Molecular Interventions Research Articles

Coinfection of EBV with other pathogens: a narrative review

The Epstein-Barr viwrus (EBV) is a common herpesvirus that affects more than 90% of people worldwide. Even while EBV infections are frequently asymptomatic, they can cause autoimmune diseases and a number of cancers, especially in those with impaired immune systems. The intricate relationships between EBV and other coinfecting pathogens, including as human immunodeficiency virus (HIV), human papilloma virus (HPV), cytomegalovirus (CMV), and Plasmodium species, are examined in this study. We investigated the fundamental processes of these coinfections, their effects on the course of the disease, and their practical ramifications. The study reviewed how co-infections with EBV might modify immune responses, promote oncogenesis, and make treatment plans more challenging. In this review, we also discussed current therapeutic strategies, such as targeted molecular interventions, EBV vaccines, and adoptive T-cell therapy. The review underscores the need for more research to provide more focused and effective therapies that address the mutually reinforcing effects of numerous infections in disorders linked with EBV.

Targeting DUSP26 to drive cardiac mitochondrial dynamics via FAK-ERK signaling in diabetic cardiomyopathy

Diabetic cardiomyopathy (DCM) is a severe cardiac complication of diabetes mellitus, characterized by structural and functional myocardial abnormalities. The molecular mechanisms underlying DCM, particularly the role of dual-specificity phosphatase 26 (DUSP26), remain insufficiently understood. Our study reveals that DUSP26 expression is markedly downregulated in the cardiomyocytes of diabetic db/db mice and under glucolipotoxic stress. Overexpression of DUSP26 in db/db mice significantly improved cardiac function, as demonstrated by enhanced left ventricular ejection fraction and fractional shortening, alongside reduced myocardial fibrosis and hypertrophy. Mitochondrial analysis indicated that DUSP26 overexpression led to increased ATP production, enhanced mitochondrial fusion, and improved structural integrity. In addition, lipid accumulation was reduced, reflecting enhanced metabolic function. We also discovered that DUSP26 is necessary for regulating the focal adhesion kinase (FAK)-extracellular signal-regulated kinase (ERK) pathway, with pharmacological activation of FAK partially offsetting the benefits of DUSP26 overexpression in rescue experiments. These findings underscore the pivotal role of DUSP26 as a potential therapeutic target, highlighting the importance of developing targeted molecular interventions to address diabetic cardiac complications.

Targeting esophageal carcinoma: molecular mechanisms and clinical studies.

Esophageal cancer (EC)is identified as a predominant health threat worldwide, with its highest incidence and mortality rates reported in China. The complex molecular mechanisms underlying EC, coupled with the differential incidence of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) across various regions, highlight the necessity for in-depth research targeting molecular pathogenesis and innovative treatment strategies. Despite recent progress in targeted therapy and immunotherapy, challenges such as drug resistance and the lack of effective biomarkers for patient selection persist, impeding the optimization of therapeutic outcomes. Our review delves into the molecular pathology of EC, emphasizing genetic and epigenetic alterations, aberrant signaling pathways, tumor microenvironment factors, and the mechanisms of metastasis and immune evasion. We further scrutinize the current landscape of targeted therapies, including the roles of EGFR, HER2, and VEGFR, alongside the transformative impact of ICIs. The discussion extends to evaluating combination therapies, spotlighting the synergy between targeted and immune-mediated treatments, and introduces the burgeoning domain of antibody-drug conjugates, bispecific antibodies, and multitarget-directed ligands. This review lies in its holistic synthesis of EC's molecular underpinnings and therapeutic interventions, fused with an outlook on future directions including overcoming resistance mechanisms, biomarker discovery, and the potential of novel drug formulations.

SMYD1 modulates the proliferation of multipotent cardiac progenitor cells derived from human pluripotent stem cells during myocardial differentiation through GSK3β/β-catenin&ERK signaling.

