The adverse impacts of chronic pain extend far beyond the physical sensation itself. Chronic pain, an age-related condition, exacerbates geriatric disease burden and drives a central sensitivity-neuropsychiatric complex, necessitating urgent preventive care. This study aimed to investigate the impact of chronic pain on two sensitive diseases, depression, and abilities decline in basic or physical activities (functional limitation) among the inpatients in older adults and explore the attributable hospital costs related to chronic pain. Participants were sourced from the 2021-2022 Inpatient Discharge Dataset of Sichuan Province, Diagnosis of depression, functional limitation, and chronic pain were identified using International Classification of Diseases, 10th Revision (ICD-10) codes. Logistic regression models were employed to analyze the association between chronic pain and depression and functional limitation. Furthermore, total hospital costs, out-of-pocket costs and length of stay (LOS) were compared between patients (depression and functional limitation) with chronic pain and without using Propensity score matching and Multivariable linear regression. The analysis included 38,372 and 4,996 inpatients in the depression and functional limitation cohorts, respectively. Chronic pain was significantly associated with both outcomes, yielding odds ratios (ORs) of 1.24 (95% CI: 1.20-1.27) for depression and 1.60 (1.44-1.78) for functional limitation (all p < 0.001), and the effect intensified as the number of painful areas increased. Compared to those without pain, depression patients with chronic pain incurred 68.2% higher total hospital costs ( β =0.52, p < 0.001), 169.1% higher out-of-pocket ( β =0.99, p < 0.001) and 60.0% higher LOS ( β =0.47, p < 0.001). Among patients with Functional limitation, chronic pain also significantly increased log-transformed total costs ( β =0.20), out-of-pocket ( β =0.51), and LOS ( β =0.30), representing relative increases of 22.1, 66.5, and 35.0%, respectively (all p < 0.05). These economic impacts were more pronounced among patients with multi-area pain. This study provides empirical evidence linking chronic pain to deteriorated psychological and physical health among older adults. It highlights the increased burden of the disease and hospitalization, with a particular emphasis on the dangers of multi-area pain. These findings emphasize that prioritizing mental health-focused pain management in outpatient and emergency settings is crucial for preventing avoidable hospitalizations and hospitalization costs in older adults.
Urinary tract infections (UTIs) and chronic kidney disease (CKD) contribute to a substantial global health issue that is closely intertwined. Research has demonstrated that CKD increases the likelihood of individuals experiencing frequent, severe, and often antibiotic-resistant UTIs, which can accelerate the diminution of kidney function and result in end-stage kidney disease. The inherent structural, metabolic, and immunological disruptions linked to CKD create a suitable environment for uropathogens to grow in the urinary tract. This risk is further heightened by ongoing exposure to antibiotics, which facilitates the emergence of multidrug-resistant (MDR) organisms, complicating treatment options. This review discusses the existing literature on the clinical and microbiological relationship between CKD and UTIs, particularly highlighting the increased vulnerability of CKD patients to MDR pathogens supported by recent studies. It also addresses the disparity in the burden of these conditions in lower-income countries where access to renal replacement therapies is limited, as illustrated by the ISN-Global Kidney Health Atlas analysis. This review emphasizes the bidirectional challenge presented by CKD, which increases the risk of significant UTIs, while UTIs can worsen kidney damage. This damaging cycle is further intensified by factors such as weakened immunity, microbiota, and rising antibiotic resistance, creating a substantial clinical issue. To effectively manage antibiotic treatment, it is necessary to transition toward a proactive, integrative strategy. Key components include early screening for CKD in high-risk populations, maintaining optimal urogenital hygiene, and implementing strong antibiotic stewardship to enhance treatment effectiveness. Additionally, this review explores promising non-antibiotic prophylactic methods, including vaccines, antimicrobial peptides, and lifestyle changes, which are critical for breaking the cycle of infection and renal decline. A comprehensive approach that incorporates preventive measures, judicious use of antimicrobials, and addressing underlying renal issues is essential for improving long-term outcomes in this vulnerable patient demographic. Breaking the cycle: understanding the link between kidney disease and urinary tract infections Urinary Tract Infections (UTIs) and Chronic Kidney Disease (CKD) are serious health problems that often occur together and make each other worse. People with CKD are more likely to get frequent and severe UTIs, which are often harder to treat because the bacteria may resist antibiotics. These repeated infections can damage the kidneys further, speeding up the loss of kidney function and leading to End-Stage Kidney Disease (ESKD). CKD weakens the body’s defenses and changes the kidney’s structure and function, making it easier for harmful bacteria to grow. At the same time, frequent use of antibiotics in these patients increases the chance of antibiotic resistance, which limits treatment options. This problem is especially severe in low-income countries, where advanced kidney treatments are less available. This review explains the two-way relationship between CKD and UTIs and highlights how antibiotic resistance adds to the challenge. It suggests that a more proactive approach is needed, including early screening for kidney disease in people at risk, better hygiene practices, and careful use of antibiotics. New strategies such as vaccines, natural antimicrobial agents, and lifestyle changes also offer hope in preventing infections without relying only on antibiotics. By combining prevention, responsible antibiotic use, and treatment of underlying kidney problems, we can improve the long-term health and quality of life for people living with CKD.
