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1.
Dev Comp Immunol ; 127: 104290, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34626690

RESUMO

Tripartite motif 35 (TRIM35) protein is a ubiquitin E3 ligase that mediates interferon-beta (IFN-ß) production via regulating ubiquitination of multiple adaptor proteins in innate immune signaling pathways. Here, we cloned the porcine TRIM35 (porTRIM35) gene and analyzed its involvement in IFN-ß expression as well as the antiviral response against Japanese encephalitis virus (JEV). The full-length porTRIM35 gene encoded a 493-amino acid protein and exhibited 79.6%-89.5% sequence similarity with its orthologues in humans, mice, monkeys and rabbits. porTRIM35 possessed typical structural features of TRIMs, including a RING domain, a B-box domain, a coiled-coil domain and a PRY/SPYR domain. Exogenous overexpression of porTRIM35 significantly up-regulated the mRNA expression level of IFN-ß in swine testicular (ST) cell in response to poly(I:C) stimulation, whereas knockdown endogenous expression of porTRIM35 lead to a decrease in the expression level of IFN-ß. Mechanically, porTRIM35 directly interacted with porcine TNF-receptor associated factor 3 (TRAF3) and catalyzed its Lys63-linked polyubiquitination, thereby leading to the up-regulation of IFN-ß production. Meanwhile, we demonstrated that the RING and PRY/SPRY domains were essential for the E3 ligase activity of porTRIM35. In response to JEV infection, the endogenous expression of porTRIM35 was markedly inhibited at the mRNA level, while exogenous expression of porTRIM35 significantly elevated the expression of IFN-ß induced by JEV infection and reduced viral titers in ST cells, suggesting that porTRIM35 is a negative regulator for JEV replication. These data demonstrate the importance of porTRIM35 in IFN-ß expression as well as the antiviral response against JEV replication.

2.
Sci Total Environ ; 806(Pt 4): 150901, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34653469

RESUMO

Foam flotation is an economical and efficient technology for microalgae harvesting. However, the mechanism of cell-collector-bubble interfacial interactions remains to be elucidated. There are two distinct hypotheses regarding the mechanism of microalgae foam flotation. In this study, the cationic surfactant N-cetyl-N-N-N-trimethylammonium bromide (CTAB), which acts as a partition between Chlorella sorokiniana cells and bubbles, is quantified and the zeta potential response of cells and bubbles after adsorption of CTAB is calculated to reveal the interfacial mechanism of the cells-collector-bubble interfacial interactions. The results indicated that more than 90% of CTAB was preferentially adsorbed on the bubbles, which reversed the surface charge of bubbles from negative (-20 mV) to positive (6.1 mV). However, only 0%-3% CTAB was observed on the microalgae cells, suggesting its limited influence on the negatively charged microalgae cells (from -22.3 to -18.6 mV). During microalgae foam flotation, the nonpolar tails of CTAB were first inserted into the bubble through hydrophobic interactions, leaving the positively charged polar heads outside; further, the CTAB-covered positively charged bubbles captured the negatively charged cells by electrostatic attraction. A feasible mechanism was proposed to understand the interfacial interaction of the microalgae cell-CTAB-bubble. By understanding the mechanism of foam flotation, efficient and cost-effective collectors and devices for microalgae harvesting using foam flotation can be developed.

3.
BMC Genom Data ; 22(1): 47, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732138

RESUMO

BACKGROUND: Our preliminary work confirmed that, SLC22A7 (solute carrier family 22 member 7), NGFR (nerve growth factor receptor), ARNTL (aryl hydrocarbon receptor nuclear translocator like) and PPP2R2B (protein phosphatase 2 regulatory subunit Bß) genes were differentially expressed in dairy cows during different stages of lactation, and involved in the lipid metabolism through insulin, PI3K-Akt, MAPK, AMPK, mTOR, and PPAR signaling pathways, so we considered these four genes as the candidates affecting milk production traits. In this study, we detected polymorphisms of the four genes and verified their genetic effects on milk yield and composition traits in a Chinese Holstein cow population. RESULTS: By resequencing the whole coding region and part of the flanking region of SLC22A7, NGFR, ARNTL and PPP2R2B, we totally found 20 SNPs, of which five were located in SLC22A7, eight in NGFR, three in ARNTL, and four in PPP2R2B. Using Haploview4.2, we found three haplotype blocks including five SNPs in SLC22A7, eight in NGFR and three in ARNTL. Single-SNP association analysis showed that 19 out of 20 SNPs were significantly associated with at least one of milk yield, fat yield, fat percentage, protein yield or protein percentage in the first and second lactations (P < 0.05). Haplotype-based association analysis showed that the three haplotypes were significantly associated with at least one of milk yield, fat yield, fat percentage, protein yield or protein percentage (P < 0.05). Further, we used SOPMA software to predict a SNP, 19:g.37095131C > T in NGFR, changed the structure of NGFR protein. In addition, we used Jaspar software to found that four SNPs, 19:g.37113872C > G,19:g.37113157C > T, and 19:g.37112276C > T in NGFR and 15:g.39320936A > G in ARNTL, could change the transcription factor binding sites and might affect the expression of the corresponding genes. These five SNPs might be the potential functional mutations for milk production traits in dairy cattle. CONCLUSIONS: In summary, we proved that SLC22A7, NGFR, ARNTL and PPP2R2B have significant genetic effects on milk production traits. The valuable SNPs can be used as candidate genetic markers for genomic selection of dairy cattle, and the effects of these SNPs on other traits need to be further verified.

