Chunyu Zhang, Xuchang Zhou, Dongxue Wang, Li Hao, Zhipeng Zeng, Lei Su
Clinical treatment strategies for musculoskeletal disorders have been a hot research topic. Accumulating evidence suggests that hydrogels loaded with MSC-derived EVs show great potential in improving musculoskeletal injuries. The ideal hydrogels should be capable of promoting the development of new tissues and simulating the characteristics of target tissues, with the properties matching the cell-matrix constituents of autologous tissues. Although there have been numerous reports of hydrogels loaded with MSC-derived EVs for the repair of musculoskeletal injuries, such as intervertebral disc injury, tendinopathy, bone fractures, and cartilage injuries, there are still many hurdles to overcome before the clinical application of modified hydrogels. In this review, we focus on the advantages of the isolation technique of EVs in combination with different types of hydrogels. In this context, the efficacy of hydrogels loaded with MSC-derived EVs in different musculoskeletal injuries is discussed in detail to provide a reference for the future application of hydrogels loaded with MSC-derived EVs in the clinical treatment of musculoskeletal injuries.
{"title":"Hydrogel-Loaded Exosomes: A Promising Therapeutic Strategy for Musculoskeletal Disorders","authors":"Chunyu Zhang, Xuchang Zhou, Dongxue Wang, Li Hao, Zhipeng Zeng, Lei Su","doi":"10.1155/2023/1105664","DOIUrl":"https://doi.org/10.1155/2023/1105664","url":null,"abstract":"Clinical treatment strategies for musculoskeletal disorders have been a hot research topic. Accumulating evidence suggests that hydrogels loaded with MSC-derived EVs show great potential in improving musculoskeletal injuries. The ideal hydrogels should be capable of promoting the development of new tissues and simulating the characteristics of target tissues, with the properties matching the cell-matrix constituents of autologous tissues. Although there have been numerous reports of hydrogels loaded with MSC-derived EVs for the repair of musculoskeletal injuries, such as intervertebral disc injury, tendinopathy, bone fractures, and cartilage injuries, there are still many hurdles to overcome before the clinical application of modified hydrogels. In this review, we focus on the advantages of the isolation technique of EVs in combination with different types of hydrogels. In this context, the efficacy of hydrogels loaded with MSC-derived EVs in different musculoskeletal injuries is discussed in detail to provide a reference for the future application of hydrogels loaded with MSC-derived EVs in the clinical treatment of musculoskeletal injuries.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"50 23","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136281639","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}
Junhua Zhang, Rui Bao, Faisal Raza, Hajra Zafar, Yingjie Qi, Yurui Geng, Ran Li, Jianqin Xue, Feng Shi
Onjisaponin B (OB) is the main active ingredient of Radix Polygalae with various bioactivities. However, the protective effect of OB in Parkinson’s disease (PD) has not been fully studied. Liposomes are ideal nanocarriers for drugs targeting the brain. In this study, we investigated the therapeutic effect of OB-loaded liposomes (lip OB) on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced mouse model of PD and 1-methyl-4-phenylpyridinium- (MPP+-) induced cell model of PD. Our results showed that lip OB significantly ameliorated MPTP-induced motor deficits and dopaminergic neuron loss in vivo and prevented MPP+-triggered cell viability reduction and apoptosis in vitro. Lip OB also improved mitochondrial dysfunction in PD models by driving PINK1/Parkin-mediated mitophagy. Furthermore, silencing PINK1 compromised the beneficial effects of lip OB on MPP+-treated PC12 cells. These findings suggested lip OB mitigates Parkinsonism in vivo and in vitro by enhancing mitochondrial dysfunction through the PINK1/Parkin pathway of mitophagy, which provides a new possibility for treating PD.
