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1.
Crit Rev Food Sci Nutr ; : 1-16, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34592876

RESUMO

Fatigue has many negative effects on human health. As such, it is desirable to develop anti-fatigue foods and understand the mechanisms of their action. Based on a comprehensive review of the literature, this article discusses the important roles of gut microbiota in fatigue and anti-fatigue. Studies have shown that an increase in pathogenic bacteria and a decrease in beneficial bacteria co-exist when fatigue is present in both rodents and humans, whereas changes in gut microbiota were reported after intervention with anti-fatigue foods. The roles of gut microbiota in the activities of anti-fatigue foods can also be explained in the causes and the effects of fatigue. Among the causes of fatigue, the accumulation of lactic acid, decrease of energy, and reduction of central nervous system function were related to gut microbiota metabolism. Among the harmful effects of fatigue, oxidative stress, inflammation, and intestinal barrier dysfunction were related to gut microbiota dysbiosis. Furthermore, gut microbiota, together with anti-fatigue foods, can inhibit pathogen growth, convert foods into highly anti-oxidative or anti-inflammatory products, produce short-chain fatty acids, maintain intestinal barrier integrity, inhibit intestinal inflammation, and stimulate the production of neurotransmitters that regulate the central nervous system. Therefore, it is believed that gut microbiota play important roles in the activities of anti-fatigue foods and may provide new insights on the development of anti-fatigue foods.

2.
Food Res Int ; 148: 110568, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507723

RESUMO

Ulcerative colitis (UC), is a chronic relapsing inflammatory condition of the gastrointestinal track. The purpose of this study is to explore whether Vitamin A (VA) can treat UC and its mechanisms. A mouse model of UC was established using 3.0% (w/v) dextran sodium sulfate (DSS). VA was used to treat UC by intragastric administration of 5000 international unit (IU) retinyl acetate. Fecal microbiota transplantation (FMT) was also used to treat the UC model mice to verify the effect of influenced gut microbiota. The content of short-chain fatty acids (SCFAs) in cecal contents was quantitatively detected by gas chromatography and mass spectrometry. VA supplementation significantly ameliorated UC. 16S rRNA sequencing indicated that VA-treated mice exhibited much more abundant gut microbial diversity and flora composition. Targeted metabolomics analysis manifested the increased production of SCFAs in VA-treated mice. Gut microbiota depletion and FMT results confirmed the gut microbiota-dependent mechanism as that VA relieved UC via regulating gut microbiota: increase in SCFA-producing genera and decrease in UC-related genera. The restore of intestinal barrier and the inhibition of inflammation were also found to contribute to the amelioration of UC by VA. It was concluded that a VA supplement was enough to cause a significant change in gut microbiota and amelioration of UC.


Assuntos
Colite Ulcerativa , Microbioma Gastrointestinal , Animais , Colite Ulcerativa/tratamento farmacológico , Sulfato de Dextrana , Suplementos Nutricionais , Cromatografia Gasosa-Espectrometria de Massas , Camundongos , RNA Ribossômico 16S/genética , Vitamina A
3.
Int J Pharm ; 608: 121059, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34474115

RESUMO

Ascorbic palmitate (AP) is widely used in the topical pharmaceutical or cosmetic formulations for melasma treatment. However, the presence of the skin barriers makes it difficult for the highly lipophilic drug molecules to traverse the stratum corneum (SC) and diffuse into the viable epidermis (EP) to reach the melanocytes, thereby exerting suboptimal antimelasma effects. Herein, AP was encapsulated into the transfersomes (TFs), yielding AP-TFs. AP-TFs utilized the deformability of TFs to squeeze through the skin pores in the SC under the transepidermal hydration gradient forces, leading to 14.1-fold increase in AP accumulation to the EP. AP-TFs could slowly release the encapsulated AP, while whether the released AP or transfersomal AP showed comparable uptake into the melanocytes, thereby exerting similar inhibitory effects on tyrosinase activity and melanogenesis. Ultimately, in the rat melasma model, AP-TFs showed superior antimelasma efficacy to free AP, with effective relief of oxidative stress and inflammation in the skin. Moreover, AP-TFs did not induce skin irritation. Therefore, the study provides a safe and effective approach to elevating the delivery of highly lipophilic drugs to the EP for enhanced treatment of melasma.


