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1.
BMC Ecol Evol ; 21(1): 21, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568067

RESUMO

BACKGROUND: Ciliated protists, a huge assemblage of unicellular eukaryotes, are extremely diverse and play important ecological roles in most habitats where there is sufficient moisture for their survivals. Even though there is a growing recognition that these organisms are associated with many ecological or environmental processes, their biodiversity is poorly understood and many biotopes (e.g. soils in desert areas of Asia) remain largely unknown. Here we document an undescribed form found in sludge soil in a halt-desert inland of China. Investigations of its morphology, morphogenesis and molecular phylogeny indicate that it represents a new genus and new species, Parasincirra sinica n. g., n. sp. RESULTS: The new, monotypic genus Parasincirra n. g. is defined by having three frontal cirri, an amphisiellid median cirral row about the same length as the adoral zone, one short frontoventral cirral row, cirrus III/2 and transverse cirri present, buccal and caudal cirri absent, one right and one left marginal row and three dorsal kineties. The main morphogenetic features of the new taxon are: (1) frontoventral-transverse cirral anlagen II to VI are formed in a primary mode; (2) the amphisiellid median cirral row is formed by anlagen V and VI, while the frontoventral row is generated from anlage IV; (3) cirral streaks IV to VI generate one transverse cirrus each; (4) frontoventral-transverse cirral anlage II generates one or two cirri, although the posterior one (when formed) will be absorbed in late stages, that is, no buccal cirrus is formed; (5) the posterior part of the parental adoral zone of membranelles is renewed; (6) dorsal morphogenesis follows a typical Gonostomum-pattern; and (7) the macronuclear nodules fuse to form a single mass. The investigation of its molecular phylogeny inferred from Bayesian inference and Maximum likelihood analyses based on small subunit ribosomal DNA (SSU rDNA) sequence data, failed to reveal its exact systematic position, although species of related genera are generally assigned to the family Amphisiellidae Jankowski, 1979. Morphological and morphogenetic differences between the new taxon and Uroleptoides Wenzel, 1953, Parabistichella Jiang et al., 2013, and other amphisiellids clearly support the validity of Parasincirra as a new genus. The monophyly of the family Amphisiellidae is rejected by the AU test in this study. CONCLUSIONS: The critical character of the family Amphisiellidae, i.e., the amphisiellid median cirral row, might result from convergent evolution in different taxa. Amphisiellidae are not monophyletic.

2.
Plant Cell ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33616649

RESUMO

Oxygen deprivation caused by flooding activates acclimation responses to stress and restricts plant growth. After experiencing flooding stress, plants must restore normal growth; however, which genes are dynamically and precisely controlled by flooding stress remains largely unknown. Here, we show that the Arabidopsis thaliana ubiquitin E3 ligase SUBMERGENCE RESISTANT1 (SR1) regulates the stability of the transcription factor WRKY33 to modulate the submergence response. SR1 physically interacts with WRKY33 in vivo and in vitro and controls its ubiquitination and proteasomal degradation. Both the sr1 mutant and WRKY33 overexpressors exhibited enhanced submergence tolerance and enhanced expression of hypoxia-responsive genes. Genetic experiments showed that WRKY33 functions downstream of SR1 during the submergence response. Submergence induced the phosphorylation of WRKY33, which enhanced the activation of RAP2.2, a positive regulator of hypoxia-response genes. Phosphorylated WRKY33 and RAP2.2 were degraded by SR1 and the N-degron pathway during reoxygenation, respectively. Taken together, our findings reveal that the on-and-off module SR1-WRKY33-RAP2.2 is connected to the well-known N-degron pathway to regulate acclimation to submergence in Arabidopsis. These two different but related modulation cascades precisely balance submergence acclimation with normal plant growth.

