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1.
Biochem Pharmacol ; : 114538, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33831397

RESUMO

Acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITD) has a dismal prognosis. FLT3 inhibitors have been developed to treat patients with FLT3-ITD AML; however, when used alone, their efficacy is insufficient. FLT3 inhibitors combined with chemotherapy may be a promising treatment for FLT3-ITD AML. Homoharringtonine (HHT) is a classical anti-leukaemia drug with high sensitivity to FLT3-ITD AML cells. Here, we showed that HHT synergizes with a selective next-generation FLT3 inhibitor, quizartinib, to inhibit cell growth/viability and induce cell-cycle arrest and apoptosis in FLT3-ITD AML cells in vitro, significantly inhibit acute myeloid leukemia progression in vivo, and substantially prolong survival of mice-bearing human FLT3-ITD AML. Mechanistically, HHT and quizartinib cooperatively inhibit FLT3-AKT and its downstream targets GSK3ß, c-Myc, and cyclin D1, cooperatively up-regulate the pro-apoptosis proteins Bim and Bax, and down-regulate the anti-apoptosis protein Mcl1. Most strikingly, HHT and quizartinib cooperatively reduce the numbers of side-population (SP) and aldehyde dehydrogenase (ALDH)-positive cells, which reportedly are rich in LSCs. In conclusion, HHT combined with quizartinib may be a promising treatment strategy for patients with FLT3-ITD AML.

2.
Clin Transl Gastroenterol ; 12(4): e00323, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33848277

RESUMO

INTRODUCTION: To evaluate the diagnostic performance of ultrasound attenuation parameter (UAP) and liver stiffness measurement (LSM) by FibroTouch for diagnosis of hepatic steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We recruited 237 patients undergoing FibroTouch and liver biopsy within 2 weeks. The pathological findings of liver biopsy were scored by Nonalcoholic Steatohepatitis Clinical Research Network, and the diagnostic accuracy of UAP for steatosis and LSM for fibrosis was evaluated by area under the receiver operating characteristic curve (AUROC). The impacts of histological parameters on UAP and LSM were analyzed, and diagnostic performance of FibroTouch UAP and LSM was compared with other noninvasive biomarkers. RESULTS: The success rate of FibroTouch examination was 96.51%. The AUROC of UAP for diagnosis of steatosis ≥S1, ≥S2, and S3 was 0.88, 0.93, and 0.88, and the cutoff values were 244, 269, and 296 dB/m, respectively. The AUROC of LSM for the diagnosis of fibrosis stages ≥F2, ≥F3, and F4 was 0.71, 0.71, and 0.77, and the cutoff values were 9.4, 9.4, and 11 kPa, respectively. Multiple regression analysis showed that LSM was positively correlated with degree of fibrosis and NAFLD activity score. UAP was positively correlated with liver steatosis. The diagnostic performance of UAP for steatosis was significantly superior to that of the hepatic steatosis index. DISCUSSION: FibroTouch has a low failure rate with moderate to high diagnostic performance for discriminating the steatosis degree and fibrosis stage and is suitable for clinical evaluation and monitoring of patients with NAFLD.

3.
J Biomed Nanotechnol ; 17(1): 1-17, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33653493

RESUMO

Soft Tissue augmentation is a way to restore lost tissue and also a way to reshape confidence for patients who suffer from soft tissue loss. Materials that can realize such a function are called soft tissue fillers. Among the large number of fillers, injectable fillers have attracted widespread attention in facial cosmetic fields due to their convenience and competitive performance. Meanwhile, there is a huge demand for better injectable soft tissue fillers in medical cosmetology market. This review introduces several fillers which were once used in clinical or are now still in use. Furthermore, we update recent improvements and progress on injectable filling materials hoping to contribute to its further developments.


