Drug Research最新文献

The study investigates the potential of combining Kaempferol (KAE) and Paclitaxel (PAC) to enhance anti-cancer effects and induce apoptosis in MDA-MB-468 triple-negative breast cancer cells and human normal foreskin fibroblast cells.For this porpose, the cells were treated with PAC, KAE, and their combination for 24, 48, and 72 hours. Cytotoxicity was assessed via MTT assay, and synergy was evaluated using Combination Index analysis. Apoptosis was quantified via Annexin V/PI staining and DAPI staining. Flow cytometry analyzed cell cycle arrest, while qPCR assessed apoptotic gene expression.The combination of KAE and PAC exhibited a synergistic anti-proliferative effect, significantly reducing MDA-MB-468 cell viability compared to monotherapies. Annexin V/PI staining revealed an increased apoptotic rate (73%) in co-treated cells, with enhanced chromatin condensation and nuclear fragmentation observed via DAPI staining. Flow cytometry indicated a marked increase in SubG1 phase cells, confirming apoptosis induction. Gene expression analysis demonstrated upregulation of pro-apoptotic BAD and downregulation of anti-apoptotic Bcl-2 and Mcl-1, highlighting the activation of apoptosis pathways.The combination of PAC and KAE enhances cytotoxicity, promotes apoptosis, and alters key apoptotic gene expressions in MDA-MB-468 cells while sparing normal fibroblast cells. These findings suggest a promising therapeutic strategy for triple-negative breast cancer.

It has been suggested that caution should be exercised when using HMG-CoA reductase inhibitor (statin) in combination with a drug of the fibrate family because of the potentially elevated risk of development of hepatic function impairment and myopathy. We conducted this present study to evaluate the efficacy and safety of treatment with a statin plus pemafibrate (a new fibrate) versus treatment with pemafibrate alone in Japanese patients with type 2 diabetes mellitus.In this study, a total of 23 Japanese patients with type 2 diabetes mellitus were divided into two groups: a group that received pemafibrate alone and a group that received pemafibrate+a statin for a period of 3 years, respectively. Blood levels of lipids and hepatic and renal function parameters were measured before and one and three years after the start of treatment.The pemafibrate-alone group showed reduction of the blood lipid levels, but no adverse changes of the hepatic or renal function parameters were observed. Similarly, the combined pemafibrate+statin treatment group also showed lowering of the blood lipid levels without any adverse changes of the parameters.Improvement of the blood lipid profile was observed in patients who received prolonged treatment with pemafibrate. Similarly, improvement of the blood lipid profile without any adverse changes of the hepatic or renal function parameters was also observed in patients who received prolonged combined pemafibrate+statin treatment. Thus, our findings confirm the safety and efficacy of pemafibrate administered either alone or in combination with a statin.

A complex and multifaceted metabolic disease, type 2 diabetes mellitus (T2DM) is becoming a significant public health concern. Due to their many biological characteristics, bioactive compounds from herbal medicine have been shown in multiple studies to have positive benefits on the prevention and control of type 2 diabetes. The scientific community is becoming more interested in curcumin, one of these therapeutic herbs. The plant Curcuma longa, often known as turmeric, has a bioactive compound called curcumin in its rhizome. Antioxidant, cardio-protective, anti-inflammatory, anti-microbial, nephro-protective, anti-neoplastic, hepato-protective, immunomodulatory, hypoglycemic, and anti-rheumatic effects are among the various pharmacological and biological effects of curcumin that have been reported by both in vitro and in vivo studies. Curcumin extract increases -cell functioning, delays the onset of diabetes, inhibits -cell death, and lowers insulin resistance in animal models. Recent preclinical studies and clinical trials have shown strong evidence of curcumin's vital roles in preventing type 2 diabetes via a number of pathways. Thus, the antidiabetic action of curcumin and its many mechanisms are comprehensively summarized in this study. The findings indicated that curcumin's anti-inflammatory, anti-oxidant, antihyperglycemic, antiapoptotic, and antihyperlipidemic properties, among others, account for its success in treating type 2 diabetes. These findings suggest that curcumin could be a potential option for T2DM prevention and management.

