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1.
Comput Vis Media (Beijing) ; 8(1): 149-163, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34721936

RESUMO

Stable label movement and smooth label trajectory are critical for effective information understanding. Sudden label changes cannot be avoided by whatever forced directed methods due to the unreliability of resultant force or global optimization methods due to the complex trade-off on the different aspects. To solve this problem, we proposed a hybrid optimization method by taking advantages of the merits of both approaches. We first detect the spatial-temporal intersection regions from whole trajectories of the features, and initialize the layout by optimization in decreasing order by the number of the involved features. The label movements between the spatial-temporal intersection regions are determined by force directed methods. To cope with some features with high speed relative to neighbors, we introduced a force from future, called temporal force, so that the labels of related features can elude ahead of time and retain smooth movements. We also proposed a strategy by optimizing the label layout to predict the trajectories of features so that such global optimization method can be applied to streaming data. Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s41095-021-0231-y.

2.
Front Pharmacol ; 12: 746964, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721036

RESUMO

Acute lung injury (ALI) is a common life-threatening lung disease, which is mostly associated with severe inflammatory responses and oxidative stress. Tanreqing injection (TRQ), a Chinese patent medicine, is clinically used for respiratory-related diseases. However, the effects and action mechanism of TRQ on ALI are still unclear. Recently, STING as a cytoplasmic DNA sensor has been found to be related to the progress of ALI. Here, we showed that TRQ significantly inhibited LPS-induced lung histological change, lung edema, and inflammatory cell infiltration. Moreover, TRQ markedly reduced inflammatory mediators release (TNF-α, IL-6, IL-1ß, and IFN-ß). Furthermore, TRQ also alleviated oxidative stress, manifested by increased SOD and GSH activities and decreased 4-HNE, MDA, LDH, and ROS activities. In addition, we further found that TRQ significantly prevented cGAS, STING, P-TBK, P-P65, P-IRF3, and P-IκBα expression in ALI mice. And we also confirmed that TRQ could inhibit mtDNA release and suppress signaling pathway mediated by STING in vitro. Importantly, the addition of STING agonist DMXAA dramatically abolished the protective effects of TRQ. Taken together, this study indicated that TRQ alleviated LPS-induced ALI and inhibited inflammatory responses and oxidative stress through STING signaling pathway.

3.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(10): 1008-1014, 2021 Oct 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34719415

RESUMO

OBJECTIVES: To study the effect of the course of treatment with broad-spectrum antibiotics on intestinal flora and short-chain fatty acids (SCFAs) in feces of very low birth weight (VLBW) infants. METHODS: A total of 29 VLBW infants who were admitted to the Neonatal Diagnosis and Treatment Center of Children's Hospital Affiliated to Chongqing Medical University from June to December 2020 were enrolled as subjects for this prospective study. According to the course of treatment with broad-spectrum antibiotics, they were divided into two groups: ≤7 days (n=9) and >7 days (n=20). Fecal samples were collected on days 14 and 28 of hospitalization, and 16S rDNA high-throughput sequencing and gas chromatography-mass spectrometry were used to analyze the flora and SCFAs in fecal samples. RESULTS: There was a significant reduction in Chao index of the intestinal flora in the ≤7 days group and the >7 days group from week 2 to week 4 (P<0.05). In the ≤7 days group, there were significant increases in the proportions of Firmicutes and Clostridium_sensu_stricto_1 and a significant reduction in the proportion of Proteobacteria from week 2 to week 4 (P<0.05). At week 4, compared with the ≤7 days group, the >7 days group had significant reductions in the proportions of Firmicutes and Clostridium_sensu_stricto_1 and a significant increase in the proportion of Proteobacteria (P<0.05), as well as significant reductions in the content of isobutyric acid and valeric acid (P<0.05). CONCLUSIONS: The course of treatment with broad-spectrum antibiotics can affect the abundance, colonization, and evolution of intestinal flora and the content of their metabolites SCFAs in VLBW infants. The indication and treatment course for broad-spectrum antibiotics should be strictly controlled in clinical practice.


