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1.
Biomedicines ; 12(5)2024 May 12.
Article in English | MEDLINE | ID: mdl-38791030

ABSTRACT

Introduction: Magnesium is a vital intracellular cation crucial for over 320 enzymatic reactions related to energy metabolism, musculoskeletal function, and nucleic acid synthesis and plays a pivotal role in human physiology. This study aimed to explore the prevalence of dysmagnesemia in patients with diabetes mellitus and evaluate its correlations with glycemic control, medication use, and diabetic complications. Methods: A cross-sectional study was conducted at Sultan Qaboos University Hospital, including 316 patients aged 18 years or older with diabetes mellitus. Data included demographics, medical history, medications, and biochemical parameters. Serum total magnesium concentrations were measured, and dysmagnesemia was defined as magnesium ≤ 0.69 mmol/L for hypomagnesemia and ≥1.01 mmol/L for hypermagnesemia. Results: The prevalence of hypomagnesemia in patients with diabetes was 17.1% (95% CI: 13.3-21.7%), and hypermagnesemia was 4.1% (95% CI: 2.4-7.0%). Females were significantly overrepresented in the hypomagnesemia group, while the hypermagnesemia group showed a higher prevalence of hypertension, retinopathy, an increased albumin/creatinine ratio, chronic kidney disease (CKD), elevated creatinine levels, and a lower adjusted calcium concentration. The multinominal logistic regression exhibited that the female sex and higher serum-adjusted calcium were independent risk factors of hypomagnesemia. In contrast, the presence of hypertension, higher levels of albumin/creatinine ratio, and stage 5 CKD were independent risk factors of hypermagnesemia. Conclusions: Hypomagnesemia was common among patients with diabetes mellitus; however, hypermagnesemia was associated with microvascular complications.

2.
Environ Pollut ; 352: 124104, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38703978

ABSTRACT

Endocrine disruptors are synthetic or natural chemicals that can agonize/antagonize hormone receptors or can interfere with the production and secretion of hormones, leading to altered tissue histology and physiology. Pyrogallol is a contaminant widely distributed in aquatic environments that presents health risks to both humans and animals. However, the potential for endocrine disruption by pyrogallol, particularly in fish, are lacking. The purpose of this study was to shed light on how pyrogallol may affect hormone signalling, histopathology, and reproductive outcomes in African catfish Clarias gariepinus. To investigate this, African catfish were exposed to one sublethal concentration of pyrogallol at either 0, 1, 5 or 10 mg/L for 15 days. We then assessed the effects of pyrogallol on the thyroid gland as well as the reproductive system by measuring sex hormone, seminal quality, gonadal histopathology, and histochemistry. Thyroid stimulating hormone and thyroxine showed notable decreases in catfish, and triiodothyronine was decreased with 10 mg/L pyrogallol. Unlike luteinizing hormone, follicle-stimulating hormone was significantly reduced in fish following exposure to pyrogallol relative to controls. Testosterone was also decreased in fish following pyrogallol exposure, whereas 17ß-estradiol increased in catfish exposed to pyrogallol. Additionally, in response to pyrogallol toxicity, sperm quality indices, including count, spermatocrit, motility, and sperm viability were adversely affected in a concentration-dependent manner. Pyrogallol exposure also induced several changes in the gonad following exposure to 1, 5, or 10 mg/L. Deformed tubular structures, vacuolation, thickening of the basement membrane, hypertrophy of the seminiferous tubules, intense melanomacrophage localization, spermatozoa loss, and necrosis were all observed in the testes. In the ovary, atretic follicles, deteriorated mature oocytes, degenerated yolk globules, and an increase in perinucleolar oocytes were observed in catfish exposed to pyrogallol. These findings suggest that pyrogallol may act as endocrine disrupting substance in aquatic environments. Further research on the mechanisms by which pyrogallol impairs endocrine systems, particularly in fish, is recommended.


