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1.
Cell Biol Int ; 46(3): 475-487, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34939719

RESUMO

Mutations of PSEN1 have been reported in dilated cardiomyopathy pedigrees. Understanding the effects and mechanisms of PSEN1 in cardiomyocytes might have important implications for treatment of heart diseases. Here, we showed that PSEN1 was downregulated in ischemia-induced failing hearts. Functionally, cardiovascular specific PSEN1 deletion led to spontaneous death of the mice due to cardiomyopathy. At the age of 11 months, the ratio of the heart weight/body weight was slightly lower in the Sm22a-PSEN1-KO mice compared with that of the WT mice. Echocardiography showed that the percentage of ejection fraction and fractional shortening was significantly reduced in the Sm22a-PSEN1-KO group compared with the percent of these measures in the WT group, indicating that PSEN1-KO resulted in heart failure. The abnormally regulated genes resulted from PSEN1-KO were detected to be enriched in muscle development and dilated cardiomyopathy. Among them, several genes encode Ca2+ ion channels, promoting us to investigate the effects of PSEN1 KO on regulation of Ca2+ in isolated adult cardiomyocytes. Consistently, in isolated adult cardiomyocytes, PSEN1-KO increased the concentration of cytosolic Ca2+ and reduced Ca2+ concentration inside the sarcoplasmic reticulum (SR) lumen at the resting stage. Additionally, SR Ca2+ was decreased in the failing hearts of WT mice, but with the lowest levels observed in the failing hearts of PSEN1 knockout mice. These results indicate that the process of Ca2+ release from SR into cytoplasm was affected by PSEN1 KO. Therefore, the abnormalities in Ca2+ homeostasis resulted from downregulation of PSEN1 in failing hearts might contribute to aging-related cardiomyopathy, which might had important implications for the treatment of aging-related heart diseases.


Assuntos
Cálcio , Cardiomiopatia Dilatada , Animais , Cardiomiopatia Dilatada/genética , Homeostase , Camundongos , Camundongos Knockout , Miócitos Cardíacos/fisiologia , Retículo Sarcoplasmático
2.
Aging (Albany NY) ; 14(undefined)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36152060

RESUMO

Chlorpyrifos (CPF), as an extensively used organophosphorus pesticide, often remains on food surfaces or contaminates water sources. CPF can cause many toxic effects on human production and life. As an additional product of non-medicinal parts of ginseng, the pharmacological activity of ginseng stem and leaf total saponin (GSLS) has been verified and applied in recent years. This study aimed to evaluate the protective effect of GSLS on CPF-induced liver damage in mice. Experimental results in vivo demonstrate that GSLS can reduce the accumulation of oxidation product MDA by relieving CPF-induced liver function indicators in mice and enhancing the antioxidant enzyme SOD and CAT activities of mice. With the decrease in mRNA expression of BAX, NF-KB, and TIMP in liver tissues, the mRNA expression of Nrf-2, HO-1, and XIAP increased. GSLS can alleviate CPF-induced liver toxicity through anti-inflammatory, antioxidant, and anti-inflammatory. In vitro experiments have proved that GSLS can show the ability to scavenge DPPH free radicals and hydroxyl radicals. In addition, GSLS can alleviate chlorpyrifos-induced ROS accumulation in L02 cells, alleviating cytokinetic potential reduction. In summary, by fighting oxidative stress, GSLS can alleviate liver damage caused by CPF.

3.
Biomater Adv ; 141: 213123, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36137446

RESUMO

Hydrogels, with a three-dimensional network of water-soluble polymer and water, could simulate the critical properties of extracellular matrix, which has been widely used in bone tissue engineering. However, most of conventional hydrogels for bone regeneration are fragile and have poor osteogenic activity, which restricts their applications. In this work, a novel nanoparticle-hydrogel composite consisting of physically cross-linked double-network loaded with MgO-Ag2O nanocomposites was developed by the sol-gel method. The Mg2+ released from MgO-Ag2O nanocomposites was used as an ionic cross-linking site of sodium alginate (SA), while the hydrophobic micelles in the polyacrylamide (PAAM) network is acted as another crosslinking point. The results indicated that the novel nanoparticle-hydrogel composites had good self-recovery ability and excellent mechanical properties compared with the conventional sodium alginate (SA)/polyacrylamide (PAAM) hydrogels. Additionally, it showed a slow release of Mg and Ag ions due to the dual function of the embedding effect of hydrogels and the increasing pH of the solution induced by the hydrolysis of sodium alginate. In terms of in vitro tests, the nanoparticle-hydrogel composites showed significantly stimulatory effects on the proliferation and differentiation of SaOS-2 cells. In addition, the antibacterial effects of the nanoparticle-hydrogel composites were gradually enhanced with the increase of MgO-Ag2O content.

