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1.
Mol Biol Rep ; 51(1): 618, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38705956

ABSTRACT

BACKGROUND: Astragalus membranaceus is a plant of the Astragalus genus, which is used as a traditional Chinese herbal medicine with extremely high medicinal and edible value. Astragalus mongholicus, as one of the representative medicinal materials with the same origin of medicine and food, has a rising market demand for its raw materials, but the quality is different in different production areas. Growth-regulating factors (GRF) are transcription factors unique to plants that play important roles in plant growth and development. Up to now, there is no report about GRF in A. mongholicus. METHODS AND RESULTS: This study conducted a genome-wide analysis of the AmGRF gene family, identifying a total of nine AmGRF genes that were classified into subfamily V based on phylogenetic relationships. In the promoter region of the AmGRF gene, we successfully predicted cis-elements that respond to abiotic stress, growth, development, and hormone production in plants. Based on transcriptomic data and real-time quantitative polymerase chain reaction (qPCR) validation, the results showed that AmGRFs were expressed in the roots, stems, and leaves, with overall higher expression in leaves, higher expression of AmGRF1 and AmGRF8 in roots, and high expression levels of AmGRF1 and AmGRF9 in stems. CONCLUSIONS: The results of this study provide a theoretical basis for the further exploration of the functions of AmGRFs in plant growth and development.


Subject(s)
Gene Expression Regulation, Plant , Phylogeny , Plant Proteins , Transcription Factors , Gene Expression Regulation, Plant/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Astragalus propinquus/genetics , Astragalus propinquus/metabolism , Multigene Family , Genome, Plant , Gene Expression Profiling/methods , Promoter Regions, Genetic/genetics , Astragalus Plant/genetics , Astragalus Plant/metabolism , Plant Roots/genetics , Plant Roots/metabolism , Stress, Physiological/genetics , Transcriptome/genetics , Plant Growth Regulators/metabolism
2.
Environ Res ; 248: 118321, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38307186

ABSTRACT

BACKGROUND: Metalloestrogens are metals and metalloid elements with estrogenic activity found everywhere. Their impact on human health is becoming more apparent as human activities increase. OBJECTIVE: Our aim is to conduct a comprehensive systematic review and meta-analysis of observational studies exploring the correlation between metalloestrogens (specifically As, Sb, Cr, Cd, Cu, Se, Hg) and Gestational Diabetes Mellitus (GDM). METHODS: PubMed, Web of Science, and Embase were searched to examine the link between metalloestrogens (As, Sb, Cr, Cd, Cu, Se, and Hg) and GDM until December 2023. Risk estimates were derived using random effects models. Subgroup analyses were conducted based on study countries, exposure sample, exposure assessment method, and detection methods. Sensitivity analyses and adjustments for publication bias were carried out to assess the strength of the findings. RESULTS: Out of the 389 articles identified initially, 350 met our criteria and 33 were included in the meta-analysis, involving 141,175 subjects (9450 cases, 131,725 controls). Arsenic, antimony, and copper exposure exhibited a potential increase in GDM risk to some extent (As: OR = 1.28, 95 % CI [1.08, 1.52]; Sb: OR = 1.73, 95 % CI [1.13, 2.65]; Cu: OR = 1.29, 95 % CI [1.02, 1.63]), although there is a high degree of heterogeneity (As: Q = 52.93, p < 0.05, I2 = 64.1 %; Sb: Q = 31.40, p < 0.05, I2 = 80.9 %; Cu: Q = 21.14, p < 0.05, I2 = 71.6 %). Conversely, selenium, cadmium, chromium, and mercury exposure did not exhibit any association with the risk of GDM in our study. DISCUSSION: Our research indicates that the existence of harmful metalloestrogens in the surroundings has a notable effect on the likelihood of GDM. Hence, we stress the significance of environmental elements in the development of GDM and the pressing need for relevant policies and measures.


Subject(s)
Arsenic , Diabetes, Gestational , Mercury , Pregnancy , Female , Humans , Cadmium , Copper , Observational Studies as Topic
3.
J Sci Food Agric ; 104(5): 2750-2760, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-37994167

