Sequencing and analysis of micro RNAs in camel milk exosomes.

In order to study the species and functions of micro (mi)RNAs in the exosomes of camel milk, non-coding small (s)RNAs were sequenced and identified by Illumina sequencing technology, and the miRNA fraction was analysed by bioinformatics. After quality control, the average length of sRNA of camel milk exosomes was 18-24 nucleotides. A total of 2,659 miRNAs were identified, including 2,458 known, and 201 new miRNAs. Among the known miRNAs, miR-148a and let-7i had the highest expression levels. The results of gene ontology enrichment analysis indicated that the target genes of camel milk exosome miRNAs were involved in multicellular organismal, catabolic and other biological processes. They play role in the extracellular region, in the cytoskeleton and other cell components, in protein binding, but also have structural molecule activity and other molecular functions. According to the results of the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, the target genes of camel milk exosome miRNAs are involved in Alzheimer's disease, non-alcoholic fatty liver disease, Staphylococcus aureus infection and other pathological pathways. We speculate that the reported beneficial effect of camel milk in various pathologic conditions may be closely related to the regulatory function of the exosomal miRNAs exerted on target genes of the diseases.

Regulatory Modeling of Pesticide Aquatic Exposures in California's Agricultural Receiving Waters.

For the aquatic exposure assessment of pesticides, the USEPA uses the Variable Volume Water Model (VVWM) to predict the estimated environmental concentrations (EECs) of a pesticide in a water body that receives runoff inputs from the Pesticide Root Zone Model (PRZM). The standard farm pond and additional generalized static and flowing water bodies used in endangered species assessment (aquatic bins) are used by USEPA to model the worst-case aquatic exposure for the nationwide exposure assessment. However, whether or not model results are relevant to state-specific conditions has not been validated. In this study, the USEPA water body scenarios are examined for their capability of providing a conservatively realistic estimate of pesticide aquatic exposures in California's agricultural settings. The sensitivity of modeled EECs to key water body parameters (dimensions, flow, and mass transfer) was explored with a one-at-a-time approach by using the standard farm pond as a baseline. The EECs generated from different USEPA water bodies for the worst-case loading were compared with the monitoring data observed in California's agriculturally influencing water bodies. Results showed that the farm pond EECs well captured the worst-case monitoring data, whereas the aquatic bins EECs, especially the flowing bins, tended to overestimate data. The conceptual model of the standard farm pond was also found to be relevant to the highly vulnerable water bodies in California's agricultural areas. The study confirms that VVWM with the standard farm pond scenario is appropriate for the screening-level regulatory exposure assessment in California's agricultural settings.

Treatment of Patients with IgA Nephropathy: Evaluation of the Safety and Efficacy of Mycophenolate Mofetil.

INTRODUCTION AND AIM: Immunoglobulin A nephropathy (IgAN), characterized by aberrant IgA immune complex deposition, is the most prevalent primary glomerular disease and the main cause of end-stage renal disease, causing a significant physical and psychological burden on people worldwide. Conventional therapeutic approaches, such as renin-angiotensin-aldosterone system inhibitors and corticosteroids, may not achieve sufficient effectiveness and may produce major side events in the past. The previous data in Asian populations indicated that mycophenolate mofetil (MMF) might significantly advance the development of a new therapy strategy for IgAN. The effectiveness and safety of MMF in patients with IgAN will be investigated in this study. METHODS: A literature search was conducted on June 30th, 2023, by searching the following databases: PubMed and the Cochrane Library according to predefined criteria. To investigate the renoprotective benefits and safety of MMF, statistical analyses were performed using Cochrane's Review Manager Version 5.3. RESULTS: The meta-analysis included nine randomized controlled studies that fulfilled the inclusion criterion. In the Asian population, the results revealed a substantial difference in remission rates between the MMF group and the control group (OR: 2.53, 95% CI: 1.02, 6.30, P = 0.05). MMF can increase the rate of decrease in proteinuria in IgAN patients when compared with controls in Asians (OR: 7.34, 95% CI: 2.69, 20.08, P = 0.0001), and MMF can reduce the urinary protein in patients with IgAN in Asians (WMD: -0.61, 95% CI: -1.15, -0.08, P = 0.02). Interestingly, these studies on Asians were conducted in China. However, the differences in remission rate, rate of decrease in proteinuria, and urinary protein reduction between the MMF group and control group were not found in overall populations and in the Caucasian population. The differences in complete remission rate, partial remission rate, serum creatinine (SCr) doubling rate, rate of 50% increase in SCr, and rate of need for renal replacement treatment between the MMF group and control group were not found in Asians, Caucasians, and overall populations. The difference in the rate of side effects between the MMF group and the control group was not found. CONCLUSION: MMF protects renal function and is a safe medication for treating Chinese IgAN patients. MMF might significantly advance the development of a new therapy strategy for IgAN in the Chinese population

