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1.
Health Sci Rep ; 7(5): e2013, 2024 May.
Article En | MEDLINE | ID: mdl-38742091

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.

2.
Plants (Basel) ; 13(6)2024 Mar 13.
Article En | MEDLINE | ID: mdl-38592805

In the quest for sustainable agricultural practices, there arises an urgent need for alternative solutions to mineral fertilizers and pesticides, aiming to diminish the environmental footprint of farming. Arbuscular mycorrhizal fungi (AMF) emerge as a promising avenue, bestowing plants with heightened nutrient absorption capabilities while alleviating plant stress. Cereal and oilseed crops benefit from this association in a number of ways, including improved growth fitness, nutrient uptake, and tolerance to environmental stresses. Understanding the molecular mechanisms shaping the impact of AMF on these crops offers encouraging prospects for a more efficient use of these beneficial microorganisms to mitigate climate change-related stressors on plant functioning and productivity. An increased number of studies highlighted the boosting effect of AMF on grain and oil crops' tolerance to (a)biotic stresses while limited ones investigated the molecular aspects orchestrating the different involved mechanisms. This review gives an extensive overview of the different strategies initiated by mycorrhizal cereal and oilseed plants to manage the deleterious effects of environmental stress. We also discuss the molecular drivers and mechanistic concepts to unveil the molecular machinery triggered by AMF to alleviate the tolerance of these crops to stressors.

3.
Int J Pharm X ; 7: 100245, 2024 Jun.
Article En | MEDLINE | ID: mdl-38633410

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.

4.
Metabolites ; 14(4)2024 Apr 03.
Article En | MEDLINE | ID: mdl-38668330

In the Mediterranean region, reforestation programs record failures following successive drought periods. The use of different plant-growth-promoting amendments and the understanding of drought-induced physiological and biochemical responses of carob will contribute to the reforestation program's success. In this study, the effects of arbuscular-mycorrhizal-fungi (AMF), vermicompost (VC), and rock phosphate (RP) on carob seedlings under drought stress (DS) and recovery (REC) conditions were evaluated. A greenhouse experiment was conducted with carob seedlings grown in the presence of AMF, VC, and RP, applied alone or in combination under well-watered (WW), DS (by stopping irrigation for 12 days), and recovery (REC) conditions. The obtained results indicated that the triple combination (AMF + VC + RP) presented the highest improvement in water potential, photosynthetic pigment content, stomatal conductance, and chlorophyll fluorescence compared to the controls under DS and after REC. In addition, this combination resulted in improved tolerance of carob seedlings to DS and a high potential for rapid recovery after rehydration due to a high accumulation of sugars, proteins, and antioxidant enzymes. In summary, the results underline the importance of inoculating carob with AMF in combination with (in)-organic amendments in improving its tolerance to DS and its recovery performances.

5.
Virol J ; 21(1): 75, 2024 03 27.
Article En | MEDLINE | ID: mdl-38539202

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.


COVID-19 , Humans , COVID-19/epidemiology , SARS-CoV-2/genetics , Viral Proteins/genetics , Phylogeny , Genomics , Disease Outbreaks
6.
Bioorg Chem ; 145: 107258, 2024 Apr.
Article En | MEDLINE | ID: mdl-38447463

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.


Escherichia coli , Urinary Tract Infections , Humans , Escherichia coli/metabolism , Fimbriae Proteins , Mannose/chemistry , Molecular Docking Simulation
7.
Int J Mol Sci ; 25(2)2024 Jan 11.
Article En | MEDLINE | ID: mdl-38255984

Mycorrhizal symbiosis, the mutually beneficial association between plants and fungi, has gained significant attention in recent years due to its widespread significance in agricultural productivity. Specifically, arbuscular mycorrhizal fungi (AMF) provide a range of benefits to grain and oil crops, including improved nutrient uptake, growth, and resistance to (a)biotic stressors. Harnessing this symbiotic interaction using molecular and systems biology approaches presents promising opportunities for sustainable and economically-viable agricultural practices. Research in this area aims to identify and manipulate specific genes and pathways involved in the symbiotic interaction, leading to improved cereal and oilseed crop yields and nutrient acquisition. This review provides an overview of the research frontier on utilizing molecular and systems biology approaches for harnessing the symbiotic interaction in mycorrhizal symbiosis for grain and oil crop cultivation. Moreover, we address the mechanistic insights and molecular determinants underpinning this exchange. We conclude with an overview of current efforts to harness mycorrhizal diversity to improve cereal and oilseed health through systems biology.