Assuntos
Técnicas Cosméticas , Envelhecimento da Pele , Materiais Biocompatíveis , Humanos , Ácido Hialurônico
4.
Mediators Inflamm ; 2021: 6636947, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33727891

RESUMO

Methods: Differential expression of five selected miRNAs (hsa-mir-1225-3p, hsa-mir-1238, hsa-miR-3162-3P, hsa-miR-4721, and hsa-miR-H7) was verified by qRT-PCR in the plasma of 83 patients and 20 healthy controls. The relative expression of these miRNAs was analyzed in different groups to screen target miRNA. A logistic regression analysis was performed to assess factors associated with fibrosis progression. The receiver operating characteristic (ROC) curve and discriminant analyses validated the ability of these predicted variables to discriminate the nonsignificant liver fibrosis group from the significant liver fibrosis group. Furthermore, the established models were compared with other prediction models to evaluate the diagnostic efficiency. Results: These five tested miRNAs all had signature correlations with hepatic fibrotic level (p < 0.05), and the upregulation trends were consistent with miRNA microarray analysis previously. The multivariate logistic regression analysis identified that a model of five miRNAs (miR-5) had a high diagnostic accuracy in discrimination of different stages of liver fibrosis. The ROC showed that the miR-5 has excellent value in diagnosis of fibrosis, even better than the Forns score, FIB-4, S index, and APRI. GO functions of different miRNAs mainly involved in various biological processes were markedly involved in HBV and revealed signaling pathways dysregulated in liver fibrosis of CHB patients. Conclusions: It was validated that the combination of these five miRNAs was a new set of promising molecular diagnostic markers for liver fibrosis. The diagnosis model (miR-5) can distinguish significant and nonsignificant liver fibrosis with high sensitivity and specificity.

5.
Exp Mol Med ; 53(2): 168-188, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33568752

RESUMO

Advanced glycation end products (AGEs) are potentially harmful and heterogeneous molecules derived from nonenzymatic glycation. The pathological implications of AGEs are ascribed to their ability to promote oxidative stress, inflammation, and apoptosis. Recent studies in basic and translational research have revealed the contributing roles of AGEs in the development and progression of various aging-related pathological conditions, such as diabetes, cardiovascular complications, gut microbiome-associated illnesses, liver or neurodegenerative diseases, and cancer. Excessive chronic and/or acute binge consumption of alcohol (ethanol), a widely consumed addictive substance, is known to cause more than 200 diseases, including alcohol use disorder (addiction), alcoholic liver disease, and brain damage. However, despite the considerable amount of research in this area, the underlying molecular mechanisms by which alcohol abuse causes cellular toxicity and organ damage remain to be further characterized. In this review, we first briefly describe the properties of AGEs: their formation, accumulation, and receptor interactions. We then focus on the causative functions of AGEs that impact various aging-related diseases. We also highlight the biological connection of AGE-alcohol-adduct formations to alcohol-mediated tissue injury. Finally, we describe the potential translational research opportunities for treatment of various AGE- and/or alcohol-related adduct-associated disorders according to the mechanistic insights presented.

6.
Acta Haematol ; : 1-9, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33631745

RESUMO

INTRODUCTION: Treatment-induced peripheral neuropathy (TIPN) is a complication of multiple myeloma (MM) treatment. OBJECTIVE: This real-world, retrospective study used electronic medical record (EMR) data from 3 Swedish clinics to assess the occurrence and economic burden of TIPN in patients with MM. METHODS: Eligible patients had an MM diagnosis in the Swedish Cancer Registry between 2006 and 2015 and initiated treatment during that period. Follow-up was until last EMR visit, death, or study end (April 2017). The current analyses included patients receiving bortezomib, lenalidomide, carfilzomib, or thalidomide at any treatment line. To discern healthcare resource utilization (HCRU) and costs associated with TIPN from other causes, patients with TIPN were matched with those without on baseline characteristics, treatment, and line of therapy. All analyses were descriptive. RESULTS: Overall, 457 patients were included; 102 (22%) experienced TIPN. Patients experiencing TIPN during first-line treatment mostly received bortezomib-based regimens (n = 48/57 [84%]); those with TIPN during second- and third/fourth-line treatment mostly received lenalidomide/thalidomide-based regimens (19/31 [61%], 8/14 [57%], respectively). Patients with TIPN had higher HCRU/costs than those without TIPN (mean differences in hospital outpatient visits: 5.2, p = 0.0031; total costs per patient-year: EUR 17,183, p = 0.0007). CONCLUSIONS: Effective MM treatments associated with a reduced incidence of TIPN could result in decreased healthcare expenditure.