Assuntos
Melanose , Palmitatos , Animais , Epiderme , Melanócitos , Melanose/tratamento farmacológico , Ratos , Pele
4.
Front Oncol ; 11: 708900, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557409

RESUMO

Background: Kinesin superfamily of proteins (KIFs) has been broadly reported to play an indispensable role in the biological process. Recently, emerging evidence reveals its oncogenic role in various cancers. However, the prognostic, oncological, and immunological values of KIFs have not been comprehensively explored in pancreatic ductal adenocarcinoma (PDAC) patients. We aimed to illustrate the relationship between KIFs and pancreatic ductal adenocarcinoma by using bioinformatical analysis. Methods: We use GEPIA, Oncomine datasets, cBioPortal, LOGpc, TIMER, and STRING bioinformatics tools and web servers to investigate the aberrant expression, prognostic values, and oncogenic role of KIFs. The two-gene prognostic model and the correlation between KIFs and KRAS and TP53 mutation were performed using an R-based computational framework. Results: Our results demonstrated that KIFC1/2C/4A/11/14/15/18A/18B/20B/23 (we name it prognosis-related KIFs) were upregulated and associated with unfavorable clinical outcome in pancreatic cancer patients. KIF21B overexpression is associated with better clinical outcome. The KIFC1/2C/4A/11/14/15/18A/18B/20B/23 profiles were significantly increased compared to grade 1 and grade 2/3. Besides, KIFC1/2C/4A/11/14/15/18A/18B/20B/23 was significantly associated with the mutation status of KRAS and TP53.Notably, most prognosis-related KIFs have strong correlations with tumor growth and myeloid-derived suppressor cells infiltration (MDSCs). A prognostic signature based on KIF20B and KIF21B showed a reliable predictive performance. Receiver operating characteristic (ROC) curve was employed to assess the predictive power of two-gene signature. Consequently, the gene set enrichment analysis (GSEA) showed that KIF20B and KIF21B's overexpression was associated with the immunological and oncogenic pathway activation in pancreatic cancer. Finally, real-time quantitative PCR (RT-qPCR) was utilized to investigate the expression pattern of KIF20B and KIF21B in pancreatic cancer cell lines and normal pancreatic cell. Conclusions: Knowledge of the expression level of the KIFs may provide novel therapeutic molecular targets and potential prognostic biomarkers to pancreatic cancer patients.

5.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3257-3269, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396745

RESUMO

Cardiovascular diseases seriously endanger human health and life. The accompanying myocardial injury has been a focus of attention in society. Chinese medicine,serving as a natural and precious reservoir for the research and development of new drugs,is advantageous in resisting myocardial injury due to its multi-component,multi-pathway,and multi-target characteristics. In recent years,with the extensive application of culture method for isolated cardiomyocytes,a cost-effective,controllable in vitro model of cardiomyocyte injury with uniform samples is becoming a key tool for mechanism research on cardiomyocyte injury and drug development.A good in vitro model can reduce experimental and manpower cost,and also accurately stimulate clinical changes to reveal the mechanism. Therefore,the selection and establishment of in vitro model are crucial for the in-depth research. This study summarized the modeling principles,evaluation indicators,and application of more than ten models reflecting different clinical conditions,such as injuries induced by hypoxia-reoxygenation,hypertrophy,oxidative stress,inflammation,internal environmental disturbance,and toxicity. Furthermore,we analyzed advantages and technical difficulties,aiming to provide a reference for in-depth research on myocardial injury mechanism and drug development.


Assuntos
Apoptose , Miócitos Cardíacos , Hipóxia Celular , Humanos , Miocárdio , Estresse Oxidativo
6.
Methods Mol Biol ; 2320: 65-73, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34302648

RESUMO

In this chapter, we introduce the method for fabricating thick and anisotropic cardiac tissue for heart regeneration. Aligned and biodegradable nanofiber can be prepared by electrospinning Food and Drug Administration-approved poly (lactic-co-glycolic acid) on a rotating drum. After the nanofibers are transferred on to a polydimethylsiloxane frame, the cardiomyocytes could be plated on the nanofiber to form thick and anisotropic cardiac tissue rapidly. Cardiac tissue-like construct could be easily created by one-step method, and transplanted onto the hearts of myocardium infarction models and lead to their functional recovery.


