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1.
J Cell Physiol ; 235(1): 480-493, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31385301

RESUMO

Alzheimer's disease (AD) is a progressive and age-related neurological dysfunction. Abundant data have profiled microRNA (miR) patterns in healthy, aging brain, and in the moderate and late-stages of AD. Herein, this study aimed to explore whether miR-326 could influence neuron apoptosis in AD mice and how miR-326 functions in this process. The candidate differentially expressed gene VAV1 was obtained by microarray analysis, and miRNAs that could regulate VAV1 candidate gene were predicted. Luciferase activity determination confirmed VAV1 as a target gene of miR-326. AD mice models were established for investigating the effect of miR-326 on AD mice. The overexpression of miR-326 contributed to decreased time of the mice to find the platform and the escape latency and increased residence time on the target area. Besides, elevation of miR-326 decreased Aß deposition and contents of Aß1-40 and Aß1-42 . Moreover, miR-326 overexpression increased neuron cell ability, mediated cell entry, and inhibited neuron apoptosis via JNK signaling pathway. Of crucial importance, miR-326 negatively regulated the expression of VAV1, inhibited tau phosphorylation, and blocked the activation of the JNK signaling pathway. Taken together these observations, we demonstrate that miR-326 improves cognitive function of AD mice and inhibits neuron apoptosis in AD mice through inactivation of the JNK signaling pathway by targeting VAV1. Based on those findings, miR-326 might exert promise as target for the treatment of AD.

2.
J Hazard Mater ; 382: 121064, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31499370

RESUMO

The development of non-cobalt-based heterogeneous catalysts with efficient catalytic activity, good stability and nontoxicity is very important for the application of peroxymonosulfate-based advanced oxidation processes (AOPs) in water treatment. In this work, with two dimensional MXene as the catalyst substrate, a novel α-Fe2O3/MXene (FM) nanocomposite was fabricated through a facile solvothermal method. Systematic characterization demonstrated that the MXene substrate could facilitate the size reduction and good dispersion of α-Fe2O3 nanoparticles. The FM nanocomposite achieved high efficiency and stability towards activating peroxymonosulfate (PMS) to produce free radicals for the degradation of salicylic acid (SA) in aqueous solution. The operating parameters, including catalyst dosage, PMS dosage, SA concentration and initial pH value, were evaluated and analysed. The co-existence of sulfate radicals (SO4-) and hydroxyl radicals (OH) was confirmed using electron paramagnetic resonance spectroscopy and radical scavenger tests, while SO4-was identified as the main reactive species in the FM/PMS catalytic system. The possible mechanisms for the electron transfer and radical generation during the process of PMS activation by the FM nanocomposite are further investigated using XPS and in situ Raman analysis. The results provide an avenue for rationally constructing and developing alternative catalysts for the treatment of organics in wastewater.

3.
AIDS Care ; : 1-8, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672027

RESUMO

China is experiencing an emerging HIV epidemic among men who have sex with men (MSM). Minority stress theory posits that marginalized populations experience additional stress, which influences experiences of psychological distress and health outcomes. This study aimed to understand psychological distress of MSM relative to men who have sex with women (MSW) in an urban Chinese setting. Cross-sectional survey data were collected from 162 HIV-positive Chinese men receiving HIV treatment at Beijing's Ditan Hospital. Multiple linear regression with imputation was used to identify correlates of psychological distress. Relative to MSW, MSM were younger, more educated, and less likely to be in a relationship or have children. While both groups reported clinically elevated levels of depression and anxiety, sexual behavior was not associated with either outcome. Higher endorsement of depression symptomology was associated with worse reported physical health (ß = -1.37, p < .05) and greater endorsement of maladaptive coping (ß = 2.39, p < .05), whereas higher endorsement of anxiety symptomology was associated with greater endorsement of adaptive coping (ß = 0.78, p < .05), diminished physical health (ß = -0.86, p < .05), and a high school or greater level of education (ß = 4.13, p < .05). These findings suggest that interventions targeting coping strategies may address psychological distress among HIV-positive Chinese men.

