Reducing the effective dose of cisplatin using cobalt modified silver nano-hybrid as a carriers on MCF7 and HCT cell models.

Cancer is a deadly illness with a convoluted pathogenesis. The most prevalent restrictions that frequently result in treatment failure for cancer chemotherapy include lack of selectivity, cytotoxicity, and multidrug resistance. Thus, considerable efforts have been focused in recent years on the establishment of a modernistic sector termed nano-oncology, which offers the option of employing nanoparticles (NPs) with the objective of detecting, targeting, and treating malignant disorders. NPs offer a focused approach compared to conventional anticancer methods, preventing negative side effects. In the present work, a successful synthetic process was used to create magnetic cobalt cores with an AgNPs shell to form bimetallic nanocomposites CoAg, then functionalized with Cis forming novel CoAg@Cis nanohybrid. The morphology and optical properties were determined by TEM, DLS, FTIRs and UV-vis spectroscopy, furthermore, anticancer effect of CoAg and CoAg@Cis nanohybrids were estimated using MTT assay on MCF7 and HCT cell lines. Our results showed that Co@Ag core shell is about 15 nm were formed with dark CoNPs core and AgNPs shell with less darkness than the core, moreover, CoAg@Cis has diameter about 25 nm which are bigger in size than Co@Ag core shell demonstrating the loading of Cis. It was observed that Cis, CoAg and CoAg@Cis induced a decline in cell survival and peaked at around 65%, 73%and 66% on MCF7 and 80%, 76%and 78% on HCT at 100 µg/ml respectively. Compared to Cis alone, CoAg and CoAg@Cis caused a significant decrease in cell viability. These findings suggest that the synthesized CoAg can be used as a powerful anticancer drug carrier.

ß-glucan mitigates ovalbumin-induced airway inflammation by preventing oxidative stress and CD8+ T cell infiltration.

BACKGROUND: Bronchial asthma is a severe respiratory condition characterized by airway inflammation, remodeling, and oxidative stress. ß-Glucan (BG) is a polysaccharide found in fungal cell walls with powerful immunomodulatory properties. This study examined and clarified the mechanisms behind BG's ameliorativeactivitiesin an allergic asthma animal model. METHOD: BG was extracted from Chaga mushroom and characterized using FT-IR, UV-visible, zeta potential, and 1H NMR analysis. The mice were divided into five groups, including control, untreated asthmatic, dexamethasone (Dexa)-treated (1 mg/kg), and BG (30 and 100 mg/kg)-treated groups. RESULTS: BG treatment reduced nasal scratching behavior, airway-infiltrating inflammatory cells, and serum levels of IgE significantly. Additionally, BG attenuated oxidative stress biomarkers by lowering malonaldehyde (MDA) concentrations and increasing the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT). Immunohistochemical and flow cytometric analyses have confirmed the suppressive effect of BG on the percentage of airway-infiltrating cytotoxic CD8+ T cells. CONCLUSION: The findings revealed the role of CD8+ T cells in the pathogenesis of asthma and the role of BG as a potential therapeutic agent for asthma management through the suppression of airway inflammation and oxidative stress.

Anticancer effect and laser photostability of ternary graphene oxide/chitosan/silver nanocomposites on various cancer cell lines.

Aims: The development of nanocomposites (NCs) of antitumor activity provides a new paradigm for fighting cancer. Here, a novel NC of green synthetic silver nanoparticles (AgNPs), graphene oxide (GO) and chitosan (Cs) NPs was developed. Materials & methods: The prepared GO/Cs/Ag NCs were analyzed using various techniques. Cytotoxicity of the NCs was evaluated against different cancer cell lines by Sulforhodamine B (SRB) assay. Results: GO/Cs/Ag NCs are novel and highly stable. UV-Vis showed two peaks at 227 and 469 nm, indicating the decoration of AgNPs on the surface of GO/Cs NPs. All tested cell lines were affected by GO/Cs NPs and GO/Cs/Ag NCs. Conclusion: The results indicate that GO/Cs/Ag NCs were present on tested cell lines and are a promising candidate for cancer therapy.

Two versus three doses of COVID-19 vaccine and post-vaccination COVID-19 infection in hemodialysis patients.