Both local and systemic medication delivery benefit greatly from the sublingual and buccal modes of administration. They have shown to be a successful substitute for the conventional oral route, particularly in situations requiring a quick commencement of action. Via venous drainage to the superior vena cava, drugs can enter the systemic circulation quickly and directly. They are therefore helpful for individuals who have trouble swallowing as well as for medications that are highly cleared by the liver or degraded in the gastrointestinal system. Traditionally, medications that are delivered through the buccal and sublingual channels are made in three different dose forms: liquid (such as sprays and drops), semi-solid (such as gels), and solid (such as pills, wafers, films, and patches). Physiological variables frequently influence conventional dose forms, which might decrease the formulation's interaction with the mucosa and result in unexpected medication absorption. Many formulation development advancements have been made to enhance medication absorption and retention in the buccal and sublingual areas. The physiological factors influencing buccal and sublingual drug delivery as well as developments in nanoparticulate drug delivery techniques for sublingual and buccal administration will be the main topics of this review. It also discusses about the clinical development pipeline, which includes formulations that have been authorized and are undergoing clinical studies.

Gynecological cancers, including ovarian, cervical, and endometrial malignancies, contribute significantly to the global cancer burden. Oncolytic virotherapy (OVT), using both double-stranded DNA viruses (such as adenovirus, vaccinia, and herpesvirus) and single-stranded RNA viruses (including positive-sense viruses like coxsackievirus and poliovirus, and negative-sense viruses like measles and Newcastle disease virus), has emerged as a promising therapeutic approach. This review aims to evaluate the current state and future prospects of OVT in treating gynecological cancers.A literature search was conducted from December 2005 to December 2024 using databases like PubMed, Scopus, and Web of Science with keywords such as "oncolytic virotherapy," "gynecological cancers," and specific virus types. Studies were included after assessing the efficacy, safety, mechanisms of action, and combinatorial use of OVT with other therapies. Exclusions included non-English publications, non-gynecological cancer studies, and those without relevant clinical or experimental data. This review thoroughly explores OVT's potential in gynecological cancer treatment.Oncolytic virotherapy demonstrates transformative potential for managing gynecological cancers. Whether used as monotherapy or in combination with other treatments, OVT shows promise in improving therapeutic outcomes and patient survival. However, further research is necessary to optimize its clinical application.

Src (non receptor tyrosine kinase) plays a role in multiple pathways leading to tumor survival, proliferation and metastasis. Inhibiting Src kinase would be a therapeutic benefit in Src dependent cancers. Most of the nitrogen containing heterocyclic moieties found to possess variety of biological activities. Combination of heterocyclic nucleus to active hybrids has proven to be a successful method of approach to augment biological activities. Hence a series of pyrimidine-morpholine hybrids were designed and its shape similarity studies calculated with the standard Dasatinib using Tanimoto coefficient. Designed molecules were docked with human tyrosine kinase (PDB ID: 2SRC) using AutoDock vina. Docked poses were ranked based on their binding affinities which are then compared with a reference. The studies revealed that docking of hybrid molecules with 2SRC showed promising interactions with affordable ADMET properties. The stability of highly docked complex was analyzed by molecular simulation studies and the results confirmed the docking outcomes thereby making it as a potential SRC kinase inhibitor. Hence these novel pyrimidine hybrids can be considered as lead molecules for developing novel druggable moieties for breast cancer research.

To detect the gender variations in adverse events (AEs) of voriconazole, promote personalised medicine.A normalized dataset from Q1 2004 to Q4 2022 from the US Food and Drug Administration's Adverse Event Reporting System (FAERS) was analyses. The reporting odds ratio (ROR), proportional reporting ratio (PRR), and P value were used to examine data from the FAERS database to detect risk signals and quantify the presence and extent of gender variations in voriconazole adverse events.A total of 7670 cases (female/male (2785/4885)) of adverse reactions to voriconazole were analysed, and drug interaction (ROR 1.30 (1.10,1.54)), death and sudden death (ROR 1.31 (1.06,1.61)), actinic keratosis (ROR 1.98 (1.10,3.57)) were found to be significantly more frequent in male patients than in female patients.We found that gender was a determinant in voriconazole-related AEs using FAERS. Our results require future validation due to the inherent limits of this open data source, but they also identify potential contributing elements for a customised side effect profiling.

