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1.
Eur J Dermatol ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021475

RESUMO

BACKGROUND: The efficacy and safety of secukinumab, an interleukin-17 inhibitor, as systemic treatment for patients with moderate-to-severe psoriasis have been demonstrated, but real-world data pertaining to this is limited in China. OBJECTIVE: To evaluate the efficacy and safety of secukinumab in clinical practice in Chinese psoriasis patients with or without psoriatic arthritis (PsA) and identify potential baseline factors that affect the response of patients to secukinumab treatment. MATERIALS AND METHODS: Data from 81 patients treated with secukinumab for at least 16 weeks were analysed in a retrospective observational study. RESULTS: After 16 weeks of treatment with secukinumab, 91.1%, 73%, and 38.3% of patients achieved a PASI 75 (75% improvement based on the Psoriasis Area and Severity Index), PASI 90, and PASI 100, respectively. A significant improvement in the quality of life of patients was also observed. Notably, baseline factors, such as young age, lower BMI, no scalp involvement and absence of concomitant PsA, were associated with better clinical response to secukinumab. Approximately 42% of patients (34/81) experienced adverse events, of which the most common was pruritus. CONCLUSIONS: The results demonstrated that secukinumab appears to be an effective treatment alternative for the majority of Chinese plaque psoriasis patients. Baseline factors, including age, BMI, scalp involvement and concomitant presence of PsA, were associated with response to secukinumab.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1762-1768, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067987

RESUMO

OBJECTIVE: To investigate the effect of dasatinib on the expansion of NK cells in vitro, as well as the subsets, receptor expression and cytotoxic function of NK cells. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy adult volunteers and cultured with SCGM added IL-2 and IL-15 for expansion of NK cells. In this culture system, dasatinib of different concentrations were added. Cell counting and phenotyping by flow cytometry were used to evaluate the amplification efficiency of NK cells. FCM was used to detect the expression of receptors on the surface of NK cells and the distribution of subsets. Subsequently, degranulation assay and CFSE/7AAD based cytotoxicity assay were used to detect the effects of dasatinib on NK cytotoxicity against leukemia cell line K562 cells. RESULTS: The expansion efficiency of NK cells in vitro could be increased by dasatinib at the concentration range of 5-50 nmol/L, and the expansion efficiency of NK cells reached the peak at 20 nmol/L of dasatinib. The NK cytotoxicity against K562 cells in dasatinib cultured group at the concentration of 20 nmol/L was significantly higher than that in control group. For the cells cultured by disatinib in vitro, the MFI of CD226, NKP46 and NKG2D was up-regulated; the ratio of NKG2A+CD57- subset was down-regulated, while the ratio of NKG2A-CD57+ subset was up-regulated.The degranulation response of NKG2A-CD57+ NK cells to K562 cells was stronger than that of NKG2A+CD57- NK cells. CONCLUSION: The results shows that appropriate dose of dasatinib(20 nmol/L) can increases the amplification efficiency of NK cells, simultaneously up-regulates the expression of NK activating receptors and increases the NKG2A-CD57+ subset, which lead to the enhancement of NK cytotoxicty against leukemia cell lines.

3.
EBioMedicine ; 61: 103048, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33039712

RESUMO

BACKGROUND: Microbial communities and their metabolic components in the gut are of vital importance for immune homeostasis and have an influence on the susceptibility of the host to a number of immune-mediated diseases like acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the functional connections between microbiome and metabolome in aGVHD due to the complexity of the gastrointestinal environment. METHOD: Initially, gut microbiota and fecal metabolic phenotype in aGVHD murine models were unleashed by performing 16S ribosomal DNA gene sequencing and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics. FINDINGS: The group with aGVHD experienced a significant drop in Lachnospiraceae_unclassified but an increase in the relative abundance of Clostridium XI, Clostridium XIVa and Enterococcus. Meanwhile, a lower content of tyrosine was observed in the gut of aGVHD mice. The correlation analysis revealed that tyrosine-related metabolites were inversely correlated with Clostridium XIVa, besides, Blautia and Enterococcus also displayed the negative tendency in aGVHD condition. Apart from exploring the importance and function of tyrosine, different tyrosine diets were offered to mice during transplantation. Additional tyrosine supplements can improve overall survival, ameliorate symptoms at the early stage of aGVHD and change the structure and composition of gut microbiota and fecal metabolic phenotype. In addition, aGVHD mice deprived from tyrosine displayed worse manifestations than the vehicle diet group. INTERPRETATION: The results demonstrated the roles and mechanisms of gut microbiota, indispensable metabolites and tyrosine in the progression of aGVHD, which can be an underlying biomarker for aGVHD diagnosis and treatment. FUNDING: This research was funded by the International Cooperation and Exchange Program (81520108002), the National Key R&D Program of China, Stem Cell and Translation Research (2018YFA0109300), National Natural Science Foundation of China (81670169, 81670148, 81870080 and 91949115) and Natural Science Foundation of Zhejiang Province (LQ19H080006).