Regulated cell death is critical in maintaining tissue homeostasis and immune functions. The most common form of physiologic cell death is the highly precise, regulated, and relatively inflammation-free pathway of apoptosis. In contrast, necrotic or lytic cell death, which involves rapid cell lysis and release of pro-inflammatory mediators, is more often associated with human pathologies. Pyroptosis and necroptosis are two regulated forms of lytic cell death and are increasingly recognized as important mediators of tissue damage in many diseases, including lung diseases. The death of lung cells is a key contributor to disease in multiple respiratory disorders. However, current interventions are limited to targeting downstream effects to help relieve symptoms without addressing the root cause driving tissue damage. Therefore, new strategies directed towards preventing tissue damage caused by detrimental cell death are desperately needed. Emerging evidence strongly implicates regulated necrosis in many acute and chronic lung diseases, but the specific form(s) of cell death driving pathology and cell types involved require nuanced evaluation. Here, we summarize current literature suggesting that pyroptosis and necroptosis facilitate lung injury and inflammation in Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) by inducing the death of airway and alveolar epithelial cells and resident immune cells, which leads to alveolar barrier disruption, release of inflammatory mediators, excessive immune cell recruitment, and ultimate lung function decline.
Dietary habits are pivotal in preventing chronic noncommunicable diseases, as vegetable-rich diets provide over 25,000 bioactive phytochemicals that modulate cell-signaling and metabolic pathways. Consequently, nutraceuticals and functional foods are increasingly recognized for their potential to prevent chronic pathologies. Among functional foods, Phaseolus vulgaris L. (common bean) stands out as a critical resource for global nutrition and disease prevention. Beyond its role in food security and environmental sustainability, the common bean offers extraordinary nutrient density, providing a unique "protein plus fiber" package and a source of health-promoting active ingredients. In this review, special emphasis is placed on the bean's role in preventing or mitigating cardiovascular diseases and cancer, driven by bioactive molecules that modulate metabolic and cell-signaling pathways. Practical evidence of this growing interest is demonstrated by the surge in scientific literature over the last 50 years, as shown by PubMed and Scopus data. By synthesizing data from original research and existing reviews, this work highlights how incorporating common beans into the diet represents a strategic, health-conscious choice with potential therapeutic benefits for human health.
