Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 284
Filtrar
1.
Neural Regen Res ; 17(1): 210-216, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34100458

RESUMO

In Alzheimer's disease and ischemic stroke, intranasal insulin can act as a neuroprotective agent. However, whether intranasal insulin has a neuroprotective effect in intracerebral hemorrhage and its potential mechanisms remain poorly understood. In this study, a mouse model of autologous blood-induced intracerebral hemorrhage was treated with 0.5, 1, or 2 IU insulin via intranasal delivery, twice per day, until 24 or 72 hours after surgery. Compared with saline treatment, 1 IU intranasal insulin treatment significantly reduced hematoma volume and brain edema after cerebral hemorrhage, decreased blood-brain barrier permeability and neuronal degeneration damage, reduced neurobehavioral deficits, and improved the survival rate of mice. Expression levels of p-AKT and p-GSK3ß were significantly increased in the perihematoma tissues after intranasal insulin therapy. Our findings suggest that intranasal insulin therapy can protect the neurological function of mice after intracerebral hemorrhage through the AKT/GSK3ß signaling pathway. The study was approved by the Ethics Committee of the North Sichuan Medical College of China (approval No. NSMC(A)2019(01)) on January 7, 2019.

2.
Nat Cancer ; 2: 978-993, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34738088

RESUMO

Multi-tyrosine kinase inhibitors (MTKIs) have thus far had limited success in the treatment of castration-resistant prostate cancer (CRPC). Here, we report a phase I-cleared orally bioavailable MTKI, ESK981, with a novel autophagy inhibitory property that decreased tumor growth in diverse preclinical models of CRPC. The anti-tumor activity of ESK981 was maximized in immunocompetent tumor environments where it upregulated CXCL10 expression through the interferon gamma pathway and promoted functional T cell infiltration, which resulted in enhanced therapeutic response to immune checkpoint blockade. Mechanistically, we identify the lipid kinase PIKfyve as the direct target of ESK981. PIKfyve-knockdown recapitulated ESK981's anti-tumor activity and enhanced the therapeutic benefit of immune checkpoint blockade. Our study reveals that targeting PIKfyve via ESK981 turns tumors from cold into hot through inhibition of autophagy, which may prime the tumor immune microenvironment in advanced prostate cancer patients and be an effective treatment strategy alone or in combination with immunotherapies.

3.
Investig Clin Urol ; 62(6): 641-649, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34729964

RESUMO

PURPOSE: Many studies identified that the preoperative neutrophil-to-lymphocyte ratio (PNLR) was associated with patient prognosis in non-muscle-invasive bladder cancer (NMIBC). We hypothesized that PNLR could be prognostic in patients with histological variants of NMIBC (VH-NMIBC). MATERIALS AND METHODS: This retrospective study included patients with VH-NMIBC admitted at our center between January 2009 and May 2019. The best cut-off value of NLR was measured by the receiver operating characteristic curve and Youden index. The Kaplan-Meier method and Cox proportional hazard regression models were employed to evaluate the association between PNLR and disease prognosis, including recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: A total of 243 patients with VH-NMIBC were enrolled in our study. According to the Kaplan-Meier method results, patients with PNLR ≥2.2 were associated with poor RFS (p<0.001), PFS (p<0.001), CSS (p<0.001), and OS (p<0.001). Multivariable analyses indicated that PNLR ≥ 2.2 was an independent prognostic factor of RFS (hazard ratio [HR], 2.11; 95% confidence interval [CI, 1.57-1.83; p<0.001), PFS (HR, 2.34; 95% CI, 1.70-3.21; p<0.001), CCS (HR, 2.87; 95% CI, 1.96-4.18; p< 0.001), and OS (HR, 2.83; 95% CI, 1.96-4.07; p<0.001). CONCLUSIONS: This study identified that PNLR ≥2.2 was usually associated with a poor prognosis for patients with VH-NMIBC.

