INTRODUCTION: Atherosclerosis, a chronic inflammatory disease driven by lipid metabolism dysregulation and vascular dysfunction, is a major contributor to cardiovascular diseases (CVDs), which is the leading cause of glo...INTRODUCTION: Atherosclerosis, a chronic inflammatory disease driven by lipid metabolism dysregulation and vascular dysfunction, is a major contributor to cardiovascular diseases (CVDs), which is the leading cause of global mortality. The present study was undertaken to explore the anti-atherosclerosis potential (targeting DPP-IV, ETB, and PPAR-α) of bioactive compounds from Ginkgo biloba L.; the corresponding commercially available drugs, viz. Evogliptin, Bosentan, and Bezafibrate were taken as controls. METHODS: Swiss ADME and Protox-II were utilized to evaluate the safety and applicability of G. biloba compounds. MGL Tools and AutoDock Vina were used for molecular docking, followed by analysis with Discovery Studio Biovia. MD simulation was performed for chosen complexes, and the resulting compound was examined for PPI, GO, and KEGG network enrichment using the Shiny GO server. RESULTS: Eight compounds were shortlisted by using SwissADME and Protox-II servers, followed by molecular docking studies with AutoDock Vina. Six compounds exhibited stronger binding affinities against DPP-IV compared to Evogliptin (-7.1 kcal/mol), five outperforming Bosentan (- 7.5 kcal/mol) against ETB, and six better than Bezafibrate (-7.5 kcal/mol) against PPAR-α. Postdocking analysis identified Isoginkgetin for both DPP-IV and ETB receptors, while Kaempferol for PPAR-α. MD simulation studies of Isoginkgetin-DPP-IV, Isoginkgetin-ETB, and Kaempferol- PPAR-α resulted in the ETB-Isoginkgetin complex with the most favourable binding stability, rapid equilibration, and consistent hydrogen bonding. Network pharmacology analysis further highlighted Isoginkgetin's ability to modulate key proteins (CYP19A1, ESR2, GSK3B, XDH, PTGS2) associated with crucial CVD-related pathways. CONCLUSION: The findings highlight the multi-target therapeutic potential of Isoginkgetin in mitigating the initiation and progression of atherosclerosis.
INTRODUCTION: Gene transfection techniques have potential therapeutic value in reducing the inflammatory response in atherosclerosis. Atherosclerosis is a chronic inflammatory disease. Its pathological process involves m...INTRODUCTION: Gene transfection techniques have potential therapeutic value in reducing the inflammatory response in atherosclerosis. Atherosclerosis is a chronic inflammatory disease. Its pathological process involves multiple types of cells and signaling pathways. METHODS: In recent years, researchers have used gene transfection techniques to introduce specific genes into vascular or immune cells in order to inhibit inflammatory responses, stabilize plaques, and slow down the process of atherosclerosis. Research progress has shown that gene transfection can exert anti-inflammatory effects through various mechanisms. IL-10 transfection suppresses atherosclerosis by activating the STAT3 pathway, reducing TNF-α and IL-6 expression in macrophages. Conversely, eNOS transfection enhances nitric oxide bioavailability, inhibiting endothelial cell adhesion molecule expression (e.g., VCAM-1) and monocyte recruitment. RESULTS: Other studies have regulated the expression of inflammation-related genes by transfecting miRNA (tiny RNA), thus inhibiting the inflammatory response of atherosclerosis. DISCUSSION: Despite preclinical efficacy, clinical translation is hindered by suboptimal vector tropism (e.g., viral vectors exhibit off-target hepatotoxicity) and immune-mediated clearance of non-viral vectors (e.g., liposomes trigger complement activation). Long-term risks of insertional mutagenesis (retroviral vectors) and epigenetic silencing of transgenes further limit durability. CONCLUSION: This paper discusses the role and mechanism of gene transfection in reducing the inflammatory response in atherosclerosis.
