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

الانتشار المصلى لفيروس الهربس البسيط (الدمط 1 والنمط 2) فى أوساط المجموعات السكانية ال هندية والفلبينية المهاجرة في قطر: مسح مقطعي

Background: The epidemiology of herpes simplex virus infections is of growing interest but information on its seroprevalence in many countries is scarce. Aims: This study aimed to measure the seroprevalence of herpes simplex virus type 1 and type 2 in Filipino and Indian men living in Qatar. Methods: Blood serum specimens were collected from male blood donors aged ≥ 18 years in Qatar from 2013 to 2016. HerpeSelect® 1/2 and Euroline‐WB assays were used to measure antibodies to herpes simplex virus types 1 and 2 in 120 Filipino and 325 Indian men. Results: The seroprevalence of herpes simplex virus‐1 was 84.9% (95% confidence interval (CI): 78.4–90.0%) in Filipino men and 48.3% (95% CI: 43.6–53.0%) in Indian men. The seroprevalence of herpes simplex virus‐2 was 8.3% (95% CI: 4.6–13.7%) in Filipinos and 3.7% (95% CI: 2.2–5.9%) in Indians. The seroprevalence of herpes simplex virus types 1 and 2 increased with age, but this trend was only statistically significant in Indian men (P = 0.013 and P = 0.011 respectively). Conclusions: The seroprevalence rates of herpes simplex virus‐2 in Filipino and Indian men living in Qatar were similar to those found in the Philippines and India. However, the seroprevalence of herpes simplex virus‐1 in Indians, while similar to that found in India, was substantially lower than that of other countries in Asia and developing countries worldwide, which needs further investigation.Contexte : L'épidémiologie des infections par le virus de l'herpès suscite un intérêt croissant, mais les informationsrelatives à sa séroprévalence dans de nombreux pays sont rares.Objectifs : La présente étude visait à mesurer la séroprévalence du virus de l'herpès de types 1 et 2 parmi les hommesphilippins et indiens vivant au Qatar.Méthodes : Des échantillons de sérum sanguin ont été prélevés sur des donneurs de sang masculins âgés d'au moinsdix-huit ans au Qatar entre 2013 et 2016. Les tests HerpeSelect® 1/2 et Euroline-WB ont été utilisés pour mesurer lesanticorps dirigés contre le virus de l'herpès de types 1 et 2 chez 120 hommes philippins et 325 hommes indiens.Résultats : La séroprévalence du virus de l'herpès de type 1 était de 84,9 % (intervalle de confiance (IC) à 95 % : 78,4-90,0 %)chez les hommes philippins et de 48,3 % (IC à 95 % : 43,6-53,0 %) chez les hommes indiens. La séroprévalence du virus del'herpès de type 2 était de 8,3 % (IC à 95 % : 4,6-13,7 %) chez les hommes philippins et de 3,7 % (IC à 95 % : 2,2- 5,9 %) chezles hommes indiens. La séroprévalence du virus de l'herpès de types 1 et 2 augmentait avec l'âge, mais cette tendancen'était statistiquement importante que chez les homme indiens (p = 0,013 et p = 0,011 respectivement).Conclusions : Les taux de séroprévalence du virus de l'herpès de type 2 parmi les hommes philippins et indiens vivantau Qatar étaient similaires à ceux constatés aux Philippines et en Inde. Toutefois, le taux de séroprévalence du virus del'herpès de type 1 chez les Indiens, bien que comparable à celui relevé en Inde, était beaucoup moins élevé que celui desautres pays d'Asie et des pays en développement, ce qui mérite d'être étudié plus attentivement.الخلفية: يتزايد الاهتمام بدراسة السمات الوبائية لحالات العدوى بفيروس الهريس البسيط. غير أن المعلومات حول انتشاره مصليا في العديد من البُلدان شحيحة للغاية. الأهداف: هدفت هذه الدراسة إلى قياس الانتشار المصلي لفيروس الحربس البسيط (النمط 1 والنمط 2) بين الرجال الذين يعيشون في قطر وينتمون إلى الجنسيتين الهندية والفلبينية. طرق البحث: أخذت عينات من مصل الدم من متبرعين بالدم من الذكور يبلغون من العمر 18 عاما أو أكثر في قطر في الفترة من 2013 وحتى 2016. واستّخدمت مقايستئ Euroline–WB و ® HerpeSelect 1/2 لقياس الأجسام المضادة لفيروس المريس البسيط (النمط 1 والنمط 2) لدى 120 رجلا فليبينيا و 325 رجلا هنديا. النتائج: كانت نسبة الانتشار المصلي لفيروس الهربس البسيط (النمط -1)(84.9%; 95% CI=78.4-90%) في صفوف الرجال من الجنسية الفليبينية و (48.3%; 95% CI=43.6-53.0%) في صفوف الرجال من الجنسية الهندية. كانت نسبة الانتشار المصلي لفيروس الهريس البسيط النمط 2 (8.3%; 95% CI=4.6-13.7%) في صفوف الرجال من الجنسية الفليبينية و (3.7%; 95% CI=2.2-5.9%) في صفوف الرجال من الجنسية الهندية. وارتفع معدل الانتشار المصلي لفيروس الهربس البسيط (النمط 1 والنمط 2) مع تقدم العمرء غير أن هذا الاتجاه لم يُظهر أهمية إحصائية يُعتد بها إلا بين الرجال من الجنسية الهندية (P=0.013; P=0.011) على التوالي. الاستنتاجات: كانت معدلات الانتشار المصلي لفيروس الهربس البسيط النمط 2 في صفوف الرجال من الجنسيتين الفليبينية والهندية الذين يعيشون في قطر ممائلة لنفس المعدلات الموجودة في الفلبين والهند. ولكن بالنسبة لمعدل الانتشار المصلي لفيروس الهربس البسيط النمط 1 في صفوف الرجال من الجنسية الهندية، وبالرغم من مماثلته للمعدل الموجود في الهند. فقد كان أقل بصورة ملحوظة من بُلدان أخرى في قارة آسيا وفي بلدان نامية أخرى حول العالم، وهو الأمر الذي يتطلب مزيدا من الدراس