The histone-lysine N-methyltransferase SMYD1, which is specific to striated muscle, plays a crucial role in regulating early heart development. Its deficiency has been linked to the occurrence of congenital heart disease. Nevertheless, the precise mechanism by which SMYD1 deficiency contributes to congenital heart disease remains unclear. We established a SMYD1 knockout pluripotent stem cell line and a doxycycline-inducible SMYD1 expression pluripotent stem cell line to investigate the functions of SMYD1 utilizing an in vitro-directed myocardial differentiation model. Cardiomyocytes lacking SMYD1 displayed drastically diminished differentiation efficiency, concomitant with heightened proliferation capacityof cardiac progenitor cells during the early cardiac differentiation stage. These cellular phenotypes were confirmed through experiments inducing the re-expression of SMYD1. Transcriptome sequencing and small molecule inhibitor intervention suggested that the GSK3β/β-catenin&ERK signaling pathway was involved in the proliferation of cardiac progenitor cells. Chromatin immunoprecipitation demonstrated that SMYD1 acted as a transcriptional activator of GSK3β through histone H3 lysine 4 trimethylation. Additionally, dual-luciferase analyses indicated that SMYD1 could interact with the promoter region of GSK3β, thereby augmenting its transcriptional activity. Moreover, administering insulin and Insulin-like growth factor 1 can enhance the efficacy of myocardial differentiation in SMYD1 knockout cells. Our research indicated that the participation of SMYD1 in the GSK3β/β-catenin&ERK signaling cascade modulated the proliferation of cardiac progenitor cells during myocardial differentiation. This process was partly reliant on the transcription of GSK3β. Our research provided a novel insight into the genetic modification effect of SMYD1 during early myocardial differentiation. The findings were essential to the molecular mechanism and potential interventions for congenital heart disease.

Identification Of Key Molecular Targets And Therapeutic Interventions In Alzheimer's Disease: An Integrative Analysis Of Differentially Expressed Genes And Regulatory Drugs

Identification Of Key Molecular Targets And Therapeutic Interventions In Alzheimer's Disease: An Integrative Analysis Of Differentially Expressed Genes And Regulatory Drugs

Posttransplant complications: molecular mechanisms and therapeutic interventions.

Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft-versus-host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients.

Multiomics: Functional Molecular Biomarkers of Micronutrients for Public Health Application.

Adequate micronutrient intake and status are global public health goals. Vitamin and mineral deficiencies are widespread and known to impair health and survival across the life stages. However, knowledge of molecular effects, metabolic pathways, biological responses to variation in micronutrient nutriture, and abilities to assess populations for micronutrient deficiencies and their pathology remain lacking. Rapidly evolving methodological capabilities in genomics, epigenomics, proteomics, and metabolomics offer unparalleled opportunities for the nutrition research community to link micronutrient exposure to cellular health; discover new, arguably essential micronutrients of microbial origin; and integrate methods of molecular biology, epidemiology, and intervention trials to develop novel approaches to assess and prevent micronutrient deficiencies in populations. In this review article, we offer new terminology to specify nutritional application of multiomic approaches and encourage collaboration across the basic to public health sciences to advance micronutrient deficiency prevention.

Unlocking Cholesterol Metabolism in Metabolic-Associated Steatotic Liver Disease: Molecular Targets and Natural Product Interventions.

Metabolic-associated steatotic liver disease (MASLD), the hepatic manifestation of metabolic syndrome, represents a growing global health concern. The intricate pathogenesis of MASLD, driven by genetic, metabolic, epigenetic, and environmental factors, leads to considerable clinical variability. Dysregulation of hepatic lipid metabolism, particularly cholesterol homeostasis, is a critical factor in the progression of MASLD and its more severe form, metabolic dysfunction-associated steatohepatitis (MASH). This review elucidates the multifaceted roles of cholesterol metabolism in MASLD, focusing on its absorption, transportation, biosynthesis, efflux, and conversion. We highlight recent advancements in understanding these processes and explore the therapeutic potential of natural products such as curcumin, berberine, and resveratrol in modulating cholesterol metabolism. By targeting key molecular pathways, these natural products offer promising strategies for MASLD management. Finally, this review also covers the clinical studies of natural products in MASLD, providing new insights for future research and clinical applications.