ABSTRACT

BACKGROUND: Cold plasma exhibits broad applicability in the realm of fish sterilization and preservation. The combination process of plasma-activated water and dielectric barrier discharge (PAW-DBD) was optimized, and its disinfection effects on bass fillets were studied. RESULTS: The best conditions for disinfection of PAW-DBD were as follows. Bass fillets were soaked in PAW for 150 s, and then treated by DBD system at 160 kV for 180 s. The total viable count (TVC) reduced by 1.68 log CFU g-1 . On the 15th day of refrigerated storage, TVC of PAW-DBD group was 7.01 log CFU g-1 , while the PAW and DBD group exhibited a TVC of 7.02 and 7.01 log CFU g-1 on day 12; the TVC of the control group was 7.13 log CFU g-1 on day 6. The sensory score, water-holding capacity, and 2-thiobarbituric acid reactive substance values of the PAW-DBD group were significantly higher than those of PAW and DBD group (P < 0.05), whereas the TVC, Pseudomonas spp. count, and pH of the group were significantly lower (P < 0.05) during refrigerated storage. CONCLUSION: PAW-DBD treatment can enhance the disinfection effect, maintain good quality, and extend the storage period of bass fillets. © 2023 Society of Chemical Industry.


Subject(s)
Bass , Perciformes , Plasma Gases , Animals , Food Preservation , Plasma Gases/pharmacology , Plasma Gases/chemistry , Seafood/analysis , Water
4.
BMC Vet Res ; 19(1): 272, 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38087269

ABSTRACT

BACKGROUND: Animal diseases have always been a serious threat to livestock breeding, and the establishment of a biosecurity barrier is important for disease prevention and control. Based on the investigations conducted in seven provinces located farms, this study aimed to explore the current biosecurity levels of farms in China, construct a biosecurity evaluation system, calculate the biosecurity levels of farms using the rank sum ratio comprehensive evaluation method, and develop an empirical analysis of the factors influencing biosecurity levels. RESULTS: The results show that the greater the cost of biosecurity invested, the greater the level of biosecurity. Male farmers, educational attainment and participation in technical training had a significant positive effect on biosecurity levels. In addition, biosecurity levels first decreased and then increased as the scale of farming increased. The study also found that the more people in the household engaged in farming, the higher the biosecurity level of the farm. And farms that joined cooperatives had higher levels of biosecurity. CONCLUSION: The rank sum ratio method can evaluate the index system, so as to obtain a comprehensive index RSR value that can be compared, and the operation steps are simple and effective. By taking measures such as improving the comprehensive quality of farmers and increasing the investment in human, material and financial resources for biosecurity, the biosecurity level of farms can be effectively improved and animal diseases can be effectively prevented and controlled.


Subject(s)
Animal Diseases , Swine Diseases , Swine , Male , Animals , Humans , Farms , Animal Husbandry/methods , Biosecurity , Animal Diseases/prevention & control , China , Swine Diseases/prevention & control
5.
Food Microbiol ; 101: 103891, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34579851

ABSTRACT

In recent years, more attention has been paid to the application of cold plasma (CP) in eliminating foodborne pathogenic bacteria. This work investigated CP effects on inactivation kinetics and cell envelopes of Listeria monocytogenes (L. monocytogenes) and Salmonella Enteritidis (S. Enteritidis). Bacterial suspensions were treated with dielectric barrier discharge atmospheric CP at 75 kV for different treatment time. Three regression models were tested for estimating inactivation kinetics. Reactive species generated in plasma, the appearance and integrity of bacterial cells, the activity and secondary structure of enzymes in the cell envelope, and molecular docking, were measured for evaluating the envelope damages. Results indicated that Log-linear model was suitable for L. monocytogenes and the Weibull model was suitable for S. Enteritidis. S. Enteritidis was more sensitive to short-lived reactive species (such as OH radicals) in plasma than L. monocytogenes, and the cell envelope of S. Enteritidis was more severely damaged (the increased membrane permeability and leakage of intracellular substances) after plasma treatment. Interestingly, compared with S. Enteritidis, the decrease in the activity of enzymes existing in the cell envelope of L. monocytogenes did not contribute significantly to the death of bacteria. Molecular docking further suggested that the decrease in the enzyme activity might be due to the modification of the enzyme, by the interaction between reactive species in plasma (H2O2) and amino acid residues of the enzyme through the hydrogen bond.


Subject(s)
Cell Membrane , Cold Temperature , Listeria monocytogenes , Plasma Gases , Salmonella enteritidis , Cell Membrane/drug effects , Hydrogen Peroxide , Kinetics , Listeria monocytogenes/drug effects , Molecular Docking Simulation , Plasma Gases/pharmacology , Salmonella enteritidis/drug effects
6.
J Cell Mol Med ; 25(10): 4814-4825, 2021 05.
Article in English | MEDLINE | ID: mdl-33792181

