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1.
Environ Int ; 136: 105462, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31924579

RESUMO

Photoinitiators (PIs) are indispensable additives in photopolymerization. PI-containing consumables, such as adhesives, coatings, UV-cured inks and light-sensitive materials, are widely used in various electronic products. Nevertheless, there is no information concerning the identification of PIs as emerging contaminants from e-waste recycling. In this study, 25 PIs, including 9 benzophenones (BZPs), 8 amine coinitiators (ACIs), 4 thioxanthones (TXs) and 4 phosphine oxides (POs), were analyzed in indoor dust from typical e-waste recycling facilities and adjacent rural communities, as well as from control urban communities. All 25 target PIs were detected in e-waste dust, while only 17 and 15 of the 25 target PIs were detected in local home dust and urban home dust, respectively. The PIs detected in all dust samples were dominated by BZPs and POs, followed by ACIs and TXs. Most PIs exhibited significantly higher levels in e-waste dust than local or urban home dust. The influence of PI contamination on the local household environment by dust diffusion and transport from near e-waste recycling facilities may be lower due to the low volatility of most PIs. Characteristic composition profiles of PIs for indoor dust from the e-waste recycling area were identified and compared to those from the control area. Significant correlations were found among almost all the frequently detected PIs in the e-waste dust, indicating their similar application in electronic products and common emission from e-waste recycling. The estimated daily intakes of PIs via dust ingestion for the e-waste dismantling workers, as determined by using Monte Carlo analysis, were several times higher than those for the local adult residents and the general urban adult residents, which should be an emerging concern. To the best of our knowledge, this is the first report showing that e-waste dismantling/recycling activities lead to largely common releases of a wide range of multiple classes of PIs.

2.
Rapid Commun Mass Spectrom ; : e8730, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31952097

RESUMO

RATIONALE: Short-chain fatty acids (SCFAs) are associated with intestinal microbiota and diseases in humans. SCFAs have a low response in mass spectrometry and in order to increase sensitivity, reduce sample consumption, shorten analysis time, and simplify sample preparation steps, a derivatization method was developed. METHODS: We converted seven SCFAs into amide derivatives with 4-aminomethylquinoline. The reaction took 20 min at room temperature. Analytes were separated on a reversed-phase C18 column and quantitated in positive ion electrospray ionization mode using multiple reaction monitoring. Acetic acid-d4 was used as the stable isotope-labelled surrogate analyte for acetic acid in the working solutions, while the other stable isotope-labelled standards were used as internal standards (ISs). RESULTS: Method validation showed that the intra-day and inter-days precision of quantitation for the seven SCFAs over the whole concentration range was ≤ 3.8% (n = 6). The quantitation accuracy ranged from 85.5% to 104.3% (n = 6). Importantly, the collected feces need to be vortexed immediately with ethanol. CONCLUSIONS: This study provides a new derivatization method for precise, accurate, and rapid quantification of SCFAs in human feces using ultra-performance liquid chromatography-tandem mass spectrometry. This method successfully determined the concentration of SCFAs in human feces and could assist in the exploration of intestinal microbiota and disease.

3.
BMC Surg ; 20(1): 16, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31952490

RESUMO

BACKGROUND: The present study aimed to compare the perioperative safety and long-term survival of patients with synchronous colorectal liver metastases undergoing sequential resection (SeR), delayed resection (DeR) and simultaneous resection (SiR). METHODS: From January 2007 to December 2016, data from patients undergoing surgery at Peking University Cancer Hospital for synchronous colorectal liver metastases were retrospectively collected. The above three different surgical strategies were compared. RESULTS: A total of 233 cases were included, with 49 in the SeR group, 98 in the DeR group and 86 in the SiR group. The incidence of severe complications was 26.7% in the SiR group, higher than that in the DeR group (11.2%, P = 0.007) and the SeR group (16.3%, P = 0.166). The overall survival at 1 and 3 years in the SeR group (93.9 and 50.1%) was lower than that in the DeR group (94.9 and 64.8%, P = 0.019), but not significantly different from that in the SiR group (93.0 and 55.2%, P = 0.378). Recurrence-free survival at 1 and 3 years in the SeR group (22.4 and 18.4%) was lower than that in the DeR group (43.9 and 24.2%, P = 0.033) but not significantly different from that in the SiR group (31.4 and 19.6%, P = 0.275). Cox multivariate analysis indicated that T4, lymph node-positive primary tumour, liver metastases > 30 mm and SiR (compared with DeR) were correlated with poor prognosis. CONCLUSION: Simultaneous resection has a relatively higher incidence of severe complications, and with a staged resection strategy, the prognosis of delayed resection was better than that of sequential resection.

