A yeast two-hybrid screen reveals a strong interaction between the Legionella chaperonin Hsp60 and the host cell small heat shock protein Hsp10

L. pneumophila is an intracellular bacterium that replicates inside a membrane-bound vacuole called Legionella-containing vacuole (LCV), where it plentifully liberates its HtpB chaperonin. From LCV, HtpB reaches the host cell cytoplasm, where it interacts with SAMDC, a cytoplasmic protein required for synthesis of host polyamines that are important for intracellular growth of L. pneumophila. Additionally, cytoplasmic expression of HtpB in S. cerevisiae induces pseudohyphal growth, and in mammalian cells recruits mitochondria to LCV, and modifies actin microfilaments organization. This led us to hypothesize here that HtpB recruits a protein(s) from eukaryotic cells that is involved in the emergence of the aforementioned phenotypes. To identify this protein, a commercially available HeLa cDNA library was screened using a yeast two-hybrid system. Approximately 5×106 yeast clones carrying HeLa cDNA library plasmid were screened. Twenty-one positive clones were identified. DNA sequence analysis revealed that all of these positive clones encoded the mammalian small heat shock protein Hsp10. Based on the fact that chaperonions are required to interact with co-chaperonins to function properly in protein folding, we believe that HtpB recruits the host cell Hsp10 to appropriately interact with SAMDC and to induce the multifunction phenotypes deemed important in L. pneumophila pathogenesis

The incidence of the novel coronavirus SARS-CoV-2 among asymptomatic patients: a systematic review

Backgroundthe recent outbreak of the coronavirus disease 2019 (COVID‐19) has quickly spread globally since its discovery in Wuhan, China, in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, and clinical treatment is urgently needed to win the battle against COVID-19. Recently, numerous studies reported the incidence of SARS-CoV-2 in asymptomatic patients. Yet, the incidence and viral transmission from the asymptomatic cases are not apparent yet. Aimthis study aims to systematically review the published literature on SARS-CoV-2 in the asymptomatic patients to estimate the incidence of COVID-19 among asymptomatic cases, as well as describe its epidemiological and clinical significance. Methodthe literature was searched through four scientific databases: PubMed, Web of Science, Scopus, and Science Direct. Resultsa total of 63 studies satisfied the inclusion criteria where the majority of the reported studies were from China. However, there was a lack of SARS-CoV-2 epidemiological studies from several countries worldwide, tracing the actual incidence of COVID-19, especially in asymptomatic patients. Studies with a large sample size (n>1000) estimated that percentage of people contracting SARS-CoV-2 and are likely to be asymptomatic ranges from 1.2-12.9%. However, the other studies with a smaller sample size reported a much higher incidence and indicated that up to 87.9% of COVID-19 infected individuals could be asymptomatic. Most of these studies indicated that asymptopatics are a potential source of infection to the community. Conclusionthis review highlighted the need for more robust and well-designed studies to better estimate COVID-19 incidence among asymptomatic patients worldwide. The early identification of the asymptomatic cases, as well as monitoring and tracing close contact, could help in mitigating the spread of COVID-19

Do preexisting antibodies against seasonal coronaviruses have a protective role against SARS-CoV-2 infections and impact on COVID-19 severity?

Because of the emergence of coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), many questions remain unresolved regarding the abundance of cross-reactivity between the SARS-CoV-2 and other human seasonal coronaviruses (sCoVs) antigens and the role of the sCoVs preexisting antibodies in protective immunity to SARS-CoV-2. Four endemic human sCoVs (NL63, 229E, OC43, and HKU1), which cause the common cold and recurrent respiratory disease, are highly prevalent worldwide. While almost everyone has been exposed to at least one of these sCoVs, immune response to each sCoV declines over time.1 These human sCoVs share striking sequence similarities with the E-envelope (96%), M-membrane (91%), and N-nucleocapsid (91%) proteins of SARS-CoV-2.2 However, they only share about 24–30% similarities with the trimeric spike S-protein (S-trimer). The S-protein is considered the major target protein/antigen for the protective humoral and cellular immunity. That is, the S-protein contains the angiotensin-converting enzyme 2 (ACE2) receptor binding domain (known as S-RBD) that is important for viral cell entry.2 Due to the apparent similarities between sCoVs, cross-reactivity between antibodies elicited by different sCoVs and cognate antibodies targeting SARS-CoV-2 antigens is expected.

