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1.
J Sci Food Agric ; 100(1): 315-324, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31525262

RESUMO

BACKGROUND: In order to utilize tilapia skin gelatin hydrolysate protein, which is normally discarded as industrial waste in the process of fish manufacture, we study the in vivo and in vitro angiotensin-I-converting enzyme (ACE) inhibitory activity of the peptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP). The aim was to provide a pharmacological basis of the development of minimal side effects of ACE inhibitors by comparative analysis with captopril in molecular docking. RESULTS: This peptide from protein-rich wastes showed excellent ACE inhibitory activity (IC50  = 2.577 µmol L-1 ) and exhibited a mixed noncompetitive inhibitory pattern with Lineweaver-Burk plots. Furthermore, LSGYGP and captopril groups both showed significant decreases in blood pressure after 6 h and maintained good digestive stability over 4 h. Molecular bond interactions differentiate competitive captopril upon hydrogen bond interactions and Zn(II) interaction. The C-terminal Pro generates three interactions (hydrogen bonds, hydrophilic interactions and Van der Waals interactions) in the peptide and effectively interacts with the S1 and S2 pockets of ACE. CONCLUSION: LSGYGP, with an IC50 value of 2.577 µmol L-1 , has an antihypertensive effect in spontaneously hypertensive rats. Through comparison with captopril, this study revealed that LSGYGP may be a potential food-derived ACE inhibitory peptide and could act as a functional food ingredient to prevent hypertension. © 2019 Society of Chemical Industry.

2.
Nat Commun ; 10(1): 5334, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767869

RESUMO

Protein products of the regenerating islet-derived (REG) gene family are important regulators of many cellular processes. Here we functionally characterise a non-protein coding product of the family, the long noncoding RNA (lncRNA) REG1CP that is transcribed from a DNA fragment at the family locus previously thought to be a pseudogene. REG1CP forms an RNA-DNA triplex with a homopurine stretch at the distal promoter of the REG3A gene, through which the DNA helicase FANCJ is tethered to the core promoter of REG3A where it unwinds double stranded DNA and facilitates a permissive state for glucocorticoid receptor α (GRα)-mediated REG3A transcription. As such, REG1CP promotes cancer cell proliferation and tumorigenicity and its upregulation is associated with poor outcome of patients. REG1CP is also transcriptionally inducible by GRα, indicative of feedforward regulation. These results reveal the function and regulation of REG1CP and suggest that REG1CP may constitute a target for cancer treatment.

3.
Environ Pollut ; : 113369, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31662254

RESUMO

Soil contains large amounts of humic acid (HA), iron ions and manganese ions, all of which affect U(VI) migration in the soil. HA interacts with iron and manganese ions to form HA salts (called HA-Fe and HA-Mn in this paper); however, the effects of HA-Fe and HA-Mn on the migration of U(VI) is not fully understood. In this study, HA-Fe and HA-Mn were compounded by HA interactions with ferric chloride hexahydrate and manganese chloride tetrahydrate, respectively. The influence of HA, HA-Fe and HA-Mn on U(VI) immobilization and migration was investigated by bath adsorption experiments and adsorption-desorption experiments using soil columns. The results showed that the presence of HA, HA-Fe and HA-Mn retarded the migration of U(VI) in soil. Supported by X-ray photoelectron spectroscopy (XPS) and BCR sequential extraction analyses, a plausible explanation for the retardation was that HA-Fe and HA-Mn could reduce hexavalent uranium to stable tetravalent uranium and increase the specific gravity of Fe/Mn oxide-bound uranium and organic/sulfide-bound uranium, which made it difficult for them to longitudinally migrate in soil. Scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and surface area and pore size analyses indicated that the complex formed between the hydroxyl, amino and carboxyl groups of HA-Fe and U(VI) increased the crystallinity of HA-Fe. The reaction between U(VI) and the hydroxyl, amino, aldehyde, keto and chlorine-containing groups of HA-Mn had no effect on the crystallinity of HA-Mn. Notably, the column desorption experiment found that the U(VI) immobilized in the soil remigrated under the effect of rain leaching, and acid rain promoted uranium remigration better than neutral rain. The findings provide some guidance for the decommissioning disposal of uranium contaminated site and it's risk assessments.

