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1.
Artículo en Inglés | MEDLINE | ID: mdl-39261391

RESUMEN

Intermittent fasting (IF) is an increasingly popular dietary approach involving alternating fasting and eating periods. This review aims to summarize the growing body of literature demonstrating that IF is a potential nutritional practice that involves alternating periods of fasting and eating and the numerous benefits of IF, especially in the modulation of healthy gut microbiota. The positive impact of intermittent fasting on gut microbiota not only promotes gastrointestinal health but also has far-reaching effects on critical systems throughout the body. Additionally, the evidence presented in this review highlights the significant preventive and therapeutic effects of intermittent fasting on a wide range of disorders. This includes reducing the risk of diabetes, and neurological disorders, alleviating obesity, and enhancing the functioning of the liver, ultimately contributing to the maintenance of metabolic equilibrium. Perhaps most notably, these effects play a substantial role in preventing diabetes, a global health concern of increasing significance. This comprehensive investigation delves into the scientific foundations of intermittent fasting's impact on gut microbiota and its implications for averting chronic diseases, providing valuable insights for future research and therapeutic applications.

2.
Food Sci Nutr ; 12(7): 4879-4892, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39055198

RESUMEN

Diabetes mellitus is a metabolic and chronic disease linked to lifestyle factors like dietary patterns and physical inactivity. This randomized clinical study aimed to develop a novel dietary intervention using pomegranate peel powder-based multigrain chapatti to prevent diabetes. The product was formulated by incorporating pomegranate peel powder into a mixture of wheat flour, pearl flour, millet flour, and chickpea flour. The study included the formulation of various treatments (Tc, T1, T2, and T3) following product development, and these treatments were subjected to comprehensive assessments. The nutritional composition and antioxidant potential of the pomegranate peel powder-based multigrain chapatti were analyzed. Sensory attributes, including taste, texture, and overall acceptability, were evaluated. Additionally, biochemical analyses, including blood glucose levels and HbA1C, were conducted to assess the impact of the interventions on blood glucose metabolism. The results revealed that the nutritional profile and phytochemical potential of the product improved significantly in treatment T3, which contained 15% pomegranate juice. Overall acceptability was found to be high for T3, indicating that the inclusion of pomegranate peel powder was well received in terms of taste and sensory qualities. Importantly, the clinical trial demonstrated positive outcomes in the intervention group receiving the pomegranate peel powder-based multigrain chapatti. Blood glucose analysis and HbA1C assessments indicated that the consumption of this innovative dietary product contributed to improved blood glucose metabolism, suggesting its potential as a preventive strategy for diabetes.

4.
BMC Complement Med Ther ; 24(1): 195, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769554

RESUMEN

BACKGROUND: The burden of breast cancer, the second leading cause of death worldwide, is increasing at an alarming rate. Cuscuta, used in traditional medicine for different ailments, including cancer, is known for containing phytochemicals that exhibit anticancer activity; however, the bioactivities of proteins from this plant remain unexplored. This study aimed to screen the cytotoxic potential of proteins from the crude herbal product of Cuscuta epithymum(L.) (CE) harvested from the host plants Alhagi maurorum and Medicago sativa. METHODS: The proteins from CE were extracted using a salting-out method, followed by fractionation with a gel filtration chromatography column. Gel-free shotgun proteomics was subsequently performed for protein characterization. The viability assay using MTT was applied to deduce the cytotoxic potential of proteins against MCF-7 breast cancer cells, with further exploration of the effect of treatment on the expression of the apoptotic mediator BCL2-associated X protein (BAX) and B-cell lymphoma protein 2 (BCL-2) proteins, using western blotting to strengthen the findings from the in vitro viability assay. RESULTS: The crude proteins (CP) of CE were separated into four protein peaks (P1, P2, P3, and P4) by gel filtration chromatography. The evaluation of potency showed a dose-dependent decline in the MCF-7 cell line after CP, P1, P2, and P3 treatment with the respective IC50 values of 33.8, 43.1, 34.5, and 28.6 µg/ml. The percent viability of the cells decreased significantly upon treatment with 50 µg/ml CP, P1, P2, and P3 (P < 0.001). Western-blot analysis revealed upregulation of proapoptotic protein BAX in the cells treated with CP, P3 (P < 0.01), and P2 (P < 0.05); however, the antiapoptotic protein, BCL-2 was downregulated in the cells treated with CP and P3 (P < 0.01), but no significant change was detected in P2 treated cells. The observed cytotoxic effects of proteins in the CP, P1, P2, and P3 from the in vitro viability assay and western blot depicted the bioactivity potential of CE proteins. The database search revealed the identities of functionally important proteins, including nonspecific lipid transfer protein, superoxide dismutase, carboxypeptidase, RNase H domain containing protein, and polyribonucleotide nucleotidyltransferase, which have been previously reported from other plants to exhibit anticancer activity. CONCLUSION: This study indicated the cytotoxic activity of Cuscuta proteins against breast cancer MCF-7 cells and will be utilized for future investigations on the mechanistic effect of active proteins. The survey of CE proteins provided substantial data to encourage further exploration of biological activities exhibited by proteins in Cuscuta.


