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Pioglitazone enhances cisplatin’s impact on triple-negative breast cancer: Role of PPARγ in cell apoptosis 吡格列酮增强顺铂对三阴性乳腺癌的影响PPARγ 在细胞凋亡中的作用
IF 4.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-04-01 DOI: 10.1016/j.jsps.2024.102059
Qamraa Hamad Alqahtani , Layla Abdullah Alkharashi , Hanaa Alajami , Ishraq Alkharashi , Layan Alkharashi , Shoug Nasser Alhinti

Peroxisome proliferator-activated receptor-gamma (PPARγ) has been recently shown to play a role in many cancers. The breast tissue of triple-negative breast cancer (TNBC) patients were found to have a significantly lower expression of PPARγ than the other subtypes. Furthermore, PPARγ activation was found to exert anti-tumor effects by inhibiting cell proliferation, differentiation, cell growth, cell cycle, and inducing apoptosis. To start with, we performed a bioinformatic analysis of data from OncoDB, which showed a lower expression pattern of PPARγ in different cancer types. In addition, high expression of PPARγ was associated with better breast cancer patient survival. Therefore, we tested the impact of pioglitazone, a PPARγ ligand, on the cytotoxic activity of cisplatin in the TNBC cell line. MDA-MB-231 cells were treated with either cisplatin (40 μM) with or without pioglitazone (30 or 60 μM) for 72 h. The MTT results showed a significant dose-dependent decrease in cell viability as a result of using cisplatin and pioglitazone combination compared with cisplatin alone. In addition, the protein expression of Bcl-2, a known antiapoptotic marker, decreased in the cells treated with cisplatin and pioglitazone combination at doses of 40 and 30 μM, respectively. On the other hand, cleaved- poly-ADP ribose polymerase (PARP) and -caspase-9, which are known as pro-apoptotic markers, were upregulated in the combination group compared with the solo treatments. Taken together, the addition of pioglitazone to cisplatin further reduced the viability of MDA-MB-231 cells and enhanced apoptosis compared with chemotherapy alone.

近来研究表明,过氧化物酶体增殖激活受体-γ(PPARγ)在多种癌症中发挥着作用。研究发现,三阴性乳腺癌(TNBC)患者乳腺组织中 PPARγ 的表达量明显低于其他亚型。此外,研究还发现 PPARγ 激活可通过抑制细胞增殖、分化、细胞生长、细胞周期和诱导细胞凋亡发挥抗肿瘤作用。首先,我们对来自 OncoDB 的数据进行了生物信息学分析,结果显示 PPARγ 在不同癌症类型中的表达模式较低。此外,PPARγ的高表达与乳腺癌患者较好的生存率相关。因此,我们测试了 PPARγ 配体吡格列酮对 TNBC 细胞系顺铂细胞毒性活性的影响。MDA-MB-231细胞经顺铂(40 μM)加或不加吡格列酮(30或60 μM)处理72小时后,MTT结果显示,与单用顺铂相比,联合使用顺铂和吡格列酮会使细胞活力显著下降,且呈剂量依赖性。此外,用顺铂和吡格列酮复方制剂(剂量分别为 40 μM 和 30 μM)处理的细胞中,已知的抗细胞凋亡标志物 Bcl-2 的蛋白表达量也有所下降。另一方面,与单独治疗相比,多聚-ADP核糖聚合酶(PARP)和天冬酶-9(已知的促凋亡标志物)在联合治疗组中上调。综上所述,与单独化疗相比,在顺铂中添加吡格列酮可进一步降低MDA-MB-231细胞的存活率,并增强细胞凋亡。
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引用次数: 0
Population pharmacokinetics of gentamicin in acute lymphoblastic leukemia pediatric patients compared to non-oncology patients 急性淋巴细胞白血病儿科患者与非肿瘤患者的庆大霉素群体药代动力学比较
IF 4.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-04-01 DOI: 10.1016/j.jsps.2024.102060
Hisham S. Abou-Auda , Fatimah Alotaibi , Sary Alsanea , Abdulrahman Alwhaibi , Mohammed M. Almutairi , Ziyad Alrabiah , Abdullah Alsultan , Majed Al Jeraisy

