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1.
Nanomaterials (Basel) ; 14(17)2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39269087

RESUMEN

Silver nanoparticles (Ag NPs) have accumulated significant interest due to their exceptional physicochemical properties and remarkable applications in biomedicine, electronics, and catalysis sensing. This comprehensive review provides an in-depth study of synthetic approaches such as biological synthesis, chemical synthesis, and physical synthesis with a detailed overview of their sub-methodologies, highlighting advantages and disadvantages. Additionally, structural properties affected by synthesis methods are discussed in detail by examining the dimensions and surface morphology. The review explores the distinctive properties of Ag NPs, including optical, electrical, catalytic, and antimicrobial properties, which render them beneficial for a range of applications. Furthermore, this review describes the diverse applications in several fields, such as medicine, environmental science, electronics, and optoelectronics. However, with numerous applications, several kinds of issues still exist. Future attempts need to address difficulties regarding synthetic techniques, environmental friendliness, and affordability. In order to ensure the secure utilization of Ag NPs, it is necessary to establish sustainability in synthetic techniques and eco-friendly production methods. This review aims to give a comprehensive overview of the synthesis, structural analysis, properties, and multifaceted applications of Ag NPs.

2.
Curr Med Chem ; 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39318001

RESUMEN

INTRODUCTION: The pandemic caused by SARS-CoV-2 significantly impacted human life around the globe. Numerous unexpected modifications of the SARS-CoV-2 genome have resulted in the emergence of new types and have caused great concern globally. METHOD: Inhibitory effects of bioactive phytochemicals derived from natural and synthetic sources are promising for pathogenic viruses. in vitro and in silico techniques were used in the current study to identify novel inhibitors of coumarin clubbed thiazolo[3,2-b][1,2,4]triazoles against the SARS-CoV-2 spike protein. RESULT: Interestingly, all the tested molecules demonstrated substantial inhibition of spike protein with 91.81-57.90% inhibition. The spike protein was remarkably inhibited by compounds 6k (91.83%), 6j (89.75%), 6m (87.69%),6i (86.60%), 6l (85.40%), 6h (84.70%), 6l (84.70%), 6g (83.40%), 6b (82.60%), 6f (81.90%), while compounds 6d 6a, 6c, and 6e exhibited significant activity against spike protein with 79.60%, 77.10%, 75.30%, and 57.90% inhibition, respectively. The binding mechanism of these novel inhibitors with spike protein was deduced in silico, which reflects that the active molecules firmly bind with the receptor binding domain (RBD) of spike protein, thereby inhibiting its function. CONCLUSION: The combined in vitro and in silico investigations unfold the therapeutic potential of coumarin-thiazolotriazole scaffolds in the treatment of SARS-CoV-2 infection.

3.
Materials (Basel) ; 17(17)2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39274586

RESUMEN

In the area of flexible electronics, pressure sensors are a widely utilized variety of flexible electronics that are both indispensable and prevalent. The importance of pressure sensors in various fields is currently increasing, leading to the exploration of materials with unique structural and piezoelectric properties. Perovskite-based materials are ideal for use as flexible pressure sensors (FPSs) due to their flexibility, chemical composition, strain tolerance, high piezoelectric and piezoresistive properties, and potential integration with other technologies. This article presents a comprehensive study of perovskite-based materials used in FPSs and discusses their components, performance, and applications in detecting human movement, electronic skin, and wireless monitoring. This work also discusses challenges like material instability, durability, and toxicity, the limited widespread application due to environmental factors and toxicity concerns, and complex fabrication and future directions for perovskite-based FPSs, providing valuable insights for researchers in structural health monitoring, physical health monitoring, and industrial applications.

4.
Stud Health Technol Inform ; 318: 168-169, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39320200

RESUMEN

Existing healthcare systems are struggling to cope with the rapid increase in mental health diseases. Wearable devices such as smartwatches introduce a new opportunity in this regard. The realisation of this opportunity depends on the engagement of the community in sharing their lived experience data. A health data marketplace is introduced in this regard, where individuals can monetise their wearable device-derived lived experience data by selling it to consumers such as researchers, medical practitioners, and artificial intelligence service providers.


