Search Results (3,985)

Exposure to low-dose environmental pollutant cadmium (Cd) increases the risks of both albuminuria and hypertension by mechanisms which are poorly understood. Here, multiple regression and mediation analyses were applied to data from 641 Thai subjects of whom 39.8%, 16.5%, 10.8%, and 4.8% had hypertension, albuminuria, diabetes, and chronic kidney disease (CKD), defined as the estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m², respectively. To correct for interindividual differences in urine dilution and surviving nephrons, the excretion rates of Cd (E_Cd), albumin (E_alb), and β₂-microglobulin (E_β2M) were normalized to the creatinine clearance (C_cr) as E_Cd/C_cr, E_alb/C_cr, and E_β2M/C_cr. The respective risks of having CKD and hypertension rose to 3.52 (95% CI: 1.75, 7.05) and 1.22 (95% CI: 1.12, 1.3) per doubling of the Cd body burden. The respective risk of having albuminuria increased 2.95-fold (p = 0.042) and 4.17-fold (p = 0.020) in subjects who had hypertension plus severe and extremely severe tubular dysfunction, defined according to the elevated β₂M excretion rates. In multiple regression analysis, the E_alb/C_cr increased linearly with both the systolic blood pressure (SBP, β = 0.263) and diastolic blood pressure (DBP, β = 0.150), while showing an inverse association with eGFR (β = −0.180). The mediation model analyses inferred that a declining eGFR induced by Cd contributed to 80.6% of the SBP increment (p = 0.005), which then fully mediated an elevation of albumin excretion (p < 0.001). The present study provides, for the first time, evidence that causally links Cd-induced eGFR reductions to blood pressure elevations, which enhance albumin excretion. Full article

Background/Objectives: IgA nephropathy (IgAN) is one of the most common forms of glomerulonephritis leading to renal failure. MicroRNAs have been shown to play an important role in the pathogenesis and clinical course of IgA nephropathy; therefore, they offer the possibility of noninvasive diagnosis of this disease and have some value in predicting disease prognosis. This study aimed to evaluate the plasma levels of miR-148a-3p, miR-425-3p, and miR-20a-5p in patients with IgA nephropathy and their correlation with selected clinical parameters. Methods: This study included 44 patients with IgA nephropathy and 46 control subjects. Results: The results of our study indicated that in patients with IgA nephropathy, the increased plasma levels of miR-148a-3p and miR-425-3p correlated negatively with eGFR values. According to the Haas classification, plasma levels of miR-20a-5p were statistically significantly increased in patients with histopathological changes classified as Stages 3, 4, and 5 compared with patients with histopathological changes classified as Stages 1 and 2. Conclusions: The results of our study suggest the possible involvement of miR-148a-3p, miR-425-3p, and miR-20a-5p in the pathogenesis of IgA nephropathy. Full article

Targeted therapies have changed the treatment landscape of non-small-cell lung cancer and led to improved patient survival across all stages of lung cancer. Newer advances in common and novel oncogenic drivers continue to occur at vigorous speed, making it challenging to stay up to date with the rapidly evolving field. In this article, we review the emerging perspectives in the treatment of actionable targets in lung cancer. We focus on the development of newer KRAS-directed therapies, particularly on non-G12C mutations, pan-RAS inhibitors, and RAS-GTP inhibitors. We also describe the current standard of care for EGFR- and ALK-altered NSCLC and dive into the novel treatments expected to be in the clinic soon. A similar approach is taken toward MET, HER2, RET, ROS1, and FGFR alterations as emerging targets in non-small-cell lung cancer. Finally, we conclude this review with the current body of evidence for targeting TROP-2 as a novel target, potentially of importance in post-targeted therapy scenarios. Full article

