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1.
J Biomol Struct Dyn ; : 1-12, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38529845

RESUMO

The COVID-19 pandemic caused by the SARS-CoV-2 virus, recognized by the World Health Organization (WHO), has led to 164,523,894 confirmed cases and 3,412,032 deaths globally as of May 20, 2021. SARS-CoV-2 encodes crucial proteases for its replication cycle, including the papain-like protease (PLpro), presenting a potential target for developing COVID-19 treatments. Mauritine, a cyclopeptide alkaloid found in the Ziziphus-spina christi plant, exhibits antiviral properties and was investigated for its affinity and toxicity towards PLpro using molecular docking through MGLTools 1.5.6 with Autodock Tools 4.2. Preceding this, toxicity and ADME prediction were performed via Toxtree 3.1.0 software and SwissADME servers. Results from molecular docking revealed free binding energy values of -8.58; -7.73; -8.36; -6.07; -6.67; -7.83; -7.67; -7.40; and -6.87 Kcal/mol for Mauritine-A, Mauritine-B, Mauritine-C, Mauritine-D, Mauritine-F, Mauritine-H, Mauritine-J, Mauritine-L, and Mauritine-M, respectively. Correspondingly, inhibition constants were 0.51724; 2.14; 0.7398; 35.43; 12.95; 1.83; 2.38; 3.80; and 9.17 µM, respectively. Interactions observed included hydrogen bonds, hydrophobic interactions, and electrostatic interactions between the Mauritine compounds and the receptor. Mauritine-A and Mauritine-C emerged as a promising anti-COVID-19 candidate due to its superior affinity compared to other derivatives, as indicated by research findings. Interestingly, Mauritine-A and Mauritine-C exhibits notable stability as depicted by the RMSD and RMSF graphs, along with a considerable MM-PBSA binding free energy value of -162.431 and -137.500 kJ/mol, respectively.Communicated by Ramaswamy H. Sarma.

2.
J Biomol Struct Dyn ; : 1-14, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38268238

RESUMO

Cigarette smoking poses various health risks, such as increasing the susceptibility to respiratory infections, contributing to osteoporosis, causing reproductive issues, delaying postoperative recovery, promoting ulcer formation and heightening the risk of diabetes. While many harmful effects of smoking are attributed to other cigarette components, it is nicotine's pharmacological effects that underlie tobacco addiction. Nicotine replacement therapy (NRT) aims to alleviate the urge to smoke and mitigate physiological and psychomotor withdrawal symptoms by delivering nicotine. This study explores the potential of sesquiterpene derivative compounds derived from the Cinnamomum genus using computational techniques. The research incorporates molecular docking analyses, Lipinski's rule of five filtration for drug-likeness, pharmacokinetic and toxicity predictions to assess safety profiles and molecular dynamics (MD) simulations to gauge interaction stability. The findings reveal that all sesquiterpene derivative compounds from the Cinnamomum genus can potentially inhibit nicotinic acetylcholine receptors (nAChRs), particularly nAChRÿ7. However, only abscisic acid exhibit active inhibition, along with suitable drug properties, pharmacokinetics and toxicity profiles. MD studies confirm the stability of interactions between abscisic acid with nAChRÿ7. Consequently, abscisic acid, as sesquiterpene derivatives from the Cinnamomum genus, holds substantial promise for further investigation as nAChRÿ7 inhibitors.Communicated by Ramaswamy H. Sarma.

