Saudi Pharmaceutical Journal最新文献

{"title":"Virtual bioequivalence-guided PBBM prediction for ibuprofen/diphenhydramine citrate tablets: impact of dissolution variability and clinical standard development.","authors":"Zilong Wang, Zhihai Cao, Chun Guo, Qian Zhang, Renpeng Zhou, Jian Chen, Feng Su, Wei Liu, Zhaoxing Chu, Liang Zheng, Wei Hu","doi":"10.1007/s44446-026-00100-3","DOIUrl":"10.1007/s44446-026-00100-3","url":null,"abstract":"<p><p>This study aimed to integrate in vitro dissolution testing, in vivo pharmacokinetic (PK) studies, and computational simulation to develop a physiologically based biopharmaceutics model (PBBM) for fixed-dose combination ibuprofen/diphenhydramine citrate tablets, thereby evaluating bioequivalence (BE) and establishing a dissolution safe space. Initially, a PBBM model was constructed using B²O Simulator software. Subsequently, an integrated approach was employed, combining dissolution profiles with physiological parameters to develop a virtual bioequivalence (VBE) model. Through simulations involving virtual batches exhibiting diverse dissolution characteristics, the safe dissolution range was determined. Consequently, the PBBM models for ibuprofen and diphenhydramine were successfully validated. Furthermore, the VBE model demonstrated favorable bioequivalence, with an absolute average fold error (AAFE) of less than 1.5 between predicted and observed values for key PK parameters (C_max and AUC). Scenario analyses supported a formulation- and medium-specific dissolution criterion of no less than 85% dissolution within 30 min for both APIs in pH 6.5 phosphate buffer. Additionally, scenario analyses suggested that, within the simulated two-treatment, two-period crossover settings evaluated in this study, a sample size of approximately 40 subjects may represent a practical lower bound for obtaining stable BE conclusions. In conclusion, this study provides a product-specific, model-informed workflow for bioequivalence risk assessment of ibuprofen/diphenhydramine citrate tablets. The application of PBBM and VBE modeling offers guidance for quantitative BE risk assessment, thereby holding promise to accelerate the development process while reducing associated costs. (The bioequivalence study in healthy subjects was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Second Affiliated Hospital of Anhui Medical University [ChiCTR registration number: ChiCTR2500106504; approved: March 12, 2023].).</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907510","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}

{"title":"Integration of network pharmacology, molecular docking, and molecular dynamics simulation to elucidate the mechanism of Psychotria rubra in depression treatment.","authors":"Li Yin, Chengshu Lu, Ju Ye, Yewen Zhang, Shirui Mo, Huakun Wang","doi":"10.1007/s44446-026-00114-x","DOIUrl":"10.1007/s44446-026-00114-x","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Depression is a chronic mental disorder with high disability and mortality rates, affecting approximately 95 million individuals in China alone. The limitations of current antidepressant therapies, including restricted efficacy, delayed onset, and significant adverse effects, have motivated the search for alternative treatments from traditional Chinese medicine. Psychotria rubra (PR), a widely distributed medicinal plant in southern China with reported antidepressant properties, represents a promising candidate; however, the molecular mechanisms underlying its antidepressant effects remain largely unexplored. This study aims to elucidate the mechanistic basis of PR in depression treatment by integrating network pharmacology, molecular docking, molecular dynamics simulation, and in vivo experimental validation. We integrated two depression-related transcriptome datasets [GSE76826 (training set: 10 depressed vs. 12 healthy blood samples) and GSE98793 (validation set: 64 depressed vs. 64 healthy blood samples)] to identify differentially expressed genes in depression. Ferroptosis-related genes were retrieved from GeneCards (score &gt; 8) and FerrDb databases, and eight machine learning models with five-fold cross-validation were employed to screen key diagnostic genes. Molecular docking and dynamics simulations validated interactions between PR's active ingredients and target genes. In vivo, eighty male C57BL/6 mice (6-week-old) were randomly allocated into eight groups (n = 10 per group): control, chronic unpredictable mild stress (CUMS) model, deacetyl asperulosidic acid (10 mg·kg⁻&lt;sup&gt;1&lt;/sup&gt;·d⁻&lt;sup&gt;1&lt;/sup&gt;, intraperitoneal), deacetyl asperulosidic acid methyl ester (10 mg·kg⁻&lt;sup&gt;1&lt;/sup&gt;·d⁻&lt;sup&gt;1&lt;/sup&gt;, intraperitoneal), Procyanidin B1 (20 mg·kg⁻&lt;sup&gt;1&lt;/sup&gt;·d⁻&lt;sup&gt;1&lt;/sup&gt;, intraperitoneal), Procyanidin B2 (20 mg·kg⁻&lt;sup&gt;1&lt;/sup&gt;·d⁻&lt;sup&gt;1&lt;/sup&gt;, intraperitoneal), Procyanidin C1 (20 mg·kg⁻&lt;sup&gt;1&lt;/sup&gt;·d⁻&lt;sup&gt;1&lt;/sup&gt;, intraperitoneal), and fluoxetine (10 mg·kg⁻&lt;sup&gt;1&lt;/sup&gt;·d⁻&lt;sup&gt;1&lt;/sup&gt;, oral gavage, positive control). Following 21 days of CUMS induction, drug treatment was administered for 14 consecutive days. Behavioral assessments (sucrose preference test, open field test, tail suspension test, and forced swimming test), inflammatory factors (serotonin, interleukin-1β, interleukin-6, tumor necrosis factor-α), oxidative stress markers (superoxide dismutase, malondialdehyde), and ferroptosis indicators (reactive oxygen species, glutathione, Fe&lt;sup&gt;2&lt;/sup&gt;⁺ levels) were measured. Machine learning analysis identified EPAS1, MAPK14, and VEGF-A as candidate diagnostic genes associated with depression and ferroptosis. Molecular docking revealed favorable binding affinities between multiple PR active ingredients (including asperuloside, asperulosidic acid, deacetyl asperulosidic acid, and deacetyl asperulosidic acid methyl ester) and EPAS1, with deacetyl asperulosidic acid showing the most favorable docking score (- 8.737 kcal/mol) and asperuloside ","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148882343","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}

