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1.
J Hazard Mater ; 471: 134252, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38657507

RESUMO

The microbiome is a key source of antibiotic resistance genes (ARGs), significantly influenced by diet, which highlights the interconnectedness between diet, gut microbiome, and ARGs. Currently, our understanding is limited on the co-occurrence among gut microbiome, antibiotic resistome in the captive giant panda and the perturbation of dietary uptake, especially for the composition and forms in dietary nutrition. Here, a qPCR array with 384 primer sets and 16 S rRNA gene amplicon sequencing were used to characterize the antibiotic resistome and microbiomes in panda feces, dietary bamboo, and soil around the habitat. Diet nutrients containing organic and mineral substances in soluble and insoluble forms were also quantified. Organic and mineral components in water-unextractable fractions were 7.5 to 139 and 637 to 8695 times higher than those in water-extractable portions in bamboo and feces, respectively, while the latter contributed more to the variation (67.5 %) of gut microbiota. Streptococcus, Prevotellaceae, and Bacteroides were the dominant genera in giant pandas. The ARG patterns in panda guts showed higher diversity in old individuals but higher abundance in young ones, driven directly by the bacterial community change and mobile genetic element mediation and indirectly by dietary intervention. Our results suggest that dietary nutrition mainly accounts for the shift of gut microbiota, while bacterial community and mobile genetic elements influenced the variation of gut antibiotic resistome.


Assuntos
Antibacterianos , Dieta , Fezes , Microbioma Gastrointestinal , Ursidae , Animais , Ursidae/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Fezes/microbiologia , Antibacterianos/farmacologia , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/classificação , RNA Ribossômico 16S/genética , Resistência Microbiana a Medicamentos/genética , Microbiologia do Solo , Farmacorresistência Bacteriana/genética
2.
Transl Cancer Res ; 13(3): 1394-1405, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38617517

RESUMO

Background: Lung cancer (LC) is a leading cause of cancer-associated mortality worldwide, with high incidence and mortality rates. Ly6/PLAUR domain containing 3 (LYPD3) is a tumorigenic and highly glycosylated cell surface protein that has been rarely reported in LC. This study aimed to explore the prognostic role and immune cell infiltration of LYPD3 in LC. Methods: We used ExoCarta, a database of exosomal proteins and RNA, to select exosomes in LC. The Tumor Immune Estimation Resource (TIMER) and Human Protein Atlas (HPA) databases were utilized to compare the expression of LYPD3 in LC. We applied Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Kaplan-Meier (KM) plotter to evaluate the prognostic prediction performance of LYPD3. Biological processes (BPs), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and gene set enrichment analysis (GSEA) analyses were performed to illustrate the possible role of LYPD3 in LC. The correlations between LYPD3 and immune cell infiltration were explored using Tumor and Immune System Interaction Database (TISIDB), GEPIA2, and TIMER. R software was used for statistical analysis and mapping. Results: A total of 904 exosome molecules were screened in LC. Further analysis showed that the up-regulation of LYPD3 in these 904 exosome molecules was associated with poor prognosis in LC. Pan-cancer analyses revealed that the expression of LYPD3 varied in many cancers, particularly in LC. Clinical correlation analysis indicated that LYPD3 was associated with stage and T classification in LC. We observed that LYPD3 co-expression genes were associated with cell cycle, DNA replication, proteasome, and regulation of the actin cytoskeleton by GSEA. Moreover, LYPD3 was associated with immune modulators. Immunophenoscores (IPS) and IPS-CTLA4 were significantly different between the high LYPD3 group and low LYPD3 group. Additionally, the median half maximal inhibitory concentration (IC50) of bexarotene, cyclopamine, etoposide, and paclitaxel in LYPD3 high group was significantly lower than that in LYPD3 low group. Conclusions: LYPD3 is involved in many BPs of LC, such as regulating immune cell infiltration and affecting prognosis. Therefore, LYPD3 may have potential value as a biomarker for prognosis and immunotherapy in LC.

