RESUMO
The fusion oncoprotein RUNX1/ETO which results from the chromosomal translocation t (8;21) in acute myeloid leukemia (AML) is an essential driver of leukemic maintenance. We have previously shown that RUNX1/ETO knockdown impairs expression of the protein component of telomerase, TERT. However, the underlying molecular mechanism of how RUNX1/ETO controls TERT expression has not been fully elucidated. Here we show that RUNX1/ETO binds to an intergenic region 18 kb upstream of the TERT transcriptional start site and to a site located in intron 6 of TERT. Loss of RUNX1/ETO binding precedes inhibition of TERT expression. Repression of TERT expression is also dependent on the destabilization of the E3 ubiquitin ligase SKP2 and the resultant accumulation of the cell cycle inhibitor CDKN1B, that are both associated with RUNX1/ETO knockdown. Increased CDKN1B protein levels ultimately diminished TERT transcription with E2F1/Rb involvement. Collectively, our results show that RUNX1/ETO controls TERT expression directly by binding to its locus and indirectly via a SKP2-CDKN1B-E2F1/Rb axis.
Assuntos
Leucemia Mieloide Aguda , Telomerase , Humanos , Linhagem Celular Tumoral , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Leucemia Mieloide Aguda/genética , Proteínas de Fusão Oncogênica/genética , Telomerase/metabolismo , Translocação GenéticaRESUMO
Mesoporous silica nanoparticles (MSNs) have great potential for applications as a drug delivery system (DDS) due to their unique properties such as large pore size, high surface area, biocompatibility, biodegradability, and stable aqueous dispersion. The MSN-mediated DDS can carry chemotherapeutic agents, optical sensors, photothermal agents, short interfering RNA (siRNA), and gene therapeutic agents. The MSN-assisted imaging techniques are applicable in cancer diagnosis. However, their synthesis via a chemical route requires toxic chemicals and is challenging, time-consuming, and energy-intensive, making the process expensive and non-viable. Fortunately, nature has provided a viable alternative material in the form of biosilica from marine resources. In this review, the applications of biosilica nanoparticles synthesized from marine diatoms in the field of drug delivery, biosensing, imaging agents, and regenerative medicine, are highlighted. Insights into the use of biosilica in the field of DDSs are elaborated, with a focus on different strategies to improve the physico-chemical properties with regards to drug loading and release efficiency, targeted delivery, and site-specific binding capacity by surface functionalization. The limitations, as well as the future scope to develop them as potential drug delivery vehicles and imaging agents, in the overall therapeutic management, are discussed.
Assuntos
Diatomáceas , Nanopartículas , Diatomáceas/metabolismo , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Técnicas de Transferência de Genes , Nanopartículas/química , Preparações Farmacêuticas/metabolismo , Porosidade , Dióxido de Silício/químicaRESUMO
Rice serves as a staple food for one-half of the global population. However, rice production, particularly the rice milling process, results in a substantial amount of paddy waste products (e.g. bran, husk and straw) annually. Because the potentials of bran have been extensively explored in prior studies, the present review focuses exclusively on the phytochemical analysis and pharmacological potentials of husk and straw. This comprehensive review establishes a solid foundation for promoting husk and straw as medicinal substances given their promising pharmacological potentials as bioactive compound sources with therapeutic functions. © 2020 Society of Chemical Industry.
Assuntos
Oryza/química , Compostos Fitoquímicos/química , Resíduos/análise , Fibras na Dieta/análiseRESUMO
Africa is faced with an increasing underrepresentation of her research progress in many fields of science including neuroscience. This underrepresentation stems from the very low investments directed towards research by African governments as these are thought to be high-priced. Scientists and researchers within the continent are left to compete highly for the very limited research grants or choose to fund research from their personal purse. Therefore, presenting a need for all possible strategies to make science and research approaches more affordable in Africa. This paper presents one of such strategy, which advocates the use of invertebrate animal models for neuroscience research in place of the commonly used vertebrate models. Invertebrates are cheaper, more available and easy to handle options and their use is on the rise, even in the developed societies of the world. Here, we investigate the current state of invertebrate neuroscience research in Africa looking at countries and institutions conducting neuroscience research with invertebrates and their publication output. We discuss the factors which impede invertebrate neuroscience research in Africa like lack of research infrastructure and adequate expert scientists and conclude by suggesting solutions to these challenges.
