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Resistance training is used to combat skeletal muscle function decline in older adults. Few studies have been designed specific for females, resulting in very limited treatment options for skeletal muscle atrophy in aging women. Here, we analyzed the gene expression profiles of skeletal muscle samples from sedentary young women, sedentary older women, and resistance-trained older women, using microarray data from public database. A total of 45 genes that were differentially expressed during female muscle aging and reversed by resistance training were identified. Functional and pathway enrichment analysis, protein–protein interaction network analysis, and receiver operating characteristic analysis were performed to reveal the key genes and pathways involved in the effects of resistance training on female muscle aging. The collagen genes COL1A1, COL3A1, and COL4A1 were identified important regulators of female muscle aging and resistance training, by modulating multiple signaling pathways, such as PI3 kinase-Akt signaling, focal adhesions, extracellular matrix-receptor interactions, and relaxin signaling. Interestingly, the expression of CDKN1A and TP63 were increased during aging, and further upregulated by resistance training in older women, suggesting they may negatively affect resistance training outcomes. Our findings provide novel insights into the molecular mechanisms of resistance training on female muscle aging and identify potential biomarkers and targets for clinical intervention. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis is an inflammatory disease dependent on immunoglobulin E and causes inflammation of the nasal mucosa, leading to decreased quality of life for affected patients. Since common treatments, including corticosteroids and antihistamines, have temporary therapeutic effects and numerous side effects, investigating natural compounds effective in improving allergic rhinitis with low complications and high efficacy can be significant and necessary. Purpose: This study aims to present a comprehensive and critical evaluation of the effect of natural compounds in improving allergic rhinitis. Methods: Studies were identified through systematic searches of ScienceDirect, PubMed, Scopus, and Web of Sciences databases. Eligibility checks were conducted based on predefined selection criteria. Forty-six articles were included in this study. Results and discussion: Phytochemicals, including flavonoids, alkaloids, terpenoids, and other compounds showed significant anti-inflammatory and antihistaminic effects. These compounds alleviate allergic rhinitis symptoms by inhibiting inflammatory mediators, oxidative stress, apoptosis, and key signaling pathways such as MAPK/NFκB and TLR4/MyD88/NF-κB. Conclusion: Phytochemicals exhibit anti-inflammatory and antioxidant properties, making them. [ABSTRACT FROM AUTHOR]

Cancer is a major global health challenge, being the second leading cause of morbidity and mortality after cardiovascular disease. The growing economic burden and profound psychosocial impact on patients and their families make it urgent to find innovative and effective anticancer solutions. For this reason, interest in using natural compounds to develop new cancer treatments has grown. In this respect, antofine, an alkaloid class found in Apocynaceae, Lauraceae, and Moraceae family plants, exhibits promising biological properties, including anti-inflammatory, anticancer, antiviral, and antifungal activities. Several molecular mechanisms have been identified underlying antofine anti-cancerous effects, including the inhibition of nuclear factor κB (NF-κB) and AKT/mTOR signaling pathways, epigenetic inhibition of protein synthesis, ribosomal targeting, induction of apoptosis, inhibition of DNA synthesis, and cell cycle arrest. This study discusses the molecular structure, sources, photochemistry, and anticancer properties of antofine in relation to its structure–activity relationship and molecular targets. Then, examine in vitro and in vivo studies and analyze the mechanisms of action underpinning antofine efficacy against cancer cells. This review also discusses multidrug resistance in human cancer and the potential of antofine in this context. Safety and toxicity concerns are also addressed as well as current challenges in antofine research, including the need for clinical trials and bioavailability optimization. This review aims to provide comprehensive information for more effective natural compound-based cancer treatments. [ABSTRACT FROM AUTHOR]

Lung cancer accounts for the highest cancer-related mortality worldwide. While immunotherapies targeting anti-tumor immune responses have demonstrated efficacy in clinical practice, the demand for novel treatment modalities remains urgent. Oncolytic viruses (OVs), which selectively kill tumor cells while stimulating an anti-tumor immune response, represent a potential breakthrough in lung cancer therapy. The induction of anti-tumor immunity by OVs is central to their overall therapeutic effectiveness. Many natural receptors on the surface of cancer cells are dysregulated, providing potential entry points for OVs. Furthermore, the inherent dysregulation of some key signaling pathways in lung cancer cells promotes proliferation, progression and metastasis, which may facilitate selective viral replication. In this review, we explore the application of OVs in lung cancer by analyzing several major OVs and their corresponding entry receptors. Then, we also examine the key signaling pathways and molecules with the potential to synergize with OVs in modulating the immune tumor microenvironment. Finally, we discuss the combination and administration strategies that warrant further clinical trials for validation. Despite certain limitations, the tolerability of OVs positions virotherapy as a promising avenue in the future of lung cancer treatment. [ABSTRACT FROM AUTHOR]

The pattern recognition receptor (PRR), which drives innate immunity, shields the host against invasive pathogens. Fish and other aquatic species with poorly developed adaptive immunity mostly rely on their innate immunity, regulated by PRRs such as inherited-encoded toll-like receptors (TLRs). The discovery of 21 unique TLR variations in various aquatic animals over the past several years has sparked interest in using TLRs to improve aquatic animal’s immune response and disease resistance. This comprehensive review provides an overview of the latest investigations on the various characteristics of TLRs in aquatic animals. It emphasizes their categorization, insights into 3D architecture, ligand recognition, signaling pathways, TLRs mediated immune responses under biotic and abiotic stressors, and expression variations during several developmental stages. It also highlights the differences among aquatic animals’ TLRs and their mammal counterparts, which signifies the unique roles that TLRs play in aquatic animal’s immune systems. This article summarizes current aquaculture research to enhance our understanding of fish immune systems for effective aquaculture -related disease management. [ABSTRACT FROM AUTHOR]

In this paper, active polysaccharides were extracted from Brassica rapa L. polysaccharide (BRP), and structural characterization was preliminarily investigated. Its immunomodulatory activity and molecular biological mechanisms in cyclophosphamide‐induced immunosuppressed mice were also explored, as well as its effects on intestinal microbiota. Results indicate that BRP is an acidic heteropolysaccharide with the main components of Ara, GalA, and GlcA and has α‐ and β‐glycosidic linkages with pyranose bonds. The results of the study showed that BRP could effectively improve the thymus and spleen indices and repair Cy‐induced immune tissue damage in immunosuppressed mice. Meanwhile, BRP increased the immune cell activity and antioxidant levels in mice. In addition, BRP increased the secretion of cytokines (IL‐1β, IL‐6, IL‐10, and TNF‐α) and immunoglobulins (IgA, IgG) in mouse serum. It also regulates the relative expression of genes related to the TLR4/NF‐κB signaling pathways as well as regulates the diversity and composition of mouse intestinal microbiota. In conclusion, BRP was able to regulated the immune function in immunosuppressed mice, providing a theoretical basis for the development of immunomodulators. [ABSTRACT FROM AUTHOR]

