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1.
Artigo em Inglês | MEDLINE | ID: mdl-32024309

RESUMO

The LACE index and HOSPITAL score models are the two most commonly used prediction models identifying patients at high risk of readmission with limited information for home care patients. This study compares the effectiveness of these two models in predicting 30-day readmission following acute hospitalization of such patients in Taiwan. A cohort of 57 home care patients were enrolled and followed-up for one year. We compared calibration, discrimination (area under the receiver operating curve, AUC), and net reclassification improvement (NRI) to identify patients at risk of 30-day readmission for both models. Moreover, the cost-effectiveness of the models was evaluated using microsimulation analysis. A total of 22 readmissions occurred after 87 acute hospitalizations during the study period (readmission rate = 25.2%). While the LACE score had poor discrimination (AUC = 0.598, 95% confidence interval (CI) = 0.488-0.702), the HOSPITAL score achieved helpful discrimination (AUC = 0.691, 95% CI = 0.582-0.785). Moreover, the HOSPITAL score had improved the risk prediction in 38.3% of the patients, compared with the LACE index (NRI = 0.383, 95% CI = 0.068-0.697, p = 0.017). Both prediction models effectively reduced readmission rates compared to an attending physician's model (readmission rate reduction: LACE, 39.2%; HOSPITAL, 43.4%; physician, 10.1%; p < 0.001). The HOSPITAL score provides a better prediction of readmission and has potential as a risk management tool for home care patients.

2.
Nat Cell Biol ; 22(2): 167-174, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32029896

RESUMO

Branched-chain amino acid (BCAA) metabolism is potentially linked with development of pancreatic ductal adenocarcinoma (PDAC)1-4. BCAA transaminase 2 (BCAT2) was essential for the collateral lethality conferred by deletion of malic enzymes in PDAC and the BCAA-BCAT metabolic pathway contributed to non-small-cell lung carcinomas (NSCLCs) other than PDAC3,4. However, the underlying mechanism remains undefined. Here we reveal that BCAT2 is elevated in mouse models and in human PDAC. Furthermore, pancreatic tissue-specific knockout of Bcat2 impedes progression of pancreatic intraepithelial neoplasia (PanIN) in LSL-KrasG12D/+; Pdx1-Cre (KC) mice. Functionally, BCAT2 enhances BCAA uptake to sustain BCAA catabolism and mitochondrial respiration. Notably, BCAA enhances growth of pancreatic ductal organoids from KC mice in a dose-dependent manner, whereas addition of branched-chain α-keto acid (BCKA) and nucleobases rescues growth of KC organoids that is suppressed by BCAT2 inhibitor. Moreover, KRAS stabilizes BCAT2, which is mediated by spleen tyrosine kinase (SYK) and E3 ligase tripartite-motif-containing protein 21 (TRIM21). In addition, BCAT2 inhibitor ameliorates PanIN formation in KC mice. Of note, a lower-BCAA diet also impedes PDAC development in mouse models of PDAC. Thus, BCAT2-mediated BCAA catabolism is critical for development of PDAC harbouring KRAS mutations. Targeting BCAT2 or lowering dietary BCAA may have translational significance.

3.
J Clin Lab Anal ; : e23243, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32068918

RESUMO

BACKGROUND: Increased levels of fetal hemoglobin (HbF) can improve the clinical course of the patients with sickle cell anemia (SCA) or ß-thalassemia. The HBG1-HBD intergenic region plays an important role in this process. However, very few studies investigated whether the variations in this region have an effect on HbF expression. METHODS: We retrieved all the SNP data in the HBG1-HBD intergenic region and defined the haplotype blocks, then performed cluster analysis and selected a tagSNP. A total of 500 normal individuals and 300 ß-thalassemia carriers were enrolled. After routine blood and hemoglobin capillary electrophoresis testing, ß-thalassemia mutations were detected using PCR-reverse dot blot. The genotypes of the rs4910736 (A > C) and rs10128556 (C > T) were determined using Sanger sequencing; the relationship between the two SNPs and the levels of HbF was analyzed. RESULTS: Two haplotype blocks were constructed. Block 1 included seven haplotypes divided into two groups M and N by 11 tagSNPs, among which rs4910736 was selected as a tagSNP, while block 2 included three haplotypes. We found that the haplotypes of block 1 were statistically associated with HbF levels, but the non-tagSNP rs10128556 was shown to be more strongly associated with HbF levels than rs4910736. CONCLUSION: This work proved that the haplotypes in the HBG1-HBD intergenic region and SNP rs10128556 are both statistically associated with HbF levels, revealing the association of polymorphisms in the HBG1-HBD intergenic region with HbF levels.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32063463

