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1.
Dev Cell ; 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32755547

RESUMO

Plant somatic embryogenesis refers to a phenomenon where embryos develop from somatic cells in the absence of fertilization. Previous studies have revealed that the phytohormone auxin plays a crucial role in somatic embryogenesis by inducing a cell totipotent state, although its underlying mechanism is poorly understood. Here, we show that auxin rapidly rewires the cell totipotency network by altering chromatin accessibility. The analysis of chromatin accessibility dynamics further reveals a hierarchical gene regulatory network underlying somatic embryogenesis. Particularly, we find that the embryonic nature of explants is a prerequisite for somatic cell reprogramming. Upon cell reprogramming, the B3-type totipotent transcription factor LEC2 promotes somatic embryo formation by direct activation of the early embryonic patterning genes WOX2 and WOX3. Our results thus shed light on the molecular mechanism by which auxin promotes the acquisition of plant cell totipotency and establish a direct link between cell totipotent genes and the embryonic development pathway.

2.
J Pathol ; : e5495, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32617978

RESUMO

The histone demethylase KDM4B functions as a key co-activator for the androgen receptor (AR) and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 methylation marks. Constitutively active androgen receptor confers anti-androgen resistance in advanced prostate cancer. However, the role of KDM4B in resistance to next-generation anti-androgens and the mechanisms of KDM4B regulation are poorly defined. Here we found that KDM4B is overexpressed in enzalutamide-resistant prostate cancer cells. Overexpression of KDM4B promoted recruitment of AR to the c-Myc (MYC) gene enhancer and induced H3K9 demethylation, increasing AR-dependent transcription of c-Myc mRNA, which regulates the sensitivity to next-generation AR-targeted therapy. Inhibition of KDM4B significantly inhibited prostate tumor cell growth in xenografts, and improved enzalutamide treatments through suppression of c-Myc. Clinically, KDM4B expression was found upregulated and to correlate with prostate cancer progression and poor prognosis. Our results revealed a novel mechanism of anti-androgen resistance via histone demethylase alteration which could be targeted through inhibition of KDM4B to reduce AR-dependent c-Myc expression and overcome resistance to AR-targeted therapies. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

3.
J Cell Physiol ; 2020 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-32592202

RESUMO

Hsa_circ_001988 has been identified as a tumor suppressor gene in several carcinomas. However, its expression pattern and role in gastric cancer (GC) have still remained elusive. This study aimed to explore the functions of hsa_circ_001988 in GC. Quantitative reverse transcription polymerase chain reaction assay was performed to assess the expressions of hsa_circ_001988, miR-197-3p, FBXW7, CCDC6, and U2AF65 in GC tissues. The correlation analysis was undertaken to find out the relationship between hsa_circ_001988 expression and clinicopathological factors. A series of cellular experiments were carried out to describe the effects of hsa_circ_001988 on GC in vivo and in vitro. Besides, RNA immunoprecipitation (RIP) assay was performed to verify the relationship among EIF4A3, U2AF65, and hsa_circ_001988. We first found that the expression of hsa_circ_001988 was decreased in 341 GC patients that was related to World Health Organization histological types, Lauren types, and tumor invasion depth (p < .05). Silencing of hsa_circ_001988 facilitated proliferation, colony formation, migration, and invasion of GC cells, while overexpression of hsa_circ_001988 reversed the effect on GC progression in vitro. Additionally, the results of subcutaneous xenotransplanted tumor model demonstrated that overexpressing hsa_circ_001988 significantly suppressed the subcutaneous tumor growth in vivo. Mechanistically, hsa_circ_001988 attenuated the miR-197-3p expression possibly due to its molecular sponge effect, and then, positively promoted FBXW7 expression. Afterwards, FBXW7 regulated the expressions of yes-associated protein 1, cyclinD1, CCDC6, and EMT-related proteins. Notably, RIP assay showed the enrichment relationship among EIF4A3, U2AF65, and hsa_circ_001988. Additionally, EIF4A3 or U2AF65 promoted cyclization of hsa_circ_001988 in GC. Hsa_circ_001988 inhibits the proliferation and metastasis of GC via modulating EIF4A3/U2AF65-mediated hsa_circ_001988/miR-197-3p/FBXW7 axis.