4.
J Pharm Sci ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34597623

RESUMO

Pravastatin is currently under evaluation for prevention of preeclampsia. Factors contributing to placental disposition of pravastatin are important in assessment of potential undesirable fetal effects. The purpose of this study was to identify the uptake transporters that contribute to the placental disposition of pravastatin. Our data revealed the expression of organic anion transporting polypeptide 1A2 (OATP1A2) and OATP2A1 in the apical, and OATP2B1 and OATP5A1 in the basolateral membranes of the placenta, while organic anion transporter 4 (OAT4) exhibited higher expression in basolateral membrane but was detected in both membranes. Preloading placental membrane vesicles with glutarate increased the uptake of pravastatin suggesting involvement of glutarate-dependent transporters such as OAT4. In the HEK293 cells overexpressing individual uptake transporters, OATP2A1, OATP1A2 and OAT4 were determined to accept pravastatin as a substrate at physiological pH, while the uptake of pravastatin by OATP2B1 (known to interact with pravastatin at acidic pH) and OATP5A1 was not detected at pH 7.4. These findings led us to propose that OATP1A2 and OATP2A1 are responsible for the placental uptake of pravastatin from the maternal circulation, while OAT4 mediates the passage of the drug across placental basolateral membrane in the fetal-to-maternal direction.

5.
Oncotarget ; 12(18): 1859-1860, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34504658

RESUMO

[This corrects the article DOI: 10.18632/oncotarget.11877.].

6.
Magnes Res ; 34(2): 64-73, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34519648

RESUMO

This study aimed to determine the relationship between hospital-acquired dysmagnesemia and in-hospital mortality in critically ill patients. A retrospective cohort study was conducted on critically ill patients who had normal serum magnesium levels on admission. Data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III database. The normal range of serum magnesium was 1.6-2.6 mg/dL. In-hospital serum magnesium levels were categorized based on the occurrence of hospital-acquired hypomagnesemia and hypermagnesemia. Hospital-acquired hypomagnesemia and hypermagnesemia in the same patient were defined as a patient with the lowest level of serum magnesium of <1.6 mg/dL and the highest level of serum magnesium of >2.6 mg/dL, respectively. The in-hospital outcomes were collected. The findings revealed that 27.2% of patients developed hospital-acquired dysmagnesemia. In-hospital mortalities were 8.8% in patients with persistently normal serum magnesium levels, 12.2% in patients with hospital-acquired hypomagnesemia only, 18.4% in patients with hospital-acquired hypermagnesemia only, and 20.6% in patients with both hospital-acquired hypomagnesemia and hypermagnesemia. Compared to patients with persistently normal serum magnesium in hospital, those with hospital-acquired hypermagnesemia only [odds ratio (OR) = 1.346, P < 0.001] and those with both hospital-acquired hypomagnesemia and hypermagnesemia (OR = 1.333, P = 0.001) were significantly associated with higher in-hospital mortality. Hospital-acquired dysmagnesemia was common among critically ill patients. Hospital-acquired dysmagnesemia, especially hospital-acquired hypermagnesemia, was significantly associated with increased in-hospital mortality in critically ill patients.

7.
Materials (Basel) ; 14(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34500939

RESUMO

To study the dynamic plastic properties of high-purity molybdenum materials at high temperature and high strain rate, we designed tests to compare the mechanical behaviour of two high-purity molybdenum materials with different purities and two with different processing deformation conditions under dynamic impact compression in the temperature range of 297-1273 K. We analysed the molybdenum materials' sensitivities to the strain-hardening effect, strain rate-strengthening effect, and temperature-softening effect as well as the comprehensive response to the combined effect of the strain rate and temperature, the adiabatic impact process, and the microstructure at high temperature and high strain rate. Furthermore, based on a modified Johnson-Cook constitutive model, we quantitatively analysed the flow stresses in these materials. The calculation results strongly agree with the test results. Our findings indicate that the high-purity molybdenum materials show consistent sensitivity to the combined effect of strain rate and temperature regarding the dynamic plastic properties. The materials with higher purity are less sensitive to the combined effect of the strain rate and temperature, and those with less processing deformation experience more pronounced strain-hardening effects. Under high strain rate at room temperature, these materials are highly susceptible to impact embrittlement and decreases in dynamic plastic properties due to intergranular fracture in the internal microstructure. However, increasing the impact environment temperature can significantly improve their plastic properties. The higher the temperature, the better the plastic properties and the higher the impact toughness.

