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1.
Spine J ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33545371

RESUMO

BACKGROUND CONTEXT: Accurately predicting the survival of patients with spinal metastases is important for guiding surgical intervention. The SORG machine-learning (ML) algorithm for the 90-day and 1-year mortality of patients with metastatic cancer to the spine has been multiply validated, with a high degree of accuracy in both internal and external validation studies. However, prior external validations were conducted using patient groups located on the east coast of the United States, representing a generally homogeneous population. The aim of this study was to externally validate the SORG algorithms with a Taiwanese population. STUDY DESIGN/SETTING: Retrospective study at a single tertiary care center in Taiwan PATIENT SAMPLE: Four hundred and twenty-seven patients who underwent surgery for metastatic spine disease from November 1, 2010 to December 31, 2018 OUTCOME MEASURES: 90-Day and 1-Year Mortality METHODS: The baseline characteristics of our validation cohort were compared with those of the previously published developmental and external validation cohorts. Discrimination (c-statistic and receiver operating curve), calibration (calibration plot, intercept, and slope), overall performance (Brier score), and decision curve analysis were used to assess the performance of the SORG ML algorithms in this cohort. RESULTS: Ninety-day and 1-year mortality rates were 110 of 427 (26%) and 256 of 427 (60%), respectively. The external validation cohort and the developmental cohort differed in body mass index (BMI), preoperative performance status, American Spinal Injury Association impairment scale, primary tumor histology and in several laboratory measurements. The SORG ML algorithm for 90-day and 1-year mortality demonstrated a high level of discriminative ability (c-statistics of 0.73 [95% confidence interval [CI], 0.67-0.78] and 0.74 [95% CI, 0.69-0.79]), overall performance, and had a positive net benefit throughout the range of threshold probabilities in decision curve analysis. The algorithm for 1-year mortality had a calibration intercept of 0.08, representing a good calibration. However, the 90-day mortality algorithm underestimated mortality for the lowest predicted probabilities, with an overall intercept of 0.81. CONCLUSIONS: The SORG algorithms for predicting 90-day and 1-year mortality in patients with spinal metastatic disease generally performed well on international external validation in a predominately Taiwanese population. However, 90-day mortality was underestimated in this group. Whether this inconsistency was due to different primary tumor characteristics, body mass index, selection bias or other factors remains unclear, and may be better understood with further validative works that utilize international and/or diverse populations.

2.
Oxid Med Cell Longev ; 2021: 8894491, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33505592

RESUMO

Ochratoxin A (OTA) is a common environmental pollutant found in a variety of foods and grains, and excessive OTA consumption causes serious global health effects on animals and humans. Astaxanthin (AST) is a natural carotenoid that has anti-inflammatory, antiapoptotic, immunomodulatory, antitumor, antidiabetes, and other biological activities. The present study is aimed at investigating the effects of AST on OTA-induced cecum injury and its mechanism of action. Eighty C57 mice were randomly divided into four groups, including the control group, OTA group (5 mg/kg body weight), AST group (100 mg/kg body weight), and AST intervention group (100 mg/kg body weight AST+5 mg/kg body weight OTA). It was found that AST decreased the endotoxin content, effectively prevented the shortening of mouse cecum villi, and increased the expression levels of tight junction (TJ) proteins, consisting of occludin, claudin-1, and zonula occludens-1 (ZO-1). AST increased the number of goblet cells, the contents of mucin-2 (MUC2), and defensins (Defa5 and ß-pD2) significantly, while the expression of mucin-1 (MUC1) decreased significantly. The 16S rRNA sequencing showed that AST affected the richness and diversity of cecum flora, decreased the proportion of lactobacillus, and also decreased the contents of short-chain fatty acids (SCFAs) (acetate and butyrate). In addition, AST significantly decreased the expression of TLR4, MyD88, and p-p65, while increasing the expression of p65. Meanwhile, the expression of inflammatory factors including TNF-α and INF-γ decreased, while the expression of IL-10 increased. In conclusion, AST reduced OTA-induced cecum injury by regulating the cecum barrier function and TLR4/MyD88/NF-κB signaling pathway.

