Gemcitabine and synthesized silver nanoparticles impact on chemically induced hepatocellular carcinoma in male rats.

Objective: Gemcitabine (GEM) is a deoxycytidine analog chemotherapeutic drug widely used to treat many cancers. Silver nanoparticles (AgNPs) are important nanomaterials used to treat many diseases. Using gamma radiation in nanoparticle preparation is a new eco-friendly method. This study aims to evaluate the efficiency of co-treating gemcitabine and silver nanoparticles in treating hepatocellular carcinoma. Method: The AgNPs were characterized using UV-visible spectroscopy, XRD, TEM, and EDX. The MTT cytotoxicity in vitro assay of gemcitabine, doxorubicin, and cyclophosphamide was assessed against Wi38 normal fibroblast and HepG2 HCC cell lines. After HCC development, rats received (10 µg/g b.wt.) of AgNPs three times a week for 4 weeks and/or GEM (5 mg/kg b.wt.) twice weekly for 4 weeks. Liver function enzymes were investigated. Cytochrome P450 and miR-21 genes were studied. Apoptosis was determined by using flow cytometry, and apoptotic modifications in signaling pathways were evaluated via Bcl-2, Bax, Caspase-9, and SMAD-4. Results: The co-treatment of GEM and AgNPs increased apoptosis by upregulating Bax and caspase 9 while diminishing Bcl2 and SMAD4. It also improved cytochrome P450 m-RNA relative expression. The results also proved the cooperation between GEM and AgNPs in deactivating miR21. The impact of AgNPs as an adjuvant treatment with GEM was recognized. Conclusions: The study showed that co-treating AgNPs and GEM can improve the efficiency of GEM alone in treating HCC. This is achieved by enhancing intrinsic and extrinsic apoptotic pathways while diminishing some drawbacks of using GEM alone.

Liver and ovarian toxicities boosted by bisphenol and gamma radiation in female albino rats.

Bisphenol A (BPA), a carbon-based synthetic polymer compound, was newly classified as an environmental toxicant and an endocrine-disrupting chemical leading to abnormalities in cell proliferation, apoptosis, or migration that contributes to cancer development and progression. This study aims to evaluate the effect of the elevation of γ- radiation dose and BPA on the liver and ovaries of female rats. In this study, eighty female albino rats (130-150 g) were used in this work. Rats in this experiment received BPA in ethanol (50 mg/kg b. wt.) for 30 days, day after day, and in the irradiated groups, animals were administered BPA and then exposed to γ- radiation in doses (2, 4, and 6 Gy) one shot dose. Several members of the cytochrome family were examined. Exposure to γ-radiation and BPA showed an increase in cytochrome P450 and b5 fold change. Further, BPA and γ-radiation activate α and ß estrogen receptors and also downregulate aromatase (CYT19) fold change. The current results also revealed that BPA and/or γ-radiation regulate the protein expression of the PI3K/Akt signaling pathway. The steroidogenic acute regulatory protein (StAR) appeared to be targeted by BPA and γ-radiation and its relative expression was elevated significantly by raising the γ-radiation dose. In conclusion, exposure to BPA, an endocrine-disrupting chemical, leads to marked toxicity. Additionally, toxicity is heightened by increasing the γ-radiation dose, either alone or in combination with BPA.

Epicardial Fat Volume as a Good Predictor for Multivessel Coronary Artery Disease.

