Biogenic silver nanoparticles eradicate of Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA) isolated from the sputum of COVID-19 patients

In recent investigations, secondary bacterial infections were found to be strongly related to mortality in COVID-19 patients. In addition, Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA) bacteria played an important role in the series of bacterial infections that accompany infection in COVID-19. The objective of the present study was to investigate the ability of biosynthesized silver nanoparticles from strawberries (Fragaria ananassa L.) leaf extract without a chemical catalyst to inhibit Gram-negative P. aeruginosa and Gram-positive Staph aureus isolated from COVID-19 patient’s sputum. A wide range of measurements was performed on the synthesized AgNPs, including UV–vis, SEM, TEM, EDX, DLS, ζ -potential, XRD, and FTIR. UV-Visible spectral showed the absorbance at the wavelength 398 nm with an increase in the color intensity of the mixture after 8 h passed at the time of preparation confirming the high stability of the FA-AgNPs in the dark at room temperature. SEM and TEM measurements confirmed AgNPs with size ranges of ∼40-∼50 nm, whereas the DLS study confirmed their average hydrodynamic size as ∼53 nm. Furthermore, Ag NPs. EDX analysis showed the presence of the following elements: oxygen (40.46%), and silver (59.54%). Biosynthesized FA-AgNPs (ζ = −17.5 ± 3.1 mV) showed concentration-dependent antimicrobial activity for 48 h in both pathogenic strains. MTT tests showed concentration-dependent and line-specific effects of FA-AgNPs on cancer MCF-7 and normal liver WRL-68 cell cultures. According to the results, synthetic FA-AgNPs obtained through an environmentally friendly biological process are inexpensive and may inhibit the growth of bacteria isolated from COVID-19 patients

Importance of carcinoma-associated fibroblasts in breast cancer and effects of CXCL12 and IGF-1 on malignant breast epithelial cells

It has become clear that the phenotypic alterations present in carcinoma-associated fibroblasts play an important role in the development and progression of breast carcinomas. To investigate these alterations, a panel of carcinoma-associated fibroblast and their counterpart fibroblast primary cell cultures were assessed for their expression of p53, p21 and survivin. The induction of p53 and p21 in response to gamma-irradiation was defective in most of the carcinoma-associated fibroblasts but not in their counterpart fibroblasts. In addition, the constitutive levels of p53 and p21 proteins were significantly lower in most of the carcinoma-associated fibroblasts and modulated in the majority of tumour counterpart fibroblasts compared to the normal breast fibroblasts. Survivin expression was higher in both carcinoma-associated fibroblasts and tumour counterpart fibroblasts as compared to in normal fibroblasts. This part of the work demonstrates that carcinoma-associated fibroblasts have undergone premalignant changes that make them resistant to irradiation. The cytokine, CXCL12 is secreted by stromal cells and can affect the growth and progression of breast tumours. In malignant breast epithelial cells, CXCL12 mRNA has been shown to be expressed also and to be increased by oestrogen. To evaluate the importance of CXCL12 in the oestrogen response of breast cancer cells, the expression of CXCL12 and both its receptors, CXCR4 and CXCR7, was assessed by quantitative real time PCR and western transfer analysis in a panel of eleven human breast cancer cell lines. Notably CXCL12 was expressed mostly in the oestrogen-responsive breast cancer cell lines, whereas CXCR4 and CXCR7 were expressed at high levels in MDA-MB-231, an oestrogen non-responsive breast cancer cell line. Furthermore, oestrogen increased CXCL12 mRNA expression in breast cancer cell lines, while the expression of CXCR4 and CXCR7 mRNAs was decreased in response to oestrogen. The effects of CXCL12 on the proliferation and migration of breast cancer cells were tested. The results of these experiments showed that CXCL12 has a motogenic effect in both oestrogen-responsive and oestrogen non-responsive breast cancer cells. Interestingly, the combined effect of CXCL12 and IGF-1 was more than additive on migration of breast cancer cells. Furthermore, phosphorylation of CXCR4, and its downstream effectors, Akt and MAPK, was studied in oestrogen-responsive breast cancer cells, ZR-75 cells, and oestrogen non-responsive breast cancer cells, MDA-MB-231 cells. Our results suggest that the phosphorylation of Akt and MAPK may be involved in mediating the effects of CXCL12 in breast cancer cells. The work described in the second part the thesis emphasis the importance of the interplay between oestrogen, CXCL12 and IGF-1 in the responsiveness of malignant breast epithelial cells.EThOS - Electronic Theses Online ServiceKing Khalid Foundation : King Faisal Specialist Hospital and Research CentreGBUnited Kingdo

