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1.
Oncol Rep ; 44(5): 2306-2316, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000240

RESUMO

The present study was performed to investigate the protective effects of tannic acid (TA) on liver injury induced by arsenic trioxide (ATO) and to elucidate the mechanism involved as related to the Kelch­like ECH­associated protein 1 (Keap1)­nuclear factor erythroid 2­related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. Adult rats were intraperitoneally injected with TA, while ATO was administered 1 h later. On the 11th day, the rats were euthanized to determine any liver histological changes, liver function, and the activities of antioxidant, antiapoptosis and proinflammatory cytokines in the liver. Furthermore, the protein expression levels of nuclear Nrf2, total Nrf2, Keap1, Heme oxygenase­1 (HO­1), NADPH quinine oxidoreductase­1 (NQO1), and γ­glutamylcysteine synthetase (γ­GCS) were determined using western blot analysis. The results showed that TA treatment ameliorated ATO­induced liver histological changes and decreased the ATO­induced increased alanine aminotransferase (ALT) and aspartate transaminase (AST) serum levels. Activities of the antioxidant enzymes significantly were increased, while the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were attenuated following TA treatment. In addition, TA treatment inhibited ATO­induced liver apoptosis and inflammatory responses, increased Bcl­2 protein expression level and reduced the levels of Bax, caspase­3, interleukin (IL)­1ß, IL­6 and tumor necrosis factor (TNF)­α. Furthermore, TA treatment increased the protein expression levels of Nrf2 and Keap1, HO­1, NQO1 and γ­GCS. The results demonstrated that TA has a protective effect on ATO­treated hepatic toxicity and that its underlying mechanism could be due to TA activation of the Keap1­Nrf2/ARE signaling pathway, to reduce oxidative stress, apoptosis and inflammation in ATO­intoxicated rats.

2.
Hematology ; 25(1): 356-365, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33054609

RESUMO

OBJECTIVES: Haploidentical hematopoietic stem cell transplantation (Haplo-SCT) and matched unrelated donor transplantation (MUD-SCT) are two important options when a matched sibling donor (MSD) is unavailable. Several studies comparing Haplo-SCT and MUD-SCT have reported inconsistent clinical outcomes. Therefore, it is necessary to synthesize the existing evidence regarding outcomes of stem cell transplantations comparing Haplo-SCT with MUD-SCT. METHODS: We searched for titles of articles in MEDLINE (PubMed), Cochrane library, EMBASE database that compared transplantation with Haplo-SCT versus MUD-SCT. To compare clinical outcomes between Haplo-SCT and MUD-SCT, we performed a meta-analysis of 17 studies and reported the pooled odd ratios (OR) of 6 endpoints including overall survival (OS), progression free survival (PFS), non-relapse mortality (NRM), relapse rate (RR), acute graft-versus-host disease (aGVHD) and chronic graft- versus-host disease (cGVHD). RESULTS: We found that Haplo-SCT was associated with a comparable OS (pooled OR of 0.99, 95% Confidence Interval (CI) 0.86-1.14), PFS (OR 1.00, 95% CI 0.88-1.15), NRM (OR 0.83, 95% CI 0.65-1.04) and RR (OR 1.08, 95% CI 0.95-1.22) compared to MUD-SCT. We also found a significantly decreased risk of aGVHD (OR 0.74, 95% CI 0.62-0.88) and cGVHD (OR 0.50, 95% CI 0.38-0.66) in Haplo-SCT group. CONCLUSION: Results of this meta-analysis demonstrates that Haplo-SCT achieves comparable clinical outcomes compared to MUD-SCT in terms of OS, PFS, TRM and RR, but is better than MUD-SCT in terms of decreased aGVHD and cGVHD risk. Haplo-SCT is a valid option for patient needing urgent transplantation.

