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1.
Front Oncol ; 12: 961257, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912204

RESUMO

Colorectal cancer (CRC) is the second most lethal cancer and the third most common cancer in the world, and its prognosis is severely affected by high intestinal mucosal permeability and increasing tumor burden. Studies have shown that the expression of hypoxia induce factor 1α (HIF1α) is up-regulated in a variety of tumor tissues, which is related to multiple metabolic reprogramming of tumor cells. However, the role of HIF1α in CRC tumor growth, tumor polyamine metabolism and intestinal mucosal barrier damage has not been studied. Here, we constructed different types of CRC tumor-bearing mice models by inoculating HCT116 cells with different levels of HIF1α expression (knockdown, wild type, overexpression) in the armpits of mice to explore the upstream and downstream regulators of HIF1α, the effects of HIF1α on the growth of CRC, and the CRC polyamine metabolism and its effect on the intestinal mucosal barrier. We found that with the increase of HIF1 gene expression, tumor growth was promoted and intestinal mucosal permeability was increased. The expression of glycolysis-related proteins was up-regulated, the rate-limiting enzyme ODC of polyamine synthesis was decreased, and the transfer protein of polyamine was increased. HPLC showed that the polyamine content in the tumor tissue of the overexpression group HIF1α OE was higher than that of the wild group HIF1α (+/+), and higher than that of the knockdown group HIF1α (-/-), but the content of polyamines in intestinal mucosa was the opposite. After supplementation of exogenous polyamines, the content of polyamines in intestinal mucosa and tumor tissue increased, and the damage of intestinal mucosa was alleviated. In conclusion, upon activation of the MYC/HIF1 pathway, tumor glycolysis is enhanced, tumors require more energy and endogenous polyamine synthesis is reduced. Therefore, in order to meet its growth needs, tumor will rob polyamines in the intestinal mucosa, resulting in intestinal mucosal epithelial barrier dysfunction.

2.
World J Surg Oncol ; 20(1): 252, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35932027

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) as a common tumor has a poor prognosis. Recently, a combination of atezolizumab and bevacizumab has been recommended as the preferred regimen for advanced HCC. However, the overall response rate of this therapy is low. There is an urgent need to identify sensitive individuals for this precise therapy among HCC patients. METHODS: The Wilcox test was used to screen the differentially expressed immune-related genes by combining the TCGA cohort and the Immunology Database. Univariate and multivariate Cox regression analysis were used to screen the immune gene pairs concerning prognosis. A predictive model was constructed using LASSO Cox regression analysis, and correlation analysis was conducted between the signature and clinical characteristics. ICGC cohort and GSE14520 were applied for external validations of the predictive risk model. The relationship between immune cell infiltration, TMB, MSI, therapeutic sensitivity of immune checkpoint inhibitors, targeted drugs, and the risk model were assessed by bioinformatics analysis in HCC patients. RESULTS: A risk predictive model consisting of 3 immune-related gene pairs was constructed and the risk score was proved as an independent prognostic factor for HCC patients combining the TCGA cohort. This predictive model exhibited a positive correlation with tumor size (p < 0.01) and tumor stage (TNM) (p < 0.001) in the chi-square test. The predictive power was verified by external validations (ICGC and GSE14520). The risk score clearly correlated with immune cell infiltration, MSI, immune checkpoints, and markers of angiogenesis. CONCLUSIONS: Our research established a risk predictive model based on 3 immune-related gene pairs and explored its relationship with immune characteristics, which might help to assess the prognosis and treatment sensitivity to immune and targeted therapy of HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Biologia Computacional , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Prognóstico
3.
Phytomedicine ; 104: 154316, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35820305