Understanding the pharmacokinetics of gentamicin is essential in special populations, such as pediatric patients with acute lymphoblastic leukemia (ALL), in light of previous studies indicating that ALL patients have a lower volume of distribution than non-ALL patients. Furthermore, validation of such results is needed to ensure their clinical application. Accordingly, this single-center, retrospective, cross-sectional study compares the pharmacokinetic parameters of volume of distribution and clearance (Cl) of gentamicin between ALL and non-ALL patients. Inclusion criteria were pediatric patients aged between 1 and 14 years with or without ALL and receiving intravenous gentamicin for treatment courses > 72 h. Patients’ characteristics, such as age, sex, height, serum albumin, diagnosis, serum creatinine (Scr) concentration, dosing, and pharmacokinetic information, including peak and trough concentrations, were retrieved. The study scrutinized a total of 115 pediatric patients, comprising toddlers (15.7 %), children (76.5 %), and adolescents (7.8 %). All patients received gentamicin every 8 h, with an average dose of 2.50 (0.64) mg/kg. Patients were divided into two groups based on disease state, with 45.2 % (n = 52) in the non-ALL group and 54.8 % (n = 63) in the ALL group. Both groups had similar characteristics in terms of gender, weight, body surface area, and dose. The only significant covariates identified were weight and creatinine clearance (Clcr) for volume of distribution (Vd). A significant difference was found in Scr, Clcr, and blood urea nitrogen (BUN); however, no significant difference between ALL and non-ALL patients emerged in the volume of distribution or Cl. In conclusion, the study findings indicate that dosing requirements were similar between the two groups. Further prospective studies with larger sample sizes are warranted.

以往的研究表明,急性淋巴细胞白血病(ALL)患者的药物分布容积低于非急性淋巴细胞白血病患者,因此了解庆大霉素在特殊人群(如急性淋巴细胞白血病儿科患者)中的药代动力学至关重要。此外,还需要对这些结果进行验证,以确保其临床应用。因此,本项单中心、回顾性、横断面研究比较了 ALL 和非 ALL 患者庆大霉素的分布容积和清除率(Cl)等药动学参数。研究检索了患者的年龄、性别、身高、血清白蛋白、诊断、血清肌酐(Scr)浓度、用药剂量、药代动力学信息(包括峰值和谷值浓度)等特征。该研究共调查了 115 名儿科患者,包括幼儿(15.7%)、儿童(76.5%)和青少年(7.8%)。所有患者每 8 小时接受一次庆大霉素治疗,平均剂量为 2.50 (0.64) mg/kg。根据疾病状态将患者分为两组,非ALL组为45.2%(n=52),ALL组为54.8%(n=63)。两组患者的性别、体重、体表面积和剂量特征相似。唯一确定的重要协变量是体重和分布容积(Vd)的肌酐清除率(Clcr)。Scr、Clcr和血尿素氮(BUN)存在明显差异;但在分布容积或Cl方面,ALL和非ALL患者没有明显差异。总之,研究结果表明,两组患者的用药要求相似。有必要进一步开展样本量更大的前瞻性研究。
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引用次数: 0
Fabrication and evaluation of ribavirin-loaded electrospun nanofibers as an antimicrobial wound dressing 制作和评估作为抗菌伤口敷料的利巴韦林电纺纳米纤维
IF 4.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-04-01 DOI: 10.1016/j.jsps.2024.102058
Khulud A. Alsulami , Abrar A. Bakr , Abdullah A. Alshehri , Alhassan H. Aodah , Fahad A. Almughem , Ali A. Alamer , Lujain A. Alharbi , Deema S. Alsuwayeh , Abdulrahman A. Halwani , Abdullah A. Alamoudi , Haya A. Alfassam , Essam A. Tawfik

Background

Skin is regarded as an essential first line of defense against harmful pathogens and it hosts an ecosystem of microorganisms that create a widely diverse skin microbiome. In chronic wounds, alterations in the host-microbe interactions occur forming polymicrobial biofilms that hinder the process of wound healing. Ribavirin, an antiviral drug, possesses antimicrobial activity, especially against Pseudomonas aeruginosa and Candida albicans, which are known as the main opportunistic pathogens in chronic wounds.

Rationale

In this study, electrospun nanofiber systems loaded with ribavirin were developed as a potential wound dressing for topical application in chronic wounds. Ribavirin was chosen in this study owing to the emerging cases of antimicrobial (antibiotics and antifungal) resistance and the low attempts to discover new antimicrobial agents, which encouraged the repurposing use of current medication as an alternative solution in case of resistance to the available agents. Additionally, the unique mechanism of action of ribavirin, i.e., perturbing the bacterial virulence system without killing or stopping their growth and rendering the pathogens disarmed, might be a promising choice to prevent drug resistance. Cyclodextrin (CD) was utilized to formulate ribavirin as an electrospun nanofibers delivery system to enhance the absorption and accelerate the release of ribavirin for topical use.