Mycorrhizae , Symbiosis , Edible Grain , Plant Structures , Systems Biology
8.
Br J Haematol ; 204(3): 1086-1095, 2024 Mar.
Article En | MEDLINE | ID: mdl-37926112

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.


Dyskeratosis Congenita , Pancytopenia , Rib Fractures , Telomerase , Humans , Telomere , Mutation , Dyskeratosis Congenita/genetics , Immunoglobulin E/genetics , Telomerase/genetics
9.
Plants (Basel) ; 12(24)2023 Dec 14.
Article En | MEDLINE | ID: mdl-38140483

Utilizing water resources rationally has become critical due to the expected increase in water scarcity. Cacti are capable of surviving with minimal water requirements and in poor soils. Despite being highly drought-resistant, cacti still faces limitations in realizing its full potential under drought-stress conditions. To this end, we investigated the interactive effect of humic substances (Hs) and arbuscular mycorrhizal fungi (AMF) on cactus plants under drought stress. In the study, a cactus pot experiment had three irrigation levels (W1: no irrigation, W2: 15% of field capacity, and W3: 30% of field capacity) and two biostimulants (Hs soil amendment and AMF inoculation), applied alone or combined. The findings show that the W1 and W2 regimes affected cactus performance. However, Hs and/or AMF significantly improved growth. Our results revealed that drought increased the generation of reactive oxygen species. However, Hs and/or AMF application improved nutrient uptake and increased anthocyanin content and free amino acids. Furthermore, the soil's organic matter, phosphorus, nitrogen, and potassium contents were improved by the application of these biostimulants. Altogether, using Hs alone or in combination with AMF can be an effective and sustainable approach to enhance the tolerance of cactus plants to drought conditions, while also improving the soil quality.

10.
Microorganisms ; 11(12)2023 Nov 30.
Article En | MEDLINE | ID: mdl-38138042

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.

11.
Int J Mol Sci ; 24(24)2023 Dec 18.
Article En | MEDLINE | ID: mdl-38139439

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.


Adenosine , COVID-19 , T-Lymphocytes, Regulatory , Humans , 5'-Nucleotidase/genetics , 5'-Nucleotidase/metabolism , Adenosine/metabolism , Adenosine Triphosphate/metabolism , Anti-Inflammatory Agents , Antigens, CD/genetics , Antigens, CD/metabolism , Disease Progression , Interleukin-10 , Receptors, Purinergic P1/genetics , Transforming Growth Factor beta/genetics , T-Lymphocytes, Regulatory/metabolism
12.
Int J Mol Sci ; 24(19)2023 Oct 01.
Article En | MEDLINE | ID: mdl-37834266

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.


Ciprofloxacin , Staphylococcus aureus , Ciprofloxacin/pharmacology , Ciprofloxacin/chemistry , Chromatography, High Pressure Liquid , Spectroscopy, Fourier Transform Infrared , Microbial Sensitivity Tests , Anti-Bacterial Agents/chemistry , DNA Gyrase , Molecular Docking Simulation , Topoisomerase II Inhibitors/pharmacology , Topoisomerase II Inhibitors/chemistry
13.
Pharmaceutics ; 15(10)2023 Oct 04.
Article En | MEDLINE | ID: mdl-37896183

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.

14.
Viruses ; 15(6)2023 06 15.
Article En | MEDLINE | ID: mdl-37376678

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.


Glomerulonephritis , Hepatitis E virus , Hepatitis E , Humans , Female , Pregnancy , Hepatitis E virus/genetics , Seroepidemiologic Studies , Hepatitis E/complications , Hepatitis E/epidemiology , Hepatitis Antibodies , Glomerulonephritis/epidemiology , RNA, Viral , Immunoglobulin M , Immunoglobulin G
15.
Int J Mol Sci ; 24(10)2023 May 22.
Article En | MEDLINE | ID: mdl-37240429