3.
Micromachines (Basel) ; 15(4)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38675296

RESUMO

The first quantum revolution has brought us the classical Internet and information technology. Today, as technology advances rapidly, the second quantum revolution quietly arrives, with a crucial moment for quantum technology to establish large-scale quantum networks. However, solid-state quantum bits (such as superconducting and semiconductor qubits) typically operate in the microwave frequency range, making it challenging to transmit signals over long distances. Therefore, there is an urgent need to develop quantum transducer chips capable of converting microwaves into optical photons in the communication band, since the thermal noise of optical photons at room temperature is negligible, rendering them an ideal information carrier for large-scale spatial communication. Such devices are important for connecting different physical platforms and efficiently transmitting quantum information. This paper focuses on the fast-developing field of optomechanical quantum transducers, which has flourished over the past decade, yielding numerous advanced achievements. We categorize transducers based on various mechanical resonators and discuss their principles of operation and their achievements. Based on existing research on optomechanical transducers, we compare the parameters of several mechanical resonators and analyze their advantages and limitations, as well as provide prospects for the future development of quantum transducers.

4.
BMB Rep ; 57(2): 71-78, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38053295

RESUMO

Melanoma is one of the most aggressive skin tumors, and conventional treatment modalities are not effective in treating advanced melanoma. Although immunotherapy is an effective treatment for melanoma, it has disadvantages, such as a poor response rate and serious systemic immune-related toxic side effects. The main solution to this problem is the use of biological materials such as hydrogels to reduce these side effects and amplify the immune killing effect against tumor cells. Hydrogels have great advantages as local slow-release drug carriers, including the ability to deliver antitumor drugs directly to the tumor site, enhance the local drug concentration in tumor tissue, reduce systemic drug distribution and exhibit good degradability. Despite these advantages, there has been limited research on the application of hydrogels in melanoma treatment. Therefore, this article provides a comprehensive review of the potential application of hydrogels in melanoma immunotherapy. Hydrogels can serve as carriers for sustained drug delivery, enabling the targeted and localized delivery of drugs with minimal systemic side effects. This approach has the potential to improve the efficacy of immunotherapy for melanoma. Thus, the use of hydrogels as drug delivery vehicles for melanoma immunotherapy has great potential and warrants further exploration. [BMB Reports 2024; 57(2): 71-78].


Assuntos
Antineoplásicos , Melanoma , Humanos , Melanoma/tratamento farmacológico , Hidrogéis , Sistemas de Liberação de Medicamentos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Imunoterapia
5.
Chem Sci ; 14(37): 10203-10211, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37772116

RESUMO

The traditional approach employed in copolymer compositional design, which relies on trial-and-error, faces low-efficiency and high-cost obstacles when attempting to simultaneously improve multiple conflicting properties. For example, designing co-cured polycyanurates that exhibit both moisture and thermal resistance, along with high modulus, is a long-term challenge because of the intrinsic trade-offs between these properties. In this work, to surmount these barriers, we developed a Bayesian optimization (BO)-guided method to expedite the discovery of co-cured polycyanurates exhibiting low water uptake, coupled with higher glass transition temperature and Young's modulus. By virtue of the knowledge of molecular simulations, benchmarking studies were carried out to develop an effective BO-guided method. Propelled by the developed method, several copolymers with improved comprehensive properties were obtained experimentally in a few iterations. This work provides guidance for efficiently designing other high-performance copolymers.

6.
Huan Jing Ke Xue ; 43(4): 1950-1957, 2022 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-35393818

RESUMO

Regional concentrations, fluorescent components, and sources of dissolved organic matter (DOM) in a drinking water source in Chaobai River across seasons were investigated here using fluorescence excitation-emission matrices, parallel factor analysis, and fluorescence indexes. Five fluorescent-DOM components were identified, including two microbial humic-like components and one autochthonous tyrosine-like, one reduced quinone-like, and one terrestrial humic-like component. DOM was mainly derived from microorganisms. The farmland-dominated region showed the highest DOM concentration and significantly lower maximum fluorescence intensities (Fmax) of almost all fluorescent components than those in the forest-dominated region. The region dominated by urban lands exhibited obviously lower DOM concentrations than those in the farmland-dominated region and lower Fmax values of fluorescent components than those in the forest-dominated region. No interaction was found between land use and season when considering their effects on DOM. Season had a significant influence on the humification degree of DOM. This study shows that agricultural land use had a greater impact on DOM than that of forests and urban areas, and the increased riverine DOM resulting from farmland was mainly non-fluorescent parts.


