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1.
Sci Rep ; 14(1): 5147, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429352

RESUMO

Rice husk, an agricultural waste from the rice industry, can cause serious environmental pollution if not properly managed. However, rice husk ash (RHA) has been found to have many positive properties, making it a potential replacement for non-renewable peat in soilless planting. Thus, this study investigated the impact of a RHA composite substrate on the growth, photosynthetic parameters, and fruit quality of cucumber (Yuyi longxiang variety) and melon (Yutian yangjiaomi variety). The RHA, peat, vermiculite, and perlite were blended in varying proportions, with the conventional seedling substrate (peat:vermiculite:perlite = 1:1:1 volume ratio) serving as the control (CK). All plants were cultivated in barrels filled with 10L of the mixed substrates. The results from this study found that RHA 40 (RHA:peat:vermiculite:perlite = 4:4:1:1 volume ratio) significantly enhanced substrate ventilation and positively influenced the stem diameter, root activity, seedling index, chlorophyll content, net photosynthetic rate (Pn), stomatal conductance (Gs), and transpiration rate (Tr) of cucumber and melon plants. Additionally, plant planted using RHA 40, the individual fruit weight of cucumber and melon found to increase by 34.62% and 21.67%, respectively, as compared to the control. Aside from that, both cucumber and melon fruits had significantly higher sucrose, total soluble sugar, vitamin C, and soluble protein levels. This subsequently improved the activity of sucrose synthase and sucrose phosphate synthase in both cucumber and melon. In conclusion, the RHA 40 found to best promote cucumber and melon plant growth, increase plant leaf photosynthesis, and improve cucumber and melon fruit quality, making it a suitable substrate formula for cucumber and melon cultivation in place of peat.


Assuntos
Óxido de Alumínio , Silicatos de Alumínio , Cucumis sativus , Cucurbitaceae , Oryza , Dióxido de Silício , Carboidratos da Dieta , Solo
2.
PLoS One ; 19(3): e0300376, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38512877

RESUMO

The trends for sustainable lifestyle and marketing motivated natural product consumption, such as natural skin care products (NSCPs). Different personal, environmental, and sociocultural factors influence purchase intention (PI) for NSCPs. However, there is a lack of evidence on the role of consumers' ethnicity in the PI model. The present study investigated the moderated mediation role of ethnicity in the relationship between related factors, including environmental concern, subjective norms, health factor, Halal certificate, packaging design, past experience factor, price factor, and PI mediated by personal attitude. A web-based survey was utilized to capture quantitative data from a random sample of 330 multicultural consumer group participants. The results of the study indicated that consumers' ethnicity substantially moderated the mediation effect of personal attitude in the relationships between subjective norms, health factor, Halal certificate, packaging design, past experience factor, price factor, and PI in the model. The findings contributed to understanding of the factors that influenced the PI of consumers from diverse sociocultural contexts in the market for natural products. It contributed directly to natural product marketing and industry.


Assuntos
Produtos Biológicos , Intenção , Humanos , Etnicidade , Comportamento do Consumidor , Higiene da Pele
3.
PeerJ ; 11: e15651, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37483971

RESUMO

A previous study has shown that synthetic antimicrobial peptides (AMPs) derived from Anabas testudineus (ATMP1) could in-vitro inhibit the progression of breast cancer cell lines. In this study, we are interested in studying altered versions of previous synthetic AMPs to gain some insight into the peptides functions. The AMPs were altered and subjected to bioinformatics prediction using four databases (ADP3, CAMP-R3, AMPfun, and ANTICP) to select the highest anticancer activity. The bioinformatics in silico analysis led to the selection of two AMPs, which are ATMP5 (THPPTTTTTTTTTTTYTAAPATTT) and ATMP6 (THPPTTTTTTTTTTTTTAAPARTT). The in silico analysis predicted that ATMP5 and ATMP6 have anticancer activity and lead to cell death. The ATMP5 and ATMP6 were submitted to deep learning databases (ToxIBTL and ToxinPred2) to predict the toxicity of the peptides and to (AllerTOP & AllergenFP) check the allergenicity. The results of databases indicated that AMPs are non-toxic to normal human cells and allergic to human immunoglobulin. The bioinformatics findings led to select the highest active peptide ATMP5, which was synthesised and applied for in-vitro experiments using cytotoxicity assay MTT Assay, apoptosis detection using the Annexin V FTIC-A assay, and gene expression using Apoptosis PCR Array to evaluate the AMP's anticancer activity. The antimicrobial activity is approved by the disc diffusion method. The in-vitro experiments analysis showed that ATMP5 had the activity to inhibit the growth of the breast cancer cell line (MDA-MB-231) after 48 h and managed to arrest the cell cycle of the MDA-MB-231, apoptosis induction, and overexpression of the p53 by interaction with the related apoptotic genes. This research opened up new opportunities for developing potential and selective anticancer agents relying on antimicrobial peptide properties.