RESUMO

BACKGROUND: Celastrol (CEL) has a great potential in the treatment of a wide variety of metabolic diseases. However, whether CEL protects pancreatic ß cells and its underlying mechanism are not yet clear. PURPOSE: This study investigates to determine the effects of CEL on the pathogenesis of pancreatic ß cells damage. METHODS: C57BLKS/Leprdb (db/db) mice and rat insulinoma INS-1 cell line or mouse J774A.1 cell line were used as in vivo and in vitro models for investigating the protective effect of CEL on pancreatic ß cells under high glucose environment and the related mechanism. The phenotypic changes were evaluated by immunofluorescence, immunohistochemical staining, flow cytometry and the measurement of biochemical indexes. The molecular mechanism was explored by biological techniques such as western blotting, qPCR, ChIP-qPCR, co-immunoprecipitation and lentivirus infection. RESULTS: Our results showed that CEL at the high dose (CEL-H, 0.2 mg/kg) protects db/db mice against increased body weight and blood glucose. CEL-H inhibits pancreatic ß cell apoptosis in db/db mice and high glucose-induced INS-1 cells. CEL-H also reduced IL-1ß production in islet macrophages. The further study found that CEL suppressed TXNIP expression and NLRP3 inflammasome activation in pancreatic ß cells and islet macrophages. Importantly, the inhibitory effect of CEL on pancreatic ß cell apoptosis and IL-1ß production was also dependent on TXNIP. Mechanically, CEL inhibits Txnip transcription by promoting the degradation of ChREBP. CONCLUSION: Celastrol inhibits TXNIP expression to protect pancreatic ß cells in vivo and in vitro. Our research pointed out another mechanism by which celastrol functions under the condition leptin signaling is ineffective.


Assuntos
Diabetes Mellitus Experimental , Células Secretoras de Insulina , Animais , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/metabolismo , Diabetes Mellitus Experimental/metabolismo , Glucose/metabolismo , Inflamassomos/metabolismo , Camundongos , Triterpenos Pentacíclicos , Ratos , Tiorredoxinas/metabolismo
4.
Blood ; 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35881840

RESUMO

Hematopoietic stem cells (HSCs) have reduced capacities to properly maintain and replenish the hematopoietic system during myelosuppressive injury or aging. Expanding and rejuvenating HSCs for therapeutic purposes has been a long-sought goal, with limited progress. Here, we show that enzyme sphingosine kinase 2 (Sphk2), which generates the lipid metabolite sphingosine-1-phosphate, is highly expressed in HSCs. The deletion of Sphk2 markedly promotes self-renewal and increases the regenerative potential of HSCs. More importantly, Sphk2 deletion globally preserves the young HSC gene expression pattern, improves the function, and sustains the multilineage potential of HSCs during aging. Mechanistically, Sphk2 interacts with prolyl hydroxylase 2 and the Von Hippel-Lindau protein to facilitate HIF1α ubiquitination in the nucleus independent of the Sphk2 catalytic activity. Deletion of Sphk2 increases hypoxic responses by stabilizing the HIF1α protein to upregulate PDK3, a glycolysis checkpoint protein for HSC quiescence, which subsequently enhances the function of HSCs by improving their metabolic fitness; specifically, it enhances anaerobic glycolysis but suppresses mitochondrial oxidative phosphorylation and generation of reactive oxygen species. Overall, targeting Sphk2 to enhance the metabolic fitness of HSCs is a promising strategy to expand and rejuvenate functional HSCs.

5.
J Environ Manage ; 319: 115656, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35810584

RESUMO

Biodrying is a promising method that produces bio-stabilized output with minimum pretreatment requirements. In this study, a hot-air supply system was added to the traditional biodrying process for kitchen waste, which showed significant reduction in moisture content in 5 days (maximum reduction of 37.45%). A series of experiments was conducted to optimize the hot-air biodrying system utilizing different aeration rates, temperatures, and mixing ratios of feedstock to bulking agents. The results showed that a 65 °C aeration temperature led to the highest water removal rate and low volatile solids consumption rate, with the biodrying index reaching 4.9 g water per gram of volatile solids. On the other hand, evaluation of the overall biodrying efficiency based on the weight loss and bio-stabilization showed that intermittent aeration temperature at 55 °C performed best, offering suitable conditions for water evaporation and bio-degradation. In combination with a flow rate of 0.8 L/kg*min and 1:1 mixing ratio, these conditions resulted in the maximum volatile solids consumption of 26.26% in 5 days. The volatile solids consumption and 34.47% water removal rate of the trial had contributed to a total of 64.13% weight loss. The weight loss was even higher than that of a conventional biodrying system which was conducted for more than 14 days.