4.
Biomed Pharmacother ; 155: 113703, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36126455

RESUMO

BACKGROUND/AIMS: Duzhi Wan (DZW) has been extensively used in the prevention and treatment of ischemic stroke, but the mechanisms underlying its effects remain unclear. In this study, a combination of transcriptomics, metabolomics and network analysis was applied to identify the preventive mechanism of DZW in middle cerebral artery occlusion (MCAO)-induced ischemia/reperfusion (I/R) injury. METHODS: The mice were divided into five groups: the sham group, I/R group, I/R + Ginaton group, I/R+DZW-L group, and I/R+DZW-H group. Neurological deficit scores and regional cerebral blood flow (rCBF), hematoxylin and eosin (H&E) and Nissl staining results were evaluated. Transcriptomics analysis and metabolomics analysis were applied to identify the key genes and metabolites, and qRT-PCR, ELISA, and immunofluorescence were applied to verify the key targets. RESULTS: DZW significantly decreased the infarction size and neurological deficit scores, increased the rCBF percentage and neuronal number and improved neuronal morphology after MCAO. Transcriptomics and metabolomics analysis revealed that C3 and C5ar1 were core targets of DZW and indirectly regulated downstream purine metabolism, the pentose phosphate pathway, and glycerophospholipid metabolism-associated pathways via inflammatory cells. Moreover, ELISA, qRT-PCR, and immunofluorescence further confirmed that DZW significantly decreased the expression of C3, C5ar1, C5 and downstream inflammatory cytokines, including IL-6, IL-1ß and MMP-9, at the gene and protein levels, suggesting that DZW decreased neuroinflammation and inhibited related metabolic pathways. CONCLUSION: C3 and C5 play important roles in the neuroprotective and antineuroinflammatory effects of DZW in protecting against cerebral I/R. This study provides novel insights into the neuroprotective effects of DZW and its clinical application.

5.
J Sci Food Agric ; 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-36054514

RESUMO

BACKGROUND: To thoroughly explore the values of Cinnamomum cassia leaf residues (CcLR), their antioxidant activity in vivo and the relationship with gut microbiota were investigated using d-galactose-induced aging mice. RESULTS: Results showed that CcLR extract treatment exerted antioxidant activity by increasing the levels of superoxide dismutase (P < 0.01) and glutathione peroxidase (P < 0.05), as well as inhibiting the formation of malondialdehyde (P < 0.01). Meanwhile, the inflammatory response was also alleviated as the ratio of pro-inflammatory tumor necrosis factor-α (P < 0.01) and interleukin-1ß (P < 0.01))/anti-inflammatory cytokines (interleukin-10; P < 0.05) in serum was decreased and the contents of inflammatory markers (induced nitrogen monoxide synthase and nitric oxide) in brain and liver tissues (P < 0.01) were reduced. Moreover, through inhibiting acetylcholinesterase activity and improving choline acetyltransferase activity, the cholinergic system in aging mice recovered to levels comparable to the normal control group. In addition, 16S rRNA sequencing results demonstrated that CcLR extract promoted the growth of beneficial bacteria. In particular, Spearman correlation analysis revealed that the abundance of Colidextribacter was negatively correlated with serum superoxide dismutase (P < 0.05, R = -0.943), and Helicobacter displayed a positive correlation with the content of brain nitric oxide (P < 0.05, R = 0.899), suggesting that regulating gut microbiota might be one of the mechanisms for reducing oxidative stress, thus postponing the aging process. CONCLUSION: It is suggested that CcLR extract could be used as a novel antioxidant and anti-aging resource in the pharmaceutical and food industries. © 2022 Society of Chemical Industry.