Asunto(s)
Dispositivos Electrónicos Vestibles , Humanos , Inteligencia Artificial
5.
Front Chem ; 12: 1462503, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39324063

RESUMEN

Depletion of oil and gas resources is a major concern for researchers and the global community. Researchers are trying to develop a way to overcome these issues using the Fischer-Tropsch synthesis (FTS) process. The FTS reaction converts a mixture of hydrogen and carbon monoxide gases into a liquid fuel. The reactions are performed in the reactor and in the presence of a catalyst. A series of catalysts, such as iron, cobalt, nickel, and ruthenium, have been used for the FTS process. In iron-based catalysts, the Fe5C phase is the active phase that produces C5+ hydrocarbons. At higher conversion rates, the presence of water in the products is a problem for cobalt catalysts because it can trigger catalyst deactivation mechanisms. Ni-based catalysts play key roles as base catalysts, promoters, and photothermal catalysts in FTS reactions to produce different useful hydrocarbons. Ruthenium catalysts offer not only high activity but also selectivity toward long-chain hydrocarbons. Moreover, depending on the Ru particle size and interaction with the oxide support, the catalyst properties can be tuned to enhance the catalytic activity during FTS. The detailed reaction pathways based on catalyst properties are explained in this article. This review article describes the issues and challenges associated with catalysts used for the FTS process.

6.
Adv Colloid Interface Sci ; 332: 103250, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39047647

RESUMEN

The pressing global issue of organic pollutants, particularly phenolic compounds derived primarily from industrial wastes, poses a significant threat to the environment. Although progress has been made in the development of low-cost materials for phenolic compound removal, their effectiveness remains limited. Thus, there is an urgent need for novel technologies to comprehensively address this issue. In this context, MXenes, known for their exceptional physicochemical properties, have emerged as highly promising candidates for the remediation of phenolic pollutants. This review aims to provide a comprehensive and critical evaluation of MXene-based technologies for the removal of phenolic pollutants, focusing on the following key aspects: (1) The classification and categorization of phenolic pollutants, highlighting their adverse environmental impacts, and emphasizing the crucial need for their removal. (2) An in-depth discussion on the synthesis methods and properties of MXene-based composites, emphasizing their suitability for environmental remediation. (3) A detailed analysis of MXene-based adsorption, catalysis, photocatalysis, and hybrid processes, showcasing current advancements in MXene modification and functionalization to enhance removal efficiency. (4) A thorough examination of the removal mechanisms and stability of MXene-based technologies, elucidating their operating conditions and stability in pollutant removal scenarios. (5) Finally, this review concludes by outlining future challenges and opportunities for MXene-based technologies in water treatment, facilitating their potential applications. This comprehensive review provides valuable insights and innovative ideas for the development of versatile MXene-based technologies tailored to combat water pollution effectively.

7.
Sci Rep ; 14(1): 15348, 2024 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961103

RESUMEN

The most serious long-term effects of diabetes is peripheral artery disease (PAD) which increases the chance of developing diabetic foot ulcers, gangrene and even lower limb amputation. The clinical manifestations of PAD which are typically not revealed until symptoms like intermittent claudication, rest pain and ischemic gangrene develop, are not present in majority of diabetes mellitus patients with PAD due to diabetic peripheral neuropathy. Therefore, current study is aimed to evaluate the inflammatory and endothelial dysfunction markers with their correlation to biomarkers that can help for in-time diagnosis and efficient prognosis of developing diabetes-associated PAD. Enzyme-linked immunosorbent assay was used to evaluate the interlukin-6, interlukin-8, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in PAD with diabetes group, diabetic group and healthy individual group while biomarkers were measured by kit method. It was observed that serum IL-6, IL-8, ICAM and VCAM levels in type II diabetes mellitus (T2DM) with PAD patients were increased significantly (85.93, 597.08, 94.80 and 80.66) as compared to T2DM patients (59.52, 231.34, 56.88 and 50.19) and healthy individuals (4.81, 16.93, 5.55 and 5.16). The overall means for the parameters, IL-6, IL-8, ICAM, VCAM, urea, S/creatinine, CK-MB, AST, ALT, cholesterol, triglyceride, HDL, LDL, PT, aPTT, INR, HbA1C, and CRP within all groups were significantly (P < 0.05) different from each other. Therefore, it was concluded that the change in IL-6, IL-8, ICAM and VCAM can serve as an accurate diagnostic indicator and successful treatment.


