DARU Journal of Pharmaceutical Sciences最新文献

{"title":"Dexmedetomidine alleviates Hypoxia/reoxygenation-induced mitochondrial dysfunction in cardiomyocytes via activation of Sirt3/Prdx3 pathway.","authors":"Qingyun Tan, Wenming Dong, Qingdong Wang, Li Gao","doi":"10.1007/s40199-024-00504-3","DOIUrl":"10.1007/s40199-024-00504-3","url":null,"abstract":"<p><strong>Background: </strong>Myocardial ischemia/reperfusion injury (MIRI) seriously threatens the health of people. The mitochondrial dysfunction in cardiomyocytes can promote the progression of MIRI. Dexmedetomidine (Dex) could alleviate the myocardial injury, which was known to reverse mitochondrial dysfunction in lung injury. However, the function of Dex in mitochondrial dysfunction during MIRI remains unclear.</p><p><strong>Objective: </strong>To assess the function of Dex in mitochondrial dysfunction during MIRI.</p><p><strong>Methods: </strong>To investigate the function of Dex in MIRI, H9C2 cells were placed in condition of hypoxia/reoxygenation (H/R). CCK8 assay was performed to test the cell viability, and the mitochondrial membrane potential was evaluated by JC-1 staining. In addition, the binding relationship between Sirt3 and Prdx3 was explored by Co-IP assay. Furthermore, the protein expressions were examined using western blot.</p><p><strong>Results: </strong>Dex could abolish H/R-induced mitochondrial dysfunction in H9C2 cells. In addition, H/R treatment significantly inhibited the expression of Sirt3, while Dex partially restored this phenomenon. Knockdown of Sirt3 or Prdx3 obviously reduced the protective effect of Dex on H/R-induced mitochondrial injury. Meanwhile, Sirt3 could enhance the function of Prdx3 via deacetylation of Prdx3.</p><p><strong>Conclusion: </strong>Dex was found to attenuate H/R-induced mitochondrial dysfunction in cardiomyocytes via activation of Sirt3/Prdx3 pathway. Thus, this study might shed new lights on exploring new strategies for the treatment of MIRI.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"189-196"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adrenergic receptors blockade alleviates dexamethasone-induced neurotoxicity in adult male Wistar rats: Distinct effects on β-arrestin2 expression and molecular markers of neural injury.","authors":"Rasha M S M Mohamed, Enssaf Ahmad Ahmad, Dalia M Amin, Samar Ahmed Abdo, Islam A A E-H Ibrahim, Mona F Mahmoud, Shimaa Abdelaal","doi":"10.1007/s40199-023-00490-y","DOIUrl":"10.1007/s40199-023-00490-y","url":null,"abstract":"<p><strong>Background: </strong>Dexamethasone-induced neurotoxicity has been previously reported. However, the molecular mechanisms are still not completely understood.</p><p><strong>Objectives: </strong>The current work aimed to investigate the modulatory effects of α- and β-adrenergic receptors on dexamethasone-induced neurotoxicity in rats focused on changes in β-arrestin2 and molecular markers of neural injury in cerebral cortex.</p><p><strong>Methods: </strong>Male Wistar rats were subcutaneously injected with dexamethasone (10 mg/kg/day) for 7 days to induce neural injury in the cerebral cortex. The experiment involved 5 groups: control, dexamethasone, carvedilol, propranolol, and doxazosin. In the last 3 groups, drugs were given 2 hours before dexamethasone injection. At the end of experiment, brain samples were collected for measurement of brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), kinase activity of protein kinase B (Akt), diacylglycerol (DAG), α-smooth muscle actin (α-SMA), Smad3, β-amyloid and phospho-tau protein levels in addition to histopathological examination of brain tissue using hematoxylin-eosin, Nissl, and Sirius red stains. Moreover, β-arrestin2 levels in the cerebral cortex were measured using immunohistochemical examination.</p><p><strong>Results: </strong>Dexamethasone slightly reduced brain weight and significantly decreased BDNF, Akt kinase activity and β-arrestin2 but markedly induced degeneration of cortical neurons and significantly increased GFAP, DAG, α-SMA, Smad3, β-amyloid and phospho-tau protein levels compared to controls. Carvedilol, propranolol, and doxazosin reversed all dexamethasone-induced molecular changes and slightly ameliorated the histopathological changes. Carvedilol significantly increased brain weight and β-arrestin2 levels compared to dexamethasone, propranolol, and doxazosin groups.