This article addresses the physical mechanics of gametogenesis in vascular plants. The earliest events that initiate reproductive differentiation in the land plants are not well understood. How are the few cells that initiate reproductive differentiation specified and how is that information translated into action at the cellular level? In this article I propose a physical mechanism that resolves the problem of spatial targeting without invoking dependence on diffusible morphogens or other external signals. I suggest that the initiation of archesporial differentiation can instead be attributed to the confluence of organ geometry, surficial topography, and the physical mechanics of sporangial growth, resulting in the spontaneous emergence of an isotropic singularity that locates and precipitates archesporial differentiation. In discussing the logic of single-cell target selection and the limits of stochastic molecular signaling I propose that the sporangium would be better understood as a pressurized stress-mechanical lens that focuses turgor-generated growth forces on a central location, generating a physical singularity that locates and specifies the cell or cells that become the archesporium and initiates their transition from somatic proliferation to reproductive differentiation. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most common harmful high-grade brain tumor with high mortality and low survival rate. Importantly, besides routine diagnostic and therapeutic methods, modern and useful practical techniques are urgently needed for this serious malignancy. Correspondingly, the translational medicine focusing on genetic and epigenetic profiles of glioblastoma, as well as the immune framework and brain microenvironment, based on these challenging findings, indicates that key clinical interventions include immunotherapy, such as immunoassay, oncolytic viral therapy, and chimeric antigen receptor T (CAR T) cell therapy, which are of great importance in both diagnosis and therapy. Relatively, vaccine therapy reflects the untapped confidence to enhance GBM outcomes. Ongoing advances in immunotherapy, which utilizes different methods to regenerate or modify the resistant body for cancer therapy, have revealed serious results with many different problems and difficulties for patients. Safe checkpoint inhibitors, adoptive cellular treatment, cellular and peptide antibodies, and other innovations give researchers an endless cluster of instruments to plan profoundly in personalized medicine and the potential for combination techniques. In this way, antibodies that block immune checkpoints, particularly those that target the program death 1 (PD-1)/PD-1 (PD-L1) ligand pathway, have improved prognosis in a wide range of diseases. However, its use in combination with chemotherapy, radiation therapy, or monotherapy is ineffective in treating GBM. The purpose of this review is to provide an up-to-date overview of the translational elements concentrating on the immunotherapeutic field of GBM alongside describing the molecular mechanism involved in GBM and related signaling pathways, presenting both historical perspectives and future directions underlying basic and clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Drug repurposing offers a valuable approach for utilizing FDA-approved drugs to address new diseases, including cancer, while significantly reducing the time and cost associated with drug development. In this review, we highlight the anticancer potential of anthelmintic benzimidazole derivatives, such as mebendazole (MBZ), fenbendazole (FBZ), flubendazole (FLBZ), and albendazole (ABZ), with a particular focus on their efficacy against blood cancers. These compounds operate through multiple mechanisms, including disrupting microtubule formation, regulating the cell cycle, inducing cellular differentiation, and modulating key signaling pathways involved in cancer progression. The ability of benzimidazoles to exert these diverse effects on malignant cells suggests their promise as therapeutic agents for hematological cancers. Furthermore, investigating their use in combination with standard-of-care treatments may lead to the development of novel, more effective therapeutic strategies, offering new avenues of hope for patients with blood malignancies. Drug repurposing is a strategy to discover new therapeutic uses for existing drugs, which have well-established toxicity profiles and are often more affordable. This approach has gained significant attention in recent years due to the high costs and low success rates associated with traditional drug development. Drug repositioning offers a more time- and cost-effective path for identifying new treatments. Several FDA-approved non-chemotherapy drugs have been investigated for their anticancer potential. Among these, anthelmintic benzimidazoles (such as albendazole, mebendazole, and flubendazole) have garnered interest due to their effects on microtubules and oncogenic signaling pathways. Blood cancers, which frequently develop resistance and have high mortality rates, present a critical need for effective therapies. This review highlights the recent advances in repurposing benzimidazoles for blood malignancies. These compounds induce cell cycle arrest, differentiation, tubulin depolymerization, loss of heterozygosity, proteasomal degradation, and inhibit oncogenic signaling to exert their anticancer effects. We also discuss current limitations and strategies to overcome them, emphasizing the potential of combining benzimidazoles with standard therapies for improved treatment of hematological cancers. [ABSTRACT FROM AUTHOR]

Proliferative vitreoretinopathy (PVR) is a pathological process characterized by the formation of fibrotic membranes that contract and lead to recurrent retinal detachment. Pars plana vitrectomy (PPV) is the primary treatment, but recurrence rates remain high, as surgery does not address the underlying molecular mechanisms driving fibrosis. Despite several proposed pharmacological interventions, no approved therapies exist, partly due to challenges in conducting preclinical and in vivo studies for ethical and safety reasons. This review explores the potential of computational models and Digital Twins, which are increasingly gaining attention in medicine. These tools could enable the development of progressively complex PVR models, from basic simulations to patient-specific Digital Twins. Nintedanib, a tyrosine kinase inhibitor targeting PDGFR, VEGFR, and FGFR, is presented as a prototype for computational models to simulate its effects on fibrotic pathways in virtual patient cohorts. Although still in its early stages, the integration of computational models and Digital Twins offers promising avenues for improving PVR management through more personalized therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a common cause of endometrial-type mucosa outside the uterine cavity with symptoms such as painful periods, chronic pelvic pain, pain with intercourse and infertility. However, the early diagnosis of endometriosis is still restricted. The purpose of this investigation is to identify and validate the key biomarkers of endometriosis. Methods: Next-generation sequencing dataset GSE243039 was obtained from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) between endometriosis and normal control samples were identified. After screening of DEGs, gene ontology (GO) and REACTOME pathway enrichment analyses were performed. Furthermore, a protein–protein interaction (PPI) network was constructed and modules were analyzed using the Human Integrated Protein–Protein Interaction rEference database and Cytoscape software, and hub genes were identified. Subsequently, a network between miRNAs and hub genes, and network between TFs and hub genes were constructed using the miRNet and NetworkAnalyst tool, and possible key miRNAs and TFs were predicted. Finally, receiver operating characteristic curve analysis was used to validate the hub genes. Results: A total of 958 DEGs, including 479 upregulated genes and 479 downregulated genes, were screened between endometriosis and normal control samples. GO and REACTOME pathway enrichment analyses of the 958 DEGs showed that they were mainly involved in multicellular organismal process, developmental process, signaling by GPCR and muscle contraction. Further analysis of the PPI network and modules identified 10 hub genes, including vcam1, snca, prkcb, adrb2, foxq1, mdfi, actbl2, prkd1, dapk1 and actc1. Possible target miRNAs, including hsa-mir-3143 and hsa-mir-2110, and target TFs, including tcf3 (transcription factor 3) and clock (clock circadian regulator), were predicted by constructing a miRNA-hub gene regulatory network and TF-hub gene regulatory network. Conclusions: This investigation used bioinformatics techniques to explore the potential and novel biomarkers. These biomarkers might provide new ideas and methods for the early diagnosis, treatment and monitoring of endometriosis. [ABSTRACT FROM AUTHOR]

Rice (Oryza sativa L.) serves as a substitute for bread and is a staple food for half of the world's population, but it is heavily affected by insect pests. The fall armyworm (Spodoptera frugiperda) is a highly destructive pest, threatening rice and other crops in tropical regions. Despite its significance, little is known about the molecular mechanisms underlying rice's response to fall armyworm infestation. In this study, we used transcriptome analysis to explore the global changes in gene expression in rice leaves during a 1 h and 12 h fall armyworm feeding. The results reveal 2695 and 6264 differentially expressed genes (DEGs) at 1 and 12 h post-infestation, respectively. Gene Ontology (GO) and KEGG enrichment analyses provide insights into biological processes and pathways affected by fall armyworm feeding. Key genes associated with hormone regulation, defense metabolic pathways, and antioxidant and detoxification processes were upregulated, suggesting the involvement of jasmonic acid (JA) signaling, salicylic acid biosynthesis pathways, auxin response, and heat shock proteins in defense during 1 h and 12 h after fall armyworm infestation. Similarly, key genes involved in transcriptional regulation and defense mechanisms reveal the activation of calmodulins, transcription factors (TFs), and genes related to secondary metabolite biosynthesis. Additionally, MYB, WRKY, and ethylene-responsive factors (ERFs) are identified as crucial TF families in rice's defense response. This study provides a comprehensive understanding of the molecular dynamics in rice responding to fall armyworm infestation, offering valuable insights for developing pest-resistant rice varieties and enhancing global food security. The identified genes and pathways provide an extensive array of genomic resources that can be used for further genetic investigation into rice herbivore resistance. This also suggests that rice plants may have evolved strategies against herbivorous insects. It also lays the groundwork for novel pest-resistance techniques for rice. [ABSTRACT FROM AUTHOR]

