Explore the vast range of titles available.

The role of magnesium sulfate (MgSO 4 ) administration to prevent diabetic nephropathy (DN) by reducing insulin resistance (IR) and the relationship of this action with gender and the expression of NOX4 and ICAM1 genes in the parents and their offspring were studied. Males and females rat, and their pups were used. Type 2 diabetes induced by high-fat diet (HFD) administration and a low dose of streptozotocin. Animals were divided into the: non-treated diabetic (DC), the diabetic group received insulin (Ins), and the diabetic group received MgSO 4 . Two groups of parents received just a normal diet (NDC). Following each set of parents for 16 weeks and their pups for 4 months, while eating normally. We assessed the amount of water consumed, urine volume, and blood glucose level. The levels of glucose, albumin, and creatinine in the urine were also measured, as well as the amounts of sodium, albumin, and creatinine in the serum. Calculations were made for glomerular filtration rate (GFR) and the excretion rates of Na and glucose fractions (FE Na and FE G, respectively). The hyperinsulinemic-euglycemic clamp was done. NOX4  and  ICAM1  gene expressions in the kidney were also measured. MgSO 4 or insulin therapy decreased blood glucose, IR, and improved GFR, FE Na, and FE G in both parents and their offspring compared to D group. MgSO 4 improved NOX4 and ICAM1  gene expressions in the parents and their offspring compared to D group. Our results indicated that MgSO 4 could reduce blood glucose levels and insulin resistance, and it could improve kidney function.

Background The objective of this study was to examine and analyze differential methylation profiles in order to investigate the influence of hyper-methioninemia (HM) on the development of diabetic nephropathy (DN). Male Wistar rats, aged eight weeks and weighing 250–300 g, were randomly assigned into four groups: a control group (Healthy, n  = 8), streptozocin-induced rats (STZ group, n  = 8), HM + STZ group ( n  = 8), and the Tangshen Formula (TSF) treatment group (TSF group, n  = 8). Blood glucose levels and other metabolic indicators were monitored before treatment and at four-week intervals until 12 weeks. Total DNA was extracted from the aforementioned groups, and DNA methylation landscapes were analyzed via reduced representative bisulfite sequencing. Results Both the STZ group and HM + STZ group exhibited increased blood glucose levels and urinary albumin/creatinine ratios in comparison with the control group. Notably, the HM + STZ group exhibited a markedly elevated urinary albumin/creatinine ratio (411.90 ± 88.86 mg/g) compared to the STZ group (238.41 ± 62.52 mg/g). TSF-treated rats demonstrated substantial reductions in both blood glucose levels and urinary albumin/creatinine ratios in comparison with the HM + STZ group. In-depth analysis of DNA methylation profiles revealed 797 genes with potential therapeutic effects related to TSF, among which approximately 2.3% had been previously reported as homologous genes. Conclusion While HM exacerbates DN through altered methylation patterns at specific CpG sites, TSF holds promise as a viable treatment for DN by restoring abnormal methylation levels. The identification of specific genes provides valuable insights into the underlying mechanisms of DN pathogenesis and offers potential therapeutic targets for further investigation.

