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1.
Artigo em Inglês | MEDLINE | ID: mdl-38321904

RESUMO

BACKGROUND: A number of research were conducted on the pyran and thiophene derivatives, which were attributed to have a wide range of biological activities, including anti-plasmodial, as well as acting as caspase, hepatitis C and cancer inhibitors. OBJECTIVE: The multicomponent reactions of the 5-acetyl-2-amino-4-(phenylamino)-thiophene-3-carbonitrile produced biologically active target molecules like pyran and their fused derivatives. Comparison between regular catalytic multi-component reactions and solvent-free ionic liquids immobilized multicomponent was studied. METHOD: The multicomponent reactions in this work were carried out not only under the reflux conditions using triethylamine as a catalyst but also in solvent-free ionic liquids immobilized magnetic nanoparticles (MNPs) catalysts. RESULTS: Through this work, thirty-one new compounds were synthesized and characterized and were evaluated toward the six cancer cell lines, namely A549, HT-29, MKN-45, U87MG, and SMMC-7721 and H460. The most active compounds were further screened toward seventeen cancer cell lines classified according to the disease. In addition, the effect of compound 11e on the A549 cell line was selected to make further morphological changes in the cell line. The Molecular docking studies of 11e and 11f were carried and promising results were obtained. CONCLUSION: The synthesis of heterocyclic compounds derived from thiophene derivatives has been receiving significant attention. After a detailed optimizing study, it has been found that the solvent-free ionic liquids immobilized multi-component syntheses afforded a high yield of compounds, opening a greener procedure for this synthetically relevant transformation. Many of the synthesized compounds can be considered anticancer agents, enhancing further studies.

2.
Int J Biol Macromol ; 264(Pt 1): 130454, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38417758

RESUMO

The demand for the functionalization of additive materials based on bacterial cellulose (BC) is currently high due to their potential applications across various sectors. The preparation of BC-based additive materials typically involves two approaches: in situ and ex situ. In situ modifications entail the incorporation of additive materials, such as soluble and dispersed substances, which are non-toxic and not essential for bacterial cell growth during the production process. However, these materials can impact the yield and self-assembly of BC. In contrast, ex situ modification occurs subsequent to the formation of BC, where the additive materials are not only adsorbed on the surface but also impregnated into the BC pellicle, while the BC slurry was homogenized with other additive materials and gelling agents to create composite films using the casting method. This review will primarily focus on the in situ and ex situ functionalization of BC then sheds light on the pivotal role of functionalized BC in advancing biomedical technologies, wound healing, tissue engineering, drug delivery, bone regeneration, and biosensors.


Assuntos
Celulose , Engenharia Tecidual , Celulose/metabolismo , Bactérias/metabolismo , Materiais Biocompatíveis/metabolismo
3.
Bioorg Chem ; 143: 107091, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38183683

RESUMO

This scientific review documents the recent progress of C3-spirooxindoles chemistry (synthesis and reaction mechanism) and their bioactivities, focusing on the promising results as well as highlighting the biological mechanism via the reported molecular docking findings of the most bioactive derivatives. C3-Spirooxindoles are attractive bioactive agents and have been found in a variety of natural compounds, including alkaloids. They are widely investigated in the field of medicinal chemistry and play a key role in medication development, such as antivirals, anticancer agents, antimicrobials, etc. Regarding organic synthesis, several traditional and advanced strategies have been reported, particularly those that started with isatin derivatives.


Assuntos
Benzopiranos , Nitrilas , Compostos de Espiro , 60492 , Simulação de Acoplamento Molecular , Compostos de Espiro/farmacologia , Compostos de Espiro/química , Oxindóis/farmacologia , Oxindóis/química
4.
J Fluoresc ; 34(2): 723-728, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37354382

RESUMO

The chalcone compound DHPO was synthesized through a chemical reaction between 1-(2-hydroxyphenyl)-ethanone and 3,4-dimethoxy benzaldehyde under ultrasound irradiation. The interaction between the DHPO compound and several metal ions was studied using fluorescence behavior, revealing that the chalcone function as a "turn on and turn off" switch fluorescent sensor, for selectively and sensitively detecting Fe3+ ions. The process of fluorescence quenching and complexation of DHPO with Fe3+ ion was further studied using methods such as Benesi-Hildebrand, Stern-Volmer plot, and job plot.