6.
Colloid Polym Sci ; : 1-9, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36090674

RESUMO

Cinnamon essential oil (CNO) is a natural and renewable antibacterial agent. However, CNO is highly volatile and unstable, which limits its practical application as a long-term and wide antibacterial agent. In order to improve the CNO stability, we have microencapsulated CNO into composite microcapsules basing on Pickering emulsion stabilized by silica (SiO2) nanoparticles. The CNO-loaded composite microcapsules possess the hybrid microcapsule shell including SiO2, xanthan gum and chitosan. Moreover, the results show that the microcapsules have spherical appearance. Microencapsulation technique effectively promotes the CNO stability, and the loaded CNO is slowly released from microcapsules. The antibacterial test indicates that the minimal inhibitory concentration of microcapsules was 2 mg mL-1 against Escherichia coli and Staphylococcus aureus, and the microcapsules can play an effective long-term antibacterial effect. Thus, Pickering emulsion templates is a convenient and effective technique to construct antibacterial essential oil-contained microcapsules, which can be used as long-term antibacterial agents.

7.
Inflamm Res ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109396

RESUMO

OBJECTIVE: The excessive proliferation of fibroblast-like synoviocytes (FLSs) is a key inducement for the occurrence and development of rheumatoid arthritis (RA). Hypoxia inducible factor-α (HIF-α) accumulation is involved in the regulation of cell biological functions in the hypoxic microenvironment of synovium. This study aimed to investigate the roles of HIF-α and its level regulator prolyl hydroxylases (PHDs) in FLSs proliferation and to explore the regulatory effect of geniposide (GE). MATERIALS AND METHODS: Adjuvant arthritis rats and RA-FLSs cell line MH7A were taken as the research objects. MH7A cells were incubated in a hypoxic chamber with 2% O2 for hypoxia treatment. CCK-8, FACS, EdU and Western blot assays were performed to evaluate MH7A cells proliferation. Iron assay was conducted to determine intracellular Fe2+ level. RESULTS: MH7A cells proliferation was significantly enhanced under hypoxia, accompanied by an increase of HIF-1α level. Decreased HIF-1α level by PX-478 inhibited MH7A cells proliferation. Furthermore, PHD2 was highly expressed in vivo and in vitro, and played a key role in modulation of HIF-1α protein level, which was confirmed by PHD2 inhibitor IOX4 and proteasome inhibitor MG132. GE treatment alleviated synovial hyperplasia in AA rats and inhibited MH7A cells proliferation with a reduction in HIF-1α level. Fe2+ acts as an enzymatic cofactor to control PHD2 activity. Iron assay showed that GE reversed the decline of Fe2+ level in MH7A cells under hypoxia. CONCLUSION: GE attenuates abnormal proliferation of RA-FLSs via inhibiting HIF-1α accumulation through enhancement of PHD2 activity.

8.
Ann Bot ; 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36111957

RESUMO

BACKGROUND AND AIMS: Cycads are regarded as an ancient lineages of living seed plants, and hold important clues to understand the early evolutionary trends of seed plants. The molecular phylogeny and spatio-temporal diversification of one of the species-rich genera of cycads, Macrozamia, has not been well reconstructed. METHODS: We analyzed a transcriptome dataset of 4,740 single-copy nuclear genes (SCGs) of 39 Macrozamia species and two outgroup taxa. Based on concatenated (Maximum Parsimony, Maximum Likelihood) and multispecies coalescent analyses, we first establish a well-resolved phylogenenetic tree of Macrozamia. To identify cyto-nuclear incongruence, the plastid protein coding genes (PCGs) from transcriptome data are extracted using software HybPiper. Furthermore, we explore the biogeographic history of the genus and shed light on the pattern of floristic exchange between three distinct areas of Australia. Six key diagnostic characters are traced on the phylogenetic framework using two comparative methods, and infra-generic classification is investigated. KEY RESULTS: The tree topologies of concatenated and multi-species coalescent analyses of SCGs are mostly congruent with a few conflicting nodes, while those from plastid PCGs show poorly supported relationships. The genus contains three major clades that corresponds to their distinct distributional areas in Australia. The crown group of Macrozamia is estimated to around 11.80 Ma, with a major expansion in the last 5-6 Myr. Six morphological characters show homoplasy, and traditional phenetic sectional division of the genus is inconsistent with this current phylogeny. CONCLUSIONS: This first detailed phylogenetic investigation of Macrozamia demonstrates promising prospects of SCGs in resolving phylogenetic relationships within cycads. Our study suggests that Macrozamia, once a widely distributed in Australia, underwent major extinctions because of fluctuating climatic conditions such as cooling and mesic biome disappearance in the past. The current close placement of morphologically distinct species in the phylogenetic tree may be related to neotenic events that occurred in the genus.