RESUMO

OBJECTIVE: This study investigated the in vitro stability of a novel sclerosant, bleomycin polidocanol foam (BPF), for venous malformation (VM) sclerotherapy. METHODS: The study was designed with control groups treated with polidocanol (0.5%, 1%, and 3%) only. The experimental groups included 21 BPFs, which was made by dissolving bleomycin at seven different concentrations (0.1%-1.5%) in polidocanol (0.5%, 1%, and 3%). The Tessari method was used to prepare sclerosant foam with a liquid:gas ratio of 1:4 at room temperature in vitro. The foam stability was measured for each group. The decay process, one component of foam stability, was recorded with a camera. Foam decay process experiments were performed 10 times per group. The stability indices included drainage rate, drainage time, half life, and microscopic measurement of the foams (mean bubble diameter, minimum and maximum bubble diameters, wall thickness, and bubble diameter distribution). RESULTS: Compared with the control groups, the half lives of BPFs mainly increased significantly with the addition of bleomycin (p < .001). BPF with 3% polidocanol and 0.1% bleomycin recorded the highest half life (246 ± 1.6 sec), and this group also achieved the smallest bubble diameter and wall thickness (69.9 µm and 5.80 µm) among the experimental groups. For the same polidocanol concentration, the bubble diameter and wall thickness increased when bleomycin was added. CONCLUSION: Bleomycin concentrations account for different BPF stability. BPF stability mainly increased significantly with the addition of a small amount of bleomycin but this advantage was no longer apparent with increasing bleomycin dose.

5.
Org Lett ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32091219

RESUMO

Leptosperols A and B (1 and 2), two cinnamoylphloroglucinol-sesquiterpenoid hybrids featuring unprecedented 1-benzyl-2-(2-phenylethyl) cyclodecane and 2-benzyl-3-phenylethyl decahydronaphthalene backbones, along with their biosynthetic precursor (3), were isolated from Leptospermum scoparium. Compounds 1 and 2 represent the first example of phloroglucinol derivatives biogenetically constructed by a De Mayo reaction. The biomimetic synthesis of leptosperol B (2) was achieved using the proposed biosynthetic pathway. In addition, compounds 1 and 2 showed significant anti-inflammatory effects in zebrafish acute inflammatory models.

6.
Curr Pain Headache Rep ; 24(4): 14, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32072323

RESUMO

PURPOSE OF REVIEW: Transcutaneous electrical nerve stimulation (TENS) is widely used as a non-pharmacological approach for pain relief in a variety of clinical conditions. This manuscript aimed to review the basic mechanisms and clinical applications regarding the use of TENS for alleviating the peripheral (PNP) and central neuropathic pain (CNP). RECENT FINDINGS: Basic studies on animal models showed that TENS could alleviate pain by modulating neurotransmitters and receptors in the stimulation site and its upper levels, including the spinal cord, brainstem, and brain. Besides, many clinical studies have investigated the efficacy of TENS in patients with CNP (caused by spinal cord injury, stroke, or multiple sclerosis) and PNP (induced by diabetes, cancer, or herpes zoster). Most clinical trials have demonstrated the efficacy of TENS in attenuating neuropathic pain and suggested that appropriate stimulation parameters (e.g., stimulation frequency and intensity) were critical to improving the analgesic effects of TENS. However, there are some conflicting findings related to the efficacy of TENS in relieving neuropathic pain. With optimized stimulation parameters, TENS would be effective in attenuating neuropathic pain. To obtain sufficient evidence to support the use of TENS in the clinic, researchers recommended performing multicenter clinical trials with optimized TENS protocols for the treatment of various CNP and PNP.