4.
Toxicol Appl Pharmacol ; : 114882, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31953203

RESUMO

Pulmonary fibrosis is a prototypic chronic progressive lung disease with high morbidity and mortality worldwide. Novel effective therapeutic agents are urgently needed owing to the limited treatment options in clinic. Herein, nagilactone D (NLD), a natural norditerpenoid obtained from Podocarpus nagi, was found to suppress transforming growth factor-ß1 (TGF-ß1)-mediated fibrotic process in vitro and bleomycin (BLM)-induced pulmonary fibrosis in vivo. NLD attenuated TGF-ß1-induced expression of fibrotic markers including type I and III collagen, fibronectin, α-SMA, and CTGF in human pulmonary fibroblasts (WI-38 VA-13 and HLF-1 cells). Mechanism study indicated that NLD suppressed TGF-ß1-induced up-regulation of TßR I, and Smad2 phosphorylation, nuclear translocation, and transcriptional activation. Moreover, NLD ameliorated BLM-induced histopathological abnormalities in the lungs of experimental fibrotic mice, suppressed synthesis of relative fibrotic markers and fibroblast-to-myofibroblast transition, as well as BLM-induced up-regulation of TßR I expression and Smad signaling in mouse lungs. These data collectively support NLD to be a potential therapeutic agent for pulmonary fibrosis.

5.
J Am Chem Soc ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31940194

RESUMO

The properties of supramolecular structures are highly dependent on their metal-centered building blocks and organic linkers, thus the search for novel systems will lead to new functions and applications for these unique assemblies. Here, two discrete triangular trimetallic sandwich building blocks were developed to construct supramolecular assemblies through coordination-driven self-assembly with organosulfur ligands. A series of tube-like (Tr2Pd3)4L6 assemblies (Tr = cycloheptatrienyl ring) were obtained from a discrete triangular tripalladium sandwich complex with bifunctional organosulfur ligands. By replacing the metal centers of the platinum analogue, the self-assembly process resulted in the clean formation of (Tr2Pt3) 2L3 triple helicates instead of tube-like species. The trimetallic sandwich building blocks were shown also to form face-capped (Tr2M3)4L4 (M = Pd or Pt) tetrahedral cages when trifunctional organosulfur ligands were used. The supramolecular assemblies were comprehensively analyzed by X-ray crystallography. A metal-cluster-induced structural transformation between (Tr2Pd3)4L4 tubes and (Tr2Pt3)2L3 triple helicates was observed. Furthermore, the face-capped (Tr2Pd3)4L4 cage possesses a tetrahedral cavity allowing encapsulation of a series of guests.

6.
Brain Behav ; : e01533, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31943832

RESUMO

INTRODUCTION: This study aims to establish a methamphetamine (METH)-induced behavioral sensitization model using tree shrews, as well as to measure the protein expression of the dopamine D3 receptor (D3R) and dopamine transporter (DAT). METHODS: Forty tree shrews were equally and randomly divided into four experimental groups: those administered with 1, 2, and 4 mg/kg METH and a control group (treated with an equal amount of normal saline). Each experimental group was repeatedly exposed to METH for nine consecutive days to induce the development of behavioral sensitization, followed by four days of withdrawal (without the METH treatment) to induce the transfer of behavioral sensitization, then given 0.5 mg/kg of METH to undergo the expression of behavioral sensitization. Altered locomotor and stereotypic behaviors were measured daily via open-field experiments during the development and expression stages, and weight changes were also recorded. Then, the Western blot method was used to detect the expression levels of D3R and DAT in three brain regions: the nucleus accumbens, prefrontal cortex, and dorsal striatum 24 hr after the last behavioral test. RESULTS: METH administration augmented motor-stimulant responses and stereotypic behaviors in all experimental groups, and stereotypic behaviors intensified more in the groups treated with 2 and 4 mg/kg METH. Motion distance, speed, and trajectory were significantly elevated in all experimental, however, METH at 4 mg/kg induced more stereotypic behaviors, decreasing these locomotor activities as compared with the 2 mg/kg METH group. 2 and 4 mg/kg METH significantly upregulated and downregulated D3R and DAT expression levels, respectively, in three brain regions, and these changes are more pronounced in 2 mg/kg METH. CONCLUSIONS: These results indicated that this animal model may be used to study the neurobiological mechanisms that underly the development and expression of behavioral sensitization to METH. Deregulated D3R and DAT expression may be involved in the METH-induced behavioral sensitization.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31905370

