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BACKGROUND: Histone acetylation is an important epigenetic modification that regulates gene activity in response to stress. Histone acetylation levels are reversibly regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). The imperative roles of HDACs in gene transcription, transcriptional regulation, growth and responses to stressful environment have been widely investigated in Arabidopsis. However, data regarding HDACs in kenaf crop has not been disclosed yet. RESULTS: In this study, six HDACs genes (HcHDA2, HcHDA6, HcHDA8, HcHDA9, HcHDA19, and HcSRT2) were isolated and characterized. Phylogenetic tree revealed that these HcHDACs shared high degree of sequence homology with those of Gossypium arboreum. Subcellular localization analysis showed that GFP-tagged HcHDA2 and HcHDA8 were predominantly localized in the nucleus, HcHDA6 and HcHDA19 in nucleus and cytosol. The HcHDA9 was found in both nucleus and plasma membranes. Real-time quantitative PCR showed that the six HcHDACs genes were expressed with distinct expression patterns across plant tissues. Furthermore, we determined differential accumulation of HcHDACs transcripts under salt and drought treatments, indicating that these enzymes may participate in the biological process under stress in kenaf. Finally, we showed that the levels of histone H3 and H4 acetylation were modulated by salt and drought stress in kenaf. CONCLUSIONS: We have isolated and characterized six HDACs genes from kenaf. These data showed that HDACs are imperative players for growth and development as well abiotic stress responses in kenaf.

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BACKGROUND: Histone acetylation is an important epigenetic modification that regulates gene activity in response to stress. Histone acetylation levels are reversibly regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). The imperative roles of HDACs in gene transcription, transcriptional regulation, growth and responses to stressful environment have been widely investigated in Arabidopsis. However, data regarding HDACs in kenaf crop has not been disclosed yet. RESULTS: In this study, six HDACs genes (HcHDA2, HcHDA6, HcHDA8, HcHDA9, HcHDA19, and HcSRT2) were isolated and characterized. Phylogenetic tree revealed that these HcHDACs shared high degree of sequence homology with those of Gossypium arboreum. Subcellular localization analysis showed that GFP-tagged HcHDA2 and HcHDA8 were predominantly localized in the nucleus, HcHDA6 and HcHDA19 in nucleus and cytosol. The HcHDA9 was found in both nucleus and plasma membranes. Real-time quantitative PCR showed that the six HcHDACs genes were expressed with distinct expression patterns across plant tissues. Furthermore, we determined differential accumulation of HcHDACs transcripts under salt and drought treatments, indicating that these enzymes may participate in the biological process under stress in kenaf. Finally, we showed that the levels of histone H3 and H4 acetylation were modulated by salt and drought stress in kenaf. CONCLUSIONS: We have isolated and characterized six HDACs genes from kenaf. These data showed that HDACs are imperative players for growth and development as well abiotic stress responses in kenaf.

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In the last two decades, trans-sialidase of Trypanosoma cruzi (TcTS) has been an important pharmacological target for developing new anti-Chagas agents. In a continuous effort to discover new potential TcTS inhibitors, 3-amino-3-arylpropionic acid derivatives (series A) and novel phthaloyl derivatives (series B, C and D) were synthesized and molecular docking, TcTS enzyme inhibition and determination of trypanocidal activity were carried out. From four series obtained, compound D-11 had the highest binding affinity value (-11.1 kcal/mol) compared to reference DANA (-7.8 kcal/mol), a natural ligand for TS enzyme. Furthermore, the 3D and 2D interactions analysis of compound D-11 showed a hydrogen bond, π-π stacking, π-anion, hydrophobic and Van der Waals forces with all important amino acid residues (Arg35, Arg245, Arg314, Tyr119, Trp312, Tyr342, Glu230 and Asp59) on the active site of TcTS. Additionally, D-11 showed the highest TcTS enzyme inhibition (86.9% ±â€¯5) by high-performance ion exchange chromatography (HPAEC). Finally, D-11 showed better trypanocidal activity than the reference drugs nifurtimox and benznidazole with an equal % lysis (63 ±â€¯4 and 65 ±â€¯2 at 10 µg/mL) and LC50 value (52.70 ±â€¯2.70 µM and 46.19 ±â€¯2.36 µM) on NINOA and INC-5 strains, respectively. Therefore, D-11 is a small-molecule with potent TcTS inhibition and a strong trypanocidal effect that could help in the development of new anti-Chagas agents.

