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1.
Int Immunopharmacol ; 93: 107393, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33529914

RESUMO

BACKGROUND: B cells play a key role in the pathogenesis of immune thrombocytopenia (ITP) by producing platelet autoantibodies. Accumulating evidence suggest that microRNA (miRNA) is a critical regulator in B cells. The contribution of miRNA to B cell dysfunction in ITP has not been described. The aim of this study was to examine the expression of miRNA let-7b-5p in B cells of ITP patients and investigate its possible association with B cell function in ITP. METHODS: The CD19+ cells were isolated from peripheral mononuclear cells of ITP patients and healthy controls using immunomagnetic microbeads. B cell survival in vitro was evaluated by cell counting. The level of let-7b-5p was quantified by quantitative PCR. The surface expression of B cell activating factor receptor (BAFF-R) was detected by flow cytometry. The role of let-7b-5p was examined in isolated B cells by transfecting miRNA mimics or inhibitors. RESULTS: The results showed that let-7b-5p in B cells was elevated, and B cell survival was enhanced in ITP patients compared with healthy controls. BAFF and B cell receptor stimulation can induce the expression of let-7b-5p in vitro. Overexpression of let-7b-5p in B cells enhanced the expression of surface BAFF-R and promoted B cell survival. Moreover, let-7b-5p enhanced the phosphorylation of NF-κB2 p100 and upregulated the expression of survival factor Bcl-xL after BAFF induction. CONCLUSION: Let-7b-5p is a pro-survival miRNA in B cells and increased let-7b-5p is associated with enhanced surface BAFF-R in ITP.

2.
Life Sci ; 270: 119088, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33482188

RESUMO

This study aimed to determine whether MG-132 as a proteasome inhibitor can effectively hinder pterygium progression, and to screen out potential regulators involved in MG-132 mediated process. Human pterygium fibroblasts (HPFs) were derived from pterygium tissues from 5 patients. Cell proliferation was examined by MTT, cell cycle and apoptosis were detected by flow cytometry. The overgrowth pterygium tissues were characterized by H&E staining and IHC compared with normal tissues. Differential mRNA expression with MG-132 treatment was determined by RNA sequencing and analyzed by GO and KEGG pathways. The expression levels of Nrf2, MCPIP1, CDKN1B and XBP1, four genes closely associated with pterygium, were detected by RT-qPCR and western blotting. MG-132 dose-dependently inhibited the growth of HPFs, induced G2/M phase arrest of cell cycle at a certain dose, and also caused cell apoptosis, with the levels of cleaved caspase3, cleaved PARP, Bax and p21 increased. Ki-67 and Bcl-2 were highly expressed while Bax was decreased in pterygium tissues. Total 7199 differentially expressed genes (DEGs) were identified, including HSPA family most significantly increased, and AL590428.1, AL122125.1 and lincRNAs such as FGF14-AS2 decreased. The up-regulated DEGs were mainly enriched in RNA degradation pathway, while down-regulated DEGs were related to the regulation of cell cycle. The expressions of Nrf2 and MCPIP1 were significantly increased, while XBP1 and CDKN1B were decreased. In conclusion, MG-132 inhibited the proliferation and induced apoptosis of HPFs in vitro with 7199 DEGs participated in, which may provide a useful reference for the exploitation of MG-132 in treating pterygium.