ABSTRACT

HYOU1 is upregulated in many kinds of cancer cells, and its high expression is associated with tumour invasiveness and poor prognosis. However, the role of HYOU1 in papillary thyroid cancer (PTC) development and progression remains to be elucidated. Here, we reported that HYOU1 was highly expressed in human PTC and associated with poor prognosis. HYOU1 silencing suppressed the proliferation, migration and invasion of PTC cells. Mechanistic analyses showed that HYOU1 silencing promoted oxidative phosphorylation while inhibited aerobic glycolysis via downregulating LDHB at the posttranscriptional level. We further confirmed that the 3'UTR of LDHB mRNA is the indirect target of HYOU1 silencing and HYOU1 silencing increased miR-375-3p levels. While LDHB overexpression significantly suppressed the inhibitory effects of HYOU1 silencing on aerobic glycolysis, proliferation, migration and invasion in PTC cells. Taken together, our findings suggest that HYOU1 promotes glycolysis and malignant progression in PTC cells via upregulating LDHB expression, providing a potential target for developing novel anticancer agents.


Subject(s)
Gene Expression Regulation, Neoplastic , Glycolysis , HSP70 Heat-Shock Proteins/metabolism , Lactate Dehydrogenases/metabolism , RNA Stability , RNA, Messenger/chemistry , Thyroid Neoplasms/pathology , Apoptosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Movement , Cell Proliferation , HSP70 Heat-Shock Proteins/genetics , Humans , Lactate Dehydrogenases/genetics , Neoplasm Invasiveness , RNA, Messenger/genetics , RNA, Messenger/metabolism , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/metabolism , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/genetics , Thyroid Neoplasms/metabolism , Tumor Cells, Cultured
7.
J Cell Mol Med ; 25(9): 4395-4407, 2021 05.
Article in English | MEDLINE | ID: mdl-33797839

ABSTRACT

Drug resistance is often developed during clinical chemotherapy of ovarian cancers. The ubiquitin-like protein interferon-stimulated gene 15 (ISG15) is possibly dependent on tumour context to promote or suppress progression of various tumours. The ubiquitin-like protein interferon-stimulated gene 15 (ISG15) was decreased in cisplatin-resistant ovarian cancer cells. The current study identified that both ectopic wild type and nonISGylatable mutant ISG15 expression inhibited CSC-like phenotypes of cisplatin-resistant ovarian cancer cells. Moreover, ectopic ISG15 expression suppressed tumour formation in nude mice. In addition, ISG15 downregulation promoted CSC-like features of cisplatin-sensitive ovarian cancer cells. Furthermore, low ISG15 expression was associated with poor prognosis in patients with ovarian cancer. Transcriptional repressor Krüppel-like factor 12 (KLF12) downregulated ISG15 in cisplatin-resistant cells. Our data indicated that downregulating ISG15 expression, via weakening effect of KLF12, might be considered as new therapeutic strategy to inhibit CSC phenotypes in the treatment of cisplatin-resistant ovarian cancer.


Subject(s)
Cisplatin/pharmacology , Cytokines/metabolism , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic/drug effects , Kruppel-Like Transcription Factors/metabolism , Neoplastic Stem Cells/pathology , Ovarian Neoplasms/pathology , Ubiquitins/metabolism , Animals , Antineoplastic Agents/pharmacology , Apoptosis , Cell Movement , Cell Proliferation , Cytokines/genetics , Female , Humans , Kruppel-Like Transcription Factors/genetics , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Tumor Cells, Cultured , Ubiquitins/genetics , Xenograft Model Antitumor Assays
8.
Cancer Cell Int ; 21(1): 446, 2021 Aug 23.
Article in English | MEDLINE | ID: mdl-34425836

ABSTRACT

BACKGROUND: Processed extracts from toad skin and parotoid gland have long been used to treat various illnesses including cancer in many Asian countries. Recent studies have uncovered a family of bufadienolides as the responsible pharmacological compounds, and the two major molecules, cinobufagin and bufalin, have been shown to possess robust antitumor activity; however, the underlying mechanisms remain poorly understood. METHODS: Intracellular reactive oxygen species (ROS) were measured by DCFH-DA staining and flow cytometry, and DNA damage was analyzed by immunofluorescent staining and the alkaline comet assay. Cytotoxicity was measured by MTT as well as colony formation assays, and cell cycle and apoptosis were analyzed by flow cytometry. In addition, apoptosis was further characterized by TUNEL and mitochondrial membrane potential assays. RESULTS: Here we showed that sublethal doses of cinobufagin suppressed the viability of many cancer but not noncancerous cell lines. This tumor-selective cytotoxicity was preceded by a rapid, cancer-specific increase in cellular ROS and was significantly reduced by the ROS inhibitor N-acetyl cysteine (NAC), indicating oxidative stress as the primary source of cinobufagin-induced cancer cell toxicity. Sublethal cinobufagin-induced ROS overload resulted in oxidative DNA damage and intense replication stress in cancer cells, leading to strong DNA damage response (DDR) signaling. Subsequent phosphorylation of CDC25C and stabilization of p53 downstream of DDR resulted in activation of the G2/M checkpoint followed by induction of apoptosis. These data indicate that cinobufagin suppresses cancer cell viability via DDR-mediated G2 arrest and apoptosis. CONCLUSION: As elevated oxidative pressure is shared by most cancer cells that renders them sensitive to further oxidative insult, these studies suggest that nontoxic doses of cinobufagin can be used to exploit a cancer vulnerability for induction of cancer-specific cytotoxicity.

