RESUMEN

In the realm of this study, obtaining a comprehensive understanding of ischemic brain injury and its molecular foundations is of paramount importance. Our study delved into single-cell data analysis, with a specific focus on sub-celltypes and differentially expressed genes in the aftermath of ischemic injury. Notably, we observed a significant enrichment of the "ATP METABOLIC PROCESS" and "ATP HYDROLYSIS ACTIVITY" pathways, featuring pivotal genes such as Pbx3, Dguok, and Kif21b. A remarkable finding was the consistent upregulation of genes like Fabp7 and Bcl11a within the MCAO group, highlighting their crucial roles in regulating the pathway of mitochondrial ATP synthesis coupled proton transport. Furthermore, our network analysis unveiled pathways like "Neuron differentiation" and "T cell differentiation" as central in the regulatory processes of sub-celltypes. These findings provide valuable insights into the intricate molecular responses and regulatory mechanisms that govern brain injury. The shared differentially expressed genes among sub-celltypes emphasize their significance in orchestrating responses post-ischemic injury. Our research, viewed from the perspective of a medical researcher, contributes to the evolving understanding of the molecular landscape underlying ischemic brain injury, potentially paving the way for targeted therapeutic strategies and improved patient outcomes.

Asunto(s)

RESUMEN

The growth, development, and milk production traits of dairy goats, which are important sources of high-quality animal protein, are significantly influenced by a combination of genetic and environmental factors. It is imperative to identify key genetic loci that govern economically valuable traits in order to enhance breeding programs. Despite advancements in genomic technologies, there are still gaps in knowledge regarding the interplay between genetic factors and environmental influences, particularly in relation to the regulation of milk production and quality. Therefore, the aim of this paper was to synthesize advancements in the genetic and environmental factors affecting milk production and quality in dairy goats and identify key regulatory mechanisms. This review summarizes the recent progress on the identification of genes associated with milk production traits using whole-genome resequencing, the use of transcriptomic profiling to identify genes linked to milk production, the exploration of regulatory mechanisms of lipid metabolism in goat mammary epithelial cells, and the evaluation of the influence of nutritional factors on milk quality. A comprehensive understanding of these interactions is essential for enhancing breeding strategies and ensuring the sustainability of dairy goat farming. Future research should incorporate multi-omics approaches to unravel the intricate regulatory processes governing milk production and adapt practices to meet global demand while upholding economic and environmental sustainability.

RESUMEN

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative primarily affecting motor neurons, leading to disability and neuronal death, and ATP-Binding Cassette (ABC) transporter due to their role in drug efflux and modulation of various cellular pathways contributes to the pathogenesis of ALS. In this article, we extensively investigated various molecular and mechanistic pathways linking ALS transporter to the pathogenesis of ALS; this involves inflammatory pathways such as Mitogen-Activated Protein Kinase (MAPK), Phosphatidylinositol-3-Kinase/Protein Kinase B (PI3K/Akt), Toll-Like Receptor (TLR), Glycogen Synthase Kinase 3ß (GSK-3ß), Nuclear Factor Kappa-B (NF-κB), and Cyclooxygenase (COX). Oxidative pathways such as Astrocytes, Glutamate, Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Sirtuin 1 (SIRT-1), Forkhead box protein O (FOXO), Extracellular signal-regulated kinase (ERK). Additionally, we delve into the role of autophagic pathways like TAR DNA-binding protein 43 (TDP-43), AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and lastly, the apoptotic pathways. Furthermore, by understanding these intricate interactions, we aim to develop novel therapeutic strategies targeting ABC transporters, improving drug delivery, and ultimately offering a promising avenue for treating ALS.

