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1.
Appl Opt ; 59(3): 607-613, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32225184

RESUMO

We present a dual-channel mobile lidar system based on laser-induced fluorescence (LIF) for real-time standoff detection and concentration distribution analysis of tryptophan. The system employs an ultraviolet laser excitation source and signal detectors for receiving fluorescence signals within two different wavelength bands. The performed experiments measured tryptophan aerosols at two different standoff distances. Moreover, distilled water and ethanol solutions were also detected for comparison. The results show that the system can detect LIF signals of tryptophan, give early warnings, locate the diffusion sources, and monitor the variation of the aerosol concentration distribution in real time.

2.
Clin Rheumatol ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32133565

RESUMO

OBJECTIVES: Fatigue is a common symptom in patients with ankylosing spondylitis (AS). However, fatigue of AS patients has not been well elucidated in China. This study aimed to evaluate the predictors of fatigue and the effects of fatigue on health-related quality of life among patients with AS. METHOD: A total of 150 AS patients were involved in the study. A series of questionnaires included the following: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), the 10-cm Visual Analog Scale (VAS), the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), the Pittsburgh Sleep Quality Index (PSQI), the Health Assessment Questionnaire-Disability Index (HAQ-DI), the Short Form 36 Health Survey (SF-36), and the Fatigue Severity Scale (FSS). Independent samples t test, Mann-Whitney U test, chi-square analysis, Pearson/Spearman correlation, and binary logistic regression were used to analyze the data. RESULTS: The results demonstrated that 48.7% individuals with AS suffered from fatigue. Binary logistic regression indicated that waist-to-hip ratio, BASDAI, and sleep disturbance were independent predictors of fatigue in AS patients. Meanwhile, severe fatigue led to lower quality of life. CONCLUSION: These findings suggested that medical personnel should pay more attention to AS patients with fatigue and take effective measures to relieve fatigue.Key Points• Incidence of fatigue in AS patients is 48.7% according to this cross-sectional study.• The occurrence of fatigue was associated with higher WHR, higher BASDAI, and sleep disturbance.• We also found that the occurrence of fatigue significantly reduced the quality of life in AS patients both physically and psychologically.

3.
J Cell Mol Med ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32135028

RESUMO

Radiation protection on male testis is an important task for ionizing radiation-related workers or people who receive radiotherapy for tumours near the testicle. In recent years, Toll-like receptors (TLRs), especially TLR4, have been widely studied as a radiation protection target. In this study, we detected that a low-toxicity TLR4 agonist monophosphoryl lipid A (MPLA) produced obvious radiation protection effects on mice testis. We found that MPLA effectively alleviated testis structure damage and cell apoptosis induced by ionizing radiation (IR). However, as the expression abundance differs a lot in distinct cells and tissues, MPLA seemed not to directly activate TLR4 singling pathway in mice testis. Here, we demonstrated a brand new mechanism for MPLA producing radiation protection effects on testis. We observed a significant activation of TLR4 pathway in macrophages after MPLA stimulation and identified significant changes in macrophage-derived exosomes protein expression. We proved that after MPLA treatment, macrophage-derived exosomes played an important role in testis radiation protection, and specially, G-CSF and MIP-2 in exosomes are the core molecules in this protection effect.

4.
Cancers (Basel) ; 12(3)2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32168902

RESUMO

Hepatitis B virus (HBV) is one of predisposing factors for hepatocellular carcinoma (HCC). The role of HBV x protein (HBx) in mediating the induction and maintenance of cancer stemness during HBV-related HCC attracts considerable attention, but the exact mechanism has not been clearly elucidated. Here, ABCG2-dependent stem-like side population cells, which are thought to be liver cancer stem cells (LCSCs), were present in HCC cells, and the fraction of this subset was increased in HBx-expressing HCC cells. In addition, glycolysis was upregulated in LCSCs and HBx-expressing HCC cells, and intervention of glycolysis attenuated cancer stem-like phenotypes. Mitochondria play an important role in the maintenance of energy homeostasis, BNIP3L-dependent mitophagy was also activated in LCSCs and HBx-expressing HCC cells, which triggered a metabolic shift toward glycolysis. In summary, we proposed a positive feedback loop, in which HBx induced BNIP3L-dependent mitophagy which upregulated glycolytic metabolism, increasing cancer stemness of HCC cells in vivo and in vitro. BNIP3L might be a potential therapeutic target for intervention of LCSCs-associated HCC. Anti-HBx, a monoclonal antibody targeting intracellular HBx, had the potential to delay the progression of HBV infection related-HCC.

