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Cost consequence analysis of adding semaglutide to treatment regimen for patients with Type II diabetes in Saudi Arabia 在沙特阿拉伯 II 型糖尿病患者的治疗方案中加入塞马鲁肽的成本后果分析
IF 4.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-29 DOI: 10.1016/j.jsps.2024.102057
Yazed AlRuthia , Khaled Hani Aburisheh , Sondus Ata , Raghad Bin Salleeh , Shahad B. Alqudhibi , Raghad B. Alqudhibi , Ziad Alkraidis , Hala Humood Alkhalaf , Abdulrahman Abdullah Almogirah , Muhammad Mujammami , Reem Al Khalifah

Introduction

Semaglutide, a Glucagon-like Peptide-1 Receptor Agonist (GLP-1 RA), is often prescribed for managing type 2 diabetes, particularly in cases unresponsive to other hypoglycemic agents. Despite its popularity, the real-world efficacy and cost-effectiveness of Semaglutide relative to other treatments remain understudied.

Objective

This study aimed to examine the direct medical cost and consequences of adding Semaglutide to the treatment regimen for patients with type 2 diabetes in Saudi Arabia.

Methods

We conducted a single-center, retrospective review of Electronic Medical Records (EMRs) for adults with type 2 diabetes. Patients who had been on Semaglutide for at least three months were matched with those receiving alternative hypoglycemic therapies. Exclusions were made for patients with cancer, incomplete EMRs, or lacking prescription data. Investigated outcomes included changes in HbA1C levels and weight, and the direct costs comprised medications, clinic visits, and emergency care. Baseline adjustments were made through inverse probability treatment weighting, and uncertainty was assessed via bootstrapping with 10,000 replications.

Results

Out of 350 patients meeting the criteria, 116 were on Semaglutide. Predominantly females (62%), the cohort had an average age of 60 and a disease duration of 22 years. The difference in HbA1C (%) reductions between Semaglutide and non-Semaglutide users over 3,6, and 12 months were 0.154 (95% CI: –0.452-0.483), –0.031(95% CI: –0.754-0.239), –0.16(95% CI: –1.425-0.840), respectively. Semaglutide users did experience modest weight reductions ranging from 0.42 kg to 1.16 kg. The annual additional direct medical cost for Semaglutide was USD 4,086.82 (95% CI: $3,710.85 - $4,294.99).

Conclusion

Although Semaglutide induced modest weight reductions, it did not offer significant advantages in lowering HbA1C levels compared to other hypoglycemic treatments. These findings suggest the need for further research involving larger and more diverse cohorts to corroborate these findings.

导言:塞马鲁肽是一种胰高血糖素样肽-1受体激动剂(GLP-1 RA),常被用于控制2型糖尿病,尤其是对其他降糖药物无效的病例。尽管塞马鲁肽很受欢迎,但与其他治疗方法相比,塞马鲁肽在现实世界中的疗效和成本效益仍未得到充分研究。 Objective This study aimed to examine the direct medical cost and consequences of adding Semaglutide to the treatment regimen for patients with type 2 diabetes in Saudi Arabia.MethodsWe conducted a single-center, retrospective review of Electronic Medical Records (EMRs) for adults with type 2 diabetes.我们对2型糖尿病成人患者的电子病历(EMRs)进行了单中心回顾性研究。将服用塞马鲁肽至少三个月的患者与接受其他降糖疗法的患者进行配对。排除了癌症患者、EMR 不完整或缺乏处方数据的患者。研究结果包括 HbA1C 水平和体重的变化,直接费用包括药物、门诊和急诊。基线调整通过反概率治疗加权法进行,不确定性通过 10,000 次重复的引导法进行评估。患者主要为女性(62%),平均年龄为 60 岁,病程为 22 年。在3个月、6个月和12个月期间,塞马鲁肽使用者与非塞马鲁肽使用者的HbA1C(%)降幅分别为0.154(95% CI:-0.452-0.483)、-0.031(95% CI:-0.754-0.239)、-0.16(95% CI:-1.425-0.840)。塞马鲁肽使用者的体重确实略有下降,从 0.42 千克到 1.16 千克不等。结论虽然塞马鲁肽可适度减轻体重,但与其他降糖治疗相比,它在降低HbA1C水平方面并无明显优势。这些研究结果表明,有必要进一步开展更大规模、更多样化的研究,以证实这些研究结果。
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引用次数: 0
The use and perceived value of electronic health information resources by health care professionals in the field of medicine, pharmacy, and nursing in Jazan province, Saudi Arabia 沙特阿拉伯贾赞省医学、药学和护理领域医护专业人员对电子健康信息资源的使用和认知价值
IF 4.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-28 DOI: 10.1016/j.jsps.2024.102056
Saad S. Alqahtani , Santhosh Joseph Menachery , Renju Ravi , Tahir Hakami , Manal Almalki

Background

Healthcare workers increasingly use Electronic Health Information Resources (EHIRs) to make evidence-based decisions. Our study was intended to assess the perception, attitude, and practice of healthcare professionals in medicine, pharmacy, and nursing regarding their perceived value and use of EHIRs.