4.
Clin Chem ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672853

RESUMO

BACKGROUND: Early detection of hepatocellular carcinoma (HCC) among hepatitis B virus (HBV)-infected patients remains a challenge, especially in China. We sought to create an online calculator of serum biomarkers to detect HCC among patients with chronic hepatitis B (CHB). METHODS: Participants with HBV-HCC, CHB, HBV-related liver cirrhosis (HBV-LC), benign hepatic tumors, and healthy controls (HCs) were recruited at 11 Chinese hospitals. Potential serum HCC biomarkers, protein induced by vitamin K absence or antagonist-II (PIVKA-II), α-fetoprotein (AFP), lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3) and α-l-fucosidase (AFU) were evaluated in the pilot cohort. The calculator was built in the training cohort via logistic regression model and validated in the validation cohort. RESULTS: In the pilot study, PIVKA-II and AFP showed better diagnostic sensitivity and specificity compared with AFP-L3 and AFU and were chosen for further study. A combination of PIVKA-II and AFP demonstrated better diagnostic accuracy in differentiating patients with HBV-HCC from patients with CHB or HBV-LC than AFP or PIVKA-II alone [area under the curve (AUC), 0.922 (95% CI, 0.908-0.935), sensitivity 88.3% and specificity 85.1% for the training cohort; 0.902 (95% CI, 0.875-0.929), 87.8%, and 81.0%, respectively, for the validation cohort]. The nomogram including AFP, PIVKA-II, age, and sex performed well in predicting HBV-HCC with good calibration and discrimination [AUC, 0.941 (95% CI, 0.929-0.952)] and was validated in the validation cohort [AUC, 0.931 (95% CI, 0.909-0.953)]. CONCLUSIONS: Our results demonstrated that a web-based calculator including age, sex, AFP, and PIVKA-II accurately predicted the presence of HCC in patients with CHB.

5.
Nat Commun ; 10(1): 4973, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672990

RESUMO

The growing demand for lithium batteries with higher energy densities requires new electrode chemistries. Lithium metal is a promising candidate as the anode material due to its high theoretical specific capacity, negative electrochemical potential and favorable density. However, during cycling, low and uneven lithium ion concentration on the surface of anode usually results in uncontrolled dendrite growth, especially at high current densities. Here we tackle this issue by using lithiophilic montmorillonite as an additive in the ether-based electrolyte to regulate the lithium ion concentration on the anode surface and thus facilitate the uniform lithium deposition. The lithiophilic montmorillonite demonstrates a pumping feature that improves the self-concentrating kinetics of the lithium ion and thus accelerates the lithium ion transfer at the deposition/electrolyte interface. The signal intensity of TFSI- shows negligible changes via in situ Raman tracking of the ion flux at the electrochemical interface, indicating homogeneous ion distribution, which can lead to a stable and uniform lithium deposition on the anode surface. Our study indicates that the interfacial engineering induced by the lithiophilic montmorillonite could be a promising strategy to optimize the lithium deposition for next-generation lithium metal batteries.

6.
Sci Total Environ ; 700: 134520, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669914

RESUMO

Microplastics (MPs) have attracted worldwide attention as the emerging persistent pollutants. Since they have been detected in raw water and the treated water of drinking water treatment plants (DWTPs), there was an urgent need to explore the properties and fates of microplastics in DWTPs. The characteristics of the effluent MPs from each treatment unit in an advanced drinking water treatment plant (ADWTP) were studied, and the relationship between the variations of MPs and the removal performances of treatment processes was also explored. Overall, both the coagulation combined with sedimentation and the granular activated carbon (GAC) filtration performed well in removing microplastics. The former had a removal efficiency of about 40.5-54.5%, mainly for fibres' removal, and the presence of GAC filtration reduced the microplastic abundance by about 56.8-60.9%, mainly for small-sized MPs. It was worthy of attention that a larger amount of polyacrylamide (PAM) was detected in the effluent of the sedimentation compared to raw water, which was caused by the usage of coagulant containing PAM. Specially, the number of 1-5 µm MPs in the effluent of ozonation tank was increased by 2.8-16.0%, resulting in a negative removal efficiency in ozonation. The removals of microplastics were depended primarily on their physical properties (size and shape).