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Invertebrados , Neurociências/educação , Pesquisa , África , Animais , Modelos AnimaisRESUMO
BACKGROUND: With the limited strategies for curative treatment of castration-resistant prostate cancer (CRPC), public interest has focused on the potential prevention of prostate cancer. Recent studies have demonstrated that an angiotensin II receptor blocker (ARB) has the potential to decrease serum prostate-specific antigen (PSA) level and improve performance status in CRPC patients. These facts prompted us to investigate the direct effects of ARBs on prostate cancer growth and progression. METHODS: Transgenic rat for adenocarcinoma of prostate (TRAP) model established in our laboratory was used. TRAP rats of 3 weeks of age received ARB (telmisartan or candesartan) at the concentration of 2 or 10 mg/kg/day in drinking water for 12 weeks. In vitro analyses for cell growth, ubiquitylation or reporter gene assay were performed using LNCaP cells. RESULTS: We found that both telmisartan and candesartan attenuated prostate carcinogenesis in TRAP rats by augmentation of apoptosis resulting from activation of caspases, inactivation of p38 MAPK and down-regulation of the androgen receptor (AR). Further, microarray analysis demonstrated up-regulation of estrogen receptor ß (ERß) by ARB treatment. In both parental and androgen-independent LNCaP cells, ARB inhibited both cell growth and AR-mediated transcriptional activity. ARB also exerted a mild additional effect on AR-mediated transcriptional activation by the ERß up-regulation. An intervention study revealed that PSA progression was prolonged in prostate cancer patients given an ARB compared with placebo control. CONCLUSION: These data provide a new concept that ARBs are promising potential chemopreventive and chemotherapeutic agents for prostate cancer.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Benzimidazóis/farmacologia , Benzoatos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Tetrazóis/farmacologia , Animais , Apoptose/efeitos dos fármacos , Compostos de Bifenilo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Terapia de Alvo Molecular , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , TelmisartanRESUMO
Epidemiological data on the relationship between hypertension and prostate cancer development are conflicting. To cast light on this question, we performed animal experiments using hybrid rats generated by crossing the spontaneously hypertensive rat (SHR) or its normotensive control Wistar Kyoto (WKY) rat with a transgenic rat for adenocarcinoma of prostate (TRAP) that features development of adenocarcinoma at high incidence by 15 weeks of age. The number of adenocarcinomatous foci in the lateral prostate of hypertensive (TRAP × SHR)F1 rats was demonstrated to be significantly increased compared with those of normotensive (TRAP × WKY)F1 rats. In the ventral prostate, increase of carcinoma foci was also observed but did not reach significance. The number of cancer foci showing microinvasion in (TRAP × SHR)F1 rats was higher than that of (TRAP × WKY)F1 rats, but again without significance, while treatment with prazosin, an anti-hypertensive agent, tended to decrease microinvasive carcinoma foci in both the ventral and lateral prostate. In conclusion, the present study provided additional evidence that high blood pressure is associated with prostate cancer risk.
Assuntos
Adenocarcinoma/complicações , Hipertensão/complicações , Neoplasias da Próstata/complicações , Animais , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Transgênicos , Ratos WistarRESUMO
An innovative nano-base polymer that scavenges radicals and reactive oxygen species exhibits potential antibacterial properties, which are crucial in the biomedical field, particularly in reducing nosocomial infections. However, the safety of this nano-based polymer, which has direct contact with the human system, has not been fully understood. The present study investigated the cytocompatibility and hemocompatibility responses of linear low-density polyethylene polymer (LLDPE) embedded with difference ratios of heterogeneous TiO2/ZnO nanocomposites. Exposure of the blood and fibroblast cells to LLDPE/100Z and LLDPE/25T75Z/10% nanocomposite films for 48 and 72 h decreased their viability by less than 40%, compared with LLDPE, LLDPE/100T and LLDPE/25T75Z/5% nanocomposite films. It also presented possible cellular damage and cytotoxicity, which was supported by the findings from the significant release of extracellular lactate dehydrogenase profiles and cell survival assay Further observation using an electron microscope revealed that LLDPE films with heterogeneous 25T75Z/5% promoted cell adhesion. Moreover, no hemolysis was detected in all ratios of heterogeneous TiO2/ZnO nanocomposite in LLDPE film as it was less than 0.2%, suggesting that these materials were hemocompatible. This study on LLDPE film with heterogeneous TiO2/ZnO nanocomposites demonstrated favorable biocompatible properties that were significant for advanced biomedical polymer application in a hospital setting.
