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1.
J Basic Microbiol ; : e202300279, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38616711

RESUMO

Hepatitis C virus (HCV) is the most common infection worldwide. The correlation between HCV and renal cell carcinoma (RCC) is still mysterious. Therefore, the relationship between HCV and RCC was investigated. The study included 100 patients with RCC; 32 with HCV infection, and 68 without HCV infection. Expressions of viral proteins (NS3 and NS5A) were tested using an immune electron-microscope (IEM) and immunohistochemistry (IHC). IHC and quantitative real time-PCR investigated the presentation of human proteins TP53 and p21 genes. Transmission electron (TEM) detected viral-like particles in infected RCC tissues. The gene and protein expression of P53 was higher in HCV positive versus HCV negative patients and p21 was lower in HCV positive versus HCV negative in both tumor and normal tissue samples. Viral like particles were observed by TEM in the infected tumor and normal portion of the RCC tissues and the plasma samples. The IEM showed the depositions of NS3 and NS5A in infected renal tissues, while in noninfected samples, were not observed. The study hypothesizes that a correlation between HCV and RCC could exist through successfully detecting HCV-like particles, HCV proteins, and (p53 and p21) in RCC-infected patients.

2.
Int J Biol Macromol ; 267(Pt 1): 131390, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38582473

RESUMO

In recent decades, bio-polymeric nanogels have become a forefront in medical research as innovative in-vivo drug carriers. This study introduces a pH-sensitive chitosan nanoparticles/P(N-Isopropylacrylamide-co-Acrylic acid) nanogel (CSNPs/P(NIPAm-co-AAc)), making significant advancements. The nanogel effectively encapsulated doxorubicin hydrochloride (Dx. HCl), a model drug, within its compartments through electrostatic binding. Comparing nano chitosan (CSNPs) before and after integrating copolymerized P(NIPAm-co-AAc), highlighting an improved and adaptable nanogel structure with responsive behaviors. The intraperitoneal delivery of Dx-loaded nanogel (Dx@N.gel) to Ehrlich ascites carcinoma (Eh)-bearing mice at doses equivalent to 1.5 and 3 mg/kg of Dx per day for 14 days exhibited superiority over the administration of free Dx. Dx@N.gel demonstrated heightened anticancer activity, significantly improving mean survival rates in Eh mice. The nanogel's multifaceted defense mechanism mitigated oxidative stress, inhibited lipid peroxidation, and curbed nitric oxide formation induced by free Dx. It effectively countered hepatic DNA deterioration, normalized elevated liver and cardiac enzyme levels, and ameliorated renal complications. This pH-responsive CSNPs/P(NIPAm-co-AAc) nanogel loaded with Dx represents a paradigm shift in antitumor drug delivery. Its efficacy and ability to minimize side effects, contrasting sharply with those of free Dx, offer a promising future where potent cancer therapies seamlessly align with patient well-being.

3.
J Enzyme Inhib Med Chem ; 39(1): 2311818, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38488131

RESUMO

In this article, a new series of 2-((3,5-disubstituted-2-thioxo-imidazol-1-yl)imino)acenaphthylen-1(2H)-ones were synthesized. Imidazole-2-thione with acenaphthylen-one gave a hybrid scaffold that integrated key structural elements essential for DNA damage via direct DNA intercalation and inhibition of the topoisomerase II enzyme. All the synthesized compounds were screened to detect their DNA damage using a terbium fluorescent probe. Results demonstrated that 4-phenyl-imidazoles 5b and 5e in addition to 4-(4-chlorophenyl)imidazoles 5h and 5j would induce detectable potent damage in ctDNA. The four most potent compounds as DNA intercalators were further evaluated for their antiproliferative activity against HepG2, MCF-7 and HCT-116 utilizing the MTT assay. The highest anticancer activity was recorded with compounds 5b and 5h against the breast cancer cell line MCF-7 which were 1.5- and 3- folds more active than doxorubicin, respectively. Therefore, imidazole-2-thione tethered acenaphthylenone derivatives can be considered as promising scaffold for the development of effective dual DNA intercalators and topoisomerase II inhibitors.