INTRODUCTION: Epicardial adipose tissue may have an important role in the pathogenesis of coronary artery disease (CAD). AIM: We aimed to study the association between epicardial fat volume (EFV) and presence of obstructive as well as multivessel CAD. METHODS: A total of 87 adult subjects with suspected CAD who underwent both quantified by multidetector computerized tomography (MDCT) and Invasive Coronary Angiography (ICA) were enrolled in this observational study. EVF was measured by MDCT by calculating the sum of cross- sectional areas of fat multiplied by slice thickness. EFV measurement and its association with the presence of obstructive CAD (defined as coronary artery stenosis > 70%) was evaluated. RESULTS: Overall, 89.6% patients had obstructive CAD with higher EFV as compared to 10.3% patients with non-obstructive CAD (57 ± 20.14 cm3 vs. 44 ± 7.4 cm3; P < 0.001). Furthermore, EFV was significantly increased in group II as compared with group I (74 ± 24.3 ml vs. 53 ± 16.2 ml; P < 0.003). On the hand, the coronary calcium score (CAC) was insignificantly increased in group II as compared with group I (486.1 vs. 211.2; P = 0.10). Multivariate analysis revealed that, EFV might be an independent risk factor for not only the presence of obstructive CAD (odds ratio [OR], 1.062; 95% CI 1.018- 1.108; P < 0.005) but also in predicting multivessel disease affection. CONCLUSIONS: Our results demonstrated that, EFV was significantly increased not only with obstructive CAD, independent of other traditional risk factors and CAC score, but also it can be considered a good predictor of multivessel disease occurrence.

Controlled release of silica-coated insulin-loaded chitosan nanoparticles as a promising oral administration system.

BACKGROUND: Oral insulin administration has recently become one of the most exciting research subjects. Different approaches have been carried out to get an effective oral insulin delivery system using nanotechnology. The development of a delivery system that overcomes the difficulties of oral insulin administration, achieving high stability and minimal side effects, is still an urgent need. Therefore, this study is considered one of the efforts to design a new prospective drug delivery nano-composite (silica-coated chitosan-dextran sulfate nanoparticles). METHODS: Chitosan-dextran sulfate nanoparticles (CS-DS NPs) were prepared via a complex coacervation method and then coated with silica. Uncoated and silica-coated CS-DS NPs were physically characterized via different techniques. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) analysis, and atomic force microscopy (AFM) have been used to investigate the chemical elements, size, morphology, and surface properties of the prepared formulations. Differential scanning calorimetry (DSC) to assess the thermal properties of formed nano-formulations. Fourier transform infrared (FT-IR) spectroscopy investigated the silica coat and chitosan interaction. The encapsulation efficiency was evaluated using high-performance liquid chromatography (HPLC) analysis. The insulin release profile of nano-formulations was performed with and without silica coat at two different pHs (5.5,7), nearly simulating the environment of the gastrointestinal tract (GIT). RESULTS: The silica-coated CS-DS NPs revealed interesting physicochemical properties exemplified by suitable core particle size obtained by TEM images (145.31 ± 33.15 nm), hydrodynamic diameter (210 ± 21 nm), high stability indicated by their zeta potential value (-32 ± 3.2 mV), and adequate surface roughness assessed by AFM. The encapsulation efficiency of insulin-loaded chitosan nanoparticles (ICN) was (66.5%) higher than that of insulin-chitosan complex nanoparticles (ICCN). The silica-coated ICN demonstrated a controlled insulin release profile at pHs (5.5 and 7) compared with uncoated ICN. CONCLUSION: The silica-coated ICN can be an efficient candidate as a desired oral delivery system, overcoming the common obstacles of peptides and proteins delivery and achieving high stability and controlled release for further applications.

Tropaeolum majus L. and low dose gamma radiation suppress liver carcinoma development via EGFR-HER2 signaling pathway.

Hepatocellular carcinoma (HCC) is one of the most fatal cancers around the world and remain asymptomatic in early stage. An alcoholic extract prepared from leaves of Tropaeolum majus L. (Tropaeolaceae) was assessed for its potential activity against diethylnitrosamine-induced liver carcinoma in vivo. Oral administration of the extract significantly decreased the inflammatory marker translation NF-kB and supressed HCC progression in combination with 0.5 Gy gamma radiation via EGF-HER-2 pathway. Histopathological and immunohistopathological features also showed the recovery of a hepatic architecture. Immunohistochemical study showed the T. majus and LDR enhancement effect on proapoptotic markers (caspase-3 and Bax) and inhibition of anti-apoptotic factor (BCl2). HPLC-DAD-MSn analysis of the extract revealed the annotation of twelve compounds. T. majus could mediate a defensive influence against diethylnitrosamine-induced hepatocarcinogenesis and serve as a respectable option in amelioration of the hepatocellular carcinoma development in combination with low dose of gamma radiation.