9.
Chemistry ; 27(5): 1713-1723, 2021 Jan 21.
Article in English | MEDLINE | ID: mdl-33201563

ABSTRACT

Urchin-type cobalt phosphide microparticles assembled by nanorod were encapsulated in a graphene framework membrane (CoP@GF), and used as a binder-free electrode for alkali metal ion batteries. Electrochemical measurements indicate that this membrane exhibits enhanced reversible lithium, sodium, and potassium storage capabilities. Moreover, the energy storage properties of CoP@GF electrodes in alkali metal ion batteries display an order of Li>Na>K. DFT calculations on adsorption energy of CoP surfaces for Li, Na, and K indicated that CoP surfaces were more favorable to transfer electrons to Li atoms than Na and K, and the surface reactivity can be ordered as Li-CoP>Na-CoP>K-CoP; thus, CoP@GF exhibits better storage capacity for lithium. This work provides experimental and theoretical basis for understanding the electrochemical performance of cobalt phosphide-based membranes for alkali metal ion batteries.

10.
Andrologia ; 53(7): e14085, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34091926

ABSTRACT

First, the bioinformatics database was used to predict the potential targets and signaling pathways of pulmonary fibrosis (PF) leading to erectile dysfunction (ED), and bleomycin sulfate was used to create a PF rat model. Then, enzyme-linked immunosorbent assay (ELISA), Western blotting, Real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect the expression of sex hormones and related proteins and mRNA, and Hematoxylin and eosin (H&E) staining was used to compare the pathological changes of penile tissue. The results showed that, compared with group A, cyclic guanosine phosphate (cGMP) content in group B decreased, protein kinase CGMP-dependent 1(PKG1) and nitric oxide synthase 3 (eNOS) protein and mRNA expression were down-regulated, and phosphodiesterase 5A (PDE5A) protein and mRNA expression was up-regulated (p < .05); the penile tissue of rats in group B had pathological damage. And there was no change in sex hormone-related indicators in the two groups (p > .05). Therefore, PF inhibits erectile function by inhibiting the cGMP-PKG pathway and reducing the expression of eNOS and PKG1 protein and mRNA. And by up-regulating the expression of PDE5A to impair erectile function.


Subject(s)
Erectile Dysfunction , Pulmonary Fibrosis , Animals , Computational Biology , Humans , Male , Nitric Oxide Synthase Type III , Penile Erection , Penis , Rats , Rats, Sprague-Dawley
11.
J Cell Mol Med ; 24(1): 562-572, 2020 01.
Article in English | MEDLINE | ID: mdl-31657880

ABSTRACT

Solid tumour frequently undergoes metabolic stress during tumour development because of inadequate blood supply and the high nutrient expenditure. p53 is activated by glucose limitation and maintains cell survival via triggering metabolic checkpoint. However, the exact downstream contributors are not completely identified. BAG3 is a cochaperone with multiple cellular functions and is implicated in metabolic reprogramming of pancreatic cancer cells. The current study demonstrated that glucose limitation transcriptionally suppressed BAG3 expression in a p53-dependent manner. Importantly, hinderance of its down-regulation compromised cellular adaptation to metabolic stress triggered by glucose insufficiency, supporting that BAG3 might be one of p53 downstream contributors for cellular adaptation to metabolic stress. Our data showed that ectopic BAG3 expression suppressed p53 accumulation via direct interaction under metabolic stress. Thereby, the current study highlights the significance of p53-mediated BAG3 suppression in cellular adaptation to metabolic stress via facilitating p53 accumulation.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Apoptosis Regulatory Proteins/genetics , Gene Expression Regulation , Glucose Metabolism Disorders/prevention & control , Transcription, Genetic , Tumor Suppressor Protein p53/metabolism , Adaptor Proteins, Signal Transducing/antagonists & inhibitors , Adaptor Proteins, Signal Transducing/metabolism , Apoptosis , Apoptosis Regulatory Proteins/antagonists & inhibitors , Apoptosis Regulatory Proteins/metabolism , Cell Cycle , Cell Movement , Cell Proliferation , Glucose Metabolism Disorders/etiology , Glucose Metabolism Disorders/metabolism , Glucose Metabolism Disorders/pathology , HCT116 Cells , Humans , MCF-7 Cells , Tumor Suppressor Protein p53/genetics
12.
Med Sci Monit ; 26: e918523, 2020 Jan 29.
Article in English | MEDLINE | ID: mdl-31995551