3.
Endocrinology ; 162(1)2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33034617

RESUMO

AbstractCentral 5-hydroxytryptamine (5-HT), which is primarily synthesized by tryptophan hydroxylase 2 (TPH2) in the dorsal Raphe nuclei (DRN), plays a pivotal role in the regulation of food intake and body weight. However, the physiological functions of TPH2 on energy balance have not been consistently demonstrated. Here we systematically investigated the effects of TPH2 on energy homeostasis in adult male and female mice. We found that the DRN harbors a similar amount of TPH2+ cells in control male and female mice. Adult-onset TPH2 deletion in the DRN promotes hyperphagia and body weight gain only in male mice, but not in female mice. Ablation of TPH2 reduces hypothalamic pro-opiomelanocortin (POMC) neuronal activity robustly in males, but only to a modest degree in females. Deprivation of estrogen by ovariectomy (OVX) causes comparable food intake and weight gain in female control and DRN-specific TPH2 knockout mice. Nevertheless, disruption of TPH2 blunts the anorexigenic effects of exogenous estradiol (E2) and abolishes E2-induced activation of POMC neurons in OVX female mice, indicating that TPH2 is indispensable for E2 to activate POMC neurons and to suppress appetite. Together, our study revealed that TPH2 in the DRN contributes to energy balance regulation in a sexually dimorphic manner.

4.
Stem Cell Reports ; 16(1): 89-105, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33382977

RESUMO

Adult neurogenesis is impaired in the hippocampus of patients with Alzheimer disease (AD) as well as AD models. However, it is far from clear how modulating adult neurogenesis affects AD neuropathology. We confirm that adult hippocampal neurogenesis is impaired in two AD models. Surprisingly, however, cognitive functions are improved in AD models after ablating adult neural stem cells (aNSCs). Ablation of aNSCs does not affect the levels of amyloid ß but restores the normal synaptic transmission in the dentate gyrus (DG) granule cells of AD models. Furthermore, calbindin depletion in the DG of AD mice is ameliorated after aNSC ablation, and knocking down calbindin abolishes the effects of aNSC ablation on synaptic and cognitive functions of AD mice. Together, our data suggest that cognitive functions of AD mice are improved after aNSC ablation, which is associated with the restoration of synaptic transmission in the DG granule cells with calbindin as an important mediator.

5.
Sci Adv ; 6(50)2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33298433

RESUMO

DNA methylation plays critical roles in vascular pathology of pulmonary hypertension (PH). The underlying mechanism, however, remains undetermined. Here, we demonstrate that global DNA methylation was elevated in the lungs of PH rat models after monocrotaline administration or hypobaric hypoxia exposure. We showed that DNA methyltransferase 3B (DNMT3B) was up-regulated in both PH patients and rodent models. Furthermore, Dnmt3b -/- rats exhibited more severe pulmonary vascular remodeling. Consistently, inhibition of DNMT3B promoted proliferation/migration of pulmonary artery smooth muscle cells (PASMCs) in response to platelet-derived growth factor-BB (PDGF-BB). In contrast, overexpressing DNMT3B in PASMCs attenuated PDGF-BB-induced proliferation/migration and ameliorated hypoxia-mediated PH and right ventricular hypertrophy in mice. We also showed that DNMT3B transcriptionally regulated inflammatory pathways. Our results reveal that DNMT3B is a previously undefined mediator in the pathogenesis of PH, which couples epigenetic regulations with vascular remodeling and represents a therapeutic target to tackle PH.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33279473

RESUMO

PURPOSE: Implant rehabilitation after jaw reconstruction is challenging, and postoperative peri-implantitis is common. Our aim was to present our management protocol for implant rehabilitation after vascularized free-flap reconstruction and report the outcomes of soft tissue management. METHODS: This retrospective cohort study included patients who received vascularized free-flap reconstruction, implant rehabilitation, apical reposition flaps (ARFs), and free gingival grafts (FGGs) at Peking University School and Hospital of Stomatology from January 1, 2009 to January 1, 2020. We assessed the association of age, gender, primary disease, flap choice, number and position of implants, timing of ARFs and FGGs, fixation stent use, and restoration type with the occurrence of peri-implantitis. Probing pocket depth, bleeding on probing, and marginal bone loss of the implants were measured as well. The data were analyzed by descriptive statistics, Kaplan-Meier statistics, and Cox regression analysis. RESULTS: In total, 19 patients with 65 implants were included. The implants were placed immediately or 7 to 44 months after reconstruction of the jaw with fibular (n = 17) or iliac flaps (n = 2). ARFs and FGGs were performed 0 to 11 months later. No implants were lost. The mean probing pocket depth, bleeding on probing, and marginal bone loss at 26.6 ± 16.8 months were 3.5 ± 0.9 mm, 70.4 ± 35.1%, and 0.6 ± 0.4 mm, respectively. The incidence of peri-implantitis was 32.3%, showing no significant associations with the gender, age, primary disease, flap choice, number and position of implants, timing of ARFs and FGGs, use of a fixation stent, and type of restoration based on the adjusted multivariate model (P > .05). CONCLUSIONS: Soft tissue management helps generate firmly attached keratinized mucosa around the implants, leads to a more precise impression, and reduces peri-implant bone loss. It should be considered as a critical part of implant rehabilitation after vascularized free-flap reconstruction.

