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Indigenous medicinal plants with naturally inherited antimicrobial properties are promising sources of antimicrobial agents. Two indigenous Ethiopian traditional medicinal plants (Rhamnus prinoide and Croton macrostachyus) extracted using different solvents and the yield percentage, phytochemical analysis and antimicrobial activity of the plant extracts were examined and compared. The results of this study revealed that Rhamnus prinoide leaf extract using aqueous methanol/ethanol (1 : 1) had the highest yield (15.12 %), a minimum inhibitory concentration of 0.625â mg/mL, and a minimum bactericidal concentration of 10â mg/mL against S. aureus. Croton macrostachyus leaves showed a yield of 14.7 ±0.37 %, a minimum inhibitory concentration of 40â mg/mL, and a minimum bactericidal concentration of 40â mg/mL against S. aureus and E. coli. GC-MS analysis revealed that aqueous methanol/ethanol (1 : 1) of Rhamnus prinoide and Croton macrostachyus leaf extracts were composed of bioactive carbohydrates, flavonoid acid phenols, and terpenoids, while Croton macrostachyus extract contained primarily phytol (30.08 %). The presence of bioactive compounds confirms the traditional use of these plant leaves to treat various diseases, including wounds, leading to the conclusion that they could be applied to textiles for wound dressing in future studies.
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Anti-Infecciosos , Plantas Medicinais , Plantas Medicinais/química , Metanol/química , Escherichia coli , Staphylococcus aureus , Bactérias , Antibacterianos/farmacologia , Antibacterianos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Anti-Infecciosos/farmacologia , EtanolRESUMO
Silicon (Si)-based anodes are currently considered a feasible solution to improve the energy density of lithium-ion batteries owing to their sufficient specific capacity and natural abundance. However, Si-based anodes exhibit low electric conductivities and large volume changes during cycling, which could easily trigger continuous breakdown/reparation of the as-formed solid-electrolyte-interphase (SEI) layer, seriously hampering their practical application in current battery technology. To control the chemoelectrochemical instability of the conventional SEI layer, we herein propose the introduction of elemental sulfur into nonaqueous electrolytes, aiming to build a sulfur-mediated gradient interphase (SMGI) layer on Si-based anodes. The SMGI layer is generated through the domino reactions (i.e., electrochemical cascade reactions) involving the electrochemical reductions of elemental sulfur followed by nucleophilic substitutions of fluoroethylene carbonate, which endows the corresponding SEI layer with strong elasticity and chemomechanical stability and enables rapid transportation of Li+ ions. Consequently, the prototype Si||LiNi0.8Co0.1Mn0.1O2 cells attain a high-energy density of 622.2 W h kg-1 and a capacity retention of 88.8% after 100 cycles. Unlike previous attempts based on sophisticated chemical modifications of electrolyte components, this study opens a new avenue in interphase design for long-lived and high-energy rechargeable batteries.
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Rechargeable lithium-based batteries built with high-energy anode materials (e.g., silicon-based and silicon-derivative materials) are considered a feasible solution to satisfy the stringent requirements imposed by emerging markets, including electric vehicles and grid storage, due to their higher energy density compared to contemporary lithium-ion batteries. The robustness of the solid electrolyte interphase (SEI) layer on high-energy anodes is critical to achieve long-term and stable cycling performances of the batteries. Herein, we propose a new type of designer cathode additive (DCA), i.e., an ultrathin coating layer of elemental sulfur on the cathode, for the in situ formation of a thin and robust SEI layer on various types of high-energy anodes. The DCA elemental sulfur undergoes simultaneous oxidation and reduction paths, forming lithium alkyl sulfate (R-OSO2OLi) and poly(ethylene oxide) (PEO)-like polymers on the anode surface. The as-formed R-OSO2OLi/PEO-modified SEI layer has good lithium cation (Li+) permeability to facilitate fast ion transportation across the interphases and superior elasticity to adapt to large volume changes, which is particularly effective for improving the cycling efficiency of high-energy anodes (e.g., ca. 14-35% increase in capacity retention for the silicon-carbon composite (SiC) or silicon-tin alloy (Si-Sn)||LiFePO4 cells). The present work opens a new avenue toward the practical deployment of high-energy rechargeable lithium-based batteries.