{"title":"In vitro study and in silico reveal Teucrium Polium L. methanolic extract as an apoptosis inducer and a potential Bcl-2 inhibitor for breast cancer.","authors":"Monira Alaujan, Sabine Matou-Nasri, Fatimah G Albani, Sahar S Alghamdi, Rasha S Suliman, Rehab AlRoshody, Sarah Huwaizi, Aljawharah Almogren, Mikhlid H Almutairi, Zeyad Alehaideb","doi":"10.1007/s44446-026-00106-x","DOIUrl":"10.1007/s44446-026-00106-x","url":null,"abstract":"<p><p>Therapy of breast cancer (BC) overexpressing the pro-survival protein Bcl-2 remains a major clinical challenge. The discovery of natural anticancer drugs with potential as Bcl-2 inhibitors has generated increasing interest. The medicinal plant Teucrium polium L. (TPL) exhibits pharmacological properties, including anticancer activities. This study aimed to assess the antiproliferative and pro-apoptotic effects of TPL extracts on BC cells and to predict the potential of TPL extract-derived metabolites as Bcl-2 inhibitors. Plant extraction was performed using several solvents, and cell viability was determined. The expression of proteins and genes related to apoptosis was evaluated using Western blot, the Proteome Profiler™ Human Apoptosis Array Kit, and qPCR, respectively. Caspase-3/7 and mitochondrial permeability transition pore opening (mPTPO) activities were visualized. GC/MS analysis, molecular docking, and in silico modeling were used for metabolite identification, prediction of their molecular interactions with Bcl-2, and their pharmacokinetic profiles. Among extracts, TPL methanolic extract (TPLME) dose-dependently reduced hormone-dependent and triple-negative BC cell viability, while sparing normal mammary epithelial cells. TPLME induced apoptosis by increasing caspase-3/7 activity, activating distinct apoptotic pathways, and modulating BAX, TP53, and BCL-2 gene expression. Differential BCL-2 expression levels in TPLME-treated BC cells were confirmed by variations in mPTPO activity. After TPLME-derived metabolite identification, molecular docking revealed interactions between key metabolites and the active site of Bcl-2. Predictive analysis revealed the safe pharmacokinetic profiles of TPLME-derived metabolites. These findings highlight the promising potential of TPLME-derived metabolites for the development of novel Bcl-2 inhibitors for BC cells, requiring further chemical development and preclinical investigations using in vivo BC models.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148882269","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}

