Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disease of the upper airway. Lipocalin-2, an inflammation-related glycoprotein involved in innate immune regulation, has been linked to several chronic inflammatory disorders, but its role in CRSwNP remains unclear. This study aimed to examine the expression of Lipocalin-2 in nasal tissues and secretions of CRSwNP patients and its relationship with inflammatory factors. Seventy patients diagnosed with CRSwNP between January 2023 and January 2025 were enrolled in the case group, while 60 patients with simple nasal septal deviation served as controls. NP tissues and nasal secretions were collected from CRSwNP patients, whereas inferior turbinate mucosal tissues and nasal secretions were obtained from controls. Levels of Lipocalin-2, interleukin-5 (IL -5), IL -6, and tumor necrosis factor-alpha (TNF-alpha) were measured and analyzed. Compared with controls, CRSwNP patients showed significantly higher levels of Lipocalin-2 and inflammatory cytokines in nasal secretions (p<0.05). Stratification based on Visual Analog Scale (VAS) scores and computed tomography Lund-Mackay (CT L -M) scores indicated that these markers were notably higher in the moderate-to-severe group than in the mild disease group (p< 0.05). Lipocalin-2 was positively correlated with IL -5, IL -6, TNF-alpha, as well as VAS, Lund-Kennedy endoscopy, and CT L -M scores (all p<0.05). In summary, Lipocalin-2 is highly expressed in nasal polyp tissues and secretions of CRSwNP patients and closely associated with inflammatory cytokine levels and clinical severity, implying its potential as a biomarker for disease activity in CRSwNP.
The aim was to investigate the effects of gavage exposure to nanoplastics (NPs) on cognitive decline and depression-like behavior was in-vestigated in mice subjected to chronic unpredictable mild stress (CUMS). BALB/c mice were randomly assigned to four experimental groups: Control (Ctrl), nanoplastics (NPs), Mod (subjected to CUMS), and NPs+Mod (nano-plastics + CUMS). We evaluated the role of the brain-derived neurotrophic fac-tor (BDNF) and its receptor, the tyrosine kinase receptor B (TrkB), signaling pathway in the hippocampus of mice. Behavioral assessments included the su-crose preference test, the open field test, the forced swim test, and the Morris water maze. Nissl staining was used to assess hippocampal neuronal morphol-ogy. BDNF and TrkB mRNA levels and protein expression in the hippocampus were measured by qPCR and Western blotting, respectively. Mice in the NPs, Mod, and NPs+Mod groups showed reduced body weight, lower sucrose pref-erence, poorer performance in the open field test, and prolonged immobility in the forced swim test. Additionally, there was a reduction in hippocampal neurons and deficits in spatial learning and memory compared with the con-trol group. BDNF mRNA and TrkB protein levels were decreased. Compared with the Mod group, the NPs+Mod group exhibited increased depression-like behaviors and cognitive impairments, greater hippocampal neuronal damage, and further reductions in BDNF and TrkB mRNA and protein levels. In conclu-sion, NP exposure has neurotoxic properties that can exacerbate CUMS-induced depression-like behavior and cognitive deficits, likely by further suppressing the hippocampal BDNF/TrkB signaling pathway.
Orientin, a natural flavonoid found in many medicinal plants, can improve lung injury through anti-inflammatory and antioxidant effects, but its role in pulmonary fibrosis (PF) remains unstudied. Human Fetal Lung 1 (HFL1) cells were stimulated with transforming growth factor-(31 (TGF-(31), and a single intratracheal bleomycin instillation in mice was used to establish a PF mouse model. Orientin, the TGF-(31/suppressor of mother against decapentaplegic 3 (Smad3) pathway agonist SRI-011381, and the inhibitor SB431542 were used for intervention. The proliferation and migration were evaluated using the Cell Counting Kit-8 (CCK-8), Edu staining (evaluated proliferative activity) and a scratch-healing assay. Fibers in HFL1 cells were detected by Sirius red staining. Inflammation and fibrosis in lung tissue were assessed by pathological staining and enzyme-linked immunosorbent assay (ELISA). PF and TGF-(31/Smad3 pathway protein expressions were evaluated by Western blot. Orientin significantly reduced TGF-(31, p-Smad3, alpha-smooth muscle actin (a-SMA), Collagen I, and matrix metallopeptidase (MMP)-2 levels. After Orientin treatment, the Edu positive cells, cell proliferation and migration were significantly reduced, and the number of red-stained collagen fibers was significantly reduced. After Orientin treatment, alveolar cavity collapse, inflammatory cell infiltration, and collagen fiber hyperplasia of mice were alleviated, and the contents of Hydroxyproline (HYP) and inflammatory factors in the alveolar lavage fluid were significantly reduced. SRI-011381 attenuated the effect of Orientin on the intervention, and inflammation and fibrosis levels were markedly increased. SB431542 enhanced the intervention effect of Orientin. Orientin inhibited TGF-(31/Smad3 signaling, inhibited fibroblast-to-myofibroblast transition (FMT) and extracellular matrix (ECM) production, and alleviated inflammatory and fibrotic damage.
