Exploring the impact of gut microbiota on liver health in mice and patients with Wilson disease.

BACKGROUND AND AIMS: Distinctive gut microbial profiles have been observed between patients with Wilson disease (WD) and healthy individuals. Despite this, the exact relationship and influence of gut microbiota on the advancement of WD-related liver damage remain ambiguous. This research seeks to clarify the gut microbiota characteristics in both human patients and mouse models of WD, as well as their impact on liver injury. METHODS: Gut microbial features in healthy individuals, patients with WD, healthy mice and mice with early- and late-stage WD were analysed using 16S rRNA gene sequencing. Additionally, WD-afflicted mice underwent treatment with either an antibiotic cocktail (with normal saline as a control) or healthy microbiota (using disease microbiota as a control). The study assessed gut microbiota composition, hepatic transcriptome profiles, liver copper concentrations and hepatic pathological injuries. RESULTS: Patients with hepatic WD and mice with WD-related liver injury displayed altered gut microbiota composition, notably with a significant reduction in Lactobacillus abundance. Additionally, the abundances of several gut genera, including Lactobacillus, Veillonella and Eubacterium coprostanoligenes, showed significant correlations with the severity of liver injury in patients with WD. In WD mice, antibiotic treatment or transplantation of healthy microbiota altered the gut microbial structure, increased Lactobacillus abundance and modified the hepatic transcriptional profile. These interventions resulted in reduced hepatic copper concentration and alleviation of WD-related liver injury. CONCLUSIONS: Individuals and mice with pronounced WD-related liver injury exhibited shifts in gut microbial composition. Regulating gut microbiota through healthy microbiota transplantation emerges as a promising therapeutic approach for treating WD-related liver injury.

The crosstalk between oxidative stress and DNA damage induces neural stem cell senescence by HO-1/PARP1 non-canonical pathway.

Neural stem cells play a crucial role in maintaining brain homeostasis. Neural stem cells senescence can lead to the decline of nerve repair and regeneration, causing brain aging and neurodegenerative diseases. However, the mechanism underlying neural stem cells senescence remains poorly understood. In this study, we report a novel HO-1/PARP1 non-canonical pathway highlighting how oxidative stress triggers the DNA damage response, ultimately leading to premature cellular senescence in neural stem cells. HO-1 acts as a sensor for oxidative stress, while PARP1 functions as a sensor for DNA damage. The simultaneous expression and molecular interaction of these two sensors can initiate a crosstalk of oxidative stress and DNA damage response processes, leading to the vicious cycle. The persistent activation of this pathway contributes to the senescence of neural stem cells, which in turn plays a crucial role in the progression of neurodegenerative diseases. Consequently, targeting this novel signaling pathway holds promise for the development of innovative therapeutic strategies and targets aimed at mitigating neural stem cells senescence-related disorders.

Washed microbiota transplantation promotes homing of group 3 innate lymphoid cells to the liver via the CXCL16/CXCR6 axis: a potential treatment for metabolic-associated fatty liver disease.

Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.

An In Vitro Evaluation of the Effect of Bifidobacterium longum L556 on Microbiota Composition and Metabolic Properties in Patients with Coronary Heart Disease (CHD).

Bifidobacterium longum (B. longum) is a beneficial anaerobic bacteria that may improve cardiovascular disease (CVD). We studied B. longum L556, isolated from healthy human feces, in coronary heart disease (CHD) patients through anaerobic fermentation in vitro. Results showed that B. longum L556 increased Lactobacillus, Faecalibacterium, Prevotella, and Alistipes, while reducing Firmicutes to Bacteroidetes, Eggerthella, Veillonella, Holdemanella, and Erysipelotrichaceae_UCG-003 in the gut microbiota of CHD patients. B. longum L556 also enhanced anti-inflammatory effects by modulating gut microbiota and metabolites like SCFAs. Additionally, it regulated lipid and amino acid metabolism in fermentation metabolites from the CHD group. These findings suggest that B. longum L556 has potential for improving CHD by modulating the intestinal microbiota, promoting SCFA production, and regulating lipid metabolism and inflammation.