INTRODUCTION: Ganoderma lucidum is considered a medicinal mushroom, as it primarily improves gut health by modulating the gut microbiota. As an abundant source of bioactive metabolites, antioxidants, and industrial enzym...INTRODUCTION: Ganoderma lucidum is considered a medicinal mushroom, as it primarily improves gut health by modulating the gut microbiota. As an abundant source of bioactive metabolites, antioxidants, and industrial enzymes, mushrooms make significant contributions to functional foods, nutrition, and pharmaceuticals. Polysaccharides derived from G. lucidum exhibit prebiotic potential, promoting the growth and activity of beneficial gut microorganisms. METHODS: This review examines the impact of white rot basidiomycetes metabolites on colorectal cancer treatment. We have compiled and analyzed data from PubMed, Google Scholar, and ResearchGate, presenting a comprehensive report with a table for clear understanding. RESULTS: Evidence from in vivo and in vitro studies demonstrates that G. lucidum has potential as a gastrointestinal cancer inhibitor by inducing pro-apoptosis, autophagy, G0/G1 cell cycle arrest, and immunomodulation. DISCUSSION: Bioactive metabolites and polysaccharides have prebiotic potential, enhancing the growth and activity of beneficial gut microorganisms that may lower the risk of gastrointestinal cancers by modifying gut bacteria. The prebiotic properties may boost immunity, reduce inflammation, and strengthen intestinal barrier integrity. CONCLUSION: The current review explores the therapeutic potential of G. lucidum and other medicinal mushrooms as dietary supplements, focusing on their impact on the gut microbiome and gastrointestinal cancer.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a global health concern. In recent years, the gut microbiota, often referred to as the body's "second genome," has been recognized as playin...Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a global health concern. In recent years, the gut microbiota, often referred to as the body's "second genome," has been recognized as playing a crucial role in the pathogenesis of MASLD. PubMed was searched for articles published in the last decade using keywords like "MASLD," "NAFLD," "gut microbiota," "FXR," and "Trace elements." The progress of the latest NAFLD clinical trial was also reviewed from the Chinese Clinical Trial Registry, organized by clinical phase. In the development of MASLD, the gut microbiota not only participates in regulating host gene expression but also exerts a core influence on immune function and affects the liver's reparative capabilities. Furthermore, the metabolic products of the gut microbiota are involved in the occurrence and development of liver diseases through the gut-liver axis. A diet high in fat can trigger metabolic inflammation, changes in gut microbiota, and abnormalities in metabolic products, all of which may initiate inflammatory responses. The emerging strategies for treating MASLD are surprising. Clinical trial information for chemical drugs was obtained from the Chinese platform for registration and disclosure of drug clinical trials, and it was found that in the current drug development, some drugs have advanced to Phase III clinical trials. The diversity of gut bacteria among individuals and the impact of microbial composition beyond bacteria should not be overlooked. Whether drug therapy combined with dietary patterns is more effective than monotherapy remains to be seen.
INTRODUCTION: Generalized anxiety disorder (GAD) is a prevalent and intricate mental disorder that significantly impairs the quality of life of patients. Currently, the exact etiology of GAD remains incompletely understo...INTRODUCTION: Generalized anxiety disorder (GAD) is a prevalent and intricate mental disorder that significantly impairs the quality of life of patients. Currently, the exact etiology of GAD remains incompletely understood. Consequently, the discovery of novel drug targets for GAD is highly important. METHODS: We obtained cis-eQTL data of druggable genes from the eQTLGen Consortium as the exposure data and GWAS data of GAD from the FinnGen Database as the outcome. The impact of druggable genes on GAD was simulated through Mendelian randomization analysis. Subsequently, a colocalization analysis was conducted to calculate the probability of shared pathogenic variants between the cis-eQTLs of druggable genes and GAD. To further validate our findings, a summary data-based Mendelian randomization (SMR) analysis was carried out. RESULTS: Mendelian randomization (MR) analysis identified 24 druggable genes with potential causal relationships, among which genetically predicted increased KDM5A levels were associated with a higher risk of GAD (OR=1.0991, 95% CI: 1.0021-1.2056, P=0.0451), suggesting a potential role of KDM5A gene expression in the pathogenesis of GAD. The GAD and KDM5A genes might share a causal variant. The SMR further verified the accuracy of the KDM5A gene. DISCUSSION: MR analysis identified KDM5A as a promising therapeutic target for GAD, with additional potential from genes, like MERTK and PPT1. However, the effectiveness of the relevant drug targets requires further validation. CONCLUSION: This study suggested that the KDM5A gene might be a potential therapeutic target for treating GAD, providing a direction for future drug development in GAD patients.
