Urinary Levels Research Articles

Mechanisms by which Mettl3 regulates pericyte-myofibroblast transdifferentiation through PI3K/AKT signaling pathway

Objective: To investigate the role and underlying mechanisms of methyltransferase (Mettl) 3 in the process of angiotensin Ⅱ (Ang Ⅱ)-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis. Methods: C57BL/6J mice were used, in cell experiments, mouse renal pericytes were isolated and cultured using magnetic bead sorting. These pericytes were then induced to transdifferentiate into myofibroblasts with 1×106 mmol/L Ang Ⅱ, which was the Ang Ⅱ group, while pericytes cultured in normal conditions served as the control group. Successful transdifferentiation was verified by immunofluorescence staining, Western blotting, and real-time reverse transcription PCR (RT-qPCR) for α-smooth muscle actin (α-SMA). The levels of m6A modifications and related enzymes (Mettl3, Mettl14), Wilms tumor 1-associated protein (WTAP), fat mass and obesity protein (FTO), ALKBH5, YTHDF1, YTHDF2, YTHDC1, YTHDC2, YTHDC3 were assessed by Dot blot, RT-qPCR and Western blot. Mettl3 expression was inhibited in cells using lentivirus-mediated Mettl3-shRNA transfection, creating sh-Mettl3 and Ang Ⅱ+sh-Mettl3 groups, while lentivirus empty vector transfection served as the negative control (Ang Ⅱ+sh-NC group). The impact of Ang Ⅱ on pericyte transdifferentiation was observed, and the expression of downstream phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway proteins, including PI3K, AKT, phosphorylated AKT at serine 473 (p-AKT (S473)), and phosphorylated AKT at threonine 308 (p-AKT (T308)), were examined. PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time. The reversibility of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was assessed by adding the AKT activator SC79 to the Ang Ⅱ+sh-Mettl3 group. In animal experiments, mice were divided into these groups: sham group (administered 0.9% sterile saline), Ang Ⅱ group (infused with Ang Ⅱ solution), sh-Mettl3 group (injected with Mettl3 shRNA lentivirus solution), Ang Ⅱ+sh-Mettl3 group (infused with Ang Ⅱ solution and injected with Mettl3 shRNA lentivirus solution), and Ang Ⅱ+sh-Mettl3+SC79 group (administered Ang Ⅱ solution and Mettl3 shRNA lentivirus, with an additional injection of SC79). Each group consisted of six subject mice. Blood pressure was measured using the tail-cuff method before and after surgery, and serum creatinine, urea, and urinary albumin levels were determined 4 weeks post-surgery. Kidney tissues were collected at 28 days and stained using hematoxylin-eosin (HE) and Masson's trichrome to assess the extent of renal fibrosis. Results: Primary renal pericytes were successfully obtained by magnetic bead sorting, and intervened with 1×106 mmol/L Ang Ⅱ for 48 hours to induce pericyte-to-myofibroblast transdifferentiation. Dot blot results indicated higher m6A modification levels in the Ang Ⅱ group compared to the control group (P<0.05). RT-qPCR and Western blot results showed upregulation of Mettl3 mRNA and protein levels in the Ang Ⅱ group compared to the control group (both P<0.05). In the Ang Ⅱ+sh-Mettl3 group, Mettl3 protein expression was lower than that in the Ang Ⅱ group, with reduced expression levels of α-SMA, vimentin, desmin, fibroblast agonist protein (FAPa) and type Ⅰ collagen (all P<0.05). Compared to the control group, PI3K mRNA expression level was elevated in the Ang Ⅱ group, along with increased p-AKT (S473) and p-AKT (T308) expressions. In the Ang Ⅱ+sh-Mettl3 group, PI3K mRNA expression and p-AKT (S473) and p-AKT (T308) levels were decreased (all P<0.05). The half-life of PI3K mRNA was shorter in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ+sh-NC group (2.34 h vs. 3.42 h). The ameliorative effect of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was reversible by SC79. Animal experiments showed higher blood pressure, serum creatinine, urea, and 24-hour urinary protein levels, and a larger fibrosis area in the Ang Ⅱ group compared to the sham group (all P<0.05). The fibrosis area was smaller in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ group (P<0.05), but increased again upon addition of SC79. Conclusion: Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.

The Association between Cadmium Exposure and Thyroid Function in Animals: A Systematic Review.

