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1.
Indian J Pharmacol ; 51(4): 263-268, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571713

RESUMO

INTRODUCTION: As a chronic, progressive, and lethal pulmonary disease, chronic obstructive pulmonary disease (COPD) is lacking effective treatment. Chronic inflammatory processes, including inflammatory cytokines, play an important role with in its pathogenesis. Jianpiyifei (JPYF) granule is a traditional Chinese herbal formula historically used to strengthen the spleen and tonify the lung. JPYF is used clinically to treat stable COPD. However, whether the purported anti-inflammatory effect of JPYF in COPD involves regulation of key inflammatory cytokines is not clear. MATERIALS AND METHODS: The mice model of pulmonary inflammation was induced by lipopolysaccharide (LPS) and cigarette smoke condensate (CSC). The influence of JPYF on airway inflammation in vivo was investigated. Mice were divided into three groups: control, model, and treatment groups. In the CSC + LPS model group and JPYF treatment group, intratracheal injection of CSC and LPS was used to induce airway inflammation for 5 days. JPYF group animals were also orally administered 5.5 g/kg JPYF granule for 12 days. RESULTS: The number of neutrophils and total cells in bronchoalveolar lavage fluid of the JPYF group were markedly lower than in the model group. The levels of interleukin (IL)-1 ß and IL-6 were lower; tumor necrosis factor-alpha was downregulated, and IL-10 was higher in the JPYF group than the model group. In the JPYF group, histone deacetylase 2 (HDAC2) activity and protein expression were restored. CONCLUSION: The anti-inflammatory activity of JPYF involves the suppression of pro-inflammatory cytokines, enhanced IL-10 secretion, and the restoration of HDAC2 activity.

2.
Nanoscale ; 11(39): 18416-18425, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31576862

RESUMO

As a widely studied photoactive antibacterial nanomaterial, the intrinsic antibacterial traits of graphitic carbon nitride (g-C3N4) as a two-dimensional nanomaterial have not been reported so far. Herein, nitrogen-plasma-treated g-C3N4 (N-g-C3N4) nanosheets and their influence on bactericidal characteristics are investigated. Bactericidal rates of more than 99% have been successfully achieved for 8 kinds of foodborne pathogenic bacteria by N-g-C3N4 with 8 h incubation in the dark. The achieved rates are percentage wise 10 times higher than those for pristine g-C3N4. Cell rupture caused by direct mechanical contact between g-C3N4 nanosheets and cell membranes is observed. X-ray photoelectron spectroscopy revealed a substantial loss of surface defects and nitrogen vacancies in N-g-C3N4. Molecular dynamics simulations further indicated that the largely sealed defects of N-g-C3N4 enhanced the electrostatic attraction between inherent pores and lipid heads; thus, further insertion of N-g-C3N4 was promoted, resulting in enhanced antibacterial activity. This study establishes novel fabrication and application strategies for carbon based antibacterial nanomaterials.

3.
J Clin Gastroenterol ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31592795

RESUMO

GOAL: To investigate the clinical characteristics of different primary constipation subtypes, including symptom clusters, psychological problems, quality of life (QOL), and to explore the role of constipation symptoms and the mental state in the QOL of constipation subtypes. BACKGROUND: Patients with chronic constipation (CC) may be unsatisfied with their therapy and suffer recurrent symptoms. Different constipation subtypes require different treatments; therefore, it is important to identify the features of different constipation subtypes. STUDY: CC patients (n=206) visiting our gastroenterology clinic were studied. CC subtypes were diagnosed using the Rome-IV criteria. We used validated questionnaires to investigate the symptom severity, mental state, and QOL of patients. QOL was assessed with the Patient Assessment of Constipation Quality of Life (PAC-QOL) and SF-36 questionnaire. Results of symptom, mental and QOL scores are expressed as means with 95% confidence interval. RESULTS: Three groups of CC patients differed in their constipation scoring system and the Patient Assessment of Constipation Symptoms (PAC-SYM) total scores, and both were significantly higher in the functional defecation disorder (FDD) group compared with that in the normal transit constipation (NTC) group. FDD patients tended to have more severe "abdominal symptoms," "rectal symptoms" than NTC group. No significant difference in General Anxiety Disorder 7-item or Patient Health Questionnaire-9 results was found among the 3 groups. Significantly more patients with FDD suffered more "physical discomfort" and had poorer QOL in the "physical function" dimension of SF-36. FDD and NTC patients mainly showed associations between CC-related QOL and constipation severity, while slow transit constipation patients' QOL was significantly associated with anxiety and depression. CONCLUSION: Patients with FDD suffer more severe constipation symptoms and have a lower QOL than patients in other CC subgroups. FDD and NTC patients' QOL is mainly linked to constipation symptoms, while that of slow transit constipation is mainly related to mental states such as anxiety and depression.