4.
Zhongguo Zhen Jiu ; 39(10): 1081-6, 2019 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-31621261

RESUMO

OBJECTIVE: To explore the action mechanism of electroacupuncture (EA) for knee osteoarthritis (KOA) based on Wnt/beta-catenin (Wnt/ß-catenin) signaling pathway. METHODS: Ten rats were randomly selected into a sham-operation group among 50 male 2-month-old SD rats, and the KOA model was established in the remaining 40 rats by modified Hulth method. Four weeks after the model establishment, the rats were randomly divided into a model group, an experimental A group, an experimental B group and an experimental C group, 10 rats in each group. The rats in the sham-operation group and model group did not receive any intervention. The rats in the experimental A group were treated with EA at "Neixiyan" (EX-LE 4) and "Dubi"(ST 35) for 15 min. The rats in the experimental B group were treated with EA at "Neixiyan" (EX-LE 4) and "Dubi"(ST 35) for 30 min. The rats in the experimental C group were treated with EA at non-acupoint for 15 min. EA intervention was given once a day, five times a week, and totally 12-week treatment was given. After 12 weeks, the knee cartilage tissues were stained and the morphological changes were observed under light microscopy; the severity of cartilage degeneration was evaluated by modified Mankin's score; the content of interleukin-1ß (IL-1ß) in synovium tissues was detected by ELISA method; the content of Wnt-4, ß-catenin and matrix metalloprotein-13 (MMP-13) in cartilage tissues was detected by Western blot method. RESULTS: Compared with the sham-operation group, in the model group the morphology and structure of cartilage were disordered, the number of cells was significantly reduced, the matrix was decontaminated and tidal line was incomplete; the Mankin's score was significantly increased (P<0.01), the content of IL-1ß in synovium tissues were significantly increased (P<0.01), and the expressions of Wnt-4, ß-catenin and MMP-13 at protein level were significantly increased (P<0.01). Compared with the model group, in the experimental A group and experimental B group the morphology and structure of cartilage were more orderly, the number of cells was increased, the matrix staining was deepened and the tidal line was more complete; Mankin's scores were decreased significantly (P<0.01); the contents of IL-1ß in synovium tissues were decreased significantly (P<0.01), and the expressions of Wnt-4, ß-catenin and MMP-13 at protein level were decreased significantly (P<0.01). Compared with the model group, no improvement was observed in the experimental C group. Compared with the experimental A group, in the experimental C group the morphology and structure of cartilage were disordered, the number of cells was significantly reduced, the matrix was decontaminated and the tidal line was incomplete; Mankin's score was significantly increased (P<0.01), the content of IL-1ß in synovium tissues was significantly increased (P<0.01), and the expressions of Wnt-4, ß-catenin and MMP-13 at protein level were significantly increased (P<0.01). The morphological structure of cartilage in the experimental B group was similar to that in the experimental A group, and there was no significant difference in Mankin's score, IL-1ß content in synovium tissues and the expressions of Wnt-4, ß- catenin and MMP-13 at protein level between the two groups (P>0.05). CONCLUSION: EA at "Neixiyan" (EX-LE 4) and "Dubi"(ST 35) may reduce the expression of MMP-13 and the production of inflammatory factor IL-1ß through Wnt/ß-catenin signaling pathway, thus inhibit the degradation of cartilage matrix and the apoptosis of chondrocyte, and improve the morphology and structure of cartilage.