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Zinc citrate (ZC) has been widely used in food as an important nutritional supplement. Accurate detection of ZC in food is important for health and safety. In this study, THz time-domain spectroscopy (THz-TDS) is used to quantitatively detect ZC in flour and milk powder mixtures. In our research, 15 different contents of ZC in flour and milk powder mixtures were prepared and measured by THz-TDS. A partial least squares (PLS) model was established based on the quantitative analysis of the absorption coefficient data of these two mixtures at 0.5-3.0 THz. The R2 and rms error (RMSE) given by the PLS model prediction were, respectively, 0.999 and 0.14% ZC in flour and 0.999 and 0.20% ZC in milk mixtures, indicating the predictions of the PLS model are in excellent agreement with the experimental measurements. The results show that combining THz-TDS with the PLS model can be used for accurate, quantitative analyses of ZC in food mixtures.
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Espectroscopia Terahertz , Animais , Citratos , Farinha , Leite , Pós , Espectroscopia Terahertz/métodos , ZincoRESUMO
The increasing demand for high-energy powers have greatly incentivized the development of lithium carbon fluoride (Li||CFx ) cells. Five kinds of non-aqueous liquid electrolytes with various kinds of lithium salts (LiX, X=PF6 - , TFSI- , BF4 - , ClO4 - , and CF3 SO3 - ) were comparatively studied. Intriguingly, the LiBF4 -based electrolyte show relatively moderate ionic conductivities; yet, the corresponding Li||CFx cells deliver the highest discharge capacities among them. A combination of morphological and compositional analyses of the discharge CFx cathode suggest that the moderate donicity of BF4 - anion is accountable for favoring the breakdown of C-F bonds, and subsequently forming crystalline lithium fluoride as the main discharge products. This work brings not only fresh understanding on the role of salt anions for Li||CFx cells, but also inspire the electrolyte design for other conversion-type (sulfur and/or organosulfur) cathode materials desired for high-energy applications.
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Loss of functional ß-cell mass caused by lipotoxicity is a key pathogenic factor in the development of type 2 diabetes mellitus (T2DM). We have previously reported that sphingosine kinase (SK)1 is an endogenous protector of ß-cells against lipotoxicity. The current study reports that SK2, another isoform of SK, is a crucial mediator of lipotoxicity in ß-cells. Exposure of ß-cells to palmitatic acid (PA), a saturated free fatty acid, resulted in a nearly 2-fold increase in SK2 expression, which paralleled the induction of cell death in a similar dose- and time-dependent fashion. Silencing SK2 expression by its specific small interfering RNAs significantly inhibited PA-induced cell death and caspase-3 activation, whereas overexpression of SK2 promoted lipotoxicity in ß-cells. Mechanistically, upon exposure to PA, endogenous SK2 was shuttled from the nucleus to the cytoplasm, where it interacted with B-cell lymphoma-extra-large (Bcl-xL), leading to mitochondrial apoptotic pathway activation and cell death. By blocking SK2 translocation and its interaction with Bcl-xL, either the nuclear export signal mutant (L423A/L425A) or the BH3 domain mutant (L219A) of SK2 significantly attenuated ß-cell lipotoxicity. Furthermore, SK2 deficiency in mice significantly prevented the loss of ß-cell mass, preserved insulin production, and ameliorated the diabetic phenotype in an established T2DM model induced by feeding a high-fat diet accompanied by administration of streptozotocin. These findings provide the first evidence, in vitro and in vivo, of a critical role for SK2 in mediating ß-cell lipotoxicity and the progression of diabetes.-Song, Z., Wang, W., Li, N., Yan, S., Rong, K., Lan, T., Xia, P. Sphingosine kinase 2 promotes lipotoxicity in pancreatic ß-cells and the progression of diabetes.