5.
Sheng Wu Gong Cheng Xue Bao ; 36(2): 295-308, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32148002

RESUMO

γ-polyglutamic acid (γ-PGA) is widely used in food processing, cosmetic production, medicinal industry, etc. Currently, the production strains used in fermentation process are commonly glutamic acid-dependent, which results in extra cost. In this study, a de novo way of producing γ-PGA from sugars was reported. To this end, the γ-polyglutamate synthase gene cluster pgsBCA was cloned from the natural γ-PGA-producing strain Bacillus subtilis (ATCC 6051-U), and was constitutively and inducibly expressed in Corynebacterium glutamicum ATCC 13032. Only inducible expression of pgsBCA can lead to the generation of γ-PGA with a titer of 1.43 g/L from glucose, without any supplementation of glutamic acid. The production was further elevated to 1.98 g/L upon optimization of the induction conditions with the induction time at 2 h post-inoculation and the IPTG concentration of 0.8 mmol/L. Moreover, to achieve a higher titer of γ-PGA, pgsBCA was inducibly expressed in C. glutamicum F343, which shows a paramount glutamate production capacity. The final γ-PGA production reached 10.23 g/L in shake flasks and 20.08 g/L in a 5-L fermentor using glucose as the substrate. The weight-average molecular weight (Mw) of γ-PGA from recombinant strain F343 showed 34.77% higher than that produced by B. subtilis. This study provides a novel way of producing γ-PGA from sugars directly and potentiates new applications of γ-PGA in the future.


Assuntos
Corynebacterium glutamicum , Fermentação , Ácido Poliglutâmico/análogos & derivados , Açúcares
6.
Br J Pharmacol ; 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32219844

RESUMO

BACKGROUND AND PURPOSE: Increasing evidence has indicated that the high risk of cardiovascular disease in chronic kidney disease (CKD) patients cannot be sufficiently explained by classic risk factors. EXPERIMENTAL APPROACH: Based on the least absolute shrinkage and selection operator method, we identified significantly altered renal tissue metabolites during progressive CKD in a 5/6 nephrectomised rat model and in CKD patients. KEY RESULTS: Six aryl-containing metabolites (ACM) were significantly increased from week 1 to week 20. They were associated with the activation of aryl hydrocarbon receptor (AhR) and its target genes including CYP1A1, CYP1A2, and CYP1B1, which were further validated by molecular docking. Our study further demonstrated that AhR signalling could be activated by ACM in patients with idiopathic membranous nephropathy, diabetic nephropathy, and immunoglobulin A nephropathy. Most importantly, 1-aminopyrene (AP) showed strong positive and negative correlation with serum creatinine and creatinine clearance, respectively. AP significantly upregulated the mRNA expressions of AhR and its three target genes in both mice and NRK-52E cells, while this effect was partially weakened in AhR shRNA-treated mice and NRK-52E cells. Furthermore, dietary flavonoid supplementation ameliorated CKD and renal fibrosis through partially inhibiting the AhR activity via lowering the ACM levels. The antagonistic effect of flavonoids on AhR was deeply influenced by the number and location of hydroxyl and glycosyl groups. CONCLUSION AND IMPLICATIONS: We uncovered that endogenous AP is a novel mediator of CKD progression via AhR activation; thus, AhR might serve as a promising target for CKD treatment.

