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Chimeric antigen receptor T cell (CAR T cell) therapy has emerged as a prominent adoptive cell therapy and a therapeutic approach of great interest in the fight against cancer. This approach has shown notorious efficacy in refractory hematological neoplasm, which has bolstered its exploration in the field of solid cancers. However, successfully managing solid tumors presents considerable intrinsic challenges, which include the necessity of guiding the modified cells toward the tumoral region, assuring their penetration and survival in adverse microenvironments, and addressing the complexity of identifying the specific antigens for each type of cancer. This review focuses on outlining the challenges faced by CAR T cell therapy when used in the treatment of solid tumors, as well as presenting optimizations and emergent approaches directed at improving its efficacy in this particular context. From precise localization to the modulation of the tumoral microenvironment and the adaptation of antigen recognition strategies, diverse pathways will be examined to overcome the current limitations and buttress the therapeutic potential of CAR T cells in the fight against solid tumors. [ABSTRACT FROM AUTHOR]

Background: Cancer genomics, as an interdisciplinary research area within the Global Cancer Research agenda, genomics and precision medicine, its important in research and clinical practice in Latin America. To date, there has been no study investigating evolution of this area in this region. The aim of this study was to evaluate for first time, the historical evolution of cancer genomics research in Latin America. Methods: Bibliometric cross-sectional study of documents on cancer genomics published by Latin American authors until 2023 in Scopus was performed. Statistical and visual analysis was performed with R programming language. Results: A total of 1534 documents were obtained. The first document of cancer genomics research was published in 1997, marking the inception of a 26-year evaluation period that extended until 2023. Among the documents, 74.3% (n = 1140) constituted original articles, followed by 22.7% (n = 349) classified as reviews. International collaboration was observed in 6.5% (n = 100) of the articles. Within the compilation of the ten most prolific authors in this region, 90% of them are from Brazil. This observed pattern extends to affiliations as well, wherein the Universidade de São Paulo emerges as the most active institution (n = 255 documents). This arrangement firmly establishes Brazil's prominence as the preeminent country in the region concerning cancer genomics research, showcasing robust collaboration networks both regionally and intercontinentally. An important transition in the studied hot topics over the last 20 years was identified, from the exploration of the human genome and the characterization of genomic and proteomic cancer profiles (1997-2010) to an indepth investigation of cancer stem cells and personalized medicine (2011-2023). Among the array of cancer types under study, predominant attention has been directed towards breast, lung, prostate, and leukemia. Conclusion: Over the course of the past 26 years, a favorable and notable evolution has characterized cancer genomics research within Latin America, with Brazil leading the way, which possess a robust network of regional and intercontinental collaboration. Furthermore, the lines of research and hot topics have change in harmony with the region's objectives, strategies, and requisites. [ABSTRACT FROM AUTHOR]

Suicide is a complex and multifaceted public health issue that affects individuals from all walks of life, including healthcare professionals such as physicians. According to research, physicians have a higher risk of suicide compared to the general population, with an estimated suicide rate that is two to three times greater than that of the general population. Suicide in physicians can have devastating consequences, not only for the individual but also for their patients and colleagues. The factors contributing to suicide in physicians are numerous and often interrelated. Physicians are exposed to numerous stressors in their daily lives, including long work hours, high workload, burnout, and exposure to traumatic events. These stressors can lead to mental health problems such as depression, anxiety, and substance use disorders, which in turn can increase the risk of suicide. In addition to work-related stressors, personal factors such as relationship problems, financial stress, and a history of mental health problems can also contribute to suicide risk in physicians. Stigma and shame around seeking help for mental health issues may also prevent physicians from seeking treatment, exacerbating the problem. Understanding the complex factors that contribute to suicide in physicians is crucial for developing effective prevention strategies. For this reason, it is necessary to know the behavior of this phenomenon and the factors associated with a higher risk of suicide in this population. However, taking into account that different regions of the world vary in socioeconomic, cultural, professional, occupational, and health attributes, it is to be expected that the behavior of these risk factors will also be heterogeneous. At present, it is presumed that there is a significant gap in the evidence, due to a predominance of evidence on this topic from high-income countries. Considering the importance of having a comprehensive understanding of the risk factors for suicide in the medical population and possible strategies to mitigate this condition, the aim of this review is to analyze the most recent evidence on these factors, and to assess the quality of the evidence and gaps that need to be studied further. [ABSTRACT FROM AUTHOR]

