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1.
Org Biomol Chem ; 22(35): 7117-7120, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39150283

RESUMEN

A practical and efficient method for the C-3 site selective alkenylation of indoles was developed for constructing novel indole-functionalized vinyl sulfonyl fluorides and indolyl allylic sulfonyl fluorides. The reaction is accomplished with exclusive regio- and stereoselectivity without using transition metal catalysts, providing novel products of great potential value in medicinal chemistry, chemical biology, and drug discovery.

2.
J Org Chem ; 89(18): 13709-13718, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39151070

RESUMEN

A practical copper-catalyzed process for the synthesis of the ß-arylethenesulfonyl fluorides is described. A series of α-bromo arylethyl sulfonyl fluorides was prepared via Meerwein reaction from arenediazonium tetrafluoroborates and ethenesulfonyl fluoride (ESF) under mild conditions. The following ß-arylethenesulfonyl fluorides were further obtained through a ß-elimination reaction. This protocol features excellent regio- and stereoselectivity and broad substrate scope.

3.
RSC Adv ; 14(34): 24781-24790, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39114435

RESUMEN

In this work, a congeneric set of quinoline-tethered cis-vinyl triamide hybrids was prepared and evaluated as EGFR tyrosine kinase inhibitors for the management of breast cancer. All of the prepared hybrids were evaluated for their antiproliferative effect against the breast MCF-7 cell line. Among the tested hybrids, compound 6f displayed the most potent antiproliferative activity with an IC50 value of 1.87 µM compared to STU (IC50 = 13.71 µM) as the standard reference. The most promising hybrid, 6f, was found to induce cellular cycle arrest at the G1 phase. Furthermore, the molecular mechanism of this hybrid revealed its ability to induce cellular apoptosis via the mitochondrial-dependent apoptotic pathway. Compound 6f decreased MCF-7 cells' MMP compared to the controls (percentage change value of 57.93%). Further investigation of the selective compound 6f showed that it can inhibit EGFR tyrosine kinase.

4.
Future Med Chem ; 16(16): 1665-1684, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-38949859

RESUMEN

Aim: To synthesize new hybrid cinnamic acids (10a, 10b and 11) and ester derivatives (7, 8 and 9) and investigate their anti-breast cancer activities.Materials & methods: Compounds 7-11 were evaluated (in vitro) for their cytotoxic activities against the MCF-7 cell line. A flow cytometry examination was performed. Protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), topoisomerase II and caspase-9 were measured by qRT-PCR. Molecular docking studies were conducted.Results: Several components were discovered to be active, mainly component 11, which induced arrest in the cell cycle at phase S, greatly decreased the expression of Nrf2 and topoisomerase II; and upregulated the expression of caspase-9.Conclusion: The newly thiohydantoin-cinnamic acid hybrids can contribute to creating promising candidates for cancer drugs.


[Box: see text].


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Cinamatos , Simulación del Acoplamiento Molecular , Humanos , Cinamatos/química , Cinamatos/farmacología , Cinamatos/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Células MCF-7 , Tiohidantoínas/farmacología , Tiohidantoínas/química , Tiohidantoínas/síntesis química , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/antagonistas & inhibidores , Relación Estructura-Actividad , Estructura Molecular , ADN-Topoisomerasas de Tipo II/metabolismo , Apoptosis/efectos de los fármacos , Caspasa 9/metabolismo
5.
Org Biomol Chem ; 22(26): 5325-5332, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38874178

RESUMEN

In this paper, the hydrogenation of aldehydes and ketones using the RANEY® nickel catalyst was successfully applied for the synthesis of alcohol compounds without additional column chromatographic purification. This synthetic strategy features a wide range of substrates, excellent atom economy, high chemical discrimination and the use of a ligand-free catalytic system. Reactions were performed at room temperature in water providing alcohols in high yields and purity.

