Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Patients with lung adenocarcinoma (LUAD) receiving radiotherapy represent an important but underexplored clinical subgroup. These patients often undergo concomitant pharmacologic treatments, yet the prognostic impact and underlying determinants of such combined regimens remain poorly understood. Objective: This retrospective observational study aimed to develop and validate a radiotherapy-specific machine learning prognostic model for LUAD and to compare survival across concomitant pharmacologic regimens. Methods: In this retrospective observational study, using genomic and clinical data from TCGA, a radiotherapy-specific prognostic model for LUAD was developed and validated through ten machine learning algorithms. Survival analyses were conducted across distinct concomitant pharmacologic strategies, followed by functional enrichment to elucidate molecular mechanisms underlying differential outcomes. Results: Demonstrating robust prognostic abilities, the model efficiently sorted patients into high- and low-risk categories. Both treatment type and risk score independently predicted overall survival, with significant interaction effects. Low-risk patients receiving targeted or combination therapy—mainly erlotinib, gefitinib, or bevacizumab—exhibited substantially improved survival compared with those receiving conventional chemotherapy. Enrichment of "Exogenous peptide presentation," "MHC class II assembly," "Peptide–MHC II assembly," and "Symbiotic interaction" pathways indicated immune modulation and host–tumor crosstalk as key mediators of treatment efficacy. Conclusion: This study establishes a radiotherapy-specific prognostic model for lung adenocarcinoma, demonstrating distinct molecular and therapeutic heterogeneity and highlighting the superior survival benefit of targeted combination therapy in low-risk patients.

Abstract: Background: Multiparticulate Drug Delivery (MDD) system are particularly considered as well suited systems for controlling oral preparations that have low risk of dose-dumping. Objectives: The current research work was aimed to prepare Fexofenadine HCl immediate release (IR) and Paracetamol sustained release (SR) pellets in a single dosage unit for the treatment of Allergic Rhinitis. Extrusion-spheronization was used to fabricate pellets. Methods: The formulations were analyzed for several parameters, including micromeritic studies, Friability, Weight variation test, Swelling, X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), in-vitro release and stability studies. Results: The results showed that the formulated pellets have an excellent flowability (23.01° to 25.23°), bulk density falls in the range of 1.23 g cm-3 to 1.42 g cm-3, tapped density ranges 1.43 g/cm3 1.58 g/cm3, carr’s compressibility index lie between 10.31 % to 15.17 %, Hausner's ratio ranges 1.11 to 1.18 which concluded pellets had good flow properties. Friability was less than 1%; the T6 formulation showed the maximum swelling of 99.28%. No interaction between excipient and drug was found. T6 showed a drug release of 99.08% in 24 hours. Conclusion: The research effectively demonstrated that preparing a single-unit dosage form of paracetamol and fexofenadine is a safe, simple and promising technique for SR of Paracetamol, thereby increasing patient compliance by reducing the dosage frequency.

Abstract: Background: Postoperative inflammation after arthroplasty contributes to pain, delayed mobilization and prolonged hospitalization. Recent randomized trials have evaluated pharmacological anti-inflammatory strategies within contemporary enhanced recovery pathways, but evidence after hip and shoulder arthroplasty remains scattered across different drug classes and perioperative regimens. Objectives: To synthesize recent randomized controlled trial (RCT) evidence on perioperative anti-inflammatory agents after hip and shoulder arthroplasty. Methods: PubMed, Embase, Cochrane Library and Web of Science were searched for English-language RCTs published from January 2020 to March 2026. The 2020-2026 window was selected to update evidence generated under modern arthroplasty, anesthesia, multimodal analgesia and enhanced recovery after surgery (ERAS) pathways. Eligible trials included adults undergoing hip or shoulder arthroplasty and compared corticosteroids, cyclooxygenase-2 (COX-2) inhibitors, nonsteroidal anti-inflammatory drug (NSAID)-based/local anti-inflammatory regimens, or related anti-inflammatory interventions with placebo, saline, no treatment, or the same regimen without the target component. Weighted mean differences (WMDs) were pooled using random-effects models. Results: Nine RCTs involving 800 patients were included. Anti-inflammatory interventions significantly reduced postoperative C-reactive protein (CRP) [WMD=-32.18, 95% confidence interval (CI) (-41.16, -23.21), P<0.001], interleukin-6 (IL-6) [WMD=-31.25, 95% CI (-41.79, -20.77), P<0.001], rest pain [WMD=-0.41, 95% CI (-0.58, -0.23), P<0.001], activity pain [WMD=-0.56, 95% CI (-0.83, -0.29), P<0.001] and hospital stay [WMD=-0.54, 95% CI (-0.92, -0.15), P=0.006]. Conclusion: Recent RCT evidence suggests that perioperative anti-inflammatory interventions can attenuate early inflammatory responses and improve short-term pain and recovery after hip and shoulder arthroplasty. Because data were limited and clinically heterogeneous, the findings should not be interpreted as evidence favoring a specific drug class, dose, route, or timing.

