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1.
Eur J Dermatol ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648912

RESUMO

BACKGROUND: Acne vulgaris is a common pilosebaceous disease associated with Propionibacterium acnes (P. acnes). Resolution of comedones may occur in association with shrunken sebaceous glands (SGs) containing de-differentiated cells, however the role of P. acnes is unclear. OBJECTIVES: To investigate the effects of P. acnes on aryl hydrocarbon receptor (AhR) activation, lipogenesis and differentiation in cultured immortalized human SZ95 sebocytes. MATERIALS & METHODS: Cultured sebocytes were incubated with formalin-killed (f-) P. acnes (f-P. acnes) at different ratios of multiplicity of infection. The mRNA levels of the AhR downstream cytochrome P450 (CYP) genes were measured by quantitative RT-PCR, nuclear translocation of AhR by western blot and immunofluorescence, lipogenesis and keratinization by gene set enrichment analysis (GSEA), lipid related analysis by Oil red O staining and Nile red staining, and sebaceous differentiation-related gene expression by western blot. RESULTS: f-P. acnes upregulated CYPs mRNA levels and induced translocation of AhR protein from the cytoplasm into the nucleus. GSEA revealed downregulation of lipogenesis and upregulation of keratinization. f-P. acnes inhibited linoleic acid-induced neutral lipid synthesis and expression of sebocyte markers, keratin 7 and mucin1/EMA, but increased expression of keratinocyte markers, keratin 10 and involucrin, which were abolished by AhR gene silencing. Inhibition of lipogenesis-related genes, such as sterol response element-binding protein, was also observed. CONCLUSIONS: f-P. acnes inhibits lipogenesis and induces terminal differentiation of sebocytes, into keratinocyte-like cells, via activation of the AhR pathway in vitro, suggesting that follicular P. acnes is not only acnegenic but also promotes acne remission through feedback regulation of sebum production.

2.
Commun Biol ; 4(1): 266, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649486

RESUMO

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.

3.
BMC Plant Biol ; 21(1): 88, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568056

RESUMO

BACKGROUND: Fruit abortion is a major limiting factor for fruit production. In flat peach, fruit abortion is present in the whole tree of some accessions during early fruit development. However, the physiological factors and genetic mechanism underlying flat fruit abortion remain largely elusive. RESULTS: In this study, we have revealed that the fertilization process was accomplished and the reduction of sucrose and starch contents might result in flat fruit abortion. By combining association and gene expression analysis, a key candidate gene, PpSnRK1ßγ, was identified. A 1.67-Mb inversion co-segregated with flat fruit shape altered the promoter activity of PpSnRK1ßγ, resulting in much lower expression in aborting flat peach. Ectopic transformation in tomato and transient overexpression in peach fruit have shown that PpSnRK1ßγ could increase sugar and starch contents. Comparative transcriptome analysis further confirmed that PpSnRK1ßγ participated in carbohydrate metabolism. Subcellular localization found that PpSnRK1ßγ was located in nucleus. CONCLUSIONS: This study provides a possible reason for flat fruit abortion and identified a critical candidate gene, PpSnRK1ßγ, that might be responsible for flat fruit abortion in peach. The results will provide great help in peach breeding and facilitate gene identification for fruit abortion in other plant species.

4.
ACS Appl Mater Interfaces ; 13(7): 8901-8908, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33587597

RESUMO

Stretchable and flexible electronics conformal to human skin or implanted into biological tissues has attracted considerable interest for emerging applications in health monitoring and medical treatment. Although various stretchable materials and structures have been designed and manufactured, most are limited to two-dimensional (2D) layouts for interconnects and active components. Here, by using projection microstereolithography (PµSL)-based three-dimensional (3D) printing, we introduce a versatile microfabrication process to push the manufacturing limit and achieve previously inaccessible 3D geometries at a high resolution of 2 µm. After coating the printed microstructures with thin Au films, the 3D conductive structures offer exceptional stretchability (∼130%), conformability, and stable electrical conductivity (<5% resistance change at 100% tensile strain). This fabrication process can be further applied to directly create complicated 3D interconnect networks of sophisticated active components, as demonstrated with a stretchable capacitive pressure sensor array here. The proposed scheme allows a simple, facile, and scalable manufacturing route for complex, integrated 3D flexible electronic systems.

