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1.
Zhen Ci Yan Jiu ; 46(9): 763-8, 2021 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-34558242

RESUMO

OBJECTIVE: To compare the effect of electroacupuncture (EA), metformin and EA plus metformin on the cognitive ability and senile plaques (SPs) in cerebral cortex and hippocampus of Alzheimer's disease (AD) mice, so as to explore a better treatment method for AD. METHODS: Twenty-four male APP/PS1 mice were randomly divided into model, metformin (medication), EA and EA+medication groups, with 6 mice in each group. Other 6 male wild C57 mice were used as the control group. EA (2 Hz, 1.0 mA) was applied to "Baihui" (GV20) and "Shenshu" (BL23) for 15 min, once a day, for 4 weeks, with 1 day's off every week. The mice of the medication group received gavage of metformin (300 mg·kg-1·d-1) once a day for 4 weeks. Morris water maze tests were used to assess the cognitive function of mice. H.E. staining was used to observe the histopathological changes of neurons in the cortex and hippocampus. Immunohistochemical method was used to observe the cerebral cortex and hippocampal SPs. The expression levels of SPs formation-related proteins: ß-site amyloid precursor protein cleaving enzyme 1(ßACE1) and insulin-degrading enzyme (IDE) in the cortex and hippocampus were detected by Western blot. RESULTS: Compared with the control group, the escape latency, number of SPs and the expression of ßACE1 in the cortex and hippocampus were ob-viously increased (P<0.01), and the times of platform quadrant crossing and the expression of IDE protein were markedly decreased in the model group (P<0.01). In comparison with the model group, the escape latency, and the number of SPs and expression of ßACE1 proteins in the cortex and hippocampus in the 3 treatment groups were significantly down-regulated (P<0.01), while the times of platform quadrant crossing, and the expression of IDE protein in both cortex and hippocampus of the three treatment groups were considerably up-regulated (P<0.01). Comparison among the three treatment groups showed that the therapeutic effect of EA+medication was significantly superior to that of medication and simple EA in down-regulating the escape latency, the number of SPs and expression of ßACE1 in the cortex and hippocampus (P<0.01), and in up-regulating the times of the platform quadrant crossing, and expression of IDE protein in both cortex and hippocampus (P<0.01). No significant differences were found between the simple medication and simple EA in all the indexes mentioned above (P>0.05). CONCLUSION: EA, metformin and EA plus metformin can improve cognitive ability and relieve SP formation in cerebral cortex and hippocampus in AD mice, which may be associated with their functions in down-regulating the expression of ßACE1 and up-regulating the expression of IDE. The therapeutic effects of EA plus metformin are apparently better than those of simple EA and simple metformin.


Assuntos
Eletroacupuntura , Metformina , Animais , Córtex Cerebral , Cognição , Hipocampo , Masculino , Camundongos , Placa Amiloide
2.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4040-4050, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467713

RESUMO

In recent years, the establishment of the commercial grade of Yinpian [traditional Chinese medicine(TCM) pieces for decoction] in the TCM industry has been hotly disputed. In this article, Sophorae Flavescentis Radix(SFR) was selected as a representative example to investigated. Through systematic comparison and analysis, the different grades of SFR slices were traced, verified and evaluated. According to the current published local grade standards of SFR slices, the results showed that the first-class of SFR slices were mostly derived from the wild medicinal materials, the second-class were mostly originated from the cultivated materials in 3-4 years, and the third-class products were from a small number of lateral roots and short-growing years or harsh habitat of wild medicinal materials. On the basis of identifying the sources of different grades of SFR slices, the contents of the active components, including matrine, oxymatrine, oxysophocarpine, sophoridine, N-methyl-cytisine, sophocarpine, were quantitatively determined in typical samples, it was found that the grades were inversely proportional to the contents of active ingredients. In order to ensure the universality of the conclusion, the contents of different grades of commercial SFR slices were determined, and the conclusion was verified as "the commercial grades of SFR slices were inversely linked to their contents of active ingredients". This phenomenon is common in the determination of the commercial grade of Yinpian of radix and rhizome. Therefore, we propose that the method or standard of the commercial grade of Yinpian of radix and rhizome based on the size of Yinpian maybe not proper. Whether and how to classify Yinpian commercial grade is not only a multi-disciplinary issue, especially in combination with clinical efficacy, but also a big problem need to consider the production, commercial circulation and other processes link of quality risk and quality assurance, and should be treated with great caution.


