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1.
Biochim Biophys Acta Gen Subj ; 1868(4): 130577, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38301858

RESUMEN

F-box only protein 8 (FBXO8) is a recently identified member of the F-box proteins, showcasing its novelty in this protein family. Extensive research has established FBXO8's role as a tumor suppressor in various cancers, including hepatocellular carcinoma, and colorectal cancer, Nevertheless, its functional, mechanistic, and prognostic roles in primary and metastatic breast cancer, particularly in different molecular subtypes of breast cancer, various stages, as well as its potential implications in immunotherapy, tumor microenvironment, and prognostic survival among breast cancer patients, remain unexplored. In this article, we employed a multi-dimensional investigation leveraging TCGA, TIMER, TISIDB, STRING, MEXPRESS, UALCAN, and cBioPortal databases to explore the underlying suppression mechanism of FBXO8 in breast cancer. FBXO8 negatively correlates with MYC, NOTCH, WNT and inflammatory signaling pathways in breast tumor microenvironment. Furthermore we conducted RT-PCR, western blot, cell proliferation, cell migration, and mRNA target gene RT-PCR analyses to elucidate the role of FBXO8 in breast cancer progression. Mechanistically, PTEN and FBXW7 expression were down-regulated and MYC, IL10, IL6, NOTCH1, WNT6 mRNA expressions were up-regulated in FBXO8 knockdown cell lines. c-MYC silenced cells showed an increase in FBXO8 protein level, which suggests a negative feedback loop between FBXO8 and c-MYC to control breast cancer metastasis. These findings illuminate the novel role of FBXO8 as a prognostic and therapeutic target across different molecular subtypes of breast cancer. Finally, through the utilization of virtual screening and Molecular Dynamics simulations, we successfully identified two FDA-approved medications, Ledipasvir and Paritaprevir, that demonstrated robust binding capabilities and interactions with FBXO8.


Asunto(s)
Neoplasias de la Mama , Neoplasias Hepáticas , Femenino , Humanos , Biomarcadores , Neoplasias de la Mama/patología , Línea Celular Tumoral , Pronóstico , ARN Mensajero , Microambiente Tumoral
2.
Biomater Sci ; 11(24): 7748-7758, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37753880

RESUMEN

Genetically encoded collagen-like protein-based hydrogels have demonstrated remarkable efficacy in promoting the healing process in diabetic patients. However, the current methods for preparing these hydrogels pose significant challenges due to harsh reaction conditions and the reliance on chemical crosslinkers. In this study, we present a genetically encoded approach that allows for the creation of protein hydrogels without the need for chemical additives. Our design involves the genetic encoding of paired-cysteine residues at the C- and N-terminals of a meticulously engineered collagen-like recombination protein. The protein-based hydrogel undergoes a gel-sol transition in response to redox stimulation, achieving a gel-sol transition. We provide evidence that the co-incubation of the protein hydrogel with 3T3 cells not only enhances cell viability but also promotes cell migration. Moreover, the application of the protein hydrogel significantly accelerates the healing of diabetic wounds by upregulating the expression of collagen-1α (COL-1α) and Cytokeratin 14 (CK-14), while simultaneously reducing oxidant stress in the wound microenvironment. Our study highlights a straightforward strategy for the preparation of redox-responsive protein hydrogels, removing the need for additional chemical agents. Importantly, our findings underscore the potential of this hydrogel system for effectively treating diabetic wounds, offering a promising avenue for future therapeutic applications.


Asunto(s)
Diabetes Mellitus , Hidrogeles , Ratones , Animales , Humanos , Hidrogeles/farmacología , Cicatrización de Heridas , Colágeno/metabolismo , Diabetes Mellitus/tratamiento farmacológico , Oxidación-Reducción
4.
Saudi J Biol Sci ; 26(7): 1602-1606, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31762633

