Prediction of incident chronic kidney disease in community-based electronic health records: a systematic review and meta-analysis.

Background: Chronic kidney disease (CKD) is a major global health problem and its early identification would allow timely intervention to reduce complications. We performed a systematic review and meta-analysis of multivariable prediction models derived and/or validated in community-based electronic health records (EHRs) for the prediction of incident CKD in the community. Methods: Ovid Medline and Ovid Embase were searched for records from 1947 to 31 January 2024. Measures of discrimination were extracted and pooled by Bayesian meta-analysis, with heterogeneity assessed through a 95% prediction interval (PI). Risk of bias was assessed using Prediction model Risk Of Bias ASsessment Tool (PROBAST) and certainty in effect estimates by Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results: Seven studies met inclusion criteria, describing 12 prediction models, with two eligible for meta-analysis including 2 173 202 patients. The Chronic Kidney Disease Prognosis Consortium (CKD-PC) (summary c-statistic 0.847; 95% CI 0.827-0.867; 95% PI 0.780-0.905) and SCreening for Occult REnal Disease (SCORED) (summary c-statistic 0.811; 95% CI 0.691-0.926; 95% PI 0.514-0.992) models had good model discrimination performance. Risk of bias was high in 64% of models, and driven by the analysis domain. No model met eligibility for meta-analysis if studies at high risk of bias were excluded, and certainty of effect estimates was 'low'. No clinical utility analyses or clinical impact studies were found for any of the models. Conclusions: Models derived and/or externally validated for prediction of incident CKD in community-based EHRs demonstrate good prediction performance, but assessment of clinical usefulness is limited by high risk of bias, low certainty of evidence and a lack of impact studies.

Cancer cell plasticity: from cellular, molecular, and genetic mechanisms to tumor heterogeneity and drug resistance.

Cancer is a complex disease displaying a variety of cell states and phenotypes. This diversity, known as cancer cell plasticity, confers cancer cells the ability to change in response to their environment, leading to increased tumor diversity and drug resistance. This review explores the intricate landscape of cancer cell plasticity, offering a deep dive into the cellular, molecular, and genetic mechanisms that underlie this phenomenon. Cancer cell plasticity is intertwined with processes such as epithelial-mesenchymal transition and the acquisition of stem cell-like features. These processes are pivotal in the development and progression of tumors, contributing to the multifaceted nature of cancer and the challenges associated with its treatment. Despite significant advancements in targeted therapies, cancer cell adaptability and subsequent therapy-induced resistance remain persistent obstacles in achieving consistent, successful cancer treatment outcomes. Our review delves into the array of mechanisms cancer cells exploit to maintain plasticity, including epigenetic modifications, alterations in signaling pathways, and environmental interactions. We discuss strategies to counteract cancer cell plasticity, such as targeting specific cellular pathways and employing combination therapies. These strategies promise to enhance the efficacy of cancer treatments and mitigate therapy resistance. In conclusion, this review offers a holistic, detailed exploration of cancer cell plasticity, aiming to bolster the understanding and approach toward tackling the challenges posed by tumor heterogeneity and drug resistance. As articulated in this review, the delineation of cellular, molecular, and genetic mechanisms underlying tumor heterogeneity and drug resistance seeks to contribute substantially to the progress in cancer therapeutics and the advancement of precision medicine, ultimately enhancing the prospects for effective cancer treatment and patient outcomes.

Evaluation of autoimmune liver disease natural history in patients referred to Middle East Liver Diseases (MELD) center.

BACKGROUND: Autoimmune liver diseases (AILD) are increasing and common forms of chronic liver disease (CLD) with different clinical responses and characteristics which can result in cirrhosis. This study aimed to investigate the natural history and characteristics of AILD in an Iranian population. METHODS: Patients with AILD [Autoimmune Hepatitis (AIH), Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC) and Overlap Syndrome (OS)] referred to Middle East Liver Diseases (MELD) center, Tehran, Iran, between January 2002 and December 2022 were included in this retrospective cohort study. The main features of natural history (the trends of liver functional tests (LFT), Auto-Antibodies, response to treatment and cirrhotic status) along with demographic data were studied. RESULTS: Two hundred sixty-five patients (160 (60.4%) AIH, 37 (14.0%) PBC, 20 (7.5%) PSC, 48 (18.1%) overlap syndrome) with a median follow-up time of 5 years (IQR 4 to 8 years) were included. Baseline laboratory tests revealed that patients with AIH exhibit elevated transaminase levels. However, patients suffering from PBC and PSC displayed increased alkaline phosphatase levels. Conversely, in overlap syndrome patients, both transaminases and alkaline phosphatase were observed at high levels. Autoantibodies represented themselves as important diagnostic markers for the AIH and PBC but not for PSC. The complete response occurred in 112 (70%) of and 28 (58.4%) patients with AIH and overlap syndrome respectively and 21 patients 11 (6.9%) of AIH and 10 (20.8%) of overlap syndrome) were non-responders. Other patients in these two categories were considered as insufficient responders. On the other side, 32 (91.9%) and 8 (40%) of patients with PBC and PSC biochemically responded to Ursodeoxycholic Acid (UDCA). Unpredictably, cirrhosis regression was observed in some AIH and PBC patients. CONCLUSION: Appropriate medication management for AILD patients may leads to regression from cirrhosis and improvement of manifestations; while discontinuation of medication may cause relapses. However, patient suffering from PSC showed limited response to treatment.

