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1.
Artigo em Inglês | MEDLINE | ID: mdl-34524632

RESUMO

Morchella esculenta (M. esculenta) is a delicious edible mushroom prized for its special flavor and strong health promoting abilities. Several bioactive ingredients including polysaccharides, polyphenolic compounds, proteins, and protein hydrolysates all contribute to the biological activities of M. esculenta. Different polysaccharides could be extracted and purified depending on the extraction methods and M. esculenta studied. Monosaccharide composition of M. esculenta polysaccharides (MEP) generally includes mannose, galactose, and glucose, etc. MEP possess multiple bioactivities such as antioxidant, anti-inflammation, immunoregulation, hypoglycemic activity, atherosclerosis prevention and antitumor ability. Other components like polyphenols, protein hydrolysates, and several crude extracts are also reported with strong bioactivities. In terms of potential applications of M. esculenta and its metabolites as nutritional supplements and drug supplements, this review aims to comprehensively summarize the structural characteristics, biological activities, research progress, and research trends of the active ingredients produced by M. esculenta. Among the various biological activities, the substances extracted from both natural collected and submerged fermented M. esculenta are promising for antioxidants, immunomodulation, anti-cancer and anti-inflammatory applications. However, further researches on the extraction conditions and chemical structure of bioactive compounds produced by M. esculenta still need investigations.

2.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(9): 794-800, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34533126

RESUMO

Objective To investigate the effect of endoplasmic reticulum stress (ERS) induced by tunicamycin on proliferation, activation, and apoptosis of HSC-T6 rat hepatic stellate cells and its possible mechanism. Methods With the expression level of glucose regulated protein 78 (GRP78) as an indicator to explore the optimal concentration and time, a cell model of tunicamycin-induced ERS in HSC-T6 cells was established. HSC-T6 cells were randomized into control group, treatment group with 1 mL/L of dimethyl sulfoxide (DMSO), and treatment group with 1 µg/mL of tunicamycin, and the cells were treated for 12 h. MTT assay was used to detect cell proliferation, flow cytometry to detect apoptosis and cell cycle, and Western blot to detect the protein expressions of α-smooth muscle actin (α-SMA), C/EBP cAMP homologous protein (CHOP), caspase-12, and cyclin D1. Results The optimal dose of tunicamycin to induce ERS in HSC-T6 cells was 1 µg/mL and the optimal time was 12 hours. Compared with the control group and treatment group with DMSO, the treatment group with 1 µg/mL of tunicamycin had no significant change in cell proliferation, but the expression of α-SMA was up-regulated with the apoptosis increased, the proportion of G1 phase cells was significantly increased and that of S phase cells decreased, the ERS induced apoptosis related signal proteins CHOP and caspase-12 were significantly up-regulated, and the expression of cyclin D1 was significantly down-regulated. Conclusion Tunicamycin treatment of HSC-T6 cells for 12 hours induces significant ERS and activation of the cells. The insignificant change in the number of cells during the activation may be related to the increased apoptosis and the cell cycle arrest induced by the activation of the GRP78/CHOP/caspase-12 pathway.


Assuntos
Estresse do Retículo Endoplasmático , Células Estreladas do Fígado , Animais , Apoptose , Pontos de Checagem do Ciclo Celular , Ratos , Tunicamicina/farmacologia
3.
Environ Int ; 157: 106848, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34467876

RESUMO

Indoor dust has been used as a proxy for estimating human indoor pollutant exposure risks, yet source identification remains challenging. This study tentatively investigated whether quantitative fatty acid signature analysis (QFASA) of dust, could be applied to indicate sources and their respective contributions for a major class of indoor organic pollutants organophosphate flame retardants (OPFRs). We observed significant correlations between OPFR concentrations and lipid content (p < 0.05) in house dusts. Using 15 signature fatty acids (FAs) in various indoor sources and the QFASA model, we found that clothing (39.1% in Australia and 36.5% in China) was the predominant contributing vector of dust OPFR followed by cooking oil and pet hair. Among these sources, clothing materials were proposed to be important vectors introducing organic pollutants to the indoor environment. Our QFASA contribution estimation analyses allowed for accurate prediction of most OPFR concentrations in clothing, validating our findings that clothing materials may serve as important carrier for OPFRs in indoor migration. This is the first study attempting to identify sources of organic pollutants using QFASA in an indoor setting and will provide important insight into the transfer of organic pollutants in indoor environment.

