Drug Design, Development and Therapy

[This corrects the article DOI: 10.2147/DDDT.S207310.].

INTRODUCTION: Itraconazole follows non-linear pharmacokinetics and hence is recommended once daily, but in real-world practice, is commonly prescribed as twice daily. Hence, this study aimed to evaluate the efficacy and safety of super-bioavailable-itraconazole-130 mg (SB-130) and conventional-itraconazole-200 mg (CITZ-200) once daily compared with conventional-itraconazole-100 mg (CITZ-100) twice daily in glabrous tinea. METHODS: A total of 261 eligible patients were enrolled in this prospective, randomized, clinical study from December-2021 to August-2022 at seven centers in India...

PURPOSE: To examine whether intraoperative dexmedetomidine reduces postoperative delirium (POD) in elderly patients who underwent a laryngectomy. METHODS: Patients were randomly assigned to receive dexmedetomidine or a saline placebo infused during surgery. The study period was July 2020 to January 2022. Participants were elderly individuals (≥65 years) who underwent a laryngectomy. Immediately after induction of anesthesia, a 0.5 μg.kg-1 bolus of study solution was administered for 10 min, followed by a maintenance infusion of 0...

Cancer, as the leading cause of death worldwide, poses a serious threat to human health, making the development of effective tumor treatments a significant challenge. Natural products continue to serve as crucial resources for drug discovery. Among them, Withaferin A (WA), the most active phytocompound extracted from the renowned dietary supplement Withania somnifera (L.) Dunal, exhibits remarkable anti-tumor efficacy. In this manuscript, we aim to comprehensively summarize the pharmacological characteristics of WA as a potential anti-tumor drug candidate, with the objective of contributing to its further development and the discovery of prospective drugs...

[This retracts the article DOI: 10.2147/DDDT.S208703.].

BACKGROUND: Remimazolam is a novel benzodiazepine narcotic. When used for gastrointestinal endoscopy or bronchoscopy, it provides adequate sedation and rapid recovery. However, studies on the optimal initial loading dose of remimazolam remain inadequate. Therefore, we conducted a randomized controlled clinical trial to investigate the efficacy and safety of different doses of remimazolam applied in upper gastrointestinal endoscopy. METHODS: A total of 218 patients scheduled for upper gastrointestinal endoscopy were included in our trial and divided into experimental and control groups: the experimental groups were the remimazolam groups (R1 of 0...

PURPOSE: Evaluate the efficacy and safety of remimazolam besylate combined with esketamine for outpatient colonoscopy. PATIENTS AND METHODS: A total of 150 outpatients undergoing colonoscopy were randomized into two groups. A MOAA/S score ≤3 was maintained. The primary outcome was the rate of successful colonoscopy completion. Time indicators, hemodynamic parameters, the consumption of lidocaine, esketamine, propofol and remimazolam besylate, MOAA/S scores and bispectral index (BIS) values, the lowest SpO2 , body movement, the use of rescue medication, endoscopist and patient satisfaction, recall of the procedure, mini-mental state examination (MMSE), fatigue level and adverse events were recorded...

Degenerative eye conditions such as age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusion are major contributors to significant vision loss in developed nations. The primary therapeutic approach for managing complications linked to these diseases involves the intravitreal delivery of anti-vascular endothelial growth factor (VEGF) treatments. Faricimab is a novel, humanised, bispecific antibody that simultaneously binds all VEGF-A isoforms and Angiopoietin-2, which has been approved by regulatory agencies, such as the US Food and Drug Administration (FDA), the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA), for the treatment of neovascular AMD and diabetic macular oedema (DMO)...

No abstract text is available yet for this article.

PURPOSE: To elucidate the potential mechanisms of QFY for the treatment of Alzheimer's Disease (AD), and explore the effective substances of QFY. MATERIALS AND METHODS: UPLC-LTQ-Orbitrap-MS was used to identify the chemical constituents of the serum samples and the cerebrospinal fluid samples of rats after QFY administration. Network pharmacology was used to predict potential targets and pathways of QFY against AD. The AD mice model was established by subcutaneous injection of D-gal for 8 consecutive weeks...

PURPOSE: Thalidomide (Tha) can be used as a selective treatment for mild pemphigus vulgaris (PV). However, the specific mechanism of action remains unclear. PATIENTS AND METHODS: PV IgG extracted from patients' serum was cocultured with HaCaT cells to construct a PV cell model, and different concentrations of Tha were used to screen the drug effect. The expression level of MYD88 was assessed in skin lesions of PV patients. Intracellular Ca2+ concentration, reactive oxygen species level, DSG3, PG, MYD88, apoptosis-related proteins (Caspase-3, Bcl-2, and Bax), NF-κB pathway-related proteins (IκBα, p-IκBα, p50, and p65), NLRP3, IFN-γ, TNF-α, IL-6, and IL-8 levels were measured...

