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1.
Psychiatry Res ; 300: 113943, 2021 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-33932639

RESUMO

GNB1L haploinsufficiency caused by 22q11.2 deletion syndrome may contribute to schizophrenia pathophysiology. We resequenced the protein-coding sequences of GNB1L in 553 patients with schizophrenia and 535 controls from Taiwan. Four common single-nucleotide polymorphisms showed no association with patients with schizophrenia. We identified 17 rare missense mutations, including three that were schizophrenia-associated and predicted as pathogenic (p.R57W, p.G68S, and p.R265C). Given that rare mutations with high penetrance contribute to schizophrenia, missense mutations of GNB1L might increase the risk of schizophrenia in some patients.

2.
Alzheimers Res Ther ; 13(1): 93, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947453

RESUMO

BACKGROUND: We aimed to investigate the tau biomarker discrepancies of Alzheimer's disease (AD) using plasma tau phosphorylated at threonine 181 (p-tau181), cerebrospinal fluid (CSF) p-tau181, and AV1451 positron emission tomography (PET). METHODS: In the Alzheimer's Disease Neuroimaging Initiative, 724 non-demented participants were categorized into plasma/CSF and plasma/PET groups. Demographic and clinical variables, amyloid-ß (Aß) burden, flortaucipir-PET binding in Braak regions of interest (ROIs), longitudinal changes in clinical outcomes, and conversion risk were compared. RESULTS: Across different tau biomarker groups, the proportion of participants with a discordant profile varied (plasma+/CSF- 15.6%, plasma-/CSF+ 15.3%, plasma+/PET- 22.4%, and plasma-/PET+ 6.1%). Within the plasma/CSF categories, we found an increase from concordant-negative to discordant to concordant-positive in the frequency of Aß pathology or cognitive impairment, rates of cognitive decline, and risk of cognitive conversion. However, the two discordant categories (plasma+/CSF- and plasma-/CSF+) showed comparable performances, resulting in similarly reduced cognitive capacities. Regarding plasma/PET categories, as expected, PET-positive individuals had increased Aß burden, elevated flortaucipir retention in Braak ROIs, and accelerated cognitive deterioration than concordant-negative persons. Noteworthy, discordant participants with normal PET exhibited reduced flortaucipir uptake in Braak stage ROIs and slower rates of cognitive decline, relative to those PET-positive. Therefore, individuals with PET abnormality appeared to have advanced tau pathological changes and poorer cognitive function, regardless of the plasma status. Furthermore, these results were found only in individuals with Aß pathology. CONCLUSIONS: Our results indicate that plasma and CSF p-tau181 abnormalities associated with amyloidosis occur simultaneously in the progression of AD pathogenesis and related cognitive decline, before tau-PET turns positive.

4.
J Alzheimers Dis ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33814452

RESUMO

Mutations in ITM2B have been found to be associated with familial Danish dementia (FDD) and familial British dementia (FBD). Here, we describe a patient with dementia caused by a novel ITM2B p. *267Leuext *11 mutation. The patient presented with dementia, ataxia, deafness, and paraplegia. Amyloid PET and Tau PET showed abnormal deposition of amyloid and tau protein in brain. Summarized from previous 26 FBD and FDD cases, the clinical phenotype of ITM2B; p. *267Leuext *11 mutation in ITM2B is different from the features of FBD and FDD. Our findings increased genetic knowledge of familial dementia and extend the ethnic distribution of ITM2B mutations.

5.
Hereditas ; 158(1): 13, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863396

RESUMO

BACKGROUND: Sepsis and septic shock are life-threatening diseases with high mortality rate in intensive care unit (ICU). Acute kidney injury (AKI) is a common complication of sepsis, and its occurrence is a poor prognostic sign to septic patients. We analyzed co-differentially expressed genes (co-DEGs) to explore relationships between septic shock and AKI and reveal potential biomarkers and therapeutic targets of septic-shock-associated AKI (SSAKI). METHODS: Two gene expression datasets (GSE30718 and GSE57065) were downloaded from the Gene Expression Omnibus (GEO). The GSE57065 dataset included 28 septic shock patients and 25 healthy volunteers and blood samples were collected within 0.5, 24 and 48 h after shock. Specimens of GSE30718 were collected from 26 patients with AKI and 11 control patents. AKI-DEGs and septic-shock-DEGs were identified using the two datasets. Subsequently, Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate molecular mechanisms of DEGs. We also evaluated co-DEGs and corresponding predicted miRNAs involved in septic shock and AKI. RESULTS: We identified 62 DEGs in AKI specimens and 888, 870, and 717 DEGs in septic shock blood samples within 0.5, 24 and 48 h, respectively. The hub genes of EGF and OLFM4 may be involved in AKI and QPCT, CKAP4, PRKCQ, PLAC8, PRC1, BCL9L, ATP11B, KLHL2, LDLRAP1, NDUFAF1, IFIT2, CSF1R, HGF, NRN1, GZMB, and STAT4 may be associated with septic shock. Besides, co-DEGs of VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 coupled with corresponding predicted miRNAs, especially miR-29b-3p, miR-152-3p, and miR-223-3p may be regarded as promising targets for the diagnosis and treatment of SSAKI in the future. CONCLUSIONS: Septic shock and AKI are related and VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 genes are significantly associated with novel biomarkers involved in the occurrence and development of SSAKI.

