Molecular Docking of Daunorubicin and Etoposide Drugs against Leishmania donovani: A Theoretical Study.

BACKGROUND OBJECTIVES: The human blood parasite Leishmania donovani causes visceral leishmaniasis or grayish discoloration of the skin (black fever/kala-azar). Antitumor drugs such as daunorubicin and etoposide can help to treat such diseases. The computational approach is used to find the better interaction of drugs with the active site of the protein and help to design new drugs. METHODS: In this study, we have optimized two antitumor drugs daunorubicin and etoposide. We have also studied frontier molecular orbitals, electrostatic potential (MEP) maps and the natural bond order analysis of these anticancer drugs followed by molecular docking with the protein Leishmania donovani. RESULTS: The crystal structure of MapK from Leishmania donovani is LDBPK-331470. Our computational calculations reveal that daunorubicin and etoposide drugs can have an affinity with the protein Leishmania donovani. INTERPRETATION CONCLUSION: Our study predicted that both daunorubicin and etoposide can have a similar affinity with the protein (UvrD) Leishmania donovani.

Influence of dietary mannan-oligosaccharides supplementation on hematological characteristics, blood biochemical parameters, immune response and histological state of laying hens.

This study aimed to determine the influence of dietary mannan-oligosaccharides (MOS) on the immune system, hematological traits, blood biochemical parameters, and histological state of laying hens. At 34 wk of age, The Mandarah chicken strain's 120 laying hens and 12 cocks were divided into 4 groups, each with 30 hens and 3 cocks. The first group performed as a control group, which nourished on a basal diet. The second, third, and fourth experimental groups received 0.1, 0.2, and 0.5 g/kg of MOS and a base diet, respectively. Birds obtained MOS at numerous doses significantly (P ˂ 0.05) raised serum levels of immunoglobulin Y (IgY), immunoglobulin M (IgM), and avian influenza (AI) antibodies compared to control birds. Furthermore, adding MOS at a level of 0.1 g/kg diet significantly improved the immune response of the control group. Additionally, compared to the control group, treated birds with MOS at various dosages did not significantly enhance hematological parameters such as red blood cells (RBCs), white blood cells (WBCs), hemoglobin, and hematocrit. Compared to control birds, birds fed MOS at all levels exhibited considerably lower serum cholesterol, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) values. Also, compared to other treated birds, MOS-treated birds displayed improved histological examination of the small intestine, isthmus, and testis compared to the control group, particularly in birds fed MOS at 0.1 and 0.2 g/kg diet. It could be concluded that using MOS at 0.1 or 2 g/kg diet can successfully improve the physiological performance and overall health of laying hens.

Immune response, hematological traits, biochemical blood parameters, and histological status of laying hens influenced by dietary chitosan-oligosaccharides.

This experiment aimed to examine the effect of chitosan-oligosaccharides (COS) supplementation in laying hens' diets affected their immune response, hematological characteristics, blood biochemical parameters, and histological status. At the age of 34 wk, 200 laying hens and 20 cocks of the Mandarah chicken strain were allotted into four groups, each consisting of 50 hens and five cocks. The first group acted as a control group, fed on a basal diet. The second, third, and fourth experimental groups each received 0.1, 0.2, and 0.5 g/kg of COS in addition to a base diet. Birds received COS at various dosages had significantly (P ˂ 0.05) increased serum concentration of immunoglobulins, avian influenza, and Newcastle disease antibodies compared with the control birds. Moreover, adding COS at level 0.2 g/kg diet insignificantly enhanced immune response than the rest of the treatment groups. Also, treated birds with COS at different levels had insignificantly improved hematological parameters such as red blood cells, white blood cells, hemoglobin and hematocrit compared to the control group. Birds fed COS at all levels had significantly decreased serum cholesterol, triglycerides, Ca++ and alanine aminotransferase concentrations compared with control birds. In addition, compared to the control group, chitosan-treated birds showed enhanced histological examination of the small intestine, isthmus, and testis, notably in birds given COS at 0.1 g/kg diet compared to other treated birds. Cocks fed COS at all levels improved testicular tissues and increased the number and diameter of seminiferous tubules compared with control birds Morphological examination of the ileum showed increased villi number, height, and crypt depth. It is possible to conclude that laying hens' physiological performance and general health can be effectively improved by using chitosan at 0.1 or 2 g/kg diet levels enhanced immune response.

Epigenetic Changes Induced by High Glucose in Human Pancreatic Beta Cells.

