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1.
Rapid Commun Mass Spectrom ; : e9219, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740284

RESUMO

RATIONALE: Panax ginseng (PG) and American ginseng (AMG) are both medicinal plants of the Panax genus in the Acanthopanax family. Although the chemical components of PG and AMG are similar, there are many differences of their bioactivities. In this study, the biochemical mechanisms of different bioactivities of PG and AMG were explored by researching the differential metabolites in plasma after administrations of PG and AMG, respectively. METHODS: In order to explore the material basis of differential bioactivities, two groups of mice were administrated orally with PG and AMG, and the method of metabonomics was used to identify the differential metabolites in the plasma. Then the network pharmacology based on the differential metabolites was processed. Afterward, the metabolite-target-pathway network of PG and AMG was constructed, thus the pathways related to different bioactivities were analyzed. RESULTS: Through the analysis of PCA and OPLS-DA, there were 10 differential metabolites identified in the PG group, and 8 differential metabolites identified in the AMG group. Based on the network pharmacology, the differential metabolites were classified and related to differential bioactivities of PG and AMG. In the PG group, there were 6 metabolites related to the effects of aphrodisiac and exiting the nerve, and 5 metabolites associated to raise blood pressure. In the AMG group, 5 metabolites were classified to the effect of inhibiting the nerve center, and 6 metabolites were related to antihypertensive. CONCLUSIONS: This study explored the material basis of the differential biological activity between PG and AMG, which was significantly to research PG and AMG used and promote human health.

2.
Chem Sci ; 12(39): 13144-13150, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34745545

RESUMO

This report describes palladium-catalyzed C-H glycosylation and retro Diels-Alder tandem reaction via structurally modified norbornadienes (smNBDs). smNBDs were proposed to regulate the reactivity of the aryl-norbornadiene-palladacycle (ANP), including its high chemoselectivity and regioselectivity, which were the key to constructing C2 and C3 unsubstituted C4-glycosidic indoles. The scope of this substrate is extensive; the halogenated six-membered and five-membered glycosides were applied to the reaction smoothly, and N-alkyl (primary, secondary and tertiary) C4-glycosidic indoles can also be obtained by this method. In terms of mechanism, the key ANP intermediates characterized by X-ray single-crystal diffraction and further controlled experiments proved that the migration-insertion of smNBDs with phenylpalladium intermediate endows them with high chemo- and regioselectivity. Finally, density functional theory (DFT) calculation further verified the rationality of the mechanism.

4.
JAMA Netw Open ; 4(11): e2135168, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34792590

RESUMO

Importance: Among older people, slow walking is an early indicator of risk for Alzheimer disease (AD). However, studies that have assessed this association have not considered that slow walking may have different causes, some of which are not necessarily associated with higher AD risk. Objective: To evaluate whether low activity fragmentation among older adults with slow gait speed indicates neurological causes of slow walking that put these individuals at higher risk of AD. Design, Setting, and Participants: This prospective cohort study performed survival analyses using data from the Baltimore Longitudinal Study of Aging. Participants included 520 initially cognitively normal persons aged 60 years or older. New diagnoses of mild cognitive impairment (MCI) or AD were adjudicated during a mean (SD) follow-up of 7.3 (2.7) years. Initial assessment of gait speed and activity fragmentation occurred from January 3, 2007, to May 11, 2015, with follow-up completed on December 31, 2020. Data were analyzed from February 1 to May 15, 2021. Exposures: Gait speed for 6 m and activity fragmentation assessed by accelerometry. Main Outcomes and Measures: Associations of gait speed, activity fragmentation, and their interaction with incident MCI/AD were evaluated using Cox proportional hazards models, adjusted for covariates. Results: Among the 520 participants (265 women [51.0%]; 125 Black participants [24.0%]; 367 White participants [70.6%]; mean [SD] age, 73 [8] years), MCI/AD developed in 64 participants. Each 0.05-m/s slower gait was associated with a 7% increase in risk of developing MCI/AD (hazard ratio [HR], 1.07 [95% CI, 1.00-1.15]; P = .04). Activity fragmentation alone was not associated with MCI/AD risk (HR, 0.83 [95% CI, 0.56-1.23]; P = .35), but there was a significant interaction between gait speed and activity fragmentation (HR, 0.92 [95% CI, 0.87-0.98]; P = .01). At low activity fragmentation (-1 SD), each 0.05-m/s slower gait speed was associated with a 19% increase in hazard of developing MCI/AD (HR, 1.19 [95% CI, 1.07-1.32]), whereas at higher activity fragmentation (+1 SD), gait speed was not associated with MCI/AD (HR, 1.01 [95% CI, 0.93-1.10]). Among participants with slow gait, higher activity fragmentation was associated with higher odds of having lower extremity osteoarthritis (odds ratio, 1.31 [95% CI, 1.01-1.69]) and less decline in pegboard dominant hand performance (ß = 0.026 [SE, 0.009]; P > .05). Conclusions and Relevance: These findings suggest that frequent rests among older adults with slow gait speed are associated with lower risk of future MCI/AD and that this behavioral strategy is associated with a lower likelihood of subclinical neurological impairment.

