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1.
Food Funct ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647565

RESUMO

The thymus and spleen are the main reservoir for T lymphocytes, which can regulate the innate immune response and provide protection against pathogens and tissue damage. Oxidative stress, excessive inflammation, abnormal autophagy and endoplasmic reticulum (ER) stress can all lead to dysfunction of the thymus and spleen. This study was conducted to investigate the effect of maternal 2-hydroxy-4-methylselenobutanoic acid (HMSeBA, an organic Se source) supplementation during pregnancy on the selenoprotein expression, inflammation, ER stress and autophagy of their young offspring's thymus and spleen. Thirty sows were randomly assigned to receive one of the following two diets during gestation: control diet (control, basal diet, n = 15) or HMSeBA supplemented diet (HMSeBA, basal diet +0.3 mg Se kg-1 as HMSeBA, n = 15). Tissues of thymus and spleen were collected from the offspring at birth and weaning after the lipopolysaccharide challenge. Results showed that maternal HMSeBA supplementation significantly up-regulated the gene expression of selenoproteins in the thymus and spleen of newborn piglets compared with the basal diet (p < 0.05), as well as the protein abundance of GPX1 and GPX4 (p < 0.05). In addition, maternal HMSeBA supplementation effectively decreased the expression of inflammation and autophagy related proteins in the thymus and spleen of newborn piglets as compared with the control group (p < 0.05). In weaning piglets, maternal HMSeBA significantly increased the antioxidative capacity of thymus and spleen (p < 0.05), and reversed LPS induced MDA content as compared with the control group (p < 0.05). Furthermore, maternal HMSeBA supplementation during gestation reversed the activation of the MAPK/NF-κB pathway, ER stress and autophagy induced by the LPS challenge in the thymus and spleen of weaning piglets (p < 0.05). In conclusion, maternal HMSeBA supplementation during gestation could decrease the level of inflammation, autophagy and ER stress in the thymus and spleen of young offspring by improving the antioxidative capacity and selenoprotein expression in these tissues. Therefore, maternal HMSeBA supplementation during gestation might be beneficial for the immune function of their offspring by alleviating inflammation, autophagy and ER stress levels in the thymus and spleen. This study showed more evidence for the function of Se on mater-offspring integrated nutrition.

2.
J Chromatogr A ; 1657: 462579, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34607292

RESUMO

Due to the extensive use of chemical substances such as pesticides, antibiotics and food additives, food safety issues have gradually attracted people's attention. The extensive use of these chemicals seriously damages human health. In order to detect trace chemical residues in food, researchers have to find several simple, economical and effective tools for qualitative and quantitative analysis. As a kind of material that specifically and selectively recognize template molecules from real samples, molecular imprinting technique (MIT) has widely applied in food samples analysis. This article mainly reviews the application of molecularly imprinted polymer (MIP) in the detection of chemical residues from food in the past five years. Some recent and novel methods for fabrication of MIP are reviewed. Their application of sample pretreatment, sensors, etc. in food analysis is reviewed. The application of molecular imprinting in chromatographic stationary phase is referred. Additionally, the challenges faced by MIP are discussed.

3.
Neuropharmacology ; 200: 108816, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34599975

RESUMO

We recently reported that intraperitoneal injection of a low dose of lipopolysaccharide (LPS) prevents chronic stress-induced depression-like behaviors in mice. In this study, we reported that a single intranasal LPS administration (10 µg/mouse) one day prior to stress exposure produced prophylactic effects on chronic social defeat stress (CSDS)-induced depression-like behaviors, which was indicated by the reduction in social interaction time in the social interaction test and the decrease in immobility time in the tail suspension test and forced swimming test. The single intranasal LPS administration prior to stress exposure was also found to prevent CSDS-induced anxiety-like behaviors, including prevention of CSDS-induced decrease in the time spent in open arms in the elevated plus maze test, decrease in the time spent in lit side in the light-dark test, and decrease in the time spent in central regions in the open field test, along with no changes in locomotor activity. Further analysis showed that the single intranasal LPS administration one day prior to stress exposure prevented CSDS-induced increase in levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß mRNA in the hippocampus and prefrontal cortex. Inhibition of innate immune stimulation by minocycline pretreatment not only abrogated the preventive effect of intranasal LPS administration on CSDS-induced depression- and anxiety-like behaviors, but also abrogated the preventive effect of intranasal LPS administration on CSDS-induced neuroinflammatory responses in the hippocampus and prefrontal cortex. These results demonstrate that intranasal administration of innate immune stimulants could be a potential approach for the prevention of depression and anxiety.