Counter-attack of biocontrol agents: Environmentally benign Approaches against Root-knot nematodes (Meloidogyne spp.) on Agricultural crops.

Root-knot nematodes (Meloidogyne spp.) are obligate sedentary endoparasites, considered severe crop-damaging taxa among all plant-parasitic nematodes globally. Their attacks through parasitic proteins alter the physiology and machinery of the host cells to favour parasitism and reduction in crop yield. Currently, the use of excessive pesticides as a fast remedy to manage this pest is hazardous for both the environment and humans. Keeping this view in mind, there is an urgent need for developing efficient eco-friendly strategies. Bio-control as an eco-friendly is considered the best approach to manage nematodes without disturbing non-target microbes. In bio-control, living agents such as fungi and bacteria are the natural enemies of nematodes and the best substitute for pesticides. Fungi, including nematode-trapping fungi, can sense host signals and produce special trapping devices viz., constricting rings and adhesive knobs/loops, to capture nematodes and kill them. Whereas, endo-parasitic fungi kill nematodes by enzymatic secretions and spore adhesion through their hyphae. Bacteria can also control nematodes by producing antibiotic compounds, competing for nutrients and rhizosphere, production of hydrolytic enzymes viz., chitinases, proteases, lipases, and induction of systemic resistance (ISR) in host plants. Scientists throughout the world are trying to evolve environmentally benign methods that sustain agricultural production and keep nematodes below a threshold level. Whatever methods evolve, in the future the focus should be on important aspects like green approaches for managing nematodes without disturbing human health and the environment.

Early-stage mapping of macromolecular content in APPNL-F mouse model of Alzheimer's disease using nuclear Overhauser effect MRI.

Non-invasive methods of detecting early-stage Alzheimer's disease (AD) can provide valuable insight into disease pathology, improving the diagnosis and treatment of AD. Nuclear Overhauser enhancement (NOE) MRI is a technique that provides image contrast sensitive to lipid and protein content in the brain. These macromolecules have been shown to be altered in Alzheimer's pathology, with early disruptions in cell membrane integrity and signaling pathways leading to the buildup of amyloid-beta plaques and neurofibrillary tangles. We used template-based analyzes of NOE MRI data and the characteristic Z-spectrum, with parameters optimized for increase specificity to NOE, to detect changes in lipids and proteins in an AD mouse model that recapitulates features of human AD. We find changes in NOE contrast in the hippocampus, hypothalamus, entorhinal cortex, and fimbria, with these changes likely attributed to disruptions in the phospholipid bilayer of cell membranes in both gray and white matter regions. This study suggests that NOE MRI may be a useful tool for monitoring early-stage changes in lipid-mediated metabolism in AD and other disorders with high spatial resolution.

Associations between telomere attrition, genetic variants in telomere maintenance genes, and non-small cell lung cancer risk in the Jammu and Kashmir population of North India.

BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of chromosomes, playing a vital role in maintaining chromosomal integrity and stability. Dysregulation of telomeres has been implicated in the development of various cancers, including non-small cell lung cancer (NSCLC), which is the most common type of lung cancer. Genetic variations within telomere maintenance genes may influence the risk of developing NSCLC. The present study aimed to evaluate the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India, and to investigate the relationship between telomere length and NSCLC risk. METHODS: We employed the cost-effective and high-throughput MassARRAY MALDI-TOF platform to assess the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India. Additionally, we used TaqMan genotyping to validate our results. Furthermore, we investigated telomere length variation and its relation to NSCLC risk in the same population using dual-labeled fluorescence-based qPCR. RESULTS: Our findings revealed significant associations of TERT rs10069690 and POT1 rs10228682 with NSCLC risk (adjusted p-values = 0.019 and 0.002, respectively), while TERF2 rs251796 and rs2975843 showed no significant associations. The TaqMan genotyping validation further substantiated the associations of TERT rs10069690 and rs2242652 with NSCLC risk (adjusted p-values = 0.02 and 0.003, respectively). Our results also demonstrated significantly shorter telomere lengths in NSCLC patients compared to controls (p = 0.0004). CONCLUSION: This study highlights the crucial interplay between genetic variation in telomere maintenance genes, telomere attrition, and NSCLC risk in the Jammu and Kashmir population of North India. Our findings suggest that TERT and POT1 gene variants, along with telomere length, may serve as potential biomarkers and therapeutic targets for NSCLC in this population. Further research is warranted to elucidate the underlying mechanisms and to explore the potential clinical applications of these findings.

Cohort profile: Evaluation of the Methods and Management of Acute Coronary Events (EMMACE) Longitudinal Cohort.

AIMS: The Evaluation of the Methods and Management of Acute Coronary Events (EMMACE) longitudinal cohort study aims to investigate health trajectories of individuals following hospitalization for myocardial infarction (MI). METHODS AND RESULTS: EMMACE is a linked multicentre prospective cohort study of 14 899 patients with MI admitted to 77 hospitals in England who participated in the EMMACE-3 and -4 studies between 1st November 2011 and 24th June 2015. Long-term follow-up of the EMMACE cohorts was conducted through the EMMACE-XL (27th September 2020 to 31st March 2022) and EMMACE-XXL (1st July 2021 to 1st July 2023) studies. EMMACE collected individual participant data for health-related quality of life (HRQoL) measured by three-level EuroQol five-dimension and visual analogy scale at admission, 1 month, 6 months, 12 months, and 10 years follow-up, as well as medications, medication adherence, beliefs about medicines, Satisfaction with Information about Medicines Scale, and illness perceptions. Participant data were deterministically linked to the Myocardial Infarction National Audit Project (MINAP) for information on baseline treatments and comorbidities, Hospital Episode Statistics Admitted Patient Care (for cause-specific hospitalization data), and the Office for National Statistics (for mortality data) up to 2020. CONCLUSION: EMMACE is a nationwide prospective cohort that will provide unique insights into fatal and non-fatal outcomes, medication adherence, and HRQoL following MI.Trial registration: ClinicalTrials.gov NCT01808027 and NCT01819103.

Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments.

Traditional cancer treatments use nonspecific drugs and monoclonal antibodies to target tumor cells. Chimeric antigen receptor (CAR)-T cell therapy, however, leverages the immune system's T-cells to recognize and attack tumor cells. T-cells are isolated from patients and modified to target tumor-associated antigens. CAR-T therapy has achieved FDA approval for treating blood cancers like B-cell acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma by targeting CD-19 and B-cell maturation antigens. Bi-specific chimeric antigen receptors may contribute to mitigating tumor antigen escape, but their efficacy could be limited in cases where certain tumor cells do not express the targeted antigens. Despite success in blood cancers, CAR-T technology faces challenges in solid tumors, including lack of reliable tumor-associated antigens, hypoxic cores, immunosuppressive tumor environments, enhanced reactive oxygen species, and decreased T-cell infiltration. To overcome these challenges, current research aims to identify reliable tumor-associated antigens and develop cost-effective, tumor microenvironment-specific CAR-T cells. This review covers the evolution of CAR-T therapy against various tumors, including hematological and solid tumors, highlights challenges faced by CAR-T cell therapy, and suggests strategies to overcome these obstacles, such as utilizing single-cell RNA sequencing and artificial intelligence to optimize clinical-grade CAR-T cells.