4.
J Transl Med ; 18(1): 393, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059689

RESUMO

BACKGROUND: Methyltransferase-like 3 (METTL3) is a member of the m6A methyltransferase family and acts as an oncogene in cancers. Recent studies suggest that host innate immunity is regulated by the enzymes controlling m6A epitranscriptomic changes. Here, we aim to explore the associations between the levels of METTL3 and CD33+ myeloid-derived suppressor cells (MDSCs) in tumour tissues and the survival of patients with cervical cancer (CC). METHODS: Specimens of paraffin embedded tumour from 197 CC patients were collected. The expression levels of METTL3 and CD33 were measured by immunohistochemical (IHC) staining. The clinical associations of the IHC variants were analysed by Pearson's or Spearman's chi-square tests. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method and log-rank test. Hazard ratios (HRs) and independent significance were obtained via Cox proportional hazards models for multivariate analyses. METTL3 in CD33+ cells or CC-derived cells was knocked down by METTL3-specific siRNA, and MDSC induction in vitro was performed in a co-culture system in the presence of METTL3-siRNA and METTL3-knockdown-CC-derived cells compared with that of the corresponding controls. RESULTS: We found that tumour tissues displayed increased levels of METTL3 and CD33+ MDSCs compared with tumour-adjacent tissues from the same CC patients. Importantly, METTL3 expression was positively related to the density of CD33+ cells in tumour tissues (P = 0.011). We further found that the direct CD33+CD11b+HLA-DR- MDSC induction and tumour-derived MDSC induction in vitro were decreased in the absence of METTL3. The level of METTL3 in tumour microenvironments was significantly related to advanced tumour stage. The levels of METTL3 and CD33+ MDSCs in tumour tissues were notably associated with reduced DFS or OS. Cox model analysis revealed that the level of METTL3 in tumour cells was an independent factor for patient survival, specifically for DFS (HR = 3.157, P = 0.022) and OS (HR = 3.271, P = 0.012), while the CD33+ MDSC number was an independent predictor for DFS (HR: 3.958, P = 0.031). Interestingly, in patients with advanced-disease stages (II-IV), METTL3 in tumour cells was an independent factor for DFS (HR = 6.725, P = 0.010) and OS (HR = 5.140, P = 0.021), while CD33+ MDSC density was an independent factor for OS (HR = 8.802, P = 0.037). CONCLUSION: Our findings suggest that CD33+ MDSC expansion is linked to high levels of METTL3 and that METTL3 and CD33+ MDSCs are independent prognostic factors in CC.

5.
Mol Biol Rep ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068229

RESUMO

Blastomere loss is a common issue during frozen-thawed embryo transfer (FET). Our previous study showed that blastomere loss was associated with an increased risk of small-for-gestational-age (SGA) neonates. The present study assessed the impact of blastomere loss during cryopreservation by comparing the mRNA profiles of umbilical cord blood of FET offspring from the prospective cohort study. Umbilical cord blood samples were collected from 48 neonates, including 12 from the loss group, 11 from the intact group, and 25 from the matched spontaneous pregnancy group. RNA-seq technology was used to compare the global gene expression profiles of the lymphocytes. Then, we used TopHat software to map the reads and quantitative real-time PCR to validate some important differentially expressed genes (DEGs). We identified 92 DEGs between the loss group and the spontaneous pregnancy group, including IGF2 and H19. Ingenuity Pathway Analysis (IPA) showed that the DEGs were most affected in the blastomere loss group. Downstream analysis also predicted the activation of organismal death pathways. In conclusions, our pilot study sheds light on the mechanism underlying how human blastomere loss may affect offspring at the gene expression level. These conclusions are, however, only suggestive, as the current study is based on a very limited sample size and type or nature of biological samples. Additional studies with larger sample sizes and independent experiments with placental samples should be conducted to verify these findings.

