Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 908
Filtrar
1.
PeerJ ; 9: e12360, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34760376

RESUMEN

The Tapejarinae are edentulous pterosaurs that are relatively common in Cretaceous continental deposits in South America, North Africa, Europe, and China (mostly Early Cretaceous). The Chinese Jiufotang Formation is particularly rich in tapejarine specimens, having yielded over 10 described specimens and dozens of undescribed ones. For the Jiufotang Formation, a total of seven nominal tapejarid species and two genera have been proposed. Some debate exists over how many of those are valid or, alternatively, sexual or ontogenetic morphs of fewer (or even a single) species. Despite the abundance of specimens and the relevant taxonomic problems involved, detailed revisions of the matter are still lacking. This is partly due to the relatively scarce knowledge on the comparative osteology of the Sinopterus complex, which is hampered by the fact that most specimens have been only preliminarily described. In this contribution, we present a new postcranial specimen, D3072, which we attribute to the type-species of the genus, Sinopterus dongi. This new specimen helps shed some new light in the osteology of Sinopterus dongi, hopefully serving as a basis for future comparative studies involving further specimens and other proposed species and, subsequently, taxonomic revisions.

2.
Xenobiotica ; : 1-48, 2021 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-34761729

RESUMEN

1. MAK683 (N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-8-(2-methylpyridin-3-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine) is a potent and orally bioavailable EED inhibitor for the potential treatment in oncology. Pharmacokinetics (PK) in preclinical species are characterized by low to moderate plasma clearances, high oral exposure and moderate to high oral bioavailability at dose of 1-2 mg/kg.2. A species comparison of the metabolic pathways of MAK683 has been made using [14C]MAK683 incubations with liver microsomes and hepatocytes from rat, dog, cynomolgus monkey and human. Overall, the in vitro hepatic metabolism pathway of MAK683 in all five species was very complex. A total of 60 metabolites with 19 metabolites greater than 1.5% of the total integrated area in the radiochromatogram of at least one species were identified in five species (rat, mouse, dog, monkey and human).3. The primary in vitro hepatic oxidative metabolism pathway identified in human involved 2-hydroxylation of the dihydrofuran ring to form an alcohol (M28), which was in a chemical equilibrium favoring the formation of its aldehyde form. The aldehyde was then oxidized to the carboxylic acid metabolite (M26) or reduced to the O-hydroxyethylphenol (M29). N-dealkylation (M1), 3-hydroxylation of the dihydrofuran ring (M27), N-oxidation of the pyridine moiety (M53) and sulfate conjugation of M28 to form M19 were also important biotransformation pathways in human hepatocytes. The above major human hepatic metabolic pathways were also observed across the animal species (rat, mouse, dog and monkey) mostly providing precursors for the formation of other metabolites via further oxygenation, glucuronidation, and sulfation pathways.4. No human specific metabolites were observed. In addition, in-vivo biotransformation was also conducted in bile-duct cannulated (BDC) rat. The metabolism in BDC rat was similar to these observed the in vitro hepatocytes.

3.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5123-5129, 2021 Oct.
Artículo en Chino | MEDLINE | ID: mdl-34738410

RESUMEN

The systematic collation and mining of ethnic medicine literature is the key to the screening and textual research of classic prescriptions. This study focused on the textual research of such key issues as the source of prescriptions, the translation of minority languages into Chinese characters and their corresponding medical terms, the original plants of drugs, and the standard dosage. It is believed that the methods and experience of textual research of classic prescriptions in traditional Chinese medicine(TCM) can be utilized by the ethnic medicine. At the same time, the prominent problems unique to ethnic medicine cannot be neglected.(1)Attention should be paid to extraterritorial traditional medical literature in the textual research of the source of prescriptions. For instance, Indian medical literature is the source of many classic prescriptions in Tibetan medicine, Ibn Sina's Canon of Medicine the source of those in Uygur and Hui medicine, and ancient Indian Buddhist classics the source of those in Dai medicine.(2)The translation and comparison of medical terms in different language systems requires the cooperation of linguists, historians, and medical experts, the combination of historical research, historical linguistics and clinical research methods, and the use of cross-language comparison. In recent years, the related research achievements like multiple translated and annotated versions of classical literature in ethnic medicine and their respective terminology standards have been constantly emerging.(3)In textual research of the original plants of drugs, the following two points deserve attention: one is that the same drug is used in different ethnic medical systems, but there are differences in the understanding of drug properties and active parts; the other is that the original plants of the same drug vary in different ethnic medical systems.(4)The derivation of some classic prescriptions in ethnic medicine from foreign classics results in the difference among measurement systems. In addition, the detailed dosage fails to be covered in some ethnic literature, so the dosage standard should be determined depending on clinical practice and expert consensus.


