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1.
PeerJ ; 12: e17220, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38618568

RESUMO

Background: Single nucleotide polymorphisms (SNPs), as the most abundant form of DNA variation in the human genome, contribute to age-related cataracts (ARC) development. Apoptosis of lens epithelial cells (LECs) is closely related to ARC formation. Insulin-like growth factor 1 (IGF1) contributes to cell apoptosis regulation. Moreover, IGF1 was indicated to exhibit a close association with cataract formation. Afterward, an investigation was conducted to examine the correlation between polymorphisms in IGF1 and the susceptibility to ARC. Methods: The present investigation was a case-control study. Venous blood draws were collected from the participants for DNA genotyping. Lens capsule samples were collected to detect mRNA and apoptosis. TaqMan RT-PCR was used to detect IGF1 polymorphism genotypes and qRT PCR was used to detect IGF1 mRNA levels in LECs. LEC apoptosis was evaluated through flow cytometry. The chi-square test was used to compare differences between ARCs and controls of each SNP. Results: We found that the G allele frequency in the IGF1-rs6218 was higher in the ARCs than in the controls. Furthermore, it was observed that the rs6218 GG genotype exhibited a positive correlation to elevated levels of IGF1 mRNA in LECs. The IGF1 mRNA in the LECs and the apoptosis of LECs in nuclear type of ARCs (ARNC) was higher than the controls. Conclusion: The susceptibility to ARC was related to IGF1-rs6218 polymorphism, and this polymorphism is associated with IGF1 expression at the mRNA level. Moreover, apoptosis in LECs of ARNCs was found to be increased.


Assuntos
Catarata , Fator de Crescimento Insulin-Like I , Humanos , Fator de Crescimento Insulin-Like I/genética , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único/genética , Catarata/genética , RNA Mensageiro/genética , DNA
2.
J Pers Soc Psychol ; 126(1): 1-4, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38386371

RESUMO

The commencement of a new editorial tenure within the Journal of Personality and Social Psychology: Attitudes and Social Cognition (JPSP: ASC) provides an opportunity for reflection regarding the journal's core mission. The editors recognize that social psychology is at a crossroads due to competing demands that may have led to reduced submissions and posed challenges for previous editors in filling the journal's pages. Now, JPSP: ASC has been allotted more pages to allow for growth during this editorial term. Although this is desirable for the field, it adds to the pressure of identifying articles for publication given the difficulties filling the pages during previous editorial terms. As the premier outlet of social psychology since 1965, JPSP: ASC will retain its centrality if we increase submissions and publish more articles, while continuing to strive to communicate methodologically trustworthy, intellectually stimulating, and socially relevant research, in a responsible fashion. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Transtornos da Personalidade , Personalidade , Humanos , Psicologia Social
3.
Org Lett ; 26(8): 1595-1600, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38373166

RESUMO

Selective transformations at the more sterically hindered sites of organic molecules represent a frontier in the ability to precisely modify molecules. The lack of effective synthetic methods stands in stark contrast to the large number of encumbered sites encountered in molecules of interest. Here, we demonstrate that 1,2-bis(boronates) undergo selective alkynylation and alkenylation at the more sterically hindered C-B bond. Our preliminary mechanistic studies disclosed that this reaction can proceed through two convergent pathways involving direct coupling of sterically encumbered site versus 1,2-boron migratory coupling. Notably, this method facilitated convenient access to alkenyl and alkynyl boron products, which can be diversified by an array of transformations.

