Current pharmaceutical design最新文献

{"title":"Inhibition of Colorectal Cancer Metastasis by Total Flavones of Abelmoschus Manihot via Lncrna AL137782-mediated STAT3/EMT Pathway Regulation","authors":"Qian Li, Hui Zhang, Yongshan He, Hao Zhang, Conghui Han","doi":"10.2174/0113816128298998240828060306","DOIUrl":"https://doi.org/10.2174/0113816128298998240828060306","url":null,"abstract":"Background: Colorectal cancer (CRC) ranks among the most lethal malignancies globally, particularly following metastasis which results in poor prognosis. In recent years, CRC incidence in China has persistently increased. Total flavonoids (TFA) from Abelmoschus manihot, a natural compound, are recognized for their anti-inflammatory, analgesic, and antioxidant properties. However, despite extensive research into the therapeutic potential of TFA, coverage of its role in cancer treatment is notably lacking. To address this research void, our study aims to unveil the role and potential mechanisms of TFA in treating CRC. Methods: We conducted a series of experiments to assess the impact of TFA on CRC cells. Two specific CRC cell lines, DLD-1 and HCT116, were employed in cell proliferation, colony formation, flow cytometry, and cell migration assays. Additionally, to test the in vivo effects of TFA, we developed a nude mouse xenograft tumor model to assess TFA's impact on tumor growth and liver metastasis. Furthermore, we meticulously analyzed the gene expression differences between CRC cells pretreated with TGF-β and those treated with TFA using RNA-seq technology. We also examined the molecular mechanisms of TFA and assessed the expression of proteins related to the STAT3/EMT signaling pathway through Western blotting and siRNA technology. Results: Our research findings reveal for the first time the effect of TFA on CRC cells. Result shows that TFA could suppress cell proliferation, migration, and induce apoptosis. In vivo results showed that TFA inhibited tumor growth and liver metastasis. Molecular mechanism studies have shown that TFA exerts these effects by upregulating the expression of non-coding RNA AL137782, inhibiting the EMT/STAT3 signaling pathway. These results suggest that TFA is a potential candidate for mitigating CRC metastasis. Conclusion: However, further research is needed to comprehensively evaluate the efficacy and safety of TFA in animal models and clinical settings. These findings bring great hope for the development of innovative CRC treatment methods.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"52 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Hepatocellular Carcinoma Pathogenesis: The Influence of Genetic Polymorphisms.","authors":"Samaneh Mollazadeh, Nikoo Saeedi, Abdulridha Mohammed Al-Asady, Elnaz Ghorbani, Majid Khazaei, Mikhail Ryzhikov, Amir Avan, Seyed Mahdi Hasanian","doi":"10.2174/0113816128327773240827062719","DOIUrl":"https://doi.org/10.2174/0113816128327773240827062719","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is influenced by several factors, among which genetic polymorphisms play a key role. Polymorphisms in various genes affect key pathways involved in HCC development, including metabolism, expression of inflammatory cytokines, cell proliferation, and apoptosis regulation. These polymorphisms induce differential effects on susceptibility to HCC, disease progression, and treatment outcomes. Understanding the effect of genetic variations on HCC pathogenesis is essential to elucidate underlying mechanisms and identify potential therapeutic targets. This review explores the diverse roles of genetic polymorphisms in HCC, providing insights into the complex interplay between genetic factors and disease development.