3.
Adv Appl Bioinform Chem ; 17: 1-19, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38282640

RESUMO

Introduction: Amorphous drug dispersion is frequently used to enhance the solubility and dissolution of poorly water-soluble drugs, thereby improving their oral bioavailability. The dispersion of these drugs into polymer matrix can inhibit their recrystallization. The inter-molecular interactions between drug and polymer plays a role in the improvement of the dissolution rate, solubility, and physical stability of drug. Aim: This study aims to investigate the formation and interactions of ritonavir (RTV)/poloxamer (PLX) amorphous formulation using a computational approach via molecular dynamics (MD) simulations, which mimicked solvent evaporation and melt-quenching method. Methods: TheRoot Mean Square Deviation (RMSD) value, Root Mean Square Fluctuation (RMSF), Radial Distribution Function (RDF), Radius of Gyration (Rg), Solvent Accessible Surface Area (SASA), and hydrogen bond interactions were analyzed to determine interaction mechanisms between RTV and PLX in amorphous solid dispersion. Results: The pi-alkyl bonds between RTV and PLX were formed after simulations of solvent evaporation, while the hydrogen bond interactions of RTV-PLX was observed during melt method simulations. These results indicate the successful formulation of amorphous solid dispersion (ASD) from RTV and PLX. The RMSD values obtained from the solvent evaporation, melt-cooling-A, melt-cooling-B, and melt-cooling-C methods were 3.33 Å, 1.97 Å, 1.30 Å, and 1.29 Å, respectively, while the average RMSF values were 2.65 Å, 1.04 Å, 1.05 Å, and 1.07 Å, respectively. This indicates that the suppression of translational motion of RTV from the melt method can be stronger than solvent evaporation caused by the intermolecular interactions of RTV-PLX. Conclusion: MD simulations helped in understanding the formation and interaction mechanisms of ASD formulations that were difficult to detect by experimental approaches.

4.
Curr Res Struct Biol ; 7: 100125, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38282755

RESUMO

The EGFR-C797S resistance mutation to third-generation drugs has been overcome by fourth-generation inhibitors, allosteric inhibitors, namely EAI045 and has reached phase 3 clinical trials, so the Allosteric Site is currently an attractive target for development. In this study, researchers are interested in knowing the activity of metabolite compounds from marine natural ingredients Clathria Sp. against the Allosteric Site of EGFR computationally. The methods used include molecular docking using Autodock4 software and Molecular Dynamics simulation performed using GROMACS software. The research began with the preparation of metabolite samples from Clathria Sp. through the KnapSack database site and the preparation of EGFR receptors that have been complexed with allosteric inhibitors, namely proteins with PDB code 5D41. Each compound was docked to the Allosteric Site of the natural ligand and then molecular dynamics simulations were performed on the compound with the best docking energy compared to the natural ligand. From the docking results, the Clathrin_A compound showed the lowest binding energy compared to other metabolites, and the value was close to the natural ligand. Then from the molecular dynamics results, the clathrin_A compound shows good stability and resembles the natural ligand, which is analyzed through RMSD, RMSF, SASA, Rg, and PCA, and shows the binding free energy from MMPBSA analysis which is close to the natural ligand. It can be concluded, Clathrin_A compound has potential as an allosteric inhibitor.

5.
PLoS One ; 18(9): e0290964, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37747884

RESUMO

BACKGROUND: Indonesia's national response to COVID-19 evolved rapidly throughout 2020. Understanding pandemic response and outcomes is crucial for better mitigation strategies ahead. This study describes the characteristics and outcomes of patients admitted to ICU during the early stages of the pandemic. METHODS: This is a multi-centre prospective observational study including patients from twelve collaborating hospitals in Indonesia. All patients were clinically suspected or laboratory-confirmed COVID-19 cases admitted to ICU between January 2020 and March 2021. The primary outcome was monthly ICU mortality. Descriptive statistics of patient characteristics and treatment were generated as secondary outcomes. RESULTS: From 559 subjects, the overall mortality was 68% and decreased over the study period, while the mortality of patients that received mechanical ventilation was 92%, consistently high over the study period. Fatal cases showed 2- and 4-day delays from symptoms onset to hospital admissions and ICU admissions, respectively. Evidence-backed approaches which could influence patient outcome, such as extracorporeal membrane oxygenation, prone positioning, renal replacement therapy, and neuromuscular blockade were scarcely administered. CONCLUSIONS: The mortality rate of COVID-19 patients in Indonesia was extremely high during the first major outbreak of disease, particularly in those mechanically ventilated. Delayed admission and unavailability of evidence-based approaches due to high burden on health facility during COVID-19 crisis could be addressed by efficient public health measures and enhancing health infrastructure to improve the future pandemic response.