4.
Food Funct ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34617945

RESUMO

In this study, the Nelumbo nucifera leaf polysaccharide (NNLP) was isolated by hot water extraction and ethanol precipitation. DEAE anion exchange chromatography and gel filtration were further performed to obtained the purified fraction NNLP-I-I, the molecular weight of which was 16.4 kDa. The monosaccharide composition analysis and linkage units determination showed that the fraction NNLP-I-I was a pectic polysaccharide. In addition, the NMR spectra analysis revealed that NNLP-I-I mainly consisted of a homogalacturonan backbone and rhamnogalacturonan I, containing a long HG region and short RG-I region, with AG-II and 1-3 linked rhamnose as side chains. The biological studies demonstrated that NNLP-I-I displayed antioxidant properties through mediating the Nrf2-regulated intestinal cellular antioxidant defense, which could protect cultured intestinal cells from oxidative stress and improve the intestinal function of aged mice.

5.
Immunity ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34626548

RESUMO

Self-reactive B cell progenitors are eliminated through central tolerance checkpoints, a process thought to be restricted to the bone marrow in mammals. Here, we identified a consecutive trajectory of B cell development in the meninges of mice and non-human primates. The meningeal B cells were located predominantly at the dural sinuses, where endothelial cells expressed essential niche factors to support B cell development. Parabiosis experiments together with lineage tracing showed that meningeal developing B cells were replenished continuously from hematopoietic stem cell (HSC)-derived progenitors via a circulation-independent route. Autoreactive immature B cells that recognized myelin oligodendrocyte glycoprotein (MOG), a central nervous system-specific antigen, were eliminated specifically from the meninges. Furthermore, genetic deletion of the Mog gene restored the self-reactive B cell population in the meninges. These findings identify the meninges as a distinct reservoir for B cell development, allowing in situ negative selection to ensure a locally non-self-reactive immune repertoire.

6.
Front Cell Infect Microbiol ; 11: 564938, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646783

RESUMO

T-cell reduction is an important characteristic of coronavirus disease 2019 (COVID-19), and its immunopathology is a subject of debate. It may be due to the direct effect of the virus on T-cell exhaustion or indirectly due to T cells redistributing to the lungs. HIV/AIDS naturally served as a T-cell exhaustion disease model for recognizing how the immune system works in the course of COVID-19. In this study, we collected the clinical charts, T-lymphocyte analysis, and chest CT of HIV patients with laboratory-confirmed COVID-19 infection who were admitted to Jin Yin-tan Hospital (Wuhan, China). The median age of the 21 patients was 47 years [interquartile range (IQR) = 40-50 years] and the median CD4 T-cell count was 183 cells/µl (IQR = 96-289 cells/µl). Eleven HIV patients were in the non-AIDS stage and 10 were in the AIDS stage. Nine patients received antiretroviral treatment (ART) and 12 patients did not receive any treatment. Compared to the reported mortality rate (nearly 4%-10%) and severity rate (up to 20%-40%) among COVID-19 patients in hospital, a benign duration with 0% severity and mortality rates was shown by 21 HIV/AIDS patients. The severity rates of COVID-19 were comparable between non-AIDS (median CD4 = 287 cells/µl) and AIDS (median CD4 = 97 cells/µl) patients, despite some of the AIDS patients having baseline lung injury stimulated by HIV: 7 patients (33%) were mild (five in the non-AIDS group and two in the AIDS group) and 14 patients (67%) were moderate (six in the non-AIDS group and eight in the AIDS group). More importantly, we found that a reduction in T-cell number positively correlates with the serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP), which is contrary to the reported findings on the immune response of COVID-19 patients (lower CD4 T-cell counts with higher levels of IL-6 and CRP). In HIV/AIDS, a compromised immune system with lower CD4 T-cell counts might waive the clinical symptoms and inflammatory responses, which suggests lymphocyte redistribution as an immunopathology leading to lymphopenia in COVID-19.