Assuntos
Antineoplásicos , Inibidores da Topoisomerase II , Inibidores da Topoisomerase II/farmacologia , Inibidores da Topoisomerase II/química , Relação Estrutura-Atividade , Substâncias Intercalantes/farmacologia , Tionas/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Imidazóis/farmacologia , DNA , Apoptose , Simulação de Acoplamento Molecular , DNA Topoisomerases Tipo II/metabolismo , Proliferação de Células
4.
Artigo em Inglês | MEDLINE | ID: mdl-38547465

RESUMO

Prompt diagnosis and early treatment are key goals to optimize the outcomes of children with growth hormone deficiency (GHD) and attain the genetically expected adult height. Nonetheless, several barriers can hinder prompt diagnosis and treatment of GHD, including payer-related issues. In Saudi Arabia, moderate-to-severe short stature was reported in 13.1 and 11.7 % of healthy boys and girls, respectively. Several access and payer barriers can face pediatric endocrinologists during the diagnosis and treatment of GHD in Saudi Arabia. Insurance coverage policies can restrict access to diagnostic tests for GHD and recombinant human growth hormone (rhGH) due to their high costs and lack of gold-standard criteria. Some insurance policies may limit the duration of treatment with rhGH or the amount of medication covered per month. This consensus article gathered the insights of pediatric endocrinologists from Saudi Arabia to reflect the access and payer barriers to the diagnostic tests and treatment options of children with short stature. We also discussed the current payer-related challenges endocrinologists face during the investigations of children with short stature. The consensus identified potential strategies to overcome these challenges and optimize patient management.

5.
J Pediatr Orthop ; 44(5): e426-e432, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38454784

RESUMO

OBJECTIVE: This work aimed to evaluate the results of using a 2-stage surgical treatment strategy without doing anterior transposition of the ulnar nerve (ATUN) for cases with long-standing nonunited fracture lateral humeral condyle (LHC) in children, accompanied by a critical review. METHODS: A consecutive 12 children with a long-standing ">2 years" nonunited LHC with evident radiologic gross anatomic distortion of the elbow were included in this study. A 2-stage surgical treatment strategy was applied, wherein the first stage, open functional reduction, osteosynthesis, and iliac bone graft were done. Then after 6 months, the second stage surgery was carried out in the form of supracondylar humeral corrective osteotomy if the cubitus valgus angle was ≥20 degrees. ATUN was not done for any of the cases even with those having ulnar nerve dysfunction. RESULTS: Union took place in 11 out of the 12 cases after a mean follow-up period of 11 weeks (range: 8 to 14 wk; SD: 1.6). All the 7 cases showed preoperative ulnar nerve dysfunction and reported clinical recovery at the end of their follow-up. CONCLUSIONS: Two-stage surgical treatment strategy without ATUN is a convenient, reproducible, and successful line of treatment for children presented with longstanding nonunited LHC with anatomically distorted elbow. LEVEL OF EVIDENCE: Level IV-case series.


Assuntos
Articulação do Cotovelo , Fraturas não Consolidadas , Fraturas do Úmero , Criança , Humanos , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/cirurgia , Fraturas do Úmero/complicações , Úmero/cirurgia , Nervo Ulnar , Fixação Interna de Fraturas/métodos , Fraturas não Consolidadas/cirurgia , Articulação do Cotovelo/cirurgia , Resultado do Tratamento , Amplitude de Movimento Articular/fisiologia , Estudos Retrospectivos
6.
Vet Microbiol ; 292: 110063, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554598