3.
J Integr Plant Biol ; 63(1): 53-78, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33399265

RESUMO

Protein kinases are major players in various signal transduction pathways. Understanding the molecular mechanisms behind plant responses to biotic and abiotic stresses has become critical for developing and breeding climate-resilient crops. In this review, we summarize recent progress on understanding plant drought, salt, and cold stress responses, with a focus on signal perception and transduction by different protein kinases, especially sucrose nonfermenting1 (SNF1)-related protein kinases (SnRKs), mitogen-activated protein kinase (MAPK) cascades, calcium-dependent protein kinases (CDPKs/CPKs), and receptor-like kinases (RLKs). We also discuss future challenges in these research fields.

4.
EMBO J ; 40(2): e104559, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33372703

RESUMO

The transient elevation of cytosolic free calcium concentration ([Ca2+ ]cyt ) induced by cold stress is a well-established phenomenon; however, the underlying mechanism remains elusive. Here, we report that the Ca2+ -permeable transporter ANNEXIN1 (AtANN1) mediates cold-triggered Ca2+ influx and freezing tolerance in Arabidopsis thaliana. The loss of function of AtANN1 substantially impaired freezing tolerance, reducing the cold-induced [Ca2+ ]cyt increase and upregulation of the cold-responsive CBF and COR genes. Further analysis showed that the OST1/SnRK2.6 kinase interacted with and phosphorylated AtANN1, which consequently enhanced its Ca2+ transport activity, thereby potentiating Ca2+ signaling. Consistent with these results and freezing sensitivity of ost1 mutants, the cold-induced [Ca2+ ]cyt elevation in the ost1-3 mutant was reduced. Genetic analysis indicated that AtANN1 acts downstream of OST1 in responses to cold stress. Our data thus uncover a cascade linking OST1-AtANN1 to cold-induced Ca2+ signal generation, which activates the cold response and consequently enhances freezing tolerance in Arabidopsis.

5.
J Integr Plant Biol ; 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33347703

RESUMO

Both plant receptor-like protein kinases (RLKs) and ubiquitin-mediated proteolysis play crucial roles in plant responses to drought stress. However, the mechanism by which E3 ubiquitin ligases modulate RLKs is poorly understood. In this study, we showed that Arabidopsis PLANT U-BOX PROTEIN 11 (PUB11), an E3 ubiquitin ligase, negatively regulates abscisic acid (ABA)-mediated drought responses. PUB11 interacts with and ubiquitinates two receptor-like protein kinases, LEUCINE RICH REPEAT PROTEIN 1 (LRR1) and KINASE 7 (KIN7), and mediates their degradation during plant responses to drought stress in vitro and in vivo. pub11 mutants were more tolerant, whereas lrr1 and kin7 mutants were more sensitive, to drought stress than the wild type. Genetic analyses show that the pub11 lrr1 kin7 triple mutant exhibited similar drought sensitivity as the lrr1 kin7 double mutant, placing PUB11 upstream of the two RLKs. ABA and drought treatment promoted the accumulation of PUB11, which likely accelerates LRR1 and KIN7 degradation. Together, our results reveal that PUB11 negatively regulates plant responses to drought stress by destabilizing the LRR1 and KIN7 receptor-like kinases. This article is protected by copyright. All rights reserved.