Learning Abstract Chemistry Concepts with Virtual Reality: An Experimental Study Using a VR Chemistry Lab and Molecule Simulation

In this 2 × 2 between-subject experimental study, a virtual reality (VR) laboratory simulation is paired with a VR molecular world intervention to teach chemistry concepts. The independent variables are the implementation timing of the molecular world intervention (Pre-lab vs. Integrated) and the level of embodiment (Traditional vs. VR). Eighty students (N = 80), ages 11–18 years old, from a community center in New York City participated, completing a pretest, a laboratory simulation, a molecular intervention, and a post-test. The pre- and post-test measures included multiple-choice, free-response, and drawing questions. A key finding was that integrating the intervention within the lab simulation, no matter which level of embodiment, led to significantly higher gains in learning. The combination of using physical manipulatives and integrating them within the lab exercise (Integrated Traditional condition) demonstrated the greatest gains overall. On drawing measures, the Integrated VR condition showed significant improvement in three out of the four drawing categories (i.e., molecule shape, atom quantity, and relative sizes). The implications are that even though using a VR molecular world intervention can lead to significant learning of abstract chemistry content, the use of physical manipulatives is still a more effective tool.

Pyridine-based small molecule inhibitors of SARM1 alleviate cell death caused by NADase activity.

Our investigation has unveiled a series of pyridine-based SARM1 inhibitors, with the lead compound TH-408 exhibiting remarkable potency, achieving an IC50 value of 0.46 μM. This exceptional inhibitory effect significantly curtailed SARM1-mediated cell death across diverse biological models. This finding highlights the promising therapeutic potential for neurodegenerative disorders by disrupting SARM1 activation and advances our understanding of molecular interventions in these complex disorders, including the regulation of NAD+ metabolism.

Machine learning-based integration develops a mitophagy-related lncRNA signature for predicting the progression of prostate cancer: a bioinformatic analysis

Prostate cancer remains a complex and challenging disease, necessitating innovative approaches for prognosis and therapeutic guidance. This study integrates machine learning techniques to develop a novel mitophagy-related long non-coding RNA (lncRNA) signature for predicting the progression of prostate cancer. Leveraging the TCGA-PRAD dataset, we identify a set of four key lncRNAs and formulate a riskscore, revealing its potential as a prognostic indicator. Subsequent analyses unravel the intricate connections between riskscore, immune cell infiltration, mutational landscapes, and treatment outcomes. Notably, the pan-cancer exploration of YEATS2-AS1 highlights its pervasive impact, demonstrating elevated expression across various malignancies. Furthermore, drug sensitivity predictions based on riskscore guide personalized chemotherapy strategies, with drugs like Carmustine and Entinostat showing distinct suitability for high and low-risk group patients. Regression analysis exposes significant correlations between the mitophagy-related lncRNAs, riskscore, and key mitophagy-related genes. Molecular docking analyses reveal promising interactions between Cyclophosphamide and proteins encoded by these genes, suggesting potential therapeutic avenues. This comprehensive study not only introduces a robust prognostic tool but also provides valuable insights into the molecular intricacies and potential therapeutic interventions in prostate cancer, paving the way for more personalized and effective clinical approaches.

Endoplasmic Reticulum Stress-Mediated Cell Death in Renal Fibrosis.

