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1.
Artigo em Inglês | MEDLINE | ID: mdl-33802442

RESUMO

The ecological system is the basis of human survival and global environmental protection. In the process of development, countries will pay close attention to the changing state of the ecosystem. Taking the ecosystem pattern as the research object, a three-layer analysis method was proposed. The transfer matrix and landscape index were used as the first layer to analyze the basic changes. Grey correlation, range-coupling coordination and relative priority were used as the second layer to analyze the reasons of the change. The interval-entropy weight, TOPSIS (Technique for Order Preference by Similarity to an Ideal Solution), was used as the third layer to evaluate the quality of the change. The ten counties in the worst-hit areas of the Wenchuan earthquake were analyzed from different angles, with county region, intensity zone and ecosystem as the objects, and the following results were obtained: (1) Taking Mianzhu City as an example, from 2000 to 2010 and 2018, the conversion ratio of forest, grassland and farmland is 54.24, 59.19, 17.21, 20.06, 37.39 and 52.86%, which were distributed in the north, central and southern parts, respectively. (2) Taking the ninth intensity zone as an example, the forest landscape fragmentation increased, disturbance decreased, and species diversity increased. There is a high influence and restriction relationship between ecosystem and landscape pattern in the total landscape area change. Additionally, the relationship between them tends to develop in a benign way. As of 2018, it is in the change state of moderate imbalance-ecosystem lag. (3) Taking the county ecosystem change as an example, urban type is the best in the counties of ecosystem change, of which Shifang is the best and Pingwu is the worst. The results show that this method can effectively compare and analyze the changes in the multi-regional ecosystem pattern, which has the characteristics of universality and can also be applied to the research of ecosystem pattern change in special regions.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33797891

RESUMO

Gram-negative bacteria are covered by both an inner cytoplasmic membrane (IM) and an outer membrane (OM). Antimicrobial peptides (AMPs) must first permeate through the OM and cell wall before attacking the IM to cause cytoplasmic leakage and kill the bacteria. The bacterial OM is an asymmetric bilayer with the outer leaflet primarily composed of lipopolysaccharides (LPSs) and the inner leaflet composed of phospholipids (PLs). Two cationic α-helical AMPs were designed to target Gram-negative bacteria, a full peptide G(IIKK)3I-NH2 (G3), and a hydrophobic lipopeptide C8-G(IIKK)2I-NH2 (C8G2, with C8 denoting the octanoyl chain). LPS dominates OM functions as the first line of defense against antibiotics, thereby reducing drug susceptibility. This work explores how the two AMPs interact with LPS through several carefully chosen OM models that facilitated measurements from solid-state nuclear magnetic resonance (ss-NMR), small-angle neutron scattering (SANS), and neutron reflectivity (NR). The results revealed that G3 molecules bound preferably to the LPS head region and functioned as bridge molecules to reassemble the dislocated lipids into bilayer stacks. In contrast, C8G2 lipopeptides could quickly penetrate into the central region of the OM to cause direct removal of some membrane lipids. Different structural disruptions implicated different antimicrobial efficacies from these AMPs. The demonstration of the structural features underlying different susceptibilities of the OM to AMPs offers a useful route for the future development of strain-specific AMPs against antimicrobial-resistant pathogens.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33666312

RESUMO

The development of efficient and sustainable methods to access saturated N-heterocycles is of great importance because of the prevalence of these structures in natural products and bioactive compounds. Pd-catalyzed aza-Wacker type cyclization is a powerful method and provides access to N-heterocycles bearing an alkene moiety available for further synthetic manipulations from readily available materials. Herein we disclose a catalyst- and reagent-free formal aza-Wacker type cyclization reaction for the synthesis of functionalized saturated N-heterocycles. Key to the success is to conduct the reactions in a continuous-flow electrochemical reactor without adding supporting electrolyte or additives. The reactions are characterized by broad tolerance of di-, tri- and tetrasubstituted alkenes.