3.
J Psychiatr Res ; 131: 255-262, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33035958

RESUMO

Altered behavioural responses to sensory stimuli, including both hypo- and hyper-reactivity, have been found in individuals with schizophrenia. However, how specific sensory responsiveness patterns are associated with symptomatology of schizophrenia remains largely unknown. The present study aimed to examine sensory responsiveness in typically-developing (TD) adolescents (n = 98) and adolescents with early-onset schizophrenia (EOS) (n = 29) and investigate the relationship between schizotypal traits and sensory responsiveness patterns. All participants completed the Adult/Adolescent Sensory Profile (AASP), the Schizotypal Personality Questionnaire (SPQ) and the Autism Spectrum Quotient (AQ). Results showed that higher levels of hypersensitivity and hyposensitivity coexisted in EOS patients and were correlated with positive and negative symptoms of schizophrenia. Atypical sensory experiences except for sensory seeking were found to be positively correlated with higher levels of schizotypal traits regardless of diagnostic status. Moreover, the strength and pattern of such correlations were comparable in both EOS and TD groups. This study also provided evidence that higher levels of autistic traits would intensify the positive correlation between schizotypal traits and sensory responsiveness abnormalities, suggesting an additive effect of co-occurring schizotypal and autistic traits on atypical sensory experiences. These findings extend previous research by depicting sensory responsiveness patterns in younger populations with schizophrenia, and may have implications for future development of sensory-related interventions in clinical settings.

4.
Lett Appl Microbiol ; 2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32981107

RESUMO

Metabolic syndrome and obesity have become serious threats to public health worldwide. This study was conducted to evaluate the anti-adipogenesis and metabolism-regulating effects of heat-inactivated Streptococcus thermophilus MN-ZLW-002 (MN-ZLW-002), which can be used as a yogurt starter. In vitro study suggested that MN-ZLW-002 stimulated the RAW264.7 macrophages to produce significant amounts of interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α and induced intense phosphorylation of P38, p44/42 MAPK, and nuclear factor κB. MN-ZLW-002-stimulated RAW264.7-conditioned medium (CM) notably suppressed the differentiation and adipogenesis of 3T3-L1 pre-adipocytes. The 12-week in vivo study suggested that orally administered MN-ZLW-002 significantly reduced the weight gain of mice caused by the high-fat diet (HFD) at weeks 3-8; decreased fasting blood glucose levels at week 4 and week 8; decreased serum total triglyceride level at week 12. MN-ZLW-002 also reduced serum IL-1ß and chemokine ligand 3 levels in the HFD-fed mice. These findings suggest that heat-inactivated MN-ZLW-002 can suppress adipocytes differentiation and lipid accumulation by regulating the immune response, possibly via the release of cytokines, particularly TNF-α; MN-ZLW-002 can improve metabolism-related indicators in the early stage of HFD intervention and regulate the related pro-inflammatory immune response.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32886402

RESUMO

As one of the emerging safe energy-storage devices with high energy-to-cost ratio, nonaqueous aluminum batteries with enhanced energy density are intensively pursued by researchers. Although significant progress has been made on positive electrode materials, the effective energy density of aluminum batteries is still limited by the presence of high-density refractory metal current collectors, which are known to be electrochemically inert in highly acidic ionic-liquid electrolytes. To address such critical issues, here, a novel low-density (<2 g cm-3 ) nonmetal current collector is presented, which uses poly(ethylene terephthalate) (PET) substrates coated with indium tin oxide (ITO), with the purpose of significantly reducing the ratio of nonactive components in the electrodes. In addition to the excellent chemical and electrochemical stability (with voltage as high as ≈2.75 V vs Al3+ /Al), this nonmetal current collector, also encompassing a carboxymethyl cellulose (CMC) binder, allows as-assembled pouch cells to deliver a reversible specific capacity of ≈120 mAh g-1 at a current density of 50 mA g-1 . In comparison with the high-density refractory metal Mo or Ta current collectors, these nonmetal current collectors offer a novel strategy for constructing high-energy-density aluminum batteries by substituting the key components, with the aim of boosting the energy density of nonaqueous aluminum batteries.