Asymptomatic hyperuricemia (AH) is common in patients with chronic kidney disease (CKD) and has been identified as a modifiable condition. Addressing it could increase the possibilities for preventing and treating kidney injury. To assess whether administering allopurinol to people with chronic kidney disease and asymptomatic hyperuricemia enhances kidney function and delays progression to kidney failure. This is a retrospective cohort study with data collection from medical records at a specialized center from 2006 to 2020. Eighty people in stages 3 and 4 of CKD with AH were divided into two groups: 40 patients received allopurinol and 40 did not receive medication. Patients were followed for 24 months, with four consultations. Serum uric acid levels and creatinine-based estimated glomerular filtration rate (eGFRcr), estimated by the CKD-EPI formula, were compared within groups and between groups using mean, standard deviation, and analysis of variance (ANOVA). Eighty patients were included in the study. Comparing 40 patients with no treatment for hypertension with 40 patients receiving hypouricemic therapy (HUT) with allopurinol, it was observed that mean serum uric acid decreased at all review visits in the allopurinol group, and there was a significant increase in mean eGFRcr after starting allopurinol (p < 0.001). None of the patients in the allopurinol group developed end-stage kidney disease (ESKD) within 24 months (p < 0.001). Similar results were not observed in the control group. Allopurinol was useful in reducing serum uric acid levels, improving kidney function, and delaying progression to kidney failure in patients with AH. A hiperuricemia assintomática (HA) é comum em pacientes com doença renal crônica (DRC) e tem sido apontada como uma condição modificável, cuja abordagem poderia ampliar as possibilidades de prevenção e tratamento da lesão renal. Avaliar se a administração de alopurinol em pessoas com doença renal crônica e hiperuricemia assintomática melhora a função renal e retarda a progressão para insuficiência renal. Este é um estudo de coorte retrospectivo, com coleta de dados de prontuários médicos em um centro especializado, entre 2006 e 2020. Oitenta indivíduos nos estágios 3 e 4 da DRC, com HA, foram divididos em dois grupos: 40 pacientes receberam alopurinol e 40 não receberam medicação. Os pacientes foram acompanhados por 24 meses, com quatro consultas. Os níveis séricos de ácido úrico e a taxa de filtração glomerular estimada com base na creatinina (eTFGcr), calculada pela fórmula CKD-EPI, foram comparados intra e intergrupos utilizando média, desvio padrão e análise de variância (ANOVA). Oitenta pacientes foram incluídos no estudo. Ao comparar 40 pacientes sem tratamento para HA com 40 pacientes em terapia hipouricemiante (THU) com alopurinol, observouse que a média do ácido úrico sérico diminuiu em todas as consultas de acompanhamento no grupo alopurinol, além de um aumento significativo na taxa de filtração glomerular estimada (eTFGcr) média após o início do tratamento (p < 0,001). Nenhum paciente do grupo alopurinol desenvolveu doença renal terminal (DRT) em 24 meses (p < 0,001). Resultados semelhantes não foram observados no grupo controle. O alopurinol mostrou-se útil na redução dos níveis de ácido úrico sérico, na melhora da função renal e no retardo da progressão para insuficiência renal em pacientes com HA.
Vascular calcification (VC) is an inflammatory disease driven by aberrant cellular processes in which macrophages play an important role. The A disintegrin and metalloproteinase 8 (ADAM8) protein is an important regulatory factor in macrophages and contributes to the development of inflammatory diseases. However, the relationship between ADAM8 and VC remains unknown. Thus, this study aimed to investigate the role of macrophage ADAM8 in VC. Plasma ADAM8 levels were compared between patients with and without aortic calcification. Immunofluorescence staining of human aortic tissue samples was performed to assess differences in ADAM8 expression between calcified and non-calcified tissues. Macrophage-specific Adam8 knockout mice (Adam8flox/flox, Lyz2-Cre; KO) and the corresponding control mice (Adam8flox/flox; Flox) were generated using CRISPR/Cas9 technology. Additionally, the adeno-associated virus AAV6-F4/80-Adam8 was employed to achieve macrophage-specific overexpression. The relationship between macrophage ADAM8 and VC was studied in a VC mouse model of chronic kidney disease (CKD) by comparing VC severity between groups. Plasma ADAM8 levels were elevated in patients with aortic calcification. Immunofluorescence staining of human aortic samples suggested that VC was associated with ADAM8-positive macrophage infiltration and ADAM8 released by macrophages. In mice, macrophage-specific Adam8 knockout attenuated the development of CKD-associated VC, whereas macrophage-specific ADAM8 overexpression reversed the VC phenotype. ADAM8 levels are elevated in patients with aortic calcification and are associated with macrophage infiltration into vascular tissue and ADAM8 release, leading to increased VC. These findings identify ADAM8 as a promising novel therapeutic target for preventing VC.