Assuntos
Infarto do Miocárdio/terapia , Miócitos Cardíacos/citologia , Nanofibras/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Anisotropia , Células Cultivadas , Masculino , Miocárdio/citologia , Ratos , Ratos Nus , Engenharia Tecidual/métodos , Tecidos Suporte/química
7.
Brain Struct Funct ; 226(7): 2295-2306, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34228220

RESUMO

Metacognition is the ability to introspect and control ongoing cognitive processes. Despite the extensive investigation of the brain architectures supporting metacognition for perception and memory, little is known about the neural basis of metacognitive capacity for motor function, a vital aspect of human behavior. Here, using functional and structural magnetic resonance imaging (MRI), we examined the brain substrates underlying self-awareness of handwriting, a highly practiced visuomotor skill. Results showed that experienced adult writers generally overestimated their handwriting quality, and such overestimation was more pronounced in men relative to women. Individual variations in self-awareness of handwriting quality were positively correlated with gray matter volume in the left fusiform gyrus, right middle frontal gyrus and right precuneus. The left fusiform gyrus and right middle frontal gyrus are thought to represent domain-specific brain mechanisms for handwriting self-awareness, while the right precuneus that has been reported in other domains likely represents a domain-general brain mechanism for metacognition. Furthermore, the activity of these structurally related regions in a handwriting task was not correlated with self-awareness of handwriting, suggesting the correlation with metacognition was independent of task performance. Together, this study reveals that metacognition for practiced motor skills relies on both domain-general and domain-specific brain systems, extending our understanding about the neural basis of human metacognition.

8.
Eur J Pharmacol ; 908: 174343, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34265296

RESUMO

Nardostachys jatamansi is a natural medicinal plant that is widely used in Asia for the treatment of various neurological and cardiac diseases, and nardosinone is the main active ingredient of N. jatamansi, which has the potential to treat a variety of diseases. Herein, we summarize the reported chemical structure, pharmacokinetics and pharmacological potential of nardosinone, and point out areas for further research. We obtained studies that were related to the chemical structure and pharmacological activities of nardosinone from several databases. Previous studies have shown that nardosinone has anti-inflammatory effects, anti-hypertrophic effect in cardiomyocytes, enhances activity of the nerve growth factor and promotes neural stem cells to proliferate and differentiate. However, the molecular mechanism of how nardosinone promotes proliferation and differentiation of neural stem cells, and its role in resisting cardiomyocyte hypertrophy remains unclear and needs to be further studied. Overall, nardosinone has the potential to treat bacterial infections, periodontitis, cardiac diseases, neurodegenerative diseases and cancer. However, the gaps found in the literature is the lack of more comprehensive information regarding the pharmacokinetics and toxicology of nardosinone.

9.
Front Oncol ; 11: 693063, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34235083

RESUMO

Surgery for pituitary adenomas (PAs) with cavernous sinus (CS) invasion in Knosp grade 4 is a great challenge and whether to adopt a conservative or aggressive surgical strategy is controversial. The aim of this study is to provide the outcomes and complications of an aggressive resection strategy for Knosp grade 4 PAs with transsphenoidal endoscopic surgery. Outcomes and complications were retrospectively analyzed in 102 patients with Knosp grade 4 PAs. Among them, primary PAs were seen in 60 patients and recurrent PAs were seen in 42 cases. Gross total resection (GTR) of the entire tumor was achieved in 72 cases (70.6%), subtotal tumor resection (STR) in 18 cases (17.6%), and partial tumor resection (PTR) in 12 cases (11.8%). Additionally, GTR of the tumor within the CS was achieved in 82 patients (80.4%), STR in 17 patients (16.7%), and PTR in 3 patients (2.9%). Statistical analyses showed that both recurrent tumors and firm consistency tumors were adverse factors for complete resection (P<0.05). Patients with GTR of the entire tumor were more likely to have favorable endocrine and visual outcomes than those with incomplete resection (P<0.05). Overall, the most common surgical complication was new cranial nerve palsy (n=7, 6.8%). The incidence of internal carotid artery (ICA) injury and postoperative cerebrospinal fluid (CSF) leakage was 2.0% (n=2) and 5.9% (n=6), respectively. Six patients (5.9%) experienced tumor recurrence postoperatively. For experienced neuroendoscopists, an aggressive tumor resection strategy via transsphenoidal endoscopic surgery may be an effective and safe option for Knosp grade 4 PAs.