4.
J Ethnopharmacol ; 319(Pt 3): 117342, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37879505

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sargentodoxa cuneata (Sargentodoxa cuneata (Oliv.) Rehder & E.H.Wilson, DXT)-Patrinia villosa(Patrinia villosa (Thunb.) Dufr, BJC) constitutes a commonly employed herb pair in Chinese medicine for colorectal cancer (CRC) treatment. Modern pharmacological investigations have revealed the anticancer activities of both Sargentodoxa cuneata and Patrinia villosa. Nevertheless, comprehensive studies are required to discern the specific antitumor active ingredients and mechanism of action when these two herbs are used in combination. AIM OF THE STUDY: Through the integration of network pharmacology, molecular docking techniques, experimental assays, and bioinformatics analysis, our study aims to forecast the active ingredients, potential targets, and molecular mechanisms underlying the therapeutic efficacy of this herb pair against CRC. MATERIALS AND METHODS: Plant names (1, Sargentodoxa cuneata (Oliv.) Rehder & E.H.Wilson; 2, Patrinia villosa (Thunb.) Dufr.) have been verified through WorldFloraOnline (www.worldFloraonline.org) and MPNs (http://mpns.kew.org). The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) were utilized for screening the active ingredients of the herb pair. The PharmMapper database was employed to predict the target proteins for each active ingredient. CRC-related targets were obtained from the Genecards database, Online Mendelian Inheritance in Man (OMIM) database, Disease Gene Network (DisGeNET) database, and Therapeutic Target Database (TTD). Common targets were identified by intersecting the target proteins of all active ingredients with CRC-related targets. Protein-protein interactions (PPI) for the common target proteins were constructed using the String database and Cytoscape 3.9.1 software. Network topology analysis facilitated the identification of core targets. These core targets were subjected to enrichment analysis of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) using the Metascape database. Molecular docking was performed using Discovery Studio 2019 to investigate the interactions between the active ingredients and core target proteins. The core targets were validated through bioinformatics analysis using GEPIA, HPA, and the cBioPortal database. Finally, a series of experiments were conducted to further validate the results in vitro. RESULT: A total of 15 active ingredients and 255 herb targets were identified, resulting in 66 common targets in conjunction with 6113 disease targets. The PPI analysis highlighted AKT1, EGFR, CASP3, SRC, and ESR1 as core targets. KEGG enrichment analysis indicated significant enrichment in the PI3K-AKT signaling pathway, a pathway associated with cancer. Molecular docking experiments confirmed favorable interactions between dihydroguaiaretic acid and the core target proteins (AKT1, EGFR, CASP3, and ESR1). Bioinformatics analysis revealed differential expression of EGFR and CASP3 in normal and CRC tissues. Cellular experiments further verified that dihydroguaiaretic acid induces apoptosis in colorectal cancer cells through the PI3K-AKT signaling pathway. CONCLUSION: Our network pharmacology study has elucidated that the Sargentodoxa cuneata-Patrinia villosa herb pair exerts the negative regulation of the PI3K/AKT/mTOR signaling pathway, ultimately leading to the induction of apoptosis in colorectal cancer cells. This research has predicted and validated the active ingredients, potential targets, and molecular mechanisms of Sargentodoxa cuneata-Patrinia villosa in the treatment of CRC, providing scientific evidence for the use of traditional Chinese medicine in managing CRC.


Assuntos
Neoplasias Colorretais , Medicamentos de Ervas Chinesas , Patrinia , Humanos , Caspase 3 , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Simulação de Acoplamento Molecular , Serina-Treonina Quinases TOR , Transdução de Sinais , Neoplasias Colorretais/tratamento farmacológico , Receptores ErbB
5.
Sci Rep ; 13(1): 21317, 2023 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-38044354

RESUMO

Hepatocellular carcinoma (HCC) is the most widespread histological form of primary liver cancer, and it faces great diagnostic and therapeutic difficulties owing to its tumor diversity. Herein, we aim to establish a unique prognostic molecular subtype (MST) and based on this to find potential therapeutic targets to develop new immunotherapeutic strategies. Using calcium channel molecules expression-based consensus clustering, we screened 371 HCC patients from The Cancer Genome Atlas to screen for possible MSTs. We distinguished core differential gene modules between varying MSTs, and Tumor Immune Dysfunction and Exclusion scores were employed for the reliable assessment of HCC patient immunotherapeutic response rate. Immunohistochemistry and Immunofluorescence staining were used for validation of predicted immunotherapy outcomes and underlying biological mechanisms, respectively. We identified two MSTs with different clinical characteristics and prognoses. Based on the significant differences between the two MSTs, we further identified Follistatin-like 3 (FSTL3) as a potential indicator of immunotherapy resistance and validated this result in our own cohort. Finally, we found that FSTL3 is predominantly expressed in HCC stromal components and that it is a factor in enhancing fibroblast-M2 macrophage signaling crosstalk, the function of which is relevant to the pathogenesis of HCC. The presence of two MSTs associated with the calcium channel phenotype in HCC patients may provide promising directions for overcoming immunotherapy resistance in HCC, and the promotion of FSTL3 expressed in stromal components for HCC hyperfibrosis may be responsible for the poor response rate to immunotherapy in Cluster 2 (C2) patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Canais de Cálcio , Carcinoma Hepatocelular/genética , Análise por Conglomerados , Imunoterapia , Neoplasias Hepáticas/genética
6.
BMC Ophthalmol ; 23(1): 514, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110879

