Virological surveillance,molecular phylogeny,and evolutionary dynamics of hepatitis C virus subtypes 1a and 4a isolates in patients from Saudi Arabia

Hepatitis C virus (HCV) subtypes are pre-requisite to predict endemicity, epidemiology, clinical pathogenesis, diagnosis, and treatment of chronic hepatitis C infection. HCV genotypes 4 and 1 are the most prevalent in Saudi Arabia, however; less consensus data exist on circulating HCV subtypes in infected individuals. This study was aimed to demonstrate the virological surveillance, phylogenetic analysis, and evolutionary relationship of HCV genotypes 4 and 1 subtypes in the Saudi population with the rest of the world. Fifty-five clinical specimens from different parts of the country were analyzed based on 5′ untranslated region (5′ UTR) amplification, direct sequencing, and for molecular evolutionary genetic analysis. Pair-wise comparison and multiple sequence alignment were performed to determine the nucleotide conservation, nucleotide variation, and positional mutations within the sequenced isolates. The evolutionary relationship of sequenced HCV isolates with referenced HCV strains from the rest of the world was established by computing pairwise genetic distances and generating phylogenetic trees. Twelve new sequences were submitted to GenBank, NCBI database. The results revealed that HCV subtype 4a is more prevalent preceded by 1a in the Saudi population. Molecular phylogeny predicts the descendants’ relationship of subtype 4a isolates very close to Egyptian prototype HCV strains, while 1a isolates were homogeneous and clustering to the European and North American genetic lineages. The implications of this study highlight the importance of HCV subtyping as an indispensable tool to monitor the distribution of viral strains, to determine the risk factors of infection prevalence, and to investigate clinical differences of treatment outcomes among intergenotypic and intragenotypic isolates in the treated population.     

Apoptotic Engulfment Pathway and Schizophrenia

Background

Apoptosis has been speculated to be involved in schizophrenia. In a previously study, we reported the association of the MEGF10 gene with the disease. In this study, we followed the apoptotic engulfment pathway involving the MEGF10, GULP1, ABCA1 and ABCA7 genes and tested their association with the disease.

Methodology/Principal Findings

Ten, eleven and five SNPs were genotyped in the GULP1, ABCA1 and ABCA7 genes respectively for the ISHDSF and ICCSS samples. In all 3 genes, we observed nominally significant associations. Rs2004888 at GULP1 was significant in both ISHDSF and ICCSS samples (p = 0.0083 and 0.0437 respectively). We sought replication in independent samples for this marker and found highly significant association (p = 0.0003) in 3 Caucasian replication samples. But it was not significant in the 2 Chinese replication samples. In addition, we found a significant 2-marker (rs2242436 * rs3858075) interaction between the ABCA1 and ABCA7 genes in the ISHDSF sample (p = 0.0022) and a 3-marker interaction (rs246896 * rs4522565 * rs3858075) amongst the MEGF10, GULP1 and ABCA1 genes in the ICCSS sample (p = 0.0120). Rs3858075 in the ABCA1 gene was involved in both 2- and 3-marker interactions in the two samples.

Conclusions/Significance

From these data, we concluded that the GULP1 gene and the apoptotic engulfment pathway are involved in schizophrenia in subjects of European ancestry and multiple genes in the pathway may interactively increase the risks to the disease.     

Compressive and tensile mechanical properties of the porcine nasal septum

The expanding nasal septal cartilage is believed to create a force that powers midfacial growth. In addition, the nasal septum is postulated to act as a mechanical strut that prevents the structural collapse of the face under masticatory loads. Both roles imply that the septum is subject to complex biomechanical loads during growth and mastication. The purpose of this study was to measure the mechanical properties of the nasal septum to determine (1) whether the cartilage is mechanically capable of playing an active role in midfacial growth and in maintaining facial structural integrity and (2) if regional variation in mechanical properties is present that could support any of the postulated loading regimens. Porcine septal samples were loaded along the horizontal or vertical axes in compression and tension, using different loading rates that approximate the in vivo situation. Samples were loaded in random order to predefined strain points (2–10%) and strain was held for 30 or 120 seconds while relaxation stress was measured. Subsequently, samples were loaded until failure. Stiffness, relaxation stress and ultimate stress and strain were recorded. Results showed that the septum was stiffer, stronger and displayed a greater drop in relaxation stress in compression compared to tension. Under compression, the septum displayed non-linear behavior with greater stiffness and stress relaxation under faster loading rates and higher strain levels. Under tension, stiffness was not affected by strain level. Although regional variation was present, it did not strongly support any of the suggested loading patterns. Overall, results suggest that the septum might be mechanically capable of playing an active role in midfacial growth as evidenced by increased compressive residual stress with decreased loading rates. However, the low stiffness of the septum compared to surrounding bone does not support a strut role. The relatively low stiffness combined with high stress relaxation under fast loading rates suggests that the nasal septum is a stress dampener, helping to absorb and dissipate loads generated during mastication.     