7.
Front Med (Lausanne) ; 7: 509, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33282881

RESUMO

Background: Superoxide dismutases (SODs) are an important family of antioxidant enzymes that modulate reactive oxygen species levels. It is largely unknown which SOD isoform(s) change in vivo in idiopathic pulmonary arterial hypertension (IPAH) patients. Methods: A total of 133 consecutive adult IPAH patients who underwent bone morphogenetic protein receptor type 2 (BMPR2) genetic counseling were enrolled in this prospective study. The plasma activities of three subtypes of SOD [copper-zinc (Cu/Zn-SOD), manganese (Mn-SOD), and extracellular SOD (Ec-SOD)] were examined. Results: The activities of SODs were significantly lower in IPAH patients than in healthy subjects. However, only Ec-SOD activity in BMPR2 mutation patients was significantly decreased compared to those in patients without a mutation. The reduced Ec-SOD activity was markedly associated with mean pulmonary arterial pressure, pulmonary vascular resistance (PVR), and 6-min walking distance (6MWD). The reduction of Mn-SOD activity was only associated with 6MWD. There was no association between Cu/Zn-SOD and hemodynamics. Patients with a lower Ec-SOD level had a worse survival compared to those with a higher baseline. The reduced Ec-SOD activity and the raised PVR increased the mortality risk. Conclusions: Ec-SOD was correlated with BMPR2 mutation, hemodynamic dysfunction, and poor outcomes. Circulating Ec-SOD could be a potentially vital antioxidant enzyme in the pathogenesis of IPAH.

8.
J Agric Food Chem ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33290066

RESUMO

Vina-ginsenoside R4 (VGN4) is the first example of protopanaxatriol saponin possessing sugar chains located at C-3 and C-20 of aglycone. However, to the best of our knowledge, no report has been published on the neuroprotective effect of VGN4. In the present work, we investigated the neuroprotective effect of VGN4 against 6-hydroxydopamine (6-OHDA)-induced toxicity and its potential mechanism. Pretreatment of PC12 cells with VGN4 attenuated 6-OHDA-induced cell damage and cell apoptosis, which was correlated with the decrease of reactive oxygen species and the increase of antioxidant enzyme activities including superoxide dismutase and catalase. In addition, VGN4 markedly decreased nuclear translation of the nuclear factor-κB and PI3K/Akt/GSK/3ß signaling pathway including p85, PDK1, Akt, and GSK-3ß. Further studies revealed that PI3K siRNA attenuated the neuroprotective effect of VGN4 on caspase-3 activity. These data indicate that VGN4 might have the potential to be developed as a new neuroprotective functional food.