7.
Biomaterials ; 227: 119570, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31670032

RESUMO

Excessive release of interleukin-1ß (IL-1ß) is well-known to provoke cascades of inflammatory responses thus contributing to the pathogenesis of alcohol-induced steatohepatitis (ASH), but the cellular mechanism that regulates IL-1ß release during ASH remains unclear. Herein, we identified that gasdermin D (GSDMD) membrane pore is critical in mediating IL-1ß hypersecretion from chronic ethanol or acetaldehyde-stimulated macrophages. Deletion of GSDMD reduced IL-1ß release and ameliorated alcoholic steatohepatitis in vivo. These findings uncovered a novel mechanism regarding the IL-1ß release in ASH, and also indicated the therapeutic potential of IL-1ß blockade. Interleukin-1 receptor antagonist (IL-1Ra) is protective to ASH by blocking IL-1ß, but it has a short biological half-life (4-6 h) and lower liver concentrations. Thus, we constructed a therapeutic plasmid pVAX1-IL-1Ra-ApoAI (pVAX1-IA) encoding IL-1Ra anchored to the liver-targeting protein apolipoprotein A-I (ApoAI), and developed hepatocyte-specific nanobiologics (Glipo-pVAX1-IA) by galactose functionalization for local and prolonged expression of IL-1Ra in liver. Data presented here showed that Glipo-pVAX1-IA facilitated efficient uptake of gene cargos by hepatocytes. The biodistribution studies confirmed a predominant hepatocytes internalization, but a minimal kupffer cells uptake of Glipo-pVAX1-IA following intravenous injection. The locally secreted IL-1Ra attenuated alcohol-induced steatohepatisis and infiltration of inflammatory cells. Together, our results unraveled the critical role of GSDMD membrane pore in IL-1ß hypersecretion and highlighted the hepatocyte-specific Glipo-pVAX1-IA nanobiologics as a promising therapeutic strategy for ASH.

8.
PLoS Genet ; 15(10): e1008460, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31671093

RESUMO

Malfunction of pre-mRNA processing factors are linked to several human diseases including cancer and neurodegeneration. Here we report the identification of a de novo heterozygous missense mutation in the SNRPE gene (c.65T>C (p.Phe22Ser)) in a patient with non-syndromal primary (congenital) microcephaly and intellectual disability. SNRPE encodes SmE, a basal component of pre-mRNA processing U snRNPs. We show that the microcephaly-linked SmE variant is unable to interact with the SMN complex and as a consequence fails to assemble into U snRNPs. This results in widespread mRNA splicing alterations in fibroblast cells derived from this patient. Similar alterations were observed in HEK293 cells upon SmE depletion that could be rescued by the expression of wild type but not mutant SmE. Importantly, the depletion of SmE in zebrafish causes aberrant mRNA splicing alterations and reduced brain size, reminiscent of the patient microcephaly phenotype. We identify the EMX2 mRNA, which encodes a protein required for proper brain development, as a major mis-spliced down stream target. Together, our study links defects in the SNRPE gene to microcephaly and suggests that alterations of cellular splicing of specific mRNAs such as EMX2 results in the neurological phenotype of the disease.

9.
Nat Commun ; 10(1): 4941, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666519

RESUMO

Protein-RNA interaction plays important roles in post-transcriptional regulation. However, the task of predicting these interactions given a protein structure is difficult. Here we show that, by leveraging a deep learning model NucleicNet, attributes such as binding preference of RNA backbone constituents and different bases can be predicted from local physicochemical characteristics of protein structure surface. On a diverse set of challenging RNA-binding proteins, including Fem-3-binding-factor 2, Argonaute 2 and Ribonuclease III, NucleicNet can accurately recover interaction modes discovered by structural biology experiments. Furthermore, we show that, without seeing any in vitro or in vivo assay data, NucleicNet can still achieve consistency with experiments, including RNAcompete, Immunoprecipitation Assay, and siRNA Knockdown Benchmark. NucleicNet can thus serve to provide quantitative fitness of RNA sequences for given binding pockets or to predict potential binding pockets and binding RNAs for previously unknown RNA binding proteins.