6.
Front Endocrinol (Lausanne) ; 13: 864703, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784533

RESUMO

Nonalcoholic steatohepatitis (NASH) has become a major cause of liver transplantation and liver-associated death. Targeting the gut-liver axis is a potential therapy for NASH. The Fufang Zhenzhu Tiaozhi (FTZ) capsule, a traditional Chinese medicine commonly used in clinical practice, has recently emerged as a promising drug candidate for metabolic diseases such as NASH. The present study aimed to investigate whether FTZ exerts an anti-NASH effect by targeting the gut-liver axis. Mice were fed with a high-fat diet (HFD) for 20 weeks to induce NASH. HFD-fed mice were daily intragastrically administrated with FTZ at 10 weeks after tbe initiation of HFD feeding. The mRNA levels of genes associated with the intestinal tight junction, lipid metabolism, and inflammation were determined by the q-PCR assay. Hepatic pathology was evaluated by H&E staining. The gut microbiota was analyzed by 16S rRNA gene sequencing. FTZ attenuated HFD-induced obesity, insulin resistance, and hepatic steatosis in mice. FTZ treatment decreased the elevated levels of serum aminotransferases and liver triglyceride in NASH mice. Furthermore, FTZ treatment reduced hepatic inflammatory cell infiltration and fibrosis in mice. In addition, FTZ attenuated the intestinal inflammatory response and improved intestinal barrier function. Mechanistically, FTZ-treated mice showed a different gut microbiota composition compared with that in HFD-fed mice. Finally, we identified eight differential metabolites that may contribute to the improvement of NASH with FTZ treatment. In summary, FTZ ameliorates NASH by inhibiting gut inflammation, improving intestinal barrier function, and modulating intestinal microbiota composition.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Dieta Hiperlipídica/efeitos adversos , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , RNA Ribossômico 16S
7.
Biology (Basel) ; 11(6)2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35741379

RESUMO

Crab-eating frogs (Fejervarya cancrivora) can live in brackish water with a salinity of up to 18‱, although most amphibians are not able to tolerate such high saline environments. To investigate its potential osmoregulation, we conducted experiments in F. cancrivora and F. multistriata. The results showed that F. cancrivora made use of ions (such as Na+ and Cl-) to increase intracellular concentrations via the Na+/K+-ATPase (NKA) enzyme. The mRNA expression of aldose reductase (AR) was significantly higher in F. cancrivora (p < 0.05), indicating that more organic osmolytes were produced and transported to maintain cellular homeosis. The mRNA expressions of Aquaporin 1 (AQP1) and AQP3 in kidney were significantly higher in F. cancrivora, while AQP expression in skin was higher in F. multistriata (p < 0.05). The mRNA level in activating the transcription of the nuclear factor of activated T cells-5 (NFAT5) which is one of the target genes of regulating the cellular response to hypertonicity, was higher in F. cancrivora. The protein expression of CDK5, the upstream protein of the NFAT5 pathway, was 2 times higher in F. cancrivora. Therefore, we can conclude that CDK5/NFAT5-regulated transporters might be involved in osmoregulation in F. cancrivora.

8.
Front Oncol ; 12: 716295, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719947

RESUMO

Inflammation is a hallmark of cancers. The purpose of the present study was to evaluate the prognostic potential of hematological inflammatory markers in glioblastoma multiforme (GBM) patients. The clinical data of 99 patients with lower-grade gliomas and 88 patients with GBMs were retrospectively analyzed. The optimal cutoff values for peripheral markers were determined by X-tile. Kaplan-Meier and Cox proportional hazard regression analyses were performed to identify markers with prognostic significance. Several scoring systems were constructed by combining these prognostic markers. The predictive accuracies of nomograms incorporating these scoring systems were evaluated by Harrell's concordance index and receiver operating characteristic curve analysis. GBM patients exhibited higher neutrophil counts (p=0.001), neutrophil-to-lymphocyte ratio (NLR) (p<0.001), and platelet-to-lymphocyte ratio (PLR) (p=0.001), as well as lower lymphocyte counts (p=0.023), lymphocyte-to-monocyte ratio (LMR) (p=0.015), and albumin-to-globulin ratio (AGR) (p=0.003) than those with lower-grade gliomas. Multivariate analysis indicated that a high NLR (> 2.0) (Hazard ratio[HR]=2.519, 95% confidence interval (CI): 1.220-5.204, p=0.013), low LMR (< 2.3) (HR=2.268, 95%CI: 1.172-4.386, p=0.015), or low AGR (< 1.7) (HR=2.924, 95%CI: 1.389-6.135, p=0.005) were associated with poor overall survival in GBM patients. The scoring systems of AGR-NLR, AGR-LMR, and LMR-NLR were associated with GBM survival. The nomogram integrating AGR-NLR score had the best efficacy in predicting GBM survival (c-index=0.874). Pretreatment scores of AGR-NLR, AGR-LMR, and LMR-NLR may serve as prognostic factors for GBM patients, and a nomogram integrating AGR-NLR may provide a reliable tool to facilitate personalized preoperative evaluations.