7.
ISME J ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33619354

RESUMO

During the decomposition process of soil organic carbon (SOC), microbial products such as microbial necromass and microbial metabolites may form an important stable carbon (C) pool, called microbially derived C, which has different decomposition patterns from plant-derived C. However, current Earth System Models do not simulate this microbially derived C pool separately. Here, we incorporated the microbial necromass pool to the first-order kinetic model and the Michaelis-Menten model, respectively, and validated model behaviors against previous observation data from the decomposition experiments of 13C-labeled necromass. Our models showed better performance than existing models and the Michaelis-Menten model was better than the first-order kinetic model. Microbial necromass C was estimated to be 10-27% of total SOC in the study soils by our models and therefore should not be ignored. This study provides a novel modification to process-based models for better simulation of soil organic C under the context of global changes.

8.
Breast J ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33464691

RESUMO

The aim of this study is to characterize and compare changes in gene expression patterns of paired axillary lymph node (ALN) metastases from estrogen receptor (ER)-positive and triple-negative (TNBC) primary breast cancer (PBC). Patients with stage 2-3 PBC with macrometastasis to an ALN were selected. Gene expression of 2567 cancer-associated genes was analyzed with the HTG EdgeSeq system coupled with the Illumina Next Generation Sequencing (NGS) platform. Changes in gene expression between ER/PR-positive, HER2-negative PBC, and their paired ALN metastases were compared with TNBC and their paired ALN metastases. Fourteen pairs of ER-positive and paired ALN metastasis were analyzed. Compared with the PBC, ALN metastasis had 673 significant differentially expressed genes, including 348 upregulated genes and 325 downregulated genes. Seventeen pairs of TNBC and paired ALN metastasis were analyzed. ALN metastasis had 257 significant differentially expressed genes, including 123 upregulated genes and 134 downregulated genes. When gene expression of the ALN for ER-positive PBC was compared to that of TNBC, 97 genes were upregulated in both, and 115 genes were similarly downregulated. Common upregulated genes were associated with cell death, necrosis, and homeostasis. Common downregulated genes were those of migration, degradation of extracellular matrix, and invasion. Although ER-positive PBC and TNBC have a distinct gene expression profiles and distinct changes from PBC to ALN metastases, a significant number of genes are similarly up- or downregulated. Understanding the role of these common genomic changes may provide clues to understanding the metastatic process itself.

9.
Int J Pharm ; 597: 120250, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33486040

RESUMO

Glioblastoma (GBM) is a difficult-to-treat cancer, likely attributed to the blood brain barrier and drug resistance. Nose-to-brain drug delivery is a direct and non-invasive pathway for brain targeting with low systemic toxicity. Disulfiram (DSF) has shown its effectiveness against GBM, especially with copper ion (Cu). In this work, we designed a DSF loaded ion-sensitive nanoemulsion in situ gel (DSF-INEG) that was delivered intranasally along with Cu to the rat brains for the GBM treatment. The developed DSF-INEG nanomedicine showed a suitable particle size of 63.4 ± 1.1 nm and zeta potential of -23.5 ± 0.2 mV with a favorable gelling ability and prolonged DSF release. The results in vitro indicate DSF-INEG/Cu effectively inhibited the proliferation of both C6 and U87 cells. Besides, the excellent brain-targeting efficacy via nose-to-brain delivery was proved by the highest fluorescence signal of Cy5.5-INEG in the rat brains. Moreover, GFP imaging showed enhanced tumor growth inhibition of the rats by the DSF-INEG/Cu treatment, and their median survival time was 1.6 and 1.2 folds than those of the rats in the control and DSF/Cu treated groups, respectively, with no obvious histopathological damage to normal tissues. Overall, DSF-INEG/Cu could be a promising intranasal nanomedicine for effective GBM treatment.

