Innovative green/non-toxic Bi2S3@g-C3N4 nanosheets for dark antimicrobial activity and photocatalytic depollution: Turnover assessment.

Herein, green and non-toxic bismuth sulphide@graphitic carbon nitride (Bi2S3@g-C3N4) nanosheets (NCs) were firstly synthesized by ultrasonicated-assisted method and characterized with different tool. Bi2S3@g-C3N4 NCs antimicrobial activity tested against three types of microbes. As well the heterostructured Bi2S3@g-C3N4 NCs was investigated for removing dye and hexavalent chromium under visible light and showed high efficiency of photocatalytic oxidation/reduction higher than g-C3N4 alone, attributing to lower recombination photogenerated electron-hole pairs. Bi2S3@g-C3N4 NCs showed high antimicrobial efficiencies against Staphylococcus aureus (S. aureus) as a Gram positive bacterium, Escherichia coli (E. Coli)as a Gram negative bacterium and Candida albicans (C. albicans) and that the disinfection rates are 99.97%, 99.98% and 99.92%, respectively. The core mechanism is that the bacterial membrane could be destroyed by reactive oxygen species. The Bi2S3@g-C3N4 NCs is promising for environmental disinfection including water and public facilities disinfection and solar photocatalytic depollution. Turnover number (TON) and Turnover frequency (TOF) are used as concise assessment indicator for photocatalytic efficiency.

Utilization of activated carbon for maximizing the efficiency of zirconium oxide for photodegradation of 4-octylphenol.

Utilization of AC/zirconium oxide (ZrO2) for the removal of 4-octylphenol (4-OP) from aqueous solution has been studied under simulated visible-light as a cost effective technique. To draw complete images for the prepared materials, a series of characterization methods was performed. Brunauer-Emmett-Teller (BET) data has proved that AC has high surface area and total pore volumes that are decreased after incorporation of ZrO2. Morphologically, TEM showed massive quantity of ZrO2 spherical shape nanoparticles loaded with carbon and EDX showed the uniform distribution of all the prepared materials. The photocatalytic performance has been traced via adopting a matrix effect analysis to correlate the photodegradation of 4-OP in the presence of visible light as a time function, pH, photocatalyst dose and initial concentration of 4-OP. The positive impact of AC content in AC/ZrO2 composite on the adsorption of 4-OP was strikingly observed with expanding the AC content in AC/ZrO2 composite up to 33% (wt/wt). Almost 97% of the 4-OP was removed within 180 min under simulated visible light. The optimum reaction conditions for 95% removal of 4-OP were 120 min, 1 g L-1 catalyst dose at pH 8. The photocatalytic degradation of the 4-OP was well fitted with pseudo first-order L-H kinetic model.

Removal of pharmaceutical pollutants from synthetic wastewater using chemically modified biomass of green alga Scenedesmus obliquus.

Pharmaceutical compounds are considered emerging environmental pollutants that have a potential harmful impact on environment and human health. In this study, the biomass of alga (Scenedesmus obliquus) was modified using alkaline solution, and used for the biosorption of tramadol (TRAM) and other pharmaceuticals. The adsorption kinetics and isotherms were investigated. The obtained results reveal high adsorption capacity of tramadol over modified algal biomass (MAB) after 45min with removal percentage of 91%. Pseudo-second order model was well fitted with the experimental data with correlation coefficient (0.999). Biosorption of tramadol on modified algal biomass proceeds with Freundlich isotherm model with correlation coefficient (0.942) that emphasized uptake of TRAM by MAB is driven by chemisorption. FTIR spectra of MAB before and after the adsorption were analyzed; some IR bands were detected with slight shift and low intensity suggesting their involving in adsorption. The tramadol biosorption by MAB is a chemical process as confirmed by Dubinin-Radushkevich. The adsorption of pharmaceutical over MAB is mainly preceded by hydrophilic interactions between amino and carbonyl groups in pharmaceutical molecules and hydroxyl and carbonyl functional groups on surface of biosorbent. It was emphasized by disappearance O-H and C-O from biomass IR spectra after adsorption. In matrix of pharmaceutical, the recorded adsorption capacities for CEFA, PARA, IBU, TRAM and CIP are 68, 58, 42, 42 and 39mg/g over MAB at natural pH and MAB dose of 0.5g/L. Furthermore, oxygen uptake by bacteria was applied for estimate the toxicity of pharmaceutical. The recorded result concluded the efficient reusability of modified algal biomass for biosorption of pharmaceuticals, as well only the adsorption efficiency decreased by 4.5% after three runs. Subsequently, the modified algal biomass is a promising reusable adsorbent for decontamination of wastewater from pharmaceuticals.

