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1.
Int J Mol Sci ; 24(7)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37047394

RESUMO

MicroRNAs (miRNAs) are a family of small, single-stranded, and non-protein coding RNAs about 19 to 22 nucleotides in length, that have been reported to have important roles in the control of bone development. MiRNAs have a strong influence on osteoblast differentiation through stages of lineage commitment and maturation, as well as via controlling the activities of osteogenic signal transduction pathways. Generally, miRNAs may modulate cell stemness, proliferation, differentiation, and apoptosis by binding the 3'-untranslated regions (3'-UTRs) of the target genes, which then can subsequently undergo messenger RNA (mRNA) degradation or protein translational repression. MiRNAs manage the gene expression in osteogenic differentiation by regulating multiple signalling cascades and essential transcription factors, including the transforming growth factor-beta (TGF-ß)/bone morphogenic protein (BMP), Wingless/Int-1(Wnt)/ß-catenin, Notch, and Hedgehog signalling pathways; the Runt-related transcription factor 2 (RUNX2); and osterix (Osx). This shows that miRNAs are essential in regulating diverse osteoblast cell functions. TGF-ßs and BMPs transduce signals and exert diverse functions in osteoblastogenesis, skeletal development and bone formation, bone homeostasis, and diseases. Herein, we highlighted the current state of in vitro and in vivo research describing miRNA regulation on the canonical TGF-ß/BMP signalling, their effects on osteoblast linage, and understand their mechanism of action for the development of possible therapeutics. In this review, particular attention and comprehensive database searches are focused on related works published between the years 2000 to 2022, using the resources from PubMed, Google Scholar, Scopus, and Web of Science.


Assuntos
MicroRNAs , Fator de Crescimento Transformador beta , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteogênese/genética , Proteínas Hedgehog/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Diferenciação Celular/genética , Transdução de Sinais , Osteoblastos/metabolismo
2.
BMC Complement Altern Med ; 19(1): 340, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783838

RESUMO

BACKGROUND: Clinacanthus nutans Lindau (C. nutans) is a species of in Acanthaceae family and primarily used in South East Asian countries. C. nutans is well known as Sabah snake grass in Malaysia, and its leaves have diverse medicinal potential in conventional applications, including cancer treatments. On the basis of literature search, there is less conclusive evidence of the involvement of phytochemical constituents in breast cancer, in particular, animal tumor models. The current study aimed to determine the antitumor and antioxidant activities of C. nutans extract in 4 T1 tumor-bearing mice. METHODS: C. nutans leaves were subjected to methanol extraction and divided into two different concentrations, 200 mg/kg (low-dose) and 1000 mg/kg (high-dose). The antitumor effects of C. nutans extracts were assessed using bone marrow smearing, clonogenic, and splenocyte immunotype analyses. In addition, hematoxylin and eosin, tumor weight and tumor volume profiles also used to indicate apoptosis appearance. Serum cytokine levels were examined using ELISA assay. In addition, nitric oxide assay reflecting antioxidant activity was performed. RESULTS: From the results obtained, the methanol extract of C. nutans leaves at 200 mg/kg (P < 0.05) and 1000 mg/kg (P < 0.05) showed a significant decrease in nitric oxide (NO) and malondialdehyde (MDA) levels in the blood. On the other hand, C. nutans extract (1000 mg/kg) also showed a significant decrease in the number of mitotic cells, tumor weight, and tumor volume. No inflammatory and adverse reactions related to splenocytes activities were found in all treated groups of mice. Despite its promising results, the concentration of both C. nutans extracts have also reduced the number of colonies formed in the liver and lungs. CONCLUSION: In conclusion, C. nutans extracts exert antitumor and antioxidant activities against 4 T1 mouse breast model with no adverse effect and inflammatory response at high dose of 1000 mg/kg, indicating an effective and complementary approach for cancer prevention and treatment.