INTRODUCTION: This study aimed to develop a local drug delivery system using pterostilbene (PTS) flexible nanoliposomes (FNL) to overcome its limitations, such as poor water solubility and instability under light and oxy...INTRODUCTION: This study aimed to develop a local drug delivery system using pterostilbene (PTS) flexible nanoliposomes (FNL) to overcome its limitations, such as poor water solubility and instability under light and oxygen. The research focused on optimizing deformability and transdermal delivery using dipotassium glycyrrhizinate and a single-chain surfactant as membrane softeners. METHODS: The encapsulation process and formulation of PTS FNL were systematically optimized through single-factor and orthogonal experiments. The physicochemical properties, stability, and transdermal performance of the optimized FNL were evaluated using dynamic light scattering, transmission electron microscopy (TEM), Turbiscan stability analysis, and in vitro/in vivo permeation studies. RESULTS: The optimized PTS FNL exhibited high encapsulation efficiency (96.49 ± 0.7%), a particle size of (60.11 ± 0.54 nm), PDI (0.237), a zeta potential of (-10.16 ± 0.54 mV), and good stability at 4°C and 25°C for three months. TEM confirmed spherical morphology, while in vitro studies demonstrated superior skin retention and prolonged permeation compared to PTS nanoliposomes (NL) and GTCC solutions. In vivo tests on human volunteers revealed that 0.4% PTS FNL cream significantly improved skin elasticity and chromaticity over 28 days without adverse effects. DISCUSSION: The enhanced deformability of PTS FNL contributed to its improved transdermal delivery, making it a promising candidate for cosmetic applications. The study highlights the effectiveness of membrane softeners in optimizing liposomal formulations, though long-term stability under varied conditions warrants further investigation. CONCLUSION: The developed PTS FNL system significantly enhances skin permeation and stability, demonstrating great potential for cosmetic use in anti-aging and skin-brightening formulations. This approach provides a viable strategy for improving the delivery of poorly soluble active ingredients.
INTRODUCTION: The current pharmaceutical industry has increasingly adopted artificial intelligence (AI), integrating it across the entire industrial chain. While AI improves efficiency and reduces costs, it also faces ch...INTRODUCTION: The current pharmaceutical industry has increasingly adopted artificial intelligence (AI), integrating it across the entire industrial chain. While AI improves efficiency and reduces costs, it also faces challenges. This study explores both the technological evolution and contemporary innovation hotspots of AI in pharmacy. METHODS: Methods: This study adopts a fusion analysis of multi-source data, constructing a bidimensional analytical framework based on patented inventions (1990-2024) and research articles (2020-2024) as research objects. The study applies the Latent Dirichlet Allocation (LDA) topic model to analyze the evolution of patent topics and employs CiteSpace to construct keyword knowledge graphs from research articles. By integrating patent and article data to define technical labels, the study identifies research hotspots from the perspective of the pharmaceutical life cycle, enabling cross-validation from both scientific and technical dimensions. RESULTS: The number of AI-related patents in the pharmaceutical field has grown rapidly over the past five years. Technological topics exhibit a distinct evolutionary trend. Research hotspots span the entire pharmaceutical life cycle, from drug development to clinical delivery. Additionally, potential directions for future technological development have been identified. DISCUSSION: Research hotspots in the application of AI in pharmaceuticals include target identification, virtual screening, drug delivery, clinical trials, and pharmacovigilance. Precision medicine and explainable AI (XAI)-driven pharmacy modeling are expected to emerge as key directions for future technological development. CONCLUSION: AI has already reshaped the pharmaceutical industry through applications across all stages of the pharmaceutical life cycle. It is poised to attract growing research attention and drive innovative applications in the years ahead.