Assuntos
Peptídeos Antimicrobianos , Neoplasias da Mama , Animais , Humanos , Feminino , Peptídeos/farmacologia , Apoptose , Morte Celular , Neoplasias da Mama/metabolismo
4.
Int J Biol Macromol ; 242(Pt 2): 124816, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37182623

RESUMO

Starch nanocrystals (SNCs) are tiny particles that possess unique qualities due to their small size, such as increased crystallinity, thin sheet structure, low permeability, and strong resistance to digestion. Although sago starch nanocrystals (SNCs) are naturally hydrophilic, their properties can be modified through chemical modifications to make them more versatile for various applications. In this study, the esterification process was used to modify SNCs using lauroyl chloride (LC) to enhance their surface properties. Three different ratios of LC to SNC were tested to determine the impact on the modified SNC (mSNC). The chemical changes in the mSNC were analyzed using FTIR and 1H NMR spectroscopy. ##The results showed that as the amount of LC increased, the degree of substitution (DS) also increased, which reduced the crystallinity of the mSNC and its thermal stability. However, the esterification process also improved the hydrophobicity of the SNC, making it more amphiphilic. The emulsification capabilities of the mSNC were investigated using a Pickering emulsion, and the results showed that the emulsion made from mSNC-1.0 had better stability than the one made from pristine SNC. This study highlights the potential of SNC as a particle emulsifier and demonstrates how esterification can improve its emulsification capabilities.


Assuntos
Nanopartículas , Amido , Amido/química , Emulsões/química , Lauratos , Tamanho da Partícula , Emulsificantes/química , Nanopartículas/química , Cloretos
5.
PeerJ ; 10: e14132, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36518267

RESUMO

Background: Primary congenital glaucoma (PCG) is the most common subtype of glaucoma caused by defects in the cytochrome P450 1B1 (CYP1B1) gene. It is developing among infants in more than 80% of cases who exhibit impairments in the anterior chamber angle and the trabecular meshwork. Thus, a comprehensive in silico approach was performed to evaluate the effect of high-risk deleterious missense variations in the CYP1B1 gene. Material and methods: All the information for CYP1B1 missense variants was retrieved from the dbSNP database. Seven different tools, namely: SIFT, PolyPhen-2, PROVEAN, SNAP2, PANTHER, PhD-SNP, and Predict-SNP, were used for functional annotation, and two packages, which were I-Mutant 2.0 and MUpro, were used to predict the effect of the variants on protein stability. A phylogenetic conservation analysis using deleterious variants was performed by the ConSurf server. The 3D structures of the wild-type and mutants were generated using the I-TASSER tool, and a 50 ns molecular dynamic simulation (MDS) was executed using the GROMACS webserver to determine the stability of mutants compared to the native protein. Co-expression, protein-protein interaction (PPI), gene ontology (GO), and pathway analyses were additionally performed for the CYP1B1 in-depth study. Results: All the retrieved data from the dbSNP database was subjected to functional, structural, and phylogenetic analysis. From the conducted analyses, a total of 19 high-risk variants (P52L, G61E, G90R, P118L, E173K, D291G, Y349D, G365W, G365R, R368H, R368C, D374N, N423Y, D430E, P442A, R444Q, F445L, R469W, and C470Y) were screened out that were considered to be deleterious to the CYP1B1 gene. The phylogenetic analysis revealed that the majority of the variants occurred in highly conserved regions. The MD simulation analysis exhibited that all mutants' average root mean square deviation (RMSD) values were higher compared to the wild-type protein, which could potentially cause CYP1B1 protein dysfunction, leading to the severity of the disease. Moreover, it has been discovered that CYP1A1, VCAN, HSD17B1, HSD17B2, and AKR1C3 are highly co-expressed and interact with CYP1B1. Besides, the CYP1B1 protein is primarily involved in the metabolism of xenobiotics, chemical carcinogenesis, the retinal metabolic process, and steroid hormone biosynthesis pathways, demonstrating its multifaceted and important roles. Discussion: This is the first comprehensive study that adds essential information to the ongoing efforts to understand the crucial role of genetic signatures in the development of PCG and will be useful for more targeted gene-disease association studies.