Assuntos
Matéria Orgânica Dissolvida , Água Potável , Água Potável/análise , Análise Fatorial , Substâncias Húmicas/análise , Rios , Espectrometria de Fluorescência
7.
Am J Chin Med ; 49(6): 1399-1415, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34137676

RESUMO

Diabetes is a group of metabolic disorders with an increased risk of developing cognitive impairment and dementia. The hippocampus in the forebrain contains an abundance of insulin receptors related to cognitive function and plays an important role in the pathophysiology of neurodegenerative disorders. Berberine from traditional Chinese medicine has been used to treat diabetes and diabetic cognitive impairment, although its related mechanisms are largely unknown. In this study, a STZ diabetes rat model feeding with a high-fat diet was used to test the effects of berberine compared with metformin. Oral glucose tolerance and hyperinsulinemic-euglycemic clamp were used for glucose metabolism and insulin resistance. The Morris water maze was used to observe the compound effects on cognitive impairment. Serum and hippocampal [Formula: see text]-amyloid peptide (A[Formula: see text], Tau and phosphorylated Tau protein deposition in the hippocampi were measured. The TUNEL assay was used to detect the neuronal apoptosis, supported by histomorphological changes and transmissional electron microscopy (TEM) image. Our data showed that the diabetic rats had a significantly cognitive impairment. In addition to improving glucose metabolism and reducing insulin resistance, berberine significantly improved the cognitive function in the rat. Berberine also effectively decreased the expression of hippocampal tau protein, phosphorylated Tau, and increased insulin receptor antibodies. Moreover, berberine downregulated the abnormal phosphorylation of A[Formula: see text] and Tau protein and improved hippocampal insulin signaling. The TUNEL assay confirmed that berberine reduced hippocampal neuronal apoptosis supported by TEM. Thus, berberine significantly improved the cognitive function in diabetic rats by changing the peripheral and central insulin resistance. The reduction of neuronal injury, A[Formula: see text] deposition, abnormal phosphorylation of Tau protein, and neuronal apoptosis in the hippocampus were observed as the related mechanisms of action.


Assuntos
Berberina/farmacologia , Disfunção Cognitiva/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Metformina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Dieta Hiperlipídica , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Resistência à Insulina/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Estreptozocina , Proteínas tau/efeitos dos fármacos
8.
J Cell Physiol ; 235(7-8): 5525-5540, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32037545

RESUMO

Early weaning usually causes intestinal disorders, enteritis, and diarrhea in young animals and human infants. Astragalus polysaccharides (APS) possesses anti-inflammatory activity. To study the anti-inflammatory mechanisms of APS and its potential effects on intestinal health, we performed an RNA sequencing (RNA-seq) study in lipopolysaccharide (LPS)-stimulated porcine intestinal epithelial cells (IPEC-J2) in vitro. In addition, LPS-stimulated BALB/c mice were used to study the effects of APS on intestinal inflammation in vivo. The results from the RNA-seq analysis show that there were 107, 756, and 5 differentially expressed genes in the control versus LPS, LPS versus LPS+APS, and control versus LPS+APS comparison groups, respectively. The results of Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways play significant roles in the regulation of inflammatory factors and chemokine expression by APS. Further verification of the above two pathways by using western blot and immunofluorescence analysis revealed that the gene expression levels of the phosphorylated p38 MAPK, ERK1/2, and NF-κB p65 were inhibited by APS, while the expression of IκB-α protein was significantly increased (p < .05), indicating that APS inhibits the production of inflammatory factors and chemokines by the inhibition of activation of the MAPK and NF-κB inflammatory pathways induced by LPS stimulation. Animal experiments further demonstrated that prefeeding APS in BALB/c mice can alleviate the expression of the jejunal inflammatory factors interleukin 6 (IL-6), IL-Iß, and tumor necrosis factor-α induced by LPS stimulation and improve jejunal villus morphology.