Background and aim: Patients with chronic kidney disease including those undergoing hemodialysis (HD) constitute a particularly challenging group regarding COVID-19 vaccination. The present study aimed to compare the rate of reinfection after two and three doses of Sinopharm COVID-19 vaccine in HD patients. Patients and methods: The study included 80 HD patients who received three doses of Sinopharm COVID-19 vaccine. In addition, there were another 80 patients who received only two doses of the vaccine. Patients in the latter group were selected based on propensity matching score with 1:1 ratio. Patients were monitored for post-vaccination COVID-19 infection using PCR examination of nasopharyngeal swabs. Patients were also monitored for post-vaccination complications including general complaints (headache, fever, fatigue), injection site complaints (arm pain, swelling, itching, rash), musculoskeletal complaints (muscle spasm or pain, joint pain) and others. All patients were followed for six months. Results: The present study included 80 patients submitted to COVID-19 vaccination with two doses of Sinopharm vaccine (GI) and other 80 patients who received three doses of the same vaccine (GII). At the end of follow up, 11 patients (13.8 %) in GI caught COVID-19 infection. In contrast, no patient in GII had infection (P<0.001). Comparison between patients who had COVID-19 infection and those without infection revealed that the former subgroup had significantly lower BMI (23.3 ± 2.3 versus 27.5 ± 8.1 Kg/m2), higher frequency of associated Hepatitis C (HCV) infection (54.6 % versus 2.9 %, P<0.001) and higher serum ferritin levels [median (IQR): 1101.0 (836.0-1564.0) versus 675.0 (467.0-767.7) ng/mL, P=0.01]. Binary logistic regression analysis identified high serum ferritin levels [OR (95% CI): 0.014 (0.001-0.15), P<0.001] and associated HCV infection [OR (95% CI): 0.99 (0.98-1.01), P=0.02] as significant predictors of post-vaccination COVID-19 infection in multivariate analysis. Conclusions: A three dose regime of Sinopharm COVID-19 vaccine associated with significantly lower rate of reinfection COVID-19 infection in HD patients. Infected patients had significantly lower BMI, higher frequency of HCV and higher ferritin levels.

Green synthesis of silver and iron oxide nanoparticles mediated photothermal effects on Blastocystis hominis.

The evolution of parasite resistance to antiparasitic agents has become a serious health issue indicating a critical and pressing need to develop new therapeutics that can conquer drug resistance. Nanoparticles are novel, promising emerging drug carriers that have demonstrated efficiency in treating many parasitic diseases. Lately, attention has been drawn to a broad-spectrum nanoparticle capable of converting absorbed light into heat via the photothermal effect phenomenon. The present study is the first to assess the effect of silver nanoparticles (Ag NPs) and iron oxide nanoparticles (Fe3O4 NPs) as sole agents and with the combined action of the light-emitting diode (LED) on Blastocystis hominins (B. hominis) in vitro. Initially, the aqueous synthesized nanoparticles were characterized by UV-Vis spectroscopy, zeta potential, and transmission electron microscopy (TEM). The anti-blastocyst efficiency of these NPs was tested separately in dark conditions. As these NPs have a wide absorption spectrum in the visible regions, they were also excited by a continuous wave LED of wavelength band (400-700 nm) to test the photothermal effect. The sensitivity of B. hominis cysts was evaluated using scanning laser confocal microscopy whereas the live and dead cells were accurately segmented based on superpixels and the k-mean clustering algorithm. Our findings showed that this excitation led to hyperthermia that induced a significant reduction in the number of cysts treated with photothermally active NPs. The results of this study elucidate the potential role of photothermally active NPs as an effective anti-blastocystis agent. By using this approach, new therapeutic antiparasitic agents can be developed.

Enhancing the antibacterial effect of iron oxide and silver nanoparticles by extremely low frequency electric fields (ELF-EF) against S. aureus.

