Development Of Chronic Disease Research Articles

Immune signature and therapeutic approach of natural killer cell in chronic liver disease and hepatocellular carcinoma.

Natural killer (NK) cells are one of the key members of innate immunity that predominantly reside in the liver, potentiating immune responses against viral infections or malignant tumors. It has been reported that changes in cell numbers and function of NK cells are associated with the development and progression of chronic liver diseases (CLDs) including non-alcoholic fatty liver disease, alcoholic liver disease, and chronic viral hepatitis. Also, it is known that the crosstalk between NK cells and hepatic stellate cells plays an important role in liver fibrosis and cirrhosis. In particular, the impaired functions of NK cells observed in CLDs consequently contribute to occurrence and progression of hepatocellular carcinoma (HCC). Chronic infections by hepatitis B or C viruses counteract the anti-tumor immunity of the host by producing the sheddases. Soluble major histocompatibility complex class I polypeptide-related sequence A (sMICA), released from the cell surfaces by sheddases, disrupts the interaction and affects the function of NK cells. Recently, the MICA/B-NK stimulatory receptor NK group 2 member D (NKG2D) axis has been extensively studied in HCC. HCC patients with low membrane-bound MICA or high sMICA concentration have been associated with poor prognosis. Therefore, reversing the sMICA-mediated downregulation of NKG2D has been proposed as an attractive strategy to enhance both innate and adaptive immune responses against HCC. This review aims to summarize recent studies on NK cell immune signatures and its roles in CLD and hepatocellular carcinogenesis and discusses the therapeutic approaches of MICA/B-NKG2D-based or NK cell-based immunotherapy for HCC.

Celiac Disease: The Importance of Studying the Duodenal Mucosa-Associated Microbiota

There is increasing evidence indicating that changes in both the composition and functionality of the intestinal microbiome are closely associated with the development of several chronic inflammatory diseases, with celiac disease (CeD) being particularly noteworthy. Thanks to the advent of culture-independent methodologies, the ability to identify and quantify the diverse microbial communities residing within the human body has been significantly improved. However, in the context of CeD, a notable challenge lies in characterizing the specific microbiota present on the mucosal surfaces of the intestine, rather than relying solely on fecal samples, which may not fully represent the relevant microbial populations. Currently, our comprehension of the composition and functional importance of mucosa-associated microbiota (MAM) in CeD remains an ongoing field of research because the limited number of available studies have reported few and sometimes contradictory results. MAM plays a crucial role in the development and progression of CeD, potentially acting as both a trigger and modulator of the immune response within the intestinal mucosa, given its proximity to the epithelial cells and direct interaction. According to this background, this review aims to consolidate the existing literature specifically focused on MAM in CeD. By elucidating the complex interplay between the host immune system and the gut microbiota, we aim to pave the way for new interventions based on novel therapeutic targets and diagnostic biomarkers for MAM in CeD.

Ten tips on how to care for your CKD patients in episodes of extreme heat

Abstract Climate change is responsible for approximately 75% of extreme heat events throughout the world. Heat events are associated with an increased risk for acute kidney injury (AKI), which contributes to the development of chronic kidney disease (CKD) and cardiovascular events. Patients with CKD are especially vulnerable to heat stress for a variety of reasons. A disproportionate percentage of patients with CKD live in poverty, experience homelessness, mental illness, or disabilities, work outside, or are elderly, all demographics that overlap with populations most susceptible to episodes of extreme heat. Therefore, it is reasonable to conclude that exposure to episodes of extreme heat can lead to the progression of CKD and increases morbidity and mortality. Given these concerns, clinicians must be prepared to recognize complications of heat in CKD patients promptly and to help patients appropriately acclimate. We propose the following tips for clinicians to care for their CKD patients effectively during extreme heat days.

#2705 Hypertension as a risk factor for mortality and the development of chronic kidney disease after an episode of acute kidney injury in the elderly

Abstract Background and Aims Acute kidney injury (AKI) is a real public health problem due to its severity and its consequences in the short, medium and long term. Hypertension is a very common disease in our country. The association between hypertension and acute and chronic renal failure is not well studied in our country, and given the lack of data, we proposed to carry out this study and even more so the elderly, who are fragile subjects with multiple illnesses. Method We undergone a retrospective study which was carried out in the nephrology department of Fattouma Bourguiba hospital in Monastir. We included patients aged > 65 years, who had an AKI with full recovery who had been hospitalized between January 2002 and December 2015. Our study aimed to assess the impact of hypertension on mortality and the development of chronic kidney disease (CKD) after an episode of AKI. Results Our population was made up of 67 men and 60 women, 30.1% had multiple comorbidities. Pre renal Aki represented the predominant mechanism of AKI which was retained in our study with a rate of 40% and dehydration as the main aetiology in 70 patients. In the short term, 15 patients had progressed to CKD. The mean overall survival in our study was 159 months with a high risk of mortality in elderly (patients aged >65 years), who had multiple comorbidities, hypertensive, diabetics, with vascular disease, Charlson Comorbidity index >5, who presented with hyperkalaemia >5.5 and pre renal mechanism of the AKI episode. In the medium term and the long term, 4 and 2 patients developed CKD respectively. Hypertension was a factor in poor prognosis and mortality in elderly subjects after an episode of acute kidney injury (p=0.005). Conclusion Hypertension is a real public health problem impacting the short, medium and long term prognosis of patients who have had an episode of AKI with full recovery.