Effect of adenovirus-mediated overexpression of decorin on metalloproteinases, tissue inhibitors of metalloproteinases and cytokines secretion by human gingival fibroblasts.

Decorin is a small leucine-rich proteoglycan that plays a role in control of cell proliferation, cell migration, collagen fibrillogenesis and modulation of the activity of TGF-beta. In the present study, we investigated the effects of decorin on the production of metalloproteinases (MMP-1, -2, -3, -9 and -13), tissue inhibitors of metalloproteinases (TIMP-1, -2) and cytokines (TGF-beta, IL-1beta, IL-4 and TNF-alpha). Decorin was overexpressed in cultured human gingival fibroblasts using adenovirus-mediated gene transfer. Decorin infection resulted in decreased protein levels of MMP-1 and MMP-3 whereas MMP-2 and TIMP-2 secretion was increased. MMP-9, MMP-13 and TIMP-1 were not affected by decorin infection. Cytokine measurements by ELISA showed that decorin overexpression reduced TGF-beta and IL-1beta. In contrast, IL-4 and TNF-alpha levels were markedly increased in decorin-infected cells. These results suggest that decorin could modulate the expression of certain metalloproteinases and their inhibitors, as well as the production of cytokines. Altogether, our data suggest that decorin might play a pivotal role in tissue remodeling by acting on the balance between extracellular matrix synthesis and degradation.     

A versatile synthetic route to chiral quinoxaline derivatives from amino acids precursors

Summary The synthesis ofN-protected L-amino acid (3-benzylquinoxalin-2-yl) hydrazide derivatives is reported here. 3-Benzyl-2-hydrazinoquinoxaline was prepared and then coupled withN-Boc-L-amino acids including; Alanine, Valine, Leucine, Phenylalanine, Tyrosine, Serine and Proline in the presence of HBTU as a coupling reagent to provide the expected product with high yield and purity. The products were deprotected by p-toluenesulphonic acid in acetonitrile and then the tosylate salts were evaluated for antibacterial and antifungal activity. Abbreviations: HBTU, N-[(1H-benzotriazol-1-yl)(dimethylamino)methylene]-N-methylmethanaminium hexafluorophosphate N-oxide Boc,t-butyloxycarbonyl, DIEA, diisopropylethylamine; DMF, N,N-dimethylformamide; PTSA, p-toluenesulphonic acid, TEA, triethyl amine. Amino acids are abbreviated and designated following the rules of the IUPAC-IUB Commission of BiochemicalNomenclature (J. Biol. Chem., 247 (1972) 977).     

Nomega-nitro-L-arginine methylester ameliorates myocardial toxicity induced by doxorubicin

The effects of Nomega-nitro-L-arginine methylester (L-NAME) and L-arginine on cardiotoxicity that is induced by doxorubicin (Dox) were investigated. A single dose of Dox 15 mg/kg i.p. induced cardiotoxicity, manifested biochemically by a significant elevation of serum creatine phosphokinase (CPK) activity [EC 2.7.3.2]. Moreover, cardiotoxicity was further confirmed by a significant increase in lipid peroxides, measured as malon-di-aldehyde (MDA) in cardiac tissue homogenates. The administration of L-NAME 4 mg/kg/d p.o. in drinking water 5 days before and 3 days after the Dox injection significantly ameliorated the cardiotoxic effects of Dox, judged by the improvement in both serum CPK activity and lipid peroxides in the cardiac tissue homogenates. On the other hand, the administration of L-arginine 70 mg/kg/d p.o. did not protect the cardiac tissues against the toxicity that was induced by the Dox treatment. The findings of this study suggest that L-NAME can attenuate the cardiac dysfunction that is produced by the Dox treatment via the mechanism(s), which may involve the inhibition of the nitric oxide (NO) formation. L-NAME may, therefore, be a beneficial remedy for cardiotoxicity that is induced by Dox and can then be used to improve the therapeutic index of Dox.     

Anopheles Midgut Epithelium Evades Human Complement Activity by Capturing Factor H from the Blood Meal

Hematophagous vectors strictly require ingesting blood from their hosts to complete their life cycles. Exposure of the alimentary canal of these vectors to the host immune effectors necessitates efficient counteractive measures by hematophagous vectors. The Anopheles mosquito transmitting the malaria parasite is an example of hematophagous vectors that within seconds can ingest human blood double its weight. The innate immune defense mechanisms, like the complement system, in the human blood should thereby immediately react against foreign cells in the mosquito midgut. A prerequisite for complement activation is that the target cells lack complement regulators on their surfaces. In this work, we analyzed whether human complement is active in the mosquito midgut, and how the mosquito midgut cells protect themselves against complement attack. We found that complement remained active for a considerable time and was able to kill microbes within the mosquito midgut. However, the Anopheles mosquito midgut cells were not injured. These cells were found to protect themselves by capturing factor H, the main soluble inhibitor of the alternative complement pathway. Factor H inhibited complement on the midgut cells by promoting inactivation of C3b to iC3b and preventing the activity of the alternative pathway amplification C3 convertase enzyme. An interference of the FH regulatory activity by monoclonal antibodies, carried to the midgut via blood, resulted in increased mosquito mortality and reduced fecundity. By using a ligand blotting assay, a putative mosquito midgut FH receptor could be detected. Thereby, we have identified a novel mechanism whereby mosquitoes can tolerate human blood.     