Assuntos
Medicamentos de Ervas Chinesas , Sophora , Medicina Tradicional Chinesa , Raízes de Plantas , Rizoma
3.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(4): 365-370, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34374255

RESUMO

Objective: To study the effects of electroacupuncture on the expressions of autophagy-related factors LC3-Ⅱ, Beclin1, Atg7, and P62 in the liver of rapidly aging (senescence accelerated mouse/prone8,SAMP8) mice, and to explore the mechanisms of electroacupuncture to improve liver lipid metabolism in mice. Methods: Thirty-week-old male SAMP8 mice were randomly divided into model group, drug group, and electroacupuncture group, with 7 mice in each group. Seven anti-rapid aging SAMR1 mice of the same age were used as the control group. The animals in the control group and the model group were bred routinely for 2 weeks without any intervention; the drug group was treated with intraperitoneal injection of rapamycin at the dose of 10 mg·kg-1·d-1, once a day, 6 consecutive days a week; the electroacupuncture group was given "Shenshu" and "Taichong" Electroacupuncture at point(15 minutes a day, 6 consecutive days a week). The serum lipid metabolism and liver lipid deposition of mice were detected, the distribution of liver autophagy body, the protein and mRNA expressions of liver LC3 - Ⅱ, Beclin1, Atg7 and P62 were determined. Results: Compared with the control group, the total cholesterol (TC), triglycerides (TG), and low density lipoprotein (LDL) of the model group were increased significantly(P<0.01). In the model group, lipid droplet deposition was obvious, autophagosomes were decreased, the protein and mRNA expression levels of autophagy- related factors LC3-Ⅱ, Beclin1 and Atg7 were decreased significantly (P<0.01), while the protein and mRNA expressions of P62 were increased significantly (P<0.01). Compared with the model group, the serum contents of TG, TC, and LDL of the mice in the electroacupuncture group and the drug group were decreased significantly (P<0.01), lipid droplet deposition was reduced, autophagosomes were increased, the protein and mRNA expression levels of LC3 -Ⅱ, Beclin1 and Atg7 were increased significantly(P<0.01), and the protein and mRNA expression levels of P62 were decreased significantly(P<0.01). The protein and mRNA expression levels of Beclin1 and Atg7 in the liver of the electroacupuncture group were not significantly different from the drug group (P>0.05). Conclusion: Electroacupuncture can alleviate liver lipid metabolism disorders, which may be related to the regulation of the expressions of liver autophagy related factors LC3-Ⅱ, Beclin1, Atg7, and P62, thereby promoting liver autophagy in SAMP8 mice.


Assuntos
Eletroacupuntura , Envelhecimento , Animais , Autofagia , Metabolismo dos Lipídeos , Lipídeos , Fígado , Masculino , Camundongos
4.
Database (Oxford) ; 20212021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34296748

RESUMO

Accumulated evidence suggests that the widely expressed long-non-coding RNAs (lncRNAs) are involved in biogenesis. Some aberrant lncRNAs are closely related to pathological changes, for instance, in cancer. Both in tumorigenesis and cancer progression, depending on the interplay with cellular molecules, lncRNAs can modulate transcriptional interference, chromatin remodeling, post-translational regulation and protein modification, and further interfere with signaling pathways. Aiming to the diagnosis/ prognosis markers or potential therapeutical targets, it is important to figure out the specific mechanism and the tissue-specific expressing patterns of lncRNAs. Generally, the bioinformatics analysis is the first step. More and more in silico databases are increasing. But the existing integrative online platforms' functions are not only having their unique features but also share some common features, which may lead to a waste of time for researchers. Here, we reviewed these web tools according to the functions. For each database, we clarified the data source, analysis method and the evidence that the analysis result is derived from. This review also illustrated examples in practical use for a specific lncRNA by these web tools. It will provide convenience for researchers to quickly choose the appropriate bioinformatics web tools in oncology studies.