Methods

We conducted an observational cross-sectional study using a pre-validated questionnaire among healthcare professionals in Jazan province from September 2022 to February 2023. We included healthcare professionals and interns with medical, pharmacy, or nursing degrees and excluded those who refused informed consent.

Results

We included fully completed data from 294 participants, with an actual response rate of just 80.1 %. Almost 87.41 % utilized the health information resources at their workplace, with UpToDate [39.45 %] and Medscape [67.01 %] being the most frequently used medical databases. The health facilities' access to electronic health resources significantly impacted healthcare professionals' [p = 0.04] and medical interns' [p = 0.02] roles. Faculty members felt the need to access electronic health information at their workplace [p = 0.00]. Lack of time to access electronic health information due to a busy schedule was a significant reason that impacted the attitude of medical professionals [p = 0.008] and nursing staff [p = 0.025]. An excessive amount of clinically unrelated data was the primary obstacle (181/294, p < 0.0001) in using electronic health information resources.

Conclusion

Our study showed the pattern of healthcare professionals using EHIRs in the Jazan province, Saudi Arabia. We believe the study's outcome can help increase the calibre of electronic health information services available to healthcare professionals and raise awareness of different EHIRs in improving clinical care.

背景医护人员越来越多地使用电子健康信息资源(EHIR)来做出循证决策。我们的研究旨在评估医学、药学和护理专业医护人员对电子健康信息资源的认知价值和使用情况的看法、态度和实践。我们将具有医学、药学或护理学位的医护人员和实习生纳入调查范围,并排除了拒绝知情同意的人员。结果我们纳入了 294 名参与者完整填写的数据,实际回复率仅为 80.1%。近 87.41% 的人在工作场所使用健康信息资源,其中 UpToDate [39.45%] 和 Medscape [67.01%] 是最常用的医疗数据库。医疗机构对电子医疗资源的使用情况对医护人员 [p = 0.04] 和实习医生 [p = 0.02] 的角色产生了重大影响。教职员工认为有必要在工作场所获取电子健康信息 [p = 0.00]。由于工作繁忙而没有时间获取电子健康信息是影响医务人员[p = 0.008]和护理人员[p = 0.025]态度的重要原因。过多与临床无关的数据是使用电子健康信息资源的主要障碍(181/294,p < 0.0001)。我们相信,研究结果有助于提高医护人员使用电子健康信息服务的水平,并提高人们对不同电子健康信息资源在改善临床护理方面的认识。
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引用次数: 0
The prevalence of cardiovascular diseases, chronic kidney disease, and obesity in patients with type 2 diabetes mellitus and the description of concurrent treatments: A two-center retrospective cross-sectional study in Saudi Arabia 2 型糖尿病患者中心血管疾病、慢性肾脏疾病和肥胖症的发病率以及并发症的治疗情况:沙特阿拉伯双中心回顾性横断面研究
IF 4.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-28 DOI: 10.1016/j.jsps.2024.102054
Omar A. Alshaya , Ghazwa B. Korayem , Munirah Alghwainm , Wed Alyami , Albandari Alotaibi , Majed S. Alyami , Omar A. Almohammed

Background

Atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), chronic kidney disease (CKD), and obesity are associated with increased morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Nonetheless, their prevalence among patients with T2DM in Saudi Arabia (SA) remains unknown. As current guidelines recommend, these comorbidities require adding certain antidiabetic agents with cardiorenal benefits. However, the prescribers' adherence to these recommendations remains unclear.

Methods

A two-center retrospective cross-sectional study was conducted including adult patients (≥18 years) with T2DM admitted to hospital or seen at outpatient clinics between January and December 2020. Patients were classified into two groups based on the presence or absence of ASCVD. Patients with no prior ASCVD history were further classified based on the 10-year ASCVD risk estimation. Endpoints of interest included the prevalence of ASCVD, HF, CKD, and obesity in patients with T2DM. We also evaluated the characteristics of the utilized antidiabetic agents, statin, and aspirin therapies..

Results

Of the 1,218 included patients with T2DM, the majority were female (57.0 %), and aged 45–64 years (53.0 %) with a mean age of 59.3 ± 13.1 years. Hypertension and dyslipidemia were the most prevalent comorbidities (67.7 % and 69.0 %, respectively). Among all patients, 18.6 % had an established ASCVD and the prevalence of HF, CKD, and obesity were 5.1 %, 8.7 %, and 58.3 %, respectively. The most common types of ASCVD witnessed were revascularization (42.3 %), myocardial infarction (36.6 %), and stroke (33.9 %); with an increased prevalence of ASCVD as the age increases (52.8 % at age ≥ 65 years). In the non‐ASCVD group, the 10-year ASCVD risk was intermediate or high in 62.7 % of these patients. The rates of utilization of guidelines-recommended therapies were 83.6 % for metformin, 9.4 % for GLP-1 RA, 10.8 % for SGLT2i, 35.2 % for aspirin alone or in combination with clopidogrel, and 79.7 % for statin therapy.

Conclusions

ASCVD, HF, CKD, and obesity are common complications in patients with T2DM in SA, with low overall utilization of the recommended guidelines-recommended medical therapies. Multimodal strategies should be utilized to assess T2DM and its complications, and to improve prescribers' adherence to guidelines-recommended therapies.