Several studies have indicated an association between cadmium (Cd) exposure and the induction of thyroid dysfunction in animal models. Objective and Aims: There are inconsistent findings on the effect of Cd on the thyroid gland. Therefore, this systematic study was designed to determine the association between changes in thyroid function markers and Cd exposure in animals. The search was performed on Scopus, PubMed, Web of Science and databases, and Google Scholar until May 2023. Studies on the relationship between Cd exposure and fish's thyroid function were conducted on rodents and fish. In total, 171 articles were obtained from the main databases using the search strategy mentioned in this study. Finally, 24 articles were selected according to our inclusion criteria for systematic studies. The findings indicated an increase/decrease or no change in triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) levels in rodents, fish, and animals exposed to Cd. Our findings indicated an association between Cd exposure and thyroid dysfunction in rodents, fish, and other animals. However, the association between urinary and blood Cd levels and thyroid function remains unclear in humans because of controversial findings and a lack of strong mechanistic evidence. We perform large cohort human studies to the answer to this question.

Association between organophosphate esters individual and mixed exposure with the risk of hyperlipidemia and serum lipid levels among adults in Wuhan, China.

Toxicologic studies reported that organophosphate esters (OPEs) may disrupt lipid metabolism, thus affecting serum lipid levels. However, epidemiological evidence regarding the association between OPEs and the risk of hyperlipidemia (HPL) as well as serum lipid levels is scarce. In the present study, our aim was to investigate the impact of individual and mixed OPE exposure on HPL. A total of 1981 Chinese adults were involved based on a cross-sectional design. Overall, we found a positive association between bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and the risk of HPL. Bis(1-chloro-2-propyl) phosphate (BCIPHIPP) showed a positive association with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). BDCIPP, diphenyl phosphate (DPHP), di-ocresyl phosphate and di-p-cresyl phosphate (Docp&Dpcp), and 4-hydroxyphenyl-diphenyl phosphate (4-OH-DPHP) exhibited a negative association with high-density lipoprotein cholesterol (HDL-C). In stratified analyses, BDCIPP and BCIPHIPP were significantly correlated with the increased risk of HPL in the age ≤ 45 group. Bis(2-butoxyethyl) phosphate (BBOEP) was in relationship with an elevated risk of HPL in the subgroup of BMI < 24kg/m2. BDCIPP was also positively associated with HPL in men. Quantile-based g computation (qgcomp) and generalized weighted quantile sum regression (gWQS) models demonstrated a negative association between OPEs mixed exposure and HDL-c in the total population, as well as a positive effect of them on HPL in the subgroup of age ≤ 45years, which is consistent with the individual analyses. Furthermore, joint effect analyses revealed that participants with detected BDCIPP urinary levels and unhealthy lifestyles had the highest risk of HPL. Our findings offer evidence supporting the correlation between exposure to OPE and the risk of HPL, necessitating further prospective studies for validation.

Moderating effect of a sodium-rich diet on the association between long-term exposure to fine particulate matter and blood lipids in children and adolescents

BackgroundSeveral studies reported that exposure to higher levels of fine particulate matter (PM2.5) was associated with deteriorated lipid profiles in children and adolescents. However, whether a sodium-rich diet could modify the associations remains unknown. We aimed to examine the associations of long-term exposure to PM2.5 with blood lipids in children and adolescents, and further examine the effect modification by dietary and urinary sodium levels based on a multi-community population in China.MethodsThe 3711 study participants were from a cross-sectional study, which interviewed children and adolescents aged 6 to 17 years across Sichuan Province, China between 2015 and 2017. Blood lipid outcomes including blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were assessed. Information on daily dietary sodium consumption was estimated with a semi-quantitative food frequency questionnaire (FFQ), and urinary sodium was used as an internal exposure biomarker. A linear regression model was applied to estimate the associations of prior 2-years’ average exposure to ambient PM2.5 with blood lipids. The effect modification by dietary and urinary sodium was examined by stratified analyses.ResultsThe participants from rural areas had higher levels of daily sodium consumptions. The results of multivariable regression analysis indicated that per 10 μg/m3 incremental change in PM2.5 was associated with a 1.56% (95% confidence interval 0.90%—2.23%) and a 2.26% (1.15%—3.38%) higher blood TC and LDL-C levels, respectively. Among the study participants with higher levels of dietary sodium or urinary sodium, exposure to higher levels of PM2.5 was significantly associated with deteriorated lipid profiles. For example, each 10 μg/m3 incremental change in exposure to PM2.5 was correlated with a 2.83 (-4.65 to -0.97) lower percentage decrease in blood HDL-C levels among the participants who were from the highest quartile of urinary sodium levels. While, these associations changed to be nonsignificant in the participants who were from the lowest quartile of dietary sodium levels.ConclusionExposure to higher levels of PM2.5 was associated with deteriorated blood lipid levels in children and adolescents. It is noteworthy that these associations might be ameliorated through the adoption of a low-sodium dietary regimen.