7.
Chemosphere ; 288(Pt 1): 132427, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34600922

RESUMO

As UV-light stabilizers, Bis(4-hydroxy)benzophenone (BBP), are extensively consumed to quench radicals from photooxidation, continuous release of BPs into the environment poses serious threats to the ecology in view of their xenohormone toxicities, and BBP shall be eliminated from water to avoid its adverse effect. Since sulfate radical (SR)-based chemical oxidation techniques have been proven as effective procedures for eliminating organic emerging contaminants, this study aims to develop useful SR-based procedures through activating Oxone for degrading BBP in water. In contrast to the conventional Co3O4, cobalt sulfide (CoS) is particularly proposed as an alternative heterogeneous catalyst for activating Oxone to degrade BBP because CoS exhibits more reactive redox characteristics. As structures of catalysts predominantly control their catalytic activities, in this study, a unique nanoplate-assembled CoS (NPCS) 3D cluster is fabricated via a convenient one-step process to serve as a promising heterogeneous catalyst for activating Oxone to degrade BBP. With NPCS = 100 mg/L and Oxone = 200 mg/L, 5 mg/L of BBP can be completely eliminated in 60 min. The catalytic activity of NPCS towards Oxone activation also significantly surpasses the reference material, Co3O4, to enhance degradation of BBP. Ea of BBP degradation by NPCS-activated Oxone is also determined as a relatively low value of 42.7 kJ/mol. The activation mechanism as well as degradation pathway of BBP degradation by NPCS-activated Oxone was investigated and validated through experimental evidences and density functional theory (DFT) calculation to offer valuable insights into degradation behaviors for developing SR-based processes of BBP degradation using CoS catalysts.

8.
Mol Imaging Biol ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34651291

RESUMO

PURPOSE: This study aimed to evaluate the value of [68 Ga]Pentixafor PET/CT for the detection of lesions in central nervous system lymphoma (CNSL) patients before chemotherapy, during treatment and suspected CSNL recurrence, compared with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT). PROCEDURES: Twenty-six patients with newly or previously diagnosed CNSL who underwent [68 Ga]Pentixafor PET/CT were included retrospectively. Histopathological results, magnetic resonance imaging (MRI), and follow-up were used as the standard reference. The accuracy of lesion detection, maximum standardized uptake value (SUVmax) of tumors, and ratio of tumor-to-normal brain (T/N) with [68 Ga]Pentixafor PET/CT were calculated and compared to those obtained with [18F]FDG PET/CT. CXCR4 expression was analyzed through immunohistochemistry. RESULTS: Of 26 patients, 18 were newly diagnosed with a total of 23 lesions, 4 had recurrent with 4 lesions, and 4 underwent a mid-term treatment assessment after 4 cycles of chemotherapy (3 achieved complete response (CR), 1 experienced progressive disease (PD) with a total of 8 lesions). Thirty-five lesions were all clearly detected with favorable contrast by [68 Ga]Pentixafor PET/CT (accuracy, 100%), consistent with the results of contrast-enhanced magnetic resonance imaging (CE-MRI). The SUVmax of positive lesions in [68 Ga]Pentixafor PET/CT was correlated with tumor size (r = 0.555, P = 0.001). In 21 patients, compared with [18F]FDG PET/CT, [68 Ga]Pentixafor PET/CT showed a remarkably higher T/N ratio (21.93 ± 10.77 vs 4.29 ± 2.16, P = 0.000) and detected 5 more lesions in the mid-term treatment assessment of patients (P = 0.026). The CXCR4 expression of CNSL lesions was correlated with SUVmax of [68 Ga]Pentixafor PET/CT (r = 0.772, P = 0.000). CONCLUSIONS: CXCR4-directed PET/CT using [68 Ga]Pentixafor, with excellent tumor-to-background contrast, might be a more promising agent for the detection of lesions in CNSL patients than [18F]FDG PET/CT.