4.
Front Cell Dev Biol ; 9: 745412, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34796175

RESUMO

Despite significant scientific advances toward the development of safe and effective radiation countermeasures, no drug has been approved for use in the clinic for prevention or treatment of radiation-induced acute gastrointestinal syndrome (AGS). Thus, there is an urgent need to develop potential drugs to accelerate the repair of injured intestinal tissue. In this study, we investigated that whether some fractions of Traditional Chinese Medicine (TCM) have the ability to regulate intestinal crypt cell proliferation and promotes crypt regeneration after radiation. By screening the different supplements from a TCM library, we found that an active fraction of the rhizomes of Trillium tschonoskii Maxim (TT), TT-2, strongly increased the colony-forming ability of irradiated rat intestinal epithelial cell line 6 (IEC-6) cells. TT-2 significantly promoted the proliferation and inhibited the apoptosis of irradiated IEC-6 cells. Furthermore, in a small intestinal organoid radiation model, TT-2 promoted irradiated intestinal organoid growth and increased Lgr5+ intestinal stem cell (ICS) numbers. More importantly, the oral administration of TT-2 remarkably enhanced intestinal crypt cell proliferation and promoted the repair of the intestinal epithelium of mice after abdominal irradiation (ABI). Mechanistically, TT-2 remarkably activated the expression of ICS-associated and proliferation-promoting genes and inhibited apoptosis-related gene expression. Our data indicate that active fraction of TT can be developed into a potential oral drug for improving the regeneration and repair of intestinal epithelia that have intestinal radiation damage.

5.
Biomater Sci ; 9(23): 7977-7983, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34709242

RESUMO

Photothermal therapy effectively ablates tumors by hyperthermia (>50 °C) under laser irradiation. However, the hyperthermia may inevitably diffuse to the surrounding healthy tissues to induce additional damage. Thus, effective cancer therapy by mild photothermal therapy at low temperatures is greatly desirable. In this study, a nanoagent (COF-GA) was designed to inhibit HSP90 for enhanced photothermal therapy against cancer at low temperatures. The nanoscale covalent organic frameworks (COFs) were able to increase the temperature of the tumor tissue under laser irradiation, which can transfer the energy of laser into heat for cancer cell killing. Gambogic acid (GA), as an inhibitor of HSP90, was used to overcome the heat resistance of tumor, achieving efficient mild-temperature photothermal therapy. As an excellent candidate for the photothermal therapy agent, COF-GA can induce the temperature to elevate as the exposure time increased when irradiated with laser. In vivo tests further demonstrated that the tumor growth was able to be significantly suppressed after being treated with COF-GA. The mild-temperature photothermal therapy exhibits an excellent antitumor efficacy at a relatively low temperature and minimizes the nonspecific thermal damage to normal tissues. This COF-GA nanoagent also enriches our understanding towards the various applications of COFs, particularly in the biomedicine field.


Assuntos
Hipertermia Induzida , Estruturas Metalorgânicas , Fototerapia , Terapia Fototérmica , Temperatura
6.
Stem Cell Res ; 57: 102581, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34688993

RESUMO

Serine hydroxymethyltransferase 2 (SHMT2), a catalytic enzyme playing an important role in aerobic cellular respiration and mitochondrial metabolism, might be pivotal in self-renewal and differentiation of human pluripotent stem cells. Herein, we used the CRISPR/Cas9 editing system to construct a homozygous SHMT2 knockout (SHMT2-KO) human embryonic stem cell (hESC) line, exhibiting a normal karyotype, colony morphology, and high expression levels of pluripotent proteins. Furthermore, SHMT2 knockout did not impact the self-renewal ability or differentiation potential into three germ layers of hESCs. Accordingly, this cell line provides a valuable model for further assessing SHMT2 functions in human embryonic development.

