Sayed Sartaj Sohrab

Complete genome sequencing and phylogenetic analysis of dengue type 1 virus isolated from Jeddah, Saudi Arabia

BackgroundDengue viruses (DENVs) are mosquito-borne viruses which can cause disease ranging from mild fever to severe dengue infection. These viruses are endemic in several tropical and subtropical regions. Multiple outbreaks of DENV serotypes 1, 2 and 3 (DENV-1, DENV-2 and DENV-3) have been reported from the western region in Saudi Arabia since 1994. Strains from at least two genotypes of DENV-1 (Asia and America/Africa genotypes) have been circulating in western Saudi Arabia until 2006. However, all previous studies reported from Saudi Arabia were based on partial sequencing data of the envelope (E) gene without any reports of full genome sequences for any DENV serotypes circulating in Saudi Arabia.FindingsHere, we report the isolation and the first complete genome sequence of a DENV-1 strain (DENV-1-Jeddah-1-2011) isolated from a patient from Jeddah, Saudi Arabia in 2011. Whole genome sequence alignment and phylogenetic analysis showed high similarity between DENV-1-Jeddah-1-2011 strain and D1/H/IMTSSA/98/606 isolate (Asian genotype) reported from Djibouti in 1998. Further analysis of the full envelope gene revealed a close relationship between DENV-1-Jeddah-1-2011 strain and isolates reported between 2004–2006 from Jeddah as well as recent isolates from Somalia, suggesting the widespread of the Asian genotype in this region.ConclusionsThese data suggest that strains belonging to the Asian genotype might have been introduced into Saudi Arabia long before 2004 most probably by African pilgrims and continued to circulate in western Saudi Arabia at least until 2011. Most importantly, these results indicate that pilgrims from dengue endemic regions can play an important role in the spread of new DENVs in Saudi Arabia and the rest of the world. Therefore, availability of complete genome sequences would serve as a reference for future epidemiological studies of DENV-1 viruses.

Detection of the Middle East Respiratory Syndrome Coronavirus Genome in an Air Sample Originating from a Camel Barn Owned by an Infected Patient

ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel betacoronavirus that has been circulating in the Arabian Peninsula since 2012 and causing severe respiratory infections in humans. While bats were suggested to be involved in human MERS-CoV infections, a direct link between bats and MERS-CoV is uncertain. On the other hand, serological and virological data suggest dromedary camels as the potential animal reservoirs of MERS-CoV. Recently, we isolated MERS-CoV from a camel and its infected owner and provided evidence for the direct transmission of MERS-CoV from the infected camel to the patient. Here, we extend this work and show that identical MERS-CoV RNA fragments were detected in an air sample collected from the same barn that sheltered the infected camel in our previous study. These data indicate that the virus was circulating in this farm concurrently with its detection in the camel and in the patient, which warrants further investigations for the possible airborne transmission of MERS-CoV. IMPORTANCE This work clearly highlights the importance of continuous surveillance and infection control measures to control the global public threat of MERS-CoV. While current MERS-CoV transmission appears to be limited, we advise minimal contact with camels, especially for immunocompromised individuals, and the use of appropriate health, safety, and infection prevention and control measures when dealing with infected patients. Also, detailed clinical histories of any MERS-CoV cases with epidemiological and laboratory investigations carried out for any animal exposure must be considered to identify any animal source. This work clearly highlights the importance of continuous surveillance and infection control measures to control the global public threat of MERS-CoV. While current MERS-CoV transmission appears to be limited, we advise minimal contact with camels, especially for immunocompromised individuals, and the use of appropriate health, safety, and infection prevention and control measures when dealing with infected patients. Also, detailed clinical histories of any MERS-CoV cases with epidemiological and laboratory investigations carried out for any animal exposure must be considered to identify any animal source.

