Current pharmaceutical design最新文献

Intrauterine adhesion (IUA) is a condition caused by damage to the basal uterine layer which can lead to partial or full occlusion of the uterine cavity. Although traditional treatment options have been useful in mild and moderate cases, they have been unsatisfactory in severe IUA cases. Therefore, it is essential to improve the treatment strategies of IUA. Recent studies have demonstrated that Mesenchymal stem cells (MSCs) exert their therapeutic effects via the paracrine secretion of several substances including extracellular vesicles (EV) also called exosomes. MSC-derived exosomes (MSC-Exos) do not have the limitations of MSCs including immunogenicity and tumorigenicity. However, exosomes have limitations in terms of identification, isolation, purification, and origin. The clinical application of exosomes requires quality control and increased standardization in isolation and culture serum. This review summarizes therapeutic potentials of MSC-Exos and explores their potential clinical implications as diagnostic, therapeutic targets as well as prognostic markers in managing IUA.

Introduction: This study aims to isolate and characterize potential cytotoxic compounds from the roots of Bauhinia variegata Linn. (Caesalpiniaceae) and evaluate their activity against human cancer cell lines. Five compounds, namely β-sitosterol (1), piperine (2), piperolein B (3), retrofractamide A (4), and dehydropipernonaline (5), were isolated from B. variegata roots using various chromatographic procedures.

Methods: The root extracts were prepared using aqueous and organic solvents, including n-hexane, ethyl acetate, and methanol. The isolated compounds were subjected to a sulforhodamine B cytotoxicity assay against DU-145 and PC-3 (prostate), HT-29 (colon), and MCF-7 (breast) human cancer cell lines. Among the isolates, compound 5 exhibited significant bioactivity against all tested cell lines. Compound 4 demonstrated in vitro activity, specifically against MCF-7 cancer cell lines.

Results: Importantly, these compounds were identified for the first time from B. variegata roots. In conclusion, this study highlights the enhanced spectrum of cytotoxic activity exhibited by the isolated compounds. These findings encourage further investigation to elucidate the mechanism of action of these compounds against the respective cell lines.

Conclusion: The identification and characterization of these bioactive compounds contribute to the understanding of the potential therapeutic applications of B. variegata in cancer treatment.

The pyrimidine nucleus is a fundamental component of human DNA and RNA, as well as the backbone of many therapeutic agents. Its significance in medicinal chemistry is well-established, with pyrimidine derivatives receiving considerable attention due to their potent anticancer properties across various cancer cell lines. Numerous derivatives have been synthesized, drawing structural inspiration from known anticancer agents like dihydropyrimidine compounds, which include the active cores of drugs such as 5-fluorouracil and monastrol, both of which have demonstrated strong anticancer efficacy. Additionally, various pyrimidine derivatives have been developed through different synthetic pathways, exhibiting promising anticancer potential. In response to the growing need for effective cancer treatments, recent efforts have focused on synthesizing and exploring novel pyrimidine derivatives with improved efficacy and specificity. This review aims to highlight the versatility of pyrimidine-based compounds in cancer therapy, emphasizing not only their potency and binding affinity but also their optimal interaction with diverse biological targets. The goal is to facilitate the design of new pyrimidine derivatives with enhanced anticancer potential, providing effective solutions for the treatment of various cancer types.

Introduction: An efficient and four-component one-pot facile synthesis of tetra-substituted imidazole is achieved by cyclo-condensation reaction of benzil with subsequent successive substitution of aromatic aldehydes, ester substituted amine and ammonium acetate via refluxing the mixture for almost two hours at 140°C.

Method: The ending point of the understudy reaction was examined by TLC after regular intervals. Synthesized 1,2,4-tetrasubstituted imidazoles were characterized by physical data and the structural features were analyzed using spectroscopic techniques such as FTIR, NMR and elemental analysis.

Results: The inhibition potential of fabricated compounds was evaluated against the mushroom based Tyrosinase (polyphenol oxidase) enzyme. Tetra-substituted imidazole derivatives demonstrated significant potent tyrosinase inhibition activities.

Conclusion: Pharmacokinetic mechanism and molecular docking studies were also carried out.

Cancer is a significant health challenge worldwide, causing social and economic burdens. Despite advancements in medicine, it remains a leading cause of death and is projected to increase by 2040. While conventional treatments like surgery, radiation, and chemotherapy are effective, they often have severe side effects. CAR T-cell (chimeric antigen receptor T-cell) treatment is a novel immunotherapy method personalized to the patient's immune system and directly targets cancer cells. It originated in the 1980s, and advancements have made it more effective. However, challenges remain, such as severe side effects, high costs, and manufacturing variability. Despite these challenges, the treatment with CAR T-cells has shown remarkable success, especially in hematologic malignancies. Though it is new to solid tumours, ongoing research looks promising. CAR T-cell therapy offers hope for fightingcancer, and it stands poised to redefine cancer treatment paradigms, giving renewed optimism to patients globally.

Introduction: The emergence of SARS-CoV-2 and the COVID-19 pandemic highlighted the urgent need for novel antiviral therapies. The main protease (Mpro) of SARS-CoV-2 is a key enzyme in viral replication and a promising therapeutic target.

