Adel Galal El-Shemi

Paper money and coins as potential vectors of transmissible disease.

Paper currency and coins may be a public health risk when associated with the simultaneous handling of food and could lead to the spread of nosocomial infections. Banknotes recovered from hospitals may be highly contaminated by Staphylococcus aureus. Salmonella species, Escherichia coli and S. aureus are commonly isolated from banknotes from food outlets. Laboratory simulations revealed that methicillin-resistant S. aureus can easily survive on coins, whereas E. coli, Salmonella species and viruses, including human influenza virus, Norovirus, Rhinovirus, hepatitis A virus, and Rotavirus, can be transmitted through hand contact. Large-scale, 16S rRNA, metagenomic studies and culturomics have the capacity to dramatically expand the known diversity of bacteria and viruses on money and fomites. This review summarizes the latest research on the potential of paper currency and coins to serve as sources of pathogenic agents.

Combined therapy with oncolytic adenoviruses encoding TRAIL and IL-12 genes markedly suppressed human hepatocellular carcinoma both in vitro and in an orthotopic transplanted mouse model

BackgroundGene-based virotherapy mediated by oncolytic viruses is currently experiencing a renaissance in cancer therapy. However, relatively little attention has been given to the potentiality of dual gene virotherapy strategy as a novel therapeutic approach to mediate triplex anticancer combination effects, particularly if the two suitable genes are well chosen. Both tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interleukin-12 (IL-12) have been emerged as promising pharmacological candidates in cancer therapy; however, the combined efficacy of TRAIL and IL-12 genes for treatment of human hepatocellular carcinoma (HCC) remains to be determined.MethodsHerein, we investigated the therapeutic efficacy of concurrent therapy with two armed oncolytic adenoviruses encoding human TRAIL gene (Ad-ΔB/TRAIL) and IL-12 gene (Ad-ΔB/IL-12), respectively, on preclinical models of human HCC, and also elucidated the possible underlying mechanisms. The effects of Ad-ΔB/TRAIL+Ad-ΔB/IL-12 combination therapy were assessed both in vitro on Hep3B and HuH7 human HCC cell lines and in vivo on HCC-orthotopic model established in the livers of athymic nude mice by intrahepatic implantation of human Hep3B cells.ResultsCompared to therapy with non-armed control Ad-ΔB, combined therapy with Ad-ΔB/TRAIL+Ad-ΔB/IL-12 elicited profound anti-HCC killing effects on Hep3B and HuH7 cells and on the transplanted Hep3B-orthotopic model. Efficient viral replication and TRAIL and IL-12 expression were also confirmed in HCC cells and the harvested tumor tissues treated with this combination therapy. Mechanistically, co-therapy with Ad-ΔB/TRAIL+Ad-ΔB/IL-12 exhibited an enhanced effect on apoptosis promotion, activation of caspase-3 and-8, generation of anti-tumor immune response evidenced by upregulation of interferon gamma (IFN-γ) production and infiltration of natural killer-and antigen presenting cells, and remarkable repression of intratumor vascular endothelial growth factor (VEGF) and cluster of differentiation 31 (CD31) expression and tumor microvessel density.ConclusionsOverall, our data showed a favorable therapeutic effect of Ad-ΔB/TRAIL+Ad-ΔB/IL-12 combination therapy against human HCC, and may therefore constitute a promising and effective therapeutic strategy for treating human HCC. However, further studies are warranted for its reliable clinical translation.

Thymoquinone subdues tumor growth and potentiates the chemopreventive effect of 5-fluorouracil on the early stages of colorectal carcinogenesis in rats

Colorectal cancer (CRC) is one of the most prevalent cancers and has a high mortality rate. Insensitivity and the limited therapeutic efficacy of its standard chemotherapeutic drug, 5-fluorouracil (5-FU), represents an important challenge in CRC treatment. The robust antitumor properties of thymoquinone (TQ), the main bioactive constituent of Nigella sativa, have recently been demonstrated on different cancers. We investigated whether TQ could potentiate the chemopreventive effect of 5-FU to eradicate the early stages of CRC and elucidated its underlying mechanisms. An intermediate-term (15 weeks) model of colorectal tumorigenesis was induced in male Wistar rats by azoxymethane (AOM), and the animals were randomly and equally divided into five groups: control, AOM, AOM/5-FU, AOM/TQ, and AOM/5-FU/TQ. TQ (35 mg/kg/d; 3 d/wk) was given during the seventh and 15th weeks post-AOM injection, while 5-FU was given during the ninth and tenth weeks (12 mg/kg/d for 4 days; then 6 mg/kg every other day for another four doses). At week 15, the resected colons were subjected to macroscopic, histopathological, molecular, and immunohistochemical examinations. Interestingly, 5-FU/TQ combination therapy resulted in a more significant reduction on AOM-induced colorectal tumors and large aberrant crypts foci than treatment with the individual drugs. Mechanistically, 5-FU and TQ remarkably cooperated to repress the expression of procancerous Wnt, β-catenin, NF-κB, COX-2, iNOS, VEGF, and TBRAS and upregulate the expression of anti-tumorigenesis DKK-1, CDNK-1A, TGF-β1, TGF-βRII, Smad4, and GPx. Overall, our findings present the first report describing the in vivo enhancement effect of combined TQ and 5-FU against early stages of CRC; however, further studies are required to determine the value of this combination therapy in an advanced long-term model of CRC and also to realize its clinical potential.

