Cholera rages in Africa and the Middle East: A narrative review on challenges and solutions.

Background and Aim: Cholera is a life-threatening infectious disease that is still one of the most common acute watery diarrheal diseases in the world today. Acute diarrhea and severe dehydration brought on by cholera can cause hypovolemic shock, which can be fatal in minutes. Without competent clinical therapy, the rate of case fatality surpasses 50%. The purpose of this review was to highlight cholera challenges in Africa and the Middle East and explain the reasons for why this region is currently a fertile environment for cholera. We investigated cholera serology, epidemiology, and the geographical distribution of cholera in Africa and the Middle East in 2022 and 2023. We reviewed detection methods, such as rapid diagnostic tests (RDTs), and treatments, such as antibiotics and phage therapy. Finally, this review explored oral cholera vaccines (OCVs), and the vaccine shortage crisis. Methods: We carried out a systematic search in multiple databases, including PubMed, Web of Science, Google Scholar, Scopus, MEDLINE, and Embase, for studies on cholera using the following keywords: ((Cholera) OR (Vibrio cholera) and (Coronavirus) OR (COVID-19) OR (SARS-CoV2) OR (The Middle East) OR (Africa)). Results and Conclusions: Cholera outbreaks have increased dramatically, mainly in Africa and many Middle Eastern countries. The COVID-19 pandemic has reduced the attention devoted to cholera and disrupted diagnosis and treatment services, as well as vaccination initiatives. Most of the cholera cases in Africa and the Middle East were reported in Malawi and Syria, respectively, in 2022. RDTs are effective in the early detection of cholera epidemics, especially with limited advanced resources, which is the case in much of Africa. By offering both direct and indirect protection, expanding the use of OCV will significantly reduce the burden of current cholera outbreaks in Africa and the Middle East.

Formulation and evaluation of azithromycin-loaded silver nanoparticles for the treatment of infected wounds.

Infected wounds pose a significant challenge in healthcare, requiring innovative therapeutic strategies. Therefore, there is a critical need for innovative pharmaceutical materials to improve wound healing and combat bacterial growth. This study examined the efficacy of azithromycin-loaded silver nanoparticles (AZM-AgNPs) in treating infected wounds. AgNPs synthesized using a green method with Quinoa seed extract were loaded with AZM. Characterization techniques, including X-ray Powder Diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), and Uv-Vis analysis were utilized. The agar diffusion assay and determination of the MIC were used to assess the initial antibacterial impact of the formulations on both MRSA and E. coli. In addition, the antimicrobial, wound-healing effects and histological changes following treatment with the AZM-AgNPs were assessed using an infected rat model. The nanoparticles had size of 24.9 ± 15.2 nm for AgNPs and 34.7 ± 9.7 nm for AZM-AgNPs. The Langmuir model accurately characterized the adsorption of AZM onto the AgNP surface, indicating a maximum loading capacity of 162.73 mg/g. AZM-AgNPs exhibited superior antibacterial properties in vivo and in vitro compared to controls. Using the agar diffusion technique, AZM-AgNPs showed enhanced zones of inhibition against E. coli and MRSA, which was coupled with decreased MIC levels. In addition, in vivo studies showed that AZM-AgNP treated rats had the best outcome characterized by improved healing process, lower bacterial counts and superior epithelialization, compared to the control group. In conclusion, AZM-AgNPs can be synthesized using a green method with Quinoa seed with successful loading of azithromycin onto silver nanoparticles. In vitro and in vivo studies suggest the promising use of AZM-AgNPs as an effective therapeutic agent for infected wounds.