Multiple factors contribute to the risk of mortality from visceral leishmaniasis (VL), including, patient genotype, comorbidities, and nutrition. Many of these factors are influenced by socioeconomic biases. Visceral leishmaniasis (VL) is a potentially fatal disease caused mainly by Leishmania infantum in South America and Leishmania donovani in Asia and Africa. Disease outcomes have been associated with patient genotype, nutrition, age, sex, comorbidities, and coinfections. In this study, we examine the effects of parasite genetic variation on VL disease severity in Brazil. We collected and sequenced the genomes of 109 L. infantum isolates from patients in northeastern Brazil and retrieved matching patient clinical data from medical records, including mortality, sex, HIV coinfection, and laboratory data (creatinine, hemoglobin, and leukocyte and platelet counts). We identified genetic differences between parasite isolates, including single nucleotide polymorphisms (SNPs), small insertions/deletions (indels), and variations in genic, intergenic, and chromosome copy numbers (copy number variants [CNVs]). To describe associations between the parasite genotypes and clinical outcomes, we applied quantitative genetics methods of heritability and genome-wide association studies (GWAS), treating clinical outcomes as traits that may be influenced by parasite genotype. Multiple aspects of the genetic analysis indicate that parasite genotype affects clinical outcomes. We estimate that parasite genotype explains 83% chance of mortality (narrow-sense heritability [ h 2 ] = 0.83 ± 0.17) and has a significant relationship with patient sex ( h 2 = 0.60 ± 0.27). Impacts of parasite genotype on other clinical traits are lower ( h 2 ≤ 0.34). GWAS analysis identified multiple parasite genetic loci that were significantly associated with clinical outcomes; 17 CNVs were significantly associated with mortality, two with creatinine, and one with bacterial coinfection, jaundice, and HIV coinfection, and two SNPs/indels and six CNVs were associated with age, jaundice, HIV and bacterial coinfections, creatinine, and/or bleeding sites. Parasite genotype is an important factor in VL disease severity in Brazil. Our analysis indicates that specific genetic differences between parasites act as virulence factors, enhancing risks of severe disease and mortality. More detailed understanding of these virulence factors could be exploited for novel therapies. IMPORTANCE Multiple factors contribute to the risk of mortality from visceral leishmaniasis (VL), including, patient genotype, comorbidities, and nutrition. Many of these factors are influenced by socioeconomic biases. Our work suggests that the virulence of the infecting parasite is an important risk factor for mortality. We pinpoint some specific genomic markers that are associated with mortality, which can lead to a greater understanding of the molecular mechanisms that cause severe VL disease, to the identification of genetic markers for virulent parasites, and to the development of drug and vaccine therapies.

Purpose of Review Immune checkpoint inhibitor (ICI)-related myocarditis poses a major clinical challenge given its non-specific presentation, rapid progression, and high mortality rate. Here, we review the role of blood-based biomarkers in the clinical management of patients with ICI-related myocarditis. Recent Findings Myocardial injury, its unique pattern, and the co-occurrence with myositis are defining features of ICI-related myocarditis. Non-cardiac biomarkers, specifically creatinine phosphokinase, precedes the symptomatic presentation and is highly sensitive for diagnosing ICI-related myocarditis, making them useful screening biomarkers. Combined elevations in cardiac troponins and non-cardiac biomarkers improve the confidence of an ICI myocarditis diagnosis. High troponin and creatinine phosphokinase levels are strongly associated with severe outcomes. We propose biomarker-based algorithms for the monitoring and diagnosis of ICI-related myocarditis. Summary Biomarkers, such as cardiac troponins and creatine phosphokinase, can be used in combination in the monitoring, diagnosis, and prognostication of patients with ICI-related myocarditis.

HIV treatment and prevention as well as other chronic disease care can require regular kidney function assessment based on a creatinine test. To assess the costs of creatinine testing in a public health care system, we conducted activity-based costing during a HIV pre-exposure prophylaxis (PrEP) demonstration project in the Hhohho region of Eswatini. Resource use was assessed by a laboratory technician and valued with government procurement prices, public sector salaries, and own cost estimates. Obtaining a blood sample in a clinic and performing a creatinine test in a high-throughput referral laboratory (> 660,000 blood tests, including > 120,000 creatinine tests, in 2018) were estimated to have cost, on average, $1.98 in 2018. Per test, $1.95 were variable costs ($1.38 personnel, ¢39 consumables, and ¢18 other costs) and ¢2.6 were allocated semi-fixed costs (¢1.1 laboratory equipment, ¢0.85 other, ¢0.45 consumables, and ¢1.3 personnel costs). Simulating different utilization of the laboratory indicated that semi-fixed costs of the laboratory (e.g., equipment purchase or daily calibration of the chemistry analyzer) contributed less than variable costs (e.g., per-test personnel time and test reagents) to the average creatinine test cost when certain minimum test numbers can be maintained. Our findings suggest, first, lower creatinine testing costs than previously used in cost and cost-effectiveness analyses of HIV services and, second, that investment in laboratory equipment imposed a relatively small additional cost on each performed test in the high-throughput referral laboratory.

