biomarkers

Background/Aim: There has been a progressive rise in the incidence and prevalence of End Stage Renal Disease (ESRD). It has also been observed that the most important reasons for a rapid increase in Chronic Kidney Disease (CKD) patients are the rapidly increasing worldwide incidence of diabetes and hypertension. The present study evaluates the effect of diabetes, hypertension, and comorbid state of hypertension and diabetes (hypertensive-diabetic) on renal function using serum creatinine and urea as markers. Method: A total number of 120 persons were recruited for the research; 30 controls, 30 hypertensive, 30 diabetic, and 30 hypertensive-diabetic persons. Of the 30 control persons, 18 were females and 12 were males; of the 30 hypertensive subjects, 17 were females and 13 were males; of the 30 diabetics subjects, 20 were females and 10 were males, whereas of the 30 hypertensive-diabetic subjects, 21 were females and 9 were males. In total, there were seventy-six (76) females and 44 males. The respondents were pulled from Central Hospital (Auchi) Diabetic and General Clinic and Auchi Polytechnic Cottage Hospital. Verbal consent was sort and questionnaires were used to extract information regarding biodata and patients’ history of diabetes and hypertension. Height and weight were measured, and blood pressure was determined taken. Blood samples were collected into fluoride oxalate and lithium heparin bottle for the assessment of FBS and (serum urea and creatinine) respectively. Results: The mean (±SD) serum creatinine was higher in the hypertensive-diabetic group (2.08 ± 1.06) and declined as follows: diabetic group (1.75 ± 1.01), hypertensive group (1.34 ± 0.96) and control group (0.70 ± 0.14). The mean (±SD) serum urea was also found to be higher in the hypertensive-diabetic group (17.5 ± 9.06) and declined as follows: diabetic group (14.5 ± 6.13), hypertensive group (12.7 ± 6.23) and control group (7.18 ± 5.06). There was a positive correlation between serum creatinine and fasting blood sugar The study also established a positive correlation between serum creatinine and blood pressure but not between serum urea and blood pressure with r values of 0.31 and 0.16 respectively. Conclusion: Good control of blood glucose and blood pressure levels reduces the likelihood of the development of renal impairment which is usually associated with both diabetes and hypertension. Co-morbidity of diabetes and hypertension poses a higher risk of developing renal disease than individual problems of diabetes and hypertension. Serum creatinine and serum urea are important biomarkers for renal impairment hence the two should be monitored on a regular basis for diabetic and hypertensive patients and much more frequently for hypertensive-diabetic patients.

Kidney transplantation is the therapy of choice for patients with end-stage kidney disease (ESKD). Nevertheless, the main limitation for long-term graft survival is immune-mediated rejection. Some authors have proposed that differences in immune effector mechanisms are influenced by underlying molecular mechanisms; thereby, the identification of differentially expressed genes in acute or chronic rejection in non-invasive samples such as urine may be essential for the identification of potential biomarkers and biological processes associated with allograft outcomes. Our aim was to explore differences in gene expression and functional categories associated with acute and chronic kidney rejection in blood, biopsy, and urine of kidney transplant patients using RNA-Seq. RNA was isolated and sequenced implementing standard protocols. Analyses were addressed to identify differentially expressed genes (DEGs) and Functional Categories of Gene Ontology comparing between samples. Then we focused on immune genes and pathways to identify their association with the allograft. We identified a significant transcriptional similarity between biopsy and urine, in comparison with blood in acute and chronic rejection. Functional analyses suggested an enrichment of immune processes such as antigen processing and presentation, and regulation of B cell receptor signaling pathway in blood of acute and chronic rejection, respectively. Additionally, we observed an increase in expression of chemokines in biopsy and urine of both outcomes along with an increase in chemokine receptors in blood. Our findings suggest that urine is suitable for identifying potential biomarkers and biological processes related to renal allograft rejection, as it shares a significant number of regulated genes with biopsy.

With the increase in incidence and prevalence of myeloid neoplasms in India, it has become a necessity to understand its molecular mechanisms, acquisition of genomic alterations, and understand its primary and secondary resistance pathways which ultimately impact the decision of therapeutics. The objective of this review is to investigate the molecular aspects of this disease type and identify the biomarkers that help with diagnosis, risk assessment, prognosis, and selecting the best line of treatment for a specific myeloid neoplasm. Advancements and innovations in molecular technologies from simplest Real-Time PCR to high throughput next-generation sequencing have played a vital role in screening the most common mutations and fusions to the novel and rare. Molecular technologies have helped to enumerate the genomic landscape of myeloid malignancies. The understanding of both- the mechanisms and the technology is a strong combination as it has helped revolutionize precision oncology and helped in giving better therapeutic choices with better clinical outcomes. The importance of cellular morphology, clinical symptoms, and molecular pathology in assessing the risk of myeloid malignancies is emphasized and summarized in the review. The review concludes that understanding molecular pathogenesis can be improved by using clinical-pathological-molecular strategies for diagnosis and therapy decision-making.