Intestinal CXCR6+ ILC3s migrate to the kidney and exacerbate renal fibrosis via IL-23 receptor signaling enhanced by PD-1 expression.

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.

In Vitro Lactic Acid Bacteria Anti-Hepatitis B Virus (HBV) Effect and Modulation of the Intestinal Microbiota in Fecal Cultures from HBV-Associated Hepatocellular Carcinoma Patients.

Hepatocellular carcinoma (HCC), being ranked as the top fifth most prevalent cancer globally, poses a significant health challenge, with a considerable mortality rate. Hepatitis B virus (HBV) infection stands as the primary factor contributing to HCC, presenting substantial challenges in its treatment. This study aimed to identify lactic acid bacteria (LAB) with anti-HBV properties and evaluate their impact on the intestinal flora in HBV-associated HCC. Initially, two LAB strains, Levilactobacillus brevis SR52-2 (L. brevis SR52-2) and LeviLactobacillus delbrueckii subsp. bulgaicus Q80 (L. delbrueckii Q80), exhibiting anti-HBV effects, were screened in vitro from a pool of 498 LAB strains through cell experiments, with extracellular expression levels of 0.58 ± 0.05 and 0.65 ± 0.03, respectively. These strains exhibited the capability of inhibiting the expression of HBeAg and HBsAg. Subsequent in vitro fermentation, conducted under simulated anaerobic conditions mimicking the colon environment, revealed a decrease in pH levels in both the health control (HC) and HCC groups influenced by LAB, with a more pronounced effect observed in the HC group. Additionally, the density of total short-chain fatty acids (SCFAs) significantly increased (p < 0.05) in the HCC group. Analysis of 16S rRNA highlighted differences in the gut microbiota (GM) community structure in cultures treated with L. brevis SR52-2 and L. delbrueckii Q80. Fecal microflora in normal samples exhibited greater diversity compared to HBV-HCC samples. The HCC group treated with LAB showed a significant increase in the abundance of the phyla Firmicutes, Bacteroidetes and Actinobacteria, while Proteobacteria significantly decreased compared to the untreated HCC group after 48 h. In conclusion, the findings indicate that LAB, specifically L. brevis SR52-2 and L. delbrueckii Q80, possessing antiviral properties, contribute to an improvement in gastrointestinal health.

Gut microbiota from essential tremor patients aggravates tremors in mice.

Background and objective: Essential tremor (ET) lacks effective treatments because its underlying mechanism is largely unknown, but may involve gut microbiota via the microbiome-gut-brain axis. We explored the effects of gut microbiota on ET in mice. Methods: Specific pathogen-free C57BL/6J mice were gavaged with stools from ET patients or matched healthy individuals. After 3 weeks of gavaging, behavioral tests were performed on all mice. Next, each mouse was injected with harmaline to induce tremors. The tremor duration was recorded; the tremor score was estimated every 30 min. Behavioral tests were repeated after modeling. Intestinal tissues and fecal samples of the mice were examined using histology and 16Sr DNA sequencing, respectively. Results: Compared with mice receiving microbiota from healthy controls, mice receiving fecal suspensions from ET patients showed worse performance in the pre-modeling behavioral tests. After modeling, ET-group mice showed significantly greater tremor scores, longer tremor duration, and worse motor performance. They also had significantly lower body weight and lower fecal pellet count. Pathological scoring revealed more severe intestinal lesions in ET-group mice. The 16S rDNA sequencing data revealed significant differences in microbiota indices, and a correlation between these indices and tremors in mice. Functional predictions indicated that the abundance of GABA-related enzymes was altered in ET-group mice. Conclusion: Mice transplanted with gut microbiota from ET patients showed worse performance in behavioral tests. After modeling, ET-group mice presented longer tremor duration, higher tremor score, and worse motor performance. This study provides evidence for gut microbiota dysbiosis that may affect the pathogenesis of ET.

Supplementation with high-GABA-producing Lactobacillus plantarum L5 ameliorates essential tremor triggered by decreased gut bacteria-derived GABA.