Assuntos
Cartilagem Articular/metabolismo , Eletroacupuntura , Osteoartrite do Joelho , Via de Sinalização Wnt , Animais , Humanos , Masculino , Osteoartrite do Joelho/terapia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
5.
Biomed Pharmacother ; 119: 109418, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31505423

RESUMO

YiQiFuMai Powder Injection (YQFM) is widely used in clinical practice for the treatment of heart failure (HF). However, its functional molecular mechanism remains to be fully uncovered. Our present study aimed to elucidate the impact of YQFM and underlying mechanisms on coronary artery ligation (CAL)-induced HF. Our results exhibited that YQFM significantly mitigated CAL-induced HF via meliorating the left ventricular contractile function and reducing the serum content of creatine kinase MB (CK-MB), aspartate aminotransferase (AST), interleukin-6 (IL-6), troponin (Tn), myosin, myoglobin (MYO) and myocilin (MYOC). Then, the relevance between circulating omentin level and cardiac function was investigated and we found that serum omentin levels positively associated with ejection fraction and negatively correlated with NT-proBNP content. Further, the effect of YQFM on cardiac function and omentin change in 1, 7 and 14 days CAL-induced HF mice was evaluated and the omentin secretion in isolated subcutaneous (SCAT) and epicardial adipose tissue (EAT) after YQFM treatment were detected. YQFM could increase the circulating omentin content both in 14 days CAL-induced HF mice and isolated EAT. And increased omentin in conditioned medium (CM) could inhibit simulated ischemic/reperfusion (SI/R)-induced cardiomyocytes apoptosis. Moreover, YQFM could ameliorate myocardial apoptosis via positive regulation of AMPK, PI3 K/Akt and negative regulation of MAPKs signaling pathways. Ginsenoside Rd might partially mediated omentin-dependent protective effect of YQFM. Our findings indicated that regulation of cross-talk between adipose tissue and cardiomyocytes might be a potential target through which YQFM exerts cardioprotective effect apart from direct cardiomyocytes protection.

6.
J Hematol Oncol ; 12(1): 87, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477147

RESUMO

BACKGROUND: Haploidentical transplantation has been proposed as an effective treatment for severe aplastic anemia (SAA). The majority of patients have more than one HLA-haploidentical donor. Herein, we compared the outcomes between different donor-recipient relationships for optimal haploidentical donor selection in acquired SAA. METHODS: We conducted a multicenter study based on a registered database of 392 patients with SAA treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) between 2006 and 2018. In total, 223 patients received grafts from father donors, 47 from mother donors, 91 from siblings, 29 from children, and 2 from collateral donors. RESULTS: Of the 381 patients who survived more than 28 days, 379 (99.5%) recipients were engrafted. The 2-year overall survival (OS) was 86.6 ± 2.5%, 87.1 ± 4.9%, 84.3 ± 3.9%, and 92.2 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.706). The 2-year failure-free survival (FFS) was 82.8 ± 2.7%, 86.7 ± 5.1%, 80.8 ± 4.2%, and 92.5 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.508). There was no difference in the incidence of either acute or chronic graft-versus-host disease (GVHD) among the different donor sources in multivariate analyses. There were also no differences in the OS or FFS among the different donor sources in the Cox regression analysis. However, OS was significantly better in the patients with a shorter history of aplastic anemia (< 12 months), better performance status (ECOG scores 0-1), or moderate graft mononuclear cell (MNC) counts (6-10 × 108/kg), and in female recipients with male donors. The FFS was also higher in patients with a shorter history of aplastic anemia (< 12 months) and better performance status (ECOG scores 0-1). CONCLUSIONS: Fathers, mothers, siblings, and children are all suitable haploidentical donors for patients with SAA.

7.
Cancer Gene Ther ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31383953

RESUMO

Several brain tumors is closely related to the disorder of chromatin histone modification, whereas the epigenetic mechanisms of the incidence of highly malignant adult glioma is not yet deeply studied. Deletion or mutation of the MEN1 gene, which encodes the epigenetic regulator menin, specifically induces poorly differentiated neuroendocrine tumors; however, the biological and clinical importance of MEN1 in the nervous system remains poorly understood. Menin expression was robustly activated in 44.4% of adult gliomas. Abnormally high expression of menin was closely related to a shorter median survival time of 20 months, a larger tumor volume and a higher percentage of Ki67 staining. Interestingly, menin expression was also activated in the cytoplasm of tumor cells (38.8%) and was also closely related to the poor prognosis of patients with glioma. Importantly, in a screening of 96 types of small-molecule targeted histone modification regulators, menin inhibitors were found to significantly block the proliferation of adult glioma cells. Our findings confirm that menin is a potential biomarker of poor prognosis in adult gliomas, independent of the WHO grade. Targeting menin may effectively inhibit certain gliomas, and this information provides novel insight into therapeutic strategies for glioma.

