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1.
Eur J Pharmacol ; 917: 174760, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35033554

RESUMO

Ursodeoxycholic acid (UDCA) is a safe bile acid effective in reducing hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). However, the mechanism of action linked to this effect is poorly defined. In the present study, we identified that UDCA acted as a free fatty acid receptor 4 (FFA4) agonist with EC50 of 10.4 ± 0.7 µM, and its activity was determined by dynamic mass redistribution, fluorometric imaging plate reader, inositol monophosphate and bioluminescence resonance energy transfer assays. Moreover, UDCA showed FFA4 selectivity over eleven other G protein-coupled receptors. Real-Time PCR and immunocytochemistry analyses showed that FFA4 was abundantly expressed in human hepatocytes HuH-7 cells. In an in vitro model of NAFLD induced by oleic acid (OA), UDCA downregulated lipid accumulation in HuH-7 cells and suppressed sterol-regulatory element binding protein-1c (SREBP-1c) mRNA expression. This suppression of SREBP-1c was restored when FFA4 expression was knocked down in siRNA assay. In a mouse model of hepatic steatosis, db/db mice were exposed to a high-fat diet (HFD), and treatment of UDCA or docosahexaenoic acid (DHA, an endogenous FFA4 agonist) effectively prevented body weight gain and hepatic fat deposition and reduced triglyceride (TG) levels in serum and liver. This study not only identified a new skeleton of FFA4 agonists, but also demonstrated that FFA4 signal was accounting for the protective effects of UDCA in the NAFLD treatment.

2.
Bioact Mater ; 7: 154-166, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34466724

RESUMO

Zinc is generally considered to be one of the most promising materials to be used in biodegradable implants, and many zinc alloys have been optimized to improve implant biocompatibility, degradation, and mechanical properties. However, long-term degradation leads to the prolonged presence of degradation products, which risks foreign body reactions. Herein, we investigated the in vivo biocompatibility and degradation of a biodegradable Zn-Mg-Fe alloy osteosynthesis system in the frontal bone, mandible, and femur in beagles for 1 year. Results of the routine blood, biochemical, trace element, and histological analyses of multiple organs, peripheral blood CD4/CD8a levels, and serum interleukin 2 and 4 levels showed good biocompatibility of the Zn-Mg-Fe alloy. Zinc content analysis revealed zinc accumulation in adjacent bone tissue, but not in the liver, kidney, and spleen, which was related to the degradation of the Zn-Mg-Fe alloy. The alloy demonstrated a uniform slowing degradation rate in vivo. No degradation differences in the frontal bone, mandible, and femur were observed. The degradation products included zinc oxide [ZnO], zinc hydroxide [Zn(OH)2], hydrozincite [Zn5(OH)6(CO3)2], and hopeite [Zn3(PO4)2·4H2O]. The good biocompatibility and degradation properties of the Zn-Mg-Fe alloy render it a very attractive osteosynthesis system for clinical applications.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34881567

RESUMO

Antiferroelectric materials has become one of the most promising candidates for pulsed power capacitors. The polarization versus electric-field hysteresis loop is the key electrical property for evaluating their energy-storage performance. Here, we applied in situ biasing transmission electron microscopy to decode two representative energy-storage behaviors-namely, multiple and double hysteresis loops-in (Pb,La)(Zr,Sn,Ti)O3 system. Simultaneous structural examination and domain/defects observation establish a direct relationship between phase transitions and hysteresis loops. Sustaining a smaller period of modulated structure to a certain applied electric field and then undergoing additional transitions among varying antiferroelectric phases with increasing modulation periods before the final antiferroelectric-ferroelectric transition leads to the favorable multiple-loop configuration that realizes a high energy-storage performance. Such phenomenon is described by a model in terms of defect-driven phase transition. The distinctive mechanisms of multiple phase transition will inspire future composition-design for high switch-fielding antiferroelectric materials.