背景动脉粥样硬化性心血管疾病(ASCVD)、心力衰竭(HF)、慢性肾病(CKD)和肥胖与 2 型糖尿病(T2DM)患者发病率和死亡率的增加有关。然而,沙特阿拉伯(SA)的 T2DM 患者中这些合并症的发病率仍然未知。根据现行指南的建议,这些合并症需要添加某些对心肾功能有益的抗糖尿病药物。方法 对 2020 年 1 月至 12 月期间入院或在门诊就诊的 T2DM 成年患者(≥18 岁)进行了一项双中心回顾性横断面研究。根据是否存在 ASCVD 将患者分为两组。既往无 ASCVD 病史的患者则根据 10 年 ASCVD 风险估计值进一步分类。我们关注的终点包括 T2DM 患者中 ASCVD、HF、CKD 和肥胖的患病率。我们还评估了所使用的抗糖尿病药物、他汀类药物和阿司匹林疗法的特点。结果 在纳入的1218名T2DM患者中,大多数为女性(57.0%),年龄在45-64岁之间(53.0%),平均年龄为(59.3 ± 13.1)岁。高血压和血脂异常是最常见的合并症(分别占 67.7% 和 69.0%)。在所有患者中,18.6%已确诊为急性心血管疾病,而高血压、慢性肾脏病和肥胖的发病率分别为5.1%、8.7%和58.3%。最常见的 ASCVD 类型为血管重建(42.3%)、心肌梗死(36.6%)和中风(33.9%);随着年龄的增长,ASCVD 的患病率也在增加(年龄≥ 65 岁时为 52.8%)。在非 ASCVD 组中,62.7% 的患者 10 年 ASCVD 风险为中度或高度。指南推荐疗法的使用率分别为:二甲双胍 83.6%、GLP-1 RA 9.4%、SGLT2i 10.8%、阿司匹林单独使用或与氯吡格雷联合使用 35.2%、他汀类药物治疗 79.7%。应采用多模式策略来评估T2DM及其并发症,并提高处方者对指南推荐疗法的依从性。
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引用次数: 0
Iron-tannic acid nano-coating: A promising treatment approach for enhancing Lactococcus lactis antibiotic resistance 纳米单宁酸铁涂层:增强乳酸乳球菌抗生素耐药性的有效处理方法
IF 4.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-27 DOI: 10.1016/j.jsps.2024.102052
Marwa M. Elmaghrabi , Naiyf S. Alharbi , Ahmed S. Alobaidi , Adel A. Abdulmanea , Shine Kadaikunnan , Asmaa A. Ramadan , Jamal M. Khaled

The objective of this study was to explore a novel methodology for the synthesis of nanocoated probiotics following their collection and cultivation under optimized conditions, in light of their significant contribution to human health. Probiotics are instrumental in sustaining immune health by modulating the gastrointestinal microbiota and facilitating digestion. However, the equilibrium they maintain can be adversely affected by antibiotic treatments. It is critical to investigate the vulnerability of probiotics to antibiotics, considering the potential implications. This research aimed to assess whether nanoparticle coating could augment the probiotics' resistance to antibiotic influence. A strain of Lactococcus lactis (L. lactis) was isolated, cultured, and comprehensively characterized utilizing state-of-the-art methodologies, including the VITEK® 2 compact system, VITEK® MS, and 16S rRNA gene sequencing. The nanoparticle coating was performed using iron (III) chloride hexahydrate and tannic acid, followed by an evaluation of the probiotics' resistance to a range of antibiotics. The analysis through scanning electron microscopy (SEM) and atomic force microscopy (AFM) demonstrated a partial nanoparticle coating of the probiotics, which was further supported by UV/Vis spectroscopy findings, suggesting enhanced resistance to standard antibiotics. The results revealed that this strain possesses a unique protein profile and is genetically similar to strains identified in various other countries. Moreover, nano-encapsulation notably increased the strain's resistance to a spectrum of standard antibiotics, including Benzylpenicillin, Teicoplanin, Oxacillin, Vancomycin, Tetracycline, Rifampicin, Erythromycin, and Clindamycin. These findings imply that nanoparticle-coated probiotics may effectively counteract the detrimental effects of extended antibiotic therapy, thus preserving their viability and beneficial influence on gastrointestinal health.