4.
Rev Esp Enferm Dig ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31599640

RESUMO

INTRODUCTION: Sixty-three patients with gastric phytobezoars were reviewed. METHODS: forty-eight (76.2%) patients received endoscopic combined with chemical therapies and 15 (23.8%) received only chemical therapy initially. Fifty-one (81.0%) patients achieved complete removal (only chemical therapy 14/15), while 12 (19.0%) received further endoscopic therapies. RESULTS: finally, 62 (98.4%) patients achieved a complete removal. Considering only patients with combined treatment as a first approach, treatment success was associated with a softer phytobezoar consistency (p = 0.023). CONCLUSION: in conclusion, most patients achieve a favorable outcome. Chemical therapy is useful in selected cases. Repeated endoscopic therapies may be needed in order to completely remove phytobezoars with a hard consistency.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31564416

RESUMO

Alzheimer's disease (AD) is a chronic neurodegenerative disease and mitochondrial impairment is a key feature of AD. The mitochondrial DNA (mtDNA) epigenetic mechanism is a relatively new field compared to nuclear DNA. The relationship between mtDNA epigenetic mechanism and AD hasn't been established. So we analyzed the mtDNA methylation in D-loop region and 12 S rRNA gene in the hippocampi in amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice by bisulfite pyrosequencing. Mitochondrial DNA copy number and gene expression were studied by quantitative real-time PCR (qRT-PCR). We observed a decrease in the displacement loop (D-loop) methylation and an increase in 12 S rRNA gene methylation, while both the mtDNA copy number and the mitochondrial gene expression were reduced in APP/PS1 transgenic mice. In summary, the present finding suggest that mtDNA methylation may play a role in AD pathology, which warrants larger future investigations.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31580067

RESUMO

Covalent organic frameworks (COFs) have obtained considerable interest because of their advanced applications. However, their low dispersibility and aqueous stability are intractable issues limiting their biomedical application. To address the issue, water-dispersible nanocomposites (COF@IR783) produced through the assembly of cyanines and COFs are proposed and prepared. Therefore, a strategy of "killing three birds with one stone" is developed. First, the nanocomposites exhibit superior dispersibility and aqueous stability compared to COFs. The nanocomposites have a nano-sized morphology and negative charges, which are beneficial in realizing long-term circulation properties and enhanced permeability and retention (EPR) mediated tumor targeted delivery for in vivo application. Secondly, the nanocomposites have enhanced photothermal therapy (PTT) ability in the near-infrared region compared to cyanines. The nanocomposites also have photoacoustic (PA) imaging ability, which can guide the antitumor therapy in vivo. Lastly, the nanocomposites can be further used as drug-delivery carriers for loading the anticancer cis-aconityl-doxorubicin (CAD) prodrug. In comparison with individual PTT or chemotherapy, the combination of PTT and chemotherapy achieved with COF@IR783@CAD synergistically induced the death of cancer cells in vitro, and intravenous injection of COF@IR783@CAD in mice resulted in significant tumor ablation. This work indicates that the dispersibility and aqueous stability of COFs can be appropriately overcome through rational design and can further expand the biomedical applications of COFs.

