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1.
Cancer Sci ; 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33932069

RESUMO

Reactive oxygen species (ROS) derived from aberrant tumor metabolism could contribute to tumor invasion and metastasis. NAD(P)HX Epimerase (NAXE), an epimerase that allows the repair of damaged forms of antioxidant NADPH, is a potential cellular ROS scavenger and its role in tumor development is still elusive. Here, we found that NAXE is significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. NAXE downregulation is associated with poor clinicopathological characteristics and is an independent risk factor for overall and disease-free survival of HCC patients after liver resection. In addition, low NAXE expression could identify worse prognosis of HCC patients before vascular invasion or in early stages of disease. In particularly, low NAXE expression in HCC is markedly associated with microvascular invasion (MVI) and its combination with MVI predicts poorer prognosis of HCC patients after liver resection. Furthermore, in vitro and in vivo experiments both showed that knockdown of NAXE expression in HCC cells promoted migration, invasion, and metastasis by inducing epithelial-mesenchymal transition (EMT), whereas NAXE overexpression causes the opposite effects. Mechanistically, low NAXE expression reduced NADPH levels and further caused ROS level increase and hypoxia-inducible factor-1α (HIF-1α) activation, thereby promoting invasion and metastasis of HCC by facilitating EMT. What is more, the tumor-promoting effect of NAXE knockdown in HCC xenograft can be abolished by giving mice N-acetyl-l-cysteine (NAC) in drinking water. Taken together, our findings uncovered a tumor suppressor role for NAXE in HCC by scavenging excessive ROS and inhibiting tumor-promoting signaling pathways, suggesting a new strategy for HCC therapy by targeting redox signaling.

2.
Cell Death Dis ; 12(5): 436, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33934111

RESUMO

Atherosclerotic plaque vulnerability and rupture increase the risk of acute coronary syndromes. Advanced lesion macrophage apoptosis plays important role in the rupture of atherosclerotic plaque, and endoplasmic reticulum stress (ERS) has been proved to be a key mechanism of macrophage apoptosis. Intermedin (IMD) is a regulator of ERS. Here, we investigated whether IMD enhances atherosclerotic plaque stability by inhibiting ERS-CHOP-mediated apoptosis and subsequent inflammasome in macrophages. We studied the effects of IMD on features of plaque vulnerability in hyperlipemia apolipoprotein E-deficient (ApoE-/-) mice. Six-week IMD1-53 infusion significantly reduced atherosclerotic lesion size. Of note, IMD1-53 lowered lesion macrophage content and necrotic core size and increased fibrous cap thickness and vascular smooth muscle cells (VSMCs) content thus reducing overall plaque vulnerability. Immunohistochemical analysis indicated that IMD1-53 administration prevented ERS activation in aortic lesions of ApoE-/- mice, which was further confirmed in oxidized low-density lipoproteins (ox-LDL) induced macrophages. Similar to IMD, taurine (Tau), a non-selective ERS inhibitor significantly reduced atherosclerotic lesion size and plaque vulnerability. Moreover, C/EBP-homologous protein (CHOP), a pro-apoptosis transcription factor involved in ERS, was significantly increased in advanced lesion macrophages, and deficiency of CHOP stabilized atherosclerotic plaques in AopE-/- mice. IMD1-53 decreased CHOP level and apoptosis in vivo and in macrophages treated with ox-LDL. In addition, IMD1-53 infusion ameliorated NLRP3 inflammasome and subsequent proinflammatory cytokines in vivo and in vitro. IMD may attenuate the progression of atherosclerotic lesions and plaque vulnerability by inhibiting ERS-CHOP-mediated macrophage apoptosis, and subsequent NLRP3 triggered inflammation. The inhibitory effect of IMD on ERS-induced macrophages apoptosis was probably mediated by blocking CHOP activation.

