Cervical cancer poses a substantial worldwide health challenge, especially in low- and middle-income nations, caused by high-risk types of human papillomavirus. It accounted for a significant percentage of cancer-related deaths among women, particularly in areas with limited healthcare resources, necessitating innovative therapeutic approaches, and single-targeted studies have produced significant results, with a considerable chance of developing resistance. Therefore, the multitargeted studies can work as a beacon of hope. This study is focused on performing the multitargeted molecular docking of FDA-approved drugs with the three crucial proteins TBK1, DNA polymerase epsilon, and integrin α-V β-8 of cervical cancer. The docking studies using multisampling algorithms HTVS, SP, and XP reveal Pixantrone Maleate (DB06193) as a multitargeted inhibitor with docking scores of -8.147, -8.206 and -7.31 Kcal/mol and pose filtration with MM\GBSA computations with scores -40.55, -33.67, and -37.64 Kcal/mol. We also have performed QM-based DFT and pharmacokinetics studies of the compound and compared it with the standard values, which results in the compound being entirely suitable against cervical cancer proteins. The interaction fingerprints have revealed that PHE, VAL, SER and ALA are the residues among most interactions. We also explore the stability of the multitargeted potential of Pixantrone Maleate through 100ns MD simulations and investigate the RMSD, RMSF and intermolecular interactions between all three proteins-ligand complexes. All computational studies favour Pixantrone Maleate as a multitargeted inhibitor of the TBK1, DNA polymerase epsilon, and integrin α-V β-8 and can be validated experimentally before use.
30 September 2024 in International Journal of Surgery
Background: Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease marked by severe gastrointestinal inflammation and a broad range of debilitating symptoms. Despite advances in medical treatments, achieving sustained remission remains challenging for many patients. This umbrella review aims to consolidate evidence from various systematic reviews to evaluate the efficacy and safety of stem cell therapies in treating Crohn’s disease. Methods: This review followed the Joanna Briggs Institute methodology and adhered to PRISMA guidelines. A literature search of PubMed, Web of Science, Embase, and the Cochrane Library covered records up to 20 April 2024. Only systematic reviews and meta-analyses on stem cell therapy for Crohn’s disease were considered. Data were extracted and analyzed for clinical efficacy indicators like remission induction and safety metrics, including adverse events and mortality rates. Results: Sixteen systematic reviews were included, spanning studies conducted between 2009 and 2023. Stem cell therapy showed a pooled risk ratio (RR) of 1.299 (95% CI: 1.192–1.420) for clinical remission, indicating a 29.9% increased likelihood of remission compared to controls. The pooled RR for healing perianal Crohn’s disease was 1.358 (95% CI: 1.13–1.631), suggesting a 35.8% increased likelihood of healing. A pooled RR of 1.481 (95% CI: 1.036–2.116) shows a 48.1% higher immediate fistula closure rate with stem cell therapy. For long-term outcomes, a RR of 1.422 (95% CI: 1.091–1.854) indicates a 42.2% increased likelihood of maintaining closure. However, stem cell therapy did not significantly impact Crohn’s Disease Activity Index (CDAI) (RR: 1.154, 95% CI: 0.193–6.883) and Perianal Disease Activity Index (PDAI) scores (mean difference at 12 weeks: −0.505, 95% CI: −2.481 to 1.471; mean difference at 24 weeks: −0.338, 95% CI: −1.638 to 0.963). The safety profile was comparable to conventional therapies, with a pooled RR of 0.972 (95% CI: 0.739–1.278) for adverse events and 1.136 (95% CI: 0.821–1.572) for serious adverse events. Conclusion: Stem cell therapy offers significant progress in treating Crohn’s disease, particularly in complex cases, by improving fistula closure rates and suggesting potential as a supplementary therapy. Its safety profile aligns with conventional treatments, yet ongoing clinical trials are crucial to optimize its use. Continual research will enable healthcare providers to tailor more effective treatment strategies for this challenging condition.
Background: Diabetic foot ulcers (DFUs) are a major complication of type 2 diabetes mellitus (T2DM). This study examined the association between the Energy-adjusted Dietary Inflammatory Index (E-DII) and odds of DFUs. Methods: In a case–control study, 100 patients with DFUs and 150 T2DM controls were recruited. Dietary intake was assessed using a validated FFQ, and E-DII scores were calculated. Logistic regression estimated odds of DFUs across E-DII tertiles. Results: DFU patients had higher E-DII scores than controls (2.1 vs. 1.5, p < 0.001). E-DII scores were positively correlated with both ulcer duration ( ρ = 0.32, p = 0.002) and PEDIS score ( ρ = 0.45, p < 0.001). Multivariable logistic regression showed that higher E-DII scores were significantly associated with increased DFU risk (OR for highest tertile: 1.94 [1.02–3.67]). Conclusion: Our findings suggest that a pro-inflammatory diet, as measured by the E-DII, is associated with an increased odds and severity of DFUs in individuals with T2DM.