6.
Enzyme Microb Technol ; 141: 109671, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33051008

RESUMO

Secretion is a common bottleneck in the production of industrial proteins. Although overexpression of the unfolded protein response regulator Hac1p has been widely used to enhance protein secretion, its effects on the physiology of host cells were often overlooked, which would attenuate and even neutralize its beneficial effects on overall protein production. In order to achieve high-level glucose oxidase (GOX) production in Pichia pastoris, we used a set of Hac1p homologues from Saccharomyces cerevisiae (ScHac1p), P. pastoris (PpHac1p), Trichoderma reesei (TrHac1p) and Homo sapiens (HsXbp1), to evaluate the effects of Hac1p overexpression on the secretion capacity, cell physiology and overall enzyme production in P. pastoris strains containing different copies of the GOX gene. Results showed that overexpression of Hac1ps was able to remarkably alleviate the secretion bottleneck in the 3-copy strain, to improve its GOX secretion capacity by 21.2-140.2 % and its overall enzyme production by 23.7-69.2 %. However, overexpression of ScHac1p, PpHac1p and TrHac1p led to reduced cell growth in GS-3GOX, possibly due to increased oxidative stress. Overexpression of ScHac1p and PpHac1p in the 6-copy strain (resulting in GS-6GOX-Sc and GS-6GOX-Pp, respectively) further increased the overall GOX production levels by 88.9-103.3 %, and GS-6GOX-Pp exhibited the highest overall GOX production and GOX secretion capacity among all constructed strains. Nevertheless, in addition of significantly reduced growth, loss of GOX gene was also observed for GS-6GOX-Pp and GS-6GOX-Sc during the fermentation process. With higher induction cell density and co-feeding of yeast extract, the GOX titer of GS-6GOX-Pp reached 2125.3 U/mL on 1-liter fermentor. This study not only achieves a record high GOX production level but also provides new insights into secretion pathway engineering using Hac1p overexpression strategy.

7.
Sci Rep ; 10(1): 17093, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051494

RESUMO

Physical therapists (PT) and clinicians must be skilled in identifying gait features through observation to assess motor deficits in patients and intervene appropriately. Inconsistent results in the literature have led researchers to question how clinical experience influences PT's gait perception and to seek the key kinematic features that should be trained to enhance PT's skill. Thus, this study investigated (1) what are the informative kinematic features that allow gait-deviation perception in amputee gait and (2) whether there are differences in observational gait skills between PT and individuals with less clinical experience (PT students [PTS] and Novices). We introduced a new method that combines biological motion and principal component analysis to gradually mesh amputee and typical walking patterns. Our analysis showed that on average the accuracy rate in identifying gait deviations between PT and PTS was similar and better than Novices. Also, we found that PT's experience was demonstrated by their better perception of gait asymmetry. The extracted principal components demonstrated that the major gait deviation of amputees was the medial-lateral body sway and spatial gait asymmetry.

8.
Int J Cardiol ; 316: 208, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32891264
9.
J Mol Model ; 26(10): 257, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32886185

RESUMO

Basing on the simplest hydrothermal system containing deionized water, hexa-ammonium molybdate, and thiourea, hydrothermal mechanism on preparation of MoS2 was studied by DFT calculation. Hydrothermal process was divided into four steps which covered ionization equilibrium, the hydrolysis of CS(NH2)2, the formation of intermediates, and the formation of MoS2. Ionization equilibrium occurs at normal condition and determines the existence of Mo in the form of molybdic acid. Thiourea hydrolysis is rate-determining step in the process of hydrothermal which contains 10 elementary reactions. The formation of intermediates includes hydrogen transfer, dehydration, and vulcanization three steps which contain 18 elementary reactions, and the energy barrier of vulcanization is the highest. The formation of MoS2 is divided into two steps, the first step is that MoO(OH)(SH)3.H2O reacts with MoO (SH)4.H2O to form layer MoS2, and the second step is a very fast process that can affect the morphology of the products.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32898433