9.
IEEE Trans Cybern ; PP2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34487509

RESUMO

A connected vehicle platoon with unknown input delays is studied in this article. The control objective is to stabilize the connected vehicles, ensuring all vehicles are traveling at the same speed while maintaining a safety spacing. A decentralized control law using only onboard sensors is designed for the connected vehicle platoon. A novel switching-type delay-adaptive predictor is proposed to estimate the unknown input delays. By using the estimated unknown input delays, the control law can guarantee the stability of the successive vehicles. The platoon control adopts a one-vehicle look-ahead topology structure and a constant time headway (CTH) policy, which makes the desired spacing between vehicles vary with time. In this framework, the stability of the connected vehicles can be derived through the analysis of each pair of two successive vehicles in the platoon. Finally, an example is presented to illustrate the applicability of the obtained results.

10.
Inorg Chem ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465086

RESUMO

Three octyl-extended bis-triamide extractants (L1-L3) were designed and synthesized for the selective solvent extraction of Th(IV) over U(VI) in a kerosene-HNO3 system. L1 and L2 exhibited good extraction property and selectivity toward Th(IV) over U(VI) and reached extraction equilibrium within 10 min. In a wide range of a HNO3 concentration from 0.1 to 3.0 M, the separation factor of Th(IV) over U(VI) (SFTh/U) of L1 and L2 ranged from 12.1 ± 1.6 to 123.0 ± 20.2 and 15.2 ± 2.4 to 88.1 ± 14.9, respectively. Slope analysis indicated that Th(IV) was extracted as different species under different HNO3 concentrations, in which the slopes were 2.08 ± 0.20, 1.61 ± 0.03, and 1.54 ± 0.03 for L1 and 2.37 ± 0.22, 2.07 ± 0.17, and 1.76 ± 0.18 for L2 under 0.1, 1.0, and 3.0 M HNO3, respectively. A continuous variation method (Job plot) illustrated a 1.5:1 ligand/thorium (L/Th) ratio in a methanol phase, indicating that L1/L2 and Th(IV) could form mixed 1:1 and 2:1 L/Th extracted complexes. Extended X-ray absorption fine structure (EXAFS) and density functional theory (DFT) calculations revealed that the extracted complexes of L1 and L2 with Th during the extraction process at 0.1 M HNO3 were [2L1·Th·3(NO3)]+ and [2L2·Th·3(NO3)]+.

11.
J Orthop Surg (Hong Kong) ; 29(3): 23094990211042674, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34550034

RESUMO

Purpose: The purpose of this study was to compare the coagulation difference in patients with either rivaroxaban or enoxaparin as thromboprophylaxis after total hip arthroplasty (THA) regarding thromboelastography (TEG) and routine coagulation tests. Patients and methods: Two hundred and twenty-eight patients undergoing primary THA were recruited in this study. They were divided into two groups according to a computer-generated random sequence. Patients in the rivaroxaban group received 10 mg of rivaroxaban orally once daily. Patients in the enoxaparin group received 4000 AxaIU (0.4 mL) of enoxaparin subcutaneously once daily. Rivaroxaban and enoxaparin were started 6-8 h after surgery. The administration of the anticoagulant prophylaxis was lasted for a minimum of 14 days. TEG and routine coagulation tests were performed on the day before the operation and 1 day and 7 days after the operation. Results: No difference was observed in the incidence of deep vein thrombosis (DVT) or pulmonary embolism (PE) between the two groups. There was no significant difference with regard to prothrombin time (PT), activated partial thromboplastin time (PTT), international normalized ratio (INR), and thrombin time (TT) between the two groups. However, while considering TEG, R time of the rivaroxaban group was significantly higher than that of the enoxaparin group (p = 0.003), whereas the maximum amplitude (MA) (p = 0.036) value and coagulation index (CI) (p = 0.002) value were significantly lower than those of the enoxaparin group. Conclusion: With regard to TEG analysis, there was coagulation difference in patients with rivaroxaban and those with enoxaparin as thromboprophylaxis after THA. Under recommended dose of rivaroxaban and enoxaparin, patients undergoing THA were in hypercoagulability on 7days postoperative.