SARS-CoV-2 outbreak: role of viral proteins and genomic diversity in virus infection and COVID-19 progression.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the cause of coronavirus disease 2019 (COVID-19); a severe respiratory distress that has emerged from the city of Wuhan, Hubei province, China during December 2019. COVID-19 is currently the major global health problem and the disease has now spread to most countries in the world. COVID-19 has profoundly impacted human health and activities worldwide. Genetic mutation is one of the essential characteristics of viruses. They do so to adapt to their host or to move to another one. Viral genetic mutations have a high potentiality to impact human health as these mutations grant viruses unique unpredicted characteristics. The difficulty in predicting viral genetic mutations is a significant obstacle in the field. Evidence indicates that SARS-CoV-2 has a variety of genetic mutations and genomic diversity with obvious clinical consequences and implications. In this review, we comprehensively summarized and discussed the currently available knowledge regarding SARS-CoV-2 outbreaks with a fundamental focus on the role of the viral proteins and their mutations in viral infection and COVID-19 progression. We also summarized the clinical implications of SARS-CoV-2 variants and how they affect the disease severity and hinder vaccine development. Finally, we provided a massive phylogenetic analysis of the spike gene of 214 SARS-CoV-2 isolates from different geographical regions all over the world and their associated clinical implications.

Design, synthesis, biological evaluation and docking study of some new aryl and heteroaryl thiomannosides as FimH antagonists.

FimH is a mannose-recognizing lectin that is expressed by Escherichia coli guiding its ability to adhere and infect cells. It is involved in pathogenesis of urinary tract infections and Chron's disease. Several X-ray structure-guided ligand design studies were extensively utilized in the discovery and optimization of small molecule aryl mannoside FimH antagonists. These antagonists retain key specific interactions of the mannose scaffolds with the FimH carbohydrate recognition domains. Thiomannosides are attractive and stable scaffolds, and this work reports the synthesis of some of their new aryl and heteroaryl derivatives as FimH antagonists. FimH-competitive binding assays as well as biofilm inhibition of the new compounds (24-32) were determined in comparison with the reference n-heptyl α-d-mannopyranoside (HM). The affinity among these compounds was found to be governed by the structure of the aryl and heteroarylf aglycones. Two compounds 31 and 32 revealed higher activity than HM. Molecular docking and total hydrophobic to topological polar surface area ratio calculations attributed to explain the obtained biological results. Finally, the SAR study suggested that introducing an aryl or heteroaryl aglycone of sufficient hydrophobicity and of proper orientation within the tyrosine binding site considerably enhance binding affinity. The potent and synthetically feasible FimH antagonists described herein hold potential as leads for the development of sensors for detection of E. coli and treatment of its diseases.

A rare homozygous variant in TERT gene causing variable bone marrow failure, fragility fractures, rib anomalies and extremely short telomere lengths with high serum IgE.

By whole exome sequencing, we identified a homozygous c.2086 C→T (p.R696C) TERT mutation in patients who present with a spectrum of variable bone marrow failure (BMF), raccoon eyes, dystrophic nails, rib anomalies, fragility fractures (FFs), high IgE level, extremely short telomere lengths (TLs), and skewed numbers of cytotoxic T cells with B and NK cytopenia. Haploinsufficiency in the other family members resulted in short TL and osteopenia. These patients also had the lowest bone mineral density Z-score compared to other BMF-patients. Danazol/zoledronic acid improved the outcomes of BMF and FFs. This causative TERT variant has been observed in one family afflicted with dyskeratosis congenita (DC), and thus, we also define a second report and new phenotype related to the variant which should be suspected in severe cases of DC with co-existent BMF, FFs, high IgE level and rib anomalies.

High Incidence of Acute Liver Failure among Patients in Egypt Coinfected with Hepatitis A and Hepatitis E Viruses.