Link Between Chronic Bacterial Inflammation and Alzheimer Disease

Alzheimers disease (AD) is a degenerative disease of brain that is associated with dementia, brain atrophy, accumulation of hyperphosphorylated tau protein and amyloid-beta peptide in hippocampus and cortex region of the brain. The development of AD is a multifactorial process that may also involve infection with bacterial pathogens. Recent studies suggest that bacteria including spirochetes have the potential to initiate cascade of events, leading to inflammatory condition of the central nervous system. Bacteria and spirochetes are activators of proinflammatory cytokines, generate free radicals, nitric oxide and further induction of apoptosis. Infection with these microbes may be considered as a risk factor for pathophysiology of AD or to cognitive changes. Recent studies have revealed that exposure to these microorganisms induces Aβ accumulation and tau protein phosphorylation, and chronic infections with these pathogenic bacteria can possibly contribute to progression of AD. In this article, we update and review the role of bacteria in the pathogenesis of AD resulting from initiation of cascade events in chronic inflammations and amyloidogenesis. Controlling these chronic infections with antibacterial or anti-inflammatory drugs will allow preventing inflammation, a risk factor for AD.

Prevalence of human papillomavirus in women from Saudi Arabia.

BACKGROUND Human papillomavirus (HPV) infection is the main causes of cervical cancer in women worldwide. The goal of the present study was to determine the prevalence and distribution of HPV genotypes in women from Saudi Arabia. Recently, several HPV detection methods have been developed, each with different sensitivities and specificities. METHODS In this study, total forty cervical samples were subjected to polymerase chain reaction and hybridization to BioFilmChip microarray assessment. RESULTS Human papillomavirus (HPV) infections were found in 43% of the specimens. The most prevalent genotypes were HPV 16 (30%) HPV 18 (8.0%) followed by type HPV 45, occurring at 5.0%. CONCLUSION Our finding showed the HPV infection and prevalence is increasing at alarming rate in women of Saudi Arabia. There was no low risk infection detected in the tested samples. The BioFilmChip microarray detection system is highly accurate and suitable for detection of single and multiple infections, allowing rapid detection with less time-consumption and easier performance as compared with other methods.

Tackling dengue fever: Current status and challenges

According to recent statistics, 96 million apparent dengue infections were estimated worldwide in 2010. This figure is by far greater than the WHO prediction which indicates the rapid spread of this disease posing a growing threat to the economy and a major challenge to clinicians and health care services across the globe particularly in the affected areas.This article aims at bringing to light the current epidemiological and clinical status of the dengue fever. The relationship between genetic mutations, single nucleotide polymorphism (SNP) and the pathophysiology of disease progression will be put into perspective. It will also highlight the recent advances in dengue vaccine development.Thus far, a significant progress has been made in unraveling the risk factors and understanding the molecular pathogenesis associated with the disease. However, further insights in molecular features of the disease and the development of animal models will enormously help improving the therapeutic interventions and potentially contribute to finding new preventive measures for population at risk.

An Association of Virus Infection with Type 2 Diabetes and Alzheimer’s Disease

Diabetes mellitus type 2 is a metabolic disorder characterized by high blood glucose due to insulin deficiency or resistance. Alzheimers disease (AD) is a complex neurodegenerative disease leading to irreversible loss of neurons, intellectual abilities, memory and reasoning. The worldwide prevalence of diabetes and AD in elderly population is a major public health concern. Interestingly, both health issues are unraveling the puzzling links. The clinico-pathological relationship between diabetes and AD has been reported at genomic and proteomic levels. The association of virus infection in type 2 diabetes mellitus and AD has been reported in few recent studies, some have shown direct evidence of virus infection in diabetes and AD while other have shown that diabetes increases the risk of developing AD. This review aims to summarize the association of few common viruses like Hepatitis C Virus and Herpes Simplex Virus-1 which affects both these two age-related devastating diseases. We also discuss the pathological links of Influenza virus, Cytomegalovirus, West Nile virus, Enterovirus, Herpes Simplex Virus-2, Hepatitis viruses in diabetes and Influenza virus, Picornavirus and Borna disease virus in AD. Establishing such relationships and defining their common pathogenesis and patho-physiological mechanisms may lead to new concepts and paths for developing novel preventive strategies and pharmacological treatment options for diabetes and AD. This study may aid in future for the identification of a single or a panel of likely blood-based viral biomarkers for early diagnosis of diabetes and AD with high sensitivity and specificity.