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Diabetes Mellitus Tipo 2/metabolismo , Células Secretoras de Insulina/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Animais , Apoptose/fisiologia , Caspase 3/metabolismo , Morte Celular/fisiologia , Células Cultivadas , Citoplasma/metabolismo , Dieta Hiperlipídica , Progressão da Doença , Humanos , Insulina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Transdução de Sinais/fisiologia , Proteína bcl-X/metabolismoRESUMO
OBJECTIVES: As a haloalkaliphilic, sulfur-oxidizing bacteria, Thialkalivibrio versutus D301 can remove sulfide, thiosulfate and polysulfide in wastewater, we investigated how it might be reused when mixed with high concentrations of elemental sulfur. RESULTS: A process is described to immobilize T. versutus cells by using superparamagnetic Fe3O4 nanoparticles (NPs) under haloalkaliphilic conditions (i.e. pH 9.5, 0.5 M Na(+)). The saturation magnetization value (δs) of immobilized cells was 55.1 emu/g. The Fe3O4 NPs-coated cells had the similar sulfur oxidization activity to that of free cells, and they could be reused six batch cycles. Analysis of hydraulic diameters showed that bacterial cells were immobilized by Fe3O4 NPs due to the nano-size effects. CONCLUSIONS: Magnetic immobilization is a convenient technique for cell immobilization under haloalkaliphilic conditions and is a promising technology for large scale application.
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Células Imobilizadas/metabolismo , Ectothiorhodospiraceae/metabolismo , Magnetismo , Nanopartículas , Compostos de Enxofre/metabolismo , Enxofre/metabolismo , Concentração de Íons de HidrogênioRESUMO
In a previous report, we identified a novel molecule, SHATI/NAT8L, having an inhibitory effect on methamphetamine (METH)-induced hyperlocomotion, sensitization, and conditioned place preference (CPP). SHATI/NAT8L attenuates the METH-induced increase in dopamine overflow in the nucleus accumbens (NAc) by promoting plasmalemmal and vesicular dopamine uptake. However, the biological functions of the protein remain unclear. In this study, we explored NAT8L-binding proteins using pull-down assays and identified a number of components of the adaptor protein (AP)-2 complex, which is a multimeric protein localized to the plasma membrane that functions to internalize cargo during clathrin-mediated endocytosis. To investigate whether NAT8L regulates the receptor localization to the cell surface, cell-surface dopamine D1 receptor in the NAc of Nat8l knockout (KO) mice was quantified. We found that dopamine D1 receptor on the cell surface was increased in the NAc of Nat8l KO mice compared with the wild type (WT) animals. Consistent with this finding, Nat8l KO mice showed higher basal locomotor activity and heightened sensitivity to D1 agonist compared with WT mice. In addition, METH-induced sensitization and CPP were enhanced in Nat8l KO mice. These results suggest that NAT8L might regulate the localization of cell-surface dopamine D1 receptor, thereby controlling basal behaviour and sensitivity to METH. Furthermore, we observed a single nucleotide polymorphism (SNP) in the human NAT8L gene related to reward dependence, a personality trait, and grey matter volume in the caudate nucleus in healthy subjects, suggesting that NAT8L might also affect human personality.