{"title":"Preparation and Evaluation of Onjisaponin B-Loaded Liposomes for Drug Delivery to Enhance Mitochondrial Function and Rescue Parkinson’s Disease by Activating Mitophagy","authors":"Junhua Zhang, Rui Bao, Faisal Raza, Hajra Zafar, Yingjie Qi, Yurui Geng, Ran Li, Jianqin Xue, Feng Shi","doi":"10.1155/2023/1262109","DOIUrl":"https://doi.org/10.1155/2023/1262109","url":null,"abstract":"Onjisaponin B (OB) is the main active ingredient of Radix Polygalae with various bioactivities. However, the protective effect of OB in Parkinson’s disease (PD) has not been fully studied. Liposomes are ideal nanocarriers for drugs targeting the brain. In this study, we investigated the therapeutic effect of OB-loaded liposomes (lip OB) on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced mouse model of PD and 1-methyl-4-phenylpyridinium- (MPP+-) induced cell model of PD. Our results showed that lip OB significantly ameliorated MPTP-induced motor deficits and dopaminergic neuron loss in vivo and prevented MPP+-triggered cell viability reduction and apoptosis in vitro. Lip OB also improved mitochondrial dysfunction in PD models by driving PINK1/Parkin-mediated mitophagy. Furthermore, silencing PINK1 compromised the beneficial effects of lip OB on MPP+-treated PC12 cells. These findings suggested lip OB mitigates Parkinsonism in vivo and in vitro by enhancing mitochondrial dysfunction through the PINK1/Parkin pathway of mitophagy, which provides a new possibility for treating PD.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":" 19","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135341259","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}
Yazheng Zhao, Qian Cheng, Shupeng Zou, Xuan Shi, Mengling Ouyang, Minghui Sun
Objectives. To investigate adverse events (AEs) associated with upadacitinib in the real world using data mining from the FDA Adverse Event Reporting System (FAERS). Methods. Disproportionality analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multiitem gamma Poisson shrinker (MGPS) algorithms, was used to quantify the signals of upadacitinib-associated AEs. Results. The study found 23683 reports of AEs associated with upadacitinib. A total of 149 substantial disproportionality preferred terms (PTs) that complied with all algorithms were identified. The infections discovered matched those mentioned in the specification and clinical trials, including pneumonia, upper respiratory tract infection, herpes zoster, and acne. Malignant and thrombotic AEs were also noted. Diverticulitis, myocardial infarction, transient ischaemic attack, and dysstasia were among the new AEs found. Upadacitinib-related AEs had a median onset time of 237 days and an interquartile range (IQR) of 78–509 days. Conclusions. The findings of our study were in line with clinical observations, and we also identified potential novel and unexpected AEs signals for upadacitinib, indicating the necessity for prospective clinical trials to corroborate these findings and demonstrate their link. Our results offered significant support for additional upadacitinib safety research.
{"title":"A Real-World Safety Analysis of Upadacitinib Based on FDA Adverse Event Reporting System (FAERS)","authors":"Yazheng Zhao, Qian Cheng, Shupeng Zou, Xuan Shi, Mengling Ouyang, Minghui Sun","doi":"10.1155/2023/8000874","DOIUrl":"https://doi.org/10.1155/2023/8000874","url":null,"abstract":"Objectives. To investigate adverse events (AEs) associated with upadacitinib in the real world using data mining from the FDA Adverse Event Reporting System (FAERS). Methods. Disproportionality analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multiitem gamma Poisson shrinker (MGPS) algorithms, was used to quantify the signals of upadacitinib-associated AEs. Results. The study found 23683 reports of AEs associated with upadacitinib. A total of 149 substantial disproportionality preferred terms (PTs) that complied with all algorithms were identified. The infections discovered matched those mentioned in the specification and clinical trials, including pneumonia, upper respiratory tract infection, herpes zoster, and acne. Malignant and thrombotic AEs were also noted. Diverticulitis, myocardial infarction, transient ischaemic attack, and dysstasia were among the new AEs found. Upadacitinib-related AEs had a median onset time of 237 days and an interquartile range (IQR) of 78–509 days. Conclusions. The findings of our study were in line with clinical observations, and we also identified potential novel and unexpected AEs signals for upadacitinib, indicating the necessity for prospective clinical trials to corroborate these findings and demonstrate their link. Our results offered significant support for additional upadacitinib safety research.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"139 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135933175","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}
Jiake He, Bo Zhu, Yang Shen, Jianping Hu, Kui Hong
Aims. The aim of this study is to assess the relationship between rivaroxaban plasma concentration quantified by the gold standard and anticoagulant activities measured by routine coagulation assays in Chinese atrial fibrillation (AF) patients. Whether the normal results of these tests were reliable to rule out clinically relevant rivaroxaban levels at various thresholds was also explored. The effect of clinical drug-drug interactions (DDIs) on the exposure and anticoagulant effect of rivaroxaban were further evaluated. Methods. 116 patients receiving rivaroxaban for the management of nonvalvular AF were recruited. Rivaroxaban concentrations and coagulation tests were measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and a blood coagulation analyzer, respectively. Results. The correlation of trough concentration (Ctrough) and prothrombin time (PT) or international normalized ratio (INR) was moderate with Spearman’s correlation coefficient of 0.495 and 0.506, respectively. A normal PT/INR was unable to rule out Ctrough levels of >30 ng/mL and >50 ng/mL, but the negative predictive value reached 100% to exclude Ctrough of >100 ng/mL. Ctrough showed a small correlation with activated partial thromboplastin time (aPTT) (Spearman’s correlation coefficient: 0.241) and no correlation with thrombin time (TT) (Spearman’s correlation coefficient: 0.074). Neither aPTT nor TT accurately predicted Ctrough at any concentration. Peak concentration (Cpeak) did not correlate with any coagulation parameters. The presence of digoxin and febuxostat significantly increased rivaroxaban Ctrough by 2.18 fold and prolonged PT and INR by 44.16% and 43.60%, respectively. Conclusions. Normal routine coagulation assays were insufficient to monitor therapy with rivaroxaban. Poor correlations between rivaroxaban concentration and routine coagulation assays were observed in Chinese AF patients. The use of digoxin/febuxostat alone had no effect on rivaroxaban concentrations; however, combined strong breast cancer resistance protein inhibitor (febuxostat) and P-glycoprotein probe (digoxin) in patients with renal impairment is likely to cause clinically significant DDI with rivaroxaban. More studies are needed to establish routine therapeutic drug monitoring of rivaroxaban in clinical practice.