Clinical and preclinical studies of mesenchymal stem cells to alleviate peritoneal fibrosis.

Peritoneal dialysis is an important part of end-stage kidney disease replacement therapy. However, prolonged peritoneal dialysis can result in peritoneal fibrosis and ultrafiltration failure, forcing patients to withdraw from peritoneal dialysis treatment. Therefore, there is an urgent need for some effective measures to alleviate the occurrence and progression of peritoneal fibrosis. Mesenchymal stem cells play a crucial role in immunomodulation and antifibrosis. Numerous studies have investigated the fact that mesenchymal stem cells can ameliorate peritoneal fibrosis mainly through the paracrine pathway. It has been discovered that mesenchymal stem cells participate in the improvement of peritoneal fibrosis involving the following signaling pathways: TGF-ß/Smad signaling pathway, AKT/FOXO signaling pathway, Wnt/ß-catenin signaling pathway, TLR/NF-κB signaling pathway. Additionally, in vitro experiments, mesenchymal stem cells have been shown to decrease mesothelial cell death and promote proliferation. In animal models, mesenchymal stem cells can enhance peritoneal function by reducing inflammation, neovascularization, and peritoneal thickness. Mesenchymal stem cell therapy has been demonstrated in clinical trials to improve peritoneal function and reduce peritoneal fibrosis, thus improving the life quality of peritoneal dialysis patients.

Relationship between Compound α-Ketoacid and Microinflammation in Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) refers to the presence of structural or functional abnormalities in the kidneys that affect health, lasting for more than 3 months. CKD is not only the direct cause of global incidence rate and mortality, but also an important risk factor for cardiovascular disease. Persistent microinflammatory state has been recognized as an important component of CKD, which can lead to renal fibrosis and loss of renal function, and plays a crucial role in the pathophysiology and progression of the disease. Simultaneously, compound α-Ketoacid can bind nitrogen-containing metabolites in the blood and accelerate their excretion from the body, thereby reducing the level of metabolic waste, alleviating gastrointestinal reactions in patients, and reducing the inflammatory response and oxidative stress state of the body. Compound α-Ketoacid contains amino acids required by CKD patients. In this review, we explore the relationship between compound α-Ketoacid and microinflammation in patients with CKD. The review indicated that compound α-Ketoacid can improve the microinflammatory state in CKD patients by improving the nutritional status of CKD patients, improving patient's acid-base balance disorder, regulating oxidative stress, improving gut microbiota, and regulating abnormal lipid metabolism.

Protonated-chitosan sponge with procoagulation activity for hemostasis in coagulopathy.