10.
Toxicol Appl Pharmacol ; : 114775, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31669778

RESUMO

Acute promyelocytic leukemia (APL) is characterized by a reciprocal translocation between chromosomes 15 and 17, t(15;17), results in the expression of PML-RARα fusion protein, which disrupts the normal PML nuclear bodies (PML-NBs) to micro-speckled pattern, leading to loss of their original functions. Moreover, reformation of PML-NBs in APL by arsenic is considered as one of the important step for APL treatment. Leptomycin B (LMB), a nuclear export inhibitor, is commonly used to inhibit the proteins export from the nucleus to the cytoplasm. In the present study, we found that LMB could induce the reformation of PML-NBs in leukemia NB4 cells as well as in APL blast cells from the patients, implying that nuclear shuttle proteins might be involved in the reformation of PML-NBs. Herein, we further found that LMB totally lost the ability to induce PML-NBs reformation when the endogenous PML gene was knocked out, indicating that endogenous PML protein is probably involved in the reformation of PML-NBs. More interestingly, among all PML isoforms (i.e., seven isoforms), reformation of PML-NBs was only observed when co-transfection of PML-RARα with PML-I after LMB treatment. Similarly, deletion of nuclear export signal (NES) of PML-I could also reform PML-NBs, suggesting that the protein level of endogenous PML-I in nucleus is important for the reformation of PML-NBs that interfered by PML-RARα fusion protein. Additionally, LMB has synergistic effect with iAsIII on enhancing PML-RARα fusion protein degradation, and it might provide new insight into APL treatment at clinical level in the near future.

11.
Metallomics ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670356

RESUMO

Arsenic trioxide (As2O3) is one of the most effective drugs for the treatment of acute promyelocytic leukemia (APL), and induces the degradation of chimeric oncoprotein PML/RARα (P/R) and APL cell differentiation. Recent evidence has suggested that P/R fusion protein degradation by arsenic occurs through two steps, namely, rapid solubility change/shift of the P/R fusion protein following arsenic treatment (i.e., transfer of P/R protein from the soluble fraction to the insoluble pellet fraction), and subsequent degradation of these insoluble proteins. However, there is little information regarding the reversibility of arsenic induced P/R fusion protein solubility change as well as protein degradation in the insoluble fraction after removing arsenic. In this study, we used APL cell line NB4 or P/R and PML over-expressed 293T cells as well as HeLa cells to reveal the solubility change of P/R and PML by arsenic exposure, and further determined the fate of these insoluble proteins after the removal of arsenic. Here, for the first time, we found that arsenic induced P/R or PML protein solubility change is an irreversible process. Once arsenic induces a P/R or PML protein solubility change, these insoluble proteins could be degraded by the proteasomal pathway even without continuous arsenic treatment. However, PML and P/R proteins can be newly synthesized after the removal of arsenic, suggesting that great caution should be taken in the clinical therapy of APL patients before ending arsenic treatment.