Organochlorine pesticide residues and urinary arsenic and fluoride levels in mothers and their newborns who are residents of rural areas in Durango State, Mexico

ABSTRACT Maternal and prenatal exposure to organochlorine pesticides (OCP), arsenic (As), and fluoride (F−) is a critical public health concern. The present study assessed serum OCP residues and urinary As and F− levels in mother and newborn pairs who are residents of rural areas of Durango State, Mexico, from August 2018 to February 2019. Levels of OCP, As, and F− were measured in serum and urine samples by Gas chromatography – Tandem mass spectrometry (GC – MS/MS), Hydride generation – Atomic fluorescent spectrometry (HG-AFS, and ion-selective electron analysis (ISE), respectively, in 60 binomial mothers – newborns. Dieldrin, endrin aldehyde, and endosulfan-II were significantly higher in newborns than in mothers (p ˂0.05). Meanwhile, no significant differences were observed for As and F− concentrations between mother – newborn pairs. Differences were observed in ∑Dienes and ∑DDTs comparing newborns with normal and low birth weights and a positive relationship in ƩDienes, ƩChlordanes, and ƩDDTs between mother and newborn pairs (p ˂ 0.05). These findings highlight the importance of extensive research regarding the influence of pollution.

Dal rene all'occhio: che cos'è la TINU?

An eight-year-old boy presenting with interstitial nephritis (abdominal pain, microhematuria, glycosuria, proteinuria, elevated urinary beta2-microglobulin levels) was eventually diagnosed with TINU syndrome (tubulointerstitial nephritis associated with uveitis) following the late onset of uveitis.

Activation of the inflammasome and pyroptosis cascade in podocytes of patients with minimal change disease

Abstract Background In contrast to childhood minimal change disease (MCD), adult-onset MCD frequently recurs and requires prolonged immunosuppressive therapy. Accordingly, an investigation of the pathogenesis of adult MCD is required. MCD is usually accompanied by severe dyslipidaemia. Oxidized low-density lipoprotein (ox-LDL) is known to function in a damage-associated molecular pattern (DAMP) through CD36, triggering the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome and programmed cell death called pyroptosis. However, the relationship between MCD pathogenesis and NLRP3 inflammasome/pyroptosis activation via CD36 is not fully understood. Methods We conducted comprehensive histological and clinical evaluations by analyzing renal biopsy (RBx) specimens and urine samples obtained from 26 patients with MCD. These samples were compared to control kidneys from 15 transplant donors and urine samples from 15 healthy volunteers. Results The number of podocytes was lower in the MCD group than in the control group. Urinary ox-LDL levels were higher in the MCD group than in the control group. Immunofluorescence staining revealed that NLRP3 and CD36 were upregulated in MCD podocytes. Urinary interleukin (IL)-18 levels increased in patients with MCD. Steroid therapy performed before RBx appeared to maintain the podocyte number and reduce urinary ox-LDL and IL-18 levels. Conclusion In MCD, the NLRP3 inflammasome and pyroptosis cascade seem to be activated via upregulation of CD36 in podocytes, associated with increased urinary ox-LDL. Elevated urinary IL-18 levels suggest that pyroptosis may occur in MCD. Further research is required to confirm the significance of the podocyte NLRP3 inflammasome/pyroptosis in MCD.

Socio-Demographic Patterning of Urinary Mono-ethyl Phthalate Levels among Children and Adults in the U.S. (1999-2018)