4.
Nat Genet ; 53(9): 1392-1402, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34493868

RESUMO

Despite early domestication around 3000 BC, the evolutionary history of the ancient allotetraploid species Brassica juncea (L.) Czern & Coss remains uncertain. Here, we report a chromosome-scale de novo assembly of a yellow-seeded B. juncea genome by integrating long-read and short-read sequencing, optical mapping and Hi-C technologies. Nuclear and organelle phylogenies of 480 accessions worldwide supported that B. juncea is most likely a single origin in West Asia, 8,000-14,000 years ago, via natural interspecific hybridization. Subsequently, new crop types evolved through spontaneous gene mutations and introgressions along three independent routes of eastward expansion. Selective sweeps, genome-wide trait associations and tissue-specific RNA-sequencing analysis shed light on the domestication history of flowering time and seed weight, and on human selection for morphological diversification in this versatile species. Our data provide a comprehensive insight into the origin and domestication and a foundation for genomics-based breeding of B. juncea.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34494808

RESUMO

Extensive studies have laid the groundwork for understanding peroxidase-like nanozymes. However, improvements are still required before their practical applications. On one hand, it is significant to explore highly reactive nanozymes. On the other hand, it is necessary to avoid fouling formed on the surface of nanozymes, which will affect their activity and the results of H2O2 sensors or H2O2-related applications. Herein, a strategy is reported to design osmium nanoclusters (Os NCs) with the existence of bovine serum albumin (BSA) through biomineralization. BSA-Os NCs were found to possess intrinsic peroxidase-like activity with a high specific activity (6120 U/g). Studies also found that the catalytic activity of BSA-Os NCs was better than those of reported protein-assisted metal nanozymes (e.g., BSA-Pt NPs and BSA-Au NCs). More significantly, BSA has been confirmed as a protective shell to give Os NCs extrinsic antifouling property in some typical ions (e.g., Hg2+, Ag+, Pb2+, I-, Cr6+, Cu2+, Ce3+, S2-, etc.), saline (0-2 M), or protein (0-100 mg/mL) conditions. Under optimal conditions, a colorimetric sensor was established to realize a linear range of H2O2 from 1.25 to 200 µM with a low detection limit of 300 nM. On this basis, remarkable features enable a BSA-Os NCs-based colorimetric sensor to detect H2O2 from complex systems with clear color gradients. Together, this work highlights the advantages of protein-assisted Os nanozymes and provides a paragon for peroxidase-like nanozymes in H2O2-related applications.