#2333 Risk of NDI and CKD in individuals treated with lithium

Abstract Background and Aims Nephrogenic diabetes insipidus (NDI) is a known side effect of lithium treatment. Lithium has also been associated with the development of chronic kidney disease (CKD). The aims of this study were to examine the risk factors for NDI among persons on lithium treatment and the association of NDI and other risk factors with the development of chronic kidney disease (CKD). Method This was a retrospective cohort study of all persons in Iceland using lithium in the years 2003-2018. Lithium exposure was defined as at least one lithium prescription or at least one serum lithium measurement with a detectable lithium level. Patients with affective disorders (ICD-10 codes F30-F39) attending the outpatient clinics of Landspitali–The National University Hospital Mental Health Services in 2014-2016, without lithium exposure, served as controls. NDI was defined as concomitant serum sodium (SNa) >144 mmol/L and urine specific gravity (SG) <1.005; individuals with no SNa measurement after 2003 were excluded from the analysis. CKD stages 3-5 were defined according to the KDIGO guidelines for CKD as estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. The eGFR was calculated from serum creatinine (SCr) using the CKD-EPI equation. The analysis of incident CKD was limited to the period when standardized SCr measurements had become available, in 2008-2018. Individuals with <2 SCr measurements after 2008 and those with CKD stages 3-5 before 2008 were excluded. In addition, this analysis specifically examined the relationship between the mean serum lithium concentration and the development of CKD, comparing those not exposed to lithium to 3 groups of lithium users with a mean serum lithium concentration of 0.3-0.59, 0.6-0.79 and 0.8-0.99 mmol/L. Acute kidney injury (AKI) was defined according to the SCr component of the KDIGO criteria for AKI, and other comorbid conditions were defined based on ICD-9 and ICD-10 diagnosis codes. Multivariable Cox regression with time-dependent covariables was used for risk assessment. Results In the analysis of the development of NDI, the group exposed to lithium consisted of 2252 individuals, of whom 58 (2.6%) met the criteria for NDI compared with 13 (1.0%) of the 1272 controls. When compared with those without lithium exposure. the risk of NDI was lithium concentration dependent, with a hazard ratio (HR) of 1.22 (95% CI, 0.50–2.98), 5.52 (95% CI, 2.81–10.85) and 10.03 (95% CI, 4.51–22.27) for groups with a mean lithium concentration of 0.3–0.59, 0.6–0.79 and 0.8–0.99 mmol/L, respectively. A previous diagnosis of CKD was also a significant risk factor (HR 3.00 [95% CI, 1.50–6.12]). In the CKD analysis, the group of lithium users comprised 1401 individuals. Of those, 192 (13.7%) developed CKD, compared with 39 (2.8%) of the 1406 controls. Analysis adjusted for initial eGFR showed that NDI was a significant risk factor for CKD (HR 1.90 [95% CI, 1.03-3.54]). Other significant risk factors were mean lithium concentration with HR of 1.25 (95% CI, 0.82–1.91), 2.84 (95% CI, 1.94–4.15) and 5.11 (95% CI, 3.22–8.07) for the groups with a mean lithium concentration of 0.6–0.79 and 0.8–0.99 mmol/L, respectively. Other significant risk factors were age per year (HR 1.03 [95% CI, 1.02–1.05]), diabetes (HR 1.62 (95% CI, 1.08–2.46]) and history of AKI (HR 1.92 [95% CI, 1.33–2.77]). Conclusion Lithium use is associated with NDI in a concentration-dependent manner. Long-term lithium treatment is associated with a risk of CKD, which also is concentration dependent, in patients with bipolar and unipolar mood disorders. NDI may be an important risk factor for CKD.

