Current pharmaceutical biotechnology最新文献

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.

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.

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 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 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.

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.

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 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, 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: Breast cancer is a global health challenge with a high mortality rate of 30% of total cases in a year. Breast cancer presents in 4 main types, namely, TNBC, HER2+, luminal A, and Luminal B. Current treatments, though not without side effects, incur substantial cost, and are rendered ineffective by rising drug resistance. Phytochemicals are being investigated for their beneficial effects on breast cancer. Systematically collecting, organizing, and analyzing this data from available literature could benefit the development of more potent chemopreventive and chemotherapeutic approaches with reduced side effects.

Methods: To overcome the challenges posed by diverse naming practices, we adopted a sentiment (subjective) based text-mining approach to systematically extract and analyze data on antibreast cancer phytochemicals from biomedical literature. This method is based on anchor and associated terms to capture authors' sentiments regarding the therapeutic potential of these compounds. Subsequently, comprehensive and objective information was extracted and curated for each phytochemical, including target genes, pathways, study type, IC50 values, PMIDs, plant sources, and geographical availability.

Results: PhytoCAT (PhytoChemical Affordable Therapeutics for Breast Cancer) is a comprehensive database of phytochemicals, plant extracts, and essential oils, enriched with links to phytogeographic data and chemical structures. PhytoCAT includes data on 28 essential oils, 470 plant extracts, and 1,649 phytochemical compounds. These compounds were classified into several chemical groups, including alkaloids (167), coumarins (43), flavonoids (290), lignans (47), quinones (43), saponins (27), sesquiterpenoid lactones (40), terpenoids (282), triterpenoid saponins (28), and xanthones (22) groups. Additionally, 505 phytochemicals belong to other subclasses such as esters, glucosides, phenanthrenes, and phenylpropanoids. Further, information on their mechanisms of action is also provided.

Discussion: Phytochemicals have gained significant attention in recent years because of their potential health benefits, particularly in the prevention and treatment of various diseases, including cancer. Compounds such as curcumin, resveratrol, and epigallocatechin gallate (EGCG) are examples of phytochemicals that have shown promise in preclinical studies. PhytoCAT offers a centralized and searchable database enriched with biological, chemical, and pharmacological details. Its structured presentation allows researchers to identify promising compounds and study patterns in chemical class-specific activity.

Conclusion: PhytoCAT provides an evidence-based platform for researchers and clinicians to explore the potential of phytochemicals in breast cancer management. Although PhytoCAT has an advanced search engine, it lacks analytical tools, which we envisage