Associations between the oxidative balance score and constipation: a cross-sectional study of the NHANES, 2005-2010.

OBJECTIVE: The oxidative balance score (OBS) reflects the overall burden of oxidative stress in an individual, with a higher OBS indicating greater antioxidant exposure. This study aimed to explore the association between constipation and OBS. METHODS: Variables were extracted from participants who completed a constipation questionnaire as part of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. The OBS was developed based on dietary and lifestyle factors, encompassing 16 nutrients and 4 lifestyle variables. Weighted logistic regression and restricted cubic spline (RCS) analyses were employed to evaluate the association between OBS and constipation. RESULTS: After adjusting for all covariates, weighted multivariate logistic regression analysis revealed a 4% reduction in the incidence of constipation for each additional unit of OBS (OR: 0.96, 95% CI: 0.95-0.97, p < 0.001). In the OBS subgroup, the risk of constipation significantly decreased compared to that in the lowest quartile (Q2: 0.72, P = 0.024; Q3: 0.59, P < 0.001; Q4: 0.54, P < 0.001). CONCLUSIONS: The present study demonstrated a significant association between constipation and the oxidative balance score (OBS), particularly dietary OBS, and that an increase in OBS may reduce the risk of developing constipation, in which oxidative stress may play an important role. This finding suggested that dietary modification could be an important approach for preventing constipation.

Red cell distribution width, anemia, and lower-extremity physical function among rural-dwelling older adults.

BACKGROUND: Elevated red cell distribution width (RDW) has been associated with degenerative conditions in aging. AIMS: We aimed to evaluate the associations of RDW and anemia with lower-extremity physical function among rural-dwelling older adults. METHODS: This population-based cross-sectional study included 5093 rural residents (age ≥ 60 years, 57.3% women) who participated in the MIND-China Study in Shandong. Data were collected via face-to-face interviews, clinical examinations, and laboratory tests. RDW was categorized according to quartiles and the lower-extremity physical function was assessed using the Short Physical Performance Battery (SPPB), RESULTS: Multiple linear regression analyses suggested that the fourth quartile of RDW (vs. first quartile) was associated with lower SPPB summary score (ß-coefficient - 0.38; 95% CI - 0.58 to - 0.18) and lower scores in balance test (- 0.09; - 0.17 to - 0.01), chair stand test (- 0.17; - 0.27 to - 0.07), and walking speed test (- 0.12; - 0.19 to - 0.05). Anemia was associated with a multiple-adjusted ß-coefficient of - 0.34 (- 0.52 to - 0.16) for SPPB summary score. Stratified analysis by anemia showed that there was a linear association between RDW and SPPB in individuals without anemia but a J-shaped association in individuals with anemia. DISCUSSION: This large-scale population-based study revealed the associations of high RDW and anemia with poor lower-extremity physical function among rural-dwelling Chinese older adults. These findings suggest that an elevated RDW might be a biochemical marker for poor lower-extremity physical function among older adults. CONCLUSIONS: Anemia and an elevated RDW are associated with poor performance in lower-extremity physical function among rural-dwelling Chinese older adults.

Accelerometer-assessed sedentary behaviour among Chinese rural older adults: Patterns and associations with physical function.

Sedentary behaviour is associated with a range of adverse health conditions. Population-based studies have rarely examined the distribution and associated factors of accelerometer-measured sedentary behaviour patterns in rural-dwelling older adults. This population-based study included 2096 rural-dwelling older adults (age ≥60 years; 59.0% women) derived from baseline participants of the MIND-China Study. Total sedentary time and patterns (e.g., uninterrupted bouts and breaks) were derived from the hip-worn accelerometers for 7 days. Physical function was assessed using the Short Physical Performance Battery test. Data were analysed using general linear models. Overall, participants spent 58.8% of daily waking time in sedentary behaviour, with nearly half of sedentary time being accumulated through sedentary bouts of 30+ minutes. Men spent more total and accumulated sedentary time than women in each sedentary bout duration, while women had more daily 1+ minute sedentary bouts than men (all P < 0.001). Controlling for moderate-to-vigorous physical activity and other confounders, more prolonged sedentary time and fewer breaks were significantly associated with poor physical function, balance, lower limb strength, and walking speed (all P < 0.001). In older adults living in rural communities, prolonged sedentary behaviour and less frequent breaks are associated with poor physical function.

