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1.
J Invest Dermatol ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32004569

RESUMO

A central feature of diabetic wounds is the persistence of chronic inflammation, which is partly due to the prolonged presence of pro-inflammatory (M1) macrophages. Using in vivo and in vitro analyses, we have tested the hypothesis that lncRNA GAS5 (Growth Arrest-Specific 5) is dysregulated in diabetic wounds. We have assessed the contribution of GAS5 to the M1 macrophage phenotype, as well as the functional consequences of knocking down its expression. We found that expression of GAS5 is significantly increased in diabetic wounds and in cells isolated from diabetic wounds. Hyperglycemia induced GAS5 expression in macrophages in vitro. Overexpression of GAS5 in vitro promoted macrophage polarization towards an M1 phenotype by upregulating STAT1. Of most significance in our judgment, GAS5 loss-of-function enhanced diabetic wound healing. These data indicate that the relative level of lncRNA GAS5 in wounds plays a key role in the wound-healing response. Reductions in the levels of GAS5 in wounds appeared to enhance healing by promoting transition of M1 macrophages to M2 macrophages. Thus, our results suggest that targeting lncRNA GAS5 may provide a therapeutic intervention for correcting impaired diabetic wound healing.

2.
Int J Biol Macromol ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32061851

RESUMO

Cellulose acetate (CA) ultrafiltration membranes are attracting more attention in wastewater purification due to its biodegradability and eco-friendly. The application of CA membranes, however, is limited by high susceptibility to bacterial corrosion and lack of mechanical tolerance that results in loss of life. To solve the above problems, we first fabricated the CA-based composite membranes incorporated with bamboo-based lignocellulose nanofibrils (LCNFs) by a strategy of phase inversion. LCNFs was prepared by using a combined method of one-step chemical pretreatment and acid hydrolysis coupled with high-pressure homogenization. The as-prepared CA/LCNFs composite membranes with 4 wt% lignin in the LCNFs exhibited high tensile strength of 7.08 MPa and strain-at-break of 12.21%, and high filtration permeability of 188.23 L·m-2·h-1 as ultrafiltration membranes for wastewater treatment, which could obviously inhibit the growth of Escherichia coli.

3.
J Am Chem Soc ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32066243

RESUMO

Semiconductor quantum dots (QDs) in conjunction with non-noble 3d-metal ions (e.g., Fe3+, Co2+, and Ni2+) have emerged as an extremely efficient, facile and cost-effective means of solar-driven hydrogen (H2) evolution. However, the exact structural change of the active sites under realistic conditions remains elusive, and the mechanism of H2 evolution behind the remarkable activity is poorly understood. Here, we successfully track the structural variation of the catalytic sites in the typical H2 photogeneration system consisting of CdSe/CdS QDs and 3d-metal ions (i.e., Ni2+ used here). That is, the nickel precursor of Ni(OAc)2 changes to Ni(H2O)62+ in neutral H2O and eventually transforms to Ni(OH)2 nanosheets in alkaline media. Furthermore, the in operando spectroscopic techniques of electron paramag-netic resonance and X-ray absorption spectroscopy reveal the photoinduced transformation of Ni(OH)2 to a defective structure [Nix0/Ni1-x(OH)2], which acts as the real catalytic species of H2 photogeneration. Density functional theory (DFT) calculations further indicate that the surface Ni-vacancies (VNi) on the Ni(OH)2 nanosheets enhance the adsorp-tion and dissociation of H2O molecules to enhance the local proton concentration, while the Ni0 clusters behave as H2-evolution sites, thereby synergistically promoting the activity of H2 photogeneration in alkaline media.