4.
J Mater Sci Mater Med ; 32(4): 31, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33751254

RESUMO

No effective treatment has been established for nerve dysfunction caused by spinal cord injury (SCI). Orderly axonal growth at the site of spinal cord transection and creation of an appropriate biological microenvironment are important for functional recovery. To axially guiding axonal growth, designing a collagen/silk fibroin scaffold fabricated with 3D printing technology (3D-C/SF) emulated the corticospinal tract. The normal collagen/silk fibroin scaffold with freeze-drying technology (C/SF) or 3D-C/SF scaffold were implanted into rats with completely transected SCI to evaluate its effect on nerve repair during an 8-week observation period. Electrophysiological analysis and locomotor performance showed that the 3D-C/SF implants contributed to significant improvements in the neurogolical function of rats compared to C/SF group. By magnetic resonance imaging, 3D-C/SF implants promoted a striking degree of axonal regeneration and connection between the proximal and distal SCI sites. Compared with C/SF group, rats with 3D-C/SF scaffold exhibited fewer lesions and disordered structures in histological analysis and more GAP43-positive profiles at the lesion site. The above results indicated that the corticospinal tract structure of 3D printing collagen/silk fibroin scaffold improved axonal regeneration and promoted orderly connections within the neural network, which could provided a promising and innovative approach for tissue repair after SCI.

5.
Neuropharmacology ; 189: 108535, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33766630

RESUMO

Neuregulin-1 (NRG1), a family of EGF-like factors that activates ErbB receptors, can regulate the proliferation, migration, and myelinating of Schwann cells. We previously reported that NRG1/ErbB signal is responsible for organophosphate (OP)-induced delayed neuropathy (OPIDN) in hens, a susceptive animal model to neuropathic organophosphorous compounds. Our previous study discovered that a neuropathic OP, tri-o-cresyl phosphate (TOCP) activated NRG1/ErbB signaling pathway in both spinal cord and sciatic nerves of hens during the formation of OPIDN and lapatinib, a non-selective antagonist of ErbB1 and ErbB2 receptors, alleviated the toxicity. In this study, we intended to further look into the potential role of NRG1 in the pathogenesis of TOCP-induced axon damage in spinal cord and sciatic nerves and whether lapatinib could also rescue this damage in mice, an OPIDN-resistant animal model. The results revealed that no obvious toxic signs were observed after single TOCP exposure. However, slight histopathological wreck in lumbar spinal cord and sciatic nerves was found following TOCP intoxication, and the damage in sciatic nerves was characterized by axon degeneration of myelin sheath but not the loss of neural skeleton. Only histopathological damage induced by TOCP in spinal cord could be prevented by lapatinib. The translational expression of NRG1/ErbB signaling molecules was analyzed by both in vivo and in vitro studies. In general, NRG1/ErbB pathway was activated by TOCP while combined treatment with lapatinib attenuated TOCP-induced NRG1/ErbB signaling cascade. The results implied that NRG1/ErbB system may predominately play functional role in spinal cord (central nervous system) but not in sciatic nerves (peripheral nervous system) of mouse subjected to neurotoxic OP, which was confirmed by the study in vitro that lapatinib was not able to attenuate TOCP-induced neurotoxicity in rodent Schwann cell line RSC 96 cells.

6.
Chem Rec ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33734572

RESUMO

Organic radicals are versatile synthetic intermediates that provide reactivities and selectivities complementary to ionic species. Despite its long history, electrochemically driven radical reactions remain limited in scope. In the past few years, there have been dramatic increase in research activity in organic electrochemistry. We have been developing electrochemical and electrophotocatalytic methods for the generation and synthetic utilization of organic radicals. In our studies, various radical species such as alkene and arene radical cations and carbon- and heteroatom-centered radicals are generated from readily available precursors through direct electrolysis, molecular electrocatalysis or molecular electrophotocatalysis. These radical species undergo various inter- and intramolecular oxidative transformations to rapidly increase molecular complexity. The simultaneous occurrence of anodic oxidation and cathodic proton reduction allows the oxidative reactions to proceed through H2 evolution without external chemical oxidants.