5.
Asian J Surg ; 47(1): 158-162, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37596230

RESUMO

INTRODUCTION: The purpose of this study is to evaluate the outcomes of endoscopic hemithyroidectomy (EH) performed via the modified unilateral axillo-breast approach (UABA) in patients with lactating and/or large ptotic breasts. METHODS: Between 2019 and 2021, we studied the records of twenty-three eligible female patients with lactating and/or large ptotic breasts who were presented with benign unilateral thyroid nodule (s) and who were treated by EH using modified UABA at Mansoura University Oncology Center or Meet Ghamr oncology center. The demographic data, clinicopathological parameters, operative and the esthetic outcomes were collected and analyzed. RESULTS: Nine patients (39%) were lactating. All patients were obese (the mean BMI was 37.82 ± 4.37). All patients were having large breasts, cup C and D sizes (34% of patients & 56% of patients respectively), except for only two lactating female patients who had Cup B breasts. All patients were having ptotic breasts. The thyroid nodules greatest dimension ranged from 2.1-6 cm. All procedures were completed successfully endoscopically without any perioperative adverse events except for one case with temporary hoarseness of voice and three cases with axillary port sites cellulitis. The mean operative time was 83.26 ± 7.92 min. The patient satisfaction scores were high. CONCLUSION: EH via modified UABA in patients with lactating and/or large ptotic breasts is safe, feasible and effective procedure without adverse events. It should be offered to this group of patients as an alternative to conventional open thyroidectomy if there is no other contraindication.


Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Feminino , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/métodos , Lactação , Mama/cirurgia , Mama/patologia , Nódulo da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/patologia , Estudos Retrospectivos
6.
Naunyn Schmiedebergs Arch Pharmacol ; 397(3): 1701-1714, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37712973

RESUMO

The mutual interplay between neuroinflammation, synaptic plasticity, and autophagy has piqued researchers' interest, particularly when it comes to linking their impact and relationship to cognitive deficits. Being able to reduce inflammation and apoptosis, melatonin has shown to have positive neuroprotective effects; that is why we thought to check the possible role of agomelatine (AGO) as a promising candidate that could have a positive impact on cognitive deficits. In the current study, AGO (40 mg/kg/day, p.o., 7 days) successfully ameliorated the cognitive and learning disabilities caused by lipopolysaccharide (LPS) in rats (250 µg/kg/day, i.p., 7 days). This positive impact was supported by improved histopathological findings and improved spatial memory as assessed using Morris water maze. AGO showed a strong ability to control BACE1 activity and to rein in the hippocampal amyloid beta (Aß) deposition. Also, it improved neuronal survival, neuroplasticity, and neurogenesis by boosting BDNF levels and promoting its advantageous effects and by reinforcing the pTrkB expression. In addition, it upregulated the pre- and postsynaptic neuroplasticity biomarkers resembled in synapsin I, synaptophysin, and PSD-95. Furthermore, AGO showed a modulatory action on Sortilin-related receptor with A-type repeats (SorLA) pathway and adjusted autophagy. It is noteworthy that all of these actions were abolished by administering PD98059 a MEK/ERK pathway inhibitor (0.3 mg/kg/day, i.p., 7 days). In conclusion, AGO administration significantly improves memory and learning disabilities associated with LPS administration by modulating the ERK/SorLA/BDNF/TrkB signaling pathway parallel to its capacity to adjust the autophagic process.


