Current drug targets最新文献

Acne vulgaris is the 8th most commonly prevailing skin disorder worldwide. Its pervasiveness has been predominant in juveniles, especially males, during adolescence and in females during adulthood. The lifestyle and nutrition adopted have been significantly reported to impact the occurrence and frequency of acne. It typically occurs over the regions of the forehead, upper chest, and back of the body, which are regions with high proportions of active sebaceous follicles. The market today is flooded with the pool of anti-acne medications (oral, topical/systemic) that contain either a single therapeutic agent or a blend targeting multiple pathological pathways. However, the clinical applicability of these preparations is limited due to formulation stability, drug penetrability, and targeting, the incidence of secondary effects, antibiotic resistance, etc. Moreover, the effectiveness of the former therapies varies as per the type and severity of acne. Therefore, it is necessary to extensively research skin physiology under normal and diseased conditions so that newer, safer, and more effective medications can be devised. Moreover, their safety and efficacy should be validated by employing various acne models, and their comparative profiling should be done with standard marketed anti-acne preparations. Acne models assist to uncover the complex disease pathogenesis and identify the potential targets for therapeutic interventions. This review is an attempt to highlight varied in-vitro, ex-vivo, and in-vivo testing procedures done to assess drug efficacy, track disease progression, and compare test substances with existing treatments. By presenting a unified approach to acne modeling, this review will assist researchers in selecting the most appropriate model for their specific research goals, helping them to generate valuable and reproducible data to support the development of effective acne therapies.

A range of heterocyclic compounds, including Isatin (oneH-indole-2, 3-dione) and its by-products, have been shown to represent potential unit blocks in the synthesis of potential medicinal agents. Numerous studies have been carried out on isatin, its synthesis, biological uses, and its chemical composition since when it was discovered. Functionally, these isatin-containing heterocycles have demonstrated antibacterial, antidiabetic, antiviral, antitubercular, and anticancer properties, among many others. In vitro and In vivo efficaciousness of several Isatin moieties has been assessed in recent years based on their antimicrobial qualities. Isatin has shown great promise as a flexible heterocycle in the realm of drug development in recent years. Many viruses have caused extensive epidemics during the last 50 years, which have had detrimental effects on social, economic, and health conditions. The current unprecedented SARS-CoV-2 epidemic necessitates intensive research into the development of potent antiviral medications. It has been shown that Isatin, a flexible heterocycle, has a great deal of potential for drug development. Appropriately functionalized Isatin compounds have shown noteworthy and extensive antiviral activities throughout the last fifty years. The goal of this study is to gather all known data on Isatin derivatives' antiviral activity, emphasizing their structure-activity correlations as well as research on mechanistic and molecular modelling. We think that the scientific community will find this review to be a useful tool in the development of more efficient and powerful antiviral treatments based on Isatin scaffolds.

Metallothionein 1J pseudogene (MT1JP) is a long non-coding RNA (lncRNA) that functions as a tumor suppressor in various malignancies. Reduced MT1JP expression is associated with increased tumor proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and treatment resistance in nine cancers, such as gastric cancer, intrahepatic cholangiocarcinoma, hepatocellular carcinoma, and breast cancer. Mechanistically, MT1JP acts as a competitive endogenous RNA (ceRNA) to regulate oncogenic microRNAs (miRNAs), including miR-92a-3p, miR-214-3p, and miR-24-3p. This regulation restores tumor suppressor genes, such as FBXW7, RUNX3, and PTEN, thereby disrupting oncogenic pathways, including PI3K/AKT, Wnt/βcatenin, and p53, promoting apoptosis, and inhibiting tumor progression. Clinically, MT1JP expression correlates with tumor grade, differentiation, TNM stage, lymph node metastasis, and patient prognosis, suggesting its potential as a diagnostic and prognostic biomarker. Furthermore, its therapeutic potential in RNA-based treatments has attracted significant attention. Despite these findings, questions remain regarding its role in epigenetic regulation, transcriptional control, and RNA delivery. This review explores the molecular mechanisms underlying MT1JP, highlighting its clinical relevance and potential as a therapeutic target. Future research should focus on elucidating its role in epigenetic regulation, overcoming challenges in therapeutic delivery, and validating its utility as a biomarker for different cancers. MT1JP holds promise for advancing precision oncology by providing innovative approaches for cancer diagnosis and treatment.