Abstract: Background: Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide and effective therapeutic targets remain limited. Objectives: This study aimed to investigate the expression and functional role of miR-326 in gastric cancer, identify its direct target gene and elucidate the underlying molecular mechanisms involving the PI3K/Akt signaling pathway and the regulation of inflammatory cytokines. Methods: miR-326 expression was detected by qRT-PCR in 56 paired GC tissues and adjacent normal tissues, as well as in GC cell lines (SGC-7901, MKN-45, AGS) and normal GES-1 cells. CCK-8 assays, flow cytometry, Transwell migration/invasion assays and ELISA were performed to assess cell proliferation, apoptosis, migration/invasion and cytokine secretion. Dual-luciferase reporter assay and Western blotting were used to validate the target gene and pathway activation. Results: miR-326 was significantly upregulated in GC tissues and cell lines. ETS1 was identified as a direct target of miR-326. Overexpression of miR-326 reduced ETS1 expression, activated the PI3K/Akt pathway (increased p-PI3K and p-AKT), promoted cell proliferation, migration and invasion, inhibited apoptosis and induced an imbalance of inflammatory cytokines (increased IL-6 and TNF-α; decreased IL-10 and IL-17). Co-overexpression of ETS1 or treatment with the PI3K inhibitor LY294002 reversed these effects. Conclusions: miR-326 promotes malignant phenotypes in gastric cancer cells by targeting ETS1, activating the PI3K/Akt signaling pathway, and inducing dysregulation of inflammatory cytokines. The miR-326/ETS1/PI3K/Akt axis may serve as a potential diagnostic biomarker and therapeutic target for gastric cancer.

Abstract: Background: Cardiac arrest (CA) is associated with high mortality and severe neurological sequelae. Artemisinin (ARS), a natural product from Artemisia annua, has potential neuroprotective effects, but its role in brain injury after CA resuscitation remains unclear. Objectives: This study investigated the effects of ARS on hippocampal neuronal apoptosis and cognitive dysfunction in rats after CA resuscitation and explored whether these effects are associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Methods: Sixty male rats were randomly assigned to six groups: sham, model, artemisinin (40 mg/kg), dimethyl sulfoxide ((DMSO, 100 mg/kg), LY294002 (a phosphatidylinositol 3-kinase inhibitor, 25 mg/kg) and artemisinin plus LY294002. Cardiac arrest was induced by transcutaneous electrical stimulation. Outcome assessors were blinded. Neurological function was evaluated using the Neurological Deficit Scale. Hippocampal damage and apoptosis were assessed by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Learning and memory were tested using novel object recognition and the Morris water maze. Protein expression was measured by Western blot. Results: Artemisinin significantly improved Neurological Deficit Scale scores, reduced terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and alleviated hippocampal damage. Artemisinin also prolonged novel object exploration time, shortened escape latency, increased target quadrant time and upregulated phosphatidylinositol 3-kinase expression and the ratio of phosphorylated protein kinase B to protein kinase B. Co-administration of LY294002 partially reversed these effects. Conclusion: Artemisinin alleviates hippocampal neuronal apoptosis and improves neurological deficits and cognitive dysfunction in rats after cardiac arrest resuscitation, suggesting a possible association with activation of the phosphatidylinositol 3-kinase/protein kinase B pathway. Limitations include use of a single pharmacological inhibitor and lack of genetic validation.