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1.
Environ Pollut ; 292(Pt B): 118469, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34752792

RESUMO

Although it is a probable human carcinogen, propylene oxide is widely applied in industry and daily life. However, data on neurodevelopmental effects of propylene oxide exposure among children are extremely limited. We aimed to determine the urinary concentrations of propylene oxide metabolite among school-aged children and evaluate the potential association of propylene oxide exposure with risk of dyslexia. A total of 355 dyslexic children and 390 controls were recruited from three cities (Jining, Wuhan, and Hangzhou) in China, between 2017 and 2020. Urinary N-acetyl-S-(2-hydroxypropyl)-L-cysteine (i.e., 2-hydroxypropyl mercapturic acid; 2-HPMA) was measured as the biomarker of propylene oxide exposure. The detection frequency of 2-HPMA was 100%. After adjusting for potential confounders, the odds ratio (OR) for dyslexia per 2-fold increase in urinary 2-HPMA was 1.19 [95% confidence interval (95% CI): 1.01, 1.40, P = 0.042]. Compared with the lowest quartile of urinary 2-HPMA concentrations, children with the highest quartile of 2-HPMA had a 1.63-fold (95% CI: 1.03, 2.56, P = 0.036) significantly increased risk of dyslexia, with a dose-response relationship (P-trend = 0.047). This study provides epidemiological data on the potential association between propylene oxide exposure and the risk of dyslexia in children. Further studies are warranted to confirm the findings and reveal the underlying biological mechanisms.


Assuntos
Dislexia , Compostos de Epóxi , Acetilcisteína , Criança , Cidades , Dislexia/induzido quimicamente , Dislexia/epidemiologia , Humanos
2.
Exp Ther Med ; 22(6): 1443, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34721685

RESUMO

Hydrogen peroxide (H2O2) can induce apoptosis by releasing reactive oxygen species (ROS) and reactive nitrogen species, which cause mitochondrial damage. The present study aimed to investigate the protective effects of flavonoids from the leaves of Carya cathayensis Sarg. against H2O2-induced oxidative damage and apoptosis in vitro. The bioactivity of total flavonoids (TFs) and five monomeric flavonoids [cardamonin (Car), pinostrobin chalcone, wogonin, chrysin and pinocembrin] from the leaves of Carya cathayensis Sarg. (LCCS) were tested to prevent oxidative damage to rat aortic endothelial cells (RAECs) induced by H2O2. Oxidated superoxide dismutase, glutathione peroxidase, malondialdehyde, lactate dehydrogenase and ROS were analyzed to evaluate the antioxidant activity. Gene and protein expression patterns were assessed using reverse transcription-quantitative PCR and western blotting, respectively. The results indicated that TFs and Car inhibited H2O2-induced cytotoxicity and apoptosis of RAECs. Additionally, they regulated the level of oxidase and inhibited the production of ROS. Overall, the TFs extracted from LCCS could potentially be developed as effective candidate drugs to prevent oxidative stress in the future; moreover, they could also provide a direction in investigations for preventing antioxidant activity through the ROS pathway.

3.
J Clin Transl Hepatol ; 9(5): 626-634, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34722177

RESUMO

Background and Aims: Acute-on-chronic liver failure (ACLF) is acute decompensation of liver function in the setting of chronic liver disease, and characterized by high short-term mortality. In this study, we sought to investigate the clinical course of patients at specific time points, and to propose dynamic prognostic criteria. Methods: We assessed the clinical course of 453 patients with ACLF during a 12-week follow-up period in this retrospective multicenter study. The clinical course of patients was defined as disease recovery, improvement, worsening or steady patterns based on the variation tendency in prothrombin activity (PTA) and total bilirubin (TB) at different time points. Results: Resolution of PTA was observed in 231 patients (51%) at 12 weeks after the diagnosis of ACLF. Among the remaining patients, 66 (14.6%) showed improvement and 156 (34.4%) showed a steady or worsening course. In patients with resolved PTA, the clinical course of TB exhibited resolved pattern in 95.2%, improved in 3.9%, and steady or worse in 0.8%. Correspondingly, in patients with improved PTA, these values for TB were 28.8%, 27.3%, and 43.9%, respectively. In patients with steady or worsening PTA, these values for TB were 5.7%, 32.3%, and 65.6%, respectively. Dynamic prognostic criteria were developed by combining the clinical course of PTA/TB and the clinical outcomes at 4 and 12 weeks after diagnosis in ACLF patients. Conclusions: We propose the following dynamic prognostic criteria: rapid progression, slow progression, rapid recovery, slow recovery, and slow persistence, which lay the foundation for precise prediction of prognosis and the improvement of ACLF therapy.