6.
BMC Musculoskelet Disord ; 21(1): 785, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33246434

RESUMO

BACKGROUND: The aim of the present study is to compare the clinical outcomes and postoperative complications of lumbar endoscopic unilateral laminotomy bilateral decompression (LE-ULBD) and minimally invasive surgery transforaminal lumbar interbody fusion (MIS-TLIF) to treat one-level lumbar spinal stenosis (LSS) without degenerative spondylolisthesis or deformity. METHODS: A retrospective analysis of 112 consecutive patients of one-level LSS undergoing either LE-ULBD or MIS-TLIF was performed. Patient demographics, operation time, estimated blood loss, time to ambulation, length of hospitalization, intraoperative and postoperative complications were recorded. The visual analog scale (VAS) score for leg and back pain, the Oswestry Disability Index (ODI) score, and the Macnab criteria were used to evaluate the clinical outcomes. The healthcare cost was also recorded. RESULTS: The operation time, estimated blood loss, time to ambulation and length of hospitalization of LE-ULBD group were shorter than MIS-TLIF group. The postoperative mean VAS and ODI scores decreased significantly in both groups. According to the modified Macnab criteria, the outcomes rated as excellent/good rate were 90.6 and 93.8% in the two groups. The mean VAS scores, ODI scores and outcomes of the modified Macnab criteria of both groups were of no significant difference. The healthcare cost of LE-ULBD group was lower than MIS-TLIF group. Two cases of intraoperative epineurium injury were observed in the LE-ULBD group. One case of cauda equina injury was observed in the LE-ULBD group. No nerve injury, dural injury or cauda equina syndrome was observed in MIS-TLIF group. However, one case with transient urinary retention, one case with pleural effusion, one case with incision infection and one case with implant dislodgement were observed in MIS-TLIF group. CONCLUSIONS: Both LE-ULBD and MIS-TLIF are safe and effective to treat one-level LSS without degenerative spondylolisthesis or deformity. LE-ULBD is a more minimally invasive option and of less economic burden compared with MIS-TLIF. Decompression plus instrumented fusion may be not necessary for one-level LSS without degenerative spondylolisthesis or deformity.

7.
Int J Biol Sci ; 16(15): 2951-2963, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061808

RESUMO

Previous studies have demonstrated that the antitumor potential of IU1 (a pharmacological compound), which was mediated by selective inhibition of proteasome-associated deubiquitinase ubiquitin-specific protease 14 (USP14). However, the underlying molecular mechanisms remain elusive. It has been well established that mdm2 (Murine double minute 2) gene was amplified and/or overexpressed in a variety of human neoplasms, including cervical cancer. Furthermore, MDM2 is critical to cervical cancer development and progression. Relatively studies have reported that USP15 and USP7 stabilized MDM2 protein levels by removing its ubiquitin chain. In the current study, we studied the cell proliferation status after IU1 treatment and the USP14-MDM2 protein interaction in cervical cancer cells. This study experimentally revealed that IU1 treatment reduced MDM2 protein expression in HeLa cervical cancer cells, along with the activation of autophagy-lysosomal protein degradation and promotion of ubiquitin-proteasome system (UPS) function, thereby blocked G0/G1 to S phase transition, decreased cell growth and triggered cell apoptosis. Thus, these results indicate that IU1 treatment simultaneously targets two major intracellular protein degradation systems, ubiquitin-proteasome and autophagy-lysosome systems, which leads to MDM2 degradation and contributes to the antitumor effect of IU1.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32974316