4.
Front Immunol ; 12: 749369, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745121

RESUMO

Ovarian cancer (OC) is one of the most malignant tumors whose mortality rate ranks first in gynecological tumors. Although immunotherapy sheds new light on clinical treatments, the low response still restricts its clinical use because of the unique characteristics of OC such as immunosuppressive microenvironment and unstable genomes. Further exploration on determining an efficient biomarker to predict the immunotherapy response of OC patients is of vital importance. In this study, integrative analyses were performed systematically using transcriptome profiles and somatic mutation data from The Cancer Genome Atlas (TCGA) based on the immune microenvironment and genomic instability of OC patients. Firstly, intersection analysis was conducted to identify immune-related differentially expressed genes (DEGs) and genomic instability-related DEGs. Secondly, Apolipoprotein B MRNA Editing Enzyme Catalytic Subunit 3A (APOBEC3A) was recognized as a protective factor for OC, which was also verified through basic experiments such as quantitative reverse transcription PCR (RT-qPCR), immunohistochemistry (IHC), Cell Counting Kit-8 (CCK-8), and transwell assays. Thirdly, the correlation analyses of APOBEC3A expression with tumor-infiltrating immune cells (TICs), inhibitory checkpoint molecules (ICPs), Immunophenoscores (IPS), and response to anti-PD-L1 immunotherapy were further applied along with single-sample GSEA (ssGSEA), demonstrating APOBEC3A as a promising biomarker to forecast the immunotherapy response of OC patients. Last, the relationship between APOBEC3A expression with tumor mutation burden (TMB), DNA damage response (DDR) genes, and m6A-related regulators was also analyzed along with the experimental verification of immunofluorescence (IF) and RT-qPCR, comprehensively confirming the intimate association of APOBEC3A with genomic instability in OC. In conclusion, APOBEC3A was identified as a protective signature and a promising prognostic biomarker for forecasting the survival and immunotherapy effect of OC patients, which might accelerate the clinical application and improve immunotherapy effect.

5.
Medicine (Baltimore) ; 100(41): e27521, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731142

RESUMO

ABSTRACT: To investigate the effect of a combined immune score including the lymphocyte-to-monocyte ratio (LMR) and uninvolved immunoglobulin (u-Ig) levels on the prognosis of newly diagnosed multiple myeloma (NDMM) patients treated with bortezomib.Clinical data of 201 NDMM patients were retrospectively analyzed. Patients with LMR ≥ 3.6 and LMR < 3.6 were scored 0 and 1, respectively. Patients with preserved u-Ig levels, suppression of 1 u-Ig, and suppression of at least 2 u-Igs were scored 0, 1, and 2, respectively. The immune score, established from these individual scores, was used to separate patients into good (0-1 points), intermediate (2 points), and poor (3 points) risk groups. The baseline data, objective remission rate (ORR), whether receive maintenance treatment regularly and overall survival of patients before treatment were analyzed.The ORR of the good-risk group was significantly higher than that of the intermediate-risk group (75.6% vs 57.7%, P = .044) and the poor-risk group (75.6% vs 48.2%, P = .007). The multivariate analysis results showed that age ≥ 65 years, International Staging System stage III, platelet count ≤ 100 × 109/L, lactate dehydrogenase (LDH) > 250 U/L, serum calcium > 2.75 mmol/L, no receipt of regular maintenance treatment, LMR < 3.6, suppressed u-Igs = 1, suppressed u-Igs ≥ 2, intermediate-risk group and poor-risk group were independent predictors of poor overall survival.In the bortezomib era, the LMR, u-Ig levels, and the immune score play an important role in the prognosis of NDMM patients. Among them, the immune score showed the strongest prognostic value, and it could be a beneficial supplement for the early identification of high-risk patients.


Assuntos
Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Fatores Etários , Idoso , Antineoplásicos/administração & dosagem , Bortezomib/administração & dosagem , Cálcio/sangue , Estudos de Casos e Controles , Feminino , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/imunologia , Imunoglobulinas/efeitos dos fármacos , Imunoglobulinas/imunologia , L-Lactato Desidrogenase/análise , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/imunologia , Estadiamento de Neoplasias/métodos , Contagem de Plaquetas/estatística & dados numéricos , Contagem de Plaquetas/tendências , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco
6.
Front Pharmacol ; 12: 675350, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737693