BACKGROUND: The γ-aminobutyric acid (GABA) hypothesis posits a role of GABA deficiency in the central nervous system in the pathogenesis and progression of essential tremor (ET). However, the specific causative factor for GABA deficiency is not clear. The gut microbiota in mammals has recently been considered as a significant source of GABA. Furthermore, the GABA-based signals originating from the intestine can be transmitted to the brain through the "enteric nervous system-vagus nerve-brain" axis. However, the plausible contribution of gut microbiota to ET seems inspiring but remains obscure. METHODS: Fecal samples from patients with ET and healthy controls were examined by metagenomic sequencing to compare the composition of gut microbiota and the expression of genes involved in GABA biosynthesis. The impact of gut microbiota on ET was explored through transplantation of fecal microbiota from patients with ET into the murine ET model. Lactic acid bacteria producing high amounts of GABA were identified through whole-genome sequencing and ultra-performance liquid chromatography-tandem mass spectrometry. Subsequently, mice were treated with the high-GABA-producing strain Lactobacillus plantarum L5. Tremor severity, behavioral tests, pro-inflammatory cytokines, GABA concentration, and gut microbiota composition were examined in these mice. RESULTS: The gut microbiota of patients with ET demonstrated an impaired GABA-producing capacity and a reduced fecal GABA concentration. Transplantation of the gut microbiota from patients with ET induced an extension of tremor duration and impaired mobility in the murine model of ET. L5 exhibited an augmented GABA-producing capacity, with the De Man-Rogosa-Sharpe culture broth containing 262 mg/l of GABA. In addition, administration of L5 significantly decreased the tremor severity and enhanced the movement capability and grasping ability of ET mice. In vivo mechanistic experiments indicated that L5 reshaped the gut microbial composition, supplemented the mucosa-associated microbiota with GABA-producing capacity, increased the GABA concentrations in the cerebellum, and diminished inflammation in the central nervous system. CONCLUSIONS: These findings highlight that deficiency of GABA-producing gut microbes plays an essential role in the pathogenesis of ET and that L5 is a promising candidate for treating ET.

Group 3 Innate Lymphoid Cells Exacerbate Lupus Nephritis by Promoting B Cell Activation in Kidney Ectopic Lymphoid Structures.

Group 3 innate lymphoid cells (ILC3s) represent a new population in immune regulation, yet their role in lupus nephritis (LN) remains elusive. In the present work, systemic increases in ILC3s, particularly in the kidney, are observed to correlate strongly with disease severity in both human and murine LN. Using MRL/lpr lupus mice and a nephrotoxic serum-induced LN model, this study demonstrates that ILC3s accumulated in the kidney migrate predominantly from the intestine. Furthermore, intestinal ILC3s accelerate LN progression, manifested by exacerbated autoimmunity and kidney injuries. In LN kidneys, ILC3s are located adjacent to B cells within ectopic lymphoid structures (ELS), directly activating B cell differentiation into plasma cells and antibody production in a Delta-like1 (DLL1)/Notch-dependent manner. Blocking DLL1 attenuates ILC3s' effects and protects against LN. Altogether, these findings reveal a novel pathogenic role of ILC3s in B cell activation, renal ELS formation and autoimmune injuries during LN, shedding light on the therapeutic value of targeting ILC3s for LN.

Washed microbiota transplantation: a case report of clinical success with skin and gut microbiota improvement in an adolescent boy with atopic dermatitis.

