biomarkers

Biomarkers have been used in the diagnosis of disease and other conditions for many decades. There are diverse ranges of analytical targets, including metabolites, nucleic acids and proteins were used as a biomarker. Clinical diagnoses already rely heavily on these for patient disease classification, management, and informing treatment and care pathways. For that there is always a need of rapid and point of care test. However, until fairly recently, studies of biomarker efficacy in a clinical setting were mainly limited to single or dual use, and the landscape was complex, confused, and often inconsistent. Few candidates emerged from this somewhat clouded picture: C-reactive protein, procalcitonin (PCT) for sepsis, ADA for mycobacterium tuberculosis and a Circulating miRNAs serve as molecular markers for diverse physiological and pathological conditions.

Inflammatory Bowel Disease (IBD)-associated arthritis is called Enteropathic Arthritis (EA) which is classified among the group of Spondyloarthritis (SpA), because its presentation is variable. The current trend is to classify them as autoinflammatory rather than autoimmune diseases, since no antibodies have yet been identified. The study of biomarkers (BM) will help us with early identification and hence, to provide treatment in the early stages, prior to radiographic progression, which will enable prompt identification of the disease phenotype. 42 patients diagnosed with IBD were included, of which 48% were females; the mean age of the study group was 48.12 ± 5.02 (95% CI). The average time of evolution of disease was 37.57 ± 14.28 months; most patients referred to the rheumatologist had a diagnosis of ulcerative colitis (83%). According to our analysis, we were able to determine that the three most significant variables influencing the development of sacroiliitis were: Lactoferrin, ANCA and HLA B27 (p < 0.5). The variable that can be ruled out because of its almost neglectable contribution was fecal calprotectin.

Airway hyperresponsiveness (AHR) is a hallmark of persistent asthma measured using direct or indirect airway bronchial challenge testing. The purpose of this study is to investigate the putative relationships between type 2 inflammatory biomarkers, airway geometry (FEV1 and FEF25-75) and specific IgE (RAST or skin prick) to AHR. We performed a retrospective analysis of our database (n = 131) of patients with asthma. Of these subjects, 75 had a histamine challenge and 56 had a mannitol challenge. Fractional exhaled nitric oxide (FeNO) and specific immunoglobulin E (IgE) but not blood eosinophils were significantly higher in patients with AHR to either histamine or mannitol. FEV1 % and FEF25 - 75 % were significantly lower in patients with AHR. Elevated Type 2 biomarkers including FeNO and specific IgE but not blood eosinophils were associated with AHR. Highlights: FeNO and specific IgE but not blood eosinophils are raised in patients with airway hyperresponsiveness.

Chronic fatigue syndrome (CFS) is a poorly-understood respiratory condition that affects millions of individuals. Hyperbaric oxygen therapy (HBOT) is a treatment option being considered to address CFS as it is suggested to combat fatigue and increase oxygenation. HBOT provides two opportunities in advancing research of CFS: it may provide data on symptom amelioration and be utilized in the search for a biomarker. By either identifying biomarkers before using HBOT to compare epigenomes of patients before and after treatment or using HBOT to find epigenetic discrepancies between patients with and without treatment, matching epigenetic regulation with symptom amelioration may significantly advance the understanding of the etiology and treatment mechanism for CFS. EPAS1/HIF-2α is a leading candidate for an epigenetic biomarker as it responds differentially to hypoxic and normoxic conditions, which degrades more slowly in hypoxic conditions. Epigenetic regulation of EPAS1/HIF-2α in such differential conditions may be explored in HBOT experiments. In addition to HBOT as a promising treatment option for CFS symptoms, it may aid the identification of biomarkers in CFS. Further research into both outcomes is strongly encouraged.

Allogeneic hematopoietic stem cell transplant (alloHSCT) is a curative treatment for many hematologic malignancies. Unfortunately, about 30-50% of all recipients undergoing alloHSCT develop acute graft-versus-host-disease (aGVHD), which is associated with high morbidity and mortality [1,2]. Treatment of aGVHD involves the use of immune suppressive drugs such as high dose of steroids that leads to further immunosuppression and risk for opportunistic infections. Often patients are refractory to steroids therapy making the prognosis dismal. Thus, it is critical to identify robust biomarkers to detect aGVHD before onset of clinical symptoms so that therapeutic strategies can be implemented that may result in better treatment responses and less toxicity. 