Serum Activins and Follistatin during the Treatment of Chronic Hepatitis C Genotypes 1 and 4 and Their Correlations with Viral Load and Liver Enzymes: A Preliminary Report

Aims. To measure the effect of pegylated interferon-α therapy on serum activin-A, activin-B, and follistatin and their correlation with viral load and liver fibrosis in chronic hepatitis C (CHC). Methods. This study was cross-sectional and sera were collected from 165 participants classified into 7 groups: 40 healthy negative control, 33 treatment naïve patients as positive control, 19 patients at week 4, 22 at week 12, and 19 at week 24 of treatment initiation and 21 responders and 11 nonresponders at the end of 48-week treatment protocol. Serum candidate proteins were measured using ELISA and liver fibrosis was assessed by AST platelet ratio index (APRI). Results. CHC significantly increased activins and decreased follistatin compared to negative control (P < 0.05). Activin-A and follistatin levels returned to the levels of negative control group at weeks 4, 12, and 24 following treatment initiation and were significantly different from positive control (P < 0.05). Both proteins were significantly different between responders and nonresponders. Activin-A correlated positively and significantly with the viral load and APRI. Conclusion. CHC modulates serum activin-A and follistatin and they appear to be influenced by pegylated interferon-α therapy. Further studies are needed to explore the role of activins in CHC.

Activins and Follistatin in Chronic Hepatitis C and Its Treatment with Pegylated-Interferon-α Based Therapy

Pegylated-interferon-α based therapy for the treatment of chronic hepatitis C (CHC) is considered suboptimal as not all patients respond to the treatment and it is associated with several side effects that could lead to dose reduction and/or termination of therapy. The currently used markers to monitor the response to treatment are based on viral kinetics and their performance in the prediction of treatment outcome is moderate and does not combine accuracy and their values have several limitations. Hence, the development of new sensitive and specific predictor markers could provide a useful tool for the clinicians and healthcare providers, especially in the new era of interferon-free therapy, for the classification of patients according to their response to the standard therapy and only subscribing the novel directly acting antiviral drugs to those who are anticipated not to respond to the conventional therapy and/or have absolute contraindications for its use. The importance of activins and follistatin in the regulation of immune system, liver biology, and pathology has recently emerged. This review appraises the up-to-date knowledge regarding the role of activins and follistatin in liver biology and immune system and their role in the pathophysiology of CHC.

Islamic Wet Cupping and Risk Factors of Cardiovascular Diseases: Effects on Blood Pressure, Metabolic Profile and Serum Electrolytes in Healthy Young Adult Men

Background: Wet cupping (Hejamah) has been used as alternative treatment for several diseases. Objectives: Materials and methods: 16 participants were treated with hejamah for 2 consecutive months. Blood pressure was measure before and 30 minutes after the treatment. Blood samples were collected from all participants before and 48 hours after hejamah and all participants were fasting for 12 hours before sample collection. Results: Fasting blood glucose was significantly decreased before the treatment in the second month only. The levels of serum triglycerides significantly decreased after the first treatment and remained low in the 2nd month. There was no significant difference between the different time points in total cholesterol except for the 48 hours of the second month compared to the samples collected before the procedure of the same month. There was a significant decrease in LDL and significant increase in HDL following hejamah therapy (P<0.05). Significant decrease in sodium and significant increase in potassium 48 hours following treatment with hejamah was observed in the 2 months (P<0.05). Conclusions: The performance of hejamah during fasting state could represent a useful complementary method for the regulation of diastolic blood pressure and prevention/treatment of risk factors associated with cardiovascular diseases. Further studies are required to explore the role of hejamah in controlling blood pressure and prevention of cardiovascular diseases.

