of hippocampal degeneration. METHODS: Male Sprague Dawley (SD) rats were randomly assigned into four groups: normal control (N), exercise control (E), TMT control (T), and exercise and TMT (ET). Rats of the exercise groups (E and ET) were forced to run on a treadmill for 30 min each day at maximum for 12 weeks. Intraperitoneal injection of 8 mg/kgBW TMT was administered as a single dose, 10 days before the last exercise treatment for the T and ET groups. The spatial memory of rats was examined using Morris water maze (MWM) test after the exercise period. After euthanasia, the hippocampal tissue was dissected out and the level of hippocampal presenilin-1 (PSEN-1) and phosphorylated tau (p-tau) protein were measured using ELISA. The total number of hippocampal pyramidal neurons was estimated using unbiased stereological analysis. Qualitative immunohistochemistry was performed to examine the expression of brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) in paraffin sections of the hippocampus. RESULTS: TMT exposure induced memory impairment indicated by the T group having the lowest percentage of time and percentage of path length in the target quadrant compared to other groups. MIIE prevented the memory impairment effect of TMT exposure indicated by the ET group having no significantly different MWM performance compared to the E and N groups. The ET group had significantly lower levels of hippocampal AD markers, p-tau and PSEN-1, as well as significantly higher estimated total number of pyramidal neurons of hippocampal CA1 and CA2-3 regions compared to the T group. Expressions of TNF-α was weak, while the expression of IL-10 was stronger in the ET group compared to the control group. The TMT-induced group exhibited stronger expression of BDNF. CONCLUSION: MIIE prevents neuronal loss and impaired spatial memory upon TMT exposure most probably via preventing elevated levels of hippocampal AD markers and neuroinflammation. WC:350.

Recent Research Progress of Surface-Enhanced Raman Scattering Dominated Analysis Strategies in Early Diagnosis of Diseases.

Timely and powerful diagnostic means can achieve better therapeutic effects, reduce disease torment, and improve survival rate. As a powerful non-invasive spectroscopy technology, surface-enhanced Raman scattering (SERS) have testified to be a great potential candidate for extensive early clinical disease diagnosis. In recent years, the introduction of SERS label, combined with other analysis modes or artificial intelligence, and the emergence of miniaturized devices have made SERS technology more advantageous in early diagnosis of diseases. This review focuses on the research progress of SERS dominated analytical strategies in the field of early disease diagnosis in the past five years. The main content includes the application of label-free SERS detection; the construction of label SERS methodologies for various disease markers; SERS dominated multimode early disease diagnosis strategies; integration of SERS and artificial intelligence; portable Raman equipment and SERS imaging; and opportunities and trends for SERS diagnostic technology in the future.