4.
Front Med (Lausanne) ; 8: 750061, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722587

RESUMO

Background and Aims: Acute-on-chronic liver failure (ACLF) is an acute deterioration of chronic liver disease with high short-term mortality. The inclusion or exclusion of previously decompensated cirrhosis (DC) in the diagnostic criteria of ACLF defined by the Asian Pacific Association for the Study of the Liver (APASL-ACLF) has not been conclusive. We aimed to evaluate the prognostic impact of decompensated cirrhosis in ACLF. Methods: We retrospectively collected a cohort of patients with a diagnosis of APASL-ACLF (with or without DC) hospitalized from 2012 to 2020 at three liver units in tertiary hospitals. Baseline characteristics and survival data at 28, 90, 180, 360, 540, and 720 days were collected. Results: Of the patients assessed using APASL-ACLF criteria without the diagnostic indicator of chronic liver disease, 689 patients were diagnosed with ACLF, of whom 435 had no decompensated cirrhosis (non-DC-ACLF) and 254 had previously decompensated cirrhosis (DC-ACLF). The 28-, 90-, 180-, 360-, 540-, and 720-day mortality were 24.8, 42.9, 48.7, 57.3, 63.4, and 68.1%, respectively, in DC-ACLF patients, which were significantly higher than in non-DC-ACLF patients (p < 0.05). DC was independently associated with long-term (180/360/540/720 days) but not short-term (28/90 days) mortality in patients with ACLF. Age, total bilirubin, international normalized ratio, and hepatic encephalopathy were independent risk factors for short- and long-term mortality risk in ACLF patients (p < 0.05). Conclusions: Patients with DC-ACLF have a higher mortality rate, especially long-term mortality, compared to non-DC-ACLF patients. Therefore, DC should be included in the diagnostic criteria of APASL-ACLF and treated according to the ACLF management process.

5.
Toxins (Basel) ; 13(11)2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34822586

RESUMO

Ochratoxin A(OTA) is considered to be one of the most important contaminants of food and feed worldwide. The liver is one of key target organs for OTA to exert its toxic effects. Due to current lifestyle and diet, nonalcoholic fatty liver disease (NAFLD) has been the most common liver disease. To examine the potential effect of OTA on hepatic lipid metabolism and NAFLD, C57BL/6 male mice received 1 mg/kg OTA by gavage daily. Compared with controls, OTA increased lipid deposition and TG accumulation in mouse livers. In vitro OTA treatment also promoted lipid droplets accumulation in primary hepatocytes and HepG2 cells. Mechanistically, OTA prevented PPARγ degradation by reducing the interaction between PPARγ and its E3 ligase SIAH2, which led to activation of PPARγ signaling pathway. Furthermore, downregulation or inhibition of CD36, a known of PPARγ, alleviated OTA-induced lipid droplets deposition and TG accumulation. Therefore, OTA induces hepatic steatosis via PPARγ-CD36 axis, suggesting that OTA has an impact on liver lipid metabolism and may contribute to the development of metabolic diseases.