6.
BMC Cardiovasc Disord ; 21(1): 420, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488649

RESUMO

BACKGROUND: Malnutrition in early life may affect health in later life. The associations between malnutrition and serum uric acid (SUA) and hypertension were inconsistent. The present study aimed to investigate the individual and combined association between famine exposure and serum uric acid and hypertension in middle-aged and older Chinese. METHODS: Data were selected from the China Health and Retirement Longitudinal Study (CHARLS) Wave2011. The analytic sample included 9368 individuals aged 45 to 90. Differences between baseline characteristics and famine exposure/SUA level were evaluated using the Chi-square test, t-test, and F-test. Then, the differences in the prevalence of hypertension between characteristic groups was also estimated by the Chi-square and t-test. Finally, multivariable-adjusted logistic regression models examined association of famine exposure and serum uric acid with odds of prevalence of hypertension. RESULTS: A total of 9368 individuals were enrolled in the study, 4366 (46.61%) and 5002 (53.39%) were male and female, respectively. Among males, 459 (10.51%) had been exposed to the Chinese famine during the fetal stage, whereas 1760 (40.31%) and 1645 (37.68%) had been exposed to the famine during childhood and adolescence/adult stage, respectively. Among females, 635 (12.69%) had been exposed to the Chinese famine during the fetal stage, whereas 1988 (39.74%) and 1569 (31.37%) had been exposed to the famine during childhood and adolescence/adult stage, respectively. Regarding the participants with SUA level measurements, 290 (6.64%) reported having Hyperuricemia (HUA) in males and 234 (4.68%) in the females. Furthermore, 1357 (31.08%) reported having hypertension in male and 1619 (32.37%) in the female. In multivariable-adjusted model, famine exposure and serum uric acid were associated with prevalence of hypertension independently in total populations [(1) Model fourd, fatal exposed group vs non-exposed group: 1.25 (95% CI 1.03, 1.52); childhood-exposed group vs non-exposed group:1.60 (95% CI 1.37, 1.87); adolescence/adult exposed group vs non-exposed group: 2.87 (95% CI 2.44, 3.37), P for trend < 0.001; (2) Model four e, high vs normal:1.73 (95% CI 1.44, 2.08)]. When stratified by sex, the results in both males and females were similar to those in the total population. In general, interaction analysis in the multivariable-adjusted model, compared with the combination of normal SUA level and no-exposed famine stage, all groups trended towards higher odds of prevalence of hypertension [the greatest increase in odds, adolescence/adult exposed stage and high SUA level in total participants: OR4.34; 95%CI 3.24, 5.81; P for interaction < 0.001]. When stratified by sex, the results in both males and females were also similar to those in the total population. CONCLUSION: Our data support a strongly positive individual and combined association of famine exposure and serum uric acid with hypertension in middle-aged and elderly Chinese.

7.
Autism ; : 13623613211041904, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465247

RESUMO

LAY ABSTRACT: Autism spectrum disorder has long been conceptualized as a disorder of "atypical development of functional brain connectivity (which refers to correlations in activity levels of distant brain regions)." However, most of the research has focused on the connectivity between cortical regions, and much remains unknown about the developmental changes of functional connectivity between subcortical and cortical areas in autism spectrum disorder. We used the technique of resting-state functional magnetic resonance imaging to explore the developmental characteristics of intrinsic functional connectivity (functional brain connectivity when people are asked not to do anything) between subcortical and cortical regions in individuals with and without autism spectrum disorder aged 6-30 years. We focused on one important subcortical structure called striatum, which has roles in motor, cognitive, and affective processes. We found that cortico-striatal intrinsic functional connectivities showed opposite developmental trajectories in autism spectrum disorder and typically developing individuals, with connectivity increasing with age in autism spectrum disorder and decreasing or constant in typically developing individuals. We also found significant negative behavioral correlations between those atypical cortico-striatal intrinsic functional connectivities and autistic symptoms, such as social-communication deficits, and restricted/repetitive behaviors and interests. Taken together, this work highlights that the atypical development of cortico-subcortical functional connectivity might be largely involved in the neuropathological mechanisms of autism spectrum disorder.

