Current drug targets最新文献

Introduction: Recent studies have established that cytokeratin 8 (CK8) is closely linked to glycogen synthesis; however, its mechanistic role in hepatic glycogen synthesis in type 2 diabetes mellitus (T2DM) remains unclear. This study aimed to elucidate the effects and underlying molecular mechanisms of CK8.

Methods: We analyzed CK8 expression and the IRS1 (Insulin Receptor Substrate 1)/PI3K (Phosphoinositide 3-Kinase)/Akt (Protein Kinase B)/GSK3β (Glycogen Synthase Kinase 3 beta) pathway in liver samples from T2DM patients, diabetic C57BL/6J mouse models, and high glucose- treated NCTC 1469 cells using Western blotting, immunohistochemistry, and PAS staining.

Results: CK8 was significantly upregulated in all T2DM models, correlating with suppressed IRS1/PI3K/Akt/GSK3β signaling and reduced glycogen synthesis. Our functional studies demonstrated that CK8 overexpression exacerbated these effects, while CK8 knockdown restored glycogen levels to near-normal.

Discussion: In our study, CK8 was identified as a negative regulator of hepatic glycogen synthesis by modulating the IRS1/PI3K/Akt/GSK3β pathway.

Conclusion: These findings position CK8 as a promising therapeutic target for T2DM, with CK8 inhibition offering a novel strategy to improve hepatic insulin resistance and glycogen storage without requiring β-cell stimulation.

Introduction: The global prevalence of Diabetes Mellitus is rising; this complex metabolic disorder marked with hyperglycemia comes with increased morbidity and more associated health risks. Type 1 Diabetes Mellitus, an autoimmune disorder primarily affecting young individuals, lacks innovative pharmacological therapies. While current treatments for Type 2 Diabetes Mellitus-including lifestyle interventions and medications-can be effective, many patients still struggle with glycemic control. This review aims to highlight recent advances in diabetes mellitus management, emphasizing novel therapeutics and drug delivery systems that aim to decrease dosage frequency, target the manifestation of side effects, and enhance anti-diabetic effectiveness.

Methods: We conducted a comprehensive review of over 300 articles published between 2017 and 2025, utilizing databases such as PubMed and ScienceDirect.

Results: Recent therapeutic innovations include nanocarrier-mediated drug delivery, microneedle patches, and mRNA- and gene-based systems.

Discussions: These technologies aim to improve glycemic control, reduce dosing frequency, and minimize side effects. The 2024 American Diabetes Association Standards of Care introduced updated diagnostic criteria and management recommendations, which are summarized herein.

Conclusion: This review outlines key developments in pharmacological and delivery strategies of the past 5 years, targeting all types of diabetes. Special focus is placed on emerging therapies such as mRNA, nanotechnology, and innovative delivery systems, which may transform future diabetes management. The content is designed to support clinicians, researchers, and healthcare professionals in developing future therapeutic strategies.

Antimicrobial peptides (AMPs), part of the body's innate immune response, are natural compounds that inhibit bacteria during bacterial infections. Despite their important role in counteracting cellular pathogens, the precise mechanism of generating AMPs in response to bacterial infection remains elusive. However, recent findings demonstrate that the proteasome, a cellular complex involved in the degradation of intracellular proteins, plays a key role in generating AMPs during bacterial infection. Intriguingly, bacterial infections have been shown to mediate the remodeling of the proteasome, resulting in altered cleavage activity that increases the generation of antimicrobial peptides and helps reduce intracellular bacterial load. Additionally, the 11S proteasome subunit PSME3 has been identified as the key regulatory particle responsible for triggering proteasome remodeling in response to bacterial stress. Remarkably, given the burgeoning research on antimicrobial agents, the recent findings uncover an important anti-bacterial functional role of the proteasome and open avenues for investigating strategies to modulate or enhance the cell's natural defense against pathogens to develop new antimicrobial therapeutics.

Cancer is a significant human health concern due to its increasing mortality rate and profound impact on public health and healthcare systems. The cytotoxic, antiproliferative, immunosuppressive, and apoptogenic properties of scorpion venom proteins and peptides have been observed in various cancer cell lines. Therefore, the purpose of this study was to investigate the potential use of proteins derived from scorpion venom in cancer treatment. In this study, the effects of different scorpion venoms on transmembrane channels, the inhibition of angiogenesis, the inhibition of invasion and metastasis, the inhibition of proliferation, and the induction of apoptosis were investigated, as were their clinical applications in the treatment of hepatocellular carcinoma and breast, cervical, prostate, colorectal, and melanoma cancers. The results showed that various scorpion venoms can suppress cell growth, stimulate apoptosis, reduce tumor size, and enhance the immune response, thereby serving as alternative drugs for treating various types of cancers and their metastasis. This review suggests a positive association between scorpion venom (SV) proteins and the treatment of these cancers. Future research should focus on understanding the underlying mechanisms, identifying biomarkers to predict response, and exploring potential combination therapies to increase the efficacy of scorpion venom proteins in cancer treatment.