5.
Clin Sci (Lond) ; 135(3): 555-574, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33480975

RESUMO

BACKGROUND: Accumulating evidence support the hypothesis that long noncoding RNAs (lncRNAs) are involved in several physiological and pathological conditions, including cancer. Here, we investigated the potential role of lncRNAs in bladder cancer. METHODS: We first looked at available datasets retrieved from the TCGA database and discovered that the lncRNA KTN 1 antisense RNA 1 (KTN1-AS1) was significantly up-regulated in several cancer types including bladder cancer, but was decreased in some other tumors. Therefore, we focused our attention on KTN1-AS1. Using both in vitro and in vivo systems that allowed the modulation of KTN1-AS1 and expression of other relevant proteins, we investigated in-depth the role of KTN1-AS1 in bladder cancer (and the mechanism behind). We further investigated the potential KTN1-AS1-interacting proteins using RNA immunoprecipitation, and explored the KTN1-AS1-related epigenetic landscape (with a particular emphasis on acetylation) using chromatin immunoprecipitation (ChIP) assays. RESULTS: KTN1-AS1 silencing inhibited the proliferation, invasion, and migration of bladder cancer cells, while KTN1-AS1 overexpression had the obvious opposite effects. Mechanistically, KTN1-AS1 promoted the recruitment of EP300, a histone acetyltransferase that enriched acetylation of histone H3 at lysine 27 (H3K27Ac) in the KTN1 promoter region. This epigenetic modulation contributed to the up-regulation of KTN1, which affected bladder cancer growth and progression via the regulation of Rho GTPase (RAC1, RHOA, and CDC42)-mediated signaling. CONCLUSION: Overall, our data support the idea that the lncRNA KTN1-AS1 promotes bladder cancer tumorigenesis via modulation of the KTN1/Rho GTPase axis and is a promising new therapeutic target for the treatment of bladder cancer.

6.
Plants (Basel) ; 10(2)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33513678

RESUMO

Previous genetic mapping helped detect a ~7.52 Mb putative genomic region for the pollen fertility trait on peach Chromosome 06 (Chr.06), which was too long for candidate gene characterization. In this study, using the whole-genome re-sequencing data of 201 peach accessions, we performed a genome-wide association study to identify key genes related to peach pollen fertility trait. The significant association peak was detected at Chr.06: 2,116,368 bp, which was in accordance with the previous genetic mapping results, but displayed largely improved precision, allowing for the identification of nine candidate genes. Among these candidates, gene PpABCG26, encoding an ATP-binding cassette G (ABCG) transporter and harboring the most significantly associated SNP (Single Nucleotide Polymorphism) marker in its coding region, was hypothesized to control peach pollen fertility/sterility based on the results of gene function comparison, gene relative expression, and nucleotide sequence analysis. The obtained results will help us to understand the genetic basis of peach pollen fertility trait, and to discover applicable markers for pre-selection in peach.

7.
Environ Pollut ; 270: 116211, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33348139

RESUMO

Evidence concerning effects of ambient air pollution on homocysteine (HCY) metabolism is scarce. We aimed to explore the associations between ambient particulate matter (PM) exposure and the HCY metabolism markers and to evaluate effect modifications by folate, vitamin B12, and methylenetetrahyfrofolate reductase (MTHFR) C677T gene polymorphism. Between December 1, 2017 and January 5, 2018, we conducted a panel study in 88 young college students in Guangzhou, China, and received 5 rounds of health examinations. Real-time concentrations of PMs with aerodynamic diameter ≤2.5 (PM2.5), ≤1.0 (PM1.0), and ≤0.1 (PM0.1) were monitored, and the serum HCY metabolism markers (i.e., HCY, S-Adenosylhomocysteine [SAH], and S-Adenosylmethionine [SAM]) were repeatedly measured. We applied linear mixed effect models combined with a distributed lag model to evaluate the associations of PMs with the HCY metabolism markers. We also explored effect modifications of folate, vitamin B12, and the MTHFR C677T polymorphism on the associations. We observed that higher concentrations of PM2.5 and PM1.0 were associated with higher serum levels of HCY, SAH, SAM, and SAM/SAH ratio (e.g., a 10 µg/m3 increase in PM2.5 during lag 0 day and lag 5 day was significantly associated with 1.3-19.4%, 1.3-28.2%, 6.2-64.4%, and 4.8-28.2% increase in HCY, SAH, SAM, and SAM/SAH ratio, respectively). In addition, we observed that the associations of PM2.5 with the HCY metabolism markers were stronger in participants with lower B vitamins levels. This study demonstrated that short-term exposure to PM2.5 and PM1.0 was deleteriously associated with the HCY metabolism markers, especially in people with lower B vitamins levels.