B 1 + $$ {\mathrm{B}}_1

PURPOSE: Nuclear Overhauser effect magnetization transfer ratio (NOEMTR ) is a technique used to investigate brain lipids and macromolecules in greater detail than other techniques and benefits from increased contrast at 7 T. However, this contrast can become degraded because of B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities present at ultra-high field strengths. High-permittivity dielectric pads (DP) have been used to correct for these inhomogeneities via displacement currents generating secondary magnetic fields. The purpose of this work is to demonstrate that dielectric pads can be used to mitigate B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities and improve NOEMTR contrast in the temporal lobes at 7 T. METHODS: Partial 3D NOEMTR contrast images and whole brain B 1 + $$ {\mathrm{B}}_1^{+} $$ field maps were acquired on a 7 T MRI across six healthy subjects. Calcium titanate DP, having a relative permittivity of 110, was placed next to the subject's head near the temporal lobes. Pad corrected NOEMTR images had a separate postprocessing linear correction applied. RESULTS: DP provided supplemental B 1 + $$ {\mathrm{B}}_1^{+} $$ to the temporal lobes while also reducing the B 1 + $$ {\mathrm{B}}_1^{+} $$ magnitude across the posterior and superior regions of the brain. This resulted in a statistically significant increase in NOEMTR contrast in substructures of the temporal lobes both with and without linear correction. The padding also produced a convergence in NOEMTR contrast toward approximately equal mean values. CONCLUSION: NOEMTR images showed significant improvement in temporal lobe contrast when DP were used, which resulted from an increase in B 1 + $$ {\mathrm{B}}_1^{+} $$ homogeneity across the entire brain slab. DP-derived improvements in NOEMTR are expected to increase the robustness of the brain substructural measures both in healthy and pathological conditions.

Neuroimaging genetics approaches to identify new biomarkers for the early diagnosis of autism spectrum disorder.

Autism-spectrum disorders (ASDs) are developmental disabilities that manifest in early childhood and are characterized by qualitative abnormalities in social behaviors, communication skills, and restrictive or repetitive behaviors. To explore the neurobiological mechanisms in ASD, extensive research has been done to identify potential diagnostic biomarkers through a neuroimaging genetics approach. Neuroimaging genetics helps to identify ASD-risk genes that contribute to structural and functional variations in brain circuitry and validate biological changes by elucidating the mechanisms and pathways that confer genetic risk. Integrating artificial intelligence models with neuroimaging data lays the groundwork for accurate diagnosis and facilitates the identification of early diagnostic biomarkers for ASD. This review discusses the significance of neuroimaging genetics approaches to gaining a better understanding of the perturbed neurochemical system and molecular pathways in ASD and how these approaches can detect structural, functional, and metabolic changes and lead to the discovery of novel biomarkers for the early diagnosis of ASD.

Ubiquitin specific peptidase 37 and PCNA interaction promotes osteosarcoma pathogenesis by modulating replication fork progression.

BACKGROUND: Osteosarcoma is a type of bone cancer that predominantly affects young individuals, including children and adolescents. The disease progresses through heterogeneous genetic alterations, and patients often develop pulmonary metastases even after the primary tumors have been surgically removed. Ubiquitin-specific peptidases (USPs) regulate several critical cellular processes, such as cell cycle progression, transcriptional activation, and signal transduction. Various studies have revealed the significance of USP37 in the regulation of replication stress and oncogenesis. METHODS: In this study, the Cancer Genome Atlas (TCGA) database was analyzed to investigate USP37 expression. RNA sequencing was utilized to assess the impact of USP37 overexpression and depletion on gene expression in osteosarcoma cells. Various molecular assays, including colony formation, immunofluorescence, immunoprecipitation, and DNA replication restart, were employed to examine the physical interaction between USP37 and PCNA, as well as its physiological effects in osteosarcoma cells. Additionally, molecular docking studies were conducted to gain insight into the nature of the interaction between USP37 and PCNA. Furthermore, immunohistochemistry was performed on archived tissue blocks from osteosarcoma patients to establish a correlation between USP37 and PCNA expression. RESULTS: Analysis of the TCGA database revealed that increased expression of USP37 was linked to decreased progression-free survival (PFS) in osteosarcoma patients. Next-generation sequencing analysis of osteosarcoma cells demonstrated that overexpression or knockdown of USP37 led to the expression of different sets of genes. USP37 overexpression provided a survival advantage, while its depletion heightened sensitivity to replication stress in osteosarcoma cells. USP37 was found to physically interact with PCNA, and molecular docking studies indicated that the interaction occurs through unique residues. In response to genotoxic stress, cells that overexpressed USP37 resolved DNA damage foci more quickly than control cells or cells in which USP37 was depleted. The expression of USP37 varied in archived osteosarcoma tissues, with intermediate expression seen in 52% of cases in the cohort examined. CONCLUSION: The results of this investigation propose that USP37 plays a vital role in promoting replication stress tolerance in osteosarcoma cells. The interaction between USP37 and PCNA is involved in the regulation of replication stress, and disrupting it could potentially trigger synthetic lethality in osteosarcoma. This study has expanded our knowledge of the mechanism through which USP37 regulates replication stress, and its potential as a therapeutic target in osteosarcoma merits additional exploration.