Chronic kidney disease (CKD) is a global health concern and early detection is crucial for preventing progression. Current screening methods are inconvenient and resource intensive. Breath ammonia has been proposed as a non-invasive biomarker for renal dysfunction but its diagnostic accuracy and the impact of fasting remain unclear. This study aimed to validate the breath ammonia test for CKD screening and assess the effect of fasting on its diagnostic performance. This prospective study included 244 participants: a derivation cohort (n = 121) and a validation cohort (n = 123). Breath ammonia was measured using a vertical-channel organic semiconductor sensor. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation. Receiver operating characteristics (ROC) curve analysis was used to evaluate diagnostic performance, and fasting was defined as ≥4 hours without intake. The average age of the participants was 60.7 years, with males comprising 51% of the cohort. Breath ammonia levels significantly correlated with serum creatinine (r = 0.695, P < .001), eGFR (r = -0.533, P < .001) and blood urea nitrogen (r = 0.765, P < .001). Using a cut-off of 886 ppb, breath ammonia predicted eGFR <60 ml/min/1.73 m2 with a sensitivity of 78.5% and a specificity of 81.6% (area under the ROC = 0.842). Fasting enhanced diagnostic accuracy, improving sensitivity and specificity to 87.9% and 91.5%, respectively (area under the ROC = 0.939). Conversely, non-fasting patients demonstrated lower sensitivity and specificity at 74.5% and 74.6%, respectively. The breath ammonia test is a promising non-invasive CKD screening tool. Standardizing pretest fasting may further improve its diagnostic accuracy.
Chronic obstructive pulmonary disease (COPD) is poorly diagnosed with millions unaware they have the condition, preventing or delaying treatment and behavioral changes. We partnered with faith-based organizations (FBOs) to raise awareness of COPD among Black Americans by facilitating diagnosis and offering self-management education in the community. Cross-sectional and pre-post study designs were applied. Three churches identified representatives to serve as COPD liaisons (CLs). CLs received training on screening procedures and an overview of COPD. Case-finding was conducted at health fairs where CLs helped administer a screening tool (COPD-population screener (PS)) to identify high-risk individuals and refer those who scored ≥5 for spirometry performed by respiratory therapists (RTs). RTs referred those with high risk of having COPD (scores ≥5 and FEV1/FVC ~ 0.70) to discuss results with their provider, and those eligible (COPD high-risk, COPD diagnosed, caregivers, and current or former smokers), to attend bi-monthly educational sessions. Bristol COPD Knowledge Questionnaire was used to assess participants' knowledge pre-post intervention and CL training. CLs also completed a self-efficacy questionnaire. Independent t-test, paired t-test, and Chi-squared test or Fisher's Exact test were applied. We attended seven health fairs and engaged four CLs. CL self-efficacy was higher, while knowledge increased by 6.2% post-training then declined by 5%. Of the 170 people who completed the screening tool, 40 received spirometry, 3 (8.1%) and 9 (24.3%) had FEV1/FVC ratios of 0.70, and >0.70 to <0.80, respectively. Prevalence of COPD was approximately 12.6%, smoking history (former: 27.3%, current: 3.6%), and sleep apnea, 23.8%. About 11/38 people attended at least one educational session and knowledge scores increased significantly from baseline to post-session, 42% to 55% (t=-4.82, df=12, p=0.00). COPD case-finding implemented in partnership with FBOs can supplement efforts in primary care. Routine educational sessions in the community improved access to self-management education for people with COPD and their caregivers. Engaging CLs in addressing respiratory health inequities can lead to greater impact in minority populations.
Hearing loss (HL) and chronic kidney disease (CKD) are both significant components of the global health burden. We explored the phenotypic association between CKD and HL, along with the underlying genetic drivers, through studies ranging from clinical cohorts to genetic analyses. First, we utilized data from the China Health and Retirement Longitudinal Study (CHARLS) and assessed the relationship between CKD and hearing loss using Cox proportional hazards models. Subsequently, we employed genome-wide genetic aggregation data to investigate the genetic drivers underlying CKD and HL. In the cohort study, 7,084 individuals were included, of whom 1,509 participants (21.3%) experienced hearing loss. Cox regression analysis showed that CKD was associated with an increased risk of hearing loss (HR=1.541, 95% CI=1.317-1.804). In genetic analysis, CKD was positively genetically correlated with HL (rg=0.155, P<0.05). Multi-trait analysis of GWAS (MTAG) and cross-phenotype association analysis (CPASSOC) from the genome-wide association study identified two significant pleiotropic SNPs (rs12149832 and rs2044993) for both CKD and HL. Transcriptome-wide association study (TWAS) identified shared tissue-specific expression-trait associations, but Mendelian randomization did not reveal causal relationships (OR=1.035, 95% CI=0.973-1.101). Our cohort study confirms the clinical association between CKD and HL. Genetic analysis reveals a shared genetic link between the two conditions and potential underlying genetic drivers. These findings may provide effective strategies for preventing and managing hearing loss in clinical CKD patients.
