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1.
J Digit Imaging ; 36(5): 2113-2124, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37369942

RESUMO

This work presents a novel approach to estimate brain functional connectivity networks via generative learning. Due to the complexity and variability of rs-fMRI signal, we consider it as a random variable, and utilize variational autoencoder networks to encode it as a confidence distribution in the latent space rather than as a fixed vector, so as to establish the relationship between them. First, the mean time series of each brain region of interest is mapped into a multivariate Gaussian distribution. The correlation between two brain regions is measured by the Jensen-Shannon divergence that describes the statistical similarity between two probability distributions, and then the adjacency matrix is created to indicate the functional connectivity strength of pairwise brain regions. Meanwhile, our findings show that the adjacency matrices obtained at VAE latent spaces of different dimensionalities have good complementarity for MCI identification in precision and recall, and the classification performance can be further boosted by an efficient cascade of classifiers. This proposal constructs brain functional networks from a statistical modeling standpoint, improving the statistical ability of population data and the generalization ability of observation data variability. We evaluate the proposed framework over the task of identifying subjects with MCI from normal controls, and the experimental results on the public dataset show that our method significantly outperforms both the baseline and current state-of-the-art methods.


Assuntos
Disfunção Cognitiva , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Disfunção Cognitiva/diagnóstico por imagem , Aprendizagem
2.
Molecules ; 22(2)2017 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-28208722

RESUMO

This study performed an optimization of the fermentation conditions to activate the expression of the zunyimycin family biosynthesis genes of the zunyimycin-producing streptomycetes strain Streptomyces sp. FJS31-2. Bioassay-guided isolation and purification by varied chromatographic methods yielded two new compounds of the zunyimycin derivatives, namely, 31-2-7 and 31-2-8, accompanied with three known anthrabenzoxocinones family members of zunyimycin A, BE24566B, and chloroanthrabenzoxocinone. Their structures were elucidated by NMR, HRESIMS, IR, UV, and CD. Results showed that these two compounds were structurally similar to the previously reported compound zunyimycin A but differed in positions and number of chlorine atom substitution. The two novel compounds were called zunyimycins B and C. Antibacterial activity assay indicated that zunyimycin C showed a good inhibitory effect on the methicillin-resistant Staphylococcus aureus and Enterococci.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Enterococcus/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Streptomyces/metabolismo , Antibacterianos/biossíntese , Dicroísmo Circular , Fermentação , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular
3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 39(2): 169-176, 2017 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-28483013

RESUMO

Objective To investigate the difference of texture on conventional T2-weighted image (T2WI) between hepatic cyst and hepatic hemangioma. Methods All the subjects included 156 patients with hepatic cyst [A group:100 cases with equi or low signal on diffusion weighted imaging (DWI);B group:56 cases with high signal on DWI] and 100 patients with hemangioma (C group). Conventional magnetic resonance imaging T2WI,DWI and dynamic contrast enhancement were performed on all the patients,and the texture analysis was applied with the images of T2WI,and the texture parameters included angular second moment,contrast,correlation,inverse difference moment,and entropy. Independent sample t-test and Aspin-Welch test were performed for the comparisons among groups. Results All the texture parameters showed significant difference among groups [(A+B) group vs. C group:ρ angular second moment=0.000,ρcontrast=0.000,ρcorrelation=0.000,Pinverse difference moment=0.822,ρentropy=0.000;A group vs. C group:ρangular second moment=0.000,ρcontrast=0.000,ρcorrelation=0.000,ρinverse difference moment=0.092,ρentropy=0.000;B group vs. C group:ρangular second moment=0.000,ρcontrast=0.000,ρcorrelation=0.000,ρinverse difference moment=0.046,ρentropy=0.009],and receiver operating characteristic curve analysis demonstrated that contrast and correlation had high differential diagnostic values between hepatic cyst and hemangioma. Conclusion Hepatic cyst and hemangioma present evident different texture characteristics,and the texture analysis may be considered as a simple and effective tool in the differential diagnosis between hepatic cyst and hemangioma based on the images of T2WI.