RESUMO

BACKGROUND: In the present study, we explored the role of N6-methyladenosine (m6A) modification of long non-coding RNAs (lncRNAs) and its association with ferroptosis in lens epithelium cells (LECs) of age-related cataract (ARC). METHODS: Through m6A RNA immunoprecipitation sequencing (m6A-RIP-seq) and RNA sequencing (RNA-seq), we identified m6A mediated and differentially expressed lncRNAs (dme-lncRNAs) in ARC patients. Based on bioinformatics analysis, we selected critical dme-lncRNAs and pathways associated with ARC formation to reveal their potential molecular mechanisms. The downregulation of glutathione peroxidase 4 (GPX4), a key component of ferroptosis, was confirmed by real-time RT-PCR (RT-qPCR) and Western blotting in age-related cortical cataract (ARCC) samples. Transmission electron microscopy was used to assess the change in mitochondrial in LECs. RESULTS: The analysis revealed a total of 11,193 m6A peaks within lncRNAs, among which 7043 were enriched and 4150 were depleted. Among those, lncRNA ENST00000586817(upstream of the GPX4 gene) was not only significantly upregulated in the LECs of ARCC but also potentially augmented the expression of GPX4 through a cis mechanism. The expression of m6A-modified lncRNA (ENST00000586817) was correlated with that of GPX4 and was downregulated in ARC patients. The TEM results indicated significant mitochondrial changes in ARCC samples. GPX4 downregulation enhanced LEC ferroptosis and decreased viability via RSL3 in SRA01/04 cells. CONCLUSIONS: Our results provide insight into the potential function of m6A-modified lncRNAs. M6A-modified lncRNA ENST00000586817 might regulate the expression of GPX4 by a cis mechanism and be implicated in ferroptosis in ARCs.


Assuntos
Catarata , Ferroptose , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , RNA Longo não Codificante , Humanos , Catarata/genética , Catarata/metabolismo , Epitélio/metabolismo , Ferroptose/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , RNA Longo não Codificante/genética
7.
Org Lett ; 25(42): 7656-7660, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37823578

RESUMO

A novel copper-catalyzed cross-coupling reaction of sulfinamides and aryl boronic acids is developed. The reaction is highly chemoselective and stereospecific, which allows mild synthesis of optically pure sulfoximines with broad scope and functional group tolerance. The utility of this method is demonstrated by the asymmetric synthesis of pharmaceutical intermediates.

8.
Sci Rep ; 13(1): 17518, 2023 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-37845352

RESUMO

We examine how cultural distance between sojourners' country of origin and their host country influences their engagement in intercultural exchange upon return. One might expect intercultural exchange to be much harder between culturally-distant countries than culturally-close ones, given that the former vary more in norms or expected behaviors from one's home country. Our novel theorizing, however, leads to precisely the opposite expectations. In particular, we hypothesized that cultural distance between the repatriates' home and host countries would be positively associated with being inspired by the host culture. In turn, this heightened inspiration would predict an increased sharing of knowledge about the host culture upon returning home (intercultural exchange). We combined measurement-of-mediation (Study 1) and experimental-causal-chain (Studies 2-3) approaches to test and confirm these hypotheses in three large samples of repatriates. We first examined whether cultural distance predicted greater intercultural exchange via repatriates' heightened inspiration (Study 1). We then tested the individual links in this postulated causal chain. In Study 2, a quasi-experiment, we examined the causal path from cultural distance to inspiration. In Study 3, we experimentally manipulated inspiration to test its causal effect on intercultural exchange. The findings advance theory and application around multicultural experience and intercultural exchange.

9.
Materials (Basel) ; 16(19)2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37834747

RESUMO

This paper mainly analyzes the typical thermodynamic response (thermal history, thermal strain and residual stress) in a conventional continuous-wave (CW) laser during Directed Energy Deposition (DED). The influence of process parameters (laser power and scanning speed) on the temperature gradient in the heat-affected zone, thermal strain and residual stress are studied, and the corresponding relationship are established. The results show that a reduction in residual stress can be obtained by decreasing the temperature gradient. However, the method of reducing the temperature gradient by changing process parameters leads to low forming quality and low density. A pulse-wave laser (PW) is proposed to actively control the residual stress of the deposited sample. This laser mode can reduce not only the temperature gradient in the process of DED but also the in situ release of thermal stress, correspondingly greatly reducing the residual stress.