{"title":"LC-ESI-TOF-MS profiling and protective effects of Psidium cattleianum extract against gentamicin-induced nephrotoxicity in rats via Nrf2/HO-1 and caspase-dependent pathway.","authors":"Hoda M Hassan, Heba T Khazaal, Fatma A Moharram, Elsayed K El-Sayed, Abdalrhman E Musa, Asmaa A Ahmed, Heba E Elsayed, Nermine M Mohammed","doi":"10.1007/s44446-026-00103-0","DOIUrl":"10.1007/s44446-026-00103-0","url":null,"abstract":"<p><p>Drug-induced nephrotoxicity is an alarming trigger for kidney injury. It is linked to a high rate of illness and fatality, with limited treatment options. Herein, we aimed to unravel the phytochemical profile and understand the protective activity of the aqueous methanolic extract (AME) of P.cattleianum Sabine (Myrtaceae) aerial parts against nephrotoxicity induced by gentamicin (GNT) in rats for the first time. The extract was chromatographed and analyzed using an LC-ESI-TOF-MS system. For the in vivo model, rats received the AME at doses of 200, 400, and 800 mg/kg/day orally for 14 days. The phytochemical results revealed the tentative identification of ninety metabolites, including twelve phenolic acids, fifty-one flavonoids, one proanthocyanidine, one lignan, four coumarins, three terpenes, four organic acids, two stilbenes, seven sugar derivatives, and five miscellaneous compounds. At 800 mg/kg, the AME significantly reduced the KW/BW ratio by 14.7%, BUN by 45.2%, creatinine by 57.6%, and Kim-1 by 57.3%. Oxidative stress markers MDA and 8-OHdG were lowered by 47.5% and 67.4%, respectively, while antioxidant markers GSH and SOD increased by 2.7- and 2.6-fold. The AME also restored HO-1 (4.6-fold increase) and Nrf2 (92.2-fold increase, relative to the GNT-treated group), and suppressed TNF-α, IL-1β, and NF-κB by 53.3%, 64.7%, and 58.9%, respectively. Apoptosis was reduced (Bax ↓64%, cytochrome c ↓58.8%, Bcl-2 ↑threefold), with marked histological improvements confirming nephroprotection. In all, the AME is promoted as an alternative remedy for controlling nephrotoxicity triggered by GNT. However, quantifying and isolating the major constituents and validating the clinical safety are among our future directions.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841905","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}

{"title":"Regional research priorities for medication safety and pharmacovigilance in gulf cooperation council countries: a modified Delphi consensus study.","authors":"Ghadah A Assiri, Wael Y Khawagi, Huda Alewairdhi, Fatema A Alqenae, Douha F Bannan, Abdullah A Alshehri, Anas Hamad, Fatma Alraisi, Ghadah H Alshehri","doi":"10.1007/s44446-026-00112-z","DOIUrl":"10.1007/s44446-026-00112-z","url":null,"abstract":"<p><p>Adverse drug reactions (ADRs) and medication errors remain major global threats to patient safety. Although Gulf Cooperation Council (GCC) countries have advanced medication safety and pharmacovigilance programs, research priorities remain fragmented and lack expert consensus. To establish consensus on medication safety and pharmacovigilance research priorities across GCC countries using a modified Delphi approach. A two-round, web-based modified Delphi study was conducted between November 2024 and September 2025. Experts from Saudi Arabia, Qatar, Oman, Kuwait, Bahrain, and the United Arab Emirates were recruited based on professional experience. Participants rated research priorities using a 9-point Likert scale. Consensus was defined as ≥ 80% of participants rating an item 7-9 and < 15% rating it 1-3. Quantitative data were analysed descriptively, and qualitative feedback informed item refinement. A total of 38 experts completed both Delphi rounds (response rate: 79.2%). In Round 1, 30 out of 47 priorities (63.8%) achieved consensus. In Round 2, five additional items reached consensus, resulting in a final set of 35 priorities (74.5%). The highest agreement was observed in the Healthcare Professionals domain (100%), followed by Medicines (77.8%), Patients and the Public (72.7%), and Systems and Practices (69.6%). Key priorities included addressing inappropriate polypharmacy, improving human factors and system design, enhancing patient safety at home, and strengthening reporting and surveillance systems. This Delphi study identified regional research priorities to guide medication safety and pharmacovigilance efforts across the GCC. The findings offer a structured research agenda to inform policy, funding decisions, and institutional strategies, while supporting global patient safety goals.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148834127","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}