Evidence from multiple studies has revealed that it's meaningful to evaluate the clinical significance of CD146 because it's related to an early diagnosis of chronic renal failure as well as to the severity of illness and the patient's prognosis. The current study intended to evaluate the therapeutic effects of Shendibushen on the clinical parameters of blood and urine and on fibrosis in the kidney in a rat model, using simulated renal tissue fibrosis that was surgically induced with unilateral ureteral obstruction (UUO). Also, our research team intended to analyze the metabolic pathway activated by Shendibushen both in rat and human kidneys through use of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and the GeneNetwork. The aim is to discover if a connection existed between CD146 and key genes in these pathways. The research team conducted an animal study in Wistar rats. The rats were divided into 5 groups of 14 animals each: (1) blank control group, (2) sham control group, (3) model group, (4) Niaoduqing group, and (5) Shendibushen group. Three groups had UUO surgically induced-the model, Niaoduqing, and Shendibushen groups. The sham control group received sham surgery, and the blank control group received no surgery. The Shendibushen and Niaoduqing groups received the relevant capsules once a day at a fixed time, for a total of 28 days. The levels of serum creatinine, blood urea nitrogen, microalbuminuria, serum soluble CD146, and urinary soluble CD146 were measured on the 14th and 28th days after modeling the rats. The degree of renal interstitial fibrosis was examined by hematoxylin and eosin (HE) staining and Masson trichrome staining. The changes at transcriptome level were obtained by target tissue sequencing. The KEGG database was used to analyze the potential pathway activated by the Shendibushen treatment. The GeneNetwork analysis was used to validate the correlation and identify the connections between CD146 and the key genes of the potential pathways. Shendibushen capsules decreased the degree of renal interstitial fibrosis in the UUO rat model and reduced the serum creatinine, blood urea nitrogen, microalbumin, serum sCD146, and urinary sCD146 significantly compared to the model group (P < .05). Upon analysis of the metabolic pathways activated by Shendibushen, the study further verified, through use of the KEGG database, that CD146 activated the nuclear factor kappa B1 (NF-κB1) and transforming growth factor beta 1 (TGF-β1)/ SMAD family member 2 (SMAD2) pathways. CD146 could become an early indicator in clinical monitoring. CD146 has a function related to the NF-κB1and TGF-β1/ SMAD2 pathways under Shendibushen treatment.

Creatine Transporter Deficiency (CTD) is an inborn error of metabolism presenting with intellectual disability, behavioral disturbances and epilepsy. There is currently no cure for this disorder. Here, we employed novel biomarkers for monitoring brain function, together with well-established behavioral readouts for CTD mice, to longitudinally study the therapeutic efficacy of cyclocreatine (cCr) at the preclinical level. Our results show that cCr treatment is able to partially correct hemodynamic responses and EEG abnormalities, improve cognitive deficits, revert autistic-like behaviors and protect against seizures. This study provides encouraging data to support the potential therapeutic benefit of cyclocreatine or other chemically modified lipophilic analogs of Cr.