Subject(s)
Catfishes , Endocrine Disruptors , Pyrogallol , Reproduction , Water Pollutants, Chemical , Animals , Catfishes/physiology , Endocrine Disruptors/toxicity , Water Pollutants, Chemical/toxicity , Reproduction/drug effects , Male , Pyrogallol/toxicity , Pyrogallol/analogs & derivatives , Female , Thyroid Gland/drug effects
3.
ACS Omega ; 9(11): 13172-13182, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38524460

ABSTRACT

Bioisosterism is strategically used in drug design to enhance the pharmacokinetic and pharmacodynamic properties of therapeutic molecules. The average electron density (AED) tool has been used in several studies to quantify similarities among nonclassical bioisosteres of carboxylic acid. In this study, the AED tool is used to quantify the similarities among nonclassical bioisosteres of an amide group. In particular, amide-to-1,2,3-triazole bioisosterism is considered. To evaluate the AED differences exhibited by isomers of nonclassical bioisosteres, both isomers of amide (cis and trans) and 1,2,3-triazole (1,4 and 1,5 disubstituted moieity) were considered. The amide and 1,2,3-triazole bioisosteric moieties were capped with various R groups (R= methyl, hydrogen, and chloro) to account for changes in their environment. Amide-to-triazole bioisosteric substitutions were then explored in a more realistic environment, that is, within the FDA-approved anticancer imatinib drug. The AED tool effectively identified similarities between substantially different moieties, 1,2,3-triazole and amide, showing AED differences of no more than 4%. The AED tool was also proven to be useful in evaluating the contribution of various factors affecting triazole-amide bioisosterism including isomerism and changes in their environment. The AED values of each bioisostere were transferable within a maximum difference of 2.6%, irrespective of the change in environment. The 1,4- and 1,5-disubstituted isomers of 1,2,3-triazole have AED values that differ by less than unity, 0.52%. Similarly, the AED values of the cis- and trans-amide isomers differ by only 1.31%. Overall, the AED quantitative tool not only replicated experimental observations regarding similarities in bioisosteres, but also explained and quantified each contributing factor. This demonstrates the extended utility of the AED tool from nonclassical carboxylic acid bioisosteres to amide equivalents.On the contrary, electrostatic potential maps, usually used in the literature to qualitatively evaluate bioisosterism, were not similar for the 1,2,3-triazole and amide bioisosteres, under different environments. Overall, the AED tool proves to be powerful in quantitatively evaluating and predicting bioisosterism across diverse moieties considering structural and environmental variations, making it valuable in drug design.

4.
J Integr Med ; 22(2): 137-162, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38462407

ABSTRACT

BACKGROUND: The field of personalized medicine has gained increasing attention in cancer care, with the aim of tailoring treatment strategies to individual patients for improved outcomes. Herbal medicine, with its long-standing historical use and extensive bioactive compounds, offers a rich source of potential treatments for various diseases, including cancer. OBJECTIVE: To provide an overview of the current knowledge and evidence associated with incorporating herbal compounds into precision medicine strategies for cancer diseases. Additionally, to explore the general characteristics of the studies included in the analysis, focusing on their key features and trends. SEARCH STRATEGY: A comprehensive literature search was conducted from multiple online databases, including PubMed, Scopus, Web of Science, and CINAHL-EBSCO. The search strategy was designed to identify studies related to personalized cancer medicine and herbal interventions. INCLUSION CRITERIA: Publications pertaining to cancer research conducted through in vitro, in vivo, and clinical studies, employing natural products were included in this review. DATA EXTRACTION AND ANALYSIS: Two review authors independently applied inclusion and inclusion criteria, data extraction, and assessments of methodological quality. The quality assessment and biases of the studies were evaluated based on modified Jadad scales. A detailed quantitative summary of the included studies is presented, providing a comprehensive description of their key features and findings. RESULTS: A total of 121 studies were included in this review for analysis. Some of them were considered as comprehensive experimental investigations both in vitro and in vivo. The majority (n = 85) of the studies included in this review were conducted in vitro, with 44 of them specifically investigating the effects of herbal medicine on animal models. Additionally, 7 articles with a combined sample size of 31,271 patients, examined the impact of herbal medicine in clinical settings. CONCLUSION: Personalized medication can optimize the use of herbal medicine in cancer treatment by considering individual patient factors such as genetics, medical history, and other treatments. Additionally, active phytochemicals found in herbs have shown potential for inhibiting cancer cell growth and inducing apoptosis, making them a promising area of research in preclinical and clinical investigations. Please cite this article as: Tayeb BA, Kusuma IY, Osman AAM, Minorics R. Herbal compounds as promising therapeutic agents in precision medicine strategies for cancer: A systematic review. J Integr Med. 2024; 22(2): 137-162.