6.
Nanoscale ; 13(15): 7202-7219, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33889875

RESUMO

Glioma stem cells (GSCs) and their complex microenvironment play a crucial role in the high invasion of cancer and therapeutic resistance and are considered to be the most likely cause of cancer relapse. We constructed a biomimetic vehicle (LDL-SAL-Ang) based on a low density lipoprotein triggered by Angiopep-2 peptide and ApoB protein, to improve the transport of an anti-GSC therapeutic agent into the brain. The LDL-SAL-Ang showed significant inhabitation for GSC microsphere formation and induced the highest apoptotic rate in two types of GSCs. LDL-SAL-Ang reduced the number of GSC-derived endothelial tubules at a lower drug concentration and inhibited endothelial cell migration and angiogenesis. The pharmacokinetic analysis showed that the brain tissue uptake rate (% ID g-1) for LDL-SAL-Ang was significantly enhanced at 0.45. For anti-glioblastoma activity in vivo, the median survival time of LDL-SAL-Ang plus temozolomide group was 47 days, which were significantly increased compared with the control or temozolomide only groups. The endogenous biomimetic nanomedicine that we designed provides a potential approach to improve treatments for intracranial tumors and reduced neurotoxicity of nanomedicine.

7.
HLA ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33880886

RESUMO

One nucleotide substitution in codon 57 of HLA-DQB1*06:02:01:01 results in a novel allele, HLA-DQB1*06:02:43.

8.
J Ethnopharmacol ; 274: 114073, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-33794335

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence and mortality rates of hepatocellular carcinoma are very high all over the world, which seriously threatens human life and health. Aidi injection as a Chinese medicine preparation has a positive curative effect on hepatocellular carcinoma, but its mechanism remains unclear. AIM OF THE STUDY: The purpose of this study is to evaluate the anti-hepatocellular carcinoma effects of Aidi injection and explore its mechanism of action vitro and vivo. MATERIALS AND METHODS: The main components of Aidi injection were determined by LC-MS/MS. The effects of Aidi injection on the viability of HepG2 and PLC/PRF/5 cells were detected via CCK-8 analysis and Calcein AM/PI staining. DAPI staining and flow cytometry were applied to analyze the apoptosis-induced effects of Aidi injection on hepatocellular carcinoma cells (HCCs). The growth inhibition of Aidi injection on hepatocellular carcinoma was observed in nude mice bearing PLC/PRF/5 cells. The related signal transduction and apoptosis pathways were investigated through assays for JC-1 mitochondrial membrane potential (MMP), RNA-seq, KEGG, PPI and WB. RESULTS: There were 12 main chemical components contained in Aidi injection, viz. cantharidin, syringin, calycosin-7-o-ß-Dglucoside, isozinpidine, ginsenosides Rd, Rc, Rb1, Re, and Rg1, astragalosides II and IV, and eleutheroside E. Aidi injection significantly inhibited the proliferation of HepG2 and PLC/PLF/5 cells with IC50 of 20.66 mg/ml and 27.5 mg/ml at 48h, respectively, increased the proportion of dead cells, induced cell apoptosis, suppressed the tumor growth of nude mice bearing PLC/PLF/5 cells, reduced MMP, activated PI3K/Akt and MAPK signal transduction pathways, down-regulated the expression of p-PI3K and Bcl-xL, and up-regulated the expression of p-JNK, p-p38 and Bim. CONCLUSION: Aidi injection inhibits the growth of liver cancer probably through regulating PI3K/Akt and MAPK signal transduction pathways, inducing MMP collapse to activate the mitochondrial apoptosis pathway, and then eliciting apoptosis of HCCs.