Atopic dermatitis (AD) is a chronic, recurrent inflammatory disease characterized by itching. The gut microbiome can help maintain skin immune homeostasis by regulating innate and adaptive immunity. Here, we report a case of AD in a 15-year-old adolescent boy who benefited from washed microbiota transplantation (WMT). WMT was performed for three courses, with each course lasting for three consecutive days and an interval of one month between two courses. Clinical assessments were conducted at each WMT course, and skin, blood, and stool samples were collected for microbial analysis. After three months of WMT treatment, the boy's itchiness was effectively controlled: his skin showed noticeable improvement, with reduced Staphylococcus aureus in the skin lesions. The scores of SCORAD (SCORing Atopic Dermatitis), EASI (Eczema Area and Severity Index), NRS (Numerical Rating Scale), and DLQI (Dermatology Life Quality Index) significantly decreased compared to the baseline. Serum levels of eosinophil ratio, tumor necrotic factor-α, and interleukin-6 also reduced to the normal levels. There was a significant decrease in S. aureus in the skin lesions. Additionally, the intestinal flora became more diverse, and the abundance of Bifidobacterium species, significantly increased after WMT. No adverse events were reported during the treatment and the 1-year follow-up period. This case report provides direct clinical evidence for WMT as a novel promising treatment strategy for AD, and preliminary experimental data suggests the existence of an intestinal-skin axis in terms of the gut microbiota and the skin immune homeostasis.

Washed microbiota transplantation improves renal function in patients with renal dysfunction: a retrospective cohort study.

BACKGROUND: Changes in the gut microbiota composition is a hallmark of chronic kidney disease (CKD), and interventions targeting the gut microbiota present a potent approach for CKD treatment. This study aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT), a modified faecal microbiota transplantation method, on the renal activity of patients with renal dysfunction. METHODS: A comparative analysis of gut microbiota profiles was conducted in patients with renal dysfunction and healthy controls. Furthermore, the efficacy of WMT on renal parameters in patients with renal dysfunction was evaluated, and the changes in gut microbiota and urinary metabolites after WMT treatment were analysed. RESULTS: Principal coordinate analysis revealed a significant difference in microbial community structure between patients with renal dysfunction and healthy controls (P = 0.01). Patients with renal dysfunction who underwent WMT exhibited significant improvement in serum creatinine, estimated glomerular filtration rate, and blood urea nitrogen (all P < 0.05) compared with those who did not undergo WMT. The incidence of adverse events associated with WMT treatment was low (2.91%). After WMT, the Shannon index of gut microbiota and the abundance of several probiotic bacteria significantly increased in patients with renal dysfunction, aligning their gut microbiome profiles more closely with those of healthy donors (all P < 0.05). Additionally, the urine of patients after WMT demonstrated relatively higher levels of three toxic metabolites, namely hippuric acid, cinnamoylglycine, and indole (all P < 0.05). CONCLUSIONS: WMT is a safe and effective method for improving renal function in patients with renal dysfunction by modulating the gut microbiota and promoting toxic metabolite excretion.

Washed Microbiota Transplantation Improves Patients with Overweight by the Gut Microbiota and Sphingolipid Metabolism.

BACKGROUND: Overweight (OW) and obesity have become increasingly serious public health problems worldwide. The clinical impact of washed microbiota transplantation (WMT) from healthy donors in OW patients is unclear. This study aimed to investigate the effect of WMT in OW patients. METHODS: The changes in body mass index (BMI = weight (kg)/height (m)2), blood glucose, blood lipids and other indicators before and after WMT were compared. At the same time, 16S rRNA gene amplicon sequencing was performed on fecal samples of OW patients before and after transplantation. Finally, serum samples were tested for sphingolipids targeted by lipid metabolomics. RESULTS: A total of 166 patients were included, including 52 in the OW group and 114 in the normal weight (NOW) group. For OW patients, WMT significantly improved the comprehensive efficacy of OW. In the short term (about 1 month) and medium term (about 2 months), a significant reduction in BMI was seen. At the same time, in the short term (about 1 month), liver fat attenuation (LFA), triglyceride (TG) and fasting blood glucose (FBG) were significantly reduced. In the long term (about 5 months), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein (non-HDL-c), etc. were significantly reduced. WMT improved the gut microbiota of OW patients, and also had an improvement effect on OW patients by regulating sphingolipid metabolism. CONCLUSION: WMT had a significant improvement effect on OW patients. WMT could restore gut microbiota homeostasis and improve OW patients by regulating sphingolipid metabolism.

Washed microbiota transplantation improves haemoglobin levels in anaemia of chronic disease.