ABSTRACT

BACKGROUND Intrathecal dexmedetomidine (DEX) can improve the blockade of spinal anesthesia, but there is no clear conclusion on whether it has an effect on the fetus during cesarean section. Our meta-analysis evaluated the safety and efficacy of intrathecal DEX in cesarean delivery. MATERIAL AND METHODS We searched Cochrane, Embase, PubMed, and CBM for eligible studies, and used the Revised Cochrane Risk of Bias Tool (RoB 2.0) to assess the risk of bias of each study. RevMan was used for statistical analyses. We have registered this meta-analysis on PROSPERO (CRD42019120995). RESULTS The meta-analysis included 10 RCTs, but only 5 were prospectively registered. The results of preregistration studies, including the 1- or 5-min Apgar score (mean difference [MD], -0.03; 95% confidence intervals [CI], -0.16 to 0.10; P=0.64 or MD, 0.00; 95% CI, -0.09 to 0.09; P=1), the umbilical arterial oxygen or carbon dioxide partial pressure (MD, 0.90; 95% CI, -4.92 to 6.72; P=0.76 or MD, 1.20; 95% CI, -2.06 to 4.46; P=0.47), and the cord blood pH (MD, -0.01; 95% CI, -0.05 to 0.03; P=0.72), showed that intrathecal DEX had no significant difference in neonatal outcomes compared with placebo. In maternal outcomes, intrathecal DEX significantly prolonged postoperative pain-free period and reduced the incidence of postoperative shivering, which did not increase spinal anesthesia-associated adverse effects. CONCLUSIONS Intrathecal DEX is safe for the fetus during cesarean section and can improve the blockade effects of spinal anesthesia on puerperae.


Subject(s)
Anesthesia, Spinal , Cesarean Section , Fetus/physiology , Apgar Score , Dexmedetomidine/adverse effects , Dexmedetomidine/pharmacology , Female , Fetus/drug effects , Humans , Infant, Newborn , Postoperative Period , Pregnancy , Pregnancy Outcome , Publication Bias , Risk , Shivering/drug effects , Visual Analog Scale
13.
J Cell Mol Med ; 23(8): 5006-5016, 2019 08.
Article in English | MEDLINE | ID: mdl-31119886

ABSTRACT

BAG3 is constitutively expressed in multiple types of cancer cells and its high expression is associated with tumour progression and poor prognosis of PDAC. However, little is known about the role of BAG3 in the regulation of stromal microenvironment of PDAC. The current study demonstrated that beside PDAC tumour cells, BAG3 was also expressed in some activated stroma cells in PDAC tissue, as well as in activated PSCs. In addition, the current study demonstrated that BAG3 expression in PSCs was involved in maintenance of PSCs activation and promotion of PDACs invasion via releasing multiple cytokines. The current study demonstrated that BAG3-positive PSCs promoted invasion of PDACs via IL-8, MCP1, TGF-ß2 and IGFBP2 in a paracrine manner. Furthermore, BAG3 sustained PSCs activation through IL-6, TGF-ß2 and IGFBP2 in an autocrine manner. Thereby, the current study provides a new insight into the involvement of BAG3 in remodelling of stromal microenvironment favourable for malignant progression of PDAC, indicating that BAG3 might serve as a potential target for anti-fibrosis of PDAC.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Apoptosis Regulatory Proteins/metabolism , Carcinoma, Pancreatic Ductal/metabolism , Pancreatic Neoplasms/metabolism , Pancreatic Stellate Cells/metabolism , Tumor Microenvironment/genetics , Adaptor Proteins, Signal Transducing/genetics , Apoptosis Regulatory Proteins/genetics , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Cytokines/metabolism , Humans , Immunohistochemistry , Insulin-Like Growth Factor Binding Proteins/genetics , Insulin-Like Growth Factor Binding Proteins/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Interleukin-8/genetics , Interleukin-8/metabolism , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism
14.
Biochem Biophys Res Commun ; 513(4): 852-856, 2019 06 11.
Article in English | MEDLINE | ID: mdl-31000199