Assuntos
Sistema Enzimático do Citocromo P-450 , Glaucoma , Lactente , Humanos , Mutação , Filogenia , Linhagem , Sistema Enzimático do Citocromo P-450/genética , Glaucoma/genética , Citocromo P-450 CYP1B1/genética
6.
Toxics ; 10(11)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36355947

RESUMO

Garcinia atriviridis Griff ex T. Anders (G. atroviridis) is one of the well-known species of the genus Garicinia that is native to Thailand, Myanmar, Peninsular Malaysia, and India. G. atroviridis is a perennial medium-sized tree that has a wide range of values, from food to medicinal use. Different parts of G. atroviridis are a great source of bioactive substances that have a positive impact on health. The extracts or bioactive constituents from G. atroviridis have demonstrated various therapeutic functions, including antioxidant, antimicrobial, anticancer, anti-inflammatory, antihyperlipidemic, and anti-diabetic. In this paper, we provide a critical review of G. atroviridis and its bioactive constituents in the prevention and treatment of different diseases, which will provide new insight to explore its putative domains of research.

7.
J Ethnopharmacol ; 283: 114751, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34662662

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Marantodes pumilum (MP) herbs, locally known as Kacip Fatimah, are widely used traditionally to improve women's health. The herb is frequently used for gynecological issues such as menstrual problems, facilitating and quickening delivery, post-partum medication, treats flatulence and dysentery, and. MP extracts are thought to aid in the firming and toning of abdominal muscles, tighten breasts and vaginal muscles, and anti-dysmenorrhea. It also was used for the treatment of gonorrhea and hemorrhoids. As MP product has been produced commercially recently, more in-depth studies should be conducted. The presence of numerous active compounds in MP might provide a synergistic effect and potentially offer other health benefits than those already identified and known. AIM OF THE STUDY: This study aimed to use a computational target fishing approach to predict the possible therapeutic effect of Marantodes pumilum and evaluated their effectivity. MATERIALS AND METHODS: This study involves a computational approach to identify the potential targets by using target fishing. Several databases were used: PubChem database to obtain the chemical structure of interested compounds; Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) server and the SWISSADME web tool to identify and select the compounds having drug-likeness properties; PharmMapper was used to identify top ten target protein of the selected compounds and Online Mendelian Inheritance in Man (OMIM) was used to predict human genetic problems; the gene id of top-10 proteins was obtained from UniProtKB to be analyzed by using GeneMANIA server to check the genes' function and their co-expression; Gene Pathway established by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) of the selected targets were analyzed by using EnrichR server and confirmed by using DAVID (The Database for Annotation, Visualization and Integrated Discovery) version 6.8 and STRING database. All the interaction data was analyzed by Cytoscape version 3.7.2 software. The protein structure of most putative proteins was obtained from the RCSB protein data bank. Thedocking analysis was conducted using PyRx biological software v0.8 and illustrated by BIOVIA Discovery Studio Visualizer version 20.1.0. As a preliminary evaluation, a cell viability assay using Sulforhodamine B was conducted to evaluate the potential of the predicted therapeutic effect. RESULTS: It was found that four studied compounds are highly correlated with three proteins: EFGR, CDK2, and ESR1. These proteins are highly associated with cancer pathways, especially breast cancer and prostate cancer. Qualitatively, cell proliferation assay conducted shown that the extract has IC50 of 88.69 µg/ml against MCF-7 and 66.51 µg/ml against MDA-MB-231. CONCLUSIONS: Natural herbs are one of the most common forms of complementary and alternative medicine, and they play an important role in disease treatment. The results of this study show that in addition to being used traditionally to maintain women's health, the use of Marantodes pumilum indirectly has the potential to protect against the development of cancer cells, especially breast cancer. Therefore, further research is necessary to confirm the potential of this plant to be used in the development of anti-cancer drugs, especially for breast cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Extratos Vegetais/farmacologia , Primulaceae/química , Antineoplásicos Fitogênicos/administração & dosagem , Linhagem Celular Tumoral , Bases de Dados Factuais , Bases de Dados Genéticas , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Humanos , Concentração Inibidora 50 , Masculino , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Farmacologia em Rede , Extratos Vegetais/administração & dosagem
8.
Gene ; 812: 146104, 2022 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-34864095

RESUMO

Among the 22 Fanconi anemia (FA) reported genes, 90% of mutational spectra were found in three genes, namely FANCA (64%), FANCC (12%) and FANCG (8%). Therefore, this study aimed to identify the high-risk deleterious variants in three selected genes (FANCA, FANCC, and FANCG) through various computational approaches. The missense variant datasets retrieved from the UCSC genome browser were analyzed for their pathogenicity, stability, and phylogenetic conservancy. A total of 23 alterations, of which 16 in FANCA, 6 in FANCC and one variant in FANCG, were found to be highly deleterious. The native and mutant structures were generated, which demonstrated a profound impact on the respective proteins. Besides, their pathway analysis predicted many other pathways in addition to the Fanconi anemia pathway, homologous recombination, and mismatch repair pathways. Hence, this is the first comprehensive study that can be useful for understanding the genetic signatures in the development of FA.