BACKGROUND: Anaemia of chronic disease (ACD) is the second most common type of anaemia and lacks an effective treatment. Patients with anaemia are reported to have altered gut microbial profiles, which may affect erythropoiesis. Here, we investigated the gut microbial features of patients with ACD and determined whether regulating gut microbiota using washed microbiota transplantation (WMT) was effective in treating ACD. METHODS: We compared the gut microbiota profile of patients with ACD and healthy controls, evaluated the efficacy of WMT on haematological parameters in the patients, and analysed the alterations in gut microbiota after WMT treatment. RESULTS: Patients with ACD had lower gut microbial richness, and differences in microbial composition and function, relative to healthy controls. Additionally, the relative abundances of two butyrate-producing genera Lachnospiraceae NK4A136 group and Butyricicoccus, were positively correlated with the haemoglobin (HGB) level and lower in patients with ACD than controls. WMT significantly increased HGB levels in patients with ACD. After the first, second and third WMT rounds, normal HGB levels were restored in 27.02%, 27.78% and 36.37% (all p < .05) of patients with ACD, respectively. Moreover, WMT significantly increased the abundance of butyrate-producing genera and downregulated gut microbial functions that were upregulated in patients with ACD. CONCLUSIONS: Patients with ACD exhibited differences in gut microbial composition and function relative to healthy controls. WMT is an effective treatment for ACD that reshapes gut microbial composition, restores butyrate-producing bacteria and regulates the functions of gut microbiota.

Anemia Is Associated with Disease Severity, Hepatic Complications, and Progression of Wilson Disease: A Retrospective Cohort Study.

INTRODUCTION: Anemia is a common manifestation of chronic liver diseases. It is a predictor of severe disease, a high risk of complications, and poor outcomes in various liver diseases. However, it remains unclear whether anemia serves as a similar indicator in patients with Wilson disease (WD). Therefore, this study aimed to investigate the relationship between anemia and severity, hepatic complications, and the progression of WD. METHODS: Medical data were collected retrospectively from January 1, 2016, to December 31, 2020. Univariate and multivariate analyses were carried out to investigate the relationship between anemia and liver-associated disease severity, hepatic complications, and the progression of WD. RESULTS: A total of 288 WD patients (48 with and 240 without anemia) were enrolled in the study. Multivariate linear regression revealed that WD patients with anemia had significantly higher levels of bilirubin, alanine transaminase, prothrombin time, international normalized ratio, type Ⅳ collagen, and hyaluronic acid and significantly lower levels of albumin, total cholesterol, and high-density lipoprotein-cholesterol (all p < 0.05). Multivariate logistic regression showed that anemia was a risk factor for gastric varices and ascites (all p < 0.05). Fully adjusted Cox regression revealed that anemia was an independent risk factor for advanced Child-Pugh classification (p = 0.034). CONCLUSIONS: Anemia was common in WD patients and was associated with greater disease severity, a higher risk of hepatic complications, and a faster progression.

Negative correlation between circulating integrin α4+ group 3 innate lymphoid cells and the severity of type 2 diabetes.

BACKGROUND: Impaired intestinal barrier and immune dysfunction promote the development of type 2 diabetes (T2D). Group 3 innate lymphoid cells (ILC3s), which are enriched in the intestinal lamina propria, are key for intestinal barrier integrity. However, there is a paucity of data on circulating ILC3s in patients with T2D. PURPOSE: To examine the characteristics of ILC3s in patients with T2D and identify the relationship between ILC3s and clinical indicators of T2D. METHODS: Fifty-nine patients with T2D and thirty controls were enrolled in this retrospective study. Peripheral blood mononuclear cells were isolated and analyzed by flow cytometry and plasma cytokine levels were measured by enzyme-linked immunosorbent assays. RESULTS: The proportion of circulating ILC3s in the T2D group was significantly lower than that in controls and showed a negative correlation with fasting glucose and glycated hemoglobin and a positive correlation with granulocyte-macrophage colony-stimulating factor (GM-CSF). Similarly, the proportion of circulating integrin α4+ ILC3s was also significantly lower in the T2D group and showed a negative correlation with fasting glucose and glycated hemoglobin and a positive correlation with GM-CSF. Moreover, the level of circulating integrin α4+ ILC3s showed a positive correlation with the proportion of circulating dendritic cells (DCs), which was also decreased in patients with T2D and positively associated with GM-CSF. CONCLUSION: ILC3s, especially integrin α4+ ILC3s, were decreased in patients with T2D and showed a negative correlation with disease severity. These cell subsets may delay the progression of T2D by promoting DC differentiation via the secretion of GM-CSF.