Abstract Background: Phthalates are chemicals used to make plastics flexible and durable. They are found in clothes, varnishes, toys, pharmaceuticals, containers, and personal care products. Phthalates make their way into human bodies through ingestion, inhalation, and dermal absorption, and the breakdown of them within bodies can be measured as phthalate metabolites in urine. They pervade all aspects of the environment and our bodies, contributing to negative health outcomes. Education, SES, and gender influence where people live (their built environment), time-use patterns, occupation, treatment at healthcare facilities, and purchasing patterns; all affect phthalate exposures, and therefore phthalate metabolites in urine are also likely to vary by socio-demographic characteristics. Objectives: To study how levels of mono-ethyl phthalate (MEP) in urine samples of children and adults in the U.S. vary among key socio-demographic groups. We expect that disadvantaged groups will have the highest levels of phthalates. Methods: Using quantitative methods, we analyze levels of urinary MEP as a biomarker indicating exposure to phthalates. Within the National Health and Nutrition Examination Survey (NHANES) (1999-2018) participants, we compare MEP levels across the following socio-demographic groups: age, gender, education, race/ethnicity, family income to poverty level, citizenship status. We use multivariate regression models to adjust results for differences in other factors that potentially influence MEP levels. Results: Historically disadvantaged groups – women, Non-Hispanic Blacks, Mexican Americans, Other Hispanics, and those with lower educational attainment – have higher predicted phthalate levels, even when holding all covariates that could be related to differences in phthalate levels by socio-demographic factors constant. Discussion: Our results suggest differences in socio-demographic factors could be leading to unequal exposures to phthalates and MEP excretions in their urine. This research contributes to understanding health experiences outside of clinical definitions, drawing attention to structural vulnerabilities and the way that environmental toxicants are embodied in individuals and populations.

Increased water intake dilutes protective uromodulin levels in urine and results in increased rates of pyelonephritis in a murine model.

Urinary tract infections (UTIs) rank among the most prevalent infections in humans, carrying substantial implications for public health. Women experiencing recurrent UTIs are often advised to boost their fluid intake to help eliminate bacteria. In this study, we explored the impact of elevated fluid consumption during UTIs using a mouse model of pyelonephritis. UTI was induced in 8-10 w female BALB/cJ-mice by surgically injecting Escherichia coli (O6:K13:H1) into the bladder whereafter mice were randomized to gel food (GF) or regular chow. Immune response and infection severity were determined 24-h post-infection. Invitro bacterial growth (OD600) was determined in urine from mice or from human volunteers. Gel feeding increased urine output (1.40 ± 0.77 μL min-1, p < 0.01) and diluted the urine (668.7 ± 177 mOsmol kg-1, p < 0.0001) compared to controls on regular chow (urine output: 0.34 ± 0.27 μL min-1, osmolality: 1439 ± 473.5 mOsmol kg-1). Mice on GF had a higher risk of pyelonephritis (87.5%) and more severe infections (26.22 ± 9.88 CFU mg-1 tissue) compared to controls (43.75%; 3.87 ± 3.56 CFU mg-1, p < 0.01). Correspondingly, the growth of E.coli was markedly reduced at osmolalities above 1200 mOsmol kg-1 compared to 600 mOsmol kg-1 and GF mice had lower urine levels of uromodulin (13.70 ± 1.89 μg mL-1, p < 0.01) compared to controls (24.65 ± 2.70 μg mL-1). Increased water intake and urine flow in mice will markedly increase the risk of pyelonephritis. The increased risk may reflect reduced urine uromodulin combined with optimized growth conditions for E. coli. The study does not immediately support the notion that established UTIs can be eliminated by increased water intake.

The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and prevalence of urinary stones in US adults: a cross-sectional NHANES study.

This study examines the association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and urinary stones in American adults. We conducted a cross-sectional study utilizing the 2007-2018 National Health and Nutrition Examination Survey (NHANES) data set. The prevalence of urinary stones was determined based on patient-reported experiences of renal colic. We converted NHHR to natural logarithm (ln-NHHR) to align it better with our statistical analyses. Our analysis methods included weighted multivariate logistic regression, generalized additive model (GAM), and application of smoothed curves to better elucidate the association between ln-NHHR and the prevalence of urinary stones. In addition, we conducted subgroup analyses and employed multiple imputation for sensitivity analyses. This study involved a total of 30,903 participants, with a 9.97% prevalence of urinary stones and reported colic experience. Elevated ln-NHHR levels were linked with a higher likelihood of urinary stones (OR = 1.20, 95% CI 1.07-1.35). Smooth curve fitting revealed an inverted U-shaped relationship, pinpointing a significant increase in urinary stone risk at ln-NHHR levels below 1.43 (OR = 1.40, 95% CI 1.19-1.64, p < 0.001). Notably, this correlation was stronger among Non-Hispanic Whites and those married or living with a partner. Multiple imputation analyses strengthened the confidence in our results. Our findings suggest a reverse U-shaped association between urinary stone occurrence and NHHR level, with a positive association at ln-NHHR < 1.43. This correlation was more pronounced in the Non-Hispanic White population and among those married or living with a partner.