12.
Curr Eye Res ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34547966

RESUMO

PURPOSE: To assess the retinal neurodegeneration in type-1 diabetes mellitus (T1DM) and type-2 diabetes mellitus (T2DM) rhesus monkeys, and to investigate whether alterations of glial cells occur in the early stage of diabetic retinopathy (DR). MATERIAL AND METHODS: T1DM rhesus monkeys were established by daily intravenous injections of streptozotocin (STZ, 25 mg/kg body weight) in citrate buffer (pH 4.5) for 5 days, while T2DM rhesus monkeys were induced by feeding with high-fat diet. The period of DR in rhesus monkeys was evaluated by fundoscopy and optical coherence tomography (OCT). Afterward, the morphological changes of inner neurons and glial cells in the retina were detected by immunofluorescence (IF). RESULTS: When compared with the control groups, no difference was observed in both T1DM and T2DM by fundus photographs, while slight exudation and effusion in the blood vessels of retina of rhesus monkeys were found by OCT in DM rhesus monkeys. In addition, the expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule (Iba1) were significantly increased in both T1DM (P<0.01) and T2DM (P<0.05) rhesus monkeys. Moreover, the positive expression of PKC-α, parvalbumin and NeuN were significantly decreased, while the positive expression of calbindin showed no difference in T1DM group. However, only the expression cells of PKC-α were reduced in T2DM group when compared with that of the control group. CONCLUSION: Astrocytes activation, reactive gliosis, and neurodegeneration were observed in both T1DM and T2DM rhesus monkey models at the early stage of DR.

13.
J Thromb Haemost ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34532927

RESUMO

BACKGROUND: Optimal risk stratification of unsuspected pulmonary embolism (UPE) in ambulatory cancer patients (ACPs) remains unclear. Existing clinical predictive rules (CPRs) are derived from retrospective databases and have limitations. The UPE registry is a prospective international registry with pre-specified characteristics of ACPs with a recent UPE. The aim of this study was to assess the utility of risk factors captured in the UPE registry in predicting proximate (30-, 90- and 180-day) mortality and how they performed when applied to an existing CPR. OBJECTIVES: To evaluate risk factors for proximate mortality, overall survival, recurrent venous thromboembolism and major bleeding, in the patients enrolled in the UPE registry cohort. METHODS: Data from the 695 ACPs in this registry were subjected to multivariate logistic regression analyses to identify predictors independently associated with proximate mortality and overall survival. The most consistent predictors were applied to the Hull CPR, an existing 5-point prediction rule. RESULTS: The most consistent predictors of mortality were patient-reported respiratory symptoms within 14 days before, and ECOG performance status at the time of UPE. These predictors applied to the Hull-CPR produced a consistent correlation with proximate mortality and overall survival (area under the curve [AUC] = 0.70 [95% CI 0.63, 077], AUC = 0.65 [95% CI 0.60, 070], AUC = 0.64 [95% CI 0.59, 068], and AUC = 0.61, 95% CI 0.57, 0.65, respectively). CONCLUSION: In ACPs with UPE, ECOG performance status logged contemporaneously to the UPE diagnosis and respiratory symptoms prior to UPE diagnosis can stratify mortality risk. When applied to the HULL-CPR these risk predictors confirmed the risk stratification clusters of low-intermediate and high-risk for proximate mortality as seen in the original derivation cohort.