RESUMO

K. galanga is an aromatic medicinal herb. It is locally to India and distributed in China, Myanmar, Indonesia, Malaysia, and Thailand. K. galanga is a Traditional Chinese Herb Medicine (TCHM), which has been applied to treat cold, dry cough, toothaches, rheumatism, hypertension and so on. In addition, it has been used widely as spices since its highly aromas. The aim of this review is to compile and update the current progresses of ethnomedicinal uses, phytochemistry, pharmacology and toxicology of K. galanga. All the data on K. galanga were based on different classical literary works, multiple electronic databases including SciFinder, Web of Science, PubMed, etc. The results showed that ninety-seven compounds have been identified from rhizome of K. galanga, including terpenoids, phenolics, cyclic dipeptides, flavonoids, diarylheptanoids, fatty acids and esters. Modern pharmacology studies revealed that extracts or secondary metabolites of the herb possessed anti-inflammatory, anti-oxidant, anti-tumorous, anti-bacterial, and anti-angiogenesis effects, which were closely related to its abundant ethnomedicinal uses. In conclusion, although previous research works have provided various information of K. galanga, more in-depth studies are still necessary to systemically evaluate phytochemistry, pharmacological activities, toxicity and quality control of this herb.

7.
Diabetes Metab Syndr Obes ; 14: 4209-4221, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703256

RESUMO

Background: Insulin resistance is a determining factor in the pathophysiology of type 2 diabetes mellitus (T2DM). Angiopoietin-like protein 8 (ANGPTL8, also known as betatrophin), associated with glucose homeostasis and lipid metabolism, has attracted attention. But its mechanism in glucose metabolism remains unclear. This study aimed to explore the effect of ANGPTL8/betatrophin on glucose tolerance in Kunming (KM) mice of different ages and metabolic profiles in insulin-resistant HepG2 cells. Our study may provide a new perspective of ANGPTL8/betatrophin in insulin resistance from the metabolic changes. Methods: Oral glucose tolerance test was performed in KM mice of different ages. Insulin concentration was measured by using a quantitative enzyme-linked immunosorbent assay (ELISA). ANGPTL8/betatrophin knockouts in HepG2 cells were established with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein 9 (CRISPR/Cas9) system. Cell counting kit-8 (CCK-8) assay was used to determine cell viability after gene knockout. The effect of ANGPTL8/betatrophin on the metabolomic changes was evaluated in high insulin-induced insulin-resistant HepG2 cells by an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Results: ANGPTL8/betatrophin improved glucose tolerance in older mice not by altering the concentration of insulin. Cell growth was affected in ANGPTL8/betatrophin knockout HepG2. Based on UPLC-MS/MS, compared with wild type insulin-resistant HepG2 cells, we identified 83 differential metabolites in ANGPTL8/betatrophin knockout HepG2 cells after high insulin induction. Among the 14 differential up-regulated metabolites, D-mannose had the highest fold change. In insulin-resistant HepG2 cells, ANGPTL8/betatrophin knockout exerted an effect on the amino acid metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, lipid metabolism, nucleotide metabolism, and genetic information processing pathway. Conclusion: This study identified the effect of ANGPTL8/betatrophin on glucose tolerance in mice of different ages and metabolic profiles in insulin-resistant HepG2 cells. These findings may contribute to a new understanding of its role in glucose metabolism in the context of insulin resistance.

8.
Front Mol Biosci ; 8: 646730, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595206

RESUMO

Background: Radiation-induced brain injury is a serious and treatment-limiting complication of brain radiation therapy. Although endothelial cell dysfunction plays a critical role in the development of this pathogenesis, the underlying molecular mechanisms remain elusive. Methods: Primary cultured rat brain microvascular endothelial cells (BMECs) were divided into five groups without or with exposure of x-rays delivered at 5 Gy or 20 Gy. For the irradiated groups, cells were continued to cultivate for 12 or 24 h after being irradiated. Then the mRNA libraries of each group were established and applied for next-generation sequencing. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted to analyze the sequencing results. Quantitative polymerase chain reaction, western blotting, cck8 assay and intracellular calcium concentration assays were conducted to analyze the role of Orai2-associated SOCE in x-ray induced cellular injury. Results: In total, 3,005 transcripts in all the four x-ray-exposed groups of BMECs showed expression level changes compared with controls. With the dose of x-ray augment and the following cultured time extension, the numbers of differentially expressed genes (DEGs) increased significantly in BMECs. Venn diagrams identified 40 DEGs common to all four exposure groups. Functional pathway enrichment analyses indicated that those 40 DEGs were enriched in the calcium signaling pathway. Among those 40 DEGs, mRNA and protein expression levels of Orai2 were significantly upregulated for 24 h. Similarly, calcium influx via store-operated calcium entry, which is modulated by Orai2, was also significantly increased for 24 h in x-ray-exposed BMECs. Moreover, the change in SOCE was suppressed by btp-2, which is a non-selective inhibitor of Orai. Additionally, x-ray exposure induced a significant decrease of proliferation in BMECs in the dose- and time-dependent manner. Conclusion: These findings provide evidence for molecular mechanisms underlying BMECs dysfunction in development of radiation-induced brain injury and suggest new approaches for therapeutic targets.