7.
Immun Inflamm Dis ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125091

RESUMO

INTRODUCTION: Alveolar macrophages (AMs) are critical in the development of lung adenocarcinoma driven by epidermal growth factor receptor (EGFR) mutations. Whether interstitial macrophages (IMs) are also involved in lung tumorigenesis is still unclear. Thus, the aim of this study is to evaluate the role of both AM and IM in the development of EGFR mutant driven lung adenocarcinoma. METHODS: We used the EGFR mutant doxycycline-inducible mouse model of lung adenocarcinoma to deplete interstitial or AMs by clodronate-encapsulated liposomes administered intravenously (IV) and intratracheally (IT), respectively. Tumor burden, AMs, and the tumor microenvironment were examined by immunohistochemistry, bronchoalveolar lavage fluid or flow cytometry. RESULTS: Clodronate treatment resulted in a significant reduction of tumor burden compared with vehicle liposomes alone. Elimination of AMs resulted in a significant reduction of proliferation compared with IV treatment. However, both treatments resulted in a significantly higher number of Ki67 positive cells compared with control mice, suggesting that tumor cells still proliferate despite the treatment. The number of natural killer cells decreased during tumor development, and it remained low even after the elimination of AMs. We also observed that IT instillation of clodronate significantly increased the number of CD8+ T cells, which was higher compared with vehicle-treated mice and mice where only IMs were depleted. The similar trend was observed in immunohistological analyses of CD8+ T cells. CONCLUSIONS: These results suggest that the reduction of AMs has a stronger impact on restricting tumor progression compared with targeting IMs. The depletion of AMs leads to an elevated infiltration of CD8+ T cells into the lung that might be responsible for tumor growth impairment. Altogether, elimination of AMs is a better strategy to reduce EGFR mutant tumor growth and is less toxic, suggesting the selectively targeting of AMs to complement established therapies.

8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 209-213, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027278

RESUMO

OBJECTIVE: To investigate the expression characteristics and clinical value of OTC4 gene in patients with myelodysplastic syndrome (MDS). METHODS: Sixty-five patients with MDS were selected from June 2017 to April 2018, and 39 healthy subjects were selected as control group. Mononuclear cells were isolated from bone marrow collected by aseptic puncture. The OTC4 gene level of MDS patients was detected by RT-PCR, and the OTC4 protein of MDS patients was detected by Western blot. The survival curve of MDS patients was drawn by Kaplan-Meier. Cox multivariate analysis was used to analyze the independent prognostic factors. RESULTS: The relative expression level of OTC4 gene in MDS patients was significantly higher than that in the control group (P<0.05). Western blot showed that the expression level of OTC4 protein in MDS patients was higher than that in the control group (P<0.05). OTC4 gene expression level closely related with the leukocyte count, and the level of hemoglobin, and lactate dehydrogenase and platelet count in MDS patients (P<0.05). CR rate of MDS patients with low OTC4 gene expression was 54.8%, which was higher than that of high OTC4 gene expression group (P<0.05), while HI, SD and PD rates of MDS patients with low OTC4 gene expression were 9.7%, 12.9% and 6.5% respectively, which were lower than those of high OTC4 gene expression group (P<0.05). Kaplan-Meier survival analysis showed that OS and DFS in patients with low OTC4 gene expression were superior to those with high OTC4 gene expression (P<0.05). Multivariate Cox regression analysis showed that leukocyte count and OTC4 gene were independent influencing factors for OS (P<0.05), platelet level and OTC4 gene expression were independent influencing factors for DFS (P<0.05). CONCLUSION: OTC4 gene closely relates with the severity of MDS. The patients with lower expression of OTC4 gene have better prognosis, the detection of OTC4 gene has higher clinical value for evaluating the prognosis of MDS patients.


