ABSTRACT
Hepatic fibrosis is a progressive disease with serious clinical complications that arise from abnormal propagation and activation of multiple inflammatory pathways. Nilotinib is an oral tyrosine kinase inhibitor with antifibrotic activity. Mesenchymal stem cells (MSCs) are blank cells and can differentiate into specific cell types. They have the potential to repair and regenerate cells. MSCs have a special paracrine fashion where they produce special exosomes, microvesicles, and cytokines like IL-6, transforming growth factor-beta (TGF-ß), and HGF as well as hepatic stellate cell suppressors. This paracrine fashion can decrease collagen deposition, enhance antifibrotic, anti-inflammatory, and angiogenic activity in vitro and in vivo. In our study, the rat's hepatic stellate cells (HSCs) in addition to different normal cell lines were treated with Nilotinib alone and in combination with liver mesenchymal stem cells conditioned medium (LMSCs-CM) for 24 h. Mono and combined therapy antifibrotic and cytotoxicity effects were evaluated using different parameters including α-SMA, cytochrome c, P53 expression, collagen deposition, DNA content, oxidative stress parameters, cell viability, and apoptosis by flow cytometry analysis. Our results showed that Nilotinib and LMSCs-CM in combination had a significantly potent antifibrotic and anti-inflammatory effect on activated hepatic stellate cells than Nilotinib alone; otherwise, this combination showed the best safety with minimal cytotoxicity on different normal cell lines.
Subject(s)
Culture Media, Conditioned/pharmacology , Hepatic Stellate Cells/pathology , Liver Cirrhosis/drug therapy , Mesenchymal Stem Cells/chemistry , Pyrimidines/therapeutic use , Animals , Apoptosis/drug effects , Cell Survival/drug effects , Cells, Cultured , Collagen/metabolism , Combined Modality Therapy , Cytochromes c/metabolism , DNA/metabolism , Hepatic Stellate Cells/drug effects , Hepatic Stellate Cells/metabolism , Inhibitory Concentration 50 , Liver Cirrhosis/pathology , Male , Models, Biological , Oxidative Stress/drug effects , Pyrimidines/pharmacology , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Tumor Suppressor Protein p53/metabolismABSTRACT
Coronaviruses are positive-sense single-strand RNA viruses that infect amphibians, birds, and mammals. Coronavirus Disease 2019 (COVID-19) has become a major health problem caused by one of the coronaviruses called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has spread fast throughout the globe since its first identification in Wuhan, China, in December 2019. Although COVID-19 is principally defined by its respiratory symptoms, it is now clear that the virus can also affect the digestive system causing gastrointestinal (GI) symptoms like diarrhea, loss of appetite, nausea/vomiting, and abdominal pain as a major complaint. GI symptoms could be the initial signs of preceding respiratory signs, carrying a potential for slowed investigation and raised disease transmission opportunities. Various studies recognized the COVID-19 RNA in stool specimens of infected patients, and its viral receptor angiotensin-converting enzyme-2 (ACE-2) is highly expressed in GI epithelial cells. Many cases were reported negative using nasopharyngeal/oropharyngeal swabs and finally, SARS-CoV-2 RNA was detected in their anal/rectal swabs and stool specimens. These suggest that COVID-19 can actively infect and replicate in the GI tract. In this review, we elaborate on the close relationship between SARS-CoV-2 and the digestive system, focusing on the current status in the field of COVID-19 in gastroenterology, liver injury, endoscopy, inflammatory bowel disease, imaging, and the potential underlying mechanisms with illustrating the current epidemiological status regarding this pandemic.