6.
J Am Chem Soc ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32997941

RESUMO

Efficient electro-reduction of CO2 over metal-organic framework (MOF) materials is hindered by the poor contact between thermally synthesized MOF particles and the electrode surface, which leads to low Faradaic efficiency for a given product and poor electrochemical stability of the catalyst. We report a MOF-based electrode prepared via electro-synthesis of MFM-300(In) on an indium foil, and its activity for the electrochemical reduction of CO2 is assessed. The resultant MFM-300(In)-e/In electrode shows a 1 order of magnitude improvement in conductivity compared with that for MFM-300(In)/carbon-paper electrodes. MFM-300(In)-e/In exhibits a current density of 46.1 mA cm-2 at an applied potential of -2.15 V vs Ag/Ag+ for the electro-reduction of CO2 in organic electrolyte, achieving an exceptional Faradaic efficiency of 99.1% for the formation of formic acid. The facile preparation of the MFM-300(In)-e/In electrode, coupled with its excellent electrochemical stability, provides a new pathway to develop efficient electro-catalysts for CO2 reduction.

7.
J Histotechnol ; : 1-10, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32909928

RESUMO

The research on hatching ecology of the Chinese softshell turtle Trionyx sinensis has essential guiding roles to clarify the physiological and ecological mechanism of reptile evolution. The aim of this study is to describe the histological changes, differentiation, and maturation of some functional cells during the genesis and development of the liver and pancreas of the Chinese softshell turtle T. sinensis. Softshell turtle eggs were incubated under artificial conditions and hatched within 41-45 days. Hematoxylin and eosin-stained embryonic pancreas and liver were examined at various time points from 2 to 31 days and compared with that of other reptiles, amphibians, fishes, and birds in the literature. Immunohistochemical assay for glucagon and insulin was performed on paraformaldehyde-fixed embryos to identify functional cells in the pancreas. Pancreatic endocrine cells of T. sinensis have secretory ability at day 26 of embryonic development, and the dispersed pancreatic endocrine cells may be the result of the incomplete pancreatic development.

8.
Biol Pharm Bull ; 43(9): 1367-1374, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32879211

RESUMO

Crocetin is a major bioactive ingredient in saffron (Crocus sativus L.) and has favorable cardiovascular effects. Here, the effects of crocetin on L-type Ca2+ current (ICa-L), contractility, and the Ca2+ transients of rat cardiomyocytes, were investigated via patch-clamp technique and the Ion Optix system. A 600 µg/mL dose of crocetin decreased ICa-L 31.50 ± 2.53% in normal myocytes and 35.56 ± 2.42% in ischemic myocytes, respectively. The current voltage nexus of the calcium current, the reversal of the calcium current, and the activation/deactivation of the calcium current was not changed. At 600 µg/mL, crocetin abated cell shortening by 28.6 ± 2.31%, with a decrease in the time to 50% of the peak and a decrease in the time to 50% of the baseline. At 600 µg/mL, crocetin abated the crest value of the ephemeral Ca2+ by 31.87 ± 2.57%. The time to half maximal of Ca2+ peak and the time constant of decay of Ca2+ transient were both reduced. Our results suggest that crocetin inhibits L-type Ca2+ channels, causing decreased intracellular Ca2+ concentration and contractility in adult rat ventricular myocytes. These findings reveal crocetin's potential use as a calcium channel antagonist for the treatment of cardiovascular disease.

9.
Biomed Pharmacother ; 131: 110713, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32920515

RESUMO

Arsenic trioxide (ATO) is an excellent therapy for acute promyelocytic leukemia; however, its use is limited due to its cardiotoxicity. Crocin (CRO) possesses abundant pharmacological and biological properties, including antioxidant, anti-inflammatory, and anti-apoptotic. This study examined the cardioprotective effects of crocin and explored their mechanistic involvement in ATO-induced cardiotoxicity. Forty-eight male rats were treated with ATO to induce cardiotoxicity. In combination with ATO, CRO were given to evaluate its cardioprotection. The results demonstrated that CRO administration not only diminished QTc prolongation, myocardial enzymes and Troponin T levels but also improved histopathological results. CRO administration reduced reactive oxygen species generation. However, the CRO administration caused an increase in glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and total sulphydryl levels and a decrease in malondialdehyde content, gamma glutamyl transferase and lipid hydroperoxides levels and proinflammatory cytokines. Importantly, immunohistochemical analysis, real time PCR and western blotting showed a reduction in Caspase-3 and Bcl-2-associated X protein expressions and enhancement of B cell lymphoma-2 expression. Real time PCR and western blotting showed a reduction in proinflammatory cytokines. Moreover, CRO caused an activation in nuclear factor erythroid-2 related factor 2, leading to enhanced Kelch-like ECH-associated protein 1, heme oxygenase-1 and nicotinamide adenine dinucleotide quinone dehydrogenase 1 expressions involved in Nrf2 signaling during ATO-induced cardiotoxicity. CRO was shown to ameliorate ATO-induced cardiotoxicity. The mechanisms for CRO amelioration of cardiotoxicity due to inflammation, oxidative damage, and apoptosis may occur via an up-regulated Keap1-Nrf2/HO-1 signaling pathway.