6.
Sci Total Environ ; : 151852, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34826485

RESUMO

Exposure to organophosphate (OP) insecticides has been found to be related to neurodevelopmental disorders in children. However, no study has examined the association between OP insecticide exposure and the risk of dyslexia among children. We aimed to explore the association between OP insecticide exposure, indicated by urinary dialkylphosphate metabolites (DAPs), and the risk of dyslexia among Chinese Han children from three cities. A total of 845 children (422 dyslexics and 423 non-dyslexics) from Tongji Reading Environment and Dyslexia research program were included in the current case-control study. We measured six DAPs in urine samples, collected from November 2017 to December 2020. Logistic regression models were used to estimate odds ratios (ORs) for the association between DAPs and dyslexia risk, adjusting for potential confounders. The detection frequencies of DAPs were above 97.5%, except for diethyldithiophosphate (DEDTP) and dimethyldithiophosphate (DMDTP). Diethyl phosphate metabolites (DEs) were significantly associated with the risk of dyslexia. Compared with the lowest quartile, the adjusted ORs of dyslexia risk for the highest quartile of urinary diethylthiophosphate (DETP) and diethylphosphate (DEP) were 1.82 (1.04, 3.20) and 1.85 (1.08, 3.17). In addition, the adjusted ORs for dyslexia per 10-fold of urinary DEP, DETP, and ∑DEs concentration were 1.87 (1.12, 3.13), 1.55 (1.03, 2.35), and 1.91 (1.13, 3.21), respectively. Analyses stratified by gender indicated that such associations were more significant among boys. This study suggested that exposure to OP insecticides may be related to dyslexia among Chinese Han children from the three studied cities. However, our results should be interpreted with caution because of the case-control design and the fact that only one-spot urine sample was collected from the children. More studies with children living in China are necessary concerning the relatively high levels of urinary OP metabolites in our study.

7.
Biochim Biophys Acta Mol Basis Dis ; : 166304, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34826585

RESUMO

OBJECTIVE: SNAP-25 is one of the key proteins involved in formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes that are at the core of hormonal secretion and synaptic transmission. Altered expression or function of SNAP-25 can contribute to the development of neuropsychiatric and metabolic disease. A dominant negative (DN) I67T missense mutation in the b-isoform of SNAP-25 (DN-SNAP25mut) mice leads to abnormal interactions within the SNARE complex and impaired exocytotic vesicle recycling, yet the significance of this mutation to any association between the central nervous system and metabolic homeostasis is unknown. METHODS: Here we explored aspects of metabolism, steroid hormone production and neurobehavior of DN-SNAP25mut mice. RESULTS: DN-SNAP25mut mice displayed enhanced insulin function through increased Akt phosphorylation, alongside increased adrenal and gonadal hormone production. In addition, increased anxiety behavior and beigeing of white adipose tissue with increased energy expenditure were observed in mutants. CONCLUSIONS: Our results show that SNAP25 plays an important role in bridging central neurological systems with peripheral metabolic homeostasis, and provide potential insights between metabolic disease and neuropsychiatric disorders in humans.

8.
Injury ; 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34689988

RESUMO

OBJECTIVE: To explore the clinical characteristics and the short-term efficacy of posterior operation for traumatic lumbar spondylolisthesis. METHODS: All 28 patients (between January 2013 and June 2018) were treated with lumbar pedicle screw fixation combined with posterior intervertebral fusion. The clinical data and imaging materials of these patients were retrospectively analyzed. RESULTS: The mean follow-up period was 24.3 months (12-36 months). The average VAS score and JOA score were significantly improved after surgery, and the difference was statistically significant (P<0.05).The last follow-up X-ray showed that 16 cases were degree 0 and 12 cases were degree I according to Meyerding grading, which were statistically improved compared with preoperative. Postoperative CT indicated lumbar internal fixation well, and the lumbar fusion rate was 100%. The Frankel grading of neurological function was significantly improved compared with preoperative. CONCLUSION: Acute traumatic lumbar spondylolisthesis is caused by severe trauma and mostly occurred at L4/L5 and L5/S1 level. Early posterior reduction, decompression and intervertebral fusion can achieve satisfactory clinical and radiological outcome.