Environmental Cadmium Exposure Induces an Increase in Systolic Blood Pressure by Its Effect on GFR

Chronic exposure to the nephrotoxic metal pollutant, cadmium (Cd), has been associated with hypertension, but the mechanism by which it raises blood pressure is not understood. We hypothesize that exposure to Cd reduces the glomerular filtration rate (GFR), which in turn causes a rise in blood pressure. Data were collected from 447 Thai subjects with a mean age of 51.1 years, of which 48.8% had hypertension, 15.4% had diabetes, and 6.9% had an estimated GFR (eGFR) below 60 mL/min/1.73 m2 (low eGFR). More than half (58.8%) and 23.9% had moderate and severe tubular proteinuria, respectively. The mean blood and urinary Cd concentrations were 2.75 and 4.23 µg/L, respectively. Doubling of body burden of Cd increased the prevalence odds ratios (POR) for low eGFR and severe tubular proteinuria 41% and 48%, respectively. The POR for hypertension rose twofold in those with blood Cd levels of 0.61–1.69 µg/L or urinary Cd excretion levels ≥ 0.98 µg/g creatinine. In the hypertensive group, the eGFR was inversely associated with age (β = −0.517), the Cd excretion rate (β = −0.177), and diabetes (β = −0.175). By mediation analysis, an increase in SBP was attributable totally to the effect of Cd on GFR. Thus, blood pressure appeared to rise as GFR fell. This finding is consistent with the well-known role of the kidney in long-term blood pressure regulation, and explains a universally high prevalence of hypertension among patients with low eGFR.

Sodium selenite attenuates inflammatory response and oxidative stress injury by regulating the Nrf2/ARE pathway in contrast-induced acute kidney injury in rats

BackgroundContrast-induced acute kidney injury (CI-AKI) is an acute renal complication that occurs after intravascular contrast agent administration. Sodium selenite (SS) is an inorganic source of Se and has potent antioxidant properties. This study intends to examine its anti-inflammatory and antioxidant effects in CI-AKI.MethodsA rat CI-AKI model was established with the pretreatment of SS (0.35 mg/kg). Hematoxylin-eosin staining was employed for histopathological analysis of rat kidney specimens. Biochemical analysis was conducted for renal function detection. Tissue levels of oxidative stress-related markers were estimated. Reverse transcription-quantitative polymerase chain reaction revealed the mRNA levels of proinflammatory cytokines. Western blotting showed the Nrf2 signaling-related protein expression in the rat kidney.ResultsSS administration alleviated the renal pathological changes and reduced the serum levels of serum creatinine, blood urea nitrogen, neutrophil gelatinase-associated lipocalin, cystatin C, and urinary level of kidney injury molecule-1 in CI-AKI rats. SS attenuated oxidative stress and inflammatory response in CI-AKI rat kidney tissues. SS activated the Nrf2 signaling transduction in the renal tissues of rats with CI-AKI.ConclusionSS ameliorates CI-AKI in rats by reducing oxidative stress and inflammation via the Nrf2 signaling.

The association between diet quality indices and oxidative stress biomarkers in male footballers and healthy active controls

ObjectiveThe aim of the present study was the association between the relationship between Dietary Quality Index-International (DQI-I) and Healthy Eating Index (HEI) and the urinary levels of F2alpha-isoprostane (F2a-IP) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) was investigated as indicators of oxidative stress.ResultsBased on HEI (low, moderate, and good), the diet quality of both groups was classified as moderate. In all participants, HEI (β=-0.29; P = 0.04) and DQI-I (β=-0.46; P = 0.005) were inversely associated with 8-OHdG. Furthermore, a negative correlation was found between HEI (mean β=-3.53; P = 0.04) and DQI-I (mean β=-5.53; P = 0.004) with F2a-IP. The quality of the footballers’ diet was higher than that of the control group. Following a high-quality diet, which is rich in antioxidants, is likely to effectively reduce oxidative stress.

Total airway mechanics and fractional exhaled nitric oxide levels of children living in banjihas (semi-basements).