8.
Transplantation ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34468429

RESUMO

BACKGROUND: As the number of donation after circulatory death(DCD) liver transplants(LTs) performed in the United States continues to increase annually, there has been interest by policy makers to develop a more robust exception point safety net for patients who develop ischemic cholangiopathy(IC) following DCD LT. As such, there is a need for better understanding of the clinical course and long-term outcomes in patients who develop IC, as well as determining if IC can be classified into distinct categories with distinctly different clinical outcomes. METHODS: All DCD LT performed at Mayo Clinic-Florida, Mayo Clinic-Arizona and Mayo Clinic-Rochester from 1/1999-3/2020 were included(N=770). Outcomes were compared between 4 distinct radiologic patterns of IC: Diffuse Necrosis(DN), Multifocal Progressive(MP), Confluence Dominant(CD) and Minor Form(MF). RESULTS: In total N=88(11.4%) patients developed IC, of which N=42(5.5%) were listed for retransplantation (ReLT). Patients with DN and MP patterns suffered from frequent hospital admissions for cholangitis in the first year following DCD LT(median 3 and 2), were largely stent dependent(100% and 85.7%) and almost universally required ReLT. Patients with CD disease were managed with multiple stents and frequently recovered, ultimately becoming stent free without need for ReLT. Patients with the MF IC did well with limited need for stent placement or repeat procedures and did not require ReLT. Graft survival was different between the 4 distinct IC patterns(p<0.001). CONCLUSIONS: The present analysis provides a detailed analysis on the natural history and clinical course of IC. Patients developing IC can be classified into 4 distinct patterns with distinct clinical courses.

9.
J Pharm Pharmacol ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34468764

RESUMO

OBJECTIVES: Cadmium (Cd) induces reactive oxygen species (ROS)-mediated hepatocyte apoptosis and consequential liver disorders. This study aimed to investigate the effect of magnesium isoglycyrrhizinate (MgIG) on Cd-induced hepatotoxicity. METHODS: L02 and AML-12 cells were used to study MgIG hepatoprotective effects. Cd-evoked apoptosis, ROS and protein phosphatase 2A (PP2A)/c-Jun N-terminal kinase (JNK) cascade disruption were analysed by cell viability assay, 6-diamidino-2-phenylindole (DAPI) and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, ROS imaging and Western blotting. Pharmacological and genetic approaches were used to explore the mechanisms. KEY FINDINGS: We show that MgIG attenuated Cd-evoked hepatocyte apoptosis by blocking JNK pathway. Pre-treatment with SP600125 or ectopic expression of dominant-negative c-Jun enhanced MgIG's anti-apoptotic effects. Further investigation found that MgIG rescued Cd-inactivated PP2A. Inhibition of PP2A activity by okadaic acid attenuated the MgIG's inhibition of the Cd-stimulated JNK pathway and apoptosis; in contrast, overexpression of PP2A strengthened the MgIG effects. In addition, MgIG blocked Cd-induced ROS generation. Eliminating ROS by N-acetyl-l-cysteine abrogated Cd-induced PP2A-JNK pathway disruption and concurrently reinforced MgIG-conferred protective effects, which could be further slightly strengthened by PP2A overexpression. CONCLUSIONS: Our findings indicate that MgIG is a promising hepatoprotective agent for the prevention of Cd-induced hepatic injury by mitigating ROS-inactivated PP2A, thus preventing JNK activation and hepatocyte apoptosis.

10.
Proc Natl Acad Sci U S A ; 118(39)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34544864

RESUMO

It is well documented that the juvenile hormone (JH) can function as a gonadotropic hormone that stimulates vitellogenesis by activating the production and uptake of vitellogenin in insects. Here, we describe a phenotype associated with mutations in the Drosophila JH receptor genes, Met and Gce: the accumulation of mature eggs with reduced egg length in the ovary. JH signaling is mainly activated in ovarian muscle cells and induces laminin gene expression in these cells. Meanwhile, JH signaling induces collagen IV gene expression in the adult fat body, from which collagen IV is secreted and deposited onto the ovarian muscles. Laminin locally and collagen IV remotely contribute to the assembly of ovarian muscle extracellular matrix (ECM); moreover, the ECM components are indispensable for ovarian muscle contraction. Furthermore, ovarian muscle contraction externally generates a mechanical force to promote ovulation and maintain egg shape. This work reveals an important mechanism for JH-regulated insect reproduction.