INTRODUCTION: Breast cancer and depression are both serious diseases that significantly impact women's physical health. The molecular mechanisms underlying their comorbidity remain elusive. This study aims to identify ke...INTRODUCTION: Breast cancer and depression are both serious diseases that significantly impact women's physical health. The molecular mechanisms underlying their comorbidity remain elusive. This study aims to identify key genes and the molecular mechanisms associated with the comorbidity of breast cancer and depression using bioinformatics analysis methods. METHODS: Data files for breast cancer and depression were obtained from the TCGA database and the NCBI GEO public database, respectively. The random survival forest algorithm was utilized to identify key genes co-expressed in both breast cancer and depression. Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA) were employed to predict biological functions and signaling pathway differences influenced by these key genes in both diseases. The R package "RcisTarget" was utilized to predict molecular transcriptional regulatory relationships of the key genes. The CIBERSORT algorithm was applied for immune function correlation analysis of comorbid key genes. The differential expression of key genes was validated in breast cancer tissue and depression blood by qPCR. RESULTS: The TCGA database provided original mRNA expression data for breast cancer, while the NCBI GEO public database offered the dataset GSE58430 related to depression. Through functional enrichment and random survival forest analysis, CCNB1, MLPH, PSME1, and RACGAP1 were identified as four key genes. The specific signaling pathways、strong correlation with immune cells, and the potential molecular mechanisms of these four key genes were analyzed in breast cancer and depression. Their expression levels were verified in blood and tissue samples. DISCUSSION: This study discovered the comorbidity genes of breast cancer and depression, providing a certain direction for the prevention and treatment of these two diseases. At present, breast cancer and depression are serious diseases that affect women's physical and mental health. The connection between the two is not very clear. This study proposes that these two diseases have comorbidity genes. The risk population of the disease can be detected early through testing, so as to intervene early and improve prognosis. However, the sample size of the database analyzed in this study was relatively small, and the sample size and methods for clinical validation were insufficient. Further in-depth research will be conducted in the future. CONCLUSION: This study identified CCNB1, MLPH, PSME1, and RACGAP1 as key genes associated with the comorbidity of breast cancer and depression.
The rising prevalence of Multidrug-Resistant (MDR) Acinetobacter baumannii, particularly in hospital environments, has become a global health concern due to its capacity to cause severe infections and its resistance to c...The rising prevalence of Multidrug-Resistant (MDR) Acinetobacter baumannii, particularly in hospital environments, has become a global health concern due to its capacity to cause severe infections and its resistance to conventional antibiotics. This article reviews the detection methods for the resistant genes, focusing on carbapenem-resistant A. baumannii (CRAB), where various phenotypic, molecular, and advanced diagnostic technologies, with particular attention to Fluorescence Resonance Energy Transfer (FRET) assays based on Quantum Dots (QDs) and Graphene Oxide (GO), are reviewed. These nanoparticle-based FRET assays show promising potential for rapid, sensitive, and multiplex detection of antibiotic resistance genes, offering significant improvements over traditional methods. In particular, integrating QDs and GO as donor-acceptor pairs in FRET allows real-time detection and high specificity of a key determinant of carbapenem resistance in A. baumannii. Adopting these advanced diagnostic tools could revolutionise infection control and management, providing timely and accurate diagnostics that are crucial in clinical settings.
INTRODUCTION: FLRCC is a rare renal carcinoma subtype caused by FH mutations, categorized into hereditary (germline mutations) and sporadic (somatic mutations) forms. These forms are clinically and pathologically similar...INTRODUCTION: FLRCC is a rare renal carcinoma subtype caused by FH mutations, categorized into hereditary (germline mutations) and sporadic (somatic mutations) forms. These forms are clinically and pathologically similar, complicating differentiation without genetic testing. The aim of this study is to investigate the clinicopathological and molecular genetic differences between hereditary and sporadic fumarate hydratase (FH)-deficient leiomyomatosis and renal cell carcinoma (FLRCC) to improve diagnostic accuracy and clinical management. METHOD: A retrospective analysis of 14 FLRCC patients was conducted(May 2020-August 2023). Immunohistochemistry (FH, 2SC, p16), HE staining, and next-generation sequencing (NGS) of tumor tissues and blood leukocytes were performed. RESULTS: The 14 patients with FH-deficient leiomyoma were 25-54 years old, with a mean age of 36.21 ± 8.16. 78.5% (11/14) had clinical symptoms and multiple, large-sized fibroids (median maximum volume was 75 mm). Patients with leiomyoma and FH deficiency were divided into hereditary and sporadic FLRCC based on FH gene sequencing. Patients with HLRCC had an earlier onset, and the serum tumor marker CA125 was more significant. Moreover, tumor tissues from patients with hereditary and sporadic FH-deficient LRCC differed in immunohistochemical and HE staining characteristics, including more positive p16 and greater susceptibility to invasion and metastasis in patients with HLRCC, as well as malignant proliferation in patients with sporadic FH-deficient LRCC. DISCUSSION: Although limited by sample size, our preliminary findings indicated subtle differences in the age of onset, as well as immunohistochemical and histopathological features of hereditary and sporadic FH-deficient LRCC, facilitating the understanding and clinical diagnosis of FLRCC. CONCLUSION: In clinical diagnosis, all information should be fully integrated, and a comprehensive judgment should be made to make a correct pathological diagnosis and provide targeted treatment for patients with an FH gene mutation.
