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2.
Pharmacology ; : 1-8, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35526525

RESUMO

INTRODUCTION: Chemoresistance remains the main cause of treatment failure in cervical cancer and novel therapeutic strategies are required. Cobimetinib, a potent yet selective inhibitor of MEK1 and 2, is currently used to treat melanoma clinically. In this work, we identified cobimetinib as a promising candidate for treating cervical cancer. METHODS: The in vitro and in vivo efficacies of cobimetinib were examined using cervical cancer cell cultures and xenograft mouse model. Its combination with paclitaxel was analyzed using the combination index. Immunoblotting was performed on MAPK and ERK pathways. RESULTS: Cobimetinib displays a potent anti-cervical cancer activity in a panel of cell lines regardless of cellular origin and HPV presence, and its combination with paclitaxel is synergistic in inhibiting cervical cancer cells. This is achieved by the growth inhibition and caspase-dependent apoptosis induction, through inhibiting MAPK/ERK activation. In addition, paclitaxel activates ERK in cervical cancer cells, and this can be reversed by cobimetinib. We finally confirm the efficacy of cobimetinib alone and its combination with paclitaxel in the cervical cancer xenograft mouse model. DISCUSSION/CONCLUSION: Our preclinical findings will accelerate the initialization of clinical trials to use combination of cobimetinib and paclitaxel for treating cervical cancer. Our work also emphasizes the therapeutic value of targeting MAPK/ERK to overcome chemoresistance in cervical cancer.

3.
J Adv Res ; 37: 107-117, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35499056

RESUMO

Introduction: Leucine-rich repetitive kinase-2 (LRRK2) is a Parkinson's disease-related gene that also participates in many inflammatory diseases. However, the functional role of LRRK2 in cardiovascular disease is not clear. Objective: In this study, we aimed to elucidate the role of LRRK2 in cardiac remodelling under pressure overload. Methods: Aortic banding surgery was performed to induce cardiac remodelling in a LRRK2 knockout mouse model. A cardiomyocyte remodelling model was established by phenylephrine (PE) stimulation in neonatal rat cardiomyocytes. Results: LRRK2 was upregulated in remodelled mouse hearts and cardiomyocytes. Cardiac hypertrophy, fibrosis and dysfunction were ameliorated in LRRK2 knockout mice. LRRK2 silencing protected against the PE-induced cardiomyocyte hypertrophic response, while LRRK2 over-expression worsened the PE-induced hypertrophic response in cardiomyocytes. Decreased autophagy was observed in remodelled cardiomyocytes, whereas LRRK2 silencing increased autophagy levels and LRRK2 overexpression reduced autophagy levels. The autophagy inhibitors 3-MA, bafilomycin and chloroquine reversed the protective effects of LRRK2 deficiency. The autophagy activator rapamycin reversed the deleterious effects of LRRK2 overexpression. We found that LRRK2 inhibited Bcl-2 phosphorylation, thus decreasing the phosphorylation of Beclin1. The protective effects of LRRK2 knockout were partly counteracted by Beclin1(+/-) in vivo and Beclin1 silencing in vitro. We also observed an interaction between LRRK2 and Rab7, an autolysosome degradation-associated protein, which caused Rab7 downregulation. Rab7 knockdown almost completely reversed LRRK2 silencing-induced protection of cardiomyocytes. Conclusion: LRRK2 deficiency protected against cardiac remodelling under pressure overload by increasing Bcl-2/Beclin1 and Rab7-regulated autophagy levels in the heart.