The use of illicit substances continues to pose a substantial threat to global health, affecting millions of individuals annually. Evidence suggests the existence of a 'brain-gut axis' as the involving connection between the central nervous system and gut microbiome (GM). Dysbiosis of the GM has been associated with the pathogenesis of various chronic diseases, including metabolic, malignant, and inflammatory conditions. However, little is currently known about the involvement of this axis in modulating the GM in response to psychoactive substances. In this study, we investigated the effect of MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy")-dependence on the behavioral and biochemical responses, and the diversity and abundance of the gut microbiome in rats post-treated (or not) with aqueous extract of Anacyclus pyrethrum (AEAP), which has been reported to exhibit anticonvulsant activity. The dependency was validated using the conditioned place preference (CPP) paradigm, behavioral, and biochemical tests, while the gut microbiota was identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The CPP and behavioral tests confirmed the presence of MDMA withdrawal syndrome. Interestingly, treatment with AEAP led to a compositional shift in the GM compared to the MDMA-treated rats. Specifically, the AEAP group yielded a higher relative abundance of Lactobacillus and Bifidobacter, while animals receiving MDMA had higher levels of E. coli. These findings suggest that A. pyrethrum therapy may directly modulate the gut microbiome, highlighting a potential target for regulating and treating substance use disorders.


Chrysanthemum cinerariifolium , Gastrointestinal Microbiome , N-Methyl-3,4-methylenedioxyamphetamine , Rats , Animals , N-Methyl-3,4-methylenedioxyamphetamine/adverse effects , Escherichia coli , Affect
16.
Pathogens ; 12(5)2023 May 08.
Article En | MEDLINE | ID: mdl-37242358

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.

17.
J Nat Prod ; 86(5): 1150-1158, 2023 05 26.
Article En | MEDLINE | ID: mdl-37098901

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.


Antineoplastic Agents , Chalcones , Tubulin Modulators/chemistry , Chalcones/pharmacology , Chalcones/chemistry , Quantitative Structure-Activity Relationship , Tubulin/metabolism , Structure-Activity Relationship , Microtubules/metabolism , Antineoplastic Agents/chemistry , Cell Proliferation , Drug Screening Assays, Antitumor , Molecular Structure , Cell Line, Tumor
18.
Infect Drug Resist ; 16: 1737-1750, 2023.
Article En | MEDLINE | ID: mdl-36999125

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.

19.
Vaccines (Basel) ; 11(3)2023 Mar 13.
Article En | MEDLINE | ID: mdl-36992224

(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.

20.
J Antibiot (Tokyo) ; 76(5): 291-300, 2023 05.
Article En | MEDLINE | ID: mdl-36854977

The multi-drug resistant Staph. aureus strain, Methicillin-resistant Staphylococcus aureus (MRSA), is an emerging pathogen that could penetrate skin cuts and wounds, causing a life-threatening condition. The green biosynthesis of silver nanoparticles with liquorice extract has been demonstrated over several years for anticancer and antioxidant effects, as well as antibacterial effect against both Gram-positive and Gram-negative bacteria. The study was designed to evaluate the synergistic in vivo and in vitro wound healing and anti-MRSA activity of decorated liquorice silver nanoparticles (LD-AgNPs). The LD-AgNPs were prepared by thoroughly mixing diluted liquorice extract with AgNO3 at room temperature. The prepared nanoparticles were characterized by size measurement, IR spectroscopy, TEM imaging, and X-ray diffraction. The in vitro and in vivo antibacterial and wound healing testing were also performed. The obtained LD-AgNPs were spherical in shape and had a hydrodynamic size of about 50.16 ± 5.37 nm. Moreover, they showed potent antibacterial activity against Gram-positive and Gram-negative resistant bacteria, produced a significantly higher level of procollagen type I compared to either liquorice extract or standard silver sulfadiazine, and promoted the wound healing process in rabbits. The formulation of silver nanoparticles with liquorice extract showed synergetic effects in enhancing the treatment of wounds, with significant antibacterial activity against E. coli and MRSA.


Glycyrrhiza , Metal Nanoparticles , Methicillin-Resistant Staphylococcus aureus , Animals , Rabbits , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Silver/pharmacology , Silver/chemistry , Metal Nanoparticles/chemistry , Escherichia coli , Gram-Positive Bacteria , Gram-Negative Bacteria , Staphylococcus aureus , Wound Healing , Microbial Sensitivity Tests
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