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1.
Viral Immunol ; 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39356231

RESUMEN

The COVID-19 pandemic has affected the global health system and economies largely. Therefore, knowledge about the clinical and laboratory profiles of patients with COVID-19 would help in the management and prognosis of the disease. The immunological and hematological indices have emerged as critical determinants for the severity of the disease and the prognosis; however, association with COVID-19 is clouded. The present study is aimed to characterize the immunological and hematological profiles of patients with COVID-19 in correlation with the disease severity. The study included 1,019 polymerase chain reaction (PCR)-confirmed patients with COVID-19 who were classified into serious and nonserious groups, considering severity criteria. Clinical laboratory investigations included hematological, biochemical, and immunological parameters regarding leukocyte counts, hemoglobin levels, and inflammatory markers. Our analysis of immunological and hematological differences between serious and nonserious patients with COVID-19 indicates that serious cases reflected elevated levels of pro-inflammatory markers such as lactate dehydrogenase, C-reactive protein (CRP), D-dimer, and ferritin, representing immune system dysregulation and systemic inflammation. Furthermore, in serious cases, discrepancies had also been noticed for many hematological parameters than nonserious ones, which also contained leukocyte count and hemoglobin level. Additionally, the CRP, D-dimer, blood urea nitrogen, alanine transaminase, and albumin levels could be independent predictors of COVID-19 severity by multivariate logistic regression analysis. Cutoff values for these biomarkers were defined by receiver operating characteristic curve analysis defining optimal parameters for the risk stratification and prognostication. The current investigation provides a comprehensive understanding of immunological and hematological correlation with COVID-19 severity, refining clinical decision-making and therapeutic interventions to improve patient outcomes.

2.
In Silico Pharmacol ; 12(2): 84, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39301086

RESUMEN

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.

3.
Microb Pathog ; 191: 106676, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38710290

RESUMEN

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.


Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana , Salmonella typhi , Fiebre Tifoidea , Fiebre Tifoidea/microbiología , Fiebre Tifoidea/epidemiología , Salmonella typhi/efectos de los fármacos , Salmonella typhi/genética , Humanos , Antibacterianos/farmacología , Masculino , Femenino , Farmacorresistencia Bacteriana Múltiple/genética , Adulto , Preescolar , Adolescente , Niño , Adulto Joven , Persona de Mediana Edad , Lactante , Prevalencia , Anciano , Farmacorresistencia Bacteriana/genética , Mutación , Proteínas Bacterianas/genética
4.
J Taibah Univ Med Sci ; 18(4): 748-754, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36852240

RESUMEN

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.

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