10.
Biomol Biomed ; 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37838927

RESUMO

Retinal vein occlusion (RVO) ranks as the second most prevalent retinal vascular disease, following diabetic retinopathy. Neutrophil extracellular traps (NETs) play an important role in vascular diseases. This study aimed to elucidate the relationship between NETs and RVO, and to discern the potential role of deoxyribonuclease I (DNase I) in the prevention and treatment of RVO through the modulation of NETs. We analyzed circulating NETs biomarkers, namely cell-free DNA (cf-DNA), myeloperoxidase (MPO)-DNA, and neutrophil elastase (NE), in 30 RVO patients and 30 healthy individuals. We established an RVO mouse model using a retinal laser, and the mice were categorized into two groups: the DNase I group and the control group. Retinal images were taken at predetermined time points, and the state of the retinal vessels was assessed. Both tissue and blood samples were harvested for analysis of NETs expression through methods such as western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assay (ELISA). Our finding indicate an increase in circulating NETs biomarkers in human and mouse RVO cases, while also verifying the presence of NETs in the retinal thrombus of the RVO model. Both in vitro and in vivo tests revealed that DNase I attenuated NETs formation. Moreover, DNase I injections led to diminished NETs biomarker levels and a reduced duration of the thrombus after the RVO model establishment. Consequently, DNase I, a well-established modulator of NETs formation, might exhibit protective properties in the prevention and treatment of RVO.

11.
Gels ; 9(9)2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37754358

RESUMO

Ocular alkali burns recruit neutrophils and triggers neutrophil extracellular trap (NET)-neovascularization cascade effects that limit ocular surface reconstruction and functional repair. However, effective inhibition of the release of neutrophil extracellular traps after a corneal chemical injury, coordination of intrinsic immunity with corneal repair, and exploration of more effective and non-invasive drug-delivery modes are still urgently needed. Using an in vitro coculture system, we found that an alkaline environment stimulates neutrophils to release NETs, which can be regulated by deoxyribonuclease I (DNase I). Inspired by this, we loaded DNase I, which effectively regulates NETs, onto chitosan nanoparticles and combined them with silk fibroin to construct a composite hydrogel that can sustainably regulate NETs. The hydrogel reduced neutrophil extracellular trap production by 50% and neovascularization by approximately 70% through sustained DNase I release after a corneal alkali burn. The complex hydrogel promotes ocular surface reconstruction by modulating the intrinsic immune-cascade neovascularization effect, providing a new research basis for the construction of nanobiomaterials that modulate pathological neovascularization.

12.
Nat Commun ; 14(1): 5168, 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620301

RESUMO

Sulfonyl and sulfonimidoyl fluorides are versatile substrates in organic synthesis and medicinal chemistry. However, they have been exclusively used as S(VI)+ electrophiles for defluorinative ligations. Converting sulfonyl and sulfonimidoyl fluorides to S(VI) radicals is challenging and underexplored due to the strong bond dissociation energy of SVI-F and high reduction potentials, but once achieved would enable dramatically expanded synthetic utility and downstream applications. In this report, we disclose a general platform to address this issue through cooperative organosuperbase activation and photoredox catalysis. Vinyl sulfones and sulfoximines are obtained with excellent E selectivity under mild conditions by coupling reactions with alkenes. The synthetic utility of this method in the preparation of functional polymers and dyes is also demonstrated.

13.
Angew Chem Int Ed Engl ; 62(32): e202307447, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37316685

RESUMO

Asymmetric cross-couplings based on 1,2-carbon migration from B-ate complexes have been developed efficiently to access valuable organoboronates. However, enantioselective reactions triggered by 1,2-boron shift have remained to be unaddressed synthetic challenge. Here, Ir-catalyzed asymmetric allylic alkylation enabled by 1,2-boron shift was developed. In this reaction, we disclosed that excellent enantioselectivities were achieved through an interesting dynamic kinetic resolution (DKR) process of allylic carbonates at the elevated temperature. Notably, the highly valuable (bis-boryl)alkenes have enabled an array of diversifications to access versatile molecules. Extensive experimental and computational studies were conducted to elucidate the reaction mechanism of DKR process and clarify the origin of excellent enantioselectivities.