Neurologic diseases are recognized to have multifactorial origins well beyond mere genetic predisposition. Nutritional burdens have been identified to contribute to neurodegeneration. Healthy diets are becoming increasingly appreciated to potentially play key roles in both the developing and developed world of reducing incidences of neurologic diseases, while unhealthy diets are acknowledged to be contributing to their rise.

Sepsis, a life-threatening condition triggered by infection, poses a significant healthcare challenge with high mortality rates. The interplay between genetics and the immune response in sepsis, particularly in surgical and trauma patients, is complex and critical. Genetic polymorphisms, particularly in cytokine genes like TNF-α, IL-6, and IL-8, have been extensively studied for their influence on sepsis susceptibility, severity, and outcomes. Polymorphisms can alter gene expression and cytokine production, leading to variations in immune responses. Studies have also explored polymorphisms concerning sepsis in genes encoding CD86, TLR4, and SIRT6. This review highlights the association between genetic polymorphisms and inflammatory responses, focusing on their impact on sepsis outcomes in surgical and trauma patients. Genetic variations play a significant role in sepsis risk, severity, and prognosis, with potential implications for personalized therapeutic strategies. Biomarkers such as cytokine gene polymorphisms may aid in predicting sepsis risk and guiding treatment decisions. Complementary therapies like acupuncture and novel biomarkers like microvesicles carrying mitochondrial content provide additional avenues for personalized sepsis management. Furthermore, multiomics approaches offer promise in predicting postoperative outcomes in surgical patients. Understanding the genetic basis of sepsis is essential for improving prevention, diagnosis, and treatment, ultimately leading to better clinical outcomes. Combining genomics, bioinformatics, and clinical expertise, precision medicine can revolutionize sepsis management by tailoring interventions to individual genetic profiles, thus enhancing patient care and outcomes.

Background: Effective medication to manage diabetes mellitus-related organ complications with minimal adverse drug toxicity is still in pursuit by scientists worldwide. This study investigated the cardio-protective of Rida herbal bitter (RHB) in a high-fat diet/streptozotocin (STZ)-induced diabetic rats.Methods: Thirty-two matured male Wistar rats (250 ± 20g) were used. The animals were fed with high-fat diet (HFD) for 6 weeks before diabetes induction. A single dose of (35 mg/kgb.wt) freshly prepared STZ was injected intraperitoneally to induce diabetes. The animals were allocated into four groups, 8rats/group. Group I: control; Group II: HFD/STZ-induced diabetic rats; Groups III & IV: HFD/STZ-induced diabetic rats treated with 0.3 ml RHB & 200 mg/kgb.wt metformin respectively. At the end of the experiment, the animals were sacrificed, blood was sample collected via cardiac puncture and the heart was excised and homogenized. The blood samples and cardiac homogenates tissue were centrifuged to retrieve clear supernatant plasma for biochemical assay.Results: Diabetic rats exhibited significant (p < 0.05) elevated blood glucose, insulin, glycated hemoglobin (HbA1c), cardiac biomarkers, lipid profile, malondialdehyde (MDA), pro-inflammatory cytokines, food, and water intake levels with a reduction in body weight, cardiac antioxidant activity, and total protein. RHB administration significantly (p < 0.05) diminished the blood glucose, insulin, HbA1c, cardiac biomarkers, MDA, pro-inflammatory cytokines, lipid profile, food, and water intake, and improved the body weight cardiac antioxidant activity, and total protein.Conclusion: Rida herbal bitter possesses a cardio-protective effect from this study and could be a better alternative medication for managing diabetes and its related cardiovascular complications.

Background: Acute leukemia is the result of clonal transformation and proliferation of a hematopoietic progenitor giving rise to poorly differentiated neoplastic cells. Reactive oxygen species play a role in maintaining the quiescence, self-renewal, and long-term survival of hematopoietic stem cells, but it is unclear how they would affect disease onset and progression. The aim is to evaluate, at the transcriptional and systemic level, the oxidative-inflammatory status in newly diagnosis acute leukemia patients. Methods: Seventy acute leukemia patients [26 acute lymphoblastic leukemia (ALL), 13 Acute Promyelocytic Leukemia (APL), and 31 Acute Myeloid Leukemia (AML)] and forty-one healthy controls were analyzed. Malondialdehyde and catalase activity were evaluated. Gene expression of NRF2, SOD, PRDX2, CAT, IL-6, and TNF-α was analyzed by real-time PCR.Results: Malondialdehyde concentration was similar in all groups studied. Catalase activity was significantly higher in AML and APL patients compared to controls, while ALL showed similar activity to the healthy group. NRF2, CAT, and PRDX2 expression levels were similar between groups, SOD expression was downregulated in all acute leukemia patients. TNF-α expression was lower in AML groups than in healthy individuals, and IL-6 mRNA expression was downregulated in ALL and APL.Conclusion: This is the first report that correlates transcriptional and systemic parameters associated with the oxidative inflammatory status in newly diagnosed acute leukemia. Some of the parameters evaluated could be used as biomarkers in the selection of an effective therapeutic strategy and will open new directions for the follow-up and evolution of this disease.