11.
Anim Sci J ; 92(1): e13631, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34545661

RESUMO

Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) plays essential roles in the proliferation of skeletal muscle satellite cells (MuSCs). Increasing evidence has shown that IGF2BP1 regulates the expression of noncoding RNAs and mRNAs. However, the related molecular network remains to be fully understood. Therefore, we performed RNA sequencing and analyzed the microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and mRNAs differentially expressed in goat MuSCs treated with IGF2BP1 overexpressing and empty vectors. A total of 36 miRNAs, 59 lncRNAs, and 44 mRNAs were differentially expressed caused by IGF2BP1. Expectedly, they were enriched in muscle development-related Rap1, PI3K-AKT, and FoxO signaling pathways. Finally, we constructed a lncRNA-miRNA-mRNA interaction network containing 30 lncRNAs, 15 miRNAs, and 34 mRNAs, in which several miRNAs, including miR-133a-3p, miR-204-5p, miR-125a-3p, miR-145-3p, and miR-423-5p, relate with cell growth and participate in muscle development. Overall, we constructed an IGF2BP1-related network, which provides new insight into the myogenic proliferation of goat.

12.
Drug Discov Today ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34537334

RESUMO

Tuberculosis (TB), an airborne infectious disease mainly caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of human morbidity and mortality worldwide. Given the alarming rise of resistance to anti-TB drugs and latent TB infection (LTBI), new targets and novel bioactive compounds are urgently needed for the treatment of this disease. We provide an overview of the recent advances in anti-TB drug discovery, emphasizing several newly validated targets for which an inhibitor has been reported in the past five years. Our review presents several attractive directions that have potential for the development of next-generation therapies.

13.
Curr Med Sci ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34542827

RESUMO

OBJECTIVE: Although relatively rare, adult immunoglobulin A vasculitis (IgAV) can lead to severe complications and longer hospitalization, and result in poor prognosis, when compared to childhood IgAV. Hence, early identification and prevention for patients prone to develop systemic involvement are essential. The purpose of this study was to explore the correlations of common serological markers with the development of systemic involvement in adult IgAV. METHODS: A retrospective analysis was performed for adult IgAV patients, who were hospitalized in Wuhan Union Hospital between January 2016 and December 2019. A total of 259 patients were enrolled, and the pre-treatment serological markers were comprehensively assessed. RESULTS: In the present study, 49.0% and 33.2% of patients developed renal and gastrointestinal (GI) involvement, respectively. Furthermore, the elevated levels of white blood cells count, D-Dimer (D-D), C-reactive protein (CRP) and neutrophil granulocyte ratio (NE%) >60% were significantly associated with GI involvement in the univariate analysis, while the decrease in high density lipoprotein level, and the elevated D-D and CRP levels were significantly associated with renal involvement (P<0.05). Moreover, a prediction model that combined multiple markers was established by performing a logistic regression analysis, and this presented a more favorable value of prediction than the individual serological markers. CONCLUSION: The present study suggests that common serological markers have close correlations with systemic involvement in adult IgAV, and that the establishment of a prediction model for systemic involvement may be helpful in facilitating personalized therapeutic strategies and clinical management for IgAV patients.

