RESUMO
BACKGROUND: Increasing evidence proves that RBP7 plays a significant role in breast cancer (BC). The present study was aimed to investigate the mechanism of RBP7. METHODS: Western Blotting and qRT-PCR were performed for evaluating the expression levels. CCK8, colony forming, xenograft mouse model, wound healing and transwell assays were conducted to examine cell ability of proliferation, invasion and migration. Nile red staining and Oil red O staining were used for testing the lipid. RESULTS: RBP7 was related to overall survival (OS) in patients with HR + BC. RBP7 protein was significantly decreased in HR + BC tissues and cells. RBP7 suppressed HR + BC cell proliferation in vitro and in vivo, and inhibited migration and invasion. RBP7 reduced fatty acid in HR + BC cells by inhibiting the AKT/SREBP1 pathway. CONCLUSIONS: RBP7 may function as a tumor suppressor in HR + BC by inhibiting the AKT/SREBP1 pathway and reducing fatty acid.
RESUMO
Immunotherapy aimed at inhibiting the negative co-stimulatory molecule programmed cell death-ligand 1 (PD-L1) has limited effectiveness, with clinical response rates remaining below 10%-15%. Therefore, new immune checkpoints need to be explored. Our study focused on human endogenous retrovirus H long terminal repeat-associating protein 2 (HHLA2), a highly glycosylated member of the B7 family that is widely expressed in colorectal cancer. HHLA2 expression negatively correlates with the prognosis of colorectal cancer. Glycosylation of HHLA2, which is regulated by the glycosyltransferase STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A), is crucial for protein stability and expression in cell membranes. Additionally, the binding of HHLA2 to the receptors killer cell immunoglobulin-like receptor, three immunoglobulin domains and long cytoplasmic tail 3 (KIR3DL3) and transmembrane and immunoglobulin (Ig) domain containing 2 (TMIGD2) is dependent on N-glycosylation. Moreover, N-glycosylation of HHLA2 promotes immune evasion in colorectal cancer by suppressing the immune response of NK cells. Notably, the STT3A inhibitor NGI-1 enhances the anti-tumor immune response of NK cells. Our findings provide new insights and a molecular basis for targeting HHLA2 in immunotherapy for colorectal cancer.
Assuntos
Neoplasias Colorretais , Imunoglobulinas , Humanos , Glicosilação , Imunoterapia , Prognóstico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genéticaRESUMO
Monocyte/macrophages constitute a significant population of tumor-infiltrating immune cells and play a crucial role in tumor growth, invasion, and metastasis. B7-H3, has immune regulatory functions, however, it is unclear whether B7-H3 expressed on monocyte/macrophages plays a significance role in tumor progression. We found B7-H3 was high-expressed on monocyte/macrophages in tumor microenvironment compared with adjacent tissues in lung cancer, and its expression level was positively correlated with the number of monocyte/macrophages. Furthermore, the expression of B7-H3 was related to clinical stage and lymph node metastasis. Moreover, miR-29a-3p negatively regulated B7-H3, and the expression of B7-H3 on THP-1-derived macrophages was regulated by secreting exosomes containing miR-29a-3p. In addition, knockdown of B7-H3 promoted macrophage apoptosis under hypoxia. Mechanistically, B7-H3 enhanced the antiapoptotic ability of macrophage by up-regulating HIF-1É via activating NF-κB. Taken together, these results imply that B7-H3 as a therapeutic target could hold promise for enhancing anti-tumor immune responses in individuals diagnosed with lung cancer.
RESUMO
Ferroptosis, a newly discovered form of regulated cell death, has been reported to be associated with multiple cancers, including colorectal cancer (CRC). However, the underlying molecular mechanism is still unclear. In this study, we identified B7H3 as a potential regulator of ferroptosis resistance in CRC. B7H3 knockdown decreased but B7H3 overexpression increased the ferroptosis resistance of CRC cells, as evidenced by the expression of ferroptosis-associated genes (PTGS2, FTL, FTH, and GPX4) and the levels of important indicators of ferroptosis (malondialdehyde, iron load). Moreover, B7H3 promoted ferroptosis resistance by regulating sterol regulatory element binding protein 2 (SREBP2)-mediated cholesterol metabolism. Both exogenous cholesterol supplementation and treatment with the SREBP2 inhibitor betulin reversed the effect of B7H3 on ferroptosis in CRC cells. Furthermore, we verified that B7H3 downregulated SREBP2 expression by activating the AKT pathway. Additionally, multiplex immunohistochemistry was carried out to show the expression of B7H3, prostaglandin-endoperoxide synthase 2, and SREBP2 in CRC tumor tissues, which was associated with the prognosis of patients with CRC. In summary, our findings reveal a role for B7H3 in regulating ferroptosis by controlling cholesterol metabolism in CRC.