9.
Huan Jing Ke Xue ; 42(3): 1433-1442, 2021 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742940

RESUMO

The loss of nitrogen (N) and phosphorus (P) from aquaculture has caused eutrophication of freshwater systems. Here, surface flow constructed wetland (SFCW) planted with Myriophyllum elatinoides were used to treat swine wastewater from a medium-sized hoggery in subtropical Central China. Inflow concentrations of NH4+-N, TN, TP, and COD ranged from 535.4 to 591.09, 682.09 to 766.96, 57.73 to 82.29, and 918.4 to 1940.43 mg·L-1, respectively. The mean removal efficiencies of NH4+-N, TN, TP, and COD were 97.4%, 97.1%, 91.0%, and 90.2%, respectively, and CW1 had the largest contributions of 37.3%, 38.4%, 43.3%, and 27.4%, respectively. Plant N and P uptake ranged 23.87-79.96 g·m-2 and 5.34-18.98 g·m-2, accounting for 19.1% and 20.2% of removal, respectively. Sediment N and P accumulation ranged 19.17-56.62 g·m-2 and 10.59-26.62 g·m-2, accounting for 19.8% and 61.7% of removal, respectively. Multiple linear regression showed that environmental factors explained 79.9% of the N removal and 70.1% of the P removal; DO was the main factor affecting N removal, and sediment adsorption was the key process in P removal. These results show that M. elatinoides constructed wetland can efficiently treat swine wastewater, thereby reduce the discharge of pollutants downstream.


Assuntos
Águas Residuárias , Áreas Alagadas , Animais , China , Nitrogênio/análise , Fósforo , Suínos , Eliminação de Resíduos Líquidos
10.
Psychooncology ; 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33689199

RESUMO

OBJECTIVE: Be Resilient to Breast Cancer (BRBC), a theoretically-derived, resilience-based, culturally-tailored, supportive-expressive group therapy (SEGT), has been developed to help promote patients' resilience in breast cancer. Data from patients receiving BRBC intervention was utilized to explore and define characteristics of resilience patterns and their transitions over time. METHODS: Resilience was used as a primary outcome and 391 patients completed Resilience Scale Specific to Cancer at enrollment (T0), 2 months (T1), 6 months(T2), and 12 months (T3) after intervention. latent profile transition analysis was performed to model the change in resilience and predict positive transitioning probabilities between resilience patterns (from one pattern to another pattern with a higher level) over time. RESULTS: One hundred and forty four resilience patterns were identified after BRBC intervention. 33.1%, 50.3%, and 40.5% of patients experienced positive resilience transitions from T0 to T1, T1 to T2, and T2 to T3, respectively. Patients with middle age, unmarried status, higher education level, and less advanced tumor stage were more likely to experience positive resilience transitions. CONCLUSION: Different transitions of resilience patterns are observed after BRBC intervention. Age, marital status, education, and tumor stage may be four factors affecting the efficacy of SEGT intervention in breast cancer.

11.
Nature ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727703

RESUMO

The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by a coronavirus, following the emergence of severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) in 20122. Treatment options for coronaviruses are limited. Here we show that clofazimine-an anti-leprosy drug with a favourable safety profile3-possesses inhibitory activity against several coronaviruses, and can antagonize the replication of SARS-CoV-2 and MERS-CoV in a range of in vitro systems. We found that this molecule, which has been approved by the US Food and Drug Administration, inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic or therapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Clofazimine, which is orally bioavailable and comparatively cheap to manufacture, is an attractive clinical candidate for the treatment of outpatients and-when combined with remdesivir-in therapy for hospitalized patients with COVID-19, particularly in contexts in which costs are an important factor or specialized medical facilities are limited. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and-possibly more importantly-in dealing with coronavirus diseases that may emerge in the future.