{"title":"Poor Correlation of Rivaroxaban Concentration with the Routine Coagulation Screening Test in Chinese Patients with Atrial Fibrillation","authors":"Jiake He, Bo Zhu, Yang Shen, Jianping Hu, Kui Hong","doi":"10.1155/2023/9962812","DOIUrl":"https://doi.org/10.1155/2023/9962812","url":null,"abstract":"Aims. The aim of this study is to assess the relationship between rivaroxaban plasma concentration quantified by the gold standard and anticoagulant activities measured by routine coagulation assays in Chinese atrial fibrillation (AF) patients. Whether the normal results of these tests were reliable to rule out clinically relevant rivaroxaban levels at various thresholds was also explored. The effect of clinical drug-drug interactions (DDIs) on the exposure and anticoagulant effect of rivaroxaban were further evaluated. Methods. 116 patients receiving rivaroxaban for the management of nonvalvular AF were recruited. Rivaroxaban concentrations and coagulation tests were measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and a blood coagulation analyzer, respectively. Results. The correlation of trough concentration (Ctrough) and prothrombin time (PT) or international normalized ratio (INR) was moderate with Spearman’s correlation coefficient of 0.495 and 0.506, respectively. A normal PT/INR was unable to rule out Ctrough levels of >30 ng/mL and >50 ng/mL, but the negative predictive value reached 100% to exclude Ctrough of >100 ng/mL. Ctrough showed a small correlation with activated partial thromboplastin time (aPTT) (Spearman’s correlation coefficient: 0.241) and no correlation with thrombin time (TT) (Spearman’s correlation coefficient: 0.074). Neither aPTT nor TT accurately predicted Ctrough at any concentration. Peak concentration (Cpeak) did not correlate with any coagulation parameters. The presence of digoxin and febuxostat significantly increased rivaroxaban Ctrough by 2.18 fold and prolonged PT and INR by 44.16% and 43.60%, respectively. Conclusions. Normal routine coagulation assays were insufficient to monitor therapy with rivaroxaban. Poor correlations between rivaroxaban concentration and routine coagulation assays were observed in Chinese AF patients. The use of digoxin/febuxostat alone had no effect on rivaroxaban concentrations; however, combined strong breast cancer resistance protein inhibitor (febuxostat) and P-glycoprotein probe (digoxin) in patients with renal impairment is likely to cause clinically significant DDI with rivaroxaban. More studies are needed to establish routine therapeutic drug monitoring of rivaroxaban in clinical practice.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"180 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135871991","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}
Rui Chen, Yan Sun, Yufan Li, Xiaoke Dou, Maosha Dai, Shujun Sun, Yun Lin
Objective. Neuromuscular blocking agents (NMBAs) are part of the three elements of general anaesthesia (sedation, analgesia, and muscle relaxation), which can relax muscles and facilitate intubation and surgery. It has been reported that cancer cells are prone to invasion or metastasis during surgery, but various anaesthetics are currently used in cancer resection, particularly NMBA, and the effects on cancer cell behavior are poorly understood. Guidelines for the correct application of NMBA in cancer surgery have not been reported; therefore, the aim of this paper is to explore the relationship between NMBA and cancer. Methods. Two investigators independently searched PubMed, Embase, the Cochrane Library, Web of Science, and CBM for articles of NMBA and cancer. Results. The available evidence suggests that cisatracurium may be more appropriate for use in anaesthesia for cancer surgery, while rocuronium deserves further attention, particularly for breast and gastric cancer surgery, and vecuronium is suitable for breast cancer and non-small-cell lung cancer, while it is used with caution in gastric cancer. Also, the relationship between NMBA (mivacurium, succinylcholine, gantacurium, and decamethonium bromide) and cancer is unclear and deserves further study. Conclusion. The effect of different NMBAs on cancer cells varies, and the effect of some NMBAs on cancer cells is unclear, and most of the current findings are only from in vitro studies, which need to be validated by further clinical studies in the future to better guide the clinical application of NMBAs.