Assuntos
Biologia Computacional/métodos , Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Proteína do Grupo de Complementação C da Anemia de Fanconi/genética , Proteína do Grupo de Complementação G da Anemia de Fanconi/genética , Anemia de Fanconi/genética , Mutação de Sentido Incorreto , Sítios de Ligação , Proteína do Grupo de Complementação A da Anemia de Fanconi/química , Proteína do Grupo de Complementação C da Anemia de Fanconi/química , Proteína do Grupo de Complementação G da Anemia de Fanconi/química , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Modelos Moleculares , Conformação Proteica , Estabilidade Proteica
9.
Front Psychiatry ; 12: 698911, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34916966

RESUMO

Background: Oxidative stress markers are found to be linked with depression and suicide attempts in bipolar disorder (BD), although the role of DNA damage as a marker of suicidal ideation and attempt has yet to be determined. We aim to investigate the association between DNA damage and suicidal behaviour, i.e., suicidal ideation and suicide attempt, among suicidal ideators in BD patients while accounting for clinical and psychosocial risk factors. Methods: A cross-sectional study was conducted in the Universiti Kebangsaan Malaysia Medical Centre on 62 consecutive BD patients diagnosed using the M.I.N.I. Neuropsychiatric Interview and 26 healthy control participants. Socio-demographic and clinical assessments were performed using the Columbia Suicide Severity Rating Scale (C-SSRS) for lifetime suicidal ideation and attempt, Quick Inventory of Depressive Symptomatology (QIDS) for depression severity, Clinical Global Impression for Bipolar Disorder (CGI-BD) for illness severity [both mania (CGI-Mania) and major depressive episode (CGI-MDE)], Social Readjustment Rating Scale (SRRS) for change in life events, and Barratt Impulsiveness Scale (BIS) for behavioural impulsivity. The degree of DNA damage in peripheral blood samples was determined using a standard protocol of comet assay. Results: Multivariable logistic regression revealed higher scores of CGI-MDE as the sole significant factor for lifetime suicidal ideation (OR = 1.937, 95% CI = 1.799-2.076). Although initial bivariate analysis showed a significant association between DNA damage, malondialdehyde (MDA), catalase (CAT), and suicidal behaviour, the findings were not seen in multivariable logistic regression. Bivariate subgroup analysis showed that moderate and severe DNA damage (p = 0.032 and p = 0.047, respectively) was significantly associated with lifetime suicide attempts among lifetime suicidal ideators. The study is the first to look at the connexion between DNA damage and suicidal risk in bipolar patients. It is limited by the small sample size and lack of information on illicit substance use. Conclusions: More severe DNA damage was significantly associated with lifetime suicide attempts among lifetime suicidal ideators in BD. However, the severity of depression was found to be independently associated with lifetime suicidal ideation per se rather than DNA damage in BD. Larger prospective studies are required to ascertain the potential of DNA damage as a biomarker for the transition from suicidal ideation to a suicide attempt.

10.
Sci Rep ; 11(1): 23182, 2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34848729

RESUMO

Previous study has shown the antimicrobial activities of mucus protein extracted from Anabas testudineus. In this study, we are interested in characterizing the anticancer activity of the A. testudineus antimicrobial peptides (AMPs). The mucus was extracted, fractioned, and subjected to antibacterial activity testing to confirm the fish's AMPs production. The cytotoxic activity of each fraction was also identified. Fraction 2 (F2), which shows toxicity against MCF7 and MDA-MB-231 were sent for peptide sequencing to identify the bioactive peptide. The two peptides were then synthetically produced and subjected to cytotoxic assay to prove their efficacy against cancer cell lines. The IC50 for AtMP1 against MCF7 and MDA-MB-231 were 8.25 ± 0.14 µg/ml and 9.35 ± 0.25 µg/ml respectively, while for AtMP2 it is 5.89 ± 0.14 µg/ml and 6.97 ± 0.24 µg/ml respectively. AtMP1 and AtMP2 treatment for 48 h induced breast cancer cell cycle arrest and apoptosis by upregulating the p53, which lead to upregulate pro-apoptotic BAX gene and downregulate the anti-apoptotic BCL-2 gene, consequently, trigger the activation of the caspase-3. This interaction was supported by docking analysis (QuickDBD, HPEPDOCK, and ZDOCK) and immunoprecipitation. This study provided new prospects in the development of highly effective and selective cancer therapeutics based on antimicrobial peptides.