10.
Eur J Pharm Sci ; 156: 105590, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33065226

RESUMO

The unique environment of brain poses a huge challenge for drug development aimed at combatting glioblastoma (GBM) due to poor organ targeting. Intranasal administration is often considered as an attractive route directly into brain by not only circumventing the blood brain barrier and but also avoiding the hepatic first-pass effect. Disulfiram (DSF) is an old alcohol-aversion drug that has anti-tumor activities against diverse cancer types such as GBM in preclinical studies, especially when it is combined with cupper ion (Cu). In this study, DSF was embedded in hydroxypropyl-ß-cyclodextrin (HP-ß-CD) to prepare a DSF inclusion complex with the enhanced solubility, anti-GBM activity and high safety in vitro. The highest fluorescence signal of Cy5.5/HP-ß-CD in the male rat brains showed the strong brain-targeting of nose-to-brain drug delivery. Therapeutic effects of DSF/HP-ß-CD combined with Cu (DSF/HP-ß-CD/Cu) on intracranial glioma-bearing male rats via different drug delivery routes were then investigated. DSF/HP-ß-CD/Cu administrated by the intranasal route effectively inhibited tumor growth and migration, promoted apoptosis, and achieved 36.8% and 18.2% prolonged median survival time comparing to those of model rats by oral and intravenous administrations, respectively. Moreover, no obvious histopathological damage to normal tissues was observed by H&E staining. Overall, DSF/HP-ß-CD/Cu could be a promising intranasal formulation for the effective GBM treatment.

11.
Nucleic Acids Res ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33290559

RESUMO

The human genome contains hundreds of large, structurally diverse blocks that are insufficiently represented in the reference genome and are thus not amenable to genomic analyses. Structural diversity in the human population suggests that these blocks are unstable in the germline; however, whether or not these blocks are also unstable in the cancer genome remains elusive. Here we report that the 500 kb block called KRTAP_region_1 (KRTAP-1) on 17q12-21 recurrently demarcates the amplicon of the ERBB2 (HER2) oncogene in breast tumors. KRTAP-1 carries numerous tandemly-duplicated segments that exhibit diversity within the human population. We evaluated the fragility of the block by cytogenetically measuring the distances between the flanking regions and found that spontaneous distance outliers (i.e DNA breaks) appear more frequently at KRTAP-1 than at the representative common fragile site (CFS) FRA16D. Unlike CFSs, KRTAP-1 is not sensitive to aphidicolin. The exonuclease activity of DNA repair protein Mre11 protects KRTAP-1 from breaks, whereas CtIP does not. Breaks at KRTAP-1 lead to the palindromic duplication of the ERBB2 locus and trigger Breakage-Fusion-Bridge cycles. Our results indicate that an insufficiently investigated area of the human genome is fragile and could play a crucial role in cancer genome evolution.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33296310

RESUMO

The key to hyperspectral anomaly detection is to effectively distinguish anomalies from the background, especially in the case that background is complex and anomalies are weak. Hyperspectral imagery (HSI) as an image-spectrum merging cube data can be intrinsically represented as a third-order tensor that integrates spectral information and spatial information. In this article, a prior-based tensor approximation (PTA) is proposed for hyperspectral anomaly detection, in which HSI is decomposed into a background tensor and an anomaly tensor. In the background tensor, a low-rank prior is incorporated into spectral dimension by truncated nuclear norm regularization, and a piecewise-smooth prior on spatial dimension can be embedded by a linear total variation-norm regularization. For anomaly tensor, it is unfolded along spectral dimension coupled with spatial group sparse prior that can be represented by the l2,1-norm regularization. In the designed method, all the priors are integrated into a unified convex framework, and the anomalies can be finally determined by the anomaly tensor. Experimental results validated on several real hyperspectral data sets demonstrate that the proposed algorithm outperforms some state-of-the-art anomaly detection methods.

