Relationship between vaginal and oral microbiome in patients of human papillomavirus (HPV) infection and cervical cancer.

BACKGROUND: The aim of this study was to assess the microbial variations and biomarkers in the vaginal and oral environments of patients with human papillomavirus (HPV) and cervical cancer (CC) and to develop novel prediction models. MATERIALS AND METHODS: This study included 164 samples collected from both the vaginal tract and oral subgingival plaque of 82 women. The participants were divided into four distinct groups based on their vaginal and oral samples: the control group (Z/KZ, n = 22), abortion group (AB/KAB, n = 17), HPV-infected group (HP/KHP, n = 21), and cervical cancer group (CC/KCC, n = 22). Microbiota analysis was conducted using full-length 16S rDNA gene sequencing with the PacBio platform. RESULTS: The vaginal bacterial community in the Z and AB groups exhibited a relatively simple structure predominantly dominated by Lactobacillus. However, CC group shows high abundances of anaerobic bacteria and alpha diversity. Biomarkers such as Bacteroides, Mycoplasma, Bacillus, Dialister, Porphyromonas, Anaerococcus, and Prevotella were identified as indicators of CC. Correlations were established between elevated blood C-reactive protein (CRP) levels and local/systemic inflammation, pregnancy, childbirth, and abortion, which contribute to unevenness in the vaginal microenvironment. The altered microbial diversity in the CC group was confirmed by amino acid metabolism. Oral microbial diversity exhibited an inverse pattern to that of the vaginal microbiome, indicating a unique relationship. The microbial diversity of the KCC group was significantly lower than that of the KZ group, indicating a link between oral health and cancer development. Several microbes, including Fusobacterium, Campylobacter, Capnocytophaga, Veillonella, Streptococcus, Lachnoanaerobaculum, Propionibacterium, Prevotella, Lactobacillus, and Neisseria, were identified as CC biomarkers. Moreover, periodontal pathogens were associated with blood CRP levels and oral hygiene conditions. Elevated oral microbial amino acid metabolism in the CC group was closely linked to the presence of pathogens. Positive correlations indicated a synergistic relationship between vaginal and oral bacteria. CONCLUSION: HPV infection and CC impact both the vaginal and oral microenvironments, affecting systemic metabolism and the synergy between bacteria. This suggests that the use of oral flora markers is a potential screening tool for the diagnosis of CC.

Progress of medicinal plants and their active metabolites in ischemia-reperfusion injury of stroke: a novel therapeutic strategy based on regulation of crosstalk between mitophagy and ferroptosis.

The death of cells can occur through various pathways, including apoptosis, necroptosis, mitophagy, pyroptosis, endoplasmic reticulum stress, oxidative stress, ferroptosis, cuproptosis, and disulfide-driven necrosis. Increasing evidence suggests that mitophagy and ferroptosis play crucial regulatory roles in the development of stroke. In recent years, the incidence of stroke has been gradually increasing, posing a significant threat to human health. Hemorrhagic stroke accounts for only 15% of all strokes, while ischemic stroke is the predominant type, representing 85% of all stroke cases. Ischemic stroke refers to a clinical syndrome characterized by local ischemic-hypoxic necrosis of brain tissue due to various cerebrovascular disorders, leading to rapid onset of corresponding neurological deficits. Currently, specific therapeutic approaches targeting the pathophysiological mechanisms of ischemic brain tissue injury mainly include intravenous thrombolysis and endovascular intervention. Despite some clinical efficacy, these approaches inevitably lead to ischemia-reperfusion injury. Therefore, exploration of treatment options for ischemic stroke remains a challenging task. In light of this background, advancements in targeted therapy for cerebrovascular diseases through mitophagy and ferroptosis offer a new direction for the treatment of such diseases. In this review, we summarize the progress of mitophagy and ferroptosis in regulating ischemia-reperfusion injury in stroke and emphasize their potential molecular mechanisms in the pathogenesis. Importantly, we systematically elucidate the role of medicinal plants and their active metabolites in targeting mitophagy and ferroptosis in ischemia-reperfusion injury in stroke, providing new insights and perspectives for the clinical development of therapeutic drugs for these diseases.

Posterior Circulation Mechanical Thrombectomy through Primitive Trigeminal Artery: A Case Report.

Introduction: Primitive trigeminal artery (PTA) is a rare intracranial vascular malformation, and mechanical thrombectomy and revascularization via PTA are rarely reported. Case Presentation: We reported a case of mechanical thrombectomy through PTA in a patient who presented with sudden slurred speech and had a National Institutes of Health Stroke Scale score of 12. Digital subtraction angiography of the cerebral vasculature showed PTA formation in the right internal carotid artery cavernous segment, with acute occlusion of the distal basilar artery at the PTA junction, and bilateral vertebral arteries and proximal basilar artery were underdeveloped. Therefore, we chose mechanical thrombectomy via PTA, but unfortunately, the vessel failed to recanalize. Follow-up at 1-month post-procedure indicated that the patient had passed away. We present the endovascular process and analyze and summarize the reasons for the failure to provide a reference for subsequent mechanical thrombectomy via PTA. Conclusions: PTA increases the risk of ischemic stroke and adds to the complexity of mechanical thrombectomy post-stroke. However, in certain situations, PTA can be used as a thrombectomy channel to increase the first-line possibility of timely endovascular treatment to save ischemic brain tissue.

