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Inhibition of Hepatitis C Virus Genotype 1a Non-Structural Proteins by Small Interference RNA in Human Hepatoma Cell Lines

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Pharmacology & Pharmacy 2015年第11期6卷 502-517页

作者： Imran Shahid Waleed Hassan AlMalki Shaia saleh R. Almalki Ismail muhammad AlTurkestany Hassan Ali AlGhamdi saleh Ali AlMenshawi Applied and Functional Genomics Laboratory Center of Excellence in Molecular Biology University of the Punjab Lahore Pakistan Department of Pharmacology and Toxicology College of Pharmacy Umm Al Qura University Makkah Saudi Arabia Laboratory Medicine Faculty of Applied Medical Sciences Albaha University Albaha Saudi Arabia Infection Control Pilgrims City Hospital Madina Saudi Arabia Toxicology Center Jeddah Saudi Arabia Toxiology Research Center Ministry of Interior Jeddah Saudi Arabia

Hepatitis C virus (HCV) infection and associated liver diseases are still challenging and represent a significant health care burden around the world. Although, the treatment strategies have been improved by the development of novel direct-acting antivirals, but such therapeutic options are still expensive and beyond the financial range of the most infected individuals in developing or even in resource replete countries. It demands an urgent need to search novel and improved alternate treatment strategies to treat the infection. The present study was aimed to develop an in vitro stable cell culture system, persistently expressing HCV genotype 1a non-structural genes and to characterize the inhibitory effects of synthetic siRNAs (short interference RNA) directed against the most conserved regions of nonstructural genes in an in vitro cell culture model. The continuous expression of nonstructural genes for more than 30 days post transfection was detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis in stable human hepatoma cell line (Huh-7). The gene expression studies revealed significantly reduced gene expression of HCV nonstructural genes (i.e., NS2, NS4A and NS5A) both at mRNA and protein levels when treated against genome specific synthetic siRNAs in stable cell lines (51%, 47% and 54% respectively, p < 0.05). Similarly, a vivid decrease in HCV viral titer was exhibited by synthetic siRNAs in an in vitro viral replicate cell culture model (58%, 48% and 50%, respectively, p < 0.05) determined by quantitative Real-Time PCR (qPCR). Our data indicate that siRNA mediated gene silencing may be considered a promising alternate treatment strategy against HCV in combination with other effective therapeutic regimens in future.

关键词： Hepatitis C Virus Non-Structural Proteins Stable Cell Line Anti-HCV Drugs Short Interference RNA

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In vitro inhibitory analysis of consensus siRNAs against NS3 gene of hepatitis C virus 1a genotype

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Asian Pacific Journal of Tropical Medicine 2017年第7期10卷 763-770页

作者： Imran Shahid Waleed Hassan Al Malki Mohammed Wanees Al Rabia Mohammed Hasan Mukhtar Shaia saleh R.Almalki Saad Ahmed Alkahtani Sami S.Ashgar Hani S.Faidah muhammad Hassan Hafeez Department of Pharmacology and Toxicology College of PharmacyUmm Al Qura University Department of Medical Microbiology College of MedicineKing Abdul Aziz University Department of Biochemistry Faculty of MedicineUmm Al Qura University Department of Laboratory Medicine Faculty of Applied Medical SciencesAlbaha University College of Pharmacy Najran University Department of Microbiology College of MedicineUmm Al Qura University Department of Gastroenterology and Hepatology Fatima Memorial College of Medicine and Dentistry

Objective: To explore inhibitory effects of genome-specific, chemically synthesized siRNAs(small interference RNA) against NS3 gene of hepatitis C virus(HCV) 1a genotype in stable Huh-7(human hepatoma) cells as well as against viral replication in serum-inoculated Huh-7 cells. Methods: Stable Huh-7 cells persistently expressing NS3 gene were produced under antibiotic gentamycin(G418) selection. The cell clones resistant to 1 000 μg antibiotic concentration(G418) were picked as stable cell clones. The NS3 gene expression in stable cell clone was confirmed by RT-PCR and Western blotting. siRNA cell cytotoxicity was determined by MTT cell proliferation assay. Stable cell lines were transfected with sequence specific siRNAs and their inhibitory effects were determined by RT-PCR, real-time PCR and Western blotting. The viral replication inhibition by siRNAs in serum inoculated Huh-7 cells was determined by real-time PCR. Results: RT-PCR and Western blot analysis confirmed NS3 gene and protein expression in stable cell lines on day 10, 20 and 30 post transfection. MTT cell proliferation assay revealed that at most concentrated dose tested(50 nmol/L), siRNA had no cytotoxic effects on Huh-7 cells and cell proliferation remained unaffected. As demonstrated by the siRNA time-dependent inhibitory analysis, siRNA NS3-is44 showed maximum inhibition of NS3 gene in stable Huh-7 cell clones at 24(80%, P=0.013) and 48 h(75%, P=0.002) post transfection. The impact of siRNAs on virus replication in serum inoculated Huh-7 cells also demonstrated significant decrease in viral copy number, where siRNA NS3-is44 exhibited 70%(P<0.05) viral RNA reduction as compared to NS3-is33, which showed a 64%(P<0.05) decrease in viral copy number. siRNA synergism(NS3-is33 + NS3-is44) decreased viral load by 84%(P<0.05) as compared to individual inhibition by each siRNA(i.e., 64%–70%(P<0.05) in serum-inoculated cells. Synthetic siRNAs mixture(NS5Bis88 + NS3-is33) targeting different region of HCV genom