6.
Front Mol Biosci ; 11: 1387919, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38872915

RESUMEN

Introduction: Increased Actin-like 6A (ACTL6A) expression is associated with various cancers, but its comprehensive investigation across different malignancies is lacking. We aimed to analyze ACTL6A as a potential oncogene and therapeutic target using bioinformatics tools. Methods: We comprehensively analyzed ACTL6A expression profiles across human malignancies, focusing on correlations with tumor grade, stage, metastasis, and patient survival. Genetic alterations were examined, and the epigenetic landscape of ACTL6A was assessed using rigorous methods. The impact of ACTL6A on immune cell infiltration in the tumor microenvironment was evaluated, along with molecular docking studies and machine learning models. Results: Our analysis revealed elevated ACTL6A expression in various tumors, correlating with poor prognostic indicators such as tumor grade, stage, metastasis, and patient survival. Genetic mutations and epigenetic modifications were identified, along with associations with immune cell infiltration and key cellular pathways. Machine learning models demonstrated ACTL6A's potential for cancer detection. Discussion: ACTL6A emerges as a promising diagnostic and therapeutic target in cancer, with implications for prognosis and therapy. Our study provides comprehensive insights into its carcinogenic actions, highlighting its potential as both a prognostic indicator and a target for anti-cancer therapy. This integrative approach enhances our understanding of ACTL6A's role in cancer pathogenesis and treatment.

7.
RSC Adv ; 14(28): 20120-20129, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38915323

RESUMEN

Development of new effective EGFR-targeted antitumor agents is needed because of their clinical significance. A new series of imidazolone-sulphonamide-pyrimidine hybrids was designed and synthesized as modified analogs of some reported EGFR inhibitors. The cytotoxic activity of all the synthesized hybrids was investigated against the breast MCF-7 cancerous cell line using doxorubicin (Dox) as a positive control. 4-(Furan-2-ylmethylene)imidazolone-sulphonamide-pyrimidine 6b had the best potent activity against MCF-7 cells with IC50 result of 1.05 µM, which was better than Dox (IC50 = 1.91 µM). In addition, mechanistic studies revealed the ability of compounds 5g, 5h and 6b to inhibit EGFR kinase. Cell cycle analysis revealed that compound 6b can halt MCF-7 cells at the G1 phase with a concomitant decrease in cellular percentage at the S and G2/M phases. This compound produced a noticeable rise in the proportion of apoptotic cells with regard to the untreated control. Furthermore, the effects of hybrid 6b on the expression levels of pro-apoptotic Bax and pro-survival Bcl2 were assessed. The results showed that this compound upregulated the level of Bax expression as well as declined the expression value of Bcl-2 with regard to the untreated control.

8.
ACS Omega ; 9(17): 19193-19202, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38708229

RESUMEN

This study aimed to verify the presence of biogenic amines (BAs) and evaluate the microbiological activity of some food samples collected from retail stores in the Kingdom of Saudi Arabia. A total of thirty-five dairy and fish products were collected and analyzed for BAs, including putrescine (PUT), cadaverine (CAD), spermidine (SPE), histamine (HIS), spermine (SPR), and tyramine (TYR), as well as for total colony count (TCC), lactic acid bacteria (LAB), Enterobacteriaceae, yeast and mold (Y and M), coliforms, and aerobic sporulation count (ASF). The thin layer chromatography (TLC) method was used in the analytical methodology to identify the BAs. The results showed the presence of BAs in all dairy products, but their concentration did not exceed the maximum permissible limit, which in contrast was established by the Food and Drug Administration (FDA) at 10 mg/100 g. The amounts of BAs in fish products varied significantly. All fish product samples contained levels of BAs below the permissible limit. Results of an independent study also indicated potential toxicity at levels of BAs (>10 mg/100 g) in Egyptian herring. Enterobacteriaceae and the coli group were present in higher concentrations in the Egyptian herring samples, whereas other samples (particularly frozen shrimp) showed increased TCC levels with a higher concentration of histamine-producing bacteria. From a consumer safety perspective, this study also indicated that food samples generally contained acceptable levels of BAs. In conclusion, there is a need to improve and standardize food quality and hygiene practices during production and storage to ensure human safety and prevent HIS formation.

9.
RSC Adv ; 14(16): 11443-11451, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38595714

RESUMEN

The present work aims at design and synthesis of a congeneric series of small hybrids 5 and 6a-i featuring the privileged quinoline scaffold tethered with 2-(arylamido)cinnamide moiety as potential anticancer tubulin polymerization inhibitors. Most of the synthesized hybrids 5 and 6a-i significantly inhibited the growth of the HepG2 cell line, with IC50 ranged from 2.46 to 41.31 µM. In particular, 2-(3,4,5-trimethoxybenzamido)-4-methoxycinnamide-quinoline hybrid 6e displayed potent IC50 value toward the examined cell line, and hence chosen for further mechanistic investigations. It is noteworthy that the antiproliferative action of compound 6e highly correlated well with its ability to inhibit tubulin polymerization. In addition, the most potent hybrid 6e demonstrated a significant modification in the cellular cycle distribution, in addition to provoke of apoptotic death within the tested HepG2 cell line. Furthermore, the mechanistic approach was confirmed by a substantial upregulation in the quantity of active caspase 9 by 5.81-fold relative to untreated control cells.