RESUMO

There is a close relationship between serotonergic (5-HT) activity and anxiety. ErbB4, a receptor tyrosine kinase, is expressed in 5-HT neurons. However, whether ErbB4 regulates 5-HT neuronal function and anxiety-related behaviors is unclear. Here, using transgenic and viral approaches, we show that mice with ErbB4 deficiency in 5-HT neurons exhibit heightened anxiety-like behavior and impaired fear extinction, possibly due to an increased excitability of 5-HT neurons in the dorsal raphe nucleus (DRN). Notably, the chemogenetic inhibition of 5-HT neurons in the DRN of ErbB4 mutant mice rescues anxiety-like behaviors. Altogether, our results unravel a previously unknown role of ErbB4 signaling in the regulation of DRN 5-HT neuronal function and anxiety-like behaviors, providing novel insights into the treatment of anxiety disorders.

8.
Food Chem ; 312: 126043, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31896450

RESUMO

Dark tea is a unique fermented tea produced by solid-state fermentation of tea leaves (Camellia sinensis). It includes ripe Pu-erh tea, Fu brick tea, Liupao tea, and other teas. Microbial fermentation is considered to be the key factor controlling the quality of dark tea. It involves a series of reactions that modify the chemical constituents of tea leaves. These chemical conversions during microbial fermentation of dark tea are associated with a variety of functional core microorganisms. Further, Multi-omics approaches have been used to reveal the microbial impact on the conversion of the chemical components in dark tea. In the present review, we provide an overview of the most recent advances in the knowledge of the microbial bioconversion of the chemical components in dark tea, including the chemical composition of dark tea, microbial community composition and dynamics during the fermentation process, and the role of microorganisms in biotransformation of chemical constituents.

9.
J Coll Physicians Surg Pak ; 30(1): 23-27, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31931927

RESUMO

OBJECTIVE: To determinate the clinical effect of butyphthalide combined with idebenone in the treatment of vascular dementia (VD) and the influence on inflammatory cytokines and vascular endothelial functions. STUDY DESIGN: Clinical comparative study. PLACE AND DURATION OF STUDY: Department of Neurology, Baoding First Central Hospital, from June 2017 to June 2018. METHODOLOGY: Eighty-eight VD patients were divided into observation group (44 cases) and control group (44 cases) at random. Idebenone was given to the control group, and butyphthalide combined with idebenone was given to the observation group for 12 weeks. C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) were detected before and after the treatment to evaluate the level of serum inflammatory factors. Peripheral blood endothelial microparticles (EMPs), endothelin (ET-1), and vascular endothelial growth factor (VEGF) were detected to evaluate vascular endothelial functions. Mini-mental state examination (MMSE), clinical dementia scale (CDR), and ability of daily life (ADL), were used to evaluate cognitive function, dementia degree, and self-care ability in daily life. The occurrences of adverse reactions were recorded. RESULTS: Before the treatment, the comparison differences in the indexes of both groups had no statistical significance (p>0.05). After the treatment, the scores of CD62E+, VEGF, and MMSE of observation group rose obviously, compared with those before the treatment, and were significantly higher than those of control group (p <0.05). After the treatment, the scores of IL-6, CRP, TNF-α, IL-1ß, CD31+, CDl44+, ET-1, CDR and ADL of observation group significantly lowered, compared with those before the treatment, and were significantly lower than those of control group (p <0.05). The differences in the adverse reactions of both groups had no statistical significance (p >0.05). CONCLUSION: Butyphthalide combined with idebenone can effectively reduce serum inflammatory factor level of VD patients, regulate vascular endothelial functions, relieve dementia degree, and improve cognitive function and daily activity ability.