14.
Lancet Digit Health ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34538736

RESUMO

BACKGROUND: Inadequate bowel preparation is associated with a decrease in adenoma detection rate (ADR). A deep learning-based bowel preparation assessment system based on the Boston bowel preparation scale (BBPS) has been previously established to calculate the automatic BBPS (e-BBPS) score (ranging 0-20). The aims of this study were to investigate whether there was a statistically inverse relationship between the e-BBPS score and the ADR, and to determine the threshold of e-BBPS score for adequate bowel preparation in colonoscopy screening. METHODS: In this prospective, observational study, we trained and internally validated the e-BBPS system using retrospective colonoscopy images and videos from the Endoscopy Center of Wuhan University, annotated by endoscopists. We externally validated the system using colonoscopy images and videos from the First People's Hospital of Yichang and the Third Hospital of Wuhan. To prospectively validate the system, we recruited consecutive patients at Renmin Hospital of Wuhan University aged between 18 and 75 years undergoing colonoscopy. The exclusion criteria included: contraindication to colonoscopy, family polyposis syndrome, inflammatory bowel disease, history of surgery for colorectal or colorectal cancer, known or suspected bowel obstruction or perforation, patients who were pregnant or lactating, inability to receive caecal intubation, and lumen obstruction. We did colonoscopy procedures and collected withdrawal videos, which were reviewed and the e-BBPS system was applied to all colon segments. The primary outcome of this study was ADR, defined as the proportion of patients with one or more conventional adenomas detected during colonoscopy. We calculated the ADR of each e-BBPS score and did a correlation analysis using Spearman analysis. FINDINGS: From May 11 to Aug 10, 2020, 616 patients underwent screening colonoscopies, which evaluated. There was a significant inverse correlation between the e-BBPS score and ADR (Spearman's rank -0·976, p<0·010). The ADR for the e-BBPS scores 1-8 was 28·57%, 28·68%, 26·79%, 19·19%, 17·57%, 17·07%, 14·81%, and 0%, respectively. According to the 25% ADR standard for screening colonoscopy, an e-BBPS score of 3 was set as a threshold to guarantee an ADR of more than 25%, and so high-quality endoscopy. Patients with scores of more than 3 had a significantly lower ADR than those with a score of 3 or less (ADR 15·93% vs 28·03%, p<0·001, 95% CI 0·28-0·66, odds ratio 0·43). INTERPRETATION: The e-BBPS system has potential to provide a more objective and refined threshold for the quantification of adequate bowel preparation. FUNDING: Project of Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision and Hubei Province Major Science and Technology Innovation Project.

15.
Clin Cancer Res ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526362

RESUMO

PURPOSE: Bladder cancer treatment remains a major clinical challenge due to therapy resistance and a high recurrence rate. Profiling intratumor heterogeneity can reveal the molecular mechanism of bladder cancer recurrence. EXPERIMENTAL DESIGN: Here, we performed single-cell RNA sequencing and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) on tumors from 13 patients with low recurrence risk, high recurrence risk, and recurrent bladder cancer. RESULTS: Our study generated a comprehensive cancer-cell atlas consisting of 54,971 single cells and identified distinct cell subpopulations. We found that the cancer stem-cell subpopulation is enriched during bladder cancer recurrence with elevated expression of EZH2. We further defined a subpopulation-specific molecular mechanism whereby EZH2 maintains H3K27me3-mediated repression of the NCAM1 gene, thereby inactivating the cell invasive and stemness transcriptional program. Furthermore, taking advantage of this large single-cell dataset, we elucidated the spectrum of epithelial-mesenchymal transition (EMT) in clinical samples and revealed distinct EMT features associated with bladder cancer subtypes. We identified that TCF7 promotes EMT in corroboration with single-cell ATAC with high-throughput sequencing (scATAC-seq) analysis. Additionally, we constructed regulatory networks specific to recurrent bladder cancer. CONCLUSIONS: Our study and analytic approaches herein provide a rich resource for the further study of cancer stem cells and EMT in the bladder cancer research field.