Assuntos
Síndromes Mielodisplásicas , Medula Óssea , Células da Medula Óssea , Regulação Neoplásica da Expressão Gênica , Humanos , Contagem de Leucócitos , Síndromes Mielodisplásicas/genética , Prognóstico
9.
Addict Biol ; : e12884, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32043707

RESUMO

Drug relapse among addicts often occurs due to the learned association between drug-paired cues and the rewarding effects of these drugs, such as morphine. Contextual memory associated with morphine has a central role in maintenance and relapse. We showed that morphine-conditioned place preference (CPP) activates extracellular-regulated protein kinase (ERK) in the nucleus accumbens (NAc). The main enzymes that mediate ERK dephosphorylation are members of the dual-specificity phosphatase (DUSP) superfamily. It is unclear which members regulate the morphine CPP-induced activation of ERK. After screening, DUSP15 was found to be decreased during both morphine CPP expression and the reinstatement period. Intra-NAc infusions of AAV-DUSP15 (overexpression) not only prevented the expression of morphine-induced CPP but also facilitated extinction, inhibited reinstatement, and abolished ERK activation. However, after repeated morphine exposure and withdrawal in mice, there was no change in the expression of p-ERK and DUSP15, and the overexpression of DUSP15 in the NAc did not improve the impaired spatial memory or anxiety-like behaviour induced by morphine. Together, these findings indicate that DUSP15 not only prevents the expression of drug-paired contextual memory but also promotes the extinction of existing addiction memories, thus providing a novel therapeutic target for the treatment of drug addiction.

10.
Int Immunopharmacol ; 81: 106195, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028242

RESUMO

Baicalin (BA), a flavone glycoside, is the constituent of Scutellaria baicalensis, a Chinese herbal medicine used to treat non-alcoholic steatohepatitis (NASH). However, the mechanism of BA on NASH is still not clear. Here, the improving effect of BA on hepatocyte through inhibition of pyroprosis was investigated in vitro. With a cell model of NASH exposing HepG2 cells in free fatty acids (FFA), we revealed that BA could improve hepatocyte from FFA-induced morphological damage and death. And then through transcriptomes screening, a significant down-regulation of NLR pyrin domain containing 3 (Nlrp3), gasdermin D (Gsdmd), andinterleukin-1 beta (IL-1ß) expression were found after BA treatment. Further analysis confirmed that BA could decrease the levels of NLRP3 and GSDMD, as well as the release of IL-1ß and IL-18, resulting in the reduction of pyroptosis. Moreover, the improving effect of BA could be attenuated by Gsdmd knockdown. In conclusion, BA can reduce pyroptosis of hepatocyte by blocking NLRP3-GSDMD signaling in vitro.

11.
Int Immunopharmacol ; 81: 106271, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32062071

RESUMO

Glaucocalyxin A (GLA) is a bioactive ent-kauranoid diterpenoid derived from the herbal medicine, Rabdosia japonica var. glaucocalyx, and it has been reported to possess marked anti-inflammatory properties. However, the underlying mechanisms are not fully understood. Here, we reported that GLA dramatically inhibited canonical and non-canonical NLRP3 inflammasome activation induced by multiple agonists. In addition, GLA also blocked NLRC4 inflammasome activation but had no effect on AIM2 inflammasome. Furthermore, we found that GLA inhibited NLRP3 or NLRC4 agonists-induced ASC oligomerization, which is an upstream event of the inflammasomes assembly. Most importantly, administration of GLA significantly reduced lipopolysaccharide (LPS)-induced mortality in septic-shock mouse model. Additionally, GLA dose-dependently inhibited the production of interleukin (IL)-1ß, but had no effect on NLRP3-independent TNF-α production induced by LPS in vivo. In conclusion, our study suggests that GLA alleviates LPS-induced septic shock and inflammation via inhibiting NLRP3 inflammasome activation and provides a promising candidate drug for the treatment of NLRP3-driven diseases.