8.
Front Cell Dev Biol ; 9: 696619, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381778

RESUMO

Background: The use of medicinal plant ingredients is one of the goals of developing potential drugs for treating depression. Compelling evidence suggests that anti-inflammatory medicines may block the occurrence of depression. We studied the effect of a natural compound, emodin, on the development of psychosocial stress-induced depression and the underlying mechanisms. Methods: Chronic unpredicted mild stress (CUMS) for 7 weeks was performed to replicate psychosocial stress in rats. The sucrose preference test, force swimming test, and open field test were used to evaluate their behaviors. The differentially expressed proteins in the hippocampus were analyzed using proteomics. Nissl staining and Golgi staining were used to detect the loss of neurons and synapses, immunohistochemical staining was used to detect the activation of microglia, and the enzyme-linked immunosorbent assay was used to detect the levels of pro-inflammatory cytokines. Western blotting, immunofluorescence, and quantitative polymerase chain reaction were also performed. Results: Hippocampal inflammation with up-regulated 5-lipoxygenase (5-LO) was observed in the depressed rats after CUMS exposure. The upregulation of 5-LO was caused by decreased miR-139-5p. To observe the effect of emodin, we screened out depression-susceptible (DeS) rats during CUMS and treated them with emodin (80 mg/kg/day). Two weeks later, emodin prevented the depression behaviors in DeS rats along with a series of pathological changes in their hippocampi, such as loss of neurons and spines, microglial activation, increased interleukin-1ß and tumor necrosis factor-α, and the activation of 5-LO. Furthermore, we demonstrated that emodin inhibited its excess inflammatory response, possibly by targeting miR-139-5p/5-LO and modulating glycogen synthase kinase 3ß and nuclear factor erythroid 2-related factor 2. Conclusion: These results provide important evidence that emodin may be a candidate agent for the treatment of depression and established a key role of miR-139-5p/5-LO in the inflammation of depression.

9.
Phytomedicine ; 90: 153630, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34217968

RESUMO

BACKGROUND: Intracerebral hemorrhage (ICH), the most fatal subtype of stroke, has no disease-modifying treatment. Da-cheng-qi decoction (DCQ), composed of rhubarb, is one of the most commonly used Chinese traditional decoctions in ICH treatment. But the mechanism is not clear. Emodin is an active compound found in rhubarb. PURPOSE: To study the protective effects of DCQ on ICH and its possible mechanisms of action. METHODS: The ICH model was reproduced by injecting collagenase-VII into the left caudate putamen (CPu) of rats. DCQ and emodin were used to treat the ICH rats for 7 days. Behavior tests, proteomic analysis, morphological studies, and western blotting were performed. RESULTS: The neurological deficits in the ICH rats recovered with DCQ and emodin on the 14th day after ICH. The proteomics data revealed that DCQ significantly corrected the pathological signals in the CPu and hippocampus after ICH. The numbers of amoebic microglia in the CPu and M2 microglia in both CPu and hippocampus were significantly increased after DCQ and emodin treatment. The increase in GluN2B-containing NMDA receptor (NR2B) and postsynaptic density protein-95, activation of mitogen-activated protein kinase (MAPK) signals in the CPu, and secondary neurodegeneration (SND) in the hippocampus were significantly recovered in DCQ-treated rats. Inhibition of MAPK p38 (p38) in the hippocampus was observed after DCQ and emodin treatment. CONCLUSION: The protective effects of DCQ on ICH were confirmed in this study, and its mechanism may be related to the inhibition of MAPK and activation of M2 microglia. These results are beneficial to the development of ICH therapeutic targets.