The endoplasmic reticulum (ER) is indispensable for maintaining normal life activities. Dysregulation of the ER function results in the accumulation of harmful proteins and lipids and the disruption of intracellular signaling pathways, leading to cellular dysfunction and eventual death. Protein misfolding within the ER disrupts its delicate balance, resulting in the accumulation of misfolded or unfolded proteins, a condition known as endoplasmic reticulum stress (ERS). Renal fibrosis, characterized by the aberrant proliferation of fibrotic tissue in the renal interstitium, stands as a grave consequence of numerous kidney disorders, precipitating a gradual decline in renal function. Renal fibrosis is a serious complication of many kidney conditions and is characterized by the overgrowth of fibrotic tissue in the glomerular and tubular interstitium, leading to the progressive failure of renal function. Studies have shown that, during the onset and progression of kidney disease, ERS causes various problems in the kidneys, a process that can lead to kidney fibrosis. This article elucidates the underlying intracellular signaling pathways modulated by ERS, delineating its role in triggering diverse forms of cell death. Additionally, it comprehensively explores a spectrum of potential pharmacological agents and molecular interventions aimed at mitigating ERS, thereby charting novel research avenues and therapeutic advancements in the management of renal fibrosis.

Sprint Interval Training Improves Brain-Derived Neurotropic Factor-Induced Benefits in Brain Health-A Possible Molecular Signaling Intervention.

Physical exercise can significantly impact our bodies, affecting our functional capacity, structure establishment, and molecular makeup. The magnitude of these changes depends on the specific exercise protocols used. For instance, low-to-moderate-intensity exercise can activate important molecular targets in the short term, such as BDNF-mediated signaling, while high-intensity exercise can maintain these signaling molecules in the active state for a longer term. This makes it challenging to recommend specific exercises for obtaining BDNF-induced benefits. Additionally, exercise-induced molecular signaling targets can have positive and negative effects, with some exercises blunting these targets and others activating them. For example, increasing BDNF concentration through exercise can be beneficial for brain health, but it may also have a negative impact on conditions such as bipolar disorder. Therefore, a deeper understanding of a specific exercise-mediated mechanistic approach is required. This review will delve into how the sprint exercise-mediated activation of BDNF could help maintain brain health and explore potential molecular interventions.

Exploring nicotinamide adenine dinucleotide precursors across biosynthesis pathways: Unraveling their role intheovary.

Natural Nicotinamide Adenine Dinucleotide (NAD+) precursors have attracted much attention due to their positive effects in promoting ovarian health. However, their target tissue, synthesis efficiency, advantages, and disadvantages are still unclear. This review summarizes the distribution of NAD+ at the tissue, cellular and subcellular levels, discusses its biosynthetic pathways and the latest findings in ovary, include: (1) NAD+ plays distinct roles both intracellularly and extracellularly, adapting its distribution in response to requirements. (2) Different precursors differs in target tissues, synthetic efficiency, biological utilization, and adverse effects. Importantly: tryptophan is primarily utilized in the liver and kidneys, posing metabolic risks in excess; nicotinamide (NAM) is indispensable for maintaining NAD+ levels; nicotinic acid (NA) constructs a crucial bridge between intestinal microbiota and the host with diverse functions; nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) increase NAD+ systemically and can be influenced by delivery route, tissue specificity, and transport efficiency. (3) The biosynthetic pathways of NAD+ are intricately intertwined. They provide multiple sources and techniques for NAD+ synthesis, thereby reducing the dependence on a single molecule to maintain cellular NAD+ levels. However, an excess of a specific precursor potentially influencing other pathways. In addition, Protein expression analysis suggest that ovarian tissues may preferentially utilize NAM and NMN. These findings summarize the specific roles and potential of NAD+ precursors in enhancing ovarian health. Future research should delve into the molecular mechanisms and intervention strategies of different precursors, aiming to achieve personalized prevention or treatment of ovarian diseases, and reveal their clinical application value.

Recent Advances in Smart Self-Assembled Bioinspired Hydrogels: A Bridging Weapon for Emerging Health Care Applications from Bench to Bedside.

