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2.
Cancer Lett ; 525: 55-66, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-34562520

RESUMO

The members of the solute carrier (SLC) superfamily are vital membrane transporters in human cells. In the present study, we determine the expression and function of SLC5 family members in colorectal cancer (CRC). Expression analysis based on The Cancer Genome Atlas database and potential clinical relation analysis based on the Oncomine database indicate that SLC5A7 is downregulated and is predicted to correlate with the staging, and prognosis response of CRC. Additional results demonstrate that SLC5A7 is downregulated and correlates with good prognosis in patients with CRC. Ectopic expression of SLC5A7 either by overexpression, or uptake of choline efficiently inhibits CRC growth. Examination of the molecular mechanism reveals that SLC5A7 promotes p53 protein expression by directly interacting with and modifying p53 and disrupting the interaction between p53 and MDM2 in wild type p53 CRC cells. Our findings establish the clear correlation between SLC5A7 and tumour growth, providing a novel potential therapeutic target for CRC.

3.
Cell Rep ; 37(5): 109913, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34731618

RESUMO

Opiates produce a strong rewarding effect, but abstinence from opiate use emerges with severe negative emotions. Depression is one of the most frequent emotion disorders associated with opiate abstinence, which is thought to be a main cause for relapse. However, neurobiological bases of such an aversive emotion processing are poorly understood. Here, we find that morphine abstinence activates κ-opioid receptors (KORs) by increasing endogenous KOR ligand dynorphin expression in the amygdala, which in turn facilitates glutamate transporter 1 (GLT1) expression by activation of p38 mitogen-activated protein kinase (MAPK). Upregulation of GLT1 expression contributes to opiate-abstinence-elicited depressive-like behaviors through modulating amygdalar glutamatergic inputs to the nucleus accumbens (NAc). Intra-amygdala injection of GLT1 inhibitor DHK or knockdown of GLT1 expression in the amygdala significantly suppresses morphine-abstinence-induced depressive-like behaviors. Pharmacological and pharmacogenetic activation of amygdala-NAc projections prevents morphine-abstinence-induced behaviors. Overall, our study provides key molecular and circuit insights into the mechanisms of depression associated with opiate abstinence.

4.
Front Endocrinol (Lausanne) ; 12: 747646, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745012

RESUMO

Obesity, especially central obesity, is a strong risk factor for developing type 2 diabetes (T2D). However, the mechanism underlying the progression from central obesity to T2D remains unknown. Therefore, we analyzed the gut microbial profiles of central obese individuals with or without T2D from a Chinese population. Here we reported both the microbial compositional and gene functional alterations during the progression from central obesity to T2D. Several opportunistic pathogens were enriched in obese T2D patients. We also characterized thousands of genes involved in sugar and amino acid metabolism whose abundance were significantly depleted in obese T2D group. Moreover, the abundance of those genes was negatively associated with plasma glycemia level and percentage of individuals with impaired plasma glucose status. Therefore, our study indicates that the abundance of those depleted genes can be used as a potential biomarker to identify central obese individuals with high risks of developing T2D.

5.
Adv Mater ; : e2107399, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34719800

RESUMO

With the development of phase engineering of nanomaterials (PEN), construction of noble metal heterostructures with unconventional crystal phases, including heterophases, has been proposed as an attractive approach towards the rational design of highly efficient catalysts. However, it still remains challenging to realize the controlled preparation of such unconventional-phase noble metal heterostructures and explore their crystal-phase-dependent applications. Here, we synthesize various Pd@Ir core-shell nanostructures with unconventional fcc-2H-fcc heterophase (2H: hexagonal close-packed; fcc: face-centered cubic) through a wet-chemical seeded method. As a result, heterophase Pd66 @Ir34 nanoparticles, Pd45 @Ir55 multi-branched nanodendrites and Pd68 @Ir22 Co10 trimetallic nanoparticles have been obtained via the phase-selective epitaxial growth of fcc-2H-fcc heterophase Ir-based nanostructures on 2H-Pd seeds. Importantly, the heterophase Pd45 @Ir55 nanodendrites exhibit excellent catalytic performance towards electrochemical hydrogen evolution reaction (HER) under acid condition. An overpotential of only 11.0 mV is required to achieve the current density of 10 mA cm-2 on Pd45 @Ir55 nanodendrites, which is lower than those of the conventional fcc-Pd47 @Ir53 counterpart, commercial Ir/C and Pt/C. Our work not only demonstrates an appealing route to synthesize novel heterophase nanomaterials for promising applications in the emerging field of PEN, but also highlights the significant role of crystal phase in determining their catalytic properties. This article is protected by copyright. All rights reserved.