Assuntos
Autofagia , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Remodelação Ventricular , Animais , Proteína Beclina-1/farmacologia , Leucina/farmacologia , Camundongos , Camundongos Knockout , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , Ratos
4.
Sheng Li Xue Bao ; 74(2): 246-254, 2022 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-35503072

RESUMO

Steroid receptor coactivators (SRCs) significantly increase the transcriptional activity of various steroid hormone receptors, and play an important regulatory role in a variety of physiological functions such as food intake, sleep, stress response and reproduction. Previous studies have found that pregnant mice carrying fetuses with SRC1/2 double-knockout (dKO) manifested delayed labor, partly due to the hypoplasia of fetal lungs and the decreased secretion of pulmonary surfactant protein-A (SP-A) and platelet activating factor (PAF). However, there is still a lack of systematic analysis of the changes in gene expression at the whole transcriptome level in the fetal lungs of SRC1/2 dKO mice. In this study, the SRC1KO, SRC2KO, SRC1/2 dKO and wild-type (WT) mouse fetal lung samples were collected at 18.5 days post coitus. The Illumina platform was employed for transcriptome mRNA sequencing, and then the differentially expressed genes (DEGs) were annotated and analyzed by GO and KEGG analysis. The results showed that the proportion of quality score of the sequencing data above Q30 in all samples was more than 92% and passed the quality control. Compared with WT fetal lungs, SRC1KO and SRC2KO fetal lungs had 61 and 32 DEGs, respectively; SRC1/2 dKO fetal lungs had 480, 11 and 901 DEGs compared with WT, SRC1KO and SRC2KO fetal lungs, respectively. Among these genes, Aspg, Crispld2, Eln, Ntsr2, Slc10a6 and Vgll3 were the unique DEGs of SRC1/2 dKO fetal lungs compared with other genotype mice. Real-time PCR and Western blotting verified the reliability of transcriptome sequencing results. The GO analysis of the DEGs between SRC1/2 dKO and WT mouse fetal lungs showed that the DEGs were significantly enriched in the extracellular space, extracellular region, and extracellular matrix in terms of cellular component. In the biological process, they were significantly enriched in the term of development of multiple organs. KEGG pathway analysis showed that the DEGs were mainly enriched in signaling pathways such as the complement system, extracellular matrix-receptor interactions, and protein digestion and absorption. In summary, this study comprehensively revealed the changes of gene expression in the fetal lungs of SRC1/2 dKO mice at the transcriptome level, which provides a new theoretical basis for the study of the developmental regulatory mechanism of the fetal lung during pregnancy, and the fetus-derived signals that affect the initiation of labor.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Animais , Feminino , Pulmão/fisiologia , Camundongos , Camundongos Knockout , Gravidez , Reprodutibilidade dos Testes
5.
Front Microbiol ; 13: 847167, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509308

RESUMO

Temperature changes have a great impact on fish feeding, intestinal microorganisms, metabolism, and immune function. Therefore, it is necessary to develop effective methods to enhance the survival rates and growth of fish under water temperature changes. Lactic acid bacteria (LAB) are promising immunostimulatory feed additive, as demonstrated by their beneficial effects in several fish species. This study investigated the short-term effects of dietary LAB on intestinal microbiota composition and immune responses of crucian carp (Carassius auratus) when water temperature decreased from 30 ± 1°C to 18 ± 1°C. Lactococcus (L.) lactis 1,209 and L. lactis 1,242 with potential probiotics isolated from the intestine of Qinghai naked carp (Gymnocypris przewalskii) were selected as feed additives for the crucian carp feeding experiment. A total of 225 commercially available healthy crucian carp (250 ± 10 g) of similar age were kept in 30°C water for a week and then immediately transferred to 18 ± 1°C water, assigned to three dietary treatments for a 16-day feeding trial randomly: (1) HC, diets without additives (the control group); (2) HT, diets with 106 CFU/ml L. lactis 1,209; and (3) HL, with 106 CFU/ml L. lactis 1,242. Each group was set up with 3 replicates and each with 25 fish. The results showed that the mortality rate of crucian carp in HC, HT, and HL group was 50, 27, and 33%, respectively. High-throughput sequencing results displayed that the composition of the intestinal microorganism varied dynamically in response to different treatments and water temperature decrease. Among them, compared with the HC group, a higher abundance of Firmicutes and Proteobacteria, and a lower of Actinobacteria appeared in HT and HL. The cytokines heat shock protein 70 (HSP-70) in crucian carp intestinal tract significantly decreased when water temperature decreased (p < 0.05).