7.
Zhongguo Zhong Yao Za Zhi ; 46(5): 1217-1223, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33787118

RESUMO

To prove that ursolic acid(UA)could activate the autophagy of colorectal cancer HCT116 cells by inhibiting hedgehog signaling pathway. The effect of UA on the viability of HCT116 cells was determined by MTT assay. The effect of UA on the proliferation and migration of HCT116 cells was detected by crystal violet staining and scratch test. In the study on autophagy, the time points were screened out first: the autophagy fluorescence intensity of UA acting on HCT116 at different time points were detected by Cell Meter~(TM) Autophagy Assay Kit; Western blot was used to detect the expression of autophagy protein P62 at different time points. Then, Cell Meter~(TM) Autophagy Assay Kit was used to detect the effect of UA on autophagy fluorescence intensity of HCT116 cells. The effect of different doses of UA on the expressions of LC3Ⅱ and P62 proteins in HCT116 cells were detected by Western blot. Further, AdPlus-mCherry-GFP-LC3 B adenovirus transfection was used to detect the effects of UA on autophagy flux of HCT116 cells; UA combined with autophagy inhibitor chloroquine(CQ) was used to detect the expression of LC3Ⅱ by Western blot. In terms of mechanism, the effect of UA on hedgehog signaling pathway-related proteins in HCT116 cells was detected by Western blot. The results showed that UA inhibited the activity, proliferation and migration of HCT116 cells. UA enhanced the fluorescence intensity of autophagy in HCT116 cells, while promoting the expression of LC3Ⅱ and inhibiting the expression of P62, in a time and dose dependent manner. UA activated the autophagy in HCT116 cells, which manifested that UA resulted in the accumulation of fluorescence spots and strengthened the fluorescence intensity of autophagosomes; compared with UA alone, UA combined with autophagy inhibitor CQ promoted the expression of LC3Ⅱ. UA reduced the expressions of PTCH1, GLI1, SMO, SHH and c-Myc in hedgehog signaling pathway, while increased the expression of Sufu. In conclusion, our study showed that UA activated autophagy in colorectal cancer HCT116 cells, which was related to the mechanism in inhibiting hedgehog signaling pathway activity.


Assuntos
Neoplasias Colorretais , Proteínas Hedgehog , Apoptose , Autofagia , Linhagem Celular Tumoral , Proteínas Hedgehog/genética , Humanos , Transdução de Sinais , Triterpenos
8.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(3): 254-258, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33691918

RESUMO

OBJECTIVE: To study the clinical features of very preterm small-for-gestational-age infants born by cesarean section due to severe preeclampsia. METHODS: Forty-two small-for-gestational-age infants who were admitted from August 2017 to July 2018 and were born due to severe preeclampsia were enrolled as the observation group. Forty very preterm infants who were born to healthy mothers since uterine contractions could not be suppressed were enrolled as the control group. Perinatal features, clinical manifestations of infection, complications, and clinical outcomes were analyzed for the two groups. RESULTS: Within 6 hours and 2-3 days after birth, the observation group had significantly lower white blood cell count (WBC), absolute neutrophil count (ANC), and platelet count (PLT) than the control group (P < 0.05). At 5-7 days after birth, there was no significant difference in WBC between the two groups (P > 0.05), while the observation group still had significantly lower ANC and PLT than the control group (P < 0.05). The observation group had a significantly higher C-reactive protein (CRP) level than the control group at 2-3 days and 5-7 days after birth (P < 0.05). The observation group had a significantly higher proportion of infants with severe infections than the control group (P < 0.05). The observation group had a significantly higher hemoglobin level than the control group within 6 hours after birth (P < 0.05). The observation group had a significantly higher incidence rate of bronchopulmonary dysplasia than the control group (P < 0.05). There was no significant difference between the two groups in the rate of pulmonary hemorrhage, intracranial hemorrhage, neonatal necrotizing enterocolitis, retinopathy of prematurity, and the rate of use of invasive ventilation, and clinical outcomes (P > 0.05). CONCLUSIONS: Very preterm small-for-gestational-age infants born due to severe preeclampsia have a high incidence rate of infection and severe conditions. Early manifestations include reductions in the infection indicators WBC, ANC, and PLT, and CRP does not increase significantly in the early stage and gradually increases at 2-3 days after birth. Most of these infants require invasive ventilation after birth, with bronchopulmonary dysplasia as the main complication. Clinical changes should be closely observed and inflammatory indicators should be monitored for early identification of infection, timely diagnosis, and timely adjustment of antibiotic treatment, so as to improve the outcome.