Hepatitis A virus (HAV) and Hepatitis E virus (HEV) are transmitted through the fecal-oral route. HAV outbreaks and one HEV outbreak have been reported in Egypt. However, the impact of HAV-HEV co-infection is not known. In this study, we assessed HEV markers in acute HAV-infected patients (n = 57) enrolled in Assiut University hospitals. We found that 36.8% of HAV-infected patients were also positive for HEV markers (anti-HEV IgM and HEV RNA), while 63.2% of the patients were HAV mono-infected. Demographic and clinical criteria were comparable in both HAV mono-infected patients and HAV-HEV co-infected patients. Although liver enzymes were not significantly different between the two groups, liver transaminases were higher in the co-infected patients. Six patients developed acute liver failure (ALF); five of them were HAV-HEV-co-infected patients. The relative risk of ALF development was 8.5 times higher in HAV-HEV co-infection compared to mono-infection. Three cases of ALF caused by HAV-HEV co-infection were reported in children (below 18 years) and two cases were reported in adults. All patients developed jaundice, coagulopathy, and encephalopathy; all were living in rural communities. In conclusion: HAV-HEV co-infection can be complicated by ALF. The risk of ALF development in HAV-infected patients is higher when coinfection with HEV is present.

Elevated CD39+T-Regulatory Cells and Reduced Levels of Adenosine Indicate a Role for Tolerogenic Signals in the Progression from Moderate to Severe COVID-19.

Viral infections trigger inflammation by controlling ATP release. CD39 ectoenzymes hydrolyze ATP/ADP to AMP, which is converted by CD73 into anti-inflammatory adenosine (ADO). ADO is an anti-inflammatory and immunosuppressant molecule which can enhance viral persistence and severity. The CD39-CD73-adenosine axis contributes to the immunosuppressive T-reg microenvironment and may affect COVID-19 disease progression. Here, we investigated the link between CD39 expression, mostly on T-regs, and levels of CD73, adenosine, and adenosine receptors with COVID-19 severity and progression. Our study included 73 hospitalized COVID-19 patients, of which 33 were moderately affected and 40 suffered from severe infection. A flow cytometric analysis was used to analyze the frequency of T-regulatory cells (T-regs), CD39+ T-regs, and CD39+CD4+ T-cells. Plasma concentrations of adenosine, IL-10, and TGF-ß were quantified via an ELISA. An RT-qPCR was used to analyze the gene expression of CD73 and adenosine receptors (A1, A2A, A2B, and A3). T-reg cells were higher in COVID-19 patients compared to healthy controls (7.4 ± 0.79 vs. 2.4 ± 0.28; p < 0.0001). Patients also had a higher frequency of the CD39+ T-reg subset. In addition, patients who suffered from a severe form of the disease had higher CD39+ T-regs compared with moderately infected patients. CD39+CD4+ T cells were increased in patients compared to the control group. An analysis of serum adenosine levels showed a marked decrease in their levels in patients, particularly those suffering from severe illness. However, this was paralleled with a marked decline in the expression levels of CD73. IL-10 and TGF-ß levels were higher in COVID-19; in addition, their values were also higher in the severe group. In conclusion, there are distinct immunological alterations in CD39+ lymphocyte subsets and a dysregulation in the adenosine signaling pathway in COVID-19 patients which may contribute to immune dysfunction and disease progression. Understanding these immunological alterations in the different immune cell subsets and adenosine signaling provides valuable insights into the pathogenesis of the disease and may contribute to the development of novel therapeutic approaches targeting specific immune mechanisms.

Synthesis, Physicochemical Characterization using a Facile Validated HPLC Quantitation Analysis Method of 4-Chloro-phenylcarbamoyl-methyl Ciprofloxacin and Its Biological Investigations.

A novel derivative of ciprofloxacin (Cpx) was synthesized and characterized using various analytical techniques, including FT-IR spectroscopy, UV-Vis spectroscopy, TEM and SEM analysis, 1H NMR, 13C NMR, and HPLC analysis. The newly prepared Cpx derivative (Cpx-Drv) exhibited significantly enhanced antibacterial properties compared to Cpx itself. In particular, Cpx-Drv demonstrated a 51% increase in antibacterial activity against S. aureus and a 30% improvement against B. subtilis. It displayed potent inhibitory effects on topoisomerases II (DNA gyrase and topoisomerase IV) as potential molecular targets, with IC50 values of 6.754 and 1.913 µg/mL, respectively, in contrast to Cpx, which had IC50 values of 2.125 and 0.821 µg/mL, respectively. Docking studies further supported these findings, showing that Cpx-Drv exhibited stronger binding interactions with the gyrase enzyme (PDB ID: 2XCT) compared to the parent Cpx, with binding affinities of -10.3349 and -7.7506 kcal/mole, respectively.