BACKGROUND: Epidemiological studies have indicated that lung injury is a frequent complication of sepsis. Mitophagy is vital to multiple pathological processes and diseases; however, its influence on sepsis-induced acute lung injury remains elusive. Melatonin has multiple antioxidant action and anti-inflammatory effects, including regulating mitophagy and inflammatory cytokine expression. Whereas, little is known about the affection of melatonin and mitophagy on CLP-induced ALI. METHODS: The in vivo effect of melatonin on OPTN-mediated mitophagy was studied by CLP-induced ALI in a mouse model using C57BL/6 followed by treatment with vehicle and melatonin (30 mg/kg/d, intraperitoneal injection)...

PURPOSE: Matrine (Mat), the main active ingredient of traditional Chinese herbal plant Sophora flavescens Ait , has significant antitumor effects, but its pharmacological mechanism on colon cancer (CC) remains unclear. This study aimed to investigate the therapeutic effect of Mat on CC as well as the potential mechanism. METHODS: The vasculogenic mimicry (VM) of CC cells was observed by three-dimensional (3D) Matrigel cell culture. Cell proliferation, apoptosis, migration, invasion, and actin filament integrity were detected by CCK8, flow cytometry, wound healing, Transwell and Phalloidin staining assays...

PURPOSE: This study aims to confirm the efficacy of Xijiao Dihuang decoction (XJDHT), a classic prescription, in treating psoriasis and to explore the potential therapeutic mechanism. METHODS: For pharmacodynamic analysis, a mouse model of imiquimod cream (IMQ)-induced psoriasis was constructed. Active ingredients and genes of XJDHT, as well as psoriasis-related targets, were obtained from public databases. Intersecting genes (IGEs) of XJDHT and psoriasis were collected by Venn Diagram...

The intestine, often referred to as the "second brain" of the human body, houses a vast microbial community that plays a crucial role in maintaining the host's balance and directly impacting overall health. Probiotics, a type of beneficial microorganism, offer various health benefits when consumed. However, probiotics face challenges such as acidic conditions in the stomach, bile acids, enzymes, and other adverse factors before they can colonize the intestinal tissues. At present, pills, dry powder, encapsulation, chemically modified bacteria, and genetically engineered bacteria have emerged as the preferred method for the stable and targeted delivery of probiotics...

Artificial intelligence (AI) and machine learning (ML) represent significant advancements in computing, building on technologies that humanity has developed over millions of years-from the abacus to quantum computers. These tools have reached a pivotal moment in their development. In 2021 alone, the U.S. Food and Drug Administration (FDA) received over 100 product registration submissions that heavily relied on AI/ML for applications such as monitoring and improving human performance in compiling dossiers. To ensure the safe and effective use of AI/ML in drug discovery and manufacturing, the FDA and numerous other U...

No abstract text is available yet for this article.

PURPOSE: To investigate the effectiveness of modified Bu-Shen-Yi-Qi decoction (MBSYQ) in the treatment of osteoporosis associated with chronic obstructive pulmonary disease (COPD) and its underlying mechanisms of action. METHODS: Disease targets, active ingredients and targets were predicted by TTD, CTD, DisGeNET, HERB (BenCaoZuJian as its Chinese name), and multiple-TCM databases; In addition, the screened targets were performed via the online platforms DAVID 6...

PURPOSE: This study aimed to investigate the molecular mechanisms of isoliensinine, a kind of bibenzyl isoquinoline alkaloid which isolated from a TCM named Lotus Plumule ( Nelumbo nucifera Gaertn ), in treating renal interstitial fibrosis (RIF) by using RNA sequencing, KEGG analysis and in vivo experimental approaches. METHODS: Spontaneous hypertension rats (SHRs) were randomly assigned into five groups, consisting of SHR, SHR+Isoliensinine-L (2.5 mg/kg/day), SHR+Isoliensinine-M (5 mg/kg/day), SHR+Isoliensinine-H (10 mg/kg/day), and SHR+Valsartan (10 mg/kg/day) groups (n = 6 for each group)...

Due to the complex mechanism and limited treatments available for pulmonary fibrosis, the development of targeted drugs or inhibitors based on their molecular mechanisms remains an important strategy for prevention and treatment. In this paper, the downstream signaling pathways mediated by VEGFR and LPAR1 in pulmonary cells and the role of these pathways in pulmonary fibrosis, as well as the current status of drug research on the targets of LPAR1 and VEGFR2, are described. The mechanism by which these two pathways regulate vascular leakage and collagen deposition leading to the development of pulmonary fibrosis are analyzed, and the mutual promotion of the two pathways is discussed...