12.
J Ethnopharmacol ; : 112260, 2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31577937

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria barbata D. Don (S. barbata) is a well-known perennial herb that is used in traditional Chinese and Korean medicine. In China, it is known as Ban Zhi Lian, while in Korea, it is known as Banjiryun. In the Traditional Chinese Medicine (TCM) system, S. barbata has heat-clearing and detoxifying properties (Qingre Jiedu in Chinese). AIM OF THE REVIEW: To provide a systematic review on current multifaceted understanding of S. barbata, with particular emphasis on the correlation between its traditional applications and pharmacological activities. MATERIALS AND METHODS: All available S. barbata-related information from internet databases, including PubMed, Science Direct, Elsevier, China National Knowledge Internet, and Google Scholar (up to October 2018) were searched. Additional information was gathered from classical books on Chinese Herbals, Chinese Pharmacopoeia, and so on. RESULTS: In the TCM system, S. barbata is mainly prescribed for its heat-clearing and detoxifying effects. More than 203 compounds have been isolated and identified from this herb, with neo-clerodane diterpenoids and flavonoids as the main compounds. Most neo-clerodanes have been demonstrated to have cytotoxic effects against different cancer cell types in vitro. The S. barbata extracts exhibited anti-inflammatory, anti-microbial, antitumor, and other pharmacological activities. To add, flavonoids, including wogonin, baicalein, apigenin, naringenin, and scutellarin, were identified as the key to quality control. CONCLUSIONS: The heat-clearing effects of S. barbata could be attributed to its anti-inflammatory and hepatoprotective activities, whereas its detoxifying effects might be due to the anti-microbial functions of neo-clerodane diterpenoids and flavones. S. barbata may display anti-tumor effects and through active ingredient analysis, neo-clerodane diterpenoids are suggested to be its representative compounds. Overall, many pre-clinical studies have been conducted but very little concrete evidences are available on its specific effects, which are of therapeutic relevance.

13.
J Cell Mol Med ; 2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31565850

RESUMO

Numerous data show that taraxacum officinale extract (TOE) exerts protective effects on inflammatory diseases. However, the underlying mechanisms by which TOE affects dextran sulphate sodium (DSS)-induced colitis remain unclear. After DSS-induced colitis were treated with different concentrations of TOE for 8 days, the bodyweight, disease activity index (DAI), colon lengths and pathological scoring were assessed, and histopathological examination was confirmed by HE staining. Furthermore, a transcriptome sequencing was performed by using the colon tissues between TOE and DSS groups, and the differentially expressed genes were conducted for the Kyoto Encyclopaedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) and were validated by qRT-PCR and immunohistochemistry analysis. In addition, a 16S rDNA sequencing was carried out to distinguish the differential gut microbiota by using the mouse faecal samples between TOE and DSS groups. We found that TOE attenuated the clinical symptoms, lowered the inflammatory scoring and inhibited the secretion of proinflammatory factors TNF-α, IL-1ß and IL-6 in DSS-induced colitis. KEGG and GSEA analysis demonstrated that fatty acid degradation and cytokine-receptor signalling were predominantly enriched in TOE-treated colitis as compared with the DSS group. Further investigations revealed that TOE increased the expression levels of Adh5, Aldh3a2 and Acox3, but decreased those of CCL20, CCR6 and CXCL1/5 in DSS-induced colitis, where TOE also induced the enrichment of S24-7 and adlercreutzia, but decreased the amount of anaerostipes, enterococcus, enterobacteriaceae and peptostreptococcaceae. In conclusion, TOE ameliorated DSS-induced colitis by regulating fatty acid degradation and microbial dysbiosis.

14.
Plant Cell ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604812

RESUMO

The conversion of etioplasts into chloroplasts in germinating cotyledons is a crucial transition for higher plants, enabling photoautotrophic growth upon illumination. Tight coordination of chlorophyll biosynthesis and photosynthetic complex assembly is critical for this process. ORANGE (OR), a DnaJ-like zinc finger domain-containing protein, was reported to trigger the biogenesis of carotenoid-accumulating plastids by promoting carotenoid biosynthesis and sequestration. Both nuclear and plastidic localizations of OR have been observed. Here, we show that Arabidopsis thaliana OR (At-OR) physically interacts with the transcription factor TCP14 in the nucleus and represses its transactivation activity. Through this interaction, the nucleus-localized OR negatively regulates expression of EARLY LIGHT-INDUCIBLE PROTEINS (ELIPs), reduces chlorophyll biosynthesis and delays development of thylakoid membranes in the plastids of germinating cotyledons. Nuclear abundance of OR decreased upon illumination. Together with an accumulation of TCP14 in the nucleus, this derepresses chloroplast biogenesis during de-etiolation. TCP14 is epistatic to OR and expression of ELIPs is directly regulated by the binding of TCP14 to Up1 elements in the ELIP promoter regions. Our results demonstrate that the interaction between OR and TCP14 in the nucleus leads to repression of chloroplast biogenesis in etiolated seedlings and provide new insights into the regulation of early chloroplast development.