目标。神经肌肉阻滞剂(nmba)是全身麻醉三要素(镇静、镇痛和肌肉松弛)的一部分，它可以放松肌肉，促进插管和手术。据报道，手术过程中癌细胞易发生侵袭或转移，但目前在肿瘤切除术中使用的麻醉药种类繁多，尤其是NMBA，对其对癌细胞行为的影响尚不清楚。在肿瘤手术中正确应用NMBA的指南尚未见报道;因此，本文的目的是探讨NMBA与癌症之间的关系。方法。两位研究者分别在PubMed、Embase、Cochrane图书馆、Web of Science和CBM中搜索NMBA和癌症的文章。结果。现有证据表明，顺阿库溴铵可能更适合用于癌症手术麻醉，而罗库溴铵值得进一步关注，特别是用于乳腺癌和胃癌手术，维库溴铵适用于乳腺癌和非小细胞肺癌，而胃癌慎用。此外，NMBA (mivacurium, succinylcholine, gantacurium, decamethonium bromide)与癌症的关系尚不清楚，值得进一步研究。结论。不同的nmba对癌细胞的作用各不相同，部分nmba对癌细胞的作用尚不清楚，目前大部分研究结果仅来自体外研究，未来需要通过进一步的临床研究进行验证，以更好地指导nmba的临床应用。
{"title":"Neuromuscular Blocking Agents and Cancer: A Narrative Review","authors":"Rui Chen, Yan Sun, Yufan Li, Xiaoke Dou, Maosha Dai, Shujun Sun, Yun Lin","doi":"10.1155/2023/5607134","DOIUrl":"https://doi.org/10.1155/2023/5607134","url":null,"abstract":"Objective. Neuromuscular blocking agents (NMBAs) are part of the three elements of general anaesthesia (sedation, analgesia, and muscle relaxation), which can relax muscles and facilitate intubation and surgery. It has been reported that cancer cells are prone to invasion or metastasis during surgery, but various anaesthetics are currently used in cancer resection, particularly NMBA, and the effects on cancer cell behavior are poorly understood. Guidelines for the correct application of NMBA in cancer surgery have not been reported; therefore, the aim of this paper is to explore the relationship between NMBA and cancer. Methods. Two investigators independently searched PubMed, Embase, the Cochrane Library, Web of Science, and CBM for articles of NMBA and cancer. Results. The available evidence suggests that cisatracurium may be more appropriate for use in anaesthesia for cancer surgery, while rocuronium deserves further attention, particularly for breast and gastric cancer surgery, and vecuronium is suitable for breast cancer and non-small-cell lung cancer, while it is used with caution in gastric cancer. Also, the relationship between NMBA (mivacurium, succinylcholine, gantacurium, and decamethonium bromide) and cancer is unclear and deserves further study. Conclusion. The effect of different NMBAs on cancer cells varies, and the effect of some NMBAs on cancer cells is unclear, and most of the current findings are only from in vitro studies, which need to be validated by further clinical studies in the future to better guide the clinical application of NMBAs.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135872485","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}
Deryl Nii Okantey Kuevi, Francis Asiedu Acquah, Amy Amuquandoh, Andrew Papa Abbey
Background. Schistosomiasis, ranked second to malaria as one of the crucial parasitic infections in the world, infects close to 240 million people as at 2019. Praziquantel, an oral anthelmintic, is the first-line drug for the treatment of schistosomiasis. Although the drug is safe and effective, the formulated tablets come with some limitations such as low bioavailability and bitter taste. This literature review aims to provide information on how to improve the issues of solubility, low bioavailability, and bitter taste associated with the praziquantel formulation and, subsequently, to be helpful in improving patient’s compliance. Materials and Methods. For gathering all pertinent data in this review on improving the praziquantel formulation, the following databases were used: Google Scholar, Science Direct, Scopus, PubMed, Springer Link, Elsevier, and Wiley online library. Results. Literature revealed that in improving the bioavailability of praziquantel, loading the drug with hydrogenated castor oil solid lipid nanoparticles has shown to be effective in prolonging systemic circulation from 7.6 to 95.9 hours after oral administration. Moreover, employing the solid dispersion technique using the fusion method increases the bioavailability of praziquantel about twice as much. Furthermore, incorporating a superdisintegrant or more than one disintegrant to the formulation can enhance the release of praziquantel. The addition of hydroxypropyl-beta-cyclodextrin (HP-β-CD) and sucralose as sweeteners can mask the bitter taste of praziquantel. Conclusion. The formulation approaches outlined in this review can be employed to greatly enhance the solubility, bioavailability, and taste of praziquantel. Although several techniques to improve praziquantel formulation have been widely studied, further studies on the release profile and compatibility studies with other excipients need to be investigated.