7.
Acta Biomater ; 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34749001

RESUMO

As cells have the capacity to respond to their mechanical environment, cellular biological behaviors can be regulated by the stiffness of extracellular matrix. Moreover, biological processes are dynamic and accompanied by matrix stiffening. Herein, we developed a stiffening cell culture platform based on polyacrylamide-Fe3O4 magnetic nanocomposite hydrogel with tunable stiffness under the application of magnetic field. This platform provided a wide range of tunable stiffness (∼0.3-20 kPa) covering most of human tissue elasticity with a high biocompatibility. Overall, the increased magnetic interactions between magnetic nanoparticles reduced the pore size of the hydrogel and enhanced the hydrogel stiffness, thereby facilitating the adhesion and spreading of stem cells, which was attributed to the F-actin assembly and vinculin recruitment. Such stiffening cell culture platform provides dynamic mechanical environments for probing the cellular response to matrix stiffening, and benefits studies of dynamic biological processes. STATEMENT OF SIGNIFICANCE: Cellular biological behaviors can be regulated by the stiffness of extracellular matrix. Moreover, biological processes are dynamic and accompanied by matrix stiffening. Herein, we developed a stiffening cell culture platform based on polyacrylamide/Fe3O4 magnetic nanocomposite hydrogels with a wide tunable range of stiffness under the application of magnetic field, without adversely affecting cellular behaviors. Such matrix stiffening caused by enhanced magnetic interaction between magnetic nanoparticles under the application of the magnetic field could induce the morphological variations of stem cells cultured on the hydrogels. Overall, our stiffening cell culture platform can be used not only to probe the cellular response to matrix stiffening but also to benefit various biomedical studies.

8.
Bioorg Chem ; 118: 105471, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34798457

RESUMO

On the basis of N-(3-amino-4-methoxyphenyl)acrylamide scaffold, a series of novel compounds containing 3-substitutional-1-methyl-1H-indole, 2-substitutional pyrrole or thiophene moieties were synthesized and their in vitro antiproliferation activities against A549 and H1975 cell lines were evaluated. The results indicated that most of the compounds showed moderate to excellent antitumor activities. Especially, compounds 9a (A549 IC50 = 1.96 µM, H1975 IC50 = 0.095 µM), 17i (A549 IC50 = 4.17 µM, H1975 IC50 = 0.052 µM), 17j (A549 IC50 = 1.67 µM, H1975 IC50 = 0.061 µM) exhibited comparable antitumor activities and selectivity ratios compared to the positive control osimertinib (A549 IC50 = 2.91 µM, H1975 IC50 = 0.064 µM). In vitro inhibitory activities against EGFR kinases containing different mutations were also tested. Compound 17i showed remarkable inhibitory activity (with IC50 value of 1.7 nM) to EGFRL858R/T790M kinase and selectivity (22-folds compared to EGFRWT kinase). Furthermore, acridine orange/ethidium bromide (AO/EB) staining assay, cell apoptosis assay, cell cycle distribution assay and wound-healing assay of the compounds 9a and 17i were performed on H1975 cell line. The results showed dose-dependent activities of the induction of apoptosis, G0/G1-phase arrestation and inhibition of migration, which were similar to the positive control osimertinib. Additionally, molecular docking analysis was performed to seek the possible binding mode between the selected compounds (9a, 17i-17j) and EGFRL858R/T790M kinase. The results demonstrated that compound 17i is a promising candidate and worth further study.