Assuntos
Microbioma Gastrointestinal , Antibacterianos , Criança , Ácidos Graxos Voláteis , Fezes , Humanos , Lactente , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Estudos Prospectivos
4.
Mikrochim Acta ; 188(11): 401, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34729650

RESUMO

The Ti3C2 MXene quantum dots (Ti3C2 MQDs) derived from Ti3C2 MXene have received much attention because of their remarkable advantages in biosensing. Nevertheless, the functionalization of Ti3C2 MQDs to improve their properties is just in its infant stage. Herein, we firstly synthesized nitrogen and boron co-doped Ti3C2 MQDs (N, B-Ti3C2 MQDs) with good water solubility, strong stability, and high optical characteristics. The N, B-Ti3C2 MQDs exhibit excitation wavelength-dependent blue photoluminescence with optimal excitation/emission peaks at 335/439 nm. Nowadays, the development of fast and real-time detection of tetracycline (TC) in animal derived food is very essential. In this work, a novel point-of-care testing (POCT) platform was established based on ratiometric fluorescence method using N, B-Ti3C2 MQDs coupled with Eu3+. Upon addition of TC in the Eu3+/N, B-MQDs system, blue fluorescence emission of N, B-Ti3C2 MQDs was quenched and red fluorescence emission of Eu3+ was enhanced gradually, which was ascribed to the synergistic inner filter effect and antenna effect. Moreover, we prepared test papers with N, B-Ti3C2 MQDs and Eu3+ for TC detection based on the change of fluorescence color, which could be recognized by color recognizer app installed in the smartphone. Therefore, great promise for POCT of TC is given with the merits of simplicity and visible detection possibility. The proposed method demonstrated a low detection limit of 20 nM. Application of the platform for TC quantification in milk samples opened a novel means for the potential use of N, B-Ti3C2 MQDs in food safety.

5.
Hepatology ; 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34735734

RESUMO

BACKGROUND & AIMS: Hepatic ischemia reperfusion (HIR) injury, a common clinical complication of liver transplantation and resection, affects patient prognosis. RNF5 is an E3 ubiquitin ligase that plays important roles in endoplasmic reticulum stress, unfolded protein reactions, and inflammatory responses; however, its role in HIR is unclear. APPROACH & RESULTS: RNF5 expression was significantly downregulated during HIR in mice and hepatocytes. Subsequently, RNF5 knockdown and overexpression cell lines were subjected to hypoxia-reoxygenation challenge. The results shown that RNF5 knockdown significantly increased hepatocyte inflammation and apoptosis, while RNF5 overexpression had the opposite effect. Furthermore, hepatocyte-specific RNF5 knockout and transgenic mice were established and subjected to HIR, and RNF5 deficiency markedly aggravated liver damage, cell apoptosis, and activated hepatic inflammatory responses. While hepatic RNF5 transgenic mice had the opposite effect compared with RNF5 knockout mice. Mechanistically, RNF5 interacted with PGAM5 and mediated the degradation of PGAM5 through K48-linked ubiquitination, thereby inhibiting the activation of ASK1 and its downstream JNK/p38. This eventually suppresses the inflammatory response and cell apoptosis in HIR. CONCLUSION: We revealed that RNF5 protected against HIR via its interaction with PGAM5 to inhibit the activation of ASK1 and the downstream JNK/p38 signaling cascade. Our findings indicate that the RNF5-PGAM5 axis may be a promising therapeutic target for HIR.

6.
Infect Agent Cancer ; 16(1): 63, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34743754

RESUMO

BACKGROUND: Gastric cancer (GC) is the second leading cause of cancer-related deaths. Because it is hard to diagnose at early stage, the overall 5 years survival rate is lower than 25%. High migration is the main hallmark of malignant cells at advanced stage of GC. Thus, it is urgent to find biomarkers for early diagnosis and more effective therapy of GC. METHODS: In this study, lentivirus-mediated silencing and overexpression lentiviruses targeting the ubiquitin-conjugating enzyme E2 D1 (UBE2D1), transwell, wound healing, and pulmonary metastasis mouse model were applied to analyze the function of UBE2D1 in vitro and in vivo. Real-time PCR and immunohistochemistry were used to elucidate the level of UBE2D1 in GC samples. RESULTS: Silencing of UBE2D1 inhibited cell migration and the levels of epithelial-mesenchymal transition makers (MMP2 and MMP9) in AGS and MKN45 cells. Silencing of UBE2D1 inhibited cell metastasis in mouse model. On the contrary, UBE2D1 overexpression increased cell migration and the levels of MMP2 and MMP9 in MGC-803 cells. Further, silencing of UBE2D1 decreased the ubiquitination level of mothers against decapentaplegic homolog 4 (SMAD4), and the increase of cell migration induced by UBE2D1 overexpression could be reversed by SMAD4. CONCLUSION: Silencing of UBE2D1 inhibited cell migration through transforming growth factor ß (TGF-ß)/SMAD4 signaling pathway in GC.

