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1.
Environ Sci Pollut Res Int ; 30(54): 115543-115555, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37884718

RESUMO

The limited application of high-sulfur coal (HSC) and the increasing severity of copper pollution in solution are two pressing issues. To alleviate such issues, a sulfur self-doped coal-based adsorbent (HSC@ZnCl2) was obtained by pyrolysis (850 °C, 60 min holding time) of HSC and ZnCl2 with a mass ratio of 1:0.5. The results adsorption experiment revealed that the endothermic and spontaneous adsorption process was consistent with the Sips isothermal model (R2 = 0.992) and pseudo-second-order kinetic (R2 = 0.994), and that the adsorption process with a maximum adsorption capacity of 11.97 mg/g. Meanwhile, the adsorption of Cu2+ onto HSC@ZnCl2 was a result of the synergistic effects of various interactions, such as the complexation by oxygen-containing functional groups, electrostatic attraction and surface precipitation by ZnS on the adsorbent surface, and the process also included redox reaction. The findings of this work indicate that the preparation of sulfur self-doped coal-based adsorbent prepared from high-sulfur coal is a promising method for its large-scale utilization.


Assuntos
Cobre , Poluentes Químicos da Água , Carvão Mineral , Adsorção , Enxofre , Cinética , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio
3.
Commun Biol ; 6(1): 509, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37169941

RESUMO

Osimertinib sensitive and resistant NSCLC NCI-H1975 clones are used to model osimertinib acquired resistance in humanized and non-humanized mice and delineate potential resistance mechanisms. No new EGFR mutations or loss of the EGFR T790M mutation are found in resistant clones. Resistant tumors grown under continuous osimertinib pressure both in humanized and non-humanized mice show aggressive tumor regrowth which is significantly less sensitive to osimertinib as compared with parental tumors. 3-phosphoinositide-dependent kinase 1 (PDK1) is identified as a potential driver of osimertinib acquired resistance, and its selective inhibition by BX795 and CRISPR gene knock out, sensitizes resistant clones. In-vivo inhibition of PDK1 enhances the osimertinib sensitivity against osimertinib resistant xenograft and a patient derived xenograft (PDX) tumors. PDK1 knock-out dysregulates PI3K/Akt/mTOR signaling, promotes cell cycle arrest at the G1 phase. Yes-associated protein (YAP) and active-YAP are upregulated in resistant tumors, and PDK1 knock-out inhibits nuclear translocation of YAP. Higher expression of PDK1 and an association between PDK1 and YAP are found in patients with progressive disease following osimertinib treatment. PDK1 is a central upstream regulator of two critical drug resistance pathways: PI3K/AKT/mTOR and YAP.


Assuntos
Neoplasias Pulmonares , Camundongos , Animais , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Receptores ErbB/genética , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Mutação , Serina-Treonina Quinases TOR/genética , Fosfatidilinositóis
4.
CNS Neurosci Ther ; 29(11): 3307-3321, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37183545

RESUMO

AIMS: Alzheimer's disease (AD) and type 2 diabetes (T2D) are two of the most common diseases in elderly population and they have a high rate of comorbidity. Study has revealed that T2D is a major risk factor of AD, and thus exploring therapeutic approaches that can target both diseases has drawn much interest in recent years. In this study, we tried to explore drugs that could be potentially used to prevent or treat both AD and T2D via a drug repositioning approach. METHODS: We first searched the known drugs that may be effective to T2D treatment based on the network distance between the T2D-associated genes and drugs deposited in the DrugBank database. Then, via molecular docking, we further screened these drugs by examining their interaction with islet amyloid polypeptide (IAPP) and Aß42 peptide, the key components involved in the pathogenesis of T2D or AD. Finally, the binding between the selected drug candidates and the target proteins was verified by molecular dynamics (MD) simulation; and the potential function of the drug candidates and the corresponding targets were analyzed. RESULTS: From multiple resources, 734 T2D-associated genes were collected, and a list of 1109 drug candidates for T2D was obtained. We found that hypericin had the lowest binding energy and the most stable interaction with either IAPP or Aß42 peptide. In addition, we also found that the target genes regulated by hypericin were differentially expressed in the tissues related to the two diseases. CONCLUSION: Our results show that hypericin may be able to bind with IAPP and Aß42 stably and prevent their accumulation, and thus could be a promising drug candidate for treating the comorbidity of AD and T2D.