Dyskinesia-hyperpyrexia syndrome in Parkinson's disease: a systematic review.

PURPOSE: Dyskinesia-hyperpyrexia syndrome (DHS) is a rare but life-threatening disease. The clinical manifestations of this syndrome overlap substantially with Parkinson hyperpyrexia syndrome and serotonin syndrome and are often confused by clinicians. The purpose of this review was to enable clinicians to recognize this syndrome and thereby reach a correct diagnosis and provide optimal treatments to improve prognosis in clinical practice. METHODS: Using the methodology described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we conducted a literature search of the PubMed, Embase, and MEDLINE databases using keywords in titles and abstracts of published literature. Quality assessment was performed using the modified Newcastle-Ottawa scale. RESULTS: A total of 11 patients obtained from nine publications were included in this systematic review. All of the cases occurred in patients with advanced Parkinson's disease (PD) of long disease duration. High ambient temperature was the most common trigger of this syndrome. Hyperpyrexia and dyskinesias were present in all cases. The consciousness disturbances of this syndrome included confusion, hallucination, and lethargy or stupor. Autonomic dysfunction (except for hyperpyrexia) is uncommon in DHS, and only two patients presented with tachycardia. The treatment of this syndrome included supportive interventions (including rehydration, anti-pyretic and anti-infection treatments, and maintaining electrolyte balance), dopaminergic drug reduction and sedation. Two patients died due to DHS. CONCLUSIONS: We summarized the triggers, clinical features, and treatments of all reported dyskinesia-hyperpyrexia syndrome cases, proposed guiding diagnostic criteria, and established a flow chart to guide diagnoses to quickly identify these three syndromes in clinical practice.

Sex disparities in cardiovascular health metrics among rural-dwelling older adults in China: a population-based study.

BACKGROUND: Cardiovascular health (CVH) metrics among Chinese older adults are poorly understood. We investigated sex disparities in CVH metrics and their management among rural-dwelling older adults in China. METHODS: This community-based study included 5026 participants (age ≥ 65 years; 57.2% women) in the baseline survey of a multimodal intervention study in rural China. In March-September 2018, data were collected through face-to-face interviews, clinical examinations, and laboratory tests. We defined six CVH metrics (three behavioral factors-smoking, body mass index, and physical activity; three biological factors-blood pressure, total cholesterol, and blood glucose) following the modified American Heart Association's recommendations. We performed descriptive analysis separately for men and women. RESULTS: Of all participants, only 0.8% achieved ideal levels in all six CVH metrics. Men were more likely than women to have ideal levels in all CVH metrics but smoking. Women had higher prevalence of ideal global (9.7% vs. 7.8%) and behavioral (18.3% vs. 9.5%) CVH metrics (p < 0.001), whereas men had higher prevalence of ideal biological CVH metrics (5.4% vs. 3.5%, p < 0.001). The prevalence of ideal global and behavioral CVH metrics increased with age in both women and men (p for trend< 0.001). Women were more likely to be aware of their hypertension and diabetes, and to receive antihypertensive treatment, while men were more likely to achieve the goal of high cholesterol treatment (p < 0.05). CONCLUSIONS: The CVH metrics among older adults living in the rural communities in China are characterized by an extremely low proportion of optimal global CVH metrics and distinct sex differences, alongside poor management of major biological risk factors. TRIAL REGISTRATION: ChiCTR1800017758 (Aug 13, 2018).

The power of the Functional Activities Questionnaire for screening dementia in rural-dwelling older adults at high-risk of cognitive impairment.