鉴于益生菌对人类健康的重大贡献,本研究旨在探索一种新方法,在优化条件下收集和培养益生菌后合成纳米涂层益生菌。益生菌通过调节胃肠道微生物群和促进消化来维持免疫健康。然而,它们所维持的平衡可能会受到抗生素治疗的不利影响。考虑到潜在的影响,研究益生菌对抗生素的脆弱性至关重要。这项研究旨在评估纳米粒子涂层是否能增强益生菌对抗生素影响的抵抗力。利用最先进的方法,包括 VITEK® 2 紧凑型系统、VITEK® MS 和 16S rRNA 基因测序,对一株乳球菌(L. lactis)进行了分离、培养和全面鉴定。使用六水氯化铁(III)和单宁酸进行了纳米颗粒涂层,然后评估了益生菌对一系列抗生素的耐药性。扫描电子显微镜(SEM)和原子力显微镜(AFM)的分析表明,益生菌有部分纳米颗粒涂层,紫外/可见光谱的研究结果进一步证实了这一点,表明益生菌对标准抗生素的耐药性增强。研究结果表明,这种菌株具有独特的蛋白质特征,在基因上与其他国家发现的菌株相似。此外,纳米封装技术显著增强了该菌株对一系列标准抗生素的耐药性,包括苄青霉素、替考拉宁、氧西林、万古霉素、四环素、利福平、红霉素和克林霉素。这些研究结果表明,纳米颗粒包裹的益生菌可有效抵消长期抗生素治疗的不利影响,从而保持其活力并对胃肠道健康产生有益影响。
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引用次数: 0
Development of a microcantilever-based biosensor for detecting Programmed Death Ligand 1 开发基于微悬臂的生物传感器,用于检测程序死亡配体 1
IF 4.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-27 DOI: 10.1016/j.jsps.2024.102051
Tajweed Neairat , Mahmoud Al-Gawati , Qura Tul Ain , Abdulaziz K. Assaifan , Aws Alshamsan , Abdulaziz Alarifi , Abdullah N. Alodhayb , Khalid E. Alzahrani , Hamad Albrithen

The ongoing global concern of cancer worldwide necessitates the development of advanced diagnostic and therapeutic strategies. The majority of recent detection strategies involve the employment of biomarkers. A critical biomarker for cancer immunotherapy efficacy and patient prognosis is Programmed Death Ligand 1 (PD-L1), which is a key immune checkpoint protein. PD-L1 can be particularly linked to cancer progression and therapy response. Current detection methods, such as enzyme-linked immunosorbent assay (ELISA), face limitations like high cost, time consumption, and complexity. This study introduces a microcantilever-based biosensor designed for the detection of soluble PD-L1 (sPD-L1), which has a specific association with PD-L1. The biosensor utilizes anti-PD-L1 as the sensing layer, capitalizing on the specific binding affinity between anti-PD-L1 and sPD-L1. The presence of the sensing layer was confirmed through Atomic Force Microscopy (AFM) and contact angle measurements. Binding between sPD-L1 and anti-PD-L1 induces a shift in the microcantilever's resonance frequency, which is proportional to the PD-L1 concentration. Notably, the resonance frequency shift demonstrates a robust linear relationship with the increasing biomarker concentration, ranging from 0.05 ng/ml to 500 ng/ml. The detection limit of the biosensor was determined to be approximately 10 pg/ml. The biosensor demonstrates excellent performance in detecting PD-L1 with high specificity even in complex biological matrices. This innovative approach not only provides a promising tool for early cancer diagnosis but also holds potential for monitoring immunotherapy efficacy, paving the way for personalized and effective cancer treatments.

全球范围内对癌症的持续关注要求开发先进的诊断和治疗策略。最近的大多数检测策略都采用了生物标记物。程序性死亡配体 1 (PD-L1)是癌症免疫疗法疗效和患者预后的关键生物标志物,它是一种关键的免疫检查点蛋白。PD-L1 与癌症进展和治疗反应尤其相关。目前的检测方法,如酶联免疫吸附试验(ELISA),面临着成本高、耗时长、操作复杂等局限性。本研究介绍了一种基于微悬臂的生物传感器,用于检测与 PD-L1 有特异性关联的可溶性 PD-L1(sPD-L1)。该生物传感器利用抗 PD-L1 与 sPD-L1 之间的特异性结合亲和力,将抗 PD-L1 用作传感层。原子力显微镜(AFM)和接触角测量证实了传感层的存在。sPD-L1 和抗 PD-L1 之间的结合会引起微悬臂共振频率的偏移,这种偏移与 PD-L1 的浓度成正比。值得注意的是,共振频率偏移与生物标记物浓度的增加呈稳健的线性关系,从 0.05 纳克/毫升到 500 纳克/毫升不等。经测定,该生物传感器的检测限约为 10 pg/ml。即使在复杂的生物基质中,该生物传感器也能以高特异性检测 PD-L1,表现出卓越的性能。这种创新方法不仅为早期癌症诊断提供了一种前景广阔的工具,还具有监测免疫疗法疗效的潜力,为个性化和有效的癌症治疗铺平了道路。
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引用次数: 0
A nanocomposite competent to overcome solubility and permeation issues of capsaicin and thiocolchicoside simultaneously in gout management: Fabrication of nanocubosomes 同时克服辣椒素和硫代小檗苷在痛风治疗中的溶解性和渗透性问题的纳米复合材料:纳米立方体的制备
IF 4.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-24 DOI: 10.1016/j.jsps.2024.102050
Barkat Ali Khan , Falak Naz , Ali Alqahtani , Muhammad Khalid Khan

This study aimed to formulate nano-cubosomes (NCs) co-loaded with capsaicin (CAP) and thiocolchicoside (TCS) to enhance their bioavailability and minimize associated potential side effects through transdermal delivery alongside their synergistic activity. Twenty seven (27) nano-cubosomal dispersions were prepared according to Box-Behnken factorial design and the effect of CAP, TCS, glyceryl mono oleate (GMO) and poloxamer 407 (P407) concentrations on particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency were assessed. The results revealed that the optimized formulation exhibited a mean droplet size of 503 ± 10.3 nm, PDI of 0.405 ± 0.02, zeta potential of −10.0 ± 1.70 mV and entrapment efficiency of 86.9 ± 3.56 %. The in vivo anti-inflammatory effect of optimized formulation was studied in rats by injecting carrageenan to induce edema. The results of in vivo study showed that transdermal application of nano-cubosomes co-loaded with CAP and TCS significantly (p value < 0.05) improved carrageenan induced inflammation compared with standard treatment. The analgesic activity of optimized formulation was evaluated in rats by using Eddy’s hot plate method. The findings of analgesic activity illustrated that the analgesic effects exhibited by test formulation may be associated with increased licking period and inhibition of prostaglandins level. In conclusion, the transdermal application of NCs co-loaded with CAP and TCS may be a promising delivery system for enhancing their bioavailability as well as synergistic analgesic and anti-inflammatory activity in gout management.