11.
Arch Pharm Res ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31894502

RESUMO

As the main metabolite of nitazoxanide, tizoxanide (TIZ) has a broad-spectrum anti-infective effect against parasites, bacteria, and virus. In this study, we investigated the effects of TIZ on autophagy by regulating the PI3K/Akt/mTOR signaling pathway. RAW264.7 macrophage cells were treated with various TIZ concentrations. Cell viability assay, transmission electron microscope, and immunofluorescence staining were used to detect the biological function of the macrophage cells, and the expression levels of the autophagy pathway-related proteins were measured by Western blot. Results revealed that TIZ promoted the conversion of LC3-I to LC3-II, the formation of autophagy vacuoles, and the degradation of SQSTM1/p62 in a concentration- and time-dependent manner in RAW264.7 cells. Treatment with TIZ increased the Beclin-1 expression level and inhibited PI3K, Akt, mTOR, and ULK1 activation. These effects were enhanced by pretreatment with rapamycin but attenuated by pretreatment with LY294002. In addition, the conversion of LC3-I to LC3-II was observed in Vero, 293T, and HepG2 cells treated with TIZ. These data suggested that TIZ may induce autophagy by inhibiting the Akt/mTOR/ULK1 signaling pathway in macrophages and other cells.

12.
Mikrochim Acta ; 187(1): 80, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897753

RESUMO

Multiwalled carbon nanotubes coated with cobalt(II) sulfide nanoparticles were prepared and used for immobilization of glucose oxidase (GOx) to obtain an electrochemical glucose biosensor. The nanocomposite was synthesized through an in-situ hydrothermal method and characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and electrochemical impedance spectroscopy. The results show that the nanocomposite possesses a large specific surface area and apparently enhances the direct electron transfer between GOx and the surface of the electrode, best at a potential near -0.43 V (vs. SCE). The immobilized GOx retains its good bioactivity even at a high surface coverage of 30 pmol cm-2. Under the optimum conditions. The biosensor exhibits a wide linear range (from 8 µM to 1.5 mM), a high sensitivity (15 mA M -1 cm-2), and a 5 µM detection limit (at S/N = 3). The sensor is selective, acceptably repeatable, specific and stable. Graphical abstractMultiwalled carbon nanotubes coated with cobalt(II) sulfide nanoparticles (CoS-MWCNTs) were synthesized through in situ hydrothermal method for the construction of a sensitive electrochemical glucose biosensor.

13.
Vet Microbiol ; 240: 108542, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31902499

RESUMO

Influenza A virus (IAV) and bacteria co-infection can influence the host clinical conditions. Both H9N2 IAV and Pseudomonas aeruginosa (P. aeruginosa) are potential pathogens of respiratory diseases in mink. In this study, to clarify the effects of H9N2 IAV and P. aeruginosa co-infections on hemorrhagic pneumonia in mink, we carried out to establish the mink models of the two-pathogen co-infections in different orders. Compared with the single infections with H9N2 IAV or P. aeruginosa, the mink co-infected with H9N2 IAV and P. aeruginosa showed severe respiratory diseases, and exacerbated histopathological lesions and more obvious apoptosis in the lung tissues. H9N2 IAV shedding and viral loads in the lungs of the mink co-infected with H9N2 IAV and P. aeruginosa were higher than those in the mink with single H9N2 IAV infection. Furthermore, the clearance of P. aeruginosa in the co-infected mink lungs was delayed. In addition, the anti-H9N2 antibody titers in mink with P. aeruginosa co-infection following H9N2 IAV infection were significantly higher than those of the other groups. This implied that H9N2 IAV and P. aeruginosa co-infection contributed to the development of hemorrhagic pneumonia in mink, and that P. aeruginosa should play a major role in the disease. The exact interaction mechanism among H9N2 IAV, P. aeruginosa and the host needs to be further investigated.