AIM: A simple approach to detecting dementia in its early stages may help improve patient care. We therefore aimed to assess the power of the Functional Activities Questionnaire (FAQ) for screening dementia among rural-dwelling older adults who are at high-risk for cognitive impairment. METHODS: This study included 961 participants at a high-risk for dementia who had been identified from a population-based survey of Chinese rural residents. All participants were aged 65 years and older and positive for cognitive impairment according to the Mini-Mental State Examination or the Ascertain Dementia 8-item Informant Questionnaire screening tests. The FAQ scale was used to evaluate daily activities. Dementia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria. Receiver operating characteristic curve analyses were used to determine the FAQ's optimal cut-offs for dementia. The power (or accuracy) of the FAQ for screening dementia was analyzed in the total sample and in subgroups categorized by age, gender, and educational level. RESULTS: Of the 961 participants, 84 (8.7%) were clinically diagnosed with dementia. Among individuals who were positive for cognitive impairment on the Mini-Mental State Examination or the Ascertain Dementia 8-item Informant Questionnaire, the parameters for an FAQ cut-off score ≥6 as a means of discriminating those with dementia from those without dementia were area under curve = 0.899, sensitivity = 94.1%, specificity = 75.1%, positive likelihood ratio = 3.78, and accuracy = 0.768. The discriminant abilities of the FAQ scale varied with age, gender, and educational level. The discriminant parameters of the FAQ scale were similar overall among individuals who were positive on either the Mini-Mental State Examination or the Ascertain Dementia 8-item Informant Questionnaire test alone. CONCLUSION: The FAQ scale has high discriminative power to screen for dementia among rural older residents with suspected cognitive impairment.

Association between different composite dietary antioxidant indexes and constipation in American male adults: a cross-sectional study.

Background: Oxidative stress is acknowledged as a pivotal factor in the intricate pathophysiological processes and pathogenesis of constipation. Modifying dietary patterns can elevate in vivo antioxidant biomarker levels, consequently mitigating oxidative stress. The Composite Dietary Antioxidant Index (CDAI) provides a dependable scoring mechanism for quantifying the potential antioxidant capacity of diets. The association between CDAI levels and the risk of constipation remains uncertain. Purpose: To investigate the potential correlation between CDAI and constipation, aiming to improve constipation management through dietary guidance. Methods: A total of 11,165 adults aged ≥20 years, drawn from the 2005-2010 National Health and Nutrition Examination Survey, were enrolled in this cross-sectional study. We evaluated the correlation between CDAI levels and the risk of constipation through three weighted logistic regression models. Restricted cubic spline (RCS) analysis was employed to assess nonlinear trends, and stratified analyses were conducted. Results: After adjusting for all confounding variables, the findings revealed an association between CDAI and constipation [OR = 0.937; 95% CI (0.892, 0.984), p = 0.012]. Moreover, individuals in the highest quartile of CDAI demonstrated a 40.1% lower likelihood of experiencing constipation compared to those in the lowest quartile [OR = 0.599; 95% CI (0.382, 0.939), p = 0.027]. The RCS analysis indicated a linear relationship between CDAI and constipation (P-non-linear =0.1016). Subgroup analysis by gender revealed a negative correlation in the male population [OR = 0.871; 95% CI (0.801, 0.947), p = 0.002], with men in the highest CDAI quartile exhibiting a 59.8% lower likelihood of experiencing constipation compared to those in the lowest quartile [OR = 0.402; 95% CI (0.206, 0.787), p = 0.010]. Furthermore, alterations in selenium [OR = 0.997; 95% CI (0.995, 1.000), p = 0.039] per milligram were independently linked to constipation. In a gender subgroup analysis of a single antioxidant, changes per milligram of vitamin E [OR = 0.904; 95% CI (0.838 to 0.975), p = 0.011] among males were independently associated with constipation. Conclusion: The fully adjusted model showed a correlation between CDAI and constipation and a significant correlation in quartiles. Meanwhile, subgroup analysis by gender showed that CDAI was negatively associated with constipation in the male population. Moreover, the findings of this study imply that investigations into antioxidant diets should be contextualized within dietary patterns.

5-HT7R enhances neuroimmune resilience and alleviates meningitis by promoting CCR5 ubiquitination.

INTRODUCTION: Excessive immune activation induces tissue damage during infection. Compared to external strategies to reconstruct immune homeostasis, host balancing ways remain largely unclear. OBJECTIVES: Here we found a neuroimmune way that prevents infection-induced tissue damage. METHODS: By FACS and histopathology analysis of brain Streptococcus pneumonia meningitis infection model and behavioral testing. Western blot, co-immunoprecipitation, and ubiquitination analyze the Fluoxetine initiate 5-HT7R-STUB1-CCR5 K48-linked ubiquitination degradation. RESULTS: Fluoxetine, a selective serotonin reuptake inhibitor, or the agonist of serotonin receptor 5-HT7R, protects mice from meningitis by inhibiting CCR5-mediated excessive immune response and tissue damage. Mechanistically, the Fluoxetine-5-HT7R axis induces proteasome-dependent degradation of CCR5 via mTOR signaling, and then recruits STUB1, an E3 ubiquitin ligase, to initiate K48-linked polyubiquitination of CCR5 at K138 and K322, promotes its proteasomal degradation. STUB1 deficiency blocks 5-HT7R-mediated CCR5 degradation. CONCLUSION: Our results reveal a neuroimmune pathway that balances anti-infection immunity via happiness neurotransmitter receptor and suggest the 5-HT7R-CCR5 axis as a potential target to promote neuroimmune resilience.

Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively.

Leukotrienes generated by 5-lipoxygenase (5-LOX)-catalyzed reaction are key regulators of inflammation. In ionophore-stimulated (A23187; 1-2.5 µM) human blood neutrophils or differentiated HL-60 cells, vitamin E forms differentially inhibited leukotriene B(4) (LTB(4)) with an IC(50) of 5-20 µM for γ-tocopherol, δ-tocopherol (δT), and γ-tocotrienol, but a much higher IC(50) for α-tocopherol. 13'-Carboxychromanol, a long-chain metabolite of δT, suppressed neutrophil- and HL-60 cell-generated LTB(4) with an IC(50) of 4-7 µM and potently inhibited human recombinant 5-LOX activity with an IC(50) of 0.5-1 µM. In contrast, vitamin E forms had no effect on human 5-LOX activity but impaired ionophore-induced intracellular calcium increase and calcium influx as well as the subsequent signaling including ERK1/2 phosphorylation and 5-LOX translocation from cytosol to the nucleus, a key event for 5-LOX activation. Further investigation showed that δT suppressed cytosolic Ca(2+) increase and/or LTB(4) formation triggered by ionophores, sphingosine 1-phosphate, and lysophosphatidic acid but not by fMLP or thapsigargin, whereas 13'-carboxychromanol decreased cellular production of LTB(4) regardless of different stimuli, consistent with its strong inhibition of the 5-LOX activity. These observations suggest that δT does not likely affect fMLP receptor-mediated signaling or store depletion-induced calcium entry. Instead, we found that δT prevented ionophore-caused cytoplasmic membrane disruption, which may account for its blocking of calcium influx. These activities by vitamin E forms and long-chain carboxychromanol provide potential molecular bases for the differential anti-inflammatory effects of vitamin E forms in vivo.

Single-Cell RNA sequencing highlights the regulatory role of T cell marker genes Ctla4, Ccl5 and Tcf7 in corneal allograft rejection of mouse model.

BACKGROUND: A mouse corneal allograft model was induced and single-cell RNA sequencing (scRNA-seq) data of corneal tissues and T cells were analyzed to reveal a T cell-mediated mechanism for corneal allograft rejection in mice. METHODS: Corneal tissue samples from a mouse model of corneal allograft were collected for scRNA-seq analysis, followed by quality control, dimensionality reduction, cluster analysis and enrichment analysis. A large number of highly variable genes were identified in mice with corneal allograft. Significant difference existed in immune T cells, especially in CD4 + T cells. RESULTS: It was found that T cell marker genes Ctla4, Ccl5, Tcf7, Lgals1, and Itgb1 may play key roles in the corneal allograft rejection. Mice with allograft rejection showed a significant increase in the proportion of CD4 + T cells in the corneal tissues. Besides, Ccl5 and Tcf7 expression was increased in mice with allograft rejection and positively linked to the proportion of CD4 + T cells. Whereas, Ctla4 expression was downregulated and negatively associated with the proportion of CD4 + T cells. CONCLUSION: Collectively, Ctla4, Ccl5 and Tcf7 may participate in the rejection of corneal allograft in mice by affecting CD4 + T cell activation.

Ketogenic diet protects MPTP-induced mouse model of Parkinson's disease via altering gut microbiota and metabolites.