8.
Chin Med J (Engl) ; 132(21): 2601-2611, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31373906

RESUMO

BACKGROUND: In consideration of characteristics and functions, extra-cellular signal-regulated protein kinase 5 (ERK5) signaling pathway could be a new target for spinal cord injury (SCI) treatment. Our study aimed to evaluate the roles of ERK5 signaling pathway in secondary damage of SCI. METHODS: We randomly divided 70 healthy Wistar rats into five groups: ten in the blank group, 15 in the sham surgery + BIX02188 (sham + B) group, 15 in the sham surgery + dimethyl sulfoxide (DMSO; sham + D) group, 15 in the SCI + BIX02188 (SCI + B) group, and 15 in the SCI + DMSO (SCI + D) group. BIX02188 is a specific inhibitor of the ERK5 signaling pathway. SCI was induced by the application of vascular clips (with the force of 30 g) to the dura on T10 level, while rats in the sham surgery group underwent only T9-T11 laminectomy. BIX02188 or DMSO was intra-thecally injected at 1, 6, and 12 h after surgery or SCI. Spinal cord samples were taken for testing at 24 h after surgery or SCI. RESULTS: Expression of phosphorylated-ERK5 (p-ERK5) significantly increased after SCI. Application of BIX02188 indeed inhibited ERK5 signaling pathway and reduced the degree of spinal cord tissue injury, neutrophil infiltration and proinflammatory cytokine expression, nuclear factor-κB (NF-κB) activation and apoptosis (measured by TdT-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling, expression of Fas-ligand, BCL2-associated X [Bax], and B-cell lymphoma-2 [Bcl-2]). Double immunofluorescence revealed activation of ERK5 in neurons and microglia after SCI. CONCLUSION: ERK5 signaling pathway was activated in spinal neurons and microglia, contributing to secondary injury of SCI. Moreover, inhibition of ERK5 signaling pathway could alleviate the degree of SCI, which might be related to its regulation of infiltration of inflammatory cells and release of inflammatory cytokines, expression of NF-κB and cell apoptosis.

9.
Cells ; 8(8)2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31382588

RESUMO

Tomato is the highest-value fruit/vegetable crop worldwide. However, the quality and yield of tomatoes are severely affected by late blight. MicroRNA482s (miR482s) are involved in the plant's immune system. In this study, miR482c was transiently and stably overexpressed in tomatoes in transgenic plants to explore its mechanism in tomato resistance against late blight. Transgenic tomato plants with transiently overexpressed miR482c displayed a larger lesion area than the control plants upon infection. Furthermore, compared with wild-type (WT) tomato plants, the transgenic tomato plants stably overexpressing miR482c displayed a decreased expression of target genes accompanied by lower peroxidase (POD), superoxide dismutase (SOD), and phenylalanine ammonia-lyase (PAL) activity activities and higher malondialdehyde (MDA) content, thereby leading to a decline in reactive oxygen species (ROS) scavenging ability and aggravating the damage of lipid peroxidation product accumulation on the cell membrane, eventually enhancing plant susceptibility. This finding indicates that miR482c may act as a negative regulator in tomato resistance by regulating nucleotide binding sites and leucine-rich repeat (NBS-LRR) expression levels and ROS levels.

