Current pharmaceutical design最新文献

{"title":"In Vitro Bioassay and In silico Pharmacokinetic Characteristics of Xanthium strumarium Plant Extract as Possible Acaricidal Agent.","authors":"Nabi Amin, Chia-Hung Wu, Nosheen Malak, Afshan Khan, Shakir Ullah, Imtiaz Ahmad, Muazzam Ali Khan, Muhammad Naveed, Zakir Ullah, Saira Naz, Adil Khan, Chien-Chin Chen","doi":"10.2174/0113816128317849241108064144","DOIUrl":"https://doi.org/10.2174/0113816128317849241108064144","url":null,"abstract":"<p><strong>Background: </strong>Effective management strategies against tick infestations are necessary because tickborne diseases represent serious hazards to the health of humans and animals worldwide. The aim of this study was to examine the larvicidal and ovicidal properties of Xanthium strumarium extract against a notorious tick species, Rhipicephalus microplus.</p><p><strong>Methodology: </strong>The maceration method was used to prepare the ethanolic extract of X. strumarium. The extract was then used in an adult immersion test (AIT) and larval packet test (LPT) to asses the plant's toxicity. To elucidate the mode of action, molecular modeling and docking studies were conducted. ADMET analysis was then carried out to find out the drug-likeness profiles of the plant phytochemicals.</p><p><strong>Results: </strong>Significant death rates and egg inhibition were found at different extract doses using the larval packet test (LPT) and adult immersion test (AIT). A concentration-dependent impact was observed at a concentration of 40 mg/mL, which resulted in the maximum larval mortality (92 ± 2.646) and egg inhibition (77.057 ± 2.186). Additionally, the potency of the extract against R. microplus was determined by calculating its fatal concentrations (LC50, LC90, and LC99). A three-dimensional model of the R. microplus octopamine receptor was created, and docking studies showed that the receptor and possible ligands, most notably Xanthatin and Xanthosin, interacted well. The potential of compounds as tick control agents was highlighted by their pharmacokinetic characteristics and toxicity profiles, as revealed by drug-likeness and ADMET studies. Molecular dynamic simulations further demonstrated the stability of the protein-ligand complex, indicating the consistent association between the ligand and the target protein.</p><p><strong>Conclusion: </strong>Overall, this study provides valuable insights into the potential use of X. strumarium extract and its compounds as larvicidal and ovicidal agents against R. microplus, paving the way for further research on tick control strategies.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853275","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":"Antibiotic Exposure and Childhood Overweight/Obesity: Evidence From Epidemiological and Experimental Studies.","authors":"Junya Wang, Shijie Geng, Xiaodie Yao, Juan Wen, Renjie Lu","doi":"10.2174/0113816128333496240911061551","DOIUrl":"https://doi.org/10.2174/0113816128333496240911061551","url":null,"abstract":"<p><p>Childhood overweight and obesity are nutritional disorders in which children's energy intake exceeds energy consumption for a long period, resulting in the excessive accumulation of body fat and weight that exceeds a certain range. It is one of the most serious public health issues. In recent years, its prevalence has shown a significant upward trend, and 41-80% of childhood obesity can persist into adulthood.Scholars are now more interested in researching this further. Since antibiotics have been used extensively since their discovery, more focus has been paid to the possible risks these medications pose to children who are exposed to them. Recently, some studies have explored the possible link between antibiotic exposure and the prevalence of overweight and obesity in children. However, their findings are inconsistent. Therefore, this review aims to synthesize and summarize the studies related to the effects of antibiotics on childhood obesity, elucidate the possible associations between the two, and provide an in-depth discussion of the potential biological mechanisms by which antibiotics exposure may contribute to childhood obesity.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853262","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":"Immunopharmacological Insights into Cordyceps spp.: Harnessing Therapeutic Potential for Sepsis.","authors":"Juhi Saxena, Gaurang Agarwal, Sarvjeet Das, Anshu Kumar, Krish Thakkar, Sanket Kaushik, Vijay Kumar Srivatsava, Arif Jamal Siddiqui, Anupam Jyoti","doi":"10.2174/0113816128326301240920040036","DOIUrl":"https://doi.org/10.2174/0113816128326301240920040036","url":null,"abstract":"<p><p>Cordyceps spp. (CS), a well-known medicinal mushroom that belongs to Tibetan medicine and is predominantly found in the high altitudes in the Himalayas. CS is a rich reservoir of various bioactive substances including nucleosides, sterols