Assuntos
Cistos/diagnóstico por imagem , Hemangioma/diagnóstico por imagem , Imageamento por Ressonância Magnética , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Humanos , Fígado/patologia
4.
Chin J Cancer Res ; 29(5): 463-470, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29142466

RESUMO

OBJECTIVE: To investigate the association between the T cell inhibitory receptor programmed death 1 (PD-1) and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia (AML) and AML in complete remission (CR). METHODS: Surface expression of PD-1 and the exhaustion and immunosenescence markers CD244 and CD57 on CD3+, CD4+ and CD8+ T cells from peripheral blood samples from 20 newly diagnosed, untreated AML patients and 10 cases with AML in CR was analyzed by flow cytometry. Twenty-three healthy individuals served as control. RESULTS: A significantly higher percentage of PD-1+ cells were found for CD3+ T cells in the de novo AML group compared with healthy controls. In addition, an increased level of PD-1+CD8+ T cells, but not PD-1+CD4+, was found for CD3+ T cells in the de novo AML and AML-CR samples. A higher percentage of CD244+CD4+, CD244+CD8+, CD57+CD4+ and CD57+CD8+ T cells was found in CD3+ T cells in samples from those with de novo AML compared with those from healthy controls. Strong increased PD-1+CD244+ and PD-1+CD57+ co-expression was found for CD4+ and CD8+ T cells in the de novo AML group compared with healthy controls. CONCLUSIONS: We characterized the major T cell defects, including co-expression of PD-1 and CD244, CD57-exhausted T cells in patients with de novo AML, and found a particular influence on CD8+ T cells, suggesting a poor anti-leukemia immune response in these patients.

5.
Zhongguo Yi Liao Qi Xie Za Zhi ; 41(1): 66-9, 2017 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-29792789

RESUMO

This paper introduces the current situation of the development of regional medical information in our country, analyzes the problem of heterogeneous data sharing, and tries to realize the heterogeneous information sharing by middleware based on HL7.


Assuntos
Sistemas de Informação em Saúde , Disseminação de Informação
6.
Molecules ; 21(6)2016 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-27248985

RESUMO

Genome mining is an effective tool used to discover novel natural products from actinomycetes. Genome sequence analysis of Streptomyces sp. FJS31-2 revealed the presence of one putative type II polyketide gene cluster (ABX), which may correspond to type II polyketide products including BE-24566B and its chloro-derivatives. The addition of natural humus acid successfully activated the biosynthsis of the abx gene cluster. BE-24566B and its chloro-derivatives, named zunyimycin A, were also detected. The targeted deletion of the polyketide skeleton synthesis genes such as abxp, abxk, and abxs was performed in the wild strain to identify the gene cluster for BE-24566B biosynthesis.


Assuntos
Família Multigênica , Policetídeos/metabolismo , Streptomyces/genética , Streptomyces/metabolismo , Antraquinonas/metabolismo , Ordem dos Genes , Metaboloma , Metabolômica/métodos , Estrutura Molecular , Policetídeos/química
7.
Pak J Pharm Sci ; 29(1 Suppl): 287-93, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27005505

RESUMO

A full length about 105 kb gene cluster containing 35 open reading frames involved in the biosynthesis of lobophorins was cloned and sequenced from a fosmid genomic library of Streptomyces olivaceus strain FXJ7.023. The cluster was identified by genome wide annotation and analysis of secondary metabolite biosynthesis gene clusters by anti SMASH and knockout of loading module-contained region of polyketide skeleton synthesis gene (the starter of lobS1). Gene cluster comparative analysis suggested that the cluster encoded the complete genes for lobophorin polyketide assembly, modification, substrate catalysis, regulation, transportation and resistance, and shows great identity to the newest reported lobophorin biosynthetic gene cluster from Streptomyces sp. SCSIO 01127, but with a significant gene rearrangement in the PKS modules.