The role of viruses in neurodegenerative and neurobehavioral diseases.

Neurodegenerative and neurobehavioral diseases may be caused by chronic and neuropathic viral infections and may result in a loss of neurons and axons in the central nervous system that increases with age. To date, there is evidence of systemic viral infections that occur with some neurodegenerative conditions such as Alzheimers disease, Parkinsons disease, amyotrophic lateral sclerosis, multiple sclerosis, autism spectrum disorders, and HIV-associated neurocognitive disorders. With increasing lifespan, the incidence of neurodegenerative diseases increases consistently. Neurodegenerative diseases affect approximately 37 million people worldwide and are an important cause of mortality. In addition to established non-viral-induced reasons for neurodegenerative diseases, neuropathic infections and viruses associated with neurodegenerative diseases have been proposed. Neuronal degeneration can be either directly or indirectly affected by viral infection. Viruses that attack the human immune system can also affect the nervous system and interfere with classical pathways of neurodegenerative diseases. Viruses can enter the central nervous system, but the exact mechanism cannot be understood well. Various studies have supported viral- and non-viral-mediated neurodegeneration at the cellular, molecular, genomic and proteomic levels. The main focus of this review is to illustrate the association between viral infections and both neurodegenerative and neurobehavioral diseases, so that the possible mechanism and pathway of neurodegenerative diseases can be better explained. This information will strengthen new concepts and ideas for neurodegenerative and neurobehavioral disease treatment.

Development of Cotton leaf curl virus resistant transgenic cotton using antisense ßC1 gene.

Cotton leaf curl virus (CLCuV) is a serious pathogen causing leaf curl disease and affecting the cotton production in major growing areas. The transgenic cotton (Gossypium hirsutum cv. Coker 310) plants were developed by using βC1 gene in antisense orientation gene driven by Cauliflower mosaic virus-35S promoter and nos (nopaline synthase) terminator and mediated by Agrobacterium tumefaciens transformation and somatic embryogenesis system. Molecular confirmation of the transformants was carried out by polymerase chain reaction (PCR) and Southern blot hybridization. The developed transgenic and inoculated plants remained symptomless till their growth period. In conclusion, the plants were observed as resistant to CLCuV.

Transcriptomics Study of Neurodegenerative Disease: Emphasis on Synaptic Dysfunction Mechanism in Alzheimer's Disease

Alzheimers disease (AD) is a common neurodegenerative disorder primarily affecting memory and thinking ability; caused by progressive degeneration and death of nerve cells. In this study, we integrated multiple dataset retrieved from the National Center for Biotechnology Informations Gene Expression Omnibus database, and took a systems-biology approach to compare and distinguish the molecular network based synaptic dysregulation associated with AD in particular and neurodegenerative diseases in general. We first identified 832 differentially expressed genes using cut off P value <0.5 and fold change > 2, followed by gene ontology study to identify genes associated with synapse (n=95) [membrane associated guanylate kinase, 2, amyloid beta precursor protein, neurotrophic tyrosine kinase, receptor, type 2], synapse part [γ-aminobutyric acid A receptor, γ1], synaptic vesicle [glutamate receptor, ionotropic, α-amino-3-hydroxy-5- methyl-4-isoxazole propionic acid receptor 2, synaptoporin], pre- and post-synaptic density [neuronal calcium sensor 1, glutamate receptor, metabotropic 3]. We integrated these data with known pathways using Ingenuity Pathway Analysis tool and found following synapse associated pathways to be most affected; γ-aminobutyric acid receptor signaling, synaptic long term potentiation/depression, nuclear factor-erythroid 2-related factor 2-mediated oxidative stress response, huntingtons disease signaling and Reelin signaling in neurons. In conclusion, synaptic dysfunction is tightly associated with the development and progression of neurodegenerative diseases like AD.