Asunto(s)
Neoplasias de la Mama , Cuscuta , Proteínas de Plantas , Proteómica , Humanos , Células MCF-7 , Proteínas de Plantas/farmacología , Cuscuta/química , Neoplasias de la Mama/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/química , Femenino , Antineoplásicos Fitogénicos/farmacología , Supervivencia Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos
5.
Crit Rev Biomed Eng ; 52(4): 17-28, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38780103

RESUMEN

In this study, we examine the behavior of articular cartilage equilibrated in a salt (NaCl) solution during non-Newtonian fluid flow that follows an Ostwald-de Waele model. A linearly elastic and isotropic rectangular strip of cartilage is considered for analysis. A continuum theory of mixtures has been employed to develop a coupled system of partial differential equations for the solid displacement and the fluid pressure by considering the important factor of the ion concentration by assuming the cartilage as a deformable porous media. The coupled system of partial differential equations is solved using the numerical method named method of lines. In most cases, shear-thinning fluid is compared to the shear-thickening fluid to magnify the difference. Graphical results show that shear-thickening fluids bring more solid deformation and shows less fluid pressure in comparison to the shear-thinning fluids.


Asunto(s)
Cartílago Articular , Presión , Cartílago Articular/fisiología , Modelos Biológicos , Humanos , Iones , Animales , Reología/métodos , Elasticidad , Cloruro de Sodio/química , Viscosidad , Porosidad
6.
Indian J Otolaryngol Head Neck Surg ; 76(2): 1965-1971, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38566720

RESUMEN

Introduction: Potentially malignant oral epithelial lesions are a group of oral conditions with an altered morphological state of the normal mucosal lining and include different lesions such as leukoplakia, erythroplakia, submucosal fibrosis, and lichen planus. Aim: To compare the outcome of premalignant oral lesions after medical therapy consisting of submucosal intralesional injection of triamcinolone with hyaluronidase and surgical excision. Materials and Methods: This was a comparative prospective interventional study and the study was conducted among 50 patients presented to the Department of Otorhinolaryngology with premalignant oral lesions from the year 2020 to 2022. Patients were divided into two groups by random allocation, group A was treated with medical therapy, and Group B was treated with surgical excision and followed for a minimum of 6 months and the outcome has been categorized. Results: All patients were divided into two groups-group A and group B, group A consisted of 22 (44%) patients who were given medical therapy, and group B consisted of 28 (56%) patients who underwent surgical excision. In group A, the clinical response was seen in 8 (36.36%) and in group B, the clinical response was seen in 18 (64.29%) patients. Conclusion: Surgical excision was found to be better with more cases of clinical response (64.29%) when compared to medical treatment (36.36%) with a p value of 0.0497 which is significant whereas malignant transformation was almost equal in medical therapy and surgical treatment which was 13.64% and 14.28%, respectively.