Subject(s)
Neoplasms , Plants, Medicinal , Animals , Humans , Precision Medicine , Neoplasms/drug therapy , Plant Extracts
5.
BMC Chem ; 18(1): 29, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38347617

ABSTRACT

VEGFR2 and FAK signaling pathways are interconnected and have synergistic effects on tumor angiogenesis, growth, and metastasis. Thus, instead of the conventional targeting of each of these proteins individually with a specific inhibitor, the present work aimed to discover novel dual inhibitors targeting both VEGFR2 and FAK exploiting their association. To this end, receptor-based pharmacophore modeling technique was opted to generate 3D pharmacophore models for VEGFR2 and FAK type II kinase inhibitors. The generated pharmacophore models were validated by assessing their ability to discriminate between active and decoy compounds in a pre-compiled test set of VEGFR2 and FAK active compounds and decoys. ZINCPharmer web tool was then used to screen the ZINC database purchasable subset using the validated pharmacophore models retrieving 42,616 hits for VEGFR2 and 28,475 hits for FAK. Subsequently, they were filtered using various filters leaving 13,023 and 6,832 survived compounds for VEGFR2 and FAK, respectively, with 124 common compounds. Based on molecular docking simulations, thirteen compounds were found to satisfy all necessary interactions with VEGFR2 and FAK kinase domains. Thus, they are predicted to have a possible dual VEGFR2/FAK inhibitory activity. Finally, SwissADME web tool showed that compound ZINC09875266 is not only promising in terms of binding pattern to our target kinases, but also in terms of pharmacokinetic properties.

6.
Rheumatology (Oxford) ; 63(1): 209-217, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-37094222

ABSTRACT

OBJECTIVE: To investigate pathogenic mechanisms underlying JDM, we defined the effect of type I IFN, IFN-α and IFN-ß, on pediatric skeletal muscle function and expression of myositis-related proteins using an in vitro engineered human skeletal muscle model (myobundle). METHODS: Primary myoblasts were isolated from three healthy pediatric donors and used to create myobundles that mimic functioning skeletal muscle in structural architecture and physiologic function. Myobundles were exposed to 0, 5, 10 or 20 ng/ml IFN-α or IFN-ß for 7 days and then functionally tested under electrical stimulation and analyzed immunohistochemically for structural and myositis-related proteins. Additionally, IFN-ß-exposed myobundles were treated with Janus kinase inhibitors (JAKis) tofacitinib and baricitinib. These myobundles were also analyzed for contractile force and immunohistochemistry. RESULTS: IFN-ß, but not IFN-α, was associated with decreased contractile tetanus force and slowed twitch kinetics. These effects were reversed by tofacitinib and baricitinib. Type I IFN paradoxically reduced myobundle fatigue, which did not reverse after JAKi. Additionally, type I IFN correlated with MHC I upregulation, which normalized after JAKi treatment, but expression of myositis-specific autoantigens Mi-2, melanocyte differentiation-associated protein 5 and the endoplasmic reticulum stress marker GRP78 were variable and donor specific after type I IFN exposure. CONCLUSION: IFN-α and IFN-ß have distinct effects on pediatric skeletal muscle and these effects can partially be reversed by JAKi treatment. This is the first study illustrating effective use of a three-dimensional human skeletal muscle model to investigate JDM pathogenesis and test novel therapeutics.


Subject(s)
Dermatomyositis , Interferon Type I , Muscular Diseases , Myositis , Humans , Child , Dermatomyositis/pathology , Muscle, Skeletal/pathology , Myositis/pathology , Muscular Diseases/pathology
7.
Chemosphere ; 349: 140792, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38016523

ABSTRACT

Pyrogallol is a naturally occurring polyphenol derived from natural plants, such as Acer rubrum and Eucalyptus sp. The current study was designed to evaluated pyrogallol-mediated toxicity at sublethal levels (1, 5, and 10 mg/L), derived from 96 h-LC50 values previously determined for African catfish (Clarias gariepinus). Immunotoxicological indices, histological, histochemical, and ultrastructural alterations in C. gariepinus were evaluated following a 15-day pyrogallol exposure. Pyrogallol decreased immune parameters [lysozyme activity (LYZ), immunoglobulin M (IgM), and phagocytic activity] and increased pro-inflammatory cytokines, interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) in the serum of C. gariepinus. In addition, histopathology analysis demonstrated that exposure to pyrogallol induced injury in the liver and spleen of fish. Cellular changes in the liver include hepatocyte hydropic degeneration, melanomacrophage, vacuolated hepatocytes, congested blood, severe structural deformation, and hemorrhage. In the spleen, ellipsoid structures, melanomacrophage centers, and infiltration of inflammatory cells were evident. Together, a high frequency of histopathological lesions was scored in both the liver and spleen of C. gariepinus, which showed a dose-dependent relationship between pyrogallol exposure and histopathological indices. Our data suggest that dysfunction in the immune system may be mediated by pyrogallol-induced changes in cytokines.