Background: Myopia is one of the most common eye diseases worldwide, with an increasing incidence observed in recent years. Globally, effective treatments for myopia have been extensively explored. In recent years, research on drugs for the treatment of myopia has become a popular topic in ophthalmology, with some breakthroughs having been achieved. Compared with surgical treatment, drug treatment is easier for people to accept. Although the efficacy of some drugs in delaying the development of myopia has been confirmed, the mechanism and site of action of some drugs are still not completely clear.

Objective: In this study, we review the recent related research on drug therapy for myopia at home and abroad, describe the mechanism of various drugs in treating myopia, evaluate their clinical application value, and identify existing problems.

Results: These drugs include atropine, a series of anticholinergic drugs, dopamine agonists, 7- methylxanthine, and intraocular pressure-lowering drugs.

Conclusion: Results highlight the efficacy of atropine in myopia treatment with minimal side effects. Anticholinergic medications, such as atropine, have demonstrated efficacy in managing the progression of myopia with a reduced incidence of adverse effects. The emphasis is placed on achieving better long-term effectiveness and minimizing the rebound effect after treatment is stopped. Furthermore, participating in outdoor activities and reducing eye strain are proven strategies for preventing myopia.

Diseases affecting bone encompass a spectrum of disorders, from prevalent conditions such as osteoporosis and Paget's disease, collectively impacting millions, to rare genetic disorders including Fibrodysplasia Ossificans Progressiva (FOP). While several classes of drugs, such as bisphosphonates, synthetic hormones, and antibodies, are utilized in the treatment of bone diseases, their efficacy is often curtailed by issues of tolerability and high incidence of adverse effects. Developing therapeutic agents for bone diseases is hampered by the fact that numerous pathways regulating bone metabolism also perform pivotal functions in other organ systems. Consequently, the selection of an appropriate target is a complicated process despite the significant demand for novel medications to address bone diseases. Research has shown the role of various cell signaling pathways, including Wnt, PTHR1, CASR, BMPRs, OSCAR, and TWIST1, in the regulation of osteogenesis, bone remodeling, and homeostasis. Disruptions in bone homeostasis can result in decreased bone density and the onset of osteoporosis. There remains a need for the development of drugs that can enhance bone remodeling with improved side effects profiles. The exploration of promising targets to stimulate bone formation has the potential to significantly advance the field of bone-related medical care, thereby improving the quality of life for millions. Additionally, a deeper understanding of anabolic and catabolic pathway mechanisms could enable future studies to explore synergistic effects between unrelated pathways. Herein, we explore potential drug targets that may be exploited therapeutically using small molecule agonists or antagonists to promote bone remodeling and discuss their advantages and limitations.

Managing diabetic wounds is a significant challenge for healthcare professionals since severe complications and delayed recovery greatly impact the patients' quality of life. This article aimed to explore various factors affecting diabetic wound healing, the mechanism of wound healing, and potential natural products having wound healing capability. It focuses on mechanisms of action and the therapeutic effectiveness of the compounds employed in the management of diabetic wounds. The review discusses the function of nutrition in wound healing, emphasizing the significance of consuming adequate amounts of protein, energy, lipids, amino acids, vitamins, minerals, and water to promote healing. Several herbs, including Rosmarinus officinalis, Carica papaya, Aloe vera, Annona squamosa, and Punica granatum, are being tested for wound healing qualities in diabetes circumstances. These plants have a variety of modes of action, including antioxidant, anti-inflammatory, antibacterial, and immunomodulatory activities that help to speed up wound healing, stimulate collagen formation, and promote tissue regeneration. The variety of action mechanisms seen in natural products, especially in plants, offers hope for the treatment of diabetic wounds. It may also be possible to improve healing results and the quality of life of diabetes individuals with chronic wounds by including these herbal treatments in wound care programs.