Photothermal effectiveness of microporous carbon nanospheres incorporated with polysulfone in direct contact membrane distillation.

Carbon nano-spheres (CNS) were synthesized via a hydrothermal method using d-glucose as a precursor, followed by pyrolysis in a nitrogen atmosphere. The resulting CNS were integrated into polysulfone (PSF) membranes to enhance their photothermal properties. Characterization using various techniques revealed improved thermal properties upon CNS inclusion, with a notable increase in membrane surface temperature and enhancement of contact angle (CA) and liquid entry pressure (LEP). Composite PSF membranes containing varying CNS concentrations (0.25-5%) exhibited optimal performance at 3% CNS concentration, demonstrating enhanced morphological conformation and photothermal attributes. Evaluation under tungsten bulbs light using a photothermal membrane distillation system showed significant improvement in membrane distillation flux, achieving a maximum water flux of 7.73 L m-2 h-1 and a salt rejection rate of 99.9%. These findings highlight the potential of hydrothermal CNS in enhancing photothermal properties and membrane performance for applications in desalination and wastewater treatment.

Mass flow and consumption calculations of pharmaceuticals in sewage treatment plant with emphasis on the fate and risk quotient assessment.

In Egypt, pharmaceuticals consumption increased dramatically owing to the population growth and the unrestricted sale manner. Accordingly, the occurrence and fate of nine common pharmaceutical active compounds (PhACs) were scrutinized at a sewage treatment plant (STP) in Giza, Egypt. The levels of these PhACs were assessed in different the wastewater treatment stages and dewatered sludge phase using high-performance liquid chromatography coupled with photodiode arrays detector. The average concentrations of the total PhACs detected in influent, primary sedimentation effluent (PSE) and final effluent (FE) were 227, 155 and 89 µg L-1, respectively. The overall removal efficiency of the individual PhACs ranged from 18 to 72% removal. The occurrence trend revealed that biodegradation and adsorption are the concurrently removal mechanisms of the studied PhACs. The overall consumption per day in West of Greater Cairo was estimated based on influent concentration of STP. Sulfamethoxazole, paracetamol and diclofenac were detected with the highest levels in the influent of STP, PSE and FE as well as in the dewatered sludge. Furthermore, the high concentrations of these compounds in the sludge confirm the adsorption pathway removal of theses PhACs. The risk quotient (RQ) assessment for the detected PhACs in FE is greatly higher than the predicted non-effect concentration (PNEC). Conclusively, the FE of STP is considered a risky source for PhACs in adjacent surface water.

Potential health risk assessment for heavy metals in Tilapia fish of different spatiotemporal monitoring patterns in Kafr El-Shaikh and El-Faiyum Governorates of Egypt.