Asunto(s)
Biomarcadores , Diabetes Mellitus Tipo 2 , Enfermedad Arterial Periférica , Molécula 1 de Adhesión Celular Vascular , Humanos , Biomarcadores/sangre , Enfermedad Arterial Periférica/sangre , Enfermedad Arterial Periférica/diagnóstico , Masculino , Femenino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Persona de Mediana Edad , Molécula 1 de Adhesión Celular Vascular/sangre , Anciano , Inflamación/sangre , Interleucina-6/sangre , Molécula 1 de Adhesión Intercelular/sangre , Interleucina-8/sangre , Endotelio Vascular/fisiopatología , Endotelio Vascular/metabolismo , Estudios de Casos y Controles
8.
Front Chem ; 12: 1403127, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855062

RESUMEN

An important component of the pathogenicity of potentially pathogenic bacteria in humans is the urease enzyme. In order to avoid the detrimental impact of ureolytic bacterial infections, the inhibition of urease enzyme appears to be an appealing approach. Therefore, in the current study, morpholine-thiophene hybrid thiosemicarbazone derivatives (5a-i) were designed, synthesized and characterized through FTIR, 1H NMR, 13C NMR spectroscopy and mass spectrometry. A range of substituents including electron-rich, electron-deficient and inductively electron-withdrawing groups on the thiophene ring was successfully tolerated. The synthesized derivatives were evaluated in vitro for their potential to inhibit urease enzyme using the indophenol method. The majority of compounds were noticeably more potent than the conventional inhibitor, thiourea. The lead inhibitor, 2-(1-(5-chlorothiophen-2-yl)ethylidene)-N-(2-morpholinoethyl)hydrazinecarbothioamide (5g) inhibited the urease in an uncompetitive manner with an IC50 value of 3.80 ± 1.9 µM. The findings of the docking studies demonstrated that compound 5g has a strong affinity for the urease active site. Significant docking scores and efficient binding free energies were displayed by the lead inhibitor. Finally, the ADME properties of lead inhibitor (5g) suggested the druglikeness behavior with zero violation.

9.
Expert Opin Ther Pat ; 34(4): 263-271, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38828613

RESUMEN

INTRODUCTION: The purinergic P2X7 receptor (P2X7R) is expressed on the surface of many different types of cells, including immune cells. Targeting P2X7R with antagonists has been studied for its potential therapeutic effects in a variety of inflammatory illnesses. AREA COVERED: Many chemical substances, including carboxamides, benzamides and nitrogen containing heterocyclic derivatives have demonstrated promising inhibitory potential for P2X7 receptor. The chemistry and clinical applications of P2X7R antagonists patented from 2018- present are discussed in this review. EXPERT OPINION: Purinergic receptor inhibitor discovery and application has demonstrated the potential for therapeutic intervention, as demonstrated by pharmacological research. Few chemical modalities have been authorized for use in clinical settings, despite the fact that breakthroughs in crystallography and chemical biology have increased the knowledge of purinergic signaling and its consequences in disease. The many research projects and pharmaceutical movements that sustain dynamic P2X receptor programs over decades are evidence of the therapeutic values and academic persistence in purinergic study. P2X7R is an intriguing therapeutic target and possible biomarker for inflammation. Although several companies like Merck and AstraZeneca have published patents on P2X3 antagonists, the search for P2X7R antagonists has not stopped. Numerous pharmaceutical companies have disclosed different scaffolds, and some molecules are presently being studied in clinical studies.