6.
Sci China Life Sci ; 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35524910

RESUMO

Autologous fat-derived stromal vascular fraction (SVF) is a mixed cell population that has been used for many years in regenerative plastic surgery. In terms of animal and clinical research, this concise review was performed to evaluate the efficacy of SVF in knee degenerative joint disease (KDJD), which could cause pain, disability and severely affect patients' lives. Thirteen studies retrieved and screened from the databases were included, including six animal studies and seven clinical trials. The meta-analysis of clinical research shows that intra-articular injection of SVF, in combination with adjuvant surgery, could alleviate pain and improve early functional recovery for patients with KDJD at Kellgren-Lawrence (KL) grades II-III.

7.
Clin Cancer Res ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35552673

RESUMO

PURPOSE: To conduct an updated exploratory analysis of overall survival (OS) with a longer median follow-up of 73.3 months and evaluate the prognostic value of molecular analysis by circulating tumor DNA (ctDNA). PATIENTS AND METHODS: Patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) were randomized 2:1 to receive palbociclib (125 mg orally/d; 3/1 week schedule) and fulvestrant (500 mg intramuscularly) or placebo and fulvestrant. This OS analysis was performed when 75% of enrolled patients died (393 events in 521 randomized patients). ctDNA analysis was performed among patients who provided consent. RESULTS: At the data cutoff (August 17, 2020), 258 and 135 deaths occurred in the palbociclib and placebo groups, respectively. The median OS (95% CI) was 34.8 months (28.8-39.9) in the palbociclib group and 28.0 months (23.5-33.8) in the placebo group (stratified hazard ratio 0.81; 95% CI, 0.65-0.99). The 6-year OS rate (95% CI) was 19.1% (14.9-23.7) and 12.9% (8.0-19.1) in the palbociclib and placebo groups, respectively. Favorable OS with palbociclib plus fulvestrant compared with placebo plus fulvestrant was observed in most subgroups, particularly in patients with endocrine-sensitive disease, no prior chemotherapy for ABC, low circulating tumor fraction, and regardless of ESR1, PIK3CA, or TP53 mutation status. No new safety signals were identified. CONCLUSIONS: The clinically meaningful improvement in OS associated with palbociclib plus fulvestrant was maintained with >6 years of follow-up in patients with HR+/HER2- ABC, supporting palbociclib plus fulvestrant as a standard of care in these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifer: NCT01942135.

8.
Sci Adv ; 8(18): eabo0375, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35507666

RESUMO

The real-time, in-line analysis of light polarization is critical in optical networks, currently suffering from complex systems with numerous bulky opto-electro-mechanical elements tandemly arranged along the optical path. Here, we design and fabricate a fiber-integrated polarimeter by vertically stacking three photodetection units based on six-layer van der Waals materials, including one bismuth selenide (Bi2Se3) layer for power calibration, two twisted black phosphorus (BP) layers for polarization detection, and three hexagonal boron nitride (hBN) layers for encapsulation. The self-power-calibrated, self-driven, and unambiguous detection of both linearly polarized (LP) and circularly polarized (CP) light is realized by the broken symmetry-induced linear photogalvanic effects (LPGEs) and circular photogalvanic effects (CPGEs) in the two BP units. Moreover, the device enables single-pixel polarimetric imaging to acquire spatial polarization information. The ultracompact device structure, free from external optical and mechanical modules, may inspire the development of miniaturized optical and optoelectronic systems.