Our current research aims to investigate how Resveratrol influences DOX-induced apoptosis in Saos-2 cells resulting from DNA damage.Saos-2 cells were cultured with DOX, and an MTT assay was conducted to evaluate cell viability. The expression levels of DNA damage markers were evaluated using qRT-PCR and western blotting methods. Apoptosis was also investigated by flow cytometry.In a dose-dependent way, DOX produced a profuse suppression of cell proliferation. This study investigates the effect of Resveratrol on DOX-induced apoptosis due to DNA damage in Saos-2 cells (P<0.05). There was an increase in H2AX, ATR, ATM, Rad51, and p53 expression, possibly contributing to subsequent apoptosis. Furthermore, Resv enhanced the apoptosis caused by DOX in Saos-2 cells.The findings from the current research provide an understanding of how Resv plays a role in potentially treating osteosarcoma by enhancing DOX-induced apoptosis.

Benign prostatic hyperplasia is a common urological condition in aging men. The anthelmintic agent niclosamide ethanolamide exhibits a wide range of pharmacological activities. This study aimed to evaluate the protective effect of niclosamide ethanolamide in testosterone propionate-induced benign prostatic hyperplasia in rats along with elucidating the probable mechanism of action by investigating the influence on PPAR-γ and Wnt/β-catenin. 40 male Wistar rats were divided randomly into 4 groups. The healthy (control) group, received daily oral and subcutaneous administration of the vehicle. The Induced (TP) group, received only a daily dose of testosterone propionate 3 mg/kg, SC for 28 days. The treated groups (TP+FIN) and (TP+NE), received a concomitant administration of a daily dose of testosterone propionate along with finasteride 5 mg/kg/day and niclosamide ethanolamide 50 mg/kg/day respectively through oral gavage. Animals were euthanized on day 30 of the experiment and prostate tissue samples were collected to evaluate prostate index, prostate hyperplastic markers by ELISA, and gene expression by RT-qPCR. Results revealed that niclosamide ethanolamide significantly reduced prostate index compared to the induced (TP) group (P<0.0001). The agent nearly normalized BPH markers including 5α-reductase type-2 enzyme, dihydrotestosterone, and PCNA compared to the induced (TP) group (P<0.0001). The agent reduced the tissue level of β-catenin while elevating PPAR-γ to control levels (P<0.05). The current study revealed that NE can help prevent BPH in rats by upregulating the PPAR-γ receptor and inhibiting the Wnt pathway.

Canagliflozin is a synthetic sodium glucose transporter inhibitor (SGLT2i). It is the latest approved class of medicine used in the treatment of type 2 diabetes mellitus. As diabetes is emerging as the most common metabolic disorder, SGLT2i has lightened up the path of treatment with additional benefits. SGLT2 is located in the proximal convoluted tubules of the nephron and is responsible for glucose reabsorption. Thus, inhibiting the SGLT2 leads to a decline in glucose concentration in the plasma. The secondary effects of canagliflozin, such as cardiac protection, renoprotective, and decreased obesity, have made it more putative in the treatment of diabetes mellitus. There are some side effects of canagliflozin, such as volume depletion, genital and urinary tract infection, and lower limb amputation, which could be a matter of concern for patients. Being an anti-diabetic drug, canagliflozin also possesses anti-inflammatory and anti-cancer properties. Several studies have been conducted to determine the efficacy of canagliflozin as an anti-cancer agent. Its pharmacokinetics indicate rapid absorption, reaching peak plasma concentrations within 1-2 hours. With a half-life of approximately 12 hours, it undergoes minimal hepatic metabolism and is primarily excreted unchanged via urine. Common adverse drug reactions (ADRs) include urinary tract infections and dehydration. Clinical trials on canagliflozin, both alone and in combination with other diabetes complications, have been conducted, with some completed and others in various phases. This review article contains information about the pharmacokinetics, drug safety, and efficacy profile of canagliflozin, along with details regarding toxicological studies of canagliflozin.