RESUMO

Pseudomonas aeruginosa (P. aeruginosa) is an ESKAPE pathogen that can quickly develop resistance to most antibiotics. This bacterium is a zoonotic pathogen that can be found in humans, animals, foods, and environmental samples, making it a One-Health concern. P. aeruginosa threatens the poultry industry in Egypt, leading to significant economic losses. However, the investigation of this bacterium using NGS technology is nearly non-existent in Egypt. In this study, 38 isolates obtained from broiler farms of the Delta region were phenotypically investigated, and their genomes were characterized using whole genome sequencing (WGS). The study found that 100% of the isolates were resistant to fosfomycin and harbored the fosA gene. They were also resistant to trimethoprim/sulfamethoxazole, although only one isolate harbored the sul1 gene. Non-susceptibility (resistant, susceptible with increased dose) of colistin was observed in all isolates. WGS analysis revealed a high level of diversity between isolates, and MLST analysis allocated the 38 P. aeruginosa isolates into 11 distinct sequence types. The most predominant sequence type was ST267, found in 13 isolates, followed by ST1395 in 8 isolates. The isolates were susceptible to almost all tested antibiotics carrying only few different antimicrobial resistance (AMR) genes. Various AMR genes that confer resistance mainly to ß-lactam, aminoglycoside, sulfonamide, and phenicol compounds were identified. Additionally, several virulence associated genes were found without any significant differences in number and distribution among isolates. The majority of the virulence genes was identified in almost all isolates. The fact that P. aeruginosa, which harbors several AMR and virulence-associated factors, is present in poultry farms is alarming and threatens public health. The misuse of antimicrobial compounds in poultry farms plays a significant role in resistance development. Thus, increasing awareness and implementing strict veterinary regulations to guide the use of veterinary antibiotics is required to reduce health and environmental risks. Further studies from a One-Health perspective using WGS are necessary to trace the potential transmission routes of resistance between animals and humans and clarify resistance mechanisms.


Assuntos
Aves Domésticas , Infecções por Pseudomonas , Humanos , Animais , Aves Domésticas/genética , Pseudomonas aeruginosa/genética , Virulência/genética , Fazendas , Tipagem de Sequências Multilocus/veterinária , Egito/epidemiologia , Galinhas/microbiologia , Antibacterianos/farmacologia , Sequenciamento Completo do Genoma/veterinária , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/veterinária , Fatores de Virulência/genética
8.
Artigo em Inglês | MEDLINE | ID: mdl-38456977

RESUMO

Silica fume is usually used in UHPC, three times more than that for normal concrete, to enhance mechanical properties and durability. However, silica fume (SF) is an expensive material and has high production costs. This work is aimed at investigating the shrinkage and durability performance of previously developed UHPC mixtures utilizing the two calcareous waste materials, namely limestone powder (LSP) and cement kiln dust (CKD), by partially replacing the silica fume. The optimally selected mixtures of UHPC, having flow and strength above the minimum required, were used for detailed investigation in terms of shrinkage and durability characteristics. The results showed that by replacing SF with up to 20% of LSP and up to 20% of CKD, the mechanical properties of UHPC remained satisfactory compared to the control mixture with 100% SF. However, the ultimate shrinkage was higher for mixtures incorporating LSP or CKD, indicating the need for more volume of steel fibers to compensate for the shrinkage strains. The developed UHPCs also exhibited high resistance against reinforcement corrosion and sulfate attack, making them suitable for use in aggressive exposure conditions. However, special attention needs to be paid to the CKD content, where it is recommended to limit the content of CKD to about 15% or less to control the durability performance of the UHPCs. In addition, the sustainability analysis of developed UHPC mixtures was carried out using the life-cycle assessment and eco-strength intensity index. The results indicated that the UHPC mixtures possess a higher life-cycle and are therefore more sustainable.

9.
BMC Vet Res ; 20(1): 90, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459498

RESUMO

BACKGROUND: Multiple sclerosis (MS) is a chronic condition that primarily manifests as demyelination of neuronal axons in the central nervous system, due to the loss or attack of oligodendroglia cells that form myelin. Stem cell therapy has shown promising results for the treatment of MS due to its capability to halt the immune attack, stop apoptosis and axonal degeneration, and differentiate into oligodendrocytes. Stem cell-derived Exosomes (Exosomes) have shown great capabilities for neuronal diseases as they have growth factors, complex sets of miRNA, enzymes, proteins, major peptides, lipids, and macromolecules with anti-inflammatory, angiogenesis, and neurogenesis activities. METHODS: This study aimed to compare the healing properties of stem cells, against Exosomes for the treatment of an experimentally induced MS dog model. Dog models of MS received either a single treatment of stem cells or a single treatment of Exosomes intrathecally and the treatment process was evaluated clinically, radiologically, histopathologically, and electron microscopy and cerebrospinal fluid analysis. RESULTS: showed marked amelioration of the clinical signs in both treated groups compared to the control one, magnetic resonance scans showed the resolution of the hyperintense lesions at the end of the study period, the histopathology and electron microscopy showed marked healing properties and remyelination in treated groups with superiority of the stem cells compared to Exosomes. CONCLUSIONS: Although stem cell results were superior to Exosomes therapy; Exosomes have proven to be effective and safe important actors in myelin regeneration, and their use in diseases like MS helps to stimulate remyelination.