Asunto(s)
Medicamentos Herbarios Chinos , Medicina China Tradicional , Medicina Tradicional Tibetana , Prescripciones , Publicaciones
4.
Mol Neurobiol ; 2021 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-34796463

RESUMEN

A common phenomenon called social buffering (SB), communication within conspecific animals is a benefit for a stressed individual to better recover from aversive events, is crucial to all mammals. Although the dopamine reward system has been implicated in SB, it is not clear which neuronal populations are relevant and how they contribute. Here, we adopted a learned helplessness (LH) animal model of depression and found that LH subjects housed with a conspecific partner show better performance in the shuttle box test, showing that SB improves the stress-coping abilities to deal with stress. Bidirectional manipulation of ventral tegmental area (VTA) dopamine neurons by chemogenetic tools can mimic or block the SB effect in LH mice. To screen for SB-induced structure plasticity of VTA dopamine neurons, we employed viral genetic tools for mapping input and output architecture and found LH- and SB-triggered circuit-level changes in neuronal ensembles. Zona incerta (ZI), an overlapping brain region, was significantly changed in both anterograde and retrograde tracing during LH and SB. These results reveal a neural loop with structural plasticity between VTA dopamine neurons and ZI underlies the SB effects in LH and lays a foundation for studying how VTA dopamine neurons regulate SB-related neural circuits.

5.
Chin Med J (Engl) ; 134(22): 2656-2665, 2021 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-34759230

RESUMEN

OBJECTIVE: Cardiovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with cardiovascular agents decreases or increases this risk. The effects of drugs on individual usage are also often unknown. This review aimed to examine the correlation between depression and common cardiovascular drugs, develop more potent interventions for depression in cardiovascular patients, and further research on the bio-behavioural mechanisms linking cardiovascular drugs to depression. DATA SOURCES: The data in this review were obtained from articles included in PubMed, EMBASE, and Web of Science. STUDY SELECTION: Clinical trials, observational studies, review literature, and guidelines about depression and cardiovascular drugs were selected for the article. RESULTS: We systematically investigated whether the seven most used cardiovascular drugs were associated with altered risk of incident depression in this literature review. Statins have been proven to have antidepressant effects. Some studies believe angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARB) can exert an antidepressant influence by acting on the renin-angiotensin system, but further clinical trials are needed to confirm this. Beta-blockers have previously been associated with depression, but the current study found no significant association between beta blockers and the risk of depression. Aspirin may have antidepressant effects by suppressing the immune response, but its role as an antidepressant remains controversial. calcium channel blockers (CCBs) can regulate nerve signal transduction by adjusting calcium channels, but whether this effect is beneficial or harmful to depression remains unclear. Finally, some cases have reported that nitrates and diuretics are associated with depression, but the current clinical evidence is insufficient. CONCLUSIONS: Statins have been proven to have antidepressant effect, and the antidepressant effects of ACEIs/ARB and aspirin are still controversial. CCBs are associated with depression, but it is unclear whether it is beneficial or harmful. No association has been found with ß-blockers, diuretics, and nitrates.