AbstractOsteoarthritis (OA) is a chronic degenerative disease caused by various factors such as aging, obesity, trauma, and genetics. It is a challenging condition faced by orthopedic doctors in clinical practice and places a heavy burden on patients and their families. Currently, the treatment of OA primarily focuses on symptomatic relief and lacks ideal therapeutic methods. Resveratrol is a natural polyphenolic compound with anti-inflammatory and antioxidant properties, and in recent years, it has gained attention as a candidate drug for OA treatment. This article provides an overview of the research status on the role and mechanisms of resveratrol in treating OA. It has been found that resveratrol can prevent the development of OA by inhibiting inflammatory responses, protecting chondrocytes, maintaining cartilage homeostasis, promoting autophagy, and has shown certain therapeutic effects. This process may be related to the regulation of signaling pathways such as nuclear factor-kappa B (NF-κB), Toll-like receptor 4 (TLR4), and silent information regulator 1 (SIRT1). We summarize the current molecular mechanisms of resveratrol in treating OA, hoping to provide a reference for further research and application of resveratrol in OA treatment. [ABSTRACT FROM AUTHOR]

Plants encounter various stresses in their natural environments and can effectively respond to only one stress at a time. Through a complex gene network, transcription factors (TFs) such as WRKY TFs regulate a diverse array of stress responses. The clarification of the structural characteristics of WRKY proteins, along with recent advancements in molecular dynamics simulations, has shed light on the formation, stability, and interactions of DNA–protein complexes. This has provided a novel viewpoint regarding the control of WRKY TFs. The investigation of superfamilies, encompassing their historical development, diversity, and evolutionary patterns, has become feasible due to the transcriptome approach's capacity to provide extensive and comprehensive transcripts. The significance of WRKY TFs lies in their pivotal role within several signaling cascades and regulatory networks that influence plant defense responses. The present review summarizes the functional aspects of the high-volume sequence data of WRKY TFs from different species studied to date. Moreover, a comparative analysis approach was utilized to determine the functions of the identified WRKY TFs in response to both abiotic and biotic stresses, as revealed through numerous studies on different plant species. The results of this review will be pivotal in understanding evolutionary events and the significance of WRKY TFs in the context of climate change, incorporating new scientific evidence to propose an innovative viewpoint. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-apoptotic modes of cell death have gained increasing attention in the past few years. Cuproptosis is a copper-dependent cell death mechanism that is involved in numerous diseases, including cancer. The relevance of cuproptosis for the survival times of cancer patients is still incompletely understood. We have investigated cuproptosis-related genes based on their mRNA expression and statistical relationship to the survival times of patients by using Kaplan–Meier statistics. Further, we have investigated the possible interactions of the genes with signaling networks. Our study has shown that cuproptosis may play an important role in hepatocellular carcinoma, renal clear cell carcinoma, papillary renal cell carcinoma, and lung adenocarcinoma. We identified gene signatures consisting of nine to twenty-one genes in the above four tumor types, and we have shown that a high mRNA expression of 63/124 cuproptosis-associated genes significantly correlated with shorter survival times of cancer patients. We investigated the mRNA expression of 124 cuproptosis-associated genes in 7489 biopsies from 20 different tumor types of The Cancer Genome Atlas (TCGA). The KM plotter algorithm has been used to calculate Kaplan–Meier statistics and false discovery rate (FDR) corrections. Interaction networks have been generated using Ingenuity Pathway Analysis (IPA). High mRNA expression of 63 out of 124 genes significantly correlated with shorter survival times of cancer patients across all 20 tumor types. IPA analyses revealed that their gene products were interconnected in canonical pathways (e.g., cancer, cell death, cell cycle, cell signaling). Four tumor entities showed a higher accumulation of genes than the other cancer types, i.e., renal clear cell carcinoma (n = 21), renal papillary carcinoma (n = 13), kidney hepatocellular carcinoma (n = 13), and lung adenocarcinoma (n = 9). These gene clusters may serve as prognostic signatures for patient survival. These signatures were also of prognostic value for tumors with high mutational rates and neoantigen loads. Cuproptosis is of prognostic significance for the survival of cancer patients. The identification of specific gene signatures deserves further exploration for their clinical utility in routine diagnostics. [ABSTRACT FROM AUTHOR]

Low back pain significantly impacts individuals' quality of life, with intervertebral disc degeneration (IDD) being a primary contributor to this condition. Currently, IDD treatment primarily focuses on symptom management and does not achieve a definitive cure. The cartilage endplate (CEP), a crucial nutrient‐supplying tissue of the intervertebral disc, plays a pivotal role in disc degeneration. This review examines the mechanisms underlying CEP degeneration, summarizing recent advancements in understanding the structure and function of CEP, the involvement of various signaling pathways, and the roles of cartilage endplate stem cells (CESCs) and exosomes (Exos) in this process. The aim of this review is to provide a comprehensive reference for future research on CEP. Despite progress in understanding the role of CEP in IDD, the mechanisms underlying CEP degeneration remain incompletely elucidated. Future research poses significant challenges, necessitating further investigations to elucidate the complexities of CEP. Significance Statement: This article provides a comprehensive review of the mechanisms underlying the degeneration of the cartilaginous endplate (CEP) and its role in intervertebral disc degeneration (IDD). It elucidates the structure and function of the CEP, the association between CEP and IDD, the involvement of various signaling pathways in CEP degeneration, and the contributions of CEP stem cells and exosomes to this process. The CEP supplies 75% of the nutrients required by the intervertebral disc, thus playing a pivotal role in the progression of IDD. This review aims to reveal key issues and development trends in research by summarizing previous studies, and to provide directional references for future research on CEP in IDD. [ABSTRACT FROM AUTHOR]

Cancer is a global health challenge with rising incidence and mortality rates, posing significant concerns. The World Health Organization reports cancer as a leading cause of death worldwide, contributing to nearly one in six deaths. Cancer pathogenesis involves disruptions in cellular signaling pathways, resulting in uncontrolled cell growth and metastasis. Among emerging players in cancer biology, Transient Receptor Potential (TRP) channels, notably TRPV1, have garnered attention due to their altered expression in cancer cells and roles in tumorigenesis and progression. TRPV1, also known as the capsaicin receptor, is pivotal in cancer cell death and pain mediation, offering promise as a therapeutic target. Activation of TRPV1 triggers calcium influx and affects cell signaling linked to growth and death. Additionally, TRPV1 is implicated in cancer-induced pain and chemo-sensitivity, with upregulation observed in sensory neurons innervating oral cancers. Also, when capsaicin, a compound from chili peppers, interacts with TRPV1, it elicits a "hot" sensation and influences cancer processes through calcium influx. Understanding TRPV1's multifaceted roles in cancer may lead to novel therapeutic strategies for managing cancer-related symptoms and improving patient outcomes. The current review elucidates the comprehensive role of capsaicin in cancer therapy, particularly through the TRPV1 channel, highlighting its effects in various cells via different signaling pathways and discussing its limitations. [ABSTRACT FROM AUTHOR]