This study examined the clinical effectiveness of vitamin D3 combined with traction therapy in patients with lumbar disc herniation. It included 112 patients who received conservative rehabilitation at our hospital from January 2021 to December 2023. Participants were randomly assigned to two groups: one received supine mechanical traction, and the other received the same traction plus oral vitamin D3 for 4 weeks. The study compared clinical outcomes and quality of life between the groups. Results showed that both groups experienced improvements in pain and lumbar spine function. However, the combined treatment group showed significantly better outcomes than the traction-only group. Inflammation and pain markers decreased significantly, and 25(OH)D3 levels increased notably in both groups, with greater improvements in the combined treatment group. Additionally, negative mood and quality of life improved more in the combined group. There was no significant difference in the measured indicators between the one-month follow-up and the one-month treatment. In conclusion, vitamin D3 combined with traction therapy can effectively enhance short-term clinical outcomes and quality of life for patients with lumbar disc herniation.
Acute pancreatitis is an acute pancreatic injury with multiple etiologies. Octreotide and somatostatin are commonly used treatments, but their clinical efficacy remains controversial. This study compares their effects on inflammatory markers and hospital length of stay. One hundred and twenty patients with acute pancreatitis admitted to The First People's Hospital of Jiashan between January 2022 and December 2024 were retrospectively included and divided into two groups based on treatment modality, namely the control group (somatostatin treatment) and the experimental group (octreotide treatment), with 60 cases in each group. Serum amylase (AMY), serum lipase (LPS), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), white blood cell count (WBC), serum albumin (ALB) content, procalcitonin (PCT), hospital stay duration, and the incidence of adverse reactions were assessed in both groups. Baseline data for the two groups were comparable, with no statistically significant differences (p>0.05). After seven days of medication, compared with the control group, patients in the experimental group had lower AMY, LPS, CRP, IL-6, TNF-alpha, WBC, and PCT (p<0.05), a shorter hospital stay (p=0.011), and a lower incidence of adverse reactions (p=0.007). ALB levels in the experimental group were significantly higher than those in the control group (p=0.039). Compared with somatostatin, octreotide shows superior therapeutic effects in acute pancreatitis, alleviating inflammation more effectively, promoting recovery, improving clinical outcomes, and shortening hospital stay. These findings provide a scientific basis for optimizing clinical medication.
This retrospective study aimed to identify histopathological and immunohistochemical predictors of malignancy requiring surgical excision among papillary breast lesions diagnosed by core-needle biopsy (CNB). Fifty-three women with CNB-diagnosed papillary breast lesions who subsequently underwent surgical excision at the İzmir Bakırçay University Çiğli Hospital be-tween January 2015 and January 2025 were included. Clinical, radiological, and pathological data were analyzed. Twenty-eight patients (52.8%) were ≤50 years of age, and 21 lesions (39.6%) were larger than 3 cm. Surgical excision revealed benign lesions in 24 cases, malignant lesions in 16 cases, and intracys-tic solid carcinoma or atypical ductal hyperplasia in 13 cases. The malignancy/atypia group (45.2%) showed a significantly higher frequency of myoepithelial cell loss (p<0.001) and microcalcifications (p=0.028), and uniform, strong es-trogen receptor positivity (100%) on CNB. Benign lesions were more commonly peripherally located (p=0.049). No significant associations were observed with age, Breast Imaging Reporting and Data System (BI-RADS) category, or lesion size. These findings indicate that loss of myoepithelial cells and estrogen re-ceptor positivity are strong predictors of malignancy and support the routine incorporation of immunohistochemical evaluation into CNB-based risk stratification.