The ketogenic diet (KD) is a low-carbohydrate, high-fat regime that is protective against neurodegenerative diseases. However, the impact of KD on Parkinson's disease (PD) and its mechanisms remains unclear. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD was fed with KD for 8 weeks. Motor function and dopaminergic neurons were evaluated. Inflammation in the brain, plasma, and colon tissue were also measured. Fecal samples were assessed by 16S rDNA gene sequencing and untargeted metabolomics. We found that KD protected motor dysfunction, dopaminergic neuron loss, and inflammation in an MPTP mouse model of PD. 16S rDNA sequencing revealed that MPTP administration significantly increased Citrobacter, Desulfovibrio, and Ruminococcus, and decreased Dubosiella, whereas KD treatment reversed the dysbiosis. Meanwhile, KD regulated the MPTP-induced histamine, N-acetylputrescine, d-aspartic acid, and other metabolites. Fecal microbiota transplantation using feces from the KD-treated mice attenuated the motor function impairment and dopaminergic neuron loss in antibiotic-pretreated PD mice. Our current study demonstrates that KD played a neuroprotective role in the MPTP mouse model of PD through the diet-gut microbiota-brain axis, which may involve inflammation in the brain and colon. However, future research is warranted to explore the explicit anti-inflammatory mechanisms of the gut-brain axis in PD models fed with KD.

Metabolic Activation of Pesticide Isoprocarb Mediated by CYP3A4 and the Possible Correlation with Its Cytotoxicity.

Isoprocarb (IPC), one of the most important carbamate pesticides, is used to control pests, such as rice planthoppers in crops. Studies have found that IPC induced hepatotoxicity in poultry chicken. However, the mechanisms of IPC-induced hepatotoxicity are unclear. The objectives of this study were to characterize reactive metabolites of IPC in vitro and in vivo, to identify cytochrome P450 enzymes for metabolic activation, and to define a possible correlation between the metabolic activation and cytotoxicity of IPC. In GSH- or NAC-supplemented microsomal incubations, one GSH conjugate (M6) and two NAC conjugates (M7 and M8) were detected after exposure to IPC. The corresponding GSH conjugate and NAC conjugates were found in the liver homogenates and urine of mice after IPC administration. IPC was found to be metabolized to a quinone intermediate reactive to GSH in vitro and in vivo. IPC was found to induce marked cytotoxicity in cultured mouse primary hepatocytes. Ketoconazole, a selective CYP3A4/5 enzyme inhibitor, attenuated the susceptibility of hepatocytes to IPC cytotoxicity.

Gamma-tocotrienol induces apoptosis and autophagy in prostate cancer cells by increasing intracellular dihydrosphingosine and dihydroceramide.

Although cell-based studies have shown that γ-tocotrienol (γTE) exhibits stronger anticancer activities than other forms of vitamin E including γ-tocopherol (γT), the molecular bases underlying γTE-exerted effects remains to be elucidated. Here we showed that γTE treatment promoted apoptosis, necrosis and autophagy in human prostate PC-3 and LNCaP cancer cells. In search of potential mechanisms of γTE-provoked effects, we found that γTE treatment led to marked increase of intracellular dihydroceramide and dihydrosphingosine, the sphingolipid intermediates in de novo sphingolipid synthesis pathway but had no effects on ceramide or sphingosine. The elevation of these sphingolipids by γTE preceded or coincided with biochemical and morphological signs of cell death and was much more pronounced than that induced by γT, which accompanied with much higher cellular uptake of γTE than γT. The importance of sphingolipid accumulation in γTE-caused fatality was underscored by the observation that dihydrosphingosine and dihydroceramide potently reduced the viability of both prostate cell lines and LNCaP cells, respectively. In addition, myriosin, a specific inhibitor of de novo sphingolipid synthesis, counteracted γTE-induced cell death. In agreement with these cell-based studies, γTE inhibited LNCaP xenograft growth by 53% (p < 0.05), compared to 33% (p = 0.07) by γT, in nude mice. These findings provide a molecular basis of γTE-stimulated cancer cell death and support the notion that elevation of intracellular dihydroceramide and dihydrosphingosine is likely a novel anticancer mechanism.

Serum 25(OH)D Levels Modify the Association between Triglyceride and IR: A Cross-Sectional Study.

Background: Triglycerides and 25(OH)D had been reported as correlates of IR, but the results suggest substantial heterogeneity across races. In addition, little research reported on whether different 25(OH)D levels affect triglycerides and IR. Therefore, a similar study on the US population would be a great addition to the current one. This study investigated the association between triglycerides and IR at different 25(OH)D levels. Methods: A total of 19,926 participants were included, each containing specific indicators for the study project. IR was estimated as a HOMA-IR index ≥2.73. Four multivariate logistic regression models were developed to analyze the association between TG and IR and whether different 25(OH)D levels influenced this association. Smoothed fitting curves were plotted. Results: Triglyceride was significantly associated with IR (OR: 1.3, 95 CI %), while this association received different 25(OH)D levels (P for interaction <0.001). The effect value OR was 1.33 with the high levels, and its effect value OR was 1.28 with the low levels. Conclusion: This study demonstrates that triglyceride levels are significantly associated with insulin in the US adult population and can be used as a predictor of IR. This correlation was compromised at different 25 (OH)D levels, so future studies need to be explored in more ethnically diverse contexts.