4.
Elife ; 92020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32519950

RESUMO

Mu-opioid receptors (MORs) are crucial for analgesia by both exogenous and endogenous opioids. However, the distinct mechanisms underlying these two types of opioid analgesia remain largely unknown. Here, we demonstrate that analgesic effects of exogenous and endogenous opioids on inflammatory pain are mediated by MORs expressed in distinct subpopulations of neurons in mice. We found that the exogenous opioid-induced analgesia of inflammatory pain is mediated by MORs in Vglut2+ glutamatergic but not GABAergic neurons. In contrast, analgesia by endogenous opioids is mediated by MORs in GABAergic rather than Vglut2+ glutamatergic neurons. Furthermore, MORs expressed at the spinal level is mainly involved in the analgesic effect of morphine in acute pain, but not in endogenous opioid analgesia during chronic inflammatory pain. Thus, our study revealed distinct mechanisms underlying analgesia by exogenous and endogenous opioids, and laid the foundation for further dissecting the circuit mechanism underlying opioid analgesia.

5.
J Am Chem Soc ; 142(29): 12669-12680, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32588627

RESUMO

The successful growth of colloidal lead halide perovskite quantum dots (PQDs) has generated tremendous interest in the community, due to the unique properties and the promise PQDs offer for use in applications involving light-emitting devices and solar cell technology. However, tangible progress in probing their fundamental properties and/or their integration into optoelectronic devices has been hampered by issues of colloidal and photophysical instability. Here, we introduce a promising surface coating strategy relying on a polyzwitterion polymer, where high-affinity binding onto the QDs is driven by multicoordinating electrostatic interactions with the ion-rich surfaces of CsPbBr3 PQDs. The polymer ligands were synthesized by installing a stoichiometric mixture of amine-modified sulfobetaine anchors and solubilizing motifs on poly(isobutylene-alt-maleic anhydride), PIMA, via nucleophilic addition reaction. We find that this coating approach imparts enhanced colloidal and photophysical stability to the nanocrystals over a broad range of solvent conditions and in powder form. This approach also allows easy phase transfer of the PQDs from nonpolar media to an array of solutions with varying polarities and properties. Additionally, the stabilization strategy preserves the photophysical and structural characteristics of the nanocrystals over a period extending to 1.5 years under certain conditions.

6.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(3): 256-262, 2020 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-32573131

RESUMO

OBJECTIVE: This study aimed to develop novel self-adhesive resin cement with antibacterial and self-healing properties. Furthermore, the dentin bonding strength, mechanical properties, self-healing efficiency, and antibacterial property of the developed cement were measured. METHODS: Novel nano-antibacterial inorganic fillers that contain quaternary ammonium salts with long-chain alkyls were synthesized. These fillers were added into self-adhesive resin cement containing self-healing microcapsules at mass fractions of 0, 2.5%, 5.0%, 7.5%, or 10.0%. The dentin shear bonding test was used to test the bonding strength, whereas the flexural test was used to measure the flexural strength and elastic modulus of the cement. The single-edge V-notched beam method was used to measure self-healing efficiency, and human dental plaque microcosm biofilms were chosen to calculate the antibacterial property. RESULTS: The dentin shear bond strength significantly decreased when the mass fraction of the nano-antibacterial inorganic fillers in the novel cement reached 7.5% (P<0.05). The incorporation of 0, 2.5%, 5.0%, 7.5%, or 10.0% mass fraction of nano-antibacterial inorganic fillers did not adversely affect the flexural strength, elastic modulus, fracture toughness, and self-healing efficiency of the cement (P>0.1). Resin cement containing 2.5% mass fraction or more nano-antibacterial inorganic fillers significantly inhibited the metabolic activity of dental plaque microcosm biofilms, indicating strong antibacterial potency (P<0.05). CONCLUSIONS: The novel self-adhesive resin cement exhibited promising antibacterial and self-healing properties, which enable the cement to be used for dental applications.