10.
Aging (Albany NY) ; 11(15): 5646-5665, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31399552

RESUMO

BACKGROUND: Long noncoding RNAs have been known to be involved in multiple types of malignancies, including invasive breast cancer (IBC). This study aimed to explore the role of long noncoding RNAs in IBC and elucidate the potential molecular mechanisms. METHODS: Using TCGA microarray data analysis, we identified a long noncoding RNA, MIR210HG, highly expressed in IBC. Kaplan-Meier method and the log-rank test were used for survival analysis. The gain-of-function experiments were performed to assess the function of MIR210HG in IBC invasion and migration in both in vitro and in vivo settings. Bioinformatic analysis as well as luciferase reporter assay, rescue experiments and western blot assay revealed the mode of action of MIR210HG. RESULTS: The aberrantly enhanced MiR210HG expression predicted poor prognosis and lower survival rate. Knockdown of MiR210HG suppressed IBC cell invasion and metastasis both in vitro and in vivo. MiR-1226-3p was identified and validated to be the target miRNA of MiR210HG. Furthermore, MiR210HG functions as a competing endogenous RNAs (ceRNA) which sponges miR-1226-3p, therefore upregulates the expression of mucin1 (MUC1-C). CONCLUSIONS: Our study demonstrated that MiR210HG sponges miR-1226-3p to facilitate invasive breast cancer cell invasion and metastasis by regulating mucin-1c and EMT pathway, revealing the oncogenic role of MiR210HG in IBC cells.

11.
Anal Chim Acta ; 1078: 135-141, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31358211

RESUMO

Hypochlorous acid (HOCl)/hypochlorite (OCl-), important reactive oxygen species, play essential roles in many physiological and pathological progresses. Accordingly, we developed a novel dicyanomethylene-4H-pyran (DCM)-based probe DCM-OCl for colorimetric and near-infrared fluorescent turn-on detection of OCl-. The probe exhibited excellent selectivity and sensitivity for OCl- over other bio-related analytes with a detection limit of 80 nM. The excellent selectivity of DCM-OCl for OCl- was ascribed to specific oxidative cleavage of the dimethylthiocarbamate (DMTC) recognition unit by OCl-. Moreover, DCM-OCl exhibited an ultrafast turn-on response (<3 s) to OCl-, potentially allowing real-time detection of OCl-. Furthermore, DCM-OCl was successfully used to image endogenous/exogenous OCl- in living cells.


Assuntos
Benzopiranos/química , Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Tiocarbamatos/química , Benzopiranos/síntese química , Benzopiranos/toxicidade , Colorimetria/métodos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Limite de Detecção , Tiocarbamatos/síntese química , Tiocarbamatos/toxicidade
12.
Food Chem Toxicol ; 132: 110655, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31271762

RESUMO

Methyl protodioscin (MPD) is a steroid saponin which has been well known for its pharmacological properties. Herein, we evaluated the anti-cancer activity of MPD for proliferation inhibition and apoptosis induction in Hela cells. MPD was purified from the rhizoma of Polygonatum sibiricum primarily and identified by HPLC, UPLC-TOF-MS/MS and NMR analysis, respectively. Results showed that MPD repressed cell proliferation at IC50 of 18.49 µM, altered cell morphology, arrested the cell cycle in G2/M phase, facilitated the generation of intracellular ROS and led to cell apoptosis in a concentration-dependent manner. Furthermore, MPD treatment promoted death receptor pathway and mitochondrial pathway efficiently. The inhibition of Caspase-8 and Caspase-9 proteins in these pathways abolished the apoptosis significantly, further demonstrated the mechanism of MPD-induced apoptosis. These findings offer novel information that MPD may be considered as a possible natural anti-cancerous agent in the form of functional foods or medicinal products.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Diosgenina/análogos & derivados , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Polygonatum/química , Saponinas/farmacologia , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Diosgenina/isolamento & purificação , Diosgenina/farmacologia , Células HEK293 , Células HeLa , Humanos , Espécies Reativas de Oxigênio/metabolismo , Saponinas/isolamento & purificação
13.
Acta Pharmacol Sin ; 40(10): 1322-1333, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31316183