Breast cancer remains the second most prevalent cancer among women in the United States. Despite advancements in surgical, radiological, and chemotherapeutic techniques, multidrug resistance continues to pose significant challenges in effective treatment. Combination chemotherapy has emerged as a promising approach to address these limitations, allowing multiple drugs to target malignancies via distinct mechanisms of action. Increasingly, the use of phytoconstituents alongside chemotherapeutic agents has shown promise in enhancing treatment outcomes. This combination therapy acts on key signaling pathways such as Hedgehog, Notch, Wnt/β- catenin, tyrosine kinases, and phosphatidylinositol 3-kinase (PI3K), which play critical roles in cellular proliferation, apoptosis, angiogenesis, differentiation, invasion, and metastasis. This review explores various signaling pathways involved in breast cancer progression, discusses conventional treatment methods like surgery, adjuvant radiotherapy, hormonal therapy, and chemotherapy, and highlights emerging nanocarrier-based drug delivery systems (DDS). Liposomes, dendrimers, exosomes, polymeric micelles, and nanoparticles (organic, inorganic, gold, magnetic, carbon-based, and quantum dots) are examined as innovative strategies for enhancing drug delivery efficacy. Furthermore, stimuli-responsive DDSs, including reactive oxygen species (ROS), enzyme-, and hypoxia- responsive systems, are presented as cutting-edge approaches to overcoming drug resistance. Special emphasis is placed on the co-delivery of chemotherapeutic agents and plant-based compounds, particularly in estrogen receptor-positive (ER+) breast cancer. This review aims to provide a comprehensive overview of novel combinatorial strategies and advanced nanocarriers for the effective and targeted treatment of breast cancer.

Currently, diabetic nephropathy (DN) stands as the predominant global cause of endstage renal disease. Many scientists believe that diabetes will eventually spread to pandemic levels due to the rising prevalence of the disease. While the primary factor leading to diabetic nephropathy is vascular dysfunction induced by hyperglycemia, several other pathological elements, such as fibrosis, inflammation, and oxidative stress, also contribute to the progression of the disease. The primary targets of current DN therapy approaches are the underlying abnormalities of hypertension and glucose. With several targets and fewer side effects, curcumin is a commonly utilized antioxidant in DN. The present study emphasizes the critical role of oxidative stress and inflammation in the development of diabetic nephropathy. It reveals how these factors induce damage in key kidney cell types, highlighting their potential as therapeutic targets for this disease. In addition, by concentrating on Nrf2, SIRT1, HMGB1, NF-κB, and NLRP3 of curcumin, has strong anti- inflammatory and antioxidant characteristics. This review describes the role of curcumin in the therapeutic application of diabetic nephropathy. In this attempt, we tried to elaborate on the bench-to-bedside aspects of curcumin in DN, including clinical and preclinical investigations. The rationales of curcumin's mechanisms in alleviating symptoms of the DN were discussed. Curcumin could serve as the potential therapeutic agent for the patient seeking to recover from DN.

Emerging challenges to human health necessitate a coordinated effort to find both preventative and therapeutic techniques, with natural products at the forefront of attempts to gain novel medicines and minimize disease transmission and related death. The medicinal potential of chemicals contained in plants has been known for centuries, leading to its use in homes and clinics for the treatment of numerous disorders. Despite global advancements, plant-based medicines continue to be utilized to treat various pathological illnesses or as alternatives to contemporary pharmaceuticals. The safety and low toxicity of natural products have led to their increasing acceptability for the prevention or treatment of many ailments. Flavonoids are biologically active compounds that are classified as polyphenols, which are a type of secondary metabolite found in all plants. Icariside II (ICA-II) is one of the secondary metabolites that belong to the flavonoid category of phytochemicals and is present in Epimedium brevicornum Maxim. In recent years, ICA-II has been discovered to show anti-inflammatory, antioxidant, anticancer, renal protecting, and cardiac protective effects, as well as several other biological characteristics. This review is focused on the exploration of the pharmacological activities of ICA-II. ICA-II is considered a prospective candidate for future clinical investigations due to a number of therapeutic properties.