Antimicrobial activity of crude and semi-purified fractions of Warburgia ugandensis against some pathogens

T annual incidence of urolithiasis in industrialized regions is considered to be 1,500-2,000 cases per millions with reoccurrence rate of 75% in 20 years. There is no effective management therapy for renal calculi. Allopathic and herbal therapies havetheir inherent limitations and side-effects. Bergenia ligulata has been used since ancient time in many herbal compositions and it is major component of Cystone® (Himalaya, herbal healthcare) for treating kidney stones. The present work has been designed to study the anti-lithiatic potential of B. ligulata, isolation of the potent metabolite(s) and its mechanism of action. Commercially available dried rhizomes of B. ligulata were powdered and subjected to activity guided fractionation using in vitro calcium oxalate crystal growth inhibition assay. Further, rat hyperoxaluric model was used to assess anti-lithiatic ability in vivo. The isolated fractions showed anti-calcifying activity in vitro. The sequential isolation of the potent fraction led to the purification of the most active molecule. The metabolite was eventually characterized as bergenin employing LC-MS, NMR, FTIR and UV spectroscopy. Bergenin was found to be effective in reducing oxidative stressmarkers like malondialdehyde (187% in diseased vs. 20% in treated) and elevating reduced glutathione levels (-46% in diseased vs. -15% in treated). It exhibited anti-lithiatic activityas assessed by measuring the activity of lactate dehydrogenase and alkaline phosphatase in serum samples. The creatinine clearance was also normalized with bergenin treatment in rat hyperoxaluric model. The present study provides significant evidence in the effectiveness of bergenin in treating and managing renal calculi.D mellitus is a metabolic disorder constituting a major health concern today whose prevalence has continuously increased in the world. The aim of this study is to evaluate the anti-diabetic potential of methanolic extract of Hyoscyamus albus (HAMeOH) in diabetic rats. Hyoscyamus albus (Solanaceae) is an herbal medicine traditionally applied as a parasympatholytic and nervous sedative. The oral glucose tolerance test (OGTT) was carried out by administering glucose (2 g/kg, b.w), to non-diabetic rats treated with HAMeOH at oral doses 100 and 200 mg/kg, b.w and glibenclamide 5 mg/kg. Also, Streptozotocin-induced diabetic rats, these diabetic rats were administered (100 and 200 mg/Kg b.w ) and standard drugs glibenclamide was given to rats for 30 days. The oral administration of both doses of HAMeOH significantly reduced the levels of blood glucose and glycosylated hemoglobin in diabetic rats. Determination of plasma insulin levels revealed the insulin stimulating action of the leaves extract. It is concluded that HAMeOH have significant anti-diabetic activity.Grewia nervosa (Lour) Panighrahi, belonging to the family Malvaceae s.l. is widely distributed along the Western Ghats of India. Although it has been commonly used in traditional medicine, the medicinal properties have not been scientifically evaluated. Phytochemical analysis established the presence of phenolic compounds, tannins, alkaloids and saponins in leaves. The aqueous and methanol extracts from leaves and bark of G. nervosa were investigated for medicinal properties using in vitro assays. The methanol extract of leaves demonstrated 97.5% inhibition of α-amylase activity. Additionally, the methanol extract of leaves also demonstrated antioxidant activity (5.41± 0.23 mmol/g, dw) that was higher compared to aqueous extract (3.32±0.45 mmol/g, dw). Further the methanol extract of bark exhibited anti-lipoxygenase activity indicative of its potential to control inflammatory activity. These results suggest that Grewia nervosa would be a potential source for treatment of diabetes and its associated complications such as oxidative stress and inflammationC herbs (Asteraceae) are extensively used as food additives and in folk medicine. Anti-cancer, anti-human immunodeficiency virus type 1 (HIV-1), anti-inflammatory, antinociceptive and antiproliferative activities as well as antioxidant effects have been reported for Chrysanthemum species. We report the isolation and identification of flavonoids and new and known terpenoids from the endemic species, C. macrocarpum and C. deserticolum “guertoufa”, used in Algerian Sahara as tea drinks and in “couscous” and soups “Chorba”. Structures of the isolated compounds