RESUMO

Objective: Precise hip cup positioning is essential for the prevention of component impingement and dislocation in robotic assisted total hip arthroplasty (THA). Currently, the robotic system uses a mechanical alignment guide (MAG) for cup placement, which is one-size-fits-all, and the optimal cup positioning is controversial. Robotic assisted THA has not used any personalized cup positioning guides. The goal of this study was to identify an optimal guide for cup placement in robotic assisted THA to improve prognosis and life quality after THA. Materials and Methods: Pelvis and femoral CT data of 47 participants were retrospectively collected for preoperative planning of robotic THA. The universal MAG guide and three personalized guides, including acetabular rim labrum guide (ARLG), transverse acetabular ligament guide (TALG), and ischiatic-pubis line guide (IPLG), were used to pose cups in the acetabulum of each participant. The position of cups was evaluated by inclination and anteversion; the function of hip joints was evaluated by hip ranges of motion, including abduction, adduction, extension, flexion, internal rotation, and external rotation. Results: In terms of cup positioning, ARLG provided a bigger cup inclination (p < 0.0001), while IPLG and TALG provided smaller cup inclination (p < 0.001) than MAG; the three personalized guides provided larger cup anteversion (p < 0.0001) than MAG. In terms of HROMs, compared with the use of MAG, the use of three personalized guides significantly decreased abduction (p < 0.0001), extension (p < 0.0001), and external rotation (p < 0.0001), but increased significantly flexion (p < 0.0001) and internal rotation (p < 0.0001); the use of ARLG significantly reduced adduction (p < 0.0001), but the use of IPLG and TALG increased adduction (p < 0.0001). Conclusion: Compared with MAG, personalized guides provided greater flexion and internal rotation, which may reduce the risk of posterior dislocation. Among the three personalized guides, IPLG is the most reliable one for the preoperative planning of robotic assisted THA.

9.
Anim Reprod Sci ; 221: 106549, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32861111

RESUMO

Cows nearing parturition have a negative energy balance (NEB), which is closely associated with lesser fertility. The NEB results in greater fat mobilisation and production of a large amount of non-esterified fatty acid (NEFA). Prostaglandins (PG), especially prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α), have important functions in regulating reproductive function. There, however, is little known about how the synthesis and release of PG are affected by NEFA. In this study, there was a focus on effects of NEFA on PG secretion as well as relative abundances of mRNA transcript and protein for PG synthetases and PG receptors in bovine endometrial (BEND) cells. Proliferation rate of BEND cells decreased in a concentration-dependent manner as NEFA increased in the media. The concentrations of PGE2 and PGF2α in NEFA treatment groups also decreased, while the ratio of PGE2/PGF2α and the relative abundances of proteins and mRNA that regulate PG synthesis and PG receptor mRNA transcripts and protein were greater as the NEFA concentration increased. Collectively, when there were large NEFA concentrations in the medium, there was a lesser release of PGE2 and PGF2α, however, there was a greater ratio of PGE2/PGF2α and relative abundances of mRNA transcripts and protein for PG synthetases and PG receptors in BEND cells, which changed the internal milieu and physiological function of the uterus with possible effects on fertility after calving. These findings provide important information that will help for further investigation of associations between NEB and fertility in dairy cows during the non-lactation to lactation-transition period.

10.
J Low Genit Tract Dis ; 24(4): 417-420, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32796264

RESUMO

OBJECTIVE: This pilot study aimed to evaluate whether different microbial compositions cause symptoms in patients with Lactobacillus overgrowth and to investigate the variation in Lactobacillus microbiome in cytolytic vaginosis (CV). MATERIALS AND METHODS: Lactobacillus species were identified from the vaginal fluid of 70 healthy women and 79 patients with CV using molecular analysis of the 16S rRNA gene. χ and Fisher exact tests were used to compare the isolated rates of Lactobacillus species between the 2 groups. The capabilities of dominant Lactobacillus strain to produce acid in the 2 groups were analyzed by repeated measures analysis of variance. RESULTS: The isolation of 2 or more Lactobacillus species per vaginal sampling was significantly less common in the CV group (1.3%) compared with the healthy control (HC) group 12.2% (p = .013). Significant differences in Lactobacillus species were observed between the 2 groups (p < .001). Lactobacillus crispatus was more often found in the CV group (88.7%) than in the HC group (56.4%, p < .001). Compared with that in the HC group, the dominant L. crispatus strain in the CV group tended to produce more acid. CONCLUSIONS: The CV group carried a less diverse Lactobacillus species, vaginally. Lactobacillus crispatus was common to both CV and HC groups but demonstrated enhanced acid-producing capability in the CV group. The pathogenesis of CV may be based, in part, on an overgrowth of L. crispatus with enhanced acid-producing capability.