12.
Sci Total Environ ; 716: 137083, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32036149

RESUMO

It is generally recognized that marginal changes in landscape characteristics can influence multiple ecosystem services, but the causal relationships involved are still very unclear due to lack of knowledge and data gaps. Planners and managers need spatial information and evidence on these causal relationships for systematic and sound land planning. This study evaluated the effects of landscape characteristics on seven types of ecosystem services and the trade-offs among the ecosystem services by combining statistical data and the InVEST model with correlation analysis across Taihu Lake Basin, China. We found that all ecosystem services except food production increased from 2005 to 2015 in the whole basin. We also found that correlations between landscape characteristic metrics and ecosystem services indicators changed over time for different types of ecosystem service indicators at the county scale, and between county and pixel scale. The results demonstrated the effects of landscape characteristic metrics on multiple ecosystem services indicators and the tradeoffs among these ecosystem services indicators, and also revealed scale effects on correlations and tradeoffs. Therefore planners and managers need to consider both landscape characteristic metrics and scale effects for effective landscape management to improve ecosystem services and reduce unwanted tradeoffs.

13.
J Cell Physiol ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32012270

RESUMO

To evaluate the effects of fatty acids on endoplasmic reticulum (ER) stress, oxidative stress, and lipid damage. We treated BRL3A rat liver cells with, linoleic (LA), linolenic, oleic (OA), palmitic (PA), palmitoleic (POA), or stearic (SA) acid for 12 hr. The characteristics of cell lipid deposition, oxidative stress indexes, ER stress markers, nuclear factor κB p65 (NF-κB p65), lipid synthesis and transport regulators, and cholesterol metabolism regulators were analyzed. Endoplasmic chaperones like glucose-regulated protein 78, CCAAT-enhancer-binding protein, NF-κB p65, hydrogen peroxide, and malonaldehyde in PA- and SA-treated cells were significantly higher than in other treated cells. Deposition of fatty acids especially LA and POA were significantly increased than in other treated cells. De novo lipogenesis regulators sterol regulatory element-binding protein 1c, fatty acid synthase, and acetyl-coenzyme A carboxylase 1 (ACC1) expression were significantly increased in all fatty acid stimulation groups, and PA- and SA-treated cells showed lower p-ACC1 expression and higher scd1 expression than other fatty acid groups. Very low-density lipoprotein synthesis and apolipoprotein B100 expression in free fatty acids treated cells were significantly lower than control. PA, SA, OA, and POA had shown significantly increased cholesterol synthesis than other treated cells. PA and SA showed the lower synthesis of cytochrome P7A1 and total bile acids than other fatty acids treated cells. Excess of saturated fatty acids led to severe ER and oxidative stress. Excess unsaturated fatty acids led to increased lipid deposition in cultured hepatocytes. A balanced fatty acid intake is needed to maintain lipid homeostasis.

14.
Cell Immunol ; 349: 104046, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32057354

RESUMO

Uncontrolled activation of NLRP3 inflammasome initiates a series of human inflammatory diseases. Targeting NLRP3 inflammasome has attracted considerable attention in developing potential therapeutic interventions. Here, we reported that dehydrocostus lactone (DCL), a main component of Saussurea lappa from the traditional Chinese medicine, inhibited NLRP3 inflammasome-mediated caspase-1 activation and subsequent interleukin (IL)-1ß production in primary mouse macrophages and human peripheral blood mononuclear cells and exerted an inhibitory effect on NLRP3-driven inflammation. Mechanistically, DCL significantly blocked the ASC oligomerization, which is essential for the assembly of activated inflammasome. Importantly, in vivo experiments showed that DCL reduced IL-1ß secretion and peritoneal neutrophils recruitment in LPS-mediated inflammation mouse model, which is demonstrated to be NLRP3 dependent. These results suggest that DCL is a potent pharmacological inhibitor of NLRP3 inflammasome and may be developed as a therapeutic drug for treating NLRP3-associated diseases.