9.
Huan Jing Ke Xue ; 43(9): 4800-4809, 2022 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-36096620

RESUMO

To investigate the soil contamination degree and potential ecological risk level of heavy metals in villages and towns in Tongling City, we collected 67 surface soil samples (including surface dusts and river sediments) from the typical districts, namely Shun'an Town, Zhongming Town, and Yi'an Economic Development Zone, and measured the contents of heavy metals including Cu, Zn, Pb, Cr, Cd, As, and Ni. Then, spatial distribution characteristics of heavy metals were analyzed, and their contamination degree and potential ecological risk were assessed. Finally, source apportionment of soil heavy metals was conducted using factor analysis. The results showed that the soil pH was weakly acidic in the study area, and the average contents of Cu, Zn, Cr, Cd, As, and Ni were 4.94, 2.89, 2.07, 0.94, 7.97, 4.03, and 2.02 times their soil background values in Tongling City, respectively. In general, the contents of soil heavy metals in the western part were higher than those in the eastern part across the studied area. According to the Nemerow pollution index, Cu, Cd, As, and Pb reached pollution levels; Zn, and Ni approached moderate pollution levels; and Cr belonged to the no pollution degree category. The Nemerow comprehensive pollution index of different land types was arranged in the order of river bed>town district>industrial land>vegetable land>agricultural land>mountain forest>village. On the whole, the contamination degree of soil heavy metals in the study area reached severe pollution levels. The order of potential ecological risk coefficients of soil heavy metals was Cd>As>Cu>Pb>Ni>Zn>Cr, in which Cd belonged to the extremely high risk level, Cu and As belonged to the medium risk level, and the others were all low risk levels. The potential ecological risk levels corresponding to different land types were as follows:river bed>town distribution>industrial land>vegetable land>agricultural land>village>mountain forest. The industrial land, vegetable land, and town district generally reached a very high risk level, and the agricultural land reached a high risk, whereas both village and mountain forest land showed a medium risk. Principal component analysis showed that Cu, Zn, Pb, Cd, and As in the study area were derived from local metal mining pollution; Cr was from both the geological background and metal mining pollution; and Ni mainly came from fossil fuel combustion.


Assuntos
Metais Pesados , Poluentes do Solo , Cádmio/análise , Cidades , Monitoramento Ambiental/métodos , Chumbo/análise , Metais Pesados/análise , Mineração , Medição de Risco , Solo/química , Poluentes do Solo/análise
10.
World J Pediatr ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36100796

RESUMO

BACKGROUND: The aim of this study was to evaluate the performance of the four scoring tools in predicting mortality in pediatric intensive care units (PICUs) in western China. METHODS: This was a multicenter, prospective, cohort study conducted in six PICUs in western China. The performances of the scoring systems were evaluated based on both discrimination and calibration. Discrimination was assessed by calculating the area under the receiver operating characteristic curve (AUC) for each model. Calibration was measured across defined groups based on mortality risk using the Hosmer-Lemeshow goodness-of-fit test. RESULTS: A total of 2034 patients were included in this study, of whom 127 (6.2%) died. For the entire cohort, AUCs for Pediatric Risk of Mortality Score (PRISM) I, Pediatric Index of Mortality 2 (PIM2), Pediatric Logistic Organ Dysfunction Score-2 (PELOD-2) and PRISM IV were 0.88 [95% confidence interval (CI) 0.85-0.92], 0.84 (95% CI 0.80-0.88), 0.80 (95% CI 0.75-0.85), and 0.91 (95% CI 0.88-0.94), respectively. The Hosmer-Lemeshow goodness-of-fit Chi-square value was 12.71 (P = 0.12) for PRISM I, 4.70 (P = 0.79) for PIM2, 205.98 (P < 0.001) for PELOD-2, and 7.50 (P = 0.48) for PRISM IV [degree of freedom (df) = 8]. The standardized mortality ratios obtained with the PRISM I, PIM2, PELOD-2, and PRISM IV models were 0.87 (95% CI, 0.75-1.01), 0.97 (95% CI, 0.85-1.12), 1.74 (95% CI, 1.58-1.92), and 1.05 (95% CI, 0.92-1.21), respectively. CONCLUSIONS: PRISM IV performed best and can be used as a prediction tool in PICUs in Western China. However, PRISM IV needs to be further validated in NICUs.