Background: Chimeric antigen receptor (CAR) T cell therapy has shown significant promise in treating hematological malignancies, yet its application in solid tumors, particularly those expressing the epidermal growth factor receptor (EGFR), remains limited. This study investigates the potential of CAR-engineered peripheral blood mononuclear cells (PBMCs) as a novel adoptive cell therapy against EGFR-positive cancers. Methods: Lentiviral transduction at an MOI of 50 was performed to generate specific anti-EGFR second generation CAR-effector cells. The transduced PBMCs were stimulated with cytokines and CD3/CD28 beads to enhance their proliferation and activation. Flow cytometric and real-time cell analysis were performed at various effector-to-target ratios to explore the cytotoxic potential of CAR-PBMCs. Results: CAR-PBMCs exhibited improved targeting and cytotoxicity against EGFR-positive cancer cell lines MDA-MB-468 and SK-BR-3, compared to untransduced controls, with unsignificant effects on allogeneic PBMCs. Conclusion: CAR-PBMCs hold considerable potential as a therapeutic strategy for EGFR-positive solid tumors, warranting further clinical investigation. Full article

Active cancer targeting consists of the selective recognition of overexpressed biomarkers on cancer cell surfaces or within the tumor microenvironment, enabled by ligands conjugated to drug carriers. Nanoparticle (NP)-based systems are highly relevant for such an approach due to their large surface area which is amenable to a variety of chemical modifications. Over the past decades, several studies have debated the efficiency of passive targeting, highlighting active targeting as a more specific and selective approach. The choice of conjugation chemistry for attaching ligands to nanocarriers is critical to ensure a stable and robust system. Among the panel of cancer biomarkers, the epidermal growth factor receptor (EGFR) stands as one of the most frequently overexpressed receptors in different cancer types. The design and development of nanocarriers with surface-bound anti-EGFR ligands are vital for targeted therapy, relying on their facilitated capture by EGFR-overexpressing tumor cells and enabling receptor-mediated endocytosis to improve drug accumulation within the tumor microenvironment. In this review, we examine several examples of the most recent and significant anti-EGFR nanocarriers and explore the various conjugation strategies for NP functionalization with anti-EGFR biomolecules and small molecular ligands. In addition, we also describe some of the most common characterization techniques to confirm and analyze the conjugation patterns. Full article

Background: Hepatitis C virus (HCV) infection accelerates the progression of chronic kidney disease (CKD), increasing the risk of kidney failure and end-stage renal disease. Direct-acting antiviral (DAA) therapies for HCV infection inhibit viral replication by 95–97%, leading to a sustained virologic response. Our objective was to assess renal function in patients with chronic HCV infection in Taiwan after receiving DAA therapy. Goal: Our study included 4823 patients with HCV infection who were undergoing DAA therapy. Renal function was evaluated by calculating the glomerular filtration rate (eGFR). eGFR assessed at the initiation of the treatment, during treatment, and at 3 months, 6 months, 1 year, and 3 years after completion of treatment. The baseline demographic and laboratory parameters of the study participants were evaluated, and the results were analyzed using statistical methods. Results: The average age of the study participants was 61.35 ± 12.50 years, and 54.5% of were male. The mean of eGFR in baseline and after treatment showed a decrease. Liver fibrosis scores (FIB4, APRI, Fibroscan) and liver function tests were significantly improved after DAA treatment (p = 0.001). However, white blood count (5.41 ± 1.7 vs. 5.73 ± 1.9), platelet count (168.04 ± 74.0 vs. 182.11 ± 69.4), and creatinine levels (1.05 ± 1.3 vs. 1.12 ± 1.3) increased after treatment (p = 0.001). The number of patients with an eGFR of 60 mL/min/1.73 m² decreased both during and after treatment (p < 0.001). Among patients with CKD, eGFR improved after DAA treatment (n = 690, 35.93 ± 19.7 vs. 38.71 ± 23.8; 95% CI −3.56–1.98; p = 0.001). Logistic regression analysis revealed that renal function improved in patients with CKD who had an eGFR of less than 60 mL/min/1.73 m² before DAA treatment (OR 1.62, 95% CI 1.37–1.91, p = 0.001). Conclusions: In individuals with CKD and a baseline eGFR < 60 mL/min per 1.73 m², eGFR level was increased during DAA treatment. This suggests that initiating DAA therapy in HCV-infected patients, even those without clinical manifestations, could be a crucial strategy to prevent further decline in renal function. Full article