9.
Acta Pharmacol Sin ; 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33311600

RESUMO

Immune checkpoint blockade therapy has become a first-line treatment in various cancers. But there are only a small percent of colorectal patients responding to PD-1/PD-L1 blockage immunotherapy. How to increase their treatment efficacy is an urgent and clinically unmet need. It is acknowledged that immunogenic cell death (ICD) induced by some specific chemotherapy can enhance antitumor immunity. Chemo-based combination therapy can yield improved outcomes by activating the immune system to eliminate the tumor, compared with monotherapy. Here, we develop a PD-L1-targeting immune liposome (P-Lipo) for co-delivering irinotecan (IRI) and JQ1, and this system can successfully elicit antitumor immunity in colorectal cancer through inducing ICD by IRI and interfering in the immunosuppressive PD-1/PD-L1 pathway by JQ1. P-Lipo increases intratumoral drug accumulation and promotes DC maturation, and thereby facilitates adaptive immune responses against tumor growth. The remodeling tumor immune microenvironment was reflected by the increased amount of CD8+ T cells and the release of IFN-γ, and the reduced CD4+Foxp3+ regulatory T cells (Tregs). Collectively, the P-Lipo codelivery system provides a chemo-immunotherapy strategy that can effectively remodel the tumor immune microenvironment and activate the host immune system and arrest tumor growth.

10.
Cereb Cortex ; 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33350441

RESUMO

Despite bariatric surgery being the most effective treatment for obesity, a proportion of subjects have suboptimal weight loss post-surgery. Therefore, it is necessary to understand the mechanisms behind the variance in weight loss and identify specific baseline biomarkers to predict optimal weight loss. Here, we employed functional magnetic resonance imaging (fMRI) with baseline whole-brain resting-state functional connectivity (RSFC) and a multivariate prediction framework integrating feature selection, feature transformation, and classification to prospectively identify obese patients that exhibited optimal weight loss at 6 months post-surgery. Siamese network, which is a multivariate machine learning method suitable for small sample analysis, and K-nearest neighbor (KNN) were cascaded as the classifier (Siamese-KNN). In the leave-one-out cross-validation, the Siamese-KNN achieved an accuracy of 83.78%, which was substantially higher than results from traditional classifiers. RSFC patterns contributing to the prediction consisted of brain networks related to salience, reward, self-referential, and cognitive processing. Further RSFC feature analysis indicated that the connection strength between frontal and parietal cortices was stronger in the optimal versus the suboptimal weight loss group. These findings show that specific RSFC patterns could be used as neuroimaging biomarkers to predict individual weight loss post-surgery and assist in personalized diagnosis for treatment of obesity.

11.
Acta Physiol (Oxf) ; : e13602, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33315278

RESUMO

AIM: Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, exerts multiple protective effects against cardiovascular diseases, including cardiac hypertrophy. However, the molecular mechanism underlying its anti-hypertrophic effect has not been clarified. This study revealed that EGCG could inhibit pressure overload-induced cardiac hypertrophy by regulating the PSMB5/Nmnat2/SIRT6-dependent signalling pathway. METHODS: Quantitative real-time polymerase chain reaction and western blotting were used to determine the expression of mRNA and protein respectively. A fluorometric assay kit was used to determine the activity of SIRT6, a histone deacetylase. Luciferase reporter gene assay and electrophoretic mobility shift assay were employed to measure transcriptional activity and DNA binding activity respectively. RESULTS: EGCG could significantly increase Nmnat2 protein expression and enzyme activity in cultured neonatal rat cardiomyocytes stimulated with angiotensin II (Ang II) and heart tissues from rats subjected to abdominal aortic constriction. Nmnat2 knockdown by RNA interference attenuated the inhibitory effect of EGCG on cardiac hypertrophy. EGCG blocked NF-κB DNA binding activity induced by Ang II, which was dependent on Nmnat2 and the subsequent SIRT6 activation. Moreover the activation of PSMB5 (20S proteasome subunit ß-5, chymotrypsin-like) was required for EGCG-induced Nmnat2 protein expression. Additionally, we demonstrated that EGCG might interact with PSMB5 and inhibit the activation of the proteasome. CONCLUSIONS: These findings serve as the first evidence that the effect of EGCG against cardiac hypertrophy may be, at least partially, attributed to the modulation of the PSMB5/Nmnat2-dependent signalling pathway, suggesting the therapeutic potential of EGCG in the prevention and treatment of cardiac hypertrophy.