7.
J Nat Prod ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31593459

RESUMO

Tetraena mongolica Maxim, a relict originating from the Tertiary Period, is an endemic species of Zygophyllaceae in China. Three new monoterpenoids (1-3), two new phenols (4, 5) with unusual O-sulfoglucosyl groups, a new flavonoid (6), and nine known compounds were isolated from the leaves of T. mongolica. The structures of these compounds were determined by interpretation of NMR, MS, and ECD data. Some of the isolated compounds showed protective effects on HEK 293t cells damaged by CdCl2, with IC50 values being 55.7 and 80.3 µM for compounds 7 and 8, respectively, at the time point of 48 h after treatment.

8.
Life Sci ; 235: 116818, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31473193

RESUMO

AIMS: Considering the potential oral administration sequences and role of microbiota for metformin (MET) and berberine (BBR) during anti-diabetic treatments, the current study aimed to investigate the pharmacokinetic interactions between MET and BBR in rats after oral administration at different sequences and impacts of microbiota on such interactions. MAIN METHODS: Sprague-Dawley rats were divided into five groups as per what was orally administered to them: MET (G1)/BBR (G2) at 200 mg/kg, BBR 2-hour (h) after dosing MET (G3), MET 2-h after dosing BBR (G4) or MET with BBR at the same time (G5) followed by monitoring their pharmacokinetic profiles. Further in vitro incubations mimicking the above five treatments in rat intestinal content (G1R-G5R), human fecalase (G1H-G5H) and selected bacteria (G1B-G5B) were conducted for both MET and BBR (10 µg/ml for G1R/H-G5R/H and 50 µM for G1B-G5B) up to 24-h. Concentrations of MET and BBR were analyzed by LC/MS/MS. KEY FINDINGS: Although BBR was barely measurable in vivo, it significantly increased systemic exposure of MET in G3/G4. Consistent with pharmacokinetic findings, sequential in vitro incubations of MET and BBR in both rat intestinal content and human fecalase demonstrated significant increase on MET persisted after 24-h incubation in G3R/H & G4R/H. Moreover, post-dose (G3B) and pre-dose (G4B) of BBR decreased the MET degradation significantly in most selected bacteria. SIGNIFICANCE: Our finding for the first time demonstrated the significant effect of sequential co-administration of BBR and MET on their pharmacokinetic interactions, which could be related to their microbiota mediated metabolisms in gastrointestinal tract (GI).

9.
Life Sci ; 235: 116863, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31513817

RESUMO

AIMS: To determine whether dimethyl fumarate (DMF) can protect against lipopolysaccharide (LPS) -induced myocardial injury. MAIN METHODS: H9c2 cells pretreated with or without DMF were stimulated with LPS. Cell viability and apoptosis were evaluated. Nrf2 and HO-1 expression were detected using Western blotting. Mitochondrial morphology, mitochondrial superoxide production were observed using confocal microscope. Mitochondrial respiration function was measured using Seahorse bioanalyzer. KEY FINDINGS: (1) The cell viability decreased, LDH release and apoptosis increased in LPS- challenged H9c2 cells. DMF pretreatment brought a higher cell viability, and a lower LDH leakage and apoptosis than those of LPS group (P < 0.01). (2) DMF pretreatment resulted in an increased Nrf2 and HO-1 expression, and enhanced nuclear Nrf2 level in LPS-challenged cells (P < 0.01). (3) Nrf2-siRNA could inhibit DMF-induced enhancement of HO-1 expression and cell viability, and partly abolish DMF-induced reduction of LDH leakage and apoptosis. (4) ERK1/2 inhibitor PD98059 could not only prevent the DMF-induced enhancement of nuclear Nrf2 and HO-1, but also inhibit DMF-induced increase in cell viability. (5) Compared with LPS-challenged cells, DMF pretreatment caused a lower production of mitochondrial superoxide and a higher mitochondrial membrane potential, which could be abolished by Nrf2-siRNA. (6) DMF could attenuate LPS-induced mitochondrial fragmentation and improve mitochondrial respiration function by enhancement of the oxygen consumption rate of basal respiration and ATP production in LPS-challenged cells (P < 0.01). SIGNIFICANCE: DMF protects cardiomyocytes against LPS-induced damage. ERK1/2-dependent activation of Nrf2/HO-1 pathway is responsible for DMF-induced cardioprotection via reduction of oxidative stress, improvement of mitochondrial morphology and energy metabolism.