7.
Sci Total Environ ; 715: 136859, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32014767

RESUMO

BACKGROUND: Little is known about whether exposure to pets influences the association between hypertension and environmental tobacco smoke (ETS). The current study aims to examine the interaction of pet ownership on ETS exposure and the development of hypertension in children. METHODS: From 2012 to 2013, a total of 9354 children, 5 to 17 years of age, were recruited from 62 schools in seven northeastern cities. BP in children was measured and hypertension was defined as an average diastolic blood pressure (DBP) or systolic blood pressure (SBP) at or above the 95th percentile for that child's age, sex, and height. Pet ownership in three different time periods (in utero, past 2 years, and currently) and ETS exposure data were collected from parents via a questionnaire. Two-level regressions were used for the data analyses. RESULTS: The data show consistent, significant interactions between exposure to pets and effects from ETS. Children who were not exposed to pets experienced stronger effects from ETS on hypertension when compared to those exposed to pets, and the protective effect of pet ownership became stronger with a greater number of pets in the home. Exposure to in utero ETS was associated with hypertension [adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI): 1.13-1.54] only for those children without pet exposure in utero but not for those with pets (aOR = 0.75; 95% CI: 0.49-1.15) (pinteraction < 0.05). Moreover, household dog ownership was related to significantly lower effects of current ETS on hypertension (aOR = 0.80, 95% CI: 0.61-1.05) compared with children without dogs (aOR = 1.26, 95% CI: 1.11-1.44) (pinteraction = 0.001). Interaction associations between ETS and pet ownership were more robust for girls than for boys and for younger than older children. CONCLUSION: This study indicates an inverse relationship between pet ownership and ETS, potentially pointing to pet ownership as protecting against the development of hypertension in children.

8.
Environ Res ; 183: 109197, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32058142

RESUMO

There is a large body of evidence linking Environmental Tobacco Smoke (ETS) exposure with impaired lung function. However, it is not known whether exposure to pets modifies this relationship. To investigate if pet ownership changes the association between ETS exposure and lung function, a population-based sample of 7326 children, 7-14 years old, were randomly recruited from 24 districts in northeast China. Lung function including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), and maximal mid-expiratory flow (MMEF) was measured by spirometry, while pet ownership time periods and ETS exposure were collected by questionnaire. Two-level regression analysis was done, with covariates controlled for. The results showed pet exposure in certain early lifetime windows modified the associations of ETS exposure on decreased lung function in children. Among children exposed to current ETS, those exposed to pets in utero had greater reductions in lung function (for instance: OR for reduced FVC (<85% predicted) = 10.86; 95% CI: 3.80-30.97) than those not exposed to pets in utero (OR = 2.32; 95% CI: 1.76-3.05) (pinteraction = 0.005). While, children exposed to current pet ownership reduced the lung function impairment induced by ETS exposure during the first 2 years of life and/or ETS exposure during pregnancy, especially for FVC impairment. For instance, OR (95%CI) for reduced FVC (<85% predicted) was 0.81 (0.56, 1.18) and 1.42 (1.15, 1.74), respectively, for children with or without current pet ownership exposed to ETS during the first 2 years of life (pinteraction = 0.010). Furthermore, pet type or number of pets did not significantly modify associations between ETS exposure and lung function. In conclusion, the timing of pet ownership modified associations between ETS exposure and lung function, pet ownership in utero and during the first 2 years of life significantly worsened the adverse impacts of passive smoking on lung function.

9.
Environ Int ; 137: 105555, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32059142

RESUMO

The detrimental effects of perfluoroalkyl substances (PFASs) on several physiological systems have been reported, but the association of PFASs with eye, one of the most sensitive and exposed organ, has never been explored. To investigate the association between eye diseases including visual impairment (VI) and PFASs isomers, a cross-sectional stratified study was conducted in 1202 Chinese population, aged 22-96 years, from Shenyang, China. A standard protocol including Snellen vision chart, slit-lamp microscopy and direct ophthalmoscopy was used to examine eye diseases/conditions relating to anterior and posterior segment of eyes. In addition, we measured the blood concentrations of 19 linear and branched PFASs at one-time point. Results indicated that blood levels of PFASs were significantly higher in eye disease group than normal group. PFASs exposure were positively associated with both combined eye diseases and individual eye diseases. Among other PFASs, linear perfluorooctane sulfonate (n-PFOS; odds ratio [OR] = 3.37, 95% confidence interval [CI]: 2.50, 4.56), branched perfluorooctane sulfonate (Br-PFOS; OR = 2.25, 95% CI: 1.72, 2.93) and linear perfluorooctanoic acid (n-PFOA; OR = 1.79, 95% CI: 1.36, 2.37) significantly increases the odds of VI. Vitreous disorder was adversely associated with long-chain PFASs exposure. For example, perfluorotridecanoic acid (PFTrDA; OR = 1.86, 95% CI: 1.51, 2.29) and perfluorodecanoic acid (PFDA; OR = 1.79, 95% CI: 1.36, 2.36) showed the most significant association. In conclusion, this study suggests higher serum PFASs levels were associated with increase odds of VI and vitreous disorder in Chinese adults.