In the field of sports medicine, repair surgery for anterior cruciate ligament (ACL) and rotator cuff (RC) injuries are remarkably common. Despite the availability of relatively effective treatment modalities, outcomes often fall short of expectations. This comprehensive review aims to thoroughly examine current strategies employed to promote tendon‐bone healing and analyze pertinent preclinical and clinical research. Amidst ongoing investigations, tendon‐derived stem cells (TDSCs), which have comparatively limited prior exploration, have garnered increasing attention in the context of tendon‐bone healing, emerging as a promising cell type for regenerative therapies. This review article delves into the potential of combining TDSCs with tissue engineering methods, with ACL reconstruction as the main focus. It comprehensively reviews relevant research on ACL and RC healing to address the issues of graft healing and bone tunnel integration. To optimize tendon‐bone healing outcomes, our emphasis lies in not only reconstructing the original microstructure of the tendon‐bone interface but also achieving proper bone tunnel integration, encompassing both cartilage and bone formation. In this endeavor, we thoroughly analyze the transcriptional and molecular regulatory variables governing TDSCs differentiation, incorporating a retrospective analysis utilizing single‐cell sequencing, with the aim of unearthing relevant signaling pathways and processes. By presenting a novel strategy rooted in TDSCs‐driven osteogenic and chondrogenic differentiation for tendon‐bone healing, this study paves the way for potential future research avenues and promising therapeutic applications. It is anticipated that the findings herein will contribute to advancing the field of tendon‐bone healing and foster the exploration of TDSCs as a viable option for regenerative therapies in the future. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) affects various brain cell types, including astrocytes, which are the most abundant cell types in the central nervous system (CNS). Astrocytes not only provide homeostatic support to neurons but also actively regulate synaptic signaling and functions and become reactive in response to CNS insults through diverse signaling pathways including the JAK/STAT, NF‐κB, and GPCR‐elicited pathways. The advent of new technology for transcriptomic profiling at the single‐cell level has led to increasing recognition of the highly versatile nature of reactive astrocytes and the context‐dependent specificity of astrocyte reactivity. In AD, reactive astrocytes have long been observed in senile plaques and have recently been suggested to play a role in AD pathogenesis and progression. However, the precise contributions of reactive astrocytes to AD remain elusive, and targeting this complex cell population for AD treatment poses significant challenges. In this review, we summarize the current understanding of astrocyte reactivity and its role in AD, with a particular focus on the signaling pathways that promote astrocyte reactivity and the heterogeneity of reactive astrocytes. Furthermore, we explore potential implications for the development of therapeutics for AD. Our objective is to shed light on the complex involvement of astrocytes in AD and offer insights into potential therapeutic targets and strategies for treating and managing this devastating neurodegenerative disorder. [ABSTRACT FROM AUTHOR]

The current understanding of the role of non-coding RNAs in the regulation of signaling pathways that control lipid accumulation and the development of inflammation in non-alcoholic fatty liver disease (NAFLD) is outlined. The contribution of peroxisome proliferator-activated receptors (PPARs) to changes in lipid metabolism and the formation of lipotoxicity as trigger mechanisms of NAFLD is considered. The role of TGFβ, TNFα/NF-κb, IL-6/JAK/STAT3 signaling pathways in the activation of stellate cells, liver fibrogenesis and the progression of NAFLD has been demonstrated. Analysis of literature data has revealed a number of microRNAs and long non-coding RNAs (lncRNAs) presumably associated with the regulation of these signaling pathways in this disease. They may probably have prognostic significance for differentiating clinical forms and severity of NAFLD. [ABSTRACT FROM AUTHOR]

In the complex landscape of cancer biology, the discovery of microproteins has triggered a paradigm shift, thereby, challenging the conventional conceptions of gene regulation. Though overlooked for years, these entities encoded by the small open reading frames (100–150 codons), have a significant impact on various cellular processes. As precision medicine pioneers delve deeper into the genome and proteome, microproteins have come into the limelight. Typically characterized by a single protein domain that directly binds to the target protein complex and regulates their assembly, these microproteins have been shown to play a key role in fundamental biological processes such as RNA processing, DNA repair, and metabolism regulation. Techniques for identification and characterization, such as ribosome profiling and proteogenomic approaches, have unraveled unique mechanisms by which these microproteins regulate cell signaling or pathological processes in most diseases including cancer. However, the functional relevance of these microproteins in cancer remains unclear. In this context, the current review aims to “rethink the essence of these genes” and explore “how these hidden players-microproteins orchestrate the signaling cascades of cancer, both as accelerators and brakes.”. [ABSTRACT FROM AUTHOR]

Multitarget histone deacetylase inhibitors (MT-HDACi) have emerged as a promising therapeutic strategy in cancer treatment, addressing the limitations of traditional single-target therapies. This review explores the role of histone deacetylases in epigenetic regulation and their implications in cancer biology. A particular focus is placed on the BRD4-LIFRJAK1-STAT3 signaling pathway, which has been implicated in promoting drug resistance. The interplay between these molecular targets highlights the complexity of oncogenic signaling and the challenges associated with effective cancer therapy. MTHDACi offer the potential to simultaneously inhibit multiple pathways, thereby disrupting the mechanisms of drug resistance mediated by BRD4 and its downstream effectors. Furthermore, this review emphasizes the importance of understanding resistance mechanisms to enhance the design and development of MT-HDACi. By integrating insights from molecular biology, pharmacology, and translational research, this work advocates for continued exploration of multitargeted approaches as a viable strategy for improving therapeutic outcomes in cancer patients. [ABSTRACT FROM AUTHOR]

Bone remodeling is an intricate process executed throughout one's whole life via the cross-talk of several cellular events, progenitor cells and signaling pathways. It is an imperative mechanism for regaining bone loss, recovering damaged tissue and repairing fractures. To achieve this, molecular signaling pathways play a central role in regulating pathological and causal mechanisms in different diseases. Similarly, microRNAs (miRNAs) have shown promising results in disease management by mediating mRNA targeted gene expression and post-transcriptional gene function. However, the role and relevance of these miRNAs in signaling processes, which regulate the delicate balance between bone formation and bone resorption, are unclear. This review aims to summarize current knowledge of bone remodeling from two perspectives: firstly, we outline the modus operandi of five major molecular signaling pathways, i.e.,the receptor activator of nuclear factor kappa-B (RANK)-osteoprotegrin (OPG) and RANK ligand (RANK-OPG-RANKL), macrophage colony-stimulating factor (M-CSF), Wnt/β-catenin, Jagged/Notch and bone morphogenetic protein (BMP) pathways in regards to bone cell formation and function; and secondly, the miRNAs that participate in these pathways are introduced. Probing the miRNA-mediated regulation of these pathways may help in preparing the foundation for developing targeted strategies in bone remodeling, repair and regeneration. [ABSTRACT FROM AUTHOR]

Diabetic eye disease (DED) encompasses a range of ocular complications arising from diabetes mellitus, including diabetic retinopathy, diabetic macular edema, diabetic keratopathy, diabetic cataract, and glaucoma. These conditions are leading causes of visual impairments and blindness, especially among working-age adults. Despite advancements in our understanding of DED, its underlying pathophysiological mechanisms remain incompletely understood. Chronic hyperglycemia, oxidative stress, inflammation, and neurodegeneration play central roles in the development and progression of DED, with immune-mediated processes increasingly recognized as key contributors. This review provides a comprehensive examination of the complex interactions between immune cells, inflammatory mediators, and signaling pathways implicated in the pathogenesis of DED. By delving in current research, this review aims to identify potential therapeutic targets, suggesting directions of research for future studies to address the immunopathological aspects of DED. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are widely acknowledged as the drivers of tumor initiation, epithelial‐mesenchymal transition (EMT) progression, and metastasis. Originating from both hematologic and solid malignancies, CSCs exhibit quiescence, pluripotency, and self‐renewal akin to normal stem cells, thus orchestrating tumor heterogeneity and growth. Through a dynamic interplay with the tumor microenvironment (TME) and intricate signaling cascades, CSCs undergo transitions from differentiated cancer cells, culminating in therapy resistance and disease recurrence. This review undertakes an in‐depth analysis of the multifaceted mechanisms underlying cancer stemness and CSC‐mediated resistance to therapy. Intrinsic factors encompassing the TME, hypoxic conditions, and oxidative stress, alongside extrinsic processes such as drug efflux mechanisms, collectively contribute to therapeutic resistance. An exploration into key signaling pathways, including JAK/STAT, WNT, NOTCH, and HEDGEHOG, sheds light on their pivotal roles in sustaining CSCs phenotypes. Insights gleaned from preclinical and clinical studies hold promise in refining drug discovery efforts and optimizing therapeutic interventions, especially chimeric antigen receptor (CAR)‐T cell therapy, cytokine‐induced killer (CIK) cell therapy, natural killer (NK) cell‐mediated CSC‐targeting and others. Ultimately use of cell sorting and single cell sequencing approaches for elucidating the fundamental characteristics and resistance mechanisms inherent in CSCs will enhance our comprehension of CSC and intratumor heterogeneity, which ultimately would inform about tailored and personalized interventions. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), characterized by cognitive impairment, brain plaques, and tangles, is a global health concern affecting millions. It involves the build-up of amyloid-β (Aβ) and tau proteins, the formation of neuritic plaques and neurofibrillary tangles, cholinergic system dysfunction, genetic variations, and mitochondrial dysfunction. Various signaling pathways and metabolic processes are implicated in AD, along with numerous biomarkers used for diagnosis, risk assessment, and research. Despite these, there is no cure or effective treatment for AD. It is critically important to address this immediately to develop novel drug delivery systems (NDDS) capable of targeting the brain and delivering therapeutic agents to modulate the pathological processes of AD. This review summarizes AD, its pathogenesis, related signaling pathways, biomarkers, conventional treatments, the need for NDDS, and their application in AD treatment. It also covers preclinical, clinical, and ongoing trials, patents, and marketed AD formulations. [ABSTRACT FROM AUTHOR]