flavonoids, peptides, and phenolic compounds. The bioactive compounds and CS extract have antibacterial, antioxidant, immunomodulatory, and inflammatory properties in addition to organ protection properties across a range of disease states. The study aimed to review the potential of CS, a medicinal mushroom, as a treatment for sepsis. While current sepsis drugs have side effects, CS shows promise due to its anti-inflammatory, antioxidant, and antibacterial properties. We have performed an extensive literature search based on published original and review articles in Scopus and PubMed. The keywords used were Cordyceps, sepsis, and inflammation. Studies indicate that CS extract and bioactive compounds target free radicals including oxidative as well as nitrosative stress, lower inflammation, and modulate the immune system, all of which are critical components in sepsis. The brain, liver, kidneys, lungs, and heart are among the organs that CS extracts may be able to shield against harm during sepsis. Traditional remedies with anti-inflammatory and protective qualities, such as Cordyceps mushrooms, are promising in sepsis. However, more research including clinical trials is required to validate the usefulness of CS metabolites in terms of organ protection and fight infections in sepsis.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853266","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":"Immunotherapy for Type 1 Diabetes: Mechanistic Insights and Impact of Delivery Systems.","authors":"Nishi Agrawal, Ganesh Kumar, Sree Prakash Pandey, Shweta Yadav, Manoj Kumar, M S Sudheesh, Ravi Shankar Pandey","doi":"10.2174/0113816128343081241030054303","DOIUrl":"https://doi.org/10.2174/0113816128343081241030054303","url":null,"abstract":"<p><p>Type 1 Diabetes is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β-cells, leading to hyperglycemia and various complications. Despite insulin replacement therapy, there is a need for therapies targeting the underlying autoimmune response. This review aims to explore the mechanistic insights into T1D pathogenesis and the impact of delivery systems on immunotherapy. Genetic predisposition and environmental factors contribute to T1D development, triggering an immune-mediated attack on β-cells. T cells, particularly CD4+ and CD8+ T cells, play a central role in β-cell destruction. Antigen- specific immunotherapy is a unique way to modify the immune system by targeting specific antigens (substances that trigger the immune system) for immunotherapy. It aims to restore immune tolerance by targeting autoantigens associated with T1D. Nanoparticle-based delivery systems offer precise antigen delivery, promoting immune tolerance induction. Various studies have demonstrated the efficacy of nanoparticle-mediated delivery of autoantigens and immunomodulatory agents in preclinical models, and several patents have been made in T1D. Combining antigen-specific immunotherapy with β-cell regeneration strategies presents a promising approach for T1D treatment. However, challenges remain in optimizing delivery systems for targeted immune modulation while ensuring safety and efficacy.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853270","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":"Understanding and Using Animal Models of Hepatotoxicity.","authors":"Verma, Preeti, Annu, Rahul Kumar Sharma, Shivani Chopra, Hitesh Chopra, Dong Kil Shin","doi":"10.2174/0113816128338726241029175250","DOIUrl":"https://doi.org/10.2174/0113816128338726241029175250","url":null,"abstract":"<p><p>Hepatotoxicity is a critical health hazard, primarily contributing to the increased incidence of deaths globally. The liver is one of the major and extremely vital organs of the human body. Autoimmune diseases, viruses, exposure to toxicants such as carcinogens, and changes in eating habits can all cause liver problems, among other things. Free radical generation, together with raised enzyme levels including SGOT, SGPT, and total bilirubin, are among the pathological changes set off by liver injury. Hepatotoxicity causes changes in cells, such as eosinophilic cytoplasm, nuclear pyknosis, fatty degeneration, too many liver lesions, and hepatic centrilobular necrosis due to lipid peroxidation. Researchers have used animal models to investigate liver diseases and toxicities. Drugs such as azathioprine, alcoholism, paracetamol intoxication, and anti-tuberculosis drugs are some of the most common causes of liver toxicity. These toxins cause calcium ions (Ca2+), reactive oxygen species (ROS), and inflammatory mediators to be released inside cells. This activates immune cells like NK cells, NKT cells, and Kupffer cells. These signaling pathways also play roles in hepatotoxicity. Due to its pathogenesis, no effective drug is currently available for hepatotoxicity due to a lack of understanding related to the signaling factors involved in it. The paper primarily examines different experimental models of hepatotoxicity, including non-invasive and invasive methods, as well as genetic models. As such, these models are crucial tools in advancing our understanding of hepatotoxicity, thus paving the way for new therapeutic interventions.