Characterization and Bio-Evaluation of the Synergistic Effect of Simvastatin and Folic Acid as Wound Dressings on the Healing Process.

Wound healing is a significant healthcare problem that decreases the patient's quality of life. Hence, several agents and approaches have been widely used to help accelerate wound healing. The challenge is to search for a topical delivery system that could supply long-acting effects, accurate doses, and rapid healing activity. Topical forms of simvastatin (SMV) are beneficial in wound care. This study aimed to develop a novel topical chitosan-based platform of SMV with folic acid (FA) for wound healing. Moreover, the synergistic effect of combinations was determined in an excisional wound model in rats. The prepared SMV-FA-loaded films (SMV-FAPFs) were examined for their physicochemical characterizations and morphology. Box-Behnken Design and response surface methodology were used to evaluate the tensile strength and release characteristics of the prepared SMV-FAPFs. Additionally, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction pattern (XRD), and animal studies were also investigated. The developed SMV-FAPFs showed a contraction of up to 80% decrease in the wound size after ten days. The results of the quantitative real-time polymerase chain reaction (RT-PCR) analysis demonstrated a significant upregulation of dermal collagen type I (CoTI) expression and downregulation of the inflammatory JAK3 expression in wounds treated with SMV-FAPFs when compared to control samples and individual drug treatments. In summary, it can be concluded that the utilization of SMV-FAPFs holds great potential for facilitating efficient and expeditious wound healing, hence presenting a feasible substitute for conventional topical administration methods.

Evidence of a Link between Hepatitis E Virus Exposure and Glomerulonephritis Development.

Viruses can trigger glomerulonephritis (GN) development. Hepatitis viruses, especially Hepatitis C virus and Hepatitis B viruses, are examples of the viruses that trigger GN initiation or progression. However, the proof of a correlation between GN and Hepatitis E virus infection is not clear. Some studies confirmed the development of GN during acute or chronic HEV infections, mainly caused by genotype 3. While others reported that there is no relation between HEV exposure and GN development. A recent study showed that a reduced glomerular filtration rate was developed in 16% of acute HEV genotype 1 (HEV-1) infections that returned to normal during recovery. HEV-1 is endemic in Egypt with a high seroprevalence among villagers and pregnant women. There is no available data about a link between HEV and GN in Egypt. METHODS: GN patients (n = 43) and matched healthy subjects (n = 36) enrolled in Assiut University hospitals were included in this study. Blood samples were screened for hepatotropic pathogens. Tests for HEV markers such as HEV RNA and anti-HEV antibodies (IgM and IgG) were performed. Laboratory parameters were compared in HEV-seropositive and HEV-seronegative GN patients. RESULTS: Anti-HEV IgG was detected in 26 (60.5%) out of 43 GN patients. HEV seroprevalence was significantly higher in GN than in healthy controls, suggesting that HEV exposure is a risk factor for GN development. None of the GN patients nor the healthy subjects were positive for anti-HEV IgM or HEV RNA. There was no significant difference between seropositive and seronegative GN patients in terms of age, gender, albumin, kidney function profiles, or liver transaminases. However, anti-HEV IgG positive GN patients had higher bilirubin levels than anti-HEV IgG negative GN patients. HEV-seropositive GN patients had a significantly elevated AST level compared to HEV-seropositive healthy subjects. CONCLUSION: exposure to HEV infection could be complicated by the development of GN.

First Report on Abnormal Renal Function in Acute Hepatitis E Genotype 1 Infection.