12.
Chin Med J (Engl) ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33186135

RESUMO

BACKGROUND: Previously, we developed a novel Coronary Artery Tree description and Lesion EvaluaTion (CatLet) angiographic scoring system, which was capable to account for the variability in the coronary anatomy and to assist in the risk-stratification of patients with acute myocardial infarction (AMI). Our preliminary study revealed that the CatLet score better predicted clinical outcomes for AMI patients than the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery score. However, the reproducibility of the CatLet score in both inter- and intra-observer remains to be evaluated. METHODS: A total of 30 consecutive AMI patients, admitted in September of 2015, were independently assessed by two experienced interventional cardiologists to evaluate the inter-observer reproducibility of the CatLet score. Another set of 49 consecutive AMI patients, admitted between September and October in 2014, were assessed by one of the two interventional cardiologists on two occasions 3 months apart to evaluate the intra-observer reproducibility of the CatLet score. The weighted kappa was used to express the degree of agreement. RESULTS: The weighted kappa values (95% confidence interval) for the intra- and inter-observer reproducibility of the CatLet Score were 0.82 (0.59-1.00, Z = 7.23, P < 0.001) and 0.86 (0.54-1.00, Z = 5.20, P < 0.001), respectively, according to the tertile analysis (≤14, 15-22, >22). Regarding the adverse characteristics pertinent to lesions and dominance parameters, the kappa values for the inter-observer variability were 0.80 (0.56-1.00, Z = 6.47, P < 0.001) for total number of lesions, 0.57 (0.28-0.85, Z = 3.03, P < 0.001) for bifurcation, 0.69 (0.43-0.96, Z = 5.06, P < 0.001) for heavy calcification, 1.00 (0.72-1.00, Z = 6.93, P < 0.001) for tortuosity, 0.54 (0.26-0.82, Z = 3.78, P < 0.001) for thrombus, 0.69 (0.48-0.91, Z = 6.29, P < 0.001) for right coronary artery dominance, 0.69 (0.41-0.96, Z = 4.91, P < 0.001) for left anterior descending artery length, and 0.22 (0.06-0.51, Z = 1.56, P = 0.06) for diagonal size. Equivalent values for the intra-observer variability were moderate to almost perfect (range 0.54-1.00). CONCLUSIONS: The reproducibility of the CatLet angiographic scoring system for evaluation of the coronary angiograms ranged from substantial to excellent. The high reproducibility of the CatLet angiographic scoring system will boost its clinical application to patients with AMI.

13.
PLoS One ; 15(11): e0242156, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33186379

RESUMO

Information on the burden of disease due to foodborne pathogens in China is quite limited. To understand the incidence of foodborne gastroenteritis due to non-typhoidal Salmonella enterica and Vibrio parahaemolyticus, population survey and sentinel hospital surveillance were conducted during July 2010 to June 2011 in Shanghai, east China, and a model for calculating disease burden was established. The multiplier for gastroenteritis caused by these pathogens was estimated at 59 [95% confidence interval (CI) 30-102]. Annual incidence per 100,000 population in Shanghai was estimated as 48 (95% CI 24-83) and 183 (95% CI 93-317) cases for foodborne non-typhoidal salmonellosis and V. parahaemolyticus gastroenteritis, respectively, illustrating that bacterial gastroenteritis due to these two pathogens poses a substantial health burden. There is a significant difference between our simulated incidence and the data actually reported for foodborne diseases, indicating significant underreporting and underdiagnosis of non-typhoidal S. enterica and V. parahaemolyticus gastroenteritis in the surveillance area. The present research demonstrates basic situation of the health burden caused by major foodborne pathogens in the surveillance area. Enhanced laboratory-based sentinel hospital surveillance is one of the effective ways to monitor food safety in east China.