RESUMEN

The cartilage growth plate is essential for maintaining skeletal growth; however, the mechanisms governing postnatal growth plate homeostasis are still poorly understood. Using approaches of molecular mouse genetics and spatial transcriptomics applied to formalin-fixed, paraffin-embedded (FFPE) tissues, we show that ADGRG6/GPR126, a cartilage-enriched adhesion G protein-coupled receptor (GPCR), is essential for maintaining slow-cycling resting zone cells, appropriate chondrocyte proliferation and differentiation, and growth plate homeostasis in mice. Constitutive ablation of Adgrg6 in osteochondral progenitor cells with Col2a1Cre leads to a shortened resting zone, formation of cell clusters within the proliferative zone, and an elongated hypertrophic growth plate, marked by limited expression of PTHrP but increased IHH signaling throughout the growth plate. Attenuation of Smoothened (SMO)-dependent hedgehog signaling restored the Adgrg6 deficiency-induced expansion of hypertrophic chondrocytes, confirming that IHH signaling can promote chondrocyte hypertrophy in a PTHrP-independent manner. In contrast, postnatal ablation of Adgrg6 in mature chondrocytes with AcanCreERT2, induced after the formation of the resting zone, does not affect PTHrP expression but causes an overall reduction of growth plate thickness marked by increased cell death specifically in the resting zone cells and a general reduction of chondrocyte proliferation and differentiation. Spatial transcriptomics reveals that ADGRG6 is essential for maintaining chondrocyte homeostasis by regulating osteogenic and catabolic genes in all the zones of the postnatal growth plates, potentially through positive regulation of SOX9 expression. Our findings elucidate the essential role of a cartilage-enriched adhesion GPCR in regulating cell proliferation and hypertrophic differentiation by regulation of PTHrP/IHH signaling, maintenance of slow-cycle resting zone chondrocytes, and safeguarding chondrocyte homeostasis in postnatal mouse growth plates.

The cartilage growth plate is an essential structure for skeletal growth, however, the mechanisms that govern growth plate homeostasis are still poorly understood. In this study, we showed that an adhesion G protein-coupled receptor (GPCR) named ADGRG6 plays an essential role in maintaining the slow-cycling cells in the resting zone of the growth plate and directing appropriate proliferation and differentiation of the growth plate chondrocytes. Using a technique called spatial transcriptomics, we compared the gene expression profiles in control and Adgrg6 mutant growth plates and found that ADGRG6 prevents premature hypertrophic differentiation of the growth plate chondrocytes by negatively regulating Indian Hedgehog (IHH) signaling. In summary, our findings highlighted the essential role of a cartilage-enriched GPCR in maintaining growth plate homeostasis through IHH signaling.

RESUMEN

Breast cancer, a pervasive and complex disease, continues to pose significant challenges in the field of oncology. Its heterogeneous nature and diverse molecular profiles necessitate a nuanced understanding of the underlying mechanisms driving tumorigenesis and progression. MicroRNA-21 (miR-21) has emerged as a crucial player in breast cancer development and progression by modulating apoptosis, a programmed cell death mechanism that eliminates aberrant cells. MiR-21 overexpression is a hallmark of breast cancer, and it is associated with poor prognosis and resistance to conventional therapies. This miRNA exerts its oncogenic effects by targeting various pro-apoptotic genes, including Fas ligand (FasL), programmed cell death protein 4 (PDCD4), and phosphatase and tensin homolog (PTEN). By suppressing these genes, miR-21 promotes breast cancer cell survival, proliferation, invasion, and metastasis. The identification of miR-21 as a critical regulator of apoptosis in breast cancer has opened new avenues for therapeutic intervention. This review investigates the intricate mechanisms through which miR-21 influences apoptosis, offering insights into the molecular pathways and signaling cascades involved. The dysregulation of apoptosis is a hallmark of cancer, and understanding the role of miR-21 in this context holds immense therapeutic potential. Additionally, the review highlights the clinical significance of miR-21 as a diagnostic and prognostic biomarker in breast cancer, underscoring its potential as a therapeutic target.

Asunto(s)

RESUMEN

Sickle cell anemia (SCA) is a genetically inherited hemoglobinopathy characterized by the abnormal morphology of red blood cells, resulting in vaso-occlusive events and diverse clinical complications. Recent investigations have unveiled a novel dimension in understanding SCA severity through the lens of eosinophilic dialogues. This review article synthesizes current knowledge on the molecular intricacies of eosinophils in the context of SCA, exploring their biology, molecular markers, and interactions with other cellular components. Eosinophil-mediated inflammation and oxidative stress are dissected to elucidate their impact on the disease course. Furthermore, the review evaluates potential therapeutic interventions and outlines future directions in this burgeoning field. The term "Eosinophilic Dialogues" encapsulates the multifaceted molecular exchanges that influence SCA severity, presenting a promising avenue for targeted interventions and improved clinical outcomes. This review serves as a comprehensive resource for researchers, clinicians, and healthcare practitioners engaged in unraveling the complex pathophysiology of SCA and exploring novel therapeutic avenues.