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health Benefits and Safety of Postbiotics Derived from Different Probiotic Species.","authors":"Siyavash Ghadiri Harat, Hadi Pourjafar","doi":"10.2174/0113816128335414240828105229","DOIUrl":"https://doi.org/10.2174/0113816128335414240828105229","url":null,"abstract":"<p><p>Nowadays, the usage of probiotics in the food industry has become common. It has been proven that probiotics have many health benefits, such as adjusting the intestinal microbiome, boosting the immune system, and enhancing anti-inflammatory and anti-cancer activities. However, in recent years, some concerns have arisen about the consumption of probiotics, especially in vulnerable populations such as elderly, infants, and people with underlying diseases. As a result, finding a new alternative to probiotics that has the same function as probiotics and is safer has been prioritized. In recent years, postbiotics have been introduced as a great replacement for probiotics. However, the safety of these compounds is not exactly confirmed due to the limited in vivo research. In this review, the definition, classification, activities, limitations, and some advantages of postbiotics over probiotics are discussed. Finally, the limited published data about the safety of postbiotics is summarized.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Revolutionary Approach for Combating Efflux Transporter-mediated Resistant Epilepsy: Advanced Drug Delivery Systems.","authors":"Megha Tonk, Indu Singh, Ram Jee Sharma, Shikha Baghel Chauhan","doi":"10.2174/0113816128332345240823111524","DOIUrl":"https://doi.org/10.2174/0113816128332345240823111524","url":null,"abstract":"<p><p>Epilepsy is a persistent neurological condition that affects 60 million individuals globally, with recurrent spontaneous seizures affecting 80% of patients. Antiepileptic drugs (AEDs) are the main course of therapy for approximately 65% of epileptic patients, and the remaining 35% develop resistance to medication, which leads to Drug-Resistant Epilepsy (DRE). DRE continues to be an important challenge in clinical epileptology. There are several theories that attempt to explain the neurological causes of pharmacoresistance in epilepsy. The theory that has been studied the most is the transporter hypothesis. Therefore, it is believed that upregulation of multidrug efflux transporters at the blood-brain barrier (BBB), such as P-glycoprotein (P-gp), which extrudes AEDs from their target location, is the major cause, leading to pharmacoresistance in epilepsy. The most effective strategies for managing this DRE are peripheral and central inhibition of P-gp and maintaining an effective concentration of the drug in the brain parenchyma. Presently, no medicinal product that inhibits P-gp is being used in clinical practice. In this review, several innovative and promising treatment methods, including gene therapy, intracranial injections, Pgp inhibitors, nanocarriers, and precision medicine, are discussed. The primary goal of this work is to review the P-gp transporter, its substrates, and the latest novel treatment methods for the management of DRE.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advancement in Drug Development for Treating Malaria using Herbal Medicine and Nanotechnological Approach.","authors":"Sarvesh Bhargava, Rohitas Deshmukh, Hitesh Kumar Dewangan","doi":"10.2174/0113816128321468240828103439","DOIUrl":"https://doi.org/10.2174/0113816128321468240828103439","url":null,"abstract":"<p><p>More than two hundred million people around the world are infected with malaria, a blood-borne disease that poses a significant risk to human life. Single medications, such as lumefantrine, primaquine, and chloroquine, as well as combinations of these medications with artemisinin or its derivatives, are currently being used as therapies. In addition, due to rising antimalarial drug resistance, other therapeutic options are needed immediately. Furthermore, due to anti-malarial medication failures, a new drug is required. Medication discovery and development are costly and time-consuming. Many malaria treatments have been developed however, most treatments have low water solubility and bioavailability. They may also cause drug-resistant parasites, which would increase malaria cases and fatalities. Nanotechnology may offer a safer, more effective malaria therapy and control option. Nanoparticles' high loading capacity, concentrated drug delivery, biocompatibility, and low toxicity make them an attractive alternative to traditional therapy. Nanotechnology-based anti-malarial chemotherapeutic medications outperform conventional therapies in therapeutic benefits, safety, and cost. This improves patient treatment compliance. The limitations of malaria treatments and the importance of nanotechnological approaches to the treatment of malaria were also topics that were covered in this review. The most recent advancements in nanomaterials and the advantages they offer in terms of medication delivery are discussed in this article. The prospective therapy for malaria is also discussed. Additionally, the limitations of malaria therapies and the importance of nanotechnology-based approaches to the treatment of malaria were explored.