Seroprevalence of Chlamydia trachomatis, cytomegalovirus, herpes simplex virus 1 and 2 in Saudi women with normal and abnormal early pregnancy: A case control study

2 HIV patients were included in this study, who were either on maintenance hemodialysis (n=14) or were renal transplant recipients (n=10). Out of the 24, most were males (85.5%). Their spouses (n=20) were also included in this study. All subjects were interrogated via a questionnaire. All 24 patients were HIV positive. Out of the 20 spouses, 8 were found to be HIV positive (40%). Probable mode of spread of infection was enquired from the patients, 20 patients out of 24 had multiple sexual contacts (83.3%), while blood transfusion and multiple needle pricks due to drug abuse were found in one each (8.4%). 2 patients were not sure of any cause (8.4%). Out of the 20 spouses, 18 were sexually active, out of which 8 were found to be HIV positive and all were of the opinion that they had received the infection due to sexual contact with their spouses who were HIV positive CKD patients. Out of the 18 sexually active couples 12 were using condoms, while 6 spouses who were not using condoms, were found to be HIV positive. Out of the 8 HIV positive spouses, 2 had received the infection in spite of using condoms, thus implying that barrier contraception, though extremely effective, is not a full proof method of protection from the spread of HIV infection. Furthermore 15 patients were chronic alcoholics (62.5%). Most of them thought that social workers are the best way of preventing the disease (n=40, 90.5%), followed by increasing awareness through newspapers and television (n=36, 81.8%). Out of 44 subjects 30 (68.2%) thought that teaching in the school on the subject would be helpful in preventing it, while 28 (63.6%) were of the opinion that the family physicians could prevent the spread of the infection by counseling the families of HIV infected patients. Thus this study concludes that multiple sexual contacts, chronic alcohol abuse, intravenous drug abuse and spouses of patients are at high risk of contracting HIV infection and that social workers may be extremely beneficial in increasing awareness of HIV and restricting its spread.Background: In the setting of progressive immunosuppression, as with a HIV infection, the incidence of cervical dysplasia is increased. Paradoxically, among certain ethnicities and economic levels, HIV-infected women have a lower rate of screening for cervical cancer via Papanicolaou smear (Pap smear) compared to HIV-negative women. Understanding barriers to cervical cancer screening among HIV-infected women is important to develop an intervention to increase adherence to guidelines.H entry is mediated by the interaction of the trimeric envelope glycoprotein (Env) on the virus membrane surface with host cell receptors. However, Env is the only virus-specific protein on the virion surface and is essential for cell receptor interactions and subsequent virus-cell fusion. Therefore, HIV-1 Env is an important target to directly inhibit and thus block the initial steps leading to host cell infection. Our lab has synthesized peptide triazoles, a class of novel entry inhibitors. These peptides contain a substituted triazole derivative formed from a synthetically introduced azido-proline amino acid and bind to gp120 with close to nanomolar affinity. Site-directed mutagenesis and molecular dynamics simulation have shown that peptide triazole binding overlaps the CD4 binding pocket. Peptide triazoles cause cell-independent gp120 shedding, and variants containing C-terminal cysteines cause cell-free virolysis as evidenced by internal p24 capsid release. We are investigating the mode of action by which the sulfhydryl group causes irreversible inactivation. We hypothesize that the thiol interferes with conserved disulfides clustered proximal to the CD4 binding site in gp120 through “disulfide exchange”, which could deform the Env protein spike, and subsequently the viral membrane, leading to p24 release. The process of disulfide exchange has been found to be necessary for HIV viral infection.T study offers a conceptual model which certainly contributes to the literature of discrimination toward people living with HIV (PLHIV) and can provide the theoretical basis for future experimental research as much as intervention actions in order to achieve the aim of Zero discrimination. The health care practitioners’ (HCP) attitudinal factors toward PLHIV as much as the institutional factors should be undertaken in HIV discrimination researches. While the most of researches have relatively done in the field of training and wide-awakening of HCP about HIV transmission in Iran and Asian countries, the process of forming the discriminatory intention among the HCP have not been studied yet. In order to explain the factors affecting the