</p><p><strong>Conclusion: </strong>blocking α- and/or β-adrenergic receptors alleviate dexamethasone-induced neurotoxicity despite their distinct effects on β-arrestin2 levels in the cerebral cortex.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"97-108"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107590495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atypical extrapyramidal manifestation of a typical antipsychotic with serotonergic antidepressant.","authors":"Rohit Singh, Sankha Shubhra Chakrabarti, Upinder Kaur","doi":"10.1007/s40199-023-00489-5","DOIUrl":"10.1007/s40199-023-00489-5","url":null,"abstract":"<p><strong>Introduction: </strong>Typical antipsychotics are known to produce extrapyramidal side effects such as drug induced parkinsonism, acute dystonia, akathisia, tardive dyskinesias and rabbit syndrome. Rabbit syndrome is characterized by vertical rhythmic motion of the mouth and lips, resembling chewing movements of a rabbit.</p><p><strong>Reason for the report: </strong>Rabbit syndrome seen in patients on antidopaminergic therapies is characterized by vertical rhythmic movements of perioral region, has a late onset, and characteristically spares the tongue. The main aim of the report is to highlight atypical manifestation of antipsychotic associated Rabbit syndrome in the presence of a serotonergic antidepressant. An elderly patient presented with atypical rabbit syndrome with relatively acute onset, horizontal movements of jaw and marked tongue involvement after haloperidol-escitalopram initiation.</p><p><strong>Outcome: </strong>The patient improved with discontinuation of antipsychotic. The tongue involvement was believed to be secondary to escitalopram use.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"439-441"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92153140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-delivery of artemisinin and metformin via PEGylated niosomal nanoparticles: potential anti-cancer effect in treatment of lung cancer cells.","authors":"Salah Jaafar Abdulkareem, Davoud Jafari-Gharabaghlou, Mahdi Farhoudi-Sefidan-Jadid, Elnaz Salmani-Javan, Fatemeh Toroghi, Nosratollah Zarghami","doi":"10.1007/s40199-023-00495-7","DOIUrl":"10.1007/s40199-023-00495-7","url":null,"abstract":"<p><strong>Purpose: </strong>Despite the advances in treatment, lung cancer is a global concern and necessitates the development of new treatments. Biguanides like metformin (MET) and artemisinin (ART) have recently been discovered to have anti-cancer properties. As a consequence, in the current study, the anti-cancer effect of MET and ART co-encapsulated in niosomal nanoparticles on lung cancer cells was examined to establish an innovative therapy technique.</p><p><strong>Methods: </strong>Niosomal nanoparticles (Nio-NPs) were synthesized by thin-film hydration method, and their physicochemical properties were assessed by FTIR. The morphology of Nio-NPs was evaluated with FE-SEM and AFM. The MTT assay was applied to evaluate the cytotoxic effects of free MET, free ART, their encapsulated form with Nio-NPs, as well as their combination, on A549 cells. Apoptosis assay was utilized to detect the biological processes involved with programmed cell death. The arrest of cell cycle in response to drugs was assessed using a cell cycle assay. Following a 48-h drug treatment, the expression level of hTERT, Cyclin D1, BAX, BCL-2, Caspase 3, and 7 genes were assessed using the qRT-PCR method.</p><p><strong>Results: </strong>Both MET and ART reduced the survival rate of lung cancer cells in the dose-dependent manner. The IC₅₀ values of pure ART and MET were 195.2 μM and 14.6 mM, respectively while in nano formulated form their IC₅₀ values decreased to 56.7 μM and 78.3 μM, respectively. The combination of MET and ART synergistically decreased the proliferation of lung cancer cells, compared to the single treatments. Importantly, the combination of MET and ART had a higher anti-proliferative impact against A549 lung cancer cells, with lower IC₅₀ values. According to the result of Real-time PCR, hTERT, Cyclin D1, BAX, BCL-2, Caspase 3, and Caspase 7 genes expression were considerably altered in treated with combination of nano formulated MET and ART compared to single therapies.</p><p><strong>Conclusion: </strong>The results of this study showed that the combination of MET and ART encapsulated in Nio-NPs could be useful for the treatment of lung cancer and can increase the efficiency of lung cancer treatment.