10.
Dev Sci ; : e13161, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34288292

RESUMO

Abundant behavioral studies have demonstrated high comorbidity of reading and handwriting difficulties in developmental dyslexia (DD), a neurological condition characterized by unexpectedly low reading ability despite adequate nonverbal intelligence and typical schooling. The neural correlates of handwriting deficits remain largely unknown; however, as well as the extent that handwriting deficits share common neural bases with reading deficits in DD. The present work used functional magnetic resonance imaging to examine brain activity during handwriting and reading tasks in Chinese dyslexic children (n = 18) and age-matched controls (n = 23). Compared to controls, dyslexic children exhibited reduced activation during handwriting tasks in brain regions supporting sensory-motor processing (including supplementary motor area and postcentral gyrus) and visual-orthography processing (including bilateral precuneus and right cuneus). Among these regions, the left supplementary motor area and the right precuneus also showed a trend of reduced activation during reading tasks in dyslexics. Moreover, increased activation was found in the left inferior frontal gyrus and anterior cingulate cortex in dyslexics, which may reflect more efforts of executive control to compensate for the impairments of motor and visual-orthographic processing. Finally, dyslexic children exhibited aberrant functional connectivity among brain areas for cognitive control and sensory-motor processes during handwriting tasks. Together, these findings suggest that handwriting deficits in DD are associated with functional abnormalities of multiple brain regions implicated in motor execution, visual-orthographic processing, and cognitive control, providing important implications for the diagnosis and treatment of dyslexia.

11.
J Heart Lung Transplant ; 40(8): 767-777, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34108109

RESUMO

BACKGROUND: Although induced pluripotent stem (iPS) cell-derived cardiac constructs may have a potential in cardiomyogenesis of a distressed myocardium, obtaining polarity in cardiac constructs, such as via myocyte alignment, may be crucial to achieve a maximum contractile force for better clinical outcomes. We herein hypothesized that transplantation of an aligned cardiac tissue derived from iPS cells has therapeutic effects in a porcine ischemic cardiomyopathy model as a preclinical trial. METHODS: Aligned cardiac tissues were developed by culturing high-purity iPS cell-derived cardiomyocytes in xeno-free conditions and transplanting them into infarct porcine hearts (iPS-CM group, n = 7; control, n = 6). Three months after treatment, therapeutic efficacy was evaluated functionally and histologically. RESULTS: In vitro assessment revealed that the aligned cardiac tissue containing high purity cardiomyocytes contracted homogeneously and had excellent mechanical properties. In the in vivo study, the left ventricular ejection fraction of the iPS-CM group was significantly greater than that of the control group, 3 months after transplantation (37.8% ± 2.3% vs 28.3% ± 2.5%, p < 0.05). Pathologically, attenuated interstitial fibrosis, attenuation of hypertrophied cardiomyocytes, and an increased capillary density were also prominent in the iPS-CM group. A limited amount of engraftment of the transplanted tissue maintaining tissue alignment was observed at 2 weeks after transplantation. CONCLUSIONS: The creation of large-scale functional aligned cardiac tissue was feasible, and the transplantation of the aligned tissue improved cardiac function with angiogenesis and antifibrotic effects in a porcine cardiomyopathy model.