Results

The results demonstrated a successful ribavirin nanofibers fabrication that lacked beads and pores on the nanofibrous surfaces. Ribavirin underwent a physical transformation from crystalline to amorphous form, as confirmed by X-ray diffraction analysis. This change occurred due to the molecular dispersion after the electrospinning process. Additionally, the CD enhanced the encapsulation efficiency of ribavirin in the nanofibers as observed from the drug-loading results. Polyvinylpyrrolidone (PVP) and CD increased ribavirin released into the solution and the disintegration of fibrous mats which shrank and eventually dissolved into a gel-like substance as the ribavirin-loaded fibers began to break down from their border toward the midpoint. Cytotoxicity of ribavirin and CD was evaluated against human dermal fibroblasts (HFF-1) and the results showed a relatively safe profile of ribavirin upon 24-hour cell exposure, while CD was safe within 24- and 48-hour.

Conclusion

This study provides valuable insights into the potential application of our nanofibrous system for treating chronic wounds; however, further antimicrobial and in-vivo studies are required to confirm its safety and effectiveness.

背景皮肤被认为是抵御有害病原体的第一道重要防线,它承载着一个微生物生态系统,形成了广泛多样的皮肤微生物群。在慢性伤口中,宿主与微生物之间的相互作用发生了改变,形成了多微生物生物膜,阻碍了伤口的愈合过程。利巴韦林是一种抗病毒药物,具有抗菌活性,尤其是对铜绿假单胞菌和白色念珠菌具有抗菌活性,而这两种细菌是慢性伤口中的主要机会致病菌。本研究之所以选择利巴韦林,是因为抗菌剂(抗生素和抗真菌剂)耐药性不断出现,而发现新抗菌剂的尝试却不多,这促使人们在现有药物出现耐药性的情况下,将现有药物重新用作替代解决方案。此外,利巴韦林的独特作用机制,即在不杀死或阻止细菌生长的情况下扰乱细菌毒力系统,使病原体失去抵抗力,可能是防止耐药性的一个有前途的选择。环糊精(CD)被用来将利巴韦林配制成电纺纳米纤维给药系统,以增强利巴韦林的吸收并加速其释放,供局部使用。经 X 射线衍射分析证实,利巴韦林发生了从结晶到无定形的物理变化。发生这种变化的原因是电纺丝过程后分子发生了分散。此外,从药物负载结果来看,CD 提高了利巴韦林在纳米纤维中的封装效率。聚乙烯吡咯烷酮(PVP)和 CD 增加了释放到溶液中的利巴韦林,也增加了纤维毡的解体,当负载利巴韦林的纤维开始从其边界向中点分解时,纤维毡收缩并最终溶解成凝胶状物质。评估了利巴韦林和 CD 对人真皮成纤维细胞(HFF-1)的细胞毒性,结果表明利巴韦林在细胞暴露 24 小时后相对安全,而 CD 在 24 小时和 48 小时内是安全的。
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引用次数: 0
Pharmacological p38 MAPK inhibitor SB203580 enhances AML stem cell line KG1a chemosensitivity to daunorubicin by promoting late apoptosis, cell growth arrest in S-phase, and miR-328-3p upregulation 药理 p38 MAPK 抑制剂 SB203580 可增强 AML 干细胞系 KG1a 对 daunorubicin 的化学敏感性:细胞死亡机制的体外综合分析
IF 4.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-30 DOI: 10.1016/j.jsps.2024.102055
Sara Bahattab , Ali Assiri , Yazeid Alhaidan , Thadeo Trivilegio , Rehab AlRoshody , Sarah Huwaizi , Bader Almuzzaini , Abir Alamro , Manal Abudawood , Zeyad Alehaideb , Sabine Matou-Nasri