10.
Environ Int ; 137: 105552, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32059144

RESUMO

Swine farm wastewaters (SFWs) are generally discharged either directly into nearby rivers or into fish ponds as a source of fertilizer/food for aquaculture in China. SFWs contain various contaminants including steroid hormones. However, there is an extreme paucity of data on their effects in fish populations. Here we investigated the endocrine disrupting effects of SFWs in G. affinis from 2 rivers (7 sites) and 2 fish ponds (2 sites) receiving SFWs and a reference site in Guangdong Province, China. In this study, a total number of 3078 adult western mosquitofish (Gambusia affinis) were collected and the sex ratio was determined. In addition, secondary sexual characteristics were examined and the transcriptional levels of target genes were analyzed. The results showed the mosquitofish populations had a significant increase in male-to-female ratio from 7 sites (including 2 fish ponds) among the 9 sampling sites. The hemal spines of females were masculinized at most sites while the hemal spines of males were feminized at approximately half of the sites (including 2 fish ponds). Significant reduction in vitellogenin (Vtg) mRNA expression was observed in females from 2 sites (including RS7) while elevated Vtg mRNA expression was noticed in males from 2 sites along the rivers (including RS7). Redundancy analysis showed that androgens in the water samples were closely related with male-to-female ratio in the mosquitofish populations and the masculinized hemal spines of females. The findings from this study demonstrated that discharge of SFWs could result in occurrence of both masculinized females and feminized males in mosquitofish population.

11.
J Antibiot (Tokyo) ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32076117

RESUMO

Multidrug-resistant (MDR) uropathogenic Escherichia coli (UPEC) are prevalent throughout the world resulting in a major public health burden. In this research, we isolated and identified 28 MDR UPEC from one university hospital in China, investigated MDR and pathogenic mechanisms by PCR, including 55 antibiotic resistance determinants (ARDs) genes, 13 genetic markers of mobile genetic elements (MGEs) and 6 virulence factors (VFs) genes. In these isolates, we identified 23 ARDs genes and 6 genetic markers of MGEs that played a key role in MDR phenotypes. In addition, we found 2 VFs genes, hofQ and ompT, which could be associated with pathogenicity and invasiveness of these strains in urinary tract infections (UTIs).

12.
Mol Genet Genomic Med ; : e1136, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31965762

RESUMO

BACKGROUND: Atherosclerosis is the primary cause of coronary artery disease (CAD), and stearoyl-CoA desaturase (SCD) is associated with atherosclerosis. However, the associations between variants of SCD and CAD have not yet been decided. METHODS: This study analyzed SCD rs41290540 single-nucleotide polymorphism (SNP) in the 3'-untranslated region for an association with a risk of CAD among the Chinese Han population. CAD patients and controls were genotyped for SNP rs41290540 in SCD by SNaPshot. The binding affinity of miR-498 to rs41290540 was determined by a luciferase assay, and SCD expression was assessed using Western blot. RESULTS: A total of 969 CAD patients and 1,095 control subjects were involved in this study. The SCD rs41290540CC genotype is associated with a decreased risk of CAD compared with the AA genotype. Furthermore, the CC genotype is associated with lower serum total cholesterol (TC). Western blot analysis demonstrated that miR-498 suppressed the expression of SCD. A luciferase assay confirmed that rs41290540 A>C variation in the SCD 3'UTR inhibits miR-498 binding. CONCLUSION: This study demonstrates that the SCD rs41290540 may be associated with a decreased risk of CAD, lower serum TC, and decreased miR-498 binding.