The growing emergence of microbes resistant to commercially available antibiotic therapies poses a threat to healthcare systems worldwide. Multiple factors have been associated with the increasing incidence of hospital-acquired infections caused by antibiotic-resistant pathogens, including the indiscriminate use of broad-spectrum antibiotics, the massive application of antibiotics in hospitals as a prophylactic measure, self-medication, and nonadherence to pharmacological therapies by patients. In this study, we developed a novel treatment to mitigate the impact of microbial resistance. We synthesized a benzoporphyrin derivative, 5,10,15,20-tetrakis (4-ethylphenyl) porphyrin (TEtPP), with a reaction yield close to 50%. TEtPP exhibited excellent photophysical properties (Φf = 0.12 ± 0.04 and ΦΔ = 0.81 ± 0.23) and was thereby assessed as a potential agent for antibacterial photodynamic therapy. The photophysical properties of the synthesized porphyrin derivative were correlated with the assayed antimicrobial activity. TEtPP showed higher activity against the MRSA strain under irradiation than in the absence of irradiation (minimum inhibitory concentration (MIC) = 69.42 µg/mL vs. MIC = 109.30 µg/mL, p < 0.0001). Similar behavior was observed against P. aeruginosa (irradiated MIC = 54.71 µg/mL vs. nonirradiated MIC = 402.90 µg/mL, p < 0.0001). TEtPP exhibited high activity against S. aureus in both the irradiated and nonirradiated assays (MIC = 67.68 µg/mL vs. MIC = 58.26 µg/mL, p = 0.87). [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and long COVID. [ABSTRACT FROM AUTHOR]

Introduction: According to the World Health Organization, overweight and obesity occur due to an abnormal or excessive accumulation of body fat that is harmful to health. During childhood and adolescence, risk factors such as dyslipidemia or obesity are detected, the maintenance of which in the adult stage has been verified, indicating that detection should be started as early as possible. It is necessary to carry out an anthropometric <- nutritional evaluation to detect a deficit or excess weight in time. A study on the topic of chronic non-communicable diseases in Colombia indicated that in 2014 more than 100,000 people died with ischemic and hemorrhagic cerebrovascular diseases (CVDs), cancer, DM and chronic obstructive pulmonary disease (COPD), by being able to carry out early detections that will allow adequate prevention of secondary complications. Methodology: An observational, descriptive, cross-sectional study was carried out with a population - sample of 36 university students of both sexes. After informed consent, those who met the inclusion criteria demanded by Bioimpedance included: weight, height, visceral fat, body fat, In addition to abdominal or waist circumference, hip and lipid profile: total cholesterol (CT), triglycerides (TG), HDLc, VLDLc. LDLc. Results: Overweight and obesity in the results of (BMI, Gf and FV)), found in young male and female sex with prevalence in the male sex group, and hyperlipidemias mainly in the female sex studied. Conclusion: High prevalence of CVD risk factors such as overweight, obesity, and hyperlipidemia in the female sex group. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVD) are a global public health problem; today they constitute the first cause of disease and death in the western world. Currently in Latin America and the Caribbean, cardiovascular diseases account for 31% of all deaths. It is estimated that 20.7 million deaths from CVD will occur during the next 10 years. Dyslipidemia is a serious current problem because the condition an increase in mortality in adults. People affected with hypercholesterolemia can avoid cholesterol-lowering medications, with a diet based on functional foods (probiotics). Having a stable and balanced intestinal microbiota is a guarantee of health. Objective: To analyze the use of probiotics in nutritional therapy on dyslipidemia as a cardiovascular risk factor. Methodology: A retrospective and comparative descriptive bibliographic review study was carried out with the following descriptors: lipid profile, probiotics, dyslipidemias, which met the inclusion criteria. The search occurred between february 2019 a february 2020. For a total of: 135 articles published between: 1965 to 2020. Results: Researchers seek to develop therapeutic strategies to prevent and treat metabolic syndrome, with the use of probiotics. A current meta-analysis found that probiotics decreased serum levels of Total Cholesterol and LDL-col in hypercholesterolemic adults, which means that probiotics can reduce CVD morbidity. Conclusion: Probiotic supplementation could be taken as a new therapy for the treatment of hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Background and Purpose: Pharmacological strategies aimed to facilitate neuronal renewal in the adult brain, by promoting endogenous neurogenesis, constitute promising therapeutic options for pathological or traumatic brain lesions. We have previously shown that non-tumour-promoting PKC-activating compounds (12-deoxyphorbols) promote adult neural progenitor cell (NPC) proliferation in vitro and in vivo, enhancing the endogenous neurogenic response of the brain to a traumatic injury. Here, we show for the first time that a diterpene with a lathyrane skeleton can also activate PKC and promote NPC proliferation.Experimental Approach: We isolated four lathyranes from the latex of Euphorbia plants and tested their effect on postnatal NPC proliferation, using neurosphere cultures. The bioactive lathyrane ELAC (3,12-di-O-acetyl-8-O-tigloilingol) was also injected into the ventricles of adult mice to analyse its effect on adult NPC proliferation in vivo.Key Results: The lathyrane ELAC activated PKC and significantly increased postnatal NPC proliferation in vitro, particularly in synergy with FGF2. In addition ELAC stimulated proliferation of NPC, specifically affecting undifferentiated transit amplifying cells. The proliferative effect of ELAC was reversed by either the classical/novel PKC inhibitor Gö6850 or the classical PKC inhibitor Gö6976, suggesting that NPC proliferation is promoted in response to activation of classical PKCs, particularly PKCß. ELAC slightly increased the proportion of NPC expressing Sox2. The effects of ELAC disappeared upon acetylation of its C7-hydroxyl group.Conclusions and Implications: We propose lathyranes like ELAC as new drug candidates to modulate adult neurogenesis through PKC activation. Functional and structural comparisons between ELAC and phorboids are included. [ABSTRACT FROM AUTHOR]