3.
Org Lett ; 23(8): 3125-3129, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33818113

RESUMO

Hymoins A-D (1-4), two pairs of light-induced transformative polyprenylated acylphloroglucinols with an unprecedented pentacyclic skeleton, were isolated from the flowers of Hypericum monogynum. The first decarbonylative ring contraction of complex natural products was investigated by light irradiation. Their structures were elucidated by nuclear magnetic resonance analysis, X-ray crystallography, and electronic circular dichroism calculations. In addition, compound 3 showed moderate inhibition efficacy of the platelet-activating-factor-induced aggregation of rabbit platelets.

4.
J Org Chem ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33881865

RESUMO

Hypermonins A-D (1-4), four rearranged nor-polycyclic polyprenylated acylphloroglucinols (PPAPs) with unprecedented skeletons, together with two new biosynthesis related PPAPs (5 and 6) were isolated and identified from the flowers of Hypericum monogynum. Hypermoins A-D represented the first examples of highly modified norPPAPs characterized by a rare 7/6/6/5-tetracyclic system. From the biogenic synthesis pathway analysis, all isolates shared the same biosynthetic intermediate, and the addition of two methyls or one methyl to this intermediate through methyltranferase could generate different types of PPAPs (1-7). Their planner structures as well as absolute configuration were confirmed via spectroscopic analysis, ECD calculation, and X-ray crystallography. All isolates potentially reversed multidrug resistance (MDR) activity in both two cancer cells, HepG2/ADR and MCF-7/ADR. Specifically, hypermoin E (5) and hyperielliptone HA (7) were found to be the best MDR modulators with the reversal fold ranging from 41 to 236, which is higher than the positive control verapamil.

5.
Hum Vaccin Immunother ; : 1-11, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33861159

RESUMO

The Hepatitis B (HB) vaccine is efficacious in preventing hepatitis B virus infection. However, the association between antibody response to the HB vaccine and dynamic immune repertoire changes in different cell subsets remains unclear. Nine healthy participants were administered three doses of HB vaccine following the 0, 1, 6 month schedule. Peripheral CD4+ T, memory B (MB), naïve B (NB), and plasma cells (PCs) were sorted before vaccination and 7 days following each dose. The complementary determining region 3 of T-cell receptor ß (TCRß) chain and B-cell receptor (BCR) heavy chain (IgG, IgM, IgA) repertoires were analyzed by high-throughput sequencing. All nine participants elicited protective antibody titers to the vaccine at the end of immunization. Compared with the baseline, MB cells showed a significant increase in IgG usage and decreased IgM usage and repertoire diversity at the end of vaccination. TCRß diversity changes were highly correlated with those of the BCR in MB cells in participants with a faster and robust antibody responses. The percentage of shared clonotypes between NB and MB cells, and MB cells and PCs were much higher than that between NB cells and PCs. The more clonotypes sharing the faster and stronger antibody responses were observed after HB vaccination. These results suggest the integral involvement of MB cells in vaccine immunization. Interaction between CD4+ T and MB cells and B cell differentiation may improve antibody response to HB vaccine.

7.
Neurol Sci ; 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33904005

RESUMO

BACKGROUND: Hemiplegic migraine (HM) is a rare type of migraine with aura. Some reports have described the clinical manifestations in HM patients with the ATP1A2 mutation. But the impact of the ATP1A2 mutation on cognitive profile in HM patients has not been evaluated in detail. Here we report a patient with cognitive dysfunction in specific area. CASE PRESENTATION: A 15-year-old boy with an aura that included disturbances in consciousness, associated with fever, vomiting, hemiplegia, and aphasia. He was diagnosed with HM with the ATP1A2 mutation before. He had trouble in mathematics and depicting three-dimensional things. CONCLUSIONS: The HM with ATP1A2 patient could develop permanent cognitive dysfunction. Therefore, the cognitive quotient should be carefully and comprehensively evaluated.