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Acetiltransferases/deficiência , Proteínas de Ciclo Celular/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Neurônios/metabolismo , Núcleo Accumbens/citologia , Receptores de Dopamina D1/metabolismo , Acetiltransferases/genética , Adulto , Animais , Benzazepinas/farmacologia , Células COS , Proteínas de Ciclo Celular/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Chlorocebus aethiops , Condicionamento Operante/efeitos dos fármacos , Agonistas de Dopamina/farmacologia , Feminino , Humanos , Masculino , Metanfetamina/farmacologia , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Atividade Motora/efeitos dos fármacos , Atividade Motora/genética , Neurônios/citologia , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
The protein-polysaccharide nanofibers have attracted intensive attention in promoting wound healing, due to their components and nanoscale fibrous structure that mimics the native extracellular matrix (ECM). For the full-thickness wounds, in addition to promoting healing, hemostatic property and antibacterial activity are also of critical importance. However, currently, protein-polysaccharide-based nanofiber membranes exhibit poor mechanical properties, lack inherent hemostatic and antibacterial capabilities, as well as the ability to promote tissue repair. In this study, we developed composited membranes, which were composed of collagen (Col) and chitosan (Chs), through solvent alteration and post-processing, the membranes showed enhanced stability under physiological conditions, proper hydrophilic performance and improved mechanical property. Appropriated porosity and water vapor transmission rate, which benefit to wound healing, were detected among all the membranes except for Col membrane. Aimed at wound dressing, hemocompatibility, antibacterial activity and cell proliferation of the electrospun membranes were evaluated. The results indicated that the Col/Chs composited membranes exhibited superior blood clotting capacity, and the membranes with Chs exceeding 60% possessed sufficient antibacterial activity. Moreover, compared with Chs nanofibers, significant increase in cell grow was detected in Col/Chs (1:3) membrane. Taken together, the electrospun membrane with multiple properties favorable to wound healing, superior blood coagulation, sufficient antibacterial performance and promoting cell proliferation property make it favorable candidate for full-thickness skin wound healing.
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Antibacterianos , Materiais Biocompatíveis , Proliferação de Células , Quitosana , Colágeno , Teste de Materiais , Membranas Artificiais , Nanofibras , Cicatrização , Quitosana/química , Cicatrização/efeitos dos fármacos , Nanofibras/química , Colágeno/química , Antibacterianos/química , Antibacterianos/farmacologia , Proliferação de Células/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Humanos , Bandagens , Animais , Porosidade , Coagulação Sanguínea/efeitos dos fármacos , Camundongos , Matriz Extracelular/metabolismoRESUMO
Non-aqueous electrolytes, generally consisting of metal salts and solvating media, are indispensable elements for building rechargeable batteries. As the major sources of ionic charges, the intrinsic characters of salt anions are of particular importance in determining the fundamental properties of bulk electrolyte, as well as the features of the resulting electrode-electrolyte interphases/interfaces. To cope with the increasing demand for better rechargeable batteries requested by emerging application domains, the structural design and modifications of salt anions are highly desired. Here, salt anions for lithium and other monovalent (e.g., sodium and potassium) and multivalent (e.g., magnesium, calcium, zinc, and aluminum) rechargeable batteries are outlined. Fundamental considerations on the design of salt anions are provided, particularly involving specific requirements imposed by different cell chemistries. Historical evolution and possible synthetic methodologies for metal salts with representative salt anions are reviewed. Recent advances in tailoring the anionic structures for rechargeable batteries are scrutinized, and due attention is paid to the paradigm shift from liquid to solid electrolytes, from intercalation to conversion/alloying-type electrodes, from lithium to other kinds of rechargeable batteries. The remaining challenges and key research directions in the development of robust salt anions are also discussed.
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Indeed, tumors are a significant health concern worldwide, and understanding the underlying mechanisms of tumor development is crucial for effective prevention and treatment. Epigenetics, which refers to changes in gene expression that are not caused by alterations in the DNA sequence itself, plays a critical role in the entire process of tumor development. It goes without saying that the effect of methylation on tumors is a significant aspect of epigenetics. Among the methylation modifications, DNA methylation is an important part, which plays a regulatory role in tumor-related genes. Ten-eleven translocation 2 (TET2) is a highly influential protein involved in the modification of DNA methylation. Its primary role is associated with the suppression of tumor development, making it a significant player in cancer research. However, TET2 is frequently mentioned in hematological diseases, its role in solid tumors has received little attention. Studying the changes of TET2 in solid tumors and the regulatory mechanism will facilitate its investigation as a clinical target for targeted therapy and may also provide directions for clinical treatment of malignant tumors.