ABSTRACT

Glucose limitation activates p53, which functions as an adaptive response to maintain cell survival. However, p53 is frequently deleted or mutated in a variety of tumors, while most cancer cells can acclimatize themselves to metabolically unfavorable surrounding, indicating that alternative mechanisms other than p53 transactivation underly adaptive response of cancer cells with p53 deletion or mutation to metabolically hostile environment. Sestrin 2 (SESN2) is a p53 downstream target, which plays a protective role against various stressful stimuli, such as genotoxic, energetic, and oxidative stress. In the current study, we demonstrated that SESN2 transcript was stabilized by glucose limitation at the posttranscriptional level irrespective of p53 status. Importantly, SESN2 also protected cells from metabolic stress triggered by glucose limitation in a p53-independent manner. Our data indicated that stabilization of SESN2 transcript might be an alternative adaptive response to metabolic stress other than p53 activation. Thereby, the current study highlights the significance of stabilization of SESN2 transcript in adaptation of cells with p53 deletion or mutation to metabolic stress.


Subject(s)
Cytoprotection , Nuclear Proteins/metabolism , Stress, Physiological , Tumor Suppressor Protein p53/metabolism , Animals , Cell Line, Tumor , Glucose/deficiency , Mice , RNA Stability , RNA, Messenger/genetics , RNA, Messenger/metabolism
15.
Microvasc Res ; 125: 103880, 2019 09.
Article in English | MEDLINE | ID: mdl-31082448

ABSTRACT

OBJECTIVE: This study aimed to compare cutaneous microvascular function in coronary artery disease (CAD) patients including obstructive CAD (ObCAD) (n = 133) and non-obstructive CAD (NObCAD) (n = 129) with that of age and gender matched healthy controls (n = 83) using laser speckle contrast imaging (LSCI) coupled with post-occlusive reactive hyperemia (PORH). METHODS: LSCI system was used to assess subjects' cutaneous blood flow at rest and during PORH. CAD patients were divided into ObCAD and NObCAD group based on coronary angiography results. RESULTS: Microvascular reactivity induced by PORH was significantly reduced in NObCAD group in comparison with control or ObCAD group (p < 0.05). Although, the PORH responses of ObCAD patients were also attenuated compared to controls, they did not reach statistical significance (p > 0.05). CONCLUSION: NObCAD patients are more likely to develop cutaneous microvascular dysfunction than ObCAD patients, which may reflect the difference in the underlying mechanisms of myocardial ischemia.


Subject(s)
Angina, Stable/diagnosis , Coronary Artery Disease/diagnosis , Coronary Stenosis/diagnosis , Laser-Doppler Flowmetry , Microcirculation , Skin/blood supply , Aged , Angina, Stable/physiopathology , Blood Flow Velocity , Case-Control Studies , Coronary Artery Disease/physiopathology , Coronary Stenosis/physiopathology , Cross-Sectional Studies , Female , Humans , Hyperemia/physiopathology , Male , Middle Aged , Predictive Value of Tests , Prognosis
16.
Nanomedicine ; 21: 102066, 2019 10.
Article in English | MEDLINE | ID: mdl-31351237

ABSTRACT

A single nanodrug delivery system for combined delivery of paclitaxel and doxorubicin that integrates high co-loading efficiency, synchronous co-delivery of combined drugs, controllable drug release, and maintains the drug combination at fixed synergistic ratios has been proven to be challenging. Here, we report a redox dual-responsive prodrug nanosystem consisting of a paclitaxel-doxorubicin heterodimeric prodrug with a thioether bond linkage to effectively co-deliver two therapeutic drugs. The heterodimeric prodrug could self-assemble into uniform nanoaggregates containing DSPE-PEG2K with a precise drug co-loading ratio in water, and possessed a high co-loading content. We demonstrated that this nanosystem provided strong synergistic effects in MCF-7 and 4 T1 cells. In vivo, this nanosystem results in a long blood circulation, high accumulation in the tumor, and significant inhibition of tumor growth in BALB/c mice bearing 4 T1 tumors. Such a simple, safe, and efficient heterodimeric prodrug nanosystem exhibits great potential for clinical translation in future combination chemotherapy treatments.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Nanoparticles , Prodrugs , Animals , Antineoplastic Combined Chemotherapy Protocols/chemistry , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Doxorubicin/chemistry , Doxorubicin/pharmacokinetics , Doxorubicin/pharmacology , Female , Humans , MCF-7 Cells , Mice, Inbred BALB C , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Paclitaxel/chemistry , Paclitaxel/pharmacokinetics , Paclitaxel/pharmacology , Prodrugs/chemistry , Prodrugs/pharmacokinetics , Prodrugs/pharmacology , Xenograft Model Antitumor Assays
17.
Med Mycol ; 56(4): 458-468, 2018 Jun 01.
Article in English | MEDLINE | ID: mdl-29420779