Asunto(s)
Inflamación , Patentes como Asunto , Antagonistas del Receptor Purinérgico P2X , Receptores Purinérgicos P2X7 , Humanos , Receptores Purinérgicos P2X7/metabolismo , Receptores Purinérgicos P2X7/efectos de los fármacos , Antagonistas del Receptor Purinérgico P2X/farmacología , Animales , Inflamación/tratamiento farmacológico , Inflamación/fisiopatología , Desarrollo de Medicamentos , Antiinflamatorios/farmacología
10.
Int J Biol Macromol ; 272(Pt 1): 132748, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38821306

RESUMEN

Neurodegenerative diseases with progressive cellular loss of the central nervous system and elusive disease etiology provide a continuous impetus to explore drug discovery programmes aiming at identifying robust and effective inhibitors of cholinesterase and monoamine oxidase enzymes. We herein present a concise library of anthranilamide derivatives involving a palladium-catalyzed Suzuki-Miyaura cross-coupling reaction to install the diverse structural diversity required for the desired biological action. Using Ellman's method, cholinesterase inhibitory activity was performed against AChE and BuChE enzymes. In vitro assay results demonstrated that anthranilamides are potent inhibitors with remarkable potency. Compound 6k emerged as the lead candidate and dual inhibitor of both enzymes with IC50 values of 0.12 ± 0.01 and 0.49 ± 0.02 µM against AChE and BuChE, respectively. Several other compounds were found as highly potent and selective inhibitors. Anthranilamide derivatives were also tested against monoamine oxidase (A and B) enzymes using fluorometric method. In vitro data revealed compound 6h as the most potent inhibitor against MAO-A, showing an IC50 value of 0.44 ± 0.02 µM, whereas, compound 6k emerged as the top inhibitor of MAO-B with an IC50 value of 0.06 ± 0.01 µM. All the lead inhibitors were analyzed for the identification of their mechanism of action using Michaelis-Menten kinetics experiments. Compound 6k and 6h depicted a competitive mode of action against AChE and MAO-A, whereas, a non-competitive and mixed-type of inhibition was observed against BuChE and MAO-B by compounds 6k. Molecular docking analysis revealed remarkable binding affinities of the potent inhibitors with specific residues inside the active site of receptors. Furthermore, molecular dynamics simulations were performed to explore the ability of potent compounds to form energetically stable complexes with the target protein. Finally, in silico ADME calculations also demonstrated that the potent compounds exhibit promising pharmacokinetic profile, satisfying the essential criteria for drug-likeness. Altogether, the findings reported in the current work clearly suggest that the identified anthranilamide derivatives have the potential to serve as effective drug candidates for future investigations.


Asunto(s)
Inhibidores de la Colinesterasa , Diseño de Fármacos , Simulación del Acoplamiento Molecular , Inhibidores de la Monoaminooxidasa , Monoaminooxidasa , Enfermedades Neurodegenerativas , ortoaminobenzoatos , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , ortoaminobenzoatos/química , ortoaminobenzoatos/farmacología , Monoaminooxidasa/metabolismo , Monoaminooxidasa/química , Humanos , Inhibidores de la Monoaminooxidasa/química , Inhibidores de la Monoaminooxidasa/farmacología , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/enzimología , Relación Estructura-Actividad , Descubrimiento de Drogas , Colinesterasas/metabolismo , Colinesterasas/química , Simulación de Dinámica Molecular
11.
Sci Rep ; 14(1): 11498, 2024 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769427