The ISAAC phase III study in Korea found a higher incidence of wheezing illnesses among residents in basements or semi-basements. This study investigates the link between living in banjihas (semi-basements) and airway resistance and Th2 airway inflammation in Korean children, compared to those on higher floors. We assessed 575 fifth- and sixth-grade students (aged 10-12) in an inner-city area of South Korea. The study utilized impulse oscillometry to measure small and total airway resistance (Rrs20-5 and Rrs0, respectively) and Fractional Exhaled Nitric Oxide (FeNO) measurements to evaluate airway inflammation. We also considered a range of biological and environmental factors, including allergen sensitization, serum 25-hydroxyvitamin D levels, and urinary metabolites like VOCs, bisphenol, and triclosan. Participants were categorized by living floors: banjihas, first-fifth floors, and sixth floors or higher. Twenty-five children (4.3%) lived in banjihas, 311 (54.1%) on the first to fifth floor, and 239 (41.6%) on the sixth floor or above. Despite similar levels of allergen sensitization and urinary pollutant metabolite levels across all groups, banjiha dwellers showed significantly higher total airway resistance (adjusted &1: 0.633, 95%CI: 0.156, 1.109; P = 0.009) and a greater prevalence of elevated FeNO levels (> 35 ppb) (P = 0.033). These findings persisted after adjusting for critical factors like height, gender, BMI z-score, and birth conditions. Children in banjihas exhibit elevated airway resistance and FeNO levels independently of allergen sensitization or pollution exposure, underscoring the necessity for enhanced focus on their respiratory health in such living conditions.

Establishing the Interrelations of the Laboratory Parameters in the Gut-Kidney Axis in Cats with Signs of Triple Phosphate Urolithiasis

Introduction. Efficient treatment of the feline urolithiasis much depends on the early diagnosis of the disease, however, the diagnostic algorithm of this type of pathology is extremely poor due to the various reasons, in particular, it does not take into account the interrelations in the gut-kidney axis. Analysis of the state of gastrointestinal tract functioning and the composition of the gut microbiota can improve the potential of diagnosing the urolithiasis, predict the risk, improve the prognosis and choose the correct treatment strategy. The aim of this publication is to establish the interrelations of the laboratory parameters in the gut-kidney axis in cats with struvite urolithiasis with the signs of cystolithiasis.Materials and Methods. The objects of the research were the outbred cats with the triple phosphate urolithiasis with the signs of cystolithiasis: 1st experimental group — females; 2nd experimental group — neutered males; the control group — clinically healthy animals of both sexes. The laboratory and clinical examinations of sick animals included: ultrasonography of abdominal organs; macroscopic and biochemical urine tests; microscopy of urine sediment and urine culture test without determination of antibiotic sensitivity; macroscopic, microscopic and simple chemical examinations of freshly excreted feces; bacteriological culture test of rectal flushes without determination of antibiotic sensitivity.Results. In the urine of cats of the experimental groups, under the activity of gram-negative microorganisms Escherichia coli (0.03±0.01×106 CFU (colony forming units) and 1.00±0.03×106 CFU) and gram-positive microorganisms Staphilococcus intermedius (1.05±0.07×106 CFU and 1.00±0.08×107 CFU) there were recorded within the microscope field of view: alkalization, development of hypersthenuria, proteinuria, hypercalciuria, hematuria, including microhematuria and leukocyturia, crystalluria. The results of coprological examinations in sick cats indicated the presence of stercobilin, well-digested muscle fibres, undigested and digested cellulose, extracellular and intracellular starch, as well as impurities of non-food origin (wool). The data of microbiological examinations of feces indicated the growth of Escherichia coli (1.00±0.05×105 CFU and 1.04±0.08×107 CFU). Along with the cystolytiasis, the acoustic shadowing of the gastrointestinal tract organs in the experimental animals revealed the hyperechogenicity of liver capsule and parenchyma and heterogeneity of the pattern.Discussion and Conclusion. The revealed character of the laboratory parameter changes in the experimental animals, such as the increase of protein and creatinine levels in urine and growth of Escherichia coli in feces, proved the existence of the pathogenetic relationship between the urogenital tract lesion caused by the gram-negative microorganisms and the gut microbiota in the gut-kidney axis. The results of our study of the sick animals’ urine indicated on the infection of the urogenital tract with the urease-producing microorganisms, which led to the alkalization of urine and formation of the infection struvite stones. Urolithiasis, in turn, had an impact on the gut microbiome due to the topographic proximity of the urogenital and gastrointestinal tracts: examination of feces in cats of the experimental group had confirmed the disorder of gastrointestinal tract functioning due to dysbiotic processes in the large intestine.

ShengqingJiangzhuo capsule ameliorates diabetic nephropathy by improving Keap1/Nrf2 signaling pathway.