Assuntos
Complexo Vitamínico B , China , Homocisteína , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Oxirredutases , Material Particulado , Polimorfismo Genético
8.
J Ethnopharmacol ; 266: 113430, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33011366

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus mongholicus, Solanum nigrum Linn, Lotus plumule, Ligusticum are widely used traditional herbal medicines for cancer treatment in China. They were typical drugs selected from Gubenyiliu II and series of formula (GYII), which were developed on the foundation of YIQIHUOXUEJIEDU theory. In the present study, four active ingredients (Astragaloside IV, α-solanine, neferine, and 2,3,5,6-tetramethylpyrazine) derived from medicines above were applied in combination as SANT. AIM OF THE STUDY: Triple-negative breast cancer (TNBC) is a serious threat to women's health worldwide. Heparanase (HPSE) is often up-regulated in breast cancer with the properties of facilitating tumorigenesis and influencing the autophagy process in cancer cells. This study aimed at evaluating the anti-tumor potential of SANT in treating HPSE related TNBC both in-vitro and in-vivo. MATERIALS AND METHODS: In this study, we explored the correlation between HPSE expression and survival of breast cancer patients in databases. We performed MTS, trans-well and wound scratch assays to assess the impact of SANT on cell proliferation and migration. Confocal microscopy observation and western blots were applied to verify the autophagy flux induced by SANT. Mice models were employed to evaluate the efficacy and safety of SANT in-vivo by tumor weights and volumes or serum index, respectively. To analyze the underlying mechanisms of SANT, we conducted human autophagy PCR array and angiogenesis proteome profiler on tumor tissues. RESULTS: Patients with elevated HPSE expression were associated with a poor outcome in both RFS (P = 1.7e-12) and OS (P = 0.00016). SANT administration significantly inhibited cancer cells' proliferation and migration, enhanced autophagy flux, and slightly reduced the active form of HPSE in-vitro. SANT also suppressed tumor growth and angiogenesis in-vivo. Human autophagy PCR array results indicated that SANT increased the ATG16L1, ATG9B, ATG4D gene expressions while decreased TMEM74 and TNF gene expressions.Angiogenesis proteome profiler results showed SANT reduced protein level of HB-EGF, thrombospondin-2, amphiregulin, leptin, IGFBP-9, EGF, coagulation factor III, and MMP-9 (pro and active form) in tumor, raised the protein expression of serpin E1 and platelet factor 4. CONCLUSIONS: These findings indicated that herbal compounds SANT may be a promising candidate in anti-cancer drug discovery. It also provides novel strategies for using natural compounds to achieve optimized effect.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Autofagia/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glucuronidase/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Am J Cancer Res ; 10(11): 3686-3704, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294261

RESUMO

Long non-coding RNAs (lncRNAs) play a vital role in the progression of several cancers, including nasopharyngeal carcinoma (NPC). However, the mechanism of lncRNA involvement in the progression of NPC remains to be elucidated. Hence, we conducted in vivo and in vitro experiments to determine the molecular mechanism of FOXD1-AS1. We found that FOXD1-AS1 was over-expressed in NPC cells and tissues, and was significantly associated with poor survival rate in patients with NPC. We also found that FOXD1-AS1 promotes cellular proliferation, migration, invasion, and glycolysis, and inhibits apoptosis by upregulating the expression of FOXD1. Furthermore, FOXD1 could transcriptionally up-regulate the expression of key glycolytic genes to promote the glycolysis levels of NPC. The identified FOXD1-AS1 may serve as a potential prognostic biomarker and therapeutic target for patients with NPC.