9.
Neurosci Bull ; 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35670952

RESUMO

Isocitrate dehydrogenase (IDH) is an essential metabolic enzyme in the tricarboxylic acid cycle (TAC). The high mutation frequency of the IDH gene plays a complicated role in gliomas. In addition to affecting gliomas directly, mutations in IDH can also alter their immune microenvironment and can change immune-cell function in direct and indirect ways. IDH mutations mediate immune-cell infiltration and function by modulating immune-checkpoint gene expression and chemokine secretion. In addition, IDH mutation-derived D2-hydroxyglutarate can be absorbed by surrounding immune cells, also affecting their functioning. In this review, we summarize current knowledge about the effects of IDH mutations as well as other gene mutations on the immune microenvironment of gliomas. We also describe recent preclinical and clinical data related to IDH-mutant inhibitors for the treatment of gliomas. Finally, we discuss different types of immunotherapy and the immunotherapeutic potential of IDH mutations in gliomas.

10.
Curr Drug Metab ; 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35702776

RESUMO

Background:Cytochrome P450 (P450) is the largest family of enzymatic proteins in the human liver, and its features have been studied in physiology, medicine, biotechnol-ogy, and phytoremediation. OBJECTIVE: The aim of this study was to assess the catalytic activities of 28 human CYP3A4 alleles by using dronedarone as a probe drug in vitro, including 7 novel al-leles recently found in the Han Chinese population. METHODS: We expressed 28 CYP3A4 alleles in insect microsomes and incubated them with 1-100 µM of dronedarone at 37℃ for 40 minutes to obtain the metabolites of N-debutyl-dronedarone. RESULTS: Compared with the wild type of CYP3A4, the 27 defective alleles can be clas-sified into four categories. Three alleles had no detectable enzyme activity leading to a lack of kinetic parameters of N-debutyl-dronedarone; Other three alleles were slightly despaired when it comes to intrinsic clearance values compared with the features of the wild type. Sixteen alleles exhibited 35.91%~79.70% relative values (in comparison to the wild-type) and could be defined as the "moderate decrease group". The rest of the alleles showed a considerable decrease in intrinsic clearance values, ranging from 11.88%~23.34%. Therefore they were classified as a "significantly decreased group". More specifically, 18 CYP3A4 alleles exhibited a substrate inhibition trend toward dronedarone when the concentration rises to 20µM. CONCLUSION: The outcomes of this novel study on the metabolism of dronedarone by CYP3A4 alleles can be used as experimental data support for the individualized use of this modern drug.

11.
12.
Acta Pharm Sin B ; 12(5): 2443-2461, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35646543

RESUMO

Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl4, α-naphthyl-isothiocyanate (ANIT), bile duct ligation (BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix (ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-ß expression as well as downstream Smad signaling pathways particularly in CCl4-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of pro-inflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha (NFκB/IKBα) pathways as well as c-Jun N-terminal kinase (JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl4-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.