9.
Pathol Oncol Res ; 27: 1609914, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646087

RESUMO

The angiopoietin-like protein (ANGPTL) family members, except for the novel atypical member ANGPTL8/betatrophin, have been reported to participate in angiogenesis, inflammation and cancer. ANGPTL8/betatrophin is a metabolic regulator that is involved in lipid metabolism and glucose homeostasis. However, little is known about the expression and prognostic value of ANGPTL8/betatrophin in human cancers. In this study, we first conducted detailed analyses of ANGPTL8/betatrophin expression in cancer/normal samples via the Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), DriverDBv3, ENCORI and UALCAN databases. ANGPTL8/betatrophin showed high tissue specificity (enriched in the liver) and cell-type specificity (enriched in HepG2 and MCF7 cell lines). More than one databases demonstrated that the gene expression of ANGPTL8/betatrophin was significantly lower in cholangiocarcinoma (CHOL), breast invasive carcinoma (BRCA), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), uterine corpus endometrial carcinoma (UCEC), and significantly higher in kidney renal clear cell carcinoma (KIRC) compared with that in normal samples. However, the protein expression of ANGPTL8/betatrophin displayed opposite results in clear cell renal cell carcinoma (ccRCC)/KIRC. Based on the expression profiles, the prognostic value was evaluated with the GEPIA, DriverDBv3, Kaplan Meier plotter and ENCORI databases. Two or more databases demonstrated that ANGPTL8/betatrophin significantly affected the survival of KIRC, uterine corpus endometrial carcinoma (UCEC), pheochromocytoma and paraganglioma (PCPG) and sarcoma (SARC); patients with PCPG and SARC may benifit from high ANGPTL8/betatrophin expression while high ANGPTL8/betatrophin expression was associated with poor prognosis in KIRC and UCEC. Functional analyses with the GeneMANIA, Metascape and STRING databases suggested that ANGPTL8/betatrophin was mainly involved in lipid homeostasis, especially triglyceride and cholesterol metabolism; glucose homeostasis, especially insulin resistance; AMPK signaling pathway; PI3K/Akt signaling pathway; PPAR signaling pathway; mTOR signaling pathway; HIF-1 signaling pathway; autophagy; regulation of inflammatory response. ANGPTL8/betatrophin may be a promising prognostic biomarker and therapeutic target, thus providing evidence to support further exploration of its role in defined human cancers.

10.
Shanghai Kou Qiang Yi Xue ; 30(4): 355-359, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34693426

RESUMO

PURPOSE: To detect the effect of DKK1 on biological behaviors of human dental pulp cells exposed to lipopolysaccharide (LPS). METHODS: The dental pulp cells were isolated and cultured by modified enzyme-tissue block method and identified by immunofluorescence staining. The effect of DKK1 on proliferation and migration of human dental pulp cells exposed to LPS were measured by cell counting kit (CCK-8) and Transwell assay. Meanwhile, the effect of DKK1 on differentiation of human dental cells exposed to LPS were studied by alizarin red staining and real-time PCR experiment, statistical analysis was performed using SPSS 20.0 software package. RESULTS: The results of immunofluorescence showed that the cultured cells were in consistent with the mesenchymal stem cells. The result of CCK-8 indicated that DKK1 had no significant effect on proliferation of dental pulp cells exposed to LPS; The result of transwell assay showed that DKK1 significantly promoted the cell migration of dental pulp cells exposed to LPS. The results of Alizarin red staining and real-time PCR revealed that DKK1 could promote cytodifferentiation of dental pulp cells exposed to LPS. CONCLUSIONS: DKK1 promotes the ability of cell migration and cytodifferentiation of LPS treated dental pulp cells, which may be resulted from inhibition of Wnt/ß-catenin pathway.