9.
Exp Ther Med ; 22(6): 1366, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34659512

RESUMO

Lower extremity deep vein thrombosis (DVT) is a common peripheral vascular disease, in which inflammation plays an important role. The aim of the present study was to investigate the expression and role of inflammatory factors in DVT. A rat model of venous thrombosis of the lower extremities was established through venous ligation surgery. The rats were examined at 2, 8, 24, 48 and 72 h after the induction of inferior venous stenosis and compared with control and sham surgery groups. The serum levels of interleukin-1ß (IL-1ß), tissue factor (TF) and xanthine oxidase (XOD) were measured using ELISAs. The morphology of the DVT tissue was observed by hematoxylin and eosin staining. Circulating endothelial cells (CECs) in peripheral blood were counted by flow cytometry. Reverse transcription-quantitative PCR and western blotting were used to detect mRNA and protein expression, respectively. The serum levels of IL-1ß, TF and XOD exhibited no significant differences between the control and sham surgery groups. However, those in the rat model of DVT presented an upward trend from 2 to 24 h and peaked at 24 h, with a significant difference from the respective levels in the control and sham surgery groups. The histopathological analysis revealed the presence of red and mixed thrombi in the rats 2-48 h following the induction of inferior venous stenosis group with inflammatory cell infiltration in the vascular wall. Thrombus formation was evident after 72 h. While significant difference was observed in the number of CECs in the peripheral blood between the control and sham surgery groups, the number of peripheral blood CECs in the rats with inferior venous stenosis group increased from 8 to 72 h, with significant differences among these groups. The mRNA levels of IL-1ß, TF, XOD and NF-κB in the tissues peaked at 24 h, with significant differences compared with those in the control and sham surgery groups. In addition, the protein expression level of NF-κB increased from 2 to 72 h. In conclusion, these results suggest that the high expression of IL-1ß, TF, XOD and NF-κB may promote thrombus formation.

10.
Zhen Ci Yan Jiu ; 46(10): 815-20, 2021 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-34698455

RESUMO

The "meridian theory" is the summary and sublimation of long-term medical practice of the Chinese ancient sages. Via reduction and reconstruction about the theoretical system, it has been put forward a doctrine of "binary structure" about the meridian and acupoints which, at the limbs, present a longitudinal arrangement, and those at the head-face and trunk present a horizontal distribution, being closely related to the "dematome" of the body. Centered on the ontogenesis of the embryonic "somite", a closely connected "structure-function unit" complex is formed with the development of the dermis-muscle-ogran-nerve within the homo-segment. This form constitutes the basic characteristics of pathological reaction rules and therapeutic effects of meridian acupoints.


Assuntos
Terapia por Acupuntura , Meridianos , Pontos de Acupuntura
11.
Front Physiol ; 12: 669202, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566670

RESUMO

Non-alcoholic fatty liver disease (NAFLD)is accompanied by typical inflammatory damage and cell death. As a pro-inflammatory form of cell death, pyroptosis participates in important pathological processes involved in NAFLD. Regulatory roles of both CCCTC-binding factor (CTCF) and dipeptidyl peptidase-4 (DPP4) have been reported in NAFLD, but it is still unclear whether the mechanism of action of gardenoside, a potential therapeutic for NAFLD, can be driven via these proteins. In this study, the direct interaction between CTCF and DPP4 was first confirmed by a dual-luciferase reporter assay system. Then, a cell model of NAFLD was established by induction with palmitic acid (PA) and lipopolysaccharide (LPS). A mouse NAFLD model was established, and the effect of gardenoside on both the cell and mouse models of NAFLD was also investigated. Increased lipid accumulation, NLRP3 inflammasome activation, and hepatocyte pyroptosis were recorded in NAFLD in vitro and in vivo. Gardenoside treatment effectively reduced the lipid accumulation, increased cell viability, reduced reactive oxygen species (ROS) generation, and attenuated pyroptosis and apoptosis in NAFLD in the in vitro and in vivo models. Alterations in these biological processes were evidenced by the decreased expression levels of several pro-pyroptotic markers including the NLR family, pyrin domain-containing 3 (NLRP3), apoptosis-related speckle-like protein (ASC), caspase-1 p20, Gasdermin D N-terminal domain (GSDMD-N), and IL-1ß, along with simultaneously decreased CTCF and DPP4 levels. Importantly, CTCF silencing or DPP4 silencing exhibited effects similar to gardenoside treatment, while CTCF overexpression counteracted this trend, which indicated that CTCF might be a target responsible for gardenoside-induced alleviation of NAFLD, such therapeutic effects might be achieved through controlling the expression of the direct target of CTCF (DPP4) and several downstream molecules. In general, the current study provides a promising strategy for NAFLD treatment.