Assuntos
Antibacterianos/biossíntese , Macrolídeos/metabolismo , Família Multigênica/genética , Streptomyces/genética , Streptomyces/metabolismo , Clonagem Molecular , DNA Bacteriano/biossíntese , DNA Bacteriano/genética , Fermentação , Técnicas de Inativação de Genes , Biblioteca Gênica , Plasmídeos
8.
Pak J Pharm Sci ; 29(5 Suppl): 1811-1815, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28476707

RESUMO

In order to obtain the natural products synthesized by the three putative xiamycin biosynthesis gene clusters which were predicted via antiSMASH during the genome mining of marine Streptomyces sp. FXJ 7.388, Streptomyces sp. FXJ 8.012, and Streptomyces olivaceus FXJ 7.023. Sixteen genes involved in xiamycin assembly, modification, and regulation with higher identity than the newest reported xiamycin biosynthetic gene cluster from marine Streptomyces sp. SCSIO 02999, Streptomyces sp. HKI0576, and Streptomyces sp. FXJ 7.388 were discovered via gene cluster comparative analysis. A ribosome engineering strategy was adopted to activate such cryptic gene clusters with different final concentrations antibiotics that act on the ribosome, and two indolosesquiterpenes were isolated from idlethaldose streptomycin-resistant Streptomyces sp. FXJ 7.388 strains. However, no such product was detected in Streptomyces sp. FXJ 8.012 and Streptomyces olivaceus FXJ 7.023 under the same treatment. This result suggested that these genes might hold the least gene content for xiamycin biosynthesis.


Assuntos
Biologia Marinha , Família Multigênica , Sesquiterpenos/metabolismo , Streptomyces/genética , Streptomyces/metabolismo
9.
World J Microbiol Biotechnol ; 31(4): 541-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25697286

RESUMO

The draft genome sequence of marine Streptomyces olivaceus strain FXJ 7.023 contains a cryptic Type III polyketide synthase (type III PKS) gene cluster, which is similar to the Streptomyces coelicolor THN biosynthesis gene cluster. A putative type III PKS (SoRppA) gene and its adjacent gene for cytochrome P450 158A2 (SoCYP158A2) of this gene cluster were cloned by PCR screening through a fosmid genomic library of S. olivaceus FXJ 7.023. Tandem expression of SoRppA and SoCYP158A2 in Escherichia coli strain BL21 (DE3) plysS resulted in obvious biosynthesis of phenol and indole, while heterologous expression of SoRppA or SoCYP158A2 alone did not. The engineered strain sorppAcyp158a2BL21 showed tolerance to phenol concentration up to 0.75 g/L. Continuous biosynthesis of phenol and indole by the immobilized engineered strain on macroporousresin was achieved, and the productivities of phenol and indole in extractant-free culture in 102 h were 0.08 and 1.525 g/L/h, respectively, with the highest production reached 0.67 and 14.48 g/L, respectively. These results suggest that the engineered strain and immobilized continuous fermentation process may provide potential for "green" production of phenol and indole.


Assuntos
Proteínas de Bactérias/genética , Sistema Enzimático do Citocromo P-450/genética , Escherichia coli/metabolismo , Indóis/metabolismo , Fenol/metabolismo , Policetídeo Sintases/genética , Água do Mar/microbiologia , Streptomyces/enzimologia , Proteínas de Bactérias/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Engenharia Metabólica , Policetídeo Sintases/metabolismo , Streptomyces/genética
10.
Cancer Cell Int ; 14(1): 137, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25530716

RESUMO

BACKGROUND: Treatment with imatinib mesylate (IM) (a tyrosine kinase inhibitor) is the first line of standard care for patients newly diagnosed with CML. Despite the success of IM and other tyrosine kinase inhibitors (TKIs), chronic myeloid leukemia (CML) remains largely incurable, and a number of CML patients die due to Abl mutation-related drug resistance and blast crisis. 3, 5-Dihydroxy-6, 7, 3'4'-tetramethoxyflavone (DHTMF) is a polymethoxyflavone isolated from Laggera pterodonta which is a herbal medicine used to treat cancer in the Chinese folk. In the previous study, we found DHTMF demonstrated good antiproliferative activities against a number of cancer cell lines and induced the apoptosis of CNE cells in vitro in a time- and dose-dependent manner while exhibiting low cytotoxicity in the two normal cell lines Vero and EVC304. The aim of the present study was to evaluate the proliferation inhibition and apoptosis induced by DHTMF alone and in combination with IM in the IM-resistant CML cell line K562R. METHODS: Cell proliferation was assayed with the cell counting kit-8 (CCK8) method. The apoptosis percentage was determined by flow cytometry (FCM). Mitochondrial transmembrane potential was detected using FCM and confocal laser-scanning microscopy. The level of proteins involved in apoptosis was detected by Western blotting. RESULTS: DHTMF suppressed K562R cell viability in both time- and dose-dependent manners. DHTMF combined with IM enhanced the inhibitory effects and apoptosis in K562R cells as compared with DHTMF alone. DHTMF alone and in combination with IM significantly decreased the mitochondrial membrane potential and increased the levels of cleaved caspase-9, caspase-7, caspase-3, and PARP in K562R cells. CONCLUSIONS: We demonstrated that DHTMF could inhibit IM-resistant K562R cell proliferation and induces apoptosis via the intrinsic mitochondrial apoptotic pathway. These results suggest that DHTMF may be a potential therapeutic drug with lower side effects against IM resistance in CML cells.