10.
Oxid Med Cell Longev ; 2020: 7413693, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908637

RESUMO

Background: The heart is one of the most commonly affected organs during sepsis. Mitsugumin-53 (MG53) has attracted attention in research due to its cardioprotective function. However, the role of MG53 in sepsis-induced myocardial dysfunction (SIMD) remains unknown. The purpose of this study was to explore the underlying mechanism of MG53 in SIMD and investigate its potential relationship with peroxisome proliferator-activated receptor-α (PPARα). Methods: The cecal ligation and puncture (CLP) model was created to induce SIMD in rats. Protein levels of MG53 and PPARα, cardiac function, cardiomyocyte injury, myocardial oxidative stress and inflammatory indicators, and cardiomyocyte apoptosis were measured at 18 h after CLP. The effects of MG53 on PPARα in SIMD were investigated via preconditioning recombinant human MG53 (rhMG53) and PPARα antagonist GW6471. Results: The expression of MG53 and PPARα sharply decreased in the myocardium at 18 h after CLP. Compared with the sham group, cardiac function was significantly depressed, which was associated with the destructed myocardium, upregulated oxidative stress indicators and proinflammatory cytokines, and excessive cardiomyocyte apoptosis in the CLP group. Supplementation with rhMG53 enhanced myocardial MG53, increased the survival rate with improved cardiac function, and reduced oxidative stress, inflammation, and myocardial apoptosis, which were associated with PPARα upregulation. Pretreatment with GW6471 abolished the abovementioned protective effects induced by MG53. Conclusions: Both MG53 and PPARα were downregulated after sepsis shock. MG53 supplement protects the heart against SIMD by upregulating PPARα expression. Our results provide a new treatment strategy for SIMD.

11.
Int Immunopharmacol ; 88: 106959, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32919218

RESUMO

Arsenic trioxide (ATO)-induced renal toxicity through oxidative stress and apoptosis restricts the therapeutic action of acute myelogenous leukemia. Crocetin (Crt) possesses antioxidant and antiapoptosis properties, and has certain renal protective effects, but it has not been reported that it has protective effect on renal injury caused by ATO. The current study explored the effects and mechanisms of Crt on kidney damage induced by ATO. Fifty Sprague-Dawley rats were randomly divided into five groups. Adult rats were given Crt concurrently with ATO for 1 week. On the 8th day, rats were killed and blood and kidney tissues were collected. Histopathological changes were measured, and kidneytissues and serum were used to determine renal function and antioxidant enzyme activity. In addition, the protein expression levels of P-PI3K, PI3K, P-AKT, AKT, CytC, Bax, Bcl-2 and Caspase-3 were determined via western blot analysis. Results revealed ATO induced renal morphological alterations and activated serum BUN and CRE. Compared with the control group, ROS, MDA, IL-1ß, TNF-α, protein carbonyls (PC), lipid hydroperoxides (LOOH) and arsenic concentration levels were found to be significantly increased and SOD, CAT, GSH-Px, GSH and total sulphydryl groups (TSH) levels were attenuated in the ATO group. Crt markedly reduced oxidative stress in ATO-induced nephrotoxicity. Further, ATO induced apoptosis by significantly enhancing CytC, Bax and Caspase-3 and inhibiting Bcl-2. Administration with Crt markedly improved the expression of apoptosis factor. Moreover, Crt treatment stimulated the expressions of P-PI3K, PI3K, P-AKT, AKT induced by ATO. This study indicates Crt could prevent renal injury caused by ATO through inhibiting oxidative stress, inflammation and apoptosis, and its mechanism may be related to activation of PI3K/Akt signaling pathway.