Assuntos
Neoplasias Colorretais , Ferroptose , Humanos , Colesterol/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Ciclo-Oxigenase 2 , Ferroptose/genética , Ferro/metabolismoRESUMO
During the processing of tobacco leaves, flue-curing and redrying can affect the structure of bacterial community, having an effect on the aging quality of tobacco leaves. In order to characterize the effects of flue-curing and redrying on the bacterial community of tobacco leaves, the bacterial community of samples at different processing stages (before flue-curing, after flue-curing, before redrying and after redrying) was analyzed using Illumina sequencing. A total of 33 phyla, 79 classes, 195 orders, 344 families, 826 genera and 7922 ASVs were obtained from 36 samples. There was no significant difference in the core bacterial groups of tobacco leaf at four processing stages. Proteobacteria dominated at the phylum level. Sphingomonas, Pseudomonas and Methylobacterium were the main genera shared by all samples. The functional prediction by PICRUSt showed an increase in the relative abundance of pathway related to metabolism after flue-curing and pathway related to environmental information processing after redrying. This study, we analyzed the changes of bacterial community and structural composition of tobacco leaves from flue-curing to redrying, and found that flue-curing had a greater effect on the microbial community than redrying. This is conducive for the exploration of microbial resources and improvement of tobacco leaf quality.
Assuntos
Vacinas Anticâncer , Nicotiana , Humanos , Folhas de Planta , Proteobactérias/genética , EnvelhecimentoRESUMO
The pectin methylesterases (PMEs) play multiple roles in regulating plant development and responses to various stresses. In our study, a total of 121 PME genes were identified in the tobacco genome, which were clustered into two groups based on phylogenetic analysis together with Arabidopsis members. The investigations of gene structure and conserved motif indicated that exon/intron and motif organizations were relatively conserved in each group. Additionally, several stress-related elements were identified in the promoter region of these genes. The survey of duplication events revealed that segmental duplications were critical to the expansion of the PME gene family in tobacco. The expression profiles analysis revealed that these genes were expressed in various tissues and could be induced by diverse abiotic stresses. Notably, NtPME029 and NtPME043, were identified as homologues with AtPME3 and AtPME31, respectively. Furthermore, NtPME029 was highly expressed in roots and the over-expression of the NtPME029 gene could promote the development of roots. While NtPME043 could be induced by salt and ABA treatments, and the over-expression of the NtPME043 gene could significantly enhance the salt-stress tolerance in tobacco. Overall, these findings may shed light on the biological and functional characterization of NtPME genes in tobacco.
RESUMO
China's government subsidies on the demand side-such as subsidizing medical insurance premiums-have accelerated progress towards universal health coverage. We examined whether the increased government subsidies had benefited the population, especially the poor. We conducted two rounds of household surveys and collected the annual claims reports of a rural medical insurance scheme in Ningxia (a relatively underdeveloped region in Western China). We used benefit incidence analysis to evaluate the distribution of benefits for different health services received by individuals with different living standards, as measured by the household wealth index. From 2009 to 2015, the benefit received per capita tripled from 101 to 332 CNY, most (>94%) of which was received for inpatient care. The overall distribution of benefits improved and became pro-poor in 2015 [the concentration index (CI) changed from -0.017 to -0.092], mainly driven by inpatient care. The poorer groups benefited disproportionately more from inpatient care from 2009 to 2015 (the CI changed from -0.013 to -0.093). County and higher-level inpatient care had the greatest improvements towards a pro-poor distribution. The distribution of subsidies for outpatient services significantly favoured the poorer groups in 2009, but less so in 2015 (CI changed from -0.093 to -0.068), and it became less pro-poor in village clinics (CI changed from -0.209 to -0.020). The increased government subsidies for the rural medical insurance scheme mainly contributed to inpatient care and allowed the poor to use more services at county and higher-level hospitals. China's government subsidies on the demand side have contributed to equity in benefit incidence, yet there is a noticeable increasing trend in utilizing services at higher levels of providers. Our findings also indicate that outpatient services need more coverage from rural medical insurance schemes to improve equity.
Assuntos
Seguro Saúde , Pobreza , Humanos , Incidência , Financiamento Governamental , China , População Rural , Assistência Ambulatorial , Governo , Disparidades em Assistência à SaúdeRESUMO
Amylose-oleic acid complexes (AOA) were exposed to microwave heat-moisture treatment (M-HMT) with different moisture content (MC), and the variations in structures and digestibility were investigated. M-HMT caused the dissociation of helical structures and destruction of short-range molecular order of AOA. Meanwhile, the molecules of amylose and oleic acid rearranged and more amylose-oleic acid complexes were formed during M-HMT, the complexing index of AOA was increased from 25.41 % to 41.20 % when treating at 35 % MC. Moreover, the relative content of single helix increased with increasing MC, resulting in higher V-type relative crystallinity. With ≥30 % MC, the treated complexes showed greater thermostability than that of original AOA. The treatment increased the enzymatic digestibility of AOA, and sample treated with 35 % MC had the highest resistant starch content of 82.33 %, which was 17.96 % higher than that of native AOA. The improved enzyme resistance should be correlated to increased molecular interplay and formation of amylose-oleic acid complexes.