Diabetic nephropathy (DN) is a major contributor to end-stage renal failure, and lacking effective treatment options. Shengqing Jiangzhuo capsule (SQJZJN), a traditional Chinese medicine prescription with known efficacy in chronic kidney disease, has not been thoroughly investigated for its potential in DN protection. Eight-week-old male C57BLKS/J db/db, C57BLKS/J db/m mice, and human glomerular mesangial cell (HMC) cells cultured with high glucose were used as experimental models in this study. The in vivo investigation showed that SQJZJN can significantly ameliorate renal pathological damage, reduce serum creatinine, and lower urinary microalbumin levels in db/db mice. In vitro, SQJZJN treatment mitigated advanced glycation end products (AGEs) and reactive oxygen species (ROS), leading to a reduction in renal cell apoptosis. Mechanistically, SQJZJN activated the Keap1/Nrf2/ARE pathway by promoting nuclear factor erythroid-derived 2-related factor 2 (Nrf2), γ-glutamylcysteine synthetase heavy subunit (γ-GCS), and Heme oxygenase-1 (HO-1) expressions, while decreasing Kelch-like ECH-associated protein 1 (KEAP1) expressions. These findings suggest that SQJZJN exerts a protective effect on DN, potentially through the activation of the Keap1/Nrf2/ARE pathway.

The ANGPTL4-HIF-1α loop: a critical regulator of renal interstitial fibrosis

BackgroundRenal interstitial fibrosis (RIF) is a progressive, irreversible terminal kidney disease with a poor prognosis and high mortality. Angiopoietin-like 4 (ANGPTL4) is known to be associated with fibrosis in various organs, but its impact on the RIF process remains unclear. This study aimed to elucidate the role and underlying mechanisms of ANGPTL4 in the progression of RIF.MethodsIn vivo, a chronic kidney disease (CKD) rat model of renal interstitial fibrosis was established via intragastric administration of adenine at different time points (4 and 6 weeks). Blood and urine samples were collected to assess renal function and 24-h urinary protein levels. Kidney tissues were subjected to HE and Masson staining for pathological observation. Immunohistochemistry and real-time quantitative PCR (qRT‒PCR) were performed to evaluate the expression of ANGPTL4 and hypoxia-inducible factor-1α (HIF-1α), followed by Pearson correlation analysis. Subsequently, kidney biopsy tissues from 11 CKD patients (6 with RIF and 5 without RIF) were subjected to immunohistochemical staining to validate the expression of ANGPTL4. In vitro, a fibrosis model of human renal tubular epithelial cells (HK2) was established through hypoxic stimulation. Subsequently, an HIF-1α inhibitor (2-MeOE2) was used, and ANGPTL4 was manipulated using siRNA or plasmid overexpression. Changes in ANGPTL4 and fibrosis markers were analyzed through Western blotting, qRT‒PCR, and immunofluorescence.ResultsANGPTL4 was significantly upregulated in the CKD rat model and was significantly positively correlated with renal injury markers, the fibrotic area, and HIF-1α. These results were confirmed by clinical samples, which showed a significant increase in the expression level of ANGPTL4 in CKD patients with RIF, which was positively correlated with HIF-1α. Further in vitro studies indicated that the expression of ANGPTL4 is regulated by HIF-1α, which in turn is subject to negative feedback regulation by ANGPTL4. Moreover, modulation of ANGPTL4 expression influences the progression of fibrosis in HK2 cells.ConclusionOur findings indicate that ANGPTL4 is a key regulatory factor in renal fibrosis, forming a loop with HIF-1α, potentially serving as a novel therapeutic target for RIF.

Association of 1-bromopropane exposure with asthma prevalence: A Korean National Health and Nutritional Examination Survey (2020–2021)-based study1

Exposure to 1-bromopropane (1-BP) is an emerging environmental and health concern due to its increasing environmental prevalence. Although the health effects of 1-BP exposure have been under-recognized, current evidence suggests the possibility of adverse pulmonary health effects due to 1-BP exposure. However, the association between 1-BP exposure and asthma prevalence remains unclear. Thus, we aimed to examine the association between 1-BP exposure and asthma prevalence in the general population. Using nationally representative data, we explored the potential impacts of indoor air quality (IAQ)-related behavioral factors on the level of 1-BP exposure. This study included 1,506 adults from the 2020-2021 Korea National Health and Nutrition Examination Survey. The prevalence of asthma was based on self-reported physician-diagnosed asthma. Urinary N-acetyl-S-(n-propyl)-L-cysteine (BPMA) levels were measured as a biomarker of 1-BP exposure, using high-performance liquid chromatography-mass spectrometry. Multiple logistic regression models were performed to investigate the associations between urinary BPMA metabolite and asthma prevalence after adjusting for potential confounders. Log-linear multiple regression models were used to examine the association between IAQ-related behavior and urinary BPMA concentration. Forty-seven individuals with asthma and 1,459 without asthma were included. Individuals in the highest quartile of urinary BPMA concentration had a 2.9 times higher risk of asthma than those in the lowest quartile (odds ratio [OR]: 2.85, 95% confidence interval [CI]: 1.02-7.98). The combination of natural and mechanical ventilation was associated with a reduced urinary BPMA concentration. Our findings suggest that 1-BP exposure is associated with the prevalence of asthma in adults and revealed higher urinary levels of BPMA in our study population compared to those in other countries. Given the emerging importance of IAQ, actively managing and modifying behavioral patterns to reduce 1-BP exposure in indoor environments could substantially attenuate the risk of asthma-related to 1-BP exposure.