7.
Chem Biol Interact ; 351: 109744, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34774545

RESUMO

Remdesivir, an intravenous nucleotide prodrug, has been approved for treating COVID-19 in hospitalized adults and pediatric patients. Upon administration, remdesivir can be readily hydrolyzed to form its active form GS-441524, while the cleavage of the carboxylic ester into GS-704277 is the first step for remdesivir activation. This study aims to assign the key enzymes responsible for remdesivir hydrolysis in humans, as well as to investigate the kinetics of remdesivir hydrolysis in various enzyme sources. The results showed that remdesivir could be hydrolyzed to form GS-704277 in human plasma and the microsomes from human liver (HLMs), lung (HLuMs) and kidney (HKMs), while the hydrolytic rate of remdesivir in HLMs was the fastest. Chemical inhibition and reaction phenotyping assays suggested that human carboxylesterase 1 (hCES1A) played a predominant role in remdesivir hydrolysis, while cathepsin A (CTSA), acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) contributed to a lesser extent. Enzymatic kinetic analyses demonstrated that remdesivir hydrolysis in hCES1A (SHUTCM) and HLMs showed similar kinetic plots and much closed Km values to each other. Meanwhile, GS-704277 formation rates were strongly correlated with the CES1A activities in HLM samples from different individual donors. Further investigation revealed that simvastatin (a therapeutic agent for adjuvant treating COVID-19) strongly inhibited remdesivir hydrolysis in both recombinant hCES1A and HLMs. Collectively, our findings reveal that hCES1A plays a predominant role in remdesivir hydrolysis in humans, which are very helpful for predicting inter-individual variability in response to remdesivir and for guiding the rational use of this anti-COVID-19 agent in clinical settings.

8.
Bioresour Technol ; : 126299, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34748976

RESUMO

2,5-Bis(hydroxymethyl)furan (BHMF) is one kind of important upgraded derivatives of biobased 5-hydroxymethylfuran (5-HMF). This study verified the feasibility of one-pot chemoenzymatic conversion of biobased D-fructose to BHMF by cascade catalysis with deep eutectic solvent Lactic acid:Betaine (LA:B) and reductase biocatalyst in LA:B - H2O. Using D-fructose (36.0 g/L) as feedstock, the yield of 5-HMF reached 91.6% in DES LA:B - H2O (15:85, v:v) at 150 °C for 1.5 h. Using D-fructose (2 mol D-fructose/mol 5-HMF) as cosubstrate, commercial 5-HMF (125 mM) was converted into BHMF at 90.7% yield by whole-cells of Pseudomonas putida S12 within 24 h at 30 °C and pH 8.0. In addition, Pseudomonas Putida S12 could efficiently transform D-fructose-valorized 5-HMF into BHMF [98.4% yield, based on 5-HMF; 90.1% yield, based on substrate D-fructose] in DES LA:B - H2O. An efficient chemoenzymatic valorization of D-fructose to BHMF was developed in a benign reaction system.

9.
Bioresour Technol ; : 126376, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34801722

RESUMO

Chemoenzymatic cascade catalysis using deep eutectic solvent-silica heterogeneous catalyst and reductase biocatalyst was constructed for synthesizing furfuryl alcohol from biomass in one-pot manner. A novel heterogeneous catalyst B:LA-SG(SiO2) was firstly prepared by immobilizing deep eutectic solvent Betaine:Lactic acid on silica with sol-gel method using tetraethyl orthosilicate as silicon source. High furfural yield (45.3%) was achieved from corncob with B:LA-SG(SiO2) catalyst (2.5 wt%) in water at 170 ˚C for 0.5 h. Possible catalytic mechanism for converting biomass into furfural was proposed. Moreover, one newly constructed recombinant E. coli KF2021 cells containing formate dehydrogenase and reductase was utilized to transform corncob-valorized furfural into furfuralcohol at 97.7% yield at pH 7.5 and 40 ˚C via HCOONa-driven coenzyme regeneration. Such a hybrid process was constructed for tandem chemocatalysis and biocatalysis in a same reactor, potentially reducing the operation cost, which had potential application for valorization of biomass to value-added furans.