Assuntos
Astrágalo/química , Inflamação/tratamento farmacológico , Inibidor de NF-kappaB alfa/genética , eIF-2 Quinase/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Inflamação/patologia , Interleucina-1beta/genética , Interleucina-6/genética , Lipopolissacarídeos/química , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , NF-kappa B/genética , Fosforilação/efeitos dos fármacos , RNA-Seq
9.
Se Pu ; 38(11): 1323-1331, 2020 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-34213104

RESUMO

Pueraria polysaccharides have been proven to possess biological activities such as bacteriostasis, anti-oxidative, anti-tumor, and immunity boosting activities. The variation in the structure, composition, and amount of monosaccharides in these polysaccharides may lead to different spatial structures and biological activities. Therefore, extraction of Pueraria polysaccharides and determination of the monosaccharide composition are of great significance for activity analysis and quality control. Direct detection of saccharides is difficult because they are strongly polar and do not show absorption in the ultraviolet region. At present, the commonly used methods for saccharide detection are liquid chromatography-ultraviolet detection, gas chromatography-ultraviolet detection, and mass spectrometry. Pressurized capillary electrochromatography is a high-efficiency microseparation technology. In this study, two kinds of Pueraria polysaccharides were extracted by an ultrasonic-assisted method, and response surface methodology was performed to explore the conditions for ultrasonic-assisted extraction of polysaccharides from Pueraria. The interaction effects of four factors, the liquid-solid ratio, ultrasonic extraction time, ultrasonic extraction temperature, and ultrasonic power, on the extraction rate of the polysaccharides were analyzed. By combining the optimal conditions predicted by the software and the actual equipment conditions, the optimal extraction conditions for Pueraria polysaccharides were chosen as follows:ultrasonic extraction temperature, 90℃; liquid-solid ratio of Pueraria thomsonii Benth, 20 mL/g; liquid-solid ratio of Pueraria lobata Ohwi, 40 mL/g; ultrasonic extraction time, 30 min; ultrasonic power, 180 W. Through data fitting, the multiple quadratic regression equation of the four factors on the extraction rate of Pueraria polysaccharides was established. A novel method based on pressurized capillary electrochromatography for the separation and analysis of eight neutral monosaccharides has been established. The monosaccharides were derivatized by the 1-phenyl-3-methyl-5-pyrazolone pre-column derivatization method. The separation conditions for these monosaccharides were explored, and the buffer concentration, buffer pH, applied voltage, type of chromatographic column, and mobile phase ratio were optimized. Finally, the established pressurized capillary electrochromatography-ultraviolet detection method was applied to the detection and identification of two kinds of actual Pueraria polysaccharide samples. The results of response surface analysis showed that among the four experimental factors, ultrasonic extraction temperature had the greatest influence on the extraction rate of polysaccharides from the two kinds of Pueraria, followed by the liquid-solid ratio; the influence of the ultrasonic extraction time and ultrasonic power was relatively weak. The experimental conditions were determined as follows:the separation of eight neutral monosaccharide derivatives could be realized within 24 min on a Halo-2.7 µm core-shell C18 capillary column with acetonitrile-50 mmol/L ammonium acetate aqueous solution (18:82, v/v, pH 4.1) as the mobile phase, by detection at 250 nm under an applied voltage of-20 kV. The separation and detection speeds and the column efficiency achieved with this method were much better than those obtained with the traditional liquid chromatography method. The results show that the proposed method has a good linear relationship and good repeatability. The separation and identification results for the actual samples showed that the polysaccharides of Pueraria thomsonii Benth were mainly composed of glucose, mannose, rhamnose, and fucose in the molar ratio 1.00:0.16:0.14:0.07. The polysaccharides of Pueraria lobata Ohwi were mainly composed of glucose and mannose in the molar ratio 1.00:0.70. This study provides a novel method for the rapid and efficient separation and detection of neutral monosaccharides, and serves as a reference for analyzing the monosaccharide composition of Pueraria polysaccharides.