14.
Cancer Res ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911552

RESUMO

Multiple myeloma (MM) is a plasma cell malignancy that thrives in the bone marrow (BM), with frequent progression to new local and distant bone sites. Our previous studies demonstrated that MM cells at primary sites secrete soluble factors and suppress osteoblastogenesis via the inhibition of Runt-related transcription factor 2 (Runx2) in pre- and immature osteoblasts (OBs) in new bone sites, prior to the arrival of metastatic tumor cells. However, it is unknown whether OB-Runx2 suppression in new bone sites feeds back to promote MM dissemination to and progression in these areas. Hence, we developed a syngeneic mouse model of MM in which Runx2 is specifically deleted in the immature OBs of C57BL6/KaLwRij mice (OB-Runx2-/- mice) to study the effect of OB-Runx2 deficiency on MM progression in new bone sites. In vivo studies with this model demonstrated that OB-Runx2 deficiency attracts MM cells and promotes MM tumor growth in bone. Mechanistic studies further revealed that OB-Runx2 deficiency induces an immunosuppressive microenvironment in BM that is marked by an increase in the concentration and activation of myeloid-derived suppressor cells (MDSCs) and the suppression and exhaustion of cytotoxic CD8+ T cells. In contrast, MDSC depletion by either gemcitabine or 5-fluorouracil treatment in OB-Runx2-/- mice prevented these effects and inhibited MM tumor growth in BM. These novel discoveries demonstrate that OB-Runx2 deficiency in new bone sites promotes MM dissemination and progression by increasing metastatic cytokines and MDSCs in BM and inhibiting BM immunity. Importantly, MDSC depletion can block MM progression promoted by OB-Runx2 deficiency.

15.
BMC Plant Biol ; 20(1): 21, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931712

RESUMO

BACKGROUND: Triacylglycerols (TAGs) are the main composition of plant seed oil. Long-chain acyl-coenzyme A synthetases (LACSs) catalyze the synthesis of long-chain acyl-coenzyme A, which is one of the primary substrates for TAG synthesis. In Arabidopsis, the LACS gene family contains nine members, among which LACS1 and LACS9 have overlapping functions in TAG biosynthesis. However, functional characterization of LACS proteins in rapeseed have been rarely reported. RESULTS: An orthologue of the Arabidopsis LACS2 gene (BnLACS2) that is highly expressed in developing seeds was identified in rapeseed (Brassica napus). The BnLACS2-GFP fusion protein was mainly localized to the endoplasmic reticulum, where TAG biosynthesis occurs. Interestingly, overexpression of the BnLACS2 gene resulted in significantly higher oil contents in transgenic rapeseed plants compared to wild type, while BnLACS2-RNAi transgenic rapeseed plants had decreased oil contents. Furthermore, quantitative real-time PCR expression data revealed that the expression of several genes involved in glycolysis, as well as fatty acid (FA) and lipid biosynthesis, was also affected in transgenic plants. CONCLUSIONS: A long chain acyl-CoA synthetase, BnLACS2, located in the endoplasmic reticulum was identified in B. napus. Overexpression of BnLACS2 in yeast and rapeseed could increase oil content, while BnLACS2-RNAi transgenic rapeseed plants exhibited decreased oil content. Furthermore, BnLACS2 transcription increased the expression of genes involved in glycolysis, and FA and lipid synthesis in developing seeds. These results suggested that BnLACS2 is an important factor for seed oil production in B. napus.

16.
Trials ; 21(1): 77, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937335

RESUMO

BACKGROUND: Acupoint selection is a key factor in the treatment of diseases and has not been well studied. The aim of this trial is to explore the differences in efficacy between compatible acupoints and a single acupoint for patients with functional dyspepsia (FD). METHODS: This randomized controlled trial will be conducted in the First Affiliated Hospital of Changchun University of Chinese Medicine in China. Two hundred and sixteen FD patients will be randomly assigned to the compatible acupoints group, single acupoint group, or sham acupuncture group. This trial will include a 1-week baseline period, a 4-week treatment period, and a 4-week follow-up period. During the 4-week treatment period, patients will receive 20 sessions of acupuncture (weekly cycles of one session per day for 5 consecutive days followed by a 2-day break). The primary outcome will be a change in the Nepean Dyspepsia Life Quality Index from baseline to after the 4-week treatment period. Secondary outcome measures will include the dyspeptic symptom sum score, Overall Treatment Effect questionnaire, and 36-item Short Form survey. Adverse events also will be recorded. Ultraweak photon emission and metabolomics tests will be performed at baseline and at the end of treatment to explore the mechanisms of the differences between compatible acupoints and a single acupoint. DISCUSSION: The results of this trial will allow us to compare the difference in efficacy between compatible acupoints and a single acupoint. The findings from this trial will be published in peer-reviewed journals. TRIAL REGISTRATION: Acupuncture-Moxibustion Clinical Trial Registry, AMCTR-IPC-18000176, registered on 4 March 2019; Chinese Clinical Trial Registry, ChiCTR1900023983, registered on 23 June 2019.