5.
Int J Mol Sci ; 22(14)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34299091

RESUMO

The differentiation of human pluripotent stem cells (hPSCs) to neural stem cells (NSCs) is the key initial event in neurogenesis and is thought to be dependent on the family of Wnt growth factors, their receptors and signaling proteins. The delineation of the transcriptional pathways that mediate Wnt-induced hPSCs to NSCs differentiation is vital for understanding the global genomic mechanisms of the development of NSCs and, potentially, the creation of new protocols in regenerative medicine. To understand the genomic mechanism of Wnt signaling during NSCs development, we treated hPSCs with Wnt activator (CHIR-99021) and leukemia inhibitory factor (LIF) in a chemically defined medium (N2B27) to induce NSCs, referred to as CLNSCs. The CLNSCs were subcultured for more than 40 passages in vitro; were positive for AP staining; expressed neural progenitor markers such as NESTIN, PAX6, SOX2, and SOX1; and were able to differentiate into three neural lineage cells: neurons, astrocytes, and oligodendrocytes in vitro. Our transcriptome analyses revealed that the Wnt and Hedgehog signaling pathways regulate hPSCs cell fate decisions for neural lineages and maintain the self-renewal of CLNSCs. One interesting network could be the deregulation of the Wnt/ß-catenin signaling pathway in CLNSCs via the downregulation of c-MYC, which may promote exit from pluripotency and neural differentiation. The Wnt-induced spinal markers HOXA1-4, HOXA7, HOXB1-4, and HOXC4 were increased, however, the brain markers FOXG1 and OTX2, were absent in the CLNSCs, indicating that CLNSCs have partial spinal cord properties. Finally, a CLNSC simple culture condition, when applied to hPSCs, supports the generation of NSCs, and provides a new and efficient cell model with which to untangle the mechanisms during neurogenesis.


Assuntos
Biomarcadores/análise , Células-Tronco Neurais/citologia , Neurogênese , Neurônios/citologia , Células-Tronco Pluripotentes/citologia , Transcriptoma , Via de Sinalização Wnt , Diferenciação Celular , Células Cultivadas , Humanos , Fator Inibidor de Leucemia/administração & dosagem , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Neurônios/metabolismo , Células-Tronco Pluripotentes/efeitos dos fármacos , Células-Tronco Pluripotentes/metabolismo
6.
Zhen Ci Yan Jiu ; 46(4): 259-65, 2021 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-33931988

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture(EA)on locomotor activity and the expression of high-mobility group box-1(HMGB1) and Toll-like receptor 4(TLR4) in mice with spinal cord injury(SCI), so as to explore its mechanisms underlying improvement of SCI at the acute stage. METHODS: Forty-eight female C57BL/6 mice were equally randomized into 3 groups: sham operation, model and EA. The SCI model was established by clamping the spinal cord with a serrefine after laminectomy at the 1st lumbar vertebra(L1). EA (1.5 Hz/7.5 Hz, 1.0 mA) was applied to "Jiaji"(EXH-B2) for 10 min, once a day for 5 and 14 days, separately. The hindlimb locomotor function was assessed by Basso, Beattie, Bresnahan Locomotor Rating Scale (BBB). Histopathological changes of the injured area of the spinal cord were determined by H.E. staining. The expression levels of spinal HMGB1, TLR4, ionized calcium binding adaptor molecule 1(Iba1) proteins were detected by Western blot, and the Iba1-positive microglial cells and HMGB1 and Iba1 co-labelled microglia were displayed by immunofluorescence staining. RESULTS: After SCI, the BBB scores on day 5 and 14 were obviously decreased (P<0.05), and the expression of HMGB1 on day 14, TLR4 on day 5 and 14, the number of Iba1-positive microglia as well as the co-expressed HMGB1/Iba1-positive microglia on day 5 and 14 were significantly increased in the model group relevant to the sham operation group (P<0.05, P<0.01). In the EA intervention group, SCI-induced reduction of BBB scores on day 5 and 14, and increases of the expression of HMGB1 and Iba1 on day 14, and TLR4 on day 5 and 14, and the number of Iba1-positive cells as well as the co-expressed HMGB1/Iba1-positive microglia on day 14 were reversed relevant to the model group (P<0.05,P<0.01). H.E. staining showed a structural disorder with lots of cavities, severe inflammatory infiltration with a large quantity of inflammatory cells, and a reduction of normal neurons in the injured spinal cord tissue in the model group, which was relatively milder, with lower activation of microglia in the EA group. CONCLUSION: EA can significantly improve locomotor function in SCI mice, which is associated with its effects in suppressing the expression of inflammatory factors such as HMGB1, TLR4, Iba1 and the over-activation of microglia.