Assuntos
COVID-19 , Terapia de Substituição Renal Contínua , Oxigenação por Membrana Extracorpórea , Humanos , Indonésia/epidemiologia , COVID-19/epidemiologia , COVID-19/terapia , Surtos de Doenças
6.
J Biomol Struct Dyn ; : 1-11, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37643016

RESUMO

The present study aimed to strategically design a Molecularly Imprinted Polymer (MIP) with selective extraction capabilities for volatile compounds found in pork. These specific volatile compounds, such as 3-methyl-1-butanol, 1-nonanal, octanal, hexanal, 2-pentyl-furan, 1-penten-3-one, N-morpholinomethyl-isopropyl-sulfide, methyl butyrate, and (E,E)-2,4-decadienal, are primarily responsible for the distinctive aroma and flavor characteristics associated with pork. Molecular dynamics simulations were employed to investigate the stability of the pre-polymerization system, simulating the interactions between the volatile compounds as templates, 4-hydroxyethyl methacrylate (HEMA) as monomers, and ethylene glycol dimethacrylate (EGDMA) as crosslinkers. Computational simulations revealed that the optimal mole ratio of 1:4:20 for templates, monomers, and crosslinkers resulted in the most favorable functional radial distribution and exhibited the strongest interactions. To validate the computational findings, additional analyses were performed utilizing Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA), radial distribution function (RDF), and hydrogen bond (HBond) occupancy. The calculated binding free energy demonstrated that all template molecules were capable to bind with both the monomers and crosslinkers, including 1-penten-3-one and N-morpholinomethyl-isopropyl-sulfide displaying the strongest interactions, with values of -12,674 kJ/mol and -11,646 kJ/mol, respectively. The congruence between the results obtained from the molecular simulation analyses highlights the crucial role of molecular dynamics simulations in the study and development of MIP for the analysis of marker compounds present in pork.Communicated by Ramaswamy H. Sarma.

7.
J Exp Pharmacol ; 15: 217-230, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37252059

RESUMO

Purpose: We unravel the effect of anthocyanin-containing purple sweet potato synbiotic yogurt (PSPY) on 3T3-L1 adipocyte differentiation and its fundamental molecular mechanisms. Methods: Molecular docking simulation was performed to observe and identify the affinity and interaction between bioactive compounds and targeted proteins. MDI (isobutylmethylxanthine, dexamethasone, and insulin)-containing medium, a cocktail that stimulates adipogenesis, was used in this study. The toxic effect possibility of the yogurt product was evaluated using 3-[4, 5-dimethylthiazol-2-yl]-2.5 diphenyl tetrazolium bromide (MTT) assay. A 0.25%, 0.5%, 1%, and 5% (v/v) plain or purple sweet potato yogurt supernatant was given to 3T3-L1 preadipocyte culture medium from 24 h after seeding until day 11 of MDI-induced differentiation. The mRNA expression and lipid accumulation were analyzed using RT-qPCR and Oil red O staining, respectively, on day 11 after differentiation induction. Results: In silico study suggested that anthocyanin-derived compounds have the potential to inhibit peroxisome proliferator activated receptor gamma (PPAR-γ), a master regulator for white adipogenesis. Anthocyanin-containing PSPY significantly suppressed the expression of Pparg, Adipoq, Slc2a4, and Pgc1a. PSPY significantly suppressed Pparg with 1% and 5% concentrations, while with a concentration of 0.25%, PSPY significantly suppressed Adipoq expression as compared to control. Significant inhibition of Slc2a4 and Pgc1a was observed starting from a 0.25% concentration of PSPY. The suppression of adipogenic genes was also observed with the treatment of plain yogurt; however, the effects were relatively lower than the PSPY. The group treated with 1% and 5% of PSPY also showed inhibition effects on lipid accumulation. Conclusion: This study demonstrated PSPY inhibition effect on white adipocyte differentiation through suppression of Pparg and its downstream genes, Adipoq and Slc2a4, indicating the potential of this yogurt as a functional food for obesity management and prevention.