13.
Front Genet ; 11: 566024, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193652

RESUMO

Background: Acute myeloid leukemia (AML) is a clonal malignant disease with poor prognosis and a low overall survival rate. Although many studies on the treatment and detection of AML have been conducted, the molecular mechanism of AML development and progression has not been fully elucidated. The present study was designed to pursuit the molecular mechanism of AML using a comprehensive bioinformatics analysis, and build an applicable model to predict the survival probability of AML patients in clinical use. Methods: To simplify the complicated regulatory networks, we performed the gene co-expression and PPI network based on WGCNA and STRING database using modularization design. Two machine learning methods, A least absolute shrinkage and selector operation (LASSO) algorithm and support vector machine-recursive feature elimination (SVM-RFE), were used to filter the common hub genes by five-fold cross-validation. The candidate hub genes were used to build the predictive model of AML by the cox-proportional hazards analysis, and validated in The Cancer Genome Atlas (TCGA) cohort and ohsu cohort, which were reliable in the experimental verification by qRT-PCR and western blotting in mRNA and protein levels. Results: Three hub genes, FLT3, CD177 and TTPAL were used to build a clinically applicable model to predict the survival probability of AML patients and divided them into high and low groups. To compare the survival ability of the model with the classical clinical features, we generated the nomogram. The model displayed the most risk points contrast to other clinical characteristics, which was compatible with the data of cox multivariate regression. Conclusion: This study reveal the novel molecular mechanism of AML, and construct a clinical model significantly related to AML patient prognosis. We showed the integrated roles of critical pathways, hub genes associated, which provide potential targets and new research ideas for the treatment and early detection of AML.

14.
Autophagy ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176558

RESUMO

Sterols are a class of lipids critical for fundamental biological processes and membrane dynamics. These molecules are synthesized in the endoplasmic reticulum (ER) and are transported bi-directionally between the ER and plasma membrane (PM). However, the trafficking mechanism of sterols and their relationship with macroautophagy/autophagy are still poorly understood in the rice blast fungus Magnaporthe oryzae. Here, we identified the VAD1 Analog of StAR-related lipid transfer (VASt) domain-containing protein MoVast1 via co-immunoprecipitation in M. oryzae. Loss of MoVAST1 resulted in conidial defects, impaired appressorium development, and reduced pathogenicity. The MoTor (target of rapamycin in M. oryzae) activity is inhibited because MoVast1 deletion leads to high levels of sterol accumulation in the PM. Site-directed mutagenesis showed that the 902T site is essential for localization and function of MoVast1. Through filipin or Flipper-TR staining, autophagic flux detection, MoAtg8 lipidation, and drug sensitivity assays, we uncovered that MoVast1 acts as a novel autophagy inhibition factor that monitors tension in the PM by regulating the sterol content, which in turn modulates the activity of MoTor. Lipidomics and transcriptomics analyses further confirmed that MoVast1 is an important regulator of lipid metabolism and the autophagy pathway. Our results revealed and characterized a novel sterol transfer protein important for M. oryzae pathogenicity.

15.
Front Plant Sci ; 11: 566824, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013988

RESUMO

Senescence is the main limitation for cut foliage display in vase. Naturally occurring polyamines such as putrescine (Put) have been considered effective anti-senescence agents. However, effect of Put on cut foliage in vase in a realistic indoor environment has not yet been revealed. In the present study, effects of Put spraying on the postharvest performance of cut foliage of Nephrolepis cordifolia L. were investigated. Cut fronds sprayed with deionized water (Put0) showed visible injuries after 10 days in vase. Meanwhile, chlorophyll (Chl), soluble protein (Sp), and proline (Pro) content were decreased by 60.15, 57.93, and 73.09% respectively, photochemical activity reflected by Chl fluorescence parameters was inhibited, whereas electrolyte leakage (EL), contents of soluble sugar (Ss), malondialdehyde (MDA), and hydrogen peroxide (H2O2) were increased (+194.29, +44.83, +34.06, and +178.01%, respectively). Put spraying extended the vase life of the cut foliage and the 2.0 mM Put had a longer vase life (21 days) than 0.2 mM (15 days). Leaf spraying of 2.0 mM Put for 10 days significantly ameliorated the losses of Chl, Sp, and Pro content (-10.72, -26.29, and -42.64%, respectively), followed by 0.2 mM Put (-27.36, -36.24, and -60.55%, respectively). Put spraying also improved photochemical capability and prevented membrane impairment as well as visible injury in comparison with Put0. In addition, 2.0 mM Put had a better mitigating ability than that of 0.2 mM. Leaf spraying of 2.0 mM Put greatly reduced the decline of the effective quantum yield of photochemical energy conversion in PSII (ΦPSII), the maximal quantum yield of PSII photochemistry measured in the dark-adapted state (Fv/Fm) and electron transport rate (ETR) (-7.89, -12.91, and -10.06%, respectively), and also inhibited the increases of EL, MDA, Ss, and H2O2 (+31.87, +6.43, +16.22, and +49.40%, respectively). Overall, Put played important roles in deterring the degradation of Chl, Ss, and Pro, detoxifying the H2O2, weakening the sugar signaling, mitigating the decline of photochemical activity, and eventually postponing the leaf senescence. The present study gives new insights into effects of Put on leaf senescence and provides a strategy for preserving post-harvest cut foliage.