The aim of this study was to identity in silico the relationships among microRNAs (miRNAs) and genes encoding transcription factors, ubiquitylation, DNA methylation, and histone modifications in systemic lupus erythematosus (SLE). To identify miRNA dysregulation in SLE, we used miR2Disease and PhenomiR for information about miRNAs exhibiting differential regulation in disease and other biological processes, and HMDD for information about experimentally supported human miRNA–disease association data from genetics, epigenetics, circulating miRNAs, and miRNA–target interactions. This information was incorporated into the miRNA analysis. High-throughput sequencing revealed circulating miRNAs associated with kidney damage in patients with SLE. As the main finding of our in silico analysis of miRNAs differentially expressed in SLE and their interactions with disease-susceptibility genes, post-translational modifications, and transcription factors; we highlight 226 miRNAs associated with genes and processes. Moreover, we highlight that alterations of miRNAs such as hsa-miR-30a-5p, hsa-miR-16-5p, hsa-miR-142-5p, and hsa-miR-324-3p are most commonly associated with post-translational modifications. In addition, altered miRNAs that are most frequently associated with susceptibility-related genes are hsa-miR-16-5p, hsa-miR-374a-5p, hsa-miR-34a-5p, hsa-miR-31-5p, and hsa-miR-1-3p. [ABSTRACT FROM AUTHOR]

Background: Renal biopsy is the gold standard for the diagnosis and classification of lupus nephritis (LN). However, a consecutive biopsy can predict the clinical course and optimize the therapeutic strategies. Objectives: To compare the histopathological findings with clinical responses. Patients and Methods: Thirty patients with active LN were included. Renal biopsies were performed at the time of diagnosis and subsequently under clinical criteria according to consensus of Spanish Society of Nephrology. The response to treatment was defined as complete response, partial responder or non-responder. The histological change in second biopsy towards LN classes I, II or III/IV-C was defined as histological response (HR). Results: In initial renal biopsy, 28 (93%) patients showed proliferative LN; III-A or A/C (n; 7), IV-A or A/C (n: 19) and mixed; III+IV/V (n; 2). LN class V was presented in two cases. The clinical response was; complete response (10%), partial response (20%), and non-response (70%). HR was manifested in 37% and non-histologic response in 63% of patients. Around 33% of patients with complete response/partial response showed active lesions in the consecutive renal biopsy. Conclusions: In Colombian Caribbean, LN is aggressive and refractory to treatment. The consecutive renal biopsy allowed to demonstrate the persistence of the activity of the lesion in almost half of the patients, which may provide additional information to create better response criteria. The consecutive renal biopsy is a tool that allows improving the evaluation of the response to treatment in the LN. [ABSTRACT FROM AUTHOR]