Assuntos
Eletroacupuntura , Proteína HMGB1 , Traumatismos da Medula Espinal , Animais , Feminino , Proteína HMGB1/genética , Camundongos , Camundongos Endogâmicos C57BL , Medula Espinal , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/terapia , Coluna Vertebral , Receptor 4 Toll-Like/genética
7.
Zhen Ci Yan Jiu ; 46(1): 45-51, 2021 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-33559425

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Jiaji" (EX-B2) on the levels of autophagy and endoplasmic reticulum stress in mice with spinal cord injury (SCI), so as to explore its mechanism underlying improvement of SCI. METHODS: A total of 60 female C57BL/6 mice were randomly divided into sham operation, model and EA groups, which were further divided into 7 d and 14 d subgroups (10 mice in each subgroup). The SCI model was established by pressing the exposed spinal cord (L1) with a vascular clamp for 15 s. EA was applied to bilateral EX-B2 3 h after modeling, once a day for 7 and 14 d, respectively. Basso Mouse Scale(BMS) for locomotion was used to evaluate hindlimb motor function on day 7 and 14 after SCI. H.E. staining was used to observe histopathologic changes of the injured spinal cord tissue, and Western blot employed to detect the expression of glucose regulatory protein-78 (GRP78), Caspase-12, microtubule-associated protein light chain 3 II (LC-II) and P62(also known as sqstm1/Sequestome1) proteins. Immunofluorescence staining was used to detect the immunoacti-vities of spinal CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP, an endoplasmic reticulum stress-inducible protein) and P62. RESULTS: On the 7th and 14th day after SCI, the BMS scores and expression levels of LC3II protein were significantly down-regulated (P<0.05), and the expression levels of P62, GRP78 and Caspase-12 proteins, the immunoactivities of CHOP and P62 were all significantly up-regulated on both day 7 and 14 in the model group than in the sham operation group (P<0.05).Compared with the model group, the BMS scores and the expression levels of LC3II protein were significantly increased on both day 7 and 14 (P<0.05), while the expression levels of P62, GRP78 and Caspase-12 proteins, and the immunoactivities of CHOP and P62 were obviously decreased on day 7 and 14 in the EA group (P<0.05). Outcomes of H.E. stain showed that the cells with nuclei pyknosis and swelling and the necrotic cells appeared in the model group, which was relatively fewer in the EA group. CONCLUSION: EA of EX-B2 can improve the locomotor function in SCI mice, which may be related to its effects in up-regulating the expression of LC3II (to promote cell autophagy), and down-regulating the expression of P62, GRP78, Caspase-12 and CHOP proteins (to inhibit endoplasmic reticulum stress) in the spinal cord tissue.


Assuntos
Eletroacupuntura , Traumatismos da Medula Espinal , Animais , Autofagia/genética , Estresse do Retículo Endoplasmático/genética , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Medula Espinal , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/terapia
8.
Breast Cancer Res ; 23(1): 12, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33494814

RESUMO

BACKGROUND: MicroRNAs have been reported to participate in tumorigenesis, treatment resistance, and tumor metastasis. Novel microRNAs need to be identified and investigated to guide the clinical prognosis or therapy for breast cancer. METHOD: The copy number variations (CNVs) of MIR3613 from Cancer Genome Atlas (TCGA) or Cancer Cell Line Encyclopedia (CCLE) were analyzed, and its correlation with breast cancer subtypes or prognosis was investigated. The expression level of miR-3613-3p in tumor tissues or serum of breast cancer patients was detected using in situ hybridization and qPCR. Gain-of-function studies were performed to determine the regulatory role of miR-3613-3p on proliferation, apoptosis, and tumor sphere formation of human breast cancer cells MDA-MB-231 or MCF-7. The effects of miR-3613-3p on tumor growth or metastasis in an immunocompromised mouse model of MDA-MB-231-luciferase were explored by intratumor injection of miR-3613-3p analogue. The target genes, interactive lncRNAs, and related signaling pathways of miR-3613-3p were identified by bioinformatic prediction and 3'-UTR assays. RESULTS: We found that MIR3613 was frequently deleted in breast cancer genome and its deletion was correlated with the molecular typing, and an unfavorable prognosis in estrogen receptor-positive patients. MiR-3613-3p level was also dramatically lower in tumor tissues or serum of breast cancer patients. Gain-of-function studies revealed that miR-3613-3p could suppress proliferation and sphere formation and promote apoptosis in vitro and impeded tumor growth and metastasis in vivo. Additionally, miR-3613-3p might regulate cell cycle by targeting SMS, PAFAH1B2, or PDK3 to restrain tumor progression. CONCLUSION: Our findings indicate a suppressive role of miR-3613-3p in breast cancer progression, which may provide an innovative marker or treatment for breast cancer patients.

