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In this study, an established ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) method was combined with multivariate statistical analysis to investigate the commonality and difference of main chemical components in the medicinal parts of Paeonia lactiflora from different cultivars; in addition, a high performance liquid chromatography(HPLC) method was established to simultaneously determine the content of eight active components in Paeoniae Radix Alba. Non-targeted analysis was carried out by UPLC-Q-TOF-MS on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 μm) column with a gradient elution of 0.1% aqueous formic acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 0.2 mL·min~(-1). The column temperature was 30 ℃, and an electrospray ionization source was used to acquire mass spectrometry data in positive and negative ion modes. According to the accurate molecular weight and fragment ion information provided by multi-stage mass spectrometry and by comparison with reference substances and literature reports, thirty-six identical components were identified in Paeoniae Radix Alba from different cultivars with positive and negative ion modes. In the negative ion mode, two groups of samples were well separated; specifically, seventeen components with significant differences in content were screened and identified, and one component unique in "Bobaishao" was obtained. Quantitative analysis was conducted by high-performance liquid chromatography(HPLC) on an Agilent HC-C_(18)(4.6 mm×250 mm, 5 μm) column with a gradient elution of 0.1% aqueous phosphoric acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 1.0 mL·min~(-1). The column temperature was 30 ℃ and the detection wavelength was at 230 nm. An HPLC method was developed for the simultaneous determination of eight active components(gallic acid, oxypaeoniflorin, catechin, albiflorin, paeoniflorin, galloylpaeoniflorin, 1,2,3,4,6-O-pentagalloylglucose, benzoyl-paeoniflorin) in Paeoniae Radix Albaa from different cultivars. Satisfactory linearity was achieved within the investigated linear ranges and with fine coefficients(r>0.999 0), and the methodological investigation showed that the method had good precision, repeatability and stability. The mean recoveries were 90.61% to 101.7% with RSD of 0.12% to 3.6%(n=6). UPLC-Q-OF-MS provided a rapid and efficient qualitative analytical method for the identification of the chemical components in Paeoniae Radix Alba, and the developed HPLC method was simple, rapid and accurate, which could provide a scientific basis for the evaluation of the germplasm resources and herbal quality of Paeoniae Radix Alba from different cultivars.
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Cromatografia Líquida de Alta Pressão , Paeonia , AcetonitrilasRESUMO
OBJECTIVE To evaluate the rationality of epinephrine in the treatment of drug-induced anaphylactic shock, and to provide a reference for further standardizing the treatment measures of anaphylactic shock. METHODS According to the relevant data of the reports of severe adverse drug reaction (ADR) of drug-induced anaphylactic shock provided by Chongqing ADR Monitoring Center from 2015 to 2022, the selection of treatment drugs, and the application of epinephrine in anaphylactic shock were analyzed retrospectively; the clinical outcomes of anaphylactic shock with different epinephrine administration methods were investigated. RESULTS A total of 1 415 cases of severe ADR related to drug-induced anaphylactic shock were reported, with a male-to-female ratio of 1.04∶1; the drugs that caused allergic shock mainly included anti-infective drugs (47.92%), TCM injections (9.12%); the patients who suffered from drug-induced anaphylactic shock within 10 min after medication accounted for 43.96%; 97.24% of patients were cured or improved, and 2.76% of patients died or did not been improved. Among 1 415 patients, 63.39% of patients were treated with epinephrine, and the patients who preferred epinephrine treatment accounted for 53.14%; the intramuscular injection, subcutaneous injection, intravenous injection and intravenous drip accounted for 33.78%, 30.32%, 25.75% and 1.23%, respectively. The initial dose range of epinephrine was 0.01-10 mg, and the most frequent single dose was 1 mg (44.70%). Excessive single doses of intramuscular injection, subcutaneous injection and intravenous injection accounted for 51.03% (148 cases), 53.13% (136 cases) and 91.47% (193 cases) respectively, and the risk of overdose in intravenous injection was higher (P<0.05). The patients receiving initial treatment with epinephrine had a higher improvement rate/cure rate than those who did not use epinephrine (98.14% vs. 96.23%, P=0.029); the patients who preferred epinephrine had a higher improvement rate/cure rate than those who did not preferred epinephrine (98.14% vs. 95.17%, P=0.031); the improvement rate/cure rate of patients receiving intramuscular injection of epinephrine was higher than those without intramuscular injection (99.01% vs. 96.69%, P=0.038). CONCLUSIONS There are some unreasonable phenomena in the treatment of drug-induced anaphylactic shock, such as inappropriate selection of drugs, insufficient use of epinephrine, delay of administration, inappropriate route of administration and excessive single dose.