Assuntos
Doença de Alzheimer , Diabetes Mellitus Tipo 2 , Idoso , Humanos , Doença de Alzheimer/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Simulação de Acoplamento Molecular , Reposicionamento de Medicamentos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/uso terapêutico , Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Peptídeos beta-Amiloides/metabolismo
5.
J Nat Prod ; 86(1): 24-33, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36634312

RESUMO

Hyperuricemia is the result of overproduction and/or underexcretion of uric acid, and it is a well-known risk factor for gout, hypertension, and diabetes. However, available drugs for hyperuricemia in the clinic are limited. Recently, a lot of research has been conducted in order to discover new uric acid-lowering agents from plants and foods. We found that the extracts from the pericarp of mangosteen reduced urate. Bioactivity-guided study showed that α-mangostin was the principal constituent. Herein, we reported for the first time the hypouricemic activities and underling mechanism of α-mangostin. The α-mangostin dose- and time-dependently decreased the levels of serum urate in hyperuricemic mice and markedly increased the clearance of urate in hyperuricemic rats, exhibiting a promotion of urate excretion in the kidney. Further evidence showed that α-mangostin significantly decreased the protein levels of GLUT9 in the kidneys. The change in the expression of URAT1 was not observed. Moreover, α-mangostin did not inhibit the activities of xanthine oxidoreductase and uricase in vitro or in vivo. Taken together, these findings suggest that α-mangostin has potential to be developed as a new anti-hyperuricemic agent with promoting uric acid excretion.


Assuntos
Garcinia mangostana , Hiperuricemia , Ratos , Camundongos , Animais , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Ácido Úrico/metabolismo , Xantina Oxidase , Rim/metabolismo
7.
Environ Sci Pollut Res Int ; 29(21): 31567-31576, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35001264

RESUMO

The pollutants degradation rate of iron ore tailings-based heterogeneous catalysts is the main factor limiting its application. Herein, an iron ore tailings-based Fenton-like catalyst (I/W(3:1)-900-60) with a relatively fast catalysis rate was constructed by co-pyrolysis (900°C, 60 min holding time) of iron ore tailings and wheat straw with a mass ratio of 3:1. With wheat straw blending, the generated I/W(3:1)-900-60 presented a larger surface area (24.53 m2/g), smaller pore size (3.76 nm), reduced iron species (Fe2+ from magnetic), and a higher catalytic activity (0.0229 min-1) than I-900-60 (1.32 m2/g, 12.87 nm, 0.012 min-1) pyrolyzed using single iron ore tailing under the same pyrolysis conditions. In addition, biochar and iron ore tailings in I/W(3:1)-900-60 were tightly combined through chemical bonding. The optimal catalyst remains active after three cycles, indicating its catalytic stability and recyclability. The good Fenton-like methylene blue degradation efficiency of I/W(3:1)-900-60 was ascribed to the sacrificial role of biochar, as well as the electron transfer between biochar and iron active sites or the redox cycles of ≡Fe3+/Fe2+. This finding provides a facile construction strategy for highly active iron ore tailings-based Fenton-like catalyst and thereby had a great potential application in wastewater treatment.