ABSTRACT
Type 2 diabetes mellitus (T2DM) is mainly characterized by insulin resistance and impaired insulin secretion, which cannot be reversed with existing therapeutic strategies. Using mesenchymal stem cells (MSCs), cell-based therapy has been demonstrated in displaying therapeutic effects in T2DM for their self-renewable, differentiation potential, and immunosuppressive properties and higher levels of angiogenic factors. Stem cell therapies are complicated and have a serious adverse effect including tumor formation and immunogenicity, while using mesenchymal stem cell-conditioned media (MSC-CM) significantly reduces stem cell risk, maintaining efficacy and showing significantly higher levels of growth factors, cytokines, and angiogenic factors that stimulate angiogenesis and promote fracture healing in diabetes. In the present study, we investigated the therapeutic potential of the liver and adipose MSC-CM in diabetic endothelial dysfunction compared with standard insulin therapy. Fifty adult male Sprague Dawley rats were divided equally into 5 groups as follows: control, diabetic, diabetic+insulin, diabetic+liver MSC-CM, and diabetic+adipose MSC-CM; all treatments continued for 4 weeks. Finally, we observed that liver MSC-CM therapy had the most apparent improvement in levels of blood glucose; HbA1c; AGEs; lipid panel (cholesterol, TG, LDL, HDL, and total lipids); renal function (urea, uric acid, creatinine, and total protein); liver function (AST, ALT, ALP, bilirubin, and albumin); CPK; C-peptide; HO-1; inflammatory markers including IL-6, TNF-α, and CRP; growth factors (liver and serum IGF-1); amylase; histopathological changes; pancreatic cell oxidative stress; and antioxidant markers (MDA, GSH, ROS, CAT, SOD, HO-1, and XO) toward the normal levels compared with insulin and adipose MSCs-CM. Moreover, both the liver and adipose MSC-CM relieved the hyperglycemic status by improving pancreatic islet ß cell regeneration, promoting the conversion of alpha cells to beta cells, reducing insulin resistance, and protecting pancreatic tissues against oxidative stress-induced injury as well as possessing the ability to modulate immunity and angiogenesis. These results indicated that MSC-CM infusion has therapeutic effects in T2DM rats and may be a promising novel therapeutic target.
Subject(s)
Adipose Tissue/cytology , Antioxidants/pharmacology , Culture Media, Conditioned/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Liver/cytology , Mesenchymal Stem Cells/metabolism , Animals , Biomarkers/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/pathology , Inflammation/complications , Inflammation/pathology , Intercellular Signaling Peptides and Proteins/metabolism , Kidney/drug effects , Kidney/physiopathology , Lipids/blood , Liver/physiopathology , Male , Mesenchymal Stem Cells/drug effects , Myocardium/enzymology , Myocardium/pathology , Oxidative Stress/drug effects , Pancreas/pathology , Rats, Sprague-DawleyABSTRACT
Lake Burullus is one of the most important coastal lakes in Egypt, as it participates with a considerable amount of fish yield in Egypt. Despite its importance, it is considered as a vulnerable lake, since it is subjected to significant environmental changes caused by various anthropogenic activities. Severe deterioration of its water quality status, as well as a decrease in its water area, has been noticed throughout the last four decades. The main objective of this study is to evaluate the ability of remote sensing for assessing the water quality status of the lake for the period from August 2010 to August 2013. Remote sensing technique was used to retrieve and predict the lake water quality parameter records through the assessment period (August 2010 to August 2013). Stepwise multi-linear regression technique was used to correlate between the field measurements of water quality parameters and the reflectance of remote sensing imageries, and then the derived models were validated. The results revealed the critical status of water quality conditions of the lake, particularly of its southern and southeastern parts. The results showed also that some water quality parameters (Chl-a, TSS, pH, Fe, Zn, Cr, and NH4) can be retrieved from remote sensing imageries with reasonable accuracy (R2 = 0.86, 0.67, 0.65, 0.63, 0.62, 0.61, and 0.6, respectively), while the water quality parameters, which can be predicted, based on calibrated and validated regression models are TSS and Chl-a, with acceptable accuracy (R2 = 0.6 and 0.43, respectively). Lake Burullus needs urgent plans and strategies to protect its water quality from the potential hazards of human activities. The study proved the ability of remote sensing as an effective technique to monitor the changes in water quality conditions of shallow coastal lagoons and to predict with some water quality parameters without field measurements; therefore, it is highly recommended to be used by decision makers.
Subject(s)
Lakes , Water Quality , Egypt , Environmental Monitoring , Humans , Satellite Imagery , WaterABSTRACT
This research was initiated to assess and manage water quality status of fourteen surface drinking water intakes in El-Beheira Governorate, Egypt. The study was conducted on four main branches of water resources in the governorate. Three water quality indices (WQIs) and two multivariate statistical techniques were applied, based on the Egyptian guidelines for the Nile River. Water quality records were collected for two successive years, 2014 and 2015, and were analyzed by descriptive statistics. The results revealed the critical water quality status of the four branches at the fourteen intakes. The multivariate statistical techniques returned the critical water quality conditions to the agricultural drainage and the domestic wastewater discharges. In addition, a new software application was developed to manage WQIs calculation. An urgent water quality monitoring and assessment system should be initiated for the drinking water resources all over Egypt, based on the developed water quality assessment techniques of this study. PRACTITIONER POINTS: Three different WQIs and two different statistics tools were applied. Critical water quality status for the investigated surface drinking water intakes was reported. Agricultural drainage then domestic effluents are the main pollution sources. A new software application was developed to calculate WQIs to support decision makers.