10.
ACS Omega ; 9(16): 18505-18515, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38680330

RESUMEN

A new series of cinnamide-fluorinated derivatives has been synthesized and characterized by using different spectroscopic and elemental microanalyses methods. All of the prepared p-fluorocinnamide derivatives were evaluated for their cytotoxic activity against the HepG2 liver cancerous cell line. The imidazolone derivative 6, which bears N-(N-pyrimidin-2-ylbenzenesulphamoyl) moiety, displayed antiproliferative activity against HepG2 liver cancerous cells with an IC50 value of 4.23 µM as compared to staurosporin (STU) (IC50 = 5.59 µM). In addition, compound 6 experienced epidermal growth factor receptor (EGFR) inhibitory activity comparable to palatinib. The cell cycle analysis by flow cytometry indicated that compound 6 arrested the cellular cycle of HepG2 cells at the G1 phase. Additionally, as demonstrated by the fluorescence-activated cell sorting (FACS) technique, compound 6 increased both early and late apoptotic ratios compared to control untreated HepG2 cells. Moreover, imidazolone compound 6 induced apoptosis via the intrinsic apoptotic pathway by decreasing the level of mitochondrial membrane polarization (MMP) compared to untreated HepG2 cells. Therefore, the new N-(N-pyrimidin-2-ylbenzenesulphamoyl)imidazolone derivative 6 could be considered a potential platform for further optimizing an antitumor agent against hepatocellular carcinoma.

11.
ACS Omega ; 9(16): 18566-18575, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38680340

RESUMEN

We generated novel elven 1,2,3,6-tetrahydrophthalimides and tetrahydroquinazoline derivatives from 1,2,3,6-tetrahydrophthalic anhydride (1) in response to our interest in using the anhydrides to produce heterocyclic nitrogen compounds. The elemental and spectral analyses of the produced compounds validated the recommended configurations and MOE 2014.09 (Molecular Operating Environment) computations were used to perform their in silico analysis. The synthesized compounds have been analyzed and put through various experiments, including in vitro and in silico methods to assess their biological activity against Escherichia coli Penicillin-Binding Protein 3 (PBP3) and Staphylococcus aureus Penicillin-Binding Protein 2 (PBP2), among these compounds showing promising data as antibacterial drugs.

12.
Environ Sci Pollut Res Int ; 31(21): 31395-31413, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38632193

RESUMEN

Soil contamination with microplastics (MPs) is a persistent threat to crop production worldwide. With a wide range of MP types, including polystyrene (PS), polyvinyl chloride (PVC) and polyethylene (PE), contaminating our environment, it is important to understand their impact on agricultural productivity. The present study was conducted to investigate the effects of different types of MPs (PS, PVC and PE) on various aspects of plant growth. Specifically, we examined growth and biomass, photosynthetic pigments, gas exchange attributes, oxidative stress responses, antioxidant compound activity (both enzymatic and non-enzymatic), gene expression, proline metabolism, the AsA-GSH cycle and cellular fractionation and nutritional status, in different parts of rice (Oryza sativa L.) seedlings, which were also exposed to plant growth promoting rhizobacteria (PGPR), i.e. Bacillus mycoides PM35, i.e. 20 µL. The research outcomes indicated that the different types of MPs in the soil notably reduced plant growth and biomass, photosynthetic pigments and gas exchange attributes. However, MP stress also induced oxidative stress in the roots and shoots of the plants by increasing malondialdehyde (MDA), hydrogen peroxide (H2O2) and electrolyte leakage (EL) which also induced increased compounds of various enzymatic and non-enzymatic antioxidants and also the gene expression. Furthermore, a significant increase in proline metabolism, the AsA-GSH cycle, and the fractionations of cellular components was observed. Although the application of B. mycoides PM35 showed a significant increase in plant growth and biomass, gas exchange characteristics, enzymatic and non-enzymatic compounds and their gene expression and also decreased oxidative stress. In addition, the application of B. mycoides PM35 enhanced cellular fractionation and decreased the proline metabolism and AsA-GSH cycle in O. sativa plants. These results open new insights for sustainable agriculture practices and hold immense promise in addressing the pressing challenges of MP contamination in agricultural soils.