Assuntos
Compostos de Ferro , Pirólise , Catálise , Peróxido de Hidrogênio/química , Ferro/química , Resíduos Sólidos , Triticum
8.
Environ Sci Pollut Res Int ; 28(32): 44277-44287, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33851292

RESUMO

Composite mineral-biochars of a homogeneous biomass (cellulose) and heterogeneous biomass (oak leaves) were fabricated with either 5 wt% or 10 wt% minerals (montmorillonite (MMT), kaolinite, and sand) and then pyrolyzed at 600 °C for 60 min. Characterizations including proximate analysis, ultimate analysis, surface area and porosity, morphology, and surface chemistry confirmed that minerals were present on the surface of biochar, and MMT/kaolinite-biochar composites showed a strengthening in the chars' aromatic structures, as well as increases in oxygen-containing surface functional groups. Methylene blue adsorption isotherms indicated that the MMT/kaolinite-biochars had higher adsorption capacities than pure biomass or biomass-sand biochars (110 mgMB/gchar and 24 mgMB/gchar for MMT-cellulose char and cellulose char, respectively). A multilinear model relating adsorption capacity and adsorbent properties was developed to measure the relative contribution of biochar properties to adsorption behavior. The model indicates that pore volume and hydrogen bonding were the dominant properties in controlling the adsorption of methylene blue onto the biochars. Findings from this work indicate that composite biochars prepared from biomass and inexpensive clay minerals are a promising adsorbent for remediating organic contaminants from water.


Assuntos
Carvão Vegetal , Minerais , Adsorção , Biomassa , Argila
9.
Basic Clin Pharmacol Toxicol ; 128(6): 747-757, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33599105

RESUMO

The effects of the combination of bis (α-furancarboxylato) oxovanadium (IV) (BFOV) and metformin (Met) on hepatic steatosis were investigated in high-fat diet-induced obese C57BL/6J mice (HFC57 mice) for 6 weeks. Oral glucose tolerance test was performed to evaluate glucose metabolism. Moreover, blood and hepatic biochemical and histological indices were detected. Besides, Affymetrix-GeneChip analysis and Western blot of the liver were performed. Comparing to the monotherapy group, BFOV + Met showed more effective improvement in glucose metabolism, which decreased the fasting blood glucose, insulin levels and improved insulin sensitivity in HFC57 mice. BFOV + Met significantly decreased serum ALT and AST activities and reduced hepatic triglyceride content and iNOS activities, accompanied by ameliorating intrahepatic fat accumulation and hepatocellular vacuolation. Enhanced hepatic insulin signalling transduction and attenuated inflammation pathway were identified as the major pathways in the BFOV + Met group. BFOV + Met significantly down-regulated the protein expression levels of MMPs, NF-κB, iNOS and up-regulated phosphorylation of AKT and AMPK levels. We concluded that a combination of BFOV and metformin ameliorates hepatic steatosis in HFC57 mice via alleviating hepatic inflammation and enhancing insulin signalling pathway, suggesting that the combination of BFOV and metformin is a potential treatment for hepatic steatosis.


Assuntos
Fígado Gorduroso/tratamento farmacológico , Inflamação/metabolismo , Metformina/farmacologia , Compostos Organometálicos/farmacologia , Quinases Proteína-Quinases Ativadas por AMP , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Dieta Hiperlipídica , Combinação de Medicamentos , Expressão Gênica , Insulina/sangue , Fígado/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/induzido quimicamente , Proteína Oncogênica v-akt/metabolismo , Proteínas Quinases/metabolismo
10.
Microbiology (Reading) ; 166(10): 988-994, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32936070

RESUMO

Borrelia burgdorferi, a causative agent of Lyme disease, encodes a protein BBB07 on the genomic plasmid cp26. BBB07 was identified as a candidate integrin ligand based on the presence of an RGD tripeptide motif, which is present in a number of mammalian ligands for ß1 and ß3 integrins . Previous work demonstrated that BBB07 in recombinant form binds to ß1 integrins and induces inflammatory responses in synovial cells in culture. Several transposon mutants in bbb07 were attenuated in an in vivo screen of the transposon library in mice. We therefore tested individual transposon mutant clones in single-strain infections in mice and found that they were attenuated in terms of ID50 but did not have significantly reduced tissue burdens in mice. Based on data presented here we conclude that BBB07 is not essential for, but does contribute to, B. burgdorferi infectivity in mice.