Increasing Prevalence of Methicillin-resistant Staphylococcus aureus among Hospital and Community acquired Infections in Khartoum State, Sudan.

BACKGROUND: Staphylococcus aureus is an important bacterium that can cause many diseases. Methicillin-resistant S.aureus (MRSA) is often sub-categorized as Hospital or Community acquired infection. MRSA causes serious problems, such as bloodstream and surgical site infections or pneumonia. OBJECTIVES: The present study aimed to identify S. aureus by 16SrRNA using PCR, estimate the antibiotic susceptibility pattern and determine the prevalence of MRSA among Hospital and community acquired infections. METHODS: A cross-sectional laboratory-based study was conducted during the period from November 2020 to January 2021. Conventional methods were used to identify S. aureus and isolate confirmation was performed by PCR targeting 16SrRNA gene. All isolated organisms were tested for their in-vitro antimicrobial susceptibility. RESULT: Among the enrolled patients (n, 300), MRSA was observed in 185 (61.7%). The highest frequency was shown in the age group over 45 years old (46.7%). The result also showed a high frequency of S. aureus among community infections (81.7%), MRSA in hospital acquired infections was 10.7% while 51% was community acquired. The antimicrobial susceptibilities against MRSA isolates showed high sensitivity to Ceftriaxone 90.0%). Most infections caused by MRSA isolates were respiratory tract infection (RTI) (28.3%) and Septicemia (22.5%). CONCLUSION: The present study highlighted a high proportion of MRSA in clinical settings at Khartoum State. Antibiotic susceptibility results showed that Ceftriaxone was the drug of choice against MRSA isolates. Overuse and misuse of antibiotics, along with self-medication, seem to be the cause of antibiotic resistance, thus should be avoided.

Detection of Helicobacter pylori in Gastric Biopsies Among Sudanese Patients with Confirmed Gastric Disorders Using Three Diagnostic Methods.

BACKGROUND: Helicobacter pylori (H. pylori) infection represents one of the most common chronic bacterial infections in developing countries. However, in Sudan, the infection is not well diagnosed with standard laboratory methods in many parts of the country. This study aimed to detect H. pylori in gastric biopsies of patients with gastric disorders, using three diagnostic methods. MATERIALS AND METHODS: A cross-sectional study was conducted among 100 patients in Gezira state, central Sudan. Giemsa stain for histopathological examination (HPE), rapid urease test (RUT), and polymerase chain reaction (PCR) techniques were performed to detect H. pylori from the gastric biopsy samples as per standard assays. RESULTS: Most of the patients were males (66%), from rural areas (72%) and in the age group 31 to 50 years. H. pylori were identified in 85% of the samples by at least one of the three tests. The highest positivity was detected by HPE (83%), followed by PCR (67%) and RUT (63%), while 59% were positive by the three diagnostic methods. PCR showed higher sensitivity (80.72% vs. 73.49%) and specificity (100% vs. 88.24%) than RUT. Positive predictive values were reported as 100% for PCR and 96.83% for RUT. Considering PCR as a gold standard method, HPE revealed higher sensitivity (100%) than RUT (88.06%). On the contrary, RUT showed higher specificity (87.88%) than PCR (51.52%). There were no significant associations between H. pylori infection patients' gender (p = 0.747). Loss of weight (p = 0.007) and nausea (p = 0.032) were significantly associated with H. pylori infection. CONCLUSIONS: There was a high prevalence of H. pylori infection in central Sudan. This highlights the need to analyze epidemiological status, virulence factors, and strain characteristics to control disease transmission. PCR is a reliable and valuable technique in detecting H. pylori infection from gastric biopsy samples.