#2025 Associations of obesity, sarcopenia, and sarcopenic obesity with chronic kidney disease development in the elderly population

Abstract Background and Aims Previous studies indicate that sarcopenia and obesity increase the risk of chronic kidney disease (CKD) in middle-aged populations. Despite noting reverse epidemiology for cardiovascular disease in the elderly, the relationship between sarcopenic obesity and CKD incidence in older populations is insufficiently explored. This study aims to assess whether obesity modifies the association between sarcopenia and CKD development in elderly adults with preserved kidney function. Method Elderly individuals aged over 65 with preserved kidney function among UK Biobank participants were examined. Participants with an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² or albuminuria were excluded. The individuals were categorized based on the presence of sarcopenia and obesity, with sarcopenia defined as hand grip strength <27 kg in males and <16 kg in females. Obesity was defined as having a BMI of 30 kg/m² or higher, and sarcopenic obesity was identified in those with concomitant obesity and sarcopenia. The development of CKD was determined using ICD-10 codes in claim and death register records. Results A total of 62,735 individuals were assessed, with a mean age of 66.9 ± 1.5 years and 44.3% being male. Sarcopenia was identified in 8,648 individuals (13.8%), while obesity was present in 13,075 individuals (20.8%), resulting in a 3.29% prevalence of sarcopenic obesity. Over a median follow-up of 13.3 years (770,179 person-years), 5,567 participants (8.9%) developed CKD. A significant interaction between sarcopenia and obesity was observed for CKD development (P < 0.001). Incident CKD rates were 7.8% in non-obese without sarcopenia, 9.5% in obese without sarcopenia, 11.7% in non-obese with sarcopenia, and 14.7% in obese with sarcopenia. Compared to the non-obese without sarcopenia group, hazard ratios (HRs) and 95% confidence intervals (CIs) were 1.26 (1.16-1.37) in the obese without sarcopenia group, 1.55 (1.45-1.65) in the non-obese with sarcopenia group, and 2.02 (1.80-2.27) in the obese with sarcopenia group. After adjusting for confounding factors, the risk of CKD development in the obese without sarcopenia group was comparable to the non-obese without sarcopenia group (HR, 1.07, 95% CI, 0.99-1.15). However, elevated risk persisted in participants with sarcopenia and was most accentuated in those with sarcopenic obesity (non-obese with sarcopenia; HR, 95% CI, 1.22 [1.11-1.34]; obese with sarcopenia, 1.32 [1.15-1.50]). Conclusion Sarcopenia, not obesity, was significantly associated with an increased risk of chronic kidney disease (CKD) development in elderly individuals, with sarcopenic obesity showing the highest risk elevation for incident CKD in this group.

#1215 Association between dietary magnesium intake and incident chronic kidney disease

Abstract Background and Aims Recent studies suggest a close association between low serum magnesium levels and kidney injury. However, whether dietary magnesium intake relates with kidney function is not well known. In this study, the relationship of dietary magnesium intake with the development of chronic kidney disease (CKD) was evaluated. Method This observational prospective study screened 210,965 European adults aged 40-70 who underwent dietary questionnaire from April 2009 to June 2012 in UK Biobank cohort. Participants with underlying CKD (baseline eGFR < 60 mL/min/1.73 m² or urine albumin-to-creatinine ratio >30 mg/g/Cr) or implausible energy intake (reported energy intake < 1.1 × basal metabolic rate [BMR] or 2.5 × BMR) were excluded. Dietary magnesium intake was assessed through online 24-hour recall dietary questionnaire and adjusted for energy intake using residual method. The participants were categorized into quartile according to energy-adjusted dietary magnesium intake. Primary outcome was incident CKD diagnosed through ICD-10 and OPCS-4 codes. Incident CKD defined as eGFR < 60 mL/min/1.73 m² was also assessed as an additional primary outcome in the sub-cohort with primary care creatinine follow-up data. Results A total of 114,916 participants was included in the final analysis. The median age was 57.0 (IQR, 50.0-63.0) years and 56.8% were female. Median magnesium intake amount per person was 345.6 (IQR, 296.8-402.5) mg/day. During a 1,095,128.6 person-year follow-up, CKD outcome occurred in 3,337 patients. Incidence of CKD was progressively lower in patients with higher magnesium intake (3.2%, 2.9%, 2.8%, and 2.7% in Q1-4, respectively). Cox regression analysis revealed that the hazard ratios (HRs) for incident CKD decreased in a stepwise manner towards higher magnesium intake quartiles (2Q: HR, 0.89; 95% CI, 0.81-0.98; 3Q: HR, 0.87; 95% CI, 0.0.79-0.95; 4Q: HR, 0.84; 95% CI, 0.76-0.92) relative to 1Q (P for trend < 0.001). This association was maintained even after adjustments were made for confounding factors. Similar results were observed with eGFR-defined CKD outcome (2Q: adjusted HR [AHR], 0.75; 95% CI, 0.64-0.89; 3Q: AHR, 0.73; 95% CI, 0.61-0.87; 4Q: AHR, 0.70; 95% CI, 0.58-0.85) relative to 1Q (P for trend < 0.001). Conclusion Higher intake of dietary magnesium may relate with lower risk of incident CKD in adults with normal kidney function.