10.
J Eukaryot Microbiol ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31486160

RESUMO

Enterocytozoon bieneusi is an important opportunistic pathogen widely distributed in humans and animals that causes diarrhea or fatal diarrhea in immunocompromised hosts. To examine the infection status and molecular characteristics of E. bieneusi in pigs, 725 fecal samples were collected from pigs in six areas of Fujian Province. The E. bieneusi genotypes were identified based on the internal transcribed spacer (ITS) regions of the ribosomal RNA (rRNA) gene by nested PCR, and its population genetics were analyzed by multilocus sequence typing (MLST). The results showed that the infection rate of E. bieneusi was 24.4% (177/725), and 11 known genotypes (EbpC, EbpA, CHN-RR2, KIN-1, CHG7, CHS5, CM11, CHG23, G, PigEBITS, and D) and 2 novel genotypes (FJF and FJS) were identified. All the genotypes were found to be clustered into zoonotic Group 1. Moreover, 52 positive samples were successfully amplified at minisatellite and microsatellite loci and formed 48 distinct multilocus genotypes (MLGs). Further population structure analyses showed strong genetic linkage disequilibrium (LD) and several recombination events (Rm), indicating that E. bieneusi has a clonal population structure. This study is the first to investigate the prevalence and molecular characteristics of E. bieneusi in Fujian Province and could provide baseline data to control E. bieneusi infection in pigs and humans and deepen our understanding of the zoonotic risk of E. bieneusi and its distribution in China.

11.
J Am Heart Assoc ; 8(19): e012441, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31549565

RESUMO

Background The potential alterations of respiratory pathophysiology after cardiopulmonary resuscitation (CPR) are relatively undefined. While untreated arrest is known to affect post-cardiopulmonary resuscitation circulation, whether it affects respiratory pathophysiology remains unclear. We aimed to investigate the post-cardiopulmonary resuscitation changes in respiratory mechanics and neural respiratory drive with varying delays (5 or 10 minutes) in the treatment of ventricular fibrillation (VF). Methods and Results Twenty-six male Yorkshire pigs were used. Anesthetized pigs weighing 38±5 kg were randomized into 3 groups (n=10 each in the VF5 and VF10 groups, with VF kept untreated for 5 and 10 minutes, respectively, and n=6 in the sham group without VF). Defibrillation was attempted after 6 minutes of cardiopulmonary resuscitation. Pulse-induced contour cardiac output, respiratory mechanics, diaphragmatic electromyogram, blood gas, lung imaging, and histopathology were evaluated for 12 hours. Significantly elevated mean root mean square of diaphragmatic electromyogram, transdiaphragmatic pressure, and minute ventilation were observed, but reduced minute ventilation/mean root mean square, dynamic pulmonary compliance, and Pao2 were noted in both VF groups. Despite recovery of spontaneous breathing, the abnormalities in respiratory mechanics and neural respiratory drive, Pao2, and extravascular lung water continued to last for >12 hours. The changes in imaging (P=0.027) and histopathology (P=0.012) were more severe in the VF10 group compared with the VF5 group. Conclusions There is an uncoupling between the respiratory center and ventilation after restoration of spontaneous circulation. Prolonged untreated arrest from cardiac arrest contributes to more serious alterations in lung pathophysiology.