RESUMO

Background: Previous studies have reported the use of microRNAs (miRNAs) as diagnostic and/or prognostic biomarkers for various cancers, including gastric cancer (GC). The aim of this study was to evaluate the diagnostic and prognostic significance of serum miR-296-5p and miR-28-3p in GC. Methods: Serum samples of 90 patients with GC and 90 healthy individuals, and 20 pairs of tissue specimens from patients with GC were collected. The expression of miR-296-5p and miR-28-3p in both the serum and tissue samples were detected using quantitative real-time polymerase chain reaction analysis. The diagnostic and prognostic values of miR-296-5p and miR-28-3p were evaluated by using receiver operating characteristic curve and Kaplan-Meier analyses, respectively. Results: Compared with the healthy controls, the expression of miR-296-5p in the serum and tissues of patients with GC was significantly upregulated, whereas that of miR-28-3p was significantly downregulated. High miR-296-5p and low miR-28-3p levels in the serum significantly correlated with larger tumor size (>5 cm), lymph node metastasis, and TNM stage III+IV. The area under the curve values of miR-296-5p and miR-28-3p were 0.919 and 0.911, respectively, with high sensitivity and specificity. Kaplan-Meier survival curves showed that patients with GC with high level of miR-296-5p or low level of miR-1236-3p in the serum had the poorest overall survival. COX analysis showed that lymphatic metastasis, high miR-296-5p expression, and low miR-28-3p expression are independent parameters indicating poor prognosis in GC. Conclusion: Our findings indicate that serum miR-296-5p and miR-28-3p levels are potential biomarkers in the diagnosis and prognosis of GC.

11.
Scand J Immunol ; : e12974, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32910495

RESUMO

High expression of suppressors of cytokine signalling (SOCS) has been detected during various viral infections. As a negative feedback regulator, SOCS participates in the regulation of multiple signalling pathways. In this study, to study the related mechanism between SOCS and BDV and to explore the effect of SOCS on IFN pathways in nerve cells, downregulated of SOCS1/3 in oligodendroglial (OL) cells and OL cells persistently infected with BDV (OL/BDV) were constructed with RNA interference technology. An interferon inducer (poly I:C, PIC) and an IFN-α/ß R1 antibody were used as stimulation in the SOCS1/3 low-expression cell models, qRT-PCR was used to detect type I IFN and BDV nucleic acid expression, western blot was used to detect the expression of BDV P40 protein. After BDV acute infection with OL cells which with downregulated SOCS expression, the virus accounting was not detected, and the viral protein expression was lower than that of OL/BDV cells; the OL/BDV cells with downregulated SOCS expression had lower virus nucleic acid and protein expression than OL/BDV cells. Stimulated by IFN-α/ß R1 Antibody, the expression of type I interferon in OL/BDV cells decreased, and the content of BDV nucleic acid and protein increased, which was higher than that of OL/BDV cells. From the results, it was concluded that downregulating SOCS1/3 can inhibit the formation of acute BDV infection and virus replication in persistent BDV infection by promoting the expression of IFN-α/ß and that SOCS can be used as a new target for antiviral therapy.

12.
Carbohydr Polym ; 248: 116796, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32919534

RESUMO

Chondroitin sulfate (CS) is one of the major and widespread glycosaminoglycans, a family of structurally complex, linear, anionic hetero-co-polysaccharides. CS plays a vital role in various normal physiological and pathological processes, thus, showing varieties of biological activities, such as anti-oxidation, anti-atherosclerosis, anti-thrombosis, and insignificant immunogenicity. However, the heterogeneity of the naturally occurring CS potentially leads to function unspecific and limits further structure-activity relationship studies. Therefore, the synthesis of CS with well-defined and uniform chain lengths is of major interest for the development of reliable drugs. In this review, we examine the remarkable progress that has been made in the chemical, enzymatic and chemoenzymatic synthesis of CS and its derivatives, providing a broad spectrum of options to access CS of well controlled chain lengths.