The Spectrum of Mutations of Homocystinuria in the MENA Region

Homocystinuria is an inborn error of metabolism due to the deficiency in cystathionine beta-synthase (CBS) enzyme activity. It leads to the elevation of both homocysteine and methionine levels in the blood and urine. Consequently, this build-up could lead to several complications such as nearsightedness, dislocated eye lenses, a variety of psychiatric and behavioral disorders, as well as vascular system complications. The prevalence of homocystinuria is around 1/200,000 births worldwide. However, its prevalence in the Gulf region, notably Qatar, is exceptionally high and reached 1:1800. To date, more than 191 pathogenic CBS mutations have been documented. The majority of these mutations were identified in Caucasians of European ancestry, whereas only a few mutations from African-Americans or Asians were reported. Approximately 87% of all CBS mutations are missense and do not target the CBS catalytic site, but rather result in unstable misfolded proteins lacking the normal biological function, designating them for degradation. The early detection of homocystinuria along with low protein and methionine-restricted diet is the best treatment approach for all types of homocystinuria patients. Yet, less than 50% of affected individuals show a significant reduction in plasma homocysteine levels after treatment. Patients who fail to lower the elevated homocysteine levels, through high protein-restricted diet or by B6 and folic acid supplements, are at higher risk for cardiovascular diseases, neurodegenerative diseases, neural tube defects, and other severe clinical complications. This review aims to examine the mutations spectrum of the CBS gene, the disease management, as well as the current and potential treatment approaches with a greater emphasis on studies reported in the Middle East and North Africa (MENA) region

Anti-cancer properties and mechanisms of action of thymoquinone, the major active ingredient of Nigella sativa

Over the past two decades, studies have documented the wide-range anti-cancer effects of Nigella sativa, known as black seed or black cumin. Thymoquinone (TQ), its major active ingredient, has also been extensively studied and reported to possess potent anti-cancer properties. Herein, we provide a comprehensive review of the findings related to the anti-cancer activity of TQ. The review focuses on analyzing experimental studies performed using different in vitro and in vivo models to identify the anti-proliferative, pro-apoptotic, anti-oxidant, cytotoxic, anti-metastatic, and NK-dependent cytotoxic effects exerted by TQ. In addition, we pinpoint the molecular mechanisms underlying these effects and the signal transduction pathways implicated by TQ. Our analysis show that p53, NF-κB, PPARγ, STAT3, MAPK, and PI3K/AKT signaling pathways are among the most significant pathways through which TQ mediates its anti-cancer activity. Experimental findings and recent advances in the field highlight TQ as an effective therapeutic agent for the suppression of tumor development, growth and metastasis for a wide range of tumor

Novel role of BRCA1 interacting C-terminal helicase 1 (BRIP1) in breast tumour cell invasion

Breast cancer (BC) is the most common malignancy and the leading cause of death in women worldwide. Only 5%-10% of mutations in BRCA genes are associated with familial breast tumours in Eastern countries, suggesting the contribution of other genes. Using a microarray gene expression profiling study of BC, we have recently identified BRIP1 (fivefold up-regulation) as a potential gene associated with BC progression in the Omani population. Although BRIP1 regulates DNA repair and cell proliferation, the precise role of BRIP1 in BC cell invasion/metastasis has not been explored yet; this prompted us to test the hypothesis that BRIP1 promotes BC cell proliferation and invasion. Using a combination of cellular and molecular approaches, our results revealed differential overexpression of BRIP1 in different BC cell lines. Functional assays validated further the physiological relevance of BRIP1 in tumour malignancy, and siRNA-mediated BRIP1 knockdown significantly reduced BC cell motility by targeting key motility-associated genes. Moreover, down-regulation of BRIP1 expression significantly attenuated cell proliferation via cell cycle arrest. Our study is the first to show the novel function of BRIP1 in promoting BC cell invasion by regulating expression of various downstream target genes. Furthermore, these findings provide us with a unique opportunity to identify BRIP1-induced pro-invasive genes that could serve as biomarkers and/or targets to guide the design of appropriate BC targeted therapies

Recent advances in functional nanostructures as cancer photothermal therapy.