12.
Biomaterials ; 223: 119470, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31526950

RESUMO

Nowadays, two-dimensional (2D) nanomaterials with many fascinating physicochemical properties have drawn extensive attention as drug delivery platforms for cancer theranostics. Nevertheless, current existing 2D nanomaterial-based drug delivery systems normally undergo the bottlenecks of hash preparation process, low drug loading content and unsatisfactory therapeutic outcome. Herein, we developed a novel nanoparticles-induced assemble strategy to construct 2D nanosheets with ultra-high curcumin loading content of 59.6 % and excellent stability in water. Furthermore, a distinct photothermal effect and multimodal imaging property after polydopamine coating could be obtained, thereby leading to precise and efficient ablation of tumor in combination of curcumin-induced chemotherapy. More importantly, the design principle of our work offers novel facile strategy to assemble metal-binding drugs into 2D nanomedicine with high drug content and well-defined shapes.

13.
Sci Total Environ ; 698: 134289, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31514034

RESUMO

Microeukaryotes are the key ecosystem drivers mediating marine productivity, the food web and biogeochemical cycles. The northwestern Pacific Ocean (NWPO), as one of the world's largest oligotrophic regions, remains largely unexplored regarding diversity and biogeography of microeukaryotes. Here, we investigated the community composition and geographical distribution of microeukaryotes collected from the euphotic zone of three different regions in the NWPO using high-throughput sequencing of the 18S rRNA gene and quantified the contributions of environmental factors on the distributions of microeukaryotes. The relative abundance of different group taxa, except for Ciliophora, presented distinct patterns in each region, and Metazoa and Dinoflagellata dominated the community, contributing approximately half of reads abundance. Spatial and environmental factors explained 66.01% of community variation in the NWPO. Temperature was the most important environmental factor significantly correlated with community structure. Bacterial biomass was also significantly correlated with microeukaryotic distribution, especially for Dinoflagellata and Diatomea. Network analysis showed strong correlations between microeukaryotic groups and free-living bacteria and different bacterial taxa were correlated with specific microeukaryotic groups, indicating that their interactions enabled microeukaryotic groups to adapt to diverse environments. This study provides a first glance at the diversity and geographical distribution of microeukaryotes in the NWPO and sheds light on the biotic and abiotic factors in shaping the microeukaryotic community in the ocean.

14.
Ultrason Sonochem ; 59: 104751, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31473421

RESUMO

Ultrasonic sterilization (US), as a promising non-thermal sterilization method, exhibits unique superiorities than traditional sterilization methods. In this study, the inactivation mechanism of E. coli O157:H7 under US was investigated in cucumber and bitter gourd vegetable juices. Results revealed that the US treatment showed good antibacterial ability in countering E. coli O157:H7. Through determinations of conductivity and ß-galactosidase activity, significant augmentation in membrane permeability of the bacteria was confirmed after the US treatment. The morphologies of the US treated E. coli O157:H7 demonstrated that the integrity of the cell membrane was disrupted by US treatment. SDS-PAGE and LSCM data further proved the disruptive action of US, leading to the leakage of proteins and DNA through the breakage on cell membrane. The decrease of metabolic-related enzyme activity was verified through investigation of bacterial metabolism. The antibacterial mechanism analysis indicated that the US can generate free radicals which resulted in the rise of intracellular oxidative stress, attenuation of energy metabolism and inhibition of hexose monophosphate pathway. As the application verification, the US treatment can cause the deprivation of E. coli O157:H7 cell viability in vegetable juices without obvious impact on the sensory quality.

15.
Ann Vasc Surg ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31536792

RESUMO

PURPOSE: This Case aimed to explore the clinical, histological, and immunohistochemical features of intravascular fasciitis (IVF) that involve a large blood vessel. CASE REPORT: A 27-year-old man presented with swelling and pain of the left lower limb for five days. The report of Doppler Ultrasonography confirmed deep-venous thrombosis (DVT) in the lower left limb (acute phase). However, laboratory value for the presence of D-dimer was negative. Thus, we performed an ascending venography and identified a mass in the common femoral vein. At operation, an incision of the left common femoral vein was made, and the mass was completely resected. CONCLUSION: The situation of IVF grew in a large vein is extremely rare and can easily be misdiagnosed as DVT. The presence of D-dimer is important for a differential diagnosis. Ascending venography can be applied in making an accurate diagnosis.