14.
Anxiety Stress Coping ; : 1-14, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33190521

RESUMO

BACKGROUND AND OBJECTIVE: An efficient stress response comprises both quick reactivity and rapid recovery. Studies have found an enhanced stress response in Chinese people with high interdependent self-construal (ISC). ISC is a personality trait that is well-matched with Chinese collectivistic culture, and whether they exhibit an efficient stress response has not been exclusively examined. DESIGN: We conducted a novel experiment to examine the stress response change rate in Chinese participants with varying levels of ISC,then performed a validation analysis against previous data to examine the reliability of current results. METHODS: In our experiment, 84 healthy (42 high-ISC and 42 low-ISC), young, native Chinese were randomly assigned to either the Trier Social Stress Test (TSST), or the control condition. In the published study, 46 native Chinese participants (23 high-ISC and 23 low-ISC) had undergone the TSST. Data were collected throughout the two experiments. RESULTS: Compared to low-ISC participants, cortisol and subjective stress levels in high-ISC participants peaked sooner and declined rapidly, suggesting quick stress reactivity and rapid recovery. This finding was supported by the previous study. CONCLUSIONS: High-ISC individuals display an efficient stress response pattern, manifested by fast reactivity and rapid recovery, which may be adaptive in Chinese collectivistic culture.

15.
ACS Appl Mater Interfaces ; 12(46): 52104-52115, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33156623

RESUMO

Plant-derived polyphenol coating offers a promising route to fabricate functional surfaces for different substrate materials. However, almost all of the deposition approaches are time-consuming and involve inefficient processes, and the mechanisms behind the coating deposition are rarely understood. Herein, we report a rational methodology to achieve the rapid deposition of poly(caffeic acid) (PCA) by using H2O2 as a trigger under the assistance of copper sulfate (CuSO4). The comparative monomer structure of PCA oxidation polymerization has illustrated a significant distinction in the reaction path for PCA coating deposition which has never been reported before. Until now, the unprecedented fast velocity for polyphenol coating has been obtained, and the PCA coating exhibits excellent homogeneity, spatiotemporal tunability, and firm stability. Moreover, three different types of filtration membranes, poly(vinylidene fluoride) microfiltration membrane (PVDF MF membrane), poly(ether sulfone) (PES) ultrafiltration (UF) hollow fiber membrane, and PCA-coated PES nanofiltration (NF) membrane, are all successfully dip-coated using H2O2-triggered PCA coating. Without synthetic complexities and intricate procedures, the formation of hydrophilic and homogeneous PCA aggregates on the surface and/or inside pore walls resulted in various membranes. The as-prepared PCA-coated PVDF MF membrane demonstrates excellent oil/water separation efficiency of less than 150 ppm and a flux recovery rate of approximately 90% even after five cycles. By one-step co-deposition of PCA and poly(2-ethyl-2-oxazoline) (PEtOx) on the PES UF membrane surface, hydrophilicity and biofouling resistance are implemented for efficient protein filtration. The PES NF membrane formed by the PCA layer exhibits high mono-/divalent ion selectivity and excellent chlorine resistance. Overall, these results represent a rapid and sustainable approach to tailor PCA coatings for versatile liquid separation processes.

16.
Acta Pharm Sin B ; 10(10): 2002-2009, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33163350

RESUMO

Polyethylene glycols (PEGs) in general use are polydisperse molecules with molecular weight (MW) distributed around an average value applied in their designation e.g., PEG 4000. Previous research has shown that PEGs can act as P-glycoprotein (P-gp) inhibitors with the potential to affect the absorption and efflux of concomitantly administered drugs. However, questions related to the mechanism of cellular uptake of PEGs and the exact role played by P-gp has not been addressed. In this study, we examined the mechanism of uptake of PEGs by MDCK-mock cells, in particular, the effect of MW and interaction with P-gp by MDCK-hMDR1 and A549 cells. The results show that: (a) the uptake of PEGs by MDCK-hMDR1 cells is enhanced by P-gp inhibitors; (b) PEGs stimulate P-gp ATPase activity but to a much lesser extent than verapamil; and (c) uptake of PEGs of low MW (<2000 Da) occurs by passive diffusion whereas uptake of PEGs of high MW (>5000 Da) occurs by a combination of passive diffusion and caveolae-mediated endocytosis. These findings suggest that PEGs can engage in P-gp-based drug interactions which we believe should be taken into account when using PEGs as excipients and in PEGylated drugs and drug delivery systems.