7.
Sci Rep ; 14(1): 9398, 2024 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658642

RESUMEN

Free Fatty Acid Receptor 4 (FFAR4), a G-protein-coupled receptor, is responsible for triggering intracellular signaling pathways that regulate various physiological processes. FFAR4 agonists are associated with enhancing insulin release and mitigating the atherogenic, obesogenic, pro-carcinogenic, and pro-diabetogenic effects, normally associated with the free fatty acids bound to FFAR4. In this research, molecular structure-based machine-learning techniques were employed to evaluate compounds as potential agonists for FFAR4. Molecular structures were encoded into bit arrays, serving as molecular fingerprints, which were subsequently analyzed using the Bayesian network algorithm to identify patterns for screening the data. The shortlisted hits obtained via machine learning protocols were further validated by Molecular Docking and via ADME and Toxicity predictions. The shortlisted compounds were then subjected to MD Simulations of the membrane-bound FFAR4-ligand complexes for 100 ns each. Molecular analyses, encompassing binding interactions, RMSD, RMSF, RoG, PCA, and FEL, were conducted to scrutinize the protein-ligand complexes at the inter-atomic level. The analyses revealed significant interactions of the shortlisted compounds with the crucial residues of FFAR4 previously documented. FFAR4 as part of the complexes demonstrated consistent RMSDs, ranging from 3.57 to 3.64, with minimal residue fluctuations 5.27 to 6.03 nm, suggesting stable complexes. The gyration values fluctuated between 22.8 to 23.5 nm, indicating structural compactness and orderliness across the studied systems. Additionally, distinct conformational motions were observed in each complex, with energy contours shifting to broader energy basins throughout the simulation, suggesting thermodynamically stable protein-ligand complexes. The two compounds CHEMBL2012662 and CHEMBL64616 are presented as potential FFAR4 agonists, based on these insights and in-depth analyses. Collectively, these findings advance our comprehension of FFAR4's functions and mechanisms, highlighting these compounds as potential FFAR4 agonists worthy of further exploration as innovative treatments for metabolic and immune-related conditions.


Asunto(s)
Aprendizaje Automático , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Receptores Acoplados a Proteínas G , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/química , Humanos , Ligandos , Unión Proteica , Teorema de Bayes , Sitios de Unión
8.
Food Sci Nutr ; 12(3): 1430-1443, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38455157

RESUMEN

Food is one of the most necessary needs since human civilization. For Muslims, it is mandatory to consume halal food. From a halal authentication perspective, adulteration of food products is an emerging challenge worldwide. The demand for halal food consumption has resulted in an ever-increasing need for halal product validity. In the market, there are several food products in which actual ingredients and their source are not mentioned on the label and cannot be observed by the naked eye. Commonly nonhalal items include pig derivatives like lard, pork, and gelatin derivatives, dead meats, alcohol, blood, and prohibited animals. Purposely, various conventional and modern methods offer precise approaches to ensure the halalness and wholesomeness of food products. Conventional methods are physiochemical (dielectric) and electrophoresis. At the same time, modern techniques include high-pressure liquid chromatography (HPLC), gas chromatography (GC), electronic nose (E-Nose), polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), near-infrared (NIR) spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. This review intends to give an extensive and updated overview of conventional and modern analytical methods for ensuring food halal authenticity.