HCPs’ discriminatory intention toward PLHIV, not only the author developed and hypothesized a model using the theory of planned behavior’s (TPB) framework but also proposed a new method of attitude measurement aims to shed a new light on predicting HIV discrimination in the health settings. The hypothesis is including: 1. The belief in the just world (BJW) among the HCPs’ affects their perception of stigma as much as their prejudice and also both of them affect the discriminatory attitude toward PLHIV 2. The perception of stigma affects the HCPs’ socio/cultural risk perception 3. The socio/cultural risk perception affects the HCPs’ discriminatory attitude 4. The transmission risk perception affects the HCPs’ discriminatory attitude 5. The discriminatory attitude affects the HCPs’ discriminatory intention toward PLHIV 6. Fuzzy method compared with the existing conventional measurement methods can measure more precisely the HCPs’ discriminatory attitudeT study determined whether socio-demographic characteristics and social support are associated with quality of life in individuals diagnosed with HIV/AIDS in Ghana. This study was guided by concepts from the intersection domains of social capital, social network, and social support theories. A convenience sample of 300 HIV/AIDS support group members were obtained via cross-sectional design survey. Data were collected from 300 participants selected because they attend support groups meetings, are a convenient sample, and also have experience in participating in research studies. The Medical Outcome Studies (MOS) HIV Health Survey and the MOS Social Support Survey (MOS-SSS) and demographic questionnaire instruments were used to assess quality of life, social support, and demographic information respectively. Multiple regression analysis was performed to determine if socio-demographic factors and social support contribute to quality of life. There was a positive association between overall social support and overall quality of life (r=0.51). The combination of socio-demographic factors and social support related to quality of life. Implications of the findings for practice, research, and policy in Ghana were discussed.T precise molecular mechanisms on how HIV-1 co-infection accelerates HCV-mediated liver disease progression are currently unknown. Our data showed that infectious HIV-1 virus particles failed to enter into human hepatocytic cell lines, and discernible virus replication was not observed, even when the hepatocytes transfected with HIV-1 proviral DNA were co-cultured with Jurkat T cells, suggesting that liver deterioration in the co-infected patients is not due to the replication of HIV-1 in the hepatocytes. Instead, HIV-1 Nef protein can be transferred from Nef-expressing or HIV-1-infected cells to hepatocytes through conduits, not exosomes, and the transferred Nef in the target hepatocytes altered lipid droplet formation, up-regulated subgenomic replicon expression of HCV, augmented reactive oxygen species (ROS) production, and enhanced ethanol-mediated up-regulation of HCV replication. Taken together, these data indicate that HIV-1 Nef plays an integral role in expedition of liver pathogenesis in the HIV-1/HCV co-infected hosts.S the beginning of the 21st century, we are facing the convergence of several epidemics. These include tobacco smoking, tuberculosis (TB) and HIV infection. These epidemics interact by way of increasing disease susceptibility and worsening outcomes. To control these interacting epidemics, it is crucial to better understand each infection and how it influences the others. The association between tobacco smoke and TB was suggested many years ago. Evidence of the impact of tobacco smoking on TB infection has been confounded by its almost universal association with poverty, overcrowding and alcohol usage. Similar pathological mechanisms induced by malnutrition, alcohol abuse and smoking may indeed all predispose an individual to TB. Although both tobacco smoking and HIV infection may be associated through their common associations with poverty and high-risk behavior, tobacco smoking appears to be an independent and important risk factor for contracting HIV. Smoking further raises the extremely high risk of contracting TB in HIV+ individuals. Individuals with HIV/AIDS are at risk for many oral health problems, particularly those who are smokers. People living with HIV/AIDS (PLWHA) are more likely to experience chronic illnesses such as cardiovascular disease and diabetes that are linked to poor oral health status. This presentation will describe the impact of HIV, TB and tobacco use on the oral health of PLWHA; it will discuss the importance of multidisciplinary health teams in the oral care for PLWHA; and it will suggest concrete steps that clinicians can take to promote positive behavioral health changes in PLWHA.