12.
Cell Death Dis ; 12(6): 580, 2021 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-34091587

RESUMO

Long noncoding RNAs (lncRNAs) and their crosstalks with other RNAs have been revealed to be closely related to tumorigenesis and development, but their role in invasive pituitary adenoma (IPA) remains largely unclear. In our study, LINC00473 was identified as the most upregulated lncRNA in IPA by whole transcriptome RNA sequencing (RNA-Seq). Further, its related signaling pathway LINC00473/miR-502-3p/KMT5A was obtained by constructing a competing endogenous RNA (ceRNA) regulatory network. Their expression in IPA and non-invasive pituitary adenoma (NIPA) tissues was verified by qRT-PCR. Then the effects and mechanisms of LINC00473 and its ceRNA network on the proliferation of pituitary adenoma (PA) cells were confirmed by gene overexpression or silencing techniques combined with CCK-8 assay, EdU staining, flow cytometry assay, and double luciferase reporter gene assay in PA cell lines AtT-20 and GT1-1 in vitro and in a xenograft model in vivo. LINC00473 is overexpressed in IPA and can promote PA cells proliferation. Mechanistically, overexpression of LINC00473 restricts miR-502-3p through the ceRNA mechanism, upregulates KMT5A expression, and promotes the expression of cyclin D1 and CDK2, which is conducive to the cell cycle process, thereby promoting the proliferation of PA cells, involving IPA progression.


Assuntos
Adenoma/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , MicroRNAs/metabolismo , Neoplasias Hipofisárias/metabolismo , RNA Longo não Codificante/metabolismo , Adenoma/genética , Adulto , Animais , Progressão da Doença , Feminino , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , Neoplasias Hipofisárias/genética , RNA Longo não Codificante/genética , Regulação para Cima
13.
Artigo em Inglês | MEDLINE | ID: mdl-34181555

RESUMO

Textbook question answering (TQA) is a task that one should answer non-diagram and diagram questions accurately, given a large context which consists of abundant diagrams and essays. Although lots of studies have made significant progress in the natural image question answering (QA), they are not applicable to comprehending diagrams and reasoning over the long multimodal context. To address the above issues, we propose a relation-aware fine-grained reasoning (RAFR) network that performs fine-grained reasoning over the nodes of relation-based diagram graphs. Our method uses semantic dependencies and relative positions between nodes in the diagram to construct relation graphs and applies graph attention networks to learn diagram representations. To extract and reason over the multimodal knowledge, we first extract the text that is the most relevant to questions, options, and the instructional diagram which is the most relevant to question diagrams at the word-sentence level and the node-diagram level, respectively. Then, we apply instructional-diagram-guided attention and question-guided attention to reason over the node of question diagrams, respectively. The experimental results show that our proposed method achieves the best performance on the TQA dataset compared with baselines. We also conduct extensive ablation studies to comprehensively analyze the proposed method.

14.
Food Funct ; 12(16): 7250-7259, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34165119

RESUMO

BACKGROUND: Alcoholic gastric ulcers are currently a common upper gastrointestinal disease with a high recurrence rate, causing gastric perforation or even gastric cancer in severe cases. Lactobacillus rhamnosus was previously found to prevent alcoholic gastric ulcers, but its therapeutic effects were not illustrated. AIMS: This study aims to illustrate the preventive and therapeutic effects of L. rhamnosus SHA113 cells and their culture supernatant on alcoholic gastric ulcers and explore the related mechanisms. METHODS: An alcoholic gastric ulcer model was established by feeding mice with 75% ethanol once at a dosage of 10 ml per kg body weight. The L. rhamnosus SHA113 cells (SHA) and their culture supernatant (SHA-FS) were separately used to feed mice for 2 weeks before ethanol injury in preventive experiments and for 2 days after ethanol injury in therapeutic experiments. The mechanisms were analyzed in view of anti-oxidant and anti-inflammatory activities and intestinal barrier functions. RESULTS: The preventive effects of SHA-FS were much better than those of SHA via similar mechanisms, such as promoting the secretion of mucus, improving the antioxidant capacity of the gastric mucosa, and inhibiting inflammation. In terms of the therapeutic effects, SHA-FS and SHA could accelerate the healing of damaged ulcers by improving the secretion of tight junction proteins and mucus proteins, increasing angiogenesis, and inhibiting the apoptosis of gastric epithelial cells. CONCLUSION: L. rhamnosus SHA113 and its culture supernatant had preventive and therapeutic effects on alcoholic gastric ulcers via anti-oxidant and anti-inflammatory pathways and the promotion of healing of damaged ulcers by enhancing intestinal barrier functions, respectively.