Subject(s)
Catfishes , Water Pollutants, Chemical , Animals , Pyrogallol/toxicity , Liver , Cytokines , Water Pollutants, Chemical/analysis
8.
J Environ Manage ; 351: 119845, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38109825

ABSTRACT

Pyrogallol promotes free radicals leading to oxidative stress and toxicity. There are however a lack of studies on oxidative stress and the antioxidant system of fish following exposure to pyrogallol. This study measured oxidative stress markers, antioxidant responses, and histological changes in catfish exposed to pyrogallol. Fish were divided into one of four experimental groups: control only, or 1, 5 or 10 mg/L pyrogallol. After 15 days, glutathione-S-transferase in the serum was decreased in fish exposed to either 5 or 10 mg/L pyrogallol relative to controls while superoxide dismutase and total antioxidant capacity were decreased significantly in fish exposed to 1, 5, or 10 mg/L pyrogallol. Conversely, catalase was increased in serum of fish exposed to 1, 5, or 10 mg/L pyrogallol compared to controls. The liver of fish treated with 1, 5, or 10 mg/L pyrogallol had significantly higher levels of oxidative stress markers (malondialdehyde, lipid peroxidation, hydroperoxide content, oxidised protein content, and DNA fragmentation %) that varied with concentration. Catfish exposed to either 1, 5, or 10 mg/L pyrogallol presented with notable histological alterations in the intestine, kidney, and muscles with prominent fibrosis, as intense deposition of collagen fibre was observed by Masson's trichrome staining. Overall, endpoints related to oxidative stress and antioxidant defence enzymes in fish may be early biomarkers of pyrogallol exposure and contamination in aquatic ecosystems. Additional studies should characterize oxidative stress indicators for their utility as biomarkers of effect.


Subject(s)
Catfishes , Water Pollutants, Chemical , Animals , Antioxidants/metabolism , Pyrogallol/toxicity , Pyrogallol/metabolism , Ecosystem , Oxidative Stress , Catfishes/metabolism , Biomarkers/metabolism , Lipid Peroxidation , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/metabolism
9.
Environ Monit Assess ; 195(9): 1130, 2023 Aug 31.
Article in English | MEDLINE | ID: mdl-37653356

ABSTRACT

The present study described the most recent findings concerning the abundance and distribution of plastic in water, sediment, and fauna in the Nile River of Upper Egypt as an interesting research point. The findings revealed that plastics were abundant in the water, sediments, fish, and crayfish throughout the sites. The Nagaa Hammadi site has the highest abundance of meso- and macroplastics in its water and sediment. African catfish had the highest abundance of meso- and macroplastics compared to the other species, while Nile tilapia had no meso- or macroplastics in its alimentary canal or gills in all sites. The Edfu site has the highest abundance of mesoplastics in the alimentary canals of African catfish, while the Nagaa Hammadi site has the highest abundance of mesoplastics in the gills, and macroplastics appeared only in the alimentary canal of African catfish from the El-wasta site. Only mesoplastics were found in the crayfish's alimentary canal, with the Nagaa Hammadi site having the highest abundance. No macroplastics were detected in the crayfish's gills or alimentary canal. Additionally, this work lets us understand how plastics behave in freshwater environments, and it is a step toward decision-makers taking appropriate measures to reduce their risk.