本研究旨在配制共同载入辣椒素(CAP)和硫代积雪草苷(TCS)的纳米立方体(NCs),通过透皮给药提高其生物利用度,并最大限度地减少相关的潜在副作用,同时发挥它们的协同作用。按照 Box-Behnken 因式设计制备了二十七(27)种纳米立方体分散体,并评估了 CAP、TCS、单油酸甘油酯(GMO)和 Poloxamer 407(P407)浓度对粒度、多分散指数(PDI)、Zeta 电位和夹带效率的影响。结果显示,优化配方的平均液滴尺寸为 503 ± 10.3 nm,PDI 为 0.405 ± 0.02,zeta 电位为 -10.0 ± 1.70 mV,夹带效率为 86.9 ± 3.56 %。通过向大鼠注射卡拉胶诱导水肿,研究了优化配方的体内抗炎效果。体内研究结果表明,与标准治疗相比,经皮应用共同负载 CAP 和 TCS 的纳米立方体能显著改善卡拉胶诱导的炎症(p 值为 0.05)。采用艾迪热板法评估了优化配方在大鼠体内的镇痛活性。镇痛活性的研究结果表明,试验配方的镇痛效果可能与舔食期的延长和前列腺素水平的抑制有关。总之,在痛风治疗过程中,经皮应用共载 CAP 和 TCS 的 NCs 可能是一种很有前景的给药系统,可提高它们的生物利用度以及协同镇痛和抗炎活性。
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引用次数: 0
The effect mechanism of ergosterol from the nutritional mushroom Leucocalocybe mongolica in breast cancer cells: Protein expression modulation and metabolomic profiling using UHPLC-ESI-Q 麦角甾醇对乳腺癌细胞的影响机制:使用超高效液相色谱-ESI-Q进行蛋白质表达调控和代谢组学分析
IF 4.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-23 DOI: 10.1016/j.jsps.2024.102045
Asmaa Hussein Zaki , Bao Haiying , Mohamed Mohany , Salim S. Al-Rejaie , Bahaa Abugammie

The ergosterol from mushrooms has gained significant ethnopharmacological importance in various cultures, including China, Japan, and Europe. This compound has been found to possess immune-boosting and anti-inflammatory properties, making it useful in the treatment of immune disorders. In this study, we focused on investigating the potential anticancer properties of ergosterol isolated from the edible mushroom Leucocalocybe mongolica in breast cancer cell lines. The ergosterol was purified and identified using advanced analytical techniques such as ESI-MS and NMR. We conducted cell proliferation assays on 4 T1 breast cancer cells to assess the cytotoxic effects of ergosterol. Furthermore, we analyzed the transcription levels of BAX, caspase-7, BCL-2, STAT-3, and PARP proteins using real-time PCR and Western blot analysis. Additionally, we employed non-targeted ultra-high-performance liquid chromatography and high-resolution mass spectrometry (UPLC-MS/MS) to study the potential mechanisms underlying the anticancer effects of ergosterol at the metabolomics level. The results demonstrated a significant reduction in cell viability and the induction of apoptosis upon treatment with ergosterol, especially at higher concentrations (P < 0.05). Moreover, ergosterol affected the expression of cancer-related genes, upregulating pro-apoptotic proteins such as BAX, caspase-7, and PARP, while downregulating the anti-apoptotic proteins BCL-2 and STAT-3 (P < 0.05). Western blot analysis confirmed these findings and provided further evidence of ergosterol's role in inducing apoptosis. Metabolomics analysis revealed substantial changes in pathways related to amino acid, antioxidant, and carbohydrate metabolism. In conclusion, our study demonstrates that ergosterol exhibits anticancer effects by inducing apoptosis and modulating metabolic pathways in breast cancer cells.