RESUMEN

Strokes are a leading global cause of mortality, underscoring the need for early detection and prevention strategies. However, addressing hidden risk factors and achieving accurate prediction become particularly challenging in the presence of imbalanced and missing data. This study encompasses three imputation techniques to deal with missing data. To tackle data imbalance, it employs the synthetic minority oversampling technique (SMOTE). The study initiates with a baseline model and subsequently employs an extensive range of advanced models. This study thoroughly evaluates the performance of these models by employing k-fold cross-validation on various imbalanced and balanced datasets. The findings reveal that age, body mass index (BMI), average glucose level, heart disease, hypertension, and marital status are the most influential features in predicting strokes. Furthermore, a Dense Stacking Ensemble (DSE) model is built upon previous advanced models after fine-tuning, with the best-performing model as a meta-classifier. The DSE model demonstrated over 96% accuracy across diverse datasets, with an AUC score of 83.94% on imbalanced imputed dataset and 98.92% on balanced one. This research underscores the remarkable performance of the DSE model, compared to the previous research on the same dataset. It highlights the model's potential for early stroke detection to improve patient outcomes.


Asunto(s)
Aprendizaje Automático , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/epidemiología , Factores de Riesgo , Masculino , Femenino , Anciano , Persona de Mediana Edad , Índice de Masa Corporal
12.
Int J Biol Macromol ; 271(Pt 1): 132502, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38768915

RESUMEN

A series of sulfonate and sulfamate derivatives bearing benzofuran or benzothiophene scaffold exhibited potent inhibitory effect on urease enzyme. Most of the derivatives exhibited significantly higher potency than thiourea, the standard inhibitor. Compound 1s was identified as the most potent urease inhibitor with an IC50 value of 0.42 ± 0.08 µM, which is 53-fold more potent than thiourea, positive control (IC50 = 22.3 ± 0.031 µM). The docking results further revealed the binding interactions towards the urease active site. Phenotypic screening revealed that compounds 1c, 1d, 1e, 1f, 1j, 1n, and 1t exhibit high potency against H. pylori with MIC values ranging from 0.00625 to 0.05 mM and IC50 values ranging from 0.0031 to 0.0095 mM, much more potent than the positive control, acetohydroxamic acid (MIC and IC50 values were 12.5 and 7.38 mM, respectively). Additional studies were performed to investigate the toxicity of these compounds against the gastric epithelial cell line (AGS) and their selectivity profile against E. coli, and five Lactobacillus species representative of the gut microflora. Permeability characteristics of the most promising derivatives were investigated in Caco-2 cell line. The results indicate that the compounds could be targeted in the GIT only without systemic side effects.


Asunto(s)
Antibacterianos , Benzofuranos , Inhibidores Enzimáticos , Helicobacter pylori , Simulación del Acoplamiento Molecular , Ácidos Sulfónicos , Tiofenos , Ureasa , Ureasa/antagonistas & inhibidores , Ureasa/metabolismo , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/enzimología , Ácidos Sulfónicos/química , Ácidos Sulfónicos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Benzofuranos/química , Benzofuranos/farmacología , Humanos , Tiofenos/química , Tiofenos/farmacología , Diseño de Fármacos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad , Descubrimiento de Drogas
13.
Front Chem ; 12: 1380523, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38694406

RESUMEN

Diabetes mellitus is a multi-systematic chronic metabolic disorder and life-threatening disease resulting from impaired glucose homeostasis. The inhibition of glucosidase, particularly α-glucosidase, could serve as an effective methodology in treating diabetes. Attributed to the catalytic function of glucosidase, the present research focuses on the synthesis of sulfonamide-based acyl pyrazoles (5a-k) followed by their in vitro and in silico screening against α-glucosidase. The envisaged structures of prepared compounds were confirmed through NMR and FTIR spectroscopy and mass spectrometry. All compounds were found to be more potent against α-glucosidase than the standard drug, acarbose (IC50 = 35.1 ± 0.14 µM), with IC50 values ranging from 1.13 to 28.27 µM. However, compound 5a displayed the highest anti-diabetic activity (IC50 = 1.13 ± 0.06 µM). Furthermore, in silico studies revealed the intermolecular interactions of most potent compounds (5a and 5b), with active site residues reflecting the importance of pyrazole and sulfonamide moieties. This interaction pattern clearly manifests various structure-activity relationships, while the docking results correspond to the IC50 values of tested compounds. Hence, recent investigation reveals the medicinal significance of sulfonamide-clubbed pyrazole derivatives as prospective therapeutic candidates for treating type 2 diabetes mellitus (T2DM).