13.
Inorg Chem ; 61(20): 7746-7753, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35544682

RESUMO

Capturing volatile radionuclide iodine produced in the nuclear industry is a crucial environmental issue. In previous studies, the principal efficient adsorbent for iodine capture was silver-containing zeolite. As silver-containing zeolites are expensive, alternate copper-loaded porous zeolites, including CuCl loaded NaY reduced by H2 (denoted as H2CuY) and CO (denoted as COCuY), were studied for iodine adsorption at moderate temperatures. The current work also discusses the influence of copper valency on iodine adsorption. Due to the copper sites and nanosized pore structure, H2CuY and COCuY showed high iodine adsorption capacities of 450 and 219 mg/g, respectively. The iodine adsorption capacity of H2CuY was higher than that of silver-loaded zeolites. Moreover, H2CuY and COCuY adsorbed volatile iodine through a chemical mechanism involving the copper sites of different valencies, and the Cu0 was more effective in adsorbing iodine than Cu+. These copper-loaded zeolites with strong chemical interactions with iodine and high iodine adsorption capacities provided the possibility for iodine adsorption application in the nuclear industry.

14.
J Neuroinflammation ; 19(1): 117, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35610704

RESUMO

BACKGROUND: Agomelatine has been shown to be effective in the treatment of depression, but the molecular mechanisms underlying its antidepressant effects have yet to be elucidated. Identification of these molecular mechanisms would not only offer new insights into the basis for depression but also provide the foundation for the development of novel treatments for this disorder. METHODS: Intraperitoneal injection of LPS was used to induce depression-like behaviors in rats. The interactions of the 5-HT2C reporter and Gαi-2 were verified by immunoprecipitation or immunofluorescence assay. Inflammatory related proteins, autophagy related proteins and apoptosis markers were verified by immunoblotting or immunofluorescence assay. Finally, electron microscopy analysis was used to observe the synapse and ultrastructural pathology. RESULTS: Here, we found that the capacity for agomelatine to ameliorate depression and anxiety in a lipopolysaccharide (LPS)-induced rat model of depression was associated with an alleviation of neuroinflammation, abnormal autophagy and neuronal apoptosis as well as the promotion of neurogenesis in the hippocampal dentate gyrus (DG) region of these rats. We also found that the 5-HT2C receptor is coupled with G alphai (2) (Gαi-2) protein within hippocampal neurons and, agomelatine, acting as a 5-HT2C receptor antagonist, can up-regulate activity of the Gαi-2-cAMP-PKA pathway. Such events then suppress activation of the apoptosis signal-regulating kinase 1 (ASK1) pathway, a member of the mitogen-activated protein kinase (MAPK) family involved in pathological processes of many diseases. CONCLUSION: Taken together, these results suggest that agomelatine plays a neuroprotective role in regulating neuroinflammation, autophagy disorder and apoptosis in this LPS-induced rat model of depression, effects which are associated with the display of antidepressant behaviors. These findings provide evidence for some of the potential mechanisms for the antidepressant effects of agomelatine.


Assuntos
Acetamidas , Naftalenos , Receptor 5-HT2C de Serotonina , Acetamidas/farmacologia , Animais , Antidepressivos/farmacologia , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Depressão/patologia , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Lipopolissacarídeos/farmacologia , MAP Quinase Quinase Quinase 5/metabolismo , Naftalenos/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ratos , Receptor 5-HT2C de Serotonina/metabolismo , Transdução de Sinais
15.
Front Microbiol ; 13: 795101, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547153

RESUMO

The acquisition and development of the mammalian microbiome early in life are critical to establish a healthy host-microbiome symbiosis. Despite recent advances in understanding microbial sources in infants, the relative contribution of various microbial sources to the colonization of the gut microbiota in pigs remains unclear. Here, we longitudinally sampled the microbiota of 20 sow-piglet pairs (three piglets per sow) reared under identical conditions from multiple body sites and the surrounding weaning environment from birth to 28 days postpartum (1,119 samples in total). Source-tracking analysis revealed that the contribution of various microbial sources to the piglet gut microbiome gradually changed over time. The neonatal microbiota was initially sparsely populated, and the predominant contribution was from the maternal vaginal microbiota that increased gradually from 69.0% at day 0 to 89.3% at day 3 and dropped to 0.28% at day 28. As the piglets aged, the major microbial community patterns were most strongly associated with the sow feces and slatted floor, with contributions increasing from 0.52 and 9.6% at day 0 to 62.1 and 33.8% at day 28, respectively. The intestinal microbial diversity, composition, and function significantly changed as the piglets aged, and 30 age-discriminatory bacterial taxa were identified with distinctive time-dependent shifts in their relative abundance, which likely reflected the effect of the maternal and environmental microbial sources on the selection and adaptation of the piglet gut microbiota. Overall, these data demonstrate that the vaginal microbiota is the primary source of the gut microbiota in piglets within 3 days after birth and are gradually replaced by the sow fecal and slatted floor microbiota over time. These findings may offer novel strategies to promote the establishment of exogenous symbiotic microbes to improve piglet gut health.