ABSTRACT

Iron-sulfur clusters (ISC) are indispensable cofactors for essential enzymes in various cellular processes. In the model yeast Saccharomyces cerevisiae, the precursor of ISCs is exported from mitochondria via a mitochondrial ABC transporter Atm1 and used for cytosolic and nuclear ISC protein assembly. Although iron homeostasis has been implicated in the virulence of the human fungal pathogen Cryptococcus neoformans, the key components of the ISC biosynthesis pathway need to be fully elucidated. In the current study, a homolog of S. cerevisiae Atm1 was identified in C. neoformans, and its function was characterized. We constructed C. neoformans mutants lacking ATM1 and found that deletion of ATM1 affected mitochondrial functions. Furthermore, we observed diminished activity of the cytosolic ISC-containing protein Leu1 and the heme-containing protein catalase in the atm1 mutant. These results suggested that Atm1 is required for the biosynthesis of ISCs in the cytoplasm as well as heme metabolism in C. neoformans. In addition, the atm1 mutants were avirulent in a murine model of cryptococcosis. Overall, our results demonstrated that Atm1 plays a critical role in iron metabolism and virulence for C. neoformans.


Subject(s)
Cryptococcus neoformans/genetics , Cryptococcus neoformans/pathogenicity , Fungal Proteins , Iron/metabolism , Mitochondria/metabolism , ATP-Binding Cassette Transporters/genetics , Animals , Cryptococcosis/metabolism , Cryptococcosis/pathology , Cryptococcus neoformans/metabolism , Cryptococcus neoformans/ultrastructure , Disease Models, Animal , Female , Fungal Proteins/genetics , Fungal Proteins/metabolism , Gene Expression Regulation, Fungal , Humans , Iron-Sulfur Proteins/biosynthesis , Iron-Sulfur Proteins/genetics , Leucine/biosynthesis , Mice , Mice, Inbred C57BL , Oxidative Stress/genetics , Saccharomyces cerevisiae/genetics , Sequence Deletion , Superoxide Dismutase/genetics , Virulence/genetics
18.
Acta Biochim Biophys Sin (Shanghai) ; 50(9): 869-879, 2018 Sep 01.
Article in English | MEDLINE | ID: mdl-30124738

ABSTRACT

To explore the association between clock circadian regulator circadian locomotor output cycles kaput gene (CLOCK) and the forming of atherosclerotic plaques and its underlying mechanisms, mouse aortic endothelial cells (MAECs) and atherosclerosis (AS) mouse model were recruited for our study. The apoE gene knockout mouse was used as the model of AS and we accelerated the formation of unstable plaques through the combination of carotid artery ligation and high-fat (HF) diet administration (0.2% cholesterol, 20% fat). The mRNA and protein expressions of CLOCK in peripheral blood monouclear cells of acute coronary syndrome (ACS) patients or mouse AS model were detected by qPCR, western blot analysis and immunohistochemical staining. The number of adherent cells and atherosclerotic plaques was counted to assess the effects of CLOCK on the progression of ACS, and adherence-associated genes, such as vascular cell adhesion molecule (VCAM)-1, C-C motif chemokine ligand 2 (CCL-2), and CCL-5. The results showed that CLOCK expression was significantly increased in both ACS patients and AS mouse model. The levels of CLOCK, leukemia inhibitory factor (LIF), intercellular adhesion molecule 1 (ICAM-1), perilipin 2 (ADFP), nuclear factor kappa B (NF-κB), and plasminogen activator inhibitor-1 (PAI-1), as well as the number of atherosclerotic plaques were elevated in the AS mouse model, as compared with the control group. Chromatin immunoprecipitation assay showed that CLOCK bound directly to the promoter of PAI-1 gene and CLOCK could positively regulate the expressions of LIF, ICAM-1, ADFP, NF-κB, and PAI-1. Reduction of CLOCK expression would decrease the expressions of VCAM-1, CCL-2, and CCL-5, and the number of adherent cells and atherosclerotic plaques, but these effects were neutralized when PAI-1 was simultaneously overexpressed in either mouse model or MAECs. Our results demonstrate that CLOCK overexpression triggers the formation of atherosclerotic plaques by directly upregulating PAI-1 expression.