16.
Biomed Pharmacother ; 143: 112105, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34560533

RESUMO

Although the main focus of immuno-oncology has been manipulating the adaptive immune system, tumor associated macrophages (TAMs) are the main infiltrating component in the tumor microenvironment (TME) and play a critical role in cancer progression. TAMs are mainly divided into two different subtypes: macrophages with antitumor or killing activity are called M1 while tumor-promoting or healing macrophages are named M2. Therefore, controlling the polarization of TAMs is an important strategy for cancer treatment, but there is no particularly effective means to regulate the polarization process. Here, combined systems pharmacology targets and pathways analysis strategy, we uncovered Scutellariae Radix (SR) has the potential to regulate TAMs polarization to inhibit the growth of non-small cell lung cancer (NSCLC). Firstly, systems pharmacology approach was used to reveal the active components of SR targeting macrophages in TME through compound target prediction and target-microenvironment phenotypic association analysis. Secondly, in vitro experiment verified that WBB (wogonin, baicalein and baicalin), major active ingredients of SR are significantly related to macrophages and survival, initiated macrophages programming to M1-like macrophages to promoted the apoptosis of tumor cells. Finally, we evidenced that WBB effectively inhibited tumor growth in LLC (Lewis lung carcinoma) tumor-bearing mice and increased the infiltration of M1-type macrophages in TME. Overall, the systems pharmacology strategy offers a paradigm to understand the mechanism of polypharmacology of natural products targeting TME.

17.
J Environ Manage ; 299: 113607, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34467864

RESUMO

Traditional Chinese medicine (TCM) has wide application and important functions in curing many diseases, but a great number of herb residues are usually generated after its manufacture and usage. Without proper and timely treatment, these traditional Chinese medicinal herb (TCMH) residues will cause some environmental pollution. In addition to treatment, bioresources utilization of TCMH residues is also important for its great potential as a suitable feedstock for the production of energy, materials, and chemicals. In this situation, advanced and well-designed solid waste management is important to make the TCM industry environmentally friendly and economically attractive. In this review article, the recent progress focusing on various methods for TCMH residues treatment and bioresources utilization are introduced in detail. In particular, the technologies for thermochemical conversion and biochemical conversion of TCMH residues are mainly focused on in order to show how to fulfill effective and efficient bioresources utilization. Besides, some other technologies which are suitable for the treatment and bioresources utilization of TCMH residues are presented as well. Finally, some industrial prospects are given from the economic, operational, and environmental aspects for the further development of treatment and bioresources utilization of TCMH residues. Overall, this work can provide some systematical and comprehensive information for the development of technologies that help sustainably manage the herb residues generated in the TCM industry.


Assuntos
Plantas Medicinais , China , Medicina Tradicional Chinesa
18.
Ecotoxicol Environ Saf ; 225: 112718, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34478984

RESUMO

As a common environmental pollutant, nickel chloride (NiCl2) poses serious threat to human and animals health. NiCl2 has adverse effects on reproductive function in male, however, the underlying mechanisms are not fully illuminated. In this study, 64 male ICR mice were divided into four groups (8 mice per each period/ group), in which mice orally administrated with 0, 7.5, 15 or 30 mg/kg body weight for 14 or 28 consecutive days, respectively. The results showed that the sperm concentration (12.95%, 29.78% and 37.63% -) and sperm motility (19.79%, 34.88% and 43.10%) were dose-dependent significantly reduced, and the total sperm malformation rates (110.15%, 206.84% and 292.27%) were dose-dependent significantly elevated in the 7.5, 15 and 30 mg/kg NiCl2 treatment groups (vs control at 28 days), respectively (P < 0.05). Meanwhile, NiCl2 also decreased the relative weights of testis and epididymis and caused histopathological lesions of testis and epididymis. Furthermore, serum testosterone levels were significantly decreased after NiCl2 treatment. And the findings showed that NiCl2 down-regulated the expression of LH-R, StAR, P450scc, 3ß-HSD, 17ß-HSD, ABP and INHßB in the testis, however, the relative genes in the hypothalamus (Kiss-1, GPR54 and GnRH) and pituitary (GnRH-R, LHß and FSHß) did not exhibit noticeable change. In summary, NiCl2 induced spermatogenesis disorder by testicular damage and hypothalamic-pituitary-testis axis disruption in mice, and only impaired the genes on the testis of HPT axis.