Assuntos
Deficiências da Aprendizagem , Lipopolissacarídeos , Ratos , Animais , Lipopolissacarídeos/toxicidade , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Secretases da Proteína Precursora do Amiloide/farmacologia , Sistema de Sinalização das MAP Quinases , Peptídeos beta-Amiloides/metabolismo , Aprendizagem em Labirinto , Ácido Aspártico Endopeptidases/metabolismo , Ácido Aspártico Endopeptidases/farmacologia , Deficiências da Aprendizagem/metabolismo , Deficiências da Aprendizagem/patologia , Hipocampo , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo
7.
Healthcare (Basel) ; 11(22)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37998466

RESUMO

(1) Background: Awareness and compliance with standard precautions (SPs) are essential health issues for both healthcare staff and patients. Hence, more research is urgently needed in the health sector worldwide, particularly in Arab countries. The purpose of this study was to investigate compliance with SPs among nurses and doctors, as well as challenges affecting their adherence to these SPs. (2) Methods: A cross-sectional descriptive study was conducted. The researchers administered the compliance with the Standard Precautions Scale (CAPS) to staff nurses and doctors from critical care units at a university-affiliated hospital in Jeddah, Kingdom of Saudi Arabia (KSA). A total of 112 nurses and 59 doctors were enrolled in the study to determine their compliance with SPs as well as the challenges affecting their adherence to these SPs. (3) Results: The overall mean percentage scores of nurses' and doctors' compliance with SPs were 36.43 ± 15.85% and 33.27 ± 15.76%, respectively. In addition, the current study identified associated challenges affecting these healthcare workers' adherence to these SPs, including the effect of sociodemographic factors, such as age and experience. (4) Conclusions: The study found that both nurses and doctors had poor compliance with all SPs except for disposal of sharps, which scored with suboptimal compliance. Nurses' compliance with recommended precautions varied significantly according to age, clinical experience, and attendance at training courses. Healthcare organizations should consider a holistic approach to promote adherence to SPs to enhance outcomes associated with optimized care delivery and stakeholder safety.

8.
J. coloproctol. (Rio J., Impr.) ; 43(2): 126-132, Apr.-June 2023. tab, graf, ilus
Artigo em Inglês | LILACS | ID: biblio-1514430

RESUMO

Background: Due to few sufficient data regarding the comparison between endoscopic and surgical resection of malignant colorectal polyps regarding outcomes and survival benefits, there are no clear guidelines of management strategies of malignant colorectal polyps. The aims of the present study were to compare endoscopic resection alone and surgical resection in patients with malignant polyps in the colon (T1N0M0) readings advantages, disadvantages, recurrence risks, survival benefits, and long-term prognosis to detect how management strategy affects outcome. Patients and methods: we included 350 patients. All included patients were divided into 2 groups; the first group included 100 patients who underwent only endoscopic polypectomy and the second group included 250 patients who underwent endoscopic polypectomy followed by definitive surgical resection after histopathological diagnosis. We followed all patients for about 5 years, ranging from 18 to 55 months. The primarily evaluated parameters are surgical consequences and patients' morbidity. The secondary evaluated parameters are recurrence risks, recurrence free survival, and overall survival rates. Results: The age of patients who underwent polypectomy is usually younger than the surgical group, males have more liability to polypectomy in comparison with females. Patients with tumors in the left colon have more liability to polypectomy in comparison with the right colon (p< 0.0001). Tumor factors associated with more liability to surgical resection are presence of lymphovascular invasion, high grade, and poor tumor differentiation (p< 0.0001). The management strategy was the most significant predictor of overall and recurrence free survival rates in patients with malignant colon polyps (p< 0.001). Conclusions: We found that survival benefits and lower incidence of recurrence are detected in the surgical resection group more than in the polypectomy group. (AU)


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Pólipos do Colo/cirurgia , Neoplasias do Colo/mortalidade , Laparoscopia , Endoscopia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias
9.
BMC Med Genomics ; 16(1): 108, 2023 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-37202765