Heavy metal (HMs) levels were evaluated in aquacultured tilapia fish collected from two highly producing districts in Egypt (Kafr El-Sheikh and El-Faiyum Governorates) during two seasons (autumn 2021 and spring 2022). As well, health risk assessment of exposure to HMs in tilapia fish was studied. The results revealed that six HMs: As, Cu, Fe, Mn, Cr and Zn were predominant in fish samples of the first season (autumn 2021), while most of HMs were existed in samples of the second season. All samples of the two seasons were free of Hg. Notably, autumn season's fish samples showed higher concentrations of HMs than those of the spring season. As well, Kafr El-Sheikh farms were highly contaminated with HMs than those of El-Faiyum governorate. Risk assessment results indicated that the THQ values of As substantially exceeded 1 either for Kafr El-Shaikh samples (3.15 ± 0.5) or for El-Faiyum samples (2.39 ± 0.8) of autumn season. Meanwhile, THQ values for all HMs, in spring season 2021, were less than one whole. These results indicated a potential health risk arising from the exposure to HMs, As in particular, in fish samples of autumn season as compared to those of spring season. Therefore, there is a need for remedial applications, in such polluted aquacultures in autumn season, which are currently under investigation as an integral part of the research project that funded the current study.

First Emergence of NDM-5 and OqxAB Efflux Pumps Among Multidrug-Resistant Klebsiella pneumoniae Isolated from Pediatric Patients in Assiut, Egypt.

Introduction: New Delhi metallo-ß-lactamase (NDM)-producing K. pneumoniae poses a high risk, especially among Egyptian pediatric patients who consume carbapenems antibiotics very widely and without adequate diagnostic sources. In addition, presence of efflux pump genes such as OqxAB increases resistance against many groups of antimicrobials which exacerbates the problem faced for human health. This study aimed to determine NDM variants among K. pneumoniae strains isolated from pediatric patients in Egypt, analyze the presence of OqxAB genes, and molecular characterization of blaNDM-5-positive K. pneumoniae. Methods: Fifty-six K. pneumoniae isolates were recovered from pediatric patients, and tested for carbapenemase by modified carbapenem inactivation methods (mCIM) test. Minimum inhibitory concentrations of meropenem and colistin were determined by meropenem E-test strips and broth microdilution, respectively. PCR was used for the detection of the resistant genes (ESBL gene (blaCTX-M), carbapenemase genes (blaNDM, blaKPC) colistin resistant (mcr1, mcr2)) and genes for efflux pump (oqxA and oqxB). BlaNDM was sequenced. The effect of efflux pump in NDM-5-producing isolates was assessed by measuring MIC of ciprofloxacin and meropenem before and after exposure to the carbonyl cyanide 3-chlorophenylhydrazone (CCCP). The horizontal gene transfer ability of blaNDM-5 was determined using liquid mating assay and PCR-based replicon typing (PBRT) was done to determine the major plasmid incompatibility group. Results: Twenty-nine isolates were positive for blaNDM-1, nine isolates were positive for blaNDM-5, and 15 isolates were positive for blaKPC. There is a significant increase of meropenem MIC of NDM-5-positive isolates compared with NDM-1-positive isolates. In addition, 38 isolates were positive for CTX-M, and 15 isolates were positive for mcr1. Both OqxA and OqxB were detected in 26 isolates and 13 isolates were positive for OqxA while 11 isolates were positive for OqxB only. All NDM-5-producing isolates except one isolate could transfer their plasmids by conjugation to their corresponding transconjugants (E. coli J53). Plasmid replicon typing showed that FII was predominant in NDM-5-producing K. pneumoniae. Similar strains were found between the three isolates and similarity was also detected between the two isolates. Conclusion: The highly resistant K. pneumoniae producing blaNDM-5 type was firstly isolated from pediatric patients. The association of efflux pump genes such as OqxAB is involved in resistance to ciprofloxacin. This highlighted the severity risk of blaNDM-5-positive K. pneumonia as it could transfer blaNDM-5 to other bacteria and has more resistance against carbapenems. This underlines the importance of continuous monitoring of infection control guidelines, and the urgent need for a national antimicrobial stewardship plan in Egyptian hospitals.

Production and Characterization of Bacterial Ghost Vaccine against Neisseria meningitidis.