Assuntos
Displasia Broncopulmonar , Doenças do Prematuro , Pré-Eclâmpsia , Cesárea , Feminino , Idade Gestacional , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Gravidez
9.
Zhongguo Gu Shang ; 34(1): 91-6, 2021 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-33666027

RESUMO

Perineuronal nets (PNNs) is a complex network composed of highly condensed extracellular matrix molecules surrounding neurons. It plays an important role in maintaining the performance of neurons and protecting them from harmful substances. However, after spinal cord injury, PNNs forms a physical barrier that surrounds the neuron and limits neuroplasticity, impedes axonal regeneration and myelin formation, and promotes local neuroinflammatory uptake. This paper mainly describes the composition and function of PNNs of neurons and its regulatory effects on axonal regeneration, myelin formation and neuroinflammation after spinal cord injury.


Assuntos
Matriz Extracelular , Traumatismos da Medula Espinal , Axônios , Humanos , Regeneração Nervosa , Plasticidade Neuronal , Neurônios , Medula Espinal
10.
J Proteome Res ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33705137

RESUMO

The ability to survive in the harsh gastrointestinal tract (GIT) environment is essential for Lactobacillus reuteri (L. reuteri) exhibiting beneficial effects. In this study, we found that the hydrophobicity and auto-aggregation of L. reuteri SH23 were significantly decreased and biofilm production was also significantly decreased when L. reuteri SH23 passes through the simulated GIT. Furthermore, according to the comparative transcriptome analysis, gene expression involved in the cell envelope, metabolic processes, common stress response, regulatory systems, and transporters were also affected. Meanwhile, label-free quantitative proteomics was used to identify the differential expression of surface proteins of L. reuteri in response to simulated gastrointestinal fluid. Proteins related to the ABC transporters (Lreu_0517, Lreu_0098, and Lreu_0296) and LPxTG anchor domain proteins were upregulated in the cell surface after gastrointestinal fluid treatment, which is useful for adherence and colonization of L. reuteri in the GIT. Additionally, the recombinant Mub protein could also enhance the survival ability of L. reuteri SH23 in GIT stress environment. This study provides a comprehensive understanding of the adaptation and adhesion mechanisms of L. reuteri SH23 under the gastrointestinal tract by the transcriptomics and proteomics analysis, and mucus-binding proteins were involved in the adhesion and GIT tolerance process.

11.
Mol Ecol Resour ; 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33665976

RESUMO

Detecting genetic regions under selection in structured populations is of great importance in ecology, evolutionary biology and breeding programmes. We recently proposed EigenGWAS, an unsupervised genomic scanning approach that is similar to F ST but does not require grouping information of the population, for detection of genomic regions under selection. The original EigenGWAS is designed for the random mating population, and here we extend its use to inbred populations. We also show in theory and simulation that eigenvalues, the previous corrector for genetic drift in EigenGWAS, are overcorrected for genetic drift, and the genomic inflation factor is a better option for this adjustment. Applying the updated algorithm, we introduce the new EigenGWAS online platform with highly efficient core implementation. Our online computational tool accepts plink data in a standard binary format that can be easily converted from the original sequencing data, provides the users with graphical results via the R-Shiny user-friendly interface. We applied the proposed method and tool to various data sets, and biologically interpretable results as well as caveats that may lead to an unsatisfactory outcome are given. The EigenGWAS online platform is available at www.eigengwas.com, and can be localized and scaled up via R (recommended) or docker.

12.
ChemSusChem ; 14(7): 1692-1695, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33605037

RESUMO

The development of efficient and sustainable methodologies for the synthesis of N-heterocycles is a constant focus of organic synthesis. Herein an electrochemical method is reported for the synthesis of benzimidazoles through dehydrogenative cyclization of easily available N-aryl amidines. The reactions were conducted under simple constant current conditions in an undivided cell without need for catalysts, chemical oxidants, or additives, and produced H2 as the only theoretical byproduct.