The use of drugs in chemotherapy poses numerous side effects. Hence the use of natural substances that can help in the prevention and cure of the disease is a dire necessity. Cancer is a deadly illness and combination of diseases, the menace of which is rising with every passing year. The research community and scientists from all over the world are working towards finding a cure of the disease. The use of polyphenols which are naturally derived from plants have a great potential to be used as anti-cancer drugs and also the use of fruits and vegetables which are rich in these polyphenols can also help in the prevention of diseases. The study aims to compile the available literature and research studies on the anti-cancer effects of polyphenols and the signaling pathways that are affected by them. To review the anti-cancer effects of polyphenols, Google Scholar, PubMed and ScienceDirect were used to study the literature available. The article that have been used for literature review were filtered using keywords including cancer, polyphenols and signaling pathways. Majorly articles from the last 10 years have been considered for the review but relevant articles from earlier than 10 years have also been considered. Almost 400 articles were studied for the review and 200 articles have been cited. The current review shows the potential of polyphenols as anti-cancer compounds and how the consumption of a diet rich in polyphenols can help in the prevention of cancer. Because of their capacity to affect a variety of oncogenic and oncosuppressive signaling pathways, phytochemicals derived from plants have been effectively introduced as an alternative anticarcinogenic medicines. [ABSTRACT FROM AUTHOR]

This review explores the molecular and genetic underpinnings of axonal regeneration and functional recovery post-nerve injury, emphasizing its significance in reversing neurological deficits. It presents a systematic exploration of the roles of various genes in axonal regrowth across peripheral and central nerve injuries. Initially, it highlights genes and gene families critical for axonal growth and guidance, delving into their roles in regeneration. It then examines the regenerative microenvironment, focusing on the role of glial cells in neural repair through dedifferentiation, proliferation, and migration. The concept of "traumatic microenvironments" within the central nervous system (CNS) and peripheral nervous system (PNS) is discussed, noting their impact on regenerative capacities and their importance in therapeutic strategy development. Additionally, the review delves into axonal transport mechanisms essential for accurate growth and reinnervation, integrating insights from proteomics, genome-wide screenings, and gene editing advancements. Conclusively, it synthesizes these insights to offer a comprehensive understanding of axonal regeneration's molecular orchestration, aiming to inform effective nerve injury therapies and contribute to regenerative neuroscience. [ABSTRACT FROM AUTHOR]

Rosacea is a chronic skin inflammatory disease with a global prevalence ranging from 1% to 20%. It is characterized by facial erythema, telangiectasia, papules, pustules, and ocular manifestations. Its pathogenesis involves a complex interplay of genetic, environmental, immune, microbial, and neurovascular factors. Recent studies have advanced our understanding of its molecular basis, focusing on toll-like receptor (TLR) 2 pathways, LL37 expression, mammalian target of rapamycin (mTOR) activation, interleukin (IL)-17 signaling, transient receptor potential vanilloid (TRPV) functions, and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways. LL37- associated signaling pathways, particularly involving TLR2 and mTORC1, are critical in the pathogenesis of rosacea. LL37 interacts with signaling molecules such as extracellular signal-regulated kinases 1 and 2 (ERK1/2), nuclear factor kappa B (NF-kB), inflammasomes, C-X-C motif chemokine ligand 8 (CXCL8), mas-related G-protein-coupled receptor X2 (MRGPRX2)-TRPV4, and vascular endothelial growth factor (VEGF). This interaction activates macrophages, neutrophils, mast cells, and vascular endothelial cells, leading to cytokine release including tumor necrosis factor-alpha (TNF-a), IL-6, IL-1b, C motif chemokine ligand (CCL) 5, CXCL9, and CXCL10. These processes contribute to immune response modulation, inflammation, and angiogenesis in rosacea pathophysiology. The IL-17 signaling pathway also plays a crucial role in rosacea, affecting angiogenesis and the production of inflammatory cytokines. In addition, recent insights into the JAK/STAT pathways have revealed their integral role in inflammatory and angiogenic mechanisms associated with rosacea. Rosacea treatment currently focuses on symptom management, with emerging insights into these molecular pathways providing more targeted and effective therapies. Biological agents targeting specific cytokines, IL-17 inhibitors, JAK inhibitors, and VEGF antagonists are promising for future rosacea therapy, aiming for enhanced efficacy and fewer side effects. This review provides a comprehensive overview of the current knowledge regarding signaling pathways in rosacea and potential targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) stands as a significant global health challenge, distinguished by its aggressive progression from the esophageal epithelium. Central to this malignancy is sphingolipid metabolism, a critical pathway that governs key cellular processes, including apoptosis and immune regulation, thereby influencing tumor behavior. The advent of single-cell and transcriptome sequencing technologies has catalyzed significant advancements in oncology research, offering unprecedented insights into the molecular underpinnings of cancer. Methods: We explored sphingolipid metabolism-related genes in ESCC using scRNA-seq data from GEO and transcriptome data from TCGA. We assessed 97 genes in epithelial cells with AUCell, UCell, and singscore algorithms, followed by bulk RNA-seq and differential analysis to identify prognosis-related genes. Immune infiltration and potential immunotherapeutic strategies were also investigated, and tumor gene mutations and drug treatment strategies were analyzed. Result: Our study identified distinct gene expression patterns, highlighting ARSD, CTSA, DEGS1, and PPTQ's roles in later cellular stages. We identified seven independent prognostic genes and created a precise nomogram for prognosis. Conclusion: This study integrates single-cell and transcriptomic data to provide a reliable prognostic model associated with sphingolipid metabolism and to inform immunotherapy and pharmacotherapy for ESCC at the genetic level. The findings have significant implications for precision therapy in esophageal cancer. [ABSTRACT FROM AUTHOR]

The rapid variation of influenza challenges vaccines and treatments, which makes an urgent task to develop the high-efficiency and low-toxicity new anti-influenza virus drugs. Selenium is one of the essential trace elements for the human body that possesses a good antiviral activity. In this study, we assessed anti-influenza A virus (H1N1) activity of polyethylene glycol (PEG)-modified gray selenium nanoparticles (PEG-SeNPs) on Madin-Darby Canine Kidney (MDCK) cells in vitro. CCK-8 assay showed that PEG-SeNPs had a protective effect on H1N1-infected MDCK cells. Moreover, PEG-SeNPs significantly reduced the mRNA level of H1N1. TUNEL-DAPI test showed that DNA damage reached a high level but effectively prevented after PEG-SeNPs treatment. Meanwhile, JC-1, Annexin V-FITC and cell cycle assay demonstrated the apoptosis induced by H1N1 was reduced greatly when treated with PEG-SeNPs. Furthermore, the downregulation of p-ATM, p-ATR and P53 protein, along with the upregualation of AKT protein indicated that PEG-SeNPs could inhibit H1N1-induced cell apoptosis through reactive oxygen species (ROS)-mediated related signaling pathways. Finally, Cytokine detection demonstrated PEG-SeNPs inhibited the production of pro-inflammatory factors after infection, including IL-1β, IL-5, IL-6, and TNF-α. To sum up, PEG-SeNPs might become a new potential anti-H1N1 influenza virus drug due to its antiviral and anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