Being a non-invasive and relatively safe technique, photothermal therapy has attracted a lot of interest in the cancer treatment field. Recently, nanostructure technology has entered the forefront of cancer therapy owing to its ability to absorb near-infrared radiation as well as efficient light to heat conversion. In this study, key nanostructures for cancer therapy including gold nanoparticles, magnetite iron oxide nanoparticles, organic nanomaterials, and novel two-dimensional nanoagents such as MXenes are discussed. Furthermore, we briefly discuss the characteristics of the nanostructures of these photothermal nanomaterial agents, while focusing on how nanostructures hold potential as cancer therapies. Finally, this review offers promising insight into new cancer therapy approaches, particularly in vivo and in vitro cancer treatments

Estimating Seroprevalence of Herpes Simplex Virus Type 1 among Different Middle East and North African Male Populations Residing in Qatar

HSV-1 epidemiology in the Middle East and North Africa (MENA) remains poorly understood. Our study aimed to measure HSV-1 antibody prevalence (seroprevalence) and its age-distribution among select MENA populations residing in Qatar. Sera were collected from male blood donors attending Hamad Medical Corporation 2013-2015. A total of 2,077 sera were tested for anti-HSV-1 antibodies using HerpeSelect® 1 ELISA IgG kits (Focus Diagnostics, USA). Robust Poisson regression was conducted to estimate adjusted infection prevalence ratios. Country-specific HSV-1 seroprevalence was estimated for 10 national populations: 97.5% among Egyptians, 92.6% among Yemenis, 90.7% among Sudanese, 88.5% among Syrians, 86.5% among Jordanians, 82.3% among Qataris, 81.4% among Iranians, 81.4% among Lebanese, 80.5% among Palestinians, and 77.0% among Pakistanis. Age-specific HSV-1 seroprevalence was estimated for Egypt, the Fertile Crescent (Iraq, Jordan, Lebanon, Palestine, and Syria), and Qatar. Seroprevalence increased with age among Fertile Crescent and Qatari nationals. Seroprevalence increased from 70.0% among those aged ≤24 years up to 98.0% among those aged ≥55 years among Fertile Crescent nationals. Seroprevalence was consistently above 90% for all ages among Egyptians. HSV-1 seroprevalence is high in MENA, though with some variation across countries. The seroprevalence appears to have declined among current young age cohorts compared to its levels a few decades ago

Immunomodulation Induced by Host Pathogen Interaction

Controlling and preventing infections require deep understanding of the complex interplay that occurs between the host and pathogen following infection. In essence, immunomodulation is any process leading to an immune response that can be altered to a desired level. In mammals, the immune system has developed an extensive array of cells and immunomodulators to recognize, identify, and eliminate foreign invaders. On the other hand, pathogens have evolved multiple mechanisms to combat the host immune system as they establish infections. In this context and under certain circumstances, an infection may result in a subverted immune system, which may lead to an exacerbated illness. Recent advances in biotechnology have enhanced our knowledge of the complex interplay that occurs between the host and invading pathogens following infection, through understanding of the microbial virulence strategies as well as the host’s approaches to combat the infection

Evaluation of antibody response in symptomatic and asymptomatic covid-19 patients and diagnostic assessment of new IgM/IgG elisa kits

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This study aims to study the immune response and evaluate the performances of four new IgM and five IgG enzyme-linked immunosorbent assay (ELISA) kits for detecting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies against different antigens in symptomatic and asymptomatic coronavirus disease 2019 (COVID-19) patients. A total of 291 samples collected from symptomatic and asymptomatic RT–PCR-confirmed patients were used to evaluate the ELISA kits’ performance (EDI, AnshLabs, DiaPro, NovaLisa, and Lionex). The sensitivity was measured at three different time-intervals post symptoms onset or positive SARS-CoV-2 RT–PCR test (≤14, 14–30, >30 days). The specificity was investigated using 119 pre-pandemic serum samples. The sensitivity of all IgM kits gradually decreased with time, ranging from 48.7% (EDI)–66.4% (Lionex) at ≤14 days, 29.1% (NovaLisa)–61.8% (Lionex) at 14–30 days, and 6.0% (AnshLabs)–47.9% (Lionex) at >30 days. The sensitivity of IgG kits increased with time, peaking in the latest interval (>30 days) at 96.6% (Lionex). Specificity of IgM ranged from 88.2% (Lionex)–99.2% (EDI), while IgG ranged from 75.6% (DiaPro)–98.3% (Lionex). Among all RT–PCR-positive patients, 23 samples (7.9%) were seronegative by all IgG kits, of which only seven samples (30.4%) had detectable IgM antibodies. IgM assays have variable and low sensitivity, thus considered a poor marker for COVID-19 diagnosis. IgG assays can miss at least 8% of RT–PCR-positive cases