Assuntos
Eletrocromatografia Capilar , Monossacarídeos/isolamento & purificação , Pueraria , Monossacarídeos/análise , Polissacarídeos/análise , Pueraria/química
10.
J Org Chem ; 85(2): 574-584, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31825216

RESUMO

An efficient organocatalytic asymmetric Michael addition of 4-substituted-pyrazol-5-ones to ß-trifluoromethyl-α,ß-unsaturated ketones was developed. In the presence of a dipeptide-based urea-amide tertiary amine catalyst, an array of chiral products containing pyrazolone and trifluoromethyl moieties bearing vicinal quaternary and tertiary stereocenters were obtained in good yields with good to excellent enantioselectivity and diastereoselectivity (up to 95% yields, up to 97% ee, and >20:1 d.r.). Moreover, the reaction was compatible with 4-substituted-pyrazol-5-ones containing either aryl or alkyl group at the C3 position.

11.
Se Pu ; 37(10): 1090-1097, 2019 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-31642288

RESUMO

A partially filled monolith was prepared by in situ polymerization, and then carrier ampholytes (CAs, pH 3-10) were immobilized on its surface. For effective utilization of capillary isoelectric focusing (cIEF) with the monolithic immobilized pH gradient (M-IPG), a new online platform was established by the introducing of an eight-way injection valve, a three-way valve and a cross-shaped unit. Besides, a capillary coated with hydroxypropyl cellulose (HPC capillary) was prepared and used to determine the isoelectric points (pI) of trastuzumab and etanercept. In parallel, using the newly built capillary isoelectric focusing platform, the pI values of trastuzumab and etanercept were measured with the M-IPG column, and compared with the results obtained using the HPC capillary. It was found that these two cIEF columns can be effectively used to separate proteins and determine the pI values of monoclonal antibodies and fusion proteins in protein drugs. Moreover, the measured pI values were consistent with those estimated using the HPC capillary.


Assuntos
Focalização Isoelétrica , Proteínas/química , Força Próton-Motriz , Anticorpos Monoclonais/química , Concentração de Íons de Hidrogênio , Ponto Isoelétrico , Polimerização
12.
Cell Cycle ; 18(20): 2614-2628, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31475609

RESUMO

The endotoxin of Gram-negative bacteria threatens the intestinal health of livestock. Ethyl pyruvate (EP) has been shown to regulate intestinal immunity and protect against cell and tissue damage. In this study, it was first verified that EP could reduce the secretion of IL-8, TNF-α, IL-6 and IL-1ß in LPS-induced IPEC-J2 cells. Then, we used RNA sequencing (RNA-seq) to analyze the differentially expressed genes (DEGs) of inflammatory factors induced by LPS in IPEC-J2 cells. It was found that LPS induced the upregulation of 377 genes and the downregulation of 477 genes compared to Vehicle; LPS+EP induced the upregulation of 258 genes and the downregulation of 240 genes compared to Vehicle; and LPS+EP induced the upregulation of 373 genes and the downregulation of 188 genes compared to LPS (fold change > 1.5 and FDR < 0.01). Their enrichment pathways included the MAPK signaling pathway, PI3K-Akt signaling pathway, Toll-like receptor signaling pathway, and other pathways. Furthermore, the mRNA level of cytokines associated with inflammation and apoptosis enriched in the MAPK pathway was verified by qRT-PCR. Western blots and immunofluorescence revealed that EP significantly inhibited phosphorylated p38 and phosphorylated-ERK1/2 protein expression levels (P < 0.05). The apoptosis due to LPS reduced by EP was significantly inhibited, as shown by Annexin V-FITC/PI staining. According to the results, EP inhibited the expression of IL-8, TNF-α, IL-6 and IL-1ß as well as apoptosis by inhibiting the phosphorylation of p38 and ERK1/2 in LPS-induced IPEC-J2 cells.


