biomarker

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.

Susceptibility-weighted imaging (SWI) is based on a 3D high-spatial-resolution, velocity-corrected gradient-echo MRI sequence that uses magnitude and filtered-phase information to create images. It SWI uses tissue magnetic susceptibility differences to generate signal contrast that may arise from paramagnetic (hemosiderin), diamagnetic (minerals and calcifications) and ferromagnetic (metal) molecules. Distinguishing between calcification and blood products is possible through the filtered phase images, helping to visualize osteoblastic and osteolytic bone metastases or demonstrating calcifications and osteoid production in liposarcoma and osteosarcoma. When acquired in combination with the injection of an exogenous contrast agent, contrast-enhanced SWI (CE-SWI) can simultaneously detect the T2* susceptibility effect, T2 signal difference, contrast-induced T1 shortening, and out-of-phase fat and water chemical shift effect. Bone and soft tissue lesion SWI features have been described, including giant cell tumors in bone and synovial sarcomas in soft tissues. We expand on the appearance of benign soft-tissue lesions such as hemangioma, neurofibroma, pigmented villonodular synovitis, abscess, and hematoma. Most myxoid sarcomas demonstrate absent or just low-grade intra-tumoral hemorrhage at the baseline. CE-SWI shows superior differentiation between mature fibrotic T2* dark components and active enhancing T1 shortening components in desmoid fibromatosis. SWI has gained popularity in oncologic MSK imaging because of its sensitivity for displaying hemorrhage in soft tissue lesions, thereby helping to differentiate benign versus malignant soft tissue tumors. The ability to show the viable, enhancing portions of a soft tissue sarcoma separately from hemorrhagic/necrotic components also suggests its utility as a biomarker of tumor treatment response. It is essential to understand and appreciate the differences between spontaneous hemorrhage patterns in high-grade sarcomas and those occurring in the therapy-induced necrosis process in responding tumors. Ring-like hemosiderin SWI pattern is observed in successfully treated sarcomas. CE-SWI also demonstrates early promising results in separating the T2* blooming of healthy iron-loaded bone marrow from the T1-shortened enhancement in bone marrow that is displaced by the tumor.SWI and CE-SWI in MSK oncology learning objectives: SWI and CE-SWI can be used to identify calcifications on MRI.Certain SWI and CE-SWI patterns can correlate with tumor histologic type.CE-SWI can discriminate mature from immature components of desmoid tumors.CE-SWI patterns can help to assess treatment response in soft tissue sarcomas.Understanding CE-SWI patterns in post-surgical changes can also be useful in discriminating between residual and recurrent tumors with overlapping imaging features.

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.

Background: The unwanted adverse toxicity displayed by synthetic antidiabetic medicine leads to the search for effective natural medicine to combat diabetes complications. This study investigated the cardioprotective of Anacardium occidentale nuts methanolic in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic rats.Materials and methods: Forty male adult Wistar were used and fed with HFD for 6 weeks before diabetes induction. The rats were grouped into 5 groups, 8 rats/group. Group I: normal control; Group II: diabetic control; Group III & IV: diabetic rats + 100 mg/kgb.wt & 200 mg/kgb.wt Anacardium occidentale nuts methanolic extract; Group V: diabetic rats + 200 mg/kgb.wt metformin. The rats were sacrificed on the experiment’s last day, blood samples were collected and the hearts were isolated for biochemical parameters estimation.Results: Food intake, water intake, plasmas insulin, Fasting Blood Glucose (FBG), glycosylated hemoglobin (HbA1c), cardiac enzymes, lipid profile, inflammatory cytokines, malondialdehyde, fibrotic marker, caspase-3 in cardiac of diabetic rats were elevated (p < 0.05) significantly. Body weight, cardiac antioxidant, and anti-apoptotic marker levels diminished (p < 0.05) significantly in diabetic rats. 100 mg/kgb.wt & 200 mg/kgb.wt of Anacardium occidentale nuts methanolic extract administration significantly suppressed the plasma insulin, FBG, HbA1c, cardiac lipid profile, cardiac enzymes biomarker, cardiac inflammatory cytokines, cardiac malondialdehyde, cardiac fibrotic marker, cardiac caspase-3, food intake & water intake and increased the body weight, cardiac antioxidant & cardiac anti-apoptotic marker in the diabetic rats.Conclusion: Anacardium occidentale nuts attenuate cardiac injury in diabetes. It could be a natural medicine to manage diabetes-cardiovascular complications.

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.

Microbiome-gut-brain axis represents a complex, bidirectional communication network connecting the gastrointestinal tract and its microbial populations with the central nervous system (CNS). This complex system is important for maintaining physiological homeostasis and has significant implications for mental health. The human gut has trillions of microorganisms, collectively termed gut microbiota, which play important roles in digestion, immune function, and production of various metabolites. Some current research shows that these microorganisms strongly influence the brain function and behaviour of individuals, forming the basis of the microbiome-gut-brain axis. The communication between gut microbiota and the brain occurs via multiple pathways: neural pathway (e.g., vagus nerve), endocrine pathway (e.g., hormone production), immune pathway (e.g., inflammation modulation), and metabolic pathway (e.g., production of short-chain fatty acids). Dysbiosis, or imbalance of gut microbiota, has been linked to mental health disorders such as anxiety, depression, multiple sclerosis, autism spectrum disorders, etc, offering new perspectives on their etiology and potential therapeutic interventions. Artificial Intelligence (AI) has emerged as a powerful tool in interpreting the complexities of the microbiome-gut-brain axis. AI techniques, such as machine learning and deep learning, enable the integration and analysis of large, multifaceted datasets, uncovering patterns and correlations that can be avoided by traditional methods. These techniques enable predictive modeling, biomarker discovery, and understanding of underlying biological mechanisms, enhancing research efficiency and covering ways for personalized therapeutic approaches. The application of AI in microbiome research has provided valuable insights into mental health conditions. AI models have identified specific gut bacteria linked to disease, offered predictive models, and discovered distinct microbiome signatures associated with specific diseases. Integrating AI with microbiome research holds promise for revolutionizing mental health care, offering new diagnostic tools and targeted therapies. Challenges remain, but the potential benefits of AI-driven insights into microbiome-gut-brain interactions are immense and offer hope for innovative treatments and preventative measures to improve mental health outcomes.

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.