Bacterial ghosts (BGS) are empty non-living envelopes produced either genetically or chemically. This study investigated a novel chemical protocol for the production of Neisseria meningitidis ghost vaccine using tween 80 followed by a pH reduction with lactic acid. For our vaccine candidate, both safety and immunogenicity aspects were evaluated. The ghost pellets showed no sign of growth upon cultivation. BGS were visualized by scanning electron microscopy, illustrating the formation of trans-membrane tunnels with maintained cell morphology. Gel electrophoresis showed no distinctive bands of the cytoplasmic proteins and DNA, assuring the formation of ghost cells. In animal model, humoral immune response significantly increased when compared to commercial vaccine (p < 0.01). Moreover, serum bactericidal assay (SBA) recorded 94.67% inhibition compared to 64% only for the commercial vaccine after three vaccination doses. In conclusion, this is the first N. meningitidis ghost vaccine candidate, proven to be effective, economic, and with significant humoral response and efficient SBA values; however, clinical studies should be performed.

An innovative dual recognition aptasensor for specific detection of Staphylococcus aureus based on Au/Fe3O4 binary hybrid.

Pathogenic bacteria cause disease outbreaks and threaten human health, prompting the research on advanced detection assays. Herein, we developed a selective molecular imprinted aptasensor for sensitive and prompt quantitation of Staphylococcus aureus (S. aureus) bacteria. The aptasensor was constructed by immobilization of aptamer on gold nanoparticles modified magnetic nanoparticles (apt-AuNPs@ Fe3O4). A functional monomer (o-phenylenediamine, o-phen) was electro-polymerized on the surface of the as-synthesized nanocomposite in the presence of a template (S. aureus). After removing S. aureus, the formed imprinted sites were available to extract pathogenic bacteria from complicated matrices. The surface morphology of the as-fabricated nanocomposites was characterized using different spectroscopic and electrochemical methods. Moreover, we thoroughly evaluated factors affecting the synthesis and determination procedures. The molecular imprinted aptasensor exhibited a wide linear range of 101-107 CFU mL-1 with a Limit of Detection, LOD (signal to noise = 3) of 1 CFU mL-1. The aptasensor detected S. aureus in milk, conduit water, and apple juice samples with good recoveries % and satisfactory relative standard deviations (RSDs %) values.

Satellite observations for monitoring atmospheric NO2 in correlation with the existing pollution sources under arid environment.

Monitoring of air pollutants using satellite data has been largely improved over the past few decades, which can provide deeper insights into the effects of anthropogenic activities on the air quality. The observations and measurements of atmospheric NO2 are poorly investigated in North Africa, therefore, the current study applied a multi-proxy approach to better understand of the ambient environment. This approach is based on satellite observations, chemical and biological analyses, and investigative information during fieldworks. The Aura satellite provides the basic data for the current study with fine resolution of atmospheric NO2 and O3 concentrations. The obtained results reveal noticeable increases of atmospheric NO2 values since the 2011, where its emission reaches the peak during summer season that is characterized by high anthropogenic activities. The study area has many sources for NO2 emissions, such as the urban region, traffic, as well as the NH3 emission that is in turn converted to NO2. Although the discharged and spreading wastewater (80,000 m3/day in summer) has a limited role in NO2 emissions, it represents an indicator of the anthropogenic activities. The wastewater analyses confirm the occurrence of nitrate (NO3 -), nitrite (NO2 -), and ammonia (NH4 +), which provide an appropriate condition for NO2 release. The analyses of multi-climate datasets (previous records and the expected scenarios) reveal an increase of temperature accompanied by decrease of precipitation which confirmed the existence of climate change. Therefore, the study presents a set of suggestions to mitigate the release of NOx gases and achieve Net-Zero emissions.

Impact of Geographical Location on the Gut Microbiota Profile in Egyptian Children with Type 1 Diabetes Mellitus: A Pilot Study.

