Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Papillary thyroid carcinoma (PTC) is a common endocrine malignancy with rising incidence. The role of LINC01116 in PTC progression and its underlying mechanisms remain unclear. Objectives: To investigate LINC01116 expression in PTC, evaluate its prognostic significance and explore its functional role in regulating bone marrow mesenchymal stem cell (BMSC) apoptosis. Methods: This was a cross-sectional observational study with a prognostic cohort component.Serum samples from 60 PTC patients and 30 healthy controls were analyzed by RT-qPCR. Prognostic value was assessed using Kaplan-Meier survival analysis and Cox regression. In vitro, LINC01116 expression was manipulated in PTC cells and BMSCs using three independent siRNAs and pcDNA3.1 overexpression plasmids. Cell proliferation was evaluated by CCK-8 and colony formation assays, migration by Transwell assays and apoptosis by flow cytometry and Western blot analysis of Bcl-2, cleaved caspase-3 and cleaved caspase-9. Rescue experiments using siRNA-resistant LINC01116 were performed to confirm specificity. Results: LINC01116 was significantly upregulated in serum from PTC patients compared with healthy controls (P < 0.001). High LINC01116 expression correlated with advanced TNM stage and predicted reduced disease-free survival (HR=2.067, P=0.026) and overall survival (HR=2.081, P=0.024), serving as an independent prognostic factor. Knockdown of LINC01116 inhibited PTC cell proliferation and migration, while overexpression enhanced these effects. Mechanistically, LINC01116 suppressed BMSC apoptosis by upregulating Bcl-2 and downregulating cleaved caspase-3/9. Knockdown of LINC01116 induced opposite effects. Rescue experiments confirmed that restoring LINC01116 expression partially reversed knockdown-induced phenotypes (50-60% reversal), demonstrating functional specificity. Conclusion: LINC01116 is significantly upregulated in PTC and serves as an independent prognostic biomarker. It promotes tumor progression by inhibiting BMSC apoptosis through modulation of the Bcl-2/caspase pathway. These findings provide new insights into PTC pathogenesis and suggest LINC01116 as a potential therapeutic target.

Abstract: Background: Delayed onset muscle soreness (DOMS) impairs exercise recovery, while current treatments remain limited. Traditional Chinese Medicine (TCM) formulas may provide safe, multi-target interventions. Objectives: This study evaluated the dose-dependent protective effects of a four-herb Chinese medicine formulation (safflower, Chinese Angelica, peach kernel and myrrh) against DOMS in a rat model. Methods: Thirty-two male SPF SD rats were randomly allocated to control or low- (1696 mg/kg), medium- (3392 mg/kg), or high-dose (6784 mg/kg) groups. The formulation was administered orally for 11 days, with DOMS induced by exhaustive swimming on day 8. Serum CK, Mb, CRP, IL-6, and PGE₂ were measured at baseline and at 24, 48, 72, and 96 h post-exercise. Results: The medium- and high-dose groups exhibited significantly lower serum CK, Mb, CRP, IL-6, and PGE₂ levels than controls, with the high-dose group showing the largest reductions. The low-dose group showed limited or no significant reductions in most markers, demonstrating a clear dose-dependent protective effect. Conclusions: The formulation dose-dependently attenuates muscle damage and inflammation in a rat DOMS model, with high-dose treatment achieving the fastest recovery. Clinical trials are warranted to confirm the efficacy and safety in humans.

Abstract: Background: Dental caries are chronic infectious diseases with a high global prevalence. Its pathogenesis is closely related to the adhesion of Streptococcus mutans (S. mutans), formation of dental plaque biofilms and acid production. Currently, only a few types of anticaries drugs are available for clinical use and the long-term use of these drugs can lead to side effects, such as drug resistance and dysbiosis of the oral microbiota. Objectives: Therefore, exploring new, safe and effective anti-caries treatments is an urgent task. Screening antimicrobial drugs from herbal medicines for non-antibiotic treatment of bacteria could provide new solutions to these problems. This study aimed to screen food-borne herbal extracts with synergistic antimicrobial potential to provide a theoretical foundation for the development of natural anticaries drugs. Methods: This in-vitro study evaluated the minimum inhibitory concentration and minimum biofilm inhibitory concentration of individual plant extracts (cinnamaldehyde, eugenol and polydatin) and a 1:1 mixture of these extracts. The effects of drug combinations were assessed using the checkerboard method. The inhibitory effects of drugs against S. mutans and their antibacterial mechanisms were evaluated through scanning electron microscopy and conductivity measurements. Their ability to inhibit S. mutans biofilms was assessed through crystal violet (Beijing Solebao Technology Co.) staining and scanning electron microscopy. Their inhibition of bacterial acid production and cytotoxicity to human gingival fibroblasts were also examined. Results: The combination groups exhibited synergistic bacteriostatic effects while reducing cytotoxicity. Individual and combined plant extracts exerted bacteriostatic effects by disrupting the bacterial cell membrane, significantly inhibiting S. mutans biofilm formation while suppressing its acid production. Conclusions: The application of combined food-borne herbal extracts inhibits the growth of S. mutans and its biofilm synergistically while reducing the required drug concentration and cytotoxicity. This provides a new approach for the development of natural anticaries preparations.