17.
Diabetes Metab Res Rev ; : e3285, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31909856

RESUMO

AIM: To investigate the association of body mass index (BMI) or BMI z-score (BMIz) at diagnosis with ß-cell function in new-onset type 1 diabetes (T1D) patients in children and adults. METHODS: This was a retrospective cohort study; 256 children (<18 years) and 245 adults (≥ 18 years) with less than one-year duration were recruited and followed for 4 years with an interval of 12 months. Smooth curve fitting, a two-piecewise linear model, and Cox proportional hazards models were utilized to investigate the influence of BMI/BMIz on C-peptide levels. RESULTS: Heavier patients (BMIz≥-1 in children and BMI in adults≥20.2 kg/m2 ) had greater C-peptide with a complicated J curve in all age groups after adjustment for age of onset, sex, and disease duration. Moreover, after 4 years of follow-up, patients with higher BMI/BMIz had a lower risk of ß-cell failure (HR=0.7; 95% CI=0.6-1.0; p=0.026). However, no association was found between baseline BMI/BMIz at diagnosis and C-peptide rate of decline during 1 year follow-up. CONCLUSION: Association between BMI/BMIz and C-peptide in T1D followed a complicated J curve pattern, and heavier patients had greater C-peptide at diagnosis and a lower risk of ß-cell failure at 4 years, suggesting that baseline BMI is a useful predictor for ß-cell function in patients with T1D. This article is protected by copyright. All rights reserved.

18.
FEBS Open Bio ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31898405

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors in the digestive system. A greater understanding of the pathogenesis of PDAC may facilitate the search for new therapeutic targets. Guanine nucleotide-binding protein subunit gamma-12 (GNG12) belongs to the G protein family, and participates in the modulation of the inflammatory signaling cascade. However, the cancer-related function and clinical relevance of GNG12 in PDAC have not previously been reported. Here, we investigated the clinical significance of GNG12 in PDAC using the Oncomine web tool, the GEPIA web tool, and tissue microarray. GNG12 expression was observed to be higher in PDAC patient specimens than in non-tumor pancreatic tissues, and high expression of GNG12 was associated with poor prognosis. We subsequently show that GNG12 promotes pancreatic cancer cell growth in vivo and in vitro, as evaluated using MTS assays, colony formation assays and a xenograft mouse model. Furthermore, our results suggest that GNG12 activates NF-κB signaling and modulates the immune response. Collectively, our findings suggest that GNG12 may be suitable as a new prognosis-related biomarker and a promising target for treatment of pancreatic cancer.

20.
Artif Cells Nanomed Biotechnol ; 48(1): 96-106, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852261

RESUMO

The diabetic foot ulcer (DFU) may be associated with late healing and septic manifestation, subsequently lead to amputation which is an overpriced incident. Neferine is an alkaloid found lotus. Neferine possesses many physiological functions such as anti-inflammatory, antioxidant, antimicrobial activity and anticancer effect. The aim of the present study was to evaluate the effect of topical application based on neferine, in streptozotocin-induced diabetic incision wound models rats. The data demonstrated wound healing activities via macroscopic, biochemical, histological, immuno-histochemical, immunofluorescent and molecular methods. There was significant acceleration in wound closure rate, decrease in the period of re-epitalization, higher amount of collagen and protein content in neferine treated group when compared with diabetic wound control. Histological data evidence collagen formation in skin and marked granulation with more connective tissue markers. The augmentation of serum insulin and HDL was dissimilar with blood glucose reduction and decreased lipid level (TC, TG and LDL). The healing effect was additionally validated by decreased lipid peroxidation and enhanced antioxidants. Concurrently, the mRNA level of Nrf-2, collagen-1, TGF-ß and α-SMA were decreased with Kaep-1 increased significantly. This enhancement was achieved through downregulation of inflammatory mediators such as nuclear factor kappa-light-chain-enhancer of activated B cells, tumour necrosis factor-α, interleukin-1ß, interleukin-8, inducible nitric oxide synthase, and cyclooxygenase-2, and upregulation of growth factor such as in groups treated with neferine. The western blot results reveal the macrophage (CD 68 and CD 163) involved in wound healing markedly elevated. Hence, the results indicate that neferine significantly promotes a fast and efficient wound healing in diabetic rats.

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