8.
BMC Pharmacol Toxicol ; 22(1): 22, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33906686

RESUMO

BACKGROUND: Low dose of NP exposure can alter adipose tissue formation, and the intake of high-fat diet (HFD) can also lead to the fatty liver disease. We investigated the combined effect of NP and HFD on the first offspring of rats, and whether this effect can be passed to the next generation and the possible mechanisms involved. METHODS: Pregnant rats had access to be treated with 5 µg/kg/day NP and normal diet. The first generation rats were given normal diet and HFD on postnatal day 21, respectively. Then the second generation rats started to only receive normal diet without NP or HFD. Body weight, organ coefficient of liver tissues, lipid profile, biochemical indexes and the expression of genes involved in lipid metabolism, as well as liver histopathology were investigated in male offspring of rats. RESULTS: NP and HFD interaction had significant effect on the birth weight, body weight and liver tissue organ coefficient of first generation male rats. And HFD aggravated abnormal lipid metabolism, even abnormal liver function and liver histopathological damage of first generation male rats produced by the NP. And this effect can be passed on to the second generation rats. HFD also accelerated the mRNA level of fatty acid synthesis genes such as Lpl, Fas, Srebp-1 and Ppar-γ of first generation rats induced by perinatal exposure to NP, even passed on to the second generation of male rats. NP and HFD resulted in synergistical decrease of the protein expression level of ERα in liver tissue in F2 male rats. CONCLUSION: HFD and NP synergistically accelerated synthesis of fatty acids in liver of male offspring rats through reducing the expression of ERα, which induced abnormal lipid metabolism, abnormal liver function and hepatic steatosis. Moreover, all of these damage passed on to the next generation rats.

9.
Microvasc Res ; 136: 104163, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33831407

RESUMO

BACKGROUND: The vascular component of the hand-arm-vibration syndrome (HAVS) is often characterized by vibration-induced white fingers (VWF). Active substances secreted by the vascular endothelial cells (VEC) maintain a dynamic balance but damage to the blood vessels may occur when the equilibrium is altered, thus forming an important pathological basis for VWF. This study was aimed at investigating vascular damage indicators as a basis for an early detection of disorders caused by vibration, using the rat tail model. METHODS AND RESULTS: Experiments were conducted using a control group of rats not exposed to vibration while two exposed groups having different exposure durations of 7 and 14 days were randomly formed. Following exposure, the structural changes of tail tissue samples in anesthetized rats were observed. Enzyme-linked immunosorbent assay (ELISA) was used for analyzing four vascular damage indicators myosin regulatory light chain (MLC2), endothelin-1 (ET-1), vinculin (VCL) and 5-hydroxytryptamine (5-HT) in tail blood samples. We found that both vascular smooth muscle and endothelial cells displayed changes in morphology characterized by vacuolization and swelling in the vibration-exposed group. The levels of vascular damage indicators were altered under the vibration. CONCLUSION: The degree of vascular pathology increased with the longer duration exposure. Furthermore, the levels of MLC2, ET-1 and 5-HT in rat plasma were associated with vascular injury caused by local vibration.

10.
Chin Med J (Engl) ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33734137

RESUMO

BACKGROUND: For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT. METHODS: A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables. RESULTS: All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR (P  < 0.001, P = 0.004, and P  < 0.001, respectively) and worse LFS (P  < 0.001, P = 0.017, and P  < 0.001, respectively), and OS (P  < 0.001, P = 0.009, and P  < 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 (P  < 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score. CONCLUSION: This new risk score system might stratify patients with different risks of relapse, which could guide treatment.

