Mohamed F. Balaha

Background: Obesity is a complex condition marked by excessive body fat, linked to comorbidities such as type 2 diabetes and cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor agonists, initially developed for diabetes, are increasingly used for weight management. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (PubMed, last 5 years, English language) evaluating GLP-1–based pharmacotherapies versus placebo or active comparators for weight loss. The primary endpoint was the proportion of participants achieving any weight loss during follow-up. Pooled odds ratios were estimated using a fixed-effect model with 95% confidence intervals; heterogeneity was quantified with I ² . A frequentist network meta-analysis generated SUCRA rankings. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. No protocol was registered. Results: Twenty-one trials met the inclusion criteria (n = 7024 in pairwise analyses). Across 16 placebo-controlled trials, a higher proportion of participants achieved weight loss with GLP- 1–based agents than with placebo: 78.54% (3231/4114) versus 26.53% (772/2910); pooled odds ratio: 11.37 (95% confidence interval: 8.10–15.98), P < .0001; I ² = 82%. In the network meta-analysis, tirzepatide and semaglutide ranked highest (surface under the cumulative ranking curve 91.2% and 85.4%, respectively). Conclusion: GLP-1 receptor agonists significantly increase the likelihood of weight loss versus placebo, with tirzepatide and semaglutide demonstrating the greatest relative efficacy among agents evaluated. These findings support GLP-1–based therapy as an effective component of clinical obesity management.

‎Purpose: The reproductive safety profiles of quetiapine (QTP) during pregnancy are not fully understood. This review primarily assesses perinatal outcomes and major malformations following exposure to quetiapine. Methods: ‎A comprehensive literature search identified 33 studies published through February 2025. Outcomes were synthesized for QTP using random-effects models and benchmarked against population surveillance and psychiatric controls when available. Results: ‎Among 13,090 pregnancies exposed to QTP with malformation outcomes, the major malformation rate was 4.1%, which is comparable to background rates. Perinatal outcomes were similar to those of the controls for QTP. Several high-quality studies have shown a dose-response relationship between higher QTP doses and the risk of gestational diabetes. Conclusions: QTP is not associated with an increased risk of major malformations and does not significantly raise adverse perinatal outcomes compared with controls. The dose-related metabolic risks of QTP underscore the importance of minimizing dosage and closely monitoring metabolism during pregnancy.

Objectives: Tissue-agnostic oncology personalizes treatments based on shared molecular biomarkers, addressing challenges like assay variability, control-arm rigor, and non-proportional hazards. Integrating efficacy, safety, and resistance factors with consistent estimands is essential for evaluating biomarker-matched therapies across histologies. This review aims to quantify and compare their efficacy and safety, and to identify determinants of resistance, using PRISMA-compliant methods. Methods: We conducted a systematic review and random-effects meta-analysis of 38 studies (15,018 participants), employing dual screening, standardized bias assessment, and evaluations of heterogeneity and small-study effects. Hazard ratios (HRs) with 95% CIs were estimated for time-to-event outcomes, and restricted mean survival times were used when the proportional hazards assumption was violated. Results: Trastuzumab deruxtecan improved objective response rates and extended progression-free survival (PFS) and overall survival (OS) in HER2-positive gastric and gastroesophageal junction cancers and in HER2-low metastatic breast cancer, showing longer response durations. In metastatic colorectal cancer with microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR), PD-1 blockade significantly increased PFS and five-year OS despite crossover, with restricted mean survival time gains of about 11 months. In endometrial cancer, dostarlimab combined with chemotherapy improved PFS in both dMMR/MSI-H and mismatch repair–proficient disease and increased OS overall. Encorafenib-based therapies reduced progression and death in BRAF V600E metastatic colorectal cancer. Safety profiles were class-specific: PD-1 inhibitors caused fewer grade 3 or higher adverse events than chemotherapy, whereas trastuzumab deruxtecan was associated with increased interstitial lung disease (ILD) or pneumonitis and higher rates of treatment discontinuation. Conclusion: Biomarker-matched therapies confer significant survival benefits with predictable toxicities. Confidence is strongest for PD-1 inhibitors in MSI-H/dMMR tumors, trastuzumab deruxtecan in HER2-low or HER2-positive cancers, and encorafenib-based regimens in BRAF V600E metastatic colorectal cancer. Implementation should include validated assays (including reconfirmation of HER2 status), prioritize earlier treatment lines where gains are greatest, and require vigilant ILD monitoring. Head-to-head trials and assay standardization, especially for tumor mutational burden, remain priorities.