RESUMEN

Experimental based evidence suggests that most of the medicinal plants possess wide-ranging pharmacological and biological activities that may possibly use in treatment of inflammation-related diseases. The current study was aimed to explore the acute toxicity, analgesic, sedative and antipyretic activities of Monotheca buxifolia and Bosea amherstiana in mices. In vivo experimental models were used in this study. Acute toxicity was evaluated for 24 h' interval at concentration of 500, 1000, 1500 and 2000 mg/kg. The analgesic activity was estimated by acetic acid induced writhing test. White wood apparatus enclosed in stainless steel was used for sedative experiment and antipyretic activity was evaluated in brewer's yeast induced hyperthermic at 50, 100 and 150 mg/kg i.p. Both plants were found safe at all tested doses. Monotheca buxifolia and Bosea amherstiana dose-dependently reduced abdominal constrictions in mice. Both plants exhibited significant (P < 0.0001) sedative effects in dose of 50, 150 and 150 mg/kg. Both plants markedly (P < 0.0001) reduced yeast induced hyperthermia. The inhibitions were dose-dependent and remained significant up to five hours of administration. These investigational results have linked a pharmacological indication for the traditional claim of the drugs to be used as an anti-inflammatory, analgesics and antipyretic agents.

5.
Saudi J Biol Sci ; 26(7): 1815-1834, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31762664

RESUMEN

Infectious (or Communicable) diseases are not only the past but also the present problem in developing as well as developed countries. It is caused by various pathogenic microbes like fungi, bacteria, parasites and virus etc. The medicinal plants and nano-silver have been used against the pathogenic microbes. Herbal medicines are generally used for healthcare because they have low price and wealthy source of antimicrobial properties. Like medicinal plants, silver nanoparticles also have emergent applications in biomedical fields due to their immanent therapeutic performance. Here, we also explore the various plant parts such as bark, stem, leaf, fruit and seed against Gram negative and Gram-positive bacteria, using different solvents for extraction i.e. methanol, ethyl acetate, chloroform, acetone, n. hexane, butanol, petroleum ether and benzene. Since ancient to date most of the countries have been used herbal medicines, but in Asia, some medicinal plants are commonly used in rural and backward areas as a treatment for infectious diseases. In this review, we provide simple information about medicinal plants and Silver nanoparticles with their potentialities such as antiviral, bactericidal and fungicidal. Additionally, the present review to highlights the versatile applications of medicinal plants against honey bee pathogen such as fungi (Ascosphaera apis), mites (Varroa spp. and Tropilaelaps sp.), bacteria (Melissococcus plutonius Paenibacillus larvae), and microsporidia (Nosema apis and Nosema ceranae). In conclusion, promising nonchemical (plant extracts) are innocuous to adult bees. So, we strongly believed that this effort was made to evaluate the status of medicinal plants researches globally.

6.
Sci Rep ; 8(1): 11028, 2018 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-30038240

RESUMEN

Atropa acuminata Royle Ex Lindl (Atropa acuminata) under tremendous threat of extinction in its natural habitat. However, the antimicrobial, antileishmanial and anticancer effects of the plant's extracts have not been reported yet. In the current study, an attempt has been made to evaluate the pharmacological potential of this plant's extracts against microbes, Leishmania and cancer. The roots, stems and leaves of Atropa acuminata were ground; then, seven different solvents were used alone and in different ratios to prepare crude extracts, which were screened for pharmacological effects. The aqueous, methanolic and ethanolic extracts of all parts carried a broad spectrum of anti-bacterial activities, while no significant activity was observed with combined solvents. Three types of cytotoxicity assays were performed, i.e., haemolytic, brine shrimp and protein kinase assays. The aqueous extract of all the parts showed significant haemolytic activity while n-hexane extracts of roots showed significant activity against brine shrimp. The acetone extracts strongly inhibited protein kinase while the methanolic extracts exhibited significant cytotoxic activity of roots and stem. The anti-leishmanial assays revealed that the methanolic extract of leaves and roots showed significant activity. These findings suggest that this plant could be a potential source of natural product based drugs.


Asunto(s)
Antibacterianos/química , Atropa/química , Plantas Medicinales/química , Animales , Antibacterianos/farmacología , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Artemia/efectos de los fármacos , Especies en Peligro de Extinción , Etanol/química , Leishmania/efectos de los fármacos , Metanol/química , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/química , Hojas de la Planta/química , Raíces de Plantas/química , Solventes/química
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