16.
Zhongguo Zhong Yao Za Zhi ; 45(15): 3719-3725, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893564

RESUMO

The aim of this paper was to investigate the effect of Schizonepetae Herba and Saposhnikoviae Radix(wind medicine) on the expression of AQP4 and AQP8 in colonic mucosa in rats with ulcerative colitis(UC). A total of 35 healthy SD male rats were randomly divided into normal group(gavaged with normal saline), DSS model group, as well as low, middle, and high dose wind medicine groups(Schizonepeta and Saposhnikovia 1∶1, gavaged at dosages of 6, 12, and 24 g·kg~(-1)·d~(-1)), with 7 in each group. UC rat model was established by free drinking of 3% dextran sulphate sodium(DSS) solution for 10 days. At the end of the 10 th day after the treatment, mice were put to death to collect colonic mucosa. The length of colon was measured; the colonic mucosal injury index(CMDI) and pathological changes of colon were observed. ELISA method was used for measuring the content of serum IL-1, IL-8, and immunohistochemical method was used to measure AQP4, AQP8 protein expressions in colon mucosa. The expressions of AQP4, AQP8 mRNA were measured by Real-time PCR. As compared with the normal group, the length of colon tissue was significantly reduced(P<0.01), CMDI scores and pathological scores were significantly increased(P<0.01), the levels of serum IL-1 and IL-8 were significantly increased(P<0.05) in model group; the immunohistochemical results showed that the protein expressions of AQP4, AQP8 were lower; the color was light yellow or brown; AQP4, AQP8 mRNA expressions in colon mucosa were significantly decreased in model group(P<0.01). CMDI scores, pathological scores, and the levels of serum IL-1, IL-8 in high, middle, low dose wind medicine groups were obvious lower than those in the model group(P<0.01 or P<0.05); the protein expressions of AQP4, AQP8 were higher; the color was chocolate brown or dark brown; the length of colon tissue, and the expressions of AQP4, AQP8 mRNA were obvious higher in wind medicine groups(P<0.01 or P<0.05). Schizonepetae Herba and Saposhnikoviae Radix could significantly improve the symptoms and histopathology of UC model rats and accelerate the intestinal mucosal healing. The mechanism may be related with up-regulating the expression level of AQP4 and AQP8 in colonic mucosa.


Assuntos
Apiaceae , Colite Ulcerativa , Animais , Aquaporina 4 , Colo , Mucosa Intestinal , Masculino , Camundongos , Raízes de Plantas , Ratos
17.
Med Sci Monit ; 26: e926651, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32969367