Assuntos
Doenças do Cão , Exossomos , Esclerose Múltipla , Cães , Animais , Esclerose Múltipla/veterinária , Esclerose Múltipla/tratamento farmacológico , Bainha de Mielina/metabolismo , Bainha de Mielina/patologia , Células-Tronco , Terapia Baseada em Transplante de Células e Tecidos/veterinária , Doenças do Cão/patologia
10.
Pathogens ; 13(2)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38392917

RESUMO

Brucellosis and coxiellosis/Q fever are bacterial infections caused by Brucella species and Coxiella burnetii, respectively; camels are highly susceptible to both pathogens. Trichinellosis is a parasitic infection caused by various Trichinella nematode species. Reportedly, camels are susceptible to experimental infection with Trichinella spp., but information on this potential host species is scarce. All three infections are of zoonotic nature and thus of great public health concern. The current study aimed to determine antibodies against the three pathogens in recently imported camels (n = 491) from Sudan at the two main ports for the entrance of camels into southern Egypt using commercial indirect ELISAs. Samples were collected in two sampling periods. The seropositivity rates of Brucella spp., C. burnetii, and Trichinella spp. were 3.5%, 4.3%, and 2.4%, respectively. Mixed seropositivity was found in 1% for Brucella spp. and C. burnetii. Marked differences were found between the two study sites and the two sampling periods for Brucella. A higher rate of seropositivity was recorded in the Red Sea/older samples that were collected between 2015 and 2016 (4.3%, 17/391; odds ratio = 9.4; p < 0.030) than in those collected in Aswan/recent samples that were collected between 2018 and 2021 (0/100). Concerning C. burnetii, samples collected during November and December 2015 had a significantly higher positivity rate than the other samples (13%, 13/100; OD = 4.8; p < 0.016). The same effect was observed for antibodies to Trichinella spp., with samples collected during November and December 2015 showing a higher positivity rate than the other samples (7%, 7/100; OD = 10.9; p < 0.001). This study provides valuable information on the seroprevalence of Brucella spp. and additional novel information on C. burnetii and Trichinella spp. in recently imported camels kept in quarantine before delivery to other Egyptian regions. This knowledge can be utilized to reduce health hazards and financial burdens attributable to brucellosis, Q fever, and trichinellosis in animals and humans in Egypt.