Conducted bidirectional two-sample MR study to explore causality between systemic diseases and periodontitis amid confounding factors. Genome-wide association study (GWAS) summary statistics were obtained from the IEU OpenGWAS project, FinnGen consortium, and GLIDE consortium. The exposures included a range of Systemic diseases, such as Diabetic ketoacidosis, Coronary heart disease, Myocardial infarction, Stroke, Coronary atherosclerosis, Diabetic nephropathy, Diabetic neuropathy, Diabetic retinopathy, Cataracts, Nonalcoholic fatty liver disease, Osteoporosis, and cardiac arrhythmia, and the outcomes were periodontitis and chronic periodontitis. The primary analytical method was inverse-variance weighted (IVW) MR, complemented by MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses, including MR-PRESSO, MR-Egger intercept test, and Cochran's Q test, were performed to assess the robustness of the findings. In the forward MR analysis, we found no significant evidence to support a causal effect of genetic liability to the selected Systemic diseases on the risk of periodontitis or chronic periodontitis (all P > 0.05). In the reverse MR analysis, a genetically predicted causal relationship was identified, suggesting that periodontitis is a risk factor for osteoporosis (IVW, OR 1.16, 95% CI 1.01-1.33, P = 0.031). No other significant causal effects of periodontitis on the other studied diseases were found. Sensitivity analyses did not detect significant horizontal pleiotropy for the positive finding. We provide novel evidence suggesting that periodontitis may causally increase the risk of osteoporosis. These findings highlight the systemic impact of oral health and suggest that preventing and treating periodontitis could be a potential strategy in osteoporosis management. Clinically, integrating periodontal screening into the risk assessment protocols for patients susceptible to osteoporosis may optimize 69 early intervention and multidisciplinary patient management.
Chronic kidney disease (CKD) is associated with increased incidence of sarcopenia and muscle weakness in aging patients. The glucocorticoid activating enzyme11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) within skeletal muscle in these patients has been implicated in driving this process. We hypothesised that skeletal muscle 11β-HSD1 is elevated in CKD and aging where it would represent a promising therapeutic target. We measured 11β-HSD1 activity in quadriceps biopsies from 17 CKD patients (eGFR <30 ml/min) and 14 age-matched controls (mean age 71±5 years). Muscle strength, mass, and gait speed were assessed in relation to tissue 11β-HSD1 activity. Primary human myotubes were treated with patient-derived sera to evaluate regulatory drivers. Murine models of CKD (adenine diet) and aging (21 months) in wild-type (WT) and 11β-HSD1 knockout (11βKO) animals were examined to model therapeutic targeting. Muscle 11β-HSD1 activity was not elevated with CKD, but increased with age (r=0.559, p=0.001), predicting lower grip strength (p=0.008). Markers of inflammation, including c-reactive protein and IL-6 strongly predicted 11β-HSD1 activity. Pro-inflammatory mediators such as TNFα, directly upregulated 11β-HSD1 activity in myotubes, whilst sera from CKD donors did not. Whilst mice with 11βKO deletion were not protected from CKD driven muscle atrophy, 11βKO animals showed marked protection against age related muscle loss. Skeletal muscle 11β-HSD1 activity is not induced by CKD itself, but increases significantly over aging, where it is a predictor of muscle weakness. Its targeted deletion, preserves muscle mass in aged mice, supporting its efficacy in preventing sarcopenia in an aging CKD population.