6.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(5): 534-537, 2021 Sep.
Artículo en Chino | MEDLINE | ID: mdl-34816668

RESUMEN

Objective: To investigate the effects of Sitagliptin on myocardial remodeling and autophagy in diabetic mice and its possible mechanisms. Methods: C57 mice aged ten weeks were treated with streptozocin (STZ) at the dose of 50 mg/(kg·d) by intraperitoneal injections for five consecutive days, and the level of fasting blood glucose concentration was higher than 16.7 mmol/l after seven days indicated that the diabetic model was established successfully. Mice were divided into four groups, including control group (n=10) which was intraperitoneally injected with the same volum of saline, the model group (n=8), Sitagliptin treatment group(diabetic mice were treated with Sitagliptin at the dose of 10 mg/(kg·d)by gavage, n=8) and the inhibitor group(diabetic mice were treated with Compound C, an AMPK inhibitor, at the dose of 10 mg/(kg·d) by intraperitoneal injection, n=8). After six weeks, all the mices were weighted and then put to death and the hearts were separated to caculate ventricular /body weight ratio. Hemaloxylin-Eosin (HE) staining was used to observe the cell morphology and masson staining was used to observe interstitial fibrosis. Western blot was used to test the heart protein expressions of Connexin43(Cx43), adenosine 5'-monophosphate -activated protein kinase (AMPK), brain natriuretic peptide(BNP), transforming growth factor(TGF-ß) and LC3B. Results: After six weeks of treatment, compared with control group, the ventricular /body weight ratio was improved (P<0.05), The cardiomyocyte hypertrophy and increased fibrosis were observed in the model group. The expression levels of BNP and TGF-ß were increased, while the expression levels of Cx43,LC3B and AMPK were decreased significantly(P<0.05). However, compared with model group, treatment with Sitagliptin decreased BNP, TGF-ß protein levels and increased Cx43 and LC3B protein levels, while Compound C could inhibit the upregulation of Cx43, LC3B and AMPK protein (P<0.05). Conclusion: Sitagliptin could improve cardiac hypertrophy and decrease interstitial fibrosis and AMPK-related signaling pathways was involved in the regulation of Cx43 and autophagy.


Asunto(s)
Diabetes Mellitus Experimental , Fosfato de Sitagliptina , Animales , Autofagia , Diabetes Mellitus Experimental/tratamiento farmacológico , Ratones , Miocardio , Fosfato de Sitagliptina/farmacología , Estreptozocina
7.
Cell Prolif ; : e13158, 2021 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-34811833

RESUMEN

OBJECTIVES: Evidences demonstrate that sorafenib alleviates liver fibrosis via inhibiting HSC activation and ECM accumulation. The underlying mechanism remains unclear. Ferroptosis, a novel programmed cell death, regulates diverse physiological/pathological processes. In this study, we aim to investigate the functional role of HSC ferroptosis in the anti-fibrotic effect of sorafenib. MATERIALS AND METHODS: The effects of sorafenib on HSC ferroptosis and ECM expression were assessed in mouse model of liver fibrosis induced by CCl4 . In vitro, Fer-1 and DFO were used to block ferroptosis and then explored the anti-fibrotic effect of sorafenib by detecting α-SMA, COL1α1 and fibronectin proteins. Finally, HIF-1α siRNA, plasmid and stabilizers were applied to assess related signalling pathway. RESULTS: Sorafenib attenuated liver injury and ECM accumulation in CCl4 -induced fibrotic livers, accompanied by reduction of SLC7A11 and GPX4 proteins. In sorafenib-treated HSC-T6 cells, ferroptotic events (depletion of SLC7A11, GPX4 and GSH; accumulation iron, ROS and MDA) were discovered. Intriguingly, these ferroptotic events were not appeared in hepatocytes or macrophages. Sorafenib-elicited HSC ferroptosis and ECM reduction were abrogated by Fer-1 and DFO. Additionally, both HIF-1α and SLC7A11 proteins were reduced in sorafenib-treated HSC-T6 cells. SLC7A11 was positively regulated by HIF-1α, inactivation of HIF-1α/SLC7A11 pathway was required for sorafenib-induced HSC ferroptosis, and elevation of HIF-1α could inhibit ferroptosis, ultimately limited the anti-fibrotic effect. CONCLUSIONS: Sorafenib triggers HSC ferroptosis via HIF-1α/SLC7A11 signalling, which in turn attenuates liver injury and fibrosis.