11.
Int J Biol Macromol ; 262(Pt 1): 129995, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38325680

RESUMO

This study aimed to develop a novel adsorbent designed for the removal of diclofenac sodium (DS) from water. The synthesized adsorbent, a composite sponge known as guava seeds activated carbon loaded calcium alginate (GSAC@CA aerogel), was created through the combination of powdered activated carbon derived from guava seeds and loaded onto a calcium alginate hydrogel. Characterization through SEM, XRD, FT-IR, BET, and XPS revealed a confirmed surface area of 738.82 m2/g. The investigation delved into assessing the influence of pH, initial DS concentration, and adsorbent dose on the adsorption of DS. Isotherm studies on adsorption suggested that a Langmuir model provided a good fit, indicating a monolayer adsorption process. Kinetic studies revealed a well-fitted pseudo-second-order model, shedding light on the dynamics of the reaction. The chemisorption nature was elucidated by the Dubinin-Radushkevich model, demonstrating an adsorption energy of 22.6 kJ/mol. These results affirm the potential of the GSAC@CA aerogel composite sponge as an efficient adsorbent for removing diclofenac sodium from water. Examination of the impact of temperature on the adsorption process revealed an endothermic behavior, indicating an increase in temperature. The positive change in entropy suggested the spontaneous nature of the reaction. Remarkably, the GSAC@CA aerogel composite sponge exhibited strong adsorption capabilities, achieving a maximum adsorption capacity of 489.97 mg/g. Across five consecutive cycles, the composite consistently demonstrated high-level adsorption, maintaining a removal efficiency of 87.77 %. The adsorption mechanism of diclofenac sodium (DS) on the GSAC@CA aerogel composite sponge was determined to encompass various processes, such as hydrogen bonding, π-π interactions, ion exchange, and electrostatic pore filling. Additionally, the adsorbent demonstrated successful regeneration over three cycles when applied to a real-world sample. The incorporation of the Box-Behnken design (BBD) introduced a strategic aspect to enhance adsorption outcomes, offering valuable insights for optimizing the adsorption process in practical applications.


Assuntos
Psidium , Poluentes Químicos da Água , Termodinâmica , Carvão Vegetal/química , Diclofenaco , Adsorção , Cinética , Espectroscopia de Infravermelho com Transformada de Fourier , Poluentes Químicos da Água/química , Água/química , Concentração de Íons de Hidrogênio
12.
Cells ; 13(3)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38334679

RESUMO

A well-known natural ingredient found in several medicinal plants, berberine (Ber), has been shown to have anticancer properties against a range of malignancies. The limited solubility and bioavailability of berberine can be addressed using Ber-loaded nanoparticles. In this study, we compared the in vitro cytotoxic effects of both Ber-loaded silver nanoparticles (Ber-AgNPs) and Ber-loaded selenium nanoparticles (Ber-SeNPs) in the human liver cancer cell line (HepG2) and mouse normal liver cells (BNL). The IC50 values in HepG2 for berberine, Ber-AgNPs, Ber-SeNPs, and cisplatin were 26.69, 1.16, 0.04, and 0.33 µg/mL, respectively. Our results show that Ber and its Ag and Se nanoparticles exerted a good antitumor effect against HepG2 cells by inducing apoptosis via upregulating p53, Bax, cytosolic cytochrome C levels, and caspase-3 activity, and the down-regulation of Bcl-2 levels. Similarly, incubation with Ber and both Ber-NPs (Ag and Se) led to a significant dose-dependent elevation in inflammatory markers' (TNF-α, NF-κB, and COX-2) levels compared to the control group. In addition, it led to the arrest of the G1 cell cycle by depleting the expression of cyclin D1 and CDK-2 mRNA. Furthermore, Ber and both Ber-NPs (Ag and Se) caused a significant dose-dependent increase in LDH activity in HepG2 cells. Furthermore, our findings offer evidence that Ber and its nanoparticles intensified oxidative stress in HepG2 cells. Furthermore, the migration rate of cells subjected to berberine and its nanoforms was notably decreased compared to that of control cells. It can be inferred that Ber nanoparticles exhibited superior anticancer efficacy against HepG2 compared to unprocessed Ber, perhaps due to their improved solubility and bioavailability. Furthermore, Ber-SeNPs exhibited greater efficacy than Ber-AgNPs, possibly as a result of the inherent anticancer characteristics of selenium.


Assuntos
Berberina , Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas Metálicas , Selênio , Camundongos , Animais , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Selênio/farmacologia , Berberina/farmacologia , Prata/farmacologia , Neoplasias Hepáticas/patologia , Linhagem Celular
13.
Coron Artery Dis ; 35(4): 309-313, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38411142