9.
Trials ; 23(1): 387, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35549757

RESUMO

BACKGROUND: Acute gouty arthritis (AGA) is an inflammatory arthritis clinically characterized by severe pain, swelling, and restricted movement of joints, which may cause physical disability and decrease quality of life. The use of recommended first-line treatment agents for AGA may be limited by adverse events. There has been a traditional use of alternative therapies for AGA. Tibetan medicine Qingpeng ointment is one of the on-market herbal products used for symptom relief of AGA. Previous clinical studies indicated that Qingpeng ointment can relieve pain, swelling, redness, and dysfunction of joints in patients with AGA. However, there is no rigorous randomized trial to demonstrate its benefit for AGA. In order to evaluate the efficacy and safety of Qingpeng ointment for AGA, we designed a randomized controlled trial. METHODS: This study is designed as a multi-center, randomized, double-blind, placebo-controlled trial. Two hundred and six adults with acute flare of gout, and visual analogue scale (VAS) score of joint pain ≥ 3 points will be recruited. Participants will be randomly assigned to herbal treatment or placebo group at a ratio of 1:1. Qingpeng ointment, or equal placebo ointment, will be applied topically at involved joints twice a day for consecutive 7 days. Patients in both groups would be allowed giving diclofenac sodium sustained-release tablets as rescue therapy when VAS score of joint pain ≥ 7 points during the treatment. The primary outcomes will be joint pain measured by VAS score, and joint swelling measured using width and thickness of affected joints and VAS score. Other outcome measures will be joint mobility, joint redness, C-reactive protein, serum uric acid, and the use of rescue medicine as well as adverse effect. DISCUSSION: To the best of our knowledge, this study is the first multi-center, randomized, double-blind, and placebo-controlled clinical trial to assess the efficacy of Tibetan medicine Qingpeng ointment for AGA. The findings of this study would provide evidence for its use to relieve symptoms of AGA. TRIAL REGISTRATION: ISRCTN ISRCTN34355813 . Registered on 25 January 2021.

10.
Front Psychiatry ; 13: 839630, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573375

RESUMO

Objectives: Both bullying and psychosis-like experiences (PLEs) have gained much attention in recent years, but their interactions are not fully unraveled. The aim of the current study was to validate the Chinese version of Bullying Scale for Adults (C-BSA), and to investigate whether past bullying experiences independently predict the presence of PLEs in university students. Methods: The validity and reliability of the C-BSA were determined in two independent samples. A battery of psychological inventories was also administered to assess the presence of PLEs, maltreatment history in the family, and current depression and anxiety, including the 15-item positive subscale of the community assessment of psychic experiences (CAPE-p15), the Chinese version of the Childhood Trauma Questionnaire (CTQ), Self-Rating Depression Scale (SDS), and Self-Rating Anxiety Scale (SAS). Results: In the construction sample (N = 629), a Cronbach's α of 0.921 indicated a good internal consistency of C-BSA. The exploratory factor analysis (EFA) yielded a four-factor model and a three-factor model, and both were verified by using the confirmatory factorial analysis (CFA) in the validation sample (N = 629). The total scores of C-BSA were significantly correlated with that of CTQ, CAPE-p15, SDS, and SAS. Multivariate logistic regression revealed that bullying was associated with 2.0 or 3.7 times of risk for the presence of PLEs (numbers of bullying types < = 3 or > 3, respectively) after controlling for CTQ, SDS, and SAS scores. Conclusions: C-BSA has shown good psychometric properties in college students. The contribution of past bullying experiences to the present PLEs seems to be independent of other childhood trauma, current depression, and anxiety.

11.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35560756

RESUMO

The endo-lysosomal pathway plays an important role in pathogen clearance and both bacteria and viruses have evolved complex mechanisms to evade this host system. Here, we describe a novel aspect of coronaviral infection, whereby the master transcriptional regulator of lysosome biogenesis - TFEB - is targeted for proteasomal-mediated degradation upon viral infection. Through mass spectrometry analysis and an unbiased siRNA screen, we identify that TFEB protein stability is coordinately regulated by the E3 ubiquitin ligase subunit DCAF7 and the PAK2 kinase. In particular, viral infection triggers marked PAK2 activation, which in turn, phosphorylates and primes TFEB for ubiquitin-mediated protein degradation. Deletion of either DCAF7 or PAK2 blocks viral-mediated TFEB degradation and protects against viral-induced cytopathic effects. We further derive a series of small molecules that interfere with the DCAF7-TFEB interaction. These agents inhibit viral-triggered TFEB degradation and demonstrate broad anti-viral activities including attenuating in vivo SARS-CoV-2 infection. Together, these results delineate a viral-triggered pathway that disables the endogenous cellular system that maintains lysosomal function and suggest that small molecule inhibitors of the E3 ubiquitin ligase DCAF7 represent a novel class of endo-lysosomal, host-directed, anti-viral therapies.