Acute myeloid leukaemia (AML) is characterized by uncontrolled proliferation of myeloid progenitor cells and impaired maturation, leading to immature cell accumulation in the bone marrow and bloodstream, resulting in hematopoietic dysfunction. Chemoresistance, hyperactivity of survival pathways, and miRNA alteration are major factors contributing to treatment failure and poor outcomes in AML patients. This study aimed to investigate the impact of the pharmacological p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 on the chemoresistance potential of AML stem cell line KG1a to the therapeutic drug daunorubicin (DNR). KG1a and chemosensitive leukemic HL60 cells were treated with increasing concentrations of DNR. Cell Titer-Glo®, flow cytometry, phosphokinase and protein arrays, Western blot technology, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were employed for assessment of cell viability, half-maximal inhibitory concentration (IC50) determination, apoptotic status detection, cell cycle analysis, apoptosis-related protein and gene expression monitoring. Confocal microscopy was used to visualize caspase and mitochondrial permeability transition pore (mPTP) activities. Exposed at various incubation times, higher DNR IC50 values were determined for KG1a cells than for HL60 cells, confirming KG1a cell chemoresistance potential. Exposed to DNR, late apoptosis induction in KG1a cells was enhanced after SB203580 pretreatment, defined as the combination treatment. This enhancement was confirmed by increased cleavage of poly(ADP-ribose) polymerase, caspase-9, caspase-3, and augmented caspase-3/-7 and mPTP activities in KG1a cells upon combination treatment, compared to DNR. Using phosphokinase and apoptosis protein arrays, the combination treatment decreased survival Akt phosphorylation and anti-apoptotic Bcl-2 expression levels in KG1a cells while increasing the expression levels of the tumor suppressor p53 and cyclin-dependent kinase inhibitor p21, compared to DNR. Cell cycle analysis revealed KG1a cell growth arrest in G2/M-phase caused by DNR, while combined treatment led to cell growth arrest in S-phase, mainly associated with cyclin B1 expression levels. Remarkably, the enhanced KG1a cell sensitivity to DNR after SB203580 pretreatment was associated with an increased upregulation of miR-328-3p and slight downregulation of miR-26b-5p, compared to DNR effect. Altogether, these findings could contribute to the development of a new therapeutic strategy by targeting the p38 MAPK pathway to improve treatment outcomes in patients with refractory or relapsed AML.

急性髓系白血病(AML)的特点是髓系祖细胞不受控制地增殖和成熟受损,导致未成熟细胞在骨髓和血液中蓄积,造成造血功能障碍。化疗抵抗、生存通路过度活跃和 miRNA 改变是导致急性髓细胞性白血病患者治疗失败和预后不良的主要因素。本研究旨在探讨药理学p38丝裂原活化蛋白激酶(MAPK)抑制剂SB203580对AML干细胞系KG1a对治疗药物达乌鲁比星(DNR)的化疗耐药性的影响。KG1a 和对化疗敏感的白血病 HL60 细胞接受浓度不断增加的 DNR 处理。采用细胞滴度-Glo®、流式细胞仪、磷酸激酶和蛋白质阵列、Western 印迹技术和反转录定量聚合酶链反应(RT-qPCR)评估细胞活力、确定半数最大抑制浓度(IC50)、检测细胞凋亡状态、分析细胞周期、监测与细胞凋亡相关的蛋白质和基因表达。共聚焦显微镜用于观察 Caspase 和线粒体通透性转换孔(mPTP)的活性。在不同的孵育时间下,KG1a 细胞的 DNR IC50 值高于 HL60 细胞,这证实了 KG1a 细胞的化疗抗性潜力。经 SB203580 预处理(即联合处理)后,KG1a 细胞暴露于 DNR 后的晚期凋亡诱导增强。与 DNR 相比,联合治疗后 KG1a 细胞中多(ADP 核糖)聚合酶、caspase-9、caspase-3 的裂解增加,caspase-3/-7 和 mPTP 活性增强,证实了这种增强。利用磷酸激酶和凋亡蛋白阵列,与 DNR 相比,联合疗法降低了 KG1a 细胞中存活的 Akt 磷酸化和抗凋亡的 Bcl-2 表达水平,同时提高了肿瘤抑制因子 p53 和细胞周期蛋白依赖性激酶抑制因子 p21 的表达水平。细胞周期分析表明,DNR会导致KG1a细胞生长停滞在G2/M期,而联合治疗会导致细胞生长停滞在S期,这主要与细胞周期蛋白B1的表达水平有关。值得注意的是,与 DNR 作用相比,SB203580 预处理后 KG1a 细胞对 DNR 的敏感性增强与 miR-328-3p 的上调增加和 miR-26b-5p 的轻微下调有关。总之,这些发现有助于通过靶向 p38 MAPK 通路开发一种新的治疗策略,以改善难治或复发急性髓细胞性白血病患者的治疗效果。
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引用次数: 0
Arabic translation and cultural adaptation of Hill-Bone compliance to high blood pressure therapy scale 希尔-伯恩高血压治疗依从性量表的阿拉伯语翻译和文化调整
IF 4.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-29 DOI: 10.1016/j.jsps.2024.102053
Ibrahim Sales , Yazed AlRuthia