11.
J Orthop Translat ; 23: 29-37, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32477867

RESUMO

Background/objectives: Accelerating the process of bone regeneration is of great interest for surgeons and basic scientists alike. Recently, umbilical cord mesenchymal stem cells (UCMSCs) are considered clinically applicable for tissue regeneration due to their noninvasive harvesting and better viability. Nonetheless, the bone regenerative ability of human UCMSCs (HUCMSCs) is largely unknown. This study aimed to investigate whether Wnt10b-overexpressing HUCMSCs have enhanced bone regeneration ability in a rat model. Method: A rat calvarial defect was performed on 8-week old male Sprague Dawley rats. Commercially purchased HUCMSCsEmp in hydrogel, HUCMSCsWnt10b in hydrogel and HUCMSCsWnt10b with IWR-1 were placed in the calvarial bone defect right after surgery on rats (N = 8 rats for each group). Calvaria were harvested for micro-CT analysis and histology four weeks after surgery. CFU-F and multi-differentiation assay by oil red staining, alizarin red staining and RT-PCR (real-time polymerase chain reaction) were performed on HUCMSCsEmp and HUCMSCsWnt10b in vitro. Conditioned media from HUCMSCsEmp and HUCMSCsWnt10b were collected and used to treat human umbilical cord vein endothelial cells in Matrigel to access vessel formation capacity by tube formation assay. Results: Alizarin red staining, oil red staining and RT-PCR results showed robust osteogenic differentiation but poor adipogenic differentiation ability of HUCMSCsWnt10b. Furthermore, HUCMSCsWnt10b could accelerate bone defect healing, which was likely due to enhanced angiogenesis after the HUCMSCsWnt10b treatment, because more CD31+ vessels and increased vascular endothelial growth factor-A (VEGF-A) expression were observed, compared with the HUCMSCsEmp treatment. Conditioned media from HUCMSCsWnt10b also induced endothelial cells to form vessel tubes in a tube formation assay, which could be abolished by SU5416, an angiogenesis inhibitor. Conclusion: To our knowledge, this is the first study providing empirical evidence that HUCMSCsWnt10b can enhance their ability to heal calvarial bone defects via VEGF-mediated angiogenesis. The translational potential of this article: HUCMSCsWnt10b can accelerate critical size calvaria and are a new promising therapeutic cell source for fracture nonunion healing.

12.
Front Chem ; 8: 413, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32582626

RESUMO

Supercapacitors (SCs) have attracted widespread attention due to their short charging/discharging time, long cycle life, and good temperature characteristics. Electrolytes have been considered as a key factor affecting the performance of SCs. They largely determine the energy density based on their decomposition voltage and the power density from their ionic conductivity. In recent years, redox electrolytes obtained a growing interest due to an additional redox activity from electrolytes, which offers an increased charge storage capacity in SCs. This article summarizes the latest progress in the research of redox electrolytes, and focuses on their properties, mechanisms, and applications based on different solvent types available. It also proposes potential solutions for how to effectively increase the energy density of the SCs while maintaining their high power and long life.