Assuntos
Proteínas de Bactérias/metabolismo , Borrelia burgdorferi/metabolismo , Doença de Lyme/microbiologia , Animais , Carga Bacteriana , Proteínas de Bactérias/genética , Borrelia burgdorferi/genética , Biblioteca Gênica , Doença de Lyme/patologia , Camundongos , Camundongos Endogâmicos C3H , Mutação
11.
Biol Pharm Bull ; 43(11): 1653-1659, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32863294

RESUMO

Hyperuricemia is mainly the result of relative underexcretion of urate. Urate is mainly eliminated by kidney and several important transporters expressed on the membrane of renal tubular cells involved in urate excretion. Olsalazine sodium was screened from 3167 authorized small compounds/drugs, targeting xanthine oxidoreductase. In previous study, we reported that olsalazine sodium significantly reduced the serum urate levels, and the anti-hyperuricemic activity linked with inhibiting urate formation by reducing the activity of xanthine oxidoreductase. The current research aimed to assess olsalazine sodium renal urate excretion and likely molecular mechanism. The results showed that administration of olsalazine sodium 5.0 mg/kg decreased the levels of serum urate in hyperuricemic rats, and noticeably improved the fractional excretion of urate and urate clearance, exhibiting an uricosuric action. Moreover, olsalazine sodium (2.5, 5.0, 10.0 mg/kg) reduced the level of blood urea nitrogen in rats. Further study showed that olsalazine sodium reduced the mRNA expression of urate reabsorptive transporter glucose transporter 9 (GLUT9), increased the mRNA expression of urate secretory transporters, organic anion transporter 1 (OAT1), OAT3 and type 1 sodium-dependent phosphate transporter (NPT1) as well as the protein expression of OAT3 in the kidney in hyperuricemic mice. In conclusion, olsalazine sodium exhibited a promotion of urate excretion in kidney by increasing the expression of OAT3.


Assuntos
Ácidos Aminossalicílicos/farmacologia , Hiperuricemia/tratamento farmacológico , Transportadores de Ânions Orgânicos Sódio-Independentes/agonistas , Eliminação Renal/efeitos dos fármacos , Ácido Úrico/metabolismo , Ácidos Aminossalicílicos/uso terapêutico , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Creatinina/urina , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Proteínas Facilitadoras de Transporte de Glucose/antagonistas & inibidores , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Humanos , Hiperuricemia/sangue , Hiperuricemia/fisiopatologia , Hiperuricemia/urina , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/fisiopatologia , Masculino , Camundongos , Proteínas de Transporte de Monossacarídeos/antagonistas & inibidores , Proteínas de Transporte de Monossacarídeos/metabolismo , Proteína 1 Transportadora de Ânions Orgânicos/agonistas , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Ratos , Ratos Sprague-Dawley , Eliminação Renal/fisiologia , Reabsorção Renal/efeitos dos fármacos , Reabsorção Renal/fisiologia , Proteínas Cotransportadoras de Sódio-Fosfato Tipo I/agonistas , Proteínas Cotransportadoras de Sódio-Fosfato Tipo I/metabolismo , Ácido Úrico/sangue , Ácido Úrico/urina
12.
Eur J Pharmacol ; 888: 173490, 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-32827538

RESUMO

Increasing evidence shows that the intestinal tract plays an important role in maintaining urate homeostasis and might be a potential therapeutic target for hyperuricaemia. However, uric acid-lowering drugs available in the clinic do not target intestinal excretion as a therapeutic strategy. We previously reported that mangiferin had potent hypouricaemic effects in hyperuricaemic animals. However, the underlying mechanisms are not completely clear. Here, we investigated the effects of mangiferin on the intestinal excretion of urate and its underlying mechanisms. The data revealed that mangiferin concentration-dependently promoted the intestinal secretion of endogenous urate in in situ intestinal closed loops in normal and hyperuricaemic mice, as well as inhibited the absorption of exogenous uric acid perfused into the intestinal loops in rats. Administration of mangiferin not only decreased the serum urate levels in the hyperuricaemic mice but also increased the protein expression of ATP-binding cassette transporter, subfamily G, member 2 (ABCG2) and inhibited the protein expression of glucose transporter 9 (GLUT 9) in the intestine. These findings suggested that intestinal ABCG2 and GLUT9 might be pivotal and possible action sites for the observed hypouricaemic effects. Moreover, no significant changes in intestinal xanthine oxidoreductase activities were observed, suggesting that mangiferin did not affect intestinal uric acid generation in the hyperuricaemic mice. Overall, promoting intestinal elimination of urate by upregulating ABCG2 expression and downregulating GLUT9 expression might be an important mechanism underlying mangiferin lowering serum uric acid levels. Mangiferin supplementation might be beneficial for the prevention and treatment of hyperuricaemia.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/biossíntese , Eliminação Intestinal/efeitos dos fármacos , Proteínas de Transporte de Monossacarídeos/biossíntese , Ácido Úrico/metabolismo , Xantonas/farmacologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/agonistas , Animais , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Eliminação Intestinal/fisiologia , Masculino , Camundongos , Proteínas de Transporte de Monossacarídeos/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Xantonas/uso terapêutico
13.
ACS Omega ; 5(20): 11291-11298, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32478216