15.
Cytogenet Genome Res ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32092754

RESUMO

DCC netrin 1 receptor (DCC) affects the structure and function of the dopamine circuitry, which in turn affects the susceptibility to developing addiction. In a previous study, we found that single nucleotide polymorphism (SNP) rs12607853 in the 3' untranslated region (3'-UTR) of DCC was significantly associated with heroin addiction. In the current study, we first used bioinformatics prediction to identify the DCC rs12607853 C allele as a potential hsa-miR-422a and hsa-miR-378c target site. We then used vector construction and dual-luciferase reporter assays to investigate the targeting relationship of DCC rs12607853 with hsa-miR-422a and hsa-miR-378c. The dual-luciferase reporter gene assay confirmed that the C allele of rs12607853 in combination with hsa-miR-422a led to repressed dual-luciferase gene expression. Moreover, gene expression assays disclosed that hsa-miR-422a inhibited DCC expression at both the mRNA and protein levels. We also found that morphine inhibited the expression of hsa-miR-422a but increased the expression of DCC mRNA, and this change in the expression of hsa-miR-422a could not be reversed by naloxone, which suggested that the role of DCC in opioid addiction might be regulated by hsa-miR-422a. In summary, this study improves our understanding of the role of hsa-miR-422a and identifies the genetic basis of rs12607853, which might contribute to the discovery of new biomarkers or therapeutic targets for opioid addiction.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32095885

RESUMO

PURPOSE: Stereotactic body radiotherapy (SBRT) is the primary treatment method for early-stage non-small cell lung cancer (NSCLC) considered inoperable due to medical comorbidities. However, the application of SBRT in patients aged ≥ 75 years has not been adequately studied. This retrospective study aimed to investigate the effectiveness and safety of SBRT in early-stage NSCLC patients aged ≥ 75 years, and the impact of treatment on nutritional status and self-care ability. METHODS: Histopathologically confirmed early-stage (T1-3N0M0) NSCLC patients aged ≥ 75 years treated with SBRT between 2013 and 2018 at our center were identified from the electronic database. Treatment efficacy, treatment toxicities, impact of treatment on nutritional status, and self-care ability were retrospectively analyzed. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Event (CTCAE) (Common 2010) version 4.0. Nutritional status was assessed by Nutritional Risk Screening 2002 criteria, and self-care ability by Barthel index and fall risk index. RESULTS: A total of 68 patients were enrolled. Median follow-up duration was 46.3 (3.9-80.1) months. The 1-, 3-, and 5-year overall survival rates were 92.6%, 77.2%, and 59.1%, respectively, and the 1-year, 3-year and 5-year local control rates were 95.6%, 88.9% and 85.6%, respectively. Grade 1-2 and grade 3 radiation pneumonitis occurred in 60/68 (96.8%) and 1/68 (1.5%) patients, respectively. Fall risk at 3 months after treatment was not significantly different from that before treatment (P = 0.22). Barthel index increased significantly after treatment (P < 0.001). CONCLUSIONS: SBRT appears to be effective and safe for NSCLC patients aged ≥ 75 years, with no adverse impact on nutritional status and self-care ability.

17.
Proc Natl Acad Sci U S A ; 117(2): 931-935, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31888989

RESUMO

Noncognitive skills (e.g., persistence and self-control) are typically measured using self-reported questionnaires in which respondents rate their own skills. In many applications-including program evaluation and school accountability systems-such reports are assumed to measure only the skill of interest. However, self-reports might also capture other dimensions aside from the skill, such as aspects of a respondent's situation, which could include incentives and the conditions in which they complete the questionnaire. To explore this possibility, this study conducted 2 experiments to estimate the extent to which survey administration conditions can affect student responses on noncognitive skill questionnaires. The first experiment tested whether providing information about the importance of noncognitive skills to students directly affects their responses, and the second experiment tested whether incentives tied to performance on another task indirectly affect responses. Both experiments suggest that self-reports of noncognitive skills are sensitive to survey conditions. The effects of the conditions are relatively large compared with those found in the program evaluation literature, ranging from 0.05 to 0.11 SDs. These findings suggest that the effects of interventions or other social policies on self-reported noncognitive skills should be interpreted with caution.