Assuntos
Acanthaceae , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Animais , Linhagem Celular Tumoral , Feminino , Inflamação , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C
3.
BMC Cancer ; 16: 461, 2016 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-27411985

RESUMO

BACKGROUND: Cancer therapies that kill cancer cells without affecting normal cells is the ultimate mode of treating cancers. The VP3, an avian virus-derived protein, can specifically initiate cell death through several signal transduction pathways leading to apoptosis. In cancer, chemoresistance and cell survivability implicate the cell surface protein, CD147. METHODS: In this study, transfection of VP3 and silencing of CD147 genes was achieved through the treatment of tumors with pVIVO1-GFP/VP3 (VP3), psiRNA-CD147/2 (shCD147/2), and their combination of CT26 colon cancer cell-induced in mice. The effectiveness of tumor-treatment was ascertained by electrophoresis, TUNEL assay, and flow cytometry analysis. While histopathological and biochemical analysis were used as toxic side effect identification. RESULTS: The tumor growth delay index (TGDI) after treatment with VP3, shCD147/2, and their combination treatments increased by 1.3-, 1.2-, 2.0- and 2.3-fold respectively, over untreated control. The VP3-shCD147/2 combination treatment was more efficacious then either VP3 or shCD147/2 alone in the retardation of mouse CT26 colorectal cell tumor allograft. CONCLUSION: The antitumor effect of the combination treatment is the result of synergistic effects of VP3 and shCD147/2 on the tumor cells resulting in apoptosis. Thus, the study shows that combination of VP3 and shCD147/2 treatment can be developed into a potential approach for anticolorectal cancer treatment regimen.


Assuntos
Apoptose/genética , Basigina/genética , Proteínas do Capsídeo/genética , Neoplasias Colorretais/terapia , Terapia Genética , Aloenxertos/transplante , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Terapia Combinada , Feminino , Citometria de Fluxo , Terapia Genética/efeitos adversos , Humanos , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais , Interferência de RNA , RNA Interferente Pequeno/genética , Transfecção
4.
BMC Complement Altern Med ; 16(1): 311, 2016 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-27558166

RESUMO

BACKGROUND: Annona muricata Linn which comes from Annonaceae family possesses many therapeutic benefits as reported in previous studies and to no surprise, it has been used in many cultures to treat various ailments including headaches, insomnia, and rheumatism to even treating cancer. However, Annona muricata Linn obtained from different cultivation area does not necessarily offer the same therapeutic effects towards breast cancer (in regards to its bioactive compound production). In this study, anti-proliferative and anti-cancer effects of Annona muricata crude extract (AMCE) on breast cancer cell lines were evaluated. METHODS: A screening of nineteen samples of Annona muricata from different location was determined by MTT assay on breast cancer cell lines (MCF-7, MDA-MB-231, and 4 T1) which revealed a varied potency (IC50) amongst them. Then, based on the IC50 profile from the anti-proliferative assay, further downward assays such as cell cycle analysis, Annexin V/FITC, AO/PI, migration, invasion, and wound healing assay were performed only with the most potent leaf aqueous extract (B1 AMCE) on 4 T1 breast cancer cell line to investigate its anti-cancer effect. Then, the in vivo anti-cancer study was conducted where mice were fed with extract after inducing the tumor. At the end of the experiment, histopathology of tumor section, tumor nitric oxide level, tumor malondialdehyde level, clonogenic assay, T cell immunophenotyping, and proteome profiler analysis were performed. RESULTS: Annona muricata crude extract samples exhibited different level of cytotoxicity toward breast cancer cell lines. The selected B1 AMCE reduced the tumor's size and weight, showed anti-metastatic features, and induced apoptosis in vitro and in vivo of the 4 T1 cells. Furthermore, it decreased the level of nitric oxide and malondialdehyde in tumor while also increased the level of white blood cell, T-cell, and natural killer cell population. CONCLUSION: The results suggest that, B1 AMCE is a promising candidate for cancer treatment especially in breast cancer and deserves further research as an alternative to conventional drugs while also stressed out the selection of soursop sample which plays a significant role in determining its potential therapeutic effect on cancer.