The Impact of Multi-Quality Renewal Elements of Residence on the Subjective Well-Being of the Older Adults - A Case Study of Dalian.

Background: With the expansion of comprehensive renovation projects in China's old residential areas, residents' actual sense of access and well-being has become a source of concern. As the population in old residential areas ages, the results of old renovation will have a significant impact on the older adults quality of life and subjective well-being. Purpose: To date, most relevant studies have focused on urban and community scales, with little discussion of the impact of neighborhood-level renewal outcomes on the well-being of older adults. As a result, the purpose of this research is to optimize the quality renewal elements of existing old residential areas based on the results of their renovation in order to create a more livable living environment for older adults in existing old residential areas. Methods: Based on a survey of old neighborhoods in Dalian, the study examines the mediating effect of psychological resilience between multi-quality renewal elements and the subjective well-being of the older adults, and it discusses the influence of multi-quality renewal elements on the subjective well-being of the older adults in different residential types. Results: According to the findings, multi-quality renewal elements of residence positively predicted the subjective well-being of the older adults; there was a significant mediating effect of psychological resilience between the renewal elements and subjective well-being of the older adults. The study confirms that multiple quality renewal elements can contribute to older people's subjective well-being, and that psychological resilience plays an important role in the selection of multiple quality renewal elements and older people's subjective well-being. Conclusion: The research provides guidance for the establishment of health-oriented approaches to environmental restoration in residential areas for the sustainable development of communities and cities.

Reduced type 3 innate lymphoid cells related to worsening kidney function in renal dysfunction.

Intestinal mucosa barrier injury and immunity imbalance contribute to chronic kidney disease (CKD) progression. Type 3 innate lymphoid cells (ILC3s) are essential for normal intestinal homeostasis. Nevertheless, the relationship between ILC3s and CKD remains largely unknown. The aim of this study was to investigate the relationship linking ILC3s to clinical indicators among patients with renal dysfunction. The levels of circulating ILC3s and dendritic cells, as well as their subsets, in patients with renal dysfunction and healthy controls were determined through flow cytometry. The levels of human plasma granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured using enzyme-linked immunosorbent assay. Renal function was evaluated by measuring the estimated glomerular filtration rate (eGFR), as well as the levels of serum creatinine, blood urea nitrogen (BUN), and uric acid. The results revealed that the proportion of peripheral ILC3s was significantly decreased in patients with renal dysfunction. This reduction was positively associated with the levels of eGFR, and inversely associated with the levels of BUN and uric acid. Similarly, the percentage of circulating C-C motif chemokine receptor 6-positive (CCR6 +) ILC3s was also obviously reduced, and demonstrated positive and negative associations with the levels of eGFR and BUN, respectively. Furthermore, the levels of CCR6 + ILC3s correlated positively with those of GM-CSF, as well as type 1 conventional dendritic cells (cDC1s), which also decreased in parallel with kidney function. Thus, the reduction of ILC3s, particularly CCR6 + ILC3s, was related to worsening kidney function in patients with renal dysfunction. This effect may delay renal function impairment by regulating cDC1s via the secretion of GM-CSF, indicating that CCR6 + ILC3s may serve as efficient biomarkers for evaluating kidney function.

Type 3 innate lymphoid cells as an indicator of renal dysfunction and serum uric acid in hyperuricemia.