#970 The impact of VEGF signalling pathway inhibitors and/or immune checkpoint inhibitors on kidney function over time

Abstract Background and Aims Treatment with vascular endothelial growth factor signalling pathway inhibitors (VSPI) and immune checkpoint inhibitors (ICI) has transformed outcomes in advanced kidney cancer. VSPI and ICI can both independently cause side effects that are risk factors for development or progression of chronic kidney disease (CKD). We analysed estimated glomerular filtration rate (eGFR) decline in people with kidney cancer following treatment with VSPI or ICI. Methods We linked routine healthcare databases in the West of Scotland, UK (spanning 2010–2020, population 1.4 million) to identify adults with advanced kidney cancer who received a VSPI and/or ICI. In the two years following therapy initiation, eGFR slope (defined as annualised rate of change in eGFR) was modelled using linear mixed-effects models for the whole group and subgroups of people who had nephrectomy, metastatic cancer and a baseline eGFR <60 mL/min/1.73 m² prior to systemic therapy. Additional outcomes were studied using competing risk regression considering the competing risk of death: 40% decline in eGFR, de-novo proteinuria (urine albumin creatinine ratio >3 mg/mmol), and progression to eGFR <15 mL/min/1.73 m2. The risk of all-cause mortality was estimated with Cox regression models. Results We studied 357 adults (62.5% male; median age 63.0 years, IQI 55.0-71.0) with kidney cancer who were treated with either VSPI and/or ICI. The median baseline eGFR before systemic therapy was 74.6 mL/min/1.73 m² (58.3-91.9) and most received VSPI monotherapy (86.0%). On average, eGFR remained relatively stable over time (average annual increase +1.03 mL/min/1.73 m²/year: 95% CI −1.64 to +3.70, p = 0.2). People who had nephrectomy prior to systemic therapy demonstrated the largest average increase in eGFR (+2.30 mL/min/1.73 m²/year: 95% CI −1.66 to + 6.26). People with baseline eGFR <60 mL/min/1.73 m² prior to systemic therapy had a small decline (−1.02 mL/min/1.73 m²/year: 95% CI −6.55 to +4.50) in eGFR (Fig. 1). A ≥40% decline in eGFR occurred in 82 people (23.0%) within one year of starting systemic therapy. People with diabetes were more likely to experience a ≥40% decline in eGFR (subdistribution HR 1.89: 95% CI 1.05-3.41, p = 0.04). A decline in eGFR to <15 mL/min/1.73 m² or kidney failure with replacement therapy was found in 4 (1.1%) people. Among the 75 people assessed for proteinuria, 30.2% developed de-novo microalbuminuria. Median overall survival was 1.36 years (IQI 1.11-1.75 years), but this was longer in people who had nephrectomy prior to systemic therapy: 2.13 years (IQI 1.82–2.57 years). A 40% acute or chronic decline in eGFR was not associated with increased hazards of death on univariable or multivariable analysis (adjusted HR: 1.11: 95% CI 0.85-1.46, p = 0.4). Conclusion Despite case series and prescribing guidelines highlighting adverse impact of VSPI/ICI therapy on kidney function, our results demonstrate that there is no significant impact on the average change in eGFR but highlights that people with diabetes are at higher risk of clinically significant renal events. With appropriate monitoring, more widespread use of these agents in patients with renal impairment may be warranted.

#1493 Upregulated miR-205 as a biomarker of diet-induced obesity-related glomerulopathy

Abstract Background and Aims Obesity is a modifiable risk factor for the development and progression of chronic kidney disease (CKD). Pathways through which obesity might cause renal disease are not completely understood, as not all obese subjects develop CKD. In terms of deepening the knowledge of the preliminary steps of obesity-related renal damage, our group has developed a diet-induced obese murine model with obesity related glomerulopathy (ORG). The objective of this study was to investigate ORG at a cellular, structural and transcriptomic level as a way to discover the triggering pathogenic phenomena of ORG and evaluate potential biomarkers. Method Thirty Wistar rats were randomized into two groups: control rats (n = 15), which were fed with standard diet (SD) and study rats (n = 15), which were fed with high-fat diet (HFD). After 10 weeks, weight, parameters of kidney function, renal histological features, transcriptomic changes, miRNA and mRNA isolation were compared. Results HFD gained significantly more weight (55.8%) than SD(29.2%), p = 0.001. Albuminuria was also significantly higher in HFD (10,384.04) compared with SD (5,845.45), p = 0.001. HFD rats showed typical lesions of early-stages of ORG, with a predominance of mesangial matrix increase (MMI) and podocyte hypertrophy (PH). All histologic lesions correlated with genes differentially expressed (DE) in kidneys of HFD group and, both MMI and PH, also correlated with specific miRNAs DE in the urine of HFD group. The functional analysis showed 4 miRNAs DE in the kidneys of HFD group that negatively regulates PTEN gene, which promotes podocyte endocytosis of lipids in ORG. The electronic microscope confirmed the spaces of lipid vacuoles in the podocytes of HFD rats. Between those 4 miRNAs DE, miR-205 was also found to be upregulated in the urine of HFD group. Conclusion Wistar rats fed with HFD for 10 weeks developed early-stages of ORG, with a specific targetome of miRNAs and gene expression. The upregulation of miR-205 in kidney and its isolation in urine is associated with lipid endocytosis of podocytes, which takes place in the early-stages of ORG and could become a plausible biomarker of early-stages of ORG and open new avenues for future therapeutics research.