3.
Eur J Protistol ; 78: 125766, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33548733

RESUMO

The morphology, morphogenesis and molecular phylogeny of a new saline soil hypotrich ciliate, Uroleptoides salina nov. spec., discovered from China, was investigated. The new species is characterized as follows: body 150-215 × 40-50 µm in vivo, slender and highly flexible; usually four ellipsoidal macronuclear nodules; contractile vacuole absent; cortical granules absent; endosymbiotic algae present; amphisiellid median cirral row consists of 14-25 cirri and terminates about 47% down length of body; usually three buccal cirri and 3-13 cirri left of anterior portion of amphisiellid median cirral row; 3-5 transverse cirri. Morphogenesis during binary fission is characterized by: (1) the parental adoral zone of membranelles is retained completely, parental paroral contributes to the formation of the undulating membranes anlage for the proter; (2) the oral primordium of the opisthe is formed apokinetally; and (3) the amphisiellid median cirral row is formed from two anlagen. Phylogenetic analyses based on SSU rDNA sequence data show that Uroleptoides salina nov. spec. has a close relationship with its morphologically similar species, U. longiseries, U. magnigranulosus, Orthamphisiella breviseries, and Parabistichella variabilis.

4.
Microsc Microanal ; : 1-9, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33478608

RESUMO

GBF1 [Golgi brefeldin A (BFA) resistance factor 1] is a member of the guanine nucleotide exchange factors Arf family. GBF1 localizes at the cis-Golgi and endoplasmic reticulum (ER)-Golgi intermediate compartment where it participates in ER-Golgi traffic by assisting in the recruitment of the coat protein COPI. However, the roles of GBF1 in oocyte meiotic maturation are still unknown. In the present study, we investigated the regulatory functions of GBF1 in mouse oocyte organelle dynamics. In our results, GBF1 was stably expressed during oocyte maturation, and GBF1 localized at the spindle periphery during metaphase I. Inhibiting GBF1 activity led to aberrant accumulation of the Golgi apparatus around the spindle. This may be due to the effects of GBF1 on the localization of GM130, as GBF1 co-localized with GM130 and inhibiting GBF1 induced condensation of GM130. Moreover, the loss of GBF1 activity affected the ER distribution and induced ER stress, as shown by increased GRP78 expression. Mitochondrial localization and functions were affected, as the mitochondrial membrane potential was altered. Taken together, these results suggest that GBF1 has wide-ranging effects on the distribution and functions of Golgi apparatus, ER, and mitochondria as well as normal polar body formation in mouse oocytes.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33404208

RESUMO

The nanowire (NW) and gate-all-around (GAA) technologies are regarded as the ultimate solutions to sustain Moore's law benefitting from the exceptional gate control ability. Herein, we conduct a comprehensive ab initio quantum transportation calculation at different diameters (single trigonal-tellurium NW (1Te) and three trigonal-tellrium NW (3Te)) sub-5 nm tellurium (Te) GAA NW metal-oxide-semiconductor field-effect transistors (MOSFETs). The results claim that the performance of 1Te FETs is superior to that of 3Te FETs. Encouragingly, the single Te (1Te) n-type MOSFET with 5 nm gate length achieves International Technology Roadmap for Semiconductors (ITRS) high-performance (HP) and low-dissipation (LP) goals simultaneously. Especially, the HP on-state current reaches 6479 µA/µm, 7 times higher than the goal (900 µA/µm). Moreover, the subthreshold swing of the n-type 1Te FETs even hits a thermionic limit of 60 mV/dec. In terms of the spin-orbit coupling effect, the drain currents of devices are further improved, particularly the p-type Te FETs can also achieve the ITRS HP goal. Hence, the GAA Te MOSFETs provide a feasible approach for state-of-the-art sub-5 nm device applications.

6.
BMC Infect Dis ; 21(1): 20, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413119

RESUMO

BACKGROUND: Globally, urogenital and intestinal parasitosis remain significant health challenges. They are associated with rising morbidity, death, and many harmful outcomes. A little is known concerning parasitosis and type 2 diabetes mellitus. Our study planned to investigate the urogenital and intestinal parasitic infections among type 2 diabetes patients compare to non-diabetic (Control) individuals and examine the intensity of helminthiasis in both groups. METHODS: At Kosti Teaching Hospital (Sudan), 300 Urine and 300 stool samples have collected from 150 type 2 diabetes and 150 control individuals, along with the socio-demographic data using a structured questionnaire. The parasitic infections were examined by direct sedimentation technique for urine specimens. Whereas, for fecal samples, simple-direct saline, formal-ether concentration, Kato-Katz, and modified Ziehl-Neelsen techniques were used. RESULTS: Out of 150 type 2 diabetes patients studied, 31 (20.6%) and 14 (9.3%) had intestinal parasitosis and urogenital schistosomiasis, respectively. Whereas, 16 (10.6%) and 8 (5.3%) of the control group were infected, respectively. Compared to the control group, the odds of testing positive for either urogenital schistosomiasis (AOR: 2.548, 95% CI: 0.836-7.761, P = 0.100) or intestinal parasitic diseases (AOR: 2.099, 95% CI: 0.973-4.531, P = 0.059) were greater in diabetic individuals. Likewise, the intensities of helminthiasis were much higher in the diabetic patients and positively correlated with the duration of illness. The rate of urogenital schistosomiasis was also significantly different among the disease duration subcategories. CONCLUSIONS: Our study has highlighted the relationship of type 2 diabetes with urogenital and intestinal parasitic infections and enhanced our knowledge about the frequency of particular urogenital and intestinal parasites as well as the intensity of helminths infection in type 2 diabetes compared to non-diabetic individuals, which are important for further studies.