Subject(s)
Catfishes , Water , Animals , Egypt , Microplastics , Rivers , Environmental Monitoring , Plastics
11.
Environ Pollut ; 333: 122074, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37331582

ABSTRACT

Pyrogallol is widely used in several industrial applications and can subsequently contaminate aquatic ecosystems. Here, we report for the first time the presence of pyrogallol in wastewater in Egypt. Currently, there is a complete lack of toxicity and carcinogenicity data for pyrogallol exposure in fish. To address this gap, both acute and sub-acute toxicity experiments were conducted to determine the toxicity of pyrogallol in catfish (Clarias gariepinus). Behavioral and morphological endpoints were evaluated, in addition to blood hematological endpoints, biochemical indices, electrolyte balance, and the erythron profile (poikilocytosis and nuclear abnormalities). In the acute toxicity assay, it was determined that the 96 h median-lethal concentration (96 h-LC50) of pyrogallol for catfish was 40 mg/L. In sub-acute toxicity experiment, fish divided into four groups; Group 1 was the control group. Group 2 was exposed to 1 mg/L of pyrogallol, Group 3 was exposed to 5 mg/L of pyrogallol, and Group 4 was exposed to 10 mg/L of pyrogallol. Fish showed morphological changes such as erosion of the dorsal and caudal fins, skin ulcers, and discoloration following exposure to pyrogallol for 96 h. Exposure to 1, 5, or 10 mg/L pyrogallol caused a significant decrease in hematological indices, including red blood cells (RBCs), hemoglobin, hematocrit, white blood cells (WBC), thrombocytes, and large and small lymphocytes in a dose-dependent manner. Several biochemical parameters (creatinine, uric acid, liver enzymes, lactate dehydrogenase, and glucose) were altered in a concentration dependent manner with short term exposures to pyrogallol. Pyrogallol exposure also caused a significant concentration-dependent rise in the percentage of poikilocytosis and nuclear abnormalities of RBCs in catfish. In conclusion, our data suggest that pyrogallol should be considered further in environmental risk assessments of aquatic species.


Subject(s)
Catfishes , Water Pollutants, Chemical , Animals , Pyrogallol/toxicity , Ecosystem , Erythrocytes , Hemoglobins , Water Pollutants, Chemical/toxicity
12.
Liver Int ; 43(7): 1417-1426, 2023 07.
Article in English | MEDLINE | ID: mdl-37073160

ABSTRACT

BACKGROUND & AIMS: Egypt used to have one of the highest prevalences of HCV infection worldwide. The Egyptian Ministry of Health launched a national campaign for the detection and management of HCV to reduce its burden. This study aims to carry out a cost-effectiveness analysis to evaluate the costs and benefits of the Egyptian national screening and treatment programme. METHODS: A disease burden and economic impact model was populated with the Egyptian national screening and treatment programme data to assess direct medical costs, health effects measured in disability-adjusted life years and the incremental cost-effectiveness ratio. The scenario was compared to a historical base case, which assumed that no programme had been conducted. RESULTS: Total number of viremic cases is expected to decrease in 2030 by 86% under the national screening and treatment programme, versus by 41% under the historical base case. Annual discounted direct medical costs are expected to decrease from $178 million in 2018 to $81 million by 2030 under the historical base case, while annual direct medical costs are estimated to have peaked in 2019 at $312 million before declining to $55 million by 2030 under the national screening and treatment programme. Under the programme, annual disability-adjusted life years are expected to decline to 127 647 by 2030, leading to 883 333 cumulative disability-adjusted life years averted over 2018-2030. CONCLUSIONS: The national screening and treatment programme is highly cost-effective by the year 2021, cost-saving by 2029 and expected to save about $35 million in direct costs and $4705 million in indirect costs by 2030.


Subject(s)
Hepatitis C , Humans , Cost-Benefit Analysis , Egypt/epidemiology , Quality-Adjusted Life Years , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Cost-Effectiveness Analysis
13.
ACS Omega ; 8(1): 588-598, 2023 Jan 10.
Article in English | MEDLINE | ID: mdl-36643455

ABSTRACT

Using the Quantum Theory of Atoms in Molecules, the average electron density (AED) tool was developed and employed to quantitatively evaluate the similarities between bioisosteric moieties in drug design. Bioisosteric replacements are valuable in drug molecules to fine-tune their pharmacokinetic and pharmacodynamic properties while maintaining their biological activity. This study was performed on non-classical bioisosteres of carboxylic acid. It was found that the AED of a given bioisostere is generally transferable, within less than 5% difference, irrespective of its environment. It was shown that the AED tool succeeds at depicting not only the similarities of bioisosteric groups but also at highlighting, as counter examples, the differences in non-bioisosteric groups. For the first time, the AED was used to evaluate bioisosterism in an FDA-approved drug molecule, furosemide, and in five analogues of this medicine. In one of the analogues, non-bioisosteric moieties were exchanged, and in four of the analogues, carboxylic acid was replaced with either furan or sulfonamide, and vice versa. It was also found that irrespective of the pH, the AED tool consistently reproduced experimental predictions. The distinct power of the AED tool in quantitatively and precisely measuring the similarity among bioisosteric groups is contrasted with the relatively ambiguous bioisosteric evaluations through the classical qualitative electrostatic potential (ESP) maps. The ESP maps were demonstrated to fail, even qualitatively, in depicting the similarities, in some cases.