Trained immunity is a phenomenon in which brief exposure to an infectious agent or a vaccine can induce long-lasting changes in the host's immune system, enhancing protection against subsequent infections. The concept of trained immunity has a significant impact on the field of immunology and has the potential to revolutionize how we approach vaccination and infectious disease control. Investigations into trained immunity are rapidly advancing and have led to the development of new vaccines and immunotherapeutic strategies that harness the power of this phenomenon. While more investigations are needed to fully understand the mechanisms of trained immunity and its potential limitations, the prospects for its future application in clinical practice are promising. Here, we describe trained immunity as a biological process and explore the innate cues, epigenetic changes, and metabolic reprogramming activities that affect how trained immunity is induced. [ABSTRACT FROM AUTHOR]

Autophagy is a cellular homeostatic mechanism characterized by cyclic degradation. It plays an essential role in maintaining cellular quality and survival by eliminating dysfunctional cellular components. This process is pivotal in various pathophysiological processes. Benign prostatic hyperplasia (BPH) is a common urological disorder in middle-aged and elderly men. It frequently presents as lower urinary tract symptoms due to an increase in epithelial and stromal cells surrounding the prostatic urethra. The precise pathogenesis of BPH is complex. In recent years, research on autophagy in BPH has gained significant momentum, with accumulating evidence indicating its crucial role in the onset and progression of the disease. This review aims to outline the various roles of autophagy in BPH and elucidate potential therapeutic strategies targeting autophagy for managing BPH. [ABSTRACT FROM AUTHOR]

Purpose: To identify the hub genes that associated with chemo-radiotherapy sensitivity for cervical cancer and to explore the relationship between hub genes and various cellular processes and potential mechanism of cervical cancer. Methods: The gene expression data of 21 patients with CESC and the mRNA expression profiles of 296 patients with CESC were obtained from the Gene Expression Omnibus(GEO) and The Cancer Genome Atlas (TCGA) databases, respectively. The potential functions and regulatory mechanisms of differentially expressed genes (DEGs) were identified using GO and KEGG enrichment analyses. Hub genes were identified using random survival forest analysis. The relationship between hub genes and various cellular processes was comprehensively analyzed. The expression of hub genes was assessed using clinical data extracted from the Human Protein Atlas (HPA) database. Results: A total of 139 and 13 DEGs were found to be upregulated and downregulated, respectively, in CESC. The six hub genes, namely, SELP, PIM2, CCL19, SDS, NRP1, and SF3A2, were significantly correlated with immune cell infiltration, chemotherapy sensitivity, disease-related genes, and enriched signaling pathways (all p-value < 0.05). A nomogram and calibration curve were generated using the six hub genes to predict prognosis with high accuracy. A regulatory network comprising TFs (ZBTB3) and mRNAs (NRP1/PIM2/SELP) and several competitive endogenous RNA (ceRNA) networks comprising mRNAs, miRNAs, and lncRNAs were constructed. Data from HPA indicated that the protein expression of the six hub genes differed significantly between patients with CESC and healthy individuals. Conclusion: Upregulation of SELP, PIM2, CCL19, SDS, NRP1, and SF3A2 is associated with radiotherapy sensitivity and is involved in various cellular processes in CESC. These six genes may serve as biomarkers for predicting the radiotherapy response and prognosis in patients with CESC. [ABSTRACT FROM AUTHOR]

KIF18B is a key member of the kinesin-8 family, involved in regulating various physiological processes such as microtubule length, spindle assembly, and chromosome alignment. This article briefly introduces the structure and physiological functions of KIF18B, examines its role in malignant tumors, and the associated carcinogenic signaling pathways such as PI3K/AKT, Wnt/β-catenin, and mTOR pathways. Research indicates that the upregulation of KIF18B enhances tumor malignancy and resistance to radiotherapy and chemotherapy. KIF18B could become a new target for anticancer drugs, offering significant potential for the treatment of malignant tumors and reducing chemotherapy resistance. [ABSTRACT FROM AUTHOR]

Infertility is a global phenomenon that impacts people of both the male and the female sex; it is related to multiple factors affecting an individual's overall systemic health. Recently, investigators have been using mesenchymal stem cell (MSC) therapy for female-fertility-related disorders such as polycystic ovarian syndrome (PCOS), premature ovarian failure (POF), endometriosis, preeclampsia, and Asherman syndrome (AS). Studies have shown promising results, indicating that MSCs can enhance ovarian function and restore fertility for affected individuals. Due to their regenerative effects and their participation in several paracrine pathways, MSCs can improve the fertility outcome. However, their beneficial effects are dependent on the methodologies and materials used from isolation to reimplantation. In this review, we provide an overview of the protocols and methods used in applications of MSCs. Moreover, we summarize the findings of published preclinical studies on infertility treatments and discuss the multiple properties of these studies, depending on the isolation source of the MSCs used. [ABSTRACT FROM AUTHOR]

Overexpression of HER2 occurs in 25% of breast cancer. Targeting HER2 has proven to be an effective therapeutic strategy for HER2-positive breast cancer. While trastuzumab is the most commonly used HER2 targeting agent, which has significantly improved outcomes, the overall response rate is low. To develop novel therapies to boost trastuzumab efficacy, it is critical to identify the mechanisms underlying trastuzumab action and resistance. We recently showed that the inhibition of breast cancer cell growth by trastuzumab is not through the inhibition of HER2 canonical signaling. Here we report the identification of a novel non-canonical HER2 signaling pathway and its interference by trastuzumab. We showed that HER2 signaled through a non-canonical pathway, regulated intramembrane proteolysis (RIP). In this pathway, HER2 is first cleaved by metalloprotease ADAM10 to produce an extracellular domain (ECD) that is released and the p95HER2 that contains the transmembrane domain (TM) and intracellular domain (ICD). p95HER2, if further cleaved by an intramembrane protease, γ-secretase, produced a soluble ICD p75HER2 with nuclear localization signal (NLS). p75HER2 is phosphorylated and translocated to the nucleus. Nuclear p75HER2 promotes cell proliferation. Trastuzumab targets this non-canonical HER2 pathway via inhibition of the proteolytic cleavage of HER2 by both ADAM10 and γ-secretase. However, p75HER2 pathway also confers resistance to trastuzumab once aberrantly activated. Combination of trastuzumab with ADAM10 and γ-secretase inhibitors completely blocks p75HER2 production in both BT474 and SKBR3 cells. We concluded that HER2 signals through the RIP signaling pathway that promotes cell proliferation and is targeted by trastuzumab. The aberrant HER2 RIP signaling confers resistance to trastuzumab that could be overcome by the application of inhibitors to ADAM10 and γ-secretase. [ABSTRACT FROM AUTHOR]

BACKGROUND: Okra contains flavonoids and vitamin C as antioxidants and it contains polysaccharides as immunomodulators. Flavonoids regulate the inflammatory response in mice and may be related to gut microbiota. This study therefore aimed to investigate the impact of okra extract (OE) on inflammation in mice and to elucidate its underlying mechanism. METHOD: Forty male Kunming (KM) mice were categorized into four groups: the control (CON) group, the lipopolysaccharide stimulation (LPS) group, the 5 mg mL−1 OE intervention (LPS + OE) group, and the 5 mg mL−1 OE supplementation plus mixed antibiotics (LPS + OE + ABX) group. RESULTS: The results showed that, compared with the OE group, the expression of inflammatory signaling pathway genes was upregulated and gut barrier genes were inhibited in the OE + ABX group. The Fxr receptor was activated and the abundance of Akkermansia was increased after OE supplementation, whereas the effect was reversed in the OE + ABX group. Meanwhile, Fxr was correlated positively with Akkermansia. CONCLUSION: The OE supplementation alleviated the inflammatory response in mice under LPS stimulation, accompanied by changes in gut microbiota and bile acid receptors, whereas the addition of antibiotics caused a disturbance to the gut microbiota in the OE group, thus reducing the effect of OE in alleviating the inflammatory response. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Introduction: Spermatogenesis is the primary process of sperm production occuring in seminiferous tubules. Spermatogonial stem cells (SSCs) have the ability for self-renewal, differentiation, and the transmission of genetic information to subsequent generations. KLF4 and POU5F1 are transcription factors expressed in a wide range of tissues and play key roles in such processes as apoptosis, differentiation, proliferation, and cellular development. The present study aimed to assess the expression levels of KLF4 and POU5F1 genes in mouse embryonic stem cells (mESCs), spermatogonial stem cells (SSCs), embryonic-like stem cells (ES-like), and testicular cells, and identify the signaling pathways associated with them in the process of spermatogenesis. Materials & Methods: In this experimental study, spermatogonial cells were extracted from mouse testes using enzymatic digestion method and cultured in GSC medium containing FGF, EGF, and GDNF. Thereafter, the expression of KLF4 and POU5F1 genes was examined in mESCs, SSCs, ES-like, and testicular cells was investigated using immunocytochemistry, immunohistochemistry, and reverse transcription-polymerase chain reaction methods, and protein-protein interactions and signaling pathways were evaluated using bioinformatics methods. Results: The KLF4 and POU5F1 genes exhibited positive expression in ES-like cells and testicular cells. The assessment of KLF4 mRNA and POU5F1 mRNA expression levels demonstrated that KLF4 expression is higher in mESCs and ES-like cells compared to other cells, while POU5F1 expression is higher in SSCs. Both KLF4 and POU5F1 are considered essential and powerful genes that share a common class and function. Conclusion: The findings of this study indicated that KLF4 and POU5F1 play crucial roles in the proper development of sperm and are present in various types of cells, including mESCs, SSCs, ES-like cells, and testicular cells. These factors are key components of sexual stem cells and contribute to stem cell proliferation, making them potential diagnostic markers for these cell lines. [ABSTRACT FROM AUTHOR]