RESUMEN

Cancer prevention is currently envisioned as a molecular-based approach to prevent carcinogenesis in pre-cancerous stages, i.e., dysplasia and carcinoma in situ. Cancer is the second-leading cause of mortality worldwide, and a more than 61% increase is expected by 2040. A detailed exploration of cancer progression pathways, including the NF-kß signaling pathway, Wnt-B catenin signaling pathway, JAK-STAT pathway, TNF-α-mediated pathway, MAPK/mTOR pathway, and apoptotic and angiogenic pathways and effector molecules involved in cancer development, has been discussed in the manuscript. Critical evaluation of these effector molecules through molecular approaches using phytomolecules can intersect cancer formation and its metastasis. Manipulation of effector molecules like NF-kß, SOCS, ß-catenin, BAX, BAK, VEGF, STAT, Bcl2, p53, caspases, and CDKs has played an important role in inhibiting tumor growth and its spread. Plant-derived secondary metabolites obtained from natural sources have been extensively studied for their cancer-preventing potential in the last few decades. Eugenol, anethole, capsaicin, sanguinarine, EGCG, 6-gingerol, and resveratrol are some examples of such interesting lead molecules and are mentioned in the manuscript. This work is an attempt to put forward a comprehensive approach to understanding cancer progression pathways and their management using effector herbal molecules. The role of different plant metabolites and their chronic toxicity profiling in modulating cancer development pathways has also been highlighted.

RESUMEN

Osteoporosis is primarily associated with bone loss, but changes in bone tissue matrix composition and osteocyte mechanotransduction have also been identified. However, the molecular mechanisms underlying these changes and their relation to bone loss are not fully understood. The objectives of this study were to (1) conduct comprehensive temporal gene expression analyses on cortical bone tissue from ovariectomized rats, with a specific focus on genes known to govern matrix degradation, matrix production, and mechanotransduction, and (2) correlate these findings with bone mass, trabecular and cortical microarchitecture, and mineral and matrix composition. Microarray data revealed 35 differentially expressed genes in the cortical bone tissue of the ovariectomized cohort. We report that catabolic gene expression abates after the initial accelerated bone loss period, which occurs within the first 4 wk of estrogen deficiency. However, in long-term estrogen deficiency, we report increased expression of genes associated with extracellular matrix deposition (Spp1, COL1A1, COL1A2, OCN) and mechanotransduction (Cx43) compared with age-matched controls and short-term estrogen deficiency. These changes coincided with increased heterogeneity of mineral-to-matrix ratio and collagen maturity, to which extracellular matrix markers COL1A1 and COL1A2 were positively correlated. Interestingly, mineral heterogeneity and collagen maturity, exhibited a negative correlation with PHEX and IFT88, associated with mechanosensory cilia formation and Hedgehog (Hh) signaling. This study provides the first insight into the underlying mechanisms governing secondary mineralization and heterogeneity of matrix composition of bone tissue in long-term estrogen deficiency. We propose that altered mechanobiological responses in long-term estrogen deficiency may play a role in these changes.

RESUMEN

Rett syndrome (RTT) and Rett-like syndromes [i.e., CDKL5 deficiency disorder (CDD) and FOXG1-syndrome] represent rare yet profoundly impactful neurodevelopmental disorders (NDDs). The severity and complexity of symptoms associated with these disorders, including cognitive impairment, motor dysfunction, seizures and other neurological features significantly affect the quality of life of patients and families. Despite ongoing research efforts to identify potential therapeutic targets and develop novel treatments, current therapeutic options remain limited. Here the potential of drug repurposing (DR) as a promising avenue for addressing the unmet medical needs of individuals with RTT and related disorders is explored. Leveraging existing drugs for new therapeutic purposes, DR presents an attractive strategy, particularly suited for neurological disorders given the complexities of the central nervous system (CNS) and the challenges in blood-brain barrier penetration. The current landscape of DR efforts in these syndromes is thoroughly examined, with partiuclar focus on shared molecular pathways and potential common drug targets across these conditions.