13.
Comput Biol Med ; 120: 103760, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32421657

RESUMO

Anterior cervical discectomy and fusion (ACDF) is a well-established surgical treatment for patients with symptomatic cervical degenerative disc disease, while the biomechanical changes of adjacent segments after ACDF using either a zero-profile device or cage plus plate remain uncertain. The present study is to compare adjacent segment biomechanical changes after one- or two-level ACDF using either a zero-profile device or cage plus plate. A three-dimensional finite element (FE) intact cervical model (C2-C7) was constructed and validated. In the one-level surgery model, either a zero-profile device or cage plus plate was implanted at the C5-C6 segment of the model; while in the two-level surgery model, the prostheses were implanted at the C4-C5 and C5-C6 segments of the model. A pure moment of 1.0 Nm combined with a follower load of 73.6 N were imposed on C2 to determine the flexion-extension, lateral bending, and axial rotation of different segments. The segmental range of motion (ROM) and maximum value of the intradiscal pressure of the surgery models were determined and compared with those of the intact model. In both one- and two-level ACDF models, the ROM of the fused segments was sacrificed, while loss of ROM at the fused segments was greater in cage plus plate models than in zero-profile device models because of structural differences of the implanted devices. However, the ROM and intradiscal pressure were increased at the C4-C5 and C6-C7 segments in the one-level model of ACDF using either a zero-profile device or cage plus plate, the ROM and intradiscal pressure were also increased at the C3-C4 and C6-C7 segments in the two-level surgery models. In conclusion, decreased ROM was observed at the fused segments, while increased ROM and intradiscal pressure were observed at the adjacent segments of the fused segments in ACDF, regardless of whether zero-profile devices or cage plus plate was used. Moreover, loss of ROM at the fused segments was greater in cage plus plate models than in zero-profile device models.

14.
Plant Cell ; 32(7): 2196-2215, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32371543

RESUMO

Phytochromes are red (R) and far-red (FR) light photoreceptors in plants, and PHYTOCHROME-INTERACTING FACTORS (PIFs) are a group of basic helix-loop-helix family transcription factors that play central roles in repressing photomorphogenesis. Here, we report that MYB30, an R2R3-MYB family transcription factor, acts as a negative regulator of photomorphogenesis in Arabidopsis (Arabidopsis thaliana). We show that MYB30 preferentially interacts with the Pfr (active) forms of the phytochrome A (phyA) and phytochrome B (phyB) holoproteins and that MYB30 levels are induced by phyA and phyB in the light. It was previously shown that phytochromes induce rapid phosphorylation and degradation of PIFs upon R light exposure. Our current data indicate that MYB30 promotes PIF4 and PIF5 protein reaccumulation under prolonged R light irradiation by directly binding to their promoters to induce their expression and by inhibiting the interaction of PIF4 and PIF5 with the Pfr form of phyB. In addition, our data indicate that MYB30 interacts with PIFs and that they act additively to repress photomorphogenesis. In summary, our study demonstrates that MYB30 negatively regulates Arabidopsis photomorphogenic development by acting to promote PIF4 and PIF5 protein accumulation under prolonged R light irradiation, thus providing new insights into the complicated but delicate control of PIFs in the responses of plants to their dynamic light environment.

15.
Food Chem Toxicol ; 141: 111405, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32389840

RESUMO

Zearalenone (ZEA) is a mycotoxin that contaminates crops worldwide and is toxic to the reproductive systems of mammals, however, the toxicological mechanism by which ZEA affects germ cells is not fully understood. In this study, proteomic analysis using iTRAQ technology was adopted to determine the cellular response of Leydig cells of rats to ZEA exposure. The results were used to elucidate the mechanisms responsible for the toxicity of the ZEA towards germ cells. After 24 h of exposure to ZEA at a concentration of 30 µmol/L, a total of 128 differentially expressed proteins (DEPs) were identified. Of these, 70 DEPs were up-regulated and 58 DEPs were down-regulated. The DEPs associated with ZEA toxicology were then screened by using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The results show that these DEPs are involved in a number of important ZEA toxicological pathways including apoptosis, immunotoxicity, DNA damage, and signaling pathways. The complex regulatory relationships between the DEPs and ZEA toxicological signaling pathways are also explicitly demonstrated in the form of a protein-protein interaction network. This study thus provides a theoretical molecular basis for understanding the toxicological mechanisms by which ZEA affects germ cells.