5.
Cardiovasc Ther ; 2021: 6139732, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737793

RESUMO

This study was aimed at identifying molecular markers associated with the pathogenesis of sudden cardiac death (SCD). It provides a proteomic analysis of human left anterior descending coronary artery from subjects diagnosed with SCD through histological examination and cases of nondisease accidental deaths through autopsy. A total of 2784 proteins were obtained from label-free quantitative proteomic analysis. This included a total of 265 differential proteins which were involved in SCD-related processes, such as inflammation, muscle system process regulation, metal ion transport, and lysosomal pathway. Western blotting was carried out to measure the expressions of cathepsin C (CTSC), focal adhesion kinase (FAK), p-FAK, and proteins related to the p38/MAPK signaling pathway, whereas immunohistochemistry was performed to determine the localization and expression of CTSC, TNF-α, and CD206 in arterial tissues. It was found that CTSC were the most expressed proteins with a significant upward trend in SCD cases. Besides, CTSC regulated macrophage polarization to M1 through the FAK-induced p38/MAPK signaling pathway. This promoted the release of inflammatory factors and eventually increased the inflammatory response. In conclusion, this study implies that CTSC may be one of the key molecular targets for promoting macrophage M1 polarization in SCD, which may provide new therapeutic insights into the treatment of inflammatory diseases.


Assuntos
Catepsina C , Proteínas Quinases p38 Ativadas por Mitógeno , Morte Súbita Cardíaca/etiologia , Humanos , Macrófagos , Proteômica
6.
Int J Biol Sci ; 17(15): 4108-4121, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803486

RESUMO

Laron syndrome (LS) is an autosomal recessive genetic disease mainly caused by mutations in the human growth hormone receptor (GHR) gene. Previous studies have focused on Ghr mutant mice, but compared with LS patients, Ghr knockout (KO) mice exhibit differential lipid metabolism. To elucidate the relationship between GHR mutation and lipid metabolism, the role of GHR in lipid metabolism was examined in GHR KO pigs and hepatocytes transfected with siGHR. We observed high levels of free fatty acids and hepatic steatosis in GHR KO pigs, which recapitulates the abnormal lipid metabolism in LS patients. RNAseq analysis revealed that genes related to the fatty acid oxidation pathway were significantly altered in GHR KO pigs. AHR, a transcription factor related to lipid metabolism, was significantly downregulated in GHR KO pigs and siGHR-treated human hepatocytes. We found that AHR directly regulated fatty acid oxidation by directly binding to the promoters of ACOX1 and CPT1A and activating their expression. These data indicate that loss of GHR disturbs the ERK-AHR-ACOX1/CPT1A pathway and consequently leads to hepatic steatosis. Our results established AHR as a modulator of hepatic steatosis, thereby providing a therapeutic target for lipid metabolism disorder.