Assuntos
Peptídeos Antimicrobianos/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Peixes/metabolismo , Muco/metabolismo , Peptídeos/farmacologia , Animais , Apoptose , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Biologia Computacional/métodos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Feminino , Perfilação da Expressão Gênica , Humanos , Concentração Inibidora 50 , Células MCF-7 , Peptídeos/química , Mapeamento de Interação de Proteínas
11.
Int J Biol Macromol ; 182: 197-206, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33774073

RESUMO

This study presents the isolation of SNC from sago starch and its performance as proficient particle emulsifier. It highlights the impact of SNC on the stability and rheological properties of oil-in-water (o/w) emulsions. The percentage yield of the SNC obtained was equivalent to 25 ± 0.1% (w/w) with particle diameters ranging from 25 to 100 nm. A series of Pickering emulsion at different ratios of oil (5%-35% v/v) and SNC (1%-4% w/v) was prepared for further investigations. The mean droplet diameter of emulsions obtained was ranged from 19.12 to 35.96 µm, confirming the effects of both SNC and oil content on the droplet's diameter distribution. Formulations with 4.0 wt% of SNC exhibited the maximum stability against coalescence. Results obtained have justified that the SNC can be used as an alternative solid emulsifier in producing stable emulsion with desired properties for various applications.


Assuntos
Arecaceae/química , Emulsões/química , Nanopartículas/química , Amido/química , Emulsificantes/química , Reologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-33737223

RESUMO

The ability of natural extracts to inhibit melanocyte activity is of great interest to researchers. This study evaluates and explores the ability of mutated Shiitake (A37) and wildtype Shiitake (WE) extract to inhibit this activity. Several properties such as total phenolic (TPC) and total flavonoid content (TFC), antioxidant activity, effect on cell and component profiling were conducted. While having no significant differences in total phenolic content, mutation resulted in A37 having a TFC content (1.04 ± 0.7 mg/100 ml) compared to WE (0.86 ± 0.9 mg/100 ml). Despite that, A37 extract has lower antioxidant activity (EC50, A37 = 549.6 ± 2.70 µg/ml) than WE (EC50 = 52.8 ± 1.19 µg/ml). Toxicity tests on zebrafish embryos show that both extracts, stop the embryogenesis process when the concentration used exceeds 900 µg/ml. Although both extracts showed pigmentation reduction in zebrafish embryos, A37 extract showed no effect on embryo heartbeat. Cell cycle studies revealed that WE significantly affect the cell cycle while A37 not. Further tests found that these extracts inhibit the phosphorylation of Glycogen synthase kinase 3 ß (pGSK3ß) in HS27 cell line, which may explain the activation of apoptosis in melanin-producing cells. It was found that from 19 known compounds, 14 compounds were present in both WE and A37 extracts. Interestingly, the presence of decitabine in A37 extract makes it very potential for use in the medical application such as treatment of melanoma, skin therapy and even cancer.


Assuntos
Antineoplásicos/farmacologia , Melanócitos/efeitos dos fármacos , Crista Neural/efeitos dos fármacos , Cogumelos Shiitake/química , Peixe-Zebra/embriologia , Animais , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Melanócitos/citologia , Melanoma/tratamento farmacológico
13.
Sci Rep ; 11(1): 1594, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452398

RESUMO

Xanthorrhizol (XNT), is a bioactive compound found in Curcuma xanthorrhiza Roxb. This study aimed to determine the potential targets of the XNT via computational target fishing method. This compound obeyed Lipinski's and Veber's rules where it has a molecular weight (MW) of 218.37 gmol-1, TPSA of 20.23, rotatable bonds (RBN) of 4, hydrogen acceptor and donor ability is 1 respectively. Besides, it also has half-life (HL) values 3.5 h, drug-likeness (DL) value of 0.07, oral bioavailability (OB) of 32.10, and blood-brain barrier permeability (BBB) value of 1.64 indicating its potential as therapeutic drug. Further, 20 potential targets were screened out through PharmMapper and DRAR-CPI servers. Co-expression results derived from GeneMANIA revealed that these targets made connection with a total of 40 genes and have 744 different links. Four genes which were RXRA, RBP4, HSD11B1 and AKR1C1 showed remarkable co-expression and predominantly involved in steroid metabolic process. Furthermore, among these 20 genes, 13 highly expressed genes associated with xenobiotics by cytochrome P450, chemical carcinogenesis and steroid metabolic pathways were identified through gene ontology (GO) and KEGG pathway analysis. In conclusion, XNT is targeting multiple proteins and pathways which may be exploited to shape a network that exerts systematic pharmacological effects.