A defining characteristic of tumor cells is their preferential reliance on aerobic glycolysis for lactate production, even under oxygen-sufficient conditions - the well-known Warburg effect. Recent advances have revealed...A defining characteristic of tumor cells is their preferential reliance on aerobic glycolysis for lactate production, even under oxygen-sufficient conditions - the well-known Warburg effect. Recent advances have revealed lactate to be far more than a metabolic waste product, establishing its role as a versatile signaling molecule with multiple functions in cancer progression. Acting simultaneously as a pro-inflammatory mediator, hypoxia surrogate, tumor burden indicator, and metastasis predictor, lactate exerts profound and wide-ranging effects on immune cell function within the tumor microenvironment (TME). The immunomodulatory properties of lactate create a profoundly immunosuppressive milieu that facilitates tumor immune evasion. It achieves this through coordinated suppression of antitumor immune effectors, including natural killer cells, dendritic cells, and cytotoxic T lymphocytes, while simultaneously enhancing the immunosuppressive functions of regulatory T cells, tumorassociated macrophages, and endothelial cells. This dual mechanism of action promotes tumor progression and metastasis through multiple pathways. The groundbreaking discovery of lysine lactylation (Kla) has further expanded our understanding of lactate's biological roles, revealing a direct molecular connection between tumor metabolism and epigenetic regulation. This review provides a comprehensive synthesis of current knowledge regarding lactate-mediated immune modulation in the TME, examines recent advances in our understanding of lactate-dependent tumor biology, and evaluates emerging therapeutic strategies that target lactate metabolism. By integrating these perspectives, we aim to offer both fundamental insights and practical guidance for the development of novel anticancer therapies that target metabolic-epigenetic crosstalk.
INTRODUCTION: This study investigated the role and potential mechanisms of discoidin domain receptor 1 (DDR1) in colon fibrogenesis. METHODS: We employed the DSS-induced chronic colitis and fibrosis model to evaluate the...INTRODUCTION: This study investigated the role and potential mechanisms of discoidin domain receptor 1 (DDR1) in colon fibrogenesis. METHODS: We employed the DSS-induced chronic colitis and fibrosis model to evaluate the therapeutic potential of DDR1 knockout on colonic fibrosis. In vitro experiments involved generating human normal colonic epithelial cells (HIEC line) with DDR1 overexpression by lentivirus transfection. Human colonic fibroblasts were exposed to conditioned medium (CM) from the stably transfected cells that had been treated with transforming growth factor-beta 1 (TGF-β1). The cells were collected for molecular and biochemical analyses. RESULTS: Our proteomics analysis of DDR1 indicated significant enrichment of proteins involved in the extracellular matrix and fibrosis. In DSS-treated DDR1-KO mice, attenuation of colonic fibrosis and reduced activation of colonic fibroblasts were observed, contrasting significantly with their counterparts in DSS-treated WT mice. Colonic fibroblasts exhibited a marked increase in α- smooth muscle actin and type I collagen expression when exposed to CM from HIEC cells with DDR1 overexpression. Finally, overexpression of DDR1 markedly elevated the levels of p-PI3K, p-Akt, p-mTOR, p62, and LC3B in HIEC cells, resulting in enhanced secretion of TGF-β1. DISCUSSION: DDR1 in HIEC cells attenuates autophagy primarily by activating the PI3K/AKT/mTOR signaling axis and concurrently increasing the autophagic markers LC3B and p62, thereby inducing paracrine secretion of TGF-β1, which drives the activation and proliferation of colonic fibroblasts and elicits a robust profibrotic response. CONCLUSION: Our study suggests that DDR1 may be a potential therapeutic target for colonic fibrosis.