9.
Microb Cell Fact ; 20(1): 216, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34838016

RESUMO

BACKGROUND: Faecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium difficile infections and chronic gastrointestional infections. However, the risks of FMT and the selection process of suitable donors remain insufficiently characterized. The eligibility rate for screening, underlying microbial basis, and core ethical issues of stool donors for FMT are yet to be elucidated in China. RESULTS: The potential stool donors were screened from December 2017 to December 2019 with the help of an online survey, clinical assessments, and stool and blood testing. Bioinformatics analyses were performed, and the composition and stability of gut microbiota in stool obtained from eligible donors were dynamically observed using metagenomics. Meanwhile, we build a donor microbial evaluation index (DoMEI) for stool donor screening. In the screening process, we also focused on ethical principles and requirements. Of the 2071 participants, 66 donors were selected via the screening process (3.19% success rate). Although there were significant differences in gut microbiota among donors, we found that the changes in the gut microbiota of the same donor were typically more stable than those between donors over time. CONCLUSIONS: DoMEI provides a potential reference index for regular stool donor re-evaluation. In this retrospective study, we summarised the donor recruitment and screening procedure ensuring the safety and tolerability for FMT in China. Based on the latest advances in this field, we carried out rigorous recommendation and method which can assist stool bank and clinicians to screen eligible stool donor for FMT.

10.
Exp Ther Med ; 22(6): 1423, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34721677

RESUMO

Pueratin (Pue) is an extract from Pueraria lobata, and exhibits therapeutic effects for the treatment of inflammation. However, the beneficial effects and mechanisms underlying Pue in the treatment of diminished ovarian reserve (DOR) remains to be fully elucidated. The aim of the present study was to investigate the effect of Pue on Bcl-2 and Bax protein expression in rats with DOR, associated with infertility within clinical practice, induced by 4-vinylcyclohexene diepoxide (VCD). A model of DOR was established in female Sprague Dawley rats by an intraperitoneal injection of 80 mg/kg VCD daily for 45 days. From day 1, the Sprague Dawley rats were orally administered with drugs daily for 45 days. They were divided into normal, model, Pue-low dose (L), Pue-medium dose (M) and Pue-high dose (H) groups (50, 100 and 300 mg/kg Pue, respectively). Follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) levels were subsequently detected using ELISA. H&E staining and TUNEL staining were used to evaluate histopathological changes and apoptosis levels in the ovary, respectively. Bcl-2 and Bax protein expression levels in rat ovaries were evaluated using immunohistochemistry and western blotting. Compared with those in the model group, FSH and LH levels in the Pue-L, -M and -H groups were significantly decreased, whilst E2 levels were significantly increased (P<0.05). After intragastric administration, the volume of the ovaries and uteri of rats in the Pue groups was increased compared with the model group, and the numbers of primordial follicles and primary follicles were also increased. The number of apoptotic cells and the expression of Bax were significantly reduced in a dose-dependent manner (P<0.05), compared with the model group. In addition, Bcl-2 protein expression and the Bcl-2/Bax ratio were found to be significantly increased in the Pue-treated groups in a dose-dependent manner (P<0.05), compared with the model group. In conclusion, Pue treatment improved ovarian function by regulating hormone balance in addition to Bcl-2 and Bax expression.