Hemostatic materials are essential for managing acute bleeding in medical settings. Chitosan (CS) shows promise in hemostasis but its underlying mechanism remains incompletely understood. We unexpectedly discovered that certain protonated-chitosan (PCS) rapidly assembled plasma proteins to form protein membrane (PM) upon contact with platelet-poor plasma (PPP). We hypothesized that the novel observation was intricately related to the procoagulant effect of chitosan. Herein, the study aimed to elucidate the conditions necessary and mechanism for PM formation, identify the proteins within the PM and PCS's procoagulant action at the molecule levels. We confirmed that the amount of -NH3 + groups (>4.9 mmol/g) on PCS molecules played a crucial role in promoting coagulation. The -NH3 + group interacted with blood's multiple active components to exert hemostatic effects: assembling plasma proteins including coagulation factors such as FII, FV, FX, activating blood cells and promoting the secretion of coagulation-related substances (FV, ADP, etc) by platelets. Notably, the hemostatic mechanism can be extended to protonated-chitosan derivatives like quaternized, alkylated, and catechol-chitosan. In the blood clotting index (BCI) experiment, compared to other groups, PCS95 achieved the lowest BCI value (∼6 %) within 30 s. Protonated-chitosan exhibited excellent biocompatibility and antibacterial properties, with PCS95 demonstrating inhibition effectiveness of over 95 % against Escherichia coli (E.coil) and Staphylococcus aureus (S. aureus). Moreover, PCS performed enhanced hemostatic effectiveness over chitosan-based commercially agents (Celox™ and ChitoGauze®XR) in diverse bleeding models. In particular, PCS95 reduced bleeding time by 70 % in rabbit models of coagulopathy. Overall, this study investigated the coagulation mechanism of materials at the molecular level, paving the way for innovative approaches in designing new hemostatic materials.

Cardiovascular outcomes and safety of SGLT2 inhibitors in chronic kidney disease patients.

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors provide cardiovascular protection for patients with heart failure (HF) and type 2 diabetes mellitus (T2DM). However, there is little evidence of their application in patients with chronic kidney disease (CKD). Furthermore, there are inconsistent results from studies on their uses. Therefore, to explore the cardiovascular protective effect of SGLT2 inhibitors in the CKD patient population, we conducted a systematic review and meta-analysis to evaluate the cardiovascular effectiveness and safety of SGLT2 inhibitors in this patient population. Method: We searched the PubMed® (National Library of Medicine, Bethesda, MD, USA) and Web of Science™ (Clarivate™, Philadelphia, PA, USA) databases for randomized controlled trials (RCTs) of SGLT2 inhibitors in CKD patients and built the database starting in January 2023. In accordance with our inclusion and exclusion criteria, the literature was screened, the quality of the literature was evaluated, and the data were extracted. RevMan 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) and Stata® 17.0 (StataCorp LP, College Station, TX, USA) were used for the statistical analyses. Hazard ratios (HRs), odds ratios (ORs), and corresponding 95% confidence intervals (CIs) were used for the analysis of the outcome indicators. Results: Thirteen RCTs were included. In CKD patients, SGLT2 inhibitors reduced the risk of cardiovascular death (CVD) or hospitalization for heart failure (HHF) by 28%, CVD by 16%. and HHF by 35%. They also reduced the risk of all-cause death by 14% without increasing the risk of serious adverse effects (SAEs) and urinary tract infections (UTIs). However, they increased the risk of reproductive tract infections (RTIs). Conclusion: SGLT2 inhibitors have a cardiovascular protective effect on patients with CKD, which in turn can significantly reduce the risk of CVD, HHF, and all-cause death without increasing the risk of SAEs and UTIs but increasing the risk of RTIs.

Gut microbiota: a newly identified environmental factor in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominantly affects women of childbearing age and is characterized by the damage to multiple target organs. The pathogenesis of SLE is complex, and its etiology mainly involves genetic and environmental factors. At present, there is still a lack of effective means to cure SLE. In recent years, growing evidence has shown that gut microbiota, as an environmental factor, triggers autoimmunity through potential mechanisms including translocation and molecular mimicry, leads to immune dysregulation, and contributes to the development of SLE. Dietary intervention, drug therapy, probiotics supplement, fecal microbiome transplantation and other ways to modulate gut microbiota appear to be a potential treatment for SLE. In this review, the dysbiosis of gut microbiota in SLE, potential mechanisms linking gut microbiota and SLE, and immune dysregulation associated with gut microbiota in SLE are summarized.