Assuntos
Hemorragia Cerebral , Medicamentos de Ervas Chinesas , Emodina/farmacologia , Hipocampo/efeitos dos fármacos , Animais , Hemorragia Cerebral/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Proteômica , Ratos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
10.
Proc Natl Acad Sci U S A ; 118(25)2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34131077

RESUMO

Permafrost degradation may induce soil carbon (C) loss, critical for global C cycling, and be mediated by microbes. Despite larger C stored within the active layer of permafrost regions, which are more affected by warming, and the critical roles of Qinghai-Tibet Plateau in C cycling, most previous studies focused on the permafrost layer and in high-latitude areas. We demonstrate in situ that permafrost degradation alters the diversity and potentially decreases the stability of active layer microbial communities. These changes are associated with soil C loss and potentially a positive C feedback. This study provides insights into microbial-mediated mechanisms responsible for C loss within the active layer in degraded permafrost, aiding in the modeling of C emission under future scenarios.

11.
Aging (Albany NY) ; 13(11): 15078-15099, 2021 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-34051074

RESUMO

Depression is a complex neuropsychiatric disease involved multiple targets and signaling pathways. Systems pharmacology studies could potentially present a comprehensive molecular mechanism to delineate the anti-depressant effect of emodin (EMO). In this study, we investigated the anti-depressant effects of EMO in the chronic unpredictable mild stress (CUMS) rat model of depression and gained insights into the underlying mechanisms using systems pharmacology and molecular simulation analysis. Forty-three potential targets of EMO for treatment of depression were obtained. GO biological process analysis suggested that the biological functions of these targets mainly involve the regulation of reactive oxygen species metabolic process, response to lipopolysaccharide, regulation of inflammatory response, etc. KEGG pathway enrichment analysis showed that the PI3K-Akt signaling pathway, insulin resistance, IL-17 signaling pathway were the most significantly enriched signaling pathways. The molecular docking analysis revealed that EMO might have a strong combination with ESR1, AKT1 and GSK3B. Immunohistochemical staining and Western blotting showed that 2 weeks' EMO treatment (80 mg/kg/day) reduced depression related microglial activation, neuroinflammation and altered PI3K-Akt signaling pathway. Our findings provide a systemic pharmacology basis for the anti-depressant effects of EMO.


Assuntos
Antidepressivos/farmacologia , Emodina/farmacologia , Animais , Antidepressivos/uso terapêutico , Comportamento Animal , Depressão/complicações , Depressão/tratamento farmacológico , Emodina/química , Emodina/uso terapêutico , Ontologia Genética , Genoma , Inflamação/patologia , Masculino , Microglia/patologia , Simulação de Acoplamento Molecular , Neurônios/metabolismo , Neurônios/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Córtex Pré-Frontal/patologia , Mapeamento de Interação de Proteínas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Transdução de Sinais , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológico
12.
Cell Metab ; 33(6): 1171-1186.e9, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33951476

RESUMO

Antihyperglycemic therapy is an important priority for the treatment of type 2 diabetes (T2D). Excessive hepatic glucose production (HGP) is a major cause of fasting hyperglycemia. Therefore, a better understanding of its regulation would be important to develop effective antihyperglycemic therapies. Using a gluconeogenesis-targeted kinome screening approach combined with transcriptome analyses, we uncovered Nemo-like kinase (NLK) as a potent suppressor of HGP. Mechanistically, NLK phosphorylates and promotes nuclear export of CRTC2 and FOXO1, two key regulators of hepatic gluconeogenesis, resulting in the proteasome-dependent degradation of the former and the inhibition of the self-transcriptional activity and expression of the latter. Importantly, the expression of NLK is downregulated in the liver of individuals with diabetes and in diabetic rodent models and restoring NLK expression in the mouse model ameliorates hyperglycemia. Therefore, our findings uncover NLK as a critical player in the gluconeogenic regulatory network and as a potential therapeutic target for T2D.