10.
Bioorg Chem ; 117: 105449, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34736136

RESUMO

Lung cancer is one of the most malignant tumors with the highest mortality and morbidity. The tubers of Bletilla striata are known as "an excellent medicine for lung diseases" in traditional Chinese medicine. This study performed a targeted study to explore compounds with anti-lung cancer activity and the molecular mechanisms using A549 cells. Eighteen bibenzyl derivatives, including four new compounds (13, 14, 16, and 18), were isolated from the tubers of B. striata. Analysis of the structure-activity relationship indicated that the cytotoxicity of the bibenzyls against A549 cells increased gradually as the number of the benzyl groups in the structures increased. Bletillain (18), an unusual benzyl polymer, was found to be the most active compound. Further flow cytometric analysis, dual-luciferase assays, real-time PCR assays, and western blot assays revealed that bletillain induced autophagy in A549 cells by regulating the Akt/GSK-3ß/ß-catenin signaling pathway. Beclin 1, LC3, and p62 are downstream autophagy factors of Akt, and Beclin 1 was the key autophagy factor. These results suggested that bibenzyls of B. striata play important roles in the treatment of lung cancer and provided scientific evidence illustrating why the tubers of B. striata are a suitable medicine for the treatment of lung cancer in traditional Chinese medicine.

11.
Phytomedicine ; 94: 153849, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34775360

RESUMO

BACKGROUND: Pyroptosis is a pro-inflammatory cell death characterized by the formation of inflammasomes. Abnormal inflammation in brain microvascular endothelial cells (BMECs) has been correlated with ischemic stroke. Protocatechuic aldehyde (PCA) is a hydrophilic phenolic acid derived from the traditional Chinese herb Salvia miltiorrhiza with significant anti-inflammatory effects. However, the mechanism of PCA on BMEC pyroptosis under ischemic injury has been largely unexplored. PURPOSE: We aimed to study the effects and mechanism of PCA on BMEC pyroptosis under ischemic injury. METHODS: Sprague-Dawley (SD) rats were injected through the tail vein with different concentrations of PCA after transient middle cerebral artery occlusion (MCAO) was performed. The protective effects of PCA in SD rats were examined via neurological scores, infarct volume evaluation, and anti-pyroptosis effects using immunofluorescence staining and western blot. Rat BMECs (rBMECs) were treated with different concentrations of PCA after oxygen and glucose deprivation (OGD). The ability of PCA to protect rBMECs was examined via cell viability, anti-oxidative activity, and anti-pyroptosis effects as determined by qRT-PCR and western blot. Additionally, the role of lncRNA Xist in anti-pyroptosis responses of PCA-treated rBMECs was validated with lncRNA Xist siRNA. RESULTS: We found that treatment with MCAO and OGD increased the expression of NOD-like receptor protein 3, gasdermin D, Caspase-1, interleukin-1ß, and NIMA-related kinase 7, which was reversed by treatment with PCA or MCC950 (a pyroptosis inhibitor). In addition, PCA reduced the cerebral infarct volume in MCAO rats and promoted cell survival and proliferation in OGD/reperfusion-treated rBMECs. PCA enhanced the antioxidant activity and mitochondrial membrane potential in rBMECs. PCA also enhanced lncRNA Xist expression, and when the expression of lncRNA Xist was silenced, PCA could not alleviate pyroptosis well in rBMECs. CONCLUSION: Protocatechuic aldehyde prevents ischemic injury by attenuating rBMEC pyroptosis via lncRNA Xist.