Negative epidemiological association between HSV-1 and HSV-2 infections

Objectives: Existing evidence on an epidemiological association between herpes simplex virus (HSV) type 1 and type 2 infections remains conflicting and inconclusive. Using a multi-national database of HSV-1/2 serological testing, we aimed to assess the existence of an association between both infections. Design, Setting, and Participants: An HSV-1/2 cross-sectional serological testing database was assembled by merging databases of seroprevalence studies on men blood donors residing currently in Qatar, but from different countries. Specimens were tested for anti-HSV-1 IgG antibodies using HerpeSelect® 1 ELISA, and for anti-HSV-2 IgG antibodies following a two-test algorithm: HerpeSelect® 2 ELISA to test the sera, and Euroline-WB to confirm positive and equivocal specimens. Logistic regressions were conducted to estimate unadjusted and adjusted infection odds ratios. Results: Serological testing for HSV-1/2 was performed on 2522 specimens. Sero-positivity for HSV-1 and HSV-2 was identified in 2053 (81.5%) and 87 (3.5%) specimens, respectively. Univariable analyses estimated higher odds of HSV-2 infection with increasing age and increasing country income level, and an unadjusted odds ratio with HSV-1 sero-positivity of 0.71 (95% CI 0.43–1.17; p-value 0.172). Adjusting for age and country income level, the adjusted odds ratio of HSV-2 infection with HSV-1 sero-positivity was 0.51 (95% CI 0.30–0.87; p-value 0.013). Sensitivity analyses confirmed this association. Conclusions: There is a negative association between HSV-1 and HSV-2 infections, suggestive of a protective effect for HSV-1 sero-positivity against HSV-2 acquisition. This finding supports earlier pooled but inconclusive evidence from prospective studies, yet contrasts with pooled findings of earlier cross-sectional studies

D-Dimer Concentrations and COVID-19 Severity: A Systematic Review and Meta-Analysis

Coronavirus disease 2019 (COVID-19) is a recently described infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since late 2019, COVID-19 has rapidly spread in virtually all countries, imposing the adoption of significant lockdown and social distancing measures. The activation of the coagulation cascade is a common feature of disseminated intravascular coagulation and adverse clinical outcomes in COVID-19 patients. In this study, we conducted a meta-analysis aiming to investigate differences in serum D-dimer concentrations in patients with and without severe COVID-19 disease. An electronic search in Medline (PubMed), Scopus and Web of Science was performed with no language restrictions, and 13 articles were reporting on 1,807 patients (585, 32.4% with severe disease) were finally identified and included in the meta-analysis. The pooled results of all studies revealed that the D-dimer concentrations were significantly higher in patients with more severe COVID-19 (SMD: 0.91 mg/L; 95% CI, 0.75 to 1.07 mg/L, p < 0.0001). The heterogeneity was moderate (I 2 = 46.5%; p = 0.033). Sensitivity analysis showed that the effect size was not modified when any single study was in turn removed (effect size range, 0.87 mg/L to 0.93 mg/L). The Begg’s (p = 0.76) and Egger’s tests (p = 0.38) showed no publication bias. In conclusion, our systematic review and meta-analysis showed that serum D-dimer concentrations in patients with severe COVID-19 are significantly higher when compared to those with non-severe forms.This research was funded by Qatar University [IRCC-2019-007] to GN and GP, Regione Autonoma della Sardegna [RASSR82005] to GP and AZ, and fondo UNISS di Ateneo per la ricerca 2019 to GP and AZ

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