Assuntos
Colagem Dentária , Cimentos de Resina , Antibacterianos , Cimentos Dentários , Análise do Estresse Dentário , Dentina , Humanos , Teste de Materiais , Resistência ao Cisalhamento , Propriedades de Superfície
7.
ACS Nano ; 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32584543

RESUMO

Material growth by van der Waals epitaxy has the potential to isolate monolayer (ML) materials and synthesize ultrathin films not easily prepared by exfoliation or other growth methods. Here, the synthesis of the early transition metal (Ti, V, and Cr) tellurides by molecular beam epitaxy (MBE) in the mono- to few-layer regime is investigated. The layered ditellurides of these materials are known for their intriguing quantum- and layer dependent- properties. Here we show by a combination of in situ sample characterization and comparison with computational predictions that ML ditellurides with octahedral 1T structure are readily grown, but for multilayers, the transition metal dichalcogenide (TMDC) formation competes with self-intercalated compounds. CrTe2, a TMDC that is known to be metastable in bulk and easily decomposes into intercalation compounds, has been synthesized successfully in the ML regime at low growth temperatures. At elevated growth temperatures or for multilayers, only the intercalation compound, equivalent to a bulk Cr3Te4, could be obtained. ML VTe2 is more stable and can be synthesized at higher growth temperatures in the ML regime, but multilayers also convert to a bulk-equivalent V3Te4 compound. TiTe2 is the most stable of the TMDCs studied; nevertheless, a detailed analysis of multilayers also indicates the presence of intercalated metals. Computation suggests that the intercalation-induced distortion of the TMDC-layers is much reduced in Ti-telluride compared to V-, and Cr-telluride. This makes the identification of intercalated materials by scanning tunneling microscopy more challenging for Ti-telluride. The identification of self-intercalation compounds in MBE grown multilayer chalcogenides may explain observed lattice distortions in previously reported MBE grown early transition metal chalcogenides. On the other hand, these intercalation compounds in their ultrathin limit can be considered van der Waals materials in their own right. This class of materials is only accessible by direct growth methods but may be used as "building blocks" in MBE-grown van der Waals heterostructures. Controlling their growth is an important step for understanding and studying the properties of these materials.

8.
Biomed Res Int ; 2020: 6726759, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32462010

RESUMO

The AT-hook transcription factor, AKNA, is a nuclear protein that affects a few physiological and pathological processes including cancer. Here, we investigated the role of AKNA in gastric cancer (GC). By using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays, AKNA was found deregulated in both GC cell lines and 32 paired GC tissues. Subsequently, Kaplan-Meier analysis and clinicopathological analysis were conducted using both 32 GC cases' data above and RNA-Seq data of AKNA in 354 GC patients and the corresponding clinical-pathological data obtained from The Cancer Genome Atlas (TCGA), and AKNA expression was found closely related to location, metastasis, and TNM staging of GC. Then, the potential molecular mechanisms of AKNA in GC were explored by gene set enrichment analysis (GSEA), qRT-PCR, and Western blot assays. AKNA was found to be a hub gene related to homotypic cell to cell adhesion, regulation of cell to cell adhesion, leukocyte cell to cell adhesion, and regulation of T cell proliferation in GC. GO analysis revealed that AKNA involved in the regulation of epithelial-mesenchymal transition (EMT)-related pathways including chemokine signaling pathway, cytokine to cytokine receptor interaction, cell adhesion molecules, and jak-stat signaling pathway in GC. To explore the regulation of AKNA expression, Targetscan and TargetMiner were used to predict the possible miRNA which targeted AKNA and found the expression of AKNA was negatively correlated to miR-762 which could be sponged by circTRNC18. In conclusion, AKNA could function as a tumor suppressor by modulating EMT-related pathways in GC. The expression of AKNA might be regulated by circTRNC18/miR-762 axis. AKNA could serve as a potential biomarker and an effective target for GC diagnosis and therapy.

