Current pharmaceutical design最新文献

Background: Diabetic Nephropathy (DN) is a Chronic Kidney Disease (CKD), and its main pathological changes are renal tubular injury and glomerulosclerosis. Semen Ziziphi Spinosae (SZS) is the seed of Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow. As a triterpene saponin, Jujuboside A (Ju A) is the main active substance isolated from SZS. This study sought to investigate the potential effect and mechanism of Jujuboside A against DN.

Methods: The anti-apoptotic effects of Ju A on renal parenchymal cells of DN were examined by in vivo and in vitro studies. Molecular docking and Molecular Dynamics (MD) simulation revealed that Ju A could bind to TNF-α and Caspase-3 via forming stable receptor-ligand complexes, respectively. Immunofluorescence (IF) staining and ELISA detection were carried out to investigate the potential mechanisms by which Ju A exerted its amelioration effect on DN.

Results: Our study showed that, accompanied by the restored renal function, Ju A inhibited apoptosis of renal tubules and glomeruli in vivo and in vitro. Network pharmacology revealed that 42 overlapping targets were related to Ju A and DN. Among them, IL6, IL1B, TNF, VEGFA, EGFR, ALB, IGF1, FGF2, CASP3, and ESR1 were the top 10 targets. Ju A could bind to TNF-α and Caspase-3 via forming stable receptor-ligand complexes, respectively, as demonstrated by molecular docking and MD simulation. Ju A decreased the protein levels of TNF-α and IL-1β in renal tubules and glomeruli of diabetic mice, and in HG-cultured HK-2 cells and podocytes, leading to the alleviation of inflammation. Besides, the up-regulated relative phosphorylation levels of NF-κB p65 and cleaved caspase-3 were also down-regulated by Ju A in vivo and in vitro.

Discussion: The research showed that Ju A had a high affinity for Caspase-3 and TNF-α, and the underlying mechanism of Ju A against DN was the inhibition of apoptosis in renal tubular epithelial cells and podocytes. These findings strengthened the evidence that Ju A could be a potential treatment strategy for DN and offered opportunities for therapeutic advances in the field.

Conclusion: Ju A could inhibit apoptosis and alleviate inflammation of renal parenchymal cells by inactivating the TNF-α/NF-κB p65/Caspase-3 signaling pathway, exerting renal protective effect against DN.

Peritoneal dialysis (PD) is one of the commonly used treatments for patients with end-stage renal disease (ESRD). Despite technological advances, mortality rates in patients with PD remain high. Nutritional status is an important factor affecting the prognosis of PD patients; low protein, as a complication of PD patients after dialysis, may lead to malnutrition, oedema of both lower limbs or whole body, decreased immunity, aggravation of the condition and other adverse consequences. It will also increase the mortality rate of patients and increase the incidence of cardiovascular and cerebrovascular diseases, which is considered to be the main limiting factor of PD. As a substitute for traditional glucose dialysate, Amino Acid Deritoneal Dialysate (AAD) stimulates protein synthesis by increasing amino acid availability in PD patients and inducing hyperamino acidemia due to its sugar-free and good biocompatibility. Based on literature retrieved from PubMed, Web of Science and Scopus, we found that AAD can not only effectively improve the nutritional status of PD patients, but also effectively alleviate the complications of low protein caused by traditional dialysate. Although AAD has shown promise in the treatment of low-protein patients, further randomized controlled trials are needed to verify its long-term efficacy and safety. AAD provides a new treatment option for patients with low protein, which has vital clinical significance.

Citrus fruits are an abundant source of the polyphenolic phytoconstituent naringenin, which belongs to the class of flavanones. NRG shows a lot of potential as a drug for treating a number of CNS disorders, such as neuroprotective activity, antiamyloidosis, antiparkinson, antialzheimer activity, and more. However, naringenin's hydrophobic nature, which results in limited absorption, limits its therapeutic potential. In this article, we provide an outline of the variety of nanocarriers employed for delivering naringenin as carriers. Some of them include solid lipid nanoparticles, liposomes, micelles, polymeric nanoparticles, nanostructured lipid carriers, nanosuspensions, and nanoemulsions, among others. These formulations of naringenin nanomedicine have been used for the potential treatment of a series of CNS disorders. Based on various research reports, it can be said that with the right nanocarriers, naringenin proves to be a promising therapeutic alternative for the treatment of several CNS ailments, including neurological diseases, Alzheimer's, Parkinson's disease, cerebral ischemia, etc. Therefore, the present manuscript highlights the various aspects of naringenin and its pharmacological activities. Further, naringenin-loaded nanocarriers have been enlisted and discussed in detail.