Assuntos
Biologia Computacional/métodos , Curcuma/química , Fenóis/química , Sítios de Ligação , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Curcuma/metabolismo , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Quinase 2 Dependente de Ciclina/metabolismo , Expressão Gênica/efeitos dos fármacos , Meia-Vida , Humanos , Simulação de Acoplamento Molecular , Peso Molecular , Fenóis/metabolismo , Fenóis/farmacologia , Mapas de Interação de Proteínas/efeitos dos fármacos , Proteínas/antagonistas & inibidores , Proteínas/genética , Proteínas/metabolismo
14.
Sci Rep ; 10(1): 14165, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843675

RESUMO

In Malaysia, Piper sarmentosum or 'kaduk' is commonly used in traditional medicines. However, its biological effects including in vivo embryonic toxicity and tissue regenerative properties are relatively unknown. The purpose of this study was to determine zebrafish (Danio rerio) embryo toxicities and caudal fin tissue regeneration in the presence of P. sarmentosum aqueous extracts. The phytochemical components and antioxidant activity of the extract were studied using GC-MS analysis and DPPH assay, respectively. Embryo toxicity tests involving survival, heartbeat, and morphological analyses were conducted to determine P. sarmentosum extract toxicity (0-60 µg/mL); concentrations of 0-400 µg/mL of the extract were used to study tissue regeneration in the zebrafish caudal fin. The extract contained several phytochemicals with antioxidant activity and exhibited DPPH scavenging activity (IC50 = 50.56 mg/mL). Embryo toxicity assays showed that a concentration of 60 µg/mL showed the highest rates of lethality regardless of exposure time. Slower embryogenesis was observed at 40 µg/mL, with non-viable embryos first detected at 50 µg/mL. Extracts showed significant differences (p < 0.01) for tissue regeneration at all concentrations when compared to non-treated samples. In conclusion, Piper sarmentosum extracts accelerated tissue regeneration, and extract concentrations at 60 µg/mL showed the highest toxicity levels for embryo viability.


Assuntos
Antioxidantes/farmacologia , Desenvolvimento Embrionário/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Piper/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Regeneração/efeitos dos fármacos , Peixe-Zebra/embriologia , Nadadeiras de Animais/efeitos dos fármacos , Nadadeiras de Animais/lesões , Nadadeiras de Animais/fisiologia , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Feminino , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/toxicidade , Cromatografia Gasosa-Espectrometria de Massas , Coração/efeitos dos fármacos , Coração/embriologia , Masculino , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Água
15.
PeerJ ; 8: e9197, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509463

RESUMO

BACKGROUND: DNA double strand break repair is important to preserve the fidelity of our genetic makeup after DNA damage. Rad50 is one of the components in MRN complex important for DNA repair mechanism. Rad50 mutations can lead to microcephaly, mental retardation and growth retardation in human. However, Rad50 mutations in human and other organisms have never been gathered and heuristically compared for their deleterious effects. It is important to assess the conserved region in Rad50 and its homolog to identify vital mutations that can affect functions of the protein. METHOD: In this study, Rad50 mutations were retrieved from SNPeffect 4.0 database and literature. Each of the mutations was analyzed using various bioinformatic analyses such as PredictSNP, MutPred, SNPeffect 4.0, I-Mutant and MuPro to identify its impact on molecular mechanism, biological function and protein stability, respectively. RESULTS: We identified 103 mostly occurred mutations in the Rad50 protein domains and motifs, which only 42 mutations were classified as most deleterious. These mutations are mainly situated at the specific motifs such as Walker A, Q-loop, Walker B, D-loop and signature motif of the Rad50 protein. Some of these mutations were predicted to negatively affect several important functional sites that play important roles in DNA repair mechanism and cell cycle signaling pathway, highlighting Rad50 crucial role in this process. Interestingly, mutations located at non-conserved regions were predicted to have neutral/non-damaging effects, in contrast with previous experimental studies that showed deleterious effects. This suggests that software used in this study may have limitations in predicting mutations in non-conserved regions, implying further improvement in their algorithm is needed. In conclusion, this study reveals the priority of acid substitution associated with the genetic disorders. This finding highlights the vital roles of certain residues such as K42E, C681A/S, CC684R/S, S1202R, E1232Q and D1238N/A located in Rad50 conserved regions, which can be considered for a more targeted future studies.