11.
Sci Rep ; 11(1): 6697, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33758291

RESUMO

Atorvastatin 40 mg (ATOR 40) and ezetimibe 10 mg/simvastatin 20 mg (EZ-SIM 20) have similar reductions of low-density lipoprotein cholesterol (LDL-C) but cardiovascular (CV) outcomes between these two therapies are unclear. Our real-world cohort study is to test the hypothesis of pleiotropic effects of purely higher dose statin on CV outcomes beyond similar reductions of LDL-C, especially for extremely CV risk patients. Between January 1, 2007 and December 31, 2013, a total of 3,372 patients with type 2 diabetes mellitus (T2DM) admitted due to acute coronary syndrome (ACS) or acute ischemic stroke (AIS) were selected as the study cohort from the Taiwan National Health Insurance Research Database. Clinical outcomes were evaluated by ATOR 40 group (n = 1686) matched with EZ-SIM 20 group (n = 1686). Primary composite outcome includes CV death, non-fatal myocardial infarction, and non-fatal stroke. Secondary composite outcome includes hospitalization for unstable angina (HUA), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). With a mean follow-up of 2.4 years, no significant difference of primary composite outcome was observed between ATOR 40 and EZ-SIM 20 groups (subdistribution hazard ratio [SHR], 1.09; 95% confidence interval [CI], 0.95-1.25). Nevertheless, ATOR 40 group had lower risks of HUA (SHR, 0.50; 95% CI, 0.35-0.72), PCI (SHR, 0.82; 95% CI, 0.69-0.97) and CABG (SHR, 0.62; 95% CI, 0.40-0.97) than EZ-SIM 20 group. For T2DM patients after ACS or AIS, ATOR 40 and EZ-SIM 20 had similar major CV outcomes, which still supported the main driver for CV risk reductions is LDL-C lowering.

12.
Vascul Pharmacol ; : 106854, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33781961

RESUMO

Sitagliptin, a dipeptidyl peptidase-4(DPP-4) Inhibitor, has been found to have an anti-atherosclerotic effect. Since apoptosis of vascular smooth muscle cells (VSMCs) contributes to the occurrence of diabetic atherosclerosis. This study aimed to examine whether sitagliptin suppresses the atherosclerosis progression to hyperglycemia in a low-dose streptozotocin (STZ)-induced diabetic mouse model, and then investigated the effect of sitagliptin on VSMCs apoptosis and its underlying mechanism. In vivo studies, eight-week-old low-dose STZ-induced diabetic apolipoprotein E (apoE)-deficient (apoE-/-) mice fed a high-fat diet were administered a DPP-4 inhibitor, sitagliptin, 200 mg/kg/day, or Lantus insulin by daily subcutaneous injection of 1 unit/mouse over a period of 12 weeks. Aortic atherosclerosis and apoptosis in the plaque were determined using dUTP-biotin nick end labeling (TUNEL) staining and immunohistochemistry. In vitro studies utilized the VSMCs for determination of glucagon-like peptide 1 receptor (GLP-1R) and DPP-4 expression and flow cytometry and Western blotting were used to determine apoptosis and protein expression, respectively. Sitagliptin significantly reduced atherosclerotic lesion area (7.00 ±â€¯0.13 vs. 12.80 ±â€¯2.7%, p = 0.003) and suppressed vascular smooth muscle cell apoptosis (2.30 ±â€¯1.34 vs. 4.8 ±â€¯1.93%, p = 0.003) compared with vehicle treatment. In addition, sitagliptin significantly increased the expression of ß-catenin in the aortic tissue(0.56 ±â€¯0.13 vs.0.17 ±â€¯0.02, p = 0.008)compared with vehicle treatment. In cultured mouse VSMCs, sitagliptin enhanced GLP-1 activity significantly retarded oxidative stress (H2O2)-induced apoptosis compared with GLP-1 or sitagliptin alone. Sitagliptin increased GLP-1-induced cytosolic levels of ß-catenin compared with GLP-1 alone, resulted in increasing the expression of survivin, and suppressed proinflammatory cytokines, i.e., interleukin-6(IL-6) and tumor necrosis factor-alpha(TNF-α), production in response to H2O2. In conclusion, these results indicated that the anti-atherosclerotic effect of sitagliptin is mediated, at least in part, by its inhibition of VSMCs apoptosis.

13.
Nanotechnology ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33657546

RESUMO

Systematic analysis of the surface morphology, crystalline phase, chemical composition and elemental distribution along depth for nitrogen-doped niobium was carried out through different ways of characterization, including SEM, AFM, GIXRD, RBS and layer-by-layer XPS analysis. The results showed that, after nitrogen doping, the surface was covered by densely distributed trigonal precipitates with average crystallite size of 32 ± 8 nm, in line with the calculation result (29.9 nm) of nitrogen-enriched ß-Nb2N from GIXRD, demonstrating the phase composion of trigonal precipitates. The depth analysis through RBS and XPS indicated that ß-Nb2N was dominant in the topmost 9.7 nm and extended to depth of 575 nm with gradually decreased content. In addition, the successive change of naturally oxidized states of niobium after nitrogen doping along depth was revealed along depth. It was interesting to find that oxygen diffusion depth could be moderately enhanced by nitridation process. These results established the near-surface phase composition of nitrided niobium, which was of great significance for evaluating the effect of nitrogen doping and further understanding the Q improvement of the SRF cavities.