#1029 Factors associated with chronic kidney disease in patients with recurrent kidney stones: a case-control study

Abstract Background and Aims Kidney stones have been described in multiple studies as an independent risk factor for chronic kidney disease (CKD). However, this relationship remains partially understood, and there is limited local, regional, and national information available. While common factors contribute to both kidney stones and CKD development, other factors favoring CKD occurrence in patients with recurrent renal lithiasis have been reported. This study aimed to identify factors associated with chronic kidney disease in patients with recurrent renal lithiasis in the city of Cartagena, Colombia. Method This was an observational nested case-control study within a cohort, where cases were patients diagnosed with recurrent kidney stones who developed CKD during follow-up, and controls were patients with recurrent kidney stones without CKD during follow-up. The cohort comprised all adult patients with recurrent kidney stones between 2010 and 2019, without an initial diagnosis of CKD, and with a minimum follow-up period of two years or more. Data on demographic variables (age, gender, type of insurance), clinical factors (overweight, history of hyperuricemia, diabetes mellitus, hypertension, dyslipidemia, alcohol consumption, smoking, exercise habits), and variables related to recurrent kidney stones (course of kidney stones, onset time of CKD, metabolic disorders, history of renal colic, stone localization, number, and size) were collected. Variables associated with the development of chronic kidney disease were identified using association measures via the chi-square test. Variables of clinical and statistical significance were further analyzed for association using multivariable logistic regression. Results The study included 31 cases and 39 controls, with mean ages of 65.2±11.5 and 51.8±14.6 years, respectively (p=0.00002). The duration of recurrent kidney stones was 174.7±148.6 and 163.3±129.5 months for cases and controls (p=0.738). The onset time of CKD was 61.1±35.4 months. Among cases, 93.5% were men, 77.4% were hypertensive, and 67.9% had dyslipidemia, significantly differing from the controls (see Table 1). There were no differences between cases and controls concerning the duration of recurrent kidney stones, type of health insurance, overweight status, hyperuricemia, diabetes mellitus, exercise habits, metabolic study alterations, history of renal colic, renal stone localization, number, and size. The difference was borderline for alcohol consumption and smoking habits. Multivariable logistic regression, incorporating variables with statistical significance (age, gender, hypertension, alcohol consumption, smoking habit) into the model, revealed that higher age corresponds to a greater risk of CKD (Odds ratio 1.052; 95% CI, 1.003 to 1.103). Furthermore, the male gender exhibited a 5.5 times higher likelihood of suffering from CKD (Odds ratio 5.5; 95% CI, 1.2 to 26.5). Conclusion In patients with recurrent kidney stones, higher age, and male gender were identified as factors associated with the development of CKD.

Tuberculosis as an interdisciplinary problem: a case of occupational damage to the organs of the genitourinary system

In the Russian Federation, genitourinary tuberculosis ranks third in the structure of extrapulmonary tuberculosis. Timely recognition of genitourinary tuberculosis is usually difficult. The authors analyzed a case of occupational infection with tuberculosis of the genitourinary system by a phthisiologist. The clinical observation ended with a clinical cure for tuberculosis of the genitourinary system, however, with the outcome in chronic prostatitis, chronic post-tuberculosis pyelonephritis with the development of chronic kidney disease. It is shown that the timely establishment of a connection between urinary syndrome and epidemiological, including professional anamnesis, contributes to the timely establishment of the professional nature of the disease. With untimely diagnosis and late initiation of treatment of tuberculosis of the genitourinary system, serious complications can develop up to the destruction of the kidney with complete loss of its function, which leads to disability and loss of ability to work. If tuberculosis of the genitourinary system is suspected, experts recommend conducting a study of urine sediment, prostate secretion to determine the deoxyribonucleic acid of mycobacterium tuberculosis by polymerase chain reaction. Any doubt in case of nonspecific inflammation of the genitourinary system should be interpreted in favor of tuberculosis with further in-depth examination and dynamic monitoring.