8.
Medicine (Baltimore) ; 102(16): e33523, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37083777

RESUMO

RATIONALE: Acute respiratory distress syndrome (ARDS) in miliary tuberculosis (TB) remains rare, especially in pregnant women. The role of blood purification is potential in managing ARDS due to miliary TB. PATIENT CONCERNS: A 36-year-old woman presenting with difficulty breathing 6 hours before admission. She never had any constitutional symptoms due to TB. DIAGNOSES: ARDS in TB was diagnosed based on the deterioration of PaO2/FiO2, increased acute phase reactants, positive gene-Xpert, and typical chest x-ray of miliary TB. INTERVENTIONS: A C-section was performed and followed by continuous venovenous hemofiltration to tackle her inflammatory condition. antituberculosis drugs were given after the transaminases showed declining trends. OUTCOMES: No major complications associated with continuous venovenous hemofiltration occurred. After 14 days of hospitalization, the patient's clinical condition improved and was finally discharged. LESSONS: This case underscores the potential role of blood purification in ARDS due to miliary TB in pregnancy.


Assuntos
Síndrome do Desconforto Respiratório , Tuberculose Miliar , Humanos , Feminino , Gravidez , Adulto , Tuberculose Miliar/complicações , Tuberculose Miliar/diagnóstico , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , Transaminases , Respiração , Antituberculosos/uso terapêutico
9.
J Med Case Rep ; 17(1): 157, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37041589

RESUMO

BACKGROUND: Miliary tuberculosis is a life-threatening disease caused by the hematogenous spread of Mycobacterium tuberculosis. It is uncommon in pregnancy. Mortality rates for patients with miliary tuberculosis who require mechanical ventilation are high (60-70%). CASE PRESENTATION: We reported a rare and challenging case, a 35-year-old Asian woman with 34 weeks of pregnancy, and miliary tuberculosis with acute respiratory distress syndrome and septic shock. The patient presented with severe acute respiratory distress syndrome, necessitating mechanical ventilation, vasopressor, and pregnancy termination with caesarean section. The patient underwent blood purification with continuous veno-venous hemofiltration using an oXiris filter for 24 hours. After continuous veno-venous hemofiltration, the patient's condition was greatly improved, and the patient was successfully extubated and was able to breathe spontaneously without vasopressor on the third day. High levels of interleukin-6, interleukin-10, procalcitonin, C-reactive protein, interferon-γ, and tumor necrosis factor-α were found postoperatively. CONCLUSION: The bacterial infection of tuberculosis, acute respiratory distress syndrome, and the stress response from the caesarean section contributed to the high levels of cytokines, which correlated with the patient's severe inflammatory condition. The cytokine levels were greatly reduced after the blood purification procedure and this might be associated with the patient's clinical improvement. Extracorporeal blood purification could help to disrupt the vicious cycle of inflammation.


Assuntos
Mycobacterium tuberculosis , Síndrome do Desconforto Respiratório , Choque Séptico , Tuberculose Miliar , Humanos , Gravidez , Feminino , Adulto , Tuberculose Miliar/complicações , Cesárea/efeitos adversos , Síndrome do Desconforto Respiratório/etiologia , Choque Séptico/complicações
10.
Germs ; 12(2): 158-168, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36504604