12.
Brain Commun ; 3(3): fcab176, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557664

RESUMO

Normal-appearing white matter is far from normal in multiple sclerosis; little is known about the precise pathology or spatial pattern of this alteration and its relation to subsequent lesion formation. This study was undertaken to evaluate normal-appearing white matter abnormalities in brain areas where multiple sclerosis lesions subsequently form, and to investigate the spatial distribution of normal-appearing white matter abnormalities in persons with multiple sclerosis. Brain MRIs of pre-lesion normal-appearing white matter were analysed in participants with new T2 lesions, pooled from three clinical trials: SYNERGY (NCT01864148; n = 85 with relapsing multiple sclerosis) was the test data set; ASCEND (NCT01416181; n = 154 with secondary progressive multiple sclerosis) and ADVANCE (NCT00906399; n = 261 with relapsing-remitting multiple sclerosis) were used as validation data sets. Focal normal-appearing white matter tissue state was analysed prior to lesion formation in areas where new T2 lesions later formed (pre-lesion normal-appearing white matter) using normalized magnetization transfer ratio and T2-weighted (nT2) intensities, and compared with overall normal-appearing white matter and spatially matched contralateral normal-appearing white matter. Each outcome was analysed using linear mixed-effects models. Follow-up time (as a categorical variable), patient-level characteristics (including treatment group) and other baseline variables were treated as fixed effects. In SYNERGY, nT2 intensity was significantly higher, and normalized magnetization transfer ratio was lower in pre-lesion normal-appearing white matter versus overall and contralateral normal-appearing white matter at all time points up to 24 weeks before new T2 lesion onset. In ASCEND and ADVANCE (for which normalized magnetization transfer ratio was not available), nT2 intensity in pre-lesion normal-appearing white matter was significantly higher compared to both overall and contralateral normal-appearing white matter at all pre-lesion time points extending up to 2 years prior to lesion formation. In all trials, nT2 intensity in the contralateral normal-appearing white matter was also significantly higher at all pre-lesion time points compared to overall normal-appearing white matter. Brain atlases of normal-appearing white matter abnormalities were generated using measures of voxel-wise differences in normalized magnetization transfer ratio of normal-appearing white matter in persons with multiple sclerosis compared to scanner-matched healthy controls. We observed that overall spatial distribution of normal-appearing white matter abnormalities in persons with multiple sclerosis largely recapitulated the anatomical distribution of probabilities of T2 hyperintense lesions. Overall, these findings suggest that intrinsic spatial properties and/or longstanding precursory abnormalities of normal-appearing white matter tissue may contribute to the risk of autoimmune acute demyelination in multiple sclerosis.

13.
Lipids Health Dis ; 20(1): 118, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587955

RESUMO

BACKGROUND: The present study was aimed to establish a prediction model for in-stent restenosis (ISR) in subjects who had undergone percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). MATERIALS AND METHODS: A retrospective cohort study was conducted. From September 2010 to September 2013, we included 968 subjects who had received coronary follow-up angiography after primary PCI. The logistic regression analysis, receiver operator characteristic (ROC) analysis, nomogram analysis, Hosmer-Lemeshow χ2 statistic, and calibration curve were applied to build and evaluate the prediction model. RESULTS: Fifty-six patients (5.79%) occurred ISR. The platelet distribution width (PDW), total cholesterol (TC), systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and lesion vessels had significant differences between ISR and non-ISR groups (all P < 0.05). And these variables were independently associated with ISR (all P < 0.05). Furthermore, they were identified as predictors (all AUC > 0.5 and P < 0.05) to establish a prediction model. The prediction model showed a good value of area under curve (AUC) (95%CI): 0.72 (0.64-0.80), and its optimized cut-off was 6.39 with 71% sensitivity and 65% specificity to predict ISR. CONCLUSION: The incidence of ISR is 5.79% in CAD patients with DES implantation in the Xinjiang population, China. The prediction model based on PDW, SBP, TC, LDL-C, and lesion vessels was an effective model to predict ISR in CAD patients with DESs implantation.