Assuntos
Apoptose/efeitos dos fármacos , Enterócitos/metabolismo , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Piruvatos/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Linhagem Celular , Citocinas/genética , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Inflamação/metabolismo , RNA Mensageiro/genética , RNA-Seq , Transdução de Sinais/efeitos dos fármacos , Suínos , Regulação para Cima/efeitos dos fármacos
13.
Anal Chim Acta ; 1079: 230-236, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31387716

RESUMO

The use of immobilized pH gradient (IPG) capillary isoelectric focusing (CIEF) was confirmed to be possible with packed capillaries. The success of this experiment was due to two key factors: first, the use of surface-confined atom transfer radical polymerization method led to an increase in active reaction sites on the surface of silica particles; second, the subsequent free radical reaction caused carrier ampholytes (CAs) to bond faster and firmer. Based on this scheme, both CIEF with free pH gradient and CIEF with IPG were performed in capillaries packed with 3 µm modified silica particles. In our online CIEF-UV platform, both reversible and irreversible adsorption of proteins was shown to be negligible. Four proteins were focused: cytochrome c (pI 10.2), myoglobin (pI 7.3), carbonic anhydrase (pI 5.9) and trypsin inhibitor (pI 4.5). The comparison of the two CIEF columns showed that the time required for focusing in the packed capillary with IPG is only increased by a factor of 1.5 compared to the packed capillary, giving complete focusing in less than 12 min at 400 V/cm. With the increment of the electric field (the maximum at 600 V/cm), the run time was continually decreasing in these packed capillaries while the peak shape was improving. The four proteins (pH 4.5-10.2) could be successfully separated in our online CIEF platform. Moreover, for the newly online CIEF platform, pressure-driven mobilization without an applied electric field was achieved in the packed capillary with immobilized pH gradient.


Assuntos
Eletroforese Capilar/instrumentação , Focalização Isoelétrica/instrumentação , Dióxido de Silício/química , Proteínas Sanguíneas/análise , Eletroforese Capilar/métodos , Humanos , Concentração de Íons de Hidrogênio , Focalização Isoelétrica/métodos
14.
Int Immunopharmacol ; 74: 105681, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31220694

RESUMO

Salmonella typhimurium (S. t.) is one of the main pathogens that causes acute gastroenteritis. To evaluate the anti-inflammatory mechanism of Astragalus polysaccharide (APS) in vivo and its influence on the intestinal flora, BALB/c mice were infected with S. t. to establish a model of diarrhea. The disease activity index (DAI) scores showed that APS attenuated S. t.-induced weight loss and diarrhea in mice. APS significantly reduced the index of the liver and spleen as well as the ALT and AST levels in serum (P < 0.05). Hematoxylin and eosin (H&E) results indicated that APS significantly increased jejunum villus height and crypt depth and reduced the infiltration of inflammatory cells (P < 0.05). Additionally, APS increased the tight junction (TJ) proteins expression levels of ZO-1, Occludin and Claudin-1 in the jejunum. The results of 16S rDNA showed that APS significantly increased the number of Lactobacillus and Bifidobacterium spp. to normal levels (compared with the control group). In addition, APS significantly decreased the mRNA expression levels of the proinflammatory cytokines TNF-α, IL-1ß, IL-6 and IL-17 in the jejunum (P < 0.01) as well as the proteins expression levels of COX-2 and iNOS (P < 0.05). Western blot confirmed that prefeeding with APS inhibited S. t.-induced expression of TLR4 and MyD88 in the jejunum and further inhibited nuclear factor-κB (NF-κB) activation, including the nuclear translocation of the p65 NF-κB subunit and the phosphorylation and degradation of IκB-α. This was the key to APS inhibition of the production of inflammatory factors and inflammatory mediators in the jejunum.