7.
J Biol Chem ; : 100276, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33428943

RESUMO

The clinical efficacy of docetaxel (DTX) in prostate cancer treatment is barely satisfactory due to diverse responses of the patients, including the development of resistance. Recently, aberrant androgen receptor (AR) signaling, including expression of the constitutively active ARV7, was reported to contribute to DTX resistance. However, the underlying molecular mechanism remains largely unknown. Of note, previous studies have highlighted that ARV7, unlike its parental AR, potentially favors the expression of some genes involved in cell cycle progression. Since DTX mainly targets microtubule dynamics and mitosis, we wanted to test whether ARV7 plays a specific role in mitotic regulation and whether this activity is involved in DTX resistance. In the present study, we found that ARV7 mediates DTX sensitivity through inactivating the spindle assembly checkpoint (SAC) and promoting mitotic slippage. By shifting the balance to the slippage pathway, ARV7-expressing cells are more likely to escape from mitotic death induced by acute DTX treatment. Furthermore, we also identified E2 enzyme UBE2C as the primary down-stream effector of ARV7 in promoting the SAC inactivation and premature degradation of cyclin B1. Moreover, we showed that combination treatment of DTX and an inhibitor of mitotic exit can exert synergistic effect in high ARV7-expressing prostate cancer cells. In sum, our work identified a novel role of ARV7 in promoting DTX resistance and offering a potential path to combat DTX resistance related to abnormal activation of the AR signaling and mitotic dysregulation.

8.
Cell Death Dis ; 12(1): 38, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33414420

RESUMO

Cancer cells secrete abundant exosomes, and the secretion can be promoted by an increase of intracellular Ca2+. Stromal interaction molecule 1 (STIM1) plays a key role in shaping Ca2+ signals. MicroRNAs (miRNAs) have been reported to be potential therapeutic targets for many diseases, including breast cancer. Recently, we investigated the effect of exosomes from STIM1-knockout breast cancer MDA-MB-231 cells (Exo-STIM1-KO), and from SKF96365-treated MDA-MB-231 cells (Exo-SKF) on angiogenesis in human umbilical vein endothelial cells (HUVECs) and nude mice. The exosomes Exo-STIM1-KO and Exo-SKF inhibited tube formation by HUVECs remarkably. The miR-145 was increased in SKF96365 treated or STIM1-knockout MDA-MB-231 cells, Exo-SKF and Exo-STIM1-KO, and HUVECs treated with Exo-SKF or Exo-STIM1-KO. Moreover, the expressions of insulin receptor substrate 1 (IRS1), which is the target of miR-145, and the downstream proteins such as Akt/mammalian target of rapamycin (mTOR), Raf/extracellular signal regulated-protein kinase (ERK), and p38 were markedly inhibited in HUVECs treated with Exo-SKF or Exo-STIM1-KO. Matrigel plug assay in vivo showed that tumor angiogenesis was suppressed in Exo-STIM1-KO, but promoted when miR-145 antagomir was added. Taken together, our findings suggest that STIM1 promotes angiogenesis by reducing exosomal miR-145 in breast cancer MDA-MB-231 cells.

