Current pharmaceutical design最新文献

Objective: This study aimed to preliminary explore the molecular mechanisms of Houttuynia cordata Thunb. (H. cordata; Saururaceae) in treating non-small cell lung cancer (NSCLC), with the goal of screening drug potential targets for clinical drug development.

Methods: This study employed a multi-omics and multi-source data integration approach to identify potential therapeutic targets of H. cordata against NSCLC from the TCMSP database, GEO database, BioGPS database, Metascape database, and others. Meanwhile, target localization was performed, and its possible mechanisms of action were predicted. Furthermore, dynamics simulations and molecular docking were used for verification. Multiomics analysis was used to confirm the selected key genes' efficacy in treating NSCLC.

Results: A total of 31 potential therapeutic targets, 8 key genes, and 5 core components of H. cordata against NSCLC were screened out. These potential therapeutic targets played a therapeutic role mainly by regulating lipid and atherosclerosis, the TNF signaling pathway, the IL-17 signaling pathway, and others. Molecular docking indicated a stable combination between MMP9 and quercetin. Finally, through multi-omics analysis, it was found that the expression of some key genes was closely related not only to the progression and prognosis of NSCLC but also to the level of immune infiltration.

Conclusion: Through comprehensive network pharmacology and multi-omics analysis, this study predicts that the core components of H. cordata play a role in treating NSCLC by regulating lipid and atherosclerosis, as well as the TNF signaling pathway. Among them, the anti-NSCLC activity of isoramanone is reported for the first time.

Alzheimer's disease (AD) is a gradual degenerative ailment of the nervous system that is marked by the buildup of amyloid-β plaques and neurofibrillary tangles. This accumulation causes problems with the connections between nerve cells and the loss of these cells. This review paper explores the complex pathophysiology of AD, analyzing the neuronal loss reported in key brain regions like the entorhinal cortex, amygdala, hippocampus, and cortical association areas. The text also examines subcortical nuclei participation, such as the noradrenergic locus coeruleus, serotonergic dorsal raphe, and cholinergic basal nucleus. Also, this review discusses the importance of tau protein hyperphosphorylation, oxidative stress, and metal ion dysregulation in the evolution of AD. Moreover, it explores the cholinergic theory and the influence of the APOE (apolipoprotein E) genotype on the effectiveness of therapy. This article thoroughly summarizes the current knowledge on AD, including its clinical symptoms and possible treatment approaches, by combining several theories and new targets. The study highlights the connection between the degree of tangle development and the severity of dementia, underlining the need for creative methods to tackle the complex difficulties of discovering drugs for AD.

Background: Several previous studies indicated that melatonin supplementation may positively affect glycemic control in patients with diabetes. However, research on the influence of melatonin supplementation on glycemic parameters remains inconclusive. Therefore, this study aimed to assess the impacts of melatonin supplementation on glycemic parameters in type 2 diabetes by conducting a meta-analysis.

Methods: PubMed/Medline, Scopus, and Web of Science were comprehensively searched until July 2024 to find eligible randomized clinical trials (RCTs). The overall effect sizes were estimated by using the randomeffect model and presented as weighted mean differences (WMD) with a 95% confidence interval (CI). Furthermore, the heterogeneity among the included trials was assessed by performing the Cochran Q test and interpreted based on the I² statistic.

Results: Of the 1361 papers, eight eligible RCTs were included in this meta-analysis. Our findings indicated that melatonin supplementation significantly decreased fasting blood glucose (WMD = -12.65 mg/dl; 95% CI: -20.38, -4.92; P = 0.001), insulin (WMD = -2.30 μU/ml; 95% CI: -3.20, -1.40; P < 0.001), hemoglobin A1c (WMD = -0.79 %; 95% CI: -1.28, -0.29; P = 0.002), and HOMA-IR (WMD, -0.83; 95% CI: -1.59 to - 0.07; P = 0.03).

Conclusion: According to the results of the current meta-analysis, persons with type 2 diabetes who supplement with melatonin had improved glycemic control. It looks that supplementing with melatonin at a dose exceeding 6 mg daily for over a period of 12 weeks may be more successful than other forms of intervention. Nevertheless, further research with larger sample sizes is necessary to draw definitive conclusions.