The reemergence of yellow fever in Venezuela poses a critical threat to the region’s health security. After years of control, the persistent crisis has shifted surveillance from proactive to reactive. As of May 2026, official public health agencies report at least 40 hu-man cases and 21 confirmed deaths, corresponding to a case fatality rate exceeding 50%. In addition to the inherent predisposing factors of arboviruses, increasing human mobility without adequate protection in jungle areas and the accumulation of susceptible, unvacci-nated individuals are identified as key determinants. The epidemiological impact shows a no-table demographic bias, predominantly affecting young men of working age (57.5% of cases), which exacerbates the socioeconomic consequences of this outbreak. Furthermore, ongoing enzootic and epizootic circulation of the virus, both in known hotspots and in border areas and regions previously considered low-risk, indicates a high potential for expansion. Under the One Health approach, given active viral circulation, it is imperative to reinstate vaccina-tion protocols to close susceptibility gaps in rural and peri-urban regions that have not yet achieved the recommended immunization coverage, thereby completely blocking transmis-sion and preventing the urban cycle. Similarly, it is necessary to optimize diagnostic turn-around times, strengthen entomological and ecological surveillance, bolster international cooperation to reduce the risk of spread to neighboring countries, provide timely alerts about epizootics, and issue travel protection recommendations.
Plasma adsorption (PA) is used to improve outcomes in liver fail-ure (LF). Data on adsorption capacity and its relationship to patient outcomes are limited. This single-center retrospective study included patients with LF who received PA at the First Affiliated Hospital of Zhejiang University School of Medicine in Hangzhou City, China, between October 2020 and October 2022, and examined the impact of adsorption volume (5 L vs. 6 L) on prognosis. The study included 230 PA treatments, of which nine were excluded due to missing data. The 5L column was used in 60 patients (118 treatments, 47 male), and the 6L column was used in 50 patients (103 treatments, 31 male). Treatment effectiveness was evaluated using length of hospital stay, liver transplantation, death, and improvement in disease-related symptoms. In both groups, PA in-creased white blood cells (WBC), international normalized ratio (INR), activated partial thromboplastin time (APTT), and prothrombin time (PT) but decreased hemoglobin, total bile acids, total bilirubin, and fibrinogen (all p<0.05). Plate-let levels decreased after 6L PA (p=0.033) but not after 5L PA (p=0.116). After PA, the 6L group had lower WBC than the 5L group (p=0.003), but there were no significant differences in the other parameters. The 5L and 6L columns did not differ significantly in hospital stay duration, liver transplantation, mortal-ity, or symptom improvement. However, the 5L column significantly reduced platelet destruction, shortened treatment time, and reduced the occurrence of complications, particularly thrombocytopenia-related risks. Hence, the results indicate that the 5L volume would be preferable clinically.
This study evaluated the predictive significance of combining carotid atherosclerotic plaques assesment with glycosylated hemoglobin A1c (HbA1c) and C-reactive protein (CRP) levels for disease progression in young acute ischemic stroke (AIS) patients.A total of 130 subjects were evenly re-cruited, comprising young patients with AIS admitted between January 2015 and March 2025 (case group) and healthy individuals undergoing physical ex-aminations during the same period (control group). Comparisons were con-ducted on the incidence rate of carotid atherosclerotic plaques and serum HbA1c and CRP levels. The case group was categorized into mild-moderate and severe groups according to the National Institute of Health Stroke Scale (NI-HSS) score.Significant differences were observed between the severe and mild-moderate groups in NIHSS scores, carotid atherosclerotic plaque incidence, and serum levels of HbA1c and CRP (p<0.05). Increased serum HbA1c levels, elevated CRP levels, and presence of carotid atherosclerotic plaques functioned as risk factors for AIS progression in young patients (odds ratio>1, p<0.05). Serum HbA1c and CRP levels, along with the presence of carotid atheroscle-rotic plaques, showed a positive correlation with NIHSS scores (r>0, p<0.05). The areas under the ROC curves of serum HbA1c and CRP levels, carotid athero-sclerotic plaques and their combination for assessing AIS progression in young patients were 0.810, 0.823, 0.781, and 0.905, respectively.Elevated HbA1c, CRP, and the presence of carotid plaques are associated with AIS severity in young patients. Combined detection improves predictive accuracy, suggesting clinical utility for risk stratification.