在包括中国、日本和欧洲在内的各种文化中,蘑菇中的麦角甾醇具有重要的民族药理学意义。研究发现,这种化合物具有增强免疫力和抗炎的特性,因此可用于治疗免疫系统疾病。在这项研究中,我们重点研究了从食用菌褐花菇中分离出来的麦角甾醇在乳腺癌细胞系中的潜在抗癌特性。我们利用 ESI-MS 和 NMR 等先进分析技术对麦角甾醇进行了纯化和鉴定。我们对 4 种 T1 乳腺癌细胞进行了细胞增殖试验,以评估麦角甾醇的细胞毒性作用。此外,我们还利用实时 PCR 和 Western 印迹分析法分析了 BAX、caspase-7、BCL-2、STAT-3 和 PARP 蛋白的转录水平。此外,我们还采用了非靶向超高效液相色谱和高分辨质谱(UPLC-MS/MS)技术,在代谢组学水平上研究麦角甾醇抗癌作用的潜在机制。结果表明,麦角甾醇能显著降低细胞活力并诱导细胞凋亡,尤其是在较高浓度下(P < 0.05)。此外,麦角甾醇还影响癌症相关基因的表达,上调促凋亡蛋白,如 BAX、caspase-7 和 PARP,同时下调抗凋亡蛋白 BCL-2 和 STAT-3(P <0.05)。Western 印迹分析证实了这些发现,并进一步证明了麦角甾醇在诱导细胞凋亡中的作用。代谢组学分析表明,与氨基酸、抗氧化剂和碳水化合物代谢相关的途径发生了重大变化。总之,我们的研究表明,麦角甾醇通过诱导乳腺癌细胞凋亡和调节代谢途径而发挥抗癌作用。
{"title":"The effect mechanism of ergosterol from the nutritional mushroom Leucocalocybe mongolica in breast cancer cells: Protein expression modulation and metabolomic profiling using UHPLC-ESI-Q","authors":"Asmaa Hussein Zaki ,&nbsp;Bao Haiying ,&nbsp;Mohamed Mohany ,&nbsp;Salim S. Al-Rejaie ,&nbsp;Bahaa Abugammie","doi":"10.1016/j.jsps.2024.102045","DOIUrl":"https://doi.org/10.1016/j.jsps.2024.102045","url":null,"abstract":"<div><p>The ergosterol from mushrooms has gained significant ethnopharmacological importance in various cultures, including China, Japan, and Europe. This compound has been found to possess immune-boosting and anti-inflammatory properties, making it useful in the treatment of immune disorders. In this study, we focused on investigating the potential anticancer properties of ergosterol isolated from the edible mushroom <em>Leucocalocybe mongolica</em> in breast cancer cell lines. The ergosterol was purified and identified using advanced analytical techniques such as ESI-MS and NMR. We conducted cell proliferation assays on 4 T1 breast cancer cells to assess the cytotoxic effects of ergosterol. Furthermore, we analyzed the transcription levels of BAX, caspase-7, BCL-2, STAT-3, and PARP proteins using real-time PCR and Western blot analysis. Additionally, we employed non-targeted ultra-high-performance liquid chromatography and high-resolution mass spectrometry (UPLC-MS/MS) to study the potential mechanisms underlying the anticancer effects of ergosterol at the metabolomics level. The results demonstrated a significant reduction in cell viability and the induction of apoptosis upon treatment with ergosterol, especially at higher concentrations (P &lt; 0.05). Moreover, ergosterol affected the expression of cancer-related genes, upregulating pro-apoptotic proteins such as BAX, caspase-7, and PARP, while downregulating the anti-apoptotic proteins BCL-2 and STAT-3 (P &lt; 0.05). Western blot analysis confirmed these findings and provided further evidence of ergosterol's role in inducing apoptosis. Metabolomics analysis revealed substantial changes in pathways related to amino acid, antioxidant, and carbohydrate metabolism. In conclusion, our study demonstrates that ergosterol exhibits anticancer effects by inducing apoptosis and modulating metabolic pathways in breast cancer cells.</p></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 5","pages":"Article 102045"},"PeriodicalIF":4.1,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1319016424000951/pdfft?md5=83de983926fb693ddfc9793c810e4986&pid=1-s2.0-S1319016424000951-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140290553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The effectiveness of hematopoietic stem cell transplantation in treating pediatric sickle cell disease: Systematic review and meta-analysis 造血干细胞移植治疗小儿镰状细胞病的有效性:系统回顾与荟萃分析
IF 4.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-22 DOI: 10.1016/j.jsps.2024.102049
Najim Z. Alshahrani, Mohammed R. Algethami

Background

Patients with sickle cell disease (SCD) have just one recognized curative therapy option: hematopoietic stem cell transplantation (HSCT), which results in a long-lasting improvement in the clinical phenotype. Here, we assessed the effectiveness of HSCT in treating children with SCD by a systematic review and meta-analysis.

Methods

Up until January 2024, a comprehensive search was done using Web of Science, CINAHL, Embase, Google Scholar, Cochrane Library, PubMed/Medline, and Embase. Two reviewers worked separately to extract the data, and Newcastle-Ottawa Quality Assessment tool was used to assess the research's quality. The outcomes analyzed were Overall survival (OS), event-free survival (EFS), graft failure (GF) and mortality.

Results

Nineteen papers satisfied our inclusion requirements and were assessed to be of fair quality. The pooled rate of OS was high (92%; 95% CI: 90.3%–93.5%). Similar finding was detected for EFS (85.8%; 95% CI: 83.7%–87.7%). In the other hand, pooled rates of GF and mortality were 6.9% (95% CI: 5.3%–8.9%) and 7.4% (95% CI: 5%–10.7%), respectively. A significant publication bias was detected for OS, EFS and GF outcomes. Subgroups analysis showed that study design was the major source of heterogeneity.

Conclusion

Our results show that HSCT is effective and safe, with pooled survival rates above 90%. It is important to assess innovative tactics in light of the alarming GF and mortality rates.