Assuntos
Polpa Dentária , Lipopolissacarídeos , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Lipopolissacarídeos/farmacologia , Via de Sinalização Wnt
11.
J Org Chem ; 86(23): 16300-16314, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34499513

RESUMO

Ten types of Tf2O/TTBP-mediated amide transformation reactions were investigated. The results showed that compared with pyridine derivatives 2,6-di-tert-butyl-4-methylpyridine (DTBMP) and 2-fluoropyridine (2-F-Pyr.), TTBP can serve as an alternative amide activation system for the direct transformation of both secondary and tertiary amides. For most surveyed examples, higher or comparable yields were generally obtained. In addition, Tf2O/TTBP combination was used to promote the condensation reactions of 2-(tert-butyldimethylsilyloxy)furan (TBSOF) with both tertiary and secondary amides, the one-pot reductive Bischler-Napieralski-type reaction of tertiary lactams, and Movassaghi and Hill's modern version of the Bischler-Napieralski reaction. The value of the Tf2O/TTBP-based methodology was further demonstrated by the concise and high-yielding syntheses of several natural products.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34471414

RESUMO

Background: Poststroke depression (PSD) is the most common and serious neuropsychiatric complication occurring after cerebrovascular accidents, seriously endangering human health while also imposing a heavy burden on society. Nevertheless, it is difficult to control disease progression. Gan-Mai-Da-Zao Decoction (GMDZD) is effective for PSD, but its mechanism of action in PSD is unknown. In this study, we explored the mechanism of action of GMDZD in PSD treatment using network pharmacology and molecular docking. Material and methods. We obtained the active components of all drugs and their targets from the public database TCMSP and published articles. Then, we collected PSD-related targets from the GeneCards and OMIM databases. Cytoscape 3.8.2 was applied to construct PPI and composite target disease networks. In parallel, the DAVID database was used to perform GO and KEGG enrichment analyses to determine the biological processes enriched in the treatment-related drugs in vivo. Finally, molecular docking was used to verify the association between the main active ingredients and their targets. Results: The network pharmacological analysis of GMDZD in PSD revealed 107 active ingredients with important biological effects, including quercetin, luteolin, kaempferol, naringenin, and isorhamnetin. In total, 203 potential targets for the treatment of this disease were screened, including STAT3, JUN, TNF, TPT53, AKT1, and EGFR. These drugs are widely enriched in a series of signaling pathways, such as TNF, HIF-1, and toll-like receptor. Moreover, molecular docking analysis showed that the core active components were tightly bound to their core targets, further confirming their anti-PSD effects. Conclusion: This prospective study was based on the integrated analysis of large data using network pharmacology technology to explore the feasibility of GMDZD for PSD treatment that was successfully validated by molecular docking. It reflects the multicomponent and multitarget characteristics of Chinese medicine and, more importantly, brings hope for the clinical treatment of PSD.