Staphylococcus aureus is the cause of many infectious and inflammatory diseases and a lot of studies aim to discover alternative ways for infection control and treatment rather than antibiotics. This work attempts to reduce bacterial activity and growth characteristics of Staphylococcus aureus using nanoparticles (iron oxide nanoparticles and silver nanoparticles) and extremely low frequency electric fields (ELF-EF). Bacterial suspensions of Staphylococcus aureus were used to prepare the samples, which were evenly divided into groups. Control group, 10 groups were exposed to ELF-EF in the frequency range (0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, and 1 Hz), iron oxide NPs treated group, iron oxide NPs exposed to 0.8 Hz treated group, silver NPs treated group and the last group was treated with silver NPs and 0.8 Hz. Antibiotic sensitivity testing, dielectric relaxation, and biofilm development for the living microbe were used to evaluate morphological and molecular alterations. Results showed that combination of nanoparticles with ELF-EF at 0.8 Hz enhanced the bacterial inhibition efficiency, which may be due to structural changes. These were supported by the dielectric measurement results which indicated the differences in the dielectric increment and electrical conductivity for the treated samples compared with control samples. This was also confirmed by biofilm formation measurements obtained. We may conclude that the exposure of Staphylococcus aureus bacteria to ELF-EF and NPs affected its cellular activity and structure. This technique is nondestructive, safe and fast and could be considered as a mean to reduce the use of antibiotics.

Bacterial Species and Inflammatory Cell Variability in Respiratory Tracts of Patients with Chronic Obstructive Pulmonary Disease Exacerbation: A Multicentric Study.

Background and Aim: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has profound effects on disease progression and patients' quality of life. Emerging evidence suggests an association between alterations in the respiratory microbiome flora species and airway inflammation in patients with AECOPD. The present study aimed to describe the inflammatory cells and bacterial microbiome distributions in respiratory tract in Egyptian patients with AECOPD. Subjects and Methods: The present cross-sectional study included 208 patients with AECOPD. Sputum and broncho-alveolar lavage samples from the studied patients were submitted to microbial cultures using appropriate media. Total and differential leukocytic counts and were done via automated cell counter. Results: The present study included 208 AECOPD patients. They comprised 167 males (80.3%) and 41 females (19.7%) with an age of 57.9 ± 4.9 years. AECOPD was categorized as mild, moderate and severe in 30.8%, 43.3% and 26%, respectively. Sputum samples had significantly higher TLC, neutrophil percent and eosinophil percent when compared with BAL samples. In contrast, lymphocyte percent was significantly higher in BAL samples. Sputum specimens had significantly lower frequency of positive growths (70.2% versus 86.5%, p = 0.001). Among the identified organisms, sputum specimens had significantly lower frequency of Strept. pneumoniae (14.4% versus 30.3%, p = 0.001), Klebsiella pneumoniae (19.7% versus 31.7%, p = 0.024), Haemophilus influenzae (12.5% versus 26.9%, p = 0.011), Pseudomonas aeruginosa (2.9% versus 10%, p = 0.019) and Acinetobacter spp. (1.9% versus 7.2%, p = 0.012) growths when compared with BAL samples. Conclusion: The present study could identify a distinctive pattern of inflammatory cell distribution in sputum and BAL samples of AECOPD patients. The most commonly isolated organisms were Klebsiella pneumoniae and Strept. pneumoniae.

Impact of miR-155 rs767649 Polymorphism on Rheumatoid Arthritis Activity in Egyptian Patients.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory condition that impacts not only the musculoskeletal system but also various other systems in the body, including the cutaneous, ocular, respiratory, cardiovascular, and circulatory systems. MicroRNAs (miRNAs) are a class of naturally occurring and highly conserved transcripts that primarily function in the regulation of gene expression. They accomplish this by facilitating the degradation of messenger RNA (mRNA) or by repressing mRNA translation. miRNAs are well-known regulators of a variety of cellular processes. Therefore, we aimed to detect the impact of miR-155 rs767649 polymorphism on RA activity. METHODS: This case-control study included 66 Egyptian patients with RA who visited Al-Zhraa University Hospital, Internal Medicine Department, Cairo, Egypt, and 50 apparently healthy control subjects matched for age and sex. The participants were subjected to full clinical evaluation, including assessments of the disease activity score (DAS), erythrocyte sedimentation rate (ESR), liver and kidney function, anti-cyclic citrullinated peptide antibody (anti-CCP), and miR-155 polymorphism using real-time polymerase chain reaction (PCR). RESULTS: In the RA group, the majority (98.5%) were female, with a mean age of 43 years, while in the control group, 94% were female, with a mean age of 43.4 years. Comparison of laboratory parameters indicated significantly lower hemoglobin levels, higher ESR, and higher serum creatinine and anti-CCP levels in the RA group than in the control group. The RA group had a significantly higher frequency of TT genotypes and significantly lower frequencies of TA and TT genotypes than the control group. Considering the TT genotype and T allele as references, TA, AA, and TA/AA genotypes in the dominant model; AA in the recessive model; and A allele were significantly associated with protective effects against RA development (p<0.05, odds ratio<1). CONCLUSION: rs767649, the functional variant of miR-155, plays an important role in susceptibility to the increased risk of RA, suggesting that miR-155 can be used as a therapeutic target for the treatment of Egyptian patients with RA.

