Uric acid (UA) is the final metabolite of purines in the human body. An imbalance in UA production and excretion that disrupts homeostasis leads to elevated blood UA levels and the development of hyperuricemia (HUA). Approximately one-third of UA is excreted through the intestinal tract. As a crucial component of the intestinal microenvironment, the gut microbiota plays a pivotal role in regulating blood UA levels. Alterations or imbalances in gut microbiota composition are linked to the onset of HUA, which implies the potential of gut microbiota as a novel target for the prevention and treatment of HUA. This review introduces the occurrence mechanism and damage of hyperuricemia, examines the association between HUA and the gut microbiota and their metabolites, and explores the molecular mechanisms underlying gut microbiota-targeted therapies for HUA. Furthermore, it discusses the potential applications of probiotics, prebiotics, and traditional Chinese medicine (including both single herbs and compound formulas) with UA-lowering effects, along with cutting-edge technologies such as fecal microbiota transplantation and machine learning in HUA treatment. This review provides valuable perspectives and strategies for improving the prevention and treatment of HUA.
Hyperuricemia/microbiology* ; Humans ; Gastrointestinal Microbiome/physiology* ; Probiotics/therapeutic use* ; Uric Acid/blood* ; Fecal Microbiota Transplantation ; Prebiotics ; Medicine, Chinese Traditional

BACKGROUND: Heavy metals are significant risk factors for kidney function. Numerous studies have shown that exposure to heavy metals negatively correlates with kidney function through oxidative stress pathways, and serum α-klotho is linked to oxidative stress. However, the role of α-klotho in the relationship between blood lead, mercury, and kidney function remains unclear. METHOD: This study evaluated the mediating role of alpha-klotho in the relationship between lead, mercury and renal function, using data from the 2007-2016 National Health and Nutrition Examination Survey (NHANES) in U.S. adults aged 40-79. The sample included 11,032 participants, with blood lead, mercury, α-klotho, and other relevant covariates measured. Inductively coupled plasma mass spectrometry was used to assess blood lead and mercury levels, and enzyme-linked immunosorbent assay (ELISA) was employed to measure serum α-klotho. Kidney function was evaluated using estimated glomerular filtration rate (eGFR) based on creatinine levels. Multivariable linear regression was conducted to analyze the relationships between blood lead, mercury, α-klotho, and eGFR. A mediation analysis model was used to assess whether α-klotho influenced these associations. RESULTS: We observed a significant association between blood lead and eGFR. Mediation analysis revealed that α-klotho accounted for 12.76% of the relationship between serum lead and eGFR in the NHANES population. Subgroup analysis showed that α-klotho mediated 12.43%, 6.87%, 21.50% and 5.44% of the relationship between blood lead and eGFR in women, middle-aged adults (40-59 years old), without cardiovascular disease and hypertension, respectively. However, α-klotho did not mediate the relationship between blood mercury and eGFR in terms of gender or age. This newly identified pathway may provide valuable insights for the prevention and treatment mechanisms related to kidney function impairment. CONCLUSION We found that blood lead was associated with renal function. According to the results of subgroup analysis, for blood lead, serum α-klotho mediated the association in females, middle aged 60-79 years. The relationship between blood mercury and renal function was not clinically significant, and serum α-Klotho mediated the relationship between blood mercury and renal function without significant clinical significance.
Humans ; Middle Aged ; Lead/blood* ; Female ; Klotho Proteins ; Male ; Aged ; Adult ; Mercury/blood* ; Glomerular Filtration Rate ; Nutrition Surveys ; United States ; Kidney/physiology* ; Glucuronidase/blood* ; Environmental Pollutants/blood*

BACKGROUND: Low-density lipoprotein cholesterol (LDLc) is regarded as a risk factor for endothelial dysfunction. However, LDLc stimulates the proliferation of hematopoietic stem cells (CD34-positive cells), which contribute to endothelial repair. Therefore, LDLc may have a beneficial influence on the endothelium of individuals with lower endothelial repair activity. METHODS: This cross-sectional study included 245 men aged 60-69 years. Endothelial repair activity was categorized by the circulating levels of CD34-positive cells based on median values. The status of endothelium was evaluated using the cardio-ankle vascular index (CAVI). RESULTS: Among individuals with low levels of circulating CD34-positive cells, LDL-c levels were significantly inversely correlated with CAVI and positively correlated with circulating CD34-positive cells. No significant correlations were observed among the participants with high levels of circulating CD34-positive cells. Among low levels of CD34-positive cells, the adjusted standardized parameter (β) and p value were -0.24 (p = 0.021) for CAVI and 0.41 (p < 0.001) for CD34-positive cells, whereas among high levels of CD34-positive cells, the corresponding values were 0.03 (p = 0.738) and -0.09 (p = 0.355). CONCLUSION LDLc has a beneficial influence on endothelial health among individuals with low endothelial repair activity, possibly by stimulating the proliferation of hematopoietic stem cells.
Humans ; Middle Aged ; Male ; Aged ; Cross-Sectional Studies ; Cholesterol, LDL/blood* ; Endothelium, Vascular/physiology* ; Antigens, CD34/blood* ; Hematopoietic Stem Cells