16.
J Sci Food Agric ; 100(3): 1012-1021, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31646636

RESUMO

BACKGROUND: Wines are produced via the alcoholic fermentation of suitable substrates, usually sugar (sugar cane, grapes) and carbohydrates (wheat, grain). However, conventional alcoholic fermentation is limited by the inhibition of yeast by ethanol produced, usually at approximately 13-14%. Aside from that, soursop fruit is a very nutritious fruit, although it is highly perishable, and thus produces a lot of wastage. Therefore, the present study aimed to produce fermented soursop juice (soursop wine), using combination of two starter cultures, namely mushroom (Pleurotus pulmonarius) and yeast (Saccharomyces cerevisiae), as well as to determine the effects of fermentation on the physicochemical and antioxidant activities of fermented soursop juice. Optimisation of four factors (pH, temperature, time and culture ratio) using response surface methodology were performed to maximise ethanol production. RESULTS: The optimised values for alcoholic fermentation were pH 4.99, 28.29 °C, 131 h and a 0.42 culture ratio (42:58, P. pulmonarius mycelia:S. cerevisiae) with a predicted ethanol concentration of 22.25%. Through a verification test, soursop wine with 22.29 ± 0.52% ethanol was produced. The antioxidant activities (1,1-diphenyl-2-picrylhydrazyl and ferric reducing antioxidant power) showed a significant (P < 0.05) increase from the soursop juice to soursop wine. CONCLUSION: The alternative fermentation technique using yeast and mushroom has successfully been optimised, with an increased ethanol production in soursop wine and higher antioxidant activities. Ultimately, this finding has high potential for application in the brewing industry to enhance the fermentation process, as well as in the development of an innovative niche product, reducing wastage by converting the highly-perishable fruit into wine with a more stable and longer shelf-life. © 2019 Society of Chemical Industry.


Assuntos
Annona/microbiologia , Microbiologia de Alimentos/métodos , Pleurotus/metabolismo , Saccharomyces cerevisiae/metabolismo , Annona/metabolismo , Antioxidantes/análise , Antioxidantes/metabolismo , Etanol/análise , Etanol/metabolismo , Fermentação , Vinho/análise
17.
J Fish Dis ; 42(12): 1761-1772, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31637743

RESUMO

Discovery of species-specific interaction between the host and virus has drawn the interest of many researchers to study the evolution of the newly emerged virus. Comparative genome analysis provides insights of the virus functional genome evolution and the underlying mechanisms of virus-host interactions. The analysis of nucleotide composition signified the evolution of nodavirus towards host specialization in a host-specific mutation manner. GC-rich genome of betanodavirus was significantly deficient in UpA and UpU dinucleotides composition, whilst the AU-rich genome of gammanodavirus was deficient in CpG dinucleotide. The capsid of MrNV and PvNV of gammanodavirus retains the highest abundance of adenine and uracil at the second codon position, respectively, which were found to be very distinctive from the other genera. ENC-GC3 plot inferred the influence of natural selection and mutational pressure in shaping the evolution of MrNV RdRp and capsid, respectively. Furthermore, CAI/eCAI analysis predicts a comparable adaptability of MrNV in squid, Sepia officinalis than its natural host, Macrobrachium rosenbergii. Thus, further study is warranted to investigate the capacity of MrNV replication in S. officinalis owing to its high codon adaptation index.


Assuntos
Composição de Bases , Decápodes/virologia , Genoma Viral , Nodaviridae/genética , Infecções por Vírus de RNA/veterinária , Animais , Proteínas do Capsídeo/genética , Uso do Códon , Evolução Molecular , Genômica , Especificidade da Espécie
18.
Toxics ; 6(4)2018 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-30304811