Photochemical effect of silver nanoparticles on flesh fly larval biological system.

With the progress of nanoscience and its applications, silver nanoparticles (AgNPs) have become one of the most interesting nanoparticles owing to their use in different fields. However, the excessive use of AgNPs and its products may cause toxicity in both the environment and in human health. The main goal of this research is to study the toxic and photochemical effects of AgNPs against Sarcophaga argyrostoma larvae through ultrastructure, morphological change, and DNA damage. Treating midgut epithelium with AgNPs led to many alterations in dark conditions, disintegrated epithelium, swollen cells, and shrunken nucleus. Organelles appeared in a loose manner and mitochondria were without cristae, endoplasmic reticulum had dark spots, and peritrophic membrane was loose in appearance. Fatty tissues were vacuolized and muscle fibers lacked normal striations and had many gaps and lysosomal bodies. In the light conditions, the epithelium appeared with detached cells and many vacuoles, organelles were ruptured with many gaps in between, and secretory vesicles were scattered. Peritrophic membrane disappeared. Muscles collapsed and vacuolized loosed fatty tissues were detected. On the other hand, control larvae epithelium appeared regularly distinct, with organelles intact and muscles had clear normal striations. Data showed that AgNPs caused ultrastructural and morphological changes of the external cuticle of the 4th instar larvae along with a significant effect on DNA damage that occurred after the larval treatment, reflecting the toxicity of AgNPs.

Urinary IgG, serum CX3CL1 and miRNA-152-3p: as predictors of nephropathy in Egyptian type 2 diabetic patients.

The purpose of this study was to assess the role of urinary IgG, serum CX3CL1 and miRNA 152-3p levels as predictors of nephropathy in type 2 Egyptian diabetic patients. Sixty type 2 diabetic patients and twenty healthy controls were enrolled in a cross-sectional study. Then they were grouped into: three groups based upon urine albumin excretion (UAE). The expression of miRNA 152-3p in serum was measured using quantitative polymerase chain reaction (RTq-PCR). Serum CX3CL1 and urinary IgG concentrations were measured by ELISA. RTq-PCR revealed that serum miRNA-152-3p levels in patients were significantly higher than in controls. There was significant differences between group with normoalbuminuria and groups with diabetic nephropathy DN as regard to age, duration of nephropathy, Albumin/Creatinine ratio (A/C ratio), creatinine, urine IgG, CX3CL1 and HbA1c. In diabetic patients, there was a significant positive correlation between miRNA-152-3p levels and disease duration only as well as significant positive correlations between urinary IgG levels and age, disease duration, serum creatinine, A/C ratio, and urea. Positive correlation between serum fractalkine CX3CL1 level and age, duration of disease, urea, creatinine, A/C ratio, HbA1C and IgG in patient with DN. Serum CX3CL1 level, urinary IgG were significantly increased with the progress of nephropathy so these integrated biomarkers could be used as good predictors for early identification of nephropathy. But miRNA- 152-3p has inadequate prognostic indicator for ESRD progression.

IR-enhanced photothermal therapeutic effect of graphene magnetite nanocomposite on human liver cancer HepG2 cell model.