14.
Curr Rheumatol Rep ; 26(7): 260-268, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38575845

RESUMEN

PURPOSE OF REVIEW: Hyperlipidemia is the major cardiovascular morbidity and mortality risk factor. Statins are the first-line treatment for hyperlipidemia. Statin-associated muscle symptoms (SAMS) are the main reason for the discontinuation of statins among patients. The purpose of this review is to guide clinicians to recognize the difference between self-limited and autoimmune statin myopathy in addition to the factors that potentiate them. Finally, treatment strategies will be discussed. This review mostly focuses on new data in the past 3 years. RECENT FINDINGS: Recent findings suggest that SAMS is a complex and multifactorial condition that involves mitochondrial dysfunction, oxidative stress, and immune-mediated mechanisms. Effective management of SAMS requires a thorough evaluation of the patient's symptoms, risk factors, and medication history, as well as consideration of alternative treatment options. While statins are effective in reducing the risk of cardiovascular events, their use is associated with a range of adverse effects, including SAMS.


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas , Enfermedades Musculares , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Enfermedades Musculares/inducido químicamente , Factores de Riesgo , Hiperlipidemias/tratamiento farmacológico
15.
ACS Omega ; 9(13): 15603-15614, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38585118

RESUMEN

In the present work, 2-imino-1,3-thiazolines featuring highly fluorinated fragments were synthesized through a straightforward cyclization of diversely substituted thioureas with 2-bromo-1-(4-fluorophenyl)ethan-1-one. The target compounds were obtained in good yields, and structures were established by FTIR and 1H- and 13C NMR spectroscopic methods. The in vitro biological assay revealed that all the compounds significantly obstruct the α-glucosidase. Compound 6d (3-fluoro-N-(3-(2-fluorophenyl)-4-(4-fluorophenyl)thiazol-2(3H)-ylidene)benzamide) showed the highest antidiabetic potential with an IC50 value of 1.47 ± 0.05 µM. In addition, computational analysis revealed the binding energy of -11.1 kcal/mol for 6d which was lower than the positive standard, acarbose (-7.9 kcal/mol). Several intermolecular interactions between the active site residues and 6d highlight the significance of 2-imino-1,3-thiazoline core in attaining the potent efficacy and making these compounds a valuable pharmacophore in drug discovery.