12.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(2): 221-226, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35538756

RESUMO

Objective To investigate the rate and correlates of receiving human immunodeficiency virus(HIV) serostatus disclosure from their most recent male sexual partners among men who have sex with men(MSM) aged 50 and above. Methods With a geosocial networking application,we recruited participants through online convenience sampling to collect the demographic variables,behavioral information,receiving HIV serostatus disclosure,etc.Univariate and multivariate analyses were performed to interpret the associated factors of receiving HIV serostatus disclosure. Results Overall,38.4%(398/1037) of participants received HIV serostatus disclosure from their most recent male sexual partners.The multivariable analysis demonstrated that the following populations were less likely to receive HIV serostatus disclosure from their most recent male sexual partners:participants with junior high school degree or below(OR=0.660,95%CI=0.473-0.922, P=0.015) compared to those with senior high school degree or above;participants unemployed(OR=0.537,95%CI=0.322-0.896, P=0.017) and employed(OR=0.663,95%CI=0.466-0.944, P=0.022) compared to those retired;participants without knowledge about HIV or acquired immune deficiency syndrome(AIDS) compared to those with knowledge about HIV/AIDS(OR=0.636,95%CI=0.466-0.868, P=0.004);participants having ≥2 male sexual partners in the last year(OR=0.433,95%CI=0.320-0.586, P<0.001) compared to those having none or one male sexual partner;participants never been tested for HIV(OR=0.544,95%CI=0.403-0.734, P<0.001) compared to those ever been tested for HIV;participants ever been diagnosed to have sexually transmitted infection(STI)(OR=0.472,95%CI=0.349-0.637, P<0.001) compared to those never diagnosed to have STI;and participants with higher level of HIV stigma(OR=0.742,95%CI=0.604-0.912, P=0.005). Conclusions Our findings indicated that the MSM aged 50 and above had low possibility of receiving HIV serostatus disclosure from the most recent male sexual partners.Education,employment status,number of sexual partners,HIV/AIDS-related knowledge,HIV testing behaviors,STI infection history,and HIV stigma contributed to this result.

14.
Acta Pharm Sin B ; 12(3): 1213-1224, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35530143

RESUMO

Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide, but the molecular basis underlying its development remains unclear. An accumulating body of evidence supports gasdermin D (GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases. However, there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis. In this work, we investigated the role of GSDMD-mediated pyroptosis in silicosis. Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression. Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica. Measurement of interleukin-1ß release, lactic dehydrogenase activity, and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages. Additionally, we verified that both canonical (caspase-1-mediated) and non-canonical (caspase-4/5/11-mediated) signaling pathways mediated silica-induced pyroptosis activation, in vivo and in vitro. Notably, Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes, which highlighted the pivotal role of pyroptosis in this disease. Taken together, our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.

15.
Acta Pharm Sin B ; 12(3): 1126-1147, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35530145

RESUMO

Autoimmune or infectious diseases often instigate the undesirable damages to tissues or organs to trigger immune-related diseases, which involve plenty of immune cells, pathogens and autoantibodies. Nanomedicine has a great potential in modulating immune system. Particularly, biomimetic nanomodulators can be designed for prevention, diagnosis and therapy to achieve a better targeted immunotherapy. With the development of materials science and bioengineering, a wide range of membrane-coated nanomodulators are available. Herein, we summarize recent advancements of bioinspired membrane-coated nanoplatform for systemic protection against immune-related diseases including autoimmune and infectious diseases. We also rethink the challenges or limitations in the progress of the therapeutic nanoplatform, and discuss the further application of the nanomodulators in the view of translational medicine for combating immune-related diseases.