4.
Br J Haematol ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32068255

RESUMO

Bortezomib is a first-in-class proteasome inhibitor, approved for the treatment of multiple myeloma. The originally approved dosing schedule of bortezomib results in significant toxicities that require dose interruptions and discontinuations. Consequentially, less frequent dosing has been explored to optimise bortezomib's benefit-risk profile. Here, we performed exposure-response analysis to compare the efficacy of the original bortezomib dosing regimen with less frequent dosing of bortezomib over nine 6-week treatment cycles using data from the VISTA clinical trial and the control arm of the ALCYONE clinical trial. The relationship between cumulative bortezomib dose and clinical response was evaluated with a univariate logit model. The median cumulative bortezomib dose was higher in ALCYONE versus VISTA (42·2 vs. 38·5 mg/m2 ) and ALCYONE patients stayed on treatment longer (mean: 7·2 vs. 5·8 cycles). For all endpoints and regimens, probability of clinical response correlated with cumulative bortezomib dose. Similar to results observed for VISTA, overall survival was longer in ALCYONE patients with ≥ 39·0 versus < 39·0 mg/m2 cumulative dose (hazard ratio, 0·119; P < 0·0001). Less frequent bortezomib dosing results in comparable efficacy, and a higher cumulative dose than the originally approved bortezomib dosing schedule, which may be in part be due to reduced toxicity and fewer dose reductions/interruptions.

5.
Diagn Pathol ; 15(1): 9, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005253

RESUMO

BACKGROUND: Non-surgical cytological specimens are adequate not only for accurate histological subtyping but also for molecular profiling. A modified amplification refractory mutation system polymerase chain reaction (ARMS PCR), known as SuperARMS PCR, was improved by optimizing the primers designation, which provides a higher sensitivity and specificity approach for free plasma DNA detection. It is unclear whether SuperARMS PCR detects epidermal growth factor receptor (EGFR) mutations in cytology samples. The aim of this study was to compare the EGFR mutations detected by ARMS PCR and SuperARMS PCR in cytology samples derived from advanced non-small cell lung cancer (NSCLC) patients. METHODS: From March 2016 to March 2018, a total of 234 cytological samples were obtained from primary or metastatic lesions of NSCLC, including 144 fine-needle aspirations (FNAs), 36 endobroncheal ultrasonography (EBUS) FNAs, 36 transbronchial needle aspirations (TBNAs) and 18 pleural effusion (PLEs). EGFR mutations were simultaneously detected using an ADx-ARMS EGFR kit (Amoy Diagnostics CO., ltd., Xiamen, China) and an ADx-SuperARMS EGFR kit (Amoy Diagnostics CO., ltd., Xiamen, China). Digital droplet PCR (ddPCR) and next-generation sequencing (NGS) were further used to verify the EGFR mutant inconsistent samples. RESULTS: All of the 234 patients with advanced or recurrent NSCLC were diagnosed and assessed by two cytopathologists, and their EGFR mutation statuses were successfully detected by ARMS and SuperARMS. Importantly, the SuperARMS and ARMS methods showed a highly concordant result of 94.0% (220/234) (95%CI: 85.0, 95.0%). The positive rate of the SuperARMS was higher than the ARMS in the cytology samples for EGFR detection (46.2% vs. 40.2%). The specific EGFR mutation sites in 16 samples (6.8%) were not completely consistent between the SuperARMS and ARMS. A total of 14 patients showed EGFR mutations when detected by SuperARMS, but by ARMS there were EGFR wild-type. Two patients were detected as having one more EGFR mutation site by SuperARMS than by ARMS. ddPCR and NGS were used to further confirm the EGFR mutations in these inconsistent samples. Eight samples had the same mutation results as the SuperARMS, and 6 samples were not verified because the remaining DNA was insufficient. A total of 78 EGFR mutation patients received Tyrosine Kinase Inhibitor (TKI) treatment. The overall objective response rate (ORR) was 88.5% (69/78) for EGFR TKI treatment. CONCLUSION: SuperARMS showed a high sensitivity and specificity for EGFR detection and thus, is expected to become a routine test in the clinic to be used as a widely available, easy-to-operate and sensitive method for EGFR mutation detection in liquid-based cytology samples.