12.
J Environ Manage ; 288: 112402, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33774564

RESUMO

Membrane is a considerable precursor for emulsions separation and organic dyes degradation used in water purification and oil reclamation. However, the tedious preparation method, the surface smears easily, and low degradation efficiency, these characteristics usually significantly hinder its applicability toward wastewater governance. Herein, a green, facile, and efficient fabrication strategy to prepare a bi-functional palladium nanoparticles (PdNPs)-loaded bacterial cellulose membrane (BCMPd) is proposed. A tri-functional bacterial cellulose membrane (BCM) was obtained by percolating bacterial cellulose (BC) on a basal membrane, and BCM served as a support, reducing agent, and stabilizer in the subsequent reduction of PdNPs. Bi-functional BCMPd was successfully obtained and used for continuously removing emulsions and reducing methylene blue (MB) from simulated wastewater via the integration of physical sieving and chemical reaction. Meanwhile, the enhancement factors for the water transfer ability and demulsification capacity correlated directly with the wettability and surface structure of BCMPd. Furthermore, the dosage of BC was adjusted to reveal the mechanism for the enhanced water transferability and demulsification capacity. Notably, PdNPs of BCMPd decreased Fermi potential difference between BH4- and MB, accelerating the electron transfer of the reduction reaction and thus exhibiting a remarkable MB degradation efficiency. Together, the information obtained in this work can be useful for comprehensively addressing the bottleneck of forming a cost-effective, eco-friendly, and bi-functional membrane reactor, providing an alternative approach for better treatment of complex wastewater.


Assuntos
Nanopartículas Metálicas , Paládio , Celulose , Corantes , Emulsões
13.
Eur Radiol ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33738596

RESUMO

OBJECTIVE: To compare the value of reduced field-of-view (FOV) intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) and arterial spin labeling (ASL) for assessing renal allograft fibrosis and predicting long-term dysfunction. METHODS: This prospective study included 175 renal transplant recipients undergoing reduced FOV IVIM DWI, ASL, and biopsies. Renal allograft fibrosis was categorized into ci0, ci1, ci2, and ci3 fibrosis according to biopsy results. A total of 83 participants followed for a median of 39 (IQR, 21-42) months were dichotomized into stable and impaired allograft function groups based on follow-up estimated glomerular filtration rate. Total apparent diffusion coefficient (ADCT), pure diffusion ADC, pseudo-perfusion ADC, perfusion fraction f from IVIM DWI, and renal blood flow (RBF) from ASL were calculated and compared. The area under the receiver operating characteristic curve (AUC) was calculated to assess the diagnostic and predictive performances. RESULTS: RBF was different in ci0 vs ci1 (147.9 ± 46.3 vs 126.0 ± 49.4 ml/min/100 g, p = .02) and ci2 vs ci3 (92.9 ± 46.9 vs 70.8 ± 37.8 ml/min/100 g, p = .03). RBF in the stable group was higher than that in the impaired group (144.73 ± 49.33 vs 102.19 ± 47.58 ml/min/100 g, p < .001). AUCs in distinguishing renal allograft fibrosis and predicting long-term allograft dysfunction for RBF were higher than cortical ADCT (ci0 vs ci1-3, 0.76 vs 0.59, p < .001; ci0-1 vs ci2-3, 0.79 vs 0.68, p = .01; ci0-2 vs ci3, 0.79 vs 0.68, p = .01; 0.76 vs 0.60, p = .04, respectively). CONCLUSION: Compared to reduced FOV IVIM DWI, ASL was a more promising technique for noninvasively distinguishing renal allograft fibrosis degree and predicting long-term allograft dysfunction. KEY POINTS: • Compared to total ADC from rFOV IVIM DWI, RBF from ASL can distinguish no fibrosis (ci0) vs mild fibrosis (ci1) (p = .02) and moderate fibrosis (ci2) vs severe fibrosis (ci3) (p = .04). • RBF had superior performance than diffusion parameters in discriminating fibrosis (no fibrosis [ci0] vs fibrosis [ci1-3], mild fibrosis [ci0-1] vs moderate to severe fibrosis [ci2-3], non-severe [ci0-2] vs severe [ci3] fibrosis; AUC = 0.76 vs 0.59, p < .001; 0.79 vs 0.68, p = .01; 0.79 vs 0.68, p = .01). • Compared to reduced FOV IVIM DWI, ASL was a more promising technique for noninvasively predicting long-term allograft dysfunction (AUC = 0.76 vs 0.60, p = .04).