Stimuli-responsive low molecular weight hydrogel interventions for Biomedical challenges are a rapidly evolving paradigm in the bottom-up approach recently. Peptide-based self-assembled nano biomaterials present safer alternatives to their non-degradable counterparts as demanded for today's most urged clinical needs.Although a plethora of work has already been accomplished, programming hydrogelators with appropriate functionalities requires a better understanding as the impact of the macromolecular structure of the peptides and subsequently, their self-assembled nanostructures remain unidentified. Henceforth this review focuses on two aspects: Firstly, the underlying guidelines for building biomimetic strategies to tailor scaffolds leading to hydrogelation along with the role of non-covalent interactions that are the key components of various self-assembly processes. In the second section, it is aimed to bring together the recent achievements with designer assembly concerning their self-aggregation behaviour and applications mainly in the biomedical arena like drug delivery carrier design, antimicrobial, anti-inflammatory as well as wound healing materials. Furthermore, it is anticipated that this article will provide a conceptual demonstration of the different approaches taken towards the construction of these task-specific designer hydrogels. Finally, a collective effort among the material scientists is required to pave the path for the entrance of these intelligent materials into medicine from bench to bedside.

Current status and perspective on molecular targets and therapeutic intervention strategy in hepatic ischemia-reperfusion injury.

Hepatic ischemia‒reperfusion injury (HIRI) is a common and inevitable complication of hepatic trauma, liver resection, or liver transplantation. It contributes to postoperative organ failure or tissue rejection, eventually affecting patient prognosis and overall survival. The pathological mechanism of HIRI is highly complex and has not yet been fully elucidated. The proposed underlying mechanisms include mitochondrial damage, oxidative stress imbalance, abnormal cell death, immune cell hyperactivation, intracellular inflammatory disorders and other complex events. In addition to serious clinical limitations, available antagonistic drugs and specific treatment regimens are still lacking. Therefore, there is an urgent need to not only clarify the exact etiology of HIRI but also reveal the possible reactions and bottlenecks of existing drugs, helping to reduce morbidity and shorten hospitalizations. We analyzed the possible underlying mechanism of HIRI, discussed various outcomes among different animal models and explored neglected potential therapeutic strategies for HIRI treatment. By thoroughly reviewing and analyzing the literature on HIRI, we gained a comprehensive understanding of the current research status in related fields and identified valuable references for future clinical and scientific investigations.

Nanocarriers: Exploring the Potential of Oligonucleotide Delivery.

Nanoparticle-based delivery systems have emerged as promising tools in oligonucleotide therapeutics, facilitating precise and targeted delivery to address several disease conditions. The multifaceted landscape of nanoparticle-based oligonucleotide delivery encompasses the fundamental aspects of nanotechnology in delivery systems, various classes of oligonucleotides, and the growing field of ON-based therapeutics. These ON-based therapeutics are utilized to target specific genetic sequences within cells, offering promising avenues for treating various diseases by regulating gene expression or interfering with specific cellular processes. The integration of nanotechnology in delivery systems offers several advantages, given their intricate systems. Being a diverse class of agents, oligonucleotides provide a wide range of potential owed to each class of agents that support therapeutic interventions. Oligonucleotide-based platforms have demonstrated their versatility in molecular targeting and intervention strategies. Moreover, the complexities and delivery challenges in oligonucleotide therapeutics are expected to be overcome by the application of nanotechnology-based platforms.Because nanoparticles can overcome biological barriers and improve bioavailability, stability, and specificity, their role in developing oligonucleotide delivery systems is greatly valued. The innovative solutions facilitated by nanoparticles are efficient strategies to address the arduous barriers. These strategies beat obstacles like enzymatic degradation, cellular uptake, and immune response, which in turn paves the way for enhanced therapeutic efficacy. This review paper intends to explore the various applications of nanoparticle-mediated oligonucleotide delivery in a variety of diseases. It outlines the promising growth of therapies enabled by these systems, extending from cancer to genetic disorders, neurodegenerative diseases, etc. We have underscored the pivotal role of nanoparticle-based delivery systems in uncovering the full potential of oligonucleotide therapeutics, thereby fostering advancements in precision medicine and targeted therapies.