9.
Front Pediatr ; 12: 1353508, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38440185

RESUMEN

Background: This study addresses the pervasive issue of heightened preoperative anxiety in healthcare, particularly among pediatric patients. Recognizing the various sources of anxiety, we explored both pharmacological and nonpharmacological interventions. Focusing on distraction techniques, including active and passive forms, our meta-analysis aimed to provide comprehensive insights into their impact on preoperative anxiety in pediatric patients. Methods: Following the PRISMA and Cochrane guidelines, this meta-analysis and systematic review assessed the efficacy of pharmaceutical and distraction interventions in reducing pain and anxiety in pediatric surgery. This study was registered on PROSPERO (CRD42023449979). Results: This meta-analysis, comprising 45 studies, investigated pharmaceutical interventions and distraction tactics in pediatric surgery. Risk of bias assessment revealed undisclosed risks in performance and detection bias. Distraction interventions significantly reduced preoperative anxiety compared to control groups, with notable heterogeneity. Comparison with Midazolam favored distraction techniques. Subgroup analysis highlighted varied efficacies among distraction methods, with a notable reduction in anxiety levels. Sensitivity analysis indicated stable results. However, publication bias was observed, suggesting a potential reporting bias. Conclusion: Our study confirms distraction techniques as safe and effective for reducing pediatric preoperative anxiety, offering a valuable alternative to pharmacological interventions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=449979, PROSPERO [CRD42023449979].

10.
Indian J Otolaryngol Head Neck Surg ; 76(1): 658-663, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38440469

RESUMEN

Objectives: 1. To determine the prevailing scenario of the bacteriological profile of patients with CRS, 2. To identify their antibiotic susceptibility profile. Material and methods: The study was conducted on 100 patients in the Department of ENT and Microbiology from December 2020-2022. Patients above the age of 12 years were evaluated. Those who received antibiotics in the last 12 months. and age < 12 years were excluded. Patients were subjected to a detailed history, clinical and radiological examination. After the informed consent of patients and ethical cleareance, samples were taken from the middle meatus area and studied for antibiotics sensitivity: levofloxacin, vancomycin, amikacin, amoxicillin-clavulanic acid and azithromycin. Results: The study was male predominance (71%), with the maximum of patients in the age group 21-30 years (38%). The most common clinical features were nasal obstruction ( 96%) and mucopurulent discharge (100%). The most common isolate was Staphylococcus aureus (45.16%). In Gram-positive, the maximum resistance was shown to azithromycin and amoxicillin-clavulanic acid and the maximum sensitivity to vancomycin, levofloxacin and amikacin. Conclusions: Antibiotic resistance seems to be emerging for azithromycin and amoxicillin-clavulanic acid at a higher rate. MRSA ( 19.35%) maintains a significant presence with associated increased levels of antibiotic resistance.

11.
Food Sci Nutr ; 12(2): 694-706, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38370053

RESUMEN

Modulatory effects of serotonin (5-Hydroxytryptamine [5-HT]) have been seen in hepatic, neurological/psychiatric, and gastrointestinal (GI) disorders. Probiotics are live microorganisms that confer health benefits to their host. Recent research has suggested that probiotics can promote serotonin signaling, a crucial pathway in the regulation of mood, cognition, and other physiological processes. Reviewing the literature, we find that peripheral serotonin increases nutrient uptake and storage, regulates the composition of the gut microbiota, and is involved in mediating neuronal disorders. This review explores the mechanisms underlying the probiotic-mediated increase in serotonin signaling, highlighting the role of gut microbiota in the regulation of serotonin production and the modulation of neurotransmitter receptors. Additionally, this review discusses the potential clinical implications of probiotics as a therapeutic strategy for disorders associated with altered serotonin signaling, such as GI and neurological disorders. Overall, this review demonstrates the potential of probiotics as a promising avenue for the treatment of serotonin-related disorders and signaling of serotonin.