11.
Zootaxa ; 5165(3): 443-450, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-36101316

RESUMO

In this study, two new species of Setostylus (Diptera: Keroplatidae: Keroplatinae), S. tridigitus sp. n. and S. triumphus sp. n. are described, with a key to all the species of the genus. Male habitus and images of diagnostic morphological characteristics are provided. Status of these two new species is also supported by the genetic distances and neighbor-joining (NJ) tree in the DNA barcode analysis.


Assuntos
Dípteros , Animais , China , Dípteros/genética , Nematóceros , Árvores
12.
Eur J Med Res ; 27(1): 176, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088368

RESUMO

Hyperuricemia can induce acute and chronic kidney damage, but the pathological mechanism remains unclear. The potential role of AMP-activated protein kinase (AMPK) α2 in hyperuricemia-induced renal injury was investigated in this study. Acute and chronic hyperuricemic nephropathy was induced by administering intraperitoneal injections of uric acid and oxonic acid to AMPK α2 knockout and wild-type mice. Changes in renal function, histopathology, inflammatory cell infiltration, renal interstitial fibrosis, and urate deposition were analyzed. In both acute and chronic hyperuricemic nephropathy mouse models, knockout of AMPK α2 significantly reduced serum creatinine levels and renal pathological changes. The tubular expression of kidney injury molecule-1 was also reduced in hyperuricemic nephropathy mice deficient in AMPK α2. In addition, knockout of AMPK α2 significantly suppressed the infiltration of renal macrophages and progression of renal interstitial fibrosis in mice with chronic hyperuricemic nephropathy. Knockout of AMPK α2 reduced renal urate crystal deposition, probably through increasing the expression of the uric acid transporter, multidrug resistance protein 4. In summary, AMPK α2 is involved in acute and chronic hyperuricemia-induced kidney injury and may be associated with increased urate crystal deposition in the kidney.


Assuntos
Hiperuricemia , Nefropatias , Falência Renal Crônica , Proteínas Quinases Ativadas por AMP/genética , Animais , Modelos Animais de Doenças , Fibrose , Hiperuricemia/induzido quimicamente , Hiperuricemia/genética , Rim/patologia , Nefropatias/genética , Nefropatias/metabolismo , Camundongos , Camundongos Knockout , Ácido Úrico/efeitos adversos , Ácido Úrico/metabolismo
13.
Front Oncol ; 12: 891221, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059659

RESUMO

Introduction: The dosimetric factors of radiotherapy have an acute impact on the host immune system during chemoradiotherapy (CRT) in locally advanced non-small cell lung cancer (NSCLC). However, even after CRT, a substantial number of patients remain immunosuppressed with delayed lymphopenia. Therefore, we aimed to evaluate clinical and dose-volumetric predictors of delayed lymphopenia after CRT in locally advanced NSCLC. Materials and methods: We retrospectively reviewed 272 patients with locally advanced NSCLC who received definitive CRT from January 2012 to August 2020. Differential blood count data, including serum albumin values, were obtained at baseline, during and at first follow up after CRT. Acute and delayed lymphopenia events were defined as grade III/IV lymphopenia developed during or 4-12 weeks after CRT completion, which accounted for 84% and 10% of cases, respectively. Dose-volume histogram parameters for planned target volume, whole body, heart, lung, great vessels, spleen, esophagus and thoracic vertebral bodies were evaluated. Results: Multivariate analysis revealed that patients with delayed lymphopenia were associated with inferior overall survival (HR 2.53, P = 0.001) and progression-free survival (HR 1.98, P = 0.006). However, there was no significant survival difference between groups stratified by acute lymphopenia. On multivariable logistic regression models, lung V5, baseline ALC, during-CRT ALC, and albumin nadir were significant predictors for delayed lymphopenia. Furthermore, the nomogram for delayed lymphopenia based on these variables had good discrimination (area under the curve, 0.905). Conclusions: In this study, we investigated the prognostic significance of delayed lymphopenia and identified clinico-dosimetric parameters to predict delayed lymphopenia.