Comprehensive analysis of the gut microbiota in patients with chronic obstructive pulmonary disease of varying severity-A prospective, observational study

Accumulating evidence has highlighted the influence of the gut microbiota on lung immunity. We examined the effects of changes in intestinal microecology on the development of Chronic Obstructive Pulmonary Disease (COPD) and identified microbial biomarkers for acute exacerbations of COPD (AECOPD). Fecal samples were collected from 30 patients with stable COPD, 30 patients with AECOPD, and 10 healthy individuals. Fecal microbiological profiles were analyzed using 16S rRNA gene sequencing. The results showed a distinct difference in the bacterial community composition between the AECOPD, COPD, and healthy control groups. The COPD and AECOPD groups had higher levels of Firmicutes but lower levels of Bacteroidetes compared to the healthy control group at the phylum level. At the genus level, there was an increased abundance of Lachnoclostridium, Alistipes, Streptococcus, and Prevotella in COPD and AECOPD patients. Increasing levels of Lachnoclostridium and Prevotella may indicate an acute exacerbation of COPD. This study identified specific microbial biomarkers associated with AECOPD and characterized the composition of gut microbiota in patients with AECOPD.

The 3'UTR Polymorphisms in the NLRP3 Gene Associated with the Risk of COPD and Their Putative Effects on the microRNA Mechanism.

Aims: Evaluating the association between a single nucleotide polymorphism in the 3' untranslated region (3'UTR) of the miRNA binding site of the NLRP3 gene and the occurrence and development of chronic obstructive pulmonary disease (COPD) and providing information to aid in the early detection and treatment of COPD. Materials and Methods: The regulatory single nuclear polymorphisms (SNPs) located in NLRP3 3'UTR were searched by using the dbSNP database and miRNA binding site prediction database. Meanwhile, samples from COPD patients and healthy controls in the same period were used for verification. The clinical baseline information of all subjects was collected, and the transcription level and protein expression level of NLRP3 and the expression level of inflammatory factors downstream of NLRP3 were detected. The effects of SNPs' single nucleotide changes on the transcription and expression of inflammatory factors were analyzed. Results: The study included 418 participants (249 in the COPD group and 169 in the control group). NLRP3 SNPs with miRNA binding sites include rs10754558 (G > C), rs1664774076 (ATAT > del), and rs1664775106 (C > G). Furthermore, two genotypes, GCG and GCA, were discovered to have a linkage mutation at 3'UTR 459-461. COPD susceptibility is tightly associated with the expression of the rs1664774076 del/del genotype, and the risk of COPD increased by 2.770 times (p = 0.003). Type 459-461 GCA was substantially related to the likelihood of developing COPD at various stages (p < 0.05). Except for rs10754558, all homozygous mutants increased NLRP3 mRNA and protein levels. NLRP3 had the greatest area under the receiver operating characteristic (ROC) curve for predicting the development and diagnosis of COPD when compared with its downstream inflammatory variables (AUC = 0.9291). Conclusions: The NLRP3 rs1664774076 del/del genotype is a COPD susceptibility gene, and the GCA genotype at 459-461 can be used as an early predictor of COPD exacerbation. The NLRP3 3'UTR polymorphism may alter the loss of miRNA binding sites, leading to an increase in NLRP3 expression. In the development of COPD, NLRP3 has a better diagnostic value than traditional inflammatory factors. The Clinical Trials Registration number Z: protocol KY01-2020-11-06.

Chronic venous diseases and obesity: pathogenetically based treatment and prevention options

This literature review analyzes relationships and correlations between obesity and chronic venous diseases. The search of scien tific publications was carried out in the Cochrane Library, PubMed, Medscape and Medline databases in accordance with the PRISMA guidelines. The review includes only publications, which were particularly relevant to our focus of research and where a significance difference between “experience and control” groups was found based on the results of statistical analysis. All studies included in the analysis defined obesity as a body mass index of 30.0 kg/m2 or more, and overweight as a BMI from 25 to 30 kg/m2 according to the criteria of the World Health Organization. The findings of publication analysis show that excess body weight, and especially obesity, is a major independent risk factor for the development and progression of chronic venous diseases and their complications. In addition, a direct cause-and-effect relationship between body weight and the severity of chronic venous insufficiency was observed. Increased intra-abdominal pressure associated with the visceral fat deposition is one of the key features of the pathogenesis of chronic venous diseases in patients with overweight and obesity. In this context, bariatric surgery, after which weight loss correlates with falling into a lower clinical class of chronic venous diseases is the most effective method for improving phlebological status. Along with bariatric surgery, the pharmacotherapeutic options are considered in patients with chronic venous diseases with underlying overweight and burdened comorbidities anamnesis. In this regard, the role of hesperidin combined and diosmin that have been shown to be most effective phlebotropic drug is discussed. Recent studies demonstrate that hesperidin has independent pluripotent properties, among which the mechanisms of action of this substance on lipid metabolism accompanied by a decrease in subjects’ body weight and visceral fat volume are a matter of interest. After completion of full-fledged clinical studies this action of hesperidin can be implemented in various treatment-and-prophylactic protocols on the management of patients with chronic venous diseases, related to underlying overweight and morbid obesity. Venarus® contains two micronized components hesperidin and diosmin at standardized dosages: 10% hesperidin and 90% diosmin, which can be used as an argument in favour of choosing this drug to treat patients with chronic venous diseases, related to underlying obesity or overweight.