Effects of Ketogenic Diet on Neuroinflammation in Neurodegenerative Diseases.

The ketogenic diet (KD) is a low-carbohydrate, high-fat and adequate-protein diet. As a diet mimicking fasting, it triggers the production of ketone bodies (KBs) and brings the body into a state of ketosis. Recent and accumulating studies on humans and animal models have shown that KD is beneficial to neurodegenerative diseases through modulating central and peripheral metabolism, mitochondrial function, inflammation, oxidative stress, autophagy, and the gut microbiome. Complicated interplay of metabolism, gut microbiome, and other mechanisms can regulate neuroinflammation in neurodegenerative diseases by activating multiple molecular and cellular pathways. In this review, we detail the physiological basis of the KD, its functions in regulating neuroinflammation, and its protective role in normal brain aging and neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). We aimed to elucidate the underlying neuroinflammatory mechanisms of KD therapies in neurodegenerative diseases and provide novel insights into their application for neurodegenerative disease prevention and treatment.

Identification of Potential miRNA-mRNA Regulatory Network Contributing to Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disease, and the mechanism underlying PD pathogenesis is not completely understood. Increasing evidence indicates that microRNAs (miRNAs) play a critical regulatory role in the pathogenesis of PD. This study aimed to explore the miRNA-mRNA regulatory network for PD. The differentially expressed miRNAs (DEmis) and genes (DEGs) between PD patients and healthy donors were screened from the miRNA dataset GSE16658 and mRNA dataset GSE100054 downloaded from the Gene Expression Omnibus (GEO) database. Target genes of the DEmis were selected when they were predicted by three or four online databases and overlapped with DEGs from GSE100054. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were then conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID) and Metascape analytic tools. The correlation between the screened genes and PD was evaluated with the online tool Comparative Toxicogenomics Database (CTD), and protein-protein interaction (PPI) networks were built by the STRING platform. We further investigated the expression of genes in the miRNA-mRNA regulatory network in blood samples collected from PD patients and healthy donors via qRT-PCR. We identified 1505 upregulated and 1302 downregulated DEGs, and 77 upregulated and 112 downregulated DEmis were preliminarily screened from the GEO database. Further functional enrichment analysis identified 10 PD-related hub genes, including RAC1, IRS2, LEPR, PPARGC1A, CAMKK2, RAB10, RAB13, RAB27B, RAB11A, and JAK2, which were mainly involved in Rab protein signaling transduction, AMPK signaling pathway, and signaling by Leptin. A miRNA-mRNA regulatory network was then constructed with 10 hub genes, and their interacting miRNAs overlapped with DEmis, including miR-30e-5p, miR-142-3p, miR-101-3p, miR-32-3p, miR-508-5p, miR-642a-5p, miR-19a-3p, and miR-21-5p. Analysis of clinical samples verified significant upregulation of LEPR and downregulation of miR-101-3p and miR-30e-5p in PD patients as compared with healthy donors. Thus, the miRNA-mRNA regulatory network was initially constructed and has the potential to provide novel insights into the pathogenesis and treatment of PD.

ß-Hydroxybutyrate alleviates pyroptosis in MPP+/MPTP-induced Parkinson's disease models via inhibiting STAT3/NLRP3/GSDMD pathway.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor symptoms and non-motor symptoms, and affects millions of people worldwide. Growing evidence implies ß-Hydroxybutyrate (BHB), one of the ketone bodies generated by ketogenesis, plays a neuroprotective role in neurodegenerative diseases. We aimed to verify the anti-inflammatory effect of BHB on PD and further explore potential molecular mechanisms. METHODS: We performed the experiments on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model in vivo and 1-methyl-4-phenylpyridinium (MPP+)-simulated BV2 cell model in vitro, with or without BHB pretreatment. Motor function was assessed by pole test, forced swimming test, traction test and open field test. Immunofluorescence was used to evaluate the loss of dopaminergic neurons and glial cell activation in MPTP-induced PD model mice. The expression of the STAT3/NLRP3/GSDMD signal pathway was measured by western blots. Proinflammatory cytokines was assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: BHB treatment reversed motor deficits, loss of dopaminergic neurons and glial cell activation in PD mice induced by MPTP. Moreover, BHB inhibited microglia pyroptosis by negatively regulating STAT3/NLRP3/GSDMD signal pathway, resulting in downregulation of proinflammatory cytokines (IL-1ß and IL-18) in vivo and vitro. CONCLUSION: These data suggested BHB supplement inhibited pyroptosis by down-regulating STAT3-mediated NLRP3 inflammasome activation for PD models in vivo and in vitro. Our findings provided novel insights and available interventions for the prevention and treatment of PD, and highlighted pyroptosis as a potential therapeutic target for PD.