9.
Neurosci Bull ; 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32451910

RESUMO

Although opioids still remain the most powerful pain-killers, the chronic use of opioid analgesics is largely limited by their numerous side-effects, including opioid dependence. However, the mechanism underlying this dependence is largely unknown. In this study, we used the withdrawal symptoms precipitated by naloxone to characterize opioid dependence in mice. We determined the functional role of mu-opioid receptors (MORs) expressed in different subpopulations of neurons in the development of morphine withdrawal. We found that conditional deletion of MORs from glutamatergic neurons expressing vesicular glutamate transporter 2 (Vglut2+) largely eliminated the naloxone-precipitated withdrawal symptoms. In contrast, conditional deletion of MORs expressed in GABAergic neurons had a limited effect on morphine withdrawal. Consistently, mice with MORs deleted from Vglut2+ glutamatergic neurons also showed no morphine-induced locomotor hyperactivity. Furthermore, morphine withdrawal and morphine-induced hyperactivity were not significantly affected by conditional knockout of MORs from dorsal spinal neurons. Taken together, our data indicate that the development of morphine withdrawal is largely mediated by MORs expressed in Vglut2+ glutamatergic neurons.

10.
Chin Med J (Engl) ; 133(10): 1144-1154, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32433046

RESUMO

BACKGROUND: The association of milk intake with cardiovascular disease (CVD) and cause-specific mortality remained controversial and evidence among the Chinese population was limited. We aimed to study the relationship between milk intake and CVDs among general Chinese adults. METHODS: A total of 104,957 participants received questionnaire survey. Results of physical examination such as anthropometric measurements and biochemical tests during 2007 to 2008, demographic data and their information on milk intake were collected through standardized questionnaires. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of CVD incidence, cause-specific mortality and all-cause mortality related to milk intake. Restricted cubic splines (RCSs) were applied to examine dose-response associations. RESULTS: Among the 91,757 participants with a median follow-up period of 5.8 years, we documented 3877 CVD cases and 4091 all-cause deaths. Compared with participants who never consumed milk, the multivariate-adjusted HRs (95% CIs) of CVD incidence for 1 to 150 g/day, 151 to 299 g/day, and ≥300 g/day were 0.94 (0.86-1.03) (P > 0.05), 0.77 (0.66-0.89) (P < 0.05), and 0.59 (0.40-0.89) (P < 0.05), respectively; each 100 g increase of daily milk intake was associated with 11% lower risk of CVD incidence (HR, 0.89; 95% CI: 0.85-0.94; P < 0.001), and 11% lower risk of CVD mortality (HR, 0.89; 95% CI: 0.82-0.97; P = 0.008) after adjustment for age, sex, residential area, geographic region, education level, family history of CVD, smoking, alcohol drinking, physical activity level, body mass index, and healthy diet status (ideal or not). RCS analyses also showed a linear dose-response relationship with CVD (P for overall significance of the curve <0.001; P for non-linearity = 0.979; P for linearity <0.001) and stroke (P for overall significance of the curve = 0.010; P for non-linearity = 0.998; P for linearity = 0.002) incidence, and CVD mortality (P for overall significance of the curve = 0.045; P for non-linearity = 0.768; P for linearity = 0.014) within the current range of daily milk intake. CONCLUSIONS: Daily milk intake was associated with lower risk of CVD incidence and mortality in a linear inverse relationship. The findings provide new evidence for dietary recommendations in CVD prevention among Chinese adults and people with similar dietary pattern in other countries.