14.
Front Immunol ; 12: 691605, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484187

RESUMO

Background: Neoantigens are critical targets to elicit robust antitumor T-cell responses. Personalized cancer vaccines developed based on neoantigens have shown promising results by prolonging cancer patients' overall survival (OS) for several cancer types. However, the safety and efficacy of these vaccine modalities remains unclear in pancreatic cancer patients. Methods: This retrospective study enrolled 7 advanced pancreatic cancer patients. Up to 20 neoantigen peptides per patient identified by our in-house pipeline iNeo-Suite were selected, manufactured and administered to these patients with low tumor mutation burden (TMB) (less than 10 mutations/Mb). Each patient received multiple doses of vaccine depending on the progression of the disease. Peripheral blood samples of each patient were collected pre- and post-vaccination for the analysis of the immunogenicity of iNeo-Vac-P01 through ELISpot assay and flow cytometry. Results: No severe vaccine-related adverse effects were witnessed in patients enrolled in this study. The mean OS, OS associated with vaccine treatment and progression free survival (PFS) were reported to be 24.1, 8.3 and 3.1 months, respectively. Higher peripheral IFN-γ titer and CD4+ or CD8+ effector memory T cells count post vaccination were found in patients with relatively long overall survival. Remarkably, for patient P01 who had a 21-month OS associated with vaccine treatment, the abundance of antigen-specific TCR clone drastically increased from 0% to nearly 100%, indicating the potential of iNeo-Vac-P01 in inducing the activation of a specific subset of T cells to kill cancer cells. Conclusions: Neoantigen identification and selection were successfully applied to advanced pancreatic cancer patients with low TMB. As one of the earliest studies that addressed an issue in treating pancreatic cancer with personalized vaccines, it has been demonstrated that iNeo-Vac-P01, a personalized neoantigen-based peptide vaccine, could improve the currently limited clinical efficacy of pancreatic cancer. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT03645148).Registered August 24, 2018 - Retrospectively registered.

15.
Mol Genet Genomic Med ; : e1800, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34498425

RESUMO

BACKGROUND: Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening pathology that remains a challenge worldwide. Up to 40% of TAAD cases are hereditary with complex heterogeneous genetic backgrounds. The purposes of this study were to determine the diagnostic rate of patients with TAAD, investigate the molecular pathologic spectrum of TAAD by next-generation sequencing (NGS), and explore the future preclinical prospects of genetic diagnosis in patients at high -risk of study. METHODS: NGS was used to screen 15 genes associated with genetic TAAD in 212 patients from northwestern China. Clinical data of patients were gathered by electrocardiography, transthoracic echocardiography, and computed tomography. RESULTS: Of the 212 patients, 67 (31.60%) tested positive for a (likely) pathogenic variant, 42 (19.81%) had a variant of uncertain significance (VUS), and 103 (48.58%) had no variant (likely benign/benign/negative). A total of 135 reportable variants were detected in our test, among which 77 (57.04%) are first reported in this paper. A genotype-phenotype correlation of FBN1 was assessed, and the data showed that the patients with truncating and splicing mutations are more prone to developing severe aortic dissection than those with missense mutations, especially frameshift mutations (82.76% vs. 42.86%). In this study, 43 (20.28%) patients had a family history of sudden death or TAAD, whereas 132 (62.26%) did not (the remaining 37 were not available), and the positive rate of genetic testing was higher in TAAD patients with family history than in those without (76.74% vs. 18.94%). CONCLUSION: Our study concludes that genetic variation is an important consideration in the risk stratification of individualized prediction and disease diagnosis.

16.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4089-4095, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467718

RESUMO

Gastric cancer(GC), one of the most common malignancies worldwide, seriously threatens human health due to its high morbidity and mortality. Precancerous lesion of gastric cancer(PLGC) is a critical stage for preventing the occurrence of gastric cancer, and PLGC therapy has frequently been investigated in clinical research. Exploring the proper animal modeling methods is necessary since animal experiment acts as the main avenue of the research on GC treatment. At present, N-methyl-N'-nitro-N-nitroso-guanidine(MNNG) serves as a common chemical inducer for the rat model of GC and PLGC. In this study, MNNG-based methods for modeling PLGC rats in related papers were summarized, and the applications and effects of these methods were demonstrated by examples. Additionally, the advantages, disadvantages, and precautions of various modeling methods were briefly reviewed, and the experience of this research group in exploring modeling methods was shared. This study is expected to provide a reference for the establishment of MNNG-induced PLGC animal model, and a model support for the following studies on PLGC.