Epigenetic changes in pancreatic beta cells caused by sustained high blood glucose levels, as seen in prediabetic conditions, may contribute to the etiology of diabetes. To delineate a direct cause and effect relationship between high glucose and epigenetic changes, we cultured human pancreatic beta cells derived from induced pluripotent stem cells and treated them with either high or low glucose, for 14 days. We then used the Arraystar 4x180K HG19 RefSeq Promoter Array to perform whole-genome DNA methylation analysis. A total of 478 gene promoters, out of a total of 23,148 present on the array (2.06%), showed substantial differences in methylation (p < 0.01). Out of these, 285 were hypomethylated, and 193 were hypermethylated in experimental vs. control. Ingenuity Pathway Analysis revealed that the main pathways and networks that were differentially methylated include those involved in many systems, including those related to development, cellular growth, and proliferation. Genes implicated in the etiology of diabetes, including networks involving glucose metabolism, insulin secretion and regulation, and cell cycle regulation, were notably altered. Influence of upstream regulators such as MRTFA, AREG, and NOTCH3 was predicted based on the altered methylation of their downstream targets. The study validated that high glucose levels can directly cause many epigenetic changes in pancreatic beta cells, suggesting that this indeed may be a mechanism involved in the etiology of diabetes.

Factors influencing the likelihood of dental service checkup: results from a survey in Saudi Arabia.

Background: The funding and delivery of healthcare including dental care in the Kingdom of Saudi Arabia (KSA, or Saudi Arabia) is undergoing a process of reform. To inform this process, it is important that policymakers are aware of the relationships between service use, specific types of use, and the factors that influence this. Currently, there is a paucity of research in this area in KSA that examines dental service use for checkups at a national level and none that examines differences in this use across regions or that examines explicitly the role of income. Aims: This study uses the most recent version of the Saudi Health Interview Survey (SHIS) to examine the relationships between the use of dental services for a checkup and socio-demographic characteristics of respondents. Particular focus is given to the differences between regions in service use and the role of socio-demographics within regions. Methods: Data were taken from SHIS 2013. Descriptive statistics (means and standard errors) were used to characterize the sample. Logistic regression analyses were used to examine the relationship between checkups in the past 12 months and a range of covariates including income and region. The analysis was repeated for sub-samples based on specific regions. No attempt was made to impute missing values. Results: A sample of 7603 respondents provided complete data for analysis. Fifty-one per cent of the respondents were male, 29% were educated at least to degree level, 25% reported that they floss at least once per day, 69% reported that they brushed their teeth at least once per day, and 11% reported that they had visited the dentist for a checkup in the preceding 12 months. Logistic regression analyses revealed income, region, and oral hygiene habits to be among the significant determinants of the likelihood of dental checkup in the preceding 12 months. In logistic regression analyses at the regional level, different relationships were evident between checkups and socio-demographic characteristics across regions. Conclusion: Region and income are significant determinants of dental service use for checkups. Differences exist between regions in the relationship between socio-demographic characteristics and the likelihood of getting checkups. Policy changes should reflect the potential differences they might have across regions for which the role of socio-demographic characteristics varies.

Impacts of Changing the Curriculum Design on the Examination Results of Anatomy and Physiology Course.

Introduction Innovating strategies have become a compulsion in all fields associated with improved outcomes. Similarly, an innovation was introduced in the curriculum design and content to be tested for the Anatomy and Physiology course at the College of Science and Health Professions (COSHP), King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), in the spring semester of 2020. Before the COVID-19 pandemic, until the spring semester of 2019, two examinations were conducted as continuous assessments (Midterm I and II), followed by a comprehensive Final examination. In the spring semester of 2020, these examinations were replaced with Block I, II, and III examinations, respectively, with modified content and weightage. The Final examination was comprehensive and included 24 Anatomy, 21 Physiology lectures, and three case-based learning (CBL) sessions, whereas Block III included only eight Anatomy, seven Physiology lectures, and 1 CBL session. Midterm I and II weighed 20% each with a comprehensive examination of 35%, while Block I, II, and III were all 25% each. This study focuses on the impact of the curriculum modifications on the results of written examinations for preprofessional students enrolled at Riyadh, Jeddah, and Al-Ahsa campuses. Methods This retrospective study included data from 2356 male and female students from Riyadh, Jeddah, and Al-Ahsa. Data included Midterm I and II grades and Final examination grades for spring semester 2019 and Block I, II, and III examination grades for spring semester 2021. The results of the spring semester 2021 examinations were compared with the spring semester 2019 examination. The spring semester of 2020 was skipped to avoid the effect of online examinations during the COVID-19 restriction period. Data were analyzed using the statistical software SPSS version 23.0 (IBM Corporation, Armonk, NY, USA). Coefficient of variation (CV) compared spring semester 2019 and spring semester 2021 examination outcomes. The findings were analyzed concerning data related to gender, student groups, and campuses. An independent t-test of proportion was used to compare the CVs for spring 2019 and 2021. Results The overall comparison showed better results in the spring semester of 2021 (p-value < 0.01). Campus-wise, the results were significantly better for Riyadh (p-value < 0.01). The gender-wise study showed better performance from male students (p-value < 0.01). Concerning campus and gender, the results of male and female students of the Riyadh campus came out to be highly significant (p-value < 0.01). Conclusions Changing from Midterms to the Block system significantly improved the Block III examination results in spring semester 2021, particularly at the Riyadh campus. Overall, the changes remained helpful to all students. Further studies are needed to investigate the long-term effect of the curriculum changes.