Asunto(s)
Microplásticos , Oryza , Contaminantes del Suelo , Contaminantes del Suelo/metabolismo , Bacillus , Estrés Oxidativo
13.
J Exp Zool A Ecol Integr Physiol ; 341(6): 647-657, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38594572

RESUMEN

Type 1 diabetes stem-cell-based treatment approach is among the leading therapeutic strategies for treating cardiac damage owing to the stem cells' regeneration capabilities. Mesenchymal stem cells derived from adipose tissue (AD-MSCs) have shown great potential in treating diabetic cardiomyopathy (DCM). Herein, we explored the antioxidant-supporting role of N, N'-diphenyl-1,4-phenylenediamine (DPPD) in enhancing the MSCs' therapeutic role in alleviating DCM complications in heart tissues of type 1 diabetic rats. Six male albinos Wistar rat groups have been designed into the control group, DPPD (250 mg/kg, i.p.) group, diabetic-untreated group, and three diabetic rat groups treated with either AD-MSCs (1 × 106 cell/rat, i.v.) or DPPD or both. Interestingly, all three treated diabetic groups exhibited a significant decrease in serum glucose, HbA1c, heart dysfunction markers (lactate dehydrogenase and CK-MP) levels, and lipid profile fractions (except for HDL-C), as well as some cardiac oxidative stress (OS) levels (MDA, AGEs, XO, and ROS). On the contrary, serum insulin, C-peptide, and various cardiac antioxidant levels (GSH, GST, CAT, SOD, TAC, and HO-1), beside viable cardiac cells (G0/G1%), were markedly elevated compared with the diabetic untreated group. In support of these findings, the histological assay reflected a marked enhancement in the cardiac tissues of all diabetic-treated groups, with obvious excellency of the AD-MSCs + DPPD diabetic-treated group. Such results strongly suggested the great therapeutic potentiality of either DPPD or AD-MSCs single injection in enhancing the cardiac function of diabetic rats, with a great noted enhancement superiority of DPPD and AD-MSCs coadministration.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Cardiomiopatías Diabéticas , Ratas Wistar , Animales , Cardiomiopatías Diabéticas/terapia , Masculino , Ratas , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/terapia , Fenilendiaminas/farmacología , Fenilendiaminas/administración & dosificación , Tejido Adiposo , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Estrés Oxidativo/efectos de los fármacos
14.
Future Med Chem ; 16(8): 707-721, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38488019

RESUMEN

Background: 4-Methylacetophenone is used in the preparation of starting materials, 4-methylphenacyle bromide (2) and 4-methylacetophenone thiosemicarbazole (3). Results: Several novel 2,4-disubstituted-1,3-thiazole analogues were obtained via the treatment of starting materials with 4-methylphenacyl bromide, acetyl chloride, aromatic aldehydes and bromination providing thiazole derivatives 5-8 respectively. Conclusion: Compounds 5-8 were investigated for their cytotoxic activity on MCF-7 and normal breast cells. Active compounds were found and in contrast to staurosporine, compound 8 displayed the most potent cytotoxic action that showed a strong inhibitory effect (aromatase) and (protein tyrosine kinase) enzymes, proving that the novel thiazole derivatives promoted the effective anticancer drug candidates.


[Box: see text].


Asunto(s)
Antineoplásicos , Inhibidores de la Aromatasa , Neoplasias de la Mama , Tiazoles , Humanos , Tiazoles/química , Tiazoles/farmacología , Tiazoles/síntesis química , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Inhibidores de la Aromatasa/farmacología , Inhibidores de la Aromatasa/química , Inhibidores de la Aromatasa/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Femenino , Relación Estructura-Actividad , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular/efectos de los fármacos , Aromatasa/metabolismo , Células MCF-7 , Estructura Molecular
15.
Antibiotics (Basel) ; 12(10)2023 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-37887209