7.
Exp Cell Res ; 409(2): 112943, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34808131

RESUMO

Rheumatoid arthritis (RA) is a chronic inflammation mediated by autoimmune responses. HOTTIP, a long noncoding RNA (lncRNA), participates in cell proliferation and invasion. However, the correlation between HOTTIP and RA remains unclear. Therefore, this study aimed to clarify how HOTTIP works in RA and to investigate its role in the development of RA. Flow cytometry was used to analyze cell cycle progression. Binding between HOTTIP, signal transducer and activator of transcription 3 (STAT3) and miR-1908-5p was demonstrated by dual-luciferase assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of T cell differentiation-related proteins. We found that HOTTIP was upregulated in rheumatoid arthritis synovial fibroblasts (RASFs). HOTTIP directly bound to miR-1908-5p and negatively modulated miR-1908-5p expression while positively regulating STAT3. The effects of HOTTIP overexpression on regulating the balance of the Th17/Treg cell ratio were partly reversed by miR-1908-5p overexpression. In addition, in vivo experiments demonstrated that overexpression of HOTTIP aggravated inflammation in RA mice, which was demonstrated by hematoxylin and eosin (HE) staining and the increased expression levels of CD4+ interleukin (IL)-17+, forkhead Box P3 (FOXP3) and retinoid-related orphan receptor gamma-t (RORγt). In summary, our study suggests that HOTTIP plays a damaging role in RA by promoting inflammation, which may be related to the regulation of miR-1908-5p expression and the STAT3 signaling pathway. These results suggest that the regulation of HOTTIP may be a promising therapeutic strategy for RA.

8.
Front Med (Lausanne) ; 8: 744518, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778306

RESUMO

Background: Galectins, a family of ß-galactoside-binding proteins, are related to the development and progression of various human diseases such as cancer, heart failure, and chronic kidney disease. However, its role in liver diseases is unclear. Methods: The PubMed, Embase, and Cochrane Library databases were searched. Hazard ratios (HRs), odds ratios (ORs), and mean differences (MDs) with 95% CIs were pooled to evaluate the association of the galectins with the outcomes and risk of liver diseases by a random effects model. Results: Thirty three studies involving 43 cohorts and 4,168 patients with liver diseases were included. In the patients with hepatocellular carcinoma (HCC), high expression of galectin-1 and -3 in the tissues was significantly associated with worse overall survival (galectin-1: HR = 1.94, 95% CI = 1.61-2.34, p < 0.001; galectin-3: HR = 3.29, 95% CI = 1.62-6.68, p < 0.001) and positive vascular invasion (galectin-1: OR = 1.74, 95% CI = 1.18-2.58, p = 0.005; galectin-3: OR = 2.98, 95% CI = 1.58-5.60, p = 0.001); but, high expression of galectin-4 and -9 in the tissues was significantly associated with better overall survival (galectin-4: HR = 0.53, 95% CI = 0.36-0.79, p = 0.002; galectin-9: HR = 0.56, 95% CI = 0.44-0.71, p < 0.001) and negative vascular invasion (galectin-4: OR = 0.36, 95% CI = 0.19-0.72, p = 0.003; galectin-9: OR = 0.60, 95% CI = 0.37-0.97, p = 0.037). Serum galectin-3 level was significantly higher in HCC (MD = 3.06, 95% CI = 1.79-4.32, p < 0.001), liver failure (MD = 0.44, 95% CI = 0.23-0.66, p < 0.001), liver cirrhosis (MD = 1.83, 95% CI = 1.15-2.51, p < 0.001), and chronic active hepatitis B (MD = 18.95, 95% CI = 10.91-27.00, p < 0.001); serum galectin-9 level was significantly higher in HCC (MD = 3.74, 95% CI = 2.57-4.91, p < 0.001) and autoimmune hepatitis (MD = 8.80, 95% CI = 7.61-9.99, p < 0.001). Conclusion: High galectin-1 and -3 and low galectin-4 and -9 expression indicate worse outcomes of patients with HCC. Serum galectin-3 and -9 levels are positively associated with the risk of chronic liver diseases.