Abstract: Background: Fibrotic liver is one of the serious pathophysiological consequences of chronic injury to the liver, may progress toward serious complications including cirrhosis and hepatic carcinoma. Objectives: Panax notoginseng is used for both therapeutic and prophylactic purposes in TCM; it is a source of Dencichine, an active substance that has been proven to exhibit antifibrotic properties in hepatic fibrosis. The present study investigated how Dencichine treatment ameliorates liver fibrosis using an animal model and a cellular fibrosis model. Methods: Randomly assigned, male C57BL/6J mice received 10% CCl4 for 15 consecutive weeks to induce hepatic fibrosis. Treatment with Dencichine was initiated from 7th week onward. To simulate in-vitro the presence of a fibrotic microenvironment, LX-2 cells were treated with PDGF-BB at a concentration of 20 ng/mL and incubated from one up to four days and then treated by various doses of Dencichine. Liver function was evaluated by measuring alanine aminotransferase (ALT), AST, HA and LN. Histopathology was evaluated by haematoxylin/eosin (HE), Masson’s trichrome and Sirius red stains. Quantitative real-time PCR and western blot analyses were used to evaluate mRNA and protein expression levels, respectively. Wound-healing assays and transwell chamber experiments were used to assess cell migration; EdU proliferation detection and flow cytometry were performed to measure cell proliferation and cell cycle, respectively. Results: The most important results are a considerable reduction of serum concentrations of AST and ALT, HA and laminin in CCl4-treated mice decreased liver injury and ECM deposition. Furthermore, this compound downregulated the expression of cyclin D1 and cyclin E1 and blocked the activation of PI3K and AKT kinases in fibrotic liver cells. Conclusion: These results indicate that Dencichine may slow the development of liver fibrosis by interfering with the PI3K-AKT signaling cascade, demonstrating significant anti-scarring properties.

Abstract: Background: Bone marrow mesenchymal stem cells (BMSCs) show promise in glioma therapy, but the underlying mechanisms remain unclear. Signal transducer and activator of transcription 3 (STAT3) is a key oncogenic driver in glioma; however, whether BMSCs exert anti-glioma effects through STAT3 modulation requires further investigation. Objectives: To investigate whether BMSCs promote glioma cell apoptosis by inhibiting STAT3 phosphorylation and to validate the causal role of STAT3 using a specific agonist. Methods: C6 glioma-bearing rats were randomized into control, model, BMSC, positive control (MS-275) and STAT3 agonist (Colivelin) groups. BMSCs (1×10⁷ cells) were injected via the tail vein on days 14 and 17. Tumor growth, apoptosis, glial fibrillary acidic protein (GFAP) expression, basic fibroblast growth factor (bFGF)/vascular endothelial growth factor (VEGF) mRNA levels and STAT3/phosphorylated STAT3 (p-STAT3) expression were assessed by magnetic resonance imaging (MRI), histology, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, flow cytometry, immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. In-vitro validation was performed using BMSC-conditioned medium and the STAT3 inhibitor Stattic in C6 cells. Results: BMSC transplantation significantly reduced the tumor area and Ki-67 proliferation index, increased the number of apoptotic cells and the apoptotic rate (P < 0.01) and decreased p-STAT3 levels and the p-STAT3/STAT3 ratio (P < 0.01) without altering total STAT3 expression. Colivelin reversed BMSC-induced apoptosis. bFGF and VEGF mRNA levels were increased in the BMSC group (P < 0.01). In-vitro, BMSC-conditioned medium suppressed STAT3 phosphorylation and induced apoptosis, effects that were enhanced by Stattic. Conclusion: BMSCs promote apoptosis in glioma cells by inhibiting STAT3 phosphorylation. The reversal of these effects by a STAT3 agonist confirms the causal role of STAT3 inhibition. These findings identify STAT3 as a key therapeutic target for BMSC-based glioma therapy.