12.
Heliyon ; 10(1): e23476, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38169832

RESUMEN

Chillies are considered a universal ingredient for imparting flavor and pungency to foods. Pakistan stood in the top twenty countries worldwide by producing 82 thousand Tons of chillies during 2022-23. Chilli fungal contamination and aflatoxin production during drying is a common problem during post-harvest process. Gasses treatment and Ionizing radiations are efficient methods for reducing toxigenic and pathogenic microbial growth in food items. The current study was designed to compare the effects of ethylene oxide (ETO), gamma (GB) & electron beam (EB) treatments on two red chilli local cultivars (Kunri and Hybrid) of Pakistan. After treatment, the chilli samples were analyzed for aflatoxins, physicochemical, quality & safety attributes. All results were subjected to Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), dendrogram and ANOVA to check the correlations, grouping and level of significance within the varieties and treatments. The results showed that moisture and water activity mainly designated PC-2 directions and are slightly positively correlated. Conversely, both fat and proteins have a negative correlation with moisture, ash and water activity. Besides, carotenoids and ABTS assay mainly designated PC-2 directions and are slightly positively correlated. Color, flavonoids and TPC also possess positive correlations among them. ETO depicts effectiveness in the reduction of E. coli but is not effective in saving antioxidant potential such as total flavonoids. Similarly, gamma irradiations showed strong reduction trends in fungal and pathogenic count, however same trend was observed in ascorbic acid too. Besides, the electron beam with dosage levels of 12 and 15 kGy has shown effectiveness against Aspergillus spp., aflatoxins and pathogenic microbial load in addition to saving antioxidant potential (phenolics and flavonoids), physicochemical parameters and color values compared to other applied methods especially in Kunri variety. It was evident from the research that varietal combination in addition to applied treatment must be specially considered while designing a treatment for chillies.

13.
Foods ; 12(21)2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37959023

RESUMEN

In the current study, whey protein-based nanofibers were fabricated to encapsulate Lactobacillus rhamnosus. Purposely, different ratios of PVA (polyvinyl alcohol) and WPI (whey protein isolate) were blended to fabricate nanofibers. Nanofiber mats were characterized in terms of particle size, diameter, tensile strength, elongation at break, and loading efficiency. Morphological and molecular characterizations were carried out using scanning electron microscopy (SEM) and Fourier transform infrared (FTIR). Moreover, in vitro viability under simulated gastrointestinal (GI) conditions and thermal stability were also assessed. The results reveal that by increasing the PVA concentration, the conductivity increased while the viscosity decreased. SEM micrographs showed that probiotics were successfully loaded within the nanofiber. The FTIR spectra show strong bonding between the encapsulating materials with the addition of probiotics. In vitro and thermal analyses revealed that the survival of encapsulated probiotics significantly (p < 0.05) improved. In a nutshell, PVA-WPI composite nanofibers have promising potential when used to enhance the viability and stability of probiotics under adverse conditions.

14.
Chem Biodivers ; 20(12): e202301190, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37963090

RESUMEN

The Epidermal Growth Factor Receptor (EGFR) is an important therapeutic target for the treatment of a variety of epithelial malignancies, including breast cancer, in which EGFR is aberrantly expressed.The fluorocyclopentenyl-purine-pyrimidines derivatives, which have previously been described as powerful compounds against breast cancer, were selected to investigate their potential against EGFR using computational tools in an effort to obtain potent inhibitors with fewer adverse effects. The molecule's chemical reactivity and stability were assessed by determining the HOMO-LUMO energy gap using density functional theory (DFT) calculations. Among all the selected compounds, PU4 displayed a HOMO-LUMO gap of 0.191 eV. Additionally, molecular docking analysis was performed to assess the binding affinities of PU4 within the active pocket of EGFR-TK. The compound PU4 showed potent interactions with EGFR exhibiting -32.3 kJ/mol binding energy which was found best as compared to gefitinib i. e., -27.4 kJ/mol which was further validated by molecular dynamics simulations and ADMET analysis. The results of these analyses indicate that the top hits obtained from the virtual screening possess the ability to act as effective EGFR inhibitor. Therefore, it is recommended to further investigate the inhibitory potential of these identified compounds using in vitro and in vivo approaches.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Receptores ErbB/metabolismo , Simulación de Dinámica Molecular , Purinas , Pirimidinas/farmacología , Pirimidinas/química
15.
Int J Surg Case Rep ; 113: 109015, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37950993