RESUMO

BACKGROUND: The role of coronary artery spasm (CAS) was extended beyond variant angina to ischemic heart disease in general, including effort angina, unstable angina, acute myocardial infarction (MI) and sudden death. It is difficult and cumbersome to examine CAS during coronary angiography. Risk factors for CAS include smoking and genetic polymorphisms. AIM: We aimed to investigate the association of the interleukin-6 (IL-6) polymorphism with catheter-induced CAS in Egyptian patients who undergo coronary angiography. METHODS: This is a case-control study. Two hundred patients with chronic coronary artery disease who underwent elective coronary angiography were included in the study. Patients were divided into two groups: the non-CAS group (100 patients) and the CAS group (100 patients). The subjects were genotyped to the -572 C>G (rs 1800796) polymorphism of the IL-6 gene by PCR-restriction fragment length polymorphism. RESULTS: We found that patients with CAS have more risk factors for atherosclerosis compared to those without CAS. Smoking, the IL-6 GG genotype, and the G allele were independent risk factors for CAS. CONCLUSION: We concluded that the GG genotype and G allele of the IL-6 gene are associated with CAS. Smoking, the GG genotype, and the G allele of the IL-6 gene are independent predictors of catheter-induced CAS.


Assuntos
Angiografia Coronária , Vasoespasmo Coronário , Predisposição Genética para Doença , Interleucina-6 , População do Norte da África , Fumar , Humanos , Egito/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Interleucina-6/genética , Vasoespasmo Coronário/genética , Vasoespasmo Coronário/diagnóstico , Vasoespasmo Coronário/epidemiologia , Estudos de Casos e Controles , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Idoso , Cateterismo Cardíaco , Frequência do Gene , Fenótipo , Cateteres Cardíacos , Estudos de Associação Genética , Polimorfismo de Nucleotídeo Único , Polimorfismo Genético
14.
J Pediatr Endocrinol Metab ; 37(2): 110-122, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38197679

RESUMO

OBJECTIVES: This study aims to explore the effects of fat mass obesity-associated (FTO) (rs9939609) and melanocortin 4 receptor (MC4R) (rs17782313) gene polymorphisms in children with type 1 diabetes (T1D) and their relation to obesity. METHODS: Fat mass obesity-associated (FTO) (rs9939609) and melanocortin 4 receptor (MC4R) (rs17782313) gene polymorphisms were evaluated in 164 patients and 100 controls, and genotypes, alleles, and haplotype frequencies were compared between cases and controls. RESULTS: A significant association with T1D development was found with the TC, CC, and TC+CC genotypes and the C allele of MC4R rs17782313. In addition, TA, AA, and TA+AA genotypes and the A allele of FTO rs9939609 may also be risky for T1D development. While the TC and TC+CC genotypes of MC4R rs17782313 may be protective against obesity development, the AA genotype and A allele of FTO rs9939609 may also be protective against obesity development. Regarding obese subjects, comparing diabetics vs. non-diabetic studied subjects, FTO rs9939609, TA, AA, and TA+AA genotypes and the A allele had significantly higher frequencies in T1D with a higher risk of developing T1D. However, conducting multivariable analysis using significant covariates in univariable analysis revealed that only earlier age of T1D onset, lower C-peptide, and the MC4R dominant model were considered independent predictors of obesity within T1D. CONCLUSIONS: The role of both genes' polymorphisms on the pathogenesis and the outcome of T1D and obesity can help in understanding the pathogenesis of both diseases and their associations with each other's and may be used as novel therapeutic targets for both diseases.


Assuntos
Diabetes Mellitus Tipo 1 , Criança , Humanos , Diabetes Mellitus Tipo 1/genética , Receptor Tipo 4 de Melanocortina/genética , Polimorfismo de Nucleotídeo Único , Índice de Massa Corporal , Obesidade/genética , Genótipo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Predisposição Genética para Doença
15.
Biomed Pharmacother ; 171: 116215, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38278024