Sulphated tubers extract from the giant taro Alocasia macrorrhiza inhibits the carcinogenesis initiation and modulates macrophage functions

Alocasia macrorrhizos (L.) G. Don, Araceae, is a traditionally edible plant known as giant taro. This work aimed to prepare sulphatedpolysaccharide extract of A. macrorrhizos tubers (SAM) and to investigate its tumor anti-initiation and anti-promotion activities. Methods:Enzymatic, colorimetric, fluorometric, and cell-based assays were used throughout the study. Tumor anti-initiation activity was investigatedby estimation of SAM effect on cytochrome P450 1A1 (Cyp1A1) glutathione-S-transferases (GST), glutathione (GSH), epoxide hydrolase(mEH), and quinone reductase (QR), while Tumor anti-promotion activity was investigated by macrophage proliferation, nitric oxide (NO),and LPS binding to macrophages. SAM inhibited the carcinogen metabolizing enzyme Cyp1A1 and it induced, to variable extent, thedetoxification enzymes (GST, mEH and QR), especially mEH. Additionally, SAM showed anti-inflammatory property by inhibiting NO andit induced the affinity of macrophage to bind pathogens and neoplastic cells. Additionally, SAM was cytotoxic to colon HCT-116 cells.The findings suggested SAM as a promising inhibitor of the carcinogenesis initiation phase.Keywords: Alocasia macrorrhiza; sulphated; Tumor anti-initiation; Cyp1A1; Epoxide hydrolase; glutathione-S-transferases; quinonereductase; FITC-LPS; macrophag

Sulphated tubers extract from the giant taro Alocasia macrorrhiza inhibits the carcinogenesis initiation and modulates macrophage functions

Alocasia macrorrhizos (L.) G. Don, Araceae, is a traditionally edible plant known as giant taro. This work aimed to prepare sulphatedpolysaccharide extract of A. macrorrhizos tubers (SAM) and to investigate its tumor anti-initiation and anti-promotion activities. Methods:Enzymatic, colorimetric, fluorometric, and cell-based assays were used throughout the study. Tumor anti-initiation activity was investigatedby estimation of SAM effect on cytochrome P450 1A1 (Cyp1A1) glutathione-S-transferases (GST), glutathione (GSH), epoxide hydrolase(mEH), and quinone reductase (QR), while Tumor anti-promotion activity was investigated by macrophage proliferation, nitric oxide (NO),and LPS binding to macrophages. SAM inhibited the carcinogen metabolizing enzyme Cyp1A1 and it induced, to variable extent, thedetoxification enzymes (GST, mEH and QR), especially mEH. Additionally, SAM showed anti-inflammatory property by inhibiting NO andit induced the affinity of macrophage to bind pathogens and neoplastic cells. Additionally, SAM was cytotoxic to colon HCT-116 cells.The findings suggested SAM as a promising inhibitor of the carcinogenesis initiation phase.Keywords: Alocasia macrorrhiza; sulphated; Tumor anti-initiation; Cyp1A1; Epoxide hydrolase; glutathione-S-transferases; quinonereductase; FITC-LPS; macrophag

Nitric Oxide Synthase potentiates the resistance of cancer cell lines to anticancer chemotherapeutics