背景镰状细胞病(SCD)患者只有一种公认的治愈性疗法:造血干细胞移植(HSCT),它能长期改善临床表型。在此,我们通过系统综述和荟萃分析评估了造血干细胞移植治疗SCD患儿的有效性。方法截至2024年1月,我们使用Web of Science、CINAHL、Embase、Google Scholar、Cochrane Library、PubMed/Medline和Embase进行了全面检索。两名审稿人分别提取数据,并使用纽卡斯尔-渥太华质量评估工具评估研究质量。分析的结果包括总生存率(OS)、无事件生存率(EFS)、移植物失败率(GF)和死亡率。总的 OS 率较高(92%;95% CI:90.3%-93.5%)。EFS也有类似结果(85.8%;95% CI:83.7%-87.7%)。另一方面,GF和死亡率的汇总率分别为6.9%(95% CI:5.3%-8.9%)和7.4%(95% CI:5%-10.7%)。在OS、EFS和GF结果中发现了明显的发表偏倚。亚组分析表明,研究设计是异质性的主要来源。结论我们的研究结果表明,造血干细胞移植有效且安全,总生存率超过90%。鉴于令人担忧的 GF 和死亡率,评估创新策略非常重要。
{"title":"The effectiveness of hematopoietic stem cell transplantation in treating pediatric sickle cell disease: Systematic review and meta-analysis","authors":"Najim Z. Alshahrani,&nbsp;Mohammed R. Algethami","doi":"10.1016/j.jsps.2024.102049","DOIUrl":"https://doi.org/10.1016/j.jsps.2024.102049","url":null,"abstract":"<div><h3>Background</h3><p>Patients with sickle cell disease (SCD) have just one recognized curative therapy option: hematopoietic stem cell transplantation (HSCT), which results in a long-lasting improvement in the clinical phenotype. Here, we assessed the effectiveness of HSCT in treating children with SCD by a systematic review and meta-analysis.</p></div><div><h3>Methods</h3><p>Up until January 2024, a comprehensive search was done using Web of Science, CINAHL, Embase, Google Scholar, Cochrane Library, PubMed/Medline, and Embase. Two reviewers worked separately to extract the data, and Newcastle-Ottawa Quality Assessment tool was used to assess the research's quality. The outcomes analyzed were Overall survival (OS), event-free survival (EFS), graft failure (GF) and mortality.</p></div><div><h3>Results</h3><p>Nineteen papers satisfied our inclusion requirements and were assessed to be of fair quality. The pooled rate of OS was high (92%; 95% CI: 90.3%–93.5%). Similar finding was detected for EFS (85.8%; 95% CI: 83.7%–87.7%). In the other hand, pooled rates of GF and mortality were 6.9% (95% CI: 5.3%–8.9%) and 7.4% (95% CI: 5%–10.7%), respectively. A significant publication bias was detected for OS, EFS and GF outcomes. Subgroups analysis showed that study design was the major source of heterogeneity.</p></div><div><h3>Conclusion</h3><p>Our results show that HSCT is effective and safe, with pooled survival rates above 90%. It is important to assess innovative tactics in light of the alarming GF and mortality rates.</p></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 5","pages":"Article 102049"},"PeriodicalIF":4.1,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1319016424000999/pdfft?md5=948fb29cf0a8dcdee8655b43ab9b3546&pid=1-s2.0-S1319016424000999-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140290541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Formulation and characterization of polymeric nanoparticle of Rivastigmine for effective management of Alzheimer’s disease 用于有效治疗阿尔茨海默病的利伐斯的明聚合物纳米粒子的制备和表征
IF 4.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-22 DOI: 10.1016/j.jsps.2024.102048
Faisal Imam , Sayantan Mukhopadhyay , Preeti Kothiyal , Samiyah Alshehri , Khalid Saad Alharbi , Muhammad Afzal , Muzaffar Iqbal , Mohammad Rashid Khan , Md. Khalid Anwer , Abdulrazaq Ahmed Hattab Alanazi , Ali Ghanem Alqahtani , Mohammed Abdullah Alhamamah

Memory loss or dementia is a progressive disorder, and one of its common forms is Alzheimer’s disease (AD), effecting mostly middle aged and older adults. In the present study, we developed Rivastigmine (RIV) nanoparticles using poly(lactic-co-glycolic acid) (RIV-loaded PLGA NPs) and polyvinyl alcohol (PVA). The prepared RIV-PLGA nanoparticles was evaluated for the management of Alzheimer's disease (AD). The nanoparticles were prepared by the slightly modified nano-precipitation technique. The developed formulations were evaluated for particle size, zeta potential (ZP), polydispersibility index (PDI) and surface morphology and drug content. The experimental result revealed that prepared RIV-loaded PLGA NPs (F1) was optimized having particle size (61.2 ± 4.6 nm), PDI (0.292), ZP (−11.2 ± 1.2). SEM study confirms the prepared nanoparticles depicted non-aggregated as well smooth surface particles without any fracture. This formulation (F1) was further assessed for in vivo studies on animal model. A pharmacological screening on an animal model of Alzheimer's disease revealed that RIV-loaded PLGA NPs formulations treat CNS disorders like Alzheimer's effectively. In addition to that, an in-vivo brain cholinesterase estimation study found that, animals treated with optimized formulation significantly (p < 0.01) reduced brain cholinesterase activity when compared to scopolamine-treated animals. According to the above results, it can be concluded that RIV-loaded PLGA NPs are ideal carriers for delivering the drug at a specific target site in the brain, thus may treat Alzheimer's disease efficiently and improve patient compliance.