14.
J Aerosol Med Pulm Drug Deliv ; 34(2): 108-114, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33691499

RESUMO

Background: Severe acute respiratory syndrome coronavirus 2 infection is associated with strong infectiousness and has no effective therapy. We aimed to explore the efficacy and safety of Mycobacterium vaccae nebulization in the treatment of Coronavirus Disease 2019 (COVID-19). Methods: In this randomized, double-blind, placebo-controlled clinical trial, we included 31 adult patients with moderate COVID-19 who were admitted to the Fourth People's Hospital of Nanning (Nanning, China) between January 22, 2020 and February 17, 2020. Patients were randomly divided into two groups: group A (standard care group) and group B (M. vaccae in combination with standard care group). The primary outcome was the time interval from admission to viral RNA negative conversion (oropharyngeal swabs were used in this study). Secondary outcomes included chest computed tomography (CT), mortality, length of hospital stay, complications during treatment, and so on. Patients were followed up to 4 weeks after discharge (reexamination of viral RNA, chest CT, etc.). Results: Nucleic acid test negative conversion time in group B was shorter than that in group A (2.9 days [2.7-8.7] vs. 6.8 days [3.3-13.8]; p = 0.045). No death and no conversion to severe or critical cases were observed in both groups. Two weeks after discharge, neither "relapse" nor "return to positive" cases were found. Four weeks after discharge, it was found that there was no case of " relapse " or "return to positive" in group B, and 1 patient in group A showed "return to positive", but there was no clinical manifestation and imaging progression. No adverse reactions related to M. vaccae were found during observation period. Conclusion: M. vaccae treatment might shorten the time interval from admission to viral RNA negative conversion, which might be beneficial to the prevention and treatment of COVID-19. Clinical Trial Registration: ChiCTR2000030016.


Assuntos
/terapia , Tempo de Internação , Mycobacteriaceae/imunologia , Tomografia Computadorizada por Raios X , Administração por Inalação , Adolescente , Adulto , Idoso , /mortalidade , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
15.
Fitoterapia ; 151: 104876, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33675885

RESUMO

Six rocaglaol derivatives were isolated from Dysoxylum gotadhora, and those compounds showed good cytotoxic activity with IC50 values ranging from 10 to 350 ng/mL against five different cancer cells. Obviously, further total synthesis of rocaglaol derivatives for medical chemistry study is of great significance. Then, twenty six rocaglaol derivatives including 25 new compounds were designed, synthesized, and evaluated for their cytotoxic activities against three human cancer cell lines: human colon cancer cells (HCT116), colorectal cancer stem cells (P6C), and human red leukocyte leukemia cells (HEL), using MTT assay. Most of derivatives showed good cytotoxic activities, with the lowest IC50 being 3.2 nM for HEL cells, which was 169 times stronger than that of the positive control (doxorubicin). Further mechanism study indicated that 11k could significantly suppress MAPK pathway in HCT116 cells, which may responsible for induction of apoptosis and cell cycle arrest.