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Chagas, or American trypanosomiasis, remains an important public health problem in developing countries. In the last decade, trans-sialidase has become a pharmacological target for new anti-Chagas drugs. In this work, the aims were to design and find a new series of benzoic acid derivatives as trans-sialidase (TS) inhibitors and anti-trypanosomal agents. Three compounds (14, 18, and 19) sharing a para-aminobenzoic acid moiety showed more potent trypanocidal activity than the commercially available drugs nifurtimox and benznidazole in both strains: the lysis concentration of 50% of the population (LC50) was <0.15 µM on the NINOA strain, and LC50 < 0.22 µM on the INC-5 strain. Additionally, compound 18 showed a moderate inhibition (47%) on the trans-sialidase enzyme and a binding model similar to DANA (pattern A).

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Abstract Diospyros kaki L.f. belonging to family Ebenaceae, commonly known as persimmon is used as a medicinal plant in Chinese traditional medicine since many years for different ailments including cosmetics and dermatologic applications. Traditionally this plant is used to treat different skin conditions including pimples, skin eruptions and eczema. Present interest has been focused toward use of natural bioactive compounds in various curative and beautifying applications in dermatological and cosmeceutical disciplines. The objective of this article is to present cumulative data on potential use of D. kaki for its possible role in dermatologic and cosmetic applications. Scientific data has revealed an excellent position of D. kaki in both dermatology and cosmetic discipline making it a valuable choice in respective field. Active principles from different plant parts have shown to possess anti-inflammatory, antiallergic, photo-protective, and anti-wrinkle effects with appreciable activities against tyrosinase, elastase, and collagenase enzymes. Promising antioxidant activity and skin whitening potential, augmented by reduction in sebum contents, and reduction in size and number of skin pores make it a suitable choice as cosmetic ingredient. Data has been summarized and presented on available molecular mechanism that can contribute toward phytoconstituents usage in cosmetics and dermatology mediated by different cellular pathways. Crude extracts and some of phytochemical obtained from this plant such as isoquercitrin and hyperin have better reported activities than well-known cosmetic ingredients viz., arbutin, kojic acid and hydroquinone with possibility of having no side effects. Photo protection against degenerative effects of UVA, UVB and gamma radiation can help skin to fight well against oxidative stress and reactive oxygen species. Further investigation need to be directed toward human subjects for evaluation of these reported activities for obtaining optimum commercial and industrial benefits from this valuable plant.

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Chagas disease is one of the most important neglected parasitic diseases afflicting developed and undeveloped countries. There are currently limited options for inexpensive and secure pharmacological treatment. In this study, we employed a structure-based virtual screening protocol for 3180 FDA-approved drugs for repositioning of them as potential trans-sialidase inhibitors. In vitro and in vivo evaluations were performed for the selected drugs against trypomastigotes from the INC-5 and NINOA strains of T. cruzi. Also, inhibition of sialylation by the trans-sialidase enzyme reaction was evaluated using high-performance anion-exchange chromatography with pulse amperometric detection to confirm the mechanism of action. Results from the computational study showed 38 top drugs with the best binding-energies. Four compounds with antihistaminic, anti-hypertensive, and antibiotic properties showed better trypanocidal effects (LC50 range = 4.5-25.8 µg/mL) than the reference drugs, nifurtimox and benznidazole (LC50 range = 36.1-46.8 µg/mL) in both strains in the in vitro model. The anti-inflammatory, sulfasalazine showed moderate inhibition (37.6%) of sialylation in a trans-sialidase enzyme inhibition reaction. Sulfasalazine also showed the best trypanocidal effects in short-term in vivo experiments on infected mice. This study suggests for the first time that the anti-inflammatory sulfasalazine could be used as a lead compound to develop new trans-sialidase inhibitors.