Assuntos
Nanocompostos , Polietileno , Óxido de Zinco , Antibacterianos , Humanos , Polímeros , TitânioRESUMO
A sustainable super-hydrophobic coating composed of silica from palm oil fuel ash (POFA) and polydimethylsiloxane (PDMS) was synthesised using isopropanol as a solvent and coated on a glass substrate. FESEM and AFM analyses were conducted to study the surface morphology of the coating. The super-hydrophobicity of the material was validated through goniometry, which showed a water contact angle of 151°. Cytotoxicity studies were conducted by assessing the cell viability and cell morphology of mouse fibroblast cell line (L929) and hamster lung fibroblast cell line (V79) via tetrazolium salt 3-(4-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and microscopic methods, respectively. The clonogenic assay was performed on cell line V79 and the cell proliferation assay was performed on cell line L929. Both results validate that the toxicity of PDMS: SS coatings is dependent on the concentration of the super-hydrophobic coating. The results also indicate that concentrations above 12.5 mg/mL invariably leads to cell toxicity. These results conclusively support the possible utilisation of the synthesised super-hydrophobic coating for biomedical applications.
RESUMO
The emerging polymer nanocomposites have received industrial interests in diverse fields because of their added value in metal oxide-based nanocomposites, such as titanium (TiO2) and zinc oxide (ZnO). Linear low-density polyethylene (LLDPE)-based polymer has recently generated a huge market in the healthcare industry. TiO2 and ZnO are well known for their instant photocatalytic killing of hospital-acquired infections, especially multidrug-resistant (MDR) pathogens. This study investigated the actions of LLDPE/TiO2/ZnO (1:3) nanocomposites in different weight% against two representative MDR pathogens, namely, methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella pneumonia (K.pneumoniae). Antibacterial activities were quantified according to international standard guidelines of CLSI MO2-A11 (static condition) and ASTM E-2149 (dynamic condition). Preliminary observation via a scanning electron microscope revealed that LLDPE matrix with TiO2/ZnO nanocomposites changed the bacterial morphology and reduced the bacterial adherence and biofilm formation. Furthermore, a high ZnO weight ratio killed both types of pathogens. The bactericidal potential of the nanocomposite is highlighted by the enhancements in photocatalytic activity, zinc ion release and reactive species, and bacteriostatic/bactericidal activity against bacterial growth. This study provides new insights into the MDR-bactericidal potential of LLDPE with TiO2/ZnO nanocomposites for targeted healthcare applications.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Nanocompostos , Óxido de Zinco , Antibacterianos/farmacologia , Hospitais , Polietileno , TitânioRESUMO
The surge of medical devices associated with nosocomial infection (NI) cases, especially by multidrug-resistant (MDR) bacterial strains, is one of the pressing issues of present health care systems. Metal oxide nanoparticles (MNPs) have become promising antibacterial agents against a wide range of bacterial strains. This work study is on the bactericidal capacity of heterogeneous TiO2/ZnO nanocomposites with different weight percentages and concentrations against common MDR and non-MDR bacterial strains. The profiles on disk diffusion, minimum inhibitory concentration, minimum bactericidal concentration, tolerance determination, time-kill, and biofilm inhibition assay were determined after 24 h of direct contact with the nanocomposite samples. Findings from this work revealed that the heterogeneous TiO2/ZnO nanocomposite with a 25T75Z weight ratio showed an optimal tolerance ratio against Gram-positive and -negative bacteria, indicating their bactericidal capacity. Further observation suggests that higher molar ratio of Zn2+ may possibly involve generation of active ion species that enhance bactericidal effect against Gram-positive bacterial strains, especially for the MDR strains. Nano-based technology using MNPs may provide a promising solution for the prevention and control of NIs. Further work on biocompatibility and cytotoxicity profiles of this nanocomposite are needed.
