Prevalence of A2 and A2B Subgroups among Blood Groups A and AB in healthy donors.

Objective: To determine the frequency of A2 and A2B subgroups among blood groups A and AB in healthy donors. Methods: It was a Cross-Sectional study, conducted at the Department of Hematology & Transfusion Medicine, UCHS, The Children's Hospital Lahore and Sundas foundation Lahore from June 2022 to December 2022 including 13,120 healthy blood donors of both genders, after taking informed consent. Venous blood samples of donors were collected in EDTA vials (3ml) and serum gel vial for routine blood grouping which was done by standard tube method. Further testing of donors positive for an antigen (blood Group-A and AB) was performed using anti-A1 lectin by standard tube method as per manufacturer's instruction. The data was analyzed using SPSS version 23. Results: Among 13120 blood donors, 12857 (97.9%) were male and 263 (2.0%) were female with mean age of 36.7 years ± 15.04 years. Majority of them (91.7%) were of Punjabi ethnicity. Donors having blood group phenotype A and AB were 3890 (29.6%). Among blood Group-A donors, A1 was found in 97.8% and A2 in 2.2% donors. While among Blood Group-AB, 96.7% donors belonged to A1B blood group and 3.2% belonged to A2B blood group. Conclusions: Blood group A2 and A2B do exist in blood donors of Punjabi ethnicity. The knowledge of presence of these blood groups' phenotypes in our population can provide a better base for transfusion staff to do troubleshooting in compatibility testing and to avoid any rare but hazardous transfusion outcome.

Anticancer Properties of Ru and Os Half-Sandwich Complexes of N,S Bidentate Schiff Base Ligands Derived from Phenylthiocarbamide.

The versatile coordinating nature of N,S bidentate ligands is of great importance in medicinal chemistry imparting stability and enhancing biological properties of the metal complexes. Phenylthiocarbamide-based N,S donor Schiff bases converted into RuII /OsII (cymene) complexes and characterized by spectroscopic techniques and elemental analysis. The hydrolytic stability of metal complexes to undergo metal-halide ligand exchange reaction was confirmed both by the DFT and NMR experimentation. The ONIOM (QM/MM) study confirmed the histone protein targeting nature of aqua/hydroxido complex 2 aH with an excellent binding energy of -103.19 kcal/mol. The antiproliferative activity against a panel of cancer cells A549, MCF-7, PC-3, and HepG2 revealed that ruthenium complexes 1 a-3 a were more cytotoxic than osmium complexes and their respective ligands 1-3 as well. Among these ruthenium cymene complex bearing sulfonamide moiety 2 a proved a strong cytotoxic agent and showed excellent correlation of cellular accumulation, lipophilicity, and drug-likeness to the anticancer activity. Moreover, the favorable physiochemical properties such as bioavailability and gastrointestinal absorption of ligand 2 also supported the development of Ru complex 2 a as an orally active anticancer metallodrug.

Effect of donor and red blood cells concentrate characteristics on recipient hemoglobin increment following red blood cells transfusion in pediatric patients.

Objectives: To determine the effects of donor and red blood cells concentrate characteristics on recipient hemoglobin increment following red blood cells transfusion in pediatric patients. Methods: This cross-sectional study was conducted at The Hematology & Transfusion Medicine Department of The UCHS & The Children's Hospital, Lahore from 23rd December 2020 to 31st July 2021 after Institutional Ethical committee approval. After taking informed consent from parents/guardians, One hundred recipients receiving RBCs unit transfusion studied along with the respective donors. The donor's details were recorded on a pre-designed proforma which included age, gender, Body Mass Index (BMI), CBC analysis (Hemoglobin [Hb] & Hematocrit) and blood group. Components' preparation, storage and modifications details were also recorded. Hb levels of recipient were determined 12 hours prior to transfusion and 12-18 hours after transfusion. The data was analyzed on SPSS version 26. Results: Among recipients, the mean age was 5.25 ±3 years and male to female ratio was 1.16:1. The mean pre-transfusion Hb level of patients was 6.48g/dl (SD: 2.15) and mean post transfusion Hb was 8.824 g/dl (SD: 2.03) with a significant raise after transfusion (p< 0.001). Majority donors (60%) were between 18 to 30 years of age and mean age was 30.7 years (SD: 9.04). The hemoglobin increment was reduced for transfusion of RBC units from donor with greater age. Post- transfusion Hb rise was more in Rh D positive donations than Rh D negative (p< 0.0001). No significance of donors' gender, BMI, Hb and hematocrit was found in relation to Hb increment. Among RBCs concentrate features, washing with normal saline found to have greater Hb increment, particularly in Thalassemia patients (p< 0.0001). Conclusion: Donors' age and Rh blood group and red blood cell concentrates' washing accounts for significant rise in recipient's post-transfusion hemoglobin. These factors may be used to predict changes in recipients' hemoglobin before transfusion.