12.
Int J Hyperthermia ; 37(1): 1066-1073, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32924654

RESUMO

PURPOSE: Quantitative dynamic contrast-enhanced ultrasonography (CEUS) reflects tumor blood perfusion. There are very few studies on the relationship between intrahepatic recurrence of hepatocellular carcinoma (HCC) and tumor perfusion. We investigated the correlation of dynamic CEUS parameters with intrahepatic recurrence after radiofrequency ablation (RFA). METHODS: This retrospective study enrolled 125 native HCC patients who underwent RFA between September 2017 and January 2019 with curative intent. Pre-ablation quantitative dynamic CEUS was performed. CEUS parameters were extracted from time-intensity curves. The correlation of CEUS parameters with intrahepatic recurrence was investigated. RESULTS: The mean follow-up time was 21.6 ± 7.9 months. The recurrence rate was 33.6%. Univariate and multivariate analyses revealed that tumor peak intensity (PI) was a significant independent risk factor for intrahepatic recurrence after RFA (hazard ratio (HR), 0.3; 95% CI, 0.1-0.9). A PI of 58.8% (area under curve, 0.72; 95% CI, 0.63-0.81) was considered as the optimal cutoff level to predict the intrahepatic recurrence of HCC in patients after RFA. The recurrence-free survival rate in patients with a PI > 58.8% was 94.4% at 1 year and 77.8% at 2 years. Subgroup analysis showed that the HR of time to peak (TTP) in intrahepatic recurrence was 1.1417 (95% CI, 0.9748-1.1436; p = 0.1973) in the patient group with tumor diameter > 31 mm. CONCLUSION: CEUS is commonly used in HCC patients who undergo RFA. The CEUS parameters PI and TTP are associated with intrahepatic recurrence after RFA, and can thus be used to identify patients at risk for intrahepatic recurrence.

13.
Ann Plast Surg ; 85(4): 430-436, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32931683

RESUMO

PURPOSE: This study aimed to investigate the repair of bone defects in rabbits with tissue-engineered bones using cocultured endothelial progenitor cells (EPCs) and bone marrow mesenchymal stem cells (BMSCs) as seeding cells. METHODS: Endothelial progenitor cells and BMSCs were isolated and purified from the peripheral blood and bone marrow, respectively, of New Zealand rabbits. The third passage of BMSCs was cultured alone or with EPCs. Cells were characterized using specific markers and then seeded on partially deproteinized biologic bones from pigs as a scaffold. The engineered bones were used to repair bone defects in rabbits. Hematoxylin and eosin and Masson staining were performed to examine vascularization and osteogenesis in the engineered bone. RESULTS: The cocultured EPCs and BMSCs grew well on the surface of the scaffold. Compared with monocultured BMSCs, cocultured EPCs and BMSCs promoted the formation of blood vessels and bone on the scaffold, in addition to accelerating the repair of bone defects. The collagen content was significantly increased in the scaffold with cocultured EPCs and BMSCs, compared with the scaffold seeded with mono-cultured BMSCs. CONCLUSIONS: Tissue-engineered bones seeded with cocultured EPCs and BMSCs may be used effectively for the repair of bone defects.

14.
Nanotechnology ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32992307

RESUMO

The manipulation of microparticles using optical forces has led to many applications in the life and physical sciences. To extend optical trapping towards the nano-regime, in this work we demonstrate trapping of single nanoparticles in arrays of plasmonic coaxial nano-apertures with various inner disk configurations and theoretically estimate the associated forces. A high normalised experimental trap stiffness of 3.50 fN/nm/mW for 20 nm polystyrene particles is observed for an optimum design of 149 nm for the nanodisk diameter at a trapping wavelength of 980 nm. Theoretical simulations are used to interpret the enhancement of the observed trap stiffness. A quick particle trapping time of less than 8 sec is obtained at a concentration of 14x10^11 particles/ml with low incident laser intensity of 0.59 mW/µm^2. This good trapping performance with fast delivery of nanoparticles to multiple trapping sites emerges from a combination of the enhanced electromagnetic near-field and spatial temperature increase. This work has applications in nanoparticle delivery and trapping with high accuracy, and bridges the gap between optical manipulation and nanofluidics.