14.
Artigo em Inglês | MEDLINE | ID: mdl-36067529

RESUMO

Circular RNAs (circRNAs) are widely expressed in cancer tissues and participate in modulating the progression of malignant tumors, playing a pro- or anti-cancer role. This work is conducted to probe the precise role of circ_0000467 in colorectal cancer (CRC) and its regulatory mechanism. The differentially expressed circRNAs in CRC tissues and paracancerous tissues were screened by bioinformatics analysis. The expression levels of circ_0000467, miR-651-5p and DNA methyltransferases 3B (DNMT3B) mRNA in CRC tissues and cells were detected by qRT-PCR. circ_0000467 knockdown cell model was constructed to investigate the effects of circ_0000467 on CRC cell growth, migration and invasion by CCK-8 and Transwell experiments. Western blot was performed to examine DNMT3B protein expression in CRC cells. Dual-luciferase reporter gene experiment was executed to validate the targeting relationship between circ_0000467 and miR-651-5p, miR-651-5p and DNMT3B. Circ_0000467 expression and DNMT3B mRNA expression were increased and miR-651-5p expression was down-regulated in CRC tissues and cell lines. Knockdown of circ_0000467 repressed CRC cell growth, migration and invasion. Dual-luciferase reporter gene experiments validated that miR-651-5p was a direct target of circ_0000467 and miR-651-5p could specifically bind with DNMT3B 3'UTR. Functional compensation experiments showed that the regulatory effect of circ_0000467 on CRC cells' behaviors could be partially counteracted by miR-651-5p. Circ_0000467 may enhance the growth and metastasis of CRC cells by targeting miR-651-5p and up-regulating DNMT3B expression. Circ_0000467 may be a potential diagnostic biomarker and therapeutic target for CRC.

15.
J Psychopharmacol ; : 2698811221122008, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069168

RESUMO

BACKGROUND: Intracerebral translocator protein 18 kDa (TSPO) mediates the transport of cholesterol from cytoplasm to mitochondria and activation of microglia. The change of TSPO and the dysfunction of microglia are closely related to the pathogenesis of Alzheimer's disease (AD). AIMS: This study aimed to investigate the effects of microglial TSPO and its selective ligand YL-IPA08 on the cognitive function of transgenic mice in 5 × familial Alzheimer's disease (FAD) mouse model of AD. METHODS: The TSPO knockout 5 × FAD transgenic mice were bred, and tested by Morris water maze. The effects of YL-IPA08 on cognitive abilities and expression of Aß in 5 × FAD mice were also explored into. RESULTS: The latency of escape by TSPO knockout 5 × FAD mice was significantly prolonged compared with the 5 × FAD group, indicating that the cognitive impairment of mice aggravated. With the attenuated phagocytic ability of microglia, the deposition of Aß in prefrontal cortex of TSPO knockout 5 × FAD mice increased, and the expression of proinflammatory factors (IL-1ß, TNF-α, IL-6) were upregulated. In addition, YL-IPA08 significantly reduced the latency of escape by 5 × FAD mice, increased the number of times of crossing over the platform by mice, and inhibited the deposition of Aß in the prefrontal cortex of 5 × FAD mice without affecting the cleavage of APP. CONCLUSION: Our findings suggested that TSPO knockout in 5 × FAD mice inhibited microglial phagocytosis, promoted Aß deposition and neuroinflammation, and aggravated cognitive dysfunction in AD mice. YL-IPA08 had a significant cognition-enhancing effect in 5 × FAD transgenic mice, which might provide a new basis for potential drug candidates in AD treatment.

16.
Front Genet ; 13: 930446, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110218

RESUMO

Background: Hepatocellular carcinoma (HCC), which has high rates of recurrence and metastasis and is the main reason and the most common tumor for cancer mortality worldwide, has an unfavorable prognosis. N7-methylguanosine (m7G) modification can affect the formation and development of tumors by affecting gene expression and other biological processes. In addition, many previous studies have confirmed the unique function of long noncoding RNAs (lncRNAs) in tumor progression; however, studies exploring the functions of m7G-related lncRNAs in HCC patients has been limited. Methods: Relevant RNA expression information was acquired from The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov), and m7G-related lncRNAs were identified via gene coexpression analysis. Afterward, univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate regression analyses were implemented to construct an ideal risk model whose validity was verified using Kaplan-Meier survival, principal component, receiver operating characteristic (ROC) curve, and nomogram analyses. In addition, the potential functions of lncRNAs in the novel signature were explored through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and gene set enrichment analysis (GSEA). At last, in both risk groups and subtypes classified based on the expression of the risk-related lncRNAs, we analyzed the immune characteristics and drug sensitivity of patients. Results: After rigorous screening processes, we built a model based on 11 m7G-related lncRNAs for predicting patient overall survival (OS). The results suggested that the survival status of patients with high-risk scores was lower than that of patients with low-risk scores, and a high-risk score was related to malignant clinical features. Cox regression analysis showed that the m7G risk score was an independent prognostic parameter. Moreover, immune cell infiltration and immunotherapy sensitivity differed between the risk groups. Conclusion: The m7G risk score model constructed based on 11 m7G-related lncRNAs can effectively assess the OS of HCC patients and may offer support for making individualized treatment and immunotherapy decisions for HCC patients.