Purpose: To investigate the compositional and functional characteristics of T1DM-associated gut microbiota in two Egyptian cities and to study the geographical locality effects. Patients and Methods: This case-control study included 32 children with controlled T1DM and 16 controls, selected from two different regions of Egypt. The gut microbiota of both diabetic and control children was analyzed through 16S rRNA gene sequencing; this was done using the Illumina MiSeq platform. Results: Consistent findings among the diabetic children included significantly lower alpha diversity than the control children, as well as a lower mean Firmicutes/Bacteroidetes (F/B) ratio, and reduced proportions of Firmicutes and the genera Prevotella and Ruminococcus. In the diabetic children, there were also significantly enriched representations of Actinobacteria, Bacteroidetes, and Proteobacteria and the genera Lactobacilli, Bacteroides, and Faecalibacterium. When comparing the two diabetic groups, the Ismailia group (IsDM) was found to have a significantly higher F/B ratio and diversity indices, with resultant differences at the functional level. Conclusion: There are a number of consistent changes in the microbiota profile characterizing the diabetic groups irrespective of the geographical location including significantly lower alpha diversity, mean Firmicutes/ Bacteroidetes (F/B) ratio, and reduced proportions of Firmicutes and genera Prevotella and Ruminococcus. There are also significantly enriched representations of Actinobacteria, Bacteroidetes, and Proteobacteria and genera Lactobacilli, Bacteroides, and Faecalibacterium pointing to the greater driving power of the disease.

Nanofiltration Process for Enhanced Treatment of RO Brine Discharge.

Brine discharge of reverse osmosis (RO) desalination plants represents a challenge for both inland and coastal desalination plants. Zero-liquid discharge (ZLD) can be accomplished by using additional stages of RO, which can recycle that brine water, but the key challenge is the high concentration of divalent salts. These divalent salts (especially calcium and magnesium salts) forms a scaling layer on the RO membrane surfaces and hence shorten the life-time of the membranes. In this study, the nanofiltration (NF) procedure was used to remove divalent ions from the brine discharge to minimize the load on additional stages of RO membranes. One of the most critical considerations influencing the selection of an effective NF is the water type, which is expected here by calculation of some hydrochemical parameters (major ions, hypothetical soluble salts (electrolyte), and saturation indices). NF experiments were undertaken on a lab-scale using a low-pressure hand-made system of 4-7 bar. Synthetic single salts solutions and two real brine water discharge (brackish (BWRO) and seawater (SWRO) desalination plants) were used as a feed solution for NF system. The chemical characteristics of the RO-feed, RO-brine, NF-permeate, and NF-reject in were investigated. Electrolyte concentrations and saturation indices were determined based on the concentration of the major ions and the NETPATH software package, respectively. Calculations reveal that the brine concentrate samples contained mostly MgSO4 and MgCl2 soluble salts. The results show that 79-89% of the total dissolved salts (TDS) and 96-98% of the total hardness (TH) were retained using the NF process. The salt rejection of the NF membrane follows the order of CaSO4, Na2SO4, MgSO4, MgCl2, and NaCl with a percent of 97.4, 97.3, 95.2, 93.4, and 79%, respectively.

Microbial aspects and potential markers for differentiation between bacterial and viral meningitis among adult patients.

OBJECTIVES: Meningitis is a medical emergency with permanent disabilities and high mortality worldwide. We aimed to determine causative microorganisms and potential markers for differentiation between bacterial and viral meningitis. METHODOLOGY: Adult patients with acute meningitis were subjected to lumber puncture. Cerebrospinal fluid (CSF) microorganisms were identified using Real-time PCR. PCT and CRP levels, peripheral and CSF-leucocyte count, CSF-protein and CSF-glucose levels were assessed. RESULTS: Out of 80 patients, infectious meningitis was confirmed in 75 cases; 38 cases were bacterial meningitis, 34 cases were viral meningitis and three cases were mixed infection. Higher PCT, peripheral and CSF-leukocytosis, higher CSF-protein and lower CSF-glucose levels were more significant in bacterial than viral meningitis patients. Neisseria meningitides was the most frequent bacteria and varicella-zoster virus was the most common virus. Using ROC analyses, serum PCT and CSF-parameters can discriminate bacterial from viral meningitis. Combined ROC analyses of PCT and CSF-protein significantly improved the effectiveness in predicting bacterial meningitis (AUC of 0.998, 100%sensitivity and 97.1%specificity) than each parameter alone (AUC of 0.951 for PCT and 0.996 for CSF-protein). CONCLUSION: CSF-protein and serum PCT are considered as potential markers for differentiating bacterial from viral meningitis and their combination improved their predictive accuracy to bacterial meningitis.