11.
ACS Omega ; 6(42): 28410-28420, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34723038

RESUMO

Oleanolic acid (OA) is a triterpenoid commonly found in plants and has shown extensive pharmaceutical activities. This study aimed to investigate the underlying mechanism of antiosteoporosis (OP) action of OA by utilizing the network pharmacology approach and molecular docking methods. First, the targets of OA were identified using the GeneCards, Stitch, and Swisstarget databases, and the targets related to OP were mined using the NCBI, Genecards, and DisGeNet databases. The overlapped targets of OA and OP were regarded as candidate targets, and the String database was used to obtain the protein-protein interactions among the targets. Then, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway enrichment pathways of the candidate targets were performed using the DAVID database. In addition, the top 16 targets in the protein interaction network were used for molecular docking. Finally, an animal model constructed using d-galactose-induced oxidative stress and a low-calcium diet with accelerated bone loss was used to verify the in vivo effects of OA on osteoporotic mice. A total of 42 candidate targets for OA to treat OP were obtained. According to the protein-protein interaction network, MAPK1 showed the highest connectivity with other proteins. Additionally, GO analysis identified the top 20 biological processes, 9 cellular components, and top 20 molecular functions. Moreover, the candidate targets were mainly involved in 13 signaling pathways such as TNF signaling pathway, insulin resistance, MAPK signaling pathway, apoptosis, and PI3K-Akt signaling pathways. Furthermore, molecular docking revealed that OA has a high degree of connections with 16 key proteins. In addition, the anti-OP effects of OA are further validated through the in vivo model. Altogether, our study elucidated the candidate targets for OA to alleviate OP, explored the protein-protein interactions and related signaling pathways of the targets, and validated the anti-OP effects of OA. It could provide a better understanding of the action mechanism in OA to treat OP.

12.
Gut ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34836916

RESUMO

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

14.
Front Oncol ; 11: 615881, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631509

RESUMO

Objective: To explore whether preoperative 18Fluorine-Fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) in combination with neutrophil-lymphocyte ratio (NLR) could accurately predict malignant lesions of upper urinary tract (UUT). Methods and Materials: The clinicopathologic data of a total of 252 patients with UUT lesions receiving surgical treatment at our center from January 2012 to November 2019 were retrospectively analyzed. All patients performed routine preoperative hematological examination, urine cytology, computed tomography urography (CTU), and 18F-FDG-PET/CT. Clinicopathologic data between 179 cases with malignancy (Group 1) and 73 cases with benign lesions (Group 2) were compared. Multivariate logistic regression analysis was used to explore the independent predictors of malignant UUT lesions. Receiver operating characteristic (ROC) curve was used to evaluate the predictive ability. Results: Among all patients, univariate analysis showed that NLR, hydronephrosis, CTU indicating malignancy, and PET/CT indicating malignancy were significantly associated with malignant UUT lesions; multivariate analysis revealed that NLR, CTU indicating malignancy, and PET/CT indicating malignancy were independent predictors of malignant UUT lesions; the area under ROC curve (AUC) of NLR, CTU, PET/CT, combining CTU and NLR, combining PET/CT and NLR, and combining PET/CT and CTU were 0.735, 0.788, 0.857, 0.863, 0.913, and 0.919, respectively, for postoperative pathological malignancy. Among 68 patients undergoing ureteroscopy biopsy, univariate analysis suggested that NLR, positive urine exfoliation cytology, CTU indicating malignancy, and PET/CT indicating malignancy were significantly associated with malignant UUT lesions; multivariate analysis demonstrated that positive urine cytology, PET/CT indicating malignancy, and NLR were independent predictors of malignant UUT lesions; the AUC of NLR, ureteroscopy biopsy, and combining PET/CT and NLR were 0.768, 0.853, and 0.839, respectively, for postoperative pathological malignancy. Conclusions: Combining preoperative NLR and PET/CT performed well in differentiating benign from malignant UUT lesions, which could not be identified by traditional imaging or urine cytology. Combining preoperative NLR and PET/CT could be used to reduce unnecessary ureteroscopy biopsy, which might result in tumor cell dissemination and risk of associated complications.

15.
J Clin Gastroenterol ; 55(10): 823-829, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34617932

RESUMO

Climate change has been described as the greatest public health threat of the 21st century. It has significant implications for digestive health. A multinational team with representation from all continents, excluding Antarctica and covering 18 countries, has formulated a commentary which outlines both the implications for digestive health and ways in which this challenge can be faced.