12.
J Healthc Eng ; 2021: 6076135, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795882

RESUMO

Objective: To investigate the application value of a deep convolutional neural network (CNN) model for cytological assessment of thyroid nodules. Methods: 117 patients with thyroid nodules who underwent thyroid cytology examination in the Affiliated People's Hospital of Ningbo University between January 2017 and December 2019 were included in this study. 100 papillary thyroid cancer samples and 100 nonmalignant samples were collected respectively. The sample images were translated vertically and horizontally. Thus, 900 images were separately created in the vertical and horizontal directions. The sample images were randomly divided into training samples (n = 1260) and test samples (n = 540) at the ratio of 7 : 3 per the training sample to test sample. According to the training samples, the pretrained deep convolutional neural network architecture Resnet50 was trained and fine-tuned. A convolutional neural network-based computer-aided detection (CNN-CAD) system was constructed to perform full-length scan of the test sample slices. The ability of CNN-CAD to screen malignant tumors was analyzed using the threshold setting method. Eighty pathological images were collected from patients who received treatment between January 2020 and May 2020 and used to verify the value of CNN in the screening of malignant thyroid nodules as verification set. Results: With the number of iterations increasing, the training and verification loss of CNN model gradually decreased and tended to be stable, and the training and verification accuracy of CNN model gradually increased and tended to be stable. The average loss rate of training samples determined by the CNN model was (22.35 ± 0.62) %, and the average loss rate of test samples determined by the CNN model was (26.41 ± 3.37) %. The average accuracy rate of training samples determined by the CNN model was (91.04 ± 2.11) %, and the average accuracy rate of test samples determined by the CNN model was (91.26 ± 1.02)%. Conclusion: A CNN model exhibits a high value in the cytological diagnosis of thyroid diseases which can be used for the cytological diagnosis of malignant thyroid tumor in the clinic.

13.
World J Urol ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34766214

RESUMO

OBJECTIVE: To compare the outcomes of mini percutaneous nephrolithotomy (mPNL) and retrograde intrarenal surgery (RIRS) for the management of 2-3 cm lower pole renal calculi (LPC) in obese patients. PATIENTS AND METHODS: 120 obese patients with 2-3 cm LPC were randomly divided into mPNL group and RIRS group. Demography, clinical characteristics, perioperative complications, and stone free rate (SFR) were recorded. Stone-free status means no stone on computed tomography 3 months after surgery, or residual fragments were less than 3 mm. RESULTS: Baseline characteristics were similar between the two groups. The mean stone burden was 585.39 ± 131.06 mm2 in the mPNL group and 548.64 ± 123.55 mm2 in the RIRS group (P = 0.125). The SFR of mPNL group was significantly better than that of RIRS group (86.2% vs 61.4%, P = 0.002). Besides, the overall complication rate was 22.4% in the mPNL group and 7% in the RIRS group (P = 0.02). Patients performed with mPNL required longer length of hospital stay than those with RIRS (P = 0.001). There were no significant differences in operative time and stone composition between the two groups. CONCLUSION: In our study, both mPNL and RIRS are safe and effective techniques for the treatment of 2-3 cm LPC in obese patients. Compared to RIRS, mPNL has better SFR at the expense of the higher incidence of complications and prolonged length of hospital stay.

14.
Front Public Health ; 9: 681255, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778161

RESUMO

The COVID-19 virus has devastated lives and economies worldwide. The responses of nursing teams to large-scale COVID-19 screening have rarely been addressed or described. The aim of this study is to introduce an efficient response strategy for nurses in large-scale COVID-19 screening. A new COVID-19 case was confirmed on Jan 14, 2021 in Nanning, China. Immediately, a large-scale COVID-19 screening was launched and ran from Jan 14 to Jan 17, 2021. Our nurse team responding to the screening included three major components: (1) establishing a leadership group and a nucleic acid sampling emergency team; (2) defining, conducting, and evaluating nurse training; (3) implementing efficient sampling schemes (10 in 1 mixed sample technique). A total of 500 nurse volunteers were recruited and divided into three echelons. A total of 353 trained nurses were sent to 65 sampling stand stations. In cooperation with nurses from other health institutions, samples were collected from a total of 854,215 people in only 4 days for 2019-nCOV nucleic acid screening. The preparation and efficient response strategies used to conduct this screening may provide a baseline reference for future large-scale COVID-19 screening worldwide.


