The prevalence of type 2 diabetes mellitus (T2DM) globally is reaching epidemic proportions. By 2035, it is projected to increase to 417 million, which is of significant concern as T2DM represents the most oversized budget item in many healthcare systems, primarily due to the high rates of morbidity and mortality associated with the disease. The worldwide cost burden of T2DM has been inexorably growing. A key contributor to the remarkably high morbidity and mortality rates is poor glycemic control potentially associated with medication non-adherence. The present research’s main objective included assessing medication adherence among patients with T2DM in a single center in Jazan Province. Three hundred nine patients with T2DM participated in a cross-sectional survey over three months (September to November 2022). The study participants comprised 50.8 % (females) and 49.2 % (males), with a mean age of 44.12 years (SD ± 12.70). A 31-item self-report questionnaire was used for data collection. Sixty-six percent of the sample were found to be adherent to their T2DM therapy. A positive association was noticed between the GMAS score and the participant’s age (r = 0.24; p < 0.01). The participants’ medication adherence was significantly associated with having age above 50 years (χ² = 13.62; p = 0.001), residing in urban localities (χ² = 21.37; p < 0.001), being married (χ² = 12.80; p = 0.002), having glycated hemoglobin level more than 8 % (χ² = 6.99; p = 0.03) and taking between one to three medications per day (χ² = 17.63; p < 0.001). The majority of T2DM patients in the present study were found adherent to their anti-diabetic medications, particularly older patients. Future studies should focus on exploring the reasons for the reported high adherence among older patients and non-adherence among younger patients, as this could facilitate the development of a strategy to enhance adherence.

One of the significant worldwide health problems associated with pharmacovigilance is the under-reporting of adverse drug reactions (ADRs). Reporting suspected ADRs is essential to ensure patient safety, medicine safety, and healthcare quality. The new policy in Saudi Arabia emphasizes pharmacists taking a new clinical role, which may facilitate and improve the documentation of ADRs. Therefore, this study aimed to assess the knowledge and perception of community pharmacists towards the ADRs and their reporting practice in Saudi Arabia. A cross-sectional study using a structured self-administered questionnaire was administered to community pharmacists working in Saudi Arabia. Data were analyzed using descriptive and inferential statistics to identify the association between perceptions and ADR reporting practices. A P value < of 0.05 was considered statistically significant. A response rate of 43% (n = 163) was achieved, of whom 55.2% demonstrated knowledge of PV. Only 16% of community pharmacists were aware of the responsible center for monitoring and collecting ADRs in Saudi Arabia. The key facilitator was offering incentives to pharmacists, and the lack of time was found to be a key barrier among reporter community pharmacists. Positive attitudes toward pharmacovigilance and ADR reporting were expressed by community pharmacists. The findings of this study emphasize the further need for education and training programs and simplifying the ADR reporting process used in Saudi Arabia to enhance the reporting practice.

Cancer stem cells (CSCs) participate in cancer initiation, metastasis, and therapy tolerance, presenting a formidable challenge in cancer treatment. Antibody-drug conjugates (ADCs) have been established as a potential strategy for selectively targeting and eradicating CSCs, thereby overcoming resistance mechanisms and preventing tumor recurrence. ADCs integrate a monoclonal antibody specific to CSC surface markers, such as CD44, CD133, EpCAM, and ALDH1, with a potent cytotoxic payload linked by a stable chemical linker. Upon antigen binding, ADCs undergo receptor-mediated internalization, leading to intracellular payload release and CSC apoptosis. Recent advances in ADC technology have enhanced selectivity and efficacy while minimizing off-target toxicity. Preclinical studies demonstrate that CSC-targeted ADCs, including CD133- and CD44-directed therapies, effectively deplete CSC populations in glioblastoma, breast, colorectal, and lung cancers. EpCAM-targeted ADCs have also shown efficacy in epithelial tumors with potential synergy in combination immunotherapies. Moreover, emerging approaches, such as bispecific antibodies and optimized linker chemistry, further refine CSC-targeted ADCs for clinical applications. Despite these advancements, challenges remain, including CSC heterogeneity, immune evasion, and limitations in biomarker specificity. Addressing these hurdles requires continued innovation in ADC engineering, novel payloads, and combinatory strategies with immune checkpoint inhibitors or CAR-T cell therapies. While clinical evaluations are still in the early phases, preliminary trials underscore the potential of CSC-targeted ADCs in revolutionizing precision oncology. This review explores the mechanisms, recent developments, and prospects of CSC-targeted ADCs, highlighting their transformative potential in cancer immunotherapy.