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853210","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":"Daidzein Inhibits Non-small Cell Lung Cancer Growth by Pyroptosis.","authors":"Fanfan Zeng, Yu Zhang, Ting Luo, Chengman Wang, Denggang Fu, Xin Wang","doi":"10.2174/0113816128330530240918073721","DOIUrl":"https://doi.org/10.2174/0113816128330530240918073721","url":null,"abstract":"<p><strong>Introduction: </strong>Non-Small-Cell Lung Cancer (NSCLC) represents the leading cause of cancer deaths in the world. We previously found that daidzein, one of the key bioactivators in soy isoflavone, can inhibit NSCLC cell proliferation and migration, while the molecular mechanisms of daidzein in NSCLC remain unclear.</p><p><strong>Methods: </strong>We developed an NSCLC nude mouse model using H1299 cells and treated the mice with daidzein (30 mg/kg/day). Mass spectrometry analysis of tumor tissues from daidzein-treated mice identified 601 differentially expressed proteins (DEPs) compared to the vehicle-treated group. Gene enrichment analysis revealed that these DEPs were primarily associated with immune regulatory functions, including B cell receptor and chemokine pathways, as well as natural killer cell-mediated cytotoxicity. Notably, the NOD-like receptor signaling pathway, which is closely linked to pyroptosis, was significantly enriched.</p><p><strong>Results: </strong>Further analysis of key pyroptosis-related molecules, such as ASC, CASP1, GSDMD, and IL-1β, revealed differential expression in NSCLC versus normal tissues. High levels of ASC and CASP1 were associated with a favorable prognosis in NSCLC, suggesting that they may be critical effectors of daidzein's action. In NSCLC-bearing mice treated with daidzein, RT-qPCR and Western blot analyses showed elevated mRNA and protein levels of ASC, CASP1, and IL-1β but not GSDMD, which was consistent with the proteomic data.</p><p><strong>Conclusion: </strong>In summary, this study demonstrated that daidzein inhibits NSCLC growth by inducing pyroptosis. Key pathway modulators ASC, CASP1, and IL-1β were identified as primary targets of daidzein. These findings offer insights into the molecular mechanisms underlying the anti-NSCLC effects of daidzein and could offer dietary recommendations for managing NSCLC.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767042","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":"Screening of Natural Compounds as Inhibitor of Mpro SARS-CoV-2 Protein; A Molecular Dynamics Approach.","authors":"Anum Javaid, Nousheen Bibi, Malik Siddique Mahmood, Hina Batool, Sana Batool, Arslan Hamid, Mahjabeen Saleem, Naeem Mahmood Ashraf, Tayyaba Afsar, Ali Almajwal, Suhail Razak","doi":"10.2174/0113816128315762240828052002","DOIUrl":"https://doi.org/10.2174/0113816128315762240828052002","url":null,"abstract":"<p><strong>Background: </strong>New strains of SARS-CoV-2 are continually emerging worldwide. Recently, WHO warned of a severe new wave in Europe. Current vaccines cannot fully prevent reinfection in vaccinated individuals.</p><p><strong>Aim: </strong>Given this issue, recent research focuses on new antiviral candidates with high efficacy and minimal side effects.</p><p><strong>Objectives: </strong>Screen natural compounds as inhibitors of Mpro SARS-CoV-2 protein using molecular dynamics.</p><p><strong>Methods: </strong>In this study, we have screened the potential of plant-based natural anti-viral compounds. A library of the 579 compounds was generated using currently available literature and online databases. All these compounds were screened based on their binding affinities as predicted by molecular docking analysis and compounds having binding affinity values ≤ -10 Kcal/mol were considered for analysis. Furthermore, from physicochemical assessment, drug-likeness initially nine compounds were identified as the antiviral targets for the selected viral proteins. After ADMET analysis and simulations, the compound 9064 with the lowest RMSD, Coul-SR interaction energy (-71.53 kJ/mol), and LJ-SR energy (-95.32 kJ/mol) was selected as the most stable drug candidate against COVID-19 main protease Mpro.</p><p><strong>Results: </strong>The ΔG value, calculated using MMGBSA also revealed strong binding of the compound with Mpro. The selected antiviral compound 9064 is an antioxidant flavonoid (Catechin or Cianidanol), which was previously known to have significant immunomodulatory, anti-inflammatory, and antioxidant properties.</p><p><strong>Conclusion: </strong>Considering the limitations of currently available vaccines, our study may provide new insight into potential drugs that may prevent SARS-CoV-2 infection in humans.