Aging is a complex biological process marked by progressive cellular and tissue decline, leading to an increased risk of age-related diseases. Plant-based natural compounds, including polyphenols, flavonoids, carotenoids, alkaloids, and terpenoids, have gained attention for their potential in mitigating aging-related damage through antioxidant, anti-inflammatory, and cellular repair mechanisms. The review identified that plant-derived bioactive compounds target key pathways involved in aging, including Sirtuins (SIRT1), AMP-activated protein kinase (AMPK), and Nuclear Factor-kappa B (NF-κB). These compounds address key hallmarks of aging, such as oxidative stress, mitochondrial dysfunction, cellular senescence, and chronic inflammation. Evidence suggests their potential in preventing or delaying age-related disorders, including neurodegenerative diseases, cardiovascular conditions, and skin aging. Plant-derived compounds offer a promising alternative to synthetic anti-aging interventions due to their efficacy, safety, and sustainability. However, challenges such as low bioavailability and limited clinical validation must be addressed. Advances in drug delivery systems and comprehensive clinical trials are critical to realizing their full therapeutic potential. Plant-based bioactive compounds represent a significant opportunity for developing safer and more sustainable anti-aging therapies. Continued research is essential to overcome existing limitations and facilitate the integration of these approaches into mainstream healthcare practices.

Introduction: Astragalus mongholicus is distributed in Inner Mongolia, China, and has a certain therapeutic effect on silicosis. However, the regulatory mechanisms of Astragalus mongholicus mediated by alternative splicing (AS) in silicosis pathology and treatment remain unclear.

Methods: The pathological examination was performed on the lung tissue of a constructed mouse model of silicosis. Then, rMATS-based AS detection, target prediction, PPI analysis, and molecular docking were conducted to investigate the mechanism of Astragalus mongholicus-mediated treatment of silicosis in mice from the perspective of AS.

Results: A total of 404 differentially alternatively spliced genes (DASGs) were identified between the Astragalus mongholicus treatment and the silicosis model group. Moreover, 194 potential targets were predicted from 33 active components of Astragalus mongholicus, of which the targets, Rps6ka2 and Clk4, underwent differential AS. Network pharmacology analysis indicated that the Isomucronulatol, 7-o-methylisomucronulatol, and Medicarpin in Astragalus mongholicus might participate in the treatment of silicosis through differential spliced of Rps6ka2 or Clk4. Molecular docking confirmed a strong binding affinity between the protein Rps6ka2 and Medicarpin.

Discussion: This study suggests that Isomucronulatol, 7-o-methylisomucronulatol, and Medicarpin, being active components in Astragalus mongholicus, may intervene in silicosis pathogenesis through differential splicing of Rps6ka2 or Clk4, involving biological processes such as protein serine/threonine kinase activity. However, further experimental validation is required to confirm these findings.

Conclusion: A large number of DASEs exist in the development and treatment of silicosis. Astragalus mongholicus may alleviate silicosis through AS-regulated mechanisms involving Rps6ka2 and Clk4. This finding provides novel strategies and potential molecular targets for silicosis treatment.

Nanotechnology in drug delivery has revolutionized modern therapeutics by addressing the limitations of conventional drug delivery methods. This review article explores the significant advancements in nanoparticle-based drug delivery systems, highlighting their role in enhancing therapeutic efficacy and overcoming drug resistance. Nanoparticles, including lipid-based, polymer- based, inorganic, and biological types, offer improved solubility, stability, targeted delivery, and controlled release of therapeutic agents. By enabling precise delivery to specific tissues or cells, these advancements minimize off-target effects and toxicity, particularly in cancer therapy. Additionally, nanomedicine facilitates the delivery of drugs across biological barriers such as the blood-brain barrier, which opens new avenues for treating neurological disorders. The ability to co-encapsulate multiple therapeutic agents in nanoparticles also supports combination therapies that target multiple pathways simultaneously, thereby reducing the development of resistance. As research progresses, the integration of nanotechnology in drug delivery promises to transform healthcare by providing more effective, safer, and personalized treatments. This article advocates for continued exploration and innovation in the field by emphasizing the need for interdisciplinary collaboration to fully realize the potential of nanomedicine in improving patient outcomes and addressing unmet clinical needs.