Assuntos
Amilose , Ácido Oleico , Amilose/química , Temperatura Alta , Micro-Ondas , Amido/químicaRESUMO
Dodona dipoea pseudokaterina subsp. nov. is described from southwestern Chongqing, China. The wing patterns of the type specimens are similar to those of D. katerina Monastyrskii Devyatkin, 2000, but the genitalic characters of both sexes show that they belong to D. dipoea Hewitson, [1866]. Adults and genitalia of both sexes of the new subspecies, and adults of the nominate subspecies are illustrated.
Assuntos
Borboletas , Animais , China , Feminino , Genitália , Masculino , Asas de AnimaisRESUMO
Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. MicroRNA-7 (miR-7) displays neuroprotective properties against PD. However, the biological roles of miR-7 and its underlying molecular mechanisms in PD remain unclear. We demonstrated herein that 1-methyl-4-phenylpyridinium ion (MPP(+)) confers toxic effects on dopaminergic neuron in a dose-dependent manner in a cellular PD model, although this phenomenon is attenuated by miR-7 treatment. Introduction of miR-7 inhibits MPP(+)-induced neuronal apoptosis as reflected by the reduced terminal transferase-mediated dUTP nick end labeling-positive rate, mitochondrial permeability potential, caspase 3 activity, and nucleosomal enrichment factor. Bax and sirtuin 2 (Sirt2) are the direct targets of miR-7. Moreover, the effects of miR-7 were counteracted by Bax and Sirt2 overexpression, respectively. The altered molecular expressions downstream of Bax and Sirt2 are also involved in miR-7 regulation of the MPP(+)-triggered neuronal apoptosis. These findings have implications on the potential application of miR-7 in PD treatment.
RESUMO
BACKGROUND: As health care dollars are stretched thinner, it is important that dietitians conduct outcomes-based research to validate their contributions to the health care system. OBJECTIVES: To determine the barriers that prevent renal dietitians from participating in research and to determine differences between those who participated in a recent national research study and those who did not. METHODS: This was a cross-sectional study conducted via e-mail. The survey was developed and distributed to members of the National Kidney Foundation's Council on Renal Nutrition. Multiple-choice questions were used to obtain data on respondent's characteristics and to identify barriers to research participation. Institutional Review Board approval was obtained from Case Western Reserve University and all participants were sent an informed consent along with the survey. Participants returned completed surveys by e-mail or fax, and all data were analyzed using SPSS 13.0 (Chicago, IL). RESULTS: Sixty-seven subjects completed the survey. Of these, 10 subjects had participated in a recent national research study and 57 had not. Dietitians, who had participated in the recent national study verses those who had not, did not differ significantly in descriptive data, educational level, nor general attitudes toward research. Barriers that were significantly different between the two groups included not having the time and energy for data collection (63% of those who did not participate versus 0% of those who participated) and family obligations (14% of those who did not participate versus 0% of those who participated). Comfort level in conducting subjective global assessment was higher in those who chose to participate than those who did not (86% versus 40%). CONCLUSION: The greatest barrier for dietitians who did not participate in the national research study was a lack of time and energy to collect data for research. The majority of the renal dietitians recognized the importance of research.
Assuntos
Dietética , Pesquisa/organização & administração , Autoimagem , Adulto , Idoso , Estudos Transversais , Coleta de Dados , Escolaridade , Medicina Baseada em Evidências , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de TempoRESUMO
The volatile constituents in the flowers of Aglaia odorata were extracted by supercritical CO2 fluid under 25 MPa and 40 degrees C for 80 min. The oil yield was 2.64%. These volatile constituents were separated and identified by capillary gas chromatography-mass spectrometry (GC-MS). Experiments were performed on an Agilent 6890 GC Chromatograph with Agilent 5973N Mass Selective Detector. The GC separation conditions was carried out on an HP-5MS capillary column (60 m x 250 microm, 0.25 microm); oven temperature, 50 degrees C (held for 2 min) to 280 degrees C at a rate of 5 degrees C/min, and held for 8 min; split ratio, 1 : 10; injector temperature, 270 degrees C. Mass spectra were collected in the scan range of m/z 50 - 550. The measurements were performed with electron bombardment ion (EI) source with electron energy of 70 eV and electron multiplier voltage of 1.65 kV. The results showed that 54 peaks were separated and 48 compounds were identified for the essential oil extracted from Aglaia odorata L. There were 18 terpenes, 12 esters and other constituents in the volatile oil fraction. The constituents in the oil fraction were alpha-humulene, followed by ethyl linolenate, germacrene D, beta-elemene, copaene, caryophyllene, methyl jasmonate, beta-humulene-7-ol, ethyl palmitate, etc.