Alterations in skin microbiome mediated by radiotherapy and their potential roles in the prognosis of radiotherapy-induced dermatitis: a pilot study.

Radiotherapy-induced dermatitis (RID) is an inflammatory cutaneous disorder that is acquired as an adverse effect of undergoing radiotherapy. Skin microbiome dysbiosis has been linked to the outcomes of several dermatological diseases. To explore the skin microbiota of RID and deduce their underlying impact on the outcome of RID, cutaneous microbiomes of 78 RID patients and 20 healthy subjects were characterized by sequencing V1-V3 regions of 16S rRNA gene. In total, a significantly apparent reduction in bacterial diversity was detected in microbiomes of RID in comparison to controls. Overall, the raised Proteobacteria/ Firmicutes ratio was significantly linked to delayed recovery or tendency toward the permanence of RID (Kruskal Wallis: P = 2.66 × 10-4). Moreover, applying enterotyping on our samples stratified microbiomes into A, B, and C dermotypes. Dermotype C included overrepresentation of Pseudomonas, Staphylococcus and Stenotrophomonas and was markedly associated with delayed healing of RID. Strikingly, coexistence of diabetes mellitus and RID was remarkably correlated with a significant overrepresentation of Klebsiella or Pseudomonas and Staphylococcus. Metabolic abilities of skin microbiome could support their potential roles in the pathogenesis of RID. Cutaneous microbiome profiling at the early stages of RID could be indicative of prospective clinical outcomes and maybe a helpful guide for personalized therapy.

Proton exchange membrane based on graphene oxide/polysulfone hybrid nano-composite for simultaneous generation of electricity and wastewater treatment.

Microbial fuel cell (MFC) is a combined technology for simultaneous generation of electricity and wastewater treatment. In MFC, the proton exchange membrane (PEM) is an essential component affecting electricity generation. In the current study, two proton exchange membranes, namely sulfonated polyethersulfone (SPES) and graphene oxide/sulfonated -polyethersulfone hybrid nanocomposite (GO-SPES), were prepared and characterized using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The collected information confirmed the successful preparation of the membranes. Moreover, contact angle measurements, ion exchange capacity and degree of sulfonation of the prepared membranes were determined. The results showed that the introduction of GO nanoparticles into SPES membrane improved its proton exchange capability and resulted in better performance. The power density and the current generated from SPES membrane were 60 mW/m2 and 425 mA/m2, respectively. For GO-SPES, the obtained power density was 101.2 mW/m2 and the current was 613 mA/m2. Both membranes showed comparable chemical oxygen demand (COD) removal efficiency of about 80%; suggesting that the prepared membranes are working efficiently in wastewater treatment as PEMs in MFCs. As a final point, the performance of GO-SPES membrane was compared to the performance of the well-known Nafion® 117 membrane and the results were promising. To conclude, the GO-SPES membrane is an outstanding membrane for use as PEM in MFCs for simultaneous generation of electricity and wastewater treatment.

Thermophysical Properties of Hybrid Nanofluids and the Proposed Models: An Updated Comprehensive Study.