6.
J Clin Neurosci ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32035795

RESUMO

Auditory aura was the very important clinical character in familial temporal Lobe epilepsy. LGI1 was the main pathogenic gene. The inheritance mode of this disease was autosomal dominant. We describes the clinical characters and gene detection in 7 patients in a temporal lobe epilepsy family with auditory aura. All patients in this family were diagnosed as temporal lobe epilepsy and had the same mutation: the splice site mutation in No. 2 base of the intron after the first exon in gene LGI1, c.215+2T>A, which induced the abnormal expression of peptide protein after the No. 71 amino acid encoded by LGI1. Some of the antiepileptic drugs, such as carbamazepine, oxcarbazepine, could be effective.

7.
Org Lett ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32052979

RESUMO

Combinatorial biosynthesis of 5/5/6 type polycyclic tetramate macrolactams (PoTeMs) was achieved in an engineered ikarugamycin (5/6/5 type) producer by introducing a set of 5/5/6 type PoTeM biosynthetic genes from Streptomyces griseus. This study supports the idea that PoTeMs share a common polyene tetramate precursor generated by the hybrid polyketide synthase/nonribosomal peptide synthetase enzymes. The X-ray crystal structure of pactamide G (7) sets an example for resolving the absolute configuration of 5/5/6 type PoTeMs.

8.
Sci Total Environ ; 715: 136963, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32014781

RESUMO

Soil acidification is a major problem in intensive agricultural systems and is becoming increasingly serious. Most research has reported the soil acidification of cereal crops, forests, and grasslands. However, there is no information about soil acidification under tea cultivation on a national scale. Therefore, we conducted a nationwide survey of soil acidification in the major tea-planting areas of China and used two nationwide surveys in three Chinese counties to evaluate changes in soil acidity over the past 20-30 years. Finally, the acidity of soil from forests and traditional and organic tea plantations was compared to evaluate the effects of agricultural management on soil acidification in tea plantations. Our results show that: (1) the average soil pH was 4.68 nationally and ranged from 3.96 to 5.48 in different provinces. Overall, 46.0% of the soil samples had a pH <4.5, which is too acidic for tea growth and only 43.9% had a soil pH of 4.5-5.5, which is optimal for tea growth. (2) In the past 20-30 years, the greatest soil acidification was observed in tea plantations; the pH decreased by 0.47 to 1.43, which is much greater than the decrease seen in fruit and vegetable systems (0.40 to 1.08) and cereals (0.30 to 0.89). (3) Compared with forests, tea cultivation with chemical fertilizer application caused serious soil acidification, while no significant acidification was observed at organic tea plantations. In conclusion, serious soil acidification occurs nationally in China, and organic management is an adaptive choice for sustainable tea growth.

9.
ISA Trans ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32044088

RESUMO

A novel back recursive estimation (BRE) scheme is proposed for superconducting radio frequency (SRF) cavities. Microphonic,the main source of cavities detuning is modeled as unknown frequency sinusoidal disturbance. The disturbance property is excited by an auxiliary filter and the frequency information is estimated in observer framework. Furthermore, the sinusoidal disturbance is rearranged as a series of dynamics form using virtual disturbances. Back recursive signal is calculated according to the correlation between virtual disturbance and equivalent input disturbance. As a result, the asymptotic stability of estimation error can be obtained based on Lyapunov function, and robustness can be obtained if another external bounded disturbance exists. Simulations verify the effectiveness of the proposed method.