15.
J Diabetes ; 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31605564

RESUMO

BACKGROUND: Male obesity is suggested to impact negatively on male fertility and semen quality in numerous studies. However, previous literatures regarding health effects of metabolic syndrome (MetS) on semen quality is rare and inconsistent. The aim of this study is to investigate the relationship between MetS and sperm parameters in a Taiwanese reproductive-age male population. METHODS: 8395 males who attended in a private medical screening program in Taiwan from 2010 to 2016 were included in this cross-sectional study. Semen analysis was assessed in accordance with the WHO guidelines such as sperm concentration, total motility, progressive motility and morphology. MetS was defined by the modified NCEP ATP III criteria with the Asian cut-off for waist circumference. The associations between MetS and semen analysis were examined by multivariable linear regressions. RESULTS: After fully adjusting for pertinent covariables, MetS was significantly associated with reduced percentage of sperm normal morphology. Blood pressure (BP), waist circumference (WC) and serum glucose had significantly negative association with sperm normal morphology. Individuals with increased number of MetS components had more closely association with reduced sperm progressive motility and percentage of normal morphology. CONCLUSION: MetS and its components exhibited deleterious effects on semen quality among reproductive-age males. Further studies are warranted to explore these pathophysiologic relationship and underlying mechanisms. This article is protected by copyright. All rights reserved.

16.
Mycopathologia ; 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31606812

RESUMO

Corynespora cassiicola is a common plant pathogen, but C. cassiicola infection in human hosts is extremely rare. In this report, we present an 84-year-old male with long-term use of inhaled corticosteroids who developed a subcutaneous infection caused by C. cassiicola. The organism was isolated from both wound culture and biopsy specimen from the skin lesion. However, no microscopic diagnostic characters could be obtained because the isolates failed to sporulate on different culture media. Molecular diagnosis by amplification and sequencing of the internal transcribed spacer regions of ribosomal DNA was performed, and the sequences of the isolates were identical to those of C. cassiicola. The patient was treated successfully with oral terbinafine therapy for 12 weeks. In this report, we also review the epidemiology, clinical and therapeutic facets of cutaneous C. cassiicola infection.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31606827

RESUMO

Pulmonary thromboembolism (PTE) is an acute and severe disease with high mortality, which is prone to be misdiagnosed or ignored especially when complicated with tuberculosis (TB). Even though TB has been considered as a risk factor for PTE, there is rare report of TB with PTE worldwide. Which TB patients are more susceptible to PTE is still not clear. Here, we described a case report of PTE with pulmonary TB in a 28-year-old man, who had no risk factors for pulmonary thrombosis at admission and developed a medium-high PTE after initiating anti-TB therapy. After local thrombolysis with interventional therapy and sequential intravenous thrombolysis, combined with long-term anticoagulation, the PTE of the patient disappeared. At follow-up of 4 months, the patient was re-examined with chest enhanced CT and no obvious emboli was found. We emphasize that acute or severe TB infection should be included in the thromboembolism risk assessment and prophylactic use of anticoagulants may be considered even if there are no other obvious risk factors. Interventional therapy is a good option for thrombolysis treatment if hospital condition permits.

18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1353-1359, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607283

RESUMO

OBJECTIVE: To study the safety and effectiveness of humanized CD19-targeted CAR-T cells (hCART19s) for treatment of patients with refractory/relapsed (R/R) B-ALL. METHODS: The analyzed patients were 15 children and adults with relapsed/refractory B-ALL who not received treatment with murine CD19 CAR-T cells. The patients received a single dose (1×106/kg) of autologous hCART19 infusion after lymphodepletion chemotherapy based on cyclophosphamide and fludarabine. RESULTS: Among the 15 patients, 13/14 (92.9%) evaluable patients achieved complete remission (CR) or CR with incomplete recovery of blood cells (CRi) on day 30 after hCART19s infusion. At day 180 after the infusion, the overall survival rate was 73.3%, and the leukemia-free survival rate was 69.2%. The cumulative incidence of relapse was 24.5% and non-relapse mortality rate was 7.7%. During treatment,12/15 patients (80%) developed cytokine release syndrome (CRS) of grade 1-2, and 3 patients (20.0%) developed CRS of grade 3-5. Only one patient (6.7%) suffered from the reversible neurotoxicity. CONCLUSION: hCART19s can effectively treat refractory/relapsed (R/R) adult and children with B-ALL, and the incidence of treatment-related CRS and neurotoxicity is low.