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women. This study was designed to investigate the associations of vitamin D receptor (VDR) gene variants with PCOS risk and the severity of the disease phenotype among Egyptian women. METHODS: In this study, 185 women with PCOS and 207 fertile women as controls were recruited. Cases were divided into phenotype groups based on their clinical and paraclinical features. Clinical and laboratory data were measured in the patient and control groups. All individuals were genotyped for nine single-nucleotide polymorphisms (SNPs) located across the VDR gene using TaqMan allelic discrimination real-time polymerase chain reaction. RESULTS: Women with PCOS were significantly (P ≤ 0.001) higher body mass index (BMI) (22.77 ± 2.5) than controls (21.68 ± 1.85 kg/m2). Women with PCOS had significantly higher anti-Mullerian hormone, prolactin, luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), free testosterone, total testosterone, and dehydroepiandrosterone sulfate levels than the control group (P ≤ 0.001). The level of FSH was significantly lower in women with PCOS than in the control group (P ≤ 0.001). Analysis of the VDR rs4516035, rs2107301, rs1544410 (BsmI), and rs731236 (TaqI) SNPs showed a significant association with PCOS phenotype A. Furthermore, rs2228570 (FokI), rs3782905, rs7975232 (ApaI), and rs739837 SNPs showed a significant association with PCOS phenotype C. Furthermore, rs11568820 SNP showed a significant association with PCOS phenotype D (P < 0.05). CONCLUSIONS: The findings of this study indicate that variations in the VDR gene were associated with an increased risk of PCOS in Egyptian women.


Assuntos
Síndrome do Ovário Policístico , Feminino , Humanos , Estudos de Casos e Controles , Hormônio Foliculoestimulante/genética , Predisposição Genética para Doença , Síndrome do Ovário Policístico/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Testosterona
10.
Eur J Breast Health ; 19(2): 134-139, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37025572

RESUMO

Objective: Seroma after mastectomy is a bothersome problem. Topical sclerosants are one method used to reduce seroma. The aim of this study was to evaluate if spraying flaps before closure with doxycycline or bleomycin after total mastectomy can prevent seroma. Materials and Methods: After institutional review board approval, using a computer-based randomization program, a prospective, double-blind, placebo-controlled randomized, superiority study was conducted during the period from the first of August 2017 to the first of August 2018. IRB proposal code was MS/17.08.66 and the trial was approved at 15/8/2017. The trial is available publicly at http://www.eulc.edu.eg/eulc_v5/Libraries/Thesis/BrowseThesisPages.aspx?fn=PublicDrawThesis&BibID=12553049. The primary outcome of the study was to assess the incidence of seroma following total mastectomy after intervention comprising spraying of skin flaps with doxycycline or bleomycin versus placebo. Patients who were candidates for total mastectomy were randomized into control, doxycycline, and bleomycin groups. The postoperative data included length of the hospital stay, pain score among the three groups, post-operative drained fluid volume, post-operative day of drain removal, complication rates including infection, flap necrosis and hematoma, the incidence of seroma and aspirated seroma volume, and total number of postoperative visits. Results: Of 125 patients, 90 were candidates for total mastectomy. Analysis of these 90 showed that the incidence of seroma was similar; 43.4%, 40% and 40% in the control, doxycycline, and bleomycin groups, respectively (p = 0.99). Furthermore, wound complication rates were similar among all groups. Conclusion: Despite improved recognition and management of risk factors, seromas remain a common clinical concern in the postoperative setting of total mastectomy. These results suggest that sclerosant agents, specifically bleomycin and doxycycline, have no utility for prevention of post mastectomy seroma.

