Protective Role of Curcumin against N-Nitrosodiethylamine (NDEA)-Induced Toxicity in Rats

The present investigation was aimed at studying the possible role of curcumin against N-nitrosodiethylamine (NDEA)-induced toxicity in albino rats. Administration of NDEA to rats at a concentration of 0.1 mg/ml in drinking water ad libitum for 21 days produced toxicity in them, which was evident from histopathological changes in the rat livers, and increased levels of blood serum enzyme markers, i.e. aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase. In addition, the levels of oxidative stress markers like lipid peroxidation (LPO), protein carbonyl (PCC), and glutathione-S-transferase (GST) activity were elevated and the total glutathione (GSH) content was reduced in the livers. The administration of curcumin to rats at concentrations of 10, 20, and 40 mg/ml in drinking water along with 0.1 mg/ml of NDEA for 21 days effectively suppressed NDEA-induced toxicity and also resulted in a dose-dependent reduction in the levels of blood serum enzyme markers (AST, ALT, ALP, and LDH). Moreover, LPO, PCC, and GST activity were reduced and the GSH level was increased upon the administration of curcumin along with NDEA. The results obtained for the comet assay in rat hepatocytes and blood lymphocytes showed a significant dose-dependent decrease in the mean tail length. The micronucleus assay performed on rat hepatocytes also showed a dose-dependent reduction in the frequency of micronucleated cells along with curcumin administration. These results suggest that curcumin has a protective role against NDEA-induced toxicity in albino rats.     

Synthesis, Raman, FT-IR, NMR spectroscopic characterization, antimicrobial activity, cytotoxicity and DNA binding of new mixed aza-oxo-thia macrocyclic compounds

Series of new mixed aza-oxo-thia macrocyclic ligands 1,9(2,6)-ditriazina-2,8,10,16-tetraaza-3,7,11,15-tetraoxo-5,13-dithia-cyclohexadecaphan-1⁴,9⁴-diphenyl (L₁); 1,10(2,6)-ditri azina-2,9,11,18-tetraaza-3,8,12,17-tetraoxo-5,6,14,15-tetrathia-cyclooctadecaphan-1⁴,10⁴-diphenyl (L₂); 1,11(2,6)-ditriazina-2,10,12,20-tetraaza-3,9,13,19-tetraoxo-6,16-dithia-cyclocosa-phan-1⁴,11⁴-diphenyl (L₃); 1,12(2,6)-ditriazina-2,11,13,22-tetraaza-3,10,14,21-tetraoxo-6,7,17,18-tetrathia-cyclodocosaphan-1⁴,12⁴-diphenyl (L₄) were synthesised. The structural features of the compounds have been studied by elemental analyses, Mass, FT-Raman, FT-IR, ¹H and ¹³C NMR spectroscopy. The antimicrobial activities of the ligands were evaluated using disk diffusion method in dimethyl sulfoxide (DMSO) as well as the minimal inhibitory concentration (MIC) dilution method, against several bacteria and yeast cultures. The obtained results from both methods were assessed in side-by-side comparison with commercial antibacterial and antifungal agents. In most cases, the compounds show strong antifungal activity in the comparison tests. Cytotoxic activities of the ligands against two different human cancer cell lines, stomach (23132/87) and lung (A549) were determined by MTT assay. DNA fragmentation assay tested cell lines were used to analyze the DNA ladder formation which is a characteristic of apoptotic cell death. The binding of the ligands with calf thymus DNA (CT-DNA) has also been investigated by absorption spectroscopy.     

Development and application of monoclonal antibodies for specific detection of human enteric adenoviruses.

Monoclonal antibodies were prepared against enteric adenovirus by fusing P3-NS1/-Ag4-1 mouse myeloma cells with lymphocytes from BALB/c mice immunized with enteric adenovirus 40 (Ad40) G2297. Of the several putative clones secreting antibodies to adenovirus, five were found to react specifically to the enteric adenovirus. The specificity of two of these monoclones which recognize a single antigen of a molecular size of 17 kilodaltons was evaluated against 78 clinical isolates. One monoclone (5D8/2C2) reacted with both Ad40 and Ad41, and the other monoclone (2H6/C11) recognized Ad40 only in an enzyme-linked immunosorbent assay (ELISA). These ELISA results correlated well with those of the specific neutralization test or DNA restriction endonuclease analysis or both. The use of this rapid ELISA with these monoclones will find applications in the diagnosis of enteric adenovirus and should facilitate the epidemiologic studies of enteric adenovirus gastroenteritis.     

Acute graft-versus-host disease and steroid treatment impair CD11c+ and CD123+ dendritic cell reconstitution after allogeneic peripheral blood stem cell transplantation.