{"title":"Challenges and Proven Recommendations of Praziquantel Formulation","authors":"Deryl Nii Okantey Kuevi, Francis Asiedu Acquah, Amy Amuquandoh, Andrew Papa Abbey","doi":"10.1155/2023/3976392","DOIUrl":"https://doi.org/10.1155/2023/3976392","url":null,"abstract":"Background. Schistosomiasis, ranked second to malaria as one of the crucial parasitic infections in the world, infects close to 240 million people as at 2019. Praziquantel, an oral anthelmintic, is the first-line drug for the treatment of schistosomiasis. Although the drug is safe and effective, the formulated tablets come with some limitations such as low bioavailability and bitter taste. This literature review aims to provide information on how to improve the issues of solubility, low bioavailability, and bitter taste associated with the praziquantel formulation and, subsequently, to be helpful in improving patient’s compliance. Materials and Methods. For gathering all pertinent data in this review on improving the praziquantel formulation, the following databases were used: Google Scholar, Science Direct, Scopus, PubMed, Springer Link, Elsevier, and Wiley online library. Results. Literature revealed that in improving the bioavailability of praziquantel, loading the drug with hydrogenated castor oil solid lipid nanoparticles has shown to be effective in prolonging systemic circulation from 7.6 to 95.9 hours after oral administration. Moreover, employing the solid dispersion technique using the fusion method increases the bioavailability of praziquantel about twice as much. Furthermore, incorporating a superdisintegrant or more than one disintegrant to the formulation can enhance the release of praziquantel. The addition of hydroxypropyl-beta-cyclodextrin (HP-β-CD) and sucralose as sweeteners can mask the bitter taste of praziquantel. Conclusion. The formulation approaches outlined in this review can be employed to greatly enhance the solubility, bioavailability, and taste of praziquantel. Although several techniques to improve praziquantel formulation have been widely studied, further studies on the release profile and compatibility studies with other excipients need to be investigated.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136112217","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}
Min Zhu, Zhaoran Wang, Ziming Zhu, Cuifeng Zhang, Fanrong Wu
Objective. To investigate the targets and mechanisms of valsartan in the treatment of chronic renal failure based on network pharmacology and animal experiment validation. Methods. The objectives of using valsartan were predicted with the PubChem and SwissTargetPrediction databases. Relevant targets of chronic renal failure have been searched in various disease databases, with the common purposes of drugs and diseases extracted. Network analysis was carried out with the STRING database to construct a protein-protein interaction (PPI) network, as Cytoscape 3.9.1 software was used to analyze network topology of the key targets and establish the “valsartan-core target gene” network. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on core targets to explore their possible molecular mechanisms. The chronic renal failure mouse model was established by the plat method. Hematoxylin-eosin (H&E) and Masson staining observed morphological changes in renal problems of each group, as levels of serum Cre, BUN, T-SOD, and MDA in each group were detected by kit; real-time PCR was used to detect the relative expression of mRNA of TNF-αIL-1β, IL-6, and IL-10 in renal disease of mice in each group, with WB detect CALM, PKCα, and CaMKIV protein expression levels in renal disease from each group. Results. The network pharmacology approach identified 10 key targets for treatment of chronic renal failure with valsartan, including EGFR, PTGS2, PPARG, and ERBB2. KEGG enrichment analysis predicted that the drug exerted neuroactive ligand-receptor interaction, the calcium signaling pathway, the HIF-1 signaling pathway, the proteoglycans in cancer, PD-L1 expression, and the PD-1 checkpoint pathway in cancer. Results from animal experiments were compared to those of the model group, as renal function was significantly improved in the valsartan-dose group. The serum levels of Cre, BUN, and MDA and relative mRNA expression of TNF-α, IL-1β, and IL-6 decreased significantly, while serum T-SOD levels, relative mRNA expression of IL-10, and the protein expression level of CALM, PKCα, and CaMKIV increased significantly ( < 0.05 and < 0.001). Conclusion. Valsartan yields certain renal protection, which may improve chronic renal failure in mice through the calcium signaling pathway.
{"title":"Exploration of the Mechanism of Valsartan Treatment in Chronic Renal Failure: Network Pharmacology and Experimental Validation","authors":"Min Zhu, Zhaoran Wang, Ziming Zhu, Cuifeng Zhang, Fanrong Wu","doi":"10.1155/2023/4837743","DOIUrl":"https://doi.org/10.1155/2023/4837743","url":null,"abstract":"Objective. To investigate the targets and mechanisms of valsartan in the treatment of chronic renal failure based on network pharmacology and animal experiment validation. Methods. The objectives of using valsartan were predicted with the PubChem and SwissTargetPrediction databases. Relevant targets of chronic renal failure have been searched in various disease databases, with the common purposes of drugs and diseases extracted. Network analysis was carried out with the STRING database to construct a protein-protein interaction (PPI) network, as Cytoscape 3.9.1 software was used to analyze network topology of the key targets and establish the “valsartan-core target gene” network. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on core targets to explore their possible molecular mechanisms. The chronic renal failure mouse model was established by the plat method. Hematoxylin-eosin (H&E) and Masson staining observed morphological changes in renal problems of each group, as levels of serum Cre, BUN, T-SOD, and MDA in each group were detected by kit; real-time PCR was used to detect the relative expression of mRNA of TNF-αIL-1β, IL-6, and IL-10 in renal disease of mice in each group, with WB detect CALM, PKCα, and CaMKIV protein expression levels in renal disease from each group. Results. The network pharmacology approach identified 10 key targets for treatment of chronic renal failure with valsartan, including EGFR, PTGS2, PPARG, and ERBB2. KEGG enrichment analysis predicted that the drug exerted neuroactive ligand-receptor interaction, the calcium signaling pathway, the HIF-1 signaling pathway, the proteoglycans in cancer, PD-L1 expression, and the PD-1 checkpoint pathway in cancer. Results from animal experiments were compared to those of the model group, as renal function was significantly improved in the valsartan-dose group. The serum levels of Cre, BUN, and MDA and relative mRNA expression of TNF-α, IL-1β, and IL-6 decreased significantly, while serum T-SOD levels, relative mRNA expression of IL-10, and the protein expression level of CALM, PKCα, and CaMKIV increased significantly ( <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M1\"> <mi>P</mi> </math> < 0.05 and <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M2\"> <mi>P</mi> </math> < 0.001). Conclusion. Valsartan yields certain renal protection, which may improve chronic renal failure in mice through the calcium signaling pathway.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136079641","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}
Background. Proton pump inhibitors (PPIs) are widely used to treat digestive system diseases. Previous studies have suggested conflicting results between PPI treatment and the risk for digestive tract cancers (DTCs). This study aimed to assess the effect of PPI use on DTCs by data mining of the FDA Adverse Event Reporting System (FAERS) database. Method. This study examined the correlations between six PPI agents and DTCs by mining the FAERS database from January 2004 to September 2021 by using OpenVigil 2.1. The reporting odds ratio (ROR) defined as the ratio between the odds of reporting a specific adverse event for one drug divided by the corresponding odds for all other drugs, with 95% confidence intervals (CIs), was used to detect statistically significant correlations between PPIs and DTCs. High-level terms (HLTs) and preferred terms (PTs) were defined by the Medical Dictionary for Regulatory Activities 24.0 (MedDRA24.0). Result. A total of 2553 DTC adverse event reports were screened, with positive signals obtained from gastric neoplasms malignant (GNM) (ROR: 1.09, 95% CI: 1.01–1.18) and bile duct neoplasms malignant (BDNM) (ROR: 1.80, 95% CI: 1.44–2.25). Esomeprazole showed the strongest signal (ROR: 1.85, 95% CI: 1.66–2.06) for GNM, while rabeprazole for BDNM (ROR: 2.94, 95% CI: 1.32–6.56), and female PPI users had a higher risk of BDNM (ROR: 2.44, 95% CI: 1.77–3.35). Among subordinate PTs, adenocarcinoma gastric and the combination of “bile duct cancer” and “cholangiocarcinoma” were highly correlated with PPI use. Conclusion. By mining the FAERS database, we provided important clues for the correlation between PPI use and DTC risk.
{"title":"Digestive Tract Cancer-Related Adverse Events Correlated with Proton Pump Inhibitors Use: A Pharmacovigilance Study of the FDA Adverse Event Reporting System","authors":"Sheng-ying Gu, Shi-dan Yu, Zhen-yu Zhou, Shuo-wen Wang, Shan-shan Hu, Chen-yang Shi, Chen-dong Qi, Guo-rong Fan","doi":"10.1155/2023/6913722","DOIUrl":"https://doi.org/10.1155/2023/6913722","url":null,"abstract":"Background. Proton pump inhibitors (PPIs) are widely used to treat digestive system diseases. Previous studies have suggested conflicting results between PPI treatment and the risk for digestive tract cancers (DTCs). This study aimed to assess the effect of PPI use on DTCs by data mining of the FDA Adverse Event Reporting System (FAERS) database. Method. This study examined the correlations between six PPI agents and DTCs by mining the FAERS database from January 2004 to September 2021 by using OpenVigil 2.1. The reporting odds ratio (ROR) defined as the ratio between the odds of reporting a specific adverse event for one drug divided by the corresponding odds for all other drugs, with 95% confidence intervals (CIs), was used to detect statistically significant correlations between PPIs and DTCs. High-level terms (HLTs) and preferred terms (PTs) were defined by the Medical Dictionary for Regulatory Activities 24.0 (MedDRA24.0). Result. A total of 2553 DTC adverse event reports were screened, with positive signals obtained from gastric neoplasms malignant (GNM) (ROR: 1.09, 95% CI: 1.01–1.18) and bile duct neoplasms malignant (BDNM) (ROR: 1.80, 95% CI: 1.44–2.25). Esomeprazole showed the strongest signal (ROR: 1.85, 95% CI: 1.66–2.06) for GNM, while rabeprazole for BDNM (ROR: 2.94, 95% CI: 1.32–6.56), and female PPI users had a higher risk of BDNM (ROR: 2.44, 95% CI: 1.77–3.35). Among subordinate PTs, adenocarcinoma gastric and the combination of “bile duct cancer” and “cholangiocarcinoma” were highly correlated with PPI use. Conclusion. By mining the FAERS database, we provided important clues for the correlation between PPI use and DTC risk.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135918578","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}
Mohamed F. Abdelhameed, Tamer I. M. Ragab, Asmaa S. Abd Elkarim, Mohamed H. Abd El-Razek, Mona F. Shabana, Sherif S. Mohamed, Suzan M. El-Morshedy, Abd El-Nasser G. El Gendy, Sherif M. Afifi, Tuba Esatbeyoglu, Abdelsamed I. Elshamy