RESUMO

Abnormal wound healing by pulmonary artery smooth muscle cells (PASMCs) promotes vascular remodeling in hypoxia-induced pulmonary hypertension (HPH). Increasing evidence shows that both the mammalian target of rapamycin complex 1 (mTORC1) and nuclear factor-kappa B (NF-κB) are involved in the development of HPH. In this study, we explored the crosstalk between mTORC1 and NF-κB in PASMCs cultured under hypoxic condition and in a rat model of hypoxia-induced pulmonary hypertension (HPH). We showed that hypoxia promoted wound healing of PASMCs, which was dose-dependently blocked by the mTORC1 inhibitor rapamycin (5-20 nM). In PASMCs, hypoxia activated mTORC1, which in turn promoted the phosphorylation of NF-κB. Molecular docking revealed that mTOR interacted with IκB kinases (IKKs) and that was validated by immunoprecipitation. In vitro kinase assays and mass spectrometry demonstrated that mTOR phosphorylated IKKα and IKKß separately. Inhibition of mTORC1 decreased the level of phosphorylated IKKα/ß, thus reducing the phosphorylation and transcriptional activity of NF-κB. Bioinformatics study revealed that dipeptidyl peptidase-4 (DPP4) was a target gene of NF-κB; DPP4 inhibitor, sitagliptin (10-500 µM) effectively inhibited the abnormal wound healing of PASMCs under hypoxic condition. In the rat model of HPH, we showed that NF-κB activation (at 3 weeks) was preceded by mTOR signaling activation (after 1 or 2 weeks) in lungs, and administration of sitagliptin (1-5 mg/kg every day, ig) produced preventive effects against the development of HPH. In conclusion, hypoxia activates the crosstalk between mTORC1 and NF-κB, and increased DPP4 expression in PASMCs that leads to vascular remodeling. Sitagliptin, a DPP4 inhibitor, exerts preventive effect against HPH.

14.
J Agric Food Chem ; 67(26): 7378-7389, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31184118

RESUMO

The molecular mechanism of Juglone-induced cell cycle arrest and apoptosis in human endometrial cancer cells was investigated. Juglone was purified from the green husk of Carya cathayensis Sarg and identified by HPLC, LC-MS/MS, and NMR. At an IC50 of 20.81 µM, juglone significantly inhibited Ishikawa cell proliferation, as shown by S phase arrest mediated by inactivation of cyclin A protein ( p < 0.05). The ROS levels increased significantly after exposure to juglone, which paralleled increases in the mRNA and protein expression of p21 and decreases in the levels of CDK2, cdc25A, CHK1, and cyclin A. The expression of Bcl-2 and Bcl-xL was significantly down-regulated, whereas the expression of Bax, Bad and cyto c was up-regulated, and we later confirmed the involvement of the mitochondrial pathway in juglone-induced apoptosis. Our in vitro results stated that juglone can be studied further as an effective natural anticancer agent.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carya/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias do Endométrio/fisiopatologia , Naftoquinonas/farmacologia , Extratos Vegetais/farmacologia , Linhagem Celular Tumoral , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Feminino , Humanos , Naftoquinonas/química , Extratos Vegetais/química , Fosfatases cdc25/genética , Fosfatases cdc25/metabolismo
15.
Biol Blood Marrow Transplant ; 25(8): 1629-1636, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31048087

RESUMO

Immune-mediated neuropathies (IMNs) following hematopoietic stem cell transplantation have been described recently, which, excluding Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, may present with atypical patterns. This retrospective, nested, case-control study reviewed data from 3858 patients who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT) during the past 10 years at a single center, and 40 patients (1.04%) with IMN following haplo-HSCT were identified. Chronic graft-versus-host disease (cGVHD) (P = .043) and cytomegalovirus (CMV) viremia (P = .035) were recognized as independent risk factors for the development of IMN after haplo-HSCT. There were no significant differences in overall survival (P = .619), disease-free survival (P = .609), nonrelapse mortality (P = .87), or the incidence of relapse (P = .583) between patients with and without IMN after haplo-HSCT. However, patients with post-transplant IMN were at higher risk of developing cGVHD (P = .012) than patients who did not develop IMN. Twenty-four of the 40 patients with IMN (60%) attained neurologic improvement after treatments including vitamins B1 and B12 and/or immunomodulatory agents. However, 19 (47.5%) patients still had persistent motor/sensory deficits despite receiving timely treatment. More studies are needed to help develop standardized diagnostic and therapeutic strategies for patients with post-transplant IMN.