BACKGROUND: Difficulty in chewing has been shown to be associated with increased mortality, geriatric syndromes, and poor activities of daily living, indicating the need for intervention. Chewing difficulties are related to tooth loss, periodontitis, dry mouth, and a number of oral health conditions. Diabetes mellitus (DM) is one of the major causes of global burden of diseases, and has been associated with poor oral health. Prospective association between oral health status and the development of diabetes has also been reported. However, relationship between glycemic control and self-reported chewing difficulty remains less explored in working-age populations. The objective of this study is to cross-sectionally explore the association between fasting blood glucose (FBG) and self-reported chewing difficulty in adults working in a Japanese worksite. METHODS: Participants from the Aichi Workers' Cohort Study who responded to the 2018 survey were included. Participants were categorized into five FBG groups (<100, 100-109, 110-125, 126-159, and ≥160 mg/dl). Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) for chewing difficulty were estimated using logistic regression adjusted for age, sex, body mass index, smoking and alcohol consumption status, number of teeth, presence of periodontal disease and the number of anti-diabetic medication classes. RESULTS: A total of 164 participants (4.2%) reported difficulty with chewing, the prevalence of which tended to increase with increasing FBG level. FBG ≥160 mg/dl was significantly and strongly associated with difficulty with chewing in the final multivariable model (multivariable OR 3.84 [95% CI 1.13-13.0]). CONCLUSIONS A relationship between higher FBG levels and difficulty with chewing was observed, independent of potential confounding factors. However, prospective or interventional studies are needed to determine causality.
Humans ; Male ; Japan/epidemiology* ; Female ; Mastication/physiology* ; Middle Aged ; Adult ; Blood Glucose/analysis* ; Cross-Sectional Studies ; Fasting/blood* ; Cohort Studies ; Oral Health ; Prevalence

OBJECTIVES: Platelet-rich plasma (PRP) treatment has been reported to improve ovarian function in women, but the relationship between the dose and frequency of PRP treatment and its therapeutic effect remains unclear. This study aims to evaluate the efficacy of single and double PRP treatments for diminished ovarian reserve (DOR). METHODS: A total of 65 patients treated at the Reproductive Center of Xiangtan Central Hospital from September 2020 to October 2022 were randomly divided into 4 groups: A single PRP treatment group (21 patients, PRP treatment once), a double PRP treatment group (15 patients, PRP treatment twice), a blank control group (15 patients), and an artificial cycle control group (14 patients, treated with estrogen and progesterone). The differences in baseline follicle-stimulating hormone (FSH), antral follicle count (AFC), ovarian volume, number of oocytes retrieved, number of good quality embryos, and pregnancy outcomes before and after treatment were compared among the 4 groups. RESULTS: Compared to before treatment, both single and double PRP treatment groups showed a significant reduction in FSH, and an increase in AFC, ovarian volume, numbers of oocytes retrieved, and number of MII oocytes (all P<0.05). Compared to the blank control group, the single and double PRP groups showed a decrease in FSH, with an increase in AFC, number of oocytes retrieved, and number of MII oocytes (all P<0.05). The rates of good quality embryos, clinical pregnancy rate, and live birth rate in the single and double PRP groups were higher than those in the blank control group and artificial cycle control groups, but the differences were not statistically significant (all P>0.05). Compared to the single PRP treatment group, the double PRP group had lower FSH and higher AFC, but the differences were not statistically significant (both P>0.05). CONCLUSIONS Both single and double PRP ovarian injections can effectively improve ovarian reserve function in DOR patients and enhance ovarian response. Compared to single PRP ovarian injection, double PRP ovarian injection shows a trend of better improvement in ovarian reserve function.
Humans ; Female ; Platelet-Rich Plasma ; Ovarian Reserve/physiology* ; Adult ; Pregnancy ; Follicle Stimulating Hormone/blood* ; Pregnancy Rate ; Ovary ; Ovulation Induction/methods* ; Ovarian Follicle ; Oocyte Retrieval

Meniscus injuries are widespread and the available treatments do not offer enough healing potential. Here, we provide critical support for using pigs as a biological model for meniscal degeneration and the development of cutting-edge therapies in orthopedics. We present a single-cell transcriptome atlas of the meniscus, consisting of cell clusters corresponding to four major cell types: chondrocytes, endothelial cells, smooth muscle cells, and immune cells. Five distinct chondrocyte subclusters (CH0‒CH4) were annotated, of which only one was widespread in both the red and white zones, indicating a major difference in the cellular makeup of the zones. Subclusters distinct to the white zone appear responsible for cartilage-specific matrix deposition and protection against adverse microenvironmental factors, while those in the red zone exhibit characteristics of mesenchymal stem cells and are more likely to proliferate and migrate. Additionally, they induce remodeling actions in other chondrocyte subclusters and promote the proliferation and maturation of endothelial cells, inducing healing and vascularization processes. Considering that they have substantial remodeling capabilities, these subclusters should be of great interest for tissue engineering studies. We also show that the cellular makeup of the pig meniscus is comparable to that of humans, which supports the use of pigs as a model in orthopedic therapy development.
Animals ; Swine ; Chondrocytes/physiology* ; Single-Cell Analysis ; Meniscus/blood supply* ; Endothelial Cells/cytology* ; Transcriptome ; Mesenchymal Stem Cells/cytology* ; Neovascularization, Physiologic ; Cell Proliferation