RESUMO

Plastic wastes are environmentally problematic and costly to treat, but they also represent a vast untapped resource for the renewable chemical and fuel production. Pyrolysis has received extensive attention in the treatment of plastic wastes because of its technical maturity. A sole polymer in the waste plastic is easy to recycle by any means of physical or chemical techniques. However, the majority of plastic in life are mixtures and they are hard to separate, which make pyrolysis of plastic complicated compared with pure plastic because of its difference in physical/chemical properties. This work focuses on the synergistic effect and its impact on chlorine removal from the pyrolysis of chlorinated plastic mixtures. The pyrolysis behavior of plastic mixtures was investigated in terms of thermogravimetric analysis, and the corresponding kinetics were analyzed according to the distributed activation energy model (DAEM). The results show that the synergistic effect existed in the pyrolysis of a plastic mixture of LLDPE, PP, and PVC, and the DAEM could well predict the kinetics behavior. The decomposition of LLDPE/PP mixtures occurred earlier than that of calculated ones. However, the synergistic effect weakened with the increase of LLDPE in the mixtures. As for the chlorine removal, the LLDPE and PP hindered the chlorine removal from PVC during the plastic mixture pyrolysis. A noticeable negative effect on dechlorination was observed after the introduction of LLDPE or PP. Besides, the chlorine-releasing temperature became higher during the pyrolysis of plastic mixtures ([LLDPE/PVC (1:1), PP/PVC (1:1), and LLDPE/PP/PVC (1:1:1)]. These results imply that the treatment of chlorinated plastic wastes was more difficult than that of PVC in thermal conversion. In other words, more attention should be paid to both the high-temperature chlorine corrosion and high-efficient chlorine removal in practical. These data are helpful for the treatment and thermal utilization of the yearly increased plastic wastes.

14.
PLoS Pathog ; 16(5): e1008423, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32365143

RESUMO

Post-transcriptional regulation via small regulatory RNAs (sRNAs) has been implicated in diverse regulatory processes in bacteria, including virulence. One class of sRNAs, termed trans-acting sRNAs, can affect the stability and/or the translational efficiency of regulated transcripts. In this study, we utilized a collaborative approach that employed data from infection with the Borrelia burgdorferi Tn library, coupled with Tn-seq, together with borrelial sRNA and total RNA transcriptomes, to identify an intergenic trans-acting sRNA, which we designate here as ittA for infectivity-associated and tissue-tropic sRNA locus A. The genetic inactivation of ittA resulted in a significant attenuation in infectivity, with decreased spirochetal load in ear, heart, skin and joint tissues. In addition, the ittA mutant did not disseminate to peripheral skin sites or heart tissue, suggesting a role for ittA in regulating a tissue-tropic response. RNA-Seq analysis determined that 19 transcripts were differentially expressed in the ittA mutant relative to its genetic parent, including vraA, bba66, ospD and oms28 (bba74). Subsequent proteomic analyses also showed a significant decrease of OspD and Oms28 (BBA74) proteins. To our knowledge this is the first documented intergenic sRNA that alters the infectivity potential of B. burgdorferi.