16.
Chemosphere ; 303(Pt 1): 134978, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35595113

RESUMO

The treatment and disposal of municipal solid waste incineration fly ash (MSWI FA) faces many challenges, such as landfill space occupation, high costs and potential environmental threats. In this study, coal fly ash (CFA), metakaolin (MK) and silica fume (SF) were used as aluminosilicate supplementary cementitious materials (ASCM), and mixed with MSWI FA as precursors for the synthesis of alkali-activated and geopolymers hybrid binder (AGHB). The results show that this alkali-activated technology efficiently immobilized the heavy metals in MSWI FA, and the ASCM contributes to the compressive strength enhancement of the AGHB. The highest compressive strength of the synthesized products that mixed MSWI FA with CFA and MK as precursors, reached 5.34 and 9.06 MPa, respectively. The compressive strength of the ASCM synthesized by mixing MSWI FA and SF in the mass ratio of 70:30 with the alkali activator modulus of 1.6 M could reach 11.2 MPa after 28 d of curing, which met the quality standard of MU10 (NY/T 671-2003) for load-bearing brick.The leaching concentrations of Hg and Pb were reduced from 0.15 to 3.96 mg/L to less than 0.003 and 0.107 mg/L, which were below the limit established by the Chinese standard (GB 8978-1996). The research provides the technical parameters of the optimization conditions on the synthesis of MSWI FA-based AGHB, for the resource utilization of MSWI FA and reduction of the environmental risk.

17.
Emerg Microbes Infect ; 11(1): 1572-1585, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35621025

RESUMO

Cryptococcal meningoencephalitis (CM) is emerging as an infection in HIV/AIDS patients shifted from primarily ART-naive to ART-experienced individuals, as well as patients with COVID-19 and immunocompetent hosts. This fungal infection is mainly caused by the opportunistic human pathogen Cryptococcus neoformans. Brain or central nervous system (CNS) dissemination is the deadliest process for this disease; however, mechanisms underlying this process have yet to be elucidated. Moreover, illustrations of clinically relevant responses in cryptococcosis are currently limited due to the low availability of clinical samples. In this study, to explore the clinically relevant responses during C. neoformans infection, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton, a major feature of HIV/AIDS patients, was a centric pathway regulated in both infection models. Notably, assays of clinical immune cells confirmed an enhanced macrophage "Trojan Horse" in patients with HIV/AIDS, which could be shut down by cytoskeleton inhibitors. Furthermore, myocilin, encoded by MYOC, was found to be a novel enhancer for the macrophage "Trojan Horse," and an enhanced fungal burden was achieved in the brains of MYOC-transgenic mice. Taken together, the findings from this study reveal fundamental roles of the cytoskeleton and MYOC in fungal CNS dissemination, which not only helps to understand the high prevalence of CM in HIV/AIDS but also facilitates the development of novel therapeutics for meningoencephalitis caused by C. neoformans and other pathogenic microorganisms.


Assuntos
COVID-19 , Criptococose , Cryptococcus neoformans , Infecções por HIV , Meningoencefalite , MicroRNAs , Animais , Encéfalo/patologia , Criptococose/microbiologia , Cryptococcus neoformans/genética , Modelos Animais de Doenças , Humanos , Macaca , Meningoencefalite/microbiologia , Camundongos , MicroRNAs/genética , Transcriptoma
18.
J Cell Mol Med ; 26(12): 3527-3537, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35593216