11.
J Clin Monit Comput ; 37(5): 1287-1293, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36961635

RESUMO

We aimed to evaluate the ability of parasternal intercostal thickening fraction (PIC TF) to predict the need for mechanical ventilation, and survival in subjects with severe Coronavirus disease-2019 (COVID-19). This prospective observational study included adult subjects with severe COVID-19. The following data were collected within 12 h of admission: PIC TF, respiratory rate oxygenation index, [Formula: see text] ratio, chest CT, and acute physiology and chronic health evaluation II score. The ability of PIC TF to predict the need for ventilatory support (primary outcome) and a composite of invasive mechanical ventilation and/or 30-days mortality were performed using the area under the receiver operating characteristic (AUC) analysis. Multivariate analysis was done to identify the independent predictors for the outcomes. Fifty subjects were available for the final evaluation. The AUC (95% confidence interval [CI]) for the right and left PIC TF ability to predict the need for ventilator support was 0.94 (0.83-0.99), 0.94 (0.84-0.99), respectively, with a cut off value of > 8.3% and positive predictive value of 90-100%. The AUC for the right and left PIC TF to predict invasive mechanical ventilation and/or 30 days mortality was 0.95 (0.85-0.99) and 0.90 (0.78-0.97), respectively. In the multivariate analysis, only the PIC TF was found to independently predict invasive mechanical ventilation and/or 30-days mortality. In subjects with severe COVID-19, PIC TF of 8.3% can predict the need to ventilatory support with a positive predictive value of 90-100%. PIC TF is an independent risk factor for the need for invasive mechanical ventilation and/or 30-days mortality.


Assuntos
COVID-19 , Respiração Artificial , Adulto , Humanos , COVID-19/terapia , Curva ROC , Valor Preditivo dos Testes , Hospitais , Estudos Retrospectivos
12.
Molecules ; 28(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36677616

RESUMO

Alzheimer's disease is a major public brain condition that has resulted in many deaths, as revealed by the World Health Organization (WHO). Conventional Alzheimer's treatments such as chemotherapy, surgery, and radiotherapy are not very effective and are usually associated with several adverse effects. Therefore, it is necessary to find a new therapeutic approach that completely treats Alzheimer's disease without many side effects. In this research project, we report the synthesis and biological activities of some new thiazole-bearing sulfonamide analogs (1-21) as potent anti-Alzheimer's agents. Suitable characterization techniques were employed, and the density functional theory (DFT) computational approach, as well as in-silico molecular modeling, has been employed to assess the electronic properties and anti-Alzheimer's potency of the analogs. All analogs exhibited a varied degree of inhibitory potential, but analog 1 was found to have excellent potency (IC50 = 0.10 ± 0.05 µM for AChE) and (IC50 = 0.20 ± 0.050 µM for BuChE) as compared to the reference drug donepezil (IC50 = 2.16 ± 0.12 µM and 4.5 ± 0.11 µM). The structure-activity relationship was established, and it mainly depends upon the nature, position, number, and electron-donating/-withdrawing effects of the substituent/s on the phenyl rings.


Assuntos
Doença de Alzheimer , Humanos , Simulação de Acoplamento Molecular , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Acetilcolinesterase/metabolismo , Relação Estrutura-Atividade , Sulfonamidas/farmacologia , Estrutura Molecular
13.
Comb Chem High Throughput Screen ; 26(7): 1437-1449, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36043774