Subject(s)
Environmental Monitoring , Water Quality , Egypt , Rivers , WastewaterABSTRACT
Coronaviruses are a group of enveloped viruses with non-segmented, single-stranded, and positive-sense RNA genomes. In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in Wuhan City, China. The World Health Organization (WHO) declared the coronavirus outbreak as a global pandemic in March 2020. Fever, dry cough and fatigue are found in the vast majority of all COVID-19 cases. Early diagnosis, treatment and future prevention are keys to COVID-19 management. Currently, the unmet need to develop cost-effective point-of-contact test kits and efficient laboratory techniques for confirmation of COVID-19 infection has powered a new frontier of diagnostic innovation. No proven effective therapies or vaccines for SARS-CoV-2 currently exist. The rapidly increasing research regarding COVID-19 virology provides a significant number of potential drug targets. Remdesivir may be the most promising therapy up till now. On May 1, 2020, Gilead Sciences, announced that the U.S. Food and Drug Administration (FDA) has granted emergency use authorization (EUA) for the investigational Remdesivir as a potential antiviral for COVID-19 treatment. On May 7, 2020, Gilead Sciences, announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has granted regulatory approval of Veklury® (Remdesivir) as a treatment for SARS-CoV-2 infection, the virus that causes COVID-19 acute respiratory syndrome, under an exceptional approval pathway. Also, Corticosteroids are recommended for severe cases only to suppress the immune response and reduce symptoms, but not for mild and moderate patients where they are associated with a high-risk side effect. Based on the currently published evidence, we tried to highlight different diagnostic approaches, side effects and therapeutic agents that could help physicians in the frontlines.
ABSTRACT
Mercury is a global environmental pollutant, accumulating mainly in the kidney and liver inducing hepatorenal toxicity, oxidative stress, and tissue damage. Oxidative stress is caused by an imbalance between free radicals' production and cellular antioxidant defense systems. In the present study, we investigated the effect of N N'-diphenyl-1, 4-phenylenediamine (DPPD) antioxidant activity against mercury chloride- (HgCl2-) induced renal and hepatic toxicity. Thirty adult female Sprague Dawley rats were divided into three equal groups: the first group was injected with saline only and served as a control, the second group was injected with HgCl2, and the third group received DPPD + HgCl2 rats injected with HgCl2 without treatment showing a significant increase in alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, and uric acids compared to control. Moreover, the second group showed a significant reduction in the activity of the antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH)) in addition to a marked increase in the malondialdehyde (MDA) content, histopathological alterations, collagen deposition, CD8%, CD4%, and TGF-ß% in kidney and liver tissues compared with the control group. Treatment with DPPD showed significant recovery (p ≤ 0.001) in all previous parameters and histopathological examination. In conclusion, we suggested that DPPD may have a promising antioxidant capacity, gives it the applicability to be used as a prophylactic agent against mercury-induced hepatorenal cytotoxicity in the future.