11.
BJU Int ; 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32438463

RESUMO

OBJECTIVE: To compare the detection rates of prostate cancer between systematic biopsy and targeted biopsy using a stereotactic robot-assisted transperineal prostate platform. MATERIALS AND METHODS: We identified consecutive patients with suspicious lesion(s) on multiparametric magnetic resonance imaging (mpMRI), who underwent both systematic and MRI-transrectal ultrasonography (US) fusion targeted biopsy using our proprietary transperineal robot-assisted prostate biopsy platform between January 2015 and January 2019 at our institution, for retrospective analysis. Comparative analysis was performed between systematic and targeted biopsy using McNemar's test, and the cohort was further stratified by prior biopsy status and Prostate Imaging Reporting and Data System (PI-RADS) v2.0 score. International Society of Urological Pathology (ISUP) grade group (GG) ≥2 cancers (previously known as Gleason grade ≥7) were considered to be clinically significant. RESULTS: A total of 500 patients were included in our final analysis, of whom 67 (13%) were patients with low-risk cancer on active surveillance. Of the 433 patients without prior diagnosis of cancer, 288 (67%) were biopsy-naïve. A total of 248 (57%) were diagnosed with prostate cancer, with 199 (46%) having clinically significant prostate cancer (ISUP GG ≥2). There were no statistically significant differences in the overall prostate cancer and clinically significant prostate cancer detection rate between systematic and targeted biopsy (51% vs 49% and 40% vs 38% respectively; P = 0.306 and P = 0.609). Of the 248 prostate cancers detected, 75% (187/248) were detected on both systematic and targeted biopsy, 14% (35/248) were detected on systematic biopsy alone and 11% (26/248) were detected on targeted biopsy alone. Of the 199 clinically significant cancers detected, 69% (138/199) were detected on both systematic and targeted biopsy, 17% (33/199) on systematic biopsy alone and 14% (28/199) on targeted biopsy alone. There were no statistically significant differences in the detection rate between systematic and targeted biopsy for both overall and clinically significant prostate cancer, even when the cohort was stratified by prior biopsy status and PI-RADS score. Targeted biopsy has greater sampling efficiency compared to systematic biopsy for both overall and clinically significant prostate cancer (23.2% vs 9.8%, P < 0.001 and 14.8% vs 5.6%, P < 0.001). CONCLUSIONS: Using our robot-assisted transperineal prostate platform, combined MRI-US targeted biopsy with concurrent systematic prostate systematic biopsy probably represents the optimal method for the detection of clinically significant prostate cancer.

12.
Fertil Steril ; 113(4): 853-864, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32228881

RESUMO

OBJECTIVE: To determine whether the incidence of chromosomal abnormalities in blastocysts is higher in patients with idiopathic recurrent pregnancy loss (iRPL) who underwent preimplantation genetic testing for aneuploidy (PGT-A) than in those who underwent preimplantation genetic testing for monogenic defects (PGT-M). DESIGN: Retrospective cohort study. SETTING: University-affiliated reproductive center. PATIENT(S): A total of 62 patients with iRPL underwent 101 PGT-A cycles (iRPL group), and 212 patients underwent 311 PGT-M cycles (control group). INTERVENTIONS(S): Blastocyst biopsy and comprehensive chromosome screening technologies, including single-nucleotide polymorphism microarrays and next-generation sequencing. MAIN OUTCOME MEASURE(S): Incidence of chromosomal abnormalities in blastocysts and clinical miscarriage (CM) rate. RESULT(S): Stratification analysis by maternal age showed an increased incidence of chromosomal abnormalities in the iRPL group aged ≤35 years (48.9% vs. 36.9%), whereas no significant increase was found in the iRPL group aged >35 years (66.9% vs. 61.4%). After transfer of euploid embryos, women aged ≤35 years with iRPL exhibited an increased CM rate compared with the control group (26.1% vs. 3.1%). CONCLUSION(S): Young patients with iRPL have a significantly higher rate of chromosomal abnormalities in blastocysts compared with patients with no or sporadic CM. Although euploid embryos were transferred after PGT-A, young patients with iRPL had a higher CM rate, which may indicate that chromosomal abnormalities might not be the only causal factor for iRPL. Therefore, the role of PGT-A in iRPL still needs to be clarified.