记忆力减退或痴呆症是一种渐进性疾病,其常见形式之一是阿尔茨海默病(AD),主要影响中老年人。在本研究中,我们利用聚乳酸-共聚乙醇酸(RIV-loaded PLGA NPs)和聚乙烯醇(PVA)开发了利伐斯的明(RIV)纳米颗粒。所制备的 RIV-PLGA 纳米粒子被评估用于治疗阿尔茨海默病(AD)。纳米颗粒是通过略微改良的纳米沉淀技术制备的。对所开发的制剂进行了粒度、ZP、多分散指数(PDI)、表面形态和药物含量的评估。实验结果表明,制备的负载 RIV 的 PLGA NPs(F1)的粒度(61.2 ± 4.6 nm)、PDI(0.292)和 ZP(-11.2 ± 1.2)均达到最佳。扫描电子显微镜研究证实,制备的纳米颗粒无聚集,表面光滑,无任何断裂。该制剂(F1)在动物模型上进行了进一步的体内研究评估。在阿尔茨海默病动物模型上进行的药理学筛选显示,负载 RIV 的 PLGA NPs 制剂能有效治疗阿尔茨海默病等中枢神经系统疾病。此外,一项体内脑胆碱酯酶估计研究发现,与东莨菪碱处理的动物相比,使用优化制剂处理的动物的脑胆碱酯酶活性显著降低(p < 0.01)。根据上述结果,可以得出结论:负载 RIV 的 PLGA NPs 是一种理想的载体,可将药物输送到大脑中的特定靶点,从而有效治疗阿尔茨海默病,并提高患者的依从性。
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引用次数: 0
Amphiphilic, lauric acid-coupled pluronic-based nano-micellar system for efficient glipizide delivery 两亲性月桂酸偶联钚基纳米胶束系统用于高效递送格列吡嗪
IF 4.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-21 DOI: 10.1016/j.jsps.2024.102046
Vipan Kumar , Neelam Poonia , Pradeep Kumar , Prabhakar Kumar Verma , Abdulrahman Alshammari , Norah A. Albekairi , Atul Kabra , Neera Yadav

Glipizide; an insulin secretagogue belonging to the sulfonylurea class, is a widely used antidiabetic drug for managing type 2 diabetes. However, the need for life-long administration and repeated doses poses challenges in maintaining optimal blood glucose levels. In this regard, orally active sustained-release nano-formulations can be a better alternative to traditional antidiabetic formulations. The present study explored an innovative approach by formulating orally active sustained-release nano-micelles using the amphiphilic lauric acid-conjugated-F127 (LAF127) block copolymer. LAF127 block copolymer was synthesized through esterification and thoroughly characterized before being employed to develop glipizide-loaded nano-micelles (GNM) via the thin-film hydration technique. The optimized formulation exhibited mean particle size of 341.40 ± 3.21 nm and depicted homogeneous particle size distribution with a polydispersity index (PDI) < 0.2. The formulation revealed a surface charge of −17.11 ± 6.23 mV. The in vitro release studies of glipizide from developed formulation depicted a sustained release profile. Drug loaded micelles exhibited a substantial reduction in blood glucose levels in diabetic rats for a duration of up to 24 h. Notably, neither the blank nano-micelles of LAF127 nor the drug loaded micelles manifested any indications of toxicity in healthy rats. This study provides an insight on suitability of synthesized LAF127 block copolymer for development of effective oral drug delivery systems for anti-diabetic activity without any significant adverse effects.

格列吡嗪是一种胰岛素分泌剂,属于磺脲类药物,是一种广泛用于控制 2 型糖尿病的抗糖尿病药物。然而,由于需要终身服药和重复给药,这给维持最佳血糖水平带来了挑战。在这方面,口服活性缓释纳米制剂可以更好地替代传统的抗糖尿病制剂。本研究探索了一种创新方法,即使用两亲性月桂酸-共轭-F127(LAF127)嵌段共聚物配制口服活性缓释纳米微胶囊。LAF127 嵌段聚合物是通过酯化法合成的,在通过薄膜水合技术开发格列吡嗪载药纳米微囊(GNM)之前,对其进行了全面的表征。优化配方的平均粒径为 341.40 ± 3.21 nm,粒径分布均匀,多分散指数(PDI)为 0.2。配方的表面电荷为 -17.11 ± 6.23 mV。对所开发制剂中格列吡嗪的体外释放研究表明,该制剂具有持续释放特性。值得注意的是,无论是空白的 LAF127 纳米胶束还是载药胶束,在健康大鼠体内都没有表现出任何毒性迹象。这项研究揭示了合成的 LAF127 嵌段共聚物是否适合用于开发有效的口服给药系统,以达到抗糖尿病的效果,且不会产生任何明显的不良影响。
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引用次数: 0
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Saudi Pharmaceutical Journal
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