10.
J Dairy Sci ; 103(3): 2303-2314, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31954586

RESUMO

Different inclusion rates of oregano essential oil (OEO) were investigated for their effects on ruminal in vitro fermentation parameters, total gas, methane production, and bacterial communities. Treatments were (1) control, 0 mg/L of OEO (CON); 13 mg/L (OEO1); 52 mg/L (OEO2); 91 mg/L (OEO3); and 130 mg/L (OEO4), each incubated with 150 mL of buffered rumen fluid and 1,200 mg of substrate for 24 h using the Ankom in vitro gas production system (Ankom Technology Corp., Fairport, NY). Treatment responses were statistically analyzed using polynomial contrasts. Digestibility of DM, NDF, and ADF increased quadratically with increasing OEO inclusion rates. Digestibility of DM and NDF were highest for OEO2, whereas ADF digestibility was highest for OEO3, compared with CON, with the remaining treatments being intermediate and similar. Ammonia nitrogen concentrations decreased from CON at a quadratic rate with increasing OEO inclusion rates, and OEO2 had the lowest concentration compared with the other groups. Total VFA, acetate, propionate, butyrate, valerate, and isovalerate concentrations linearly decreased with increasing OEO inclusion rates. Total gas production levels by CON and OEO4 were greater than those of OEO1, OEO2, and OEO3 in a quadratic response, and methane production linearly decreased from CON, compared with OEO4, at a decreasing rate with OEO inclusion rates. As determined by 16S rRNA sequencing, the α biodiversity of ruminal bacteria was similar among OEO inclusion rates. Increasing OEO inclusion rates linearly increased the relative abundance of Prevotella and Dialister bacteria. Several bacteria demonstrated different polynomial responses, whereas several bacteria were similar among increasing OEO inclusion rates. These results suggested that OEO supplementation can modify ruminal fermentation to alter VFA concentrations and reduce methane emissions by extensively altering the ruminal bacterial community, suggesting an optimal feeding rate for future animal studies of approximately 52 mg/L for mature ruminants.

11.
J Parkinsons Dis ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31958096

RESUMO

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disease for which there is no cure. In a clinical trial, the glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 has shown good protective effects in PD patients. The hormone glucose-dependent insulinotropic polypeptide (GIP) has also shown protective effects in animal models of PD. OBJECTIVE: We tested DA-CH5, a novel dual GLP-1/GIP receptor agonist. METHODS: DA-CH5 activity was tested on cells expressing GLP-1, GLP-2, GIP or glucagon receptors. The ability to cross the blood-brain barrier (BBB) of DA-CH5, exendin-4, liraglutide or other dual receptor agonists was tested with fluorescein-labelled peptides. DA-CH5, exendin-4 and liraglutide were tested in the MPTP mouse model of PD. RESULTS: Analysing the receptor activating properties showed a balanced activation of GLP-1 and GIP receptors while not activating GLP-2 or glucagon receptors. DA-CH5 crossed the BBB better than other single or other dual receptor agonists. In a dose-response comparison, DA-CH5 was more effective than the GLP-1 receptor agonist exendin-4. When comparing the neuroprotective effect of DA-CH5 with Liraglutide, a GLP-1 analogue, both DA-CH5 and Liraglutide improved MPTP-induced motor impairments. In addition, the drugs reversed the decrease of the number of neurons expressing tyrosine hydroxylase (TH) in the SN, alleviated chronic inflammation, reduced lipid peroxidation, inhibited the apoptosis pathway (TUNEL assay) and increased autophagy -related proteins expression in the substantia nigra (SN) and striatum. Importantly, we found DA-CH5 was superior to Liraglutide in reducing microglia and astrocyte activation, improving mitochondrial activity by reducing the Bax/Bcl-2 ratio and normalising autophagy as found in abnormal expression of LC3 and p62. CONCLUSION: The results demonstrate that the DA-CH5 is superior to liraglutide and could be a therapeutic treatment for PD.

12.
Mol Cancer ; 19(1): 1, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31901224

RESUMO

Hepatocellular carcinoma (HCC) is the most commonmalignancy. Exsome plays a significant role in the elucidation of signal transduction pathways between hepatoma cells, angiogenesis and early diagnosis of HCC. Exosomes are small vesicular structures that mediate interaction between different types of cells, and contain a variety of components (including DNA, RNA, and proteins). Numerous studies have shown that these substances in exosomes are involved in growth, metastasis and angiogenesis in liver cancer, and then inhibited the growth of liver cancer by blocking the signaling pathway of liver cancer cells. In addition, the exosomal substances could also be used as markers for screening early liver cancer. In this review, we summarized to reveal the significance of exosomes in the occurrence, development, diagnosis and treatment of HCC, which in turn might help us to further elucidate the mechanism of exosomes in HCC, and promote the use of exosomes in the clinical diagnosis and treatment of HCC.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31915845