Assuntos
Mudança Climática , Gastroenterologia , Humanos
16.
Cell Regen ; 10(1): 32, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34599392

RESUMO

Pig and monkey are widely used models for exploration of human diseases and evaluation of drug efficiency and toxicity, but high cost limits their uses. Organoids have been shown to be promising models for drug test as they reasonably preserve tissue structure and functions. However, colonic organoids of pig and monkey are not yet established. Here, we report a culture medium to support the growth of porcine and monkey colonic organoids. Wnt signaling and PGE2 are important for long-term expansion of the organoids, and their withdrawal results in lineage differentiation to mature cells. Furthermore, we observe that porcine colonic organoids are closer to human colonic organoids in terms of drug toxicity response. Successful establishment of porcine and monkey colonic organoids would facilitate the mechanistic investigation of the homeostatic regulation of the intestine of these animals and is useful for drug development and toxicity studies.

17.
Adv Mater ; : e2106115, 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34601769

RESUMO

The crystal phase of nanomaterials is one of the key parameters determining their physicochemical properties and performance in various applications. However, it still remains a great challenge to synthesize nanomaterials with different crystal phases while maintaining the same composition, size, and morphology. Here, a facile, one-pot, wet-chemical method is reported to synthesize Pd3 Sn nanorods with comparable size and morphology but different crystal phases, that is, an ordered intermetallic and a disordered alloy with L12 and face-centered cubic (fcc) phases, respectively. The crystal phase of the as-synthesized Pd3 Sn nanorods is easily tuned by altering the types of tin precursors and solvents. Moreover, the approach can also be used to synthesize ternary PdCuSn nanorods with the L12 crystal phase. When used as electrocatalysts, the L12 Pd3 Sn nanorods exhibit superior electrocatalytic performance toward the ethanol oxidation reaction (EOR) compared to their fcc counterpart. Impressively, compared to the L12 Pd3 Sn nanorods, the ternary L12 PdCuSn nanorods exhibit more enhanced electrocatalytic performance toward the EOR, yielding a high mass current density up to 6.22 A mgPd -1 , which is superior to the commercial Pd/C catalyst and among the best reported Pd-based EOR electrocatalysts.

19.
Plants (Basel) ; 10(10)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34686030

RESUMO

Elucidating the origin of flowers has been a challenge in botany for a long time. One of the central questions surrounding the origin of flowers is how to interpret the carpel, especially the relationship between the phyllome part (carpel wall) and the ovule. Recently, consensus favors the carpel originating from the fusion of an ovule-bearing part and the phyllome part that subtends it. Considering the carpel is a complex organ, the accurate presentation of the anatomical structure of the carpel is necessary for resolving this question. Anaxagorea is the most basal genus in a primitive angiosperm family, Annonaceae. The conspicuous stipe at the base of each carpel makes it an ideal material for exploring the histological relationships among the receptacle, the carpel, and the ovule. In the present study, floral organogenesis and vasculature were delineated in Anaxagorea luzonensis and Anaxagorea javanica, and a three-dimensional model of the carpel vasculature was reconstructed based on serial sections. The results show that in Anaxagorea, the vasculature in the carpel branches in the form of shoots. The radiosymmetrical vasculature pattern is repeatedly presented in the receptacle, the carpel, and the funiculus of the ovule. This provides anatomical evidence of the composite origin of the carpel.

20.
medRxiv ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34704095

RESUMO

To characterize Coronavirus Disease 2019 (COVID-19) transmission dynamics in each of the 15 most populous metropolitan statistical areas (MSAs) in the United States (US) from January 2020 to September 2021, we extended a previously reported compartmental model accounting for effects of multiple distinct periods of social distancing by adding consideration of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants Alpha (lineage B.1.1.7) and Delta (lineage B.1.617.2). For each MSA, we found region-specific parameterizations of the model using daily reports of new COVID-19 cases available from January 21, 2020 to August 24, 2021. In the process, we obtained estimates of the relative infectiousness of Alpha and Delta as well as their takeover times in each MSA. We find that 14-d ahead forecasts are reasonably accurate; these forecasts are being updated daily. Projections made on August 24, 2021 suggest that 5 of the 15 MSAs have already achieved herd immunity.

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