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Chagas is a lethal chronic disease that currently affects 8-10 million people worldwide, primarily in South and Central America. Trypanosoma cruzi trans-sialidase is an enzyme that is of vital importance for the survival of the parasite due to its key role in the transfer of sialic acid from the host to the parasite surface and it also helps the parasite combat the host's immune system. This enzyme has no equivalent human enzyme; thus, it has become an interesting target for the development of inhibitors that combat the parasite. In this review, we summarize three classes of inhibitors (acceptor, donor and unrelated) with their inhibition values and their mode of action against this enzyme. Based on molecular docking, molecular dynamics and structure-activity relationship studies, it has been discovered that the molecules with -NH2, -OH and -COOH groups on an aromatic ring could be used as a scaffold for the development of new and potent trans-sialidase inhibitors due to their key interaction with active enzyme sites. In particular, carboxylic acid derivatives have importance over the sugar moiety due to their ease of synthesis and unique structure-activity relationship.

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Abstract: introduction: regulatory T-cells are the main component of peripheral tolerance and their level is decreased in autoimmunity. In dental amalgam, a mixture of metals is used as a restorative material. During daily a ctivities, these metals are ingested and affect renal, neurosensory and immune systems. Studies have demonstrated an increased risk of autoimmune diseases in patients with dental amalgam fillings. It was hypothesized that the percentage of regulatory T-cells decreases in individuals with amalgam fillings. Therefore this study was designed to determine and compare the percentage of regulatory T-cells in individuals with and without amalgam fillings. Material and Methods: This was a cross-sectional study. Subjects were divided into two groups with each group consisting of 40 individuals. Group I (study group) comprised individuals with amalgam fillings, and Group II (control group), individuals without amalgam fillings in their teeth. Blood samples of all the participants were collected and tagged with CD4 FITC, CD25 PE and CD127 PerCP-Cy monoclonal antibodies for the detection of regulatory T-cells, FACSCalibur was used for this purpose. Results: The percentage of regulatory T-cells in the control group was high (77.77 +/- 5.54 percent) compared to the study group (76.09 +/- 7.68 percent), however, on comparison, the difference was not statistically significant (p=0.25). Conclusion: Dental amalgam fillings did not show a declining effect on the percentage of regulatory T-cells.

Resumen: introducción: las células T reguladoras son el principal componente de la tolerancia periférica y su nivel se reduce en la autoinmunidad. En las obturaciones de amalgama, una mezcla de metales se utiliza como un material de restauración. Durante las actividades diarias, estos metales se ingieren y afectan el sistema renal, neurosensorial e inmunológico. Los estudios han demostrado un aumento del riesgo de enfermedades autoinmunes en pacientes con amalgamas dentales. Se planteó la hipótesis que el porcentaje de células T reguladoras disminuye en individuos con obturaciones de amalgama. Por tanto, este estudio fue diseñado para determinar y comparar el porcentaje de células T reguladoras en individuos con y sin obturaciones de amalgama. Material y Métodos: Se realizó un estudio de corte transversal. Los sujetos fueron divididos en dos grupos, cada uno con 40 individuos. El grupo I (de estudio) estuvo conformado por individuos con obturaciones de amalgama y el grupo II (de control) por individuos sin obturaciones de amalgma. Se colectaron muestras de sangre, las que fueron marcadas con anticuerpos monoclonales CD4 FITC, CD25 PE y CD127 PerCP-C para detectar las células T reguladoras, se utilizó FACSCalibur para este propósito. Resultados: El porcentaje de células T reguladoras en el grupo control fue alta (77,77 +/- 5,54 por ciento) en comparación con el grupo de estudio (76,09 +/- 7,68 por ciento), pero esta diferencia no fue estadísticamente significativa (p=0,25). Conclusión: Las obturaciones de amalgama no se asociaron con una disminución en el porcentaje de células T reguladoras.

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