Background

Adherence to prescription medications is vital to the success of any treatment plan, especially for chronic health conditions, such as hypertension (HTN). Although there are different scales used in assessing adherence to prescription medications, most if not all, of those scales are not available in Arabic. The absence of essential assessment tools makes the appraisal of adherence to prescription medications very difficult for native Arabic speakers. Therefore, this study aimed to translate and validate the Hill-Bone Compliance to High Blood Pressure Therapy (CHBPT) scale, which is commonly used to assess adherence to antihypertensive medications, among a sample of Arabic-speaking patients with HTN.

Methods

This was a single-center cross-sectional study that took place at a university-affiliated hospital. It interviewed adult (≥18 years) patients with HTN who were visiting the primary care clinics between January and November 2020. Non-Arabic speakers, those under 18 years of age, individuals without a diagnosis of HTN, and patients without any previously filled prescription medications for HTN within the past three months were excluded. The forward–backward translation method was used after receiving permission from the originators of the questionnaire to translate their scale to Arabic. Test-retest and Cronbach alpha methods were used to assess the reliability. Principal component analysis with varimax rotation was used to examine the construct validity.

Results

One hundred and forty-one patients consented and participated in the study. Most of the patients were ≥ 50 years old (75 %), male (72 %), and had another chronic health condition besides HTN (99 %). The translated scale had good internal consistency (Cronbach alpha = 0.83) and reliability (intraclass correlation coefficient of 0.9). The Kaiser-Meyer-Oklin was 0.82 indicating adequate sampling to conduct factor analysis; hence, three factors (e.g., subscales) were extracted similar to the original scale. The mean scores for appointment keeping, medication taking, and reducing sodium intake subscales, as well as for the overall scale were 5.62 ± 1.39, 33.94 ± 3.87, 9.73 ± 2.1, and 49.29 ± 5.21, respectively.

Conclusion

The translated version of the Hill-Bone CHBPT scale has both good reliability and validity and will hopefully help healthcare providers assess and monitor HTN patients’ adherence to their antihypertensive medication regimens. Multicenter studies should be conducted to verify the validity and reliability of the translated questionnaire among different Arabic-speaking patient populations with HTN.

背景坚持服用处方药对于任何治疗计划的成功都至关重要,尤其是对于高血压(HTN)等慢性疾病。虽然有不同的量表可用于评估处方药的依从性,但大部分量表(如果不是全部的话)都没有阿拉伯语版本。缺乏必要的评估工具使得以阿拉伯语为母语的人很难评估处方药的依从性。因此,本研究旨在翻译并验证希尔骨高血压治疗依从性量表(CHBPT),该量表通常用于评估阿拉伯语高血压患者服用降压药物的依从性。研究访问了 2020 年 1 月至 11 月期间在初级保健诊所就诊的成年(≥18 岁)高血压患者。不讲阿拉伯语者、18 岁以下者、未确诊为高血压患者以及在过去三个月内未服用过任何高血压处方药的患者被排除在外。在征得问卷制作者的同意后,我们采用了正向-反向翻译法将其量表翻译成阿拉伯语。采用重测法和克朗巴赫α法评估信度。结果 141 名患者同意并参与了研究。大多数患者年龄≥50岁(75%),男性(72%),除高血压外还患有其他慢性疾病(99%)。翻译后的量表具有良好的内部一致性(Cronbach alpha = 0.83)和可靠性(类内相关系数为 0.9)。Kaiser-Meyer-Oklin 为 0.82,表明有足够的取样来进行因子分析;因此,提取出的三个因子(如子量表)与原始量表相似。结论Hill-Bone CHBPT量表的翻译版具有良好的信度和效度,有望帮助医疗服务提供者评估和监测高血压患者对降压药物治疗的依从性。应开展多中心研究,在不同的阿拉伯语高血压患者群体中验证翻译问卷的有效性和可靠性。
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引用次数: 0
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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Saudi Pharmaceutical Journal
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