BACKGROUND: Type 3 innate lymphoid cells (ILC3s) are a newly identified group of innate immune cells that participate in the progression of several metabolic diseases by secreting interleukin (IL)-17 and IL-22. These cytokines are associated with hyperuricemia (HUA) severity and development; however, the relationship between ILC3s and HUA remains unclear. OBJECTIVES: To determine the characteristics of circulating ILC3s in patients with HUA. MATERIAL AND METHODS: Type 3 innate lymphoid cells and their subsets were detected using flow cytometry in peripheral blood mononuclear cells (PBMCs) of 80 HUA patients and 30 healthy controls (HC). Plasma levels of IL-17A and IL-22 were measured with enzyme-linked immunosorbent assay (ELISA). Clinical data of enrolled subjects were collected from electronic medical records. RESULTS: In patients with HUA, the frequency of circulating ILC3s was elevated and positively correlated with levels of serum uric acid and serum creatinine (Scr). Although there was no significant difference in the plasma concentration of IL-17A between the patients with HUA and healthy controls, positive correlations between plasma IL-17A and the concentration of serum uric acid and frequency of circulating ILC3s were observed in the patients with HUA. CONCLUSIONS: In patients with HUA, positive correlations were detected between circulating ILC3 levels, plasma IL-17A and serum uric acid. Therefore, ILC3s and IL-17A may be useful indicators of disease severity, and are potential new therapeutic targets in HUA.

Magnetic biochar based on furfural residue as an excellent candidate for efficient adsorption of Tetracycline, Bisphenol A, Congo red, and Cr6.

Magnetic porous adsorbent materials are widely favored for their large specific surface area, good adsorption performance, and ease of separation. This work provided a magnetic biochar derived from furfural residue (M-FRAC) with excellent adsorption properties for various pollutants, including Congo red (CR), Tetracycline (TC), Bisphenol A (BPA), and Cr6+. The influence of experimental parameters, such as pollutant concentration, contact time, and pH, on the adsorption properties of M-FRAC was studied in detail. The adsorption process was highly dependent on pH and initial contaminant concentration. All pollutant adsorption was favorable under acidic conditions. The optimal pH of the CR, TC, and Cr6+ adsorption was 5, 4, and 2, respectively, while that of BPA was in the range of 2-5. The experimental equilibrium adsorption amount of CR, TC, BPA, and Cr6+ by M-FRAC was 110.89, 602.81, 157.76, and 265.31 mg/g, respectively. The adsorption processes of pollutants on M-FRAC were in accordance with the Langmuir isotherm model. The adsorption kinetics fitted the pseudo-second-order (PSO) kinetics model. In addition, M-FRAC could be readily separated from solution by applying an external magnetic field. Therefore, the M-FRAC has a good application prospect in practical industrial wastewater treatment.

Gut microbiota as an antioxidant system in centenarians associated with high antioxidant activities of gut-resident Lactobacillus.

The gut microbiota plays an important role in human health and longevity, and the gut microbiota of centenarians shows unique characteristics. Nowadays, most microbial research on longevity is usually limited to the bioinformatics level, lacking validating information on culturing functional microorganisms. Here, we combined metagenomic sequencing and large-scale in vitro culture to reveal the unique gut microbial structure of the world's longevity town-Jiaoling, China, centenarians and people of different ages. Functional strains were isolated and screened in vitro, and the possible relationship between gut microbes and longevity was explored and validated in vivo. 247 healthy Cantonese natives of different ages participated in the study, including 18 centenarians. Compared with young adults, the gut microbiota of centenarians exhibits higher microbial diversity, xenobiotics biodegradation and metabolism, oxidoreductases, and multiple species (the potential probiotics Lactobacillus, Akkermansia, the methanogenic Methanobrevibacter, gut butyrate-producing members Roseburia, and SCFA-producing species uncl Clostridiales, uncl Ruminococcaceae) known to be beneficial to host metabolism. These species are constantly changing with age. We also isolated 2055 strains from these samples by large-scale in vitro culture, most of which were detected by metagenomics, with clear complementarity between the two approaches. We also screened an age-related gut-resident Lactobacillus with independent intellectual property rights, and its metabolite (L-ascorbic acid) and itself have good antioxidant effects. Our findings underscore the existence of age-related trajectories in the human gut microbiota, and that distinct gut microbiota and gut-resident as antioxidant systems may contribute to health and longevity.