15.
Clin Transl Med ; 10(5): e167, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32997401

RESUMO

Checkpoint blockade therapy has shown significant therapeutic benefits and resulted in durable responses in patients with various tumors. However, accumulating evidence has demonstrated that 4-29% of all patients with cancers with various histologies may suffer from tumor flare following such therapy. This novel tumor response pattern, termed hyperprogression, is a potentially deleterious side effect of checkpoint blockade therapy that accelerates disease progression in a subset of patients. In this review, we describe possible immune checkpoint blockade biomarkers and the epidemiology, different definitions, and predictors of hyperprogression based on the research findings and further present the available evidence supporting pathophysiological hypotheses that might explain hyperprogression during checkpoint blockade therapy. We also compare hyperprogression and pseudoprogression. Finally, we discuss areas requiring further study.

16.
J Autism Dev Disord ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978707

RESUMO

Atypical sensory processing has recently gained much research interest as a key domain of autistic symptoms. Individuals with autism spectrum disorder (ASD) exhibit difficulties in processing the temporal aspects of sensory inputs, and show altered behavioural responses to sensory stimuli (i.e., sensory responsiveness). The present study examined the relation between sensory responsiveness (assessed by the Adult/Adolescent Sensory Profile) and audiovisual temporal integration (measured by unisensory temporal order judgement (TOJ) tasks and audiovisual simultaneity judgement (SJ) tasks) in typically-developing adolescents (n = 94). We found that adolescents with higher levels of autistic traits exhibited more difficulties in separating visual stimuli in time (i.e., larger visual TOJ threshold) and showed a stronger bias to perceive sound-leading audiovisual pairings as simultaneous. Regarding the associations between different measures of sensory function, reduced visual temporal acuity, but not auditory or multisensory temporal processing, was significantly correlated with more atypical patterns of sensory responsiveness. Furthermore, the positive correlation between visual TOJ thresholds and sensory avoidance was only found in adolescents with relatively high levels of autistic traits, but not in those with relatively low levels of autistic traits. These findings suggest that reduced visual temporal acuity may contribute to altered sensory experiences and may be linked to broader behavioural characteristics of ASD.

17.
Life Sci ; 263: 118490, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32979357

RESUMO

AIMS: The development of type 1 diabetes is associated with inflammatory lesion of the pancreatic islets, known as insulitis. In this study, we focused on the protective effects of acarbose against insulitis in streptozotocin (STZ)-induced diabetic mice and the underlying mechanisms. MAIN METHODS: The mouse models were established via intraperitoneal injection of multiple low-dose STZ. Blood glucose level and body weight were measured. The severity of insulitis and inflammatory parameters in pancreatic tissues were evaluated. Insulin levels in pancreas and serum were also assessed. In vitro, MIN6 ß cells were exposed to pro-inflammatory cytokines to assess the protective effects of acarbose. Cell function and apoptosis were evaluated. KEY FINDINGS: We found that acarbose administration by gavage reduced the severity of insulitis and improved insulin levels in the experimental diabetic mice. ELISA revealed decreased levels of the inflammatory response markers IL-1ß and TNF-α in mouse pancreatic tissues following acarbose treatment. In vitro, acarbose increased cell viability, decreased cell apoptosis, and improved GSIS in MIN6 ß cells exposed to pro-inflammatory cytokines. In addition, caspase-3 level and p-p53/p53 ratio in ß cells were reduced by acarbose treatment. SIGNIFICANCE: Taken together, these results revealed a novel function of acarbose in attenuating insulitis. The protective effects of acarbose elicited in vitro and in vivo were shown to be mediated, at least in part, through its anti-inflammatory action.