Interventions to reduce smoking prevalence aim to help patients quit smoking to cut down its hazards and related impairments in human beings. Pharmacological treatments are recommended for those with high levels of addiction because of severe physical and psychological dependence. Use of pharmacotherapy can double the odds of successful quitting. Nicotine replacement therapy (NRT), drug treatment regimens including nicotinic receptor agonists (varenicline), dopamine and norepinephrine reuptake inhibitors (bupropion), cytisinicline (cytisine), and combination therapy (NRT + medication) can be employed on a case-by-case basis. Furthermore, varenicline has been found to be more effective than the other agents in most studies. The most common adverse effects of pharmacological agents include depression, nausea, anxiety, abnormal dreams, and insomnia. On the other hand, electronic cigarettes offer another alternative to aid in smoking cessation (SC). Endurance of SC is mostly related to the employment of combined approaches, such as counselling and pharmacotherapy. This study is designed to provide an up-to-date overview of the contemporary approach to interventions aimed at helping patients in SC.

The potential of nanomedicine in cancer treatment is highlighted through the development of novel carriers for delivering anticancer drugs. By using advanced drug delivery techniques, nanomedicine, a rapidly developing therapeutic strategy, aims to maximize therapeutic efficacy while reducing adverse effects on healthy tissues. With significant benefits in targetability, stability, drug loading efficiency, and safety, nanomedicine has great potential to improve treatment outcomes and reduce off-target toxicity. More effective drugs are required for the treatment of cancer, given the annual number of new cases and millions of deaths due to the disease worldwide. Traditional cancer treatments are still not very effective against advanced metastatic cancers, despite their success in treating early-stage cancers. Thus, a vital path towards enhancing patient outcomes and lowering death rates in cancer remains a promising strategy. Porphyrin-derived nanomedicines play a crucial role in cancer treatment. Because of their specific characteristics-such as higher singletoxygen quantum yields and precise targeting-porphyrin-based nanomaterials have attracted significant interest. Such nanomaterials have great potential to maximize therapeutic effectiveness while reducing the side effects of cancer treatment. The most recent advancements in the use of porphyrin-based nanomedicine for drug delivery, imaging, and phototherapy are analyzed in this review. Drawing on a comprehensive analysis of current research, this review offers significant insights into the prospective applications of porphyrin-based nanomedicine as a flexible and potent weapon in the fight against cancer.

Objective: In this study, the causation between serum metabolites and the risk of Diabetic Nephropathy (DN) was investigated by means of a Mendelian Randomization (MR) analysis.

Methods: Our data on diabetic nephropathy were obtained from the IEU OpenGWAS Project database, while serum metabolite data originated came from the GWAS summary statistics by Chen et al. The Inverse Variance Weighted (IVW) method was the main analysis approach, with Weighted Median (WME) and MREgger regression serving as supplementary approaches to construing the causalities between serum metabolites and the DN risk. In addition to the MR-Egger regression intercept, Cochran's Q test was utilized for sensitivity analysis, with P values used as the metric to assess the results.

Results: In total, 14 SNPs regarding serum metabolites were chosen as Instrumental Variables (IVs). The IVW results indicated that levels of Behenoylcarnitine (C22), Arachidoylcarnitine (C20), and the ratio of 5-methylthioadenosine (MTA) to phosphate exerted a positive causal effect on the DN risk. Conversely, levels of 5-hydroxylysine, Butyrylglycine, 1-stearoyl-glycerophosphocholine (18:0), Isobutyrylglycine, 1-stearoyl-2- oleoyl-GPE (18:0/18:1), N2,N5-diacetylornithine, 2-butenoylglycine, 3-hydroxybutyroylglycine, N-acetylisoputreanine, the ratio of Arginine to Ornithine, and the ratio of Aspartate to Mannose exerted a negative impact of causality on the DN risk. By identifying these serum metabolites, high-risk patients can be recognized in the early stages of diabetic nephropathy, enabling preventive measures or delaying its progression. These findings also provide a solid foundation for further research into the underlying etiology of diabetic nephropathy.

Conclusion: The translation of serum metabolites into clinical applications for DN aims to utilize changes in serum metabolites as biomarkers for early diagnosis, thereby monitoring the progression of DN and providing a foundation for personalized treatment. For instance, the development of serum metabolite diagnostic kits could be used for early detection and prevention of DN. Changes in metabolites can help identify different stages of DN.

This review discusses the latest progress in using smart polymeric materials for making medical implants with advanced three-dimensional (3D) and four-dimensional (4D) printing techniques. These smart polymers, also known as stimuli-responsive polymers, can change their properties when exposed to external triggers like temperature, pH, light, or magnetic fields. Integrating these materials with 3D/4D printing allows the creation of highly customizable and functional implants that can adapt to the body's environment. This means implants can now perform additional tasks, such as releasing drugs or changing shape when needed. The review covers different 3D/4D printing methods, the types of smart polymers available, and the benefits of using these materials in medical implants. It also addresses the challenges faced in developing these advanced implants, such as finding suitable materials that are safe for the body and ensuring precise manufacturing. The future prospects of these innovative implants are promising, with potential applications in personalized medicine and non-invasive treatments. This review aims to provide a detailed analysis of recent advancements in stimuli-responsive polymeric materials utilized in additive manufacturing of medical implants. The objective is to explore these materials' clinical implications, address the unique challenges in their development and fabrication, and outline their future potential in enhancing personalized and non-invasive medical treatments.