9.
Insect Sci ; 28(1): 77-92, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32039551

RESUMO

Swarming behavior facilitates pair formation, and therefore mating, in many eusocial termites. However, the physiological adjustments and morphological transformations of the flight muscles involved in flying and flightless insect forms are still unclear. Here, we found that the dispersal flight of the eusocial termite Reticulitermes chinensis Snyder led to a gradual decrease in adenosine triphosphate supply from oxidative phosphorylation, as well as a reduction in the activities of critical mitochondrial respiratory enzymes from preflight to dealation. Correspondingly, using three-dimensional reconstruction and transmission electron microscopy (TEM), the flight muscles were found to be gradually deteriorated during this process. In particular, two tergo-pleural muscles (IItpm5 and III-tpm5) necessary to adjust the rotation of wings for wing shedding behavior were present only in flying alates. These findings suggest that flight muscle systems vary in function and morphology to facilitate the swarming flight procedure, which sheds light on the important role of swarming in successful extension and fecundity of eusocial termites.


Assuntos
Voo Animal , Isópteros , Animais , Feminino , Isópteros/anatomia & histologia , Isópteros/química , Isópteros/fisiologia , Isópteros/ultraestrutura , Masculino , Microscopia Eletrônica de Transmissão , Músculos/anatomia & histologia , Músculos/química , Músculos/fisiologia , Músculos/ultraestrutura , Reprodução
10.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-377333

RESUMO

The ongoing SARS-CoV-2 pandemic has brought an urgent need for animal models to study the pathogenicity of the virus. Herein, we generated and characterized a novel mouse-adapted SARS-CoV-2 strain, named MASCp36, that causes severe acute respiratory symptoms and mortality in standard laboratory mice. Particularly, this model exhibits age and gender related skewed distribution of mortality akin to severe COVID-19, and the 50% lethal dose (LD50) of MASCp36 was 58 PFU in 9-month-old, male BALB/c mice. Deep sequencing identified three amino acid substitutions, N501Y, Q493H, and K417N, subsequently emerged at the receptor binding domain (RBD) of MASCp36, during in vivo passaging. All three mutations in RBD significantly enhanced the binding affinity to its endogenous receptor, mouse ACE2 (mACE2). Cryo-electron microscopy (cryo-EM) analysis of human ACE2 (hACE2) or mACE2 in complex with the RBD of MASCp36 at 3.1 to 3.7 angstrom resolution elucidates molecular basis for the receptor-binding switch driven by specific amino acid substitutions. Interestingly, N501Y and Q493H enhanced the binding affinity to human ACE2 (hACE2); while triple mutations N501Y/Q493H/K417N decreased affinity to hACE2, thus led to the reduced infectivity of MASCp36 to human cells. Our study not only provides a robust platform for studying the pathogenesis of severe COVID-19 and rapid evaluation of coutermeasures against SARS-CoV-2, but also unveils the molecular mechanism for the rapid adaption and evolution of SARS-CoV-2 in human and animals. One sentence summaryA mouse adapted SARS-CoV-2 strain that harbored specific amino acid substitutions in the RBD of S protein showed 100% mortality in aged, male BALB/c mice.

11.
Mol Med Rep ; 22(4): 3347-3357, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945505

RESUMO

Ovarian cancer (OC) is a frequently occurring malignant tumor in women. Increasing evidence has indicated that long non­coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) participates in OC pathogenesis. Thus, the aim of the present study was to explore the function of NEAT1 during OC progression. The expression levels of NEAT1, microRNA (miR)­4500 and basic leucine zipper and W2 domain­containing protein 1 (BZW1) were assessed via reverse transcription­quantitative PCR and western blotting. Furthermore, cell proliferation, colony formation, apoptosis, migration and invasion were assessed using Cell­Counting Kit 8, colony formation, flow cytometry and Transwell assays, respectively. Cell glycolysis was analyzed using an XF96 metabolic flux analyzer, and the relationship between miR­4500 and NEAT1 or BZW1 was verified via dual­luciferase reporter and RNA binding protein immunoprecipitation assays. miR­4500 expression levels were low, whereas NEAT1 expression levels were high in OC tissues and cell lines compared with control tissues and cell lines. Moreover, the results indicated that NEAT1 was a sponge of miR­4500, which directly targeted BZW1. NEAT1 knockdown induced OC cell apoptosis, and inhibited OC cell proliferation, colony formation, migration, invasion and glycolysis. miR­4500 inhibitor reversed NEAT1 knockdown­mediated effects. Similarly, miR­4500 mimic­mediated effects on cell functions were reversed by BZW1 overexpression. In addition, the results indicated that BZW1 expression was regulated by NEAT1 and miR­4500. Collectively, the present study suggested that NEAT1 modulated cell proliferation, colony formation, apoptosis, migration, invasion and glycolysis via the miR­4500/BZW1 axis in OC; therefore, NEAT1 may serve as a therapeutic target for OC.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , MicroRNAs/genética , Neoplasias Ovarianas/genética , RNA Longo não Codificante/genética , Apoptose , Estudos de Casos e Controles , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteínas de Ligação a DNA/metabolismo , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Glicólise , Humanos , Neoplasias Ovarianas/metabolismo
12.
J Immunol ; 205(10): 2916-2925, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32989094