Infections caused by carbapenem-resistant Enterobacterales, which are considered last-line antibiotics, represent a growing threat to public health. The primary resistance mechanism is carbapenemase production, and characterizing these enzymes is essential for guiding therapeutic decisions. Likewise, molecular epidemiology provides critical information for monitoring and controlling these microorganisms. In this context, we reviewed reports of carbapenemase-producing Enterobacterales in Venezuela, synthesizing avail-able data on bacterial species, antibiotic susceptibility, resistance-conferring enzymes, associated mobile genetic elements, molecular typing, and epidemio-logical trends. Analysis of these studies revealed that KPC-producing Klebsiella pneumoniae has been the most frequently reported carbapenemase-producing enterobacterium, although NDM (NewDelhi metallo-beta-lactamase) is on the rise, consistent with the situation in the rest of Latin America. Overall, we iden-tified a knowledge gap, especially in the molecular characterization of carbape-nem-resistant isolates, that requires systematic studies to better understand the dynamics and impact of these pathogenic agents in Venezuela.
The rise in older adults experiencing deterioration in quality of life and mental health underscores the need to deepen our understanding of the effects of complementary therapies on this population. Therefore, this study aimed to describe changes in quality-of-life scores following laughter therapy among adults residing in gerontological centers. An exploratory quasi-experi-mental study was conducted with 25 volunteers aged 60 and older. The SF-12 survey, which assesses physical and mental health dimensions, was adminis-tered before and after eight laughter therapy sessions. Statistically significant improvements were observed in the total quality-of-life score after completing the therapy sessions (p = 0.001), particularly in the mental health dimension (p = 0.001), whereas changes in the physical health dimension were not sig-nificant (p = 0.281). By sociodemographic variables, those who benefited most were women, those over 80 years of age, single individuals, and those with a monetary income. Regarding education and the type of institution (private or public), all groups improved their quality-of-life scores. In conclusion, laughter therapy applied to older adult residents in nursing homes significantly increas-es quality-of-life scores in the mental health dimension and on the total scale.
This study aimed to investigate the relationship between circulating white blood cells (cWBC) and the risk of tonsillar and base of tongue squamous cell carcinoma (TSCC/BOT SCC) using retrospective clinical data and Mendelian randomization (MR) analysis. A retrospective cohort of 239 TSCC/BOT SCC patients was analyzed for cWBC subtypes and their association with clinicopathological variables, stratified by human papillomavirus (HPV) status. Blood tests, tumor staging, and immunological markers were included. For causal inference, MR analysis was performed using genome-wide association study (GWAS) data on cWBC from the Blood Cell Consortium (UK Biobank) and TSCC/BOT SCC outcome data from the FinnGen consortium. Single-nucleotide polymorphisms (SNPs) were chosen based on genome-wide significance (p<5 & times; 10(-8)), low linkage disequilibrium (r(2) < 0.001), and F-statistic >10. The inverse-variance weighted (IVW) method was used as the primary MR approach, supplemented by MR-Egger, weighted median, and weighted mode analyses. The retrospective analysis showed significant differences in cWBC subtypes by gender, age, lifestyle factors, and HPV status. Notably, neutrophils (cNEU) and monocytes (cMON) were strongly associated with tumor stage and immune markers. MR analysis confirmed a causal link between total cWBC count and TSCC/BOT SCC risk (OR = 1.516, p = 0.005), with no evidence of heterogeneity or pleiotropy. No causal relationship was identified for cWBC subtypes or other head and neck squamous cell carcinoma (HNSCC) sites. This study provides the first comprehensive evidence supporting a causal role of elevated cWBC in the development of TSCC/BOT SCC. These findings indicate that cWBC may serve as a potential biomarker and therapeutic target in HPV-related or unrelated TSCC/BOT SCC.