RESUMO

BACKGROUND: The lack of anti-COVID-19 treatment to date warrants urgent research into potential therapeutic targets. Virtual drug screening techniques enable the identification of novel compounds that target the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Main Protease (Mpro). OBJECTIVE: The binding of the halogenated compounds to Mpro may inhibit the replication and transcription of SARS-CoV-2 and, ultimately, stop the viral life cycle. In times of dire need for anti- COVID-19 treatment, this study lays the groundwork for further experimental research to investigate these compounds' efficacy and potential medical uses to treat COVID-19. METHODS: New heterocyclic compounds were synthesized through the first reaction of cyclohexane- 1, 3-dione (1a) or dimedone (1b) with trichloroacetonitrile (2) to give the 2,2,2-trichloroethylidene) cyclohexane-1,3-dione derivatives 3a and 3b, respectively. The latter compounds underwent a series of heterocyclization reactions to produce biologically active compounds. RESULTS: Novel compounds, including fused thiophene, pyrimidine and pyran derivatives, were synthesized and tested against human RNA N7-MTase (hRNMT) and selected viral N7-MTases such as SARS-CoV nsp14 and Vaccinia D1-D12 complex to evaluate their specificity and their molecular modeling was also studied in the aim of producing anti-COVID-19 target molecules. CONCLUSION: The results showed that compounds 10a, 10b, 10c, 10e, 10f, 10g and 10h showed high % inhibitions against SARs-Covnsp 14. Whereas compounds 5a, 7a, 8b, 10a, 10b, 10c and 10i showed high inhibitions against hRNMT. This study explored the binding affinity of twenty-two halogenated compounds to the SARS-CoV-2 MPro and discovered fifteen compounds with higher binding affinity than Nelfinavir, of which three showed remarkable results. c-Met kinase inhibitions of 10a, 10f, 10g and 10h showed that all compounds exhibited higher inhibitions than the reference Foretinib.


Assuntos
COVID-19 , Humanos , Simulação de Acoplamento Molecular , SARS-CoV-2/metabolismo , Proteínas não Estruturais Virais/química , Cicloexanos , Inibidores de Proteases/farmacologia , Simulação de Dinâmica Molecular
14.
Int J Biol Macromol ; 225: 1462-1475, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36435457

RESUMO

Modified magnetite chitosan with silver nanoparticles was synthesized and tested for removing cationic and anionic dyes in aqueous solutions. Initial dye concentration, pH, and contact time were examined. Results showed that pH (4.0) was optimal for removing anionic dyes (methyl orange) and pH 8.0 for removing cationic dyes (methylene blue). According to these results, zeta potentials were found to be 8.43 and - 39.17 mV at pH 4.0 and 8.0, respectively. So, it is attracted to positively charged cationic dyes in an alkaline medium and negatively charged anionic dyes in an acidic medium because of their opposite charges. Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectra (XPS), thermal gravimetric analysis (TGA), and zeta potential measurements were used to characterize the synthesized nanosorbents. A pseudo-second-order kinetic model is fitted with the Langmuir adsorption model, with an adsorption capacity of 417 and 476 mg/g for methyl orange and methylene blue, respectively. For both dyes, modified magnetite chitosan with silver nanoparticles showed high regeneration capability and recovery for up to four cycles without adsorption efficiency loss. Furthermore, modified magnetite chitosan with silver nanoparticles, as prepared in the present study, was demonstrated to be an effective adsorbent for organic pollutants in wastewater.


Assuntos
Quitosana , Nanopartículas de Magnetita , Poluentes Químicos da Água , Corantes/química , Óxido Ferroso-Férrico , Quitosana/química , Prata , Cinética , Azul de Metileno/química , Água/química , Cátions , Nanopartículas de Magnetita/química , Adsorção , Poluentes Químicos da Água/química , Concentração de Íons de Hidrogênio
15.
Antioxidants (Basel) ; 11(11)2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36358524

