Tao-Hong-Si-Wu-Tang Improves the Depressive-like Behaviors in Mice Experiencing Perimenopausal Depression Through Modulating Activity of the Hypothalamic-Pituitary-Adrenal-Ovary Axis and Activating the BDNF-TrkB-CREB Signaling Pathway.

Tao-Hong-Si-Wu-Tang (THSWT), a traditional Chinese herbal remedy, is commonly utilized for the treatment of female perimenopausal depression through regulating menstruation, but the mechanism remains unknown. In this study, ICR mice were randomly divided into six groups: low, medium, and high dose of THSWT (0.5, 1.5, and 4.5 g/kg), soy isoflavone (250 mg/kg), ovariectomy group, and control group. All mice, except the control group, had ovaries removed and were exposed to hypoxic stimulation for 28 days to establish a perimenopausal depression mice model. The mice, having unrestricted access to food and water, were administered THSWT treatment for a duration of 14 days. The Western blotting and Enzyme linked immunosorbent assay kits were used to determine protein and hormone levels, respectively. Experimental results showed that THSWT reduced the immobility time of mice from 150.8 s to 104.9 s in the tail suspension test, and it decreased the immobility time of mice from 165.7 s to 119.0 s in the forced swimming test, outperforming the results obtained with soy isoflavones. In addition, THSWT upregulated the protein expression of follicle-stimulating hormone receptor and downregulated the protein expression of corticotropin-releasing hormone-receptor 1 in the hippocampus. Compared with the oophorectomized group, treatment with THSWT decreased the levels of corticosterone and adrenocorticotropic hormone in serum by 173.7 and 23.4 ng/mL, respectively. These findings showed that THSWT could stimulate the perimenopausal nerve tissue and regulate the level of serum hormones in mice. THSWT exhibited promising potential as a viable alternative drug for hormone treatment of perimenopause in clinical use.

The construction and validation of ECM-related prognosis model in laryngeal squamous cell carcinoma.

Background: Laryngeal squamous cell carcinoma (LSCC) is a kind of common and aggressive tumor with high mortality. The application of molecular biomarkers is useful for the early diagnosis and treatment of LSCC. Methods: The expression and clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Principal components analysis (PCA) was used to discriminate between LSCC and normal samples. The hub genes were screened out through univariate and multivariate cox analyses. The Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curve was used to validate the predictive performance. The single sample gene set enrichment analysis (ssGSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to determine the enrichment function. Protein-Protein Interaction (PPI) network was constructed in STRING. The immune analysis was performed by ESTIMATE, IPS and xCELL. The drug sensitivity was identified with GSCA database. Results: We identified that 47 extracellular matrix (ECM) genes were differentially expressed in LSCC compared with normal group. Univariate and multivariate cox analysis determined that leucine-rich glioma-inactivated 4 (LGI4), matrilin 4 (MATN4), microfibrillar-associated protein 2 (MFAP2) and fibrinogen like 2 (FGL2) were closely related to the disease free survival (DSS) of LSCC. ROC curve determined that the risk model has a good predictive performance. PPI network showed the top 100 genes with high correlation of hub genes. The ssGSEA, GO and KEGG enrichment analyses determined that immune response was significantly involved in the development of LSCC. Immune infiltration analysis showed that most immune cells and immune checkpoints were inhibited in high risk score group. Drug sensitivity analysis showed that MATN4, FGL2 and LGI4 were negatively related to various drugs, while MFAP2 was positively related to many drugs. Conclusion: We established a risk model constructed with four ECM-related genes, which could effectively predict the prognosis of LSCC.

Interactions between glial cells and the blood-brain barrier and their role in Alzheimer's disease.

Alzheimer's disease (AD), which is an irreversible neurodegenerative disorder characterized by senile plaques and neurofibrillary tangles, is the most common form of dementia worldwide. However, currently, there are no satisfying curative therapies for AD. The blood-brain barrier (BBB) acts as a selective physical barrier and plays protective roles in maintaining brain homeostasis. BBB dysfunction as an upstream or downstream event promotes the onset and progression of AD. Moreover, the pathogenesis of AD caused by BBB injury hasn't been well elucidated. Glial cells, BBB compartments and neurons form a minimal functional unit called the neurovascular unit (NVU). Emerging evidence suggests that glial cells are regulators in maintaining the BBB integrity and neuronal function. Illustrating the regulatory mechanism of glial cells in the BBB assists us in drawing a glial-vascular coupling diagram of AD, which may offer new insight into the pathogenesis of AD and early intervention strategies for AD. This review aims to summarize our current knowledge of glial-BBB interactions and their pathological implications in AD and to provide new therapeutic potentials for future investigations.

Helicobacter pylori infection and risk for developing dementia: an evidence-based meta-analysis of case-control and cohort studies.

BACKGROUND: Infection with multiple pathogens may play a key role in the pathogenesis of dementia. Whether Helicobacter pylori (H. pylori) infection is associated causally with dementia is controversial. OBJECTIVE: We conduct a meta-analysis of case-control and cohort studies on the association between H. pylori infection and the risk for all-cause and Alzheimer's disease (AD) dementia. METHODS: Two independent reviewers searched the PubMed, Cochrane Library, and Embase databases with English language restrictions from the date of conception to September 18, 2020. The primary analysis was as follows: the exposure variable was H. pylori infection, and the outcome was incident all-cause and AD dementia. Pooled odds ratios (OR), relative risk (RR), and corresponding 95% confidence intervals (CI) were obtained using the fixed-or random-effect model. Forest plots were generated to summarize the results. RESULTS: Ten studies involving 96,561 participants were included in the meta-analysis: 5 case-control studies and 5 cohort studies. The overall pooled cohort studies showed a significant positive association between H. pylori infection and all-cause dementia with pooled RR of 1.36 (95% CI, 1.11-1.67). There was no association between H. pylori infection and risk for developing AD: RR of 1.33 (95% CI, 0.86-2.05) in cohort studies, and OR of 1.72 (95% CI, 0.97-3.04) in case-control studies. Significant heterogeneity was showed in each comparison group. CONCLUSION: This meta-analysis supports a positive association between H. pylori infection and the risk of all-cause dementia, but not AD dementia. Due to the interference of confounding factors, randomized controlled trials are needed to prove their causality.

Bifidobacterium lactis BB-12 Attenuates Macrophage Aging Induced by D-Galactose and Promotes M2 Macrophage Polarization.

Immunosenescence comprises a set of dynamic changes occurring in innate and adaptive immune systems, and macrophage aging plays an important role in innate and adaptive immunosenescence. However, function and polarization changes in aging macrophages have not been fully evaluated, and no effective method for delaying macrophage senescence is currently available. The results of this study reveal that D-galactose (D-gal) can promote J774A.1 macrophage senescence and induce macrophage M1 polarization differentiation. Bifidobacterium lactis BB-12 can significantly inhibit J774A.1 macrophage senescence induced by D-gal. IL-6 and IL-12 levels in the BB-12 groups remarkably decreased compared with that in the D-gal group, and the M2 marker, IL-10, and Arg-1 mRNA levels increased in the BB-12 group. BB-12 inhibited the expression of p-signal transducer and activator of transcription 1 (STAT1) and promoted p-STAT6 expression. In summary, the present study indicates that BB-12 can attenuate the J774A.1 macrophage senescence and induce M2 macrophage polarization, thereby indicating the potential of BB-12 to slow down immunosenescence and inflamm-aging.