Complement C1q/tumor necrosis factor-related protein 6 (CTRP6) has anti-inflammatory and metabolic regulatory properties, but its role in ameliorating post-myocardial infarction (MI) myocardial fibrosis via pyroptosis inhibition is unclear. This study investigated whether CTRP6 improves post-MI myocardial fibrosis and cardiac dysfunction by suppressing cardiomyocyte pyroptosis through the NLRP3/caspase-1/GSDMD pathway. Thirty Sprague-Dawley rats were randomized to sham-operated (Sham), MI model (MI), or CTRP6-treated (MI+CTRP6) groups. MI was induced by left anterior descending coronary artery ligation; MI+CTRP6 rats received daily subcutaneous recombinant CTRP6 (0.2 mg/kg) from day 3 post-surgery for 28 days. Cardiac function, fibrosis markers, pyroptosis-related proteins, and inflammatory cytokines were assessed via Western blot, Masson staining, and ELISA. CTRP6 expression was lower in MI vs. Sham (p<0.05). CTRP6 treatment restored its expression, reduced fibrosis markers and collagen deposition, and improved cardiac function (p<0.05). It also downregulated pro-inflammatory cytokines and increased anti-inflammatory cytokines (p<0.05). In other words, exogenous CTRP6 ameliorated fibrosis and cardiac function by directly inhibiting the NLRP3/caspase-1/GSDMD pyroptosis pathway.
Heart failure (HF) is a condition in which the heart cannot pump blood effectively to the body. Isoproterenol (ISO) induces HF in rodents by affecting the renin-angiotensin system (RAS). Astaxanthin (AST) is known to have protective effects on the cardiovascular system. However, clear evidence showing that AST improves HF through RAS regulation has not yet been reported. This study aimed to investigate the role of AST in ISO-induced HF in rats. HF was induced by intraperitoneal (i.p.) injection of ISO (5 mg/kg/day) for seven consecutive days. AST (25 and 50 mg/kg), aliskiren (30 mg/kg), ramipril (4 mg/kg), and telmisartan (8 mg/kg) were administered orally for 21 days, starting from the last dose of ISO (day 8). Changes in systolic and diastolic blood pressure and heart rate associated with HF were measured on days 0, 7, 14, 21, and 28. Additionally, changes in heart-to-body weight ratio, serum creatine kinase-MB (CK-MB), serum angiotensin-converting enzyme (ACE) activity, plasma renin activity (PRA), tissue hydroxyproline, and lactate dehydrogenase (LDH) activity, along with histopathological alterations, were evaluated. The administration of AST and RAS-modulating agents reduced ISO-induced changes in cardiac function and biochemical markers. It also demonstrated cardioprotective effects. Therefore, AST may be useful for treating cardiotoxic HF due to its RAS-regulatory actions. However, further studies are needed to confirm this therapeutic potential across different HF models and animal species.
This work evaluates the efficacy and safety of bispecific antibodies (BsAbs) in lung cancer immunotherapy through a meta-analysis, providing more comprehensive evidence for their clinical application. A systematic search was conducted in PubMed, Embase, Cochrane Library, and various Chinese databases to identify eligible randomized controlled trials and quasi-randomized controlled trials. Clinical data on bispecific antibody therapy for lung cancer were collected. The primary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the incidence of immune-related adverse events (irAEs). Data analysis was performed using RevMan 5.3 software, with fixed-effect or random-effects models. Nine studies were included, with a total sample size of 588 patients. The meta-analysis revealed no statistically significant differences between the bispecific antibody group and the traditional treatment group in ORR, OS and PFS, with combined effect sizes of odds ratio (OR)=1.31 and 95% confidence interval (CI)=0.98-1.76, OR=1.36 and 95%CI=0.99-1.87 and OR=1.07 and 95%CI=0.80-1.43, respectively (p 0.07, 0.06, and 0.64, respectively). However, the incidence of irAEs was significantly lower in the bispecific antibody group (OR = 1.56; p = 0.0007), indicating a reduction in such events. Bispecific antibodies demonstrate good safety in lung cancer immunotherapy, particularly in reducing irAEs. Despite some improvements in efficacy (e.g., ORR and OS), BsAbs do not demonstrate a significant superiority over conventional treatments.