14.
Front Endocrinol (Lausanne) ; 14: 1161521, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37152942

RESUMO

The prevalence of obesity and diabetes mellitus (DM) has been consistently increasing worldwide. Sharing powerful genetic and environmental features in their pathogenesis, obesity amplifies the impact of genetic susceptibility and environmental factors on DM. The ectopic expansion of adipose tissue and excessive accumulation of certain nutrients and metabolites sabotage the metabolic balance via insulin resistance, dysfunctional autophagy, and microbiome-gut-brain axis, further exacerbating the dysregulation of immunometabolism through low-grade systemic inflammation, leading to an accelerated loss of functional ß-cells and gradual elevation of blood glucose. Given these intricate connections, most available treatments of obesity and type 2 DM (T2DM) have a mutual effect on each other. For example, anti-obesity drugs can be anti-diabetic to some extent, and some anti-diabetic medicines, in contrast, have been shown to increase body weight, such as insulin. Meanwhile, surgical procedures, especially bariatric surgery, are more effective for both obesity and T2DM. Besides guaranteeing the availability and accessibility of all the available diagnostic and therapeutic tools, more clinical and experimental investigations on the pathogenesis of these two diseases are warranted to improve the efficacy and safety of the available and newly developed treatments.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Obesidade , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/terapia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/terapia , Resistência à Insulina , Insulina/metabolismo , Resultado do Tratamento
15.
Life (Basel) ; 13(5)2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37240851

RESUMO

Water quality is directly linked to drinking water safety for millions of people receiving the water. The Danjiangkou Reservoir is the main water source for the Middle Route of the South-to-North Water Diversion Project (MR-SNWDP), located in the vicinity of Henan and Hubei provinces in China. Aquatic microorganisms are key indicators of biologically assessing and monitoring the water quality of the reservoir as they are sensitive to environmental and water quality changes. This study aimed to investigate the spatiotemporal variations in bacterioplankton communities during wet (April) and dry (October) seasons at eight monitoring points in Hanku reservoir and five monitoring points in Danku reservoir. Each time point had three replicates, labeled as wet season Hanku (WH), wet season Danku (WD), dry season Hanku (DH), and dry season Danku (DD) of Danjiangkou Reservoir in 2021. High-throughput sequencing (Illumina PE250) of the 16S rRNA gene was performed, and alpha (ACE and Shannon) and beta (PCoA and NDMS) diversity indices were analyzed. The results showed that the dry season (DH and DD) had more diverse bacterioplankton communities compared to the wet season (WH and WD). Proteobacteria, Actinobacteria, and Firmicutes were the most abundant phyla, and Acinetobacter, Exiguobacterium, and Planomicrobium were abundant in the wet season, while polynucleobacter was abundant in the dry season. The functional prediction of metabolic pathways revealed six major functions including carbohydrate metabolism, membrane transport, amino acid metabolism, signal transduction, and energy metabolism. Redundancy analysis showed that environmental parameters greatly affected bacterioplankton diversity during the dry season compared to the wet season. The findings suggest that seasonality has a significant impact on bacterioplankton communities, and the dry season has more diverse communities influenced by environmental parameters. Further, the relatively high abundance of certain bacteria such as Acinetobacter deteriorated the water quality during the wet season compared to the dry season. Our findings have significant implications for water resource management in China, and other countries facing similar challenges. However, further investigations are required to elucidate the role of environmental parameters in influencing bacterioplankton diversity in order to devise potential strategies for improving water quality management in the reservoir.

16.
J Hepatocell Carcinoma ; 10: 497-515, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37020465

RESUMO

Background: The Proteasome (PSM) is a large multi-catalytic protease complex consisting of a 20S core particle and a 19S regulatory particle whose main function is to accept and degrade ubiquitinated substrates, are now considered as one of the potential regulators of tumor proliferation, and stemness maintenance. However, to date, studies on the relationship between PSM and hepatocellular carcinoma (HCC) are limited. Methods: This study used a bioinformatics approach combining validation experiments to investigate the biological mechanisms that may be related with PSM. A series of experiments in vivo and in vitro were performed to explore the function of the 26S proteasome non-ATPase regulatory subunit 13 (PSMD13) in HCC. Results: HCC patients can be divided into two clusters. Cluster 1 (C1) patients having a significantly worse prognosis than Cluster (C2). Two subtypes had significant differences in proliferation-related signaling. In particular, the frequency of TP53 mutation was significantly higher in C1 than in C2. In addition, PSM-associated genes were highly consistent with the expression of DNA repair-related signatures, suggesting a potential link between PSM and genomic instability. We also found that downregulation of PSMD13 expression significantly inhibited stemness of tumor cells and impaired the Epithelial mesenchymal transition (EMT) process. Finally, the correlation between the PSMD13 and Ki67 was found to be strong. Conclusion: PSM is a valid predictor of prognosis and therapeutic response in patients with HCC disease. Furthermore, PSMD13 may be a potential therapeutic target.