Assuntos
Annona/química , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Camundongos , Óxido Nítrico/metabolismo , Extratos Vegetais/química
5.
Front Pharmacol ; 15: 1387866, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39104398

RESUMO

Cancer refers to the proliferation and multiplication of aberrant cells inside the human body, characterized by their capacity to proliferate and infiltrate various anatomical regions. Numerous biochemical pathways and signaling molecules have an impact on the cancer auto biogenesis process. The regulation of crucial cellular processes necessary for cell survival and proliferation, which are triggered by phytochemicals, is significantly influenced by signaling pathways. These pathways or components are regulated by phytochemicals. Medicinal plants are a significant reservoir of diverse anticancer medications employed in chemotherapy. The anticancer effects of phytochemicals are mediated by several methods, including induction of apoptosis, cessation of the cell cycle, inhibition of kinases, and prevention of carcinogenic substances. This paper analyzes the phytochemistry of seven prominent plant constituents, namely, alkaloids, tannins, flavonoids, phenols, steroids, terpenoids, and saponins, focusing on the involvement of the MAPK/ERK pathway, TNF signaling, death receptors, p53, p38, and actin dynamics. Hence, this review has examined a range of phytochemicals, encompassing their structural characteristics and potential anticancer mechanisms. It has underscored the significance of plant-derived bioactive compounds in the prevention of cancer, utilizing diverse molecular pathways. In addition, this endeavor also seeks to incentivize scientists to carry out clinical trials on anticancer medications derived from plants.

6.
Aerosp Med Hum Perform ; 94(6): 485-487, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37194178

RESUMO

INTRODUCTION: An episode of prolonged exposure to high altitude can cause hypoxia and have significant health consequences. In people with a high-altitude disorder, the body reacts by producing a protein called hypoxia-inducible factor (HIF), which triggers a series of physiological changes and serves a central role in the hypoxia response. Its activity is regulated by the oxygen-dependent degradation of the HIF-1α protein (HIF-1A gene). Therefore, the effects of low oxygen tension in high altitude were explored using fluorescent sensors of hypoxia.METHODS: The development of the sensor provided more sensitivity for detecting hypoxia by generating a calibration of optimized parameters such as reagent concentrations, reagent volumes, and device dimensions.RESULTS: There is a high sensitivity and specificity in detecting the changes of HIF-1α protein hypoxia using the feasibility hypoxia test. This would enable point-of-care (POC) testing and individual self-administration, resulting in faster and more accurate results that can be used for a robust diagnostic approach and enhanced health surveillance, particularly in high-altitude exposure.Shaharuddin S, Rahman NMANA, Masarudin MJ, Alamassi MN, Saad FFA. HIF-1 sensor in detecting hypoxia tolerance at high altitude. Aerosp Med Hum Perform. 2023; 94(6):485-487.


Assuntos
Altitude , Fator 1 Induzível por Hipóxia , Humanos , Hipóxia/diagnóstico , Hipóxia/metabolismo , Oxigênio
7.
Cells ; 11(22)2022 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-36428985

RESUMO

Tumour heterogeneity refers to the complexity of cell subpopulations coexisting within the tumour microenvironment (TME), such as proliferating tumour cells, tumour stromal cells and infiltrating immune cells. The bidirectional interactions between cancer and the surrounding microenvironment mark the tumour survival and promotion functions, which allow the cancer cells to become invasive and initiate the metastatic cascade. Importantly, these interactions have been closely associated with metabolic reprogramming, which can modulate the differentiation and functions of immune cells and thus initiate the antitumour response. The purpose of this report is to review the CD36 receptor, a prominent cell receptor in metabolic activity specifically in fatty acid (FA) uptake, for the metabolic symbiosis of cancer-macrophage. In this review, we provide an update on metabolic communication between tumour cells and macrophages, as well as how the immunometabolism indirectly orchestrates the tumour metastasis.