RESUMO

Tumor-associated macrophages (TAMs) play a critical role in the tumor inflammatory microenvironment and facilitate tumor growth and metastasis. Most types of tumors aberrantly express microRNAs (miRNAs), which can be transferred between cells by exosomes and can regulate gene expression in recipient cells, but it remains unclear whether tumor-derived miRNAs are transferred by exosomes and regulate the TAM phenotype. We report that mouse 4T1 breast cancer cell-derived exosomes enhanced TAM expression of IL-1ß, IL-6, and TNF-α and that inhibition of 4T1-cell exosome secretion through short hairpin RNA-mediated Rab27a/b depletion repressed tumor growth and metastasis and markedly downregulated IL-1ß, IL-6, and TNF-α in a 4T1 breast tumor model. Furthermore, miRNA expression profiling revealed that three miRNAs (miR-100-5p, miR-183-5p, and miR-125b-1-3p) were considerably more abundant in 4T1 cell exosomes than in mouse bone marrow-derived macrophages, indicating potential exosome-mediated transfer of the miRNAs, and, notably, miR-183-5p was found to be transferred from 4T1 cells to macrophages through exosomes. Moreover, PPP2CA was verified as an miR-183-5p target gene, and PPP2CA downregulation enhanced NF-κB signaling and promoted macrophage expression of IL-1ß, IL-6, and TNF-α. Lastly, when miR-183-5p was downregulated in exosomes through miR-183-5p sponge expression in 4T1 cells, these 4T1-derived exosomes triggered diminished p65 phosphorylation and IL-1ß, IL-6, and TNF-α secretion, and the miRNA downregulation also led to repression of tumor growth and metastasis in the 4T1 breast tumor model in vivo. Thus, miR-183-5p expressed in tumor cells was transferred to macrophages by exosomes and promoted the secretion of proinflammatory cytokines by inhibiting PPP2CA expression, which contributed to tumor progression in a breast cancer model.


Assuntos
Neoplasias da Mama/imunologia , Exossomos/metabolismo , MicroRNAs/metabolismo , Proteína Fosfatase 2/genética , Macrófagos Associados a Tumor/imunologia , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Comunicação Celular/genética , Comunicação Celular/imunologia , Linhagem Celular Tumoral , Citocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Camundongos , Macrófagos Associados a Tumor/metabolismo
13.
Org Biomol Chem ; 18(24): 4599-4603, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32500892

RESUMO

An expedient cyclopropanation of α-methylene-ß-lactams with α-ketoesters mediated by P(NMe2)3 has been developed. This reaction enables rapid access to a series of functionalized spirocyclopropyl ß-lactams in good yields from bench-stable starting materials under mild conditions. The experimental results indicated that the C3-substituent of the α-methylene-ß-lactam not only significantly impacted the reaction efficiency and stereochemistry but also played a pivotal role in determining the chemoselectivity of the reaction.

14.
Ann Palliat Med ; 9(4): 1851-1858, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32576016

RESUMO

BACKGROUND: The application of factor analysis in the study of the clinical symptoms of coronavirus disease 2019 (COVID-19) was investigated, to provide a reference for basic research on COVID-19 and its prevention and control. METHODS: The data of 60 patients with COVID-19 in Jingzhou Hospital of Traditional Chinese Medicine and the Second People's Hospital of Longgang District in Shenzhen were extracted using principal component analysis. Factor analysis was used to investigate the factors related to symptoms of COVID-19. Based on the combination of factors, the clinical types of the factors were defined according to our professional knowledge. Factor loadings were calculated, and pairwise correlation analysis of symptoms was performed. RESULTS: Factor analysis showed that the clinical symptoms of COVID-19 cases could be divided into respiratory-digestive, neurological, cough-wheezing, upper respiratory, and digestive symptoms. Pairwise correlation analysis showed that there were a total of eight pairs of symptoms: fever-palpitation, coughexpectoration, expectoration-wheezing, dry mouth-bitter taste in the mouth, poor appetite-fatigue, fatiguedizziness, diarrhea-palpitation, and dizziness-headache. CONCLUSIONS: The symptoms and syndromes of COVID-19 are complex. Respiratory symptoms dominate, and digestive symptoms are also present. Factor analysis is suitable for studying the characteristics of the clinical symptoms of COVID-19, providing a new idea for the comprehensive analysis of clinical symptoms.