15.
Zhongguo Zhong Yao Za Zhi ; 46(9): 2254-2259, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34047128

RESUMO

Rhus chinensis is an important resource plant. The aqueous extract of R. chinensis roots or stems was to produce Shuguantong Syrup, which is mainly used for the treatment of coronary heart disease and angina pectoris with definite curative effect. On this basis, the crude phenolic part of R. chinensis prepared by macroporous resin was evaluated for the cardio protective effect against myocardial ischemia in mice. The results showed that the phenolic part group with oral administration at the dosages of 190.8-381.6 mg·kg~(-1), compared with the model group, reduced the values of left ventricular end systolic diameter(LVEDs) and the left ventricular end diastolic diameter(LVEDd), and increased the cardiac ejection fraction(EF) and left ventricular fractional shortening(FS) rate, which could effectively improve cardiac function and exert its anti-myocardial ischemia effect, and reduce the rising levels of creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH) in serum. HE staining showed that the phenolic part group reduced the infiltration of myocardial inflammatory cells and alleviated the degree of myocardial fibrosis and collagen deposition. TUNEL staining showed that the blue-green fluorescence of the phenolic part group decreased successively, and the degree of myocardial cell apoptosis was reduced. Immunohistochemical staining suggested that it could reduce the number of positive cells for p53 protein expression and significantly improve myocardial cell damage. All above data suggested that the phenolic part group had an anti-mycardial ischemis effect. Related mechanism studies revealed that the crude phenolic part could regulate the expressions of the p53 gene(p53), Bcl-2-associated X protein(Bax), B lymphoma-2 gene(Bcl-2), and caspase-3 protein(caspase-3) in myocardial tissue, suggesting that it could reduce cardiac remodeling and myocardial ischemic damage, and improve cardiac function by inhibiting myocardial apoptosis.This research laid a foundation for the elucidation of the pharmacological ingredients R. chinensis.


Assuntos
Isquemia Miocárdica , Extratos Vegetais/farmacologia , Rhus , Animais , Apoptose , Camundongos , Isquemia Miocárdica/tratamento farmacológico , Miocárdio , Miócitos Cardíacos , Proteína X Associada a bcl-2
16.
Food Funct ; 12(11): 5171-5186, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-33977948

RESUMO

Gut microbiota imbalance is one of the major causes of ulcerative colitis (UC). L. rhamnosus SHA113 (LRS), a strain isolated from healthy human milk, influences the regulation of gut flora. This study aims to determine whether this strain can ameliorate UC by modulating gut microbiota. Mouse models of UC were established using C57BL/6Cnc mice with intragastric administration of 3.0% (w/v) dextran sodium sulfate (DSS). LRS was used to treat the mouse models of UC with 109 cfu mL-1 cell suspension via intragastric administration. To verify the effect of gut microbiota on UC, fecal microbiota collected from the mice after the treatment with LRS were also used to treat the UC mouse models (FMT). The severity of UC was evaluated based on body weight, colon length, disease activity index (DAI), and hematoxylin-eosin staining. The microbial composition was analyzed by 16S rRNA sequencing. The mRNA expression levels of cytokines, mucins, tight junction proteins, and antimicrobial peptides in the gastrointestinal tract were detected by quantitative real-time polymerase chain reaction. The short-chain fatty acid (SCFAs) in the cecal contents of all mice were quantitatively detected by gas chromatography and mass spectrometry. Both LRS and FMT exerted excellent therapeutic effects on UC, as evidenced by the reduction in body weight loss, colon length, and colon structural integrity, as well as the increase in the DAI (disease activity index). LRS and FMT treatments showed similar effects: (1) an increase of total SCFA production in the cecal contents and the abundance of gut microbial diversity and flora composition; (2) decreases in two genera (Parabacteroides and Escherichia/Shigella) related to the DAI and the enhancement of SCFAs and IL-10 positively related genera in the gut microbiota (Bilophila, Roseburia, Akkermansia, and Bifidobacterium); (3) downregulation of the expression of tumor necrosis factor-α, interleukin IL-6, and IL-1ß, and upregulation of the expression of the anti-inflammatory cytokine IL-10; and (4) upregulation of the expression of mucins (Muc1-4) and tight junction protein ZO-1. Overall, L. rhamnosus SHA113 relieves UC via the regulation of gut microbiota: increases in SCFA-producing genera and decreases in UC-related genera. In addition, a single strain is sufficient to induce a significant change in the gut microbiota and exert therapeutic effects on UC.