13.
Mater Sci Eng C Mater Biol Appl ; 117: 111299, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32919660

RESUMO

Recently, microneedle systems have become an attractive solution for drug delivery. Traditionally, microneedle systems were fabricated via template molding methods. In this study, we present a novel method for the fabrication of a microneedle patch system. We used extrusion-based 3D printing and post stretching to fabricate a microneedle patch system for minimally invasive and glucose-responsive insulin delivery for diabetes treatment. First, we investigated the printability of various bioinks composed of alginate with hydroxyapatite as an additive. After printing the substrate and a cylindrical array of the patch, we stretched the top surface of the cylindrical array to form needle-like tips. The prepared microneedle patch contained 6 × 6 microneedles, and only the microneedles performed glucose-responsive release of insulin. Each microneedle was conical in shape, with a base diameter of 601 µm, a tip diameter of 24 µm, and a height of 643 µm. The fabricated microneedles exhibited sufficient mechanical strength to penetrate the skin of mice and responsively released insulin according to the glucose levels both in glucose solution and in type 1 diabetic mice. When transdermal application was performed only once on the skin of mice, the microneedle patches regulated the blood glucose levels of diabetic mice in normoglycemic ranges for up to 40 h and alleviated the diabetic symptoms of the mice. Our study proposed a method for the fabrication of microneedle patch systems, which can be potentially applied for transdermal drug delivery.

14.
Trends Biotechnol ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32943212

RESUMO

Microalgae have potential for environmental remediation, but they must better tolerate stress. Adaptive laboratory evolution (ALE) is effective to construct evolved strains, but its efficiency is low. Highly efficient ALE relies on selecting suitable environmental stress, original strain selection, and optimizing initial cell density and stress strategy.

16.
J Hematol Oncol ; 13(1): 128, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32977829

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is a fatal hematopoietic malignancy and has a prognosis that varies with its genetic complexity. However, there has been no appropriate integrative analysis on the hierarchy of different AML subtypes. METHODS: Using Microwell-seq, a high-throughput single-cell mRNA sequencing platform, we analyzed the cellular hierarchy of bone marrow samples from 40 patients and 3 healthy donors. We also used single-cell single-molecule real-time (SMRT) sequencing to investigate the clonal heterogeneity of AML cells. RESULTS: From the integrative analysis of 191727 AML cells, we established a single-cell AML landscape and identified an AML progenitor cell cluster with novel AML markers. Patients with ribosomal protein high progenitor cells had a low remission rate. We deduced two types of AML with diverse clinical outcomes. We traced mitochondrial mutations in the AML landscape by combining Microwell-seq with SMRT sequencing. We propose the existence of a phenotypic "cancer attractor" that might help to define a common phenotype for AML progenitor cells. Finally, we explored the potential drug targets by making comparisons between the AML landscape and the Human Cell Landscape. CONCLUSIONS: We identified a key AML progenitor cell cluster. A high ribosomal protein gene level indicates the poor prognosis. We deduced two types of AML and explored the potential drug targets. Our results suggest the existence of a cancer attractor.

17.
Int J Gynecol Cancer ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973117

RESUMO

BACKGROUND: There is no accepted strategy for applying sentinel lymph node (SLN) biopsy as an alternative to pelvic lymphadenectomy in cervical cancer. It is unclear whether and when pelvic lymphadenectomy can be safely replaced by SLN biopsy alone. PRIMARY OBJECTIVE: To comprehensively compare the oncological outcomes of SLN biopsy with pelvic lymphadenectomy in patients with and without SLN metastasis. STUDY HYPOTHESIS: It is hypothesized that the oncological outcomes provided by SLN biopsy are non-inferior to those of pelvic lymphadenectomy in patients with clinically early-stage cervical cancer if risk-adapted adjuvant treatments are given. TRIAL DESIGN: All eligible patients will undergo SLN biopsy at the start of surgery. The resected SLNs will be submitted for frozen section examination. and patients will be triaged into the PHENIX-I (SLN-negative) or PHENIX-II (SLN-positive) cohort. In each cohort of this trial, patients will be randomized in a 1:1 ratio into the experimental (SLN biopsy alone) or reference (pelvic lymphadenectomy) arm. Radical hysterectomy will be performed for all patients, and adjuvant treatments will be planned according to post-operative pathological factors. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients aged between 18 and 65 years with histologically confirmed, untreated stage IA1 (lymphovascular space involvement), IA2, IB1, and IB2 cervical squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma. PRIMARY ENDPOINT: The primary endpoint is disease-free survival. SAMPLE SIZE: Estimated sample sizes of 830 and 250 are required to fulfill the study objectives of PHENIX-I and II, respectively. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: As of May 2020, more than 600 eligible patients have been enrolled. Enrollment is expected to be completed by December 2022, and presentation of results is expected in 2026. TRIAL REGISTRATION: NCT02642471.