RESUMEN

INTRODUCTION: Acute disseminated encephalomyelitis (ADEM) is a demyelinating immune-mediated condition of the central nervous system, whereas antiphospholipid antibody syndrome (APLA) is an autoimmune disorder accompanied by thrombosis and pregnancy-related problems. We present a unique case of a 30-year-old female with ADEM coexisting with APLA, highlighting the importance of early identification and specialized care. PRESENTATION OF CASE: We present a case of a 30-year-old woman with a history of hypertension, multiple miscarriages, and non-compliance with medication, who presented with altered consciousness and weakness in all four limbs. Laboratory tests revealed positive anti-cardiolipin and lupus anticoagulant antibodies, confirming APLA. A neurological examination revealed increased limb tone, heightened reflexes, and extensor plantar responses. MRI revealed confluent white matter lesions that were consistent with ADEM. The patient received prompt treatment with intravenous methylprednisolone and then received oral prednisone, leading to a rapid improvement in neurological status. DISCUSSION: The intricate interaction between ADEM and APLA remains enigmatic. The plausible connection between "molecular mimicry" and weakened blood-brain barrier, substantiated by antiphospholipid antibodies, may help explain their concurrent occurrence. CONCLUSION: This case highlights the significance of early diagnosis and management of the rare and complex coexistence of ADEM and APLA to attain optimal outcomes, as well as the significance of careful examination for simultaneous autoimmune markers in individuals presenting with neurological disturbances.

16.
Protein J ; 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37940790

RESUMEN

AKR1B1 and AKR1B10 are important members of aldo-keto reductase family which plays a significant role in cancer progression by modulating cellular metabolism. These enzymes are involved in various metabolic processes, including the synthesis and metabolism of hormones, detoxification of reactive aldehydes, and the reduction of various endogenous and exogenous compounds. This study aimed to explore the potential of strychnine as an anticancer agent by targeting AKR1B1 and AKR1B10 via drug repurposing approach. To assess the drug-like properties of strychnine, a physiologically based pharmacokinetic (PKPB) model and High Throughput Pharmacokinetics (HTPK) approach were employed. The obtained results fell within the expected range for drug molecules, confirming its suitability for further investigation. Additionally, density functional theory (DFT) studies were conducted to gain insight into the electronic properties contributing to the drug molecule's reactivity. Building upon the promising DFT results, molecular docking analysis using the AutoDock tool was performed to examine the binding interactions between strychnine and the proposed targets, AKR1B1 and AKR1B10. Findings from the molecular docking studies suggested a higher probability of strychnine acting as an inhibitor of AKR1B1 and AKR1B10 with docking scores of - 30.84 and - 29.36 kJ/mol respectively. To validate the stability of the protein-ligand complex, Molecular Dynamic Simulation (MDS) studies were conducted, revealing the formation of a stable complex between the enzymes and strychnine. This comprehensive approach sheds light on the potential effectiveness of strychnine as a treatment for breast, lung, liver, and pancreatic cancers, as well as related malignancies. The novel insights gained from the physiologically based pharmacokinetic modeling, density functional theory, molecular docking, and molecular dynamics simulations collectively support the prospect of strychnine as a promising molecule for anticancer therapy. Further investigations are warranted to validate these findings and explore the therapeutic potential of strychnine in preclinical and clinical settings.

17.
Artículo en Inglés | MEDLINE | ID: mdl-37818567

RESUMEN

Cancer stem cells (CSCs) play an essential role in tumour progression and metastasis. These cells have the unique ability to self-renew and differentiate into specific tissue cell types. Their capacity for self-renewal enables CSCs to persist over time, thereby contributing to cancer relapse and therapy resistance. Therefore, targeting CSCs has emerged as a promising cancer treatment strategy. CSCs exhibit differentiation, self-renewal, and plasticity, and they contribute to multiple aspects of malignant tumours, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. While conventional treatments predominantly target cancer cells that are not CSCs, CSCs frequently survive, resulting in tumour recurrence and relapse. This article concentrates on the development of novel therapeutic strategies that combine conventional treatments with CSC inhibitors to eradicate cancer cells and CSCs, thereby treating cancer and preventing its recurrence. However, the diversity of CSCs poses a significant obstacle to the development of CSC-targeted therapies, necessitating extensive research for a better understanding and exploration of therapeutic approaches. Future development of CSC-targeted therapies will rely heavily on overcoming this obstacle.