RESUMO

Introduction: Coronavirus disease-2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) manifests in a broad clinical spectrum. COVID-19 survivors report various symptoms up to several months after being infected. The purpose of this study was to determine the prevalence of persistent COVID-19 syndrome in Indonesia, the factors that influence the incidence, and the quality of life. Methods: This was a cross-sectional study with an online questionnaire conducted in January 2021. Inclusion criteria were: adult Indonesian citizens who had recovered from COVID-19, and were confirmed negative by RT-PCR of nasal swabs or had undergone an isolation period for a minimum of 14 days. Data analysis was performed by the Chi-square test, followed by multivariate analysis with the backward likelihood ratio method. Results: From a total of 385 respondents, 256 (66.5%) experienced persistent COVID-19 syndrome. The most prevalent symptoms were fatigue (29.4%), cough (15.5%), and muscle pain (11.2%). Of the five aspects of quality of life, the most commonly reported aspects were pain/discomfort and anxiety/depression. The risk of persistent COVID-19 syndrome was significantly higher in subjects with older age, comorbidities, higher clinical severity, previous treatment in hospital, presence of pneumonia, and those who had required oxygen therapy. In the multivariate analysis, the most influential factor for the incidence of persistent COVID-19 syndrome was pneumonia (aOR 2.31, 95% CI 1.29-4.11, p<0.002). Conclusions: The prevalence of the persistent COVID-19 syndrome in Indonesia was high, which affects the quality of life of COVID-19 survivors. Pneumonia was the main factor that influenced the incidence of persistent COVID-19 syndrome. Further research with a larger sample size and a longer study time is recommended to control COVID-19 and its impact on the health and quality of life of COVID-19 survivors.

11.
Water Sci Technol ; 86(12): 3093-3112, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36579872

RESUMO

Treatment of ammonia- and nitrate-rich wastewater, such as that generated in the aquaculture industry, is important to prevent environmental pollution. The anaerobic ammonium oxidation (anammox) process has been reported as a great alternative in reducing ammoniacal nitrogen concentration in aquaculture wastewater treatment compared to conventional treatment systems. This paper will highlight the impact of the anammox process on aquaculture wastewater, particularly in the regulation of ammonia and nitrogen compounds. The state of the art for anammox treatment systems is discussed in comparison to other available treatment methods. While the anammox process is viable for the treatment of aquaculture wastewater, the efficiency of nitrogen removal could be further improved through the proper use of anammox bacteria, operating conditions, and microbial diversity. In conclusion, a new model of the anammox process is proposed in this review.


Assuntos
Compostos de Amônio , Águas Residuárias , Amônia , Oxidação Anaeróbia da Amônia , Anaerobiose , Oxirredução , Nitrogênio , Aquicultura , Reatores Biológicos/microbiologia , Desnitrificação
12.
Pak J Biol Sci ; 25(1): 67-77, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35001577

RESUMO

<b>Background and Objectives:</b> Blue swimming crab, <i>Portunus pelagicus</i> (Linnaeus, 1758) are economically important sources of soft-shell products for export demand. However, increasing over-exploitation and pollution towards the sea resources affected the production of the <i>P. pelagicus</i>. The study aimed to determine the microalgal preference and feeding density of the monospecific (<i>Nannochloropsis oculata</i>, <i>Chlorella vulgaris</i>, <i>Isochrysis galbana</i> and <i>Chaetoceros wighamii </i>) by individual <i>P. pelagicus </i>larvae. <b>Materials and Methods:</b> In the microalgal preference study, one polystyrene tray with 100 holes was set up in the experimental tank (200 L) to place the 50 mL centrifuges tube. For feeding density study, the survival rate, Specific Growth Rate (SGR), Body Weight (BW) and Larvae Stage Index (LSI) of each larvae stage were collected from Zoea 1 (Z<sub>1</sub>) till megalopa. <b>Results:</b> Results for mean microalgal preference of individual larvae preferred most <i>Chlorella vulgaris</i> during Zoea 1 and 2, the larvae consumed the highest of <i>Nannochloropsis</i> <i>oculata</i>. For Zoea 3 and 4, the highest preference is <i>Isochrysis galbana</i>. For feeding regime, Zoea 1, larvae fed rotifer, <i>Artemia</i> and <i>Chlorella vulgaris</i> (T<sub>3</sub>), was the highest survival rate, Zoea 2 was larvae fed rotifer, <i>Artemia</i> and <i>Nannochloropsis oculata</i> (T<sub>5</sub>) and both Zoea 3 and Zoea 4, larvae fed rotifer, <i>Artemia</i> and <i>Isochrysis galbana</i> (T<sub>4</sub>) was the highest survival rate. The highest SGR and LSI were obtained in T<sub>4</sub> cultured in 14 days. <b>Conclusion:</b> In conclusion, the microalgal preference and feeding density of the selected microalgae are different depending on each larvae stage.