16.
Sci Total Environ ; 692: 1037-1047, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31539936

RESUMO

Dinoflagellates represent major contributors to the harmful algal blooms in the oceans. Phosphorus (P) is an essential macronutrient that limits the growth and proliferation of dinoflagellates. However, the specific molecular mechanisms involved in the P acclimation of dinoflagellates remain poorly understood. Here, the transcriptomes of a dinoflagellate Prorocentrum donghaiense grown under inorganic P-replete, P-deficient, and inorganic- and organic P-resupplied conditions were compared. Genes encoding low- and high-affinity P transporters were significantly down-regulated in the P-deficient cells, while organic P utilization genes were significantly up-regulated, indicating strong ability of P. donghaiense to utilize organic P. Up-regulation of membrane phospholipid catabolism and endocytosis provided intracellular and extracellular organic P for the P-deficient cells. Physiological responses of P. donghaiense to dissolved inorganic P (DIP) or dissolved organic P (DOP) resupply exhibited insignificant differences. However, the corresponding transcriptomic responses significantly differed. Although the expression of multiple genes was significantly altered after DIP resupplementation, few biological processes varied. In contrast, various metabolic processes associated with cell growth, such as translation, transport, nucleotide, carbohydrate and lipid metabolisms, were significantly altered in the DOP-resupplied cells. Our results indicated that P. donghaiense evolved diverse DOP utilization strategies to adapt to low P environments, and that DOPs might play critical roles in the P. donghaiense bloom formation.

17.
Sci Total Environ ; 692: 1250-1256, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31539956

RESUMO

To investigate the effects of human activity on contaminants in regional soil, hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) were measured in 187 surface soil samples of different land-use types collected from the Pearl River Delta (PRD), South China. The concentrations of Σ9OH-PAH (sum of nine target analytes) ranged from 0.36 to 252ng/g (median: 5.98ng/g), with phenanthrene derivatives as the dominant components, accounting for ~70%. Among different land-use types, residency soil contained the highest levels of Σ9OH-PAH (median: 11.3ng/g), followed by landfill soil (9.28ng/g), industry soil (7.51ng/g), agriculture soil (6.04ng/g), forestry soil (4.28ng/g) and drinking water source soil (4.20ng/g). A higher value was also observed in soil from the central PRD (6.94ng/g) than the surrounding areas (5.94ng/g), which indicated a significant impact of human activity on OH-PAH contamination in soil. Correlation and principal component analysis indicated that OH-PAHs in PRD soil are likely derived from the degradation of their parent PAHs in the atmosphere and/or soil and not directly from the same source as the parent PAHs. The ratios of OH-PAHs to their parent PAHs also varied among different land-use types, which may be partly attributed to the different populations of microorganisms in different soil types or the different chemical properties of PAHs and their metabolites.

18.
Acta Dermatovenerol Croat ; 27(3): 142-145, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31542056

RESUMO

Pemphigus is an autoimmune bullous disease, and although several diagnostic methods are now in use indirect immunofluorescence (IIF) is still considered an important tool for diagnosing pemphigus because of its convenience, repeatability, and reduced pain for patients. The goal of the present study was to evaluate the diagnostic value of IIF on normal human skin (NS), monkey esophagus (ME), and salt-split skin (SS) for better diagnosis of pemphigus. Clinical data of 70 patients with pemphigus and 56 control were collected. IIF on NS, ME, and SS were assessed separately by observing fluorescein deposition and comparing its differentiation to different kinds of pemphigus and its sensitivities and specificities to different substrates. Intercellular deposition of IgG was visible when IIF on NS, ME, and SS were positive in patients with pemphigus. Their corresponding sensitivities and specificities were 30.0%, 84.3%, and 70.0% and 96.4%, 96.4%, and 94.6%, respectively. The differences in sensitivity were statistically significant between NS and ME and between NS and SS (P<0.001) and the specificities among the three substrates were not statistically significantly different (P>0.05). As for different types of pemphigus, the sensitivities between NS and ME and between NS and SS were statistically significantly different in both Dsg1- and Dsg3-positive and only Dsg1-positive patients with pemphigus (P<0.01); the sensitivities between NS and ME were statistically significantly different only in Dsg3-positive patients with pemphigus (P<0.001); there were no statistically significant differences between ME and SS. We therefore propose that ME is a good substrate for pemphigus diagnosis with higher sensitivity and superior to NS, particularly for patients with anti-Dsg3 antibodies. SS is a good alternative substrate to ME with almost identical higher sensitivities and specificities for diagnosis of pemphigus.