16.
Front Cell Infect Microbiol ; 12: 824597, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35531334

RESUMO

Aim: To investigate the treating effect of Yiqi-Bushen-Tiaozhi (YBT) recipe on nonalcoholic steatohepatitis (NASH) mice, determine whether the outcome was associated with gut microbiota, and clarify the regulating mechanism. Methods: NASH mice were induced by high-fat and high-fructose diets (HFFD). In the fifth week, mice in the YBT group were orally administrated YBT (22.12g·kg-1·d-1) daily for 12 weeks. Fresh stool of mice was collected at the 16th week for fecal 16S rDNA analysis. Hepatic pathology and biochemical indicators were used to reflect the improvement of YBT on hepatic inflammation and lipid metabolism in NASH mice. Quantitative real-time PCR (qRT-PCR) was used to verify the results of PICRUSt analysis. Results: Results of the pathological and biochemical index showed that YBT could improve NASH mice. Compared with improving inflammation and hepatocyte damage, YBT may be more focused on enhancing metabolic disorders in mice, such as increasing HDL-c level. The diversity and richness of the gut microbiota of NASH mice induced by HFFD are significantly different from the normal control (NC) group. After YBT treatment, the diversity and richness of the mice microbiota will be increased to similar NC mice. Intestinimonas, Acetatifactor, Alistipes, Intestinimonas, Acetatifactor, and Alistipes have the most significant changes in the class level. PICRUSt analysis was performed to predict genomic functions based on the 16S rDNA results and reference sequencing. The efficacy of YBT in the treatment of NASH can be achieved by regulating the diversity and richness of gut microbiota. PICRUSt analysis results showed that the most relevant function of the microbiota construction variations is α- Linolenic acid (ALA) metabolism. Results of qRT-PCR showed significant differences between groups in the expression of Fatty acid desaturase 1 (FADS1), Fatty acid desaturase 2 (FADS2), Acyl-CoA Oxidase 1 (ACOX1), and Acyl-CoA Oxidase 2 (ACOX2) related to ALA metabolism. The expression of the above genes will be inhibited in the liver and small intestine of the HFFD group mice, and the expression can be restored after YBT treatment. Conclusion: YBT could treat NASH mice by improving the diversity and richness of gut microbiota and further the improvement of ALA metabolism.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Acil-CoA Oxidase/metabolismo , Animais , DNA Ribossômico , Dieta , Ácidos Graxos Dessaturases , Frutose/efeitos adversos , Frutose/metabolismo , Microbioma Gastrointestinal/fisiologia , Inflamação/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo
17.
Zhongguo Zhong Yao Za Zhi ; 47(9): 2480-2490, 2022 May.
Artigo em Chinês | MEDLINE | ID: mdl-35531704

RESUMO

The fingerprint of Boenninghausenia albiflora var. albiflora was established by ultra performance liquid chromatography(UPLC), and the content of 12 active components including chlorogenic acid was determined. Multivariate statistical analysis was used to explore the indicator components of B. albiflora var. albiflora and a comprehensive evaluation system was created for the quality of B. albiflora var. albiflora. In this study, 33 batches of B. albiflora var. albiflora with different sources were collected and studied, and the UPLC fingerprint of B. albiflora var. albiflora was developed. There were 37 common peaks, of which 12 components were identified, and the content of these 12 components was measured. In combination of the common peaks and the content of chemical components, multivariate statistical analysis was performed, and the results showed that 6 components [daphnoretin, isoimperatorin, astragalin, imperatorin, neochlorogenic acid, and isoquercitrin(weight coefficient>0.1)] were selected as chemical markers for the quality of B. albiflora var. albiflora. Technique for order of preference by similarity to ideal solution(TOPSIS) analysis and chemometrics revealed that the quality of S32, S28 and S29 were superior, while that of S12, S7 and S16 were inferior. The quality evaluation method of B. albiflora var. albiflora constructed in this study was accurate and reliable, with simpleness and easiness to operate. It is suggested that the 6 above-mentioned active components could be used as indicator components for quality control of B. albiflora var. al-biflora. The samples were harvested during the flowering and fruiting period, which is from the beginning of July to the end of August.