Assuntos
Ração Animal/normas , Braquiúros/crescimento & desenvolvimento , Microalgas/metabolismo , Ração Animal/microbiologia , Animais , Braquiúros/metabolismo
13.
J Biomol Struct Dyn ; 40(22): 11526-11532, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34338602

RESUMO

The target for COVID-19 has been successfully crystallized along with its inhibitor, named SARS-CoV-2 main protease, making it easier for drug discovery and development. Sponge (Clathria Sp.) is a marine species that can be found in Indonesia and has a unique chemical structure that is still rarely explored in its properties. Therefore, this study aims to examined the potential of marine natural products from sponge (Clathria Sp.) as SARS-CoV-2 main protease inhibitor using in silico method. The ligand structures were obtained from the Knapsack database and the protein structure obtained from the RCSB site with the PDB code: 6LU7. The molecular docking method was validated by re-docked the native ligand and calculated the RMSD value. The compounds contained in Sponge were docked into the active site of the protein based on the validated methods. Afterward, the molecular dynamics were performed for 100 ns simulation, then analyzed its system complex stability. The RMSD 1.329 Å was obtained by re-docked of native ligand which indicates that the docking method was valid. Molecular docking of the ligands showed mirabilin_G has binding energy -7.38 kcal/mol, compared to the native ligand N3 inhibitor that is -7.30 kcal/mol, and the ligand showed good stability from molecular dynamics simulation indicated by RMSD, RMSF and MM-PBSA binding free energy similar to the inhibitor during 100 ns simulation. Its indicated the potential of the compounds contained in the sponge as inhibitor of SARS-CoV-2 main protease.Communicated by Ramaswamy H. Sarma.


Assuntos
Produtos Biológicos , COVID-19 , Humanos , Ligantes , Simulação de Acoplamento Molecular , SARS-CoV-2 , Produtos Biológicos/farmacologia , Simulação de Dinâmica Molecular , Inibidores de Proteases/farmacologia
14.
Pak J Biol Sci ; 24(4): 461-467, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34486305

RESUMO

<b>Background and Objective:</b> The rate of population growth is not balanced with the rate of increase in national rice production. The attention of the government and researchers in Southeast Sulawesi on upland rice is still very low, even though the potential for increased upland rice production is quite promising. The research aimed to study the influence of KCl fertilizer and <i>Trichoderma </i>spp. on the growth and yield of upland rice. <b>Materials and Methods:</b> The study was conducted in a Randomized Block Design (RBD) consisting of 6 treatments i.e.: without KCl fertilizer and <i>T. asperellum</i> (K<sub>0</sub>), KCl 0.15 g/polybag+<i>T. asperellum </i>50 g/polybag (K<sub>1</sub>), KCl 0.30 g/polybag+<i> T. asperellum </i>40 g/polybag (K<sub>2</sub>), KCl 0.45 g/polybag+<i>T. asperellum </i>30 g/polybag (K<sub>3</sub>), KCl 0.60 g/polybag+<i>T. asperellum </i>20 g/polybag (K<sub>4</sub>) and KCl 0.75 g/polybag+<i>T. asperellum </i>10 g/polybag (K<sub>5</sub>) with 4 replication for each treatment. The data obtained were analyzed by analysis of variance (ANOVA) and conducted further tests with the Duncan Multiple Range Test (DMRT) at a 95% confidence level. <b>Results:</b> The results of the research revealed KCl fertilizer combination with <i>T. asperellum</i> in general, can increase the growth and yield of upland local aromatic red rice. Application of KCl fertilizers as 0.45 g/polybag equivalent to 90 kg ha<sup>1</sup> (K<sub>3</sub>) can provide optimal potassium nutrients for vegetative growth of upland rice. <b>Conclusion:</b> The treatment of KCl fertilizer as 0.45 g/polybag with <i>T. asperellum </i>30 g/polybag (K<sub>3</sub>) provides growth and yield of upland rice with an average production of4.95 t ha<sup>1</sup>.