were established by 1-D and 2-D homo and hetero-nuclear NMR (1H, 13C, COSY, HSQC, HMBC, and NOESY), mass spectrometry, UV and comparison with literature data. C. deserticolum extracts were tested by four methods to identify the antioxidant activity namely, ABTS•+, DPPH• scavenging, CUPRAC and ferrous-ions chelating activity methods. The in vitro anticholinesterase activity was achieved by the use of the basic enzymes that occur in causing Alzheimer’s disease: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Anti-inflammatory, antinociceptive, antiproliferative and antioxidant activities of C. macrocarpum extracts and isolated compounds are also reported here.T practice of traditional medicine for the control of fertility in most parts of India is based on the uses of plant medicines for many years. The aim of the present study was to evaluate the post coital antifertility activity of different varieties of Curcuma longa and underlying mechanism thereof. The effects of n-hexane, chloroform and acetone fraction of hydroalcoholic extract of three different varieties i.e. Salem, Krishna and Rajapore of Curcuma longa rhizomes were studied at three different doses to evaluate their antifertility, early abortifacient, antiovulatory activities and underlying mechanism thereof. Acute toxicity and thin layer chromatographic studies of same were also carried out. All varieties found to have significant antifertility activity (p<0.01). The n-hexane fraction of all varieties showed anti-implantation activity at the dose of 150 mg/kg weight whereas chloroform and acetone fraction of all varieties exhibited 100% reduction in pregnancy at the dose of 300 mg/kg body weight. Antifertility activity of test drugs was found through its antizygotic mechanism whereas all test drugs devoid of any antiovulatory and early abortifacient activity at all doses.M charantia (MC) fruits have previously been reported to reduce blood glucose in laboratory animals and human subjects with diabetes. Increase in insulin secretion is one of the chief mechanisms of antidiabetic action of MC extracts or their purified molecules. In present study the effect of aqueous extracts of MC (AEMC) was studied on insulin secretion in isolated pancreatic islets from normal Wistar rats with an attempt to evaluate the mechanism of action. Islets were incubated in HBBS buffer containing 3.3 or 16.7mM glucose, and AEMC, diazoxide, nimodipine and calphostin C, alone and in combinations. Release of insulin in external media was measured by ELISA. Cytotoxicity studies, to assess the integrity of the islets cells, were carried out by trypan blue uptake and LDH release assay. Trypan blue gained access to 9.6 ± 1.2% cells and 8.3 ± 1.1% dead islet cells were observed in LDH release assay on AEMC exposure, suggesting that the extract was non-toxic at tested concentration. AEMC stimulated insulin secretion from the isolated islets at 3.3 and 16.7 mM glucose. The effect of AEMC was dose dependent. As loss of cell integrity was not observed on AEMC exposure, hence, alteration of membrane integrity as the possible mechanism of insulin release is ruled out by this study. Addition of dizoxide and nimodipine completely diminished glucose induced insulin secretion. AEMC induced insulin secretion at 16.7mM glucose was partially inhibited by dizoxide and nimodipine, however no reduction was observed at 3.3mM of glucose. No change in insulin secretion at basal level of 3.3 mM of glucose suggests that the phytochemicals of AEMC may not be binding to either KATP or Ca channels. Calphostin C significantly (p<0.01) reduced AEMC induced insulin production both at 3.3 mM and 16.7 mM. The finding suggests that PKC inducing activity of AEMC phytochemical/s may be responsible for its insulin secretagogues potential.Bioassay-guided fractionation of the CH2Cl2/MeOH extract of the Thai marine sponge Acanthodendrilla sp. resulted in the isolation of six bromotyrosine-derived alkaloids; aerothionin (1), homoaerothionin (2), 2-hydroxy-3,5-dibromo,4methoxyphenylacetamide (3), 2,4-cyclohexadiene-1-acetamide-3,5-dibromo-1,6-dihydroxy-4-methoxy (4), 11-oxoaerothionin (5), and 11,19-dideoxyfistularin (6) . The structures of the isolated compounds were identified on the basis of detailed spectroscopic analysis. The compounds were tested for the acetylcholinesterase-inhibiting activity, and 3 showed the best acetylcholinesterase-inhibiting activity (92.0% at 0.1 mg/mL).T hepatoprotective activity of methanolic extract of bark of Ficus bengalensis