Assuntos
Lesões Pré-Cancerosas , Neoplasias Gástricas , Animais , Mucosa Gástrica , Metilnitronitrosoguanidina/toxicidade , Lesões Pré-Cancerosas/induzido quimicamente , Ratos , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/tratamento farmacológico
17.
BMC Ophthalmol ; 21(1): 331, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507529

RESUMO

BACKGROUND: To evaluate macular microstructure alterations in the parafoveal nonperfusion areas of eyes with branch retinal vein occlusions (BRVO), and to investigate their impact on retinal sensitivity. METHODS: This was a cross-sectional study including thirteen BRVO patients with parafoveal capillary nonperfusion areas (NPA). Multiple modalities including microperimetry, optical coherence tomography angiography, and optical coherence tomography were performed to measure retinal sensitivity and thickness, and to identify the microstructure changes and perfusion status. RESULTS: The retinal sensitivity and thickness in the NPA were significantly lower than those in the perfusion areas (PA) (P = 0.001, P = 0.003). Microstructure changes, including disorganization of the retinal inner layers (DRIL), disruption of the outer retinal layers, and cysts were more frequently observed in NPA (P = 0.002, P = 0.018, P = 0.068). Within NPA, the retinal sensitivity of areas with DRIL, and outer retinal layers disruption was significantly lower than that of the areas without DRIL (P = 0.016), and with intact outer retinal layers (P < 0.001), respectively. 1dB increase in retinal sensitivity was correlated with 2.2 µm (95 % confidence interval, 1.71-2.7) increase of the thickness (P < 0.001). The retinal sensitivity was significantly lower at points with both DRIL and outer retinal layers disruption than at the points with DRIL or outer retina layers disruption alone (P = 0.001, P = 0.001). CONCLUSIONS: Alterations in the macular microstructure are associated with ischemia, especially DRIL. DRIL and outer retinal layers disruption are imaging features that have important implications for local retinal sensitivity in the ischemic areas, and where the microstructure of both inner and outer retinal layers is disrupted the function is further destructed.


Assuntos
Oclusão da Veia Retiniana , Estudos Transversais , Angiofluoresceinografia , Humanos , Retina/diagnóstico por imagem , Oclusão da Veia Retiniana/diagnóstico , Vasos Retinianos/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual
18.
Front Immunol ; 12: 705378, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526987

RESUMO

Intrahepatic cholangiocarcinoma (ICC) is highly invasive and carries high mortality due to limited therapeutic strategies. In other solid tumors, immune checkpoint inhibitors (ICIs) target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD1), and the PD1 ligand PD-L1 has revolutionized treatment and improved outcomes. However, the relationship and clinical significance of CTLA-4 and PD-L1 expression in ICC remains to be addressed. Deciphering CTLA-4 and PD-L1 interactions in ICC enable targeted therapy for this disease. In this study, immunohistochemistry (IHC) was used to detect and quantify CTLA-4, forkhead box protein P3 (FOXP3), and PD-L1 in samples from 290 patients with ICC. The prognostic capabilities of CTLA-4, FOXP3, and PD-L1 expression in ICC were investigated with the Kaplan-Meier method. Independent risk factors related to ICC survival and recurrence were assessed by the Cox proportional hazards models. Here, we identified that CTLA-4+ lymphocyte density was elevated in ICC tumors compared with peritumoral hepatic tissues (P <.001), and patients with a high density of CTLA-4+ tumor-infiltrating lymphocytes (TILsCTLA-4 High) showed a reduced overall survival (OS) rate and increased cumulative recurrence rate compared with patients with TILsCTLA-4 Low (P <.001 and P = .024, respectively). Similarly, patients with high FOXP3+ TILs (TILsFOXP3 High) had poorer prognoses than patients with low FOXP3+ TILs (P = .021, P = .034, respectively), and the density of CTLA-4+ TILs was positively correlated with FOXP3+ TILs (Pearson r = .31, P <.001). Furthermore, patients with high PD-L1 expression in tumors (TumorPD-L1 High) and/or TILsCTLA-4 High presented worse OS and a higher recurrence rate than patients with TILsCTLA-4 LowTumorPD-L1 Low. Moreover, multiple tumors, lymph node metastasis, and high TumorPD-L1/TILsCTLA-4 were independent risk factors of cumulative recurrence and OS for patients after ICC tumor resection. Furthermore, among ICC patients, those with hepatolithiasis had a higher expression of CTLA-4 and worse OS compared with patients with HBV infection or undefined risk factors (P = .018). In conclusion, CTLA-4 is increased in TILs in ICC and has an expression profile distinct from PD1/PD-L1. TumorPD-L1/TILsCTLA-4 is a predictive factor of OS and ICC recurrence, suggesting that combined therapy targeting PD1/PD-L1 and CTLA-4 may be useful in treating patients with ICC.