RESUMO

To date, no total curative therapy for hepatocellular carcinoma (HCC) is available. This study aimed to evaluate the anticancer effect of black Vitis vinifera (VV) seed oil saponifiable (Sap) fraction (BSap) using five different cancer cell lines. The apoptotic and anti-inflammatory impacts of BSap on the cell line with the highest cytotoxic effect were studied. Furthermore, its therapeutic effect on p-dimethylaminoazobenzene (p-DAB)-induced HCC in mice was investigated. The phenolic and vitamin content, as well as the antiradical activities of BSap, were assessed. BSap demonstrated a greater cytotoxic effect on HepG-2 cells (lowest IC50 and highest SI values) than did the other tested cell lines. BSap showed superior anticancer efficacy to 5-FU on all examined cancer cells, particularly HepG-2 cells, by inducing apoptosis and downregulating NF-κB. In HCC-bearing mice, BSap reduced hepatic lipid peroxidation and boosted GSH levels due to its potent antiradical activities and high reducing power. In addition, it had an apoptotic effect by upregulating p53 and BAX and downregulating Bcl-2 fold expression. Moreover, BSap lowered the fold expression of various crucial HCC-related genes: CD133, ALAD1α1, COX-2, ABCG1, AKT1, Gli, Notch1, and HIF1α. Liver function markers and histopathology showed significant improvements in HCC-bearing mice after BSap administration compared to 5-FU. In silico analysis revealed that the most abundant phenolic and fatty acid ingredients of BSap exhibited competitive inhibitory effects on valuable HCC-associated enzymes (NADPH oxidase, histone deacetylase 1, and sepiapterin reductase). Thus, BSap fraction may be a promising treatment of HCC.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Vitis , Camundongos , Animais , Humanos , Carcinoma Hepatocelular/patologia , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Hepáticas/patologia , Linhagem Celular Tumoral , Células Hep G2 , Apoptose , Antineoplásicos/farmacologia , Fluoruracila/farmacologia , Óleos de Plantas/farmacologia
16.
iScience ; 27(1): 108583, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38226158

RESUMO

Water pollution and the global energy crisis are two significant challenges that the world is facing today. Ultrasound-assisted synthesis offers a simple, versatile, and green synthetic tool for nanostructured materials that are often unavailable by traditional synthesis. Furthermore, the integration of ultrasound and photocatalysis has recently received considerable interest due to its potential for environmental remediation as a low-cost, efficient, and environmentally friendly technique. The underlying principles and mechanisms of sonophotocatalysis, including enhanced mass transfer, improved catalyst-pollutant interaction, and reactive species production have been discussed. Various organic pollutants as dyes, pharmaceuticals, pesticides, and emerging organic pollutants are targeted based on their improved sonophotocatalytic degradation efficiency. Additionally, the important factors affecting sonophotocatalytic processes and the advantages and challenges associated with these processes are discussed. Overall, this review provides a comprehensive understanding of sono-assisted synthesis and photocatalytic degradation of organic pollutants and prospects for progress in this field.

17.
Microb Cell Fact ; 23(1): 25, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238770

RESUMO

BACKGROUND: Although E. coli is generally a well-opted platform for the overproduction of recombinant antigens as heterologous proteins, the optimization of expression conditions to maximize the yield of functional proteins remains empirical. Herein, we developed an optimized E. coli (BL21)-based system for the overproduction of soluble immunoreactive HCV core/envelope proteins that were utilized to establish a novel immunoassay for discrimination of active HCV infection. METHODS: The core/E1-E2 genes were amplified and expressed in E. coli BL21 (DE3) in the absence/presence of glycylglycine. The antigenic performance of soluble proteins was assessed against 63 HCV-seronegative (Ab-) sera that included normal and interferent sera (HBV and/or chronic renal failure), and 383 HCV-seropositive (Ab+) samples that included viremic (chronic/relapsers) and recovered patients' sera. The color intensity (OD450) and S/Co values were estimated. RESULTS: The integration of 0.1-0.4M glycylglycine in the growth media significantly enhanced the solubility/yield of recombinant core and envelope proteins by ~ 225 and 242 fold, respectively. This was reflected in their immunoreactivity and antigenic performance in the developed immunoassay, where the soluble core/E1/E2 antigen mixture showed 100% accuracy in identifying HCV viremic sera with a viral RNA load as low as 3800 IU/mL, without cross-reactivity against normal/interferent HCV-Ab-sera. The ideal S/Co threshold predicting active viremia (> 2.75) showed an AUC value of 0.9362 (95% CI: 0.9132 to 0.9593), with 87.64, 91.23% sensitivity and specificity, and 94.14, 82.11% positive and negative predictive values, respectively. The different panels of samples assayed with our EIA showed a good concordance with the viral loads and also significant correlations with the golden standards of HCV diagnosis in viremic patients. The performance of the EIA was not affected by the immunocompromised conditions or HBV co-infection. CONCLUSION: The applicability of the proposed platform would extend beyond the reported approach, where glycylglycine, low inducer concentration and post-induction temperature, combined with the moderately-strong constitutive promoter enables the stable production of soluble/active proteins, even those with reported toxicity. Also, the newly developed immunoassay provides a cost-effective point-of-care diagnostic tool for active HCV viremia that could be useful in resource-limited settings.