Breast Cancer stands on the second position in the world in being common and women happen to have it with high rate of about five-folds around the world. The causes of occurrence can matter with different humans be it external factors or the internal genetic ones. Breast cancer is primarily driven by mutations in the BRCA1 and BRCA2 susceptibility genes. These BC susceptibility genes encode proteins critical for DNA homologous recombination repair (HRR). Poly (ADP ribose) polymerases (PARP) are the essential enzymes involved in the repairing of the damaged DNA. So the inhibition of these inhibitors can be considered as the promising strategy for targeting cancers with defective damage in the deoxyribonucleic acid. Olaparib and talazoparib are PARP inhibitors (PARPi) are being employed for the monotherapies in case of the deleterious germline HER2-negative and BRCA-mutated breast cancer. The potency of PARP for trapping on DNA and causes cytotoxicity may have difference in the safety and efficacy with the PARPi. The PARPi have been found its place in the all different types of Breast Cancers and have shown potential benefits. The purpose of this review is to provide an update on the oral poly(ADP-ribose) polymerase (PARP)inhibitors for the improvement in the treatment and management of Breast Cancer.

Diabetic nephropathy (DN) is increasing worldwide in parallel with type 2 diabetes mellitus. Identifying diagnostic biomarkers for DN at an early stage is crucial due to the considerable societal and economic burden associated with diabetes mellitus (DM) and its risk factors. In the past, early indicators of microvascular problems, such as microalbuminuria (MA), have been used to predict the possibility of developing advanced chronic kidney disease (CKD). However, because of the incapacity of MA to appropriately estimate DN, particularly, non-albuminuric DN, additional markers have been suggested for recognizing the early renal abnormalities and structural lesions, even before MA. This study aims to assess the existing and future biomarkers used to diagnose or predict early DN. This review provides comprehensive insight into diagnostic approaches for early detection of CKD, addressing the following areas: (i) markers of glomerular damage, (ii) markers of tubular damage, (iii) oxidative stress biomarkers, (iv) inflammatory biomarkers and (v) futuristic biomarkers such as micro-ribonucleic acids (miRNAs), proteomics, metabolomics and genomics and gut microbiota. Early detection of DN may lead to improvement in clinical management and quality of life, emphasizing the importance of identifying a specific and reliable predictive biomarker. Emerging serum and urinary biomarkers offer promise for early DN diagnosis, potentially reducing prevalence and preventing progression to end-stage renal disease (ESRD). Further advancements in miRNAs, proteomics, metabolomics genomics and gut microbiota offer prospects for even earlier and more precise DN diagnosis.

Saffron, derived from the Crocus sativus plant, has been revered for centuries for its culinary, medicinal, and cultural significance. This review provides a comprehensive overview of saffron's chemical constituents and phytochemistry, elucidating its rich profile of bioactive compounds. Emphasis is placed on exploring the bio-accessibility, bioavailability, and bioactivity of saffron's phytochemicals, laying the foundation for understanding its pharmaceutical significance. The pharmaceutical importance of saffron and its phytochemicals is thoroughly examined, focusing on their diverse therapeutic properties. These include anticancer, antidiabetic, antioxidant, antimicrobial, anti-inflammatory, antinociceptive, anticonvulsant, antidepressant, learning and memory enhancement, cardiovascular, and antihypertensive properties. Such multifaceted pharmacological activities underscore saffron's potential as a valuable medicinal resource. Clinical studies investigating the efficacy and safety of saffron in various health conditions are synthesized, providing insights into its clinical applications. Moreover, toxicity assessments in animal models, encompassing acute, subacute, subchronic, and developmental toxicity, are discussed to delineate the safety profile of saffron and its bioactive constituents. Finally, recent advances and future perspectives in saffron research are highlighted, underscoring emerging trends and potential avenues for further exploration. This review serves as a comprehensive resource for researchers, clinicians, and stakeholders interested in harnessing the therapeutic potential of saffron while ensuring its safe and effective utilization in healthcare settings.