Neutrophil-to-lymphocyte ratio associated with renal function in type 2 diabetic patients.

Type 2 diabetes mellitus (T2DM) is a leading risk factor for the development and progression of chronic kidney disease (CKD). However, an accurate and convenient marker for early detection and appropriate management of CKD in individuals with T2DM is limited. Recent studies have demonstrated a strong correlation between the neutrophil-to-lymphocyte ratio (NLR) and CKD. Nonetheless, the predictive value of NLR for renal damage in type 2 diabetic patients remains understudied. To investigate the relationship between NLR and renal function in T2DM patients. This study included 1040 adults aged 65 or older with T2DM from Shanghai's Community Health Service Center. The total number of neutrophils and lymphocytes was detected, and NLR levels were calculated. CKD was defined as an estimated glomerular filtration rate ≤ 60 mL/min/1.73 m². Participants were divided into four groups based on NLR levels. The clinical data and biochemical characteristics were compared among groups. A multivariate logistic regression model was used to analyze the association between NLR levels and CKD. Significant differences were found in terms of sex, serum creatinine, blood urea nitrogen, total cholesterol, and low-density lipoprotein cholesterol among patients with T2DM in different NLR groups (P < 0.0007). T2DM patients in the highest NLR quartile had a higher prevalence of CKD (P for trend = 0.0011). Multivariate logistic regression analysis indicated that a high NLR was an independent risk factor for CKD in T2DM patients even after adjustment for important clinical and pathological parameters (P = 0.0001, odds ratio = 1.41, 95% confidence intervals: 1.18-1.68). An elevated NLR in patients with T2DM is associated with higher prevalence of CKD, suggesting that it could be a marker for the detection and evaluation of diabetic kidney disease.

Evaluation of antioxidant and anti-inflammatory activity and identification of bioactive compound from the marine diatom, Odontella aurita extract

Increased production of reactive oxygen species (ROS) leads to oxidative stress, with its damaging effect extending to the mitochondria and plasma membrane. Further, prolonged inflammation can result in chronic disease development. The marine microdiatom Odontella aurita is recognized for its potential in food and pharmaceutical development. Moreover, it contains antioxidant and anti-inflammatory properties. However, studies regarding the efficacy of their varying extract forms and their underlying mechanisms remain scarce. Therefore, this study aims to explore the antioxidant and anti-inflammatory effects of Odontella aurita extracts obtained using various extraction methods (hot water, 70% ethanol, and chloroform:methanol (CM)). Among the three Odontella aurita extracts, the CM extract demonstrated superior efficacy in protecting RAW 264.7 cells from H2O2-induced cytotoxicity. It significantly lowered the levels of ROS and enhanced the expression of superoxide dismutase and glutathione peroxidase. Furthermore, the CM extract outperformed other extracts in inhibiting LPS-induced nitric oxide production, reducing mRNA levels in nitric oxide synthase, cyclooxygenase, and the proinflammatory cytokines interleukin IL-1β, IL-6, TNFα. Additionally, CM extract effectively suppressed the activation of NF-κB/IκBα and JAK2-STAT3 in LPS-induced RAW 264.7 cells. HPLC–UV analysis revealed a remarkable 33-fold higher fucoxanthin content in CM compared to the ethanol extract. GC–MS analysis identified elevated levels of cholest-5-en-3-ol, phytol, eicosapentaenoic acid methyl ester, methyl palmitate, palmitoleic acid methyl ester, and neophytadiene in the CM extract. These findings suggest that Odontella aurita CM extract is a promising antioxidant candidate for preventing or treating inflammatory diseases, consequently emphasizing its potential for further development.Graphical

Prevalence, Medicaid use and mortality risk of low FEV1 in adults aged 20–35 years old in the USA: evidence from a population-based retrospective cohort study

BackgroundThe prevalence, Medicaid use and mortality risk associated with low forced expiratory volume in 1 s (FEV1) among young adults aged 20–35 years are not well understood, despite its potential...