Gastric cancers (GCs) are among the most common and fatal malignancies in the world. Despite our increasing understanding of the molecular mechanisms underlying GC, further biomarkers are still needed for more in-depth examination, focused prognosis, and treatment. GC is one among the long non-coding RNAs, or lncRNAs, that have emerged as key regulators of the pathophysiology of cancer. This comprehensive review focuses on the diverse functions of long noncoding RNAs (lncRNAs) in the development of GC and their interactions with important intracellular signaling pathways. LncRNAs affect GC-related carcinogenic signaling cascades including pathways for EGFR, PI3K/AKT/mTOR, p53, Wnt/β-catenin, JAK/STAT, Hedgehog, NF-κB, and hypoxia-inducible factor. Dysregulated long non-coding RNA (lncRNA) expression has been associated with multiple characteristics of cancer, such as extended growth, apoptosis resistance, enhanced invasion and metastasis, angiogenesis, and therapy resistance. For instance, lncRNAs such as HOTAIR, MALAT1, and H19 promote the development of GC via altering these pathways. Beyond their main roles, GC lncRNAs exhibit potential as diagnostic and prognostic biomarkers. The overview discusses CRISPR/Cas9 genome-modifying methods, antisense oligonucleotides, small molecules, and RNA interference as potential therapeutic approaches to regulate the expression of long noncoding RNAs (lncRNAs). An in-depth discussion of the intricate functions that lncRNAs play in the development of the majority of stomach malignancies is provided in this review. It provides the groundwork for future translational research in lncRNA-based whole processes toward GC by highlighting their carcinogenic effects, regulatory roles in significant signaling cascades, and practical scientific uses as biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

This study explored the effect of Eupatilin on postmenopausal osteoporosis and explored the mechanisms associated with miR-211-5p. First, the rats were given intragastric administration of Eupatilin every day and subcutaneously injected once a week with oligonucleotides or plasmids that interfered with the expression of miR-211-5p or Janus kinase 2 (JAK2). After 4 weeks, a rat model of osteoporosis was established. Then, serum alkaline phosphatase, calcium and phosphorus levels were detected, as well as femur bone mineral density and biomechanical parameters. HE staining and Masson staining were applied for detecting the pathological condition of femur while immunohistochemical staining was for detecting the positive expression of osteocalcin. In addition, MC3T3-E1 cells were transfected with plasmid vectors interfering with miR-211-5p or JAK2, and cell viability, lactate dehydrogenase cytotoxicity, and cell mineralization were subsequently examined. The relationship between miR-211-5p and JAK2/Signal transducer and activator of transcription 3 (STAT3) pathway was analyzed, and the targeting of miR-211-5p and JAK2 was also verified. The experimental results found that Eupatilin improved the pathological conditions of osteoporotic rats by promoting the proliferation and mineralization of osteoblasts. miR-211-5p was down-regulated and JAK2/STAT3 were up-regulated in osteoporotic rats. Upregulation of miR-211-5p further improved the pathological conditions of osteoporotic rats based on Eupatilin treatment. MiR-211-5p inhibited the JAK2/STAT3 pathway. Upregulation of JAK2 reversed the effects of elevated miR-211-5p on osteoporotic rats. Overall, Eupatilin attenuates postmenopausal osteoporosis through elevating miR-211-5p and repressing JAK2/STAT3 pathway. [ABSTRACT FROM AUTHOR]

Main conclusion: Our data link the miR165/166- and miR160-mediated regulatory modules to ROS and seed formation. Trade-offs of seed size, weight, and number probably require control of the expression of miR165/166 by miR160, modulation of ROS metabolism by miR165/166, and miR160 abundance by ROS-induced oxidative modifications The cycle of plant life and its yield productivity depends fundamentally on the establishment of the trade-offs of seed size, weight, and number. For annual plants, seed number should simply be a positive function of vegetative biomass and a negative function of seed size and/or weight. However, extensive natural variation within species is observed for these traits, for which an optimal solution is environmentally dependent. Understanding the miRNA-mediated post-transcriptional regulation of gene expression determining seed phenotype and number is crucial from both an evolutionary and applied perspective. Although extensive research has concentrated on the individual roles of miRNAs in plant life, fewer studies have centred on their functional interactions, hence this study aimed to examine whether the module of miR165/miR166 and/or miR160 interactions is involved in forming Arabidopsis thaliana seeds, and/or has an impact on their features. Considering that reactive oxygen species (ROS) are among key players in seed-related processes, it was also intriguing to verify if the mechanism of action of these miRNAs is associated with the ROS pathway. The plant material used in this study consisted of flower buds, green siliques, and freshly harvested seeds, of wild type (WT), and STTM165/166 and STTM160 × 165/166 mutants of A. thaliana plants which are powerful tools for functional analysis of miRNAs in plants. The novel results obtained during physiological phenotyping together with two-tailed qRT-PCR analysis of mature miR165, miR166, miR160, and spectrofluorimetric measurement of apoplastic hydrogen peroxide (H2O2) for the first time revealed that interaction between miR165/miR166 and miR160 may regulate seed size, weight and number in ROS-dependent manner. [ABSTRACT FROM AUTHOR]

Abstract Glioblastoma multiforme (GBM) is the most common harmful high-grade brain tumor with high mortality and low survival rate. Importantly, besides routine diagnostic and therapeutic methods, modern and useful practical techniques are urgently needed for this serious malignancy. Correspondingly, the translational medicine focusing on genetic and epigenetic profiles of glioblastoma, as well as the immune framework and brain microenvironment, based on these challenging findings, indicates that key clinical interventions include immunotherapy, such as immunoassay, oncolytic viral therapy, and chimeric antigen receptor T (CAR T) cell therapy, which are of great importance in both diagnosis and therapy. Relatively, vaccine therapy reflects the untapped confidence to enhance GBM outcomes. Ongoing advances in immunotherapy, which utilizes different methods to regenerate or modify the resistant body for cancer therapy, have revealed serious results with many different problems and difficulties for patients. Safe checkpoint inhibitors, adoptive cellular treatment, cellular and peptide antibodies, and other innovations give researchers an endless cluster of instruments to plan profoundly in personalized medicine and the potential for combination techniques. In this way, antibodies that block immune checkpoints, particularly those that target the program death 1 (PD-1)/PD-1 (PD-L1) ligand pathway, have improved prognosis in a wide range of diseases. However, its use in combination with chemotherapy, radiation therapy, or monotherapy is ineffective in treating GBM. The purpose of this review is to provide an up-to-date overview of the translational elements concentrating on the immunotherapeutic field of GBM alongside describing the molecular mechanism involved in GBM and related signaling pathways, presenting both historical perspectives and future directions underlying basic and clinical practice. Graphical Abstract