11.
IEEE Trans Vis Comput Graph ; 30(1): 295-305, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37878445

RESUMO

Generative text-to-image models have gained great popularity among the public for their powerful capability to generate high-quality images based on natural language prompts. However, developing effective prompts for desired images can be challenging due to the complexity and ambiguity of natural language. This research proposes PromptMagician, a visual analysis system that helps users explore the image results and refine the input prompts. The backbone of our system is a prompt recommendation model that takes user prompts as input, retrieves similar prompt-image pairs from DiffusionDB, and identifies special (important and relevant) prompt keywords. To facilitate interactive prompt refinement, PromptMagician introduces a multi-level visualization for the cross-modal embedding of the retrieved images and recommended keywords, and supports users in specifying multiple criteria for personalized exploration. Two usage scenarios, a user study, and expert interviews demonstrate the effectiveness and usability of our system, suggesting it facilitates prompt engineering and improves the creativity support of the generative text-to-image model.

12.
Phytomedicine ; 130: 155742, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38838635

RESUMO

PURPOSE: It is unclear whether traditional Chinese patent medicines can resist premature aging. This prospective study investigated the effects of Bazi Bushen Capsule (BZBS) which is a traditional Chinese patent medicine for tonifying the kidney essence on premature senility symptoms and quality of life, telomerase activity and telomere length. STUDY DESIGN AND METHODS: It was a parallel, multicenter, double-blind, randomized, and placebo-controlled trial. Subjects (n = 530) aged 30-78 years were randomized to receive BZBS or placebo capsules 12 weeks. The primary outcome was the clinical feature of change in kidney deficiency for aging evaluation scale (CFCKD-AES) and tilburg frailty indicator (TFI). The secondary outcomes were SF-36, serum sex hormone level, five times sit-to-stand time (FTSST), 6MWT, motor function test-grip strength, balance test, walking speed, muscle mass measurement, telomerase and telomere length. RESULTS: After 12 weeks of treatment, the CFCKD-AES and TFI scores in the BZBS group decreased by 13.79 and 1.50 respectively (6.42 and 0.58 in the placebo group, respectively); The SF-36 in the BZBS group increased by 98.38 (23.79 in the placebo group). The FTSST, motor function test grip strength, balance test, walking speed, and muscle mass in the elderly subgroup were all improved in the BZBS group. The telomerase content in the BZBS group increased by 150.04 ng/ml compared to the placebo group. The fever led one patient in the placebo group to discontinue the trial. One patient in the placebo group withdrew from the trial due to pregnancy. None of the serious AEs led to treatment discontinuation, and 3 AEs (1.14%) were assessed as related to BZBS by the primary investigator. CONCLUSIONS: BZBS can improve premature aging symptoms, frailty scores, and quality of life, as well as improve FTSST, motor function: grip strength, balance test, walking speed, and muscle mass in elderly subgroups of patients, and enhance telomerase activity, but it is not significantly associated with increasing telomere length which is important for healthy aging. TRIAL REGISTRY: https://www.chictr.org.cn/showproj.html?proj=166181.