Cardiovascular Dysautonomy as a Sequel of SARS COV 2. Case Series

The impact of COVID-19, caused by the SARS-CoV-2 virus, a pandemic that originated in Wuhan, China, can lead to serious complications, in addition to mild symptoms, with special interest in the autonomic nervous system (ANS). Damage to the ANS by SARS-CoV-2 can cause dysautonomia, an imbalance between the sympathetic and parasympathetic system, with unclear mechanisms such as cytokine storm, excessive inflammation, and virus neurotropism. A significant sequelae of COVID-19 is cardiac dysautonomia, which affects heart rate, blood pressure and other autonomic reflexes, causing postural tachycardia, orthostatic hypotension, arrhythmias and fatigue. There is decreased heart rate variability (HRV) in patients, suggesting dysautonomia. Long COVID syndrome can also include cardiac dysautonomia. To diagnose cardiac autonomic neuropathy, at least two of six criteria must be met, such as an SDNN less than 50 ms and an RMSSD less than 15 ms. The cases of cardiac dysautonomia below present several of these criteria met. Methods to evaluate cardiac dysautonomia include the COMPASS 31 scale and the orthostatic hypotension questionnaire (OHQ), but more research is still needed, especially in Mexico. The case study shows that those who followed non-pharmacological recommendations such as cardiovascular exercise, increased water intake and BMI control had improvement, while cases that did not follow these recommendations did not show significant improvements. Cardiac dysautonomia is a post-COVID-19 sequelae with high prevalence, highlighting the importance of non-invasive methods for its diagnosis. Even without symptoms, people can have this sequelae, so it is important to suspect cardiovascular disorders. The need for early intervention and monitoring of hygienic-dietary measures is emphasized to avoid the worsening and chronicity of cardiac dysautonomia, with the hope of preventing the development of chronic diseases and fatal outcomes.

Associations of systemic inflammatory regulators with CKD and kidney function: evidence from the bidirectional mendelian randomization study

BackgroundPrevious observational studies have reported that systemic inflammatory regulators are related to the development of chronic kidney disease (CKD); however, whether these associations are causal remains unclear. The current study aimed to investigate the potential causal relationships between systemic inflammatory regulators and CKD and kidney function.MethodWe performed bidirectional two-sample Mendelian randomization (MR) analyses to infer the underlying causal associations between 41 systemic inflammatory regulators and CKD and kidney function. The inverse-variance weighting (IVW) test was used as the primary analysis method. In addition, sensitivity analyses were executed via the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test and the weighted median test.ResultsThe findings revealed 12 suggestive associations between 11 genetically predicted systemic inflammatory regulators and CKD or kidney function in the forward analyses, including 4 for CKD, 3 for blood urea nitrogen (BUN), 4 for eGFRcrea and 1 for eGFRcys. In the other direction, we identified 6 significant causal associations, including CKD with granulocyte-colony stimulating factor (GCSF) (IVW β = 0.145; 95% CI, 0.042 to 0.248; P = 0.006), CKD with stem cell factor (SCF) (IVW β = 0.228; 95% CI, 0.133 to 0.323; P = 2.40 × 10− 6), eGFRcrea with SCF (IVW β =-2.90; 95% CI, -3.934 to -1.867; P = 3.76 × 10− 8), eGFRcys with GCSF (IVW β =-1.382; 95% CI, -2.404 to -0.361; P = 0.008), eGFRcys with interferon gamma (IFNg) (IVW β =-1.339; 95% CI, -2.313 to -0.366; P = 0.007) and eGFRcys with vascular endothelial growth factor (VEGF) (IVW β =-1.709; 95% CI, -2.720 to -0.699; P = 9.13 × 10− 4).ConclusionsOur findings support causal links between systemic inflammatory regulators and CKD or kidney function both in the forward and reverse MR analyses.

Expansion of a food composition database for the food frequency questionnaire in the Korean Genome and Epidemiology Study (KoGES): a comprehensive database of dietary antioxidants and total antioxidant capacity.

This study constructed a comprehensive database of dietary antioxidants and total antioxidant capacity (TAC) to facilitate the estimation of daily antioxidant intake using a food frequency questionnaire (FFQ). This database was applied to 3 general population-based cohorts (n=195,961) within the Korean Genome and Epidemiology Study (KoGES). To establish a database of 412 foods derived from recipes of a 106-item FFQ, we followed a pre-established standardized protocol. This included the selection of source databases, matching of foods, substitution of unmatched items with identical foods and input of values, and assessment of coverage. For each food, the TAC was estimated by summing the individual antioxidant capacities, calculated by multiplying the amount of each antioxidant by its vitamin C equivalent antioxidant capacity. We identified 48 antioxidants across 5 classes: retinol, carotenoids, vitamins C and E, and flavonoids, with flavonoids divided into 7 subclasses. TAC values were then established. Coverage exceeded 90.0% for retinol, carotenoids, vitamin C, and vitamin E, while coverage for flavonoids was 60.9%. The daily intakes of 4 antioxidant classes-all but vitamin E-were higher in women than in men. The Ansan-Ansung cohort exhibited the highest levels of dietary TAC, vitamin E, and flavonoids, while the Health Examinees Study cohort displayed the highest values for retinol, carotenoids, and vitamin C. We customized a comprehensive antioxidant database for the KoGES FFQ, achieving relatively high coverage. This expansion could support research investigating the impact of dietary antioxidants on the development of chronic diseases targeted by the KoGES.