Thermal performance of energy conversion systems is one of the most important goals to improve the system's efficiency. Such thermal performance is strongly dependent on the thermophysical features of the applied fluids used in energy conversion systems. Thermal conductivity, specific heat in addition to dynamic viscosity are the properties that dramatically affect heat transfer characteristics. These features of hybrid nanofluids, as promising heat transfer fluids, are influenced by different constituents, including volume fraction, size of solid parts and temperature. In this article, the mentioned features of the nanofluids with hybrid nanostructures and the proposed models for these properties are reviewed. It is concluded that the increase in the volume fraction of solids causes improvement in thermal conductivity and dynamic viscosity, while the trend of variations in the specific heat depends on the base fluid. In addition, the increase in temperature increases the thermal conductivity while it decreases the dynamic viscosity. Moreover, as stated by the reviewed works, different approaches have applicability for modeling these properties with high accuracy, while intelligent algorithms, including artificial neural networks, are able to reach a higher precision compared with the correlations. In addition to the used method, some other factors, such as the model architecture, influence the reliability and exactness of the proposed models.

Role of Serum Vitamin D, Interleukin 13, and microRNA-135a in Hepatocellular Carcinoma and Treatment Failure in Egyptian HCV-Infected Patients Receiving Direct Antiviral Agents.

Direct-acting antivirals (DAAs) are used for hepatitis C virus (HCV) treatment. However, treatment failure and hepatocellular carcinoma (HCC) development following treatment was reported. In this study, we assessed the role of serum vitamin D, interleukin 13 (IL-13), and microRNA-135a in the prediction of treatment failure with DAA and HCC development among Egyptian HCV-infected patients. A total of 950 patients with HCV-related chronic liver disease underwent DAA treatment. Before DAAs, serum vitamin D and IL-13 were determined by ELISA, and gene expression of miRNA-135a was assessed in serum by real-time PCR. The predictive abilities of these markers were determined using the receiver operating characteristic (ROC) curve. Sustained virological response (SVR) was achieved in 92.6% of HCV-infected patients (responders). High viral load, IL-13, miRNA-135a, and low vitamin D levels were associated with treatment failure and HCC development. HCC development was recorded in non-responders, but not in the responders (35.7% vs. 0% p < 0.001). In conclusion: serum IL-13, Vitamin D, and miRNA-135a could be potential biomarkers in monitoring DAA treatment and HCC prediction. DAAs-induced SVR may decrease the incidence of HCC.

Hepatitis E Virus Persistence and/or Replication in the Peripheral Blood Mononuclear Cells of Acute HEV-Infected Patients.

BACKGROUND: Hepatitis E virus (HEV) causes about 14 million infections with 300,000 deaths and 5,200 stillbirths worldwide annually. Extrahepatic manifestations are reported with HEV infections, such as renal, neurological, and hematological disorders. Recently, we reported that stool-derived HEV-1 replicates efficiently in human monocytes and macrophages in vitro. However, another study reports the presence of viral RNA but no evidence of replication in the PBMCs of acute hepatitis E (AHE) patients. Therefore, the replication of HEV in PBMCs during AHE infection is not completely understood. METHODS: PBMCs were isolated from AHE patients (n = 17) enrolled in Assiut University Hospitals, Egypt. The viral load, positive (+) and negative (-) HEV RNA strands and viral protein were assessed. The gene expression profile of PBMCs from AHE patients was assessed. In addition, the level of cytokines was measured in the plasma of the patients. RESULTS: HEV RNA was detected in the PBMCs of AHE patients. The median HEV load in the PBMCs was 1.34 × 103 IU/ml. A negative HEV RNA strand and HEV open reading frame 2 protein were recorded in 4/17 (23.5%) of the PBMCs. Upregulation of inflammatory transcripts and increased plasma cytokines were recorded in the AHE patients compared with healthy individuals with significantly elevated transcripts and plasma cytokines in the AHE with detectable (+) and (-) RNA strands compared with the AHE with the detectable (+) RNA strand only. There was no significant difference in terms of age, sex, and liver function tests between AHE patients with detectable (+) and (-) RNA strands in the PBMCs and AHE patients with the (+) RNA strand only. CONCLUSION: Our study shows evidence for in vivo HEV persistence and replication in the PBMCs of AHE patients. The replication of HEV in the PBMCs was associated with an enhanced immune response, which could affect the pathogenesis of HEV.