Chemotherapy-induced kidney damage is an emerging problem that restricts cancer treatment effectiveness. The proteasome inhibitor carfilzomib (CFZ) is primarily used to treat multiple myeloma and has been associated with severe renal injury in humans. CFZ-induced nephrotoxicity remains an unmet medical need, and there is an urgent need to find and develop a nephroprotective and antioxidant therapy for this condition. Thymoquinone (TQ) is a bioactive compound that has been isolated from Nigella sativa seeds. It has a wide range of pharmacological properties. Therefore, this experimental design aimed to study the effectiveness of TQ against CFZ-induced renal toxicity in rats. The first group of rats was a normal control (CNT); the second group received CFZ (4 mg/kg b.w.); the third and fourth groups received TQ (10 and 20 mg/kg b.w.) 2 h before receiving CFZ; the fifth group received only TQ (20 mg/kg b.w.). This experiment was conducted for 16 days, and at the end of the experiment, blood samples and kidney tissue were collected for biochemical assays. The results indicated that administration of CFZ significantly enhanced serum marker levels such as BUN, creatinine, and uric acid in the CFZ group. Similarly, it was also noticed that CFZ administration induced oxidative stress by reducing antioxidants (GSH) and antioxidant enzymes (CAT and SOD) and increasing lipid peroxidation. CFZ treatment also enhanced the expression of IL-1β, IL-6, and TNF-α production. Moreover, CFZ increased caspase-3 concentrations and reduced Nrf2 expression in the CFZ-administered group. However, treatment with 10 and 20 mg/kg TQ significantly decreased serum markers and increased antioxidant enzymes. TQ treatment considerably reduced IL-1β, IL-6, TNF-α, and caspase-3 concentrations. Overall, this biochemical estimation was also supported by histopathological outcomes. This study revealed that TQ administration significantly mitigated the negative effects of CFZ treatment on Nrf2 expression. Thus, it indicates that TQ may have utility as a potential drug to prevent CFZ-induced nephrotoxicity in the future.

Hyperuricemia contributes significantly to gout arthritis pathogenesis, which promotes urate crystal deposition in the joints and activates joint-resident macrophages and circulating monocytes to initiate a state of inflammatory arthritis. In the joint, macrophages have an immune defense role where the presence of urate crystals results in the inflammatory mediators secretion, inflammatory cells recruitment to the joint, and shift macrophage population toward M1 pro-inflammatory phenotypes. Current treatment modalities of gout arthritis have side effects that limit their use in the elderly. A novel treatment that targets macrophage polarization to re-establish homeostasis may initiate a drug discovery program of novel disease-modifying agents for gout. Zerumbone (Zer) is a sesquiterpenoid bioactive compound found in the rhizome of Zingiberaceae family and possesses anti-inflammatory, antioxidant, and anti-proliferative activity. Our study hypothesized that soluble uric acid (sUA) and Pam3CSK4 (TLR2 agonist) reduce the anti-inflammatory function of murine M2 bone marrow-derived macrophages and change the expression of M2 genetic markers toward M1 phenotypes. We observed that priming of M2 macrophages with sUA and Pam3CSK4 significantly decreased M2 specific markers expression, e.g., Arg-1, Ym-1, and Fizz-1, enhanced mRNA expression of IL-1β, TNF-α, CXCL2, and iNOS and increased oxidative stress in M2 macrophages, as exhibited by a reduction in Nrf2 expression. We also aimed to study the impact of Zer on reducing the pro-inflammatory effect of sUA in TLR2-stimulated M2 macrophages. We noticed that Zer treatment significantly reduced L-1β and TNF-α production following Pam3CSK4 + sUA treatment on M2 macrophages. Furthermore, Zer reduced the caspase-1 activity without altering cytosolic NLRP3 content in challenged M2 BMDMs. We also observed that Zer significantly enhanced M2-associated marker’s expression, e.g., Arg-1, Ym-1, and Fizz-1, and augmented Nrf-2 and other antioxidant proteins, including HMOX1 and srxn1expression following Pam3CSK4 + sUA treatment. We draw the conclusion that Zer is a potentially effective anti-inflammatory treatment for gout arthritis linked to hyperuricemia.

Background: Tirzepatide (Mounjaro or Zepbound), a dual GLP-1/GIP receptor agonist, is approved for type 2 diabetes and weight management. Despite its efficacy, real-world safety data remain limited. This study analyzed post-marketing adverse events (AEs) associated with tirzepatide using the FDA Adverse Event Reporting System (FAERS) to identify emerging safety concerns. Methods: FAERS reports from 2022 to Q1 2025 were analyzed. Disproportionality analyses (proportional reporting ratio [PRR], reporting odds ratio [ROR], empirical Bayes geometric mean [EBGM], and information component [IC]) were performed to detect safety signals. Reports were stratified by year, demographics, and AE type, focusing on cases in which tirzepatide was the primary suspect. Results: Among 65,974 reports, the majority originated from the U.S. (96%), with middle-aged females (40–59 years; 67%) most frequently affected. Incorrect dose administration was the top AE, increasing 8-fold from 1248 (2022) to 9800 (2024), with strong risk signals (ROR 22.15, 95% CI (20.75–23.65), and ROR 23.43, 95% CI (22.82–24.05), respectively, and PRR 16.80, 95% CI (15.74–17.93), and PRR 17.62, 95% CI (17.16–18.09), respectively). Other common AEs included injection-site reactions (e.g., pain [5273 cases in 2024]), gastrointestinal issues (nausea [3602 in 2024]), and off-label use. Class-related AEs (e.g., decreased appetite and blood glucose fluctuations) were also reported. Conclusions: Tirzepatide is associated with significant dosing errors, injection-site reactions, and gastrointestinal AEs in real-world use. The rising trend in reports underscores the need for enhanced provider and patient education, clearer dosing guidelines, and proactive monitoring. Further research is warranted to explore causative factors and optimize risk mitigation strategies.