RESUMO

Abnormal neuroinflammation ignited by overproduction of chemokines and cytokines via microglial cells can induce the occurrence and development of neurodegenerative disorders. The aim of this study is to investigate the effects of dexamethasone sodium phosphate (Dex-SP) on chemokine and cytokine secretion in lipopolysaccharide (LPS)-activated microglial cells. LPS markedly enhanced the secretion of pro-inflammatory factors such as regulated on activation, normal T cell expressed and secreted (RANTES), transforming growth factor beta-ß1 (TGF-ß1) and nitric oxide (NO), but decreased the production of macrophage inflammatory protein-1α (MIP-1α) and interleukin 10 (IL-10) in BV-2 microglial cells. Furthermore, LPS increased BV-2 microglial cell migration. However, Dex-SP treatment had the opposite effect, dampening the secretion of RANTES, TGF-ß1, and NO, while increasing the production of MIP-1α and IL-10 and blocking migration of LPS-stimulated BV-2 microglial cells. Furthermore, Dex-SP markedly suppressed the LPS-induced degradation of IRAK-1 and IRAK-4, and blocked the activation in TRAF6, p-TAK1, and p-JNK in BV-2 microglial cells. These results showed that Dex-SP inhibited the neuroinflammatory response and migration in LPS-activated BV-2 microglia by inhibiting the secretion of RANTES, TGF-ß1, and NO and increasing the production of MIP-1α and IL-10. The molecular mechanism of Dex-SP may be associated with inhibition of TRAF6/TAK-1/JNK signaling pathways mediated by IRAK-1 and IRAK-4.

14.
PLoS One ; 15(1): e0228152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995601

RESUMO

BACKGROUND: The psychological health (PH) of doctors affects the quality of medical service and is related to the safety of patients. The serious problems with the doctor-patient relationship in China can lead to long-term imbalances in doctor PH, and the poor PH status of doctors has raised scholars' concern. Current research mainly focuses on how factors such as social support and the impact of the residential environment correlate with individual PH. We continue this direction of research to see how the mechanism of social support impacts physician PH, also investigating the moderating effect of demographic indicators on physician PH. METHODS: Based on a survey of 399 physicians, a descriptive analysis of measured data was done using SPSS 19.0. Pearson correlation coefficient analysis was used to examine the correlations between PH and the social support rating scale (SSRS) and the demographic variables. KMO and Bartlett methods were used to examine the correlations between PH and SDS (a scale to measure depression) and between PH and SAS (a scale to measure anxiety). The method of factor analysis was used for multicollinearity tests, and multiple stepwise regression analysis was used to explore the demographic factors correlated with PH and SSRS. Two-way interactions in moderated multiple regression were used to test the moderating effect of education level and title on SSRS, SDS, and SAS. RESULTS: Our results indicate that the level of PH is influenced by the age, education, and title of a doctor. A physician's title is significantly and positively correlated with PH, but age and education are significantly negatively related. Age, education, and title also affect the level of SSRS in physicians. SSRS is positively correlated with age, education, and title, and SSRS positively influences PH. Education and title had significant effects on the moderating influences of SSRS, SDS, SAS, and PH. CONCLUSION: The factors directly affecting PH include SSRS, age, and title, while education was found to be an indirect influencing factor. To meet goals expressed in Chinese government policy related to these issues, we suggest strengthening the guidance of the media, introducing laws and regulations on doctor-patient risk management and control, reforming the review mechanism of hospital job titles, improving the education level of doctors, building a comprehensive evaluation system of "practice performance + doctor-patient satisfaction", and strengthening doctor-patient empathy. Through such measures, the level of PH in physicians will improve.