8.
Materials (Basel) ; 14(22)2021 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-34832291

RESUMEN

The appearance of the ε phase during the welding process can severely weaken the welding strength of dissimilar metals of Mg-Zn-Al alloy systems. An understanding of the accurate phase diagram, especially the equilibrium phase relation around the ε phase, is thus of particular importance. However, the phase interrelation near the ε-Mg23(Al, Zn)30 phase has not yet been fully studied. In this work, the local phase diagrams of the ε phase and its surrounding phases in the Mg-Zn-Al system are systematically determined by experimental investigation and thermodynamic verification. Five Mg-Zn-Al alloys and one diffusion couple were fabricated and analyzed to get accurate phase constituents and relationships adjacent to ε phase. The current experimental data obtained from Scanning Electron Microscope (SEM), X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), and Electron Probe Micro Analysis (EPMA) were further compared with the thermodynamically computed phase relations around ε phase for verification, showing good agreements. Several important conclusions are drawn based on current experimental work, which can provide supporting information for the follow-up studies on ε phase in the Mg-Zn-Al alloy systems.

9.
Nanoscale ; 13(44): 18507-18519, 2021 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-34730159

RESUMEN

As important artificial photosynthesis, the construction of core-shell heterojunction materials is considered to be one of the effective strategies for designing highly active photocatalysts. Here, the Step-scheme (S-scheme) heterojunction photocatalyst is firmly grown by in situ phosphating. The calcination method uses MoO3 nanoparticles as the substrate, and the surface of MoO3 is phosphatized and etched gradually from the outside to the inside using the phosphine gas. The introduced phosphorus atoms can replace MoO3 oxygen atoms to form Mo-P bonds to generate molybdenum phosphide. The interface interaction dominated by chemical bonds has a stronger interface interaction force, which can promote the interface charge transfer leading to optimizing the MoP@MoO3 core-shell composite material, adjusting the quality of sodium hypophosphite, and phosphating MoO3 to varying degrees, producing the best hydrogen production H2 evolution rate is 10 000.02 µmol h-1 g-1. Density functional theory (DFT) calculations and a series of experiments were used to determine the S-scheme charge transfer mechanism in MoP@MoO3. This design provides a new idea for the introduction of surface-active sites and the construction of mixed anion photocatalysts. At the same time, a new design scheme is provided for the in situ construction of S-scheme interface heterojunction materials.

10.
MedComm (Beijing) ; 2(3): 297-314, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34766148

RESUMEN

As key performers in intercellular communication, exosomes released by tumor cells play an important role in cancer development, including angiogenesis, cancer-associated fibroblasts activation, epithelial-mesenchymal transformation (EMT), immune escape, and pre-metastatic niche formation. Meanwhile, other cells in tumor microenvironment (TME) can secrete exosomes and facilitate tumor progression. Elucidating mechanisms regarding these processes may offer perspectives for exosome-based antitumor strategies. In this review, we mainly introduce the versatile roles of tumor or stromal cell derived exosomes in cancer development, with a particular focus on the biological capabilities and functionalities of their diverse contents, such as miRNAs, lncRNAs, and circRNAs. The potential clinical application of exosomes as biomarkers in cancer diagnosis and prognosis is also discussed. Finally, the current antitumor strategies based on exosomes in immunotherapy and targeted delivery for chemotherapeutic or biological agents are summarized.