Renal Protection and Safety of Sodium-glucose Cotransporter-2 Inhibitors in Chronic Kidney Disease.

INTRODUCTION: Chronic kidney disease (CKD) has a clinical characteristic of progressive loss of kidney function and becomes a serious health and social concern. SGLT2i (sodium-glucose cotransporter 2 inhibitors), a class of anti-diabetic medications, are shown to reduce cardiovascular and renal events. This systematic review and meta-analysis aimed to assess whether SGLT2i could become a new treatment strategy for CKD for its renal protection and safety. METHODS: Based on predetermined criteria, a bibliographical search was performed on May 31, 2022, by searching the following databases: ISI Web of Science, Embase, PubMed, and the Cochrane Library. Statistical analysis was conducted to assess renal protection and safety of SGLT2i by using Cochrane Review Manager Version 5.3. RESULTS: Thirty randomised controlled trials fulfilled the inclusion criteria and were eligible for this meta-analysis. Our study found that the SGLT2i can sustainably reduce the urine albumin/creatinine ratio (UACR) at different time points and prevent the progression to macroalbuminuria. Before 24 weeks, SGLT2i can decrease the estimated glomerular filtration rate (eGFR) compared to the control group. Interestingly, after 24 weeks, SGLT2i can continuously maintain the increase in eGFR when compared with the control group. Furthermore, SGLT2i can reduce the event rates of incident or worsening nephropathy, a decline in estimated eGFR of ≥ 50%, doubling of serum creatinine level, acute renal failure and renal failure. Interestingly, the renoprotective effects of SGLT2i are independent of its glycemic effects. SGLT2i can reduce the morbidity rate of any related adverse events, any related severe adverse events and SGLT2i have not increased the event rates of urinary tract infection, bone fractures, amputation, and acute pancreatitis when compared with the control group. CONCLUSION: SGLT2i can protect renal function and are safe drug for CKD. SGLT2i are promising therapeutic agents for CKD patients.

Assessing pesticide uses with potentials for down-the-drain transport to wastewater in California.

Pesticides and degradates are ubiquitously detected in municipal wastewater influent in the United States. However, little detailed information exists on their sources. The aim of this study is to investigate California Pesticide Use Report (PUR) and sales data to identify pesticide uses with a high potential for indoor down-the-drain (DtD) transport. The DtD transport of pesticides could result from direct applications to drains and sewers or through indirect activities such as washing pets, treated textiles, laundries, and cleaning surfaces treated with pesticides. An initial screening on pesticide products registered in California with DtD potentials showed that fipronil, imidacloprid, and seven pyrethroids were pesticides of concern due to the relatively high sales in DtD use patterns and high toxicity to aquatic organisms; and thus prioritized for additional evaluation. Uses and sales data of products containing the selected pesticides were analyzed for mass of active ingredient applied with specific DtD pathways and by different user groups. Professional uses were retrieved from the PUR and consumer uses were estimated by comparing PUR data to sales data. Overall, approximately 38,615 kg fipronil, 44,561 kg imidacloprid, and 240,550 kg pyrethroids were used annually in California from 2011 to 2015 with some likelihoods of DtD transport. The shares of professional use ranged from 56% (cypermethrin) to 98% (cyfluthrin), depending on the pesticide, with the majority of the mass applied in and around structures and for some pesticides (imidacloprid and permethrin) on landscapes as well. The remaining mass was applied by consumers on various DtD sources, including pet treatments (fipronil, imidacloprid, and permethrin), treated textiles (permethrin), indoor-only uses (cypermethrin), and mixed indoor/outdoor or outdoor-only applications (other pyrethroids). Results from this study help elucidate the relative significance of specific DtD pathways and pesticide occurrence in California waste streams.