Molecular mechanisms and therapeutic possibilities of short-chain fatty acids in posttraumatic stress disorder patients: a mini-review.

This mini-review explores the role of short-chain fatty acids (SCFAs) in posttraumatic stress disorder (PTSD). Highlighting the microbiota-gut-brain axis, this study investigated the bidirectional communication between the gut microbiome and mental health. SCFAs, byproducts of gut microbial fermentation, have been examined for their potential impact on PTSD, with a focus on molecular mechanisms and therapeutic interventions. This review discusses changes in SCFA levels and bacterial profiles in individuals with PTSD, emphasizing the need for further research. Promising outcomes from clinical trials using probiotics and fermented formulations suggest potential avenues for PTSD management. Future directions involve establishing comprehensive human cohorts, integrating multiomics data, and employing advanced computational methods, with the goal of deepening our understanding of the role of SCFAs in PTSD and exploring microbiota-targeted interventions.

Revealing Hidden Genes in Botrytis cinerea: New Insights into Genes Involved in the Biosynthesis of Secondary Metabolites.

Utilizing bioinformatics tools, this study expands our understanding of secondary metabolism in Botrytis cinerea, identifying novel genes within polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS), sesquiterpene cyclase (STC), diterpene cyclase (DTC), and dimethylallyltryptophan synthase (DMATS) families. These findings enrich the genetic framework associated with B. cinerea's pathogenicity and ecological adaptation, offering insights into uncharted metabolic pathways. Significantly, the discovery of previously unannotated genes provides new molecular targets for developing targeted antifungal strategies, promising to enhance crop protection and advance our understanding of fungal biochemistry. This research not only broadens the scope of known secondary metabolites but also opens avenues for future exploration into B. cinerea's biosynthetic capabilities, potentially leading to novel antifungal compounds. Our work underscores the importance of integrating bioinformatics and genomics for fungal research, paving the way for sustainable agricultural practices by pinpointing precise molecular interventions against B. cinerea. This study sets a foundation for further investigations into the fungus's secondary metabolism, with implications for biotechnology and crop disease management.

Exploring biological mechanisms in orthodontic tooth movement: Bridging the gap between basic research experiments and clinical applications – A comprehensive review

ObjectivesThe molecular mechanisms behind orthodontic tooth movements (OTM) were investigated by clarifying the role of chemical messengers released by cells. MethodsUsing the Cochrane library, Google scholar, and PubMed databases, a literature search was conducted, and studies published from 1984 to 2024 were considered. ResultsBoth bone growth and remodeling may occur when a tooth is subjected to mechanical stress. These chemicals have a significant effect on the stimulation and regulation of osteoblasts, osteoclasts, and osteocytes during alveolar bone remodeling. This regulation can take place in pathological conditions, such as periodontal diseases, or during OTM alone. This comprehensive review outlines key molecular mechanisms underlying OTM and explores various clinical assumptions associated with specific molecules and their functional domains during this process. Furthermore, clinical applications of certain molecules such as relaxin, prostaglandin E (PGE), and interleukin-1β (IL-1β) in accelerating OTM have been reported. Our findings underscore the existing gap between OTM clinical applications and basic research investigations. ConclusionA comprehensive understanding of orthodontic treatment is enriched by insights into biological systems. We reported the activation of osteoblasts, osteoclast precursor cells, osteoclasts, and osteocytes in response to mechanical stress, leading to targeted cellular and molecular interventions and facilitating rapid and regulated alveolar bone remodeling during tooth movement. Despite the shortcomings of clinical studies in accelerating OTM, this review highlights the crucial role of biological agents in this process and advocates for prioritizing high-quality human studies in future research to gain further insights from clinical trials.