14.
Arch Virol ; 166(12): 3269-3274, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34536128

RESUMO

Enterovirus 71 (EV71) poses a major threat to public health globally due to severe and even fatal hand, foot, and mouth disease (HFMD). However, no effective antiviral agents are available to treat HFMD caused by this virus. Polysaccharides have been shown to exhibit antiviral activity, and polysaccharides extracted from Picochlorum sp. 122 (PPE) could potentially be used to treat HFMD, but reports on their antiviral activity are limited. In this study, the antiviral activity of PPE against EV71 was verified in Vero cells. PPE was shown to limit EV71 infection, as demonstrated using an MTT assay and by observing the cellular cytopathic effect. In addition, a decrease in VP1 RNA and protein levels indicated that PPE effectively inhibits proliferation of EV71 in Vero cells. An annexin V affinity assay also indicated that PPE protects host cells from apoptosis through the AKT and ATM/ATR signalling pathways. These results demonstrate that PPE has potential as an antiviral drug to treat HFMD caused by EV71.

15.
Zhongguo Zhen Jiu ; 41(9): 943-50, 2021 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-34491640

RESUMO

Although acupuncture has spanned thousands of years in the history of traditional medicine, still some basic questions are not clarified. Acupuncture is the theory based on long time medical practice of the ancient sage, combined with objectivesymptom and medical expertise from diseases, and being applied for the instruction in clinic. In this way, acupoint is discovered by doctors in the practice of disease treatment other than a natural occurrence in the healthy population. And acupoint specificity is attached to the target organ involved in pathological condition. In our opinion, acupoint originates from somatic referred area reactive to visceral disorders. And accordingly, referred hyperesthesia of the somatic area is phenomenon of acupoint sensitization. Acupoint is the situ having health code formed in the biological evolution. Corresponding acupoint of a given organ is the alarmer for the state of health, and also is the trigger for self-healing where acupuncture can work as a gating-button. Therefore, acupoint must be accompanied with diseases in that it is reinforced by, relayed on, responsive to and neutralize by the pathological course. In conclusion, acupoint cannot exist without the disease. In another word, acupoint will be unshown, or be functionally hidden, under physiological condition.


Assuntos
Terapia por Acupuntura , Acupuntura , Médicos , Pontos de Acupuntura , Humanos , Medicina Tradicional
16.
Cancer Prev Res (Phila) ; 14(11): 995-1008, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34584001

RESUMO

Previous studies have reported that phosphodiesterase 10A (PDE10) is overexpressed in colon epithelium during early stages of colon tumorigenesis and essential for colon cancer cell growth. Here we describe a novel non-COX inhibitory derivative of the anti-inflammatory drug, sulindac, with selective PDE10 inhibitory activity, ADT 061. ADT 061 potently inhibited the growth of colon cancer cells expressing high levels of PDE10, but not normal colonocytes that do not express PDE10. The concentration range by which ADT 061 inhibited colon cancer cell growth was identical to concentrations that inhibit recombinant PDE10. ADT 061 inhibited PDE10 by a competitive mechanism and did not affect the activity of other PDE isozymes at concentrations that inhibit colon cancer cell growth. Treatment of colon cancer cells with ADT 061 activated cGMP/PKG signaling, induced phosphorylation of oncogenic ß-catenin, inhibited Wnt-induced nuclear translocation of ß-catenin, and suppressed TCF/LEF transcription at concentrations that inhibit cancer cell growth. Oral administration of ADT 061 resulted in high concentrations in the colon mucosa and significantly suppressed the formation of colon adenomas in the Apc+/min-FCCC mouse model of colorectal cancer without discernable toxicity. These results support the development of ADT 061 for the treatment or prevention of adenomas in individuals at risk of developing colorectal cancer. PREVENTION RELEVANCE: PDE10 is overexpressed in colon tumors whereby inhibition activates cGMP/PKG signaling and suppresses Wnt/ß-catenin transcription to selectively induce apoptosis of colon cancer cells. ADT 061 is a novel PDE10 inhibitor that shows promising cancer chemopreventive activity and tolerance in a mouse model of colon cancer.