13.
Oncol Res ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969212

RESUMO

MafF is a member of the bZIP transcription factor Maf family and commonly down-regulated inmultiple cancers. But the expression and function of MafF in HCC remain unclear. In thisstudy, we investigated the relationship between endogenous MafF expression and HCCprogression, and explored the regulatory mechanism of MafF expression in HCC. We found thatMafF decreased in HCC tissues and cells. Lentivirus-mediated MafF overexpression inhibitedHCC cell proliferation and induced cell apoptosis. Bioinformatics analysis and luciferase assayidentified MafF was a direct target of miR-224-5p. RNA pull down assay demonstrated thatcircular RNA circ-ITCH could sponge miR-224-5p specifically in HCC. The rescueexperiments further elucidated that the expression and antitumor effects of MafF could beregulated via circ-ITCH/miR-224-5p axis. This study verified that MafF acted as a tumorsuppressor in HCC and revealed the upstream regulation mechanism of MafF, which provided anew perspective for potential therapeutic targets of HCC.

14.
J Magn Reson Imaging ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31975534

RESUMO

BACKGROUND: Right ventricular dilation and dysfunction is a common long-term complication in patients with repaired pulmonary stenosis (rPS). Additionally, abnormal right and left ventricular interactions have been reported in right-sided heart defect after intervention, including in pulmonary stenosis. PURPOSE: To analyze ventricular strain, remodeling, and left and right ventricular interactions in rPS patients with preserved right ventricular ejection fraction (RVEF) compared with healthy children using cardiac magnetic resonance. STUDY TYPE: A cross-sectional study. POPULATION: In all, 34 rPS patients and 10 healthy children volunteers (controls). FIELD STRENGTH/SEQUENCE: 3.0T/2D balanced steady-state free precession (2D b-SSFP) cine, late gadolinium enhancement (LGE), and 2D phase contrast (2D-PC). ASSESSMENT: Pulmonary regurgitation (PR) fractions of the main pulmonary artery, biventricular volumes, masses, function, and cardiac strain. STATISTICAL TESTS: Mann-Whitney U-test, t-test, Pearson correlation coefficients, Spearman's correlation coefficients, and intraclass correlation coefficients analysis were performed. RESULTS: For group analysis, the right ventricular (RV) global circumferential strain and radial strain were significantly increased in patients when compared with controls (-13.57 ± 2.69 vs. -5.91 ± 3.16, P < 0.001; 25.31 ± 8.12 vs. 9.87 ± 5.32, P < 0.001, respectively). The fraction of PR displayed moderate correlation with right ventricular end-diastolic volume index (RVEDVi) (r = 0.452, P = 0.022). RVEDVi and mass index were larger in patients vs. control (104.92 ± 27.46 vs. 85.15 ± 11.98, P = 0.016; 18.28 ± 4.95g/m2 vs. 11.67 ± 2.14 g/m2 , P < 0.001, respectively). Patients presented with preserved left ventricular ejection function, but was lower than healthy controls (60.89% ± 4.89% vs. 65.95% ± 4.56%, P = 0.006). Regional circumferential strain of segment 3 of left ventricle (LV) were significantly decreased in patients (-7.79 ± 6.52 vs. -13.56 ± 3.22, P = 0.003). DATA CONCLUSION: Compensated increased RV strain, myocardial remodeling of RV, and adverse right and left ventricular interactions occur in rPS patients with preserved RVEF. The decreased interventricular septum strain may lead to impaired LV function due to RV dilation as a result of PR. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020.