RESUMO

Xanthone is an organic compound mostly found in mangosteen pericarp and widely known for its anti-proliferating effect on cancer cells. In this study, we evaluated the effects of xanthone crude extract (XCE) and α-mangostin (α-MG) on normoxic and hypoxic human hepatocellular carcinoma (HepG2) cells and their toxicity towards zebrafish embryos. XCE was isolated using a mixture of acetone and water (80:20) and verified via high performance liquid chromatography (HPLC). Both XCE and α-MG showed higher anti-proliferation effects on normoxic HepG2 cells compared to the control drug, 5-fluorouracil (IC50 = 50.23 ± 1.38, 8.39 ± 0.14, and 143.75 ± 15.31 µg/mL, respectively). In hypoxic conditions, HepG2 cells were two times less sensitive towards XCE compared to normoxic HepG2 cells (IC50 = 109.38 ± 1.80 µg/mL) and three times less sensitive when treated with >500 µg/mL 5-fluorouracil (5-FU). A similar trend was seen with the α-MG treatment on hypoxic HepG2 cells (IC50 = 10.11 ± 0.05 µg/mL) compared to normoxic HepG2 cells. However, at a concentration of 12.5 µg/mL, the α-MG treatment caused tail-bend deformities in surviving zebrafish embryos, while no malformation was observed when embryos were exposed to XCE and 5-FU treatments. Our study suggests that both XCE and α-MG are capable of inhibiting HepG2 cell proliferation during normoxic and hypoxic conditions, more effectively than 5-FU. However, XCE is the preferred option as no malformation was observed in surviving zebrafish embryos and it is more cost efficient than α-MG.

19.
J Neurooncol ; 138(3): 509-518, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29564746

RESUMO

Glioblastoma (GBM) is a highly fatal disease with a 5 year survival rate of less than 22%. One of the most effective treatment regimens to date is the use of radiotherapy which induces lethal DNA double-strand breaks to prevent tumour growth. However, recurrence occurs in the majority of patients and is in-part a result of robust radioresistance mechanisms. In this study, we demonstrate that the multifunctional cytokine, interleukin-6 (IL-6), confers a growth advantage in GBM cells but does not have the same effect on normal neural progenitor cells. Further analysis showed IL-6 can promote radioresistance in GBM cells when exposed to ionising radiation. Ablation of the Ataxia-telangiectasia mutated serine/threonine kinase that is recruited and activated by DNA double-strand breaks reverses the effect of radioresistance and re-sensitised GBM to DNA damage thus leading to increase cell death. Our finding suggests targeting the signaling cascade of DNA damage response is a potential therapeutic approach to circumvent IL-6 from promoting radioresistance in GBM.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Proliferação de Células/efeitos da radiação , Neoplasias do Sistema Nervoso Central/radioterapia , Glioblastoma/radioterapia , Interleucina-6/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Morte Celular/fisiologia , Morte Celular/efeitos da radiação , Linhagem Celular , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Sobrevivência Celular/efeitos da radiação , Neoplasias do Sistema Nervoso Central/metabolismo , Dano ao DNA/efeitos da radiação , Glioblastoma/metabolismo , Humanos , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/efeitos da radiação , RNA Mensageiro/metabolismo , Tolerância a Radiação/fisiologia , Radiação Ionizante , Receptores de Interleucina-6/metabolismo
20.
Int J Biol Macromol ; 107(Pt B): 2412-2421, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29056465

RESUMO

Starch-based hydrogels are promising smart materials for biomedical and pharmaceutical applications, which offer exciting perspectives in biophysical research at molecular level. This work was intended to develop, characterize and explore the properties of hydrogel from starch extracted from new source, Dioscorea hispida Dennst. Starch-mediated hydrogels were successfully synthesized via free radical polymerization method with varying concentrations of acrylic acid (AA),N,N'-methylenebisacrylamide (MBA) and sodium hydroxide (NaOH) in aqueous system. The grafting reaction between starch and AA was examined by observing the decline in intensity peak of hydrogel FTIR spectrum at 3291cm-1 and peak around 1600-1680cm-1, indicating the stretching of hydroxyl group (OH) and stretching of carbon-carbon double bond (CC) respectively. The effects of cross-linker, monomer and NaOH concentration on swelling ratio and gel content in different medium and conditions were also evaluated. The thermal stability and structural morphology of as-synthesized hydrogels were studied by thermogravimetry analysis (TGA) and scanning electron microscopy (SEM). In-vitro cytotoxicity study using small intestine cell line (FHS-74 Int) revealed that the as-formulated eco-friendly-hydrogel was free from any harmful material and safe to use for future product development.


Assuntos
Dioscorea/química , Hidrogéis/química , Intestino Delgado/efeitos dos fármacos , Amido/química , Acrilatos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos/química , Radicais Livres/química , Humanos , Hidrogéis/síntese química , Hidrogéis/farmacologia , Cinética , Microscopia Eletrônica de Varredura , Espectroscopia de Infravermelho com Transformada de Fourier , Amido/síntese química , Amido/farmacologia , Termogravimetria , Água/química
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