16.
J Orthop Translat ; 23: 21-28, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32455113

RESUMO

Background/objectives: Articular cartilage erosion probably plays a substantial role in osteoarthritis (OA) initiation and development. Studies demonstrated that umbilical cord-derived mesenchymal stem cells (UCMSCs) could delay chondrocytes apoptosis and ameliorate OA progression in patients, but the detailed mechanisms are largely uncharacterised. In this study, we aimed to study the effects of UCMSCs on monosodium iodoacetate (MIA)-induced rat OA model, and explore the cellular mechanism of this effect. Methods: Intra-articular injection of 0.3 â€‹mg MIA in 50 â€‹µL saline was performed on the left knee of the 200 â€‹g weight male Sprague-Dawley rat to induce rat knee OA. A single dose of 2.5 â€‹× â€‹105 undifferentiated UCMSCs one day after MIA or three-time intra-articular injection of 2.5 â€‹× â€‹105 UCMSCs on Days 1, 7 â€‹and 14 were given, respectively. Four weeks after MIA, joints were harvested and processed for paraffin sections. Safranine-O staining, haematoxylin and eosin staining â€‹and immunohistochemistry of MMP-13, ADAMTS-5, Col-2, CD68 â€‹and CD4 were performed to observe cartilage erosion and synovium. For in vitro â€‹studies, migration ability of cartilage superficial layer cells (SFCs) by UCMSCs were accessed by transwell assay. Furthermore, catabolism change of MIA-induced SFCs by UCMSCs was performed by real-rime polymerase chain reaction of Col-X and BCL-2 genes. CCK-8 assay was performed to check proliferation ability of SFCs by UCMSCs-conditioned media. Result: In this study, we locally injected human UCMSCs, which is highly proliferative and noninvasively collectible, into MIA-induced rat knee OA. An important finding is on obviously ameliorated cartilage erosion and decreased OA Mankin score by repeated UCMSCs injection after MIA injection compared with single injection, both of which attenuated OA progression compared with vehicle. Interestingly, we observed significantly increased number of SFCs on the articular cartilage surface, probably related to elevated proliferation, mobilisation and inhibited catabolism marker: Col-X and BCL-2 gene expression of cultured SFCs by UCMSCs-conditioned media treatment in vitro. In addition to the change of unique SFCs, catabolism markers of ADAMTS-5 and MMP-13 were substantially upregulated in the whole cartilage layer chondrocytes as well. Strikingly, MIA-induced inflammatory cells infiltration, on both CD4+ Th cells and CD68+ macrophages, and hyperplasia of the synovium, which was alleviated by repeated UCMSCs injection. Conclusion: Our study demonstrated a critical role of repeated UCMSCs dosing on preserving SFCs function, cartilage structure and inhibiting synovitis during OA progression, and thus provided mechanistic proof of evidence for the use of UCMSCs on OA patients in the future. The translational potential of this article: UCMSCs are a relatively "young" stem cell, and noninvasively collectible. In our study, we clearly demonstrated that it could effectively delay OA progression, possibly through reserving SFCs function and inhibiting synovitis. Therefore, it could be a new promising therapeutic cell source for OA after further clinical trials.

17.
EMBO J ; 39(13): e103630, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32449547

RESUMO

Light and temperature are two core environmental factors that coordinately regulate plant growth and survival throughout their entire life cycle. However, the mechanisms integrating light and temperature signaling pathways in plants remain poorly understood. Here, we report that CBF1, an AP2/ERF-family transcription factor essential for plant cold acclimation, promotes hypocotyl growth under ambient temperatures in Arabidopsis. We show that CBF1 increases the protein abundance of PIF4 and PIF5, two phytochrome-interacting bHLH-family transcription factors that play pivotal roles in modulating plant growth and development, by directly binding to their promoters to induce their gene expression, and by inhibiting their interaction with phyB in the light. Moreover, our data demonstrate that CBF1 promotes PIF4/PIF5 protein accumulation and hypocotyl growth at both 22°C and 17°C, but not at 4°C, with a more prominent role at 17°C than at 22°C. Together, our study reveals that CBF1 integrates light and temperature control of hypocotyl growth by promoting PIF4 and PIF5 protein abundance in the light, thus providing insights into the integration mechanisms of light and temperature signaling pathways in plants.