RESUMEN

Urinary tract infections (UTIs) are healthcare problems that commonly involve bacterial and, in some rare instances, fungal or viral infections. The irrational prescription and use of antibiotics in UTI treatment have led to an increase in antibiotic resistance. Urine samples (145) were collected from male and female patients from Lower Dir, Khyber Pakhtunkhwa (KP), Pakistan. Biochemical analyses were carried out to identify uropathogens. Molecular analysis for the identification of 16S ribosomal RNA in samples was performed via Sanger sequencing. Evolutionary linkage was determined using Molecular Evolutionary Genetics Analysis-7 (MEGA-7). The study observed significant growth in 52% of the samples (83/145). Gram-negative bacteria were identified in 85.5% of samples, while Gram-positive bacteria were reported in 14.5%. The UTI prevalence was 67.5% in females and 32.5% in males. The most prevalent uropathogenic bacteria were Klebsiella pneumoniae (39.7%, 33/83), followed by Escherichia coli (27.7%, 23/83), Pseudomonas aeruginosa (10.8%, 9/83), Staphylococcus aureus (9.6%, 8/83), Proteus mirabilis (7.2%, 6/83) and Staphylococcus saprophyticus (4.8%, 4/83). Phylogenetic analysis was performed using the neighbor-joining method, further confirming the relation of the isolates in our study with previously reported uropathogenic isolates. Antibiotic susceptibility tests identified K. pneumonia as being sensitive to imipenem (100%) and fosfomycin (78.7%) and resistant to cefuroxime (100%) and ciprofloxacin (94%). Similarly, E. coli showed high susceptibility to imipenem (100%), fosfomycin (78.2%) and nitrofurantoin (78.2%), and resistance to ciprofloxacin (100%) and cefuroxime (100%). Imipenem was identified as the most effective antibiotic, while cefuroxime and ciprofloxacin were the least. The phylogenetic tree analysis indicated that K. pneumoniae, E. coli, P. aeruginosa, S. aureus and P. mirabilis clustered with each other and the reference sequences, indicating high similarity (based on 16S rRNA sequencing). It can be concluded that genetically varied uropathogenic organisms are commonly present within the KP population. Our findings demonstrate the need to optimize antibiotic use in treating UTIs and the prevention of antibiotic resistance in the KP population.

16.
ACS Omega ; 8(41): 38394-38405, 2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37867686

RESUMEN

A variety of 3-(4-chlorophenyl) acrylic acids 4a,b and 3-(4-chlorophenyl)acrylate esters 5a-i were synthesized and structurally proven by spectroscopic studies such as IR, 1H NMR, and 13C NMR as well as mass spectrometry. All substances were investigated for their antiproliferative efficacy against the MDA-MB-231 cell line. Among these, acrylic acid compound 4b demonstrated the most potent cytotoxic effect with an IC50 value of 3.24 ± 0.13 µM, as compared to CA-4 (IC50 = 1.27 ± 09 µM). Additionally, acrylic acid molecule 4b displayed an inhibitory effect against ß-tubulin polymerization with a percentage inhibition of 80.07%. Furthermore, compound 4b was found to produce considerable cell cycle arrest at the G2/M stage and cellular death, as demonstrated by FACS analysis. In addition, the in vivo antitumor screening of the sodium salt of acrylic acid 4b was carried out, and the results have shown that the tested molecule showed a significant decrease in viable EAC count and EAC volume, accompanied by a considerable increase in the life span prolongation, if compared to the positive control group. Furthermore, molecular modeling studies were performed to understand how the highly efficient chemicals 4b and 5e interact with the colchicine-binding region on tubulin. This work aims to shed light on the reasons behind their exceptional cytotoxicity and their better capacity to inhibit tubulin in comparison to CA-4.

17.
Biomedicines ; 11(8)2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37626750

RESUMEN

Cyclin dependent kinase inhibitor 2A (CDKN2A) is a well-known tumor suppressor gene as it functions as a cell cycle regulator. While several reports correlate the malfunction of CDKN2A with the initiation and progression of several types of human tumors, there is a lack of a comprehensive study that analyzes the potential effect of CDKN2A genetic alterations on the human immune components and the consequences of that effect on tumor progression and patient survival in a pan-cancer model. The first stage of the current study was the analysis of CDKN2A differential expression in tumor tissues and the corresponding normal ones and correlating that with tumor stage, grade, metastasis, and clinical outcome. Next, a detailed profile of CDKN2A genetic alteration under tumor conditions was described and assessed for its effect on the status of different human immune components. CDKN2A was found to be upregulated in cancerous tissues versus normal ones and that predicted the progression of tumor stage, grade, and metastasis in addition to poor prognosis under different forms of tumors. Additionally, CDKN2A experienced different forms of genetic alteration under tumor conditions, a characteristic that influenced the infiltration and the status of CD8, the chemokine CCL4, and the chemokine receptor CCR6. Collectively, the current study demonstrates the potential employment of CDKN2A genetic alteration as a prognostic and immunological biomarker under several types of human cancers.