9.
Clin Res Hepatol Gastroenterol ; : 101563, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33272888

RESUMO

BACKGROUND AND AIMS: Immune tolerance is defined as HBeAg positive, high hepatitis B virus load (HBV), persistent normal alanine aminotransferase (ALT), no or slight inflammation or fibrosis in liver histology. However, it is still unclear the threshold of high hepatitis B virus load and how to predict histology without liver biopsy. The aim of this study was to predict immune tolerance in HBeAg positive, alanine aminotransferase -normal populations with non-invasive indicators. METHODS: Two multi-center prospective cohort study recruited 907 treatment-naïve chronic hepatitis B (CHB) patients who had undergone liver biopsy in mainland China from August 2013 to September 2016 and April 2018 to June2019. Quantitative hepatitis B core antibody, AST and HBV DNA were investigated using commercial diagnostic assays and histological grading and staging was assessed by the Ishak scoring system. RESULTS: One hundred and thirteen untreated CHB patients with HBeAg-positive, normal alanine aminotransferase (ALT) and high level of HBV DNA (≥5log10 IU/mL) were enrolled in this study. The area under the receiver operating characteristic curves (AUROCs) of qHBcAb, AST, HBV DNA and qHBcAb-AST index were 79.6%, 80.5%, 76.4% and 87.7%. Our novel qHBcAb-AST index, which combined qHBcAb and AST showed better performance with higher sensitivity (88.6% [95% confidence interval (CI) 72.3% - 96.3%]) and negative predictive value (NPV) (93.8% [95% CI 84.2% - 98.0%]). CONCLUSIONS: The combination of qHBcAb and AST can more accurately predict the immune tolerance of people with HBeAg-positive, normal alanine aminotransferase (ALT).

10.
Artigo em Inglês | MEDLINE | ID: mdl-33275526

RESUMO

Pathological cardiac remodeling is a leading cause of mortality in diabetic patients. Given the glucose and lipid metabolism disorders (GLD) in diabetic patients, it is urgent to conduct a comprehensive study of the myocardial damage under GLD and find key mechanisms. Apolipoprotein E knockout (ApoE-/-) mice, low-density lipoprotein receptor heterozygote (Ldlr+/-) syrian golden hamsters or H9C2 cells were used to construct GLD models -. And GLD significantly promoted cardiomyocyte fibrosis, apoptosis and hypertrophy in vivo and in vitro, while inhibition of galectin-3 (Gal-3) could significantly reverse this process. Then, the signal transmission pathways were determined. It was found that GLD considerably inhibited the phosphorylation of Akt at Thr308 / Ser473, whereas the silencing of Gal-3 could reverse the inhibition of Akt activity through PI3K-AktThr308 and AMPK-mTOR2-AktSer473 pathways. Finally, the PI3K, mTOR, AMPK inhibitor and Akt activator were used to investigate the role of pathways in regulating cardiac remodeling. Phospho-AktThr308 could mediate myocardial fibrosis, while myocardial apoptosis and hypertrophy were regulated by both phospho-AktThr308 and phospho-AktSer473. In conclusion, Gal-3 was an important regulatory factor in GLD-induced cardiac remodeling, and Gal-3 could suppress the phosphorylation of Akt at different sites in mediating cardiomyocyte fibrosis, apoptosis and hypertrophy.

11.
Eur J Protistol ; 77: 125748, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33279756

RESUMO

A soil hypotrich ciliate, Afrokahliella paramacrostoma n. sp., was discovered in China. Its morphology, morphogenesis and molecular phylogeny were investigated using standard methods. The new species is characterized as follows: body about 140-180 × 60-70 µm in vivo, cortical granules absent, contractile vacuole positioned about 40% down length of body, 5-9 macronuclear nodules, 34-49 adoral membranelles, 3-5 buccal and 3-6 parabuccal cirri, usually two frontoventral rows, three or four left and two or three right marginal rows, three dorsal kineties and one dorsomarginal kinety; 1-3 and one or two caudal cirri located at the ends of dorsal kineties 1 and 2, respectively. The ontogenetic process is characterized by: (1) the marginal anlagen on each side develop in the outer right and the inner left marginal rows, respectively; (2) five frontoventral-transverse cirral anlagen, anlagen II-IV develop in secondary mode; (3) dorsal morphogenesis follows a typical Urosomoida-pattern, no parental dorsal kineties are retained; (4) caudal cirri are generated at the ends of dorsal kineties 1 and 2. Phylogenetic analyses based on SSU rDNA sequence data reveals that Afrokahliella paramacrostoma n. sp. is closely related to Parakahliella macrostoma and Hemiurosomoida longa.