Assuntos
Senilidade Prematura , Medicamentos de Ervas Chinesas , Qualidade de Vida , Humanos , Método Duplo-Cego , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Pessoa de Meia-Idade , Feminino , Idoso , Senilidade Prematura/tratamento farmacológico , Adulto , Telomerase , Força da Mão , Estudos Prospectivos , Telômero/efeitos dos fármacos
13.
Cancer Cell Int ; 13(1): 37, 2013 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-23627638

RESUMO

To elucidate the characteristics of T-cell receptor (TCR) signal transduction in T-cells from acute myeloid leukemia (AML), the mucosa-associated-lymphoid-tissue lymphoma-translocation gene 1 (MALT1), A20, NF-κB and MALT1-V1 gene expression levels in CD3+ T cells sorted from the peripheral blood of patients with AML were analyzed by real-time PCR. A significantly lower MALT1 and A20 expression level was found in T cells from patients with AML compared with healthy controls (p = 0.045, p < 0.0001); however, the expression level of MALT1-V1 (variant 1) was significantly higher in the AML group than in the healthy control group (p = 0.006), and the expression level of NF-κB was increased in the AML group. In conclusion, the characteristics of the expression pattern of MALT1-A20-NF-κB and the distribution of MALT1 variants in T cells from AML were first characterized. Overall, low TCR-CD3 signaling is related to low MALT1 expression, which may related to T cell immunodeficiency, while the up-regulation of MALT1-V1 may play a role in overcoming the T cell activity by downregulating A20 in patients with AML, which may be related to a specific response to AML-associated antigens.

14.
Proc Natl Acad Sci U S A ; 107(5): 2201-6, 2010 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-20133863

RESUMO

Inhibitors of poly(ADP-ribose) polymerase (PARP) are in clinical trials for cancer therapy, on the basis of the role of PARP in recruitment of base excision repair (BER) factors to sites of DNA damage. Here we show that PARP inhibition to block BER is toxic to hypoxic cancer cells, in which homology-dependent repair (HDR) is known to be down-regulated. However, we also report the unexpected finding that disruption of PARP, itself, either via chemical PARP inhibitors or siRNAs targeted to PARP-1, can inhibit HDR by suppressing expression of BRCA1 and RAD51, key factors in HDR of DNA breaks. Mechanistically, PARP inhibition was found to cause increased occupancy of the BRCA1 and RAD51 promoters by repressive E2F4/p130 complexes, a pathway prevented by expression of HPV E7, which disrupts p130 activity, or by siRNAs to knock down p130 expression. Functionally, disruption of p130 by E7 expression or by siRNA knockdown also reverses the cytotoxicity and radiosensitivity associated with PARP inhibition, suggesting that the down-regulation of BRCA1 and RAD51 is central to these effects. Direct measurement of HDR using a GFP-based assay demonstrates reduced HDR in cells treated with PARP inhibitors. This work identifies a mechanism by which PARP regulates DNA repair and suggests new strategies for combination cancer therapies.


Assuntos
Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Proteína Substrato Associada a Crk/metabolismo , Fator de Transcrição E2F4/metabolismo , Genes BRCA1 , Inibidores de Poli(ADP-Ribose) Polimerases , Rad51 Recombinase/genética , Linhagem Celular Tumoral , Proteína Substrato Associada a Crk/antagonistas & inibidores , Proteína Substrato Associada a Crk/genética , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/fisiologia , Regulação para Baixo/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Genes BRCA1/efeitos dos fármacos , Humanos , Fenantrenos/farmacologia , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/metabolismo , Regiões Promotoras Genéticas , RNA Interferente Pequeno/genética , Radiossensibilizantes/farmacologia
15.
Yale J Biol Med ; 86(4): 443-51, 2013 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-24348208

RESUMO

Hypoxia is a characteristic feature of solid tumors and occurs very early in neoplastic development. Hypoxia transforms cell physiology in multiple ways, with profound changes in cell metabolism, cell growth, susceptibility to apoptosis, induction of angiogenesis, and increased motility. Over the past 20 years, our lab has determined that hypoxia also induces genetic instability. We have conducted a large series of experiments revealing that this instability occurs through the alteration of DNA repair pathways, including nucleotide excision repair, DNA mismatch repair, and homology dependent repair. Our work suggests that hypoxia, as a key component of solid tumors, can drive cancer progression through its impact on genomic integrity. However, the acquired changes in DNA repair that are induced by hypoxia may also render hypoxic cancer cells vulnerable to tailored strategies designed to exploit these changes.