9.
Medicine (Baltimore) ; 100(39): e27304, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596127

RESUMO

BACKGROUND: Osteosarcoma is one of the most common bone tumors, with a high degree of malignancy and a poor prognosis. Recent studies have shown that THZ2, a cyclin-dependent kinase 7 inhibitor, can exhibit strong antibone tumor effects in vivo and in vitro by inhibiting transcriptional activity. In this study, by screening the differentially expressed genes (DEGs) of osteosarcoma cells before and after THZ2 treatment, it provides new possible targets for the future targeted therapy of osteosarcoma. METHODS: Download the gene expression profile of GSE134603 from the Gene Expression Omnibus database, and use the R software package "limma Geoquery" to screen DEGs. DAVID database was used for gene ontology analysis of DEGs. Use search tool for the retrieval of interacting genes online database and Cytoscape software to construct protein-protein interaction network. Use the "MCODE" plugin in Cytoscape to analyze key molecular complexes (module) of DEGs, and use the "Cluego" plugin to perform Kyoto Encyclopedia of Genes and Genomes enrichment analysis on module genes. The Hub gene is selected from the genes in DEGs that coexist in the top 30 Degree and the Kyoto Encyclopedia of Genes and Genomes pathway. RESULTS: A total of 1033 DEGs were screened, including 800 up-regulated genes and 233 down-regulated genes. Gene ontology analysis showed that cell component is the main enrichment area of DEGs, mainly in the nucleus, cytoplasm, and nucleoplasm. In addition, in molecular function analysis, DEGs are mainly enriched in the process of protein binding. In biological process analysis, changes in DEGs can also be observed in transcription and regulation using DNA as a template. Twenty-nine module genes are enriched in the Ribosome biogenesis in eukaryotes pathway. Finally, 4 key genes are drawn: essential for mitotic growth 1, U3 SnoRNP protein 3 homolog, U3 small nucleolar RNA-associated protein 15 homolog, and WD repeat domain 3. CONCLUSION: This study found that the 4 genes essential for mitotic growth 1, U3 SnoRNP protein 3 homolog, U3 small nucleolar RNA-associated protein 15 homolog, WD repeat domain 3, and the ribosome biogenesis in eukaryotes pathway play a very important role in the occurrence and development of osteosarcoma, and can become a new target for molecular targeted therapy of osteosarcoma in the future.


Assuntos
Neoplasias Ósseas/genética , Genes Neoplásicos/genética , Osteossarcoma/genética , Neoplasias Ósseas/tratamento farmacológico , Quinases Ciclina-Dependentes/antagonistas & inibidores , Humanos , Osteossarcoma/tratamento farmacológico , Células Tumorais Cultivadas/efeitos dos fármacos
10.
Int J Gen Med ; 14: 6713-6724, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675632

RESUMO

Background and Aim: Long-term use of non-selective beta blockers (NSBBs) is essential for the prevention of esophageal variceal bleeding in liver cirrhosis but may impair the patient's adherence. The present study aimed to investigate the adherence to NSBBs to prevent variceal bleeding in cirrhotic patients. Methods: All patients who had an indication of NSBBs for the prophylaxis of variceal bleeding between February 2018 and June 2019 were screened. Clinical pharmacists gave pre-medication education and recorded the adherence to NSBBs during the patients' hospitalizations. Factors associated with poor adherence were evaluated by univariate logistic regression analysis. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. The relationship between poor adherence during follow-up and variceal bleeding after discharge was also evaluated. Results: Overall, 108 patients were screened, of whom 12 were intolerant to NSBBs. Among the 96 remaining patients who could take NSBBs, the average change of heart rate after NSBBs was -10.49 b.p.m. Twenty-two (22.9%) patients had poor adherence to NSBBs due to their refusal to take NSBBs (n = 2), complete forgetfulness to take NSBBs (n = 10), and refusal or forgetfulness to monitor heart rate (n = 10). Univariate logistic regression analysis demonstrated that only older age was significantly associated with poor adherence (OR: 1.065, 95% CI: 1.019-1.114, P = 0.005). Patients with poor adherence during follow-up were more likely to develop variceal bleeding after discharge. Conclusion: A significant proportion of cirrhotic patients had poor adherence to NSBBs during their hospitalizations. Further studies should explore how to improve the patient's adherence to NSBBs.

11.
Tissue Eng Regen Med ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618337

RESUMO

BACKGROUND: As a contour-supporting material, the cartilage has a significant application value in plastic surgery. Since the development of hydrogel scaffolds with sufficient biomechanical strength and high biocompatibility, cell-laden hydrogels have been widely studied for application in cartilage bioengineering. This systematic review summarizes the latest research on engineered cartilage constructed using cell-laden hydrogel scaffolds in plastic surgery. METHODS: A systematic review was performed by searching the PubMed and Web of Science databases using selected keywords and Medical Subject Headings search terms. RESULTS: Forty-two studies were identified based on the search criteria. After full-text screening for inclusion and exclusion criteria, 18 studies were included. Data collected from each study included culturing form, seed cell types and sources, concentration of cells and gels, scaffold materials and bio-printing structures, and biomechanical properties of cartilage constructs. These cell-laden hydrogel scaffolds were reported to show some feasibility of cartilage engineering, including better cell proliferation, enhanced deposition of glycosaminoglycans and collagen type II in the extracellular matrix, and better biomechanical properties close to the natural state. CONCLUSION: Cell-laden hydrogels have been widely used in cartilage bioengineering research. Through 3-dimensional (3D) printing, the cell-laden hydrogel can form a bionic contour structure. Extracellular matrix expression was observed in vivo and in vitro, and the elastic modulus was reported to be similar to that of natural cartilage. The future direction of cartilage tissue engineering in plastic surgery involves the use of novel hydrogel materials and more advanced 3D printing technology combined with biochemistry and biomechanical stimulation.