14.
J Mol Struct ; 1276: 134690, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36465802

ABSTRACT

In the current investigation, two novel series of (tetrahydro)thioquinazoline-N-arylacetamides and (tetrahydro)thioquinazoline-N-arylacetohydrazides were designed, synthesized and investigated for their antiviral activity against SARS-CoV-2. The thioquinazoline-N-arylacetamide 17g as well as the tetrahydrothioquinazoline-N-arylacetohydrazides 18c and 18f showed potent antiviral activity with IC50 of 21.4, 38.45 and 26.4 µM, respectively. In addition, 18c and 18f demonstrated potential selectivity toward the SARS-CoV-2 over the host cells with SI of 10.67 and 16.04, respectively. Further evaluation of the mechanism of action of the three derivatives 17g, 18c, and 18f displayed that they can inhibit the virus at the adsorption as well as at the replication stages, in addition to their virucidal properties. In addition, 17g, 18c, and 18f demonstrated satisfactory physicochemical properties as well as drug-likeness properties to be further optimized for the discovery of novel antiviral agents. The docking simulation on Mpro binding site predicted the binding pattern of the target compounds rationalizing their differential activity based on their hydrophobic interaction and fitting in the hydrophobic S2 subsite of the binding site.

15.
Int J Cardiovasc Imaging ; 39(3): 607-620, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36471104

ABSTRACT

Acute ST-segment elevation myocardial infarction (STEMI) is associated with left ventricular (LV) structural and functional consequences. We aimed to elucidate LV geometric changes following STEMI using three-dimensional (3D) echocardiography (3DE) and to assess their functional implications using two-dimensional (2D) speckle tracking echocardiography (STE). The study included 71 patients with STEMI who underwent baseline and 6-month follow-up 2D- and 3DE. Measured parameters included LV dimensions, biplane volumes, wall motion assessment, 2D LV global longitudinal strain (GLS), and 3D LV volumes, sphericity index and systolic dyssynchrony index. According to 3DE, LV geometric changes were classified as, adverse remodeling, reverse remodeling, and minimal LV volumetric changes. The occurrence of in-hospital and follow-up major adverse cardiovascular events (MACE) was assessed among the study population. The incidence of developing adverse remodeling was 25.4% while that of reverse remodeling was 36.6%. Adverse remodeling patients had significantly higher in-hospital MACE. Reverse remodeling was associated with significantly improved GLS, that was less evident in those with minimal LV geometric changes, and non-significant improvement for adverse remodeling group. LV baseline 2D GLS significantly correlated with follow-up 3D volumes among both reverse and adverse remodeling groups. Female gender and higher absolute GLS change upon follow-up were significantly associated with reverse remodeling. ROC-derived cutoff for adverse remodeling reallocated a substantial number of patients from the minimal change group to the adverse remodeling. Following acute STEMI, two-dimensional GLS was associated with and potentially predictive of changes in LV volumes as detected by three-dimensional echocardiography.


Subject(s)
Anterior Wall Myocardial Infarction , Echocardiography, Three-Dimensional , Myocardial Infarction , ST Elevation Myocardial Infarction , Humans , Female , ST Elevation Myocardial Infarction/complications , Predictive Value of Tests , Echocardiography, Three-Dimensional/methods , Echocardiography/methods , Anterior Wall Myocardial Infarction/complications , Ventricular Function, Left
17.
Pharmaceutics ; 13(11)2021 Oct 21.
Article in English | MEDLINE | ID: mdl-34834174

ABSTRACT

In 2019, the world suffered from the emergence of COVID-19 infection, one of the most difficult pandemics in recent history. Millions of confirmed deaths from this pandemic have been reported worldwide. This disaster was caused by SARS-CoV-2, which is the last discovered member of the family of Coronaviridae. Various studies have shown that natural compounds have effective antiviral properties against coronaviruses by inhibiting multiple viral targets, including spike proteins and viral enzymes. This review presents the classification and a detailed explanation of the SARS-CoV-2 molecular characteristics and structure-function relationships. We present all currently available crystal structures of different SARS-CoV-2 proteins and emphasized on the crystal structure of different virus proteins and the binding modes of their ligands. This review also discusses the various therapeutic approaches for COVID-19 treatment and available vaccinations. In addition, we highlight and compare the existing data about natural compounds extracted from algae, fungi, plants, and scorpion venom that were used as antiviral agents against SARS-CoV-2 infection. Moreover, we discuss the repurposing of select approved therapeutic agents that have been used in the treatment of other viruses.