Association of Cardiovascular Health Metrics with Dementia in Rural Chinese Older Adults: A Population-Based Study.

Purpose: We explore the associations of individual and composite cardiovascular health metrics with all-cause dementia, Alzheimer's disease, and vascular dementia among rural-dwelling older adults and the potential age variations in their associations. Patients and Methods: This community-based cross-sectional study included 4980 older adults (age ≥65 years; 57.23% women) from the baseline examination of MIND-China. In March-September 2018, data were collected via face-to-face interviews, clinical examinations, and laboratory test. We defined six cardiovascular health metrics according to the modified American Heart Association's recommendations. We diagnosed dementia and its subtypes following the international criteria. Data were analyzed using logistic regression models. Results: Of all the participants, 250 were diagnosed with dementia, including 165 with Alzheimer's disease and 75 with vascular dementia. Ideal composite global cardiovascular health metrics (vs poor composite metrics) were associated with a multi-adjusted odds ratio (95% confidence interval) of 0.62 (0.42-0.93) for dementia, 0.88 (0.52-1.48) for Alzheimer's disease, and 0.31 (0.16-0.60) for vascular dementia. Moreover, ideal biological cardiovascular health metrics were associated with multi-adjusted odds ratio of 0.52 (0.28-0.95) for dementia and 0.21 (0.06-0.77) for vascular dementia in young-old adults (65-74 years), whereas ideal behavioral cardiovascular health metrics were associated with multi-adjusted odds ratio of 0.48 (0.26-0.89) for dementia and 0.16 (0.06-0.43) for vascular dementia in old-old adults (≥75 years). Conclusion: Our results suggest that ideal cardiovascular health metrics are cross-sectionally associated with a low likelihood of dementia and vascular dementia among rural-dwelling older Chinese adults. The associations vary with age, components of cardiovascular health metrics, and dementia subtypes.

Red Cell Distribution Width and Dementia Among Rural-Dwelling Older Adults: The MIND-China Study.

BACKGROUND: Evidence has emerged that anemia is associated with dementia, but data on the relationships of red blood cell distribution width (RDW) with dementia and cognitive function in older adults are sparse. OBJECTIVE: We sought to investigate the associations of RDW with dementia and global cognitive performance among rural-dwelling Chinese older adults and further to examine their associations by anemia status. METHODS: This population-based cross-sectional study included 5,115 participants (age≥65 years, 57.0%women) in the baseline examination (March-September 2018) of the Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-CHINA). We collected data through face-to-face interviews, clinical examinations, and laboratory tests. Global cognitive function was evaluated using the Mini-Mental State Examination (MMSE). We defined dementia, Alzheimer's disease (AD), and vascular dementia (VaD) following the respective international criteria. Data were analyzed using multinomial logistic and general linear regression models. RESULTS: Of all participants, 300 were diagnosed with dementia, including 195 with AD and 95 VaD. The multiple-adjusted odds ratio of dementia associated with quartiles of RDW were 1.45 (95%CI: 0.87-2.44), 1.00 (reference), 1.77 (1.07-2.93), and 2.28 (1.40-3.72). Similar J-shaped patterns existed for the association of RDW with odds ratio of AD and VaD. Anemia was not significantly associated with dementia. The J-shaped associations of RDW with dementia and subtypes were statistically evident only among participants without anemia. There was an inverted J-shaped relationship between RDW quartiles and ß-coefficients of MMSE score. CONCLUSION: There is a J-shaped association between RDW level and likelihood of dementias among rural-dwelling Chinese older adults, especially among people without anemia.