Assuntos
Borrelia burgdorferi/genética , Pequeno RNA não Traduzido/metabolismo , Tropismo/genética , Borrelia burgdorferi/metabolismo , Borrelia burgdorferi/patogenicidade , Regulação Bacteriana da Expressão Gênica/genética , Biblioteca Gênica , Genoma Bacteriano , Doença de Lyme/microbiologia , Proteômica , RNA Bacteriano/genética , Pequeno RNA não Traduzido/genética , Transcriptoma/genética , Virulência
15.
J Food Biochem ; 44(6): e13182, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32189353

RESUMO

Yunnan Baiyao (YNBY) has been refined for hundreds of years and has become a treasure of proprietary Chinese medicine that has significant curative effects in the field of hemostasis, blood circulation, and callus. In past years, YNBY has been demonstrated to play an anti-inflammatory role in bone-related diseases, such as rheumatoid arthritis and osteoporosis. However, the osteoclasts are multinucleated giant cells that resorb bone and participate in the occurrence, development, and progression of these bone-related diseases. Previous studies have reported that the inflammatory function is closely associated with arachidonic acid (AA) metabolism, as well as some inflammatory-related pathways, including the nuclear factor кB (NF-кB), mitogen-activated protein kinase (MAPK), and Wnt5a pathways. Therefore, we speculated that the anti-inflammatory effect of YNBY might be associated with the NF-кB, MAPK, and Wnt5a pathways. In order to further excavate the anti-inflammatory roles of YNBY, lipopolysaccharide (LPS) with an optimal concentration of 1,000 pg/ml was used to induce inflammation in osteoclasts. Our results showed that YNBY with a time- and dose-dependent method decreased the concentration of pro-inflammatory cytokines and the expression levels of cyclooxygenase-1 (COX-1), COX-2, 5-lipoxygenase, and prostaglandin E2. Moreover, it was found that COX-2 was the target gene regulated by YNBY. Finally, using NF-кB and MAPK pathway inhibitors or miRNA101b (involved in the Wnt5a pathway) in tandem with YNBY and the results exhibited that these groups caused a reduction in COX-1 and COX-2 expression, indicating that the anti-inflammatory function of YNBY might directly affect the NF-кB, MAPK, and Wnt5a pathways. PRACTICAL APPLICATIONS: Yunnan Baiyao (YNBY) is mainly extracted from precious Chinese medicines such as Panax notoginseng, borneol, musk, and yam and has a wide range of clinical applications. It is not only used to treat various types of traumatic injuries, but also used for upper gastrointestinal bleeding and wound ulcers, neonatal umbilitis, recurrent oral ulcers, esophagitis, bacterial dysentery, and so on. Although the detailed mechanism of action is not clear at present, it is believed that this is related to its anti-inflammatory, hemostatic, and immune-enhancing effects. Many bone-related diseases, such as rheumatoid arthritis and osteoporosis, are regarded to be intimately related to the inflammatory reaction. Thus, this study aimed to explore the underlying mechanisms of YNBY at anti-inflammatory roles. And our results suggested that YNBY directly affected the inflammatory cytokines and AA metabolic products which referred to the NF-кB, MAPK, and Wnt5a pathways, as well as AA metabolism, respectively. Hence, the practical applications of YNBY are the anti-inflammatory effects used to treat for bone-related diseases.


Assuntos
Lipopolissacarídeos , NF-kappa B , China , Medicamentos de Ervas Chinesas , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Lipopolissacarídeos/toxicidade , Osteoclastos
16.
RSC Adv ; 10(26): 15098-15106, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35495444