Background: Lung cancer remains the leading cause of cancer mortality globally with EGFR mutations representing a significant driver in advanced non-small cell lung cancer (aNSCLC). The timely detection of these mutations is critical for initiating targeted therapy, yet tissue biopsy limitations often delay treatment. Methods: This multicenter prospective study evaluated the clinical utility of liquid biopsy (LBx) in real-life settings for the early diagnosis of EGFR mutations in patients with suspected aNSCLC. Circulating tumor DNA (ctDNA) was analyzed using the Cobas EGFR Mutation Test and compared to tissue-based next-generation sequencing (NGS). Results: Among 366 aNSCLC patients tested, LBx demonstrated a significantly shorter median turnaround time (TAT) of 3 days compared to 26 days for tissue NGS (p < 0.001) with 100% specificity and 65% sensitivity for EGFR mutation detection. LBx identified actionable EGFR mutations in cases where tissue biopsy was insufficient or unavailable, enabling 43.7% of patients to commence targeted therapy based on ctDNA results prior to biopsy confirmation. Conclusions: These findings highlight the potential of LBx to reduce diagnostic delays and improve access to personalized therapies in a real-world setting. Integrating LBx into routine diagnostic workflows may address current gaps in molecular testing, ensuring timely and precise treatment for aNSCLC patients. Full article

Cancer remains a leading cause of morbidity and mortality worldwide, highlighting the urgent need for novel therapeutic agents. This study investigated the synthesis and biological evaluation of O-alkyl (E)-chalcone derivatives (4a–4v) as potential anticancer agents. The compounds were synthesized via aldol condensation of substituted aldehydes and acetophenones, with structures confirmed by IR, NMR, and mass spectrometry. In vitro cytotoxicity assays revealed varying effectiveness, with compounds 4a, 4b, 4q, and 4v exhibiting potent activity against MDA-MB-231 and MCF-7, showing IC₅₀ values between 2.08 and 13.58 µM, besides HCT-116 and HeLa cancer cell lines (IC₅₀ values between 6.59 and 22.64 µM). Notably, compound 4b displayed remarkable selectivity, with an IC₅₀ of 54.59 µM against the non-cancerous WI-38 cell line. Additionally, protein kinase inhibition assays indicated that compounds 4b and 4q effectively inhibited EGFR and VEGFR-2, with 4b outperforming the standard inhibitor erlotinib. Molecular docking studies of compound 4q showed strong binding affinities in the ATP-binding pockets of EGFR, HER2, VEGFR2, and CDK2. In silico analyses further highlighted the favorable pharmacokinetic properties of compound 4q, underscoring its potential as a selective tyrosine kinase inhibitor. These findings suggest the therapeutic promise of O-alkyl (E)-chalcone derivatives in cancer treatment. Full article

Historically, EGFR and KRAS mutations were believed to be mutually exclusive. However, over the past few years, there have been emerging case reports showing the co-existence of both mutations in a single case. The majority of these co-occurring alterations were detected in samples collected from patients with resistance to tyrosine kinase inhibitor (TKI) treatment, indicating a potential functional role in driving resistance to therapy. These co-occurring tumor genomic alterations are not necessarily mutually exclusive, and evidence suggests that multiple clonal and sub-clonal cancer cell populations can co-exist and contribute to EGFR TKI resistance. We have reported such a case of concomitant EGFR and KRAS mutation in a 64-year-old female. This case highlights the importance of continuous molecular testing in managing NSCLC, especially in cases with rare mutation profiles. The emergence of new mutations during treatment can significantly impact the course of therapy and patient outcomes. In this case, the detection of both EGFR and KRAS mutations guided the selection of an appropriate targeted therapeutic strategy, including the use of Amivantamab. Full article