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OBJECTIVE To evalu ate the effects of perimenopausal one-day outpatient multidisciplinary model on the cognition of women to menopause hormone therapy (MHT). METHODS The perimenopausal one-day outpatient service opened by the Third Affiliated Hospital of Chongqing Medical University in 2017 was introduced ,which was participated by doctors ,pharmacists, nutritionists,music psychotherapists ,nurses and other multidisciplinary members to provide systematic ,all-round,humanistic and face-to-face group science popularization and education ,practical experience and Q&A for women in perimenopause or about to enter perimenopause (called“students”). The students who participated in one-day outpatient service in 2020 were selected as the survey object , and the questionnaire was CMEI2020KPYJ(ZAMM)00206] designed to analyze the understanding of perimenopausal syndrome,awareness rate of MHT ,willingness to use and concerns. RESULTS A total of 295 students completed the questionnaire. Compared with before participation , after participated in one-day outpatient service ,the cognition level of the students were all improved significantly ,including perimenopausal age (96.61% vs. 99.32%,P=0.037),the importance of perimenopausal health care knowledge (91.19% vs. 96.95%,P<0.001),whether the perimenopausal syndrome needs treatment (88.47% vs. 99.32%,P<0.001),willingness to use MHT (70.59% vs. 94.48% ,P<0.001),MHT treatment timing (60.50% vs. 95.17% ,P<0.001),reducing the risk of cardiovascular disease (51.68% vs. 96.55% ,P<0.001),delaying aging (69.75% vs. 97.59% ,P<0.001),preventing osteoporosis(65.13% vs. 97.59%),P<0.001);the medical staff were higher than the non-medical staff (P<0.05). Totally 90% of the students said they had gained knowledge about the prevention and treatment of common diseases ,nutrition and guidance, psychological regulation guidance hormone therapy related knowledges and exercise methods ;the proportion of the students who were willing to use MHT for 1 to 5 years(31.09% vs. 47.93%)increased significantly. The proportion of the students who concerned about the risk of thrombosis (60.24% vs. 36.81%),weight gain (59.64% vs. 14.84%)and life-long dependence (52.41% vs. 18.13%)was significantly reduced ,but that of the students who concerned about cancer risk was not diminished. From 2017 to 2020,the utilization rate of MHT was increased from 2.22% to 62.16% in non-medical staff among the students. CONCLUSIONS The multidisciplinary model of perimenopausal one-day outpatient service can improve the awareness of MHT among perimenopausal women ,eliminate misunderstandings ,and increase the utilization rate of MHT.
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OBJE CTIVE To investigate the clinical characteristics of a dverse drug reactions of asparaginase-associated pancreatitis(AAP),so as to provide reference for clinical safe medication. METHODS Analysis and identification were performed on a severe adverse reaction case of acute pancreatitis complicated with diabetic ketoacidosis and liver injury in a patient with acute lymphoblastic leukemia in our hospital after using pegaspargase. Retrieved from Wanfang database ,CNKI,PubMed and Embase database,case reports of AAP were collected and summarized in terms of patient demographics ,drug use ,incubation period and adverse reaction outcome. Combined with this case ,the disease characteristics and potential risk factors of AAP were analyzed and discussed. RESULTS After analysis and identification ,it was determined that AAP occurred in this patient. A total of 47 case reports were retrieved from the database ,and a total of 52 patients(including this patient )were included in the analysis ,including 29 males and 23 females,mainly minors (65.4%). L-asparaginase was the main asparaginase preparation that causes AAP (80.8%). Gastrointestinal symptoms were the main prodromal symptoms (92.3%),which could be accompanied by other asparaginase related adverse reactions. AAP could occur after 1-33 times of administration ,and the median latency was 14 days after administration;compared with children ,median latency of AAP in adult patients was shortened significantly (11 d vs. 16 d,P= 0.049);the median latency of AAP had longer tendency in patients treated with pegaspargase than that of L-asparaginase (17 d vs. 12.5 d,P=0.490). Of the cases included in the analysis ,8 patients died due to AAP ,1 of which was related to re-exposure to asparaginase preparations. CONCLUSIONS Acute pancreatitis is a serious and potentially fatal adverse drug reaction of ; asparaginase preparations. Clinical medical staff should pay attention to the characteristics of AAP ,consider the possibility : of AAP when the patients have gastrointestinal symptoms and do a good job in patient education and pharmaceutical care to minimize the damage caused by AAP to patients.