7.
Chem Commun (Camb) ; 57(91): 12087-12097, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34714302

RESUMO

Inducing the immunogenic cell death (ICD) of cancer cells is an important method to improve the immunogenicity of tumor cells for enhanced cancer immunotherapy. Therefore, we discuss the ICD process and then highlight various ICD inducers and strategies for triggering the ICD of cancer cells. We hope that this Feature Article will inspire readers to develop more effective ICD inducers.

8.
Plant Cell Rep ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34647139

RESUMO

KEY MESSAGE: Methyl jasmonate treatment and aphid resistance assays reveal different roles in herbivore defensive responses between tobacco glandular and non-glandular trichomes. These roles correlate with trichome gene expression patterns. In plants, trichomes greatly contribute to biotic stress resistance. To better understand the different defensive functions between glandular and non-glandular trichomes, we used Nicotiana tabacum as a model. This species bears three types of trichomes: long and short stalk glandular trichomes (LGT and SGT, respectively), and non-glandular trichomes (NGT). Tobacco accession T.I.1068 (lacking NGT) and T.I.1112 (lacking LGT) were used for the experiment. After methyl jasmonate (MeJA) treatment, LGT formation was promoted not only in T.I.1068, but also in T.I.1112, whereas NGT remained absent in T.I.1068, and was slightly reduced in T.I.1112. Diterpenoids, which play important roles in herbivore resistance, accumulated abundantly in T.I.1068 and were elevated by MeJA; however, they were not found in T.I.1112 but became detectable after MeJA treatment. The aphid resistance of T.I.1068 was higher than that of T.I.1112, and both were enhanced by MeJA, which was closely correlated with LGT density. Trichomes detached from T.I.1068 and T.I.1112 were used for RNA-Seq analysis, the results showed that pentose phosphate, photosynthesis, and diterpenoid biosynthesis genes were much more expressed in T.I.1068 than in T.I.1112, which was consistent with the vigorous diterpenoid biosynthesis in T.I.1068. In T.I.1112, citrate cycle, propanoate, and glyoxylate metabolism processes were enriched, and some defensive protein genes were expressed at higher levels than those in T.I.1068.These results suggested that LGT plays a predominant role in aphid resistance, whereas NGT could strengthen herbivore resistance by accumulating defensive proteins, and the roles of LGT and NGT are associated with their gene expression patterns.

9.
Mol Neurobiol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618332

RESUMO

Macrophage/microglial modulation plays a critical role in the pathogenesis of multiple sclerosis (MS), which is an inflammatory disorder of the central nervous system. Dynamin-related protein 1 is a cytoplasmic molecule that regulates mitochondrial fission. It has been proven that mitochondrial fission inhibitor 1 (Mdivi-1), a small molecule inhibitor of Drp1, can relieve experimental autoimmune encephalomyelitis (EAE), a preclinical animal model of MS. Whether macrophages/microglia are involved in the pathological process of Mdivi-1-treated EAE remains to be determined. Here, we studied the anti-inflammatory effect of Mdivi-1 on mice with oligodendrocyte glycoprotein peptide35-55 (MOG35-55)-induced EAE. We found that Drp1 phosphorylation at serine 616 in macrophages/microglia was decreased with Mdivi-1 treatment, which was accompanied by decreased antigen presentation capacity of the macrophages/microglia in the EAE mouse spinal cord. The Mdivi-1 treatment caused macrophage/microglia to produce low levels of proinflammatory molecules, such as CD16/32, iNOS, and TNF-α, and high levels of anti-inflammatory molecules, such as CD206, IL-10, and Arginase-1, suggesting that Mdivi-1 promoted the macrophage/microglia shift from the inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Moreover, Mdivi-1 was able to downregulate the expression of TRL2, TRL4, GSK-3ß, and phosphorylated NF-κB-p65 and prevent NF-κB-mediated IL-1ß and IL-6 production. In conclusion, these results indicate that Mdivi-1 significantly alleviates inflammation in mice with EAE by promoting M2 polarization by inhibiting TLR2/4- and GSK3ß-mediated NF-κB activation.