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"133-144"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prophylactic norepinephrine combined with 6% hydroxyethyl starch (130/0.4) co-load infusion for preventing postspinal anesthesia hypotension during cesarean section: a randomized, controlled, dose-finding trial.","authors":"Lei Guo, Xiangsheng Xiong, Rui Qin, Zhenzhou Li, Yongqiang Shi, Wei Xue, Ling He, Shuqin Ma, Yi Chen","doi":"10.1007/s40199-023-00479-7","DOIUrl":"10.1007/s40199-023-00479-7","url":null,"abstract":"<p><strong>Purpose: </strong>Colloid and/or co-load may be more effective than crystalloid for preventing postspinal anesthesia hypotension. We tested five different prophylactic norepinephrine dosages combined with colloid co-load infusion in patients receiving cesarean section and spinal anesthesia.</p><p><strong>Methods: </strong>Patients were randomly allocated to receive different prophylactic norepinephrine dosages (0 [NE 0 group], 0.025 [NE 25 group], 0.05 [NE 50 group], 0.075 [NE 75 group], or 0.1 [NE 100 group] µg/kg/min) combined with 500 mL 6% hydroxyethyl starch (130/0.4) immediately following spinal anesthesia (n = 35 per group). The primary endpoint was the incidence of postspinal anesthesia hypotension (systolic blood pressure [SBP] < 80% of baseline). Secondary endpoints included severe hypotension, bradycardia, nausea or vomiting, hypertension, SBP stability control versus baseline, the 50% (effective dose, ED50) and 90% (ED90) dose effective for preventing postspinal anesthesia hypotension, Apgar scores, and umbilical cord blood gases.</p><p><strong>Results: </strong>The incidence of postspinal anesthesia hypotension was 48.6%, 31.3%, 17.1%, 14.3%, and 5.7% in the respective groups. As the prophylactic norepinephrine dosage increased, the incidence of postspinal anesthesia hypotension declined (p < 0.001), and SBP remained stable relative to baseline (median performance error [MDPE], p < 0.001; median absolute performance error [MDAPE], p = 0.001). The ED50 and ED90 values were -0.006 (95% CI -0.046-0.013) and 0.081 (95% CI 0.063-0.119) µg/kg/min. Other endpoints were comparable across the groups.</p><p><strong>Conclusion: </strong>An initial prophylactic norepinephrine dosage of 0.05 µg/kg/min combined with 500 mL 6% hydroxyethyl starch (130/0.4) co-load infusion was optimal for preventing postspinal anesthesia hypotension during cesarean section.</p><p><strong>Trial registration: </strong>NCT05133817, registration date: 12 Nov, 2021.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"1-9"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41106497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chidamide inhibits cell glycolysis in acute myeloid leukemia by decreasing N6-methyladenosine-related GNAS-AS1.","authors":"Changmei Hu, Xiao Fu, Shujun Li, Cong Chen, Xielan Zhao, Jie Peng","doi":"10.1007/s40199-023-00482-y","DOIUrl":"10.1007/s40199-023-00482-y","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is a hematopoietic malignancy. Chidamide has shown anti-cancer effect in different malignancies. The function of Chidamide in glycolysis in AML cells remains unclear.</p><p><strong>Methods: </strong>AML cells were treated with 1000 nM Chidamide for 48 h. The levels of long non-coding RNA-GNAS-AS1, miR-34a-5p, glycolysis-related proteins, and Ras homolog gene family (RhoA)/Rho-associated protein kinase (ROCK) signaling-related proteins were detected by qRT-PCR or western blot. Cell viability and apoptosis were measured by CCK-8 and flow cytometry. Glycolysis levels were measured by assay kits. GNAS-AS1 N6-methyladenosine (m6A) modification level was detected by methylated RNA immunoprecipitation sequencing. The combined targets of miR-34a-5p were validated using a dual-luciferase reporter assay. BALB/C nude mice were selected for subcutaneous tumor validation. Chidamide at a dosage of 25 mg/kg was used in the animal study.</p><p><strong>Results: </strong>GNAS-AS1 promoted glycolysis in AML cells by upregulating the expression of glycolysis-related proteins and increasing glucose consumption, lactate production, ATP generation, and the extracellular acidification rate. Chidamide treatment suppressed WT1-associated protein (WTAP)-mediated RNA m6A modification of GNAS-AS1. Chidamide downregulated GNAS-AS1 to inhibit glycolysis in AML cells. GNAS-AS1 targeted miR-34a-5p to promote insulin-like growth factor 2 mRNA-binding protein (IGF2BP2) expression. IGF2BP2 inhibition reversed the promoting effect of miR-34a-5p knockdown on glycolysis and RhoA/ROCK pathway in Chidamide-treated cells. GNAS-AS1 overexpression abolished the inhibitory effect of Chidamide on AML tumorigenesis in vivo by modulating the RhoA/ROCK pathway.