Introduction: Immune checkpoint inhibitors (ICI) have significantly improved cancer treatment outcomes, but cardiovascular complications such as ICI-associated myocarditis are a major concern. Diagnosing myocarditis requires integrating biomarkers, electrocardiogram (EKG), cardiac imaging, and endomyocardial biopsy. We present a case illustrating these diagnostic challenges, involving a female patient treated with pembrolizumab who developed fatal acute myocarditis mimicking infiltrative cardiomyopathy.Case report: A 54-year-old woman with mucosal melanoma, treated with pembrolizumab, was hospitalized in May 2023 due to dyspnea and elevated troponin levels. Initial cardiac workups were normal, but subsequent tests revealed borderline cardiac magnetic resonance imaging findings. In late May 2023, the patient was admitted with worsening dyspnea, elevated NT-pro-BNP, and severe hyperlactatemia. Imaging and endomyocardial biopsy confirmed acute myocarditis with atypical presentation, mimicking infiltrative cardiomyopathy. Despite aggressive immunosuppressive therapy, the patient’s condition deteriorated, resulting in cardiogenic shock and death seven days post-admission.Conclusion: This case underscores the diagnostic and management challenges of ICI-associated myocarditis, particularly with atypical presentations. It highlights the need for vigilant, comprehensive monitoring and further research to improve diagnostic and therapeutic strategies for managing these severe side effects in patients undergoing ICI therapy.

Non-small-cell lung cancer (NSCLC) accounts for 85% of lung cancer cases and is associated with different risk factors (smoking habits, gender, and age). In this scenario, many studies have been conducted to pursue improvement of survival, faster and better therapy response, reduced adverse events, and expanded available therapies and treatments against tumor resistance to drugs. These studies have focused on defining the most prevalent NSCLC biomarkers (EGFR, HER2, ALK, MET, ROS1, BRAF, KRAS G12C, HER3, NTRK, and NRG1) and their actionability. It is noteworthy that expressed kinase receptors can have overlapping mechanisms of activation of different pathways (JAK-STAT, MAPK, PI3K-AKT-mTOR, and PLC-c), which can lead to the same outcome of cell proliferation, migration, and survival resulting in increased tumor resistance to treatment. This review provides an overview of the latest findings regarding NSCLC treatment, emphasizing particular biomarkers and potential molecularly altered pathways implicated as targeted therapies. Additionally, it explores the clinical significance of the proposed treatments, their implication on progression-free survival, ongoing clinical trials, and their perspective of evolution so far.

Neurotoxicity is increasingly recognized as a critical factor impacting long-term health, with growing evidence linking it to both neurodevelopmental and neurodegenerative diseases. Pesticides, widely used in agriculture and industry, have emerged as significant contributors to neurotoxic risk, given their capacity to disrupt key neurodevelopmental processes at low exposure levels. As conventional animal models present limitations in interspecies translation, human-derived neuron-based in vitro screening strategies are urgently needed to assess potential toxicants accurately. Human-induced pluripotent stem cells (hiPSCs) offer an innovative and scalable source for human-specific neuronal models that complement traditional animal-based approaches and support the development of predictive assays for neurotoxicity. Recent various stem cell models, including 2D cultures, 3D organoids, and microfluidic systems, are now available, advancing predictive neurotoxicology by simulating key aspects of human neural development and function. With the integration of High-Throughput (HT) and High-Content (HC) screening methodologies, these hiPSC-based systems enable efficient, large-scale evaluation of chemical effects on neural cells, enhancing our ability to detect early biomarkers of neurotoxic effects. Identifying early biomarkers of neurotoxic is essential to developing therapeutic interventions before irreversible damage occurs. This is particularly crucial in the context of developmental neurotoxicity, where early exposure to toxicants can have lifelong consequences. This review specifically presents an in-depth overview of the current progress in hiPSC-derived neural models and their applications in neurotoxicity testing, with a specific focus on their utility in assessing pesticide-induced neurotoxicity. Emphasizing future research priorities, we highlight the potential of these models to transform predictive toxicology, offering more human-relevant assessments and advancing the field toward a more precise evaluation of environmental neurotoxicants.

Chronic Kidney Disease (CKD) is a significant public health issue with a rising prevalence globally. Diabetic kidney disease (DKD), a leading cause of CKD, necessitates improved biomarkers for early detection and effective management. Traditional markers such as serum creatinine, estimated glomerular filtration rate (eGFR), and albuminuria have notable limitations in sensitivity and specificity, especially for early detection. Fetuin-A, specifically its post-translationally modified form (PTM-Fetuin-A), has emerged as a potential novel biomarker for DKD. This study evaluates PTM-Fetuin-A in a cohort of Bulgarian patients with type 1 and type 2 diabetes, assessing its correlation with traditional markers such as albuminuria and eGFR. Significant correlations were observed between PTM-Fetuin-A and these indicators (e.g., Pearson’s r = 0.447, p = 0.025 for albuminuria), highlighting its ability to detect early kidney function decline. Furthermore, PTM-Fetuin-A demonstrated potential as a non-invasive tool for identifying normoalbuminuric DKD, addressing gaps left by conventional biomarkers. By offering additional prognostic value, PTM-Fetuin-A could improve the early diagnosis and clinical management of diabetic patients, reducing the burden of CKD.