This study systematically examined how vitamin D metabolic imbalance impacts 25(OH)D3 levels and neuropsychological development in premature infants and proposed a personalized supplementation approach. Premature infants were classified as adequate, insufficient, or deficient based on umbilical cord blood 25(OH)D3 levels and then randomly assigned to either a standard-dose group (800 IU/d) or an individualized supplementation group (400-1000 IU/d) with vitamin D. In the vitamin D-deficient group, infants receiving personalized supplementation had significantly higher 25(OH)D3 levels at three and nine months, adjusted for gestational age, than those receiving the fixed dose, indicating that 1000 IU/d is more effective than 800 IU/d for correcting deficiency (p<0.05). At nine and 18 months adjusted gestational age, infants in the vitamin D-insufficient and deficient groups scored significantly lower on the Gesell Developmental Scales across categories such as gross motor, fine motor, language, adaptive, and social skills compared to the adequate group (p<0.05). Within the deficient group, those receiving personalized supplementation scored higher in all five areas at both nine and 18 months adjusted gestational age compared to those on the fixed dose (p<0.05). The study highlights notable differences in umbilical cord blood 25(OH)D3 levels among premature infants, emphasizing that a customized vitamin D supplement protocol is more effective for correcting deficiencies.
This study aimed to evaluate the effectiveness of tamsulosin combined with potassium citrate in promoting the spontaneous passage of ureteral stones <= 10 mm. A retrospective analysis was performed on 100 patients admit-ted between January 2020 and December 2023. Patients were divided into four groups: tamsulosin (0.4 mg/day), potassium citrate (3 g/day), combined treatment (tamsulosin + potassium citrate), and a control group (analgesics only + regular water intake). Primary outcomes assessed over four weeks included stone passage rate, passage time, stone location and composition, and safety. Secondary outcomes covered pain control, imaging and laboratory indicators, and quality of life. Baseline characteristics were comparable across groups. The combined treatment group showed the highest stone expulsion rate, which was significantly higher than that of the tamsulosin, potassium citrate, and control groups (p<0.05). The median stone expulsion time was also shortest in the combined group (p<0.05). Expulsion rates for lower ureteral stones, uric acid stones, and calcium stones were significantly higher in the combined group (p<0.05), while the rate for upper stones was not statistically significant (p>0.05). No serious adverse events occurred, and safety profiles were similar across all groups. Secondary outcomes, including pain control and quality of life, showed significant improvements in the combined group compared with the other groups (p<0.05). The combination of tamsulosin and potassium citrate significantly increases the rate and shortens the time of spontaneous ureteral stone expulsion, with good safety and improved quality of life, supporting its role in medical expulsive therapy.
This study aimed to develop a predictive model for how patients with inflammatory bowel disease (IBD) respond to infliximab (IFX) treatment. One hundred adult IBD patients admitted to Shulan (Hangzhou) Hospital from August 2023 to November 2024 were included and divided into response and non-response groups based on their reaction to IFX. The response group consisted of 57 patients (57.0%), while the non-response group had 43 patients (43.0%). Clinical data, including gender, age, BMI, disease type (Crohn's disease/ulcerative colitis), disease activity indices (CDAI/UCAI), history of IFX treatment, and infusion reactions, were collected and compared between the two groups. Additionally, biomarker levels, such as TNF-alpha, CRP, calprotectin, anti-infliximab antibody (ATI), IL-6, and IL-8, were measured during the midcourse of IFX treatment. Single-factor analysis identified variables that differed, and logistic regression showed that calprotectin level (OR=1.099, 95%CI=1.039-1.163), ATI (OR=3.756, 95%CI=1.222-11.546), IL-6 (OR=1.261, 95%CI=1.069-1.488), and IL-8 (OR=1.014, 95%CI=1.004-1.024) were key factors influencing treatment response (p < 0.05). A nomogram was created using these factors to predict treatment response in IBD patients. ROC analysis showed AUC values of 0.809, 0.762, 0.850, and 0.775 for calprotectin, ATI, IL-6, and IL-8, respectively, with corresponding 95% confidence intervals. The calibration curve indicated good model fit. These findings underscore the important roles of these cytokines in IBD pathogenesis and the action of IFX, as well as the high predictive power of the nomogram model.