Methods: This study employed virtual screening approaches to identify potential Mpro inhibitors, leveraging both structure- and ligand-based methods.

Results: Two optimum pharmacophore models were built from hundreds of crystallographic structures of Mpro, validated through ROC curve analysis and Dynophores dynamic simulations. These models captured ≈ 60K hits from six diverse compound libraries made of more than 3 million compounds. Additionally, a ligandbased similarity search using ROCS software identified 1024 potential hits based on shape and atom-based comparisons with co-crystallized ligands. Subsequent molecular docking and filtering based on physicochemical properties and structural diversity yielded 16 and 6 hits from structure- and ligand-based screening, respectively. Molecular dynamics simulations were conducted on the top-scoring hits to assess their binding stability within the Mpro active site. SCR00943 demonstrated stable binding, interacting favorably with key residues, including the catalytic dyad, resulting in a binding affinity of -61.2 kcal/mol.

Conclusion: This virtual screening campaign identified promising Mpro inhibitors, showcasing the potential of computational approaches to accelerate drug discovery efforts against COVID-19.

Mucosal Melanoma (MM) is an aggressive disease that is distinct from cutaneous melanoma risk in risk factors, prognosis, and treatment. Surgical treatment is currently the treatment of choice for localized disease; however, the recurrence rate is common. For advanced or metastatic disease, immunotherapy with PD-1 inhibitors and anti-CTLA is generally first-line treatment, however the overall responses to immunotherapy in MM are often lower and less robust when compared to that observed in cutaneous melanoma. Adoptive-TIL therapy have shown great promise. Other advances, particularly through the exploration of novel and combination therapies is a step forward and a hope to improve outcomes in patients with mucosal melanoma. In this review, we summarize current treatment options for MM, and we updated future clinical trials available for this population of patients.

Klebsiella pneumoniae (KP) is a common and highly pathogenic pathogen, which often causes several serious infections in humans. The rampant and inappropriate use of broad-spectrum antibiotics has fueled a worrisome surge in Multidrug Resistance (MDR) among the strains of K. pneumoniae, which has significantly boosted the risk and complexity of nosocomial infection transmission in clinical settings. Consequently, this situation presents a substantial challenge to the efficacy of anti-infective treatments, making the development of new and innovative therapeutic approaches important. Bacteriophages (phages) are viruses that can infect and kill bacteria. They and their derived products are now being considered as promising alternatives or adjuncts to antimicrobial therapies for treating bacterial infections in humans, which exhibit a remarkable safety profile and precise host specificity. Numerous studies have also unequivocally demonstrated the remarkable potential of phages in effectively combating MDR K. pneumoniae infections both in vitro and in vivo. These studies have explored various approaches to K. pneumoniae phages, such as phage cocktails, phage-derived enzymes, and the synergistic utilization of phages and antibiotics. Therefore, phage therapy is old but not obsolete, particularly in light of the escalating problem of antimicrobial-resistant K. pneumoniae infections. Here, we have presented a comprehensive summary of the current knowledge on phage therapy for K. pneumoniae infections, including phage distribution, in vitro characterization of phages, in vivo investigations, and cases of clinical study. This review highlights the rapid advancements in phage therapy for K. pneumoniae, offering a promising avenue for combating this global public health threat.

Background: The Prickle2 (Pk2) gene shows promising potential in uncovering the underlying causes of epilepsy, a neurological disorder that is currently not well understood. This paper utilizes the online tool PubMed to gather and condense information on the involvement of PCP channels and the associated roles of PCP pathway molecules in the onset of epilepsy. These findings are significant for advancing epilepsy treatment. Additionally, the paper discusses future directions for clinical trials and outlines potential therapeutic targets.

Methods: This review systematically analyzes the biological functions and mechanisms of the Prickle2 gene in epilepsy. Studies were retrieved from PubMed using keywords such as "Prickle2," "epilepsy," and "PCP pathway," focusing on research published between 2000 and 2023 in English. Inclusion criteria included original studies and reviews on Prickle2's role in epilepsy. Studies unrelated to these topics or lacking sufficient data were excluded. Key data on Prickle2's functions and its link to epilepsy were extracted, and findings were summarized after a quality assessment of the literature.

Results: Although there are currently conflicting results regarding the possibility that Prickle2 may cause epilepsy in different organisms, we believe that as more cases involving Prickle2 mutations are reported and more related animal experiments are conducted, the findings will become clearer.

Conclusion: Due to the biological functions and mechanisms associated with the Prickle2 protein, it may serve as a useful biomarker or potential therapeutic target for epilepsy treatment.

Intrauterine Adhesions (IUA) are a significant cause of infertility and miscarriage, often resulting from trauma to the endometrium. While hysteroscopic adhesiolysis is the primary treatment, the use of hydrogels as anti-adhesion barriers and drug delivery systems is gaining traction for improving patient outcomes. This review aims to explore various hydrogel types, their role in tissue repair, and the integration of stem cell therapy. Recent advancements in biomaterial scaffolds have demonstrated potential in preventing adhesion recurrence and promoting endometrial regeneration. These emerging treatments provide promising avenues for enhancing the efficacy of traditional therapies in IUA management.