Medicinal herbs and herbal formulations have garnered increasing attention in skincare and anti-aging due to their versatility, safety, and potential effectiveness. Korean medicinal herbs and herbal formulations have a r...Medicinal herbs and herbal formulations have garnered increasing attention in skincare and anti-aging due to their versatility, safety, and potential effectiveness. Korean medicinal herbs and herbal formulations have a rich history in traditional Asian medicine, and they are increasingly gaining recognition as anti-aging and skincare treatments. Korean herbal medicine, known as Hanbang, draws from various natural ingredients, like ginseng, green tea, and licorice, to create herbal formulations passed down for centuries. These formulations are recognized for their potential to promote healthy, youthful skin. Ingredients such as ginseng and green tea possess antioxidant properties that combat free radicals and reduce oxidative stress on the skin, preventing premature aging. Korean skincare treatments often incorporate these herbal formulations, emphasizing natural ingredients and techniques such as herbal masks, teas, and acupuncture to enhance skin vitality and combat aging signs. Understanding the role of major bioactive compounds in Korean herbal medicine is essential for bridging traditional practices with modern dermatological science. Because of the increasing global demand for natural, effective, and safe skincare products, it is increasingly important for natural agents' mechanisms, efficacy, and commercial value to be systematically evaluated and documented. This review aims at fulfilling this knowledge gap as well as providing directions for future research and product development. Considering all the beneficial effects of Korean medicinal herbs, the current review discusses major bioactive compounds present in these herbs and formulations used in anti-aging and skincare treatments, along with their extraction procedure, commercialization, and patents. The review highlights the potential benefits of Korean herbal medicine in promoting youthful, radiant skin through natural and time-honored practices.
Niacinamide, a water-soluble derivative of vitamin B3, has emerged as a versatile compound with wide-ranging therapeutic potential in dermatology. This review critically examines its formulation strategies, mechanisms of...Niacinamide, a water-soluble derivative of vitamin B3, has emerged as a versatile compound with wide-ranging therapeutic potential in dermatology. This review critically examines its formulation strategies, mechanisms of action, clinical benefits, safety profile, and advancements in delivery technologies. Niacinamide exhibits anti-inflammatory, antioxidant, and barrier-strengthening properties, making it valuable in the treatment of acne, rosacea, hyperpigmentation, and skin aging. It regulates sebum secretion, diminishes inflammatory lesions, supports collagen production, and protects against photoaging. Clinical studies affirm its effectiveness in enhancing skin tone, texture, and barrier integrity, with minimal adverse effects, even with prolonged use. Innovations in drug delivery, such as microencapsulation, liposomal carriers, and nanoparticle-based systems, have enhanced its dermal absorption and stability. Looking ahead, the integration of niacinamide into combination therapies and tailored skincare regimens offers promising opportunities to maximize its clinical utility. Overall, niacinamide stands out as a multifunctional dermatological agent with significant potential for promoting skin health and rejuvenation.
INTRODUCTION: Psoriasis is a chronic inflammatory skin disease characterized by excessive keratinocyte proliferation, abnormal differentiation, and infiltration of inflammatory cells. Central to its pathogenesis are the...INTRODUCTION: Psoriasis is a chronic inflammatory skin disease characterized by excessive keratinocyte proliferation, abnormal differentiation, and infiltration of inflammatory cells. Central to its pathogenesis are the PI3K/AKT/mTOR and JNK signaling pathways, which regulate inflammation and keratinocyte behavior. METHODS: This study reviewed experimental data reported in the scientific literature and utilized network pharmacology to investigate the interplay between the PI3K/AKT/mTOR and JNK pathways, aiming to elucidate the underlying mechanisms of psoriasis. 709 records from Scopus, Web of Sciences, Cochrane Library and PubMed were reviewed without limitations until October 3, 2023. 85 articles were included in the systematic review. RESULTS: Key molecules, including EGFR, Sortilin, and Cyr61, were identified as important links between these pathways, influencing cell survival and apoptosis. Flavonoids such as Rhododendrin, Erianin, and Fisetin were found to effectively target both of these pathways, potentially modifying cellular behavior and offering therapeutic benefits. The network analysis revealed that EGFR and AKT serve as critical connectors between hub genes CDC42 and GAPDH, with these flavonoids impacting downstream signaling molecules, including PI3K, AKT, mTOR, Grb2, JAK, STAT, Cyclooxygenase, HIF-1α, and MAPKs. DISCUSSION: The findings highlight the pivotal role of the PI3K/AKT/mTOR pathway in promoting inflammation and cellular proliferation by activating NF-κB and HIF-1α. CONCLUSION: This comprehensive review underscores the importance of the PI3K/AKT/mTOR and JNK pathways in understanding psoriasis mechanisms. Targeting these pathways with flavonoids may offer promising therapeutic strategies by modulating key molecular hubs involved in disease progression.