13.
J Ethnopharmacol ; 280: 114488, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358653

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has a long history in the prevention and treatment of pandemics. The TCM formula Lung Cleansing and Detoxifying Decoction (LCDD), also known as Qing Fei Pai Du Decoction, has been demonstrated effective against Coronavirus Disease 2019 (COVID-19). AIM OF THE STUDY: This work aimed to elucidate the active ingredients, targets and pathway mechanism of LCDD related to suppression of inflammatory, immunity regulation and relaxation of airway smooth muscle for the treatment of COVID-19. MATERIALS AND METHODS: Mining chemical ingredients reported in LCDD, 144 compounds covering all herbs were selected and screened against inflammatory-, immunity- and respiratory-related GPCRs including GPR35, H1, CB2, B2, M3 and ß2-adrenoceptor receptor using a label-free integrative pharmacology method. Further, all active compounds were detected using liquid chromatography-tandem mass spectrometry, and an herb-compound-target network based on potency and content of compounds was constructed to elucidate the multi-target and synergistic effect. RESULTS: Thirteen compounds were identified as GPR35 agonists, including licochalcone B, isoliquiritigenin, etc. Licochalcone B, isoliquiritigenin and alisol A exhibited bradykinin receptor B2 antagonism activities. Atractyline and shogaol showed as a cannabinoid receptor CB2 agonist and a histamine receptor H1 antagonist, respectively. Tectorigenin and aristofone acted as muscarinic receptor M3 antagonists, while synephrine, ephedrine and pseudoephedrine were ß2-adrenoceptor agonists. Pathway deconvolution assays suggested activation of GPR35 triggered PI3K, MEK, JNK pathways and EGFR transactivation, and the activation of ß2-adrenoceptor mediated MEK and Ca2+. The herb-compound-target network analysis found that some compounds such as licochalcone B acted on multiple targets, and multiple components interacted with the same target such as GPR35, reflecting the synergistic mechanism of Chinese medicine. At the same time, some low-abundance compounds displayed high target activity, meaning its important role in LCDD for anti-COVID-19. CONCLUSIONS: This study elucidates the active ingredients, targets and pathways of LCDD. This is useful for elucidating multitarget synergistic action for its clinical therapeutic efficacy.


Assuntos
Técnicas Biossensoriais/métodos , COVID-19/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Animais , Linhagem Celular Tumoral , Chalconas/farmacologia , Cricetulus , Medicamentos de Ervas Chinesas/análise , Efedrina/farmacologia , Células HEK293 , Humanos , Imunidade/efeitos dos fármacos , Inflamação/metabolismo , Pneumopatias/metabolismo , Músculo Liso/efeitos dos fármacos , Receptores Acoplados a Proteínas G/metabolismo , Respiração/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
14.
Front Psychol ; 12: 619657, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393873

RESUMO

Previous research about organizational citizenship behavior (OCB) and counterproductive work behavior (CWB) has produced contradictory results. Drawing from the conservation of resources (COR) theory, the present study tries to explain the contradictory findings by examining the curvilinear relationship between OCB and CWB. Using data collected at three time points from 426 employees and 110 supervisors in Chinese companies, data analysis shows that OCB has an inverted U-shaped relationship with CWB. The results also demonstrate that citizenship fatigue mediates the relationship between OCB and CWB, perceived organizational support (POS) moderates the relationship between OCB and citizenship fatigue. In addition, POS moderates the mediating effect of citizenship fatigue in the inverted U-shaped curvilinear relationship between OCB and CWB. This mediating effect is stronger under conditions of low POS than high POS. The findings present a complementary explanation of the conflicting relationships between OCB and CWB.

15.
Acupunct Med ; 39(6): 708-715, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34308662

RESUMO

BACKGROUND: Hyperalgesic priming (HP) is a model of the transition from acute to chronic pain. Electroacupuncture (EA) could inhibit pain development through the peripheral dorsal root ganglia; however, it is unclear whether it can mitigate the transition from acute to chronic pain by attenuating protein expression in the p38 MAPK (mitogen-activated protein kinase)/tumour necrosis factor alpha (TNF-α) pathway in the spinal dorsal horn. AIMS: We aimed to determine whether EA could prevent the transition from acute to chronic pain by affecting the p38 MAPK/TNF-α pathway in the spinal dorsal horn in a rat model established using HP. METHODS: We first randomly subdivided 30 male Sprague-Dawley (SD) rats into 5 groups (n = 6 per group): control (N), sham HP (Sham-HP), HP, HP + SB203580p38 MAPK (HP+SB203580), and HP + Lenalidomide (CC-5013) (HP+Lenalidomide). We then randomly subdivided a further 30 male SD rats into 5 groups (n = 6 per group): Sham-HP, HP, sham EA (Sham EA), EA (EA), and EA + U-46619 p38 MAPK agonist (EA+U-46619). We assessed the effects of EA on the mechanical paw withdrawal threshold and p38 MAPK/TNF-α expression in the spinal dorsal horn of rats subjected to chronic inflammatory pain. RESULTS: Rats in the EA group had reduced p38 MAPK and TNF-α expression and had significantly reduced mechanical hyperalgesia compared with rats in the other groups. CONCLUSION: Our findings indicate that EA could increase the mechanical pain threshold in rats and inhibit the transition from acute pain to chronic pain. This mechanism could involve reduced p38 MAPK/TNF-α expression in the spinal dorsal horn.