17.
Brain Lang ; 219: 104962, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33984629

RESUMO

This study aimed to identify the functional brain networks underlying the distinctions between automatic and controlled handwriting in Chinese. Network-based analysis was applied to functional magnetic resonance imaging data collected while adult participants performed a copying task under automatic and speed-controlled conditions. We found significant differences between automatic and speed-controlled handwriting in functional connectivity within and between the frontoparietal network, default mode network, dorsal attention network, somatomotor network and visual network; these differences reflect the variations in general attentional control and task-relevant visuomotor operations. However, no differences in brain activation were detected between the two handwriting conditions, suggesting that the reorganization of functional networks, rather than the modulation of local brain activation, underlies the dissociations between automatic and controlled handwriting in Chinese. Our findings illustrate the brain basis of handwriting automaticity, shedding new light on how handwriting automaticity may be disrupted in individuals with neurological disorders.

19.
Bioengineered ; 12(1): 1676-1688, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33960283

RESUMO

Colorectal cancer (CRC) is one of the most common tumors, ranking second in the global cause of death from cancer. The prognosis of advanced patients is still very poor. In this study, hub modules with the highest association with tumor-infiltrating immune cells were identified by weighted gene co-expression network analysis based on CRC expression data from the Gene Expression Omnibus database. Next, three hub genes (ADAM8, IL-1A, VAV3) related to infiltrating immune cells were identified by co-expression network and prognostic analysis. After analysis and verification of the TIMER database, ADAM8 was selected as a prognostic biomarker. Finally, the result of functional test showed that ADAM8 gene expression down-regulation partially reversed the immune tolerance of CRC cells to TILs. By bioinformatics analysis methods and the experimental techniques, we identified ADAM8 as a prognostic biomarker and clinical therapeutic target related to tumor-infiltrating immune cells in CRC.

20.
Hum Mol Genet ; 30(15): 1384-1397, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-33949662

RESUMO

Desmoglein-2, encoded by DSG2, is one of the desmosome proteins that maintain the structural integrity of tissues, including heart. Genetic mutations in DSG2 cause arrhythmogenic cardiomyopathy, mainly in an autosomal dominant manner. Here, we identified a homozygous stop-gain mutations in DSG2 (c.C355T, p.R119X) that led to complete desmoglein-2 deficiency in a patient with severe biventricular heart failure. Histological analysis revealed abnormal deposition of desmosome proteins, disrupted intercalated disk structures in the myocardium. Induced pluripotent stem cells (iPSCs) were generated from the patient (R119X-iPSC), and the mutated DSG2 gene locus was heterozygously corrected to a normal allele via homology-directed repair (HDR-iPSC). Both isogenic iPSCs were differentiated into cardiomyocytes [induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs)]. Multielectrode array analysis detected abnormal excitation in R119X-iPSC-CMs but not in HDR-iPSC-CMs. Micro-force testing of three-dimensional self-organized tissue rings (SOTRs) revealed tissue fragility and a weak maximum force in SOTRs from R119X-iPSC-CMs. Notably, these phenotypes were significantly recovered in HDR-iPSC-CMs. Myocardial fiber structures in R119X-iPSC-CMs were severely aberrant, and electron microscopic analysis confirmed that desmosomes were disrupted in these cells. Unexpectedly, the absence of desmoglein-2 in R119X-iPSC-CMs led to decreased expression of desmocollin-2 but no other desmosome proteins. Adeno-associated virus-mediated replacement of DSG2 significantly recovered the contraction force in SOTRs generated from R119X-iPSC-CMs. Our findings confirm the presence of a desmoglein-2-deficient cardiomyopathy among clinically diagnosed dilated cardiomyopathies. Recapitulation and correction of the disease phenotype using iPSC-CMs provide evidence to support the development of precision medicine and the proof of concept for gene replacement therapy for this cardiomyopathy.

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