Assuntos
Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Infecções por Coronavirus/terapia , Doenças do Sistema Digestório/etiologia , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Doenças Respiratórias/etiologia , Adulto Jovem
15.
Zookeys ; 935: 93-101, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32508503

RESUMO

A new genus of Languriinae, Tomolanguria Huang, gen. nov. is erected for a single species, Languria aculeata Gorham, 1887 from Mexico. It is similar to the Neotropical genus Languria Latreille, 1802. The differential diagnosis of this new genus is based on the structural features of the elytral apices and slight impressions present on each elytron. Languria aculeata is designated as the type species of the new genus. This species is redescribed and illustrated (all the three specimens examined are shown in the dorsal, ventral, and lateral views). Finally, a mimic relationship between this new genus and genus Paederus Fabricius, 1775 (Staphylinidae) is discussed.

16.
Environ Sci Pollut Res Int ; 27(34): 42276-42282, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32266623

RESUMO

Colony formation in Microcystis aeruginosa played important roles in blooms formation. To study the effects of plant allelopathy on colony formation in M. aruginosa, unicellular M. aeruginosa was cultivated under laboratory conditions treated with various extract concentration of Carex cinerascens. The growth of M. aeruginosa in the treatments with 0.05 and 0.1 mg L-1 extract of C. cinerascens was promoted but the growth in the treatments with 1.5, 3.0, and 6.0 mg L-1 C. cinerascens extract was inhibited. Obvious colony formation in M. aeruginosa was observed in all treatments while no colony formation was detected in the control. The cell number per colony at the first day was the largest and decreased along with culture time. The cell number per colony in the control ranged from 3.0 to 4.0 during the experiment. However, the values in the five treatments at the first day were 33, 80, 58, 41, and 30, respectively. A positive exponential relationship between cell number per colony of M. aeruginosa and extracellular polysaccharides (EPS) content was found as well. Compared the fold-increase in cell number per colony and the fold-increase in total biomass of M. aeruginosa at various day, it was found that colony formation induced by extract of C. cinerascens was primarily dependent on promotion of cell adhesion during the first 2 days. The cell number per colony decreased afterward was due to the increasing proportion of single cells in the culture because single cells had a great higher growth rate than M. aeruginosa colonies under culture condition. Our results suggested that plant allelopathy be one of the major factor contributing to colony formation in M. aeruginosa.


Assuntos
Carex (Planta) , Cianobactérias , Microcystis , Alelopatia , Extratos Vegetais
17.
Zookeys ; 911: 113-137, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104141

RESUMO

Aurivillius's work entitled "Neue oder wenig bekannte ColeopteraLongicornia" was published in parts over a period of over four decades. There were two page numbers on most pages of these publications, one ordered by Aurivillius, the other by the journal. Historically, different authors have used different page numbers, and sometimes different years for these publications, which has caused chaos in the citations. Herein, accurate dates of publications for this work, and correct page numbers that should be used are provided and discussed.

18.
Ying Yong Sheng Tai Xue Bao ; 31(1): 266-274, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31957404

RESUMO

The success of microbial enhanced oil recovery (MEOR) relies on complex microbial processes. Nevertheless, the contribution and mechanism of in-situ denitrification to microbial oil recovery remain unclear. In this study, eight denitrifying bacterial strains, designated T1, D1, D44, D46, D15, S1, S2 and S6, were isolated from the produced water of Xinjiang Oilfield, China, by a double layered plate method. The16S rDNA gene sequences of these denitrifying strains shared 100% similarity with Pseudomonas stutzeri (T1, D1, and D44), Pseudomonas putida (D46 and D15), and Pseudomonas aeruginosa (S1, S2, S6), respectively. The N2O production effects of these strains on the physical properties of crude oil were evaluated with batch experiment. Results showed that the highest total gas yield was observed with sucrose as carbon source, and the maximal concentration of N2O occurred with glycerol as carbon source. The denitrification process by these bacterial strains led to volume expansion and viscosity reduction of crude oil. Crude oil expansion rate was positively correlated with the concentration of N2O, with a correlation coefficient of 0.983, but not correlated with the volume of total gas production. Strain S1, S2, and S6 produced 530-730 mg·L-1 of surfactant using glycerol as ole carbon source, which could reduce surface tension and emulsify crude oil. However, these surfactant-producing strains produced less N2O, exhibited weaker effects on oil swelling and viscosity reduction, compared to the none-surfactant-producing denitrifying strains. Our results suggested that more attention should be paid to the ability of N2O production by denitrifying bacteria when exploiting microbial resources towards enhancing oil recovery.