Assuntos
Anti-Inflamatórios/uso terapêutico , Bifidobacterium/genética , Diarreia/terapia , Microbioma Gastrointestinal/genética , Lactobacillus/genética , Fígado/metabolismo , Polissacarídeos/uso terapêutico , Infecções por Salmonella/terapia , Salmonella typhimurium/fisiologia , Junções Íntimas/metabolismo , Animais , Astrágalo/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Mediadores da Inflamação/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Transdução de Sinais , Junções Íntimas/patologia
15.
Org Lett ; 21(9): 3271-3275, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-30998021

RESUMO

An asymmetric, phase-transfer-catalyzed vinylogous conjugate addition-vinylogous cyclization cascade of olefinic azlactones with 4-nitro-5-styrylisoxazoles is reported. In the presence of an l- tert-leucine-derived urea-quaternary ammonium salt as a bifunctional phase-transfer catalyst and KF, two series of valuable optically pure cyclohexenones featuring two and three stereocenters were obtained in high yields with good to excellent enantio- and diastereoselectivities.

16.
Int Immunopharmacol ; 71: 155-163, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30901678

RESUMO

Salmonella typhimurium is one of the main causes of intestinal diseases, affecting the health of humans and livestock. Ethyl pyruvate (EP), which is ordinarily an edible spice, has been indicated to exert anti-inflammatory effects and preserve intestinal barrier function. In this study, intestinal immune function and signaling pathways activated by EP were investigated in vivo in S. typhimurium-challenged BALB/c mice and in vitro in RAW264.7 cells. EP improved body weight loss and the organ index of the liver and spleen (p < 0.05). Serum IgA and IgM levels were significantly increased in EP-treated mice (p < 0.05). According to histopathological and immunohistochemical staining, EP significantly increased the villus height, reduced edema in the jejunum and increased the levels of claudin-1, occludin-1 and ZO-1 proteins compared to the Salmonella-treated group (p < 0.05). In addition, EP decreased the levels of the IL-6, IL-1ß and TNF-α mRNA levels in jejunum, liver, spleen and RAW264.7 cells (p < 0.05). EP decreased the levels of TLR4, phosphorylated p38MAPK and ERK1/2 in mice infected with S. typhimurium (p < 0.05). In conclusion, EP effectively protected BALB/c mice from an intestinal S. typhimurium infection by improving the activity of the humoral immune system, reducing intestinal barrier damage, and inhibiting proinflammatory cytokine production in the jejunum by modulating the TLR4/MAPK signaling pathway. Based on these findings, EP has the potential to inhibit inflammation or to serve as an immune-enhancing adjuvant.


Assuntos
Anti-Inflamatórios/uso terapêutico , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Intestinos/patologia , Piruvatos/uso terapêutico , Infecções por Salmonella/dietoterapia , Salmonella typhimurium/fisiologia , Receptor 4 Toll-Like/metabolismo , Animais , Formação de Anticorpos , Citocinas/metabolismo , Dietoterapia , Regulação para Baixo , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células RAW 264.7 , Transdução de Sinais
17.
J Cancer Res Ther ; 14(Supplement): S1012-S1018, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30539838