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The ecological corridors considering bird movement characteristics and habitat requirements would mitigate species extinction caused by habitat loss or habitat fragmentation and facilitate species gene dispersal and exchange. These functions may in turn benefit urban residents' physical and mental health as well as appreciation of real estates. Nonetheless, main ecological corridor construction methods developed by foreign scholars have not internally considered the movement and habitat characteristics of birds, while corridor research for birds by domestic scholars have focused on explorations of foreign technical methods yet lacked enough knowledge on studied birds' characteristics. Therefore, there is still much room for improvement in the study of urban ecological corridor construction from the perspective of birds. Based on the analyses of domestic and foreign related research from 1975 to 2020, we identified seven corridor construction methods and three corridor optimization methods within which bird ecology can be integrated. The advantages, drawbacks, and applicable scenarios of all the methods were explored accordingly. Finally, we argued that the develop-ment of computational models, which could not only combine bird species' observation data and spatial movement data with landscape structures but could also possess efficient computation power as well as simulate corridor's ecological benefits, would be a trend for constructing ecological corridor for birds.
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Conservação dos Recursos Naturais , Ecossistema , Animais , AvesRESUMO
Infectious disease surveillance is vitally important to maintaining health security, but these efforts are challenged by the pace at which new pathogens emerge. Wastewater surveillance can rapidly obtain population-level estimates of disease transmission, and we leverage freedom from disease principles to make use of non-detection of SARS-CoV-2 in wastewater to estimate the probability that a community is free from SARS-CoV-2 transmission. From wastewater surveillance of 24 treatment plants across upstate New York beginning in May 2020, we observed a reliable limit of detection of 0.3--0.5 cases per 10,000 population. No COVID-19 cases were reported 40% of the time following a non-detection of SARS-CoV-2 in wastewater, and cases were less than 1 daily case per 10,000 population 97% of the time following non-detection. Trends in the intensity of SARS-CoV-2 in wastewater correlate with trends in COVID-19 incidence and test positivity ({rho}>0.5), with the greatest correlation observed for active cases and a three-day lead time between wastewater sample date and clinical test date. Wastewater surveillance can cost-effectively demonstrate the geographic extent of the transmission of emerging pathogens, confirming that transmission is absent or under control and alerting of an increase in transmission. If a statewide wastewater surveillance platform had been in place prior to the onset of the COVID-19 pandemic, policymakers would have been able to complement the representative nature of wastewater samples to individual testing, likely resulting in more precise public health interventions and policies.
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In this paper, the current situation and existing problems of spinal surgery practice are analyzed and summarized. Combined with the review of the structure and function of spinal region, we have expounded the application and advantages of Essential Anatomy software in the clinical practice teaching of spinal surgery. This software has a friendly interface, simple operation, real content, intuitive and visual model, and it can provide videos and slice function, which makes the original complex and abstract spinal anatomy practice content become novel and vivid, and greatly deepens doctors' understanding of the structure, function, movement and the disease pathogenesis of spinal region. At the same time, it also greatly mobilizes the learning interest and initiative of the clinical practice doctors, and improves the effect of clinical practice.
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OBJECTIVE@#To investigate whether there is a difference in cerebellar development between appropriate -for-gestational-age (AGA) infants and small-for-gestational-age (SGA) infants.@*METHODS@#A total of 165 AGA infants and 105 SGA infants, with a gestational age of 26-40 weeks, were enrolled in this study. Within 24-48 hours after birth, ultrasound examination was performed to measure the transverse diameter of the cerebellum, the height of the vermis, the area of the vermis, the perimeter of the vermis, and the area and perimeter of the cerebellum on transverse section. A Pearson correlation analysis was used to investigate the correlation between cerebellar measurements and gestational age.@*RESULTS@#In both AGA and SGA infants, all cerebellar measurements were positively correlated with gestational age (r=0.50-0.81, P0.05), while in the 34-36 weeks and 37-40 weeks subgroups, the SGA infants had significantly lower measurements than the AGA infants (P<0.05).@*CONCLUSIONS@#The SGA infants with a gestational age of <34 weeks have intrauterine cerebellar development similar to AGA infants, but those with a gestational age of ≥34 weeks have poorer intrauterine cerebellar development than AGA infants.