RESUMO

The processing of low-rank coal is becoming more urgent with depletion of high-rank coal and severe environmental pollution in China. The flotation of low-rank coal suffers poor efficiency with hydrocarbon oils unless it is at a high dose. A representative non-polar oil, diesel oil (DO), was used as a collector to float a long-frame coal. The feasibility of oxidized paraffin soap (OPS) was explored to improve flotation performance. Experimental measurements (polarized optical microscopy, zeta potential, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, contact-angle analysis) were used to explore the influence of OPS in low-rank-coal flotation. Poor flotation performances of coal samples were received using OPS or DO as collectors at an economical dose. The flotation efficiency of coal samples was improved considerably upon addition of OPS plus DO. OPS reduced the surface tension of aqueous solutions and promoted dispersion of DO in suspensions. Addition of OPS plus DO reduced the absolute value of the zeta potential on coal particles. Moreover, OPS improved DO adsorption on low-rank coal particles, and the hydrophobicity of low-rank coal was improved visibly. OPS reduced the contact angles of coal-bubble and coal-DO in aqueous solution, which enhanced the adhesion probability of particles to bubbles. This study suggests that OPS is an effective surfactant for improving the floatability of low-rank coal.

17.
PLoS Pathog ; 15(5): e1007644, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31086414

RESUMO

Borrelia burgdorferi, the causative agent of Lyme disease in humans, is maintained in a complex biphasic life cycle, which alternates between tick and vertebrate hosts. To successfully survive and complete its enzootic cycle, B. burgdorferi adapts to diverse hosts by regulating genes required for survival in specific environments. Here we describe the first ever use of transposon insertion sequencing (Tn-seq) to identify genes required for B. burgdorferi survival in its tick host. We found that insertions into 46 genes resulted in a complete loss of recovery of mutants from larval Ixodes ticks. Insertions in an additional 56 genes resulted in a >90% decrease in fitness. The screen identified both previously known and new genes important for larval tick survival. Almost half of the genes required for survival in the tick encode proteins of unknown function, while a significant portion (over 20%) encode membrane-associated proteins or lipoproteins. We validated the results of the screen for five Tn mutants by performing individual competition assays using mutant and complemented strains. To better understand the role of one of these genes in tick survival, we conducted mechanistic studies of bb0017, a gene previously shown to be required for resistance against oxidative stress. In this study we show that BB0017 affects the regulation of key borrelial virulence determinants. The application of Tn-seq to in vivo screening of B. burgdorferi in its natural vector is a powerful tool that can be used to address many different aspects of the host pathogen interaction.


Assuntos
Proteínas de Bactérias/genética , Borrelia burgdorferi/crescimento & desenvolvimento , Elementos de DNA Transponíveis , Regulação Bacteriana da Expressão Gênica , Doença de Lyme/microbiologia , Carrapatos/crescimento & desenvolvimento , Fatores de Virulência/genética , Animais , Proteínas de Bactérias/metabolismo , Borrelia burgdorferi/genética , Borrelia burgdorferi/imunologia , Modelos Animais de Doenças , Vetores de Doenças , Sequenciamento de Nucleotídeos em Larga Escala , Interações Hospedeiro-Patógeno , Doença de Lyme/imunologia , Camundongos , Carrapatos/microbiologia , Fatores de Virulência/metabolismo
18.
Eur J Pharmacol ; 853: 371-380, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31009635

RESUMO

Hyperuricaemia, which results from the overproduction and underexcretion of uric acid, has been linked with chronic renal dysfunction, cardiovascular diseases, diabetes and metabolic syndrome. However, available clinical drugs cannot simultaneously target the production and excretion of uric acid. Norathyriol, a natural xanthone, was expected to have the dual actions. We previously reported that norathyriol possessed potent anti-hyperuricaemic activity related to the inhibition of uric acid production. Here, we investigated the uricosuric actions in hyperuricaemic animals and explored the possible molecular mechanisms associated with renal urate transporters and xanthine oxidase (XO). The results showed that norathyriol (0.5-4.0 mg/kg) dose- and time-dependently decreased serum urate levels in uric acid-induced hyperuricaemic mice and markedly increased the fractional excretion of urate in oxonate-induced hyperuricaemic rats, demonstrating a promotion of urate excretion in the kidney. Further evidence showed that norathyriol markedly increased renal mRNA and protein expression of the secretory organic anion transporter 1 (OAT1) in hyperuricaemic mice and strengthened its transport function in vitro. Moreover, norathyriol also upregulated the mRNA expression of the secretory transporters OAT3, ATP-binding cassette transporter G2 and multidrug resistance protein 4, but not their protein expression. Changes in the expression of the reabsorptive transporters were not observed. This is the first report that norathyriol has uricosuric effects by targeting OAT1. Moreover, norathyriol significantly inhibited XO activity in an uncompetitive manner. Taken together, these findings suggest that norathyriol has the potential to be developed as a new anti-hyperuricaemic agent with dual actions that activate OAT1 and inhibit XO activity.