16.
Front Pharmacol ; 15: 1325359, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38449804

RESUMEN

Background: Liver disease is a serious health concern in today's world, posing a challenge to both healthcare providers and pharmaceutical companies. Most synthetic drugs and chemicals cause liver damage accounting for approximately 10% of acute hepatitis and 50% of acute liver failure. Purpose: The present study aimed to evaluate the hepato-protective activity of an extract of chicory formulation assisted by silver nanoparticles against carbon tetra chloride (CCl4)-induced hepatic damage in rat's liver. Methods: Rats of the Wistar strain (Rattus norvegicus) were used to test the in vivo hepato-protective efficacy at various doses. Rats were randomly divided into nine groups, each containing six rats. The groups were as follows: first group (control), second group (CCl4), third group, silymarin (20 mg/kg of body weight), fourth group (CCl4+chicory) (1.75 mg/kg of b. wt), fifth group (CCl4 + chicory at the dose of 2.35 mg/kg), sixth group (CCl4 + chicory of 3.25 mg/kg), seventh group (CCl4 +AgNPs 1.75 mg/kg of b. wt.), eighth group (CCl4 + AgNPs 2.35 mg/kg of body weight), and ninth group (CCl4 + AgNPs 3.25 mg/kg of b. wt.). Blood samples were taken 24 h after the last administration (i.e., 30th day). The blood samples were analyzed for different serum enzymes such as ALP (alkaline phosphatase), ALT (alanine transaminase), bilirubin (Blr), triglyceride, and cholesterol. Histology liver sections were performed. Results: Treatment with AgNPs and chicory extract showed significant hepato-protective activity in a dose-dependent manner. In three doses, the chicory extract at a rate of 3.25 mg/kg of body weight significantly reduced elevated levels of biochemical markers in comparison to CCl4-intoxicated rats. Histology of the liver sections from CCl4-treated rats revealed inflammation of hepatocytes, necrosis, cytoplasmic degeneration, vacuolization, and a deformed central vein. The chicory formulation extract exhibited a remarkable recovery percentage in the liver architecture that was higher than the drug (i.e., silymarin). While treatment with AgNPs also repaired the degenerative changes and restored the normal form of the liver, chicory formulation extract possessed more hepato-protective potential as compared to AgNPs by regulating biochemical and histo-pathological parameters. Conclusion: This study can be used as confirmation of the hepato-protective potential of chicory compounds for possible use in the development programs of drugs to treat liver diseases.

17.
J Biomol Struct Dyn ; : 1-18, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38321911

RESUMEN

Dwarfism is a medical term used to describe individuals with a height-vertex measurement that falls below two standard deviations (-2SD) or the third percentile for their gender and age. Normal development of growth is a complicated dynamic procedure that depends upon the coordination of different aspects involving diet, genetics, and biological aspects like hormones in equilibrium. Any severe or acute pathologic procedure may disturb the individual's normal rate of growth. In this research, we examined four (A-D) Pakistani consanguineous families that exhibited syndromic dwarfism, which was inherited in an autosomal recessive pattern. The genomic DNA of each family member was extracted by using phenol-chloroform and Kit methods. Whole Exome Sequencing (WES) of affected family members (IV-11, III-5, IV-4 and III-13) from each group was performed at the Department of Medical Genetics, University of Antwerp, Belgium. After filtering the exome data, the mutations in PPM1F, FGFR3, ERCC2, and PCNT genes were determined by Sanger sequencing of each gene by using specific primers. Afterward, FGFR3 was found to be a suitable drug target among all the mutations to treat achondroplasia also known as disproportionate dwarfism. BioSolveIT softwares were used to discover the lead active inhibitory molecule against FGFR3. This research will not only provide short knowledge to the concerned pediatricians, researchers, and family physicians for the preliminary assessment and management of the disorder but also provide a lead inhibitor for the treatment of disproportionate dwarfism.Communicated by Ramaswamy H. Sarma.

18.
Curr Med Chem ; 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38275065

RESUMEN

Ovarian cancer is the fifth leading cause of mortality and the most lethal gynecologic malignancy among females. It may arise from atypical borderline tumors (Type I) or serous tubal intraepithelial carcinoma (Type II). The diagnosis of cancer at its early stages is difficult because of non-specific symptoms, most patients are diagnosed at the advanced stage. Several drugs and therapeutic strategies are available to treat ovarian cancer such as surgery, chemotherapy, neoadjuvant therapy, and maintenance therapy. However, the cancer cells have developed resistance to a number of available therapies causing treatment failure. This emerging chemoresistance in ovarian cancer cells is becoming an obstacle due to alterations in multiple cellular processes. These processes involve altered drug target response, drug pumps, detoxification systems, lower sensitivity to apoptosis, and altered proliferation, and are responsible for developing resistance to anticancer medicines. Various research reports have evidenced that these altered processes might play a role in the emergence of resistance. This review addresses the recent advances in understanding the underlying mechanisms of ovarian cancer resistance and covers sophisticated alternative pathways to overcome these resistance mechanisms in patients.