Assuntos
Ácidos Graxos , Neoplasias , Humanos , Ácidos Graxos/metabolismo , Neoplasias/metabolismo , Microambiente Tumoral , Antígenos CD36/metabolismo , Macrófagos/metabolismo
8.
Artigo em Inglês | MEDLINE | ID: mdl-32831872

RESUMO

The present study aimed to evaluate the potential of standardized methanolic extracts from seven Ficus deltoidea varieties in inhibiting the formation of AGEs, protein oxidation, and their antioxidant effects. The antiglycation activity was analyzed based on the inhibition of AGEs, fructosamine, and thiol groups level followed by the inhibition of protein carbonyl formation. The antioxidant activity (DPPH radical scavenging activity and reducing power assay) and total phenolic contents were evaluated. After 28 days of induction, all varieties of Ficus deltoidea extracts significantly restrained the formation of fluorescence AGEs by 4.55-5.14 fold. The extracts also reduced the fructosamine levels by 47.0-86.5%, increased the thiol group levels by 64.3-83.7%, and inhibited the formation of protein carbonyl by 1.36-1.76 fold. DPPH radical scavenging activity showed an IC50 value of 66.81-288.04 µg/ml and reducing power activity depicted at 0.02-0.24 µg/ml. The extent of phenolic compounds present in the extracts ranged from 70.90 to 299.78 mg·GAE/g. Apart from that, correlation studies between the activities were observed. This study revealed that seven varieties of Ficus deltoidea have the potential to inhibit AGEs formation and possess antioxidant activity that might be attributed to the presence of phenolic compounds.

9.
Materials (Basel) ; 12(19)2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31590332

RESUMO

The aim was to isolate cellulose nanocrystals (CNC) from commercialized oil palm empty fruit bunch cellulose nanofibre (CNF) through sulphuric acid hydrolysis and explore its safeness as a potential nanocarrier. Successful extraction of CNC was confirmed through a field emission scanning electron microscope (FESEM) and attenuated total reflection Fourier transmission infrared (ATR-FTIR) spectrometry analysis. For subsequent cellular uptake study, the spherical CNC was covalently tagged with fluorescein isothiocyanate (FITC), resulting in negative charged FITC-CNC nanospheres with a dispersity (Ð) of 0.371. MTT assay revealed low degree cytotoxicity for both CNC and FITC-CNC against C6 rat glioma and NIH3T3 normal fibroblasts up to 50 µg/mL. FITC conjugation had no contribution to the particle's toxicity. Through confocal laser scanning microscope (CLSM), synthesized FITC-CNC manifested negligible cellular accumulation, indicating a poor non-selective adsorptive endocytosis into studied cells. Overall, an untargeted CNC-based nanosphere with less cytotoxicity that posed poor selectivity against normal and cancerous cells was successfully synthesized. It can be considered safe and suitable to be developed into targeted nanocarrier.

10.
PLoS One ; 13(6): e0199742, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29944726

RESUMO

In order to clarify the in vitro cytotoxicity effect of superheated steam (SHS) treated poly((R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate) (PHBHHx) for biomaterial applications, SHS-treated PHBHHx oligoester samples: P(HB-co-6%-HHx) and P(HB-co-11%-HHx) with low and high percentages of unsaturated chain ends were evaluated for their cytotoxicity effects toward the growth of mouse fibroblast cell line NIH 3T3. From the results obtained after 24 and 48 h of the growth test, the SHS-treated PHBHHx oligoesters were found to be nontoxic to the growth of mouse fibroblast NIH 3T3 cell line with cell viability percentages of more than 95%. In order to serve as a potential resorbable medical suture, PHBHHx oligoesters were blended with poly(L-lactic acid) (PLLA) with a weight ratio of PHBHHx oligoester/PLLA = 20:80 (wt/wt) to improve mechanical properties of PHBHHx oligoesters. The PHBHHx oligoesters/PLLA blend films were evaluated for their thermal, mechanical, and surface wetting properties. Thermal properties of the blend films suggested a good compatibility between PHBHHx oligoesters and PLLA components. Mechanical properties of the blend films were determined to be close enough to a desirable strength range of medical sutures. Moreover, contact angle range of 65 < θ < 70° for the blend samples could provide desirable cell adhesion when used as biomaterials. Therefore, the blend of SHS-treated PHBHHx oligoesters and PLLA would be an ideal choice to be used as biomedical materials.