Introduction: Urinary tract infections (UTIs) range from mild to severe cases, commonly caused by uropathogenic Escherichia coli (E. coli). The growing concern about antibiotic resistance demands alternative treatment strategies. Nanotechnology, particularly nanocarriers, presents a promising solution by enhancing drug delivery, antibacterial activity, and targeted therapy. This review focuses on the emerging role of combining herbal remedies with nanotechnology for more effective and personalized management of UTIs, aiming to overcome the limitations of conventional antibiotic therapies.

Methods: The review involved an extensive search of scientific databases and relevant literature, including studies published to date from PubMed, Science Direct, and Google Scholar. Urinary tract infections (UTI), antibiotic resistance, nanotechnology, drug delivery, targeted drug delivery, and herbal drugs were among the search phrases used.

Result: According to studies, combining herbal extracts such as neem and turmeric with nanotechnology significantly enhances antimicrobial activity against UTI pathogens. These nanoformulations show enhanced bacterial inhibition, reduced inflammation, and increased therapeutic precision with minimal side effects.

Discussion: The synergistic use of herbal remedies and nanocarriers offers a novel approach to managing UTIs. Nanotechnology not only enhances drug delivery but also improves diagnostic accuracy through fluorescence markers and biomolecule tagging. This strategy effectively addresses growing antibiotic resistance and supports the development of personalized treatments. The combination of natural bioactives and advanced delivery systems offers a safer, more effective alternative to conventional antibiotics in treating UTIs.

Conclusion: The integration of nanotechnology and herbal therapies revolutionizes UTI management through precision medicine. This approach enhances treatment efficacy, diagnostic accuracy, and patient outcomes, offering a personalized solution to combat antibiotic resistance and urinary tract abnormalities with improved targeting and minimal side effects.

B-cell lymphoma-2 (BCL-2) plays a key role in regulating apoptosis. Venetoclax (VEN), a BCL-2 inhibitor, has been approved for the treatment of a variety of haematologic malignancies. VEN is primarily metabolized by CYP3A, and a variety of factors (such as CYP3A inhibitors, as well as food and hepatic functions) have been reported to significantly influence the metabolic process. There is significant interindividual variability in VEN plasma concentrations, and studies have shown that its exposure levels are correlated with efficacy, although the relationship with adverse effects remains controversial. The value of applying of therapeutic drug monitoring (TDM) in individualized VEN therapy has been confirmed by some studies, but the optimal therapeutic window for different malignancies is still unclear. This review summarizes the pharmacokinetic characteristics, along with the factors influencing VEN pharmacokinetics, drug-drug interactions, and advancements in TDM research on VEN, aiming to provide a theoretical basis for TDM-guided individualized therapy.

Introduction/objective: Heterocyclic molecules, a mainstay of contemporary medicinal chemistry, are essential in developing antibacterial and anticancer treatments. Their distinct structural features-one or more heteroatoms within the ring-allow for a wide range of biological activities. With a focus on their modes of action and insights into the structure-activity relationship (SAR), this study examines the therapeutic uses of heterocyclic compounds in antibacterial, antifungal, antiviral, and anticancer treatments.

Methods: The review uses search engines like PubMed and Google Scholar, with a preference for English as the major language, to gather and analyse recent research on the antibacterial and anticancer applications of diverse heterocyclic compounds.

Results: It has been discovered that heterocyclic chemicals are useful in blocking microbial enzymes, including DNA gyrase and the machinery involved in protein synthesis. Heterocyclic compounds such as benzimidazoles, quinolines, and acridines have demonstrated noteworthy efficacy in cancer therapy through their targeting of tubulin inhibition, DNA intercalation, and signalling pathways like PI3K/Akt/mTOR and MAPK. The pharmacological characteristics of these compounds were improved by the addition of electron-withdrawing groups, halogenation, and heteroatom replacements, according to SAR investigations.

Conclusion: Heterocyclic compounds have great promise for antibacterial and anticancer treatments. They are crucial in drug development because of their structural flexibility, which enables the targeted suppression of vital biological processes. The effectiveness of heterocyclic compounds will continue to be improved by ongoing advancements in drug design and SAR optimization, opening new possibilities for the creation of more potent and selective medicinal treatments.