Microbiome signatures in ischemic stroke: A systematic review.

Microbial structural changes and dysfunction play an important role in the development of cerebral ischemia. We searched PubMed, Embase, Web of Science, and Cochrane Library and conducted a systematic review to assess the relationship between the human microbiome and ischemic stroke. A total of 24 studies were included, and the intestinal bacterial communities detected in both stroke and healthy people were dominated by 4 main phyla, including Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Significant diversity (alpha and beta) in patients with ischemic versus nonischemic stroke was observed in nine out of 18 studies, and 3 studies showed that the severity of ischemic stroke affected microbial diversity. The imbalance of bacteria that produce short-chain fatty acids (SCFAs) changes the bacterial metabolic pathway, and disorders in the level of bacterial metabolites (trimethylamine N-oxide TMAO) lead to significant changes in intestinal flora function, which may aggravate the severity of stroke and affect its prognosis. Further studies are needed to explore the relationship between the microbiome and ischemic stroke.

Influence of Environmental Factors on Salivary Microbiota and Their Metabolic Pathway: Next-Generation Sequencing Approach.

The current study aimed to investigate the effect of periodontitis and long-term heavy metal (HM) exposure on the salivary microbiome. The patients were divided into four groups as Wu Wei control (WWC) group involved healthy individuals, Wu Wei periodontitis (WWP) patients having periodontitis, Jing Chang with metal pollution periodontally healthy individuals (JCP), and Kuang periodontitis (KP). The most abundant bacteria identified at the phylum level in the WWC group were Bacteroides, Firmicutes, and Fusobacteria. Firmicutes were observed in a significantly higher proportion in the KP group than in the WWC, WWP, and JCP. At the genus level, the WWC has major dominating bacterial genera (such as Leptotrichia, Neisseria, and Fusobacterium) which were similar to WWP and KP group. The significant difference (p < 0.05) was found in alpha diversity while in beta diversity, the significant (p = 0.005) results were found among the four groups. The correlation of oral microbiota revealed that HMs present in the soil (Cr, Ni, and Cu) are associated with the growth of Capnocytophaga, Selenomonas, Aggregatibacter, and Campylobacter. The bacterial functions in the KP group were higher in translation and nucleotide metabolism than in the WWP group. This demonstrated that long-term exposure to HMs can influence the salivary microbiota which can alter the functioning, and diversity of bacteria.

Protective Effect of Hydroxysafflor Yellow A against Chronic Mild Stress-induced Memory Impairments by Suppressing Tau Phosphorylation in Mice.

Chronic stress plays a critical role in the etiology of sporadic Alzheimer's disease (AD). However, there are currently no effective drugs that can target chronic stress to prevent AD. In this study, we explored the neuroprotective effect of hydroxysafflor yellow A (HSYA) against chronic mild stress (CMS)-induced memory impairments in mice and the underlying mechanism. The Morris water maze test showed that HSYA significantly reduced CMS-induced learning and memory impairments in mice. HSYA increased the expression of brain-derived neurotrophic factor (BDNF) and activated downstream tropomyosin-related kinase B (TrkB) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B(Akt)/mammalian target of rapamycin (mTOR) signaling. HSYA decreased the expression of regulator of calcineurin 1-1L (RCAN1-1L) that could promote the activity of glycogen synthase kinase-3ß (GSK-3ß). HSYA also attenuated tau phosphorylation by inhibiting the activity of GSK-3ß and cyclin-dependent kinase-5 (Cdk5). Our data indicated that HSYA has protective effects against CMS-induced BDNF downregulation, tau phosphorylation and memory impairments. HSYA may be a promising therapeutic candidate for AD by targeting chronic stress.

Effect of alcohol intake on the development of mild cognitive impairment into dementia: A protocol for systematic review and dose-response meta-analysis.

OBJECTIVE: To assess the dose-response relationship between alcohol consumption and the progression of MCI to dementia. METHOD: This study adheres to the Preferred Reporting Items for Systematic Reviews and Meta analysis for Protocols. Chinese Biomedical Literature Database (CBM), PubMed, Cochrane Library, EMBASE will be searched for all relevant published articles, with no restrictions on the year of publication or language. Case-control and cohort studies explored the relationship between alcohol exposure and the incidence of dementia in patients with MCI will be included. Study selection, data collection and assessment of study bias will be conducted independently at each level by a pair of independent reviewers. The Newcastle-Ottawa Scale (NOS) tool will be used for the risk of bias assessment. The methodological quality of systematic review will be based on A measurement Tool to Assess Systematic Review (AMSTAR 2). The Grading of Recommendations Assessment Development and Evaluation (GRADE) system will be used to assess the quality of evidence. Stata 15.0 will be used for general meta-analysis and exploring the dose-response relationship. Piecewise linear regression model and the restricted cubic spline model will be used for nonlinear trend estimation, and the generalized least-square method will be used to estimate the parameters. DISCUSSION: This dose-response meta-analysis is the first to investigate the dose-effect relationship between alcohol exposure and the incidence of dementia in patients with MCI, providing a comprehensive understanding of the prevention of alcohol-related cognitive impairment. REGISTRATION: The dose-response meta-analysis is registered in the PROSPERO (CRD42019127226) international prospective register of systematic review.