RESUMO

OBJECTIVE: To evaluate Xi huang pill combined with chemotherapy for tumor treatment in a meta-analysis. MATERIALS AND METHODS: We searched PubMed, Excerpta Medica Database, the Cochrane Library, the China National Knowledge Infrastructure, and the Weipu database and Wanfang Databases for eligible studies. We manually searched for printed journals and relevant textbooks. Statistical analyses were performed with Review Manager 5.3 (Cochrane Community, London, United Kingdom) and STATA 12.0 software packages. RESULTS: Fifteen studies were included. Xi huang pill combined with chemotherapy could enhance response (risk ratio [RR] =1.35, 95% confidence interval [95% CI]: 1.14-1.60, P < 0.0004), improve disease control (RR = 1.13, 95% CI: 1.05-1.21, P = 0.0006), prolong overall survival (hazard ratio = 0.80, 95% CI: 0.08-0.98, P = 0.03), improve patient quality of life (RR = 1.35, 95% CI: 1.10-1.67, P < 0.004), reduce 2-4° leukocyte (white blood cell) and platelet count due to chemotherapy (pooled RR = 0.42, 95% CI = 0.30-0.60, pooled RR = 0.42, 95% CI = 0.25-0.72, respectively). CONCLUSION: Xi huang pill combined with chemotherapy can enhance the short-term efficacy and overall survival, alleviate treatment-induced side effects, and serve as a suitable regimen for the treatment of patients with tumors. However, the findings of the current study require validation in further high-quality trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Neoplasias Pulmonares/mortalidade , Análise de Sobrevida , Resultado do Tratamento
18.
Artigo em Inglês | MEDLINE | ID: mdl-30254688

RESUMO

Gastric cancer has a high morbidity and mortality. Chemotherapy regimens are routine advanced stage gastric cancer (AGC) treatment protocols, but most of these drugs have side-effects such as myelosuppression and gastrointestinal disorders. Cinobufacini, an extractive from TCM, could suppress cell proliferation and inhibit gastric cancer. In this study, we comprehensively reviewed the literature on the efficacy comparison between Cinobufacini injection combined with chemotherapy and chemotherapy solely used in AGC treatment. We extracted data for from six electronic databases to evaluate the efficacy of Cinobufacini injection on AGC patients. Twelve studies with a total of 853 patients were finally included in our study. The results indicated that Cinobufacini injection could increase response rate and disease control rate of chemotherapy on AGC, improve the life quality of AGC patients, increase leukocytes, improve anemia, improve hand-foot syndrome induced by chemotherapy, and relieve cancer pain. This study has its own limitations that prevented us from drawing a definite conclusion and more well-designed clinical trials of TCM are needed.

20.
Oncotarget ; 8(16): 26532-26551, 2017 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-28460447

RESUMO

Host defense peptides (HDPs) are an important component of the innate immune system and possess direct antimicrobial and immunomodulatory activities. Dietary regulation of HDPs synthesis has emerged as a novel non-antibiotic approach to combat pathogen infection. There are species- and tissue-dependent characteristics of the regulation and mechanism of HDPs. In this study, we investigated whether the histone deacetylase inhibitor (HDACi) sodium butyrate (NaB) could induce HDP expression and the mechanism underlying NaB-regulated HDP expression in PK-15 cells. Our results revealed that NaB augmented HDP expression in PK-15 cells, including porcine ß-defensin 3 (pBD3), epididymis protein 2 splicing variant C (pEP2C), pBD128, pBD123, and pBD115, but no inflammatory response occurred. Inhibition of HDAC activity was not sufficient to induce the expression of pBD3 and pEP2C in comparisons of NaB and another HDACi, trichostatin A (TSA). Concomitantly, NF-κB activation was involved in the induction of HDP expression by NaB. MAPK pathway inhibition also prevented pBD3 and pEP2C induction by NaB. Furthermore, NaB could still promote pBD3 and pEP2C expression and inhibit IL-6 production in the presence of the toll-like receptor 2 (TLR2) ligand peptidoglycan. Moreover, TLR2 could be activated by both NaB and peptidoglycan, and blocking TLR2 expression suppressed HDP induction. Finally, we further showed that increased pBD3 could decrease cytokine interleukin-18 (IL-18) and increase porcine claudin 15 (pCLDN15) contents, suggesting an immunoregulatory function of pBD3. In conclusion, this work paves the way for using HDACi-NaB to induce porcine kidney defense peptides while limiting the deleterious risk of an inflammatory response.


Assuntos
Ácido Butírico/farmacologia , Defensinas/genética , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Receptor 2 Toll-Like/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Linhagem Celular , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Mediadores da Inflamação , Rim , Ligantes , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Suínos , Receptor 2 Toll-Like/agonistas
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