16.
Aging (Albany NY) ; 13(4): 5164-5184, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33535178

RESUMO

The Notch1-mediated inflammatory response participates in the development of abdominal aortic aneurysm (AAA). The vascular endogenous bioactive peptide intermedin (IMD) plays an important role in maintaining vascular homeostasis. However, whether IMD inhibits AAA by inhibiting Notch1-mediated inflammation is unclear. In this study, we found Notch intracellular domain (NICD) and hes1 expression were higher in AAA patients' aortas than in healthy controls. In angiotensin II (AngII)-induced AAA mouse model, IMD treatment significantly reduced AAA incidence and maximal aortic diameter. IMD inhibited AngII-enlarged aortas and -degraded elastic lamina, reduced NICD, hes1 and inflammatory factors expression, decreased infiltration of CD68 positive macrophages and the NOD-like receptor family pyrin domain containing 3 protein level. IMD inhibited lipopolysaccharide-induced macrophage migration in vitro and regulated macrophage polarization. Moreover, IMD overexpression significantly reduced CaCl2-induced AAA incidence and down-regulated NICD and hes1 expression. However, IMD deficiency showed opposite results. Mechanically, IMD treatment significantly decreased cleavage enzyme-a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) level. Pre-incubation with IMD17-47 (IMD receptors blocking peptide) and the phosphatidylinositol 3-kinase/protein kinase b (PI3K/Akt) inhibitor LY294002 reversed ADAM10 level. In conclusion, exogenous and endogenous IMD could inhibit the development of AAA by inhibiting Notch1 signaling-mediated inflammation via reducing ADAM10 through IMD receptor and PI3K/Akt pathway.

17.
Pharmacol Res ; 166: 105497, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33609697

RESUMO

Osteoarthritis (OA) is a major cause of disability in the elderly population and represents a significant public health problem and socioeconomic burden worldwide. However, no disease-modifying therapeutics are currently available for OA due to an insufficient understanding of the pathogenesis of this disability. As a unique cell type in cartilage, chondrocytes are essential for cartilage homeostasis and play a critical role in OA pathogenesis. Mitochondria are important metabolic centers in chondrocytes and contribute to cell survival, and mitochondrial quality control (MQC) is an emerging mechanism for maintaining cell homeostasis. An increasing number of recent studies have demonstrated that dysregulation of the key processes of chondrocyte MQC, which involve mitochondrial redox, biogenesis, dynamics, and mitophagy, is associated with OA pathogenesis and can be regulated by the chondroprotective molecules 5' adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 3 (SIRT3). Moreover, AMPK and SIRT3 regulate each other, and their expression and activity are always consistent in chondrocytes, which suggests the existence of an AMPK-SIRT3 positive feedback loop (PFL). Although the precise mechanisms are not fully elucidated and need further validation, the current literature indicates that this AMPK-SIRT3 PFL regulates OA development and progression, at least partially by mediating chondrocyte MQC. Therefore, understanding the mechanisms of AMPK-SIRT3 PFL-mediated chondrocyte MQC in OA pathogenesis might yield new ideas and potential targets for subsequent research on the OA pathomechanism and therapeutics.

18.
Radiother Oncol ; 157: 247-254, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33587972

RESUMO

PURPOSE: To verify clinical significance of submandibular gland (SMG)-sparing during helical tomotherapy (HT) for nasopharyngeal carcinoma (NPC) from the perspective of imaging by using diffusion weighted imaging (DWI). MATERIALS AND METHODS: In this prospective study, 60 NPC patients scheduled for radical SMG-sparing HT were enrolled. All patients underwent DWI examinations prior to HT (pre-HT) and 1, 3, 6, 9, 12 months post HT. Mean apparent diffusion coefficient (ADC) values of bilateral parotid glands (PGs) and submandibular glands (SMGs) were measured. Differences of ADC and changes of ADC pre and pro HT (ΔADC) among SMG-spared, SMG-unspared and PGs were compared and the associations betweenΔADC and variations of patient-rated xerostomia questionnaire summary scores (XQ-sum) were further tested. RESULTS: ADCpost-HT and ΔADCpost-HT of SMG-spared were both much lower than of SMG-unspared and a strong dose-response relationship was detected between mean radiation dose and ΔADC of SMGs. Dynamic change trends of PGs, SMG-spared and SMG-unspared were similar, with initial increase at 1 m-post-HT followed by little change at 3 m-post-HT and then gradual decrease over time. But for SMG-unspared, there was no obvious change of ADC from 6 m-post-HT to 12 m-post-HT. The dynamic change trend of XQ-sum was nearly in line with that of ADC on the whole. And a positive correlation between mean ΔADC1m-post-HT of bilateral SMGs and variation of XQ-sum1m-post-HT in patients with bSMG-unspared were found (r = 0.693, P < 0.001). Multivariate stepwise regression analysis showed that whether spared SMG or not was the only independent predictor correlated to XQ-sumpost-HT at each follow-up timepoint. CONCLUSION: SMG-sparing technique could significantly improve subjective xerostomia post HT in NPC patients from the perspective of imaging.