ABSTRACT
Cancer, as a group, represents the most important cause of death worldwide. Unfortunately, the available therapeutic approaches of cancer including surgery, chemotherapy, radiotherapy, and immunotherapy are unsatisfactory and represent a great challenge as many patients have cancer recurrence and severe side effects. Methotrexate (MTX) is a well-established (antineoplastic or cytotoxic) chemotherapy and immunosuppressant drug used to treat different types of cancer, but its usage requires high doses causing severe side effects. Therefore, we need a novel drug with high antitumor efficacy in addition to safety. The aim of this study was the evaluation of the antitumor efficacy of zinc oxide nanoparticle (ZnO-NPs) and sorafenib alone or in combination on solid Ehrlich carcinoma (SEC) in mice. Sixty adult female Swiss-albino mice were divided equally into 6 groups as follows: control, SEC, MTX, ZnO-NPs, sorafenib, and ZnO-NPs+sorafenib; all treatments continued for 4 weeks. ZnO-NPs were characterized by TEM, zeta potential, and SEM mapping. Data showed that ZnO-NPs synergized with sorafenib as a combination therapy to execute more effective and safer anticancer activity compared to monotherapy as showed by a significant reduction (P < 0.001) in tumor weight, tumor cell viability, and cancer tissue glutathione amount as well as by significant increase (P < 0.001) in tumor growth inhibition rate, DNA fragmentation, reactive oxygen species generation, the release of cytochrome c, and expression of the apoptotic gene caspase-3 in the tumor tissues with minimal changes in the liver, renal, and hematological parameters. Therefore, we suggest that ZnO-NPs might be a safe candidate in combination with sorafenib as a more potent anticancer. The safety of this combined treatment may allow its use in clinical trials.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Metal Nanoparticles/chemistry , Sorafenib/pharmacology , Zinc Oxide/pharmacology , Animals , Caspase 3/metabolism , Cell Proliferation/drug effects , Cell Survival/drug effects , Cytochromes c/metabolism , DNA/metabolism , DNA Fragmentation/drug effects , Female , Metal Nanoparticles/ultrastructure , Mice , Oxidative Stress/drug effects , Tumor Burden/drug effectsABSTRACT
Egyptian Mediterranean coast hosts five shallow lagoons which play a vital role in the national economy. Lake Burullus is the second largest one that is located in the Nile Delta and is connected to the Mediterranean by a narrow outlet. This lagoon faces various anthropogenic-induced implications that threat its ecosystem and biodiversity. The prime objective of this study is investigating the impacts of future climate change (CC) on its characteristics. A 2-D hydro-ecological modeling for the lagoon was implemented, using MIKE21FM. The proposed model was calibrated and validated against the collected water quality records, for two successive years (2011-2013), at twelve monitoring stations throughout the lagoon. The simulations were executed for various parameters, including water depth, salinity, DO, BOD, and nutrient components. Six simulations from different regional climate models (RCMs) were obtained and examined to extract the most accurate climatic projections for the lagoon coordinates. These climatic estimates cover three Representative Concentration Pathways (RCPs) scenarios according to the IPCC's Fifth Assessment Report (AR5). A moderate sea level rise (SLR), locally projected offshore from the Nile Delta coast, was obtained. The validated model was forced with the climatic and SLR projections of 2 years representing the mid and long-term future of the twenty-first century. The model results showed that the developed model is an efficient tool to simulate the lagoon characteristics. The results of the modified model showed that CC has the potential to radically alter the physical and chemical structure of Lake Burullus. The results emphasized that the lagoon is expected to be warmer and more saline. The risk of oxygen depletion is firmly predictable with significant spatial differences of DO decreasing. A prolonged residence time is expected, accompanied by an increasing trend of phosphate and chlorophyll-a and a decreasing trend of nitrate. CC impacts on Lake Burullus should be considered in its urgently required management plan.
Subject(s)
Lakes , Water Quality , Climate Change , Ecosystem , Egypt , Environmental MonitoringABSTRACT
Currently, the search for suitable hepatocellular carcinoma (HCC) biomarkers is very intensive. Besides, efficacy and cost/effectiveness of screening and surveillance of cirrhotics for the diagnosis of HCC is still debated. So, the present study is concerned with the evaluation of cytokeratin-1 (CK-1) and nuclear matrix protein-52 (NMP-52) for identifying HCC. Two-hundred and eighty individuals categorized into three groups [liver fibrosis (F1-F3), cirrhosis (F4), and HCC] constituted this study. Western blot was used for identifying CK-1 and NMP-52 in serum samples. As a result, a single immunoreactive band was shown at 67 and 52 kDa corresponding to CK-1 and NMP-52, respectively. Both CK-1 and NMP-52 bands were cut and electroeluted separately. These markers were quantified in sera using ELISA. Patients with HCC were associated with higher concentrations of CK-1 and NMP-52 than those without HCC with a significant difference (P < 0.0001). CK-1 showed an area under receiver-operating characteristic curve (AUC) of 0.83 with 75 % sensitivity and 82 % specificity while NMP-52 yielded 0.72 AUC with 62 % sensitivity and 70 % specificity for identifying HCC. HCC-DETECT comprising CK-1 and NMP-52 together with AFP was then constructed yielding 0.90 AUC for identifying HCC with 80 % sensitivity and 92 % specificity. HCC-DETECT was then tested for separating HCC from F1-F3 showing 0.94 AUC with 80 % sensitivity and 93 % specificity. In conclusion, CK-1 in conjunction with NMP-52 and AFP could have a potential role for improving the detection of HCC with a high degree of accuracy.