11.
Front Pharmacol ; 12: 750857, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34630121

RESUMEN

Gliomas are the most common primary tumors of the central nervous system. Due to the existence of the blood-brain barrier and its unique regional immune characteristics, the study of the immune microenvironment of gliomas is particularly important. Glioma stem cells are an important cause of initiating glioma, promoting tumor progression and leading to tumor recurrence. Immunotherapeutic strategies targeting glioma stem cells have become the focus of current research. This paper will focus on the research progress of glioma stem cells in the immune microenvironment of glioma to provide the basis for the immunotherapy of glioma.

12.
Adv Sci (Weinh) ; : e2102653, 2021 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-34716691

RESUMEN

The Hippo pathway effector TAZ promotes cellular growth, survival, and stemness through regulating gene transcription. Recent studies suggest that TAZ liquid-liquid phase separation (LLPS) compartmentalizes key cofactors to activate transcription. However, how TAZ LLPS is achieved remains unknown. Here, it is shown that the paraspeckle protein NONO is required for TAZ LLPS and activation in the nucleus. NONO is a TAZ-binding protein. Their interaction shows temporal regulation parallel to the interaction between TAZ and TEAD as well as to the expression of TAZ target genes. NONO depletion reduces nuclear TAZ LLPS, while ectopic NONO expression promotes the LLPS. Accordingly, NONO depletion reduces TAZ interactions with TEAD, Rpb1, and enhancers. In glioblastoma, expressions of NONO and TAZ are both upregulated and predict poor prognosis. Silencing NONO expression in an orthotopic glioblastoma mouse model inhibits TAZ-driven tumorigenesis. Together, this study suggests that NONO is a nuclear factor that promotes TAZ LLPS and TAZ-driven oncogenic transcriptional program.

13.
Front Public Health ; 9: 710810, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34604156

RESUMEN

Elite hospitals represent the highest level of Chinese hospitals in medical service and management, medical quality and safety, technical level and efficiency, which are also one of the important indicators reflecting high-quality medical resources in the region, and their spatial allocation is directly related to the fairness of health resource allocation. We explored the allocation pattern of high-quality resources and its influencing factors in the development of China's health system using geographic weighted regression (GWR), Multi-scale Geographically Weighted Regression (MGWR), GWR and MGWR with Spatial Autocorrelation(GWR-SAR and MGWR-SAR), spatial lag model (SLM), and spatial error model (SEM). The results of OLS regression showed that city level, number of medical colleges, urbanization rate, permanent population and GDP per capita were its significant variables. And spatial auto-correlation of elite hospitals in China is of great significance. Further, its spatial agglomeration phenomenon was confirmed through SLM and SEM. Among them, the city level is the most important factor affecting the spatial allocation of elite hospitals in China. Its action intensity shows a solid and weak mosaic trend in the Middle East, relatively concentrated in some areas with medium intensity and concentrated in the West China. Obviously, China's elite hospitals are unevenly distributed and have evident spatial heterogeneity. Therefore, we suggest that we should pay attention to the spatial governance of high-quality medical resources, attract medical elites in the region, increase investment in medical education in the scarce areas of elite hospitals and develop tele-medicine service.


Asunto(s)
Regresión Espacial , Urbanización , China , Ciudades , Hospitales
14.
J Mol Med (Berl) ; 2021 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-34698870

RESUMEN

Development and progression of many kidney diseases are substantially influenced by aberrant protein acetylation modifications of gene expression crucial for kidney functions. Histone deacetylase (HDAC) expression alterations are detected from renal samples of patients and animal models of various kidney diseases, and the administrations of HDAC inhibitors display impressive renal protective effects in vitro and in vivo. However, when the expression alterations of multiple HDACs occur, not all the HDACs causally affect the disease onset or progression. Identification of a single HDAC as a disease-causing factor will allow subtype-targeted intervention with less side effect. HDAC3 is a unique HDAC with distinct structural and subcellular distribution features and co-repressor dependency. HDAC3 is required for kidney development and its aberrations actively participate in many pathological processes, such as cancer, cardiovascular diseases, diabetes, and neurodegenerative disorders, and contribute significantly to the pathogenesis of kidney diseases. This review will discuss the recent studies that investigate the critical roles of HDAC3 aberrations in kidney development, renal aging, renal cell carcinoma, renal fibrosis, chronic kidney disease, polycystic kidney disease, glomerular podocyte injury, and diabetic nephropathy. These studies reveal the distinct characters of HDAC3 aberrations that act on different molecules/signaling pathways under various renal pathological conditions, which might shed lights into the epigenetic mechanisms of renal diseases and the potentially therapeutic strategies.