关键词： Hepatitis C virus NS3 protein Stable Huh-7 cell culture system RNA interference NS5B HCV therapeutics

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Six Years Clinical Experience and Surgical Considerations in Management of Cardiac Myxoma in Iraqi Center for Heart Disease—Single Center Experience

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World Journal of Cardiovascular Surgery 2022年第8期12卷 173-183页

作者： Hozhan Hussein Blbas Abdulameer Mohsin Hussein muhammad Mahmud Salim Laith saleh Alkaaby Abdulsalam Y. Taha Department of Cardiac Surgery Surgical Specialty Hospital—Cardiac Center College of Medicine Hawler Medical University Erbil Iraq Department of Thoracic and Cardiovascular Surgery College of Medicine University of Baghdad Baghdad Iraq Department of Cardiac Surgery Surgical Specialty Hospital—Cardiac Center Erbil Iraq Department of Cardiac Surgery Iraqi Center for Heart Diseases Baghdad Iraq Department of Thoracic and Cardiovascular Surgery College of Medicine University of Sulaimani Sulaymaniyah Iraq

Background: Cardiac myxomas are the most frequently encountered benign cardiac tumors that if left untreated are inexorably progressive and potentially fatal. Surgery is the only way of treatment, and if not treated with the right surgical technique recurrence occurs. Objectives: In this single center study we documented the patterns of presentation, localization, surgical approaches and outcome of cardiac myxomas. Methods: This is a retrospective study of 20 patients who underwent surgical removal of atrial myxoma from January 2010 to December 2015. All patients underwent general investigations, and echocardiography was performed on all patients and surgery was done using extracorporeal circulation and mild hypothermia. Results: The ages of the patients ranged from 14 years to 71 years, with a mean of 51.45 years. Most myxomas (75%) originated from left atrium, 20% from right atrium and biatrial in 5% of cases. The male-to-female ratio was 1:2.3 (14 females and 6 males). Myxomas were more common in blood group A+ and B+. Chief complaints were dyspnea (70%) and palpitation (50%). The majority of masses were attached to the interatrial septum (65%) and four of cases (20%) arose from the lateral wall. Right atrial trans-septal incision was used in 55% of cases. No recurrence was recorded in our study. Six patients had postoperative complications, mainly in the form of arrhythmia (3 cases), bleeding (0ne case) and renal failure (one case) which resulted in the death of the patient. Conclusions: Cardiac myxoma excision account for a very small percentage of cardiac procedures. Immediate surgical treatment is indicated because of high risk of embolization and sudden death. Cardiac myxomas can be excised with a low rate of mortality and morbidity. Follow-up examination, including echocardiography, should be performed regularly.

关键词： Atrial Myxoma Cardiac Tumors Cardiac Surgery

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Properties of luminescent silicon nanocrystallines doped sol gel for laser applications

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材料科学与工程（中英文版） 2009年第12期3卷 44-51,72页

作者： Abdullah saleh AI Dwayyan muhammad Naziruddin Khan Mohamad saleh AI Salhi Abdurahman AI Dukhai Mansour AI Hoshan Attieh Ali AI Ghamdi King Abdullah Institute for Nanotechnology King Saud University Riyadh 11451 Saudi Arabia College of Science King Saud University Riyadh 11451 Saudi Arabia College of Engineering King Saud University Riyadh 11451 Saudi Arabia King Abdul Aziz City for Science and Technology （KACST） Riyadh 11451 Saudi Arabia