RESUMEN

Nephritis and osteoporosis are debilitating medical conditions that significantly impact human health and reduce quality of life. To develop potential therapeutic strategies for these disorders necessitates understanding the genetic and molecular mechanisms. Here, we employed bioinformatics techniques purposed to find key genes and associated pathways responsible for nephritis-osteoporosis comorbidity. Six microarray datasets of systemic lupus erythematosus (SLE) and osteoporosis were retrieved from the Gene Expression Omnibus (GEO) database. Post normalization of data sets LIMMA package was utilized for differential expression analysis, among the datasets 44 differentially expressed genes (DEGs) were identified. The identified 44 genes were further analyzed for gene ontology (GO) where it was found that these genes are involved in defense response, organism interactions, and response to external stimuli. In predicting the molecular function, they were involved in several biological processes including binding to lipopolysaccharides and having peptidase and hydrolase activities. Firstly, the identified genes were primarily associated with certain granules such as specific granules and secretory granules in the aspect of cellular components. Enrichment analysis pointed out the potential pathways linked to the immune system, neutrophil degranulation, innate immunity, and immune response to tuberculosis. To examine interactions among DEGs, a complex protein-protein interaction (PPI) network was built, resulting in the identification of seven hub genes, CXCL8, ELANE, LCN2, MMP8, IFIT1, MX1, and ISG15. The study suggests that these elucidated hub genes might have high potential to be exploited as promising biomarkers and therapeutic targets in nephritis-osteoporosis. Taken together, this study provided deeper insights into the genetic and molecular basis for the comorbidity of nephritis and osteoporosis.

RESUMEN

Dupuytren's contracture (DC) is a fibroproliferative disorder of the palmar fascia characterised by the digits' flexion contractures and is associated with abnormal build-up of type III collagen. The prevalence of the disease is reported to be highest among Northern European descendants. However, the disease is widespread globally with varying prevalence. DC is a multifactorial disease, having both genetic and environmental factors contributing to the causality of the disease. Over the years, various studies have been conducted to understand the molecular mechanism and genetic aspects of DC but there is a lack of reports on the variants found in the exonic regions. Most reports are backdated making it necessary to re-evaluate the variants to further understand the genetic aetiology of DC. In this review, we first highlight the genetic aspects and previous genetic studies on DC. The report is followed by a discussion on the molecular pathways suggested to be associated with DC and a summary of the genetic variants in the exonic regions found in DC and their connections with the molecular pathways. A total of nine variants were reported originating from six genes comprising three pathways. Most variants reported are involved in the Wnt signalling pathway. Moreover, all variants identified are in European/Caucasian subjects and the variants found in the exonic regions are missense variants. A comparison of these findings with variants from populations of other regions can be conducted to identify the variants with the most occurrence to act as biomarkers or therapeutic targets for DC.

RESUMEN

Neuroendocrine neoplasms (NENs) are a diverse group of malignancies with a shared phenotype but varying prognosis and response to current treatments. Based on their morphological features and rate of proliferation, NENs can be classified into two main groups with a distinct clinical behavior and response to treatment: (i) well-differentiated neuroendocrine tumors (NETs) or carcinoids (with a low proliferation rate), and (ii) poorly differentiated small- or large-cell neuroendocrine carcinomas (NECs) (with a high proliferation rate). For certain NENs (such as pancreatic tumors, higher-grade tumors, and those with DNA damage repair defects), chemotherapy is the main therapeutic approach. Among the different chemotherapic agents, cisplatin and carboplatin, in combination with etoposide, have shown the greatest efficacy in treating NECs compared to NETs. The cytotoxic effects of cisplatin and carboplatin are primarily due to their binding to DNA, which interferes with normal DNA transcription and/or replication. Consistent with this, NECs, which often have mutations in pathways involved in DNA repair (such as Rb, MDM2, BRCA, and PTEN), have a high response to platinum-based chemotherapy. Identifying mutations that affect molecular pathways involved in the initiation and progression of NENs can be crucial in predicting the response to platinum chemotherapy. This review aims to highlight targetable mutations that could serve as predictors of therapeutic response to platinum-based chemotherapy in NENs.

Asunto(s)

RESUMEN

The substantial heterogeneity exhibited by head and neck cancer (HNC), encompassing diverse cellular origins, anatomical locations, and etiological contributors, combined with the prevalent late-stage diagnosis, poses significant challenges for clinical management. Genomic sequencing endeavors have revealed extensive alterations in key signaling pathways that regulate cellular proliferation and survival. Initiatives to engineer therapies targeting these dysregulated pathways are underway, with several candidate molecules progressing to clinical evaluation phases, including FDA approval for agents like the EGFR-targeting monoclonal antibody cetuximab for K-RAS wild-type, EGFR-mutant HNSCC treatment. Non-coding RNAs (ncRNAs), owing to their enhanced stability in biological fluids and their important roles in intracellular and intercellular signaling within HNC contexts, are now recognized as potent biomarkers for disease management, catalyzing further refined diagnostic and therapeutic strategies, edging closer to the personalized medicine desideratum. Enhanced comprehension of the genomic and immunological landscapes characteristic of HNC is anticipated to facilitate a more rigorous assessment of targeted therapies benefits and limitations, optimize their clinical deployment, and foster innovative advancements in treatment approaches. This review presents an update on the molecular mechanisms and mutational spectrum of HNC driving the oncogenesis of head and neck malignancies and explores their implications for advancing diagnostic methodologies and precision therapeutics.