18.
J Biomol Struct Dyn ; : 1-11, 2023 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-37855364

RESUMEN

Diabetes results in substantial disabilities, diminished quality of life, and mortality that imposes a huge economic burden on societies and governments worldwide. Despite the absence of specific oral therapies at present, there exists an urgent requirement to develop a novel drug for the treatment of diabetes mellitus. The membrane protein sodium glucose co-transporters (SGLT1) present a captivating therapeutic target for diabetes, given its pivotal role in facilitating glucose absorption in the small intestine, offering immense promise for potential therapeutic intervention. In this connection, the present study is aimed at identifying potential inhibitors of SGLT1 from a small molecule database, including compounds from both natural as well as synthetic origins. A comprehensive approach was employed, by integrating homology modeling, ligand-based pharmacophore modeling, virtual screening, and molecular docking simulation. The process resulted in the identification of 16 new compounds, featuring similar attributes as observed for the documented actives. In a systematic screening procedure, five potential virtual hits were selected for simulation studies followed by subsequent binding free energy calculations, providing deeper insight into the time-dependent behavior of protein-ligand complexes in a dynamic state. In conclusion, our findings demonstrated that the identified compounds, particularly compounds 81 and 91, exhibit enhanced stability and favorable binding affinities with the target protein, marking them promising candidates for further investigations.Communicated by Ramaswamy H. Sarma.

19.
Food Sci Nutr ; 11(9): 5004-5027, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37701195

RESUMEN

Calcium is imperative in maintaining a quality life, particularly during later ages. Its deficiency results in a wide range of metabolic disorders such as dental changes, cataracts, alterations in brain function, and osteoporosis. These deficiencies are more pronounced in females due to increased calcium turnover throughout their life cycle, especially during pregnancy and lactation. Vitamin D perform a central role in the metabolism of calcium. Recent scientific interventions have linked calcium with an array of metabolic disorders in females including hypertension, obesity, premenstrual dysphoric disorder, polycystic ovary syndrome (PCOS), multiple sclerosis, and breast cancer. This review encompasses these female metabolic disorders with special reference to calcium and vitamin D deficiency. This review article aims to present and elaborate on available data regarding the worldwide occurrence of insufficient calcium consumption in females and allied health risks, to provide a basis for formulating strategies and population-level scientific studies to adequately boost calcium intake and position where required.

20.
Artículo en Inglés | MEDLINE | ID: mdl-37755639

RESUMEN

Increasing evidence has demonstrated that mesenchymal stem cells (MSCs) have been linked to tissue regeneration both in vitro and in vivo. However, poor engraftment and low survival rate of transplanted MSCs are still a major concern. It has been found that the proliferation, survival, and migration of MSCs are all increased by hypoxic preconditioning. However, the molecular mechanism through which hypoxic preconditioning enhances these beneficial properties of MSCs remains to be fully investigated. Therefore, the present study is aimed to investigate the mechanism by which hypoxic preconditioning enhances the survival of MSCs. We used proteomic analysis to explore the molecules that may contribute to the survival and proliferation of hypoxic preconditioned (HP) MSCs. The analysis revealed a higher expression of prelamin A/C (Lmna), glutamate dehydrogenase 1(Glud1), Actin, cytoplasmic 1(Actb), Alpha-enolase (Eno1), Glucose-6-phosphate 1-dehydrogenase (G6pd), Protein disulfide-isomerase A3 (Pdia3), Malate dehydrogenase (Mdh1), Peroxiredoxin-6 (Prdx6), Superoxide dismutase (Sod1), and Annexin A2 (Anxa2) in HP-MSCs. These proteins are possibly involved in cellular survival and proliferation through various cellular pathways. This research could aid in understanding the processes involved in hypoxic preconditioning of MSCs and designing of cell-based therapeutic strategies for tissue regeneration.

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