15.
Front Genet ; 12: 722064, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34659343

RESUMEN

Background: Acute myeloid leukemia (AML) is one of the most common cancers in the world, and oxidative stress is closely related to leukemia. A lot of effort has been made to improve the prognosis of AML. However, the situation remains serious. Hence, we focused on the study of prognostic genes in AML. Materials and Methods: Prognostic oxidative stress genes were screened out. The gene expression profile of AML patients was downloaded from the The Cancer Genome Atlas (TCGA) database. The oxidative stress-related model was constructed, by which the prognosis of AML patients was predicted using the two GEO GSE23143 datasets and the stability of the GSE71014 authentication model. Results: The prognostic oxidative stress genes were screened out in AML, and the prognostic genes were significantly enriched in a large number of pathways based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. There was a complex interaction between prognostic genes and transcription factors. After constructing the prediction model, the clinical predictive value of the model was discussed in a multi-omic study. We investigated the sensitivity of risk score to common chemotherapeutic agents, the influence of signaling pathways on the prognosis of AML patients, and the correlation of multiple genes with immune score and immune dysfunction. Conclusions: A highly effective prognostic risk model for AML patients was established and validated. The association of prognostic oxidative stress genes with drug sensitivity, signaling pathways, and immune infiltration was explored. The results suggested that oxidative stress genes promised to be potential prognostic biomarkers for AML, which may provide a new basis for disease management.

16.
Int J Mol Sci ; 22(19)2021 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-34638868

RESUMEN

Mechanical unloading contributes to significant cardiovascular deconditioning. Endothelial dysfunction in the sites of microcirculation may be one of the causes of the cardiovascular degeneration induced by unloading, but the detailed mechanism is still unclear. Here, we first demonstrated that mechanical unloading inhibited brain microvascular endothelial cell proliferation and downregulated histone deacetylase 6 (HDAC6) expression. Furthermore, HDAC6 promoted microvascular endothelial cell proliferation and attenuated the inhibition of proliferation caused by clinorotation unloading. To comprehensively identify microRNAs (miRNAs) that are regulated by HDAC6, we analyzed differential miRNA expression in microvascular endothelial cells after transfection with HDAC6 siRNA and selected miR-155-5p, which was the miRNA with the most significantly increased expression. The ectopic expression of miR-155-5p inhibited microvascular endothelial cell proliferation and directly downregulated Ras homolog enriched in brain (RHEB) expression. Moreover, RHEB expression was downregulated under mechanical unloading and was essential for the miR-155-5p-mediated promotion of microvascular endothelial cell proliferation. Taken together, these results are the first to elucidate the role of HDAC6 in unloading-induced cell growth inhibition through the miR-155-5p/RHEB axis, suggesting that the HDAC6/miR-155-5p/RHEB pathway is a specific target for the preventative treatment of cardiovascular deconditioning.


Asunto(s)
Proliferación Celular , Células Endoteliales/metabolismo , Regulación de la Expresión Génica , Histona Desacetilasa 6/metabolismo , MicroARNs/biosíntesis , Microvasos/metabolismo , Proteína Homóloga de Ras Enriquecida en el Cerebro/metabolismo , Animales , Línea Celular , Células Endoteliales/citología , Ratones , Microvasos/citología
17.
Infect Drug Resist ; 14: 3949-3960, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34594118