Assuntos
Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Xerostomia , Humanos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/radioterapia , Glândula Parótida , Estudos Prospectivos , Glândula Submandibular/diagnóstico por imagem , Xerostomia/etiologia
19.
Curr Med Sci ; 41(1): 173-179, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33582923

RESUMO

The correlations between shear wave velocity (SWV) calculated from virtual touch tissue imaging quantification (VTIQ) technique and histological prognostic factors of invasive ductal carcinoma was investigated. A total of 76 breast tumors histologically confirmed as invasive ductal carcinomas were included in this study. SWV values were measured by VTIQ for each lesion preoperatively or prior to breast biopsy. The maximum values were recorded for statistical analysis. Medical records were reviewed to determine tumor size, histological grade, lymph node status and immunohistochemical results. Tumor subtypes were categorized as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive and triple negative. The correlations between SWV and histological prognostic factors were analyzed. It was found that tumor size showed positive association with SWV (r=0.465, P<0.001). Larger tumors had significantly higher SWV than smaller ones (P=0.001). Histological grade 1 tumors had significantly lower SWV values than those with higher histological grade (P=0.015). The Ki67 expression, tumor subtypes and lymph node status showed no statistically significant correlations with SWV, although triple negative tumors and lymph node-positive tumors showed higher SWV values. It was concluded that tumor size was significantly associated with SWV. Higher histological grade was associated with increased SWV. There was no statistically significant correlations between SWV and other histological prognostic factors.

20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 43-48, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554795

RESUMO

OBJECTIVE: To investigate the predict significance of the high aldehyde dehydrogenase activity (ALDH+) propitiation to the relapse of t(8;21) acute myeloid leukemia(AML) patients before and after treatment. METHODS: Bone marrow samples of 23 t(8;21) AML patients diagnosis and achieved complete remission in our hospital from April 2015 to June 2016 were collected, then flow cytometry method was used to detect the activity of ALDH, relationship between it and relapse was analyzed. RESULTS: All the patients were followed up for a median of 32 (2-52) months. The median percentage of CD34+CD38- and CD34+CD38-ALDH+ cells among nucleated cells were 2.7 (0.36-35.7)% and 0.017 (0.0013-0.62)% at diagnosis, respectively. Among the bone marrow samples in patients achieved CR, the median percentage of CD34+CD38- cells was 0.035 (0.0064-0.66)%, and it was significantly decreased as compared with the percentage at diagnosis (P<0.001); The median percentage of CD34+CD38-ALDH+ cells was 0.014 (0.0019-0.24)%, and it showed no different as compared with the percentage at diagnosis (P=0.45). Survival analysis showed that patients with higher percentage of CD34+CD38- and CD34+CD38-ALDH+ cells at diagnosis tended to the lower 3-year relapse-free survival (RFS) (P=0.27 and 0.21). Furthermore, patients with higher percentage of CD34+CD38- and CD34+CD38-ALDH+ cells when achieved CR had a significant lower 3-year RFS rates (P=0.010 and 0.0044) as compared with those with lower percentage of CD34+CD38- and CD34+CD38-ALDH+ cells. Multivariate analysis showed that higher percentage of CD34+CD38-ALDH+ cells when achieved CR was an independent factor affecting RFS of the patients. CONCLUSION: The percentage of CD34+CD38-ALDH+ cells at CR in t(8;21) AML patients could predicts relapse, and had more profound predictive significance for relapse than the percentage of CD34+CD38- cells.


Assuntos
Leucemia Mieloide Aguda , ADP-Ribosil Ciclase 1 , Antígenos CD34 , Citometria de Fluxo , Humanos , Células-Tronco Neoplásicas , Prognóstico , Recidiva , Indução de Remissão
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