Background: Graphene magnetite nanocomposites (G/Fe3O4) exhibit light photothermal conversion upon enhancement by 808 nm IR laser excitation. We evaluated the cytotoxic and photothermal effects of G/Fe3O4 on a HepG2 human liver cancer cell model. Methods: Graphene nanosheets (rGO), magnetite nanoparticles (Fe3O4), and G/Fe3O4 were prepared by chemical methods and characterized using transmission electron microscopy, Raman spectroscopy, zeta analysis, and vibrating sample magnemeter. Dark and light cytotoxicity were screened with colorimetric Sulforhodamine B cell viability assay after 24 and 48 hours. DNA fragmentation and some apoptotic genes on a transcriptional RNA level expression were performed. All prepared nanomaterials were evaluated for their photothermal effect at concentrations of 10 and 50 µg/mL. The power density incident on the cells by 300 mW 808 IR diode laser was 0.597 W/cm2. Results: Treatment of HepG2 with 400 µg/mL of rGO, Fe3O4, and G/Fe3O4 showed alteration in cell morphology after 24 hours of cell treatment and revealed toxic effects on cellular DNA. Evaluation of the cytotoxic effects showed messenger RNA (mRNA) in ß-actin and Bax apoptotic genes, but no expression of mRNA of caspase-3 after 24 hours of cell exposure, suggesting the involvement of an intrinsic apoptotic caspase-independent pathway. A photothermal effect was observed for G/Fe3O4 after irradiation of the HepG2 cells. A marked decrease was found in cell viability when treated with 10 and 50 µg/mL G/Fe3O4 from 40% to 5% after 48 hours of cell treatment. Conclusion: Results indicate that G/Fe3O4 nanocomposite was effective at transformation of light into heat and is a promising candidate for cancer therapy.

Synthesis, Characterization and Cytotoxic Evaluation of Graphene Oxide Nanosheets: In Vitro Liver Cancer Model

Background: Graphene nanosheets have a broad spectrum of biomedical applications. Hepatocellular cancer (HCC) is a major health problem in the Egyptian population. Currently, treatment strategies are invasive and have several adverse side effects. Thus, other approaches are required for managing this aggressive type of cancer. Our objective here was to prepare and characterize graphene oxide nanosheets and evaluate cytotoxic effect at the molecular level in an in vitro human liver cancer cell model (HepG2). Methods: Graphene oxide nanosheets were generated by chemical oxidation and characterized by transmission electron microscopy and X-ray diffraction. Cytotoxic effects in HepG2 cells were monitored by sulforhodamine B (SRB) colorimetric assay followed by flow cytometric analysis. Molecular investigations of DNA fragmentation and expression of some apoptotic genes at the transcriptional RNA level were also performed. Results: Treatment of HepG2 cells with 400µg/ml graphene oxide nanosheets showed alteration in cell morphology after 24 h. Flow cytometry revealed accumulation of cells in S phase of cell cycle followed by dramatic effects on cellular DNA. Extensive evaluation of the cytotoxic effects of graphene oxide showed increased mRNA Bax apoptotic gene expression with not of P53 and caspase-3 mRNA after 24h, suggesting involvement of an intrinsic apoptotic caspase-independent pathway. Conclusion. Graphene oxide can mediate apoptotic gene signaling in human liver cancer cells opening a novel approach to cancer management. Further analyses at the molecular level are now required to confirm our results and facilitate biomedical applications in vivo.

Rapid and sensitive microplate assay for screening the effect of silver and gold nanoparticles on bacteria.

BACKGROUND & AIM: Nanomaterials are the leading requirement of the rapidly developing field of nanomedicine and bionanotechnology, and in this respect, nanotoxicology research is gaining great importance. In the field of infections, nanoparticles are being utilized as therapeutic tools against microbes, thus understanding the properties of nanoparticles and their effect on microbes is essential prior to clinical application. The aim of this study was to evaluate a microplate-based assay for monitoring the toxicity of silver and gold nanoparticles on bacteria. METHOD: Escherichia coli, a Gram-negative bacteria, and Staphylococcus capitis, a Gram-positive bacteria, were exposed to different concentrations of gold and silver nanoparticles. RESULTS: Analysis of bacterial growth showed that the toxicity of silver nanospheres is higher than that of gold nanospheres. The toxicity of silver nanoparticles is dependent on their concentration, whereas in the case of gold nanoparticles, there is no significant toxic effect. Therefore, the described microplate assay could be used as a rapid and sensitive method for detection of bacterial growth inhibition.