Impaired renal functions have been reported with Hepatitis E virus (HEV) infections, especially with genotypes 3 and 4. These complications were reported during the acute and chronic phases of infection. HEV genotype 1 causes acute infection, and the effect of HEV-1 infections on renal functions is not known. We examined the kidney function parameters in the serum of HEV-1 patients (AHE, n = 31) during the acute phase of infection. All of the included patients developed an acute self-limiting course of infection, without progression to fulminant hepatic failure. We compared the demographic, laboratory, and clinical data between AHE patients with normal kidney function parameters and those with abnormal renal parameters. Out of 31 AHE patients, 5 (16%) had abnormal kidney function tests (KFTs) during the acute phase of infection. Three patients had abnormal serum urea and creatinine, and two patients had either abnormal urea or creatinine. Four out of five patients had an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2. AHE patients with abnormal KFTs were older and had a lower level of albumin, but a slightly elevated alanine transaminase (ALT) compared to AHE patients with normal KFTs. There were no significant differences between the two groups in terms of age, sex, liver transaminase levels, and the viral load. Similarly, the clinical presentations were comparable in both groups. Interestingly, these KFTs in patients with abnormal renal parameters returned to normal levels at the recovery. The serum creatinine level was not correlated with patients' age or liver transaminase levels, but it was significantly negatively correlated with albumin level. In conclusion, this study is the first report that evaluated KFTs in patients during the acute phase of HEV-1 infections. Impaired KFTs in some AHE patients resolved at convalescence. KFTs and renal complications should be monitored during HEV-1 infections.

Fatty Acid Conjugated Chalcones as Tubulin Polymerization Inhibitors: Design, Synthesis, QSAR, and Apoptotic and Antiproliferative Activity.

Cancer is often associated with an aberrant increase in tubulin and microtubule activity required for cell migration, invasion, and metastasis. A new series of fatty acid conjugated chalcones have been designed as tubulin polymerization inhibitors and anticancer candidates. These conjugates were designed to harness the beneficial physicochemical properties, ease of synthesis, and tubulin inhibitory activity of two classes of natural components. New lipidated chalcones were synthesized from 4-aminoacetophenone via N-acylation followed by condensation with different aromatic aldehydes. All new compounds showed strong inhibition of tubulin polymerization and antiproliferative activity against breast and lung cancer cell lines (MCF-7 and A549) at low or sub-micromolar concentrations. A significant apoptotic effect was shown using a flow cytometry assay that corresponded to cytotoxicity against cancer cell lines, as indicated by a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. Decanoic acid conjugates were more potent than longer lipid analogues, with the most active being more potent than the reference tubulin inhibitor, combretastatin-A4 and the anticancer drug, doxorubicin. None of the newly synthesized compounds caused any detectable cytotoxicity against the normal cell line (Wi-38) or hemolysis of red blood cells below 100 µM. It is unlikely that the new conjugates described would affect normal cells or interrupt with cell membranes due to their lipidic nature. A quantitative structure-activity relationship analysis was performed to determine the influence of 315 descriptors of the physicochemical properties of the new conjugates on their tubulin inhibitory activity. The obtained model revealed a strong correlation between the tubulin inhibitory activity of the investigated compounds and their dipole moment and degree of reactivity.

Clinical and Bacteriological Analyses of Biofilm-Forming Staphylococci Isolated from Diabetic Foot Ulcers.