12.
Ann Palliat Med ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33302639

RESUMO

BACKGROUND: Pulse-taking is widely used for diagnosis and treatment in traditional Chinese medicine (TCM), and protein complexes in serum perform various biological functions. The Balanced constitution is one of the major constitutions in TCM, people with Balanced constitution can also share some common characteristics with unbalanced constitution types. METHODS: Blue native polyacrylamide gel electrophoresis (BN-PAGE) was applied to the serum of 25 people with balanced constitutions. The patterns of the protein complexes could be recognized according to the number, molecular weight, and intensity of the gel bands. All of the individual bands from these patterns were cut and in-gel-digested with trypsin, followed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analysis for protein identification and biological function analysis. RESULTS: The protein complex patterns were roughly categorized as type A and B with high stability and reproducibility, and there were 15 and 16 gel bands in type A and type B, respectively. Among the 25 serum samples, 14 belonged to type A, and 11 belonged to type B. High-abundance proteins significantly decreased from 99% to 44% after BN-PAGE separation. The unique proteins in type A were mainly related to lipid metabolism, while the unique proteins in type B were involved in biological processes related to immune response and inflammatory regulation. The Qi-deficiency constitution converted score of type A was higher than that of type B, while the Damp-heat constitution converted score of type A was lower than that of type B. CONCLUSIONS: Our study provided an objective reference for diagnosis and prognosis, which might lay a foundation for establishing the characteristic protein complex spectra of all of the TCM constitutions.

13.
J Cell Physiol ; 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33368268

RESUMO

Obesity causes many reproductive dysfunctions such as reduced conception, infertility, and early pregnancy loss, and this is largely due to the negative effects of obesity on oocyte and embryo quality. In the present study, we employed single-cell RNA transcriptome sequencing to investigate the potential causes for the maternal obesity effects on mouse embryos. Our results showed that the 4-cell and morula/blastocyst rates were all significantly decreased during embryo development in obese mice. Genome-wide analysis indicated that obesity altered the expression of more than 1100 genes in 2-cell embryos, including the genes which were related to the p53 signaling pathway and apoptosis. Further analysis showed that the expression of 47 genes related to DNA damage was changed, and a positive γH2A signal and the altered expression of Rad51 and Tex15 were observed in the obese embryos. Obesity also affected histone methylation, shown by the decrease of the H3K4-me2 level. Besides this, we observed the occurrence of autophagy and apoptosis in the embryos of obese mice. There were 42 genes that were related to autophagy/apoptosis that showed aberrant expression, and the positive LC3 signal and the decrease of Clec16a, Rraga, and Atg10 level were also observed. In summary, our study suggested that obesity affected early embryonic development by inducing DNA damage, aberrant histone methylation, and autophagy levels in mice.

14.
Eur J Surg Oncol ; 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33349524

RESUMO

INTRODUCTION: Survival of patients with the same clinical stage varies widely and effective tools to evaluate the prognosis utilizing clinical staging information is lacking. This study aimed to develop a clinical nomogram for predicting survival of patients with Esophageal Squamous Cell Carcinoma (ESCC). MATERIALS AND METHODS: On the basis of data extracted from the SEER database (training cohort, n = 3375), we identified and integrated significant prognostic factors for nomogram development and internal validation. The model was then subjected to external validation with a separate dataset obtained from Jinling Hospital of Nanjing Medical University (validation cohort, n = 1187). The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index), Akaike information criterion (AIC) and calibration curves. And risk group stratification was performed basing on the nomogram scores. RESULTS: On multivariable analysis of the training cohort, seven independent prognostic factors were identified and included into the nomogram. Calibration curves presented good consistency between the nomogram prediction and actual observation for 1-, 3-, and 5-year OS. The AIC value of the nomogram was lower than that of the 8th edition American Joint Committee on Cancer TNM (AJCC) staging system, whereas the C-index of the nomogram was significantly higher than that of the AJCC staging system. The risk groups stratified by CART allowed significant distinction between survival curves within respective clinical TNM categories. CONCLUSIONS: The risk stratification system presented better discriminative ability for survival prediction than current clinical staging system and might help clinicians in decision making.