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ETHNOPHARMACOLOGICAL RELEVANCE: Porcupine bezoar (PB) is used as folk medicine for various medical conditions including cancer treatment in Malaysia. However, its toxicity profile has never been thoroughly ascertained to confirm its safe nature as an efficacious traditional medicine in the treatment of cancer as well as other ailments. AIM OF THE STUDY: This study was aimed to reveal three different PBs' aqueous extracts(viz. PB-A, PB-B, PB-C) chemical constituent's profile using GC-MS analysis, anticancer property on A375, HeLa and MCF7 cancer cells, toxicity profile on zebrafish embryo morphology, EC50, LC50 and teratogenicity index. MATERIALS AND METHODS: PBs' extracts characterization was performed through GC-MS analysis, in vitro anticancer effect was carried out on A375, HeLa and MCF7 cancer cell lines and finally and toxicity properties on three different PBs aqueous extracts (viz. PB-A, PB-B, PB-C) were determined using zebrafish embryo model. RESULTS: The GC-MS analysis revealed 10 similar compounds in all PBs' extracts. Dilauryl thiodipropionate was found to be a major compound in all PBs' extracts followed by tetradecanoic acid. An in vitro anticancer study revealed PB extracts exerted median inhibition concentration (IC50) <50 µg/mL, on cancer cells viz. A375, HeLa and MCF7 with no significant toxicity on normal cells viz. NHDF cells. In vivo toxicity of PBs extracts found affecting tail detachment, hatching, craniofacial, brain morphology, soft tissues, edema, spinal, somites, notochord and cardiovascular system (brachycardia, disruption of blood circulation) deformities. The LC50 and EC50 demonstrated PB extracts effect as dose and time dependent with median concentration <150.0 µg/mL. Additionally, teratogenicity index (TI) viz. >1.0 revealed teratogenic property for PB extracts. CONCLUSIONS: The findings revealed that all three PBs aqueous extracts possessed anticancer activity and exhibited significant toxicological effects on zebrafish embryos with high teratogenicity index. Hence, its use as an anticancer agent requires further investigation and medical attentions to determine its safe dose.
Assuntos
Antineoplásicos/toxicidade , Bezoares , Fatores Biológicos/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Porcos-Espinhos , Animais , Antineoplásicos/análise , Antineoplásicos/isolamento & purificação , Fatores Biológicos/análise , Fatores Biológicos/isolamento & purificação , Braquiúros , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Desenvolvimento Embrionário/fisiologia , Feminino , Células HeLa , Humanos , Células MCF-7 , Masculino , Peixe-ZebraRESUMO
BACKGROUND: Epidemiological data indicate that intake of one form of vitamin E, gamma-tocopherol, may reduce prostate cancer risk, and several in vitro studies have demonstrated that gamma-tocopherol can inhibit prostate cancer cell growth. The purpose of the present study was to confirm effects of gamma-tocopherol on prostate cancer in the transgenic rat for adenocarcinoma of prostate (TRAP) model established in our laboratory. METHODS: In Experiment 1, heterozygous male TRAP rats 5 weeks of age received alpha-tocopherol at the concentration of 50 mg/kg in the diet, or gamma-tocopherol at 50 or 100 mg/kg for 10 weeks. In Experiment 2, TRAP rats of 3 weeks of age were given gamma-tocopherol at 50, 100, or 200 mg/kg diet for 7 weeks. RESULTS: gamma-Tocopherol did not affect body weight gain, organ weights or serum levels of either testosterone or estradiol. However, quantitative evaluation of prostatic lesions demonstrated significantly suppression of sequential progression from PIN to adenocarcinoma in a dose-dependent manner, along with clear activation of caspases 3 and 7 in the ventral lobe in both experiments. CONCLUSIONS: The present study clearly demonstrated that gamma-tocopherol suppresses prostate tumor progression in an in vivo TRAP model, and could be a candidate chemopreventive agent for human prostate cancer.