Background: Despite the advancement in the fields of medical science and molecular biology, cancer is still the leading cause of death worldwide. Chemotherapy is a choice for treatment; however, the acquisition of chemoresistance is a major impediment for cancer management. Many mechanisms have been postulated regarding the acquisition of chemo-resistance in breast cancer and the impact on cellular signalling and the induction of apoptosis in tumour cells. The mechanism of the apoptotic mutation ofp53 and bcl-2 proteins is commonly associated with increased resistance to apoptosis and, therein, to chemotherapy. Objectives: The current study was aimed to investigate A172 and MDA-MB-231 cancer cells’sensitivity against chemotherapeutic drugs, including cisplatin, doxorubicin, and paclitaxel with different doses. Moreover, it estimates resistance of cancer cells by evaluating Nitric Oxide Synthase (NOS) expression and evaluate its correlation with the expression profile proteins of the apoptosis regulating Bcl-2 family. Methods: Dose-dependent sensitivity to cisplatin, doxorubicin or paclitaxel was evaluated on spheroid cultured A172 and MDA-MB-231 cells lines, was measured by time-lapse microscopy over a 72h period. Expressions of two Nitric Oxide (NO) synthases isoforms (iNOS, eNOS), anti-apoptotic (Bcl-2, phospho-Bcl-2, Mcl-1, and Bcl-xL) and proapoptotic (BID, Bim, Bok, Bad, Puma, and Bax) were evaluated by Western blot. The effect of NO modulation on antiand pro-apoptotic molecule expression was also studied using Western blot. Result: A172 cells show more resistance to chemotherapy drugs than MDA-MB-231 cancer cells, therefore, they need higher doses for apoptosis. Resistance of gliomas might be returned to higher significant expression of endothelial eNOS expression. It was clear that there is not a significant effect of NO modulation on the expression of pro- andantiapoptotic proteins on both cell lines. Conclusion: The present work provides a putative mechanism for the acquisition of drug resistance in breast cancer and glioma, which might be significant for clinical outcomes

Genotypes of Hepatitis C Virus and Efficacy of Direct-Acting Antiviral Drugs among Chronic Hepatitis C Patients in a Tertiary Care Hospital

Hepatitis C virus (HCV) chronic infection is a major causative factor for several chronic liver diseases, including liver cirrhosis, liver cell failure, and hepatocellular carcinoma. The HCV has seven major genotypes. Genotype 4 is the most prevalent genotype in the Middle East, including Saudi Arabia, followed by genotype 1. The HCV genotype affects the response to different HCV treatments and the progression of liver disease. Currently, combinations of direct-acting antiviral drugs (DAAs) approved for the treatment of HCV achieve high cure rates with minimal adverse effects. Because real-world data from Saudi Arabia about the efficacy of DAAs are still limited, this study was conducted to assess the effectiveness of DAAs in treating patients with chronic hepatitis C and to identify the variables related to a sustained virologic response (SVR) in a real-world setting in Saudi Arabia. This prospective cohort study included 200 Saudi patients with chronic HCV who were 18 years of age or older and had been treated with DAAs at King Abdul-Aziz Specialized Hospital in Taif, Saudi Arabia, between September 2018 and March 2021. The response to treatment was assessed by whether or not an SVR had been achieved at week 12 post treatment (SVR12). An SVR12 was reached in 97.5% of patients. SVR12 rates were comparable for patients of different ages, between men and women, and between patients with and without cirrhosis. In addition, the SVR12 rates did not differ according to the infecting HCV genotype. In this study, the presence of cirrhosis and the patient’s gender were independent predictors of who would not reach an SVR12 (known here as the non-SVR12 group) according to the results of univariate and multivariate binary logistic regression analyses based on the determinants of SVR12. In this population of patients with chronic HCV infection, all DAA regimens achieved very high SVR12 rates. The patients’ gender and the presence of cirrhosis were independent factors of a poor response

Impact of the International Nosocomial Infection Control Consortium (INICC)’s multidimensional approach on rates of ventilator-associated pneumonia in intensive care units in 22 hospitals of 14 cities of the Kingdom of Saudi Arabia

To analyze the impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Approach (IMA) and use of INICC Surveillance Online System (ISOS) on ventilator-associated pneumonia (VAP) rates in Saudi Arabia from September 2013 to February 2017. A multicenter, prospective, before–after surveillance study on 14,961 patients in 37 intensive care units (ICUs) of 22 hospitals. During baseline, we performed outcome surveillance of VAP applying the definitions of the CDC/NHSN. During intervention, we implemented the IMA and the ISOS, which included: (1) a bundle of infection prevention practice interventions, (2) education, (3) outcome surveillance, (4) process surveillance, (5) feedback on VAP rates and consequences and (6) performance feedback of process surveillance. Bivariate and multivariate regression analyses were performed using generalized linear mixed models to estimate the effect of intervention. The baseline rate of 7.84 VAPs per 1000 mechanical-ventilator (MV)-days―with 20,927 MV-days and 164 VAPs―, was reduced to 4.74 VAPs per 1000 MV-days―with 118,929 MV-days and 771 VAPs―, accounting for a 39% rate reduction (IDR 0.61; 95% CI 0.5–0.7; P 0.001). Implementing the IMA was associated with significant reductions in VAP rates in ICUs of Saudi Arabia