RESUMO

Oxidative stress appears to play a role in the pathogenesis of diabetes mellitus erectile dysfunction (DMED). This study aimed to investigate the effect of N-acetylcysteine (NAC) on DMED in streptozotocin-induced diabetic mice and to explore potential mechanisms. In the present study, we show that an erectile dysfunction is present in the streptozotocin-induced mouse model of diabetes as indicated by decreases in intracavernous pressure responses to electro-stimulation as well as from results of the apomorphine test of erectile function. After treatment of NAC, the intracavernous pressure was increased. In these DMED mice, oxidative stress and inflammatory responses were significantly reduced within the cavernous microenvironment, while activity of antioxidant enzymes in this cavernous tissue was enhanced after NAC treatment. These changes protected mitochondrial stress damage and a significant decreased in apoptosis within the cavernous tissue of DMED mice. This appears to involve activation of the nuclear factor erythroid 2-like-2 (Nrf2) signalling pathway, as well as suppression of the mitogen-activated protein kinase (MAPK) p38/ NF-κB pathway within cavernous tissue. In conclusion, NAC can improve erectile function through inhibiting oxidative stress via activating Nrf2 pathways and reducing apoptosis in streptozotocin-induced diabetic mice. NAC might provide a promising therapeutic strategy for individuals with DMED.


Assuntos
Diabetes Mellitus Experimental , Disfunção Erétil , Acetilcisteína/metabolismo , Acetilcisteína/farmacologia , Acetilcisteína/uso terapêutico , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Disfunção Erétil/complicações , Disfunção Erétil/tratamento farmacológico , Humanos , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Estreptozocina/farmacologia
19.
Ultrason Sonochem ; 86: 106004, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35429900

RESUMO

Kiwi starch (KS) is a fruit-derived starch; in order to improve its processing performance and increase its added value, it is necessary to modify KS to enhance the positive attributes and to enlarge its application. In this study, KS was modified by high-power ultrasound treatment (HUT) to reveal the relationship between the structure and function of KS with different treatment powers (0, 200, 400, and 600 W) and different treatment times (0, 10, 20, and 30 min). The results showed that HUT destroyed the granular morphology of KS, formed holes and cracks on the surface, and reduced the particle size and the short-range molecular order of KS. After different HUTs, the apparent amylose content (AAC), swelling power (SP), water solubility index (WSI), viscosity and setback value (SB) of KS were significantly increased, while the gelatinization temperature was significantly decreased. In addition, HUT significantly reduced the content of rapidly digestible starch (RDS) and slowly digestible starch (SDS), while it significantly enhanced the content of resistant starch (RS) (64.08-72.73%). In a word, HUT as a novel physical modification method for KS, enlarged its application, and fulfilled different demands of a starch-based product, which introduces another possibility for kiwi fruit further processing.


Assuntos
Amilose , Amido , Amilose/química , Digestão , Solubilidade , Amido/química , Viscosidade
20.
Front Immunol ; 13: 866040, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432349

RESUMO

The biliary system is comprised of cholangiocytes and plays an important role in maintaining liver function. Under normal conditions, cholangiocytes remain in the stationary phase and maintain a very low turnover rate. However, the robust biliary repair is initiated in disease conditions, and different repair mechanisms can be activated depending on the pathological changes. During biliary disease, immune cells including monocytes, lymphocytes, neutrophils, and mast cells are recruited to the liver. The cellular interactions between cholangiocytes and these recruited immune cells as well as hepatic resident immune cells, including Kupffer cells, determine disease outcomes. However, the role of immune cells in the initiation, regulation, and suspension of biliary repair remains elusive. The cellular processes of cholangiocyte proliferation, progenitor cell differentiation, and hepatocyte-cholangiocyte transdifferentiation during biliary diseases are reviewed to manifest the underlying mechanism of biliary repair. Furthermore, the potential role of immune cells in crucial biliary repair mechanisms is highlighted. The mechanisms of biliary repair in immune-mediated cholangiopathies, inherited cholangiopathies, obstructive cholangiopathies, and cholangiocarcinoma are also summarized. Additionally, novel techniques that could clarify the underlying mechanisms of biliary repair are displayed. Collectively, this review aims to deepen the understanding of the mechanisms of biliary repair and contributes potential novel therapeutic methods for treating biliary diseases.


Assuntos
Neoplasias dos Ductos Biliares , Sistema Biliar , Colangiocarcinoma , Ductos Biliares Intra-Hepáticos/patologia , Sistema Biliar/patologia , Humanos , Fígado/patologia
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