18.
Front Physiol ; 12: 742922, 2021.
Article in English | MEDLINE | ID: mdl-34650449

ABSTRACT

This study aims to assess the impact of microplastics (MPs) on erythrocytes using eryptosis (apoptosis) and an erythron profile (poikilocytosis and nuclear abnormalities), considered to be novel biomarkers in Nile tilapia (Oreochromis niloticus). In this study, four groups of fish were used: The first was the control group. In the second group, 1 mg/L of MPs was introduced to the samples. The third group was exposed to 10 mg/L of MPs. Finally, the fourth group was exposed to 100 mg/L of MPs for 15 days, following 15 days of recovery. The fish treated with MPs experienced an immense rise in the eryptosis percentage, poikilocytosis, and nuclear abnormalities of red blood cells (RBCs) compared with the control group in a concentration-dependent manner. Poikilocytosis of MP-exposed groups included sickle cell shape, schistocyte, elliptocyte, acanthocyte, and other shapes. Nuclear abnormalities of the MPs-exposed groups included micronuclei, binucleated erythrocytes, notched, lobed, blebbed, and hemolyzed nuclei. After the recovery period, a greater percentage of eryptosis, poikilocytotic cells, and nuclear abnormalities in RBCs were still evident in the groups exposed to MPs when crosschecked with the control group. The results show concerning facts regarding the toxicity of MPs in tilapia.

19.
Mar Pollut Bull ; 173(Pt A): 112966, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34563956

ABSTRACT

This study records the extent of microplastics (MPs) in the surface water, sediments, and fishes of the Mediterranean and Red seas in Egypt. In sediment and water samples, the Ras Gharib station in the Red sea and Damietta and Port Said stations in the Mediterranean sea exhibited the highest microplastic abundance, while the lowest concentration was found in the Ain Sukhna station in the Red Sea and Marsa Matruh station in the Mediterranean sea. Rayon and polyethylene terephthalate were the most frequently found polymers in fishes. The results highlighted the abundant existence of microplastics in sediments, water, and fishes of the Mediterranean and Red seas, thereby improving our understanding of the environmental risks posed by microplastics to fisheries and marine ecosystems and the need for measures to diminish the flux of plastics to the marine settings.


Subject(s)
Microplastics , Water Pollutants, Chemical , Animals , Ecosystem , Egypt , Environmental Monitoring , Fishes , Geologic Sediments , Mediterranean Sea , Plastics , Water , Water Pollutants, Chemical/analysis
20.
Future Med Chem ; 13(20): 1743-1766, 2021 10.
Article in English | MEDLINE | ID: mdl-34427113

ABSTRACT

Thiazole-substituted pyrazole is an important structural feature of many bioactive compounds, including antiviral, antitubercular, analgesic and anticancer agents. Herein we describe an efficient and facile approach for the synthesis of two series of 36 novel N-bridged pyrazole-1-phenylthiazoles. The antiproliferative activity of a set of representative compounds was evaluated in vitro against different human cancer cell lines. Among the identified compounds, compound 18 showed potent anticancer activity against the examined cancer cell lines. The in silico molecular docking study revealed that compound 18 possesses high binding affinity toward both SK1 and CDK2. Overall, these results indicate that compound 18 is a promising lead anticancer compound which may be exploited for development of antiproliferative drugs.


Subject(s)
Antineoplastic Agents/pharmacology , Bridged-Ring Compounds/pharmacology , Drug Design , Protein Kinase Inhibitors/pharmacology , Thiazoles/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Bridged-Ring Compounds/chemical synthesis , Bridged-Ring Compounds/chemistry , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Humans , Molecular Docking Simulation , Molecular Structure , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Protein Kinases/metabolism , Thiazoles/chemical synthesis , Thiazoles/chemistry , Tumor Cells, Cultured
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