RESUMO

BACKGROUND Use of renin-angiotensin-aldosterone system inhibitors in coronavirus disease 2019 (COVID-19) patients lacks evidence and is still controversial. This study was designed to investigate effects of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on clinical outcomes of COVID-19 patients and to assess the safety of ACEIs/ARBs medication. MATERIAL AND METHODS COVID-19 patients with hypertension from 2 hospitals in Wuhan, China, from 17 Feb to 18 Mar 2020 were retrospectively screened and grouped according to in-hospital medication. We performed 1: 1 propensity score matching (PSM) analysis to adjust for confounding factors. RESULTS We included 210 patients and allocated them to ACEIs/ARBs (n=81; 46.91% males) or non-ACEIs/ARBs (n=129; 48.06% males) groups. The median age was 68 [interquartile range (IQR) 61.5-76] and 66 (IQR 59-72.5) years, respectively. General comparison showed mortality in the ACEIs/ARBs group was higher (8.64% vs. 3.88%) but the difference was not significant (P=0.148). ACEIs/ARBs was associated with significantly more cases 7-categorical ordinal scale >2 at discharge, more cases requiring Intensive Care Unit (ICU) stay, and increased values and ratio of days that blood pressure (BP) was above normal range (P<0.05). PSM analysis showed no significant difference in mortality, cumulative survival rate, or other clinical outcomes such as length of in-hospital/ICU stay, BP fluctuations, or ratio of adverse events between groups after adjustment for confounding parameters on admission. CONCLUSIONS We found no association between ACEIs/ARBs and clinical outcomes or adverse events, thus indicating no evidence for discontinuing use of ACEIs/ARBs in the COVID-19 pandemic.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/complicações , Hipertensão/complicações , Pandemias , Pneumonia Viral/complicações , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , China , Comorbidade , Feminino , Mortalidade Hospitalar , Humanos , Hipertensão/tratamento farmacológico , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/biossíntese , Peptidil Dipeptidase A/efeitos dos fármacos , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
18.
BMC Complement Med Ther ; 20(1): 289, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962697

RESUMO

BACKGROUND: In recent years, it has been reported that Qinbai Qingfei Concentrated Pellet (QQCP) has the effect of relieving cough and reducing sputum. However, the therapeutic potentials of QQCP on post-infectious cough (PIC) rat models has not been elucidated. So the current study was aimed to scientifically validate the efficacy of QQCP in post infectious cough. METHODS: All rats were exposed to sawdust and cigarette smokes for 10 days, and intratracheal lipopolysaccharide (LPS) and capsaicin aerosols. Rats were treated with QQCP at dose of 80, 160, 320 mg/kg. Cough frequency was monitored twice a day for 10 days after drug administration. Inflammatory cell infiltration was determined by ELISA. Meanwhile, the histopathology of lung tissue and bronchus in rats were evaluated by hematoxylin-eosin staining (H&E). Neurogenetic inflammation were measured by ELISA and qRT-PCR. RESULTS: QQCP dose-dependently decreased the cough frequency and the release of pro-inflammatory cytokines TNF-α, IL-1ß, IL-6 and IL-8, but exerted the opposite effects on the secretion of anti-inflammatory cytokines IL-10 and IL-13 in BALF and serum of PIC rats. The oxidative burden was effectively ameliorated in QQCP-treated PIC rats as there were declines in Malondialdehyde (MDA) content and increases in Superoxide dismutase (SOD) activity in the serum and lung tissue. In addition, QQCP blocked inflammatory cell infiltration into the lung as evidenced by the reduced number of total leukocytes and the portion of neutrophils in the broncho - alveolar lavage fluid (BALF) as well as the alleviated lung damage. Furthermore, QQCP considerable reversed the neurogenetic inflammation caused by PIC through elevating neutral endopeptidase (NEP) activity and reducing Substance P (SP) and Calcitonin gene related peptide (CGRP) expression in BALF, serum and lung tissue. CONCLUSIONS: Our study indicated that QQCP demonstrated a protective role of PIC and may be a potential therapeutic target of PIC.

20.
Bioorg Chem ; 103: 104109, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32768741

RESUMO

Histone deacetylases (HDACs) have been indicated important roles in neurodegenerative disorders including Alzheimer's disease (AD). Herein, a series of novel compounds that contain a memantine moiety were designed to target HDACs and N-methyl-d-aspartate receptor (NMDAR) which are related to the treatment of AD. Biological characterization established that compound 9d exhibited a balanced inhibitory activity on NMDAR and HDACs. This compound is relatively selective to HDAC6 with IC50 of 0.18 µM and also maintains comparable activity on NMDAR (Ki = 0.59 µM) as memantine. Functionally, treatment with 9d increased the level of AcTubulin in MV4-11 cells and rescued PC-12 cells from H2O2-induced cytotoxicity with EC50 of 0.94 µM. Studies in mice also demonstrated that compound 9d efficiently penetrates the blood brain barrier to reach the brain tissue. Collectively, the results strongly encourage further development of 9d as a potential therapeutic agent for AD.

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