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oligoprotective Activity of Levetiracetam Against Glutamate Toxicity: An in vitro Study.","authors":"Mohaddeseh Sadat Alavi, Abdulridha Mohammed Al-Asady, Farzaneh Abbasinezhad- Moud, Arezoo Rajabian, Zahra Rastegartizabi, Hamid R Sadeghnia","doi":"10.2174/0113816128327215240827071257","DOIUrl":"https://doi.org/10.2174/0113816128327215240827071257","url":null,"abstract":"<p><strong>Introduction: </strong>The role of glutamate in the development of some brain pathological conditions, such as multiple sclerosis, has been well described. Levetiracetam (LEV), a new broad-spectrum antiseizure medicine, is widely used to control certain types of seizures.</p><p><strong>Method: </strong>Apart from its anti-seizure activity, LEV exerts neuroprotection via anti-inflammatory, antioxidant, and antiapoptotic effects. The current study was designed to evaluate the protective potential of LEV against glutamate-induced injury in OLN-93 oligodendrocytes.</p><p><strong>Method: </strong>At first, the potential negative impact of LEV on OLN-93 viability was evaluated. After that, the cells were concurrently treated with LEV (0-100 μM) and glutamate (8 mM) for 24 h. The viability, redox status, and the rate of apoptosis of OLN-93 cells were then assessed using 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl-2H-tetrazolium bromide (MTT), 2',7' dichlorodihydrofluorescein diacetate (H2DCFDA), 2-thiobarbituric acid reactive substances (TBARS) and annexin V/propidium iodide (PI) assays, respectively. Moreover, caspase-3 expression, as a marker of cell apoptosis, was evaluated by western blotting.</p><p><strong>Results: </strong>LEV at 1-800 μM did not have any negative effect on cell survival. Treatment with LEV (50 and 100 μM) substantially enhanced the cell viability following glutamate insult. The cytoprotective activity of LEV (50 and 100 μM) against glutamate toxicity was accompanied by reduced Reactive Oxygen Species (ROS) accumulation and Malondialdehyde (MDA) level. Moreover, 100 μM of LEV inhibited apoptosis and decreased the expression level of cleaved caspase-3 following glutamate exposure.</p><p><strong>Conclusion: </strong>Taken together, the results suggested that LEV has protective effects against glutamate-mediated cytotoxicity in OLN-93 cells. The oligoprotective action of LEV was shown to be exerted via inhibition of oxidative stress and cellular apoptosis.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer Potential of Pineapple and its Bioactive Compound Bromelain.","authors":"Davinder Kumar, Suchitra, Jyoti Mundlia, Shiv Kumar Yadav, Deepika Yadav, Navidha Aggarwal, Hitesh Chopra, Virender Kumar, Mohammad Amjad Kamal","doi":"10.2174/0113816128303910240713180835","DOIUrl":"https://doi.org/10.2174/0113816128303910240713180835","url":null,"abstract":"<p><p>Various ailments have been treated with pineapple [Ananas comosus (L.) Merr.] throughout medicinal history. Pineapple and its bioactive compound bromelain possess health-promoting benefits. Detailed information on the chemotherapeutic activities of pineapple and its bioactive compound bromelain is provided in this review, which analyses the current literature regarding their therapeutic potential in cancer. Research on disease models in cell cultures is the focus of much of the existing research. Several studies have demonstrated the benefits of pineapple extract and bromelain for in vitro and in vivo cancer models. Preliminary animal model results show promise, but they must be translated into the clinical setting. Research on these compounds represents a promising future direction and may be well-tolerated.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving Vaccine Response through Probiotics and Micronutrient Supplementation: Evaluating the Role of TLR5 in Adult Female BALB/c Mice.","authors":"Zohre Eftekhari, Delaram Doroud, Maryam Tajabadi-Ebrahimi, Fatemeh Kazemi-Lomedasht","doi":"10.2174/0113816128310203240823053538","DOIUrl":"https://doi.org/10.2174/0113816128310203240823053538","url":null,"abstract":"<p><strong>Background: </strong>The role of probiotics and micronutrients in improving immune system function and response to vaccination has been proven. Hence, this study aimed to investigate the effects of probiotics enriched with micronutrients on the immunogenicity of PastoCovac® vaccine.