16.
Plant Sci ; 283: 375-384, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31128708

RESUMO

High temperature directly affects the yield and quality of crops. Plant Hsfs play vital roles in plant response to heat shock. In the present study, ZmHsf05 was isolated from maize (Zea mays L.) using homologous cloning methods. The sequencing analysis demonstrated that CDS of ZmHsf05 was 1080 bp length and encoded a protein containing 359 amino acids. The putative amino acid sequence of ZmHsf05 contained typical Hsf domains, such as DBD, OD, NLS and AHA motif. Subcellular localization assays displayed that the ZmHsf05 is localized to the nucleus. ZmHsf05 was expressed in many maize tissues and its expression level was increased by heat stress treatment. ZmHsf05 rescued the reduced thermotolerance of the athsfa2 mutant in Arabidopsis seedlings. Arabidopsis seedlings of ZmHsf05-overexpressing increased both the basal and acquired thermotolerances. After heat stress, the ZmHsf05-overexpressing lines showed enhanced survival rate and chlorophyll content compared with WT seedlings. The expression of Hsps was up-regulated in the ZmHsf05-overexpressing Arabidopsis lines after heat stress treatment. These results suggested that ZmHsf05 plays an important role in both basal and acquired thermotolerance in plants.


Assuntos
Fatores de Transcrição de Choque Térmico/fisiologia , Proteínas de Plantas/fisiologia , Termotolerância , Zea mays/fisiologia , Arabidopsis/genética , Fatores de Transcrição de Choque Térmico/genética , Resposta ao Choque Térmico , Mutação , Filogenia , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Termotolerância/genética , Técnicas do Sistema de Duplo-Híbrido , Zea mays/genética , Zea mays/metabolismo
17.
Expert Opin Ther Targets ; 23(6): 485-493, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30995133

RESUMO

INTRODUCTION: Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) is a novel negative regulator of innate and adaptive immune responses by binding to caspase-8. The binding of TIPE2 and caspase-8 can inhibit the activity of activating protein-1(AP-1) and nuclear factor-κB (NF-κB), ultimately promoting Fas-induced apoptosis in immune cells. Therefore, TIPE2-caspase-8-NF-κB signaling might serve as a biomarker and a potential target for therapeutic intervention. Areas covered: This review summarizes the biological functions of TIPE2 in the regulation of immune homeostasis and the underlying mechanism by which TIPE2 is regulated in the human immune response. The molecular pathway of TIPE2-caspase-8 signaling in chronic infections of hepatitis B virus and hepatitis C virus is also explained. Expert opinion: Considering the essential role of TIPE2 in linking immunity and inflammation, this protein may be a promising therapeutic target in chronic viral hepatitis. However, studies are necessary to elucidate the molecular mechanism of TIPE2 in the immunogenesis of viral hepatitis and to develop potential interventions for breaking immune tolerance in chronic hepatitis B virus infection. Additional studies are required to understand how TIPE2 binds to caspase-8.