Inflammatory bowel disease (IBD)-including Crohn's disease, ulcerative colitis, and indeterminate colitis-is a chronic immune-mediated condition that primarily affects the intestinal mucosa but often presents with extraintestinal digestive manifestations, which are important yet frequently underrecognized sources of morbidity. These heterogeneous manifestations reflect diverse genetic, microbial, immunologic, and environmental influences, highlighting the value of a personalized medicine approach. Hepatobiliary involvement affects IBD adults patients and is even more common in children, ranging from mild liver enzyme elevations to severe complications such as liver failure, with autoimmune disorders, cholelithiasis, portal vein thrombosis, and non-alcoholic fatty liver disease as key considerations. Pancreatic manifestations may include autoimmune or acute pancreatitis, often linked to gallstones, thiopurine exposure, or duodenal Crohn's disease, while splenic abnormalities, such as granulomatous lesions, splenomegaly, or functional hyposplenism, reflect systemic immune dysregulation. Oral findings-including aphthous ulcers, periodontitis, pyostomatitis vegetans, and granulomatous cheilitis-can serve as early, patient-specific indicators of disease activity. Personalized approaches, encompassing investigations tailored to the individual profile and selected targeted therapies, are essential for improving diagnostic accuracy, preventing complications, and optimizing multidisciplinary care in patients with IBD.
Increased colonization of typically oral microorganisms is frequently observed in the gut mucosa or lumen of individuals with gastrointestinal disorders, including patients with inflammatory bowel disease and colorectal cancer. Accumulating clinical and experimental evidence indicates that this phenomenon, known as "gut oralization," plays an important role in the pathogenesis of these diseases. Although several physiological barriers normally restrict the translocation and ectopic colonization of microorganisms from the oral cavity to the gut, certain oral pathobionts-often enriched in individuals with oral diseases such as periodontitis-have evolved specialized strategies to overcome these defenses. This review examines the bidirectional interactions through which bacterial traits, including unique adhesion systems and metabolic adaptations, support colonization and expansion within the gastrointestinal tract, as well as how disease-associated alterations in the gut environment and increased host vulnerability facilitate ectopic colonization by bacteria of oral origin. By integrating clinical and mechanistic evidence, this review highlights the potential of targeting the oral-gut microbial axis as a therapeutic approach for preventing and treating chronic gastrointestinal disorders.
The link between lifestyle-related conditions and fatty liver disease has attracted considerable attention in recent years. The number of patients with metabolic dysfunction-associated steatotic liver disease (MASLD), often co-occurring with obesity, diabetes, and dyslipidemia, continues to rise. Accumulating evidence suggests that these conditions synergistically increase the risk of progression to cirrhosis and hepatocellular carcinoma (HCC). Consequently, there is a growing need for testing to identify high-risk liver disease patients based on lifestylerelated conditions, distinct from chronic viral hepatitis or alcohol-induced liver disease, and to determine the most appropriate treatments for these conditions, especially obesity, diabetes, and dyslipidemia. This review outlines the strategy for treating fatty liver disease currently being used in community hospitals, with the goal of reducing HCC and preventing cardiovascular disease.
This study aims to investigate the impact and molecular mechanism of ELAVL1 in promoting macrophage M1 polarization in Crohn's disease (CD) by upregulating S100A8 expression. Peripheral blood mononuclear cells (PBMCs) from CD patients were collected to assess the expression of S100A8 and ELAVL1. The effect of ELAVL1/S100A8 on THP1 derived macrophage polarization and pro-inflammatory mediator secretion were evaluated via siRNA silencing and rescue experiments. RNA-binding protein immunoprecipitation (RIP) and RNA pull-down assays validated the interaction between ELAVL1 and S100A8. Both S100A8 and ELAVL1 were significantly overexpressed in CD patients. Knockdown of S100A8 or ELAVL1 in M1-polarized macrophages marked reduced the expression of M1 biomarkers (CD80, CD86) and pro-inflammatory mediators. However, S100A8 overexpression reversed the inhibitory effects of ELAVL1 knockdown on M1 polarization, thereby promoting the M1 polarization and inflammatory response. RIP and RNA pull-down assays confirmed that ELAVL1 directly binds to S100A8 mRNA to regulate its expression. ELAVL1 promotes M1 polarization of macrophages to exacerbate intestinal inflammation in CD via up-regulating S100A8 expression. These findings highlight the ELAVL1/S100A8 axis as a potential therapeutic target or diagnostic biomarker for managing CD. Crohn’s disease (CD) is a chronic condition where the immune system mistakenly attacks the digestive tract, causing severe inflammation. A specific type of immune cell, called a “macrophage,” acts like a double-edged sword: while it usually protects us, in CD, it can become overactive (known as M1 polarization) and release harmful chemicals that damage the gut.Our study identified a new biological “switch” involving two molecules, ELAVL1 and S100A8, that controls this overactive state. We found that in patients with CD, ELAVL1 levels are high and act like a stabilizer for S100A8, preventing it from breaking down. This buildup of S100A8 signal macrophages to stay in a highly aggressive, pro-inflammatory state.By using laboratory techniques to turn off this ELAVL1/S100A8 switch, we successfully reduced the inflammation produced by these immune cells. This discovery is important because it highlights ELAVL1 and S100A8 as potential markers to help doctors diagnose the disease or predict how it will progress. More importantly, it opens the door for new “precision” treatments that could 1-day target this specific pathway to calm the immune system in Crohn’s patients without affecting the whole body.
Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as a widespread chronic hepatic disorder worldwide. Early identification of individuals at elevated likelihood of MAFLD is crucial for preventing disease progression. The C-reactive protein-albumin-lymphocyte (CALLY) index, a novel composite biomarker reflecting systemic inflammation, nutritional status, and immune competence, offers potential utility in risk stratification. This study analyzed the relationship between the CALLY index and MAFLD prevalence utilizing cross-sectional data from three ethnically diverse cohorts in the U.S., the U.K and China. This cross-sectional study employed data from the US NHANES (2017-2020), the UK Biobank, and a Chinese hospital cohort. MAFLD was diagnosed via ultrasound-based controlled attenuation parameter (CAP) or the fatty liver index (FLI). The CALLY index was calculated from serum albumin, lymphocyte count, and CRP, and was natural log-transformed (ln-CALLY). Its association with prevalent MAFLD was assessed using multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals, with restricted cubic splines (RCS) and subgroup analyses used to evaluate robustness and potential non-linearity. In NHANES, a per standard deviation (SD) increment in ln-CALLY was inversely associated with the odds of having MAFLD, corresponding to 24% lower odds (OR = 0.76, 95% CI: 0.64-0.90, p = 0.009). Similarly, in the UK Biobank cohort, each SD increase in ln-CALLY corresponded to 33% lower odds of MAFLD (OR = 0.67, 95% CI: 0.67-0.68, p < 0.001). A more pronounced risk reduction was observed in the Chinese population, where each SD rise in ln-CALLY was linked to 40% lower odds of MAFLD (OR = 0.60, 95% CI: 0.51-0.71, p < 0.001). The RCS analysis confirmed a non-linear inverse correlation between ln-CALLY and the odds of MAFLD, validating the dose-response protection identified through logistic regression. The area under the curve (AUC) of the ROC curve was 0.650 (95% CI: 0.636-0.665), indicating modest discriminative ability for identifying prevalent MAFLD. The CALLY index demonstrates an inverse relationship with MAFLD prevalence. This biomarker may help identify individuals with a higher likelihood of MAFLD, which could inform screening and risk assessment in clinical and population settings.
Women with Parkinson's Disease (PD) have higher plasma exposure to levodopa and are particularly prone to developing complications during chronic levodopa therapy. However, there are no longitudinal studies focusing on differences in levodopa pharmacokinetics and their correlation with clinical outcomes. This multicenter longitudinal study aimed to investigate sex-related differences in levodopa pharmacokinetics in levodopa-naïve PD patients, and to evaluate relationships with levodopa-related complications. After a single dose of levodopa/DOPA-decarboxylase inhibitor, blood samples were collected at baseline and at two-year follow-up to measure pharmacokinetic parameters using UHPLC-MS. Clinical assessment included wearing-off Questionnaire and MDS-UPDRS scale. Multiple linear regression analyses were performed to identify predictors of pharmacokinetic parameters and levodopa-related complications. The study population consisted of 28 PD patients (18 men, 10 women) followed for 2 years from the start of levodopa therapy. No differences were found between the sexes in clinical characteristics, daily levodopa-dosage, and use of other antiparkinsonian drugs. AUC and Cmax were higher in females than in males (p < 0.001), and sex influenced both of these parameters regardless of whether pharmacokinetic analysis was performed at baseline or at follow-up. Female sex was the best predictor of AUC and Cmax. DYS was found in 20% of females but in no males, and 90% of females showed wearing-off compared to 50% of males (p = 0.022). In females but not in males, the presence of wearing -off was correlated with AUC and Cmax at baseline and after 2 years of treatment. Compared to men, women with PD showed higher plasma levodopa levels since the initial administration and after chronic treatment. Measuring exposure to levodopa may be useful for optimising levodopa dosage since the start of treatment, thus preventing levodopa-related complications.