Paricalcitol Enhances the Chemopreventive Efficacy of 5-Fluorouracil on an Intermediate-Term Model of Azoxymethane-Induced Colorectal Tumors in Rats

Colorectal cancer is a common cancer with high mortality rate. Despite being the standard anti–colorectal cancer drug, 5-fluorouracil (5-FU) exhibits only limited therapeutic benefits. Herein, we investigated whether paricalcitol, a synthetic vitamin D analogue with potential antitumor properties, would enhance the chemopreventive efficacy of 5-FU on an intermediate-term (15 weeks) model of colorectal tumors induced by azoxymethane (AOM) in rats. After AOM injection, 5-FU was administered during the 9th and 10th weeks (12 mg/kg/day for 4 days, then 6 mg/kg every other day for another 4 doses), whereas paricalcitol (2.5 μg/kg/day; 3 days/week) was given from the 7th to the 15th week. At week 15, the animals were euthanized and their resected colons were examined macroscopically and microscopically. Quantitative RT-PCR was used to measure the transcription activities of Wnt, β-catenin, DKK-1, CDNK-1A, NF-κB, and COX-2 genes, and ELISA was used to quantify the protein levels of β-catenin, COX-2, HSP90, and VEGF. IHC was additionally used to measure β-catenin, HSP90, and inducible nitric oxide synthase (iNOS). Compared with their individual therapy, combination of 5-FU and paricalcitol showed more significant reducing effect on numbers of grown tumors and large aberrant crypts foci. Mechanistically, paricalcitol and 5-FU had cooperated together to repress the expression of procancerous Wnt, β-catenin, NF-κB, COX-2, iNOS, VEGF, and HSP-90 more, and to upregulate the expression of antitumorigenesis DKK-1 and CDNK-1A, compared with their monotherapies. Our findings suggest that combined use of paricalcitol with 5-FU exhibits an augmenting chemopreventive effect against colorectal tumors, and might potentially be useful for chemoprevention in colorectal cancer patients. Cancer Prev Res; 9(6); 491–501. ©2016 AACR.

Pegylated Interferon-α Modulates Liver Concentrations of Activin-A and Its Related Proteins in Normal Wistar Rat.

Aims. To measure the expression of activin βA-subunit, activin IIA and IIB receptors, Smad4, Smad7, and follistatin in the liver and the liver and serum concentrations of mature activin-A and follistatin in normal rat following treatment with pegylated interferon-α (Peg-INF-α) and ribavirin (RBV). Materials and Methods. 40 male Wistar rats were divided equally into 4 groups: “control,” “Peg-only” receiving 4 injections of Peg-INF-α (6 µg/rat/week), “RBV-only” receiving ribavirin (4 mg/rat/day) orally, and “Peg & RBV” group receiving both drugs. The expression of candidate molecules in liver was measured by immunohistochemistry and quantitative PCR. The concentrations of mature proteins in serum and liver homogenate samples were measured using ELISA. Results. Peg-INF-α  ± RBV altered the expression of all candidate molecules in the liver at the gene and protein levels (P < 0.05) and decreased activin-A and increased follistatin in serum and liver homogenates compared with the other groups (P < 0.05). There were also significant correlations between serum and liver activin-A and follistatin. Conclusion. Peg-INF-α modulates the hepatic production of activin-A and follistatin, which can be detected in serum. Further studies are needed to explore the role of Peg-INF-α on the production of activins and follistatin by the liver and immune cells.

Combinatorial strategies based on CRAd-IL24 and CRAd-ING4 virotherapy with anti-angiogenesis treatment for ovarian cancer

BackgroundA major hurdle incurrent to the human clinical application of conditionally replicative adenovirus (CRAd)-based virotherapy agents is their limited therapeutic efficacy. In this study we evaluated whether arming our previously reported Ad5/3Δ24 CRAd vector containing a 24-base pair deletion in the E1A conserved region 2, which allows selective replication within Rb-p16-deficient tumor cells, to express therapeutic genes could improve oncolytic virus potency in ovarian cancer cells. We choose to assess the therapeutic benefits achieved by virus-mediated expression of interleukin 24 (IL-24), a cytokine-like protein of the IL-10 family, and the inhibitor of growth 4 (ING4) tumor suppressor protein.ResultsThe generated CRAd-IL24 and CRAd-ING4 vectors were tested in ovarian cancer cell lines in vitro to compare their replication, yield, and cytotoxic effects with control CRAd Ad5/3∆24 lacking the therapeutic gene. These studies showed that CRAd-IL24 infection resulted in significantly increased yield of infectious particles, which translated to a marked enhancement of virus-induced cytotoxic effects as compared to CRAd-ING4 and non-armed CRAd. Testing CRAd-IL24 and CRAd-ING4 vectors combined together did not revealed synergistic effects exceeding oncolytic potency of single CRAD-IL24 vector. Both CRAds were also tested along with anti-VEGF monoclonal antibody Avastin and showed no significant augmentation of viral cytolysis by anti-angiogenesis treatment in vitro.ConclusionsOur studies validated that arming with these key immunomodulatory genes was not deleterious to virus-mediated oncolysis. These findings thus, warrant further preclinical studies of CRAd-IL24 tumoricidal efficacy in murine ovarian cancer models to establish its potential utility for the virotherapy of primary and advanced neoplastic diseases.