Nanotechnology - A new frontier of nano-farming in agricultural and food production and its development.

The potential of nanotechnology for the development of sustainable agriculture has been promising. The initiatives to meet the rising food needs of the rapidly growing world population are mainly powered by sustainable agriculture. Nanoparticles are used in agriculture due to their distinct physicochemical characteristics. The interaction of nanomaterials with soil components is strongly determined in terms of soil quality and plant growth. Numerous research has been carried out to investigate how nanoparticles affect the growth and development of plants. Nanotechnology has been applied to improve the quality and reduce post-harvest loss of agricultural products by extending their shelf life, particularly for fruits and vegetables. This review assesses the latest literature on nanotechnology, which is used as a nano-biofertilizer as seen in the agricultural field for high productivity and better growth of plants, an important source of balanced nutrition for the crop, seed germination, and quality enrichment. Additionally, post-harvest food processing and packaging can benefit greatly from the use of nanotechnology to cut down on food waste and contamination. It also critically discusses the mechanisms involved in nanoparticle absorption and translocation within the plants and the synthesis of green nanoparticles.

Synthesis, Characterization and Biological Activity of Benzimidazoleacrylonitrile Derivatives.

BACKGROUND: Benzimidazoles have a wide range of synthetic applications in medicinal chemistry and biological activities like anti-tumor/anti-proliferative activities etc. Moreover, different heterocyclic moieties attached to the benzimidazole ring improved anticancer activities. METHODS: All the chemicals were purchased from Aldrich Chemical Company, are of AR grade and used as received. Microanalytical data (C, H, and N) were analyzed on a Carlo Erba model 1108 analyzer. Melting points were measured by the Kofler apparatus and were uncorrected. Spectroscopic data were obtained using the following instruments: Fourier transform infrared spectra (KBr discs, 4000-400 cm-1) by Shimadzu IR-408 Perkin Elmer 1800 instrument; 1H NMR and 13C NMR spectra by JEOL Resonance Inc. Tokyo, Japan, JNM-ECZ400S/L1 using DMSO-d6 as a solvent containing TMS as the internal standard. Chemical shifts (δ) are reported in parts per million (ppm), and coupling constants (J) are reported in Hertz (Hz). RESULTS: We chose sulfosalicylic acid as a promoter for forming benzimidazole-acrylonitrile derivatives, which is an eco-friendly reaction, and we applied a series of synthesized compounds 3a-g in nematicidal activity. The results indicate that the concentrations of all treatments significantly kill M. incognita. CONCLUSION: This model reaction procedure provides a better method for preparing benzimidazoleacrylonitrile, which is superior to other methods. This protocol simplifies handling model reactions with mild reaction conditions, a short time period, a simple set-up, a fast reaction rate, and so on.

Integration of CRISPR/Cas9 with artificial intelligence for improved cancer therapeutics.

Gene editing has great potential in treating diseases caused by well-characterized molecular alterations. The introduction of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-based gene-editing tools has substantially improved the precision and efficiency of gene editing. The CRISPR/Cas9 system offers several advantages over the existing gene-editing approaches, such as its ability to target practically any genomic sequence, enabling the rapid development and deployment of novel CRISPR-mediated knock-out/knock-in methods. CRISPR/Cas9 has been widely used to develop cancer models, validate essential genes as druggable targets, study drug-resistance mechanisms, explore gene non-coding areas, and develop biomarkers. CRISPR gene editing can create more-effective chimeric antigen receptor (CAR)-T cells that are durable, cost-effective, and more readily available. However, further research is needed to define the CRISPR/Cas9 system's pros and cons, establish best practices, and determine social and ethical implications. This review summarizes recent CRISPR/Cas9 developments, particularly in cancer research and immunotherapy, and the potential of CRISPR/Cas9-based screening in developing cancer precision medicine and engineering models for targeted cancer therapy, highlighting the existing challenges and future directions. Lastly, we highlight the role of artificial intelligence in refining the CRISPR system's on-target and off-target effects, a critical factor for the broader application in cancer therapeutics.

Cytokine- and chemokine-induced inflammatory colorectal tumor microenvironment: Emerging avenue for targeted therapy.