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A nonparametric point-by-point (NPP) method is presented for high-accuracy measurement of the time-dependent frequency (laser frequency) in tunable laser absorption spectroscopy, crucial for ensuring ultimate measurement accuracy. In wavelength modulation spectroscopy in particular, the parametric methods in current use for time-dependent frequency measurement are insufficiently accurate and are difficult to apply to complex modulation scenarios. Based on a multi-scale viewpoint, point-by-point measurement of the frequency is realized by linear superposition of the frequency information mapped from the interferometric signal on a unit scale and on a local scale. Validation experiments indicate that the measurement accuracy of the proposed NPP method is three times that of the existing parametric methods, while effectively immunizing against non-ideal tuning effects. Additionally, the NPP method is suitable for use with arbitrarily complex modulations such as square wave modulation, for which parametric methods are inapplicable.
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Background: Deposition of immune complexes drives podocyte injury acting in the initial phase of lupus nephritis (LN), a process mediated by B cell involvement. Accordingly, targeting B cell subsets represents a potential therapeutic approach for LN. Ginsenoside compound K (CK), a bioavailable component of ginseng, possesses nephritis benefits in lupus-prone mice; however, the underlying mechanisms involving B cell subpopulations remain elusive. Methods: Female MRL/lpr mice were administered CK (40 mg/kg) intragastrically for 10 weeks, followed by measurements of anti-dsDNA antibodies, inflammatory chemokines, and metabolite profiles on renal samples. Podocyte function and ultrastructure were detected. Publicly available single-cell RNA sequencing data and flow cytometry analysis were employed to investigate B cell subpopulations. Metabolomics analysis was adopted. SIRT1 and AMPK expression were analyzed by immunoblotting and immunofluorescence assays. Results: CK reduced proteinuria and protected podocyte ultrastructure in MRL/lpr mice by suppressing circulating anti-dsDNA antibodies and mitigating systemic inflammation. It activated B cell-specific SIRT1 and AMPK with Rhamnose accumulation, hindering the conversion of renal B cells into plasma cells. This cascade facilitated the resolution of local renal inflammation. CK facilitated the clearance of deposited immune complexes, thus reinstating podocyte morphology and mobility by normalizing the expression of nephrin and SYNPO. Conclusions: Our study reveals the synergistic interplay between SIRT1 and AMPK, orchestrating the restoration of renal B cell subsets. This process effectively mitigates immune complex deposition and preserves podocyte function. Accordingly, CK emerges as a promising therapeutic agent, potentially alleviating the hyperactivity of renal B cell subsets during LN.
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Sulfite-based advanced oxidation technology has received considerable attention for its application in organic pollutants elimination. However, the potential of natural sediments as effective catalysts for sulfite activation has been overlooked. This study investigates a novel process utilizing suspended sediment/sulfite (SS/S(IV)) for degradation of metronidazole (MNZ). Our results demonstrate that MNZ degradation efficiency can reach to 93.1 % within 90 min with 12.0 g SS and 2.0 mM sulfite. The influencing environmental factors, including initial pH, SS dosage, S(IV) concentration, temperature, and co-existing substances were systematically investigated. Quenching experiments and electron paramagnetic resonance analyses results indicate that SO3â¢- is the primary active substance responsible for MNZ degradation, with involvement of SO4â¢-, SO5â¢-, and â¢OH. X-ray photoelectron spectroscopy and Mössbauer spectra reveal that Fe (III)-silicates play a crucial role in activating S(IV). Furthermore, analysis of degradation intermediates and pathways of MNZ is conducted using liquid chromatography with mass spectrometry (LC -MS). The toxicity of MNZ and its intermediates were also systematically evaluated by the T.E.ST. program and wheat seeds germination test. This study offers valuable insight into the activation of sulfite by natural sediments and could contribute to the development of SS-based advanced oxidation processes (AOPs) for the in-situ remediation of antibiotics-contaminated water environments.