14.
Acta Pharmacol Sin ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33633363

RESUMO

Immune checkpoint inhibition is an important strategy in cancer therapy. Blockade of CTLA-4 and PD-1/PD-L1 is well developed in clinical practice. In the last few years, LAG-3 has received much interest as an emerging novel target in immunotherapy. It was recently reported that FGL1 is a major ligand of LAG-3, which is normally secreted by the liver but is upregulated in several human cancers. FGL1 is a crucial biomarker and target for cancer immunotherapy. As the efficacy of immunotherapy is limited to specific types of patients, the subset of patients needs to be selected appropriately to receive precise treatment according to different biomarkers. To date, there is no test to accurately assess FGL1 expression levels. Nanobodies have some outstanding features, such as high stability, solubility and affinity for diagnostic and therapeutic applications. Here, we report the development and validation of a rapid, sensitive, and cost-effective nanobody-based immunoassay for the detection of FGL1 in human serum. In this study, human FGL1 recombinant protein was expressed and purified for the first time as an immunized antigen. Then, we constructed a nanobody phage display library and screened several nanobodies that bind FGL1 with high affinity. We selected two nanobodies targeting different epitopes of FGL1, one as a capture and the other conjugated with HRP as a probe. The double nanobody-based sandwich ELISA to detect the concentration of FGL1 showed a good response relationship in the range of 15.625-2000 ng/mL, and the recoveries from the spiked sample were in the range of 78% and 100%. This assay could be used as a potential approach for evaluating FGL1 expression for patient stratification and for predicting the therapeutic efficacy of targeting the LAG3/FGL1 axis.

15.
Medicine (Baltimore) ; 100(5): e23976, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592852

RESUMO

ABSTRACT: This pilot study retrospectively assessed the feasible efficacy of TurboHawk plaque rotation system (THPRS) for treatment of arteriosclerosis occlusion in lower extremities (AOLE).A total of 36 eligible patients with AOLE were included in this pilot retrospective study. We divided all those patients into a treatment group and a control group, each group 18 patients. All patients in both groups administered conventional therapy. Additionally, all patients in the treatment group received THPRS, while all patients in the control group received percutaneous transluminal angioplasty (PTA) and percutaneous transluminal stenting (PTS). All outcomes were evaluated and analyzed at 3-month after surgery.At 3-month postsurgery, there were not significant statistical differences in clinical manifestations (intermittent claudication, P = .49; resting pain, P = .28), ankle brachial index change (P = .07), 6-minute walk distance (P = .43), and complications between 2 groups.This pilot study did not show better outcome improvement of THPRS for patients with AOLE. We cautiously draw the present conclusion, because it suffers from several major restrictions. Thus, further studies with larger sample size and longer term follow-up are still needed to warrant the current conclusion.


Assuntos
Técnicas de Ablação/instrumentação , Extremidade Inferior/cirurgia , Doença Arterial Periférica/cirurgia , Placa Aterosclerótica/cirurgia , Procedimentos Cirúrgicos Vasculares/instrumentação , Idoso , Angioplastia/métodos , Estudos de Viabilidade , Feminino , Humanos , Extremidade Inferior/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Rotação , Resultado do Tratamento
16.
J Phys Chem Lett ; : 1612-1630, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33555195

RESUMO

Electrically conductive coordination polymers (generally known as metal-organic frameworks, MOFs) are a class of crystalline hybrid materials produced by the reasonable self-assembly of metal nodes and organic linkers. The unique and intriguing combination of inorganic and organic components endows coordination polymers with superior optical and electrical properties, which have recently aroused much attention in several electronic and optoelectronic technological applications. However, there are many challenging obstacles and issues that need to be addressed in this burgeoning field. In this Perspective, we first provide a fundamental understanding about the electronic design strategies that provide better guidance for realizing high conductivities and good mobilities in coordination polymers. We then examine the current established synthetic approaches to construct high-quality working samples of electrically conductive coordination polymers for device integration. This is followed by a discussion of the current state-of-the-art progress toward the preliminary achievements in (opto)electronic devices spanning chemiresistive sensors, field-effect transistors, organic photovoltaics, photodetectors, etc. Finally, we conclude this Perspective with the existing hurdles and limitations in this area, along with the critical directions and opportunities for future research.