18.
Sci China Life Sci ; 63(5): 635-674, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32246404

RESUMO

Abiotic stresses and soil nutrient limitations are major environmental conditions that reduce plant growth, productivity and quality. Plants have evolved mechanisms to perceive these environmental challenges, transmit the stress signals within cells as well as between cells and tissues, and make appropriate adjustments in their growth and development in order to survive and reproduce. In recent years, significant progress has been made on many fronts of the stress signaling research, particularly in understanding the downstream signaling events that culminate at the activation of stress- and nutrient limitation-responsive genes, cellular ion homeostasis, and growth adjustment. However, the revelation of the early events of stress signaling, particularly the identification of primary stress sensors, still lags behind. In this review, we summarize recent work on the genetic and molecular mechanisms of plant abiotic stress and nutrient limitation sensing and signaling and discuss new directions for future studies.


Assuntos
Plantas/genética , Plantas/metabolismo , Solo/química , Estresse Fisiológico/fisiologia , Canais de Cálcio/metabolismo , Regulação da Expressão Gênica de Plantas , Metais Pesados/metabolismo , Fosforilação , Desenvolvimento Vegetal/genética , Proteínas de Plantas/metabolismo , Transdução de Sinais , Estresse Fisiológico/genética , Fatores de Transcrição/metabolismo
19.
Food Chem Toxicol ; 141: 111385, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32348814

RESUMO

The toxic effect of zearalenone (ZEA) is not fully understood and there is an urgent need for the development of effective agents to protect against the toxic effects of ZEA. In this study, we detected whether curcumin (CUR) can reduce Leydig cells apoptosis induced by ZEA. The Effects of ZEA and CUR on cell viability was evaluated using a Cell Counting kit-8 assay (CCK-8). Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and flow cytometry. The protective effect of CUR on oxidative stress induced by ZEA was determined by ROS, MDA, T-SOD, GSH and GSH-Px levels. In addition, we also determined effects of key signaling pathways and proteins involved in the apoptotic, PI3K-AKT, Nrf2 and endoplasmic reticulum stress signaling pathways by Western blotting. The expressions of proteins (PTEN, AKT, p-AKT, Bax, Bcl-2, GRP78, CHOP, JNK, P-JNK, Caspase-12, Caspase-9, Caspase-3, Nrf2, Keap1 and HO-1) were measured. The experimental results showed that CUR can alleviate oxidative stress and apoptosis caused by ZEA through the PI3K-AKT, Nrf2 and endoplasmic reticulum stress signaling pathways. Our results provide a theoretical basis for molecular studies of ZEA toxicology and clinical application of CUR.

20.
Mol Plant ; 13(6): 894-906, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32311530

RESUMO

Growth inhibition and cold-acclimation strategies help plants withstand cold stress, which adversely affects growth and survival. PHYTOCHROME B (phyB) regulates plant growth through perceiving both light and ambient temperature signals. However, the mechanism by which phyB mediates the plant response to cold stress remains elusive. Here, we show that the key transcription factors mediating cold acclimation, C-REPEAT BINDING FACTORs (CBFs), interact with PHYTOCHROME-INTERACTING FACTOR 3 (PIF3) under cold stress, thus attenuating the mutually assured destruction of PIF3-phyB. Cold-stabilized phyB acts downstream of CBFs to positively regulate freezing tolerance by modulating the expression of stress-responsive and growth-related genes. Consistent with this, phyB mutants exhibited a freezing-sensitive phenotype, whereas phyB-overexpression transgenic plants displayed enhanced freezing tolerance. Further analysis showed that the PIF1, PIF4, and PIF5 proteins, all of which negatively regulate plant freezing tolerance, were destabilized by cold stress in a phytochrome-dependent manner. Collectively, our study reveals that CBFs-PIF3-phyB serves as an important regulatory module for modulating plant response to cold stress.

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