15.
Trials ; 21(1): 110, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992367

RESUMO

BACKGROUND: Many studies have shown the potential therapeutic effect of acupuncture on allergic rhinitis. Most of these studies were limited by low-quality evidence. Preliminary experiments showed that the use of acupuncture at three nasal acupoints plus acupoint application (AAP) achieves a more persistent effect in the treatment of perennial allergic rhinitis than acupuncture alone. In this study, a multicenter, single-blind, randomized controlled trial will be performed, in which acupuncture at nonmeridian acupoints and sham AAP will be used as the control group to evaluate the effect of AAP through long-term observation. METHODS: The trial is designed on the basis of the Consolidated Standards of Reporting Trials 2010 guidelines and Standards for Reporting Interventions in Controlled Trials of Acupuncture. A total of 120 participants with perennial allergic rhinitis will be randomly assigned to a treatment or control group. A specially appointed investigator will be in charge of randomization. The participants in the treatment group will be treated with acupuncture at EX-HN3, LI20, and EX-HN8 thrice per week for a total of 12 sessions. In addition, they will undergo AAP at DU14, BL13, EX-BI, and RN22. The participants in the control group will be treated with sham AAP. The primary outcome will be the change in the Total Nasal Symptom Score from baseline to the completion of 4-week treatment. Secondary outcomes include changes in visual analog scale and total non-nasal symptom scores from baseline to the second and fourth weeks of treatment, as well as 1, 3, and 6 months after the completion of treatment. Peripheral blood IL-4, IL-5, IL-6, IL-8, and IL-10 levels will be measured, and any side effects related to treatment will be observed and recorded. DISCUSSION: It is expected that this randomized clinical trial will provide evidence to determine the effects of AAP compared with acupuncture at nonmeridian acupoints and sham AAP, particularly the long-term effect. These findings will help improve the clinical application of this technique. TRIAL REGISTRATION: Acupuncture-Moxibustion Clinical Trial Registry AMCTR-ICR-18000179. Registered on 12 April 2018.

16.
Cell Signal ; 69: 109433, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31982551

RESUMO

In mammals, 24-h rhythms of behaviour and physiology are regulated by the circadian clock. The circadian clock is controlled by a central clock in the brain's suprachiasmatic nucleus (SCN) that synchronizes peripheral clocks in peripheral tissues. Clock genes in the SCN are primarily entrained by light. Increasing evidence has shown that peripheral clocks are also regulated by light and hormones independent of the SCN. How the peripheral clocks deal with internal signals is dependent on the relevance of a specific cue to a specific tissue. In different tissues, most genes that are under circadian control are not overlapping, revealing the tissue-specific control of peripheral clocks. We will discuss how different signals control the peripheral clocks in different peripheral tissues, such as the liver, gastrointestinal tract, and pancreas, and discuss the organ-to-organ communication between the peripheral clocks at the molecular level.

17.
J Craniofac Surg ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31977686

RESUMO

BACKGROUND: Large maxillofacial venous malformation (VM) lesions can affect the craniofacial skeleton, causing occlusal and craniofacial deformity. Few studies have discussed the management of these skeletal disorders. It is unclear whether orthodontic treatment and orthognathic surgery are necessary after such a VM lesion has been significantly reduced. METHODS: A 13-year-old boy with a large, extensive maxillofacial VM lesion, severe facial asymmetry, macroglossia, and lower lip hypertrophy visited our department in 2010. He received more than 100 sclerotherapy treatments and 20 laser treatments in the past 8 years. RESULTS: The patient's cosmetic disfigurement greatly improved, and the VM lesion diminished by more than 80%. Changes in the bite and craniofacial skeleton progressed from "normal" to "open bite with skeletal deformity" and finally to "spontaneously close to normal". CONCLUSIONS: During the progression of VM, removal of pathogenic factors can inhibit the aggravation of open bite deformity and promote the spontaneous improvement, thereby circumventing the need for complicated osteotomy, orthodontic intervention and/or orthognathic surgery.