15.
Clin Transl Sci ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33650272

RESUMO

Apomorphine is an on-demand treatment of "OFF" episodes in patients with Parkinson's disease (PD). A joint parent-metabolite population pharmacokinetic (PK) model characterized apomorphine and apomorphine-sulfate following administration of apomorphine sublingual film (APL) and two formulations of subcutaneous apomorphine. Overall, 2485 samples from 87 healthy subjects and 71 patients with PD and "OFF" episodes were analyzed using nonlinear mixed-effects modeling. Apomorphine PK was adequately described by a two-compartment model with first-order transit absorption via both routes of administration and first-order metabolism to apomorphine-sulfate with one-compartment disposition and first-order elimination. Bioavailability of apomorphine sublingual film was ~ 18% relative to subcutaneous apomorphine. Among covariates tested, only body weight had a large effect on apomorphine exposure (maximum plasma concentration and area under the concentration-time curve [AUC0-∞ ]), with greater weight resulting in lower exposure. Model-predicted apomorphine exposure was similar between apomorphine sublingual film 30 mg and subcutaneous apomorphine 5 mg (median AUC0-24 , 66.7 ng•h/mL, geometric mean ratio of 0.99; 90% confidence interval [CI], 0.96-1.03) and was comparable between apomorphine sublingual film 35 mg and subcutaneous apomorphine 6 mg (median AUC0-24 , 75.4 and 80.0 ng•h/mL, respectively; geometric mean ratio of 0.94; 90% CI, 0.90-0.97) administered every 2 h for a maximum of 5 doses per day. In a typical patient with PD, predicted apomorphine exposure increased with increasing doses of apomorphine sublingual film; however, the increase was less than dose proportional. Similar apomorphine exposure was predicted in patients with mild renal impairment versus normal renal function. PK properties of apomorphine sublingual film support its administration for a wide range of patients with PD and "OFF" episodes, regardless of demographic and clinical characteristics.

16.
Pharmacol Res ; 166: 105429, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33529753

RESUMO

Increasing studies demonstrated that ubiquitination plays a vital role in the pathogenesis of pancreatic cancer, and targeting regulation of the ubiquitination process is a potential means for cancer treatment. However, the role of tripartite motif 47 (TRIM47) in pancreatic cancer is still unclear. Here, significantly upregulated TRIM47 and decreased FBP1 expressions were found in pancreatic cancer patient tissues and pointed to a lower survival rate. In addition, we show that TRIM47 was upregulated in pancreatic cancer cells and promoted cell proliferation in vitro and in vivo. Mechanistic investigations showed that TRIM47 promoted the aerobic glycolysis of pancreatic cancer cells, which was largely dependent on the direct binding to and ubiquitination of fructose-1, 6-biphosphatase (FBP1). Furthermore, the promotion of TRIM47 on the Warburg effect and pancreatic cancer progression was abolished by the overexpression of FBP1. Therefore, targeting TRIM47/FBP1 axis might provide a novel strategy to suppress the development of pancreatic cancer.

17.
J Biol Chem ; : 100435, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33610551

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents a global threat, and the interaction between the virus and Angiotensin-converting enzyme 2 (ACE2), the primary entry receptor for SARS-CoV-2, is a key determinant of the range of hosts that can be infected by the virus. However, the mechanisms underpinning ACE2-mediated viral entry across species remains unclear. Using infection assay, we evaluated SARS-CoV-2 entry mediated by ACE2 of 11 different animal species. We discovered that ACE2 of Rhinolophus sinicus (Chinese rufous horseshoe bat), Felis catus (domestic cat), Canis lupus familiaris (dog), Sus scrofa (wild pig), Capra hircus (goat) and Manis javanica (Malayan pangolin) facilitated SARS-CoV-2 entry into nonsusceptible cells. Moreover, ACE2 of the pangolin also mediated SARS-CoV-2 entry, adding credence to the hypothesis that SARS-CoV-2 may have originated from pangolins. However, the ACE2 proteins of Rhinolophus ferrumequinum (greater horseshoe bat), Gallus gallus (red junglefowl), Notechis scutatus (mainland tiger snake), or Mus musculus (house mouse) did not facilitate SARS-CoV-2 entry. In addition, a natural isoform of the ACE2 protein of Macaca mulatta (rhesus monkey) with the Y217N mutation was resistant to SARS-CoV-2 infection, highlighting the possible impact of this ACE2 mutation on SARS-CoV-2 studies in rhesus monkeys. We further demonstrated that the Y217 residue of ACE2 is a critical determinant for the ability of ACE2 to mediate SARS-CoV-2 entry. Overall, these results clarify that SARS-CoV-2 can use the ACE2 receptors of multiple animal species and show that tracking the natural reservoirs and intermediate hosts of SARS-CoV-2 is complex.