13.
Mod Pathol ; 34(8): 1596-1607, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33854184

RESUMO

Microphthalmia-associated transcription factor (MiT) family aberration-associated renal cell carcinoma (MiTF-RCC) is a subtype of renal cell carcinoma harboring recurrent chromosomal rearrangements involving TFE3 or TFEB genes. MiTF-RCC is morphologically diverse, can histologically resemble common RCC subtypes like clear cell RCC and papillary RCC, and often poses a diagnostic challenge in genitourinary clinical and pathology practice. To characterize the MiTF-RCC at the molecular level and identify biomarker signatures associated with MiTF-RCC, we analyzed RNAseq data from MiTF-RCC, other RCC subtypes and benign kidney. Upon identifying TRIM63 as a cancer-specific biomarker in MiTF-RCC, we evaluated its expression independently by RNA in situ hybridization (RNA-ISH) in whole tissue sections from 177 RCC cases. We specifically included 31 cytogenetically confirmed MiTF-RCC cases and 70 RCC cases suspicious for MiTF-RCC in terms of clinical and morphological features, to evaluate and compare TRIM63 RNA-ISH results with the results from TFE3/TFEB fluorescence in situ hybridization (FISH), which is the current clinical standard. We confirmed that TRIM63 mRNA was highly expressed in all classes of MiTF-RCC compared to other renal tumor categories, where it was mostly absent to low. While the TRIM63 RNA-ISH and TFE3/TFEB FISH results were largely concordant, importantly, TRIM63 RNA-ISH was strongly positive in TFE3 FISH false-negative cases with RBM10-TFE3 inversion. In conclusion, TRIM63 can serve as a diagnostic marker to distinguish MiTF-RCC from other renal tumor subtypes with overlapping morphology. We suggest a combination of TFE3/TFEB FISH and TRIM63 RNA-ISH assays to improve the accuracy and efficiency of MiTF-RCC diagnosis. Accurate diagnosis of MiTF-RCC and other RCC subtypes would enable effective targeted therapy and avoid poor therapeutic response due to tumor misclassification.

14.
Int J Mol Sci ; 22(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807157

RESUMO

Alzheimer's disease (AD) is a growing concern in modern society, and effective drugs for its treatment are lacking. Uncaria rhynchophylla (UR) and its main alkaloids have been studied to treat neurodegenerative diseases such as AD. This study aimed to uncover the key components and mechanism of the anti-AD effect of UR alkaloids through a network pharmacology approach. The analysis identified 10 alkaloids from UR based on HPLC that corresponded to 90 anti-AD targets. A potential alkaloid target-AD target network indicated that corynoxine, corynantheine, isorhynchophylline, dihydrocorynatheine, and isocorynoxeine are likely to become key components for AD treatment. KEGG pathway enrichment analysis revealed the Alzheimers disease (hsa05010) was the pathway most significantly enriched in alkaloids against AD. Further analysis revealed that 28 out of 90 targets were significantly correlated with Aß and tau pathology. These targets were validated using a Gene Expression Omnibus (GEO) dataset. Molecular docking studies were carried out to verify the binding of corynoxine and corynantheine to core targets related to Aß and tau pathology. In addition, the cholinergic synapse (hsa04725) and dopaminergic synapse (hsa04728) pathways were significantly enriched. Our findings indicate that UR alkaloids directly exert an AD treatment effect by acting on multiple pathological processes in AD.