The use of standard synthetic medications to treat inflammatory illnesses is associated with several negative effects. It has been shown that medicinal plants and their by-products are useful for safely treating inflammation. Herein, the essential oil of Eugenia supra-axillaris (family: Myrtaceae, ESA-EO) was isolated and further chemically characterized by GC-MS, and then, its nanoemulsion (ESA-EO-NE) was prepared. In addition, the anti-inflammation against the carrageenan-induced rats, the analgesic, and antipyretic activities of ESA-EO and ESA-EO-NE were evaluated in rats. Forty-three compounds were identified via GC-MS and categorized as mono- (61.38%) and sesquiterpenes (34.86%). d-limonene (32.82%), α-pinene (24.33%), germacrene-D (4.88%), α-humulene (4.73%), α-cadinol (3.39%), and trans-caryophyllene (3.15%) represented the main components. The administration of ES-EO and ES-EO-NE (50 and 100 mg/kg) demonstrated strong, dose-dependent inflammation inhibition capabilities in the model of rat paw edema, in comparison with both the reference drug and control. Reduced levels of malondialdehyde (MDA), increased levels of glutathione (GSH), and decreased levels of the proinflammatory cytokines (TNF-α), nitrosative (NO), and prostaglandin E2 (PGE2) in paw tissues all contributed to these substantial reductions in inflammation. Moreover, the oral administration of ESA-EO and ESA-EO-NE (50 and 100 mg/kg) exhibited potent analgesic and antipyretic activities in rats. Although the higher dose of ESA-EO and ESA-EO-NE (100 mg/kg) displayed delayed anti-inflammatory activity, they have long-lasting inflammation inhibition with fast onset and long-standing analgesic effects better than reference drugs. Furthermore, the most effective antipyretic efficacy was provided by ESA-EO-NE (100 mg/kg). These results provide insight into the possible therapeutic application of ESA-EO and its nanoemulsion against various inflammatory and painful illnesses as well as hyperthermia ailments.
{"title":"Eugenia supra-axillaris Essential Oil and Its Nanoemulsion: Chemical Characterization, In Vivo Anti-Inflammatory, Analgesic, and Antipyretic Activities","authors":"Mohamed F. Abdelhameed, Tamer I. M. Ragab, Asmaa S. Abd Elkarim, Mohamed H. Abd El-Razek, Mona F. Shabana, Sherif S. Mohamed, Suzan M. El-Morshedy, Abd El-Nasser G. El Gendy, Sherif M. Afifi, Tuba Esatbeyoglu, Abdelsamed I. Elshamy","doi":"10.1155/2023/4594990","DOIUrl":"https://doi.org/10.1155/2023/4594990","url":null,"abstract":"The use of standard synthetic medications to treat inflammatory illnesses is associated with several negative effects. It has been shown that medicinal plants and their by-products are useful for safely treating inflammation. Herein, the essential oil of Eugenia supra-axillaris (family: Myrtaceae, ESA-EO) was isolated and further chemically characterized by GC-MS, and then, its nanoemulsion (ESA-EO-NE) was prepared. In addition, the anti-inflammation against the carrageenan-induced rats, the analgesic, and antipyretic activities of ESA-EO and ESA-EO-NE were evaluated in rats. Forty-three compounds were identified via GC-MS and categorized as mono- (61.38%) and sesquiterpenes (34.86%). d-limonene (32.82%), α-pinene (24.33%), germacrene-D (4.88%), α-humulene (4.73%), α-cadinol (3.39%), and trans-caryophyllene (3.15%) represented the main components. The administration of ES-EO and ES-EO-NE (50 and 100 mg/kg) demonstrated strong, dose-dependent inflammation inhibition capabilities in the model of rat paw edema, in comparison with both the reference drug and control. Reduced levels of malondialdehyde (MDA), increased levels of glutathione (GSH), and decreased levels of the proinflammatory cytokines (TNF-α), nitrosative (NO), and prostaglandin E2 (PGE2) in paw tissues all contributed to these substantial reductions in inflammation. Moreover, the oral administration of ESA-EO and ESA-EO-NE (50 and 100 mg/kg) exhibited potent analgesic and antipyretic activities in rats. Although the higher dose of ESA-EO and ESA-EO-NE (100 mg/kg) displayed delayed anti-inflammatory activity, they have long-lasting inflammation inhibition with fast onset and long-standing analgesic effects better than reference drugs. Furthermore, the most effective antipyretic efficacy was provided by ESA-EO-NE (100 mg/kg). These results provide insight into the possible therapeutic application of ESA-EO and its nanoemulsion against various inflammatory and painful illnesses as well as hyperthermia ailments.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135854509","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}
What is Known and Objective. To explore the effects of traditional Chinese medicine (TCM) combined with levothyroxine (L-T4) on thyroid autoantibodies, inflammation, and sleep quality in Hashimoto’s thyroiditis patients. Methods. Patients were randomly divided into group A and group B. Group A was treated with L-T4 alone, while group B was treated with integrated TCM and L-T4. TCM symptoms were quantified before and after treatment as well as PSQI. Blood samples were taken to detect clinical indicators and thyroid autoantibodies. Cytokines in serum and thyroid tissues were analyzed by ELISA and RT-PCR. Results and Discussion. Totally, 196 patients were enrolled in the study, and there were no differences between group A and group B at the baseline. TCM treatment effectively reduced the levels of TGAb and TPOAb and was a protective factor for the improvement of Hashimoto’s thyroiditis antibody titers, . The serum expressions of IL-17A, IL-6, and IFN-γ in group B after treatment were lower than those in group A and before, while the IL-10 level was raised from the baseline, . Similar results were found in the comparison of IL-17A, IFN-γ, and IL-10 in thyroid tissues of group A, B, and control, . Besides, with integrated treatment, all TCM symptoms except for poor memory were improved as well as sleep quality and mood, . However, these changes were not observed before and after treatment with L-T4 in group A. What is New and Conclusion. The integrated treatment with TCM had a significant effect on thyroid autoantibodies, inflammation, and sleep quality in Hashimoto’s thyroiditis patients and provided a new and effective method for future treatment.