Project-based learning course on metabolic network modelling in computational systems biology.

Project-based learning (PBL) is a dynamic student-centred teaching method that encourages students to solve real-life problems while fostering engagement and critical thinking. Here, we report on a PBL course on metabolic network modelling that has been running for several years within the Master in Integrated Systems Biology (MISB) at the University of Luxembourg. This 2-week full-time block course comprises an introduction into the core concepts and methods of constraint-based modelling (CBM), applied to toy models and large-scale networks alongside the preparation of individual student projects in week 1 and, in week 2, the presentation and execution of these projects. We describe in detail the schedule and content of the course, exemplary student projects, and reflect on outcomes and lessons learned. PBL requires the full engagement of students and teachers and gives a rewarding teaching experience. The presented course can serve as a role model and inspiration for other similar courses.

Design of a novel multiple epitope-based vaccine: An immunoinformatics approach to combat SARS-CoV-2 strains.

BACKGROUND: Since the SARS-CoV-2 outbreak in December 2019 in Wuhan, China, the virus has infected more than 153 million individuals across the world due to its human-to-human transmission. The USA is the most affected country having more than 32-million cases till date. Sudden high fever, pneumonia and organ failure have been observed in infected individuals. OBJECTIVES: In the current situation of emerging viral disease, there is no specific vaccine, or any therapeutics available for SARS-CoV-2, thus there is a dire need to design a potential vaccine to combat the virus by developing immunity in the population. The purpose of present study was to develop a potential vaccine by targeting B and T-cell epitopes using bioinformatics approaches. METHODS: B- and T-cell epitopes are predicted from novel M protein-SARS-CoV-2 for the development of a unique multiple epitope vaccine by applying bioinformatics approaches. These epitopes were analyzed and selected for their immunogenicity, antigenicity scores, and toxicity in correspondence to their ability to trigger immune response. In combination to epitopes, best multi-epitope of potential immunogenic property was constructed. The epitopes were joined using EAAAK, AAY and GPGPG linkers. RESULTS: The constructed vaccine showed good results of worldwide population coverage and promising immune response. This constructed vaccine was subjected to in-silico immune simulations by C-ImmSim. Chimeric protein construct was cloned into PET28a (+) vector for expression study in Escherichia coli using snapgene. CONCLUSION: This vaccine design proved effective in various computer-based immune response analysis as well as showed good population coverage. This study is solely dependent on developing M protein-based vaccine, and these in silico findings would be a breakthrough in the development of an effective vaccine to eradicate SARS-CoV-2 globally.

Targeting STAT-3 signaling pathway in cancer for development of novel drugs: Advancements and challenges.

Signal transducers and activators of transcription 3 (STAT-3) is a transcription factor that regulates the gene expression of several target genes. These factors are activated by the binding of cytokines and growth factors with STAT-3 specific receptors on cell membrane. Few years ago, STAT-3 was considered an acute phase response element having several cellular functions such as inflammation, cell survival, invasion, metastasis and proliferation, genetic alteration, and angiogenesis. STAT-3 is activated by several types of inflammatory cytokines, carcinogens, viruses, growth factors, and oncogenes. Thus, the STAT3 pathway is a potential target for cancer therapeutics. Abnormal STAT-3 activity in tumor development and cellular transformation can be targeted by several genomic and pharmacological methodologies. An extensive review of the literature has been conducted to emphasize the role of STAT-3 as a unique cancer drug target. This review article discusses in detail the wide range of STAT-3 inhibitors that show antitumor effects both in vitro and in vivo. Thus, targeting constitutive STAT-3 signaling is a remarkable therapeutic methodology for tumor progression. Finally, current limitations, trials and future perspectives of STAT-3 inhibitors are also critically discussed.