Emerging evidence suggests that dysbiosis of the gut microbiota is associated with the pathogenesis of Parkinson's disease (PD), a prevalent neurodegenerative disorder. The microbiota-gut-brain axis plays a crucial role in the development and progression of PD, and numerous studies have demonstrated the potential therapeutic benefits of modulations in the intestinal microbiota. This review provides insights into the characterization of the gut microbiota in patients with PD and highlights associations with clinical symptoms and underlying mechanisms. The discussion underscores the increased influence of the gut microbiota in the pathogenesis of PD. While the relationship is not fully elucidated, existing research demonstrates a strong correlation between changes in the composition of gut microbiota and disease development, and further investigation is warranted to explain the specific underlying mechanisms.
Humans ; Parkinson Disease/microbiology* ; Gastrointestinal Microbiome/physiology* ; Dysbiosis/microbiology*

OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Hydrogen-rich water (HRW) shows excellent antibacterial, anti-inflammatory, antioxidant, and wound-healing properties and plays a positive role in the treatment of various diseases, such as brain injury, kidney injury, and periodontitis. Current studies found that HRW can inhibit periodontopathogenic biofilm formation, inhibit oral connective tissue and bone tissue destruction, and show anti-inflammatory and antioxidant properties in periodontitis. Additionally, HRW can alleviate periodontal tissue damage by inhibiting oxidative stress and up-regulating the expression of antioxidant enzymes, such as glutathione peroxidase and superoxide dismutase. HRW exerts anti-inflammatory effects by regulating the nuclear factor erythroid 2-related factor 2 and mitogen-activated protein kinase pathways, which are closely associated with inflammation. Additionally, HRW inhibits the expression of inflammatory cytokines, such as interleukins, inhibits the growth and proliferation of bacterial plaque biofilms, and down-regulates glycosyltransferases and glucan-binding proteins to prevent bacterial adhesion and subsequent development of periodontitis. Furthermore, HRW has a positive effect on the expression of various cell growth factors, α-smooth muscle actin, and type I collagen, which promotes wound healing. Current clinical studies have demonstrated the biological safety of HRW (to a certain extent) and reported no adverse reactions. However, most studies on HRW in oral diseases are preclinical in vivo and in vitro studies. Therefore, further clinical studies are required to validate the therapeutic significance and optimal therapeutic regimen of HRW in human periodontitis. This article aims to review the therapeutic role and the underlying mechanisms of HRW in periodontitis.

BACKGROUND:There is a central sensitization mechanism for lumbar disc herniation-specific pain sensitization,and it is unclear whether cyclic RNAs in the paraventricular nucleus brain region are involved in lumbar disc herniation-specific pain sensitization.OBJECTIVE:To investigate the mechanism by which cyclic RNA circ05188 in the paraventricular nucleus of rats with lumbar disc herniation regulates the participation of microRNAs in pain sensitization.METHODS:Fifty-two Sprague-Dawley rats were randomly divided into a sham operation group,a lumbar disc herniation group,a knockdown control group and a circ05188 knockdown group,with 13 rats in each group.Except for the sham operation group,the lumbar disc herniation model was established in the other three groups.On the 7th day after modeling,the hypothalamic paraventricular nucleus of the knockdown control group and circ05188 knockdown group were injected with siRNA-NC and siRNA-circ05188,respectively,at 1 day intervals,for a total of three injections.On the 7th day after modeling,high-throughput sequencing technology was used to detect the expression of differential circRNAs in the hypothalamic paraventricular nucleus of rats in the sham operation group and the lumbar disc herniation group,and RT-qPCR was used to detect the expression of circ05188 and miR-199a-5p in the hypothalamic paraventricular nucleus.On the 3rd,7th,14th,21st,and 28th days after modeling,we detected the mechanical and thermal mechanical paw withdrawal thresholds of the rat's hindfoot in the modeled side of rats in the sham operation group and the lumbar disc herniation group.On the 3rd day after siRNA injection,immunofluorescence staining was used to detect the expression of c-Fos in the hypothalamic paraventricular nucleus of rats in the knockdown control group and circ05188 knockdown group;RT-qPCR was used to detect the expression of circ05188 and miR-199a-5p in the hypothalamic paraventricular nucleus of rats in the knockdown control group and circ05188 knockdown group;on the 5th day after siRNA injection,mechanical and thermal mechanical paw withdrawal thresholds of the rat's hindfoot were detected in the knockdown control group and circ05188 knockdown group.Bioinformatics analysis and dual luciferase reporter elucidated the underlying molecular mechanism of circ05188 in pain sensitization after lumbar disc herniation.RESULTS AND CONCLUSION:High-throughput sequencing results showed that circRNAs were differentially expressed in the paraventricular nucleus brain region of rats with lumbar disc herniation.The expression of circ05188 was higher in the lumbar disc herniation group than in the sham operation group(P<0.05),the expression of miR-199a-5p was lower than in the sham operation group(P<0.05),and the mechanical and thermal mechanical paw withdrawal thresholds of the hindfoot were lower than those of the sham operation group at 3,7,14,and 21 days after modeling.RT-qPCR results showed that compared with the knockdown control group,the expression of c-Fos and circ05188 was lower in the circ05188 knockdown group(P<0.05),while the expression of miR-199a-5p was higher(P<0.05).The mechanical and thermal mechanical paw withdrawal thresholds of the rat's hindfoot in the circ05188 knockdown group were higher than those in the knockdown control group at 1,2,and 3 days after injection.Bioinformatics analysis and dual luciferase reporter assay results showed that miR-199a-5p had a binding site with circ05188 and circ05188/miR-199a-5p competitive endogenous RNA axis.To conclude,lumbar disc herniation induces an increase in circ05188 expression in the paraventricular nucleus of the hypothalamus,which produces central sensitization through the inhibition of miR-199a-5p and ultimately triggers neuropathic pain.

Immunotherapy has demonstrated significant efficacy in hematologic malignancies and certain solid tumors,but its efficacy for prostate cancer remains suboptimal.This is largely due to the immunosuppressive tumor microenvironment,which involves factors such as tumor heterogeneity,a paucity of infiltrating lymphocytes,and the absence of inflammatory features.Therefore,developing novel immunotherapeutic targets and combining multiple immunotherapy modalities to activate the host immune system and reverse the immunosuppressive tumor microenvironment are crucial for improving immunotherapy for prostate cancer.This review systematically summarizes the current research on prostate cancer immunotherapy,covering the challenges and advances of prostate cancer vaccines,the application of immune checkpoint inhibitors,targeted therapeutic strategies involving chimeric antigen receptor T cells,bispecific antibodies,and emerging strategies in prostate cancer immunotherapy.Furthermore,the review discusses the future directions for the development of prostate cancer immunotherapy.