Background: Chronic kidney disease (CKD) patients have an increased risk of cardiovascular disease (CVD), necessitating effective risk assessment methods. This study evaluates the calcium–phosphorus product (Ca × P) to estimated glomerular filtration rate (Ca × P/eGFR) ratio as a potential biomarker for predicting CV risk in pre-dialysis CKD patients. Methods: Eighty-four CKD patients in stages G1–G4, according to the KDIGO criteria, were classified into CVD (n = 43) and non-CVD (n = 41) groups. Biochemical parameters, including serum creatinine (SCr), blood urea nitrogen (BUN), calcium (Ca), inorganic phosphate (Pi), parathyroid hormone (PTH), alkaline phosphatase (ALP), Ca × P, eGFR, and the Ca × P/eGFR ratio, were measured and calculated. Statistical analyses were performed to identify predictors of CV risk and evaluate the diagnostic reliability of the Ca × P/eGFR ratio for predicting the risk. Results: Significant differences were observed in SCr, BUN, eGFR (p < 0.001), and the Ca × P/eGFR ratio (p = 0.007) between the groups. Regression analysis indicated the Ca × P/eGFR ratio as a significant CVD risk predictor (p = 0.012, OR = 1.206, 95% CI: 1.042–1.395). Receiver Operating Characteristic (ROC) curve analysis revealed an AUC of 0.751 (p < 0.001, 95% CI: 0.645–0.857), with a sensitivity and specificity of the method of 74.4% and 70.7%, respectively. Significant correlations were found between the Ca × P/eGFR ratio and SCr, BUN, UA, Ca, Pi, PTH, and ALP. Conclusions: The Ca × P/eGFR ratio may serve as a significant predictor of CVD risk in pre-dialysis CKD patients, suggesting that its integration into routine evaluations could enhance CV risk stratification and management. Full article

Trifolirhizin is an important flavonoid glycoside reported from the roots of medicinal plants such as Astragalus membranaceus, Sophora tonkinensis, Ononis vaginalis, Euchresta formosana, Sophora Subprostrate, Ononis spinose, and Sophora flavescens. It is considered one of the important constituents responsible for the various medicinal properties of these medicinal plants. Studies have revealed the multiple pharmacological properties of trifolirhizin: anti-inflammatory, antioxidant, antibacterial, anti-ulcerative colitis, antiasthma, hepatoprotective, osteogenic, skin-whitening, wound-healing, and anticancer (against various types of cancers). Mechanistic studies of trifolirhizin showed that it could act on important target genes and pathways such as the NF-κB-MAPK, EGFR-MAPK, AMPK/mTOR, and PI3K/Akt signaling pathways. These pathways are also implicated in various other diseases, suggesting the potential of trifolirhizin in therapeutic applications. Initial pharmacokinetic studies support the therapeutic candidature of trifolirhizin and provide the initial track that may be pursued for its development. Still, a compilation of pharmacological activities and target pathways of trifolirhizin is missing in the literature. This review uniquely compiles the pharmacological properties and mechanistic insights of trifolirhizin, addressing critical gaps in its therapeutic development and proposing strategies for future research. Full article

Background: Physical Activity (PA) provides numerous biological and psychological benefits, especially for cancer patients. PA mitigates treatment side effects, influences hormones, inflammation, adiposity, and immune function, and reduces symptoms of anxiety, depression, and fatigue. This study evaluates the impact of PA on these positive outcomes. Materials and Methods: An observational retrospective study enrolled 81 patients: 31 with CKD stages II–V and 50 with CKD and urological malignancies. Baseline and 6-month follow-up visits included clinical (Iohexol, Creatinine, Cystatin C) and anthropometric parameters (Bioimpedance Analysis, body circumferences). Physical activity levels were assessed using the Rapid Assessment of Physical Activity (RAPA) test. Patients followed a Mediterranean-like diet with controlled protein intake (MCPD) and received PA improvement advice. Statistical analysis was performed using linear regression and Pearson’s Chi-Squared test with R programming. Results: Significant reductions in total adiposity and abdominal fat and improved body fluid distribution were observed. Post intervention, there was a 25.4% reduction in inactive individuals and an 88% increase in active lifestyles. Patients aged 75+ were more likely to be sedentary, indicating a need for increased professional attention. No correlation was found between increased PA and creatinine, cystatin, and eGFR values, but a positive correlation with GFR measured by iohexol clearance remained significant in multivariate analysis. Post intervention, regular PA engagement increased from 12.3% to 48% (p < 0.002). Conclusions: Incorporating PA and nutritional assessments into standard clinical care, supported by a collaborative nephrologist–nutritionist approach, can enhance the quality of life of CKD patients. Full article

