Investigation of therapeutic potential of the Il24-p20 fusion protein against breast cancer: an in-silico approach.

Targeted delivery of therapeutic anticancer chimeric molecules enhances drug efficacy. Numerous studies have focused on developing novel treatments by employing cytokines, particularly interleukins, to inhibit the growth of cancer cells. In the present study, we fused interleukin 24 with the tumor-targeting peptide P20 through a rigid linker to selectively target cancer cells. The secondary structure, tertiary structure, and physicochemical characteristics of the constructed chimeric IL-24-P20 protein were predicted by using bioinformatics tools. In-silico analysis revealed that the fusion construct has a basic nature with 175 amino acids and a molecular weight of 20 kDa. By using the Rampage and ERRAT2 servers, the validity and quality of the fusion protein were evaluated. The results indicated that 93% of the chimeric proteins contained 90.1% of the residues in the favoured region, resulting in a reliable structure. Finally, docking and simulation studies were conducted via ClusPro and Desmond Schrödinger, respectively. Our results indicate that the constructed fusion protein exhibits excellent quality, interaction capabilities, validity, and stability. These findings suggest that the fusion protein is a promising candidate for targeted cancer therapy.

Uncovering the growing burden of enteric fever: A molecular analysis of Salmonella Typhi antimicrobial resistance.

Enteric fever, a persistent public health challenge in developing regions, is exacerbated by suboptimal socioeconomic conditions, contaminated water and food sources, and insufficient sanitation. This study delves into the antimicrobial susceptibility of Salmonella Typhi, uncovering the genetic underpinnings of its resistance. Analyzing 897 suspected cases, we identified a significant prevalence of typhoid fever, predominantly in males (58.3 %) and younger demographics. Alarmingly, our data reveals an escalation in resistance to both primary and secondary antibiotics, with cases of multi-drug resistant (MDR) and extensively drug-resistant (XDR) S. Typhi reaching 14.7 % and 43.4 %, respectively, in 2021. The Multiple Antibiotic Resistance (MAR) index exceeded 0.2 in over half of the isolates, signaling widespread antibiotic misuse. The study discerned 47 unique antibiotic resistance patterns and pinpointed carbapenem and macrolide antibiotics as the remaining effective treatments against XDR strains, underlining the critical need to preserve these drugs for severe cases. Molecular examinations identified blaTEM, blaSHV, and blaCTX-M genes in ceftriaxone-resistant strains, while qnrS was specific to ciprofloxacin-resistant variants. Notably, all examined strains exhibited a singular mutation in the gyrA gene, maintaining wild-type gyrB and parC genes. The erm(B) gene emerged as the primary determinant of azithromycin resistance. Furthermore, a distressing increase in resistance genes was observed over three years, with erm(B), blaTEM and qnrS showing significant upward trends. These findings are a clarion call for robust antimicrobial stewardship programs to curtail inappropriate antibiotic use and forestall the burgeoning threat of antibiotic resistance in S. Typhi.

Dyslipidemia and impaired liver function biomarkers in patients with hepatitis B liver cirrhosis.

Objective: This study was conducted to determine changes in lipid metabolism and liver enzyme status among HBV-positive patients with liver cirrhosis. Methods: A total of 300 HBV-positive patients with liver cirrhosis and 200 healthy controls were included in this case-control study. The patients were recruited from several tertiary care hospitals in Lahore from March to October 2021. Their blood samples were collected and analyzed for HBsAg, HBeAg, liver function biomarkers, and serum lipids. Liver cirrhosis was confirmed by ultrasonography and liver biopsy. The data were analyzed with chi-square test, Student's t-test, logistic regression, and ROC curve analysis. Results: Serum liver function biomarkers were significantly higher, and serum lipid levels were substantially lower, in HBV-infected patients with liver cirrhosis than in controls. No significant associations of sex and age with dyslipidemia were observed in patients with cirrhosis. Grading and staging scores for liver cirrhosis were negatively associated with total cholesterol levels. Moreover, sex and high levels of liver enzymes were significant risk factors associated with dyslipidemia in HBV-positive patients with liver cirrhosis. The optimum cut-off values of liver enzymes and serum lipids for the prognosis of liver cirrhosis exceeded normal ranges. Conclusion: Serum lipid concentrations may serve as a clinical index to assess liver damage in HBV-positive patients.