Assuntos
Reparo do DNA/genética , Regulação Neoplásica da Expressão Gênica , Hipóxia , Neoplasias/genética , Hipóxia Celular , Linhagem Celular Tumoral , Instabilidade Genômica , Humanos , Modelos Genéticos , Neoplasias/metabolismo , Neoplasias/patologia , Transdução de Sinais/genética
16.
Front Nutr ; 10: 1089909, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36814514

RESUMO

The gut microbiota is a complex ecosystem that has coevolved with the human body for hundreds of millions of years. In the past 30 years, with the progress of gene sequencing and omics technology, the research related to gut microbiota has developed rapidly especially in the field of digestive system diseases and systemic metabolic diseases. Mechanical, biological, immune, and other factors make the intestinal flora form a close bidirectional connection with the liver and gallbladder, which can be called the "gut-liver-biliary axis." Liver and gallbladder, as internal organs of the peritoneum, suffer from insidious onset, which are not easy to detect. The diagnosis is often made through laboratory chemical tests and imaging methods, and intervention measures are usually taken only when organic lesions have occurred. At this time, some people may have entered the irreversible stage of disease development. We reviewed the literature describing the role of intestinal flora in the pathogenesis and biotherapy of hepatobiliary diseases in the past 3-5 years, including the dynamic changes of intestinal flora at different stages of the disease, as well as the signaling pathways involved in intestinal flora and its metabolites, etc. After summarizing the above contents, we hope to highlight the potential of intestinal flora as a new clinical target for early prevention, early diagnosis, timely treatment and prognosis of hepatobiliary diseases. GRAPHICAL ABSTRACT.

17.
Front Immunol ; 14: 1078118, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36742315

RESUMO

Background: Immunological phenotypes and differentiation statuses commonly decide the T cell function and anti-tumor ability. However, little is known about these alterations in CML patients. Method: Here, we investigated the immunologic phenotypes (CD38/CD69/HLA-DR/CD28/CD57/BTLA/TIGIT/PD-1) of T subsets (TN, TCM, TEM, and TEMRA) in peripheral blood (PB) and bone marrow (BM) from de novo CML patients (DN-CML), patients who achieved a molecular response (MR) and those who failed to achieve an MR (TKI-F) after tyrosine kinase inhibitor (TKI) treatment using multicolor flow cytometry. Results: CD38 or HLA-DR positive PB CD8+TN and TCM cells decreased in the DN-CML patients and this was further decreased in TKI-F patients. Meanwhile, the level of PD-1 elevated in CD8+ TEM and TEMRA cells from PB in all groups. Among BM sample, the level of HLA-DR+CD8+TCM cells significantly decreased in all groups and CD8+TEMRA cells from TKI-F patients exhibited increased level of TIGIT and CD8+ tissue-residual T cells (TRM) from DN-CML patients expressed a higher level of PD-1 and TIGIT. Lastly, we found a significantly decreased proportion of CD86+ dendritic cells (DCs) and an imbalanced CD80/CD86 in the PB and BM of DN-CML patients, which may impair the activation of T cells. Conclusion: In summary, early differentiated TN and TCM cells from CML patients may remain in an inadequate activation state, particularly for TKI-F patients. And effector T cells (TEM, TEMRA and TRM) may be dysfunctional due to the expression of PD-1 and TIGIT in CML patients. Meanwhile, DCs cells exhibited the impairment of costimulatory molecule expression in DN-CML patients. Those factors may jointly contribute to the immune escape in CML patients.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide , Humanos , Receptor de Morte Celular Programada 1/metabolismo , Subpopulações de Linfócitos T , /uso terapêutico
18.
Front Pharmacol ; 14: 1124607, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37180713