18.
Genes (Basel) ; 12(2)2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33573315

RESUMO

c-Fos is an immediate-early gene that modulates cellular responses to a wide variety of stimuli and also plays an important role in tissue regeneration. However, the sequence and functions of c-Fos are still poorly understood in newts. This study describes the molecular cloning and characterization of the c-Fos gene (Co-c-Fos) of the Chinese fire-bellied newt, Cynops orientalis. The full-length Co-c-Fos cDNA sequence consists of a 1290 bp coding sequence that encoded 429 amino acids. The alignment and phylogenetic analyses reveal that the amino acid sequence of Co-c-Fos shared a conserved basic leucine zipper domain, including a nuclear localization sequence and a leucine heptad repeat. The Co-c-Fos mRNA is widely expressed in various tissues and is highly and uniformly expressed along the newt limb. After limb amputation, the expression of Co-c-Fos mRNA was immediately upregulated, but rapidly declined. However, the significant upregulation of Co-c-Fos protein expression was sustained for 24 h, overlapping with the wound healing stage of C. orientalis limb regeneration. To investigate if Co-c-Fos participate in newt wound healing, a skin wound healing model is employed. The results show that the treatment of T-5224, a selective c-Fos inhibitor, could largely impair the healing process of newt's skin wound, as well as the injury-induced matrix metalloproteinase-3 upregulation, which is fundamental to wound epithelium formation. These data suggest that Co-c-Fos might participate in wound healing by modulating the expression of its potential target gene matrix metalloproteinase-3. Our study provides important insights into mechanisms that are responsible for the initiation of newt limb regeneration.

19.
J Neurosci Res ; 99(6): 1632-1645, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33638209

RESUMO

The conserved bilateral habenular nuclei (HA) in vertebrate diencephalon develop into compartmentalized structures containing neurons derived from different cell lineages. Despite extensive studies demonstrated that zebrafish larval HA display distinct left-right (L-R) asymmetry in gene expression and connectivity, the spatial gene expression domains were mainly obtained from two-dimensional (2D) snapshots of colorimetric RNA in situ hybridization staining which could not properly reflect different HA neuronal lineages constructed in three-dimension (3D). Combing the tyramide-based fluorescent mRNA in situ hybridization, confocal microscopy and customized imaging processing procedures, we have created spatial distribution maps of four genes for 4-day-old zebrafish and in sibling fish whose L-R asymmetry was spontaneously reversed. 3D volumetric analyses showed that ratios of cpd2, lov, ron, and nrp1a expression in L-R reversed HA were reversed according to the parapineal positions. However, the quantitative changes of gene expression in reversed larval brains do not mirror the gene expression level in the obverse larval brains. There were a total 87.78% increase in lov+ nrp1a+ and a total 12.45% decrease in lov+ ron+ double-positive neurons when the L-R asymmetry of HA was reversed. Thus, our volumetric analyses of the 3D maps indicate that changes of HA neuronal cell fates are associated with the reversal of HA laterality. These changes likely account for the behavior changes associated with HA laterality alterations.

20.
Eur Heart J Acute Cardiovasc Care ; 10(1): 6-15, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33620438

RESUMO

AIMS: To investigate the association between levels of highly sensitive troponin I (hs-troponin I) and mortality in novel coronavirus disease 2019 (COVID-19) patients with cardiac injury. METHODS AND RESULTS: We retrospectively reviewed the medical records of all COVID-19 patients with increased levels of hs-troponin I from two hospitals in Wuhan, China. Demographic information, laboratory test results, cardiac ultrasonographic findings, and electrocardiograms were collected, and their predictive value on in-hospital mortality was explored using multivariable logistic regression. Of 1500 patients screened, 242 COVID-19 patients were enrolled in our study. Their median age was 68 years, and (48.8%) had underlying cardiovascular diseases. One hundred and seventy-six (72.7%) patients died during hospitalization. Multivariable logistic regression showed that C-reactive protein (>75.5 mg/L), D-dimer (>1.5 µg/mL), and acute respiratory distress syndrome were risk factors of mortality, and the peak hs-troponin I levels (>259.4 pg/mL) instead of the hs-troponin I levels at admission was predictor of death. The area under the receiver operating characteristic curve of the peak levels of hs-troponin I for predicting in-hospital mortality was 0.79 (95% confidence interval, 0.73-0.86; sensitivity, 0.80; specificity, 0.72; P < 0.0001). CONCLUSION: Our results demonstrated that the risk of in-hospital death among COVID-19 patients with cardiac injury can be predicted by the peak levels of hs-troponin I during hospitalization and was significantly associated with oxygen supply-demand mismatch, inflammation, and coagulation.


Assuntos
/sangue , Cardiopatias/sangue , Cardiopatias/mortalidade , Mortalidade Hospitalar , Troponina I/sangue , Idoso , Feminino , Cardiopatias/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
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