17.
Toxics ; 11(4)2023 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37112580

RESUMO

Difenoconazole is a type of triazole fungicide that is widely used in the treatment of plant diseases. Triazole fungicides have been shown in several studies to impair the development of the nervous system in zebrafish embryos. There is still little known about difenoconazole-induced neurotoxicity in fish. In this study, zebrafish embryos were exposed to 0.25, 0.5, and 1 mg/L of difenoconazole solution until 120 h post-fertilization (hpf). The difenoconazole-exposed groups showed concentration-dependent inhibitory tendencies in heart rate and body length. Malformation rate and spontaneous movement of zebrafish embryos increased, and the locomotor activity decreased in the highest exposure group. The content of dopamine and acetylcholine was reduced significantly in difenoconazole treatment groups. The activity of acetylcholinesterase (AChE) was also increased after treatment with difenoconazole. Furthermore, the expression of genes involved in neurodevelopment was remarkably altered, which corresponded with the alterations of neurotransmitter content and AChE activity. These results indicated that difenoconazole might affect the development of the nervous system through influencing neurotransmitter levels, enzyme activity, and the expression of neural-related genes, ultimately leading to abnormal locomotor activity in the early stages of zebrafish.

18.
Front Endocrinol (Lausanne) ; 14: 1031610, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36875493

RESUMO

Pancreatic ß-cell function impairment and insulin resistance are central to the development of obesity-related type 2 diabetes mellitus (T2DM). Bariatric surgery (BS) is a practical treatment approach to treat morbid obesity and achieve lasting T2DM remission. Traditionally, sustained postoperative glycemic control was considered a direct result of decreased nutrient intake and weight loss. However, mounting evidence in recent years implicated a weight-independent mechanism that involves pancreatic islet reconstruction and improved ß-cell function. In this article, we summarize the role of ß-cell in the pathogenesis of T2DM, review recent research progress focusing on the impact of Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) on pancreatic ß-cell pathophysiology, and finally discuss therapeutics that have the potential to assist in the treatment effect of surgery and prevent T2D relapse.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Derivação Gástrica , Células Secretoras de Insulina , Ilhotas Pancreáticas , Humanos
19.
Int Immunopharmacol ; 117: 109886, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36805200

RESUMO

The tumor microenvironment (TME) contains complex components, of which the most well-known one is the tumor-associated fibroblast (CAF) that participates in the development and progression of tumors. A high abundance of CAFs implies that tumor stroma is also abundant and often predicts a poor prognosis, especially in terms of immunotherapeutic resistance. In this study, DAZ interacting zinc finger protein 1 (DZIP1) was identified to be upregulated in CAFs and malignant epithelial cells based on single-cell sequencing. Furthermore, results from The Cancer Genome Atlas database showed that this gene was highly positively associated with the mesenchymal phenotype in gastric cancer (GC). In addition, molecular experiments verified that DZIP1 directly promoted the proliferation of CAFs and enhanced the epithelial-mesenchymal transition (EMT) of GC cells to drive angiogenesis. Also, the upregulated DZIP1 in GC cells was found to directly promote invasion and metastasis. Finally, multiplex immunofluorescence and immunohistochemistry showed that DZIP1 was correlated with the immunosuppressive microenvironment of GC and resulted in a poor response to immunotherapy. Overall, our findings suggest that DZIP1 is expressed in both tumor parenchyma and mesenchyme and that it is involved in shaping the immunosuppressive microenvironment and inducing EMT by participating in tumor-stromal signaling crosstalk.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Fibroblastos/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Tolerância Imunológica , Terapia de Imunossupressão , Microambiente Tumoral/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
20.
Curr Opin Psychol ; 49: 101553, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36696865

RESUMO

We identify three themes in the current research on nostalgia and acculturation. First, different types of nostalgia (i.e., home-culture and host-culture nostalgia) have distinct effects on immigrants' and sojourners' identification with home or host culture, affecting the integration of home and host cultural identities. Second, nostalgia during acculturation plays a crucial role in facilitating self-continuity among immigrants and sojourners moving across different cultures. Third, nostalgia affects the majority-group members' attitude towards immigrants and sojourners in the host culture. We conclude by highlighting three challenges for future research on nostalgia and acculturation: the content of types of nostalgia, the moderating role of individual differences, and the functions of nostalgia at various acculturation stages.


Assuntos
Aculturação , Emigrantes e Imigrantes , Humanos , Atitude
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