Sodium arsenite is a common and highly toxic inorganic arsenic compound that causes liver and kidney damage. Phyllanthus amarus is well known for its protective effects on these organs. This study aimed to identify the active phytoconstituents of the methanolic extract of P. amarus (PAME) and to explore their effects on arsenite-induced liver and kidney toxicity in experimental rats. The standardization of P. amarus extract was performed using highperformance liquid chromatography (HPLC). Male Wistar rats developed liver and kidney toxicity after daily oral administration of sodium arsenite (5 mg/ kg) for 4 weeks. The rats were simultaneously given coenzyme Q10 (CoQ10; 10 mg/kg) or PAME (50, 100, and 200 mg/kg). Results showed that HPLC analysis detected phyllanthin at a retention time of 25.41 minutes with an area of 71.84%. Arsenite treatment caused a significant (p<0.001) increase in hepatic enzymes (ALT, AST, and ALP), renal markers (BUN, uric acid, and creatinine), and direct and total bilirubin in the serum. It also significantly increased hepatic and renal levels of malondialdehyde, nitric oxide, NF-kappa B p65, interleukins (ILs), and TNF-alpha (p<0.001), while decreasing hepatic antioxidant enzymes (GSH and SOD) and overall hepatic antioxidant capacity. Notably, P. amarus extract (200 mg/kg) markedly (p<0.001) mitigated arsenite-induced changes in these serum markers, oxidative stress indicators, NF-kB p65, and inflammatory cytokines. It also improved the structure of liver and kidney tissues, maintained cellular architecture, and reduced necrosis and inflammation. In conclusion, these results suggest that phyllanthin from P. amarus protects against arsenite-induced liver and kidney damage by inhibiting NF-kappa B activation, reducing inflammatory cytokine release, and decreasing oxidative and nitrosative stress, thereby enhancing overall antioxidant capacity. Therefore, P. amarus extract may be a promising treatment for pesticide-related liver and kidney injuries in rats.
Colorectal cancer (CRC) remains the third most common malignancy worldwide, and there is an urgent need for low-toxicity, mechanism-based preventives or adjuvants. Withaferin-A (WA), a plant-derived steroidal lactone, exhibits broad antitumor activity; however, its role in CRC and its interactions with epigenetic regulators, such as histone deacetylase 1 (HDAC1), remain unclear. Therefore, we investigated whether WA suppresses CRC growth by down-regulating HDAC1 while inducing apoptosis and autophagy. Caco2 and HT-29 cells were treated with 0-5 & micro;M WA; viability, colony formation, and migration decreased significantly (IC50 0.70-1.52 & micro;M). Techniques such as Annexin-V/7-AAD flow cytometry, MDC staining, TEM, and LC3B immunofluorescence showed that 1 & micro;M WA notably increased apoptosis and autophagic flux, along with reduced HDAC1 and p62 levels, higher LC3B-II/I ratios, and an increased Bax/Bcl-2 ratio. Overexpression of HDAC1 via a lentiviral vector reversed these effects, confirming dependence on HDAC1. For translational relevance, eight-week-old C57BL/6J mice were first exposed to the food-borne carcinogen IQ (2-amino-3-methyl-3H-imidazo[4,5-f]quinoline, 100 mg/kg) every other day for three weeks to induce aberrant crypt foci (ACF). Starting the day after the first IQ dose, animals received WA (2 mg/kg) or vehicle (corn oil) by gavage every other day for the same period. WA reduced the number of macroscopic ACF by more than 60%, restored HDAC1-related LC3B and p62 expression to normal levels, and showed no toxicity based on body weight or general health assessments. These findings suggest that WA provides potent, low-toxicity chemopreventive effects against CRC lesion formation through HDAC1-dependent induction of apoptosis and autophagy, supporting its further consideration as a preventive or adjuvant agent.