16.
Leuk Res ; 109: 106638, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34116372

RESUMO

Cytoplasmic vacuoles, which are a morphological feature of dysplasia, can be observed under a microscope at initial diagnosis. Recently, this typical morphological feature has been found to be associated with impaired survival. To investigate the clinical significance of the grading of blasts with vacuoles in acute myeloid leukemia (AML), we retrospectively studied 152 patients newly diagnosed with non-M3 AML. The patients were categorized into three groups according to the percentage of blasts with vacuoles (>20 %, 11-20 %, 0-10 %). A high percentage of blasts with vacuoles (>20 %) was positively associated with the European Leukemia Net (2017-ELN) high-risk AML, a complex karyotype, TP53 and IDH1/2 mutations, and CD71 expression and negatively associated with the ELN low-risk category. Importantly, patients who had a higher percentage of blasts with vacuoles had a lower complete remission rate in response to first-cycle induction chemotherapy. The overall survival and event-free survival of patients who had a higher percentage of blasts with vacuoles were significantly shorter. Moreover, multivariate analysis showed that blast vacuolization was an independent high prognostic factor for AML. In conclusion, a higher percentage of leukemic blasts with vacuoles predicts worse outcomes in AML and may have potential as a prognostic marker.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Crise Blástica/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Quimioterapia de Indução/mortalidade , Leucemia Mieloide Aguda/mortalidade , Vacúolos/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Crise Blástica/patologia , Crise Blástica/terapia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
17.
Front Genet ; 12: 663617, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34108992

RESUMO

The cross-talk between tumor cells and the tumor microenvironment (TME) is an important factor in determining the tumorigenesis and progression of cervical cancer (CC). However, clarifying the potential mechanisms which trigger the above biological processes remains a challenge. The present study focused on immune-relevant differences at the transcriptome and somatic mutation levels through an integrative multi-omics analysis based on The Cancer Genome Atlas database. The objective of the study was to recognize the specific immune-related prognostic factors predicting the survival and response to immunotherapy of patients with CC. Firstly, eight hub immune-related prognostic genes were ultimately identified through construction of a protein-protein interaction network and Cox regression analysis. Secondly, 32 differentially mutated genes were simultaneously identified based on the different levels of immune infiltration. As a result, an immune gene-related prognostic model (IGRPM), including six factors (chemokine receptor 7 [CCR7], CD3d molecule [CD3D], CD3e molecule [CD3E], and integrin subunit beta 2 [ITGB2], family with sequence similarity 133 member A [FAM133A], and tumor protein p53 [TP53]), was finally constructed to forecast clinical outcomes of CC. Its predictive capability was further assessed and validated using the Gene Expression Omnibus validation set. In conclusion, IGRPM may be a promising prognostic signature to predict the prognoses and responses to immunotherapy of patients with CC. Moreover, the multi-omics study showed that IGRPM could be a novel therapeutic target for CC, which is a promising biomarker for indicating the immune-dominant status of the TME and revealing the potential mechanisms responsible for the tumorigenesis and progression of CC.

18.
Eur Radiol ; 31(12): 9131-9138, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34109487

RESUMO

OBJECTIVE: To predict early intracerebral haemorrhage expansion (HE) by comprehensive evaluation of commonly used noncontrast computed tomography (NCCT) features. METHODS: Two hundred eighty-eight patients who had a spontaneous intracerebral haemorrhage (ICH) were included. All of the patients had undergone baseline NCCT within 6 h after ICH symptom onset. Ten NCCT features were extracted. Univariate analysis and multivariable logistic regression analysis were used to select the features. Using the finally selected features, a logistic regression model was built with a training cohort (n = 202) and subsequently validated in an independent test cohort (n = 86). Additionally, stratification analysis was performed in cases with and without anticoagulant therapy. RESULTS: HE was found in 78 patients (27.1%). The blend sign and black hole sign were finally selected. The logistic regression model built with the two features exhibited accuracies of 76.7% and 75.6%, specificities of 98.6% and 98.4%, and positive predictive values (PPVs) of 83.3% and 75.0% for the training and test cohorts, respectively. The model also showed specificities of 100% and 98.5% and PPVs of 100% and 76.9% for the anticoagulant and non-anticoagulant drug use groups, respectively. These performances were better than those of each of the separate features. CONCLUSIONS: By comprehensive evaluation, the model comprising the blend sign and black hole sign showed good performance for predicting early intracerebral haemorrhage expansion, particularly for high specificity and PPV, regardless of the anticoagulant status. KEY POINTS: • Early identification of patients who are more likely to have haematoma expansion is important for therapeutic intervention. • Many radiological features have been reported to correlate with intracerebral haemorrhage expansion. • By integrating only the blend sign and black hole sign, the logistic regression model showed good performance for predicting early intracerebral haemorrhage expansion.