Assuntos
Motilidade Espermática , Testículo , Animais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Níquel , Espermatogênese , Testosterona
19.
Ecotoxicol Environ Saf ; 225: 112760, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34509165

RESUMO

Obesity is a risk factor of many diseases, but could be beneficial to the individuals with bacterial infection. The present study was conducted to investigate the relationship between obesity and heart during nonfatal bacterial infection. Male normal (lean) and diet-induced obesity mice (DIO, fed with high-fat diet) were chosen to perform nasal instillation with E. coli to establish a nonfatal acute mouse model. The cardiac histopathology, inflammation and oxidative damage, as well as apoptosis were detected post-infection. The results revealed that the Escherichia coli (E.coli)-infected mice exhibited increased cardiac index, contents of IL-1ß, IL-6, IL-8, TNF-α, leptin and resistin, levels of apoptotic proteins (caspase-3 and caspase-9, and bax/bcl-2 ratio), cardiac pathological changes and oxidative stress. Furthermore, these parameters were more serious in the lean mice than those in the DIO mice. In summary, our findings gave a new sight that E.coli infection impaired heart via histopathological lesions, inflammation and oxidative stress and excessive apoptosis of cardiomyocytes. Interestingly, obesity exerted attenuated effects on the heart of mice with non-fatal infection of E.coli through decreased inflammation, oxidative stress and apoptosis of cardiac tissue.


Assuntos
Escherichia coli , Estresse Oxidativo , Animais , Apoptose , Inflamação , Masculino , Camundongos , Camundongos Obesos
20.
Genes (Basel) ; 12(9)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34573362

RESUMO

Enhancing resistance and tolerance to pathogens remains an important selection objective in the production of livestock animals. Single nucleotide polymorphisms (SNPs) vary gene expression at the transcriptional level, influencing an individual's immune regulation and susceptibility to diseases. In this study, we investigated the distribution of SNP sites in immune-related genes and their correlations with cell surface markers of immune cells within purebred (Taiwan black, Duroc, Landrace and Yorkshire) and crossbred (Landrace-Yorkshire) pigs. Thirty-nine SNPs of immune-related genes, including 11 cytokines, 5 chemokines and 23 Toll-like receptors (TLRs) (interferon-α and γ (IFN-α, γ), tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), Monocyte chemoattractant protein-1 (MCP-1) and TLR3, TLR4, TLR7, TLR8, and TLR9) were selected, and the percentages of positive cells with five cell surface markers of CD4, CD8, CD80/86, MHCI, and MHCII were analyzed. There were 28 SNPs that were significantly different among breeds, particularly between Landrace and Taiwan black. For instance, the frequency of SNP1 IFN-α -235A/G in Taiwan black and Landrace was 11.11% and 96.15%, respectively. In addition, 18 SNPs significantly correlated with the expression of cell surface markers, including CD4, CD8, CD80/86, and MHCII. The percentage of CD4+ (39.27%) in SNP33 TLR-8 543C/C was significantly higher than those in A/C (24.34%), at p < 0.05. Together, our findings show that Taiwan black pigs had a unique genotype distribution, whereas Landrace and Yorkshire had a more similar genotype distribution. Thus, an understanding of the genetic uniqueness of each breed could help to identify functionally important SNPs in immunoregulation.

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