19.
Oncol Rep ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31545455

RESUMO

Poly(ADP­ribose) polymerase (PARP) inhibitors have little effect on homologous recombination repair (HRR)­proficient tumor types, such as cervical cancer. In addition to catalytic activity, the PARP inhibitor, BMN673, traps PARP1 on damaged DNA and induces cytotoxic effects. The aim of the present study was to evaluate the therapeutic effect of PI3K inhibitors and BMN673 on cervical cancer cells. The Chou­Talalay method was used to assess the synergistic effect of drug combinations on cervical cancer cells. The effect of PI3K inhibitors and BMN673 on cell growth and survival were also assessed via a Cell Counting Kit­8 assay and three­dimensional sphere culture. Cell migration and invasion were assessed via Transwell migration and Matrigel invasion assays, respectively. In addition, DNA damage and HRR competency were assessed via immunofluorescent staining analysis of γH2AX and RAD51 foci, and tail moment in a comet assay. PARP1 binding in chromatin was assessed via a cellular trapping assay. Ex vivo cultured sections of patient­derived cervical tumors were subjected to drug exposure followed by histological and immunohistochemical analyses. The results revealed that the PI3K p110α inhibitor BYL719 and the PARP inhibitor BMN673 synergized to inhibit cervical cancer cell proliferation, migration and invasion in vitro and ex vivo. However, the pan­PI3K inhibitor BKM120 did not produce the aforementioned effects. Additionally, cervical cancer cells exhibiting aberrant PI3K activation were more responsive to the combined inhibition of PI3K p110α and PARP. Mechanistically, BYL719 co­operated with BMN673 to increase PARP1 trapping on chromatin, induce severe DNA damage and exert cytotoxic effects. The combined use of BMN673 and BYL719 may serve as a promising therapeutic strategy for patients with cervical cancer exhibiting aberrant PI3K activation.

20.
Biomolecules ; 9(9)2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31480670

RESUMO

Tannins biodegradation by a microorganism is one of the most efficient ways to produce bioproducts of high value. However, the mechanism of tannins biodegradation by yeast has been little explored. In this study, Aureobasidium melanogenum T9 isolated from red wine starter showed the ability for tannins degradation and had its highest biomass when the initial tannic acid concentration was 20 g/L. Furthermore, the genes involved in the tannin degradation process were analyzed. Genes tan A, tan B and tan C encoding three different tannases respectively were identified in the A. melanogenum T9. Among these genes, tan A and tan B can be induced by tannin acid simultaneously at both gene transcription and protein expression levels. Our assay result showed that the deletion of tanA and tanB resulted in tannase activity decline with 51.3 ± 4.1 and 64.1 ± 1.9 U/mL, respectively, which is much lower than that of A. melanogenum T9 with 91.3 ± 5.8 U/mL. In addition, another gene coding gallic acid decarboxylase (gad) was knocked out to better clarify its function. Mutant Δgad completely lost gallic acid decarboxylase activity and no pyrogallic acid was seen during the entire cultivation process, confirming that there was a sole gene encoding decarboxylase in the A. melanogenum T9. These results demonstrated that tanA, tanB and gad were crucial for tannin degradation and provided new insights for the mechanism of tannins biodegradation by yeast. This finding showed that A. melanogenum has potential in the production of tannase and metabolites, such as gall acid and pyrogallol.

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