18.
Oral Oncol ; 102: 104559, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31923856

RESUMO

Oral mucositis (OM) is a common and troublesome adverse side effect of many cancer therapy modalities (chemotherapy, radiotherapy, and chemo-radiotherapy), which can cause pain, ulceration, dysphagia, malnutrition, even treatment interruption. Probiotics may be effective in preventing and treating of cancer therapy-induced OM. We performed a systematic review and meta-analysis of the effectiveness of probiotics in prevention and treatment of cancer therapy-induced OM. Four databases and one trial registry were searched as of the 12th of May 2019 to identify all eligible randomized controlled trials (RCT). Five studies involving 435 patients were included in this study. Methodological quality and outcomes were evaluated in every study included. Pooled results showed a moderate heterogeneity (P = 0.15, I2 = 44%). The pooled RRs indicated that the use of probiotics decreased the risk of OM for grade ≥3 (RR = 0.66, 95%CI = 0.54-0.81, P < 0.0001) as well as all grades (RR = 0.83, 95% CI = 0.72-0.97, P = 0.02). There was no significant difference between probiotics and placebo for cancer therapy completion rate (RR = 1.14, 95%CI = 0.65-2.00, P = 0.64). The subgroup analysis indicated that the use of probiotics was not statistically significant for patients receiving chemo-radiotherapy (RR = 0.52, 95% CI = 0.26-1.04, P = 0.07). In conclusion, probiotics may reduce the incidence and mitigate the severity of cancer therapy-induced OM. Further trials with a randomized, double-blind and multicentric study design are needed to confirm this effect. The PROSPERO registration number of this systematic review and meta-analysis is CRD42019130414.

19.
Biomed Pharmacother ; 122: 109619, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31919040

RESUMO

FLT3-ITD+ acute myeloid leukemia (AML) is an important subtype of AML, accounting for approximately 25 % of all AML cases in the world. Recently, increasing evidence has shown that circular RNAs (circRNAs) can act as effective biomarkers of various human cancers. However, the roles of circRNAs in AML remain largely unclear. In the present study, circ_0000370 was found to be significantly increased in FLT3-ITD+ AML and was demonstrated to act as an oncogenic circRNA of AML in vitro. TargetScan results showed that miR-1299, miR-370-3p, miR-502-5p, miR-1281 and miR-640 were potential targets of circ_0000370, and miR-1299 had the broadest range of interactome compared with other microRNAs of interest. Moreover, we demonstrated that S100A7A was a target gene of miR-1299, and circ_0000370 could regulate S100A7A expression by sponging miR-1299 in AML cell lines. Therefore, we suggest that the promoting effects of circ_0000370 on the progression of FLT3-ITD+ AML might be relevant to the inhibition of miR-1299 and the upregulation of S100A7A.

20.
Curr Microbiol ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932996

RESUMO

In this work, the high-level expression of the human lysozyme (HLY) was achieved by both optimization of the gene copy number and co-expression of the transcription factor Hac1p for the unfolded protein response (UPR) in the host strain Pichia pastoris KM71H. A series of recombinant constructs with various numbers of HLY expression cassettes was generated for the production of recombinant strains integrated with different copies of the HLY gene. The copy number of the HLY gene was determined by real-time quantitative polymerase chain reaction, and the recombinant strains of P. pastoris carrying one, two, three, four, or six copies of the HLY gene were obtained. Maximum extracellular protein and lysozyme enzyme activity reached 436.99 ± 26.08 µg/mL and 61,900 ± 2036.47 U/mL, respectively, in the recombinant strain HLYH4-3 with the four copies of the HLY gene after shaking flask fermentation. Moreover, the co-expression of the transcription factor Hac1p in the recombinant strains further enhanced the HLY yields. Extracellular protein and lysozyme enzyme activity, respectively, reached 517.82 ± 4.19 µg/mL and 78,600 ± 1134.95 U/mL by using the Hac1p co-expression strain HLYH4-3/Hac1p. These values are the highest recorded level of human lysozyme expressed by P. pastoris in shaking flask fermentation so far.

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