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Humanos , Lactente , Cerebelo , Idade Gestacional , Recém-Nascido Pequeno para a Idade Gestacional , UltrassonografiaRESUMO
Hypoxia-activated prodrugs that specifically target tumor tissues were designed by attaching the nitro-aromatic ring carrier molecules that can be degraded in the hypoxic microenvironment of the tumor to the hydroxyamidine group of IDO1 inhibitor compound B and epacadostat. Eleven prodrug compounds were synthesized and their structures were confirmed by 1H NMR and HR-MS. Compounds F-1 and F-6, which had a higher stability and drug release rate, were identified by an in vitro stability assay, nitroreductase reduction assay, MTT assay, and an in vivo tumor tissue hypoxia degradation assay, and then evaluated for anti-tumor efficacy in vivo. The results showed that prodrug F-1 inhibited tumor growth by 67.41%, which was significantly higher than 42.31% for the starting drug group. It appeared that the inhibition of IDO1 in the tumor tissue was different from the overall inhibition of IDO1 in vivo. Animal treatment procedures were carried out with the approval of the Animal Care and Use Committee of the Chinese Academy of Medical Sciences and Peking Union Medical College.
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OBJECTIVE@#To analyze the expression profile of serum cytokines in patients with systemic sclerosis (SSc) and explore its possible regulatory mechanisms.@*METHODS@#Serum and DNA of peripheral blood mononuclear cells were collected from 30 SSc patients and 80 normal controls (NCs). According to the presence or absence of interstitial lung disease (ILD) in SSc, the patients were divided into SSc with ILD group and SSc without ILD group. According to the degree of skin involvement, the patients were divided into diffuse systemic scleroderma (dcSSc) group and limited systemic scleroderma (lcSSc) group. According to the presence of anti-topoisomerase-1 antibody (anti-Scl-70 antibody) in the serum of patients with SSc, they were divided into SSc Scl-70 (+) group and SSc Scl-70 (-) group. 27 cytokines in serum were detected by Luminex MAGPIX detection system and Bio-Plex Pro Human Cytokine 27-plex Assay kit: interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1ra), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12P70, IL-13, IL-15, IL-17, basic fiber growth factor (BASIC FGF), eotaxin, granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), interferon-gamma induced protein 10(IP-10), monocyte chemotactic protein 1(MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein 1β(MIP-1β), platelet-derived growth factor BB (PDGF-BB), regulated on activation in normal T-cell expressed and secreted (RANTES), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor(VEGF). Methylation sites were detected by Illumina 450K methylation chip.@*RESULTS@#Compared with NCs group, the expression of 12 cytokines (BASIC FGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IL-1β, IL-1ra, IL-6, IP-10, MCP-1, TNF-α and RANTES) in the SSc group significantly increased (P<0.05), IL-5 was decreased expression in the SSc group (P<0.05), there was no significant difference in the expressions of the other 14 cytokines. Compared with lcSSc group, 9 cytokines (eotaxin, IL-5, MCP-1, IL-2, RANTES, IL17A, IL-8, MIP-1β and PDGF-BB) increased in dcSSc group, but there was no significant difference. Compared with SSc without ILD group, IL-15 increased in SSC with ILD group [18.2 (172.97) ng/L vs. 2.03(0.05) ng/L, P<0.05]. Compared with SSc Scl-70 (-) group, the expression of IP-10 decreased in SSc Scl-70 (+) group [1 030 (2 196.6) ng/L vs. 1 878 (2 964) ng/L, P<0.05]. The correlation analysis of serum cytokines with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) showed that IL-6 was positively correlated with ESR (r =0.04, P= 0.017), MCP-1 (r=0.49, P=0.043) and MIP-1β (r=0.41, P=0.007) positively correlated with CRP. By analyzing the changes of methylation sites of cytokines, it was found that cg17744604 in IL-10 TSS1500 region, cg06111286 in IL-12P70 TSS200 region, cg07935264 in IL-1β TSS200 region, cg01467417 in IL-1ra TSS1500 region, cg03989987 in IL-1ra 5'UTR region and cg21099624 in VEGF TSS200 region were all hypomethylated.@*CONCLUSION@#There were different cytokines expression profiles in the serum of SSc patients, and the altered cytokines were correlected with the degree of skin damage and pulmonary fibrosis. Many cytokines were regulated by methylation.