RESUMEN

Aortic aneurysm (AA) refers to the persistent dilatation of the aorta, exceeding three centimeters. Investigating the pathophysiology of this condition is important for its prevention and management, given its responsibility for more than 25000 deaths in the United States. AAs are classified based on their location or morphology. various pathophysiologic pathways including inflammation, the immune system and atherosclerosis have been implicated in its development. Inflammatory markers such as transforming growth factor ß, interleukin-1ß, tumor necrosis factor-α, matrix metalloproteinase-2 and many more may contribute to this phenomenon. Several genetic disorders such as Marfan syndrome, Ehler-Danlos syndrome and Loeys-Dietz syndrome have also been associated with this disease. Recent years has seen the investigation of novel management of AA, exploring the implication of different immune suppressors, the role of radiation in shrinkage and prevention, as well as minimally invasive and newly hypothesized surgical methods. In this narrative review, we aim to present the new contributing factors involved in pathophysiology of AA. We also highlighted the novel management methods that have demonstrated promising benefits in clinical outcomes of the AA.

RESUMEN

This review systematically examines gender differences in hepatocellular carcinoma (HCC), identifying the influence of sex hormones, genetic variance, and environmental factors on the disease's epidemiology and treatment outcomes. Recognizing the liver as a sexually dimorphic organ, we highlight how gender-specific risk factors, such as alcohol consumption and obesity, contribute differently to hepatocarcinogenesis in men and women. We explore molecular mechanisms, including the differential expression of androgen and estrogen receptors, which mediate diverse pathways in tumor biology such as cell proliferation, apoptosis, and DNA repair. Our analysis underscores the critical need for gender-specific research in liver cancer, from molecular studies to clinical trials, to improve diagnostic accuracy and therapeutic effectiveness. By incorporating a gender perspective into all facets of liver cancer research, we advocate for a more precise and personalized approach to cancer treatment that acknowledges gender as a significant factor in both the progression of HCC and its response to treatment. This review aims to foster a deeper understanding of the biological and molecular bases of gender differences in HCC and to promote the development of tailored interventions that enhance outcomes for all patients.

RESUMEN

The human transcriptome predominantly consists of noncoding RNAs (ncRNAs), transcripts that do not encode proteins. The noncoding transcriptome governs a multitude of pathophysiological processes, offering a rich source of next-generation biomarkers. Toward achieving a holistic view of disease, the integration of these transcripts with clinical records and additional data from omic technologies ("multiomic" strategies) has motivated the adoption of artificial intelligence (AI) approaches. Given their intricate biological complexity, machine learning (ML) techniques are becoming a key component of ncRNA-based research. This article presents an overview of the potential and challenges associated with employing AI/ML-driven approaches to identify clinically relevant ncRNA biomarkers and to decipher ncRNA-associated pathogenetic mechanisms. Methodological and conceptual constraints are discussed, along with an exploration of ethical considerations inherent to AI applications for healthcare and research. The ultimate goal is to provide a comprehensive examination of the multifaceted landscape of this innovative field and its clinical implications.

Asunto(s)