Assuntos
Petróleo , Pseudomonas stutzeri , China , Desnitrificação , Óxido Nitroso , Campos de Petróleo e Gás
19.
Med Biol Eng Comput ; 58(4): 725-737, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31965407

RESUMO

Interstitial lung disease (ILD) refers to a group of various abnormal inflammations of lung tissues and early diagnosis of these disease patterns is crucial for the treatment. Yet it is difficult to make an accurate diagnosis due to the similarity among the clinical manifestations of these diseases. In order to assist the radiologists, computer-aided diagnosis systems have been developed. Besides, the potential of deep convolutional neural networks (CNNs) is also expected to exert on the medical image analysis in recent years. In this paper, we design a new deep convolutional neural network (CNN) architecture to achieve the classification task of ILD patterns. Furthermore, we also propose a novel two-stage transfer learning (TSTL) method to deal with the problem of the lack of training data, which leverages the knowledge learned from sufficient textural source data and auxiliary unlabeled lung CT data to the target domain. We adopt the unsupervised manner to learn the unlabeled data, by which the objective function composed of the prediction confidence and mutual information are optimized. The experimental results show that our proposed CNN architecture achieves desirable performance and outperforms most of the state-of-the-art ones. The comparative analysis demonstrates the promising feasibility and advantages of the proposed two-stage transfer learning strategy as well as the potential of the knowledge learning from lung CT data. Graphical Abstract The framework of the proposed two-stage transfer learning method.


Assuntos
Diagnóstico por Computador/métodos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Redes Neurais de Computação , Bases de Dados Factuais , Aprendizado Profundo , Humanos , Tomografia Computadorizada por Raios X
20.
Cancer Res ; 80(2): 219-233, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31551365

RESUMO

ZFP36L1 is a tandem zinc-finger RNA-binding protein that recognizes conserved adenylate-uridylate-rich elements (ARE) located in 3'untranslated regions (UTR) to mediate mRNA decay. We hypothesized that ZFP36L1 is a negative regulator of a posttranscriptional hub involved in mRNA half-life regulation of cancer-related transcripts. Analysis of in silico data revealed that ZFP36L1 was significantly mutated, epigenetically silenced, and downregulated in a variety of cancers. Forced expression of ZFP36L1 in cancer cells markedly reduced cell proliferation in vitro and in vivo, whereas silencing of ZFP36L1 enhanced tumor cell growth. To identify direct downstream targets of ZFP36L1, systematic screening using RNA pull-down of wild-type and mutant ZFP36L1 as well as whole transcriptome sequencing of bladder cancer cells {plus minus} tet-on ZFP36L1 was performed. A network of 1,410 genes was identified as potential direct targets of ZFP36L1. These targets included a number of key oncogenic transcripts such as HIF1A, CCND1, and E2F1. ZFP36L1 specifically bound to the 3'UTRs of these targets for mRNA degradation, thus suppressing their expression. Dual luciferase reporter assays and RNA electrophoretic mobility shift assays showed that wild-type, but not zinc-finger mutant ZFP36L1, bound to HIF1A 3'UTR and mediated HIF1A mRNA degradation, leading to reduced expression of HIF1A and its downstream targets. Collectively, our findings reveal an indispensable role of ZFP36L1 as a posttranscriptional safeguard against aberrant hypoxic signaling and abnormal cell-cycle progression. SIGNIFICANCE: RNA-binding protein ZFP36L1 functions as a tumor suppressor by regulating the mRNA stability of a number of mRNAs involved in hypoxia and cell-cycle signaling.


Assuntos
Neoplasias da Mama/genética , Fator 1 de Resposta a Butirato/metabolismo , Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias da Bexiga Urinária/genética , Regiões 3' não Traduzidas/genética , Animais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Fator 1 de Resposta a Butirato/genética , Carcinogênese/genética , Ciclo Celular/genética , Hipóxia Celular/genética , Linhagem Celular Tumoral , Ciclina D1/genética , Fator de Transcrição E2F1/genética , Epigênese Genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Mutação , Processamento Pós-Transcricional do RNA , Estabilidade de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Dedos de Zinco/genética
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