18.
Chin Med J (Engl) ; 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32842016

RESUMO

With the increasing use of immune checkpoint inhibitors (ICI) including anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) in cancers, ICI-induced type 1 diabetes has been reported throughout the world. In this review, we aim to summarize the characteristics of this disease and discuss the mechanism of it. As an immune-related adverse event, type 1 diabetes developed after the administration of anti-PD-1 or anti-PD-ligand 1 (PD-L1) in the combination with or without anti-CTLA-4. It usually presented with acute onset, and 62.1% of the reported cases had diabetic ketoacidosis. Only a third of them had positive autoantibodies associated with type 1 diabetes. Susceptible HLA genotypes might be associated. T-cell-stimulation by blocking of the interaction of PD-1 and PD-L1 in pancreatic ß cells was the main mechanism involved in the pathology. Insulin was the only effective treatment of ICI-induced type 1 diabetes. In conclusions, ICI-induced type 1 diabetes is a potentially life-threating adverse event after the immunotherapy of cancers. Screening and early recognition is important. Further investigation of the mechanism may help to better understand the pathology of type 1 diabetes.

19.
Food Res Int ; 136: 109610, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32846630

RESUMO

The elevated intestinal oxygen in certain unhealthy conditions (e.g., mucosa injury) enhances the expansion of aerobic/facultative anaerobic bacteria (mainly Proteobacteria) in gut microbiota (GM) and is strongly linked to various diseases. The alteration of GM, influenced by oxygen, may affect the bioavailability of dietary polyphenols. In vitro digestion, dialysis and fermentation of phenolic blueberry extract (BE) were performed here using the GM of mice under different oxygen conditions. Oxygen delayed the degradation of the main phenolic components, including quercetin, kaempferol and their rutinose-conjugates, in BE during in vitro fermentation. In addition, the metabolites of BE were also influenced by oxygen. Oxygen skewed the production of 3-hydroxyphenylacetatic acid to 4-hydroxyphenylacetatic acid. Moreover, oxygen also blunted hippuric, 3-phenylpropionic, and 3-hydroxycinnamic acids production. Furthermore, oxygen enhanced the expansion of Salmonella and Escherichia belonging to phylum Proteobacteria and suppressed the proliferation of the anaerobic bacteria Clostridium and Bacteroides belonging to phyla Firmicutes and Bacteroidetes, respectively, which was reversed by BE supplementation.

20.
Theranostics ; 10(19): 8606-8618, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32754266

RESUMO

Rationale: Fructose-1, 6-bisphosphatase 1 (FBP1), a rate-limiting enzyme in gluconeogenesis, was recently shown to be a tumor suppressor and could mediate the activities of multiple transcriptional factors via its non-canonical functions. However, the underlying mechanism of posttranscriptional modification on the non-canonical functions of FBP1 remains elusive. Methods: We employed immunoaffinity purification to identify binding partner(s) and used co-immunoprecipitation to verify their interactions. Kinase reaction was used to confirm PIM2 could phosphorylate FBP1. Overexpression or knockdown proteins were used to assess the role in modulating p65 protein stability. Mechanistic analysis was involved in protein degradation and polyubiquitination assays. Nude mice and PIM2-knockout mice was used to study protein functions in vitro and in vivo. Results: Here, we identified Proviral Insertion in Murine Lymphomas 2 (PIM2) as a new binding partner of FBP1, which could phosphorylate FBP1 on Ser144. Surprisingly, phosphorylated FBP1 Ser144 abrogated its interaction with NF-κB p65, promoting its protein stability through the CHIP-mediated proteasome pathway. Furthermore, phosphorylation of FBP1 on Ser144 increased p65 regulated PD-L1 expression. As a result, phosphorylation of FBP1 on Ser144 promoted breast tumor growth in vitro and in vivo. Moreover, the levels of PIM2 and pSer144-FBP1 proteins were positively correlated with each other in human breast cancer and PIM2 knockout mice. Conclusions: Our findings revealed that phosphorylation noncanonical FBP1 by PIM2 was a novel regulator of NF-κB pathway, and highlights PIM2 inhibitors as breast cancer therapeutics.

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