{"title":"Effect of alpha-lipoic acid supplementation on polycystic ovary syndrome clinical outcome in infertile females treated with letrozole: a randomized controlled trial.","authors":"Moaz Ahmed Sallam, Haitham Hamza, Sara Mahmoud Shaheen, Marwa Adel Ahmed","doi":"10.1007/s44446-026-00084-0","DOIUrl":"10.1007/s44446-026-00084-0","url":null,"abstract":"<p><p>Non-responsive cycles during ovulation induction with letrozole (LZ) often necessitate the use of human menopausal gonadotropin (HMG), which may be associated with undesirable adverse effects. Therefore, strategies to improve the therapeutic outcomes of LZ are needed. This trial aimed to evaluate the impact of combining alpha-lipoic acid (ALA) with LZ on ovulation induction in women with polycystic ovary syndrome (PCOS). This randomized controlled trial included 151 infertile women with PCOS who were randomly allocated to either the LZ group (n = 76) or the ALA group (n = 75). The LZ group received LZ (2.5-7.5 mg) with lifestyle modification for up to three treatment cycles or until pregnancy occurred. The ALA group received the same regimen in addition to ALA (1800 mg/day), which was discontinued on the day of human chorionic gonadotropin (HCG) injection in ovulatory patients. Ovulation and pregnancy rates were assessed, along with hormonal parameters. Ovulation per cycle was significantly higher in the ALA group [153/166 (92.2%)] compared with the LZ group [146/203 (71.9%)] (P = 0.035). Moreover, pregnancy per cycle was significantly higher in the ALA group than in the LZ group (P = 0.033). Although serum estradiol, mid-luteal progesterone, and endometrial thickness showed numerically higher values in the ALA group, the differences between the groups were not statistically significant after Bonferroni adjustment. The addition of ALA to LZ improved ovulation and pregnancy outcomes and was associated with favorable metabolic and hormonal effects in women with PCOS.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148799906","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}

{"title":"Rhein and its derivatives: potential anti-tumor drugs and corresponding targeted mechanism.","authors":"Xiaoli Li, Taotao Li, Yuan Ma, Zhaocui Zhang, Yunfei Hao, Li Zhao","doi":"10.1007/s44446-026-00109-8","DOIUrl":"10.1007/s44446-026-00109-8","url":null,"abstract":"<p><p>Cancer remains a major global health threat with high morbidity and mortality, and clinical treatment is plagued by drug resistance, poor efficacy and severe side effects, driving the search for novel anti-tumor agents from natural products. Rhein, a natural anthraquinone abundant in Rheum palmatum and other medicinal plants, has emerged as a promising anti-tumor phytochemical due to its diverse pharmacological activities and multi-target action characteristics. This review systematically summarizes the natural distribution, chemical structure and structural modification strategies of rhein, and further elaborate the core targeted signaling pathways of rhein in exerting anti-tumor effects. Finally, we propose future research directions for rhein and its derivatives, including accelerating preclinical-to-clinical translation, optimizing structural modification and developing targeted delivery systems to reduce side effects and improve therapeutic efficacy.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148799980","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}

{"title":"Developing a medical-device formulary for council of health insurance beneficiaries in Saudi Arabia: stakeholder challenges and policy recommendations.","authors":"Shabab Alghamdi, Ibrahim Aljuffali, Nada Alagil, Amer Alanazi, Azzam Alothman, Wael Yar, Mohammed Aljumah, Saeed Mastour Alshahrani, Hadeel Alkofide","doi":"10.1007/s44446-026-00113-y","DOIUrl":"10.1007/s44446-026-00113-y","url":null,"abstract":"<p><p>Ensuring equitable access to dispensed-to-patient (DTP) medical devices is an important policy priority for health insurance systems. This mixed-method study examined stakeholder perspectives on barriers and policy priorities for developing a DTP medical-device formulary for health insurance beneficiaries in Saudi Arabia. An exploratory online survey was distributed to 58 purposively selected stakeholders, and 17 responded (29.3%). Survey findings were summarized descriptively as n/N (%) with 95% confidence intervals. A subsequent stakeholder consultation workshop with 42 stakeholders was used to explore survey themes and identify policy-relevant recommendations. Survey respondents identified several recurring barriers, including lack of standardized evaluation criteria for including new devices (15/17, 88.2%; 95% CI 65.7-96.7), lack of clarity on reimbursement policies (13/17, 76.5%; 95% CI 52.7-90.4), limited reimbursement coverage for certain devices (10/17, 58.8%; 95% CI 36.0-78.4), and fragmented coding and categorization systems. Qualitative findings highlighted the need for explicit eligibility criteria, transparent pricing, risk-based assessment pathways, and coding systems that support claims processing and post-market evidence generation. The findings support an evidence-informed, stakeholder-informed formulary process with clear governance, standardized assessment criteria, transparent reimbursement rules, and improved coding infrastructure. Given the small exploratory survey sample, the quantitative findings should be interpreted as preliminary and validated in larger stakeholder studies.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13469036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148727331","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}