Human dendritic cells (DC) comprise 2 subsets-plasmacytoid CD123(+) and myeloid CD11c(+) DC-that may have distinct roles in the regulation of immunity after allogeneic hematopoietic stem cell transplantation. In this study, we analyzed the kinetics of CD123(+) DC and CD11c(+) DC reconstitution in 31 patients who underwent transplantation with allogeneic granulocyte colony-stimulating factor-mobilized peripheral blood (PB) stem cells from HLA-identical sibling donors after myeloablative conditioning. Lineage marker-negative HLA-DR(+) CD11c(+) CD11c(+) DC and lineage marker-negative HLA-DR(+) CD123(+) CD123(+) DC, as well as monocytes and lymphoid subsets, were enumerated in donor grafts and in the PB of patients at various time points after transplantation. Reconstitution of both CD11c(+) DC and CD123(+) DC to normal levels occurred within 6 to 12 months and was not affected by the diagnosis, preparatory regimen, or graft composition. However, PB CD11c(+) DC and CD123(+) DC counts were significantly reduced in patients with acute GVHD grade II to IV (at 1 and 3 months) and grade I (at 1 month). Patients with chronic GVHD instead showed reduced CD123(+) DC counts only 6 months after transplantation. Moreover, treatment with steroids (>0.1 mg/kg) was significantly associated with reduced PB CD11c(+) DC and CD123(+) DC counts at all time points after transplantation. In multivariate analysis, only acute GVHD affected DC reconstitution early after transplantation. These results will prompt new studies addressing whether DC reconstitution correlates with immunity against infectious agents or with graft-versus-tumor reactions after PB stem cell allotransplantation.     

Extraintestinal Seeding of Salmonella enterica Serotype Typhi,Pakistan

We evaluated Salmonella enterica serotype Typhi strains isolated from all body sites in Pakistan during 2013–2018. Despite an increase in overall number of localized, extensively drug-resistant Salmonella Typhi in organ infections during 2018, there was no increase in the proportion of such isolates in comparison with non–extensively drug-resistant isolates.     

Community-Based Assessment of Knowledge,Attitude, Practices and Risk Factors Regarding COVID-19 Among Pakistanis Residents During a Recent Outbreak: A Cross-Sectional Survey

Exceptional precautionary measures have been adopted to stop the transmission and control of COVID-19 through the world and Pakistan is facing lockdown in this scenario. Public loyalty to precautionary measures is affected by their knowledge, attitude, risk factors and practices (KAP) towards COVID-19. The present study was conducted among the Pakistani residents to observe the knowledge, attitude, practices and risk factors towards COVID-19 outbreak in Pakistan. A questionnaire was designed, and a cross-sectional survey was conducted among participants of the study area. Participants were asked the questions regarding knowledge, attitude, practices and risk factors towards COVID-19. Data were analyzed by SPSS and t/F test and correlation was applied among the knowledge, attitude, risk factors and practices. A total of 1060 questionnaires were received. 1004 were included while 56 were excluded. The highest representation was from Punjab province (65.6%), female (63%) and age group of 21–30 years (62.1%). Most participants were single (85%), Muslim (99.4%), Urdu speaking (45.6%) and were graduates (51.5%). Most of the participants were students (52.9%) and were from economically middle-class families (40.8%). The knowledge was positively correlated with attitude and practices whereas negatively correlated with risk factors (P?<?0.05). The attitude was negatively correlated with risk factor and positively correlated with practices. The risk factors and practices were positively correlated with each other. Health education program to improve the COVID-19 knowledge, attitude, practices and risk factors should be initiated to combat current health challenge.

     

Antibodies to human sperm YLP12 peptide that is involved in egg binding inhibit human sperm capacitation/acrosome reaction

Recently, the authors reported a novel dodecamer peptide sequence, designated as YLP12 on human sperm, that is involved in binding to zona pellucida (ZP) of human oocyte [10]. This unique sequence is present on the acrosomal region of the human sperm cell and is expressed only in human testis/ sperm. The aim of the present study was to examine whether YLP12 sequence is involved in capacitation/acrosome reaction. Swim-up sperm were capacitated with anti-YLP12 Fab' antibodies or control Fab's (40 and 85 microg/mL) and then the acrosome reaction was induced with calcium ionophore. An average of 64-73% sperm underwent acrosome reaction when they were capacitated in the presence of 40-85 microg/mL of bovine serum albumin or control Fab's. A significant (p < .01 to < .001) reduction (58-75%) in the percentage of acrosome-reacted sperm was observed when the sperm were capacitated in the presence of YLP12 Fab's. These data indicate that the YLP12 peptide sequence is involved in sperm capacitation / acrosome reaction, and may find clinical applications in the diagnosis and treatment of male infertility and immunocontraception.