13.
J Dig Dis ; 21(5): 279-286, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32336033

RESUMO

OBJECTIVE: We aimed to estimate the optimal cut-off values of liver stiffness measurement (LSM) for diagnosing and staging fibrosis in non-obese and obese patients with nonalcoholic fatty liver disease (NAFLD). METHODS: NAFLD patients diagnosed by liver biopsy according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system were enrolled in this study. Non-obesity was defined as a body mass index (BMI) less than 25 kg/m2 . LSM was performed by experienced physicians within 2 weeks before or after liver biopsy. RESULTS: A total of 158 patients were included. Average BMI of the non-obese (n = 68) and obese (n = 90) groups was 23.2 ± 1.6 and 27.9 ± 2.5 kg/m2 , respectively. After adjusted for age, fibrosis stage, steatosis grade and type 2 diabetes mellitus, the obese group had a LSM of 3.522 kPa higher than the non-obese patients (P = 0.003). LSM values of the non-obese patients had a lower trend when stratified by fibrosis stage, especially in cirrhosis (F4; P = 0.021). Applying separate cut-off values for patients with NAFLD in individual fibrosis stage, 5.8 vs 7.5 kPa (≥ F1), 7.6 vs 8.5 kPa (≥ F2), 9.1 vs 11.2 kPa (≥ F3), and 12.5 vs 14.3 kPa (F4), improved their diagnostic odds ratios compared with overall cut-off values. In the non-obese NAFLD group, using a separate cut-off avoided underestimating 9.1% of patients with cirrhosis. CONCLUSIONS: Non-obese NAFLD group had lower LSM than the obese group. Different cut-off values should be used to measure liver fibrosis stage in non-obese and obese NAFLD patients.

14.
Zhongguo Zhen Jiu ; 40(4): 352-6, 2020 Apr 12.
Artigo em Chinês | MEDLINE | ID: mdl-32275360

RESUMO

OBJECTIVE: To observe the effect of electronic moxibustion on memory function in the patients with amnestic mild cognitive impairment (aMCI). METHODS: A total of 59 aMCI patients were randomized into an electronic moxibustion group (30 cases) and a placebo moxibustion group (29 cases). In the electronic moxibustion group, the electronic moxibustion was applied to Baihui (GV 20), Dazhui (GV 14), Mingmen (GV 4) and Taixi (KI 3), 45 ℃ in temperature, 20 min each time. The treatment was given once a day, 5 times a week. The treatment for 4 weeks was as one course and 2 courses were required totally. In the placebo moxibustion group, the moxa-free patch was used, 38 ℃ in temperature. The acupoint selection and the treatment frequency were same as the electronic moxibustion group. Before and after treatment, Rivermead behavior memory test (RBMT) was adopted to evaluate the global memory function of the patients in the two groups and the N-back task test was adopted to evaluate working memory function separately. Additionally, the mini-mental state examination (MMSE) and its immediate memory, Montreal cognitive assessment (MoCA) and its delay recall were adopted to evaluate the global cognitive function and memory function. RESULTS: In the electronic moxibustion group, after treatment, RBMT score, N-back accuracy rates, MMSE and MoCA scores and the scores of immediate memory and delay recall were improved significantly as compared with those before treatment (P<0.01). In the placebo moxibustion group, the accuracy rates of 1-back and 2-back task and the scores of immediate memory and delay recall were improved obviously as compared with those before treatment (P<0.05, P<0.01). After treatment, the improvements of RBMT score, the accuracy rates of N-back task and MMSE and MoCA scores in the electronic moxibustion group were higher than those in the placebo moxibustion group (P<0.05). CONCLUSION: Electronic moxibustion improves memory function in the patients with amnestic mild cognitive impairment.


Assuntos
Amnésia/terapia , Disfunção Cognitiva/terapia , Memória , Moxibustão/métodos , Pontos de Acupuntura , Humanos , Testes de Estado Mental e Demência
15.
Zhen Ci Yan Jiu ; 45(4): 264-8, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32333529