12.
Org Lett ; 23(20): 7961-7965, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34612651

RESUMO

This report describes a palladium-catalyzed Catellani reaction consisting of amination/[2 + 3] or [2 + 4] cyclization via a carboxylate ligand-exchange strategy. This method effectively activates ortho-substituents that avoid a second C-H palladation. The scope of substrates was broad, o-methyl-substituted iodoarenes were applied to the reaction smoothly, and o-phenyl-substituted iodoarenes can also be obtained by this method. In terms of mechanism, density functional theory calculations proved the sequence of the key five-membered aryl-norbornene-palladacycle intermediate formation and C(sp3 or sp2)-H activation.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34628503

RESUMO

BACKGROUND: Higher energetic costs for mobility are associated with declining gait speed and slow gait is linked to cognitive decline and Alzheimer's disease. However, the physiological underpinnings of gait and brain health have not been well explored. We examined the associations of the energetic cost of walking with brain volume in cognitively unimpaired adults from the Baltimore Longitudinal Study of Aging. METHODS: We used brain MRI data from 850 participants (mean baseline age 66.3±14.5 years), of whom 451 had longitudinal MRI data (2.8±1.0 MRI scans over 4.0±2.0 years). The energetic cost of walking was assessed as the average energy expended (V̇O2) during 2.5 minutes of customary-paced overground walking. Multivariable linear mixed effects models examined the associations between baseline energetic cost of walking and regional brain volumes adjusting for covariates. RESULTS: At baseline, higher energetic cost of walking was cross-sectionally associated with lower gray and white matter volumes within the frontal, parietal, and temporal lobes, as well as hippocampal, total brain, and larger ventricular volumes (all FDR p< 0.05). A baseline energetic cost of walking × time interaction demonstrated that participants with higher energetic cost of walking had faster annual decline in hippocampal volume (FDR p= 0.01) and accelerated annual increase in ventricular volumes (FDR p= 0.01). CONCLUSIONS: The energetic cost of walking is associated with gray and white matter volumes and subsequent hippocampal atrophy and ventricular enlargement. Collectively, these data suggest the energetic cost of walking may be an early marker of neurodegeneration that contributes to the gait brain connection.

14.
Eur Phys J C Part Fields ; 81(9): 789, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512143

RESUMO

We clarify the problem in which occasions can gravitational force be regarded emergent from thermodynamics, by proposing an entropic mechanism that can extract the entropic gradient existing in spacetime, due to the variation of the Casini-Bekenstein bound in specific quasi-static processes with the heat flux δ Q into the whole casual wedge. We explicitly formulate the derivation of inertial force as the emergent gravitational attraction from the Entanglement First Law. We find the saturation of the bound along with the vanishing relative entropy corresponds to the variation of minimal surface. To covariant meaning, it is the Bousso bound. Besides, this understanding is connected to recent Pennington's work on Black Hole Information Paradox, suggesting a Page-Curve function origins from removing attraction by the external heat bath. Our theory from entanglement now overcomes several criticism towards Verlinde's original entropic force proposal, and is able to co-exist with Susskind's Complexity Tendency. This entropic mechanism reproduces the Newton's Second Law in Rindler space and the gravitational force (together with derivation of the Einstein equation) beyond the near-horizon region, and can be adapted into AdS/CFT and other generic situations.