Parkinson’s disease (PD) is thought to be the most common neurodegenerative disease with movement disorder. The key motor symptoms are rigidity, tremor, akinesis/hypokinesia/bradykinesia, and postural instability. However, in our day-to-day clinical practice we tend to see several other symptoms which may be motor or non-motor. Non-motor symptoms (NMS) are quite common and debilitating. The pathological hallmarks of PD are loss of dopaminergic neurons in the substantia nigra pars compacta (SNPc) and accumulation of unfolded or misfolded alpha-synuclein. Diagnosis of PD is difficult in the pre-motor stage. Late diagnosis renders a substantial loss of dopaminergic neurons in SNPc and spread of disease in other parts of the brain. This may manifest as either full blown symptoms requiring multiple medications or may even lead to life threatening condition due to lack of early diagnostic tools and techniques. Biomarkers are required to diagnose PD at a very early stage when prevention is possible. Hence, we see a lot of interest among researchers involved in finding a biomarker specific to the disease. Biomarkers may be clinical, image based, genetic, and biochemical. Cerebrospinal fluid (CSF) and serum markers which may correlate with disease pathophysiology are of great significance. One such molecule which recently gained a lot of attention is neuron-specific enolase (NSE). The main aim of this paper is to highlight the role of NSE in predicting neurodegeneration and neuroinflammation ultimately reflecting damage of brain cells in PD.

Background: Perinatal asphyxia (PA) which may result in hypoxic ischaemic encephalopathy (HIE) affects four million neonates worldwide and accounts for the death of one million of affected babies. The science of metabolomics has become an area of growing interest in neonatal research, with a potential role in identifying useful biomarkers that can accurately predict injury severity in perinatal asphyxia and HIE.The aim of this review is to look at the evidence of the usefulness of urine metabolomics in predicting outcome in PA/HIE. Methods: The key words used in the advanced search ‘urine metabolomics’ AND ‘perinatal asphyxia’ OR ‘hypoxic ischaemic encephalopathy’, yielded 13 articles. Results: Of the selected thirteen studies, 38% (n = 5) were human studies, 31% (n = 4) were animal studies and 31% (n = 4) were review articles. The studies confirmed the involvement of known pathways in the development of PA/HIE, primarily the Krebs cycle evidenced by accumulation of TCA cycle intermediates (citrate, α-ketoglutarate, succinate) and anaerobic pathways indicated by increased lactate. Other pathways involved include amino acid and carbohydrate pathways. Conclusion: Metabolomic studies so far are promising in highlighting potential biomarker profiles in PA/HIE. Further research is necessary to further clarify the role of identified metabolites in predicting outcome and prognosis in neonates affected by PA/HIE.

The SARS-CoV-2 pandemic is still ongoing. Previously, several studies have been conducted to investigate laboratory markers as a tool for severity assessment during COVID-19 infections. Biological markers such as Platelet count, D-dimer and IL-6, Lymphocytopenia and others have been used for assessment of severity in COVID-19 disease patients (infected by SARS-CoV-2 Alpha, Beta, Gamma, Delta, Epsilon, and other variants). We observed a significant drop in lymphocyte count among suspected SARS-CoV-2 clinical patients with symptoms of fever, running nose, breathing discomfort, cough, and others during Omicron and Centaurus variants spread in Pakistan. A multicenter, cross-sectional study was conducted from Jan 2021 to Aug 2022, on 118,561 subjects to evaluate hematological abnormalities among suspected patients. Of note, significantly decreased lymphocyte levels (lymphocytopenia) were observed among 43.05% of infected patients. Also, the levels of NA (39.03%), HGB (28.27%), MCV (22.62%), PLT (8.17%), and ALB (4.30%) were also reduced among infected patients. This suggests that lymphopenia can be used as an alternative, cost-effective, early diagnostic biomarker for clinical COVID-19 patients, even before the diagnosis via real-time PCR. In resource-limited countries, the current study is critical for policy-making strategic organizations for prioritizing lymphocytopenia-based screening (as an alternative, cost-effective diagnostic test) in clinical COVID-19 patients, before real-time PCR-based diagnosis.