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The Relationship between Time Pressure and Burnout Syndrome: A Cross-Sectional Survey among Jordanian Nurses

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Health 2015年第1期7卷 14-22页

作者： muhammad W. Darawad Hani Nawafleh Mahmoud Maharmeh Ayman M. Hamdan-Mansour saleh N. Azzeghaiby Faculty of Nursing The University of Jordan Amman Jordan Faculty of Nursing Al-Hussein Bin Talal University Maan Jordan Al-Farabi College for Dentistry and Nursing Al-Farabi College Riyadh KSA

Burnout among nurses is well documented in literature. Precursors of burnout such as time pressure need further study for better understanding. In Jordan literature, studies regarding time pressure and burnout among Jordanian nurses are scarce. This study aimed to 1) evaluate the relationship between time pressure and burnout, and 2) identify participants’ characteristics that may have relationship with time pressure and burnout. A descriptive correlational design was utilized using a self-reported cross-sectional survey to collect data from 175 Jordanian nurses. Participants reported high level of time pressure (24.8 out of 126) and burnout (72.9 out of 126). Time pressure was correlated with emotional exhaustion and depersonalization (r = 0.561, 0.491, P < 0.01, respectively). Burnout was highest on the emotional exhaustion (72%) compared to 53.9% for depersonalization and 49.2% for personal achievement. Depersonalization showed the most frequent correlation with participants’ characteristics. Burnout was found to be common among Jordanian nurses, and time pressure is a precursor of this phenomenon, giving rise to the consequences on both patients’ and nurses’ health. Healthcare administrators have to modify the nursing work environment to be less stressful and more appealing to overcome the causes of nurses’ burnout.

关键词： Time Pressure Burnout Work Environment Nurses Jordan

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Exploring Criminology in Literary Texts： Robert Browning --An Example

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Journal of Literature and Art Studies 2012年第4期2卷 454-463页

作者： Afra saleh Alshiban Al-Imam muhammad Ibn Saud University Riyadh Saudi Arabia

The association between literature and criminology is undeniable, and yet, for too long, those studying crime and literature respectively have failed to see the connection between the two, or dismissed it as being irrelevant. This study explores literary pieces, which deal exclusively with murder in order to prove that the two disciplines literature and criminology, are intimately connected and essentially inseparable. Some literary pieces which deal with identifying the thought processes of murderers have been so insightful that crime experts applied them to certain high-profile cases. That so much violent crime is depicted in literature should stimulate further research into the links between criminology and literature. Robert Browning＇s “The Laboratory： Ancien Regime” （1844） is selected as a case study in order to demonstrate how criminological theories can successfully be applied to literary pieces. Browning＇s protagonist will prove to be a fictional manifestation of a female sadistic criminal as defined by psychiatrist/criminologist Paul De River in his criminology/sexology textbook for law enforcement personnel The Sexual Criminal（1949） .

关键词： cross-disciplinary approach literature criminology interchangeable correlated disciplines fictional manifestation

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Effects of cumulative COVID-19 cases on mental health:Evidence from multi-country survey

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World Journal of Psychiatry 2023年第7期13卷 461-477页

作者： Shanaya Rathod Saseendran Pallikadavath Elizabeth Graves Mohammad M Rahman Ashlea Brooks Pranay Rathod Rachna Bhargava muhammad Irfan Reham Aly Haifa Mohammad saleh Al Gahtani Zahwa Salam Steven Wai Ho Chau Theone S E Paterson Brianna Turner Viktoria Gorbunova Vitaly Klymchuk Peter Phiri Department of Research and Innovation Southern Health NHS Foundation TrustSouthampton SO303JBUnited Kingdom Portsmouth-Brawijaya Centre for Global Health University of PortsmouthPortsmouth PO12UPUnited Kingdom Salford Business School University of SalfordSalford M54WTUnited Kingdom Patient and Public Involvement Southern Health NHS Foundation TrustSouthampton SO303JBUnited Kingdom Department of Psychiatry All India Institute of Medical SciencesNew Delhi 110029India Department of Mental Health Psychiatry and Behavioral SciencesPeshawar Medical CollegeRiphah International UniversityIslamabad 46000Pakistan Department of Clinical Services Ministry of HealthCairo 4262114Egypt College of Medicine and Medical Sciences Arabian Gulf UniversityBahrain 329Bahrain Peshawar Dental College Ripah International UniversityIslamabad 46000Pakistan Department of Psychiatry The Chinese University of Hong KongHong KongChina Department of Psychology University of VictoriaVictoria BC V8P 5C2Canada Department of Social Psychology Zhytomyr State UniversityZhytomyr 10002Ukraine National Psychological Association Mental Health for Ukraine ProjectEuropean Federation of Psychologists'AssociationGFAKyiv 04071Ukraine School of Psychology Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUnited Kingdom