Assuntos
Ácido 3-Hidroxibutírico , Caproatos , Teste de Materiais , Membranas Artificiais , Poliésteres , Ácido 3-Hidroxibutírico/farmacologia , Animais , Caproatos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Células NIH 3T3 , Poliésteres/química , Poliésteres/farmacologia
11.
Integr Cancer Ther ; 16(4): 540-555, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-27338742

RESUMO

Although it may sound unpleasant, camel urine has been consumed extensively for years in the Middle East as it is believed to be able to treat a wide range of diseases such as fever, cold, or even cancer. People usually take it by mixing small drops with camel milk or take it directly. The project aims to study the effects of camel urine in inhibiting the growth potential and metastatic ability of 4T1 cancer cell line in vitro and in vivo. Based on the MTT result, the cytotoxicity of camel urine against 4T1 cell was established, and it was dose-dependent. Additionally, the antimetastatic potential of camel urine was tested by running several assays such as scratch assay, migration and invasion assay, and mouse aortic ring assay with promising results in the ability of camel urine to inhibit metastatic process of the 4T1 cells. In order to fully establish camel urine's potential, an in vivo study was carried out by treating mice inoculated with 4T1 cells with 2 different doses of camel urine. By the end of the treatment period, the tumor in both treated groups had reduced in size as compared to the control group. Additional assays such as the TUNEL assay, immunophenotyping, cytokine level detection assay, clonogenic assay, and proteome profiler demonstrated the capability of camel urine to reduce and inhibit the metastatic potential of 4T1 cells in vivo. To sum up, further study of anticancer properties of camel urine is justified, as evidenced through the in vitro and in vivo studies carried out. Better results were obtained at higher concentration of camel urine used in vivo. Apart from that, this project has laid out the mechanisms employed by the substance to inhibit the growth and the metastatic process of the 4T1 cell.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Camelus/urina , Proliferação de Células/efeitos dos fármacos , Metástase Neoplásica/tratamento farmacológico , Urina/química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Feminino , Camundongos , Camundongos Endogâmicos BALB C
12.
Chin Med ; 10: 3, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25699088

RESUMO

BACKGROUND: Pineapple (Ananas comosus) was demonstrated to be hepatoprotective. This study aims to investigate the reversing effects of pineapple vinegar on paracetamol-induced liver damage in murine model. METHODS: Pineapple juice was fermented via anaerobic and aerobic fermentation to produce pineapple vinegar. Male BALB/c mice (n = 70) were separated into 7 treatment groups (n = 10). Pineapple vinegar (0.08 and 2 mL/kg BW) and synthetic vinegar were used to treat paracetamol-induced liver damage in mice. The hepatoprotective effects were determined by serum biochemistry profiles (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and triglyceride (TG)), liver antioxidant levels (ferric-reducing ability plasma (FRAP), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione assays (GSH)) and histopathological examination with hematoxylin and eosin (H&E) staining. The effects were further evaluated by the expression levels of iNOS, NF-κB, and cytochrome P450 2E1 by quantitative real-time PCR and Western blot analyses. Vinegar samples were also tested for in vitro antioxidant (FRAP, 2,2-diphenyl-2-picrylhydrazyl (DPPH), and total phenolic content (TPC)). Soluble phenolic acid contents in the samples were identified by HPLC. RESULTS: Pineapple vinegar contained 169.67 ± 0.05 µg GAE/mL of TPC, with 862.61 ± 4.38 µg/mL gallic acid as the main component. Oral administration of pineapple vinegar at 2 mL/kg BW reduced serum enzyme biomarker levels, including AST (P = 0.008), ALT (P = 0.006), ALP (P = 0.002), and TG (P = 0.006) after 7 days of paracetamol treatment. Liver antioxidant levels such as hepatic glutathione (P = 0.003), SOD (P < 0.001), lipid peroxidation (P = 0.002) and FRAP (P <0.001) were restored after the treatment. Pineapple vinegar reduced the expressions of iNOS (P = 0.003) and NF-kB (P = 0.003) and the level of NO (P = 0.003) significantly. Pineapple vinegar also downregulated liver cytochrome P450 protein expression. CONCLUSIONS: Oral administration of pineapple vinegar at 0.08 and 2 mL/kg BW reduced serum enzyme biomarker levels, restored liver antioxidant levels, reduced inflammatory factor expressions, and down regulated liver cytochrome P450 protein expression in paracetamol-induced liver damage in mice.

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