19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1602-1606, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607319

RESUMO

OBJECTIVE: To investigatc the curative efficacy of low dose rituximab for glucocorticoid ineffective on dependent ITP patients and its relation with sensitivity to glucocorticoid so as to provide reference basis for rational use of drugs in clinical treatmant. METHODS: Seventy-ninth ITP patients enrolled in this study included the glucocorticoid-ineffective patients (19 cases) and glucocorticoid-dependent patients (60 cases). All ITP patients were treated with regimen consisted of high dose dexamethasone plus low dose rituximab (dexal-methasone 40 mg/d for 4 days per os, ritaximab 100 mg by intravenous infusion at D7, 14, 21 and 28 respectively). The patients after treatment were followed-up for 12 month, and the relation of patients sensitivity to glucocorticoid with therapentic response of rituximab was analyzed. The changes of Treg cell ratio and BAFF, IL-2 and sCD40L levels before and after treatment were detected by flow cytometry and ELISA respectively. RESULTS: The overall response rate (ORR) of patients treated with above- mentioned regemen at 1, 3, 6 and 12 months after treatment was 79.7% (63/79), 69.6% (55/79), 63.3% (50/79) and 60.8% (48/79) respectivcly, out of which the ORR of glucocorticoid ineffective and glucocorticoid-dependent ITP patients treated with above-mentioned regimen at 1, 3, 6 and 12 months after treatment was 47.4% (9/19) vs 90.0% (54/60), 36.8% (7/19) vs 80.0% (48/60), 21.1% (4/19) vs 76.7% (46/60), 21.1% (4/19) vs 73.3% (44/60), and the difference between 2 groups was statistically significant. The detection of T reg cell showed that the T reg cell ratio in glucocorticoid- ineffective and dependent patients at 1, 3, 6 and 12 months after treatment was (1.70±0.43)% vs (3.47±0.72)%, (1.66±0.33)% vs (4.29±0.91)%, (1.71±0.37)% vs (4.44±0.97)%, (3.36±0.54)% vs (4.29±1.04)%, respectively. The detection of cytokines showed that the levels of BAFF, IL-2 and sCD40L in plasma of glucocorticoid-dependent patients at 1 month after treatment significanlly decreased (P<0.05), the levels of BAFF, IL-2 and sCD40L in plasma of glucocorticoid-ineffective patients although decreased at 1 mouth after treatment, but there was no statistical difference as compared with glucocosticoid-depenment patients. CONCLUSION: The treatment of glucocorticoid-dependent ITP patients with rituximab is more effective. The regulatory effect of rituximab on the T-reg cells, BAFF, IL-2 and sCD40L may be one of its mechanisms.

20.
J Alzheimers Dis ; 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31594221

RESUMO

Apolipoproteins (APOs) have been implicated in the pathogenesis of Alzheimer's disease (AD). In the present study, we aimed to investigate if patterns of cerebrospinal fluid (CSF) APOs (APOA-I, APOC-III, APOD, APOE, APOH, and APOJ) levels are associated with changes over time in cognition, memory performance, neuroimaging markers, and AD-related pathologies (CSF Aß42, t-tau, and p-tau) in non-demented older adults. At baseline, a total of 241 non-demented older adults with CSF APOs data was included in the present analysis. Hierarchical agglomerative cluster analysis including the six CSF APOs was carried out. Among non-demented older adults, we identified two clusters. Compare with the first cluster, the second cluster had higher levels of APOs in CSF. Additionally, the second cluster showed a more benign disease course, including slower cognitive decline and slower p-tau accumulation in CSF. Our data highlight the importance of APOs in the pathogenesis of AD.

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