Background Although vitamin D deficiency is highly prevalent in the Middle East, very few studies have attempted to measure its health impact. Aims We aimed to assess whether vitamin D3 and calcium, either alone or in combination, have health benefit. Methods In a 2 × 2 factorial design double-blind, placebo-controlled trial, Community free living adults living in the city of Al Ain, UAE were randomly assigned to receive daily 2000 IU oral vitamin D3 alone, 600 mg calcium alone, oral vitamin D3 (2000 IU per day) combined with 600 mg calcium, or a placebo for 6 months. Primary outcomes were self-rated health and bone turnover markers. Results Of the 545 randomized, 277 subjects completed 6 months follow up. 25(OH)D levels marginally increased in the two groups received vitamin D3 alone or combined with calcium compared to the decline seen in those who received calcium supplement alone or a placebo. Sub-group analysis revealed that parathyroid hormone (PTH) concentration decreased and Calcium/creatinine ratio increased significantly in the combined vitamin D and Calcium group compared to the vitamin D alone or Calcium alone in contrast to the increase seen in the placebo group [ p  < 0.05 for between group difference at 6 months]. There were no statistically significant differences between the supplement and placebo groups at the 6 months follow-up in body weight, body mass index (BMI), blood pressure, body pains and general health. Conclusion PTH concentration decreased and calcium/creatinine ratio increased in subjects who received vitamin D and Calcium together compared to those who received vitamin D alone. Trial registration NCT02662491 , First registered on 25 January 2016 ( https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S00060CE&selectaction=Edit&uid=U0001M6P&ts=3&cx=scu4cb , Last update: 05 August 2019.

Evidence on the influence of patient characteristics on HbA treatment response for add-on medications in patients with type 2 diabetes (T2D) is unclear. This study aims to investigate the predictors of HbA treatment response for three add-on medications (sulfonylureas (SU), dipeptidyl peptidase-4 (DPP-4) and sodium-glucose cotransporter-2 (SGLT-2) inhibitor) in metformin monotherapy treated patients with T2D. This retrospective cohort study was conducted using the electronic health record data from six primary care clinics in Singapore. A total of 9748 adult patients with T2D on metformin monotherapy receiving SU, DPP-4 or SGLT-2 add-on were 1:1 propensity score matched to patients receiving other add-on medications. Patient demographics, laboratory results, diabetes related complications, comedications, and treatment response at two endpoints (HbA reduction ≥ 1% at 6th month, HbA goal attainment < 7% at 12th month) were examined. Multiple logistic regression analyses were used to identify patient characteristics associated with the treatment responses. After matching, there were 1073, 517, and 290 paired cohorts of SU, DPP-4 and SGLT-2 respectively. Besides baseline HbA , patients with longer hypertension disease duration and higher cholesterol HDL were associated with better treatment response to SU medication add-on. Lower estimated glomerular filtration rate (eGFR), and angiotensin-II receptor medications were associated with better treatment response to DPP-4 add-on. Lower cholesterol HDL, higher creatinine serum, absence of renal complications and beta-blockers medications were associated with better treatment response to SGLT-2 add-on. The cholesterol HDL, creatinine serum, eGFR, hypertension disease duration, angiotensin-II receptors and beta-blockers class of medications can influence the HbA treatment response for SU, DPP-4 and SGLT-2 add-on medications. Knowing the patients' characteristics that influence treatment response can assist in guiding clinical decisions when selecting the appropriate add-on medication, ultimately helping to prevent the development of diabetes-related complications.

Objective Our study evaluated the renal safety of abemaciclib plus endocrine therapy (ET) with bisphosphonate as a treatment option for hormone receptor positive, human epidermal growth factor receptor 2 (HER‐2) negative (HR+/HER2−) advanced breast cancer (ABC), especially with bone metastasis. Methods Data were collected from HR+/HER2− ABC patients who received abemaciclib with ET between March 2021 and May 2022 in a single medical center in China. We performed an analysis of the change in serum creatine (Cr) and creatine clearance (CrCl), time to first abnormal Cr value, and Common Terminology Criteria for Adverse Events grade of increased creatinine. Results A total of 210 patients were included in the final analysis, with a median age of 56 years and a median weight of 65 kg. Any grade laboratory‐assessing increased Cr occurred in 87.1% of patients, while CrCl rarely went down to 30 ml/min. Associations between start dose with grade of increased Cr and menopausal status with alert value, which is defined as creatinine clearance <30 ml/min, were indicated. Conclusion This study shows that abemaciclib combined with bisphosphonate would be safe for renal function in HR+/HER2− ABC patients with bone metastases.