Assuntos
Fertilizantes/normas , Oryza/crescimento & desenvolvimento , Cloreto de Potássio/metabolismo , Trichoderma/metabolismo , Fertilizantes/análise , Fertilizantes/estatística & dados numéricos , Indonésia , Cloreto de Potássio/química , Solo/química , Trichoderma/enzimologia
15.
Molecules ; 26(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071361

RESUMO

Nuclear receptor REV-ERBß is an overexpressed oncoprotein that has been used as a target for cancer treatment. The metal-complex nature of its ligand, iron protoporphyrin IX (Heme), enables the REV-ERBß to be used for multiple therapeutic modalities as a photonuclease, a photosensitizer, or a fluorescence imaging agent. The replacement of iron with cobalt as the metal center of protoporphyrin IX changes the ligand from an agonist to an antagonist of REV-ERBß. The mechanism behind that phenomenon is still unclear, despite the availability of crystal structures of REV-ERBß in complex with Heme and cobalt protoporphyrin IX (CoPP). This study used molecular dynamic simulations to compare the effects of REV-ERBß binding to Heme and CoPP, respectively. The initial poses of Heme and CoPP in complex with agonist and antagonist forms of REV-ERBß were predicted using molecular docking. The binding energies of each ligand were calculated using the MM/PBSA method. The computed binding affinity of Heme to REV-ERBß was stronger than that of CoPP, in agreement with experimental results. CoPP altered the conformation of the ligand-binding site of REV-ERBß, disrupting the binding site for nuclear receptor corepressor, which is required for REV-ERBß to regulate the transcription of downstream target genes. Those results suggest that a subtle change in the metal center of porphyrin can change the behavior of porphyrin in cancer cell signaling. Therefore, modification of porphyrin-based agents for cancer therapy should be conducted carefully to avoid triggering unfavorable effects.


Assuntos
Cobalto/química , Neoplasias/tratamento farmacológico , Protoporfirinas/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/química , Proteínas Repressoras/química , Sítios de Ligação , Química Farmacêutica/métodos , Heme/química , Humanos , Ferro/química , Cinética , Ligantes , Metais , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Peptídeos/química , Fármacos Fotossensibilizantes/química , Porfirinas/química , Ligação Proteica , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/metabolismo , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/genética , Transdução de Sinais
16.
Trop Life Sci Res ; 31(2): 79-105, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32922670

RESUMO

Nutritional quality of the hepatopancreas and gonads of orange portunid mud crab, Scylla olivacea was evaluated for each gender under four treatment of different water velocities (0, 20, 40 and 60 cm s-1), in terms of nutrient reserve and nutrient for reproduction. About 56 crabs were used in this study in which fatty acids composition was analysed using gas chromatography mass-spectrometry (GC-MS). For hepatopancreas analysis, monounsaturated fatty acids (MUFAs) were present in the highest fatty acids concentration, followed by polyunsaturated fatty acids (PUFAs) and, saturated fatty acids (SFAs). However, long-chain polyunsaturated fatty acids (LC-PUFAs) were displayed in low concentration in the hepatopancreas. Total fatty acid (TFAs) composition was significantly higher at moderate velocity of 20 cm s-1 compared to other water velocity treatments. For gonad analysis, 20 cm s-1 showed the highest TFA concentration of 93.34 mg g-1 while, the lowest concentration of 3.90 mg g-1 occurred at 0 cm s-1. There were significant differences in male and female crab's fatty acids contents of gonads at all flow velocities challenged (p < 0.05). PUFAs and MUFAs were dominant while, SFAs were observed at low concentration. This study revealed that, concentration of PUFAs increased as gonad maturation increased. The decreasing concentration of hepatopancreas fatty acids over the culture period indicated that nutrient was shifted from the hepatopancreas, to be used as energy reserved to gonads for further growth of eggs and offspring. The linkages between water flow strength, hepatopancreas, and gonad fatty acids concentrations, is fundamental knowledge useful in establishing efficient habitat velocities selection which will improve aquaculture production of mud crabs with high quality broodstock.