BACKGROUND Depression and anxiety were both ranked among the top 25 leading causes of global burden of diseases in 2019 prior to the coronavirus disease 2019(COVID-19)*** pandemic affected,and in many cases threatened,the health and lives of millions of people across the globe and within the first year,global prevalence of anxiety and depression increased by 25%with the greatest influx in places highly affected by *** To explore the psychological impact of the pandemic and resultant restrictions in different countries using an opportunistic sample and online questionnaire in different phases of the *** A repeated,cross-sectional online international survey of adults,16 years and above,was carried out in 10 countries(United Kingdom,India,Canada,Bangladesh,Ukraine,Hong Kong,Pakistan,Egypt,Bahrain,Saudi Arabia).The online questionnaire was based on published approaches to understand the psychological impact of COVID-19 and the resultant *** standardised measures were included to explore levels of depression[patient health questionnaire(PHQ-9)],anxiety[generalized anxiety disorder(GAD)assessment],impact of trauma[the impact of events scale-revised(IES-R)],loneliness(a brief loneliness scale),and social support(The Multidimensional Scale of Perceived Social support).RESULTS There were two rounds of the online survey in 10 countries with 42866 participants in Round 1 and 92260 in Round *** largest number of participants recruited from the United Kingdom(112985 overall).The majority of participants reported receiving no support from mental health services throughout the *** study found that the daily cumulative COVID-19 cases had a statistically significant effect on PHQ-9,GAD-7,and IES-R *** scores significantly increased in the second round of surveys with the ordinary least squares regression results with regression discontinuity design specification(to control lockdown effects)confirming these ***

关键词： COVID-19 Mental health Global research International Pandemic Impact

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Assessment of the Cost-returns and Profitability Patterns of Tomato Production in Yamaltu-Deba Local Government Area of Gombe State,Nigeria

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Journal of Economic Science Research 2021年第3期4卷 1-9页

作者： saleh Abdullahi JIBO Mohammed Ibrahim AHMAD muhammad El-hafeez BAKO Bulus Danladi muhammad Abbas muhammad Department of Agricultural Economics and Extension Federal University of Kashere Gombe StateNigeria

The study examined profitability of tomato production in Yamaltu-Deba Local Government Area of Gombe State.A three-stage sampling technique was used to select 96 tomato *** were collected using a structured questionnaire and were analysed using descriptive statistics,farm budget model,and t-test *** results revealed that,the mean age of tomato producers was 38.94 years,92.48%were males,71.56%were married with the majority(95.44%)had family size ranging from 1-6 persons,and had 6.55 mean years of farming experience,having an average of 0.6 ha farm size ***,the result revealed that only 8.74%that have attained tertiary *** results also revealed average variable costs constituted 88.98%and 88.84%of the average total costs of production in the dry and rainy seasons *** per hectare average net income realised were found to be₦154,444.20($398.05)and₦39,725.14($102.38)in the dry and rainy seasons ***,the returns per naira invested was₦0.67($0.00173)in dry season and₦0.18($0.00046)in rainy season(P<0.05).Moreover,the results revealed positive and desirable gross and operating ratios of<1;implying the tomato farms in the study area maintained profitability levels both in the short and long ***,inadequate capital was critical;which was attributed to lack of affordable sources of *** of storage and processing facilities were among the impediments to large scale tomato production in the study ***,improvement in the existing patterns and as well as the provision of adequate essential factors of production will help expand the present scale of ***,governments and other financial institutions should do more to provide soft loans to the farmers to improve efficiency.

关键词： Profitability Assessment Tomato Production Yamaltu-Deba Gombe

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油气藏井间监测新技术及其应用

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国外测井技术 2010年第3期25卷 64-71页

作者： Zaki A.Al-Ali muhammad H.Al-Buali saleh AIRuwaili Shouxiang Mark Ma Alherto F.Marsala David Alumbaugh Luis DePavia Cyrille Levesque Ajay Nalonnil Ping Zhang Colin Hulme Michael Wilt 沙特国家石油公司

目前，井间监测技术正朝着将地层测量从近井区域推向储层深处这一方向发展。油气藏管理人员可以利用根据测量结果获得的层析成像来监测地层深处流体的流动情况。

关键词：井间监测油气藏新技术应用地层测量近井区域监测技术地层深处

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