Impaired renal function can influence biomarker levels through mechanisms involving blood–brain barrier integrity and clearance pathways; however, the impact of variations within normal renal function remains unclear. The main aim of this study was to determine whether adjustment for the specific level of renal function is necessary when renal function remains within physiological levels. We studied n = 183 patients (NID n = 122; other neurological diseases n = 39; somatoform controls n = 22) who underwent lumbar puncture at University Hospital Frankfurt. Serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tau protein (tTAU), and ubiquitin C-terminal hydrolase-L1 (UCHL1) were measured using the single molecule array (SIMOA) technique. Estimated glomerular filtration rate (eGFR) correlated negatively with CSF GFAP (r = −0.217, p = 0.004) and serum NfL (r = −0.164, p = 0.032). Patients with impaired renal function exhibited higher CSF NfL (p = 0.036) and CSF GFAP (p = 0.026) levels. However, these findings did not remain significant after adjusting for BMI and age. Importantly, in patients with normal renal function, no significant correlations with eGFR and biomarker levels were observed after adjustment. Our findings indicate that serum and CSF concentrations of NfL, GFAP, tTAU, and UCHL1 are not significantly affected by fluctuations in physiological kidney function but emphasize the importance of considering comorbidities in impaired renal function when interpreting biomarker levels. Full article

C-reactive protein (CRP) and estimated glomerular filtration rate (eGFR) are key biomarkers reflecting systemic inflammation and metabolic dysfunction. This study explored systemic and oral health indicators, including CRP and eGFR, as potential factors associated with periodontitis, using a longitudinal clinical dataset comprising 23,742 records from patients identified by ICD-10 codes between 2015 and 2022. Univariate Cox analysis and Gompertz models, selected based on AIC and BIC after evaluating alternative models, were employed to assess the predictive roles of CRP and eGFR in periodontitis incidence, adjusting for oral and systemic health factors. Elevated CRP (>15 mg/L) and reduced eGFR (<60 mL/min/1.73 m²) were significant predictors of periodontitis, with hazard ratios (HR) of 1.36 [1.05–1.77] and 1.39 [1.08–1.78], respectively. Atherosclerosis (HR: 2.12 [1.11–4.06]), diseases of the hard tissues of the teeth (HR: 7.30 [5.45–9.78]), and disorders of the teeth and supporting structures (HR: 3.02 [2.05–4.43]) also demonstrated strong predictive associations. CRP and eGFR emerged as potential biomarkers for predicting periodontitis, enabling early interventions to prevent tooth loss and systemic complications. Patients with chronic kidney disease, atherosclerotic heart disease, and lipid metabolism disorders are at higher risk, emphasizing the need for integrated care addressing both systemic and oral health factors. Full article

The scorpion Buthus martensii Karsch is edible and has been an essential resource in traditional Chinese medicine for treating numerous diseases. In this study, two small peptides from B. martensii hydrolysates were examined to elucidate their potential against gastric cancer. The small peptides (AK and GK) were identified using the LC-QTOF-MS-based approach. In silico prediction of therapeutic targets, MGC-803 cells and transgenic zebrafish models, and immunoblotting experiments were used to reveal the molecular mechanism of action of the peptides. The peptides AK and GK competitively bound to the receptor to modulate the TNF/TNFR-signaling cascade and alter the tumor microenvironment. EGFR, TP53, MYC, PTEN, and STAT3 were also identified as major functional targets of the peptides. Mechanistically, AK and GK inactivated the TNF-α/EGFR/STAT3-signaling pathway, decreased c-myc protein expression levels, and upregulated p53 and PTEN expression, thereby preventing TNF-α-induced tumor growth. Our findings indicated that AK and GK played a pivotal role in offsetting the inflammatory stimuli that caused gastric cancer cell invasion and highlighted the use of B. martensii resources as functional products with health benefits. Full article