10.
Front Vet Sci ; 8: 724491, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671661

RESUMO

Stress diarrhea is a major challenge for weaned piglets and restricts pig production efficiency and incurs massive economic losses. A traditional Chinese medicine prescription (QJC) composed of Astragalus propinquus Schischkin (HQ), Zingiber officinale Roscoe (SJ), and Plantago asiatica L. (CQC) has been developed by our laboratory and shows marked anti-stress diarrhea effect. However, the active compounds, potential targets, and mechanism of this effect remain unclear and warrant further investigation. In our study, we verified the bioactive compounds of QJC and relevant mechanisms underlying the anti-stress diarrhea effect through network pharmacology and in vivo experimental studies. After establishing a successful stress-induced diarrhea model, histomorphology of intestinal mucosa was studied, and Quantitative real-time PCR (RT-qPCR) probe was used for the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway to verify the therapeutic effect of QJC on diarrhea. First, using the network pharmacology approach, we identified 35 active components and 130 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in QJC. From among these, we speculated that quercetin, luteolin, kaempferol, scutellarein, and stigmasterol were the main bioactive compounds and assumed that the anti-diarrhea effect of QJC was related to the PI3K-Akt signaling pathway. The RT-qPCR indicated that QJC and its bioactive components increased the expression levels of PI3K and Akt, inhibited the expression of phosphatase and tensin homolog (PTEN), and activated the PI3K-Akt signaling pathway to relieve stress-induced diarrhea. Furthermore, we found that QJC alleviated the pathological condition of small intestine tissue and improved the integrity of the intestinal barrier. Taken together, our study showed that the traditional Chinese medicine QJC, quercetin, luteolin, kaempferol, scutellarein, and stigmasterol alleviated the pathological condition of small intestine tissue and relieved stress-induced diarrhea by increasing the expression levels of PI3K and Akt and inhibiting the expression levels of PTEN.

11.
Front Plant Sci ; 12: 709534, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630461

RESUMO

Cysteine proteases, belonging to the C1-papain family, play a major role in plant growth and development, senescence, and immunity. There is evidence to suggest that pollen cysteine protease (CP) (ZmCP03) is involved in regulating the anther development and pollen formation in maize. However, there is no report on the genome-wide identification and comparison of CPs in the pollen coat and other tissues in maize. In this study, a total of 38 homologous genes of ZmCP03 in maize were identified. Subsequently, protein motifs, conserved domains, gene structures, and duplication patterns of 39 CPs are analyzed to explore their evolutionary relationship and potential functions. The cis-elements were identified in the upstream sequence of 39 CPs, especially those that are related to regulating growth and development and responding to environmental stresses and hormones. The expression patterns of these genes displayed remarked difference at a tissue or organ level in maize based on the available transcriptome data in the public database. Quantitative reverse transcription PCR (RT-qPCR) analysis showed that ZmCP03 was preferably expressed at a high level in maize pollen. Analyses by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot, immunofluorescence and immunogold electron microscopy all validated the cellular localization of ZmCP03 in both the pollen coat and pollen cytoplasm. In addition, 142 CP genes from Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa) and cotton (Gossypium hirsutum), together with 39 maize CPs, were retrieved to analyze their evolution by comparing with orthologous genes. The results suggested that ZmCP03 was relatively conservative and stable during evolution. This study may provide a referential evidence on the function of ZmCP03 in pollen development and germination in maize.

12.
Biochem Biophys Res Commun ; 577: 95-102, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34509725

RESUMO

OBJECTIVE: Long non-coding RNAs (lncRNAs) are implicated in cancer-related cellular behaviors. Our research aimed to explore the biological functions of lncRNA AL592284.1 (AL592284.1) in cervical cancer (CC). METHODS: qRT-PCR was performed to examine AL592284.1 expressions in cell lines and tumor specimens. To study the roles of AL592284.1 on malignant behaviors in both in vitro and in vivo, Loss-of-function assays were carried out. Besides, bioinformatics prediction and dual-luciferase reporter assays were performed to reveal the interaction among AL592284.1 and its target genes. The functions of the AL592284.1/miR-30a-5p/Vimentin axis in CC cells was clarified by rescue assays. RESULTS: We observed that the levels of AL592284.1 in CC were distinctly increased. Functional assays revealed that knockdown of AL592284.1 suppressed the proliferation, migration, invasion and EMT progress of CC cells. Luciferase reporter assay confirmed that miR-30a-5p/Vimentin regulatory axis is the direct downstream of AL592284.1. Rescue experiments indicated that AL592284.1 induced overexpression of Vimentin via sponging miR-30a-5p, resulting in the promotion of CC progression. CONCLUSION: The present study proves that AL592284.1 plays an tumor-promotive role in CC via regulating the miR-30a-5p/Vimentin axis, and inhibition of AL592284.1 may pave the way for CC treatment.