15.
Toxins (Basel) ; 13(1)2020 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-33375470

RESUMO

Fusarium fungi are the cause of an array of devastating diseases affecting yield losses and accumulating mycotoxins. Fungicides can be exploited against Fusarium and deoxynivalenol (DON) production. However, Fusarium resistance to common chemicals has become a therapeutic challenge worldwide, which indicates that new control agents carrying different mechanisms of action are desperately needed. Here, we found that a nonantibiotic drug, ethylenediaminetetraacetic acid disodium salt (EDTANa2), exhibited various antifungal activities against Fusarium species and DON biosynthesis. The infection of wheat seeding caused by F. graminearum was suppressed over 90% at 4 mM EDTANa2. A similar control effect was observed in field tests. Mycotoxin production assays showed DON production was significantly inhibited, 47% lower than the control, by 0.4 mM EDTANa2. In vitro experiments revealed a timely inhibition of H2O2 production as quickly as 4 h after amending cultures with EDTANa2 and the expression of several TRI genes significantly decreased. Chitin synthases of Fusarium were Mn2+-containing enzymes that were strongly inhibited by Mn2+ deficiency. EDTANa2 inhibited chitin synthesis and destroyed the cell wall and cytomembrane integrity of Fusarium, mainly via the chelation of Mn2+ by EDTANa2, and thus led to Mn deficiency in Fusarium cells. Taken together, these findings uncover the potential of EDTANa2 as a fungicide candidate to manage Fusarium head blight (FHB) and DON in agricultural production.

16.
Aging (Albany NY) ; 12(22): 22700-22718, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33196458

RESUMO

Malignant cancer may contain highly heterogeneous populations of cells, including stem-like cells which were resistant to chemotherapy agents, radiation, mechanical stress, and immune surveillance. The characterization of these specific subpopulations might be critical to develop novel strategy to remove malignant tumors. We selected and enriched small population of human melanoma A2058 cells by repetitive selection cycles (selection, restoration, and amplification). These subpopulation of melanoma cells persisted the characteristics of slower cell proliferation, enhanced drug-resistance, elevated percentage of side population as analyzed by Hoechst33342 exclusion, in vitro sphere formation, and in vivo xenograft tumor formation by small amount of tumor cells. The selected populations would be melanoma stem-like cells with high expression of stem cell markers and altered kinase activation. Microarray and bioinformatics analysis highlighted the high expression of angiopoietin-like 4 protein in drug-selected melanoma stem-like cells. Further validation by specific shRNA demonstrated the role of angiopoietin-like 4 protein in drug-selected subpopulation associated with enhanced drug-resistance, sphere formation, reduced kinase activation, in vitro tube-forming ability correlated with heparan-sulfate proteoglycans. Our finding would be applicable to explore the mechanism of melanoma stemness and use angiopoietin-like 4 as potential biomarkers to identify melanoma stem-like cells.

17.
Diabetes Metab Syndr Obes ; 13: 4141-4151, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33177854

RESUMO

Background and Aims: To investigate the role of Sortilin and matrix vesicles (MVs) in Nε-Carboxymethyl-lysine (CML)-induced diabetic atherosclerotic calcification (AC). Methods: At human level, the correlation between Sortilin and CD9 (marker proteins of MVs) in serum MVs and CML in serum was explored by enzyme-linked immunosorbent assay (ELISA) detection and Pearson correlation analysis. After a diabetic apoE-/- mouse model was constructed, the calcification of aorta and the expressions of related proteins under CML and MVs injection were observed by calcification staining, immunofluorescence staining, and Western blot. MVs levels released by smooth muscle cells (SMCs) under different treatments was detected by nanometer tracking analysis (NTA). After treating SMCs with MVs and Anti-Sortilin, cell calcification was observed by Alizarin red staining. Results: Serological analysis of patients showed that the concentrations of Sortilin and CD9 in serum MVs were positively correlated with the concentration of CML in serum. Animal experiments showed that CML could promote the progression of diabetic AC and the high expression of Sortilin in plaques. Diabetic apoE-/- mouse tail vein injection of CML-induced SMCs-derived MVs obviously aggravated AC. Cell experiment results showed that a high concentration of CML significantly promoted the release of MVs from SMCs. MVs from this source could markedly worsen cell calcification, while the administration of GW4869 (a widely used extracellular vesicles biogenesis inhibitor) significantly reduced cell calcification. Finally, treatment of high concentrations of CML could also promote the recruitment of Sortilin to MVs, and administration of Anti-Sortilin could markedly reduce cell calcification caused by MVs. Conclusion: We proved that CML not only affects the release of MVs from SMCs but also affects the recruitment of Sortilin to MVs, thereby promoting diabetic AC. This discovery may provide a new strategy for targeted prevention of vascular calcification in diabetes.