Leukemia is one of the most widespread and life-threatening malignancies that originates in the blood and bone marrow. Despite advances in treatment, there remains a need for safer and more effective therapeutic agents w...Leukemia is one of the most widespread and life-threatening malignancies that originates in the blood and bone marrow. Despite advances in treatment, there remains a need for safer and more effective therapeutic agents with fewer side effects. This review investigates the therapeutic potential of curcumin (CUR), a naturally derived polyphenol, in leukemia management, with a focus on its molecular mechanisms and regulatory effects on various signaling pathways. Peer-reviewed publications were considered till March 2025. Various scientific databases, including PubMed, Scopus, Science Direct, SciFinder, Medline, and Google Scholar, were used to collect the literature knowledge. The review focuses on the role of curcumin in modulating key cellular processes, such as apoptosis, cell cycle arrest, and gene regulation, along with its interaction with several oncogenic and protective signaling cascades. Accordingly, CUR demonstrates potent antileukemic effects by promoting apoptosis and cell cycle arrest. It downregulates oncogenes, such as FLT3, Akt, ROS, and NF-κB, while protecting normal cells through upregulation of NRF-2, which enhances antioxidant production. Additionally, CUR modulates multiple signaling pathways, including NF-κB, JAK/STAT, PI3K/AKT, JNK/ERK, MAPK, Ras/Raf, and MMP, thereby affecting leukemia initiation, progression, and metastasis. CUR exhibits strong potential as a therapeutic agent for leukemia by targeting multiple molecular signaling pathways and promoting selective cytotoxicity against cancer cells. Further preclinical and clinical studies are necessary to validate its efficacy and overcome the limitations of the bioavailability parameters.
INTRODUCTION: Healthy aging involves consistently maximizing opportunities to maintain and enhance physical and mental well-being, fostering independence, and sustaining a high quality of life. This review examines recen...INTRODUCTION: Healthy aging involves consistently maximizing opportunities to maintain and enhance physical and mental well-being, fostering independence, and sustaining a high quality of life. This review examines recent technological innovations aimed at promoting the well-being of older adults. The scope encompasses wearable devices and telemedicine, showcasing their potential to enhance the health and overall well-being of older individuals. The review highlights the crucial role of assistive technologies, including mobility aids, hearing aids, and adaptive home devices, in addressing the specific challenges associated with aging. METHODS: The relevant literature was collected and selected based on the objective of the study and reviewed. RESULTS: Digital technologies, including brain-computer interfaces (BCIs), are explored as potential solutions to enhance communication between healthcare providers and aging patients, considering engagement levels and active interaction. Sophisticated BCIs, such as electroencephalograms, electrocorticography, and signal modeling for real-time identification, play a crucial role in event detection, with machine learning algorithms enhancing signal processing for accurate decoding. The exploration of smart wearable systems for health monitoring emerges as a dynamic and promising field in the context of aging. DISCUSSION: Fitbit® showcases accurate step counting, making it suitable for monitoring physical activity in older adults engaged in slow walking. ActiGraph™ is evaluated for accuracy in monitoring physical activity in older adults, with results indicating reliable concurrence with Fitbit® devices. The study identifies several limitations, including sample size constraints, challenges in keeping pace with technological advancements, and the need for further investigation into the suitability of fitness trackers for individuals with significant mobility impairments. CONCLUSION: The evolving landscape of wearable technologies, exemplified by Fitbit®, Acti- Graph™, and other interventions, holds substantial promise for reshaping healthcare approaches for the aging population. Addressing the limitations will be crucial as research progresses to ensure the effective and ethical integration of wearables into geriatric care, maximizing their potential benefits.