Endocrine-disrupting effects of bisphenol-A, thiamethoxam, and fipronil in hormone-naïve transmen compared to cis-women.

Current evidence suggests that the etiology of gender dysphoria (GD) is multifactorial: this, however, remains unclear. Endocrine-disrupting chemicals (EDCs) are one of the etiological hypotheses. In this study, we aimed to evaluate the urinary levels of bisphenol A (BPA), thiamethoxam, and fipronil in hormone-naïve transmen compared with case-matched cis-women as well as the relation between sex hormone levels and EDCs. Drug-naïve transmen diagnosed with GD and who were referred from the psychiatry outpatient clinic to the outpatient clinic of the Department of Endocrinology, Marmara University Hospital, were included in the study. These individuals were assessed for eligibility; 38 drug-naïve transmen and 22 cis-women were recruited as the control group. After anthropometric evaluation laboratory tests for FSH, LH, total testosterone, and estradiol were carried out, spot urine samples were collected to evaluate the urine metabolic excretion of BPA, thiamethoxam, and fipronil. We found that androgens, total testosterone, androstenedione, and DHEAS levels were significantly higher in transmen than in cis-women. Thiamethoxam was considerably higher in cis-women than in transmen, whereas fipronil and BPA levels were similar in both groups. A negative correlation was found between thiamethoxam and testosterone and between thiamethoxam and BPA levels. The available data suggest that the EDCs that we are most exposed to in our lives are not the only factor in GD development. Even transmen who have not taken hormone replacement have high testosterone levels; however, the mechanism has not as yet been elucidated. The challenge is to determine whether this is a factor leading to GD or a condition that develops in common with GD.

Association of the hemoglobin, albumin, lymphocyte, and platelet score with the risk of Erectile dysfunction: a cross-sectional study

Erectile dysfunction (ED) is related to nutritional and inflammatory factors. The hemoglobin, albumin, lymphocyte, and platelet score (HALP), a new index reflecting the nutritional and inflammatory status, has been associated with a higher risk of diabetic retinopathy, particularly at lower values (≤ 42.9). However, studies focusing on the relationship between HALP and ED risk are scarce. Hence, this study aimed to investigate the association between HALP and ED. Data were extracted from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2004. Based on self-reported data, participants were classified into either the ED group or the non-ED group. Next, the HALP score was categorized into four quartiles (Q1–4). Weighted multivariate regression analysis was performed to assess the relationship between categorical HALP and ED risk. Additionally, restricted cubic spline (RCS) analysis was conducted to examine the association between continuous HALP scores and ED risk. Furthermore, subgroup analyses were conducted to examine the association between categorical HALP and the risk of ED based on age, as well as the status of hypertension, diabetes and cardiovascular disease. Finally, a mediation analysis was carried out to investigate the mediating effect of HALP and related parameters on the association between urinary cobalt levels and ED. Initially, the data of 21,161 participants were collected. After implementing the inclusion and exclusion criteria, 3406 participants were included in the final analyses. Weighted multivariate regression analysis demonstrated that the Q4 HALP group was associated with a lower risk of ED (OR 0.96, 95% confidence intervals 0.92–1.00, P = 0.037). Meanwhile, RCS analysis showed that HALP was nonlinearly associated with the risk of ED. In addition, subgroup analyses demonstrated that participants in the Q3/4 HALP group had a significantly lower ED risk than those in the Q1 group among patients aged ≥ 50 years, as well as those with hypertension and diabetes. Lastly, mediation analysis revealed that HALP and its associated parameters had a marginal average causal mediation effect on the relationship between urinary cobalt levels and ED risk (P > 0.05). In US adults, high HALP scores were correlated with a lower risk of ED. The relationship was more pronounced in participants aged ≥ 50 years with hypertension and diabetes. Furthermore, HALP and its parameters may not mediate the association between urinary cobalt levels and ED risk.