RESUMO

OBJECTIVE: To investigate the autonomic nervous mechanism of acupuncture therapy in the treatment of ischemic cardiomyopathy by observing the influence of electroacupuncture (EA) at "Neiguan"(PC6) on the superior cervical cardiac nerve activity and cardiac function in chronic myocardial ischemia (CMI) rats. METHODS: Male SD rats were randomly divided into control, model and EA groups (n=8 in each group). The CMI model was established by ligating the anterior descending branch of the left coronary artery. EA (15 Hz, 1.5 mA) was applied to bilateral PC6 for 20 min, once a day for 28 consecutive days. Cardiac sympathetic nerve electrical activities (CSNEA), electrocardiogram (ECG) of the standard limb lead Ⅱ and ultrasonic cardiogram (UCG) were recorded for observing changes of ST segment height, left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS).. RESULTS: The CSNEA was significantly increased(P<0.001), and the hight of ECG-STⅡ, LVEF and LVFS were considerably decreased in the model group relevant to the control group (P<0.01, P<0.001), while after the intervention, modeling induced increase of CSNEA and decrease of ECG-STⅡ, LVEF and LVFS were obviously suppressed in the EA group in comparison with the model group (P<0.01, P<0.05, P<0.001). CONCLUSION: EA of PC6 can improve cardiac function and myocardial ischemia in CMI rats, which is possibly related to its effect in decreasing cardiac sympathetic hyperactivity.


Assuntos
Eletroacupuntura , Isquemia Miocárdica , Pontos de Acupuntura , Animais , Doença Crônica , Modelos Animais de Doenças , Masculino , Extratos Vegetais , Ratos , Ratos Sprague-Dawley , Volume Sistólico , Função Ventricular Esquerda
17.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(3): 215-220, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: covidwho-13573

RESUMO

OBJECTIVE: To study the clinical features and chest CT findings of coronavirus disease 2019 (COVID-19) in infants and young children. METHODS: A retrospective analysis was performed for the clinical data and chest CT images of 9 children, aged 0 to 3 years, who were diagnosed with COVID-19 by nucleic acid detection between January 20 and February 10, 2020. RESULTS: All 9 children had an epidemiological history, and family clustering was observed for all infected children. Among the 9 children with COVID-19, 5 had no symptoms, 4 had fever, 2 had cough, and 1 had rhinorrhea. There were only symptoms of the respiratory system. Laboratory examination showed no reductions in leukocyte or lymphocyte count. Among the 9 children, 6 had an increase in lymphocyte count and 2 had an increase in leukocyte count. CT examination showed that among the 9 children, 8 had pulmonary inflammation located below the pleura or near the interlobar fissure and 3 had lesions distributed along the bronchovascular bundles. As for the morphology of the lesions, 6 had nodular lesions and 7 had patchy lesions; ground glass opacity with consolidation was observed in 6 children, among whom 3 had halo sign, and there was no typical paving stone sign. CONCLUSIONS: Infants and young children with COVID-19 tend to have mild clinical symptoms and imaging findings not as typical as those of adults, and therefore, the diagnosis of COVID-19 should be made based on imaging findings along with epidemiological history and nucleic acid detection. Chest CT has guiding significance for the early diagnosis of asymptomatic children.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Betacoronavirus , Pré-Escolar , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
18.
Inflamm Res ; 69(6): 559-568, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32221619

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) cancer susceptibility candidate 9 (CASC9) is reported to be linked to cancers. This research aims to explore the role and possible mechanism of CASC9 in lung injury induced by sepsis. METHODS: Lipopolysaccharide (LPS) induced human small airway epithelial cells (HSAECs) were established in vitro to mimic sepsis-induced lung injury. The effects of CASC9 and miR-195-5p on HSAECs viability were studied by CCK-8 assay. Interactions between CASC9 and miR-195-5p were determined by bioinformatics analysis, RT-PCR, dual luciferase reporter assay, and RNA immunoprecipitation assay. Pyruvate dehydrogenase kinase 4 (PDK4) and apoptosis-related molecules including Bcl2 and Bad were detected by western blot. Additionally, sepsis-induced lung injury model in rats was established by intraperitoneal injection of LPS in vivo to validate the demonstrations of in vitro studies. RESULTS: CASC9 was markedly down-regulated while miR-195-5p was significantly up-regulated in HSAECs treated by LPS and lung tissues of rats with sepsis. CASC9 interacted with miR-195-5p, and negatively regulated its expression level. Overexpression of CASC9 or transfection of miR-195-5p inhibitors significantly promoted the viability of HSAECs. The transfection of miR-195-5p mimics effected oppositely. For mechanism, miR-195-5p targeted the 3'UTR of pyruvate dehydrogenase kinase 4 (PDK4) gene and depressed the protein level, and PDK4 was regulated indirectly by CASC9. Restoration of CASC9 in the lung tissues of rats with sepsis ameliorated lung injury. CONCLUSION: CASC9 protects lung epithelial cells from sepsis-induced injury via regulating miR-195-5p/PDK4 axis.