18.
RSC Adv ; 13(34): 23538-23546, 2023 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-37546218

RESUMEN

A new series of acrylic acid and acrylate ester derivatives as modified analogs of tubulin polymerization inhibitors were designed and synthesized. The antiproliferative activity of the constructed molecules was investigated against MCF-7 breast carcinoma cells using CA-4 as positive molecule. Methyl acrylate ester 6e emerged as the most potent cytotoxic agent against MCF-7 cells, with an IC50 value of 2.57 ± 0.16 µM. Also, methyl acrylate ester molecule 6e showed good ß-tubulin polymerization inhibition activity. Cellular cycle analysis showed that compound 6e can arrest MCF-7 cells at the G2/M phase. In addition, this compound produced a significant increase in apoptotic power as compared to control untreated MCF-7 cells. Furthermore, the effect of acrylate ester 6e on the gene expression levels of p53, Bax and Bcl-2 was investigated. This molecule increased the expression levels of both p53 and Bax, and decreased the gene expression level of Bcl-2 as compared to control untreated MCF-7 carcinoma cells.

19.
Infect Drug Resist ; 16: 4463-4469, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37449247

RESUMEN

Background & Aims: This research aimed to determine how variations in the vitamin D receptor gene affected the response of H. pylori infections to eradication therapy. Patients and Methods: On 105 adult H. Pylori-positive patients, a prospective cohort study was carried out. PCR was used to genotype all patients' VDR gene polymorphisms. The patients in the study received standard triple eradication medication (clarithromycin 500 mg, amoxicillin 1000 mg, and omeprazole 20 mg) twice daily for 14 days. A stool test for H. pylori Ag was conducted 4 weeks following the end of treatment. Results: In our study, the usual triple therapy's H. pylori eradication rate was 75.2%. The successful eradication of H. pylori and VDR rs 2228570 gene polymorphisms was more prevalent in CT gene polymorphism (64.6%) compared to non-responders (19.2%), while treatment failure was more prevalent in CC gene polymorphism (73.1% in non-responders compared to responders 24.1%), which is statistically significant. In regards to the eradication of H. pylori and VDR rs7975232 gene polymorphisms, the success of eradication was more prevalent in AC gene polymorphism (54.4%) vs non-responders (30.4%), while all patients (14) with gene AA (17.7%) are responders to standard treatment, while the failure of treatment was more prevalent in CC gene polymorphism (69.2% in non-responder vs 27.8% in responders) which is statistically significant. Our findings demonstrated a strong correlation between patients' responses to H. pylori treatment and polymorphisms in the VDR gene (ApaI and TaqI) (P 0.05). Conclusion: As far as we are aware, this is the first study to identify a potential link between the FokI and Apal VDR polymorphism and treatment response in H pylori-positive patients. To evaluate the findings, more research with larger number of patients and different population is required.

20.
Int J Pharm ; 640: 123023, 2023 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-37150270

RESUMEN

A newly synthesized nanoplatform of hyaluronic acid and chitosan nanoparticles (HA/CNPs) was applied to improve the therapeutic efficacy and protection of bone marrow mesenchymal stem cells (BM-MSCs) against cisplatin (CDDP)-induced nephrotoxicity in rats. CDDP administration causes significant increases in levels of serum creatinine (SCr), urea, and KIM-1 coupled with significant albumin level falls, as indicative of acute renal dysfunction. Moreover, the level of the antioxidant enzyme (GSH) was significantly decreased, while the levels of lipid peroxidation (MDA) and inflammatory (IL-6) and apoptotic (caspase-3) markers were significantly increased, indicating a decline in the kidney's antioxidant defense and increased inflammation. In contrast, when rats were pre-treated with either MSCs or MSCs-HA/CNPs before receiving CDDP, the levels of SCr, urea, KIM-1, MDA, IL-6, and caspase-3 were significantly decreased with simultaneous significant rises in GSH and albumin, impelling a great improvement in the antioxidant and anti-inflammatory defenses of the kidney as well as its functions. Intriguingly, MSCs-HA/CNPs were more effective against caspase-3 than MSCs alone, revealing the high anti-apoptotic capability of HA/CNPs. This finding suggests that HA/CNPs could effectively protect MSCs from oxidative stress and apoptosis and thus increase their stability and longevity.


Asunto(s)
Quitosano , Células Madre Mesenquimatosas , Ratas , Animales , Cisplatino/toxicidad , Cisplatino/metabolismo , Ácido Hialurónico/farmacología , Caspasa 3/metabolismo , Quitosano/farmacología , Antioxidantes/farmacología , Antioxidantes/metabolismo , Interleucina-6/metabolismo , Riñón , Adyuvantes Inmunológicos/farmacología , Estrés Oxidativo , Urea/metabolismo , Apoptosis
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