17.
J Environ Manage ; 322: 116100, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36058072

RESUMO

Firescapes of the Mid-Atlantic are understudied compared to other ecosystems in the United States, and little is known about the acceptance of prescribed fire as a forest management tool. Yet, this region harbors high levels of wildland-urban interface (WUI), has a close intermingling of land ownerships, and reflects substantial regional heterogeneity in burning histories and fire hazards. As prescribed fire is increasingly applied in the Mid-Atlantic as a critical tool to meet various land management objectives, research is needed to help managers understand community perceptions of prescribed fire implementation. Through intercept surveys of forest recreationists and online surveys of fire managers, this study investigates perceptions about prescribed fire use in the Mid-Atlantic, in addition to the critical contributing factors of public support toward prescribed fires. Two states, Pennsylvania and New Jersey, were selected as case studies to explore regional differences in social perception due to their contrasts in fire history, policy, management objectives, and social exposure. Our results show moderate social awareness of local prescribed fires, moderate to high familiarity with prescribed burning, high agency trust, and strong community support toward prescribed fires. However, the perceived concerns and benefits differed between managers and forest recreationists and between recreationists from Pennsylvania and New Jersey. The factors influencing the support of prescribed burning practices included forest management beliefs, concern about prescribed fire effects, familiarity with prescribed fires as a forest management tool, and awareness of local prescribed fires. Collectively, these results highlighted needs in public outreach to strengthen education, build broader community awareness, engage critical stakeholder groups such as forest recreationists, and re-align public outreach messages based on community-level concerns and perceived benefits. Additionally, it will be vital for the scientific community to help monitor critical shifts in forest value orientations and fill in significant research gaps regarding prescribed fire benefits.

18.
Cells ; 11(17)2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36078164

RESUMO

Pancreatic cancer (PC) patients are highly prone to cachexia, a lethal wasting syndrome featuring muscle wasting with an undefined etiology. Recent data indicate that certain murine cancer cells induce muscle wasting by releasing Hsp70 and Hsp90 through extracellular vesicles (EVs) to activate p38ß MAPK-mediated catabolic pathways primarily through Toll-like receptor 4 (TLR4). However, whether human PC induces cachexia through releasing Hsp70 and Hsp90 is undetermined. Here, we investigated whether patient-derived PC cells induce muscle cell atrophy directly through this mechanism. We compared cancer cells isolated from patient-derived xenografts (PDX) from three PC patients who had cachexia (PCC) with those of three early-stage lung cancer patients without cachexia (LCC) and two renal cancer patients who were not prone to cachexia (RCC). We observed small increases of Hsp70 and Hsp90 released by LCC and RCC in comparison to non-cancer control cells (NCC). However, PCC released markedly higher levels of Hsp70 and Hsp90 (~ 6-fold on average) than LCC and RCC. In addition, PCC released similarly increased levels of Hsp70/90-containing EVs. In contrast to RCC and LCC, PCC-conditioned media induced a potent catabolic response in C2C12 myotubes including the activation of p38 MAPK and transcription factor C/EBPß, upregulation of E3 ligases UBR2 and MAFbx, and increase of autophagy marker LC3-II, resulting in the loss of the myosin heavy chain (MHC ~50%) and myotube diameter (~60%). Importantly, the catabolic response was attenuated by Hsp70- and Hsp90-neutralizing antibodies in a dose-dependent manner. These data suggest that human PC cells release high levels of Hsp70 and Hsp90 that induce muscle atrophy through a direct action on muscle cells.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Pancreáticas , Animais , Caquexia/etiologia , Carcinoma de Células Renais/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Neoplasias Renais/patologia , Camundongos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/patologia , Neoplasias Pancreáticas/patologia
19.
Pract Radiat Oncol ; 12(5): 397-408, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36058618