RESUMEN

BACKGROUND: Exposure to chemical mixtures inherent in air pollution, has been shown to be associated with the risk of breast and lung cancers. However, studies on the molecular mechanisms of exposure to a mixture of these pollutants, such as hydrocarbons, in the development of breast and lung cancers are scarce. We utilized in silico toxicogenomic analysis to elucidate the molecular pathways linked to both cancers that are influenced by exposure to a mixture of selected hydrocarbons. The Comparative Toxicogenomics Database and Cytoscape software were used for data mining and visualization. RESULTS: Twenty-five hydrocarbons, common in air pollution with carcinogenicity classification of 1 A/B or 2 (known/presumed or suspected human carcinogen), were divided into three groups: alkanes and alkenes, halogenated hydrocarbons, and polyaromatic hydrocarbons. The in silico data-mining revealed 87 and 44 genes commonly interacted with most of the investigated hydrocarbons are linked to breast and lung cancer, respectively. The dominant interactions among the common genes are co-expression, physical interaction, genetic interaction, co-localization, and interaction in shared protein domains. Among these genes, only 16 are common in the development of both cancers. Benzo(a)pyrene and tetrachlorodibenzodioxin interacted with all 16 genes. The molecular pathways potentially affected by the investigated hydrocarbons include aryl hydrocarbon receptor, chemical carcinogenesis, ferroptosis, fluid shear stress and atherosclerosis, interleukin 17 signaling pathway, lipid and atherosclerosis, NRF2 pathway, and oxidative stress response. CONCLUSIONS: Within the inherent limitations of in silico toxicogenomics tools, we elucidated the molecular pathways associated with breast and lung cancer development potentially affected by hydrocarbons mixture. Our findings indicate adaptive responses to oxidative stress and inflammatory damages are instrumental in the development of both cancers. Additionally, ferroptosis-a non-apoptotic programmed cell death driven by lipid peroxidation and iron homeostasis-was identified as a new player in these responses. Finally, AHR potential involvement in modulating IL-8, a critical gene that mediates breast cancer invasion and metastasis to the lungs, was also highlighted. A deeper understanding of the interplay between genes associated with these pathways, and other survival signaling pathways identified in this study, will provide invaluable knowledge in assessing the risk of inhalation exposure to hydrocarbons mixture. The findings offer insights into future in vivo and in vitro laboratory investigations that focus on inhalation exposure to the hydrocarbons mixture.

RESUMEN

Targeted NGS allows a fast and efficient multi-gene analysis and the detection of key gene aberrations in melanoma. In this study, we aim to describe the genetic alterations in a series of 87 melanoma cases using the oncomine focus assay (OFA), relate these results with the clinicopathological features of the patients, and compare them with our previous study results in which we used a smaller panel, the oncomine solid tumor (OST) DNA kit. Patients diagnosed with advanced melanoma at our center from 2020 to 2022 were included and DNA and RNA were extracted for sequencing. Common mutated genes were BRAF (29%), NRAS (28%), ALK, KIT, and MAP2K1 (5% each). Co-occurring mutations were detected in 29% of the samples, including BRAF with KIT, CTNNB1, EGFR, ALK, HRAS, or MAP2K1. Amplifications and rearrangements were detected in 5% of cases. Only BRAF mutation showed a significant statistical association with sun exposure. For patients with a given genetic profile, the melanoma survival and recurrence-free survival rates were equivalent, but not for stage and LDH values. This expanded knowledge of molecular alterations has helped to more comprehensively characterize our patients and has provided relevant information for deciding the best treatment strategy.

Asunto(s)

RESUMEN

Combining immune checkpoint inhibitors, specifically nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4), holds substantial promise in revolutionizing cancer treatment. This review explores the transformative impact of these combinations, emphasizing their potential for enhancing therapeutic outcomes across various cancers. Immune checkpoint proteins, such as PD1 and CTLA4, play a pivotal role in modulating immune responses. Blocking these checkpoints unleashes anticancer activity, and the synergy observed when combining multiple checkpoint inhibitors underscores their potential for enhanced efficacy. Nivolumab and ipilimumab harness the host's immune system to target cancer cells, presenting a powerful approach to prevent tumor development. Despite their efficacy, immune checkpoint inhibitors are accompanied by a distinct set of adverse effects, particularly immune-related adverse effects affecting various organs. Understanding these challenges is crucial for optimizing treatment strategies and ensuring patient well-being. Ongoing clinical trials are actively exploring the combination of checkpoint inhibitory therapies, aiming to decipher their synergistic effects and efficacy against diverse cancer types. This review discusses the mechanisms, adverse effects, and various clinical trials involving nivolumab and ipilimumab across different cancers, emphasizing their transformative impact on cancer treatment.

RESUMEN

The process of identification and management of neurological disorder conditions faces challenges, prompting the investigation of novel methods in order to improve diagnostic accuracy. In this study, we conducted a systematic literature review to identify the significance of genetics- and molecular-pathway-based machine learning (ML) models in treating neurological disorder conditions. According to the study's objectives, search strategies were developed to extract the research studies using digital libraries. We followed rigorous study selection criteria. A total of 24 studies met the inclusion criteria and were included in the review. We classified the studies based on neurological disorders. The included studies highlighted multiple methodologies and exceptional results in treating neurological disorders. The study findings underscore the potential of the existing models, presenting personalized interventions based on the individual's conditions. The findings offer better-performing approaches that handle genetics and molecular data to generate effective outcomes. Moreover, we discuss the future research directions and challenges, emphasizing the demand for generalizing existing models in real-world clinical settings. This study contributes to advancing knowledge in the field of diagnosis and management of neurological disorders.

Asunto(s)