Assuntos
Adenocarcinoma/prevenção & controle , Neoplasias da Próstata/prevenção & controle , gama-Tocoferol/uso terapêutico , Fosfatase Ácida/genética , Adenocarcinoma/tratamento farmacológico , Animais , Animais Geneticamente Modificados , Antioxidantes/uso terapêutico , Ceramidas/metabolismo , Cromatografia Líquida de Alta Pressão , Humanos , Isoenzimas/genética , Masculino , Camundongos , Neoplasias da Próstata/tratamento farmacológico , Ratos , Fosfatase Ácida Resistente a Tartarato , Tocoferóis/sangueRESUMO
Zinc oxide eugenol (ZOE) cements are generally made up of 80%-90% ZnO powder while the remaining content consists of eugenol bonding resin. ZnO structure plays a major role in the morphology and mechanical properties of ZOE. In this study, we investigated the effects of different particle sizes/shapes of ZnO particles on the surface and mechanical properties of ZOE. Three samples were prepared namely ZnO-Ax, ZnO-B and ZnO-K. The crystallite sizes calculated from XRD were 37.76â¯nm (ZnO-Ax), 39.46â¯nm (ZnO-B) and 42.20â¯nm (ZnO-K) while the average particle sizes obtained by DLS were 21.11nm (ZnO-Ax), 56.73â¯nm (ZnO-B) and 2012â¯nm (ZnO-K). Results revealed that the compressive strengths of ZOE-Ax and ZOE-B were improved by 87.92% and 57.16%, respectively, relative to that of commercial ZOE-K. Vickers hardness test demonstrated that the hardness of ZOE-Ax and ZOE-B also increased by 74.9% and 31.1%, respectively. The ZnO-Ax nanostructure possessed a small average particle size (21.11â¯nm), a homogeneous size distribution (DLS) and an oxygen-rich surface (from EDS and elemental mapping). Meanwhile, ZnO-B exhibited a slightly larger average particle size of 56.73â¯nm compared with that of other samples. Sample ZnO-Ax demonstrated the highest compressive strength which was attributed to its large particle surface area (21.11â¯nm particle size) that provided a large contact area and greater interfacial (or interlock) bonding capability if compared to that of ZnO-K sample (2012â¯nm particle size).
Assuntos
Eugenol/química , Nanopartículas/química , Óxido de Zinco/química , Força Compressiva , Microscopia de Força Atômica , Nanopartículas/ultraestrutura , Tamanho da Partícula , Pós , Propriedades de Superfície , Difração de Raios XRESUMO
Cancer is increasing in incidence and the leading cause of death worldwide. Controlling and reducing cancer requires early detection and technique to accurately detect and quantify predictive biomarkers. Optical spectroscopy has shown promising non-destructive ability to display distinctive spectral characteristics between cancerous and normal tissues from different part of human organ. Nonetheless, not many information is available on spectroscopic properties of cancer cell lines. In this research, the visible-near infrared (VIS-NIR) absorbance spectroscopy measurement of cultured cervical cancer (HeLa) and prostate cancer cells (DU145) lines has been performed to develop spectral signature of cancer cells and to generate algorithm to quantify cancer cells. Spectroscopic measurement on mouse skin fibroblast (L929) was also taken for comparative purposes. In visible region, the raw cells' spectra do not produce any noticeable peak absorbance that provides information on color because the medium used for cells is colorless and transparent. NIR wavelength between 950 and 975â¯nm exhibit significant peak due to water absorbance by the medium. Development of spectral signature for the cells through the application of regression technique significantly enhances the diverse characteristics between L929, HeLa and DU145. The application of multiple linear regression allows high measurement accuracy of the cells with coefficient of determination above 0.94.
Assuntos
Neoplasias da Próstata/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Neoplasias do Colo do Útero/química , Algoritmos , Animais , Linhagem Celular , Linhagem Celular Tumoral , Feminino , Células HeLa , Humanos , Modelos Lineares , Masculino , Camundongos , Neoplasias da Próstata/diagnóstico , Neoplasias do Colo do Útero/diagnósticoRESUMO
The objective of this research is to examine the relationship between the color changes of phenol red and the growth of cancer cells, i.e., HeLa and DU145 cells, over a specific period of time. Normal mouse skin fibroblasts (L929 cells) were used as a reference. In this research, the color changes of phenol red due to the acidification of the cell culture medium from the growth of the cells over a period of nine hours showed potential colorimetric characteristics of cancer cells. The color changes of phenol red were observed using visible absorbance spectroscopy. The transformation of the absorbance spectra into coefficients of determination against the examined range of wavelengths created a distinctive spectral signature that signifies phenol red discoloration in cancer and normal cell culture lines.