已知的和客观的。探讨中药联合左旋甲状腺素(L-T4)对桥本甲状腺炎患者甲状腺自身抗体、炎症及睡眠质量的影响。方法。将患者随机分为A组和B组。A组采用L-T4单药治疗，B组采用中医联合L-T4治疗。量化治疗前后中医症状及PSQI。采血检测临床指标及甲状腺自身抗体。ELISA和RT-PCR检测血清和甲状腺组织细胞因子。结果和讨论。研究共纳入196例患者，A组和B组在基线时无差异。中医药治疗可有效降低TGAb和TPOAb水平，是桥本甲状腺炎抗体效价提高的保护因素，p <0.05。治疗后B组血清IL-17A、IL-6、IFN-γ表达均低于A组及治疗前，IL-10水平较治疗前升高，p <0.05。比较A组、B组和对照组甲状腺组织中IL-17A、IFN-γ和IL-10, p <0.05。综合治疗后，除记忆力差外，其他中医症状均有改善，睡眠质量和情绪均有改善，p <0.05。而a组在L-T4治疗前后未见上述变化。中医综合治疗对桥本甲状腺炎患者甲状腺自身抗体、炎症及睡眠质量均有显著影响，为今后治疗提供了新的有效方法。
{"title":"Effect of Integrated Treatment with Traditional Chinese Medicine on Hashimoto’s Thyroiditis Patients","authors":"Xudan Lou, Yuxin Huang, Jieyuzhen Qiu, Jiao Sun, Qin Gu, Haidong Wang, Xiaoming Tao, Cuiping Jiang","doi":"10.1155/2023/5574095","DOIUrl":"https://doi.org/10.1155/2023/5574095","url":null,"abstract":"What is Known and Objective. To explore the effects of traditional Chinese medicine (TCM) combined with levothyroxine (L-T4) on thyroid autoantibodies, inflammation, and sleep quality in Hashimoto’s thyroiditis patients. Methods. Patients were randomly divided into group A and group B. Group A was treated with L-T4 alone, while group B was treated with integrated TCM and L-T4. TCM symptoms were quantified before and after treatment as well as PSQI. Blood samples were taken to detect clinical indicators and thyroid autoantibodies. Cytokines in serum and thyroid tissues were analyzed by ELISA and RT-PCR. Results and Discussion. Totally, 196 patients were enrolled in the study, and there were no differences between group A and group B at the baseline. TCM treatment effectively reduced the levels of TGAb and TPOAb and was a protective factor for the improvement of Hashimoto’s thyroiditis antibody titers, <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M1\"> <mi>p</mi> <mtext> </mtext> <mo><</mo> <mtext> </mtext> <mn>0.05</mn> </math> . The serum expressions of IL-17A, IL-6, and IFN-γ in group B after treatment were lower than those in group A and before, while the IL-10 level was raised from the baseline, <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M2\"> <mi>p</mi> <mtext> </mtext> <mo><</mo> <mtext> </mtext> <mn>0.05</mn> </math> . Similar results were found in the comparison of IL-17A, IFN-γ, and IL-10 in thyroid tissues of group A, B, and control, <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M3\"> <mi>p</mi> <mtext> </mtext> <mo><</mo> <mtext> </mtext> <mn>0.05</mn> </math> . Besides, with integrated treatment, all TCM symptoms except for poor memory were improved as well as sleep quality and mood, <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M4\"> <mi>p</mi> <mtext> </mtext> <mo><</mo> <mtext> </mtext> <mn>0.05</mn> </math> . However, these changes were not observed before and after treatment with L-T4 in group A. What is New and Conclusion. The integrated treatment with TCM had a significant effect on thyroid autoantibodies, inflammation, and sleep quality in Hashimoto’s thyroiditis patients and provided a new and effective method for future treatment.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"247 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136294752","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：