15.
Org Biomol Chem ; 18(4): 707-714, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31907494

RESUMO

Fluorescence bioimaging is very significant in studying biological processes. Fluorescent nanoparticles (NPs) manufactured from aggregation-induced emission (AIE) materials, as promising candidates, have attracted more attention. However, it is still a challenge to explore suitable AIE NPs for bioimaging. Herein, we synthesized pyrazoline-BODIPY (PZL-BDP) with a donor and acceptor (D-A) structure by a condensation reaction, cultured its single crystal, and studied its twisted intramolecular charge transfer (TICT) and AIE effects. PZL-BDP could self-assemble to form red fluorescent nanoparticles (PZL-BDP NPs) which showed a good fluorescence quantum yield of 15.8% in water. PZL-BDP NPs with excellent stability and biocompatibility exhibited a large Stokes shift (Δλ = 111 nm) which resulted in the reduction of external interference and enhancement of the fluorescence contrast. Furthermore, these nanoparticles could be readily internalized by HeLa cells and they stain the cells in just five seconds, indicating an ultrafast bioimaging protocol. Moreover, long-term tracking fluorescence signals in vivo for about 12 days were obtained. The bright red fluorescence, ultrafast cell staining ability, and long-term in vivo tracking competence outline the great potential of rational design nanomaterials with AIE characteristics for monitoring biological processes.

16.
Int J Biol Macromol ; 142: 384-394, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31593737

RESUMO

Amphioxus belongs to the subphylum cephalochordata, an extant representative of the most basal chordates, whose regulation of endocrine system remains ambiguous. Here we clearly demonstrated the existence of a functional GRP neuropeptide in amphioxus, which was able to interact with GRP receptor, activate both PKC and PKA pathways, increase gh, igf, and vegf expression. We also showed that the transcription level of amphioxus grp was affected by temperature and light, indicating the role of this gene in the regulation of energy balance and circadian rhythms. In addition, the expression of the amphioxus grp was detected in cerebral vesicle that has been proposed to be the homologous organ of vertebrate brain. These data collectively suggested that a functional GRP neuropeptide had already emerged in amphioxus, which provided insights into the evolutionary origin of GRP in chordate and the functional homology between the cerebral vesicle and vertebrate brain.

17.
J Cell Biochem ; 121(1): 93-102, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31081181

RESUMO

Porphyromonas gingivalis, as a major pathogen of periodontitis, could rapidly adhere to and invade host gingival epithelial cells (GECs) for the induction of infection. One ATP-binding cassette (ABC) transporter gene was found to be upregulated during this infection process, however, the molecular mechanisms remain unclear. In this study, we systemically investigated the messenger RNA level changes of all ABC transporter family genes in P. gingivalis while being internalized within GECs by real-time polymerase chain reaction. We identified that two ABC transporter genes, PG_RS04465 (PG1010) and PG_RS07320 (PG1665), were significantly increased in P. gingivalis after coculturing with GECs. Mutant strains with knockout (KO) of these two genes were generated by homogenous recombination. PG_RS04465 and PG_RS07320 KO mutants showed no change in the growth of bacteria per se. Knockdown of PG_RS07320, but not PG_RS04465, caused decreased endotoxin level in the bacteria. In contrast, both mutant strains showed decreased Arg- and Lys-gingipains activities, with significantly reduced adhesion and invasion capabilities. Secreted interleukin-1ß (IL-1ß) and IL-6 levels in GECs cocultured with PG_RS04465 or PG_RS07320 KO mutants were also decreased, whereas, only the cells cocultured with PG_RS07320 KO mutants showed significant decrease. In addition, virulence study using mouse revealed that both KO mutant strains infection caused less mouse death than wild-type strains, showing reduced virulence of two KO strains. These results indicated that ABC transporter genes PG_RS04465 and PG_RS07320 are positive regulators of the virulence of P. gingivalis.