Assuntos
Colorimetria/métodos , Fenolsulfonaftaleína/farmacologia , Animais , Meios de Cultura , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Análise Espectral , Células Tumorais CultivadasRESUMO
Porcupine bezoar (PB) is a calcified undigested material generally found in porcupine's (Hystrix brachyura) gastrointestinal tract. The bezoar is traditionally used in South East Asia and Europe for the treatment of cancer, poisoning, dengue, typhoid, etc. However, limited scientific studies have been performed to verify its anticancer potential to substantiate its traditional claims in the treatment of cancers. Hence, this study was aimed at investigating the in vitro and in vivo anticancer properties of two grassy PB aqueous extract (PB-A and PB-B) using A375 cancer cell line and zebrafish model, respectively. This paper presents the first report on in vitro A375 cell viability assay, apoptosis assay, cell cycle arrest assay, migration assay, invasion assay, qPCR experimental assay and in vivo anti-angiogenesis assay using the grassy PBs. Experimental findings revealed IC50 value are 26.59 ± 1.37 µg/mL and 30.12 ± 3.25 µg/mL for PB-A and PB-B respectively. PBs showed anti-proliferative activity with no significant cytotoxic effect on normal human dermal fibroblast (NHDF). PBs were also found to induce apoptosis via intrinsic pathway and arrest cell cycle at G2/M phase. Additionally, the findings indicated its ability to debilitate migration and invasion of A375 cells. Further evaluation using embryo zebrafish model revealed LC50 = 450.0 ± 2.50 µg/mL and 58.7 ± 5.0 µg/mL for PB-A and PB-B which also exerted anti-angiogenesis effect in zebrafish. Moreover, stearic acid, ursodeoxycholic acid and pregnenolone were identified as possible metabolites that might contribute to the anticancer effect of the both PBs. Overall, this study demonstrated that PB-A and PB-B possess potential in vitro and in vivo anticancer effects which are elicited through selective cytotoxic effect, induction of apoptosis, inhibition of migration and invasion and anti-angiogenesis. This study provides scientific evidence that the porcupine bezoar do possess anti-cancer efficacy and further justifies its traditional utility. However, more experiments with higher vertebrae models are still warranted to validate its traditional claims as an anticancer agent.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Bezoares/metabolismo , Braquiúros/química , Neoplasias/tratamento farmacológico , Porcos-Espinhos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Fibroblastos/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Peixe-ZebraRESUMO
Aging is an inevitable and ubiquitous progress that affects all living organisms. A total of 18 strains of lactic acid bacteria (LAB) were evaluated on the activation of adenosine monophosphate-activated protein kinase (AMPK), an intracellular energy sensor mediating lifespan extension. The cell-free supernatant (CFS) of Lactobacillus fermentum DR9 (LF-DR9), Lactobacillus paracasei OFS 0291 (LP-0291), and Lactobacillus helveticus OFS 1515 (LH-1515) showed the highest activation of AMPK and was further evaluated. The phosphorylation of AMPK by these three LAB strains was more evident in U2OS and C2C12 cells, compared to the other cell lines and control (P < .05). Using premature senescent Sprague-Dawley rats induced by D-galactose (D-gal), the administration of LAB (10 log CFU/rat/day) for 12 weeks prevented the shortening of telomere length in D-gal-treated rats compared to the untreated control (P < .05). LF-DR9 lowered gene expression of p53, a known senescent biomarker, in gastrocnemius muscle and tibia compared to the control. The selected LAB strains also enhanced lipid, renal, and liver profile of rats, suggesting added potential of the strains in preventing aging-induced metabolic diseases. Strain LP-0291 and LH-1515 showed ability to adhere to mucin, no antibiotic resistance, tolerated and proliferated under gastric and intestinal simulated conditions, and inhibited the growth of pathogens Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis, comparable to commercial probiotic LF-DR9 and Lactobacillus sakei Probio 65. This study provided an insight into the potential of LAB for exhibiting antisenescence effects, with potentials as new medicinal foods for targeted antiaging therapies.