Background: Diabetes mellitus is a chronic disease that is associated with increased morbidity and mortality. Unfortunately, foot ulcers and amputations due to diabetes are very common in developing countries. The purpose of this study was to characterize the clinical presentation of diabetic foot ulcer (DFU) infections, isolate the causative agent, and analyze the biofilm formation and distribution of biofilm-related genes among isolated Staphylococci. Material and Methods: The study included 100 diabetic patients suffering from DFUs attending Assiut University Hospital. Swabs were collected and antimicrobial susceptibility testing of the isolates was performed. Biofilm formation was tested phenotypically among staphylococcal isolates and the frequency of different biofilm genes was analyzed by PCR. Clinical presentations of diabetic foot ulcers were correlated with bacterial genetic characteristics. Spa types were determined using DNA Gear-a software. Results: Microbiological analysis showed that 94/100 of the DFUs were positive for bacterial growth. The majority of infections were polymicrobial (54%, n=54/100). Staphylococci were the most commonly detected organisms, of which S. aureus represented 37.5% (n=24/64), S. haemolyticus 23.4% (n=15/64), S. epidermidis 34.3% (n=22/64) and other CNS 4.7% (n=3/64). Interestingly, co-infection with more than one species of Staphylococci was observed in 17.1% (n=11/64) of samples. A high level of antibiotic resistance was observed, where 78.1% (n=50/64) of Staphylococci spp were multidrug-resistant (MDR). Phenotypic detection showed that all isolated Staphylococci were biofilm-formers with different grades. Analysis of biofilm-forming genes among Staphylococci showed that the most predominant genes were icaD, spa, and bap. Isolates with a higher number of biofilm-related genes were associated with strong biofilm formation. Sequencing of the spa gene in S. aureus showed that our isolates represent a collection of 17 different spa types. Conclusion: The majority of DFUs in our hospital are polymicrobial. Staphylococci other than S.aureus are major contributors to infected DFUs. MDR and biofilm formation are marked among isolates, which is paralleled by the presence of different categories of virulence-related genes. All severely infected wounds were associated with either strong or intermediate biofilm formers. The severity of DFU is directly related to the number of biofilm genes.

Risks and Preventions for Pregnant Women and Their Preterm Infants in a World with COVID-19: A Narrative Review.

(1) Background and Aim: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is linked to increasing cases of coronavirus disease 2019 (COVID-19) around the world. COVID-19 infections have an important impact on pregnancy, preterm birth (PTB) and delivery. Although several complications have been reported in infected pregnant women, the effect of infection on PTB is controversial. The purpose of this study was to summarize the existing literature on the effects and complications of COVID-19 on the health of pregnant women and preterm babies and its impact on the incidence of PTB. We also discuss the effect of current COVID-19 vaccines during pregnancy. (2) Methods: We carried out a systematic search of MEDLINE, Embase, and PubMed for studies on preterm births associated with COVID-19. (3) Results and Conclusions: We discovered contradictory results regarding the prevalence of PTB during the pandemic compared to earlier years. While most studies indicated an increase in PTBs with COVID-19, some indicated a decline in the preterm delivery rate during this time. During pregnancy, COVID-19 infection can increase the incidence of cesarean section, stillbirth, ICU admission, preeclampsia/eclampsia, and mortality rates. In the treatment of pregnant women with severe COVID-19, methylprednisolone was favored over prednisolone, and a brief course of dexamethasone is advised for pregnant women with anticipated PTB to accelerate the development of the fetal lung. Generally, vaccination for COVID-19 in pregnant and lactating women stimulates anti-SARS-CoV2 immune responses, and it does not result in any noteworthy negative reactions or outcomes for the mother or baby.

The Role of Cluster of Differentiation 39 (CD39) and Purinergic Signaling Pathway in Viral Infections.

CD39 is a marker of immune cells such as lymphocytes and monocytes. The CD39/CD73 pathway hydrolyzes ATP into adenosine, which has a potent immunosuppressive effect. CD39 regulates the function of a variety of immunologic cells through the purinergic signaling pathways. CD39+ T cells have been implicated in viral infections, including Human Immunodeficiency Virus (HIV), Cytomegalovirus (CMV), viral hepatitis, and Corona Virus Disease 2019 (COVID-19) infections. The expression of CD39 is an indicator of lymphocyte exhaustion, which develops during chronicity. During RNA viral infections, the CD39 marker can profile the populations of CD4+ T lymphocytes into two populations, T-effector lymphocytes, and T-regulatory lymphocytes, where CD39 is predominantly expressed on the T-regulatory cells. The level of CD39 in T lymphocytes can predict the disease progression, antiviral immune responses, and the response to antiviral drugs. Besides, the percentage of CD39 and CD73 in B lymphocytes and monocytes can affect the status of viral infections. In this review, we investigate the impact of CD39 and CD39-expressing cells on viral infections and how the frequency and percentage of CD39+ immunologic cells determine disease prognosis.