Astroglia, an extended class of homeostatic and defensive cells of the central nervous system (CNS), contribute to the pathogenesis of all known neurological and neuropsychiatric disorders. The pathophysiology of astrocytes is complex, mutable, disease and disease-stage specific. In neuroinflammatory lesions and in various chronic conditions, astrocytes undergo an evolutionary conserved defensive remodeling known as reactive astrogliosis, which produces highly heterogeneous reactive astrocytic phenotypes. Broadly, reactive astrogliosis can be classified into proliferative anysomorphic barrier-forming astrogliosis characteristic of traumatic CNS lesions and nonproliferative isomorphic gliosis widely manifested in chronic neuropathologies. In addition, in many pathologies, astrocytes undergo atrophy and asthenia with resulting loss of homeostatic support and neuroprotection precipitating neuronal damage. Reactive and atrophic astrocytes may coexist or emerge in sequence in a disease-stage-dependent manner. Several classes of astrocyte-specific molecules and processes implicated in various diseases of the CNS represent therapeutic targets. Astrocyte-specific therapeutic strategies may improve both disease-preventing and disease-modifying therapeutic outcomes.
Retinal photographs offer great opportunity to early detect systemic disorders related to diabetes, including Chronic Kidney Disease (CKD). To develop and validate a novel deep learning model to detect CKD among diabetic patients. We developed an EfficientNet-B2 Deep Learning (DL) model utilizing a weighted cross-entropy loss function to address class imbalance and distinguish retinal images among healthy controls, patients with isolated type 2 diabetes mellitus (T2DM), and patients with CKD stage 3 due to T2DM. The dataset was partitioned using a strict 80/20 patient-level split to evaluate bilateral eyes while strictly preventing data leakage. Model performance was evaluated using sensitivity, specificity, and area under the curve (AUC), alongside Grad-CAM visualizations for clinical interpretability. The study included 225 participants. Among the evaluated DL architectures, the EfficientNet-B2 model demonstrated the best performance, achieving an overall AUC of 0.96. The model exhibited a sensitivity of 82%, specificity of 94%, precision of 81%, and an F1-score of 0.80. Class-specific AUCs were 0.99 for healthy controls, 0.90 for T2DM without CKD, and 0.90 for T2DM with CKD stage 3. Grad-CAM heatmaps indicated that the model primarily focused on the peripapillary and macular regions to make predictions. This study presents a three-class fundus-based DL model, trained with a weighted-loss strategy, to differentiate controls, isolated T2DM, and T2DM with CKD stage 3. Further external and prospective validation is needed before it can be considered for screening/triage use.
Digestive disorders such as inflammatory bowel disease (IBD) and colorectal cancer are among the most significant global health challenges, largely driven by chronic inflammation and oxidative stress. Over centuries, traditional medical systems have relied on medicinal plants to alleviate gastrointestinal conditions, and current pharmacological research is beginning to validate these ancestral practices. Many plants contain a rich diversity of bioactive compounds, including polyphenols, flavonoids, terpenes, and alkaloids, that exert antioxidant, anti-inflammatory, and anticancer effects, making them promising candidates for complementary therapy. This review compiles and critically analyzes data from the past decade on plant extracts and isolated natural compounds tested in vitro, in vivo, and ex vivo for their protective effects on intestinal health. Evidence consistently indicates that plant-derived molecules can suppress inflammatory mediators, modulate oxidative stress responses, restore epithelial barrier integrity, and induce apoptosis in neoplastic cells. Among these, polyphenols and flavonoids emerge as key contributors, demonstrating efficacy across multiple biological models. The findings support the growing integration of traditional herbal knowledge with modern biomedical science. Plant-based compounds represent not only valuable sources of therapeutic agents but also a foundation for developing functional foods and nutraceuticals aimed at reducing inflammation and preventing colon-related pathologies.