</p><p><strong>Conclusion: </strong>Chidamide inhibited glycolysis in AML by repressing WTAP-mediated GNAS-AS1 m6A modification and then regulating the miR-34a-5p/IGF2BP2 axis.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"11-24"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imiquimod as a new treatment in refractory idiopathic granulomatous mastitis: report of two cases.","authors":"Sadaf Alipour, Bardia Gholami, Marzieh Orouji, Samareh Heydari","doi":"10.1007/s40199-023-00501-y","DOIUrl":"10.1007/s40199-023-00501-y","url":null,"abstract":"<p><strong>Introduction: </strong>Idiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory lesion of the breast that mimics breast cancer or infection. Immunological pathogenesis is strongly suggested for the disease.</p><p><strong>Reason for the report: </strong>The treatment remains controversial, comprising a spectrum from observation or NSAIDs to immunosuppressive agents and surgery. Intractable cases are not uncommon and represent a major treatment challenge. Therefore in this study, we examine the effect of a topical immunomodulator agent, imiquimod, on refractory IGM. Patient 1 had IGM for 9 months and had not responded to the existing treatments. She responded to a 7-week course of imiquimod. In patient 2, the disease had begun 4 months sooner and had been resistant to all treatments; it responded to imiquimod after 4 weeks. Ulcers appeared on the skin of both patients but resolved safely.</p><p><strong>Outcome: </strong>Both patients were very satisfied with the results. Imiquimod can be an appropriate local treatment with limited adverse effects in refractory IGM. We propose similar studies to assess the efficacy of imiquimod in IGM further, paying attention to the possibility of developing skin wounds.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"443-447"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activity of zinc oxide and zinc borate nanoparticles against resistant bacteria in an experimental lung cancer model.","authors":"Demet Celebi, Ozgur Celebi, Ali Taghizadehghalehjoughi, Sumeyye Baser, Elif Aydın, Daniela Calina, Ekaterina Charvalos, Anca Oana Docea, Aristidis Tsatsakis, Yaroslav Mezhuev, Serkan Yildirim","doi":"10.1007/s40199-024-00505-2","DOIUrl":"10.1007/s40199-024-00505-2","url":null,"abstract":"<p><strong>Background: </strong>Recent research indicates a prevalence of typical lung infections, such as pneumonia, in lung cancer patients. Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii stand out as antibiotic-resistant pathogens. Given this, there is a growing interest in alternative therapeutic avenues. Boron and zinc derivatives exhibit antimicrobial, antiviral, and antifungal properties.</p><p><strong>Objectives: </strong>This research aimed to establish the effectiveness of ZnO and ZB NPs in combating bacterial infections in lung cancer cell lines.</p><p><strong>Methods: </strong>Initially, this study determined the minimal inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) of zinc oxide nanoparticles (ZnO NPs) and zinc borate (ZB) on chosen benchmark strains. Subsequent steps involved gauging treatment success through a lung cancer-bacteria combined culture and immunohistochemical analysis.</p><p><strong>Results: </strong>The inhibitory impact of ZnO NPs on bacteria was charted as follows: 0.97 µg/mL for K. pneumoniae 700603, 1.95 µg/mL for P. aeruginosa 27853, and 7.81 µg/mL for Acinetobacter baumannii 19,606. In comparison, the antibacterial influence of zinc borate was measured as 7.81 µg/mL for Klebsiella pneumoniae 700603 and 500 µg/mL for both P. aeruginosa 27853 and A.baumannii 19606. After 24 h, the cytotoxicity of ZnO NPs and ZB was analyzed using the MTT technique. The lowest cell viability was marked in the 500 µg/mL ZB NPs group, with a viability rate of 48.83% (P < 0.001). However, marked deviations appeared at ZB concentrations of 61.5 µg/mL (P < 0.05) and ZnO NPs at 125 µg/mL.</p><p><strong>Conclusion: </strong>A synergistic microbial inhibitory effect was observed when ZnO NP and ZB were combined against the bacteria under investigation.