RESUMO

Hepatic fibrosis causes severe morbidity and death. No viable treatment can repair fibrosis and protect the liver until now. We intended to discover the empagliflozin's (EMPA) hepatoprotective efficacy in thioacetamide (TAA)-induced hepatotoxicity by targeting AMPK/SIRT-1 activity and reducing HIF-1α. Rats were treated orally with EMPA (3 or 6 mg/kg) with TAA (100 mg/kg, IP) thrice weekly for 6 weeks. EMPA in both doses retracted the serum GGT, ALT, AST, ammonia, triglycerides, total cholesterol, and increased serum albumin. At the same time, EMPA (3 or 6 mg/kg) replenished the hepatic content of GSH, ATP, AMP, AMPK, or SIRT-1 and mitigated the hepatic content of MDA, TNF-α, IL-6, NF-κB, or HIF-1α in a dose-dependent manner. Likewise, hepatic photomicrograph stained with hematoxylin and eosin or Masson trichrome stain of EMPA (3 or 6 mg/kg) revealed marked regression of the hepatotoxic effect of TAA with minimal injury. Similarly, in rats given EMPA (3 or 6 mg/kg), the immunohistochemically of hepatic photomicrograph revealed minimal stain of either α-SMA or caspase-3 compared to the TAA group. Therefore, we concluded that EMPA possessed an antifibrotic effect by targeting AMPK/SIRT-1 activity and inhibiting HIF-1α. The present study provided new insight into a novel treatment of liver fibrosis.

16.
Molecules ; 27(20)2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36296520

RESUMO

Diabetes mellitus is one of the most chronic metabolic diseases. In the past few years, our research group has synthesized and evaluated libraries of heterocyclic analogs against α-glucosidase and α-amylase enzymes and found encouraging results. The current study comprises the evaluation of benzimidazole-bearing thiosemicarbazone as antidiabetic agents. A library of fifteen derivatives (7-21) was synthesized, characterized via different spectroscopic techniques such as HREI-MS, NMR, and screened against α-glucosidase and α-amylase enzymes. All derivatives exhibited excellent to good biological inhibitory potentials. Derivatives 19 (IC50 = 1.30 ± 0.20 µM and 1.20 ± 0.20 µM) and 20 (IC50 = 1.60 ± 0.20 µM and 1.10 ± 0.01 µM) were found to be the most potent among the series when compared with standard drug acarbose (IC50 = 11.29 ± 0.07 and 11.12 ± 0.15 µM, respectively). These derivatives may potentially serve as the lead candidates for the development of new therapeutic representatives. The structure-activity relationship was carried out for all molecules which are mainly based upon the pattern of substituent/s on phenyl rings. Moreover, in silico docking studies were carried out to investigate the active binding mode of selected derivatives with the target enzymes.


Assuntos
Inibidores de Glicosídeo Hidrolases , Tiossemicarbazonas , Inibidores de Glicosídeo Hidrolases/química , alfa-Amilases , Simulação de Acoplamento Molecular , alfa-Glucosidases/metabolismo , Acarbose , Tiossemicarbazonas/farmacologia , Relação Estrutura-Atividade , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Benzimidazóis/química , Estrutura Molecular
17.
Molecules ; 27(18)2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-36144820

RESUMO

Twenty-four analogues of benzimidazole-based thiazoles (1-24) were synthesized and assessed for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory potential. All analogues were found to exhibit good inhibitory potential against cholinesterase enzymes, having IC50 values in the ranges of 0.10 ± 0.05 to 11.10 ± 0.30 µM (for AChE) and 0.20 ± 0.050 µM to 14.20 ± 0.10 µM (for BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 and 4.5 ± 0.11 µM, respectively). Among the series, analogues 16 and 21 were found to be the most potent inhibitors of AChE and BuChE enzymes. The number (s), types, electron-donating or -withdrawing effects and position of the substituent(s) on the both phenyl rings B & C were the primary determinants of the structure-activity relationship (SAR). In order to understand how the most active derivatives interact with the amino acids in the active site of the enzyme, molecular docking studies were conducted. The results obtained supported the experimental data. Additionally, the structures of all newly synthesized compounds were elucidated by using several spectroscopic methods like 13C-NMR, 1H-NMR and HR EIMS.