The central amygdala (CeA) is a crucial modulator of emotional, behavioral, and autonomic functions, including cardiovascular responses. Despite its importance, the specific circuit by which the CeA modulates blood pressure remains insufficiently explored. Our investigations demonstrate that photostimulation of GABAergic neurons in the centromedial amygdala (CeM^GABA), as opposed to those in the centrolateral amygdala (CeL), produces a depressor response in both anesthetized and freely-moving mice. In addition, activation of CeM^GABA axonal terminals projecting to the nucleus tractus solitarius (NTS) significantly reduces blood pressure. These CeM^GABA neurons form synaptic connections with NTS neurons, allowing for the modulation of cardiovascular responses by influencing the caudal or rostral ventrolateral medulla. Furthermore, CeM^GABA neurons targeting the NTS receive dense inputs from the CeL. Consequently, stimulation of CeM^GABA neurons elicits hypotension through the CeM-NTS circuit, offering deeper insights into the cardiovascular responses associated with emotions and behaviors.
Animals ; GABAergic Neurons/physiology* ; Male ; Central Amygdaloid Nucleus/physiopathology* ; Hypotension/physiopathology* ; Mice ; Blood Pressure/physiology* ; Mice, Inbred C57BL ; Solitary Nucleus/physiology* ; Photic Stimulation ; Neural Pathways/physiology*

Mild repetitive head injury is a serious health problem with long-term negative consequences. Changes in brain neurobiology were assessed with MRI in a model of head injury designed to reflect the human experience. Rats were maintained on a reverse light-dark cycle and head impacted daily at 24 h intervals over three days while fully awake under red light illumination. There was no neuroradiological evidence of brain damage. Rats were imaged for changes in blood brain barrier permeability, edema and gray matter microarchitecture, and resting state functional connectivity. Data were registered to a 3D MRI rat atlas with 173 segmented brain areas providing site-specific information on each imaging modality. Changes in BBB permeability were minimal and localized to the hippocampus and cerebellum. There was evidence of cytotoxic edema in the basal ganglia, thalamus, and cerebellum. There was a global decrease in connectivity and an increase in gliosis in the thalamus, cerebellum, and hippocampus. This study shows a sequelae of neuropathology caused by mild repetitive head injury that is commonly observed in clinical practice using MRI in patients. As such, it may serve as a model for testing the efficacy of new therapeutics using any or all of the measures as biomarkers to assess drug efficacy.
Animals ; Magnetic Resonance Imaging/methods* ; Disease Models, Animal ; Brain/physiopathology* ; Male ; Rats ; Rats, Sprague-Dawley ; Blood-Brain Barrier/diagnostic imaging* ; Multimodal Imaging ; Wakefulness/physiology* ; Craniocerebral Trauma/physiopathology*

OBJECTIVE: To examine the mechanistic of organochlorine-associated changes in lung function. METHODS: This study investigated 76 healthy older adults in Jinan, Shandong Province, over a five-month period. Personal exposure to organochlorines was quantified using wearable passive samplers, while inflammatory factors and thyroid hormones were analyzed from blood samples. Participants' lung function was evaluated. After stratifying participants according to their thyroid hormone levels, we analyzed the differential effects of organochlorine exposure on lung function and inflammatory factors across the low and high thyroid hormone groups. Mediation analysis was further conducted to elucidate the relationships among organochlorine exposures, inflammatory factors, and lung function. RESULTS: Bis (2-chloro-1-methylethyl) ether (BCIE), was negatively associated with forced vital capacity (FVC, -2.05%, 95% CI: -3.11% to -0.97%), and associated with changes in inflammatory factors such as interleukin (IL)-2, IL-7, IL-8, and IL-13 in the low thyroid hormone group. The mediation analysis indicated a mediating effect of IL-2 (15.63%, 95% CI: 0.91% to 44.64%) and IL-13 (13.94%, 95% CI: 0.52% to 41.07%) in the association between BCIE exposure and FVC. CONCLUSION Lung function and inflammatory factors exhibited an increased sensitivity to organochlorine exposure at lower thyroid hormone levels, with inflammatory factors potentially mediating the adverse effects of organochlorines on lung function.
Environmental Exposure ; Hydrocarbons, Chlorinated/metabolism* ; China ; Ethyl Ethers/metabolism* ; Environmental Monitoring ; Thyroid Hormones/blood* ; Lung/physiology* ; Inhalation Exposure/statistics & numerical data* ; Air Pollution/statistics & numerical data* ; Air Pollutants/metabolism* ; Humans ; Male ; Female ; Middle Aged ; Aged

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*