10.
Inorg Chem ; 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33378622

RESUMO

An in situ Pd-NHC catalyzed selective B(3,6)-H activation for hydroboration of internal alkynes has been accomplished under mild conditions. This work offers a facile approach for the synthesis of alkenyl-o-carboranes and has important reference for selective functionalization of B(3,6)-H bonds.

11.
Future Microbiol ; 15: 1697-1712, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33350865

RESUMO

Aim: The resident bacterial microbiome may shape and protect the health of vertebrate host. An array of molecules secreted by microbiome may contribute to the ecological stability of the microbiome itself. Material & methods: ELISA, radioactivity, immunofluorescence and cytokines measurements were used to observe the bioactivity and stability of colicin Ia level in oviparous and viviparous animal circulation. Results: Colicin Ia, a protein antimicrobial produced by Escherichia coli, is not present in animals at birth, but increases in concentration with the establishment of a stable gut microbiome and drops when the microbiome is experimentally disrupted. Colicin introduced in vivo is transported to tissues at concentrations able to prevent or eliminate bacterial infection. Conclusion: Our findings suggest an unexpected benefit provided by the presence of a resident microbiome in the form of active, circulating, bacterially-synthesized antimicrobial molecules.

12.
Inorg Chem ; 59(23): 17340-17346, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33232154

RESUMO

A palladium catalyzed selective B(3)-H activation/oxidative dehydrogenative coupling for the synthesis of bis(o-carborane)s connected with B(3)-B(3') and B(3)-B(6') bonds has been developed for the first time. A plausible mechanism involving stepwise activation of B(3)-H and B(3'/6')-H bonds by PdII and PdIV was proposed. This work is the first example and the most efficient protocol for synthesis of bis(o-carborane)s connected with B(3)-B(3') and B(3)-B(6') bonds, which has important reference for design, synthesis, and application of bis(o-carborane)s in related fields.

13.
Aging (Albany NY) ; 12(21): 21904-21922, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33147570

RESUMO

BACKGROUND: Long non-coding RNAs (LncRNAs) have been associated with several types of cancer. However, little is known about their role in lung adenocarcinoma (LUAD). RESULTS: LINC00968 was significantly differentially expressed in LUAD tissues. Downregulated LINC00968 was associated with clinicopathological features of LUAD. LINC00968 inhibited cell growth and metastasis by regulating the Hippo signaling pathway We demonstrated that LINC00968 acts as a ceRNA to consume miR-21-5p, enhancing the accumulation of SMAD7, a miR-21-5p target. CONCLUSIONS: LINC00968 limits LUAD progression via the miR-21-5p/SMAD7 axis and may serve as a prognostic biomarker and therapeutic target for LUAD. METHODS: We conducted comprehensive data mining on LINC00968 based on the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. The expression of LINC00968 in LUAD cells was determined using in situ hybridization. We detected LINC00968 function in LUAD cells using the MTT, clone formation, and transwell assays, and tumor xenografts. Label-free quantitative proteomics, western blotting, a dual-luciferase reporter assay, immunofluorescence, and RNA immunoprecipitation assays were used to determine the correlations among LINC00968, miR-21-5p, and SMAD7. Gain- and loss-function approaches were used to explore the effects of LINC00968, miR-21-5p, and SMAD7 on cell proliferation, migration, and invasion.

14.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1104-1108, 2020.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33051425

RESUMO

OBJECTIVES: To study the effect of rotation errors on the γ pass rate of volume-modulated arc therapy (VMAT) plan in rectal cancer based on the ArcCheck phantom. METHODS: CT data from 20 rectal cancer patients underwent VMRT were selected randomly for this study. Targeting areas were selected, and clinical radiotherapy and validation plans were formulated. ArcCheck model was selected to validate the radiotherapy plans. The effect of the rotation errors on the dosimetric verification for VMAT in rectal cancer was simulated and analyzed with ArcCheck model software. RESULTS: When there was no rotation errors, the γ pass rate of VMRT plans was more than 95%. When the absolute rotation angle was less than or equal to 1°, the γ pass rate of VMAT plans was more than 90%, meeting the clinical requirements. When the absolute rotation angle was greater than 1°, the γ pass rate was less than 90%, which did not meet clinical requirements. CONCLUSIONS: The rotation errors affect the γ pass rate of VMAT plans. The larger the rotation angle, the lower the γ pass rate. It meets clinical requirements when the rotation error is less than or equal to 1°.