Assuntos
Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Transporte de Cátions Orgânicos/genética , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/genética , Vimentina/genética , Animais , Linhagem Celular Tumoral , Feminino , Células HEK293 , Células HeLa , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Metástase Neoplásica , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Interferência de RNA , Transdução de Sinais/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Vimentina/metabolismo
13.
Nano Lett ; 21(18): 7862-7869, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34494442

RESUMO

Blocking energy metabolism of cancer cells and simultaneously stimulating the immune system to perform immune attack are significant for cancer treatment. However, how to potently deliver different drugs with these functions remains a challenge. Herein, we synthesized a nanoprodrug formed by a F127-coated drug dimer to inhibit glycolysis of cancer cells and alleviate the immunosuppressive microenvironment. The dimer was delicately constructed to connect lonidamine (LND) and NLG919 by a disulfide bond which can be cleaved by excess GSH to release two drugs. LND can decrease the expression of hexokinase II and destroy mitochondria to restrain glycolysis for energy supply. NLG919 can reduce the accumulation of kynurenine and the number of regulatory T cells, thus alleviating the immunosuppressive microenvironment. Notably, the consumption of GSH by disulfide bond increased the intracellular oxidative stress and triggered immunogenic cell death of cancer cells. This strategy can offer more possibilities to explore dimeric prodrugs for synergistic cancer therapy.


Assuntos
Antineoplásicos , Neoplasias , Pró-Fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Glicólise , Morte Celular Imunogênica , Imunossupressão , Neoplasias/tratamento farmacológico , Polímeros/uso terapêutico , Pró-Fármacos/uso terapêutico
15.
Front Pharmacol ; 12: 728354, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456739

RESUMO

Staphylococcus xylosus (S. xylosus) has become an emerging opportunistic pathogen due to its strong biofilm formation ability. Simultaneously, the biofilm of bacteria plays an important role in antibiotic resistance and chronic infection. Here, we confirmed that rutin can effectively inhibit biofilm formation in S. xylosus, of which the inhibition mechanism involves its ability to interact with imidazole glycerol phosphate dehydratase (IGPD), a key enzyme in the process of biofilm formation. We designed experiments to target IGPD and inhibited its activities against S. xylosus. Our results indicated that the activity of IGPD and the amount of histidine decreased significantly under the condition of 0.8 mg/ml rutin. Moreover, the expression of IGPD mRNA (hisB) and IGPD protein was significantly down-regulated. Meanwhile, the results from molecular dynamic simulation and Bio-layer interferometry (BLI) technique showed that rutin could bind to IGPD strongly. Additionally, in vivo studies demonstrated that rutin treatment reduced inflammation and protect mice from acute mastitis caused by S. xylosus. In summary, our findings provide new insights into the treatment of biofilm mediated persistent infections and chronic bacterial infections. It could be helpful to design next generation antibiotics to against resistant bacteria.

16.
Microb Biotechnol ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34427997
17.
Medicine (Baltimore) ; 100(33): e26834, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414934

RESUMO

ABSTRACT: Anti-differentiation non-coding RNA (ANCR), a long non-coding RNA, is involved in the development, progression and metastasis of various human cancers. However, its clinical significance in nasopharyngeal carcinoma (NPC) still remains unknown. This study aimed to investigate ANCR expression and its clinical significance in NPC.Totally, 96 NPC tissues and 24 non-cancerous nasopharyngeal mucosa tissues were used. The levels of ANCR were determined by qRT-PCR. Relationship of ANCR with patient clinical characteristics, disease-free survival and overall survival (OS) was evaluated.ANCR expression was increased in NPC tissues compared to non-cancerous nasopharyngeal mucosae. ANCR expression was significantly related to lymph node metastasis, clinical stage, and tumor differentiation (P < .05). Kaplan-Meier survival analysis revealed that high level of ANCR expression was significantly associated with poor disease-free survival but not with OS in NPC patients. Univariate analysis showed a significant association between increased ANCR expression and adverse OS (P < .05), but multivariate analysis suggested that ANCR could not be used as an independent prognostic factor for NPC patients.ANCR is involved in the development and progression of NPC, but whether it can be used as an effective therapeutic target for NPC needs further study.