18.
Blood Adv ; 3(8): 1303-1317, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015207

RESUMO

Poor graft function (PGF) and prolonged isolated thrombocytopenia (PT) remain life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Endothelial cells (ECs) play a crucial role in regulating hematopoiesis in the bone marrow (BM) microenvironment. However, whether the impaired BM ECs are responsible for defective hematopoiesis in PGF and PT patients requires clarification, and clinical management is challenging. Two prospective clinical trials were included in the current study. In the first trial (N = 68), PGF and PT patients demonstrated defective BM ECs pre-HSCT and impaired BM EC dynamic reconstitution at early time points post-HSCT, which was positively correlated with reactive oxygen species (ROS) levels. Receiver operating characteristic curves showed that BM EC < 0.1% pre-HSCT could identify high-risk patients with PGF and PT. The second trial enrolled patients (N = 35) with EC < 0.1% who accepted oral N-acetyl-l-cysteine (NAC; 400 mg 3 times per day) from -14 days pre-HSCT to +2 months post-HSCT continuously, whereas the remaining EC ≥ 0.1% patients (N = 39) received allo-HSCT only. Prophylactic NAC intervention was safe and effective in preventing the occurrence of PGF and PT in EC < 0.1% patients by promoting the dynamic reconstitution of BM ECs and CD34+ cells, along with reducing their ROS levels, which was further confirmed by in situ BM trephine biopsy analyses. These findings suggest that the impaired BM ECs pre-HSCT are responsible for the defective hematopoiesis in PGF and PT patients. Therefore, improvement of BM ECs through prophylactic NAC intervention may be a promising therapeutic approach to promote hematopoietic reconstitution post-HSCT. This trial was registered at www.clinicaltrials.gov as #NCT03236220 and #NCT02978274.

19.
Mar Drugs ; 17(4)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022939

RESUMO

Vasculogenic mimicry (VM) formed by tumor cells plays a vital role in the progress of tumor, because it provides nutrition for tumor cells and takes away the metabolites. Therefore, the inhibition of VM is crucial to the clinical treatment of tumors. In this study, we investigated the anti-tumor effect of a novel peptide, KVEPQDPSEW (AATP), isolated from abalone (Haliotis discus hannai) on HT1080 cells by migration, invasion analysis and the mode of action. The results showed that AATP effectively inhibited MMPs by blocking MAPKs and NF-κB pathways, leading to the downregulation of metastasis of tumor cells. Moreover, AATP significantly inhibited VM and pro-angiogenic factors, including VEGF and MMPs by suppression of AKT/mTOR signaling. In addition, molecular docking was used to study the interaction of AATP and HIF-1α, and the results showed that AATP was combined with an active site of HIF-1α by a hydrogen bond. The effect of AATP on anti-metastatic and anti-vascular in HT1080 cells revealed that AATP may be a potential lead compound for treatment of tumors in the future.


Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Gastrópodes/química , Neoplasias/tratamento farmacológico , Peptídeos/farmacologia , Adulto , Inibidores da Angiogênese/química , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Metaloproteinases da Matriz/metabolismo , NF-kappa B/metabolismo , Metástase Neoplásica , Neoplasias/irrigação sanguínea , Neoplasias/metabolismo , Neoplasias/patologia , Proteína Oncogênica v-akt/metabolismo , Peptídeos/química , Peptídeos/isolamento & purificação , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Esferoides Celulares/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , eIF-2 Quinase/metabolismo
20.
J Neuroimmunol ; 330: 143-151, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30884275

RESUMO

Seahorse has been used as a traditional medicine in Southeast Asian countries for a long time. A compound, 2'-Hydroxy-5'-Methoxyacetophenone (2H5M) isolated from seahorse, Hippocampus kuda, was tested for its anti-inflammatory effect in lipopolysaccharides (LPS)-stimulated BV-2 cells and RAW264.7 cells. MTT assay indicated that 2H5M has no cytotoxicity on two kinds of cells. The concentration of nitric oxide (NO) measured by Griess Reaction System showed that 2H5M could significantly inhibit the NO concentration. The ELISA results showed that 2H5M could suppress the secretion of TNF-α in a dose-dependent manner. Moreover, western blot analysis was utilized to measure the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways. Electrophoretic mobility shift assay (EMSA) demonstrated that 2H5M reduced NF-κB DNA binding activity. Furthermore, the molecular docking study showed that 2H5M can form active sites with NF-κB. Collectively, these results indicated that 2H5M possesses anti-inflammatory effects and may have a potential application in inflammatory disorders in the future.


Assuntos
Anti-Inflamatórios/farmacologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Inflamatórios/isolamento & purificação , Relação Dose-Resposta a Droga , Mediadores da Inflamação/antagonistas & inibidores , Camundongos , NF-kappa B/antagonistas & inibidores , Células RAW 264.7 , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologia , Smegmamorpha
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