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Humanos , Citocinas , Leucócitos Mononucleares , Escleroderma Sistêmico , Fator de Necrose Tumoral alfa , Fator A de Crescimento do Endotélio VascularRESUMO
Objective:To prepare magnetic solid lipid nanoparticles co-loaded quercetin and resveratrol(QR-MSLN),develop the reasonable characterization method,and investigate its inhibitory effect on transplanted hepatocarcinoma H22 tumor in mice. Method:Magnetic Fe3O4 particles coated with oleic acid(OA-Fe3O4) were synthesized and its structure was confirmed by Fourier transform infrared spectrometer(FT-IR).QR-MSLN was prepared by emulsion ultrasonic dispersion method,its morphology was examined by transmission electron microscopy,its particle size was determined by laser particle sizer.Concentration of Fe in the preparation was determined by phenanthroline spectrophotometry.The entrapment efficiency,saturation magnetization,in vitro release behavior were investigated by ultrafiltration centrifugation,vibrating sample magnetometer(VSM) and dialysis method,respectively.Mouse tumor model transplanted with hepatoma H22 ascites tumor was established and antitumor effect of QR-MSLN on H22 bearing mice were observed in the presence of an applied magnetic field. Result:Morphology of QR-MSLN was round,and black magnetic particles could be observed inside it,its particle size was (171.9±2.2) nm,the concentration of Fe was (1.40±0.46) g·L-1.The preparation exhibited apparent superparamagnetism and the saturation magnetization was 7.75 A·m2·kg-1.The entrapment efficiencies of quercetin and resveratrol in QR-MSLN were 99.10% and 80.83%,respectively.QR-MSLN had a significantly higher effect of tumor inhibition than SLN(containing quercetin and resveratrol) and free drug(PConclusion:QR-MSLN has uniform particle size and good magnetic response,and shows remarkable antitumor effect on H22 bearing mice.
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Forensic DNA phenotyping (FDP) analysis uses DNA from biological samples left in crime scenes to predict individual phenotypic traits, such as geographical origin of ethnic group, height, weight, skin color, hair color and shape, iris color, male baldness, facial morphology, age, etc., thereby providing clues for case investigations. Among these traits, features of facial morphology are relatively more complicated. This paper makes an overall analysis of the measurement and collection of facial morphology, research on facial morphology related genes, forensic application and establishment of facial morphology depiction model, ethical issues, etc., then summarizes the latest research progress on features of facial morphology.
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Humanos , Masculino , DNA/genética , Face , Genética Forense/métodos , Fenótipo , Aparência Física/genéticaRESUMO
This study aimed to explore the anti-tumor activity and mechanisms of action of isorhamnetin, a compound isolated from Astragalus membranaceus, in combination with sorafenib for treatment of renal cell carcinoma (RCC). The anti-tumor activity of isorhamnetin in combination with sorafenib was detected by MTT assay with cells in culture or Renca xenograft model in mice. Western blot was used to study the mechanisms of isorhamnetin in combination with sorafenib. Lymphocyte proliferation assay was also used to investigate the effects of the two drugs in combination. The results indicated that isorhamnetin inhibited the proliferation of RCC cells, with IC50 for A498, 786-O and Renca cell lines with being 31.7, 28.8 and 106.0 μmol·L-1, respectively. Isorhamnetin in combination with sorafenib improved the anti-lymphocyte proliferation activity of sorafenib with the IC50 down to 12.0 μmol·L-1. Isorhamnetin inhibited the growth of RCC in mice slightly with the inhibition efficiency at 26.9%. With 50.0 mg·kg-1 isorhamnetin in combination with 20.0 mg·kg-1 sorafenib, the anti-tumor activity of sorafenib was enhanced, with inhibition of growth rate increased to 60.7%. Meanwhile, isorhamnetin in combination with sorafenib could promote the lymphocytes proliferation in Renca xenograft model. Western blot results showed that combination of isorhamnetin and sorafenib could inhibit c-Raf/MEK/ERK and AKT/mTOR signaling pathways. In conclusion, the combination of isorhamnetin with sorafenib could increase the anti-tumor activity of sorafenib in RCC in vitro and in vivo. The mechanisms may be related to the inhibition of c-Raf/MEK/ERK and AKT/mTOR signaling pathways. Procedures for animal study were performed with approval of the Animal Care and Use Committee of the Chinese Academy of Medical Sciences and Peking Union Medical College.