{"title":"Gut microbiota modulation of systemic immunity and cancer immunotherapy: mechanisms, evidence, and therapeutic implications.","authors":"Bader S Alotaibi","doi":"10.1007/s44446-026-00107-w","DOIUrl":"10.1007/s44446-026-00107-w","url":null,"abstract":"<p><p>The gut microbiota plays a critical role in regulating systemic immune responses and has emerged as a key determinant of therapeutic efficacy and toxicity in cancer immunotherapy. Accumulating evidence indicates that specific microbial taxa and microbiota-derived metabolites modulate antitumor immunity by shaping immune cell maturation, cytokine signaling, and the tumor microenvironment. In particular, gut microbial metabolites such as short-chain fatty acids, bile acids, and inosine influence immune checkpoint inhibitor responses by regulating T-cell activation, dendritic cell function, and immune homeostasis beyond the intestinal compartment. Preclinical and clinical studies have demonstrated that alterations in gut microbiota composition are associated with variability in immunotherapy outcomes, including treatment resistance and immune-related adverse events. Importantly, microbiota-targeted interventions such as dietary modulation, probiotics, prebiotics, antibiotics, and fecal microbiota transplantation have shown promise in enhancing immunotherapy efficacy and reducing toxicity. This review synthesizes current mechanistic insights and clinical evidence linking the gut microbiota to systemic immunity and cancer immunotherapy outcomes, highlighting microbiome modulation as a potential therapeutic adjuvant to optimize immunotherapy response and support precision oncology.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13462036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714354","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}

{"title":"A real-world, bottom-up cost of illness analysis of type 2 diabetes mellitus from a tertiary hospital in Saudi Arabia.","authors":"Saleh Alyahya, Saif Alhawwashi, Saad Saeed Alqhatani, Mohammed Ayoob Asseri, Afaf Alshehri, Najla Saleh, Khalid Alshahrani, Amjad Alqahtani, Abdulmohsen Yahya Asseri, Ali Alshahrani, Bander Albalkhi, Abdullah Mohammed Al Shahrani","doi":"10.1007/s44446-026-00104-z","DOIUrl":"10.1007/s44446-026-00104-z","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a major contributor to global morbidity, mortality, and healthcare expenditure. In the context of Saudi Arabia, it is concerningly notable that the prevalence of T2DM is particularly high and rising. Existing cost estimates have previously relied rely on aggregate methodologies, potentially an approach that limits their usefulness for hospital-level decision-making. Accordingly, the primary goal in the current study was to estimate the direct medical costs of T2DM using a real-world, bottom-up micro-costing approach. We carried out a retrospective, cross-sectional cost-of-illness study using electronic medical records from a tertiary hospital in Saudi Arabia. The data collection happened between January and December, 2024. We included adult patients with T2DM, and we calculated direct healthcare costs from the hospital payer perspective, including outpatient care, hospitalizations, laboratory investigations, and medications. In data analysis, we used descriptive statistics, one-way ANOVA, and log-transformed ordinary least squares regression in order to assess cost differences and identify predictors of total cost. A total of 431 patients participated and findings showed that the mean annual cost per patient was SAR 15,396.24 (4,103 USD), and a total cost of SAR 6,635,779.57 (1,768,209 USD). Medications (52.9%) and laboratory tests (40.6%) were the main cost drivers, and higher costs were significantly associated with elevated glycated hemoglobin levels (β = 0.067, p < 0.001), longer disease duration (β = 0.019, p = 0.003), and greater number of comorbidities (β = 0.070, p < 0.001). Going from the above findings, we concluded that T2DM imposes a substantial economic burden on tertiary healthcare systems, importantly indicating that improving glycemic control and managing comorbidities may reduce costs and enhance healthcare efficiency.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"34 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13447626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680505","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}