Assuntos
Regulação Neoplásica da Expressão Gênica , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , RNA Longo não Codificante/genética , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/química , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/secundário , Neoplasias Nasofaríngeas/química , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , RNA Longo não Codificante/análise , Estudos Retrospectivos , Taxa de Sobrevida
18.
Int J Biol Macromol ; 188: 450-459, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34371041

RESUMO

The bacterial type VI secretion system (T6SS) is a powerful arsenal that fires many toxic effectors into neighboring cells to gain advantage over inter-bacterial competition and eukaryotic host infection. Meanwhile, the cognate immunity proteins of these effectors are employed to protect themselves from the virulence. TseT-TsiT is a newly discovered effector-immunity (E-I) protein pair secreted by T6SS of Pseudomonas aeruginosa. Our group had reported the crystal structure of TsiT before. Here, we report the crystal structure of P. aeruginosa TseT-TsiT complex at 3.1 Å resolution. The interface of TseT-TsiT is characterized in this work. Through structure and small angle X-ray scattering (SAXS) studies, we discover that the long C-terminal helix of TseT may be flexible. Combining the homolog comparison results, we propose that TseT may form an oligomer in favor of its putative nuclease activity. Although TsiT doesn't directly block the putative active-site of TseT, it may hinder the TseT's oligomerization process to neutralize its virulence.

19.
Front Oncol ; 11: 644670, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34221966

RESUMO

Purpose: This study aimed to elucidate the prognostic significance of a novel inflammation-joined and nutrition-related clinicopathological marker for colorectal cancer (CRC). Methods: Various factors from preoperative fasting blood samples from 2471 patients with CRC were retrospectively analyzed. Factors related to prognosis were evaluated using univariate and multivariate analyses. The Kaplan-Meier method was used to generate survival curves, while the log-rank test was used to measure survival differences between groups. Results: Univariate analysis revealed that C-reactive protein (CRP)/mean corpuscular volume (MCV) ratio, TNM stage, differentiation, right-sided tumor, age, carcinoembryonic antigen (CEA) level, and CRP level were significantly associated with poor prognosis in CRC. In contrast, adjuvant chemotherapy is regarded as a protective factor. Elevation of CRP/MCV ratio (odds ratio [OR]: 1.535, 95% confidence interval [CI]: 1.121-2.104, P = 0.008), TNM stage (OR: 2.747, 95% CI: 2.175-3.469, P < 0.001), and differentiation (OR, 1.384; 95% CI, 1.150-1.666; P = 0.001) were prognostic risk factors in the multivariate analyses. Subgroup analysis showed that CRP/MCV, TNM staging system, and differentiation also independently affected survival in patients with lymph node-positive CRC. The nomogram based on these three indicators showed that CRP/MCV had a greater prognostic value and clinical significance for lymph node-positive patients with poorly differentiated tumors at the late stage. Conclusion: A novel nomogram using the clinicopathologic index of inflammation and nutrition was constructed to predict the prognosis of CRC. Early interventions should be emphasized for advanced-stage patients with severe inflammation and poor nutritional status.

20.
Neuroreport ; 32(12): 1058-1064, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34232129

RESUMO

The predominant form of edema that occurs during the early stage of ischemic stroke is cytotoxic, resulting in neuronal injury during brain ischemia and reperfusion. Intracellular calcium (Ca2+) is elevated following brain ischemia leading to increased cell membrane permeability. Ca2+/calmodulin-dependent protein kinase II (CaMK II), the downstream molecular signal of N-methyl-d-aspartate receptors (NMDARs), is sensitive to elevations in intracellular Ca2+. Aquaporin-4 (AQP4), which is expressed primarily in the brain, is a water-transport protein. However, it is unclear whether CaMK II regulates AQP4 expression to modulate cellular water permeability. We exposed cultured astrocytes to a hypoxic and glucose-free environment to mimic an ischemic environment in vitro. We investigated the effects of oxygen-glucose deprivation (OGD) on astrocytic viability and swelling, as well as CaMK II and AQP4 expression. We also studied the effects of CaMK II inhibition on cell swelling, viability and AQP4 expression. OGD increased astrocytic swelling and expression of CaMK II and AQP4, and it decreased astrocyte viability. Inhibition of CaMK II resulted in reduced astrocyte water permeability and AQP4 expression. We concluded that the upregulation of CaMK II promoted astrocyte swelling by increasing the expression of AQP4 after OGD.

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