Assuntos
Radioterapia de Intensidade Modulada , Neoplasias Retais , Humanos , Radiometria , Planejamento da Radioterapia Assistida por Computador , Neoplasias Retais/radioterapia , Rotação
15.
Am J Transl Res ; 12(9): 4923-4940, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042398

RESUMO

PURPOSE: This study explored the effects of phosphofructokinase-1 (PFK1) on the radiosensitivity of colorectal cancer (CRC) in vivo and in vitro and the underlying mechanisms. METHODS: Tissue samples from 48 patients with rectal cancer who had received neoadjuvant radiotherapy followed by surgery were analyzed. The expression of PFK1 in tissue samples was semi-quantitated by immunohistochemistry, and its relationship with clinicopathological features was analyzed. The effects of PFK1 knockdown on the survival, apoptosis, migration, and radiosensitivity of CRC cells were evaluated. Glycolysis-related indicators were used to examine glycolytic activity. The effects of PFK1 on the radiosensitivity of CRC in vivo were assessed by measuring tumor formation in nude mice. RESULTS: PFK1 was overexpressed in rectal cancer and was higher in radiation-resistant tumors than in radiation-sensitive tumors. SiRNA-induced PFK1 silencing increased apoptosis and inhibited migration and proliferation of CRC cells. Knockdown of PFK1 made the CRC cells sensitive to ionizing radiation in vivo. Oligomycin partially restored the expression of PFK1, enhanced glycolysis, and reversed the enhanced radiosensitivity of CRC cells induced by siRNA-PFK1. Downregulation of PFK1 combined with irradiation inhibited growth of nude mice xenografts, which was related to an increase in apoptosis. CONCLUSIONS: Our study indicates that high expression of PFK1 is negatively correlated with radiosensitivity in CRC and likely accelerates the proliferation and migration of CRC cells. Downregulation of PFK1 may enhance the radiosensitivity of CRC cells in vivo and in vitro by inhibiting glycolysis.

16.
Materials (Basel) ; 13(19)2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32998283

RESUMO

Alkali activated slag (AAS) mortar is becoming an increasingly popular green building material because of its excellent engineering properties and low CO2 emissions, promising to replace ordinary Portland cement (OPC) mortar. However, AAS's high shrinkage and short setting time are the important reasons to limit its wide application in engineering. This paper was conducted to investigate the effect of internal curing(IC) by super absorbent polymer (SAP) on the autogenous shrinkage of AAS mortars. For this, an experimental study was carried out to evaluate the effect of SAP dosage on the setting time, autogenous shrinkage, compressive strength, microstructure, and pore structure. The SAP were incorporated at different dosage of 0, 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 percent by weight of slag. The workability, physical (porosity), mechanical, and shrinkage properties of the mortars were evaluated, and a complementary study on microstructure was made. The results indicated that the setting time increased with an increase of SAP dosage due to the additional activator released by SAP. Autogenous shrinkage decreased with an increase of SAP dosage, and was mitigated completely when the dosage of SAP ≥ 0.2% wt of slag. Although IC by means of SAP reduced the compressive strength, this reduction (23% at 56 days for 0.2% SAP) was acceptable given the important role that it played on mitigating autogenous shrinkage. In the research, the 0.2% SAP dosage was the optimal content. The results can provide data and basis for practical application of AAS mortar.