RESUMO

Introduction: Phellinus igniarius (P. igniarius) (Sanghuang) is a widely used traditional Chinese medicine fungus, and its natural products have great potential for clinical application in immune enhancement. This study aimed to explore the immune-enhancing activity and underlying mechanisms of the polysaccharides and flavonoids derived from Phellinus igniarius (P. igniarius) and to provide a theoretical and experimental basis for the development of novel drugs. Methods: Wild P. igniarius YASH1 from the Loess Plateau in Yan'an region was collected, and polysaccharides and total flavonoids were extracted, isolated and identified from mycelium and sporophore. In vitro antioxidant activity was detected through the scavenging activity of hydroxyl radicals and total antioxidant capacity. Cell Counting Kit-8 and trypan blue detection kit were used to detect the effect of extract polysaccharides and flavonoids on the proliferation and phagocytosis ability of immune cells. To assess the effect of the drugs on cytokine secretion by immune cells and immune recovery in immunocompromised mice, the expression of interleukin (IL)-2, IL-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were examined at the cellular and animal levels. The species composition, abundance of gut microbiota and the altered content of short-chain fatty acids in the feces were analyzed to elucidate the possible mechanisms of drugs by 16S ribosomal RNA (rRNA) amplifiers sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Both polysaccharides and flavonoids derived from mycelium or sporophore had antioxidant activity and may stimulate the expression and secretion of IL-2, IL-6, and IFN-γ in immune cells while inhibiting TNF-α expression and secretion and increasing IL-2, IL-6, and IFN- γ expression levels in mice. Furthermore, polysaccharides and flavonoids from mycelium and sporophore showed different effects on the metabolic response of intestinal short-chain fatty acids (SCFAs) in mice, and the use of these drugs remarkably changed the species composition and abundance of intestinal flora in mice. Discussion: Polysaccharides and flavonoids from P. igniarius YASH1 mycelium and sporophore have in vitro antioxidant activity, and they affect the promotion of cell proliferation, stimulation of IL-2, IL-6, and IFN-γ secretion, and inhibition of TNF-α expression in immune cells. Polysaccharides and flavonoids from P. igniarius YASH1 may enhance immunity in immunocompromised mice and remarkably affect the intestinal flora and content of SCFAs.

19.
Med Image Anal ; 88: 102837, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37216736

RESUMO

Efficient and accurate distinction of histopathological subtype of lung cancer is quite critical for the individualized treatment. So far, artificial intelligence techniques have been developed, whose performance yet remained debatable on more heterogenous data, hindering their clinical deployment. Here, we propose an end-to-end, well-generalized and data-efficient weakly supervised deep learning-based method. The method, end-to-end feature pyramid deep multi-instance learning model (E2EFP-MIL), contains an iterative sampling module, a trainable feature pyramid module and a robust feature aggregation module. E2EFP-MIL uses end-to-end learning to extract generalized morphological features automatically and identify discriminative histomorphological patterns. This method is trained with 1007 whole slide images (WSIs) of lung cancer from TCGA, with AUCs of 0.95-0.97 in test sets. We validated E2EFP-MIL in 5 real-world external heterogenous cohorts including nearly 1600 WSIs from both United States and China with AUCs of 0.94-0.97, and found that 100-200 training images are enough to achieve an AUC of >0.9. E2EFP-MIL overperforms multiple state-of-the-art MIL-based methods with high accuracy and low hardware requirements. Excellent and robust results prove generalizability and effectiveness of E2EFP-MIL in clinical practice. Our code is available at https://github.com/raycaohmu/E2EFP-MIL.


Assuntos
Inteligência Artificial , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Área Sob a Curva , China , Redes Neurais de Computação
20.
Chem Biodivers ; 9(7): 1349-55, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22782880

RESUMO

A new compound, named jiangxienone, has been isolated from a culture of the traditional Chinese medicinal mushroom Cordyceps jiangxiensis, and its chemical structure was established on the basis of spectroscopic and chemical techniques. Jiangxienone showed potent cytotoxic effects against human gastric adenocarcinoma SGC-7901 cell and human lung carcinoma A549 cell with IC(50) values ranging from 1.38 to 2.93 µM, i.e., with at least approximately six-fold stronger cytotoxicity than cisplatin, a first-line chemotherapy drug for cancer patients.


Assuntos
Agaricales/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Cicloexanonas/química , Cicloexanonas/farmacologia , Indanos/química , Indanos/farmacologia , Medicina Tradicional Chinesa , Linhagem Celular Tumoral , Sobrevivência Celular , Relação Dose-Resposta a Droga , Humanos , Concentração Inibidora 50
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