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"197-206"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139746285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost minimization analysis of subcutaneous trastuzumab versus intravenous biosimilar trastuzumab: policy recommendations for breast cancer treatment in Malaysia.","authors":"Jin Ee Heng, Sivaraj Raman, Zhi Yen Wong, Valerine Jen Nin Beh","doi":"10.1007/s40199-023-00485-9","DOIUrl":"10.1007/s40199-023-00485-9","url":null,"abstract":"<p><strong>Purpose: </strong>Current clinical practice recommends switching innovator intravenous trastuzumab (IV-TZM_i) to subcutaneous trastuzumab (SC-TZM) to save healthcare resources. However, with the availability of biosimilar intravenous trastuzumab (IV-TZM_b), there is a need to re-evaluate the recommendation. Hence, this study aims to compare the cost and resource use of SC-TZM and IV-TZM_b in a Malaysian public healthcare facility.</p><p><strong>Methods: </strong>This activity-based costing study consists of (1) a retrospective medical record abstraction to determine patient details to estimate drug costs and (2) a time-motion study to quantify personnel time, patient time, and consumables used. The total cost of both SC-TZM and IV-TZM_b were then compared using a cost-minimization approach, while differences were explored using an independent t-test. A sensitivity analysis was also conducted to determine the impact of uncertainties in the analysis.</p><p><strong>Results: </strong>The mean total cost of SC-TZM and IV-TZM_b was USD 13,693 and USD 5,624 per patient respectively. The cost difference was primarily contributed by savings in drug cost of IV-TZM_b, a reduction of USD 8,546 (SD = 134), p < 0.001 compared to SC-TZM. Interestingly, SC-TZM had a significantly lower cost than IV-TZM_b for both the consumable and personnel cost, a reduction by USD 300 (SD = 17.6); p < 0.001 and USD 176 (SD = 7.3); p < 0.001 respectively. The sensitivity analysis demonstrated that the total cost difference between the formulation was mainly driven by drug costs.</p><p><strong>Conclusion: </strong>The study evidenced that IV-TZM_b was a more economically viable option in Malaysian public healthcare currently compared to SC-TZM.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"67-76"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71411060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ropivacaine suppresses the progression of renal cell carcinoma through regulating the lncRNA RMRP/EZH2/CCDC65 axis.","authors":"Yingfen Xiong, Xiaolan Zheng, Huangying Deng","doi":"10.1007/s40199-023-00492-w","DOIUrl":"10.1007/s40199-023-00492-w","url":null,"abstract":"<p><strong>Background: </strong>Renal cell carcinoma (RCC) is a common malignancy. Local anesthetics were displayed powerful effects against various cancers. This study aims to probe the functions and molecular mechanism of ropivacaine in RCC.</p><p><strong>Methods: </strong>Different concentrations of ropivacaine were performed to administrate RCC cells including 786-O and Caki-1 cells. Cell viability and cell apoptosis were examined using CCK-8 and flow cytometry, respectively. Cell migration and invasion were determined by transwell assay. RMRP and CCDC65 expression was firstly predicted using TCGA dataset and further validated in RCC cells using qRT-PCR and western blot. The interactions among RMRP, EZH2 and CCDC65 were verified by RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays.</p><p><strong>Results: </strong>Ropivacaine effectively suppressed RCC cell viability, migration and invasion and enhanced cell apoptosis rate. Aberrantly elevated RMRP expression in RCC tissues was predicted by TCGA database. Interestingly, overexpressed RMRP observed in RCC cells could be also blocked upon the administration of ropivacaine. Likewise, RMRP knockdown further strengthened ropivacaine-mediated tumor suppressive effects on RCC cells. In terms of mechanism, RMRP directly interacted with EZH2, thereby modulating the histone methylation of CCDC65 to silence its expression. Moreover, ropivacaine inhibited tumor growth in mice bearing RCC tumor through regulating RMRP/EZH2/CCDC65 axis.</p><p><strong>Conclusion: </strong>In sum up, our work revealed that ropivacaine suppressed capacities of RCC cell viability, migration and invasion through modulating the RMRP/EZH2/CCDC65 axis, which laid the experimental foundation of ropivacaine for clinical application in the future.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"121-132"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}