Assuntos
Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Medicamentos de Ervas Chinesas/química , Análise Multivariada , Controle de Qualidade
18.
Chemosphere ; 302: 134864, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35537633

RESUMO

The harm caused by indoor dust has received increasing attention in recent years. However, current studies have ignored comparisons with the corresponding outdoor dust. This study aimed to investigate the distribution of heavy metals in indoor and corresponding outdoor dust and the ecological and health risks they pose in Hefei, Central China. We analyzed O/I (outdoor/indoor concentration ratios) values, background comparison, and correlation analysis (heavy metal concentrations vs. particle size) and found that Cu, Zn, and Cd mainly existed in indoor sources, while V, Co, and As mainly existed in outdoor sources, and both family sizes and floor number influenced the variation of O/I. Through a new potential ecological risk assessment method, we determined that Cd risk levels in indoor and outdoor dust were extreme and high to extreme, respectively. Additionally, the carcinogenic risks of Ni, As, and Cr were not negligible. The risk of indoor dust was higher than that of outdoor dust for the heavy metals studied, implying a poor indoor environment. Notably, indoor dust from families with smaller sizes, lower floors, and smokers had higher ecological and carcinogenic risks.

19.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(4): 431-442, 2022 Apr 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35545338

RESUMO

OBJECTIVES: There are clinical reports of nerve injury caused by ropivacaine. The mechanism for nerve injury induced by ropivacaine has not been fully clarified. This study aims to investigate the changes of pain threshold and L3 spinal cord genomics at 6 h and 24 h after intrathecal injection of 0.5% and 1.0% ropivacaine, and to explore the underlying mechanisms for nerve injury caused by ropivacaine. METHODS: A total of 30 male Sprague Dawley rats weighing 220-260 g were successfully implanted with microspinal catheter. The rats were randomly divided into 5 groups (each n=6): a control group (given saline), a ropivacaine group 1 and a ropivacaine group 2 (both given 1% ropivacaine), a ropivacaine group 3 and a ropivacaine group 4 (both given 0.5% ropivacaine). The rats received continuous intrathecal injection of corresponding drugs at 8.3 µL/h for 24 h via an implanted intrathecal catheter followed by 24 h-pause of injection for the ropivacaine group 2, the ropivacaine group 4 and the control group, 6 h-pause of injection for the ropivacaine group 1 and the ropivacaine group 3. For each group, the observation of behavioral change and the paw withdrawal mechanical threshold (PWMT) was conducted immediately after the injection and again after the pause of injection. After the PWMT observation, the rats were dissected to acquire L3 spinal cords. Illumina sequencing was applied to construct gene libraries. Then the statistical methods were used to find out differentially expressed genes between the groups. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis were conducted for those genes. Real-time RT-PCR was used to determine different expressions of some of those genes. RESULTS: Compared with control group, the PWMT got higher in the ropivacaine group 1-4 and was positively correlated with concentration, negatively correlated with discontinuation duration. Compared with control group, the ropivacaine group 1 had 488 differentially expressed genes, of which 456 were up-regulated and 32 were down-regulated; the ropivacaine group 2 had 1 194 differentially expressed genes, of which 1 092 were up-regulated and 102 were down-regulated; the ropivacaine group 3 had 518 differentially expressed genes, of which 384 were up-regulated and 134 were down-regulated; and the ropivacaine group 4 had 68 differentially expressed genes, of which 46 were up-regulated and 22 were down-regulated. GO enrichment analysis and KEGG signaling pathway analysis showed that most of these differentially expressed genes were related to signaling pathways of inflammatory response. CONCLUSIONS: After intrathecal injection of 0.5% ropivacaine and 1.0% ropivacaine for 24 h, the differentially expressed genes in L3 spinal cord of rats are mainly related to signaling pathways of inflammatory response.


Assuntos
Genômica , Medula Espinal , Animais , Injeções Espinhais , Masculino , Ratos , Ratos Sprague-Dawley , Ropivacaina , Medula Espinal/metabolismo
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