Assuntos
Inibidores Enzimáticos/farmacologia , Hiperuricemia/tratamento farmacológico , Ácido Úrico/sangue , Ácido Úrico/urina , Xantenos/farmacologia , Xantina Oxidase/antagonistas & inibidores , Animais , Inibidores Enzimáticos/uso terapêutico , Células HEK293 , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Camundongos , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Xantenos/uso terapêutico
19.
RSC Adv ; 9(28): 16018-16027, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35521413

RESUMO

While we have started down the path towards a global transition to a green economy, as with most things we began with the "low-hanging fruit," such that increasingly difficult material and chemical conversions remain. Coking is one such example; it is unlikely that steel production will transition away from using coking coal anytime in the near future, such that coking wastewater remains a global environmental challenge. However, we can develop greener methods and materials to treat such waste. The present work demonstrates how wheat straw, an abundant agricultural residue, can be co-pyrolyzed and co-activated with coal fly ash to produce a high surface area biochar. Coal fly ash has previously been shown to promote devolatilization and deoxygenation of pyrolyzed biofuels. This work shows how coal fly ash increases microporosity as well as aromaticity of the surface functional groups, while decreasing carbonyl but preserving or only slightly decreasing ketones and carboxylic acids. CO2-activation of 5 and 10 wt% fly ash with wheat straw blends yields heterogeneous biochars with adsorption capacities upwards of 170 mgmetal gchar -1, with 5 wt% blends showing higher capacity and adsorption uptake rates than the 0 or 10 wt% blends. The adsorption of the four heavy metals ions (Ni2+, Co2+, Zn2+, and Mn2+) was chemical in nature, with cobalt preferentially adsorbing to the char surface. The overall adsorption rate is limited by an initial rapid uptake to fill available surface adsorption sites.

20.
Int J Biol Macromol ; 120(Pt A): 1232-1239, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30171949

RESUMO

A manganese Schiff base complex with N,N'-1,2-phenylenediamine-bis(salicyladimine) was synthesized and characterized by X-ray crystallography. This complex was administered intragastrically to alloxan-diabetic mice 3 weeks. In vivo tests showed that the complex significantly lowered serum glucose levels in alloxan-diabetic mice at doses of 77 mg V kg-1. Meanwhile, this complex was investigated as dipeptidyl peptidase IV (DPP-IV) inhibitor for the treatment of type 2 diabetes. The compound exhibit moderate inhibition against DPP-IV and possessed an IC50 value of 30 µM. Lineweaver-Burk transformation of the inhibition kinetics data demonstrated that it was a noncompetitive inhibitor of DPP-IV and Ki value was 136.3 µM. Moreover, molecular modeling studies suggested that the complex could fit well within the active-site cleft of DPP-IV. An acute toxicity study showed that animals treated intragastically with complex 1 at a dose of 5.0 g/kg did not show any significantly abnormal signs. These preliminary results suggest that the manganese Schiff base complex can induce a hypoglycemic effect in alloxan-diabetic mice.


Assuntos
Complexos de Coordenação/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Etilenodiaminas/administração & dosagem , Compostos Organometálicos/administração & dosagem , Animais , Glicemia/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Dipeptidil Peptidase 4/química , Inibidores da Dipeptidil Peptidase IV/síntese química , Inibidores da Dipeptidil Peptidase IV/química , Etilenodiaminas/síntese química , Etilenodiaminas/química , Teste de Tolerância a Glucose , Humanos , Camundongos , Camundongos Endogâmicos NOD , Simulação de Acoplamento Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Bases de Schiff/química
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