</p><p><strong>Methods: </strong>The probiotic supplement BioBoost® and PastoCovac® vaccine, which contain six expressed receptor-binding domains (RBD) and conjugated with tetanus toxin, were administered concurrently. The safety and efficacy were assessed by determining Immunoglobulin G (IgG) antibody titers to RBD and cytokines, mRNA expression of Toll-like Receptors (TLRs) 5, and clinical symptoms.</p><p><strong>Results: </strong>Results revealed that the administration of the probiotics enriched with micronutrients and vitamins for 14 days before the first vaccine dose, followed by continued supplementation for 14 days after the first dose, and in conjunction with the second vaccine dose, yielded the most significant elevation in interleukin 4 (IL-4), Tumor Necrosis Factor-alpha (TNF alpha), Interferon-gamma (IFN-gamma), and anti-SARS-CoV-2 RBD IgG levels within the supernatant samples collected from spleen cultures with the highest expression of TLR5 genes in intestinal samples, compared to the control group.</p><p><strong>Conclusion: </strong>Our results indicated that the inclusion of probiotics enriched with micronutrients and vitamins significantly enhanced the immunogenicity of the PastoCovac® vaccine. Based on the recommendation to administer third and fourth vaccine doses, particularly for vulnerable and elderly individuals, the utilization of supplements containing probiotics is expected to favorably influence immune responses.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Signal Pathways and Therapeutic Effects of Mesenchymal Stem Cell on Oxidative Stress in Diseases.","authors":"Yina Xie, Lingqian Zheng, Wenmin Chen, Yang Zeng, Kaijin Yao, Tianbiao Zhou","doi":"10.2174/0113816128308454240823074555","DOIUrl":"https://doi.org/10.2174/0113816128308454240823074555","url":null,"abstract":"<p><p>Oxidative stress is a biological stress response produced by the destruction of redox equilibrium in aerobic metabolism in organisms, which is closely related to the occurrence of many diseases. Mesenchymal stem cells (MSCs) have been found to improve oxidative stress injury in a variety of diseases, including arthritis, chronic obstructive pulmonary disease, asthma, multiple sclerosis, focal segmental glomerulosclerosis, diabetic nephropathy, ischemia-reperfusion injury, hepatic fibrosis, myocardial infarction, diabetes, inflammatory bowel disease, etc. The antioxidant stress capacity of MSCs may be a breakthrough in the treatment of these diseases. This review found that MSCs have the ability to resist oxidative stress, which may be achieved through MSCs involvement in mediating the Nrf2, MAPK, NF-κB, AMPK, PI3K/AKT and Wnt/b-catenin signaling pathways.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Some Highly Potent Nepalese Medicinal Plants with Antimicrobial Properties","authors":"Asmita Khanal, Sabina Shrestha, Rameshwar Adhikari","doi":"10.2174/0113816128309718240822060114","DOIUrl":"https://doi.org/10.2174/0113816128309718240822060114","url":null,"abstract":": In recent years, microbial infections have emerged as a serious global health problem, necessitating the search for novel and effective treatments. Medicinal plants contain phytochemicals that can be used to prevent and treat various infections. Traditional medicinal practices have long relied on the healing properties of herbs, and Nepal is particularly rich in this knowledge. Bioactive compounds found in plants possess antibacterial, antifungal, and antiviral properties, making them a valuable resource for the fight against microbial infections. This review focuses on three medicinal plants native to Nepal, Amomum subulatum, Cymbopogon jwarancusa, and Cinnamomum glaucescens, which contain potent antimicrobial phytochemicals. The traditional uses, bioactive components, and biological activities of these plants are discussed, providing valuable insights into their potential as natural remedies to combat microbial infections.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"8 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}