Collagenase loaded chitosan nanoparticles for digestion of the collagenous scar in liver fibrosis: The effect of chitosan intrinsic collagen binding on the success of targeting.

A variety of hepatic insults result in the accumulation of collagen-rich new extracellular matrix in the liver, ultimately culminating in liver fibrosis and cirrhosis. For such reasons, approaches looking into digestion of the collagen-rich extracellular matrix present an interesting therapeutic approach for cases of chronic liver disease, where the fibrotic scar is well established. Portal collagenase administration has recently led to the successful reversion of cirrhosis in an experimental rabbit model. Notwithstanding, the question of how such a sensitive therapeutic macromolecule could be administered in a less invasive manner, and in a way that preserves its functionality and avoids digestion of other non-hepatic vital collagen presents itself. Chitosan is a biodegradable polymer that has been reported to interact and bind to collagen. Chitosan nanoparticles (CS NPs) have also been reported to encapsulate therapeutic proteins, maintaining their functional form and protecting them from in-vivo degradation. For such reasons, CS NPs were loaded with collagenase and evaluated in-vitro and in-vivo for their ability to target and digest collagen. CS NPs were able to encapsulate collagenase (≈ 60% encapsulation efficiency) and release its content in active form. To determine whether chitosan's collagen interaction would enable NP collagen binding or whether the modification with collagen binding peptides (CBPs) is necessary, CS NPs were modified with the CBP; CCQDSETRTFY. Since the density of targeting ligand and the length of tether play a significant role in the success of active targeting, the surface of NPs was modified with different densities of the CBP either directly or using a polyethylene glycol (PEG) spacer. PEGylated NPs showed higher levels of CBP tagging; high, intermediate and low density of CBPs corresponded to 585.8 ± 33, 252.9 ± 25.3 and 56.5 ± 8.8 µg/mL for PEGylated NPs and 425.56 ± 12.67, 107.91 ± 10.3 and 49.86 ± 3.2 µg/mL for unPEGylated NPs, respectively. In-vitro collagen binding experiments showed that unmodified CS NPs were able to bind collagen and that modification with CBPs either directly or via PEG did not enhance collagen binding. In-vivo experiments demonstrated that unmodified CS NPs were able to reverse fibrosis with a survival rate of 100% at the end of the study, indicating the ability of CS NPs to deliver functional collagenase to the fibrotic liver and making the use of CBPs unnecessary.

Autoimmune Hepatitis: Shifts in Gut Microbiota and Metabolic Pathways among Egyptian Patients.

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder with complex immunopathogenesis. Dysbiosis has been linked to many autoimmune diseases, but its detailed role in autoimmune hepatitis (AIH) still needs rigorous evaluation, especially in Egypt. We aimed to identify the shift in the gut microbiota profile and resultant metabolic pathways in AIH Egyptian patients compared to healthy individuals. Stool samples were collected from 15 AIH-naive patients and from 10 healthy individuals. The V3-V4 hyper-variable regions in16S rRNA gene was amplified and sequenced using Illumina MiSeq platform. Significantly lower bacterial diversity in AIH patients was found compared to the controls. A phylum-level analysis showed the overrepresentation of Firmicutes, Bacteroides, and Proteobacteria. At the genus level, AIH-associated enrichment of Faecalibacterium, Blautia, Streptococcus, Haemophilus, Bacteroides, Veillonella, Eubacterium, Lachnospiraceae and Butyricicoccus was reported in contrast to Prevotella, Parabacteroides and Dilaster, which were significantly retracted in such patients. Overall, the predicted metabolic pathways associated with dysbiosis in AIH patients could orchestrate the potential pathogenic roles of gut microbiota in autoimmune disease, though not in a disease-specific manner, calling for future large-scale studies.