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Objective To explore the characteristics of Xianling Gubao Capsule (XGC) induced adverse reactions, especially drug-induced liver injury, and the occurrence and prognosis of ADR, aiming to provide a reference for clinical rational drug use, and ideas for after-marketing re-evaluation of Chinese materia medica. Methods A total of 788 patients were enrolled in one tertiary hospital to observe the clinical application safety of XGC based on real-word study. Results Compared with the conventional treatment group, the incidence of ADR in the treatment group showed no significant difference (P > 0.05) in XGC group. XGC group had the highest incidence of adverse gastrointestinal reactions (83.0%), and a higher incidence of abdominal distension (P 0.05). Pre-drug liver abnormalities or patients with underlying liver disease were more likely to have drug induced liver injury (30.4%). Conclusion Monitoring adverse reactions of XGC should be enhanced in order to promote the rational use and ensure the safety in clinic.
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Systemic sclerosis (SSc) is an autoimmune disease with unknown etiology, characterized by vasculopathy, inflammation, and extensive fibrosis in the skin and organs. Fibrosis is the hallmark of SSc and contributes to its high mortality. In recent years, with the in-depth study of the epigenetics of SSc (DNA methylation, histone modification, and non-coding RNA), the DNA methylation and miRNA has been the most widely studied. Abnormal DNA methylation can influence the function of vascular endothelial cells, CD4+ T cells, and fibroblasts in SSc. MiRNAs in serum is closely related to autoantibodies, SSc disease activity and complications, and miRNAs in fibroblasts can directly affect the activation of fibroblasts.
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Humanos , Metilação de DNA , Epigênese Genética , Epigenômica , Fibroblastos , Fibrose , Pesquisa , Escleroderma SistêmicoRESUMO
Aim To observe the effect of capsaicin on the experimental autoimmune neuritis (EAN) in rats and explore the mechanism.Methods To induce EAN,male Lewis rats were immunized with peripheralnerve myelin sheath antigen (P257481) peptide and complete Freund's adjuvant (CFA) mixed liquor.Rapamycin (RAPA,2.5 mg · kg-1) was administered by intraperitoneal injection 0.5 h after immunization and capsaicin (1 mg · kg-1 · d-1) was administered by intragastric administration 1.0 h after immunization for 15 days.The incidence and clinical characteristics of EAN were observed.The clinical scores of neurological signs were completed and body weight was measured.Pathological morphology of sciatic nerve was observed by HE staining and Lauck fast blue staining.Ultrastructure of sciatic nerve was observed by transmission electron microscope.Levels of serum tumor necrosis factor alpha (TNF-α),interferon gamma (IFN-γ),interleukin 1β (IL-1β) and intedeukin-6 (IL-6) were tested by enzyme linked immunosorbent assay (ELISA).Expressions of autophagy related protein were measured by Western blot.Results Compared with EAN group,the clinical scores of neurological signs significantly decreased from day 7 to day 16 of post-immunization (P < 0.05),body weight significantly increased from day 3 to day 16 of post-immunization (P < 0.05),demyelination obviously decreased,inflammatory cell infiltration number obviously decreased (P < 0.05),the levels of TNF-α,IFN-γ,IL-1β and IL-6 significantly decreased (P < 0.05),the number of autophagosome in axon of sciatic nerve significantly decreased (P < 0.05),and expressions of Beclin-1 and LC3-Ⅱ and the ratio of LC3-Ⅱ and LC3-Ⅰ were significantly down-regulated,and the expression of p62 was significantly up-regulated (P < 0.05) in EAN + capsaicin group.Rapamycin partially reversed the action of capsaicin.Conclusions Capsaicin inhibits EAN in rats,and the mechanism may be related with the inhibition of autophagy activity.