against paracetamol and CCl4 induced liver damage was investigated. Treatment of rats with paracetamol and CCl4 produced a significant increase in the levels of serum glutamate pyruvate transaminase SGPT, serum glutamate oxaloacetate transaminase SGOT, alkaline phosphatase ALP, total and direct bilirubin. Rats pretreated with methanolic extract of barks of F. bengalensis 100 and 250 mg/kg body weight p.o. exhibited rise in the levels of these enzymes but it was significantly less as compared to those treated with paracetamol or CCl4 alone. The results of methanolic extract of F. bengalensis were comparable with the standard hepatoprotective agent silymarin 100 mg/kg. Maximum hepatoprotective effect was found to be at the dose of 250 mg/kg body weight in case of CCl4 induced hepatic damage while 500 mg/kg body weight in case of paracetamol induced hepatic damage. Obtained data suggest that methanolic extract of F. bengalensis bark possesses a potential antihepatotoxic activity.The medicinal quality of plants has been known and exploited by man for centuries. A large number of modern drugs have been isolated from traditional herbal plants[1]. Numerous secondary metabolites obtained from plants, with previously unknown pharmacological activities, have been extensively investigated as a source of medicinal agents[1,2]. The acceptance of traditional medicine as an alternative form of health care and the development of microbial resistance to the available antibiotics led to investigation on the antimicrobial activity of medicinal plants. The increasing failure of chemotherapeutics and antibiotic resistance exhibited by pathogenic agents has led to the screening of several PEER REVIEW ABSTRACTT genus of Phoebe of family Lauraceae is found the most abundance in Borneo and the Malaysian Peninsular. Phoebe tavoyana is locally known as ‘medang rungkoi.’ The woods of Phoebe species have the commercial values usually for housebuilding. As a wood of a good type soft to moderately hard, light, slightly colored than the hardwood used for carving and sculpture, paneling for doors altars wardrobes, carriages and ceiling. Phytochemical study on the leaves of Phoebe tavoyana (Meissn.) H.K.F. from Chebar Besar Reserved Forest, Kuala Kangsar, Perak, Malaysia has resulted the isolation of four known aporphines; laurolitsine (1), roemerine (2), laetanine (3), boldine (4) and one morphinandienone type, sebiferine (5). The structures of alkaloids were determined by spectroscopic analysis. This paper reports the antiplasmodial activity of three alkaloids from the leaves of Phoebe tavoyana (Lauraceae). The results showed that (1), (2) and (5) have shown potent inhibitory activity against the growth of Plasmodium falciparum 3D7 clone, with IC50 1.49, 0.89 and 2.76μg/mL respectively. No previous phytochemical investigation has been performed on this plant.Natural polysaccharides have been widely used because of their biocompatibility and biodegradabilityproperties. An attempt has been made to explore tamarind seed xyloglucan (TSX), a glucosaminoglycan polysaccharide extracted from the kernels of seeds of Tamarindus indica Linn., family Fabaceae for bimodal(immediate and controlled)drug release of multilayer tablet. Chemically TSX powder is highly branched carbohydrate polymer. High drug holding capacity of this polysaccharide was investigated for bimodal release.An in-house extracted TSX polysaccharide was characterized for swelling index, flow property, viscosity and compatibility with drug. Multilayer tablet was comprised of immediate release layer of tramadol hydrochloride (an analgesic agent), followed by tri-layer. This tri-layer consisted of upper and lower barrier layers of TSX and middle layer of drug granular matrix. Multilayer tablets were compressed based on 3 2 factorial design consideringconcentrations of matrix and barrier TSX layers as independent variables. Immediate release layer released the drug within 90 min in acidic media, revealing the retarded action showed bypolysaccharide layer attached to this layer. Granules of matrix layer were prepared by wet granulation technology.Multiplayer tablet of TSX was evaluated for hardness, thickness and drug content. Dissolution test in presence of rat caecal content was found to control the drug release rate for more than 9h. Stability studies confirmed the stable formulation. Thus, this study suggested that inexpensiveand abundantly available natural TSX can act as a potential polymer for bimodal releaseof a multilayer tablet.