Assuntos
Envelhecimento/fisiologia , Lactobacillus , Doenças Metabólicas/prevenção & controle , Probióticos/uso terapêutico , Encurtamento do Telômero , Proteínas Quinases Ativadas por AMP/metabolismo , Alcadienos/metabolismo , Animais , Células CACO-2 , Galactose , Humanos , Rim/metabolismo , Limosilactobacillus fermentum , Lactobacillus helveticus , Lacticaseibacillus paracasei , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Doenças Metabólicas/etiologia , Camundongos , Músculo Esquelético/metabolismo , Polímeros/metabolismo , Ratos Sprague-DawleyRESUMO
Neuroscience research and training in many African countries are difficult due to funding and infrastructure deficit. This has resulted in few neuroscientists within Africa. However, invertebrates such as Drosophila and Caenorhabditis elegans could provide the perfect answer to these difficulties. These organisms are cheap, easy to handle and offer a comparable advantage over vertebrates in neuroscience research modeling because they have a simple nervous system and exhibit well-defined behaviors. Studies using invertebrates have helped to understand neurosciences and the complexes associated with it. If Africa wants to catch up with the rest of the world in neuroscience research, it needs to employ this innovative cost-effective approach in its research. To improve invertebrate neuroscience within the Africa continent, the authors advocated the establishment of invertebrate research centers either at regional or national level across Africa. Finally, there is also a need to provide public funding to consolidate the gains that have been made by not-for-profit international organizations over the years.
Assuntos
Pesquisa Biomédica/métodos , Invertebrados , Modelos Animais , Neurociências/métodos , África , Animais , Pesquisa Biomédica/economia , Neurociências/economiaRESUMO
Metal oxide-polymer nanocomposite has been proven to have selective bactericidal effects against the main and common pathogens (Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli)) that can cause harmful infectious diseases. As such, this study looked into the prospect of using TiO2/ZnO with linear low-density polyethylene (LLDPE) to inactivate S. aureus and E. coli. The physical, structural, chemical, mechanical, and antibacterial properties of the nanocomposite were investigated in detail in this paper. The production of reactive species, such as hydroxyl radicals (â¢OH), holes (hâº), superoxide anion radicals (O2⢯), and zinc ion (Zn2+), released from the nanocomposite were quantified to elucidate the underlying antibacterial mechanisms. LLDPE/25T75Z with TiO2/ZnO (1:3) nanocomposite displayed the best performance that inactivated S. aureus and E. coli by 95% and 100%, respectively. The dominant reactive active species and the zinc ion release toward the superior antibacterial effect of nanocomposite are discussed. This work does not only offer depiction of the effective element required for antimicrobial biomedical appliances, but also the essential structural characteristics to enhance water uptake to expedite photocatalytic activity of LLDPE/metal oxide nanocomposite for long term application.
RESUMO
ZnO with two different morphologies were used to study the inhibition of Streptococcus sobrinus and Streptococcus mutans which are closely associated with tooth cavity. Rod-like shaped ZnO-A and plate-like shaped ZnO-B were produced using a zinc boiling furnace. The nanopowders were characterized using energy filtered transmission electron microscopy (EFTEM), X-ray diffraction (XRD), photoluminescence (PL) spectroscopy, Raman spectroscopy and dynamic light scattering (DLS) to confirm the properties of the ZnO polycrystalline wurtzite structures. XRD results show that the calculated crystallite sizes of ZnO-A and ZnO-B were 36.6 and 39.4nm, respectively, whereas DLS revealed particle size distributions of 21.82nm (ZnO-A) and 52.21nm (ZnO-B). PL spectra showed ion vacancy defects related to green and red luminescence for both ZnO particles. These defects evolved during the generation of reactive oxygen species which contributed to the antibacterial activity. Antibacterial activity was investigated using microdilution technique towards S. sobrinus and S. mutans at different nanopowder concentrations. Results showed that ZnO-A exhibited higher inhibition on both bacteria compared with ZnO-B. Moreover, S. mutans was more sensitive compared with S. sobrinus because of its higher inhibition rate.