Mangosteen Hinders Gamma Radiation-Mediated Oxidative Stress and Liver Injury by Down-Regulating TNF-α/NF-κB and Pro-Fibrotic Factor TGF-ß1 Inducing Inflammatory Signaling.

BACKGROUND: Liver injury due to ionizing radiation exposure either accidental or after radiotherapy treatment, may lead to many alterations in proteins expression related to inflammation or apoptosis. Our study investigated the curative effect of Mangosteen (MGS) extract (fruit rind) against ionizing radiation (IR) induced liver damage. METHODS: Hepatotoxicity was induced in Wister rats by exposure to an acute single dose (6 Gy) of IR while MGS was given orally to rats (500 mg/kg bwt) and administered daily for 30 days after irradiation. RESULTS: MGS treatment has significantly attenuated redox imbalance state and toxicity induced by protracted exposure to gamma-rays in liver tissues, which was substantiated by the significant amelioration of liver function tests, MDA contents, antioxidant enzymes (SOD and CAT) activities and NO level. MGS inhibited also the inflammatory markers (TNF-alpha, IL-6 and CRP) and downregulated transcriptional factor NF-Kappa-B/TGF-ß1. These alterations were concomitant with an improvement of the Proliferating cell nuclear antigen (PCNA) which is a protein expressed in the nuclei of cells during cell cycle and is important for both DNA synthesis and DNA repair. These results were confirmed by amelioration in histological and ultrastructural examinations. CONCLUSION: We concluded that MGS could ameliorate via minimizing significantly the amount of oxidative damage, inflammations disturbances and pro-apoptotic alternations induced by IR. MGS may be a promising supplement with protective effects from irradiation-induced injury such as TNF-α/NF-κB/TGF-ß1 management.

Surface modifications affect iron oxide nanoparticles' biodistribution after multiple-dose administration in rats.

Iron oxide nanoparticles (IONPs) possess many utilizable physical and chemical properties and have an acceptable level of biocompatibility. Therefore, they are extensively used in different medical applications. Hence, the challenge is to modify the surfaces of prepared iron oxide nanoformulations with a biocompatible coat to enhance their biosafety. In this study, different formulations of IONPs with different capping agents (citrate [Cit-IONPs], curcumin [Cur-IONPs], and chitosan [CS-IONPs]) were prepared and characterized using various physicochemical techniques. The biodistribution of iron and the histopathology of affected tissues were assessed after Cit-IONPs, Cur-IONPs, CS-IONPs, and commercial ferrous sulfate were orally administered to adult female Wistar rats for 10 consecutive days at a dose of 4 mg/kg of body weight/day. The results were compared with a control group injected orally with saline. The iron content in the kidneys, liver, and spleen was measured by atomic absorption spectroscopy. Histopathological alterations were also examined. The biodistribution results demonstrate that iron accumulated mainly in the liver tissue, whereas the lowest liver accumulation was observed after the administration of Cit-IONPs or CS-IONPs, respectively. In contrast, the administration of CS-IONPs displayed the highest spleen iron accumulation. The ferrous sulfate (FeSO4 )-treated group showed the highest kidney iron accumulation as compared with the other groups. The histopathological examination revealed that signs of toxicity were predominant for groups treated with Cit-IONPs or commercial FeSO4 . However, Cur-IONPs and CS-IONPs showed mild toxicity when administered at the same doses. The results obtained in the present study will provide insights into the expected in vivo effects after administration of each nanoformulation.

Liver stiffness as a predictor of hepatocellular carcinoma behavior in patients with hepatitis C related liver cirrhosis.