17.
Genome Biol ; 21(1): 258, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023652

RESUMO

BACKGROUND: Genome structural variations (SVs) have been associated with key traits in a wide range of agronomically important species; however, SV profiles of peach and their functional impacts remain largely unexplored. RESULTS: Here, we present an integrated map of 202,273 SVs from 336 peach genomes. A substantial number of SVs have been selected during peach domestication and improvement, which together affect 2268 genes. Genome-wide association studies of 26 agronomic traits using these SVs identify a number of candidate causal variants. A 9-bp insertion in Prupe.4G186800, which encodes a NAC transcription factor, is shown to be associated with early fruit maturity, and a 487-bp deletion in the promoter of PpMYB10.1 is associated with flesh color around the stone. In addition, a 1.67 Mb inversion is highly associated with fruit shape, and a gene adjacent to the inversion breakpoint, PpOFP1, regulates flat shape formation. CONCLUSIONS: The integrated peach SV map and the identified candidate genes and variants represent valuable resources for future genomic research and breeding in peach.

18.
Neuropeptides ; 83: 102082, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32863068

RESUMO

Acute ischemic stroke is one of the main causes of mortality and morbidity worldwide. The present study aimed to explore the effects of exogenous insulin-like growth factor 1 (IGF-1) on the cognitive injuries induced by acute ischemic stroke and the underlying mechanisms. Acute ischemic stroke rat model was established via transient occlusion of the left middle cerebral artery to male Sprague-Dawley rats. IGF-1 was administered intravenously every other day 24 h after surgery for 14 days. Cognitive functions were determined by Morris water maze assay. Cerebral infarction and edema were determined by riphenyltetrazolium chloride staining and cerebral water content measurement. ELISA and Western blot were performed to detect concentrations of target proteins. Ischemic stroke rats exhibited reduced plasma IGF-1 level and impaired cognitive functions. Intravenous IGF-1 delivery increased the IGF-1 levels in plasma, ischemic amygdala, hippocampus and cortex, improved the neurological dysfunction, cognitive deficits, cerebral infarction and brain edema. Furthermore, IGF-1 relieved the systemic and cerebral inflammatory response by inhibiting the secretion of pro-inflammatory cytokines, interleukin (IL)-6, IL-1ß, and tumor necrosis factor alpha (TNF-α), in serum and ischemic hippocampus of ischemic rats. Additionally, IGF-1 attenuated tau phosphorylation in ischemic hippocampus. In short, intravenous IGF-1 administration attenuates acute ischemic stroke-induced cognitive injuries in the experimental rat model possibly via modulating inflammatory response and tau phosphorylation, and might be of promising therapeutic value to ischemic stroke in the future.

19.
J Cell Mol Med ; 24(20): 11949-11959, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32902157

RESUMO

Sphingolipids constitute a class of bio-reactive molecules that transmit signals and exhibit a variety of physical properties in various cell types, though their functions in cancer pathogenesis have yet to be elucidated. Analyses of gene expression profiles of clinical specimens and a panel of cell lines revealed that the ceramide synthase gene CERS6 was overexpressed in non-small-cell lung cancer (NSCLC) tissues, while elevated expression was shown to be associated with poor prognosis and lymph node metastasis. NSCLC profile and in vitro luciferase analysis results suggested that CERS6 overexpression is promoted, at least in part, by reduced miR-101 expression. Under a reduced CERS6 expression condition, the ceramide profile became altered, which was determined to be associated with decreased cell migration and invasion activities in vitro. Furthermore, CERS6 knockdown suppressed RAC1-positive lamellipodia/ruffling formation and attenuated lung metastasis efficiency in mice, while forced expression of CERS6 resulted in an opposite phenotype in examined cell lines. Based on these findings, we consider that ceramide synthesis by CERS6 has important roles in lung cancer migration and metastasis.

20.
J Exp Clin Cancer Res ; 39(1): 204, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32993787

RESUMO

Tumor angiogenesis is necessary for the continued survival and development of tumor cells, and plays an important role in their growth, invasion, and metastasis. The tumor microenvironment-composed of tumor cells, surrounding cells, and secreted cytokines-provides a conducive environment for the growth and survival of tumors. Different components of the tumor microenvironment can regulate tumor development. In this review, we have discussed the regulatory role of the microenvironment in tumor angiogenesis. High expression of angiogenic factors and inflammatory cytokines in the tumor microenvironment, as well as hypoxia, are presumed to be the reasons for poor therapeutic efficacy of current anti-angiogenic drugs. A combination of anti-angiogenic drugs and antitumor inflammatory drugs or hypoxia inhibitors might improve the therapeutic outcome.

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