18.
J Neuroinflammation ; 17(1): 15, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924219

RESUMO

BACKGROUND: Microglial mediated neuroinflammation in the rostral ventrolateral medulla (RVLM) plays roles in the etiology of stress-induced hypertension (SIH). It was reported that autophagy influenced inflammation via immunophenotypic switching of microglia. High-mobility group box 1 (HMGB1) acts as a regulator of autophagy and initiates the production of proinflammatory cytokines (PICs), but the underlying mechanisms remain unclear. METHODS: The stressed mice were subjected to intermittent electric foot shocks plus noises administered for 2 h twice daily for 15 consecutive days. In mice, blood pressure (BP) and renal sympathetic nerve activity (RSNA) were monitored by noninvasive tail-cuff method and platinum-iridium electrodes placed respectively. Microinjection of siRNA-HMGB1 (siHMGB1) into the RVLM of mice to study the effect of HMGB1 on microglia M1 activation was done. mRFP-GFP-tandem fluorescent LC3 (tf-LC3) vectors were transfected into the RVLM to evaluate the process of autolysosome formation/autophagy flux. The expression of RAB7, lysosomal-associated membrane protein 1 (LAMP1), and lysosomal pH change were used to evaluate lysosomal function in microglia. Mitophagy was identified by transmission electron microscopic observation or by checking LC3 and MitoTracker colocalization under a confocal microscope. RESULTS: We showed chronic stress increased cytoplasmic translocations of HMGB1 and upregulation of its receptor RAGE expression in microglia. The mitochondria injury, oxidative stress, and M1 polarization were attenuated in the RVLM of stressed Cre-CX3CR1/RAGEfl/fl mice. The HMGB1/RAGE axis increased at the early stage of stress-induced mitophagy flux while impairing the late stages of mitophagy flux in microglia, as revealed by decreased GFP fluorescence quenching of GFP-RFP-LC3-II puncta and decreased colocalization of lysosomes with mitochondria. The expressions of RAB7 and LAMP1 were decreased in the stressed microglia, while knockout of RAGE reversed these effects and caused an increase in acidity of lysosomes. siHMGB1 in the RVLM resulted in BP lowering and RSNA decreasing in SIH mice. When the autophagy inducer, rapamycin, is used to facilitate the mitophagy flux, this treatment results in attenuated NF-κB activation and reduced PIC release in exogenous disulfide HMGB1 (ds-HMGB1)-stimulated microglia. CONCLUSIONS: Collectively, we demonstrated that inhibition of the HMGB1/RAGE axis activation led to increased stress-induced mitophagy flux, hence reducing the activity of microglia-mediated neuroinflammation and consequently reduced the sympathetic vasoconstriction drive in the RVLM.

19.
Environ Pollut ; 260: 113996, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31991359

RESUMO

Per-and polyfluoroalkyl substances (PFASs) are a group of chemicals with a wide range of industrial and commercial applications, but little is known about the contamination of PFASs in groundwater and their linkage to surface water. Here we investigated the occurrence of PFASs in groundwater and surface water at the Maozhou River basin in order to understand their contamination profiles and potential health risks. The results showed that total PFASs concentrations ranged from 9.9 to 592.2 ng/L, 50.2-339.9 ng/L and 3.7-74.3 ng/g in groundwater, river water and sediment, respectively. The detection frequencies of C4-C8 chains (C4-C8) PFASs were higher than C9-C14 chains PFASs in the river and groundwater. Statistical analysis showed an obvious correlation between the major contaminants in the river and those in the groundwater, indicating the potential linkage of PFASs in the groundwater to the surface water. The wastewater indicator found in groundwater suggested domestic wastewater was only one of the source for the PFASs in the river and groundwater of Maozhou River basin. Moreover, human health risk assessment showed low risks from the PFASs to the residents by drinking groundwater.

20.
Biochim Biophys Acta Mol Cell Res ; 1867(2): 118617, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31785334

RESUMO

Sequestration of misfolded proteins into distinct cellular compartments plays a pivotal role in proteostasis and proteopathies. Cytoplasmic ubiquitinated proteins are sequestered by p62/SQSTM1 to deposit in sequestosomes or aggresome-like induced structures (ALIS). Most aggresome or ALIS regulators identified thus far are recruiters, while little is known about the disaggregases or dissolvers. In this research, we showed that lanosterol synthase and its enzymatic product lanosterol effectively reduced the number and/or size of sequestosomes/ALIS/aggresomes formed by endogenous proteins in the HeLa and HEK-293A cells cultured under both non-stressed and stressed conditions. Supplemented lanosterol did not affect the proteasome and autophagic activities, but released the trapped proteins from the p62-positive inclusions accompanied with the activation of HSF1 and up-regulation of various heat shock proteins. Our results suggested that the coordinated actions of disaggregation by lanosterol and refolding by heat shock proteins might facilitate the cells to recycle proteins from aggregates. The disaggregation activity of lanosterol was not shared by cholesterol, indicating that lanosterol possesses additional cellular functions in proteostasis regulation. Our findings highlight that besides protein modulators, the cells also possess endogenous low-molecular-weight compounds as efficient proteostasis regulators.

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