Assuntos
Glicilglicina , Hepatite C , Humanos , Viremia/diagnóstico , Escherichia coli , Sistemas Automatizados de Assistência Junto ao Leito , Solubilidade , Anticorpos Anti-Hepatite C , Hepacivirus/genética , Imunoensaio , Proteínas Recombinantes
19.
J Cardiovasc Dev Dis ; 11(1)2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38276658

RESUMO

(1) Background: This study examines frailty's impact on proximal aortic surgery outcomes. (2) Methods: All patients with a thoracic aortic aneurysm who underwent aortic root, ascending aorta, or arch surgery from the 2016-2017 National Inpatient Sample were included. Frailty was defined by the Adjusted Clinical Groups Frailty Indicator. Outcomes of interest included in-hospital mortality and a composite of death, stroke, acute kidney injury (AKI), and major bleeding (MACE). (3) Results: Among 5745 patients, 405 (7.0%) met frailty criteria. Frail patients were older, with higher rates of chronic pulmonary disease, diabetes, and chronic kidney disease. There was no difference in in-hospital death (4.9% vs. 2.4%, p = 0.169); however, the frail group exhibited higher rates of stroke and AKI. Frail patients had a longer length of stay (17 vs. 8 days), and higher rates of non-home discharge (74.1% vs. 54.3%) than non-frail patients (both p < 0.001). Sensitivity analysis confirmed increased morbidity and mortality in frail individuals. After adjusting for patient comorbidities and hospital characteristics, frailty independently predicted MACE (OR 4.29 [1.88-9.78], p = 0.001), while age alone did not (OR 1.00 [0.99-1.02], p = 0.568). Urban teaching center status predicted a lower risk of MACE (OR 0.27 [0.08-0.94], p = 0.039). (4) Conclusions: Frailty is associated with increased morbidity in proximal aortic surgery and is a more significant predictor of mortality than age. Coordinated treatment in urban institutions may enhance outcomes for this high-risk group.

20.
Antioxidants (Basel) ; 13(1)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38247490

RESUMO

The prolonged use of exogenous glucocorticoids, such as dexamethasone (Dex), is the most prevalent secondary cause of osteoporosis, known as glucocorticoid-induced osteoporosis (GIO). The current study examined the preventative and synergistic effect of aqueous chicory extract (ACE) and ethanolic purslane extract (EPE) on GIO compared with Alendronate (ALN). The phytochemical contents, elemental analysis, antioxidant scavenging activity, and ACE and EPE combination index were evaluated. Rats were randomly divided into control, ACE, EPE, and ACE/EPE MIX groups (100 mg/kg orally), Dex group (received 1.5 mg Dex/kg, Sc), and four treated groups received ACE, EPE, ACE/EPE MIX, and ALN with Dex. The bone mineral density and content, bone index, growth, turnover, and oxidative stress were measured. The molecular analysis of RANK/RANKL/OPG and Nrf2/HO-1 pathways were also evaluated. Dex causes osteoporosis by increasing oxidative stress, decreasing antioxidant markers, reducing bone growth markers (OPG and OCN), and increasing bone turnover and resorption markers (NFATc1, RANKL, ACP, ALP, IL-6, and TNF-α). In contrast, ACE, EPE, and ACE/EPE MIX showed a prophylactic effect against Dex-induced osteoporosis by modulating the measured parameters and the histopathological architecture. In conclusion, ACE/EPE MIX exerts a powerful synergistic effect against GIO by a mode of action different from ALN.

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