Assuntos
Doença de Alzheimer , Inibidores da Colinesterase , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Aminoácidos , Benzimidazóis/química , Butirilcolinesterase/química , Inibidores da Colinesterase/química , Donepezila , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Tiazóis/farmacologia
18.
Behav Sci (Basel) ; 12(9)2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36135131

RESUMO

Dubai was one of the top three real estate destinations in the world for investment in 2020. This paper aims to understand the order of preference for various housing determinants by housing consumers in Dubai. As a methodology, a survey was conducted on Dubai residents, and Analytic Hierarchy Process (AHP) was performed to identify the housing determinants and consumers' preferences. In addition, the respondents' demographic characteristics identified priorities by income, place of residence, age, gender, and type of house. The results showed that housing consumers place importance on housing price and rent (0.0918), and the investment value (0.0866). However, there was no serious consideration for social and psychological factors, other than safety (0.0730). Regarding gender, men place more importance on the housing price and rent (0.113), and the investment value (0.110). In comparison, women place more importance on factors such as the convenience of transportation (0.104), safety (0.093), and residential environment (0.082). In the age groups, the interest in the educational environment (0.081) among the 40-year-olds was relatively high. In terms of monthly income, the higher the income, the higher the interest in investment value (0.086).

19.
Pharmaceuticals (Basel) ; 15(8)2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-36015126

RESUMO

Wound dressings created using nanotechnology are known as suitable substrates to speed up the healing of both acute and chronic wounds. Therapeutic substances can be delivered using these materials. In this study, a hydrogel loaded with Cu (II) Schiff base 8-hydroxy quinoline complex (CuSQ) solid lipid nanoparticles (SLN) was formulated to investigate its wound healing potential in an excision wound healing model in rats. The CuSQ SLN were spherical shaped with sizes ranging from 111 to 202 nm and a polydispersity index (PDI) ranging from 0.43 to 0.76, encapsulation efficiency (EE) % between 85 and 88, and zeta potential (ZP) of -11.8 to -40 mV. The formulated hydrogel showed good homogeneity, good stability, and a pH of 6.4 which indicates no skin irritation and had no cytotoxicity on the human skin fibroblast (HSF) cell line. In the in vivo study, animals were placed in five groups: control, standard, plain hydrogel, low dose, and high dose of CuSQ hydrogel. Both doses of CuSQ showed significantly faster healing rates compared to standard and control rats. In addition, the histopathology study showed more collagen, improved angiogenesis, and intact re-epithelization with less inflammation. A significant increase in transforming growth factor-beta1 (TGF-ß1) level and increased immune expression of vascular endothelial growth factor (VEGF) by CuSQ treatment validates its role in collagen synthesis, proliferation of fibroblasts and enhancement of angiogenesis. Matrix metalloproteinase-9 (MMP-9) was found to be significantly reduced after CuSQ treatment. Immunohistochemistry of tumor necrosis factor alpha (TNF-α) revealed a marked decrease in inflammation. Thus, we concluded that CuSQ would be a beneficial drug for cutaneous wound healing since it effectively accelerated wound healing through regulation of various cytokines and growth factors.

20.
J Surg Case Rep ; 2022(4): rjac149, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35422989

RESUMO

Surgical aortic valve replacement represents a class one indication in the setting of aortic valve endocarditis and decompensated heart failure secondary to aortic regurgitation as per the European Society of Cardiology. However, extreme obesity, whereby the body mass index (BMI) >40 kg/m2, represents a challenging cohort of patients. Performing cardiac surgery in the bariatric population is fraught with challenges pertaining to intraoperative issues of surgical access and approach. We describe the case of a 45-year-old gentleman who had previous been diagnosed with infective endocarditis of the aortic valve and with a BMI of 68.2 (228 kg). Surgical aortic valve replacement in extreme obesity is associated with deep sternal wound infection, requirement and duration of mechanical ventilation, atrial fibrillation and renal failure. The 'obesity paradox' of overweight and class I obesity (BMI <35) has demonstrated favourable long-term results compared with underweight patients or even those with normal BMI undergoing cardiac surgery.

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