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OBJECTIVE The aim of the present study was to investigate the anti-tumor effect and mechanism of a novel compound, C3C12PPD, a bioactive unnatural ginsenoside by metabolically engi-neered yeasts based on a new UDP-glycosyl- transferase from Bacillus subtilis. METHODS MTT assay was used to analyze the anti-proliferation activity of C3C12PPD in vitro. The effect of anti-tumor activity was observed by mouse Lewis xenograft model in vivo.The effects of C3C12PPD on suppressing the angio-genesis and invasion of A549 cells were investigated in vitro using Transwell and tube formation assays. RNAseq was used to find tagets of C3C12PPD. Western blotting was performed to investigate the expres-sion level of proteins in tumor tissues treated with C3C12PPD. RESULTS C3C12PPD could inhibit the growth of lung cancer in vitro and in viv o. At the dosage of 10.0 mg·kg-1, C3C12PPD inhibited tumor growth by 40.0% (P<0.05) in tumor weight in mouse Lewis xenograft. The inhibition of tube formation was 77.5%(P<0.01)and 80.3%(P<0.01)following treatment with 1×10-4and 2×10-4mol·L-1C3C12PPD for 5 h, whereas the proliferation of EA.hy926 cells was not influenced under the above concentrations. Under the concentrations of 1×10-4mol·L-1,C3C12PPD inhibited invasive ability of A549 cells(P<0.05).The results of RNAseq susgested that antitumor activity of C3C12PPD were associated with epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, the proteins related to EMT, Raf/MEK/ERK and AKT/mTOR signal pathways were effected by C3C12PPD analysed by western blotting. CONCLUSION These data suggested that C3C12PPD was able to supress lung cancer through inhibit EMT, invision and angiogenesis.
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The abnormal activation of hedgehog (HH) signaling pathway plays an important role in the development and progression of glioblastoma (GBM). As a transcription factor at the end of the HH pathway, the final effector of glioma-associated oncogene homoglog-1 (GLI1) is an important target in the treatment of GBM. The study was designed to evaluate the anti-tumor activities and mechanisms of a novel GLI1 inhibitor FL18 in GBM. MTT and colony formation assay were performed to determine anti-proliferation activity of FL18 in vitro. The effect of FL18 on cell apoptosis was measured by flow cytometry (FCM) analysis. Transwell experiment was used to explore the inhibitory activity of FL18 in cell invasion. In vivo experiments, the subcutaneously transplanted and orthotopic U-87 MG GBM xenograft model were used to study the activity of FL18 on tumor growth. The optimized dual report gene screening model was used to detect the effect of FL18 on the transcriptional activity of GLI1. Western blot assay was used to study the mechanisms of action of FL18. The results showed that the IC50 of FL18 in glioblastoma was in the nanomole level in vitro. It was observed that 22.5 and 45 mg·kg-1 FL18 reduced the tumor volume with the rate of 55.4% and 89.8% in xenograft model in mice in situ. The IC50 of FL18 on the inhibition of GLI1 transcriptional activity was 3.32×10-11 mol·L-1 analyzed by the optimized dual report gene screening model. By the Western blot experiments, it was proved that FL18 inhibited expression of GLI1 without influencing the upstream canonical HH/SMO signaling and cross-talk oncogenic pathway, such as ERK and AKT signaling. The results also demonstrated that FL18 significantly downregulated GLI1 target genes such as Bcl-2, MMP2 and MMP9 and increased the expression of c-caspase3, c-PARP and Bax. These data suggest that FL18 may generate the anti-glioma activity by inhibition of GLI1.
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Acquired syphilis uveitis,due to lack of the characteristic features,presents with various types.The most common type is posterior uveitis and panuveitis,including chorioretinitis,retinal vasculitis,optic nerve retinitis.The diagnosis and assessment of response to treatment depends mainly on the serological diagnostic tests,including nontreponemal and treponemal test.Acquired syphilis uveitis often presents with manifestations similar to various types of uveitis,especially to autoimmune uveitis and other infectious uveitis,so differential diagnosis is important.The gold standard treatment for active syphilitic uveitis is penicillin G,or doxycycline if patient is allergy to penicillin.Clinically misdiagnosis and delayed treatment may result in irreversible visual impairment and severe systemic and eye complications.However such timely treatment always has a good prognosis.