The present review offers comprehensive data on the roles of Peptidyl Arginine Deiminase 4 (PAD4) in various diseases, including rheumatoid arthritis (RA). PAD4, an enzyme responsible for converting arginine to citrulline, has been linked to the development of chronic inflammation. The current study is a narrative review to determine whether PAD4 is a potential therapeutic target for RA and other illnesses. We searched PubMed and Google Scholar for studies published before 2024. The potential therapeutic utility of PAD4 in various diseases such as cancer, miscarriage, multiple sclerosis, retinopathy, and RA is emphasized in the article. This paper explores the advancements in the development of small-molecule inhibitors and monoclonal antibodies targeting PAD4. It stresses the importance of conducting additional research to resolve specificity, safety, and sustained effectiveness concerns. The review emphasizes the need for a comprehensive approach to completely comprehend the varied attributes and potential therapeutic applications of PAD4.

Background and objectives: Cyclophosphamide (CPA) is an alkylating agent that is used for the management of various types of malignancies and as an immunosuppressive agent for the treatment of immunological disorders. However, its use is limited by its potential to cause a wide range of pulmonary toxicities. Amentoflavone (AMV) is a flavonoid that had proven efficacy in the treatment of disease states in which oxidative stress, inflammation, and apoptosis may play a pathophysiologic role. This study investigated the potential ameliorative effects of the different doses of AMV on CPA-induced pulmonary toxicity, with special emphasis on its antioxidant, anti-inflammatory, and apoptosis-modulating effects. Materials and methods: In a rat model of CPA-induced pulmonary toxicity, the effect of AMV at two dose levels (50 mg/kg/day and 100 mg/kg/day) was investigated. The total and differential leucocytic counts, lactate dehydrogenase activity, and levels of pro-inflammatory cytokines in the bronchoalveolar lavage fluid were estimated. Also, the levels of oxidative stress parameters, sirtuin-1, Keap1, Nrf2, JAK2, STAT3, hydroxyproline, matrix metalloproteinases 3 and 9, autophagy markers, and the cleaved caspase 3 were assessed in the pulmonary tissues. In addition, the histopathological and electron microscopic changes in the pulmonary tissues were evaluated. Results: AMV dose-dependently ameliorated the pulmonary toxicities induced by CPA via modulation of the SIRT-1/Nrf2/Keap1 axis, mitigation of the inflammatory and fibrotic events, impaction of JAK-2/STAT-3 axis, and modulation of the autophagic and apoptotic signals. Conclusions: AMV may open new horizons towards the mitigation of the pulmonary toxicities induced by CPA.

Acute coronary syndrome (ACS) is a leading cause of cardiovascular-related morbidity and mortality worldwide. The present study investigated the health-related quality of life (HRQOL) and drug prescribing patterns in ACS patients at Riyadh hospitals in Saudi Arabia. This study was a 12-month prospective cross-sectional study that included 356 patients with ACS. The current study showed that younger male (67.42%) and urban (75.84%) patients suffered more from ACS. Moreover, most patients with NSTEMI (51.69%) experienced Grade 1 dyspnea (33.43%) and NYHA Stage 2 (29.80%); however, STEMI patients were at greater mortality risk. The HRQOL questionnaire showed that ACS patients were significantly impaired in all QOL domains (emotional [23.0%, p = 0.001], physical [24.4%, p = 0.003], and social [27.2%, p = 0.002]). Furthermore, the most commonly prescribed medications were statins (93%), antiplatelets (84%), anticoagulants (79%), coronary vasodilators (65%), and beta-blockers (63%). Additionally, 64% of patients received PCIs or CABGs, with the majority of cases receiving PCIs (49%), whereas 9% received dual anticoagulant therapy. Thus, there is an urgent need to educate healthcare teams about the relevance of QOL in ACS control and prevention and the new ACS management recommendations. ACS is also growing among younger people, requiring greater attention and prevention.