RESUMO

PURPOSE: To estimate the variations in clinical target volumes (CTVs) and organs at risk delineation within the quality assurance (QA) program of the POTENTIAL trial, which is a multicenter, randomized phase 3 trial evaluating postmastectomy radiation therapy (RT), with or without internal mammary nodal irradiation, for patients with high-risk breast cancer. METHODS AND MATERIALS: The simulating computed tomography scan data set of a benchmark case was sent to the participating centers, and the delineation of CTVs and organs at risk was required to be completed by the investigators following protocol guidelines. All submitted contours were reviewed and compared with the reference contours created by the QA team, using quantitative geometric analysis regarding volume and the Jaccard Index (JCI), Dice similarity coefficient, Geographic Miss Index, Discordance Index, and mean distance to agreement. In addition to the whole-volume analysis of all structures, the combination contour of the supraclavicular fossa and level III and II axilla (CTVsc + axIII + axII) was further analyzed on a slice-by-slice basis. RESULTS: The contours from 26 centers were reviewed and variations were observed between submission and reference. The variations of the CTV of the chest wall, contralateral breast, and heart were small, for which the mean JCI values were 0.62, 0.68, and 0.87, respectively. However, the mean JCI values of the CTV of the internal mammary nodal region, ipsilateral brachial plexus, left anterior descending coronary artery, and right coronary artery were 0.38, 0.21, 0.29, and 0.18, respectively, suggesting marked variations. In addition, marked under- and overoutlining variations were identified on 4 slices of CTVsc + axIII + axII on slice-by-slice analysis. CONCLUSIONS: There were residual contouring variations despite a detailed protocol being provided, confirming the importance of pretrial QA in RT and highlighting the need for education and consideration of a real-time central review of the target delineation before the trial participants begin RT.


Assuntos
Neoplasias da Mama , Órgãos em Risco , Benchmarking , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Órgãos em Risco/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos
20.
Surg Endosc ; 36(10): 7859-7860, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36071260

RESUMO

BACKGROUND: With the advancement of laparoscopic technology, more precise anatomical hepatectomies such as segmentectomy or even bi-segmentectomy have been recommended by updated expert consensus to treat a single small hepatocellular carcinoma (HCC) [1, 2]. Herein, we presented a video of laparoscopic anatomic bi-segmentectomy (S3 and S4b) using the Glisson's pedicle-first and intrahepatic anatomic markers approach. METHODS: A 66-year-old male was referred for treatment of a single HCC adjacent to the Sagittal part of the left portal vein. The procedure was performed according to the following steps: (1) dissecting and transecting the Glisson's pedicle to S3 and S4b based on Laennec's capsule [3]; (2) identification of the ischemia boundary on the liver surface and confirming the presence of adequate surgical margins within the boundary, ensuing the integrity of segment 2 and 4a by the intraoperative ultrasonography meanwhile; (3) the left parenchymal transection was begun along the demarcation line, exposing the Glisson's pedicle to S2, left hepatic vein, and umbilical fissure vein; (4) the right parenchymal transection was performed to expose the V5, V4b, and V4a. And this operation was approved by the Institutional Review Board of the West China Hospital and written informed consent was obtained from patient of Sichuan University and written informed consent was obtained from patient. (5) The blood supply of residual liver surface was observed, and the integrity of segment 2 and 4a hepatic pedicle was ensured by intraoperative ultrasonography. RESULTS: The operative time was 224 min and blood loss during operation was 50 ml. The histopathologic examination showed a solitary HCC, 4 cm in diameter, with negative surgical margin and no microvascular invasion. The patient had an uneventful postoperative recovery and was discharged on postoperative day 5. CONCLUSION: Laparoscopic bi-segmentectomy (S3 and S4b) using the Glisson's pedicle-first and intrahepatic anatomic markers approach is feasible and effective. Its advantages lie in obtaining the benefits of anatomical hepatectomy, while maximizing the postoperative functional hepatic reserve [4-6].


Assuntos
Carcinoma Hepatocelular , Laparoscopia , Neoplasias Hepáticas , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Humanos , Laparoscopia/métodos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pneumonectomia
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