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Sedimentos Geológicos , Metronidazol , Rios , Poluentes Químicos da Água , Sedimentos Geológicos/química , Poluentes Químicos da Água/análise , Rios/química , China , OxirreduçãoRESUMO
The minimization of irreversible active lithium loss stands as a pivotal concern in rechargeable lithium batteries, particularly in the context of grid-storage applications, where achieving the utmost energy density over prolonged cycling is imperative to meet stringent demands, notably in terms of life cost. Departing from conventional methodologies advocating electrode prelithiation and/or electrolyte additives, a new paradigm is proposed here: the integration of a designer lithium reservoir (DLR) featuring lithium orthosilicate (Li4SiO4) and elemental sulfur. This approach concurrently addresses active lithium consumption through solid electrolyte interphase (SEI) formation and mitigates minor yet continuous parasitic reactions at the electrode/electrolyte interface during extended cycling. The remarkable synergy between the Li-ion conductive Li4SiO4 and the SEI-favorable elemental sulfur enables customizable compensation kinetics for active lithium loss throughout continuous cycling. The introduction of a minute quantity of DLR (3 wt% Li4SiO4@S) yields outstanding cycling stability in a prototype pouch cell (graphite||LiFePO4) with an ampere-hour-level capacity (≈2.3 Ah), demonstrating remarkable capacity retention (≈95%) even after 3000 cycles. This utilization of a DLR is poised to expedite the development of enduring lithium batteries for grid-storage applications and stimulate the design of practical, implantable rechargeable batteries based on related cell chemistries.
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OBJECTIVE: The purpose of the present study was to investigate whether gamma-glutamyltransferase (GGT) is an independent predictor for future cardiovascular (CV) and all-cause mortality with prospective observational studies by meta-analysis. METHODS: Electronic literature databases (Cochrane Library, Medline, and Embase) were searched for relevant prospective observational studies on the association between baseline GGT and CV and all-cause mortality published prior to June 2012. Pooled adjust relative risk (RR) and corresponding 95% confidence intervals(CI) were calculated separately for categorical risk estimates(highest vs. lowest GGT quartile) and continuous risk estimates (per unit-log GGT increment). RESULTS: Seven studies with 273,141 participants were identified and analyzed. The pooled RR of CV mortality for highest vs. lowest GGT quartile was 1.52 (95% CI 1.36-1.70). The pooled RR of CV mortality for per unit-log (GGT) increment was 1.76 (95% CI 1.60-1.94). The pooled RR for all-cause mortality for highest vs. low GGT quartile was 1.56 (95% CI 1.34-1.83). Subgroup analyses based on region, gender, follow-up duration, and sample size showed that the positive association between GGT and risk of CV mortality was consistently observed in each subgroup except for the Asia subgroup (RR=1.59, 95% CI 0.76-3.30). CONCLUSIONS: GGT is an independent predictor for future CV mortality and all-cause mortality, and might be independent of alcohol intake.
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Doenças Cardiovasculares/mortalidade , gama-Glutamiltransferase/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Risco , Tamanho da Amostra , Adulto JovemRESUMO
For amine-based carbon dioxide capture, nitrogen oxides and sulfur oxides were the main pollutants that had a negative effect on the regeneration of solvent. Before carbon dioxide capture, the sulfur oxides in flue gas should be removed by the method of calcium salt, and then washed by alkaline solution to eliminate the residual nitrogen oxides and sulfur oxides. The washing wastewater containing sulfate and nitrate needs to be treated. In this study, a novel anaerobic-anoxic process was built up for the treatment of this washing wastewater. Nitrate was reduced to nitrogen by denitrifying bacteria. Sulfate was firstly reduced to sulfide by sulfate reducing bacteria, and then selectively oxidized to element sulfur by sulfide oxidizing bacteria. The treated liquid could be reused as absorption after the adjustment of pH value. The performances of this bioprocess were investigated under various pH values and S/N ratios. It was found that the optimal pH value of influent was 6.0, the percentages of denitrification and sulfate reducing could reach 90 and 89%, respectively. Seventy-six percent of sulfate was transformed into element sulfur. Nitrate significantly had a negative effect on sulfate reduction above 10 mM. As 20 mM nitrate, the sulfate reducing percentage would drop to 67%. These results showed that the anaerobic-anoxic process was feasible for the treatment of flue gas washing wastewater. It would be prospectively applied to other wastewater with the higher ratio of SO4(2-)/NO3(-).