One prevalent neurological disorder is epilepsy. Modulating GABAergic/glutamatergic neurotransmission, Nrf2/HO-1, PI3K/Akt, and TLR-4/NF-B pathways might be a therapeutic strategy for epilepsy. Eight-week-old BALB/c mice were administered 12.5, 25, or 50 mg/kg (-) pseudosemiglabrin orally one hour before inducing epilepsy with an i.p. injection of 360 mg/kg pilocarpine. (-) Pseudosemiglabrin dose-dependently alleviated pilocarpine-induced epilepsy, as revealed by the complete repression of pilocarpine-induced convulsions and 100% survival rate in mice. Furthermore, (-) pseudosemiglabrin significantly enhanced mice’s locomotor activities, brain GABA, SLC1A2, GABARα1 levels, glutamate decarboxylase activity, and SLC1A2 and GABARα1mRNA expression while decreasing brain glutamate, SLC6A1, GRIN1 levels, GABA transaminase activity, and SLC6A1 and GRIN1 mRNA expression. These potentials can be due to the suppression of the TLR-4/NF-κB and the enhancement of the Nrf2/HO-1 and PI3K/Akt pathways, as demonstrated by the reduction in TLR-4, NF-κB, IL-1β, TNF-α mRNA expression, MDA, NO, caspase-3, Bax levels, and Bax/Bcl-2 ratio, and the enhancement of Nrf2, HO-1, PI3K, Akt mRNA expression, GSH, Bcl-2 levels, and SOD activity. Additionally, (-) pseudosemiglabrin abrogated the pilocarpine-induced histopathological changes. Interestingly, the (-) pseudosemiglabrin intervention showed a comparable effect to the standard medication, diazepam. Therefore, (-) pseudosemiglabrin can be a promising medication for the management of epilepsy.

Aegle mamelons (A. marmelos) or Indian Bael leaves possess anti-cancerous and antibacterial properties and are used in the traditional medicine system for the treatment of oral infections. In the present study, the essential oil of the leaves of A. marmelos was explored for its anticancer, antioxidant, and anti-cariogenic properties. The hydro-distilled oil of A. marmelos leaves was analyzed using gas chromatography coupled with mass spectrometry (GC-MS). Monoterpene limonene (63.71%) was found to have the highest percentage after trans-2-Hydroxy-1,8-cineole and p-Menth-2,8-dien-1-ol. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay was used to investigate the anticancer activity of the extracted oil against human oral epidermal carcinoma (KB), and the results showed significantly higher (**** p < 0.0001) anticancer activity (45.89%) in the doxorubicin (47.87%) when compared to the normal control. The antioxidant activity of the essential oil was evaluated using methods of DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)). The results showed a significant (*** p < 0.001) percentage of inhibition of DPPH-induced free radical (70.02 ± 1.6%) and ABTS-induced free radical (70.7 ± 1.32%) at 100 µg/mL with IC₅₀, 72.51 and 67.33 µg/mL, respectively, comparatively lower than standard compound ascorbic acid. The results of the molecular docking study of the significant compound limonene with the receptors tyrosinase and tyrosine kinase 2 supported the in vitro antioxidant potential. The anti-cariogenic activity was evaluated against Streptococcus mutans (S. mutans). Results showed a significant minimum inhibitor concentration of 0.25 mg/mL and the killing time was achieved at 3 to 6 h. The molecular-docking study showed that limonene inhibits the surface receptors of the S. mutans c-terminal domain and CviR protein. The study found that A. marmelos leaves have potential anti-carcinoma, antioxidant, and anti-cariogenic effects on human oral epidermal health, making them a valuable natural therapeutic agent for managing oral cancer and infections.