19.
Int J Biol Macromol ; 259(Pt 2): 129241, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38199537

RESUMEN

Diabetes mellitus, one of the major health challenges of the 21st century, is associated with numerous biomedical complications including retinopathy, neuropathy, nephropathy, cardiovascular diseases and liver disorders. To control the chronic hyperglycemic condition, the development of potential inhibitors of drug targets such as α-glucosidase and α-amylase remains a promising strategy and focus of continuous efforts. Therefore, in the present work, a concise library of isobenzofuranone derivatives (3a-q) was designed and synthesized using Suzuki-Miyaura cross-coupling approach. The biological potential of these heterocyclic compounds against carbohydrate-hydrolyzing enzymes; α-glucosidase and α-amylase, was examined. In vitro inhibitory results demonstrated that the tested isobenzofuranones were considerably more effective and potent inhibitors than the standard drug, acarbose. Compound 3d having an IC50 value of 6.82 ± 0.02 µM was emerged as the lead candidate against α-glucosidase with ⁓127-folds strong inhibition than acarbose. Similarly, compound 3g demonstrated ⁓11-folds higher inhibition strength against α-amylase when compared with acarbose. Both compounds were tested in vivo and results demonstrate that the treatment of diabetic rats with α-amylase inhibitor show more pronounced histopathological normalization in kidney and liver than with α-glucosidase inhibitor. The Lineweaver-Burk plot revealed an uncompetitive mode of inhibition for 3d against α-glucosidase whereas compound 3g exhibited mixed inhibition against α-amylase. Furthermore, in silico molecular docking and dynamics simulations validated the in vitro data for these compounds whereas pharmacokinetics profile revealed the druglike properties of potent inhibitors.


Asunto(s)
Diabetes Mellitus Experimental , Hipoglucemiantes , Ratas , Animales , Hipoglucemiantes/farmacología , Acarbosa , Simulación de Dinámica Molecular , alfa-Glucosidasas/metabolismo , Simulación del Acoplamiento Molecular , Diabetes Mellitus Experimental/tratamiento farmacológico , alfa-Amilasas , Inhibidores de Glicósido Hidrolasas/farmacología
20.
Chemosphere ; 351: 141113, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38185428

RESUMEN

In this study, the optimization of potassium carbonate (K2CO3) exposure conditions for CO2 capture with the use of 2-methypiperazine (2MPz) and monoethanolamine (MEA) as promoters was investigated. The tested operating conditions for the CO2 capture process included the pH, temperature, K2CO3 dose, gas flow rate, and pressure, and their effect on the CO2 absorption/desorption rate and CO2 absorption efficiency was assessed. Response surface methodology (RSM) was also employed to determine the equations for the optimal long-term operating conditions. The results showed that the CO2 absorption rate and efficiency increased under K2CO3 exposure with an increase in the pressure and loading rate. Moreover, for the temperature the absorption efficiency first increase and then decreases with increase in temperature, however, the with increase in temperature the faster absorption were observed with lower absorption loading rate. Furthermore, pH had a more complex effect due to its variable effects on the speciation of bicarbonate ions (HCO3-) and carbonate ions (CO32-). Under higher pH conditions, there was an increase in the concentration of HCO3-, which has a higher CO2 loading capacity than CO32-. Contouring maps were also used to visualize the effect of different exposure conditions on the CO2 absorption rate and efficiency and the role of 2MPz and MEA as promoters in the K2CO3 solution for CO2 absorption. The results showed that the mean CO2 absorption rate was 6.76 × 10-4 M/L/s with an R2 of 0.9693 for the K2CO3 solution containing 2MPz. The highest absorption rate (6.56-7.20 × 10-4 M/L/s) was observed at a temperature of 298-313 K, a pressure of >2 bar, a pH of 8-9, and a loading rate of 80-120 L/h for a concentration of 1-3 M K2CO3 and 0.05-1.5 M 2MPz. The CO2 absorption efficiency exhibited a variation of 56-70% under the same conditions.


Asunto(s)
Dióxido de Carbono , Etanolamina , Piperazinas , Temperatura
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