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675283","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":"The Rise of FLiRT Variants in the COVID-19 Pandemic: What We Know So Far.","authors":"Md Sadique Hussain, Gaurav Gupta","doi":"10.2174/0113816128355749241111045626","DOIUrl":"10.2174/0113816128355749241111045626","url":null,"abstract":"","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616322","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":"Therapeutic Potential of Neutralizing Monoclonal Antibodies (nMAbs) against SARS-CoV-2 Omicron Variant.","authors":"Pijus Parua, Somnath Ghosh, Koushik Jana, Arnab Seth, Biplab Debnath, Saroj Kumar Rout, Manoj Kumar Sarangi, Rasmita Dash, Jitu Halder, Tushar Kanti Rajwar, Deepak Pradhan, Vineet Kumar Rai, Priyanka Dash, Chandan Das, Biswakanth Kar, Goutam Ghosh, Goutam Rath","doi":"10.2174/0113816128334441241108050528","DOIUrl":"10.2174/0113816128334441241108050528","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic has spurred significant endeavors to devise treatments to combat SARS-CoV-2. A limited array of small-molecule antiviral drugs, specifically monoclonal antibodies and interferon therapy, have been sanctioned to treat COVID-19. These treatments typically necessitate administration within ten days of symptom onset. There have been reported reductions in the effectiveness of these medications due to mutations in non-structural protein genes, particularly against Omicron subvariants. This underscores the pressing requirement for healthcare systems to continually monitor pathogen variability and its impact on the efficacy of prevention and treatments.</p><p><strong>Aim: </strong>This review aimed to comprehend the therapeutic benefits and recent progress of nMAbs for preventing and treating the Omicron variant of SARS-CoV-2.</p><p><strong>Results and discussion: </strong>Neutralizing monoclonal antibodies (nMAbs) provide a treatment avenue for severely affected individuals, especially those at high risk for whom vaccination is not viable. With their specific epitope affinity, they pose no significant risk of severe adverse effects. The degree of reduction in neutralization varies significantly across different monoclonal antibodies and variant combinations. For instance, Sotrovimab maintained its neutralization effectiveness against Omicron BA.1, but exhibited diminished efficacy against BA.2, BA.4, BA.5, and BA.2.12.1.</p><p><strong>Conclusion: </strong>Bebtelovimab has been observed to preserve its efficacy against all subtypes of the Omicron variant. Subsequently, WKS13, mAb-39, 19n01, F61-d2 cocktail, etc., have become effective. This review has highlighted the therapeutic implications of nMAbs in SARS-CoV-2 Omicron treatment and the progress of COVID-19 drug discovery.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616323","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":"Co-loading Radio-photosensitizer Agents on Polymer and Lipid-based Nanocarriers for Radio-photodynamic Therapy Purposes: Review.","authors":"Kave Moloudi, Heidi Abrahamse, Blassan P George","doi":"10.2174/0113816128335001241020162217","DOIUrl":"https://doi.org/10.2174/0113816128335001241020162217","url":null,"abstract":"<p><p>Polymer and lipid-based nanocarriers are a state-of-art in nanomedicine and in co-drug delivery of drugs that could merges various diagnostic and treatment modalities such radiotherapy (RT), photodynamic therapy (PDT) and chemotherapy (CT) in cancer therapy. Among various shapes and nanostructures, polymer and lipid-based nanocarriers have the potential to carry two drugs in same time to cells. However, hydrophobic and hydrophilic drug can be loaded in between layers as well as in the core of these nanocarriers, simultaneously. This advantage of NPs can be employed in combination therapy. Radiosensitizer and photosensitizer agents play a critical role in radio-photodynamic therapy (RT-PDT) of cancer. Co-delivery of these agents to cancerous cells is advantageous to cancer therapy but still remain as a challenge of RT-PDT. However, in this review, we have highlighted the challenges of RT-PDT and role of polymer and lipid-based nanocarriers to codelivery of hydrophobic and hydrophilic agents as radio-photosensitizers. Hence, the different kinds of Poly (lactic-co-glycolic acid) nanoparticles (NPs) have been categorized. Then, the biophysical mechanism of radio- photosensitizer agents with co-loading on polymer and lipid-based nanocarriers in RT-PDT treatment of cancer has been outlined. Finally, attention has been drawn to polymer and lipid-based nanocarriers in codrugs delivery. Taken together, this work presents the latest updates on this area and highlighted the pros and cons of co-delivery for RT-PDT purposes.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616319","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}