Assuntos
COVID-19 , Emergências , Humanos , Liderança , Equipe de Enfermagem , SARS-CoV-2
15.
Biomed Environ Sci ; 34(10): 789-802, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34782045

RESUMO

Objective: The expression patterns of ribosomal large subunit protein 23a (RPL23a) in mouse testes and GC-1 cells were analyzed to investigate the potential relationship between RPL23a expression and spermatogonia apoptosis upon exposure to X-ray. Methods: Male mice and GC-1 cells were irradiated with X-ray, terminal dUTP nick end-labelling (TUNEL) was performed to detect apoptotic spermatogonia in vivo. Apoptotic rate and cell cycle phase of GC-1 cells were analyzed with flow cytometry. Protein interactions were detected by Immunoprecipitation and protein localization as studied by immunofluorescence. Immunoblotting and real-time PCR were applied to analyze to protein and gene expression. Results: Ionizing radiation (IR) increased spermatogonia apoptosis, the expression of RPL11, MDM2 and p53, and decreased RPL23a expression in mice spermatogonia in vivo and in vitro. RPL23a knockdown weakened the interaction between RPL23a and RPL11, leading to p53 accumulation. Moreover, knockdown and IR decreased RPL23a that induces spermatogonia apoptosis via RPL23a-RPL11-MDM2-p53 pathway in GC-1 cells. Conclusion: These results suggested that IR reduced RPL23a expression, leading to weakened the RPL23a-RPL11 interactions, which may have activated p53, resulting in spermatogonia apoptosis. These results provide insights into environmental and clinical risks of radiotherapy following exposure to IR in male fertility. The graphical abstract was available in the web of www.besjournal.com.

16.
J Cell Physiol ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34812495

RESUMO

Dunaliella salina can accumulate a large amount of ß-carotene which is generally considered to be its terminal product of carotenoid metabolism. In this study, it was proved that D. salina has the ketolase (DsBKT) of catalyzing the synthesis of astaxanthin, the downstream products of ß-carotene. Therefore, the reason why D. salina does not synthesize astaxanthin is the purpose of this study. The enzymatic activity of DsBKT was detected by functional complementation assays in Escherichia coli, results showed that DsBKT had efficient ketolase activity toward ß-carotene and zeaxanthin to produce astaxanthin, indicating that there were complete astaxanthin-producing genes in Dunaliella. Unlike the induced expression of Lycopene cyclase (catalyzing ß-carotene synthesis) under salt stress, the expression of DsBKT was very low under both normal and stress conditions, which may be the main reason why D. salina cannot accumulate astaxanthin. On the contrary, with the astaxanthin-rich Haematococcus pluvialis as a control, its BKT gene was significantly upregulated under salt stress. Further study showed that DsBKT promoter had strong promoter ability and could stably drive the expression of ble-egfp in D. salina. Obviously, DsBKT promoter is not the reason of DsBKT not being expressed which may be caused by Noncoding RNA.

17.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5064-5071, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738402

RESUMO

The present study investigated the effects of chikusetsu saponin Ⅳa(CHS Ⅳa) on isoproterenol(ISO)-induced myocardial hypertrophy in rats and explored the underlying molecular mechanism. ISO was applied to establish a rat model of myocardial hypertrophy, and CHS Ⅳa(5 and 15 mg·kg~(-1)·d~(-1)) was used for intervention. The tail artery blood pressure was measured. Cardiac ultrasound examination was performed. The ratio of heart weight to body weight(HW/BW) was calculated. Morphological changes in the myocardial tissue were observed by HE staining. Collagen deposition in the myocardial tissue was observed by Masson staining. The mRNA expression of myocardial hypertrophy indicators(ANP and BNP), autophagy-related genes(Atg5, P62 and beclin1), and miR199 a-5 p was detected by qRT-PCR. Atg5 protein expression was detected by Western blot. The results showed that the model group exhibited increased tail artery blood pressure and HW/BW ratio, thickened left ventricular myocardium, enlarged myocardial cells, disordered myocardial fibers with widened interstitium, and a large amount of collagen aggregating around the extracellular matrix and blood vessels. ANP and BNP were largely expressed. Moreover, P62 expression was up-regulated, while beclin1 expression was down-regulated. After intervention by CHS Ⅳa at different doses, myocardial hypertrophy was ameliorated and autophagy activity in the myocardial tissue was enhanced. Meanwhile, miR199 a-5 p expression declined and Atg5 expression increased. As predicted by bioinformatics, Atg5 was a target gene of miR199 a-5 p. CHS Ⅳa was capable of preventing myocardial hypertrophy by regulating autophagy of myocardial cells through the miR-199 a-5 p/Atg5 signaling pathway.