Colorectal cancer (CRC) is a predominant life-threatening cancer, with liver and peritoneal metastases as the primary causes of death. Intestinal inflammation, a known CRC risk factor, nurtures a local inflammatory environment enriched with tumor cells, endothelial cells, immune cells, cancer-associated fibroblasts, immunosuppressive cells, and secretory growth factors. The complex interactions of aberrantly expressed cytokines, chemokines, growth factors, and matrix-remodeling enzymes promote CRC pathogenesis and evoke systemic responses that affect disease outcomes. Mounting evidence suggests that these cytokines and chemokines play a role in the progression of CRC through immunosuppression and modulation of the tumor microenvironment, which is partly achieved by the recruitment of immunosuppressive cells. These cells impart features such as cancer stem cell-like properties, drug resistance, invasion, and formation of the premetastatic niche in distant organs, promoting metastasis and aggressive CRC growth. A deeper understanding of the cytokine- and chemokine-mediated signaling networks that link tumor progression and metastasis will provide insights into the mechanistic details of disease aggressiveness and facilitate the development of novel therapeutics for CRC. Here, we summarized the current knowledge of cytokine- and chemokine-mediated crosstalk in the inflammatory tumor microenvironment, which drives immunosuppression, resistance to therapeutics, and metastasis during CRC progression. We also outlined the potential of this crosstalk as a novel therapeutic target for CRC. The major cytokine/chemokine pathways involved in cancer immunotherapy are also discussed in this review.

Targeting cancer signaling pathways by natural products: Exploring promising anti-cancer agents.

Cancer is one of the leading causes of death and significantly burdens the healthcare system. Due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. The use of natural products as anticancer agents is an acceptable therapeutic approach due to accessibility, applicability, and reduced cytotoxicity. Natural products have been an incomparable source of anticancer drugs in the modern era of drug discovery. Along with their derivatives and analogs, natural products play a major role in cancer treatment by modulating the cancer microenvironment and different signaling pathways. These compounds are effective against several signaling pathways, mainly cell death pathways (apoptosis and autophagy) and embryonic developmental pathways (Notch pathway, Wnt pathway, and Hedgehog pathway). The historical record of natural products is strong, but there is a need to investigate the current role of natural products in the discovery and development of cancer drugs and determine the possibility of natural products being an important source of future therapeutic agents. Many target-specific anticancer drugs failed to provide successful results, which accounts for a need to investigate natural products with multi-target characteristics to achieve better outcomes. The potential of natural products to be promising novel compounds for cancer treatment makes them an important area of research. This review explores the significance of natural products in inhibiting the various signaling pathways that serve as drivers of carcinogenesis and thus pave the way for developing and discovering anticancer drugs.

Cross-talk between the microbiome and chronic inflammation in esophageal cancer: potential driver of oncogenesis.

Esophageal cancer (EC) is frequently considered a lethal malignancy and is often identified at a later stage. It is one of the major causes of cancer-related deaths globally. The conventional treatment methods like chemotherapy, radiotherapy, and surgery offer limited efficacy and poor clinical outcome with a less than 25% 5-year survival rate. The poor prognosis of EC persists despite the growth in the development of diagnostic and therapeutic modalities to treat EC. This underlines the need to elucidate the complex molecular mechanisms that drive esophageal oncogenesis. Apart from the role of the tumor microenvironment and its structural and cellular components in tumorigenesis, mounting evidence points towards the involvement of the esophageal microbiome, inflammation, and their cross-talk in promoting esophageal cancer. The current review summarizes recent research that delineates the underlying molecular mechanisms by which the microbiota and inflammation promote the pathophysiology of esophageal cancer, thus unraveling targets for potential therapeutic intervention.

Genetics of glutamate and its receptors in autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental impairment characterized by deficits in social interaction skills, impaired communication, and repetitive and restricted behaviors that are thought to be due to altered neurotransmission processes. The amino acid glutamate is an essential excitatory neurotransmitter in the human brain that regulates cognitive functions such as learning and memory, which are usually impaired in ASD. Over the last several years, increasing evidence from genetics, neuroimaging, protein expression, and animal model studies supporting the notion of altered glutamate metabolism has heightened the interest in evaluating glutamatergic dysfunction in ASD. Numerous pharmacological, behavioral, and imaging studies have demonstrated the imbalance in excitatory and inhibitory neurotransmitters, thus revealing the involvement of the glutamatergic system in ASD pathology. Here, we review the effects of genetic alterations on glutamate and its receptors in ASD and the role of non-invasive imaging modalities in detecting these changes. We also highlight the potential therapeutic targets associated with impaired glutamatergic pathways.