17.
Front Oncol ; 11: 735447, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381736

RESUMO

Increasing evidence has shown that the metabolism and clearance of molecular targeted agents, such as sorafenib, plays an important role in mediating the resistance of HCC cells to these agents. Metabolism of sorafenib is performed by oxidative metabolism, which is initially mediated by CYP3A4. Thus, targeting CYP3A4 is a promising approach to enhance the sensitivity of HCC cells to chemotherapeutic agents. In the present work, we examined the association between CYP3A4 and the prognosis of HCC patients receiving sorafenib. Using the online tool miRDB, we predicted that has-microRNA-4277 (miR-4277), an online miRNA targets the 3'UTR of the transcript of cyp3a4. Furthermore, overexpression of miR-4277 in HCC cells repressed the expression of CYP3A4 and reduced the elimination of sorafenib in HCC cells. Moreover, miR-4277 enhanced the sensitivity of HCC cells to sorafenib in vitro and in vivo. Therefore, our results not only expand our understanding of CYP3A4 regulation in HCC, but also provide evidence for the use of miR-4277 as a potential therapeutic in advanced HCC.

18.
Zhen Ci Yan Jiu ; 46(7): 625-30, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34369686

RESUMO

The skin microecology interacts with the immune system for a lifetime, and the skin microecology is in dynamic balance in the physiological state. The flora with the same physical and chemical properties on the surface of the skin can maintain a relatively stable state in a certain period of time, and there are dynamic changes of microflora in both physiology and disease state. Combined with the study of the relationship among skin microorganisms, skin diseases and visceral diseases, the relationship between skin microecological changes and visceral pathological state is explored. On this basis, it is proposed that the sensitized acupoint is an abnormal manifestation of the body homeostasis imbalance on the body surface, and the local substance variation on the sensitization acupoint may induce microbial changes. In terms of treatment, moxibustion and other surface treatments that function through immunity may also involve microorganisms.


Assuntos
Terapia por Acupuntura , Moxibustão , Pontos de Acupuntura , Humanos , Pele
19.
Pathogens ; 10(8)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34451426

RESUMO

Ehrlichia chaffeensis modulates numerous host cell processes, including gene transcription to promote infection of the mononuclear phagocyte. Modulation of these host cell processes is directed through E. chaffeensis effectors, including TRP120. We previously reported that TRP120 moonlights as a HECT E3 Ub ligase that ubiquitinates host cell transcription and fate regulators (PCGF5 and FBW7) to promote infection. In this study, we identified a novel TRP120 substrate and examined the relationship between TRP120 and α-enolase (ENO1), a metalloenzyme that catalyzes glycolytic pathway substrate dehydration. Immunofluorescence microscopy and coimmunoprecipitation demonstrated interaction between ENO1 and TRP120, and ubiquitination of ENO-1 by TRP120 was detected in vivo and in vitro. Further, ENO-1 degradation was observed during infection and was inhibited by the proteasomal inhibitor bortezomib. A direct role of TRP120 Ub ligase activity in ENO-1 degradation was demonstrated and confirmed by ectopic expression of TRP120 HECT Ub ligase catalytic site mutant. siRNA knockdown of ENO-1 coincided with increased E. chaffeensis infection and ENO-1 knockdown disrupted glycolytic flux by decreasing the levels of pyruvate and lactate that may contribute to changes in host cell metabolism that promote infection. In addition, we elucidated a functional role of TRP120 auto-ubiquitination as an activating event that facilitates the recruitment of the UbcH5 E2 ubiquitin-conjugating enzyme. This investigation further expands the repertoire of TRP120 substrates and extends the potential role of TRP120 Ub ligase in infection to include metabolic reprogramming.

20.
Prep Biochem Biotechnol ; : 1-11, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34339343

RESUMO

The optimization of extraction of Tetrastigma hemsleyanum Diels et Gilg polysaccharides (THP) using ultrasonic with enzyme method and its monosaccharide compositions and antioxidant activity were investigated in this work. Single-factor experiments and response surface methodology (RSM) were performed to optimize conditions for extraction, and the independent variables were (XA) dosage of cellulase, (XB) extraction time, (XC) ultrasonic power, and (XD) ratio of water to the material. The extraction rate of THP was increased effectively under the optimum conditions, and the maximum (4.692 ± 0.059%) was well-matched the predicted value from RSM. THP was consisted of mannose, glucuronic acid, rhamnose, galacturonic acid, glucose, galactose, and arabinose, while glucose was the dominant (26.749 ± 0.634%). According to the total antioxidant capacity assay with the FRAP method, DPPH, and hydroxyl radical scavenging assay, THP showed strong antioxidant activity with a dose-dependent behavior. The results indicated that THP has the potential to be a novel antioxidant and could expand its application in food and medicine.

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