Assuntos
Alcaloides/farmacologia , Doença de Alzheimer/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Alcaloides/análise , Alcaloides/química , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Humanos , Indóis/farmacologia , Simulação de Acoplamento Molecular , Extratos Vegetais/análise , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Compostos de Espiro/farmacologia , Uncaria/química
15.
J Neurochem ; 158(2): 119-137, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33930186

RESUMO

Long-term or severe lack of protective factors is important in the pathogenesis of neurodegenerative dementia. Progranulin (PGRN), a neurotrophic factor expressed mainly in neurons and microglia, has various neuroprotective effects such as anti-inflammatory effects, promoting neuron survival and neurite growth, and participating in normal lysosomal function. Mutations in the PGRN gene (GRN) have been found in several neurodegenerative dementias, including frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). Herein, PGRN deficiency and PGRN hydrolytic products (GRNs) in the pathological changes related to dementia, including aggregation of tau and TAR DNA-binding protein 43 (TDP-43), amyloid-ß (Aß) overproduction, neuroinflammation, lysosomal dysfunction, neuronal death, and synaptic deficit have been summarized. Furthermore, as some therapeutic strategies targeting PGRN have been developed in various models, we highlighted PGRN as a potential anti-neurodegeneration target in dementia.


Assuntos
Demência/genética , Doenças Neurodegenerativas/genética , Progranulinas/genética , Doença de Alzheimer/genética , Animais , Degeneração Lobar Frontotemporal/genética , Humanos
16.
Chem Commun (Camb) ; 57(31): 3761-3764, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33729261

RESUMO

The new oxonitridosilicates Ln4-xSr2+xSi5N12-xOx (Ln = La, Ce) were synthesized by high temperature solid-state reactions. The crystal structures were solved and refined from both single-crystal and powder X-ray diffraction data. These oxonitridosilicate compounds crystallize in the monoclinic space group P21/n (no. 14) and exhibit a double-layer structure made up of corner-sharing Si(O/N)4 tetrahedra. When excited with near-UV and blue light, the Pr3+ doped La2.31Sr3.69Si5N10.31O1.69 phosphor shows a narrow-band red emission peaking at 625 nm with a full width at half-maximum of 40 nm.

17.
PeerJ ; 9: e10675, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33505807

RESUMO

Background: Ulcerative colitis (UC) is one of the most challenging human diseases. Natural shikonin (SK) and its derivatives (with have higher accumulation) isolated from the root of Lithospermum erythrorhizon have numerous beneficial effects, such as wound healing and anti-inflammatory activities. Some researchers have reported that hydroxynaphthoquinone mixture (HM) and SK attenuate the acute UC induced by dextran sulfate sodium (DSS). However, no existing study has systemically investigated the effectiveness of SK and other hydroxynaphthoquinone natural derivative monomers on UC. Methods: In this study, mice were treated with SK and its derivatives (25 mg/kg) and mesalazine (200 mg/kg) after DSS administration daily for one week. Disease progression was monitored daily by observing the changes in clinical signs and body weight. Results: Intragastric administration natural single naphthoquinone attenuated the malignant symptoms induced by DSS. SK or its derivatives remarkably suppressed the serum levels of pro-inflammatory cytokines while increasing the inflammatory cytokine interleukin (IL)-10 . Additionally, both SK and alkanin restrained the activities of cyclooxygenase-2 (COX-2), myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) in serum and colonic tissues. SK and its derivatives inhibited the activation of nucleotide binding oligomerization domain-like receptors (NLRP3) inflammasome and NF-κB signaling pathway, thereby relieving the DSS-induced disruption of epithelial tight junction (TJ) in colonic tissues. Conclusions: Our findings shed more lights on the pharmacological efficacy of SK and its derivatives in UC against inflammation and mucosal barrier damage.