Introduction: Endometriosis, a prevalent women's health condition, is associated with persistent pelvic pain and infertility. Despite ongoing research, its precise disease mechanism remains elusive, impeding the discovery of a definitive cure. However, the progression of this disease is driven by three central factors, namely estrogen, progesterone, and inflammatory processes. The current work summarizes an evaluation of hormonal drug therapy in endometriosis, highlighting pathogenesis, clinical studies, and the anticipated role of AI in improving diagnostic accuracy and therapeutic results.

Methods: Current information related to endometriosis and the application of AI in its diagnosis and treatment were evaluated through an in-depth literature search in the PubMed database and Google Scholar search engine.

Results: The current treatment modalities for this disease encompass drug therapy and surgery. In line with key contributing factors, the first-line pharmaceutical treatment revolves around progestin therapy, which involves administration either alone or in combination with a small amount of estrogen. Each medication is linked to certain drawbacks, encompassing bone loss associated with progesterone-only therapy, considerable cost implications, and heightened risks of bleeding, spotting, and drug intolerance when utilizing combined progesterone-estrogen therapy.

Conclusion: Many clinical studies on endometriosis are currently investigating the overall impact of the therapeutic approach involving progesterone-estrogen therapy with respect to the treatment of pelvic pain, health-related quality of life, cost-effectiveness, and tolerability. The rise of artificial intelligence and its advanced data processing capabilities present a promising opportunity to revolutionize endometriosis diagnosis and treatment by offering novel approaches.

Introduction: In this study, pure and cobalt manganese-doped ZnO nanoparticles (Zn_(1-x-y)Mn_xCo_yO NPs) at varying concentrations were synthesized through sol-gel method, and zinc acetate dihydrate, manganese nitrate, cobalt acetate, and diethyl amine were used as precursors, with samples finally calcined at 700oC.

Methods: The hexagonal wurtzite structure of pure and co-doped ZnO NPs was confirmed by X-ray diffraction (XRD). The computed grain sizes of pure and co-doped ZnO NPs, according to Scherrer's formula, were 32 nm, 32.5 nm, 36.3 nm, and 36.5 nm, respectively. Scanning electron microscope (SEM) was used to observe the morphology of nanoparticles. FTIR spectroscopy was used to examine the chemical make-up and vibrational modes of pure and co-doped ZnO NPs. The bandgaps of pure and doped ZnO were examined using UV-Vis spectroscopy.

Results: It was found that the optical bandgap of ZnO was lowered by 3.21 eV by manganese and cobalt doping. Elemental composition analysis was performed by using EDX analysis. Finally, anticancer activity of pure and co-doped ZnO NPs was assessed by employing MTT assay, which indicated that Zn_0.8 Mn_0.1 Co_0.1O NPs showed significant anticancer results against liver cancer (HepG2) cells as compared to ZnO, Zn_0.98 Mn_0.01Co_0.01O and Zn_0.90 Mn_0.05 Co_0.05O NPs. Moreover, Zn_0.8 Mn_0.1 Co_0.1O NPs showed low toxicity and good biocompatibility comparable to doxorubicin (DOX).

Conclusion: Comprehensive experimental findings have demonstrated an authentic way of obtaining feasible in vivo liver cancer therapy.

With the development of microfluidics technology, it is now possible in medical biotechnology to examine clinical and rapid diagnostic operations involving pathogens, like bacteria and viruses. The method of separating bacteria from complicated homogeneous and heterogeneous samples is one of the most important steps in the diagnostic process. The microfluidic technology for bacterial separation offers a better and more promising platform by combining several physical properties and characteristics of bacteria. In contrast, the conventional method is time-consuming, limited to a few cell properties, and necessitates the completion of several challenging steps and processes involving skilled manpower. The microfluidics platform also has a number of advantages, including small-scale size, low cost, high efficiency, and simultaneous detection and execution of further steps. This enables cell separation, analysis, and experimental processing on a single chip. In this paper, we have analysed the mechanism of the bacterial separation process depending on phenocharacteristics along with their benefits, constraints, and applications. In addition, the performance metrics needed for the separation of the devices along with the challenges and future possibilities of developed devices, which are described in the literature, are discussed in detail. Thus, this review offers a holistic analysis of the separation of bacteria using microfluidic technology.