Uric acid (UA), the end-product of purine metabolism, has a complicated physiological role in the body, showing the combination of regulating inflammatory response, promoting oxidation/anti-oxidation, and modifying autophagy activity in vivo. Meanwhile, various research and theories support that inflammation, oxidative stress, and other risk factors promote the onset and progression of affective disorders and neurodegenerative diseases. Existing studies suggest that UA may be involved in the pathophysiological processes of affective disorders in various ways, and there has been a gradual advance in the understanding of the interplay between UA levels and affective disorders and neurodegenerative diseases. This review summarized the role of UA in the process of inflammation, oxidative stress, and autophagy. On this basis, we discussed the correlation between UA and affective disorders and several neurodegenerative diseases, and simultaneously analyzed the possible mechanism of its influence on affective disorders and neurodegenerative diseases, to provide a theoretical basis for UA as a biomarker or therapeutic target for the diagnosis of these diseases.

Background: Dyslipidemia and obesity hypercaloric diet-induced lead to kidney damage. We investigated the effect of curcumin on the expression of proteins related to inflammation, fibrosis, fatty acids metabolism, kidney damage, and morphological changes in the kidneys of mice hypercaloric diets-fed.

Methods: Groups of 5-week-old C57BL/6 mice (n=6) were formed: Control (C), High-fructose diet (F), Highfructose diet and curcumin (F+Cur), High-fat diet (HFD), High-fat diet and curcumin (HFD+Cur), High-fat diet and fructose (HFD+F), High-fat diet, fructose and curcumin (HFD+F+Cur), treated for 16 weeks with 30% (w/v) fructose, 60% (w/w) fat and 0.75% (w/w) curcumin. Kidneys were obtained for histomorphological and Western Blot analysis.

Results: Curcumin prevented TNF-α overexpression in the F and HFD+F groups. VLCAD expression was higher in the F, HFD, and HFD+F groups. PPARγ expression was lower in the F+Cur, HFD+Cur, and HFD+F+Cur groups. Curcumin prevented overexpression of CPT1 and KIM1 in the HFD+F and HFD groups. Curcumin prevented morphological lesions, fibrosis, and lipid deposition that were hypercaloric diet-induced.

Conclusion: Chronic consumption of hypercaloric diets causes inflammation, fibrosis, and lipid deposition in the kidney. It is suggested that curcumin prevents renal structural damage, limits tissue lipid deposition, and differentially modulates renal injury depending on diet composition in mice fed high-fat and/or high-fructose diets.

The management of neurological disorders is very challenging due to the presence of the bloodbrain barrier (BBB) that prevents the entry of drugs into the central nervous system (CNS). The advancement of metallic nanoparticles (NPs) provides a novel direction for the treatment of neurological disorders. However, there is a significant concern regarding the toxic effects of metal NPs on biological tissues like the brain. The green synthesis strategy offers a superior alternative to the traditional methods for the development of metallic NPs. Notable metal and metal oxide NPs can be produced using various bio-reductants derived from natural sources such as plant tissues, fungi, bacteria, yeast, and alga. These biological agents play double roles as they expedite the reduction process and act as capping and stabilizing agents. In this paper, we discuss the major neurological disorders and the physical barriers limiting the transport of therapeutics to the CNS. Moreover, a special focus is given to the unique features of green synthesized metallic NPs for therapeutic purposes in various neurological disorders. The insights provided will guide future research toward better outcomes and facilitate the development of innovative treatments for neurological disorders.

The oral route of drug administration is often preferred by patients and healthcare providers due to its convenience, ease of use, non-invasiveness, and patient acceptance. However, traditional oral dosage forms have several limitations, including low bioavailability, limited drug loading capacity, and stability and storage issues, particularly with solutions and suspensions. Over the years, researchers have dedicated considerable effort to developing novel oral drug delivery systems to overcome these limitations. This review discusses various challenges associated with oral drug delivery systems, including biological, pharmaceutical, and physicochemical barriers. It also explores common delivery approaches, such as gastroretentive drug delivery, small intestine drug delivery, and colon-targeting drug delivery systems. Additionally, numerous strategies aimed at improving oral drug delivery efficiency are reviewed, including solid dispersion, absorption enhancers, lipidbased formulations, nanoparticles, polymer-based nanocarriers, liposomal formulations, microencapsulation, and micellar formulations. Furthermore, innovative approaches like orally disintegrating tablets (ODT), orally disintegrating films (ODF), layered tablets, micro particulates, self-nano emulsifying formulations (SNEF), and controlled release dosage forms are explored for their potential in enhancing oral drug delivery efficiency and promoting patients' compliance. Overall, this review highlights significant progress in addressing challenges in the pharmaceutical industry and clinical settings, offering novel approaches for the development of effective oral drug delivery systems.