18.
Biomed Res Int ; 2020: 4264291, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32953881

RESUMO

Background: Prostate cancer (PCa) is the most common malignancy and the leading cause of cancer death in men. Recent studies suggest the molecular signature was more effective than the clinical indicators for the prognostic prediction, but all of the known studies focused on a single RNA type. The present study was to develop a new prognostic signature by integrating long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) and evaluate its prognostic performance. Methods: The RNA expression data of PCa patients were downloaded from The Cancer Genome Atlas (TCGA) or Gene Expression Omnibus database (GSE17951, GSE7076, and GSE16560). The PCa-driven modules were identified by constructing a weighted gene coexpression network, the corresponding genes of which were overlapped with differentially expressed RNAs (DERs) screened by the MetaDE package. The optimal prognostic signature was screened using the least absolute shrinkage and selection operator analysis. The prognostic performance and functions of the combined prognostic signature was then assessed. Results: Twelve PCa-driven modules were identified using TCGA dataset and validated in the GSE17951 and GSE7076 datasets, and six of them were considered to be preserved. A total of 217 genes in these 6 modules were overlapped with 699 DERs, from which a nine-gene prognostic signature was identified (including 3 lncRNAs and 6 mRNAs), and the risk score of each patient was calculated. The overall survival was significantly shortened in patients having the risk score higher than the cut-off, which was demonstrated in TCGA (p = 5.063E - 03) dataset and validated in the GSE16560 (p = 3.268E - 02) dataset. The prediction accuracy of this risk score was higher than that of clinical indicators (the Gleason score and prostate-specific antigen) or the single RNA type, with the area under the receiver operator characteristic curve of 0.945. Besides, some new therapeutic targets and mechanisms (MAGI2-AS3-SPARC/GJA1/CYSLTR1, DLG5-AS1-DEFB1, and RHPN1-AS1-CDC45/ORC) were also revealed. Conclusion: The risk score system established in this study may provide a novel reliable method to identify PCa patients at a high risk of death.

19.
Ann Hematol ; 99(11): 2639-2648, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32889611

RESUMO

Extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) continues to remain a clinical challenge. The data on EMR in acute lymphoblastic leukemia (ALL) are currently limited. Herein, a retrospective analysis of 268 adult ALL patients who underwent allo-HSCT in our center between March 2008 and December 2017 was performed to analyze post-HSCT EMR. Ninety patients (33.58%) experienced relapse; 51(19.03%) experienced bone marrow relapse (BMR), whereas 39 (14.55%) experienced EMR. The 5-year cumulative EMR incidence (CEMRI) revealed that matched sibling donor (MSD)-HSCTs were more likely to develop EMR than unrelated donor (URD)- and haploidentical-related donor (HRD)-HSCTs (CEMRI: 24.02%, 7.69%, and 14.69% for MSD, URD, and HRD, respectively). Notably, MSD-HSCTs (URD vs MSD hazard ratio (HR) = 0.26, p = 0.015; HRD vs MSD HR = 0.46, p = 0.032), history of extramedullary disease (EMD) (HR = 2.45, p = 0.041), and T cell ALL (HR = 2.80, p = 0.012) were independent risk factors for EMR in the multivariate analysis. The median overall survival (OS) for all patients was 15.23 months. However, the OS of EMR patients was significantly longer (19.50 months) than that of BMR patients (12.90 months) (p = 0.003). Multivariate analyses revealed that the leading risk factors for post-relapse deaths were shorter intervals between HSCT and relapse (> 12 months vs ≤ 12 months, HR = 0.30, p < 0.001) and BMR (HR = 0.41, p = 0.002). In conclusion, EMR patients have better survival than BMR patients. ALL patients with allo-HSCT from MSDs, a history of EMD, and the T cell type were significantly associated with EMR.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Aloenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
20.
Curr Top Med Chem ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962620

RESUMO

Tanshinones are a class of bioactive compounds present in the Chinese herbal medicine Danshen (Salvia miltiorrhiza Bunge), containing among others abietane diterpene quinone scaffolds. Chemical synthesis and biological activity studies of natural and unnatural tanshinone derivatives have been reviewed in this article.

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