Impact of innovative nanoadditives on biodigesters microbiome.

Nanoparticles (NPs) supplementation to biodigesters improves the digestibility of biowaste and the generation of biogas. This study investigates the impact of innovative nanoadditives on the microbiome of biodigesters. Fresh cow manure was anaerobically incubated in a water bath under mesophilic conditions for 30 days. Three different NPs (zinc ferrite, zinc ferrite with 10% carbon nanotubes and zinc ferrite with 10% C76 fullerene) were separately supplemented to the biodigesters at the beginning of the incubation period. Methane and hydrogen production were monitored daily. Manure samples were collected from the digesters at different time points and the microbial communities inside the biodigesters were investigated via real-time PCR and 16 S rRNA gene amplicon-sequencing. The results indicate that zinc ferrite NPs enhanced biogas production the most. The microbial community was significantly affected by NPs addition in terms of archaeal and bacterial 16 S rRNAgene copy numbers. The three ZF formulations NPs augmented the abundance of members within the hydrogenotrophic methanogenic phyla Methanobacteriaceae. While Methanomassiliicoccacaea were enriched in ZF/C76 supplemented biodigester due to a significant increase in hydrogen partial pressure, probably caused by the enrichment of Spirochaetaceae (genus Treponema). Overall, NPs supplementation significantly enriched acetate-producing members within Hungateiclostridiaceae in ZF/CNTs, Dysgonomonadaceae in ZF and Spirochaetaceae ZF/C76 biodigesters.

Characteristics and outcomes of acute hepatitis of unknown etiology in Egypt: first report of adult adenovirus-associated hepatitis.

PURPOSE: Several outbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in 2022 in many countries, with adenovirus identified as the etiological agent in most of them. We aimed to evaluate the characteristics and outcomes of AHUE cases in Egypt. METHODOLOGY: Hospitalized patients with acute hepatitis were included in the study. Drug-induced, alcoholic hepatitis, autoimmune hepatitis, and Wilson's disease were identified either by medical history or by routine laboratory diagnosis. Molecular and serological approaches were used to investigate common viral causes of hepatitis, such as hepatitis A-E viruses, cytomegalovirus, Epstein-Barr virus, herpes simplex viruses (HSV1/2), adenovirus, parvovirus B19, and coxsackie virus. RESULTS: A total of 42 patients were recruited and divided into two groups: 24 cases of unknown hepatitis after excluding the common causes and 18 cases of known hepatitis. About two-thirds of the patients were male (61.9%), and the mean age was 34.55 ± 16.27 years. Jaundice, dark urine, abdominal pain and diarrhea were recorded at a higher incidence in group 1, while jaundice and fever were frequent in group 2. Fulminant hepatitis occurred in 28.6% of the cases, but the two groups did not differ significantly in terms of patient outcome, duration of hospitalization, ascites, and development of fulminant hepatitis. Adenovirus was detected in five cases (20.8%) in group 1, and one case co-infecting with hepatitis E virus in group 2. Herpes simplex virus 1/2, coxsackie virus, and parvovirus B19 were not detected in any case, while etiologies of 75% of the cases were still not confirmed. One out of the six adenovirus-infected patients died. The outcome significantly correlated with the severity of the liver disease. CONCLUSION: This is the first report describing etiologies and characteristics of AHUE cases in Egypt, and interestingly, adenovirus was detected in adults. Further studies are required to determine the prevalence of this newly emerging viral hepatitis pathogens.

The First Report of Coxiella burnetii as a Potential Neglected Pathogen of Acute Hepatitis of Unknown Causes in Egypt.