Originating from China in 2019, the novel Coronavirus Disease 2019 (COVID-19) pandemic had badly affected most of the world causing immense morbidity and mortality. The disease in moderate to severe cases was characterized by intense inflammation leading to ARDS and hypercoagulable states leading to thrombo-embolism and mortality.Aim: This study aimed to explore the association of inflammatory biomarkers with COVID-19 disease severity in our hospital which became a dedicated COVID hospital during the pandemic.

Cancer is a major public health issue and the main cause of death worldwide. Despite improvements in diagnostic techniques and treatment methods, cancer still seriously affects the quality of life of patients, which cause serious social and economic burdens. Therefore, there is an urgent need to identify potential biomarkers to improve diagnosis, treatment, and prognosis of cancer. BTG2 is a cell proliferation suppressor gene that serves as a tumor suppressor gene in the occurrence and development of various tumors. Many studies have shown that BTG2 can serve as a prognostic marker in various tumors. So, fully tap the potentials of BTG2 as a tumor prognostic marker will bring more possibilities to provide a new method or new diagnostic and therapeutic tool for treating cancer.

Pre-eclampsia is a pregnancy-associated condition, which is characterized by the onset of hypertension and proteinuria. It is one of the leading causes of maternal and neonatal mortality and this affliction has been recorded in around 8% of all pregnancies in the world. In addition to this, the etiopathology of this condition is very less understood and the resources available to diagnose and treat it are limited. Prior studies suggest more than a hundred possible diagnostic biomarkers that could be used to detect this disease early on. However, most of them are not feasible due to several reasons including stability, cost, safety, etc. Here two biomarkers HtrA3 (high-temperature requirement A3) and NGAL (Neutrophil Gelatinase Associated Lipocalin) are selected for the detection of pre-eclampsia, and we compare their efficacy in the detection of pre-eclampsia based on their specificity, ease of use, speed, stage of detection and source (invasiveness). We found that these two biomarkers are efficient under some parameters, and inefficient under others. The scoring system used in the current study suggests that NGAL is a superior biomarker. The results of this study help to develop a stronger understanding of both these biomarkers in the short and long term to classify the biomarkers more efficiently and understand the complicated pathologies of pre-eclampsia.

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: 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.

Background: Monotherapy for liver dysfunction in diabetes is less effective. This study investigated the effect of combined linagliptin and metformin therapy on liver function in diabetic rats. Methods and materials: Sixty-four mature male (200-300 g) Wistar rats were used. Streptozotocin (35 mg/kgb.wt) was repeatedly injected intraperitoneally to induce diabetes. The rats were grouped into eight groups (n = 8). Group I: control; Group II: control + 10 mg/kgb.wt linagliptin; Group III: control + 200 mg/kgb.wt metformin; Group IV; control + 10 mg/kgb.wt linagliptin + 200 mg/kgb.wt metformin; Group V: diabetic; Group VI: diabetic + 10 mg/kgb.wt linagliptin; Group VII: diabetic + 200 mg/kgb.wt metformin; Group VIII: diabetic + 10 mg/kgb.wt linagliptin + 200 mg/kgb.wt metformin. The animals were sacrificed on the last day of the experiment, blood and liver samples were collected for biochemical assay. Results: Insulin, blood glucose, glycated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-cholesterol), liver function biomarkers, liver glucose metabolic enzymes, malondialdehyde and inflammatory markers increased (p < 0.05) significantly. High-density lipoprotein-cholesterol (HDL-cholesterol), liver antioxidant, glycogen, and glycogen synthase were reduced significantly in diabetic rats. Linagliptin and metformin administration single and combined reduced the insulin, blood glucose, glycated hemoglobin, total cholesterol, triglycerides, LDL-cholesterol, liver function biomarkers, liver glucose metabolic enzymes, malondialdehyde, and inflammatory markers, and increased the HDL-cholesterol, liver antioxidant, glycogen and glycogen synthase in diabetic rats.Conclusion: Linagliptin monotherapy alone efficiently controls hyperglycemia and remarkably improves liver functions. Combining linagliptin and metformin could be used as safe and effective therapy for liver dysfunction progression in diabetes.