Assuntos
Hemorragia Cerebral , Hematoma , Hemorragia Cerebral/diagnóstico por imagem , Progressão da Doença , Humanos , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X
19.
J Hypertens ; 39(9): 1918-1925, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34039913

RESUMO

BACKGROUND: Adrenal vein sampling (AVS) is recommended for discriminating patients with unilateral primary aldosteronism from bilateral disease. However, it is a technically demanding procedure that is markedly underused. We developed a computed tomography image fusion, coaxial guidewire technique, fast intraprocedural cortisol testing (CCF) technique to improve AVS success rate, which combines CT image fusion, coaxial guidewire technique, and fast intraprocedural cortisol testing. OBJECTIVE: To evaluate the effectiveness and safety of the AVS--CCF technique. METHODS: We retrospectively evaluated 105 patients who undervent AVS from June 2016 to October 2020. There were 51 patients in the AVS--CCF group and 54 patients in the AVS group. We compared two groups with technical success rate, procedure time, radiation exposure, volume of contrast medium, and complications (adrenal vein rupture, dissection, infarction, or thrombosis; intraglandular or periadrenal hematoma; and contrast-induced nephropathy). RESULTS: The technical success rate was higher for AVS--CCF than for AVS without CCF (98 vs. 83.3% for bilateral adrenal veins, P = 0.016). AVS--CCF was associated with a shorter procedure time (63.6 ±â€Š24.6 vs. 94.8 ±â€Š40.8 min, P < 0.001), shorter fluoroscopy time (15.6 ±â€Š12.6 vs. 20.4 ±â€Š15.0 min, P = 0.043), and lower contrast medium volume (25.10 ±â€Š21.82 vs. 44.1 ±â€Š31.0 ml, P < 0.001). There were no significant differences between groups with respect to the time for cannulating the left or right adrenal vein or the peak skin radiation dose. Adrenal vein rupture occurred in 14 patients and intraglandular hematoma in 1 patient. CONCLUSION: The CCF technique during AVS not only contributed to improved technical success rates but also associated with decreased procedure time, radiation exposure, and contrast medium volume.


Assuntos
Hiperaldosteronismo , Exposição à Radiação , Glândulas Suprarrenais , Aldosterona , Humanos , Hidrocortisona , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
20.
Cancer Manag Res ; 13: 4135-4146, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34045900

RESUMO

Background: Hemorrhagic complications are the most common cause of early death in patients with APL and remain a major challenge in the management of APL. Early fatal bleeding events occur not only in high-risk but also in non-high-risk acute promyelocytic leukemia (APL) patients with normal or low WBC counts. Objectives and Methods: To demonstrate the role of the absolute number of circulating leukemic cells in early bleeding events in APL patients. Clinical and laboratory characteristics of 149 patients newly diagnosed with APL were obtained from medical records and retrospectively investigated. Results: In this study, circulating absolute leukemic cells were positively correlated with the WBC count (r=0.9813, p<0.001) in all patients with APL, and importantly, they were strongly associated with significant bleeding events in non-high-risk patients. Multivariate logistic regression analysis showed that the absolute number of leukemia cells was an independent risk factor for significant bleeding events in APL patients. A cut-off value of 2.59×109/L for circulating leukemic cells to predict significant bleeding events in APL patients was obtained by ROC curve analysis. We further confirmed that the significant bleeding rate of patients with non-high-risk APL was statistically increased when the absolute number of circulating leukemic cells was ≥2.59×109/L. Conclusion: Circulating leukemic cell content has great clinical value for predicting early bleeding events in APL patients, especially in non-high-risk APL.

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