Seroprevalence Rates of Helicobacter pylori and Viral Hepatitis A among Adolescents in Three Regions of the Kingdom of Saudi Arabia: Is There Any Correlation?

Background: The seroprevalence rate of Helicobacter pylori in the Kingdom of Saudi Arabia (KSA) was reported to be in the range of 50–80% among mostly symptomatic patients in non‐community‐based studies. However, the seroprevalence of viral hepatitis A (HAV) underwent a marked decline in the last two decades from over 50% in 1989 to 25% in 1997 among Saudi children under the age of 12 years. The aim of this paper was to study seroprevalence rates of H. pylori and HAV among the adolescent population in three regions of KSA and to determine whether there was any correlation between them. Materials and methods: We randomly selected 1200 16–18‐year‐old students from three regions around KSA. Demographic data, including socioeconomic status (SES), were recorded, and each student was tested for the presence of H. pylori‐IgG antibodies and anti‐HAV‐IgG. Results: The results indicate a high H. pylori infection rate (47%) among this age group. Boys had a higher prevalence than girls (p = .03), and the Al‐Qaseem region had the highest prevalence (51%, p = .002). SES did not contribute to the high prevalence rates (p = .83). A cross‐tabulation of data showed that 88 (8%) of the teenagers were seropositive and that 512 (44%) were negative for both H. pylori and HAV antibodies (χ² = 0.03, OR = 0.97, CI = 0.70–1.34). The agreement between H. pylori and HAV seropositivity was lower than would be predicted by chance (κ = ?0.03). The variables that were independently associated with seropositivity to H. pylori were being female (OR = 0.75, 95% CI = 0.60–0.95) and living in the Madinah region (OR = 0.72, 95% CI = 0.55–0.94). Conclusion: The prevalence of H. pylori in this group of adolescents was high. However, there was no correlation between H. pylori and HAV infection rates. Hence, factors contributing to the transmission source and route seem to be different.     

Potential impacts of COVID-19 on reproductive health: Scientific findings and social dimension

COVID-19 virus is classified as a respiratory disease that can be mainly transmitted via respiratory droplets, however, there are recently published reports suggested its ability to transmit via sexual intercourse, assisted reproductive technology (ART) treatments, pregnancy, and nursing. Although SARS‐CoV‐2 mainly attacks respiratory systems, manifestations of multiple organs have been detected. A significant concern was raised about whether COVID‐19 may affect female and male reproductive functions. These findings imposed more restrictions on social relationships between individuals even if inside the family, adding more physiologic load. In this context, there is a crucial need to identify the biological and behavioral reproductive risk factors associated with COVID­19 disease. Questions regarding the potential risks of sexual transmission during intercourse and/or application of ART, vertical transmission (throughout pregnancy, delivery, and breastfeeding), the health of pregnant and postpartum women, and fetal or postnatal health problems of neonates/children remain largely unanswered. The contribution of individuals to different social and economic activities depends on the maintenance of good quality life and health. The ongoing COVID-19 pandemic raised on the end of December 2019 has drastically affected different aspects of human wellbeing. The pandemic not only affected the health of individuals, but also negatively affected mental health and social interaction. This review illustrates: a) scientific findings related to the impact of the COVID-19 pandemic on the reproductive process, considering gender, hormonal balance, gonad functions, pregnancy, and ART, b) the sociosexual dimension of COVID-19 disease and precautions that should be taken to avoid infection via sexual transmission or vertical transmission, which may alleviate the fear associated with continuing normal social relationships and economic activities.     

The large carpenter bees of central Saudi Arabia, with notes on the biology of Xylocopa sulcatipes Maa (Hymenoptera, Apidae, Xylocopinae)

The large carpenter bees (Xylocopinae, Xylocopa Latreille) occurring in central Saudi Arabia are reviewed. Two species are recognized in the fauna, Xylocopa (Koptortosoma) aestuans (Linnaeus) and Xylocopa (Ctenoxylocopa) sulcatipes Maa. Diagnoses for and keys to the species of these prominent components of the central Saudi Arabian bee fauna are provided to aid their identification by pollination researchers active in the region. Females and males of both species are figured and biological notes provided for Xylocopa sulcatipes. Notes on the nesting biology and ecology of Xylocopa sulcatipes are appended. As in studies for this species from elsewhere, nests were found in dried stems of Calotropis procera (Aiton) (Asclepiadaceae) and Phoenix dactylifera L. (Arecaceae).