Subject(s)
Acute Coronary Syndrome/genetics , CLOCK Proteins/genetics , Plaque, Atherosclerotic/genetics , Plasminogen Activator Inhibitor 1/genetics , Up-Regulation/genetics , Acute Coronary Syndrome/metabolism , Acute Coronary Syndrome/pathology , Aged , Animals , Apolipoproteins E/genetics , Apolipoproteins E/metabolism , CLOCK Proteins/metabolism , Cells, Cultured , Diet, High-Fat/adverse effects , Endothelial Cells/metabolism , Humans , Male , Mice, Inbred C57BL , Mice, Knockout , Middle Aged , Plaque, Atherosclerotic/etiology , Plaque, Atherosclerotic/metabolism , Plasminogen Activator Inhibitor 1/metabolism , RNA Interference
19.
Appl Microbiol Biotechnol ; 101(7): 2967-2978, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28097405

ABSTRACT

Mesorhizobium alhagi, a legume-symbiont soil bacterium that forms nodules with the desert plant Alhagi sparsifolia, can produce large amounts of exopolysaccharide (EPS) using mannitol as carbon source. However, the role of EPS in M. alhagi CCNWXJ12-2T, an EPS-producing rhizobium with high salt resistance, remains uncharacterized. Here, we studied the role of EPS in M. alhagi CCNWXJ12-2T using EPS-deficient mutants constructed by transposon mutagenesis. The insertion sites of six EPS-deficient mutants were analyzed using single primer PCR, and two putative gene clusters were found to be involved in EPS synthesis. EPS was extracted and quantified, and EPS production in the EPS-deficient mutants was decreased by approximately 25 times compared with the wild-type strain. Phenotypic analysis revealed reduced salt resistance, antioxidant capacity, and cell motility of the mutants compared with the wild-type strain. In conclusion, our results indicate that EPS can influence cellular Na+ content and antioxidant enzyme activity, as well as play an important role in the stress adaption and cell motility of M. alhagi CCNWXJ12-2T.


Subject(s)
Mesorhizobium/drug effects , Mesorhizobium/physiology , Polysaccharides, Bacterial/genetics , Polysaccharides, Bacterial/metabolism , Sodium Chloride/pharmacology , Stress, Physiological/drug effects , Antioxidants/metabolism , Base Sequence , DNA Transposable Elements , Fabaceae/microbiology , Mesorhizobium/genetics , Movement/drug effects , Multigene Family , Mutagenesis , Plant Roots/microbiology , Polysaccharides, Bacterial/biosynthesis , Polysaccharides, Bacterial/deficiency , Stress, Physiological/genetics , Symbiosis
20.
Food Microbiol ; 60: 142-6, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27554156

ABSTRACT

The effect of in-package cold plasmas (CP) was studied on microbiological shelf life and surface lightness of fresh chicken fillets (pectoralis major). Chicken fillets were packaged in food trays in air or modified atmosphere (MA) gas (O2:CO2:N2 = 65:30:5) and stored at 4 °C after exposed to an in-package cold plasma (80 kV for 180 s) treatment. Populations of mesophiles, psychrophiles, and pseudomonas spp. were measured as indicators for microbiological shelf life and CIELAB L(∗) values as an indicator for raw meat appearance. Results show that regardless of microbial type, there were no significant differences in microbial counts between the control and CP treated chicken fillets packed in air. However, in the MA packages, microbial counts were consistently lower than the non-treated control during refrigerated storage. Regardless of CP treatment, the microbial counts on the samples packed in air were much higher than in MA. They were more than 6 logs cfu/g in air compared to fewer than 4 logs cfu/g in MA after 7 d storage and fewer than 6 logs cfu/g after 14 d storage. Regardless of CP treatment and gas composition in package, there were no significant differences in the surface L(∗) value between the fillets pre-treatment and those after storage at 4 °C. These results demonstrate that the effects of in-package CP treatments on microbiological shelf life of fresh chicken fillets depend upon headspace composition in packages. When fresh chicken fillets are packed in air, CP treatment has no effect on microbiological shelf life. MA packages with high O2 and CO2 significantly extend shelf life and CP treatment with MA can at least double shelf life of fresh chicken meat (more than 14 days). Regardless of headspace composition, in-package CP does not have negative effects on chicken meat appearance.


Subject(s)
Bacteria/growth & development , Food Packaging , Food Storage/methods , Meat/microbiology , Microbial Viability , Plasma Gases , Poultry/microbiology , Animals , Bacteria/drug effects , Bacteria/isolation & purification , Chickens , Colony Count, Microbial , Food Contamination/analysis , Food Microbiology , Food Quality , Plasma Gases/pharmacology , Refrigeration
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