15.
Pathol Oncol Res ; 27: 1609859, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381313

RESUMO

Colorectal signet ring cell carcinoma (SRCC) is a rare subtype of colorectal cancer (CRC) with unique characteristics. Due to the limited researches on it, a comprehensive and in-depth understanding of this subtype is still lacking. In this article, we summarize the clinicopathological features and molecular characteristics of colorectal SRCC based on a literature review. Clinically, SRCC has been associated with young age, proximal site preference, advanced tumor stage, high histological grade, high rate of lymph node involvement, frequent peritoneal metastasis, and a significantly poor prognosis. Regarding molecular characteristics, in SRCC, the mutation burden of the classic signaling pathways that include WNT/ß-catenin, RAS/RAF/MAPK, and PI3K/AKT/mTOR signaling pathways are generally reduced. In contrast, some genes related to the "epithelial-mesenchymal transition (EMT) process" and the "stem cell properties", including RNF43, CDH1, and SMAD4, as well as the related TGF-ß signaling pathway have been observed more frequently altered in SRCC than in conventional adenocarcinoma (AC). In many studies but not in others, SRCC showed a higher frequency of BRAF mutation, microsatellite instability-high (MSI-H) and CpG island methylator phenotype (CIMP) positive status compared to AC. It has been proposed that colorectal SRCC consists of two subtypes, in which the MSI+/CIMP+/BRAF +/CD3+/PD-L1+ hypermethylated genotype is more common in the proximal colon, and may represent the potential candidate for immunotherapy. Understanding the special molecular mechanisms related to the aggressive biology of SRCC is of great importance, which may provide a theoretical basis for the development of more targeted and effective treatments for this refractory disease.

16.
Alzheimers Dement (Amst) ; 13(1): e12228, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34458552

RESUMO

Introduction: Higher energetic costs for mobility predict gait speed decline. Slow gait is linked to cognitive decline and Alzheimer's disease (AD). Whether the energetic cost of walking is linked to AD pathology is unknown. We investigated the cross-sectional association between the energetic cost of walking, gait speed, and amyloid beta (Aß) status (+/-) in older adults. Methods: One hundred forty-nine cognitively normal adults (56% women, mean age 77.5 ± 8.4 years) completed customary-paced walking assessments with indirect calorimetry and 11C-Pittsburgh compound B positron emission tomography. Logistic regression models examined associations adjusted for demographics, body composition, comorbid conditions, and apolipoprotein E ε4. Results: Each 0.01 mL/kg/m greater energy cost was associated with 18% higher odds of being Aß+ (odds ratio [OR] = 1.18; 95% confidence interval [CI]: 1.04 to 1.34; P = .011). These findings were not observed when investigating gait speed (OR = 0.99; 95% CI: 0.97 to 1.01; P = .321). Discussion: High energetic cost of walking is linked to AD pathology and may be a potential target for therapeutic intervention.

17.
Front Endocrinol (Lausanne) ; 12: 605797, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234737

RESUMO

Pheochromocytoma (PCC) is a rare neuroendocrine tumor of the adrenal gland with a high rate of mortality if diagnosed at a late stage. Common symptoms of pheochromocytoma include headache, anxiety, palpitation, and diaphoresis. Different treatments are under observation for PCC but there is still no effective treatment option. Recently, the gene expression profiling of various tumors has provided new subtype-specific options for targeted therapies. In this study, using data sets from TCGA and the GSE19422 cohorts, we identified two distinct PCC subtypes with distinct gene expression patterns. Genes enriched in Subtype I PCCs were involved in the dopaminergic synapse, nicotine addiction, and long-term depression pathways, while genes enriched in subtype II PCCs were involved in protein digestion and absorption, vascular smooth muscle contraction, and ECM receptor interaction pathways. We further identified subtype specific genes such as ALK, IGF1R, RET, and RSPO2 for subtype I and EGFR, ESR1, and SMO for subtype II, the overexpression of which led to cell invasion and tumorigenesis. These genes identified in the present research may serve as potential subtype-specific therapeutic targets to understand the underlying mechanisms of tumorigenesis. Our findings may further guide towards the development of targeted therapies and potential molecular biomarkers against PCC.