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Bactérias/metabolismo , Gases , Nitratos/isolamento & purificação , Oxigênio/química , Enxofre/isolamento & purificação , Águas Residuárias , Anaerobiose , Biodegradação Ambiental , Reatores Biológicos , Concentração de Íons de HidrogênioRESUMO
BACKGROUND: Genistein (GEN) is one of the most well-known phytoestrogens identified in various legumes. Although increasing evidence shows GEN has a potential use in phytotherapy to regulate lipid metabolism, its therapeutic mechanisms have not yet been completely elucidated, especially epigenetic alterations of miRNAs to alleviate lipid accumulation in the liver remains unknown. PURPOSE: To clarify how GEN modulates the miRNA profile in HepG2 cells and investigate molecular mechanisms of the modulated miRNA on regulating hepatic lipid metabolism. METHODS: The miRNA microarray was performed to compare the miRNAs expression patterns, followed by determining principal miRNA and its target gene associated with hepatic lipid metabolism modulated by GEN. miR-363-3p mimics (mi) and phosphatase and tensin homolog (PTEN)-siRNA were transfected into HepG2 cells and GEN was further treated with the cells for 24 h RESULTS: GEN induced downregulation of miR-363-3p and upregulation of PTEN, which was a target mRNA of miR-363-3p. The miR-363-3p mi led to an upregulation of sterol-regulatory element-binding protein-1c (SREBP-1c) and its downstream lipid synthesis-related factors in HepG2 cells. In addition, the inhibition of PTEN led to an increase of lipogenesis, which was associated with the AKT/mTOR signal regulation. However, GEN treatment could abrogate the lipogenic effects of miR-363-3p mi or PTEN siRNA. The modulation was associated with estrogen receptor ß (ERß). CONCLUSION: We discerned a new mechanism that GEN regulated hepatic lipid metabolism by inhibiting miR-363-3p, which could be mediated via ERß and by targeting PTEN in HepG2 cells. Additionally, GEN reduced hepatic lipid accumulation by regulating PTEN-AKT/mTOR signal. It implicated a protective role of GEN by elucidating its epigenetic modification of the miRNA modulated by ERß on improving hepatic lipid metabolism and provided novel evidence of the mechanism on targeting miR-363-3p/PTEN in treating hepatic lipid disorders.