RESUMEN

Purpose: Infection and transmission of carbapenem-resistant Aeromonas is a serious threat to public health. Rapid and accurate detection carbapenem-resistant of these organisms is essential for reasonable treatment and infection control. This study aimed to find a simple and effective method to detect carbapenem-resistant phenotype in Aeromonas. Methods: A total of 131 clinical preserved Aeromonas strains were used in this study. The carbapenemase genes were detected by PCR. Modified carbapenem inactivation method (mCIM) in conjunction with EDTA-modified carbapenem inactivation method (eCIM) and simplified carbapenem inactivation method (sCIM) were performed to detect carbapenemases. We also designed a simple method, carbapenem inactivation method using supernatant (CIM-s), to detect the carbapenemase activity in the medium. Results: Of the 131 Aeromonas strains, 79 contained carbapenemase genes, including 68 blaCphA , 6 blaKPC-2 , 2 blaNDM-1 and 3 blaKPC-2+CphA . However, routine antibiotic susceptibility testing could not completely identify carbapenemase-producing Aeromonas. In phenotypic assays, the sensitivity and specificity of mCIM were 100%. The combined mCIM and eCIM could distinguish serine carbapenemase and metallo-ß-carbapenemases except co-producing organisms. The sensitivity and specificity of sCIM were 92.4% and 100%, respectively, which could not detect CphA totally. CIM-s results indicate that these carbapenemases could secrete into the medium to perform their hydrolytic activities and had a sensitivity and specificity of 97.5% and 100%, respectively. Conclusion: The combination of mCIM and eCIM can effectively detect and distinguish different types of carbapenemase in Aeromonas, and could be used as an important supplement approach to the antibiotic susceptibility testing.

18.
Biomed Res Int ; 2021: 5507003, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34595237

RESUMEN

Lonicerae japonicae flos (LJF) is widely used for the treatment of inflammation-related diseases in traditional Chinese medicine (TCM). To clarify the anti-inflammatory mechanism of LJF, 29 compounds with high content in LJF were selected for network pharmacology. Then, a comprehensive network pharmacology strategy was implemented, which involved compound-inflammation-target construction, protein-protein interaction (PPI) network analysis, and enrichment analysis. Finally, molecular docking and in vitro experiments were performed to verify the anti-inflammatory activity and targets of the key compound. As a result, 279 inflammation-associated proteins were identified, which are mainly involved in the AGE/RAGE signaling pathway in diabetic complications, the HIF-1 signaling pathway, the PI3K-AKT signaling pathway, and EGFR tyrosine kinase inhibitor resistance. A total of 12 compounds were linked to more than 35 targets, including apigenin, kaempferol, quercetin, luteolin, and ferulic acid. The results of molecular docking showed that AKT has the most binding activity, exhibiting certain binding activity with 10 compounds, including vanillic acid, protocatechuic acid, secologanic acid, quercetin, and luteolin; the results of qRT-PCR and WB confirmed that two key compounds, secologanic acid and luteolin, could significantly decrease the secretion of TNF-α and the AKT expression of RAW264.7 murine macrophages stimulated by LPS (lipopolysaccharide). These results demonstrate that the comprehensive strategy can serve as a universal method to illustrate the anti-inflammatory mechanisms of traditional Chinese medicine by identifying the pathways or targets.