18.
Aesthetic Plast Surg ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312695

RESUMO

Once cartilage is damaged, its self-repair capacity is very limited. The strategy of tissue engineering has brought a new idea for repairing cartilage defect and cartilage regeneration. In particular, nasal cartilage regeneration is a challenge because of the steady increase in nasal reconstruction after oncologic resection, trauma, or rhinoplasty. From this perspective, three-dimensional (3D) printing has emerged as a promising technology to address the complexity of nasal cartilage regeneration, using patient's image data and computer-aided deposition of cells and biomaterials to precisely fabricate complex, personalized tissue-engineered constructs. In this review, we summarized the major progress of three prevalent 3D printing approaches, including inkjet-based printing, extrusion-based printing and laser-assisted printing. Examples are highlighted to illustrate 3D printing for nasal cartilage regeneration, with special focus on the selection of seeded cell, scaffolds and growth factors. The purpose of this paper is to systematically review recent research about the challenges and progress and look forward to the future of 3D printing techniques for nasal cartilage regeneration.Level of Evidence III This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

19.
Regen Biomater ; 8(3): rbab019, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34211731

RESUMO

Cartilage has limited self-repair ability due to its avascular, alymphatic and aneural features. The combination of three-dimensional (3D) printing and tissue engineering provides an up-and-coming approach to address this issue. Here, we designed and fabricated a tri-layered (superficial layer (SL), middle layer (ML) and deep layer (DL)) stratified scaffold, inspired by the architecture of collagen fibers in native cartilage tissue. The scaffold was composed of 3D printed depth-dependent gradient poly(ε-caprolactone) (PCL) impregnated with methacrylated alginate (ALMA), and its morphological analysis and mechanical properties were tested. To prove the feasibility of the composite scaffolds for cartilage regeneration, the viability, proliferation, collagen deposition and chondrogenic differentiation of embedded rat bone marrow mesenchymal stem cells (BMSCs) in the scaffolds were assessed by Live/dead assay, CCK-8, DNA content, cell morphology, immunofluorescence and real-time reverse transcription polymerase chain reaction. BMSCs-loaded gradient PCL/ALMA scaffolds showed excellent cell survival, cell proliferation, cell morphology, collagen II deposition and hopeful chondrogenic differentiation compared with three individual-layer scaffolds. Hence, our study demonstrates the potential use of the gradient PCL/ALMA construct for enhanced cartilage tissue engineering.

20.
JAMA Netw Open ; 4(7): e2117416, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34269806

RESUMO

Importance: Associations between visual and global cognitive impairments have been previously documented, but there is limited research examining these associations between multiple measures of vision across cognitive domains. Objective: To examine the association between vision and cognitive across multiple cognitive domains using multiple measures of vision. Design, Setting, and Participants: This longitudinal cohort study used data from the Baltimore Longitudinal Study of Aging for 2003 to 2019. Participants in the current study were aged 60 to 94 years with vision and cognitive measures. Data analysis was performed from May 2020 to May 2021. Main Outcomes and Measures: Cognitive function was measured across multiple domains, including language, memory, attention, executive function, and visuospatial ability. Cognitive domain scores were calculated as the mean of standardized cognitive test scores within each domain. Visual function was assessed using measures of visual acuity, contrast sensitivity, and stereo acuity at baseline. Results: Analyses included 1202 participants (610 women [50.8%]; 853 White participants [71.0%]) with a mean (SD) age of 71.1 (8.6) years who were followed up for a mean (SD) of 6.9 (4.7) years. Worse visual acuity (per 0.1 logarithm of the minimal angle of resolution) at baseline was associated with greater declines in language (ß, -0.0035; 95% CI, -0.007 to -0.001) and memory (ß, -0.0052; 95% CI, -0.010 to -0.001) domain scores. Worse contrast sensitivity (per 0.1 log units) at baseline was associated with greater declines in language (ß, -0.010; 95% CI, -0.014 to -0.006), memory (ß, -0.009; 95% CI, -0.015 to -0.003), attention (ß, -0.010; 95% CI, -0.017 to -0.003), and visuospatial ability (ß, -0.010; 95% CI, -0.017 to -0.002) domain scores. Over the follow-up period, declines on tests of language (ß, -0.019; 95% CI, -0.034 to -0.005) and memory (ß, -0.032; 95% CI, -0.051 to -0.012) were significantly greater for participants with impaired stereo acuity compared with those without such impairment. Conclusions and Relevance: These findings suggest that the association between vision and cognition differs between visual acuity, contrast sensitivity, and stereo acuity and that patterns of cognitive decline may differ by type of vision impairment, with impaired contrast sensitivity being associated with declines across more cognitive domains than other measures of visual functioning.

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