17.
Data Brief ; 29: 105232, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32099875

RESUMO

The present datasets were conducted to investigate glucose concentration in hemolymph, energy levels at selected body parts (hepatopancreas, muscle, gonad), and feces among different sexes of crabs cultured at four different water velocities (0, 20, 40, and 60 cm/s) during a 60-day culture period. A total of 102 immature crabs (51 males, and 51 females) were sampled from Kuala Muda, Kedah coastal water, Peninsular Malaysia (5°39'N 100°19'E) from April to November of 2018. Results indicated that glucose concentration was the highest at water velocity of 60 cm/s for both male and female crabs (♂: 3.76 ± 0.08 mmol/L; ♀: 3.63 ± 0.06 mmol/L), whereas at 0 cm/s, the lowest levels of glucose concentration (♂: 0.13 ± 0.08 mmol/L; ♀: 0.19 ± 0.06 mmol/L) were recorded. As for energy analysis in hepatopancreas, results showed that both male and female crabs recorded the highest levels at 0 cm/s (no flow) with 37.919 ± 0.07 KJ/g and 34.636 ± 0.50 KJ/g, respectively. Energy for locomotion (muscle) of male crabs recorded the highest at 0 cm/s (♂: 26.823 ± 0.06 KJ/g), meanwhile for females, the highest was recorded at 20 cm/s (26.607 ± 0.34 KJ/g). Energy for reproduction of males could not be compared due to an insufficient available amount of testes/vas deferens, whereas female crabs recorded the highest energy usage at 20 cm/s water velocity (♀: 37.895 ± 0.08 KJ/g). For feces, both male and female crabs recorded the lowest energy at 60 cm/s (♂: 5.841 ± 0.03 KJ/g; ♀: 5.393 ± 0.01 KJ/g). Glucose assessment showed a direct relationship between increased velocity and glucose secretion in hemolymph at high velocity of 60 cm/s (stress condition) compared to other treatments. Regarding energy analysis, this research improved the mechanism of hepatopancreas, gonad, muscle and feces functions in development and reproduction, while it shed light on the influence of velocity on energy metabolism of S. olivacea.

18.
J Parasitol Res ; 2019: 6438497, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863624

RESUMO

Soil transmitted helminths (STH) infection is a major health problem in tropical countries such as Indonesia. Albendazole is an effective and widely used anthelmintic agent to treat STH; however, it is not effective towards T. trichiura and its effectiveness varies between populations. Hence, we conducted a study to determine the effectiveness of triple dose albendazole in children of Perobatang village, Southwest Sumba, Indonesia. A pre-post study was carried out in Perobatang village on July 2016. Children aged 1-15 years old were enrolled in the study and asked to collect stool samples which were then examined using Kato-Katz method. The children infected with STH were given albendazole 400 mg for three consecutive days. From 246 subjects examined, 192 (78%) were positive for any STH consisting of T. trichiura (64%), A. lumbricoides (60%), and hookworms (10%). After treatment, the prevalence of STH decreased significantly (McNemar test, p<0.001) to 27%, T. trichiura 25%, A. lumbricoides 2%, and hookworm 0%. Cure rate for T. trichiura, A. lumbricoides, and hookworms was 61%, 97%, and 100%, respectively. Significant decrease of eggs per gram of feces was found in all STH (Wilcoxon test, p value <0.001 for A. lumbricoides and T. trichiura, p value = 0.027 for hookworms); egg reduction rate for T. trichiura was 91%, A. lumbricoides was 100%, and hookworms was 100%. In conclusion, triple dose albendazole is effective in controlling STH in children of Perobatang village, Southwest Sumba, Indonesia.

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