17.
Biomater Sci ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33169732

RESUMO

The tumor microenvironment (TME) and its major component tumor-associated macrophages (TAM) play a pivotal role in the development of non-small cell lung cancer (NSCLC). An epigenetic drug-based combinatory therapeutic strategy was proposed and a deformable liposome system (D-Lipo) was developed for vorinostat and simvastatin codelivery for remodeling the TME. The application of deformable liposomes in systemic cancer drug delivery has been underexplored and its potential in cancer therapy is largely unknown. This work revealed that D-Lipo exhibited an enhanced intratumor infiltration ability. The proposed therapeutic strategy was characterized by a chemo-free regimen and TME remodeling function. D-Lipo efficiently inhibited the growth of the xenografted lung tumor. The anti-tumor mechanisms involved the repolarization of TAM from the M2 to M1 phenotype, anti-angiogenesis, and the consequent TME remodeling. As a result, the amounts of the anti-tumor M1 macrophages and the cytotoxic CD8+ T cells increased, while the amounts of the pro-tumor M2 macrophages and regulatory T cells (Tregs) reduced. It provides a promising avenue for epigenetic drug-based combination therapy for treating solid tumors.

18.
Front Oncol ; 10: 581364, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194715

RESUMO

Helicobacter pylori is designated as a class I carcinogen of human gastric cancer following long-term infection. During this process, H. pylori bacteria persist in proliferation and death, and release bacterial components that come into contact with gastric epithelial cells and regulate host cell function. However, the impact of long-term exposure to H. pylori lysate on the pathological changes of gastric cells is not clear. In this study, we aimed to investigate the regulation and mechanisms involved in gastric cell dysfunction following continuous exposure to H. pylori lysate. We co-cultured gastric cell lines GES-1 and MKN-45 with H. pylori lysate for 30 generations, and we found that sustained exposure to H. pylori lysate inhibited GES-1 cell invasion, migration, autophagy, and apoptosis, while it did not inhibit MKN-45 cell invasion or migration. Furthermore, Mongolian gerbils infected with H. pylori ATCC 43504 strains for 90 weeks confirmed the in vitro results. The clinical and in vitro data indicated that sustained exposure to H. pylori lysate inhibited cell apoptosis and autophagy through the Nod1-NF-κB/MAPK-ERK/FOXO4 signaling pathway. In conclusion, sustained exposure to H. pylori lysate promoted proliferation of gastric epithelial cells and inhibited autophagy and apoptosis via Nod1-NF-κB/MAPK-ERK/FOXO4 signaling pathway. In the process of H. pylori-induced gastric lesions, H. pylori lysate plays as an "accomplice" to carcinogenesis.

19.
J Int Med Res ; 48(11): 300060520972073, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33213251

RESUMO

OBJECTIVE: To comprehensively review the literature and summarize the results from human and animal studies related to the possible causes and pathogenesis of traumatic temporomandibular joint ankylosis (TMJA). MATERIALS AND METHODS: The Google Scholar, Embase, and Web of Science databases were used to search for articles related to traumatic TMJA from 2011 to 2020. All articles were screened according to the inclusion and exclusion criteria, collected, and analyzed. RESULTS: Nineteen relevant articles were collected. These articles were classified into three groups: predisposing and etiological factors, cellular studies, and molecular studies. CONCLUSION: The pathological mechanisms are similar between TMJA and nonunion hypertrophy. Aberrant structural and etiological factors as well as disordered cellular and molecular mechanisms might contribute to TMJA formation. Although preclinical and clinical data have provided new evidence on the pathogenesis of traumatic TMJA, the molecular mechanisms and biological events require further exploration.

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