18.
FEBS J ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206458

RESUMO

Protein regulator of cytokinesis 1 (PRC1) is a microtubule bundling protein that is involved in the regulation of the central spindle bundle and spindle orientation during mitosis. However, the functions of PRC1 during meiosis have rarely been studied. In this study, we explored the roles of PRC1 during meiosis using an oocyte model. Our results found that PRC1 was expressed at all stages of mouse oocyte meiosis, and PRC1 accumulated in the midzone/midbody during anaphase/telophase I. Moreover, depleting PRC1 caused defects in polar body extrusion during mouse oocyte maturation. Further analysis found that PRC1 knockdown did not affect meiotic spindle formation or chromosome segregation; however, deleting PRC1 prevented formation of the midzone and midbody at the anaphase/telophase stage of meiosis I, which caused cytokinesis defects and further induced the formation of two spindles in the oocytes. PRC1 knockdown increased the level of tubulin acetylation, indicating that microtubule stability was affected. Furthermore, KIF4A and PRC1 showed similar localization in the midzone/midbody of oocytes at anaphase/telophase I, while the depletion of KIF4A affected the expression and localization of PRC1. The PRC1 mRNA injection rescued the defects caused by PRC1 knockdown in oocytes. In summary, our results suggest that PRC1 is critical for midzone/midbody formation and cytokinesis under regulation of KIF4A in mouse oocytes.

19.
J Thorac Dis ; 12(10): 5580-5592, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209391

RESUMO

Background: Current preoperative staging for lymph nodal status remains inaccurate. The purpose of this study was to build an artificial neural network (ANN) model to predict pathologic nodal involvement in clinical stage I-II esophageal squamous cell carcinoma (ESCC) patients and then validated the performance of the model. Methods: A total of 523 patients (training set: 350; test set: 173) with clinical staging I-II ESCC who underwent esophagectomy and reconstruction were enrolled in this study. Their post-surgical pathological results were assessed and analysed. An ANN model was established for predicting pathologic nodal positive patients in the training set, which was validated in the test set. A receiver operating characteristic (ROC) curve was also created to illustrate the performance of the predictive model. Results: Of the enrolled 523 patients with ESCC, 41.3% of the patients were confirmed pathologic nodal positive (216/523). The ANN staging system identified the tumour invasion depth, tumour length, dysphagia, tumour differentiation and lymphovascular invasion (LVI) as predictors for pathologic lymph node metastases. The C-index for the ANN model verified in the test set was 0.852, which demonstrated that the ANN model had a good predictive performance. Conclusions: The ANN model presented good performance for predicting pathologic lymph node metastasis and added indicators not included in current staging criteria and might help improve the staging strategies.

20.
Curr Genet ; 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33130939

RESUMO

ß-tubulin, a component of microtubules, is involved in a wide variety of roles in cell shape, motility, intracellular trafficking and regulating intracellular metabolism. It has been an important fungicide target to control plant pathogen, for example, Fusarium. However, the regulation of fungicide sensitivity by ß-tubulin-interacting proteins is still unclear. Here, ASK1 was identified as a ß-tubulin interacting protein. The ASK1 regulated the sensitivity of Fusarium to carbendazim (a benzimidazole carbamate fungicide), and multiple cellular processes, such as chromatin separation, conidiation and sexual production. Further, we found the point mutations at 50th and 198th of ß2-tubulin which caused carbendazim resistance decreased the binding between ß2-tubulin and ASK1, resulting in the deactivation of ASK1. ASK1, on the other hand, competed with carbendazim to bind to ß2-tubulin. The point mutation F167Y in ß2-tubulin broke the intermolecular H-bonds and salt bridges between ß2-tubulin and ASK1, which reduced the competitive effect of ASK1 to carbendazim and resulted in the similar carbendazim sensitivities in F167Y-ΔASK1 and F167Y. These findings have powerful implications for efforts to understand the interaction among ß2-tubulin, its interacting proteins and fungicide, as well as to discover and develop new fungicide against Fusarium.

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