19.
Medicine (Baltimore) ; 100(43): e27605, 2021 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-34713838

RESUMEN

ABSTRACT: The objective of our study is to investigate mortality pattern and quantitatively assess prognostic risk for cause-specific death among T1-2N0M0 breast cancer survivors.The representative data of T1-2N0M0 breast cancer patients diagnosed between 2010 and 2016 was retrieved from the Surveillance, Epidemiology, and End Results program. Standardized mortality ratios (SMRs) were calculated taking US population as a reference. Cox regression analysis was conducted to analyze the potential prognostic factors for cause-specific mortality.A total of 161,966 patients were identified from the Surveillance, Epidemiology, and End Results database. After a median follow-up of 41 months, mortality occurred in 10,567 patients, of which 30.9% and 22.7% were attributed to breast cancer and cardiovascular diseases (CVDs). The standardized mortality ratios of CVD were 4.78, 4.27, 3.78, and 4.95 in patients with HR+/HER2+, HR-/HER2+, HR+/HER2-, and HR-/HER2- breast cancer compared to general US population, respectively. Cox proportional hazards regression analysis showed that the adjusted HRs of breast cancer-specific mortality were 0.999 (95% confidence interval [CI]: 0.879-1.135), 1.454 (95% CI: 1.246-1.697), 2.145 (95% CI: 1.962-2.345) for HR+/HER2+, HR-/HER2+, and HR-/HER2- breast cancer, respectively, as compared with HR+/HER2- subtype; HRs of CVD-specific death were 1.215 (95% CI: 1.041-1.418), 1.391 (95% CI: 1.209-1.601), and 1.515 (95% CI: 1.213-1.892), respectively. In addition, we found that older age at diagnosis, and black race were also independent predictors of CVD-specific death.In the present study, we revealed the mortality pattern of cause-specific mortality, and identified prognostic factors of overall mortality, breast cancer-specific mortality, and CVD-specific mortality in T1-2N0M0 breast cancer survivors, supporting early detection and more efficient CVD care for these patients.


Asunto(s)
Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Supervivientes de Cáncer/estadística & datos numéricos , Adulto , Factores de Edad , Edad de Inicio , Anciano , Anciano de 80 o más Años , Causas de Muerte , Grupos de Población Continentales/estadística & datos numéricos , Femenino , Humanos , Persona de Mediana Edad , Mortalidad/tendencias , Clasificación del Tumor , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Regresión , Programa de VERF
20.
Mol Clin Oncol ; 15(6): 257, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34712487

RESUMEN

An immunoscore for colorectal cancer (CRC) has higher prognostic significance than the TNM staging system. However, the tumor immune microenvironment contains various components that affect clinical prognosis. Therefore, a broader range of immune markers is required to establish an accurate immunoprofile to assess the prognosis of patients with CRC. Using immunohistochemistry combined with multispectral immunohistochemistry and objective assessments, the infiltration of four immune cell types (CD4+/CD8+/forkhead box p3+/CD33+ cells), as well as the expression of six co-signaling molecules [programmed cell death 1 (PD1) ligand 1/PD1/T-cell immunoglobulin mucin family member 3/lymphocyte-activating 3/tumor necrosis factor receptor superfamily, member 4/inducible T-cell costimulator] and indoleamine 2,3-dioxygenase 1 were investigated in two independent cohorts of CRC. The patients' overall survival (OS) was evaluated using the Kaplan-Meier method. Using the Cox proportional hazards model, independent prognostic factors of patients were assessed and a nomogram-based immunoprofile system was developed. The predictive ability of the nomogram was determined using a concordance index (C-index) and calibration curve. To facilitate clinical application, a simplified nomogram-based immunoprofile was constructed. Using receiver operating characteristic (ROC) analysis, the predictive accuracy for OS was compared between the immunoprofile and the TNM staging system for patients with stage II/III CRC. According to multivariate analysis for the primary cohort, independent prognostic factors for OS were CD8+ tumor-infiltrating lymphocytes, CD33+ myeloid-derived suppressor cells and TNM stage, which were included in the nomogram. The C-index of the nomogram for predicting OS was 0.861 (95% CI: 0.796-0.925) for the internal validation and 0.759 (95% CI: 0.714-0.804) for the external validation cohort. The simplified nomogram-based immunoprofile system was able to separate same-stage patients into different risk subgroups, particularly for TNM stage II (P<0.0001) and III (P=0.0002) patients. Pairwise comparison of ROC curves for the immunoprofile and TNM stage systems for patients with stage II/III CRC revealed statistically significant differences (P=0.046) and the Z-statistic value was 1.995. In conclusion, the nomogram-based immunoprofile system provides prognostic accuracy regarding clinical outcomes and is a useful supplement to the TNM staging system for patients with stage II/III CRC.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...