19.
J Neuroinflammation ; 17(1): 75, 2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32113469

RESUMO

BACKGROUND: Cinobufagin is the major bufadienolide of Bufonis venenum (Chansu), which has been traditionally used for the treatment of chronic pain especially cancer pain. The current study aimed to evaluate its antinociceptive effects in bone cancer pain and explore the underlying mechanisms. METHODS: Rat bone cancer model was used in this study. The withdrawal threshold evoked by stimulation of the hindpaw was determined using a 2290 CE electrical von Frey hair. The ß-endorphin and IL-10 levels were measured in the spinal cord and cultured primary microglia, astrocytes, and neurons. RESULTS: Cinobufagin, given intrathecally, dose-dependently attenuated mechanical allodynia in bone cancer pain rats, with the projected Emax of 90% MPE and ED50 of 6.4 µg. Intrathecal cinobufagin also stimulated the gene and protein expression of IL-10 and ß-endorphin (but not dynorphin A) in the spinal cords of bone cancer pain rats. In addition, treatment with cinobufagin in cultured primary spinal microglia but not astrocytes or neurons stimulated the mRNA and protein expression of IL-10 and ß-endorphin, which was prevented by the pretreatment with the IL-10 antibody but not ß-endorphin antiserum. Furthermore, spinal cinobufagin-induced mechanical antiallodynia was inhibited by the pretreatment with intrathecal injection of the microglial inhibitor minocycline, IL-10 antibody, ß-endorphin antiserum and specific µ-opioid receptor antagonist CTAP. Lastly, cinobufagin- and the specific α-7 nicotinic acetylcholine receptor (α7-nAChR) agonist PHA-543613-induced microglial gene expression of IL-10/ß-endorphin and mechanical antiallodynia in bone cancer pain were blocked by the pretreatment with the specific α7-nAChR antagonist methyllycaconitine. CONCLUSIONS: Our results illustrate that cinobufagin produces mechanical antiallodynia in bone cancer pain through spinal microglial expression of IL-10 and subsequent ß-endorphin following activation of α7-nAChRs. Our results also highlight the broad significance of the recently uncovered spinal microglial IL-10/ß-endorphin pathway in antinociception.

20.
Support Care Cancer ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32140974

RESUMO

PURPOSE: Primary central nervous system lymphoma (PCNSL) is a very rare type of malignancy with a poor prognosis. The role of whole brain radiotherapy (WBRT) in PCNSL has been questioned due to the significant neurotoxicity and lack of convincing data for survival benefit. Even its role in a palliative setting remains to be clearly elucidated. Our study aims to investigate the benefit of WBRT in patients who are ineligible for systemic therapy. METHODS: A single-institution retrospective study was conducted on patients diagnosed with PCNSL between 2002 and 2017. Patients were excluded if they received systemic therapy or focal radiation only. Data on patient demographics and WBRT were collected and correlated with clinical outcomes. RESULTS: A total of 48 patients were selected for analysis, among which 31 (64.6%) patients received WBRT and 17 (35.4%) patients received supportive care only. Patient baseline characteristics were similar between the two groups. Median overall survival (OS) was 4.3 months among the entire cohort. WBRT was associated with improved median OS (8.0 months, range 1.4-62.3 months) compared with supportive care only (3.3 months, range 0.7-18.3 months) (HR 0.39, 95% CI 0.20-0.75, p = 0.005). Among patients who received WBRT, higher radiation dose to the whole brain was not associated with survival (p = 0.10), but higher radiation dose to the gross tumor was associated with improved survival (p = 0.007). CONCLUSION: Patients with PCNSL who are ineligible for systemic therapy may still benefit from WBRT with improvement in survival, compared with the best supportive care. Dose escalation through the addition of a gross tumor boost in these patients was associated with improved overall survival. Further studies in the prospective setting are necessary to confirm the findings from the study.

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