18.
J Proteomics ; 210: 103526, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31605788

RESUMO

Small Tail Han sheep have attracted attention for their high fecundity and year-round estrus. However, the molecular mechanisms of this fecundity are unknown. Polymorphism of the FecB gene has been shown to be associated with the ovulation rate and litter size in sheep. In this study, we used tandem mass tag quantitative proteomic techniques to identify the differentially abundant proteins in polytocous and monotocous Small Tail Han sheep (FecB++) uterine tissues in the follicular and luteal phases. In total, 41 and 43 differentially abundant proteins were identified in the follicular and luteal phases, respectively. Correlation analysis between the transcriptome and proteome revealed a positive correlation at the two omics levels of prolificacy. GO and KEGG pathway analyses indicated that the mRNAs and proteins upregulated in the polytocous group relative to the monotocous group are involved in sphingolipid metabolism and amino acid metabolism, and may be important in maintaining uterine functions and increasing the embryo survival rate during the estrus cycle of polytocous sheep. In conclusion, our work provides a prospective understanding of the molecular mechanism underlying the high prolificacy of Small Tail Han sheep. SIGNIFICANCE: Fecundity critically affects the profitability of sheep production, but the genetic mechanism of high-prolificacy is still unclear in sheep. We identified potential signaling pathways and differentially abundant proteins associated with reproductive performance through a combination of sheep uterus tissues proteome and transcriptome analyses. These findings will facilitate a better revealing the mechanism and provide possible targets for molecular design breeding for the formation of polytocous traits in sheep.

19.
Mater Sci Eng C Mater Biol Appl ; 106: 110288, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31753411

RESUMO

A new kind of core-crosslinked zwitterionic polymer nano aggregates was prepared by two steps: (1) terpolymers of lipoic acid, polyethylene glycol diglycidyl ether and l-lysine were prepared, forming nano aggregates with hydrodynamic radius of 80 nm-183 nm by self-assembly; (2) the crosslinking of the nano aggregates took place through a reaction of side chain group in lipoic acid structural unit with 1,4-dimercaptothreotol, producing zwitterionic polymer core-crosslinked nano aggregates. The aggregates were stable against dilution and protein adsorption, and they demonstrated good pH/redox dual-responsiveness due to the introduction of disulfide bonds and zwitterionic groups to the nano aggregates. Doxorubicin (DOX) was loaded into the nano aggregates for controlled release. The drug-loaded nano aggregates exhibited obvious pH and reduction sensitivities in response to the environmental conditions in tumor cells. The nano aggregates were biocompatible and could be potentially applied as anticancer drug vehicles for enhancement of cellular uptake of anticancer drugs.

20.
Sci Total Environ ; 709: 135802, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-31887498

RESUMO

Although carbon black (CB) particles have potential hazards to human health, the toxicological studies on CB are still limited. The purpose of this study was to investigate the effect of oxidative stress induced by ultrafine CB particles on apoptosis in vivo and vitro. Male C57BL/6 mice were inhalation exposed to CB for 28 days, and 16HBE cells were treated by CB particles and also added antioxidant (NAC). Antioxidant enzymes activities (CAT, SOD, GSH-Px) and ROS in the lungs and cells were evaluated. Apoptosis-related proteins (Bcl-2, Bax, Cleaved Caspase-3, pro-Caspase-3, Caspase-7, Caspase-8, Caspase-9, PARP-1) were tested by Western blot (WB), immunohistochemistry (IHC), and real-time PCR. The reduction of antioxidant enzymes activities and the addition of ROS in CB exposure groups were observed, and the gene and apoptosis-related proteins levels were increased in CB exposure mice. The results of CB-treated 16HBE cells were consistent with those of mice, and apoptosis rate was increased in CB-treated 16HBE cells. When the cells were treated with NAC, ROS induced by CB decreased, SOD and CAT activities of CB-treated 16HBE cells were increased. Apoptosis rate of 16HBE cells treated with NAC and CB was significantly decreased, and the expression of C-Caspase-3 was also decreased. Therefore, oxidative stress induced by ultrafine CB particles can elicit apoptosis in vivo and vitro. Antioxidants can significantly reduce oxidative damage and apoptosis induced by CB.

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