Renal involvement in Systemic Lupus Erythematous (SLE) patients is one of the leading causes of morbidity and a significant contributor to mortality. It’s estimated that nearly 50% of SLE individuals develop kidney disease in the first year of the diagnosis. Class IV lupus nephritis (LN-IV) is the class of lupus nephritis most common in Colombian patients with SLE. Altered miRNAs expression levels have been reported in human autoimmune diseases including lupus. Variations in the expression pattern of peripheral blood circulating miRNAs specific for this class of lupus nephritis could be correlated with the pathophysiological status of this group of individuals. The aim of this study was to evaluate the relative abundance of circulating microRNAs in peripheral blood from Colombian patients with LN-IV. Circulating miRNAs in plasma of patients with diagnosis of LN-IV were compared with individuals without renal involvement (LNN group) and healthy individuals (CTL group). Total RNA was extracted from 10 ml of venous blood and subsequently sequenced using Illumina. The sequences were processed and these were analyzed using miRBase and Ensembl databases. Differential gene expression analysis was carried out with edgeR and functional analysis were done with DIANA-miRPath. Analysis was carried out using as variables of selection fold change (≥2 o ≤-2) and false discovery rate (0.05). We identified 24 circulating microRNAs with differential abundance between LN-IV and CTL groups, fourteen of these microRNAs are described for the first time to lupus nephritis (hsa-miR-589-3p, hsa-miR-1260b, hsa-miR-4511, hsa-miR-485-5p, hsa-miR-584-5p, hsa-miR-543, hsa-miR-153-3p, hsa-miR-6087, hsa-miR-3942-5p, hsa-miR-7977, hsa-miR-323b-3p, hsa-miR-4732-3p and hsa-miR-6741-3p). These changes in the abundance of miRNAs could be interpreted as alterations in the miRNAs-mRNA regulatory network in the pathogenesis of LN, preceding the clinical onset of the disease. The findings thus contribute to understanding the disease process and are likely to pave the way towards identifying disease biomarkers for early diagnosis of LN. [ABSTRACT FROM AUTHOR]