BACKGROUND: Risk stratification and prognostication of hepatocellular carcinoma (HCC) help to improve patient outcome. Herein we investigated the role of liver stiffness measurement (LSM) in the prediction of HCC behavior. METHODS: Totally 121 naïve patients with HCC were included. HCC radiological evaluation and staging were done. LSM was measured using virtual touch quantification. Patients were divided into early to intermediate HCC (BCLC-0, A and B) and late HCC (BCLCC and D). HCC was treated according to the BCLC stage. HCC recurrence-free interval was estimated. RESULTS: The mean LSM inside the tumor was significantly lower than the peri-tumoral area and the cirrhotic non-cancerous liver parts (P < 0.001). In late HCCs stage, the mean LSM inside the tumor and in the peri-tumoral tissue was lower than the corresponding values in the early to intermediate HCCs stage (P < 0.001). LSM inside the tumor and in the peri-tumoral tissue negatively correlated with serum AFP, tumor vascular invasion, and stage (P < 0.05). The recurrence-free interval was directly correlated to LSM inside the tumor and inversely to LSM in cirrhotic non tumorous liver part. Kaplan-Meier analysis showed that the recurrence-free interval was significantly longer in patients with LSM inside the tumor of ≥1.25 m/s compared to those with LSM inside the tumor of <1.25 m/s. CONCLUSIONS: LSM can serve as a potential non-invasive predictor for HCC clinical behavior and the recurrence-free interval following loco-regional treatments.

Hyaluronan as a mediator for the hepatoprotective effect of Diosmin/Hesperidin complex.

Daflon is a phlebotonic drug widely used in chronic venous or lymphatic insufficiency. This study designed to investigate the relation of daflon with hyaluronan as a mediator for the hepatoprotective effect against Carbon tetrachloride (CCl4) and/or γ-radiation induced liver damage. Animals of this study were administered CCl4 (1 ml/kg b.wt.), exposed to γ-radiation (1Gy) and treated with daflon (100 mg/kg/day). Our results showed the ameliorative effect of daflon on cytochrome P450 (CYT P450), lipid peroxidation (MDA), liver enzymes (aspartate amino transferase; AST, alanine aminotransferase; ALT and gamma glutamyl transferase; γ-GT), antioxidant capacity (reduced glutathione; GSH and glutathione per oxidase; GPx), inflammatory markers (C-reactive protein; CRP and interlukin- 6; IL-6), alpha-fetoprotein (AFP) and extra cellular matrix proteins (hyaluronan; HA and hyaluronidase; HAase) which was supported by histopathological examination of liver sections compared to the damage induced in CCL4 and/or rats exposed to radiation. It could be concluded that the hepatoprotective effect of daflon is mediated via antioxidant and anti-inflammatory activity in addition to preserving native tissue hyaluronan by preventing its degradation.

Endothelial monocyte activating polypeptide II in children and adolescents with type 1 diabetes mellitus: Relation to micro-vascular complications.

OBJECTIVES: Endothelial monocyte-activating polypeptide II (EMAP II) is a multifunctional polypeptide with proinflammatory and antiangiogenic activity. Hyperglycemia and dyslipidemia appears to be significant factors contributing to increased EMAP-II levels. We determined serum EMAP II in children and adolescents with type 1 diabetes as a potential marker for micro-vascular complications and assessed its relation to inflammation and glycemic control. METHODS: Eighty children and adolescents with type 1 diabetes were divided into 2 groups according to the presence of micro-vascular complications and compared with 40 healthy controls. High-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c) and EMAP II levels were assessed. RESULTS: Serum EMAP II levels were significantly increased in patients with micro-vascular complications (1539 ± 321.5 pg/mL) and those without complications (843.6 ± 212.6 pg/mL) compared with healthy controls (153.3 ± 28.3 pg/mL; p<0.001). EMAP II was increased in patients with microalbuminuria than normoalbuminuric group (p<0.001). Significant positive correlations were found between EMAP II levels and body mass index, fasting blood glucose, HbA1c, serum creatinine, triglycerides, total cholesterol, urinary albumin creatinine ratio (UACR) and hs-CRP (p<0.05). A cutoff value of EMAP II at 1075 pg/mL could differentiate diabetic patients with and without micro-vascular complications with a sensitivity of 93% and specificity of 82%. CONCLUSIONS: We suggest that EMAP II is elevated in type 1 diabetic patients, particularly those with micro-vascular complications. EMAP II levels are related to inflammation, glycemic control, albuminuria level of patients and the risk of micro-vascular complications.