19.
BMJ Open ; 11(9): e048530, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493513

RESUMO

OBJECTIVE: To investigate the association between maternal pregestational blood glucose level and adverse pregnancy outcomes. DESIGN: Retrospective cohort study. SETTING: This study was conducted in the Chongqing Municipality of China between April 2010 and December 2016. PARTICIPANTS: A total of 60 222 women (60 360 pregnancies) from all 39 counties of Chongqing who participated in the National Free Preconception Health Examination Project and had pregnancy outcomes were included. PRIMARY OUTCOME MEASURES: Adverse pregnancy outcomes included spontaneous abortion, induced abortion or labour due to medical reasons, stillbirth, preterm birth (PTB), macrosomia, large for gestational age, low birth weight (LBW) and small for gestational age. RESULTS: Of the 60 360 pregnancies, rates of hypoglycaemic, normoglycaemia, impaired fasting glycaemia (IFG) and diabetic hyperglycaemic before conception were 5.06%, 89.30%, 4.59% and 1.05%, respectively. Compared with women with normoglycaemia, women with pregestational glucose at the diabetic level (≥7.0 mmol/L) might have a higher rate of macrosomia (6.18% vs 4.16%), whereas pregestational IFG seemed to be associated with reduced risks of many adverse outcomes, including spontaneous abortion, induced abortion due to medical reasons, PTB and LBW. After adjusting for potential confounders, pregestational diabetic hyperglycaemic was remained to be significantly associated with an increased risk of macrosomia (adjusted risk ratio 1.49, 95% CI 1.07 to 2.09). Abnormal maternal glucose levels before pregnancy (either hypoglycaemic or hyperglycaemic) seemed to have no significant negative effect on spontaneous abortion or induced abortion due to medical reasons. CONCLUSION: Although without overt diabetes mellitus, women with once diabetic fasting glucose level during their preconception examinations could be associated with an increased risk for macrosomia. Uniform guidelines are needed for maternal blood glucose management during pre-pregnancy care to improve pregnancy outcomes.


Assuntos
Nascimento Prematuro , Estudos de Coortes , Feminino , Macrossomia Fetal/epidemiologia , Glucose , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos
20.
Curr Neuropharmacol ; 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34525934

RESUMO

Oxytocin (OXT) is a nine amino acid neuropeptide hormone that has become one of the most intensively studied molecules in the past few decades. The vast majority of OXT is synthesized in the periventricular nucleus and supraoptic nucleus of the hypothalamus, and a few are synthesized in some peripheral organs (such as the uterus, ovaries, adrenal glands, thymus, pancreas, etc.) OXT modulates a series of physiological processes, including lactation, parturition, as well as some social behaviors. In addition, more and more attention has recently been focused on the analgesic effects of oxytocin. It has been reported that OXT can relieve tension and pain without other adverse effects. However, the critical role and detailed mechanism of OXT in analgesia remain unclear. Here, this review aims to summarize the mechanism of OXT in analgesia and some ideas about the mechanism.

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