18.
Nucl Med Commun ; 42(5): 528-534, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33481504

RESUMO

OBJECTIVE: The aim of this study was to investigate the expression of TP53-inducible glycolysis and apoptosis regulator (TIGAR) and its relationship with clinical pathology and prognosis; and to analyze the correlation between TIGAR expression and 18F-labeled fluoro-2-deoxyglucose (18F-FDG) PET/computed tomography (CT) parameters in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: We retrospectively analyzed the data of 23 patients who underwent preoperative 18F-FDG PET/CT examinations and were confirmed to have PDAC by postoperative pathology. TIGAR was detected using immunohistochemistry. The relationships between TIGAR expression and clinicopathology and its value in predicting the prognosis of patients with PDAC were analyzed. The correlations between TIGAR expression and 18F-FDG PET/CT parameters [standard uptake value (SUV) max, SUVmean, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were analyzed. RESULTS: The expression of TIGAR was low in 34.8% of patients and high in 65.2% of patients. There was no correlation between TIGAR expression and clinicopathology. The overall survival of patients with high TIGAR expression was significantly shorter than that of patients with low TIGAR expression (11.2 vs. 35.4 months). The 18F-FDG PET/CT parameters: SUVmax, SUVmean, SUVpeak, MTV, and TLG were positively correlated with TIGAR expression, but only the MTV correlation with TIGAR expression was statistically significant. CONCLUSION: TIGAR is highly expressed in PDAC. Its expression is independent of clinicopathological data and can be used as an independent prognostic factor. TIGAR expression was significantly positively correlated with the 18F-FDG PET/CT parameter MTV.


Assuntos
Adenocarcinoma/patologia , Proteínas Reguladoras de Apoptose/metabolismo , Fluordesoxiglucose F18 , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/patologia , Monoéster Fosfórico Hidrolases/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/metabolismo , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/metabolismo , Prognóstico , Estudos Retrospectivos
19.
Nat Prod Bioprospect ; 11(1): 73-79, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33083968

RESUMO

A phytochemical investigation of the EtOH extract of the flowers of Lagerstroemia indica L. led to the isolation and characterization of a new pyrrole alkaloid, named lagerindicine (1), along with four known compounds (2-5). Their structures were elucidated by the detailed spectroscopic analysis and comparison with literature data, whereas the structure, in particularly, the absolute configuration (AC) of 1, was firmly determined by total synthesis. All the isolates were evaluated for their cytotoxic effects against human colon cancer cell (HCT-116), and compound 3 exhibited weak cytotoxicity with IC50 value of 28.4 µM.

20.
Brain Imaging Behav ; 15(3): 1313-1322, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32748315

RESUMO

Panic disorder (PD) is a prevalent anxiety disorder but its neurobiology remains poorly understood. It has been proposed that the pathophysiology of PD is related to an abnormality in a particular neural network. However, most studies investigating resting-state functional connectivity (FC) have relied on a priori restrictions of seed regions, which may bias observations. This study investigated changes in intra and internetwork FC in the whole brain of patients with PD using resting-state functional magnetic resonance imaging. A voxel-wise data-driven independent component analysis was performed on 26 PD patients and 27 healthy controls (HCs).We compared the differences in the intra and internetwork FC between the two groups of subjects using statistical parametric mapping with two-sample t-tests. PD patients exhibited decreased intra-network FC in the right anterior cingulate cortex (ACC) of the anterior default mode network, the left precentral and postcentral gyrus of the sensorimotor network, the right lobule V/VI, the cerebellum vermis, and the left lobule VI of the cerebellum network compared with the HCs. The intra-network FC in the right ACC was negatively correlated with symptom severity. None of the pairs of resting state networks showed significant differences in functional network connectivity between the two groups. These results suggest that the brain networks associated with emotion regulation, interoceptive awareness, and fear and somatosensory processing may play an important role in the pathophysiology of PD.


Assuntos
Transtorno de Pânico , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Giro do Cíngulo , Humanos , Imageamento por Ressonância Magnética , Transtorno de Pânico/diagnóstico por imagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...