Abstract The mechanisms underlying myopia pathogenesis are not well understood. Using publicly-available human and animal datasets, we expound on the roles of known, implicated proteins, and new myopia-related signaling pathways were hypothesized. Proteins identified from human serum or ocular fluids, and from ocular tissues in myopic animal models, were uploaded and analyzed with the QIAGEN Ingenuity Pathway Analysis (IPA) software (March 2023). With each IPA database update, more potentially-relevant proteins and signaling pathways previously unavailable during data acquisition are added, allowing extraction of novel conclusions from existing data. Canonical pathway analysis was used to analyze these data and calculate an IPA activation z-score—which indicates not only whether an association is significant, but also whether the pathway is likely activated or inhibited. Cellular immune response and cytokine signaling were frequently found to be affected in both human and animal myopia studies. Analysis of two publicly-available proteomic datasets highlighted a potential role of the innate immune system and inflammation in myopia development, detailing specific signaling pathways involved such as Granzyme A (GzmA) and S100 family signaling in the retina, and activation of myofibroblast trans-differentiation in the sclera. This perspective in myopia research may facilitate development of more effective and targeted therapeutic agents.

In the field of sports medicine, repair surgery for anterior cruciate ligament (ACL) and rotator cuff (RC) injuries are remarkably common. Despite the availability of relatively effective treatment modalities, outcomes often fall short of expectations. This comprehensive review aims to thoroughly examine current strategies employed to promote tendon‐bone healing and analyze pertinent preclinical and clinical research. Amidst ongoing investigations, tendon‐derived stem cells (TDSCs), which have comparatively limited prior exploration, have garnered increasing attention in the context of tendon‐bone healing, emerging as a promising cell type for regenerative therapies. This review article delves into the potential of combining TDSCs with tissue engineering methods, with ACL reconstruction as the main focus. It comprehensively reviews relevant research on ACL and RC healing to address the issues of graft healing and bone tunnel integration. To optimize tendon‐bone healing outcomes, our emphasis lies in not only reconstructing the original microstructure of the tendon‐bone interface but also achieving proper bone tunnel integration, encompassing both cartilage and bone formation. In this endeavor, we thoroughly analyze the transcriptional and molecular regulatory variables governing TDSCs differentiation, incorporating a retrospective analysis utilizing single‐cell sequencing, with the aim of unearthing relevant signaling pathways and processes. By presenting a novel strategy rooted in TDSCs‐driven osteogenic and chondrogenic differentiation for tendon‐bone healing, this study paves the way for potential future research avenues and promising therapeutic applications. It is anticipated that the findings herein will contribute to advancing the field of tendon‐bone healing and foster the exploration of TDSCs as a viable option for regenerative therapies in the future.

Abstract Background Esophageal squamous cell carcinoma (ESCC) stands as a significant global health challenge, distinguished by its aggressive progression from the esophageal epithelium. Central to this malignancy is sphingolipid metabolism, a critical pathway that governs key cellular processes, including apoptosis and immune regulation, thereby influencing tumor behavior. The advent of single-cell and transcriptome sequencing technologies has catalyzed significant advancements in oncology research, offering unprecedented insights into the molecular underpinnings of cancer. Methods We explored sphingolipid metabolism-related genes in ESCC using scRNA-seq data from GEO and transcriptome data from TCGA. We assessed 97 genes in epithelial cells with AUCell, UCell, and singscore algorithms, followed by bulk RNA-seq and differential analysis to identify prognosis-related genes. Immune infiltration and potential immunotherapeutic strategies were also investigated, and tumor gene mutations and drug treatment strategies were analyzed. Result Our study identified distinct gene expression patterns, highlighting ARSD, CTSA, DEGS1, and PPTQ's roles in later cellular stages. We identified seven independent prognostic genes and created a precise nomogram for prognosis. Conclusion This study integrates single-cell and transcriptomic data to provide a reliable prognostic model associated with sphingolipid metabolism and to inform immunotherapy and pharmacotherapy for ESCC at the genetic level. The findings have significant implications for precision therapy in esophageal cancer.

Abstract Trained immunity is a phenomenon in which brief exposure to an infectious agent or a vaccine can induce long-lasting changes in the host's immune system, enhancing protection against subsequent infections. The concept of trained immunity has a significant impact on the field of immunology and has the potential to revolutionize how we approach vaccination and infectious disease control. Investigations into trained immunity are rapidly advancing and have led to the development of new vaccines and immunotherapeutic strategies that harness the power of this phenomenon. While more investigations are needed to fully understand the mechanisms of trained immunity and its potential limitations, the prospects for its future application in clinical practice are promising. Here, we describe trained immunity as a biological process and explore the innate cues, epigenetic changes, and metabolic reprogramming activities that affect how trained immunity is induced.

Abstract The rapid variation of influenza challenges vaccines and treatments, which makes an urgent task to develop the high-efficiency and low-toxicity new anti-influenza virus drugs. Selenium is one of the essential trace elements for the human body that possesses a good antiviral activity. In this study, we assessed anti-influenza A virus (H1N1) activity of polyethylene glycol (PEG)-modified gray selenium nanoparticles (PEG-SeNPs) on Madin-Darby Canine Kidney (MDCK) cells in vitro. CCK-8 assay showed that PEG-SeNPs had a protective effect on H1N1-infected MDCK cells. Moreover, PEG-SeNPs significantly reduced the mRNA level of H1N1. TUNEL-DAPI test showed that DNA damage reached a high level but effectively prevented after PEG-SeNPs treatment. Meanwhile, JC-1, Annexin V-FITC and cell cycle assay demonstrated the apoptosis induced by H1N1 was reduced greatly when treated with PEG-SeNPs. Furthermore, the downregulation of p-ATM, p-ATR and P53 protein, along with the upregualation of AKT protein indicated that PEG-SeNPs could inhibit H1N1-induced cell apoptosis through reactive oxygen species (ROS)-mediated related signaling pathways. Finally, Cytokine detection demonstrated PEG-SeNPs inhibited the production of pro-inflammatory factors after infection, including IL-1β, IL-5, IL-6, and TNF-α. To sum up, PEG-SeNPs might become a new potential anti-H1N1 influenza virus drug due to its antiviral and anti-inflammatory activity.

Abstract Purpose To identify the hub genes that associated with chemo-radiotherapy sensitivity for cervical cancer and to explore the relationship between hub genes and various cellular processes and potential mechanism of cervical cancer. Methods The gene expression data of 21 patients with CESC and the mRNA expression profiles of 296 patients with CESC were obtained from the Gene Expression Omnibus(GEO) and The Cancer Genome Atlas (TCGA) databases, respectively. The potential functions and regulatory mechanisms of differentially expressed genes (DEGs) were identified using GO and KEGG enrichment analyses. Hub genes were identified using random survival forest analysis. The relationship between hub genes and various cellular processes was comprehensively analyzed. The expression of hub genes was assessed using clinical data extracted from the Human Protein Atlas (HPA) database. Results A total of 139 and 13 DEGs were found to be upregulated and downregulated, respectively, in CESC. The six hub genes, namely, SELP, PIM2, CCL19, SDS, NRP1, and SF3A2, were significantly correlated with immune cell infiltration, chemotherapy sensitivity, disease-related genes, and enriched signaling pathways (all p-value

Abstract KIF18B is a key member of the kinesin-8 family, involved in regulating various physiological processes such as microtubule length, spindle assembly, and chromosome alignment. This article briefly introduces the structure and physiological functions of KIF18B, examines its role in malignant tumors, and the associated carcinogenic signaling pathways such as PI3K/AKT, Wnt/β-catenin, and mTOR pathways. Research indicates that the upregulation of KIF18B enhances tumor malignancy and resistance to radiotherapy and chemotherapy. KIF18B could become a new target for anticancer drugs, offering significant potential for the treatment of malignant tumors and reducing chemotherapy resistance.