The World Health Organization (WHO) recently alerted the emergence of new pathogens causing acute hepatitis in children across several countries. This new situation directs us to the screening of neglected pathogens that cause acute hepatitis. Q-fever is a zoonotic disease, caused by Coxiella burnetii. Although a high seroprevalence of Coxiella burnetii was recorded in animals present in Egypt, Q-fever is still a neglected disease, and the diagnosis of Q-fever is not routinely performed in Egyptian hospitals. In this study, we performed a retrospective assessment for Coxiella burnetii in cases of hepatitis of unknown causes (HUC) enrolled in Assiut University hospitals, in Egypt. Out of 64 samples of HUC, 54 samples were negative for all hepatitis markers, labeled as acute hepatitis of unknown etiology (AHUE), and 10 samples tested positive for adenovirus and Hepatitis E virus (HEV). Q-fever was detected in 3 out of 54 (5.6%) of AHUE, and one sample was confirmed as coinfection of HEV/Q-fever. Jaundice was the most common clinical symptom developed in the patients. In conclusion, Coxiella burnetii was found to be a potential cause of acute hepatitis in HUC. The diagnosis of Q-fever should be considered in acute hepatitis cases in Egyptian hospitals.

Hepatitis E virus (HEV) open reading frame 2: Role in pathogenesis and diagnosis in HEV infections.

Hepatitis E virus (HEV) infection occurs worldwide. The HEV genome includes three to four open reading frames (ORF1-4). ORF1 proteins are essential for viral replication, while the ORF3 protein is an ion channel involved in the exit of HEV from the infected cells. ORF2 proteins form the viral capsid required for HEV invasion and assembly. They also suppress interferon production and inhibit antibody-mediated neutralisation of HEV, allowing the virus to hijack the host immune response. ORF2 is the only detectable viral protein in the human liver during HEV infection and it is secreted in the plasma, stool, and urine of HEV-infected patients, making it a reliable diagnostic marker. The plasma HEV ORF2 antigen level can predict the outcome of HEV infections. Hence, monitoring HEV ORF2 antigen levels may be useful in assessing the efficacy of anti-HEV therapy. The ORF2 antigen is immunogenic and includes epitopes that can induce neutralising antibodies; therefore, it is a potential HEV vaccine candidate. In this review, we highlighted the different forms of HEV ORF2 protein and their roles in HEV pathogenesis, diagnosis, monitoring the therapeutic efficacy, and vaccine development.

A Novel C@Fe@Cu Nanocomposite Loaded with Doxorubicin Tailored for the Treatment of Hepatocellular Carcinoma.

High mortality and morbidity rates are related to hepatocellular carcinoma (HCC), which is the most prevalent type of liver cancer. A new vision for cancer treatment and cancer cell targeting has emerged with the application of nanotechnology, which reduces the systemic toxicity and adverse effects of chemotherapy medications while increasing their effectiveness. It was the goal of the proposed work to create and investigate an anticancer C@Fe@Cu nanocomposite (NC) loaded with Doxorubicin (DOX) for the treatment of HCC. Scanning and transmission electron microscopes (SEM and TEM) were used to examine the morphology of the produced NC. The formulation variables (DOX content, C@Fe@Cu NC weight, and stirring speed) were analyzed and optimized using Box-Behnken Design (BBD) and Response Surface Methodology (RSM). Additionally, X-ray diffraction patterns (XRD) and Fourier Transform Infrared (FTIR) were investigated. Doxorubicin and DOX- loaded C@Fe@Cu NC (DOX-C@Fe@Cu NC) were also assessed against HEPG2 cells for anticancer efficacy (Hepatic cancer cell line). The results revealed the formation of C@Fe@Cu NC with a mean size of 7.8 nm. A D-R model with a mean size of 24.1 nm best fits the adsorption behavior of DOX onto the C@Fe@Cu NC surface. DOX-C@Fe@Cu NC has also been demonstrated to have a considerably lower IC50 and higher cytotoxicity than DOX alone in an in vitro investigation. Therefore, DOX-C@Fe@Cu NC is a promising DOX delivery vehicle for the full recovery of HCC.