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Renal involvement is one of the most severe manifestations of systemic lupus erythematosus (SLE). Renal biopsy is the gold standard when it comes to knowing whether a patient has lupus nephritis, and the degree of renal disease present. However, the biopsy has various complications, bleeding being the most common. Therefore, the development of alternative, non-invasive diagnostic tests for kidney disease in patients with SLE is a priority. Micro RNAs (miRNAs) are differentially expressed in various tissues, and changes in their expression have been associated with several pathological processes. The aim of this study was to identify changes in the abundance of miRNAs in plasma samples from patients with lupus nephritis that could potentially allow the diagnosis of renal damage in SLE patients. This is an observational case-control cross-sectional study, in which we characterized the differential abundance profiles of miRNAs among patients with different degrees of lupus compared with SLE patients without renal involvement and healthy control individuals. We found 89 miRNAs with changes in their abundance between lupus nephritis patients and healthy controls, and 17 miRNAs that showed significant variations between SLE patients with or without renal involvement. Validation for qPCR of a group of miRNAs on additional samples from lupus patients with or without nephritis, and from healthy individuals, showed that five miRNAs presented an average detection sensitivity of 97%, a specificity of 70.3%, a positive predictive value of 82.5%, a negative predictive value of 96% and a diagnosis efficiency of 87.9%. These results strongly suggest that miR-221-5p, miR-380-3p, miR-556-5p, miR-758-3p and miR-3074-3p are potential diagnostic biomarkers of lupus nephritis in patients with SLE. The observed differential pattern of miRNA abundance may have functional implications in the pathophysiology of SLE renal damage. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Post-translational modifications (PTMs) have been extensively studied in malignancies due to its relevance in tumor pathogenesis and therapy. This review is focused on the dysregulation of glycosyltransferase expression in CRC and its impact in cell function and in several biological pathways associated with CRC pathogenesis, prognosis and therapeutic approaches. Glycan structures act as interface molecules between cells and their environment and in several cases facilitate molecule function. CRC tissue shows alterations in glycan structures decorating molecules, such as annexin-1, mucins, heat shock protein 90 (Hsp90), β1 integrin, carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR), insulin-like growth factor-binding protein 3 (IGFBP3), transforming growth factor beta (TGF-β) receptors, Fas (CD95), PD-L1, decorin, sorbin and SH3 domain-containing protein 1 (SORBS1), CD147 and glycosphingolipids. All of these are described as key molecules in oncogenesis and metastasis. Therefore, glycosylation in CRC can affect cell migration, cell–cell adhesion, actin polymerization, mitosis, cell membrane repair, apoptosis, cell differentiation, stemness regulation, intestinal mucosal barrier integrity, immune system regulation, T cell polarization and gut microbiota composition; all such functions are associated with the prognosis and evolution of the disease. According to these findings, multiple strategies have been evaluated to alter oligosaccharide processing and to modify glycoconjugate structures in order to control CRC progression and prevent metastasis. Additionally, immunotherapy approaches have contemplated the use of neo-antigens, generated by altered glycosylation, as targets for tumor-specific T cells or engineered CAR (Chimeric antigen receptors) T cells. [ABSTRACT FROM AUTHOR]

Ciguatera is a food intoxication caused by the consumption of primarily coral fish; these species exist in large numbers in the seas that surround the Colombian territory. The underreported diagnosis of this clinical entity has been widely highlighted due to multiple factors, such as, among others, ignorance by the primary care practitioner consulted for this condition as well as clinical similarity to secondary gastroenteric symptoms and common food poisonings of bacterial, parasitic or viral etiology. Eventually, it was found that people affected by ciguatoxins had trips to coastal areas hours before the onset of symptoms. Thanks to multiple studies over the years, it has been possible to identify the relation between toxigenic dinoflagellates and seagrasses, as well as its incorporation into the food chain, starting by fish primarily inhabiting reef ecosystems and culminating in the intake of these by humans. Identifying the epidemiological link, its cardinal symptoms and affected systems, such as gastrointestinal, the peripheral nervous system and, fortunately with a low frequency, the cardiovascular system, leads to a purely clinical diagnostic impression without necessitating further complementary studies; in addition, what would also help fight ciguatera poisoning is performing an adequate treatment of the symptoms right from the start, without underestimating or overlooking any associated complications. [ABSTRACT FROM AUTHOR]

The complex physiology of eukaryotic cells is regulated through numerous mechanisms, including epigenetic changes and posttranslational modifications. The wide-ranging diversity of these mechanisms constitutes a way of dynamic regulation of the functionality of proteins, their activity, and their subcellular localization as well as modulation of the differential expression of genes in response to external and internal stimuli that allow an organism to respond or adapt to accordingly. However, alterations in these mechanisms have been evidenced in several autoimmune diseases, including systemic lupus erythematosus (SLE). The present review aims to provide an approach to the current knowledge of the implications of these mechanisms in SLE pathophysiology. [ABSTRACT FROM AUTHOR]

The defining characteristic of neural stem cells (NSCs) is their ability to multiply through symmetric divisions and proliferation, and differentiation by asymmetric divisions, thus giving rise to different types of cells of the central nervous system (CNS). A strict temporal space control of the NSC differentiation is necessary, because its alterations are associated with neurological dysfunctions and, in some cases, death. This work reviews the current state of the molecular mechanisms that regulate the transcription in NSCs, organized according to whether the origin of the stimulus that triggers the molecular cascade in the CNS is internal (intrinsic factors) or whether it is the result of the microenvironment that surrounds the CNS (extrinsic factors). [ABSTRACT FROM AUTHOR]