INTRODUCTION: Rabies Virus (RV or RABV) is a neurophilic pathogen predominantly transmitted to humans through bites, scratches, or wounds. Upon entering the central nervous system, the virus can cause severe symptoms, in...INTRODUCTION: Rabies Virus (RV or RABV) is a neurophilic pathogen predominantly transmitted to humans through bites, scratches, or wounds. Upon entering the central nervous system, the virus can cause severe symptoms, including acute encephalitis and paralysis, ultimately leading to death with an almost 100% mortality rate. Hence, it is essential to develop an effective oral rabies vaccine. METHODS: We designed and synthesized three modified 5'-cap mRNA vaccines (RV-01(CAP- 01), RV-01(CAP-02) and RV-01(CAP-03)) encoding rabies virus glycoproteins in vitro and evaluated their immunogenicity and protective effect in mice. RESULTS: The modified 5'-cap vaccine was successfully constructed and could be effectively expressed in HEK293 cells. The antibody detection results revealed the abundance of RABV-G in RV-01(CAP-01), RV-01(CAP-02) and RV-01(CAP-03). ELISPOT assays indicated that these variants promoted the production of immune-related cytokines. Furthermore, the modified 5'-cap vaccines could reduce the rabies viral load of mice and effectively prolong their survival. DISCUSSION: The rabies mRNA vaccine had high efficacy and safety in preventing rabies, suggesting the great potential of mRNA as a promising candidate for RABV vaccines. However, the potential causes of the differences in the performance of the three modified 5'-cap rabies mRNA vaccines and the clinical application of 5'-Cap altered rabies mRNA vaccines need to be explored. CONCLUSION: Hence, these results demonstrated that the modified 5'-cap mRNA vaccine was effective in inducing immune responses, which might be considered a promising prophylactic strategy for rabies.
INTRODUCTION: The rise of Vancomycin-Resistant Enterococcus (VRE) has become a major public health concern due to its resistance to conventional antibiotics and ability to form biofilms. The urgent need for novel therape...INTRODUCTION: The rise of Vancomycin-Resistant Enterococcus (VRE) has become a major public health concern due to its resistance to conventional antibiotics and ability to form biofilms. The urgent need for novel therapeutic strategies has led to increased interest in natural compounds with antimicrobial potential. Pubescine (PBN), a steroidal alkaloid isolated from Holarrhena pubescens, has demonstrated antimicrobial properties, but its efficacy against VRE remains unexplored. METHODS: PBN was isolated and purified from Holarrhena pubescens using chromatographic techniques and identified through spectroscopic analysis. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were determined via broth microdilution assays. Time-kill assays assessed the bacteriostatic or bactericidal nature of PBN. Resistance development was evaluated through prolonged bacterial exposure to subinhibitory concentrations. Synergistic interactions with vancomycin and cefoxitin were analyzed using checkerboard microdilution assays. Biofilm formation and eradication were assessed via crystal violet staining and fluorescence imaging. Metabolic activity and oxidative stress induction were measured using the Alamar Blue assay and Reactive Oxygen Species (ROS) quantification, respectively. RESULTS: PBN exhibited concentration-dependent inhibition of VRE growth, primarily exerting a bacteriostatic effect without promoting the development of resistance. Checkerboard assays revealed strong synergy between PBN and vancomycin (FICI = 0.1875) and cefoxitin (FICI = 0.3125), suggesting that PBN enhances the efficacy of these antibiotics. DISCUSSION: PBN significantly reduced biofilm formation and facilitated biofilm disruption at concentrations as low as 4 μg/mL. Metabolic assays demonstrated that PBN suppresses bacterial metabolic activity, while ROS quantification indicated a substantial increase in oxidative stress, suggesting a multi-targeted mechanism of action. CONCLUSION: These findings establish PBN as a promising antimicrobial agent with potent activity against vancomycin-resistant Enterococcus faecalis. Its ability to enhance antibiotic efficacy, inhibit biofilm formation, and induce oxidative stress underscores its potential as a novel therapeutic strategy against multidrug-resistant infections. Further in vivo studies and pharmacokinetic evaluations are warranted to assess its clinical applicability.