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Metabolismo dos Lipídeos , MicroRNAs , Humanos , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Transdução de Sinais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Genisteína/farmacologia , Células Hep G2 , MicroRNAs/genética , MicroRNAs/metabolismo , Serina-Treonina Quinases TOR/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , RNA Interferente Pequeno/metabolismo , LipídeosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The Aconitum genus plants as a natural pesticide for insecticide and rodent control has been recorded in Chinese folk. However, the insecticide effect, mechanism, and active composition of Aconitum polycarpum Chang ex W.T.Wang have not been studied further. AIM OF THE STUDY: This study was designed to analyze the chemical composition, evaluate contact toxicity of petroleum ether extracts (PEEs) and essential oils (EOs) of A. polycarpum, and further explore their possible insecticidal mechanism. MATERIALS AND METHODS: The roots of A. polycarpum were extracted with 90% methanol, and then extracted with petroleum ether to obtain PEEs; the EOs was extracted by distillation. The chemical compositions of PEEs and EOs were analyzed by GC-MS. Contact toxicity was evaluated by the immersion method. Exploring insecticidal mechanisms through in vitro enzyme inhibitory activity. RESULTS: 12 compounds were identified from PEEs by GC-MS, mainly including aliphatic (94.8%), the main compositions were Octadecadienol (ODO) (aliphatic, 53.2%) and L-Ascorbyl dipalmitate (LADP) (aliphatic, 36.1%). 24 compounds were identified in EOs. About 44.6% of the identified components were terpenoids and their derivatives, and the rest were mainly aliphatic (34.7%) and phenols (3.0%). The main chemical components were L (-)-Borneol (LB) (terpenoid, 28.3%), LADP (aliphatic, 19.1%), and Isoborneol (terpenoid, 9.1%). The contact toxicity indicated that the PEEs showed great contact toxicity against Spodoptera exigua (LC50â¯=â¯126.2â¯mg/L). Meanwhile, LADP (LC50â¯=â¯128.1â¯mg/L) and ODO (LC50â¯=â¯121.3â¯mg/L) was similar to that of Cyhalothrin (LC50â¯=â¯124.2â¯mg/L) in contact toxicity. In addition, we found that LADP and ODO exhibited excellent inhibitory activity against CarE (IC50â¯=â¯58.0, 56.1â¯mg/L, respectively) by measuring in vitro enzyme inhibitory activity, which was superior than Cyhalothrin (IC50â¯=â¯68.1â¯mg/L). CONCLUSIONS: The chemical compositions and contact toxicity of EOs and PEEs of A. polycarpum were analyzed and evaluated, and their insecticidal mechanisms were preliminarily discussed for the first time. It proved PEEs of A. polycarpum and its main components (LADP and ODO) exhibited excellent contact toxicity against S. exigua, and CarE was identified as a potential target for contact toxicity. This study indicated that the insecticidal activity of petroleum ether extracts from A. polycarpum is quite promising, and provides a practical and scientific basis for the development and application of botanical pesticides.
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Aconitum , Inseticidas , Óleos Voláteis , Inseticidas/farmacologia , Óleos Voláteis/toxicidade , Óleos Voláteis/química , TerpenosRESUMO
BACKGROUND: Currently, the mainstream treatments for systemic lupus erythematosus (SLE) are based on glucocorticoids and immunosuppressants, which are known to have considerable adverse effects. This meta-analysis is aimed at confirming the efficacy and safety of acupuncture therapy in combination with traditional medications in the treatment of SLE. METHODS: Multiple databases were searched for randomized controlled trials using acupuncture therapy in combination with conventional pharmacotherapy for the treatment of SLE, from the establishment of the database to March 2023. Study selection, data collection, as well as quality assessment were conducted by 2 reviewers independently. RevMan 5.4 and Stata 17 software were used for Meta-analysis. RESULTS: Seven eligible studies involving 514 patients with SLE were included. Meta-analysis demonstrated that in SLE patients, extra treatment with acupuncture was superior to drug therapy alone in improving the overall response rate (RR = 1.20, 95% confidence intervals [1.11, 1.29], P < .00001, heterogeneity P = .69, I2 = 0%) and regulating immunological indicators (C3, C4, IgG, T lymphocyte subpopulation, IL-6, ds-DNA, ESR) while reducing TCM symptom scores, the SLE Disease Activity Index (SLEDAI) and the incidence of adverse events on treatment (P ≤ 0.05). Additionally, it was able to reduce BUN, Scr and 24 hours urine protein, suggesting that acupuncture treatment had a protective effect on the kidneys. CONCLUSIONS: Acupuncture therapy combined with conventional pharmacotherapy is an efficient and safe way in the treatment of SLE. However, the conclusions drawn from this meta-analysis have some limitations due to the small number and uneven quality of the included studies, leading to heterogeneity and bias. Thus more relevant high-quality randomized controlled trials are needed for further evaluation in the future.