Current pharmaceutical biotechnology最新文献

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

Introduction: Enterococci are common commensals in the gastrointestinal tract and are opportunistic organisms that can cause urinary tract infections, bacteremia, endocarditis, and pelvic infections. The study aimed to investigate antibiotic resistance, biofilm formation, and the presence and expression of virulence factors in clinical isolates of E. faecalis from Jordan.

Methods: Clinical isolates (n=89) of E. faecalis isolated from patients in Jordan were collected. Antibiotic resistance, biofilm formation, and the presence/expression of virulence genes asa1, gelE, esp, cylA, and efaA were examined.

Results: High resistance of E. faecalis was detected for ampicillin (98.9%), followed by quinupristin-dalfopristin (96.6%), tetracycline (83.1%), erythromycin (78.6%), and rifampin (68.5%). Most isolates (93.3%) were found to be biofilm producers. The prevalence of virulence genes was efaA (77.5%), asa1 (77.5%), gelE (69.7%), esp (50.6%), and cylA (30%). About 25.8% of the isolates were found to be gelatinase producers. In addition, hemolysin production was observed in 37.1% of the isolates.

Discussion: The esp gene was associated with tetracycline resistance. The asa1 gene was associated with susceptibility to vancomycin. CylA was associated with resistance to tetracycline and erythromycin, as well as susceptibility to ciprofloxacin and gentamicin. The presence of gelE was associated with susceptibility to chloramphenicol, tetracycline, levofloxacin, and erythromycin. The cylA gene was associated with esp and asa1 genes, while the efaA was found to be associated with gelE and asa1 genes (P<0.05). Finally, biofilm formation was not associated with antimicrobial resistance (P > 0.05).

Conclusions: The antibiotic resistance profiles and associated genes of E. faecalis isolates from Jordanian patients were reported. The efaA, asa1, and gelE virulence genes were highly prevalent among the isolates. The present findings can be used in the management of E. faecalis infection in Jordan.

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.

Background: Alzheimer's disease poses a major challenge as a widespread and fatal neurodegenerative disorder, primarily affecting the elderly population worldwide.

Objective: This study aimed to assess the potential protective and therapeutic effects of virgin olive oil and tiger nut essential oil on Alzheimer's dementia in male rats while also analyzing serum biomarker gene expression profiles in both Alzheimer's and control groups.

Methods: Rats were fed basal diets supplemented with 5% virgin olive oil or tiger nut essential oil, along with high-fat meals containing trans fats, butter (25%), margarine (25%), and hydrogenated shorten oils (25%) to evaluate lipid profiles and serum biomarkers. Gene expression analysis revealed a significant upregulation of acetylcholinesterase, P53, BCL2, Mouse ICAM-1, PSEN, and BACE genes in the Alzheimer's disease group compared to controls. Real-time PCR analysis also identified inflammatory biomarkers and Alzheimer's disease-associated risk factors in high-fat diet-treated, virgin olive oil-treated, and control samples.

Results: The study found significant correlations between serum biomarker levels, lipid profiles, and dietary treatments. The activities of acetylcholinesterase, glutathione, catalase, and superoxide dismutase differed notably between virgin olive oil and tiger nut essential oil treatments. High-fat dietary treatments resulted in substantial increases in serum lipid profiles due to trans-fat intake compared to the control group. Overall, both virgin olive oil and tiger nut essential oil demonstrated cognitive enhancement and potential therapeutic effects against Alzheimer's disease symptoms induced by trans-fat feeding, including inhibition of acetylcholines-terase activity, reduction of amyloid-beta accumulation, and mitigation of inflammation.

Conclusion: The study suggests that serum biomarker gene expression profiles could serve as valuable indicators for differentiating between Alzheimer's disease, virgin olive oil, and dietary treatments. Both virgin olive oil and tiger nut essential oil demonstrated protective effects, enhancing cognitive function and offering therapeutic potential against AD symptoms. These effects were achieved through the reduction of inflammation, the inhibition of AChE activity, and the reduction of amyloid-beta accumulation.