Assuntos
Ácido Oleanólico , Saponinas , Animais , Cardiomegalia/induzido quimicamente , Cardiomegalia/tratamento farmacológico , Cardiomegalia/genética , Isoproterenol , Miocárdio , Miócitos Cardíacos , Ácido Oleanólico/análogos & derivados , Ratos , Saponinas/farmacologia
18.
Clin Rheumatol ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34757493

RESUMO

OBJECTIVE: To identify clinical characteristics and risk factors related to the progression of interstitial lung disease (ILD) in patients with primary Sjögren's syndrome (pSS). METHODS: In this single-centered, retrospective study, a total of 83 identified pSS-ILD patients with relatively complete clinical data were finally enrolled. Clinical symptoms, laboratory data, high-resolution computed tomography (HRCT), and pulmonary function test (PFT) results were collected. A logistic regression analysis was performed to determine the independent risk factors for ILD progression, and a nomogram was plotted to construct a predictive model. RESULTS: The prevalence of pSS-ILD in our study was 18.89%. Among the 83 enrolled patients, 32 (38.6%) underwent ILD progression. The characteristic features associated with the progression of ILD included male sex, non-sicca onset, reticular pattern on HRCT, higher levels of baseline lactic dehydrogenase (LDH), and low baseline forced vital capacity (FVC). The results of multivariate logistic regression indicated that LDH (OR 1.008, p = 0.030) was an independent risk factor for ILD progression, while sicca onset (OR 0.254, p = 0.044) and FVC (OR 0.952, p = 0.003) were protective factors for ILD progression. A simple predictive model for ILD progression in pSS was developed and validated. CONCLUSION: pSS patients with non-sicca onset, high baseline LDH level, and low baseline FVC were at higher risk of ILD progression.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34613377

RESUMO

OBJECTIVES: In this study, we developed an IS26-based CRISPR/Cas9 system as a proof-of-concept study to explore the potential of a re-engineered bacterial translocatable unit (TU) for curing and immunizing against the replication genes and antimicrobial resistance genes. METHODS: A series of pIS26-CRISPR/Cas9 suicide plasmids were constructed, and specific guide RNAs were designed to target the replication gene of IncX4, IncI2 and IncHI2 plasmids, and the antibiotic resistance genes mcr-1, blaKPC-2 and blaNDM-5. Through conjugation and induction, the transposition efficiency and plasmid-curing efficiency in each recipient were tested. In addition, we examined the efficiency of the IS26-CRISPR/Cas9 system of cell immunity against the acquisition of the exogenous resistant plasmids by introducing this system into antimicrobial-susceptible hosts. RESULTS: This study aimed to eliminate the replication genes and antimicrobial resistance genes using pIS26-CRISPR/Cas9. Three plasmids with different replicon types, including IncX4, IncI2 and IncHI2 in three isolates, two pUC19-derived plasmids, pUC19-mcr-1 and pUC19-IS26mcr-1, in two lab strains, and two plasmids bearing blaKPC-2 and blaNDM-5 in two isolates were all successfully eliminated. Moreover, the IS26-based CRISPR/Cas9 system that remained in the plasmid-cured strains could efficiently serve as an immune system against the acquisition of the exogenous resistant plasmids. CONCLUSIONS: The IS26-based CRISPR/Cas9 system can be used to efficiently sensitize clinical Escherichia coli isolates to antibiotics in vitro. The single-guide RNAs targeted resistance genes or replication genes of specific incompatible plasmids that harboured resistance genes, providing a novel means to naturally select bacteria that cannot uptake and disseminate such genes.

20.
Food Funct ; 12(19): 9360-9371, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606545

RESUMO

Anhydrosafflor yellow B (AHSYB) is a major active water-soluble pigment in Safflower, but it has not received enough attention yet. In this study, high-speed counter-current chromatography (HSCCC) was used to prepare AHSYB from safflower. The parameters of the separation process were optimized by response surface methodology for the first time. The entropy weight method (EWM) was applied to calculate the information entropy and the weight of five indexes, and then figure out a comprehensive index of the HSCCC separation effect. Under the optimized separation conditions, a HSCCC apparatus speed of 850 rpm, a flow rate of 2 mL min-1 for the mobile phase and a separation temperature of 40 °C for AHSYB were achieved with a purity of 98%. Furthermore, AHSYB was found to have cardio-protective effects by inhibiting apoptosis via the mitochondrial-mediated pathway in oxygen-glucose deprivation/reoxygenation-induced H9c2 cells. This research provides good method guides for the rapid and efficient separation of active compounds from food-grade Chinese herb medicines.

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