17.
Phytomedicine ; 83: 153479, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33561764

RESUMO

BACKGROUND: The fruit of Terminalia chebula Retz. is one of the most widely used herbal drug in Traditional medicine prescriptions including those for liver diseases. In the screening of bioactive constituents that have potential hepatoprotective activity, chebulinic acid (CA) which is a major chemical constituent of T. chebula fruit showed potent activity. PURPOSE: This work was conducted to investigate the hepatoprotective activity and mechanisms of CA. METHODS: The hepatoprotective effect of CA was examined on hepatotoxic models of cells, zebrafish larvae and mice caused by tert-butyl hydrogen peroxide (t-BHP), acetaminophen (APAP) and CCl4, respectively. RESULTS: Pretreatment with CA could prevent t-BHP-induced damage in L-02 hepatocytes by blocking the production of ROS, reducing LDH levels and enhancing HO-1 and NQO1 expression via MAPK/Nrf2 signaling pathway. In animal experiments, CA significantly protected mice from CCl4-induced liver injury, as demonstrated by reduced ALT, AST and MDA levels, enhanced SOD activity, improved liver histopathological changes, and the activation of the Nrf2/HO-1 signaling pathway. CA metabolized to chebulic acid isomers with DPPH radical scavenging activity. In a transgenic zebrafish line with liver specific expression of DsRed RFP, CA diminished the hepatotoxicity induced by 10 mM APAP. CONCLUSION: Experiments in cell and two animal models demonstrated consistent results and comprehensively expounded the hepatoprotective effects of CA.

18.
PLoS Genet ; 17(2): e1009312, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33561165

RESUMO

Wing polymorphism is an evolutionary feature found in a wide variety of insects, which offers a model system for studying the evolutionary significance of dispersal. In the wing-dimorphic planthopper Nilaparvata lugens, the insulin/insulin-like growth factor signaling (IIS) pathway acts as a 'master signal' that directs the development of either long-winged (LW) or short-winged (SW) morphs via regulation of the activity of Forkhead transcription factor subgroup O (NlFoxO). However, downstream effectors of the IIS-FoxO signaling cascade that mediate alternative wing morphs are unclear. Here we found that vestigial (Nlvg), a key wing-patterning gene, is selectively and temporally regulated by the IIS-FoxO signaling cascade during the wing-morph decision stage (fifth-instar stage). RNA interference (RNAi)-mediated silencing of Nlfoxo increase Nlvg expression in the fifth-instar stage (the last nymphal stage), thereby inducing LW development. Conversely, silencing of Nlvg can antagonize the effects of IIS activity on LW development, redirecting wing commitment from LW to the morph with intermediate wing size. In vitro and in vivo binding assays indicated that NlFoxO protein may suppress Nlvg expression by directly binding to the first intron region of the Nlvg locus. Our findings provide a first glimpse of the link connecting the IIS pathway to the wing-patterning network on the developmental plasticity of wings in insects, and help us understanding how phenotypic diversity is generated by the modification of a common set of pattern elements.

19.
Medicine (Baltimore) ; 100(5): e24625, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592915

RESUMO

RATIONALE: Primary breast angiosarcoma (PBA) is a rare and overly aggressive entity and account for less than 1% of all breast cancer cases. PBA had a high rate of delayed preoperative diagnosis due to absent distinctive radiographic characteristics. PATIENT CONCERNS: We report a case of a 47-year-old female patient who had a previous history of luminal cancer in the right breast with mastectomy; the patient complained of asymmetrically diffuse enlarged, accompanying with a painless mass in the left breast 12 years after the mastectomy of her right breast. DIAGNOSES: The tumor mimicked idiopathic granulomatous mastitis on magnetic resonance imaging (MRI) at the first presentation. Contrast-enhanced ultrasound (CEUS) was performed for further lesion characterization and showed heterogeneous rapid hyper enhanced. An ultrasound-guided core needle biopsy was performed, and the pathology report indicated a breast angiosarcoma. INTERVENTIONS: The patient underwent a nipple-sparing simple mastectomy with immediate reconstruction of the left breast. OUTCOMES: After 8 months later, the tumor recurred, CEUS and MRI examination suggested PBA recurrence, then re-excision with implant removal was performed, the patient had a lung metastasis 4 months later eventually died 22 months after diagnosis. LESSONS: It is not easy to diagnose PBA with the radiographic examination. This case's importance is by combining CEUS and MRI to reflect enhanced morphology and hemodynamic characteristics of PBA and help diagnose breast angiosarcomas.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Hemangiossarcoma/diagnóstico por imagem , Hemangiossarcoma/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Feminino , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Ultrassonografia Mamária
20.
J Immunother Cancer ; 9(2)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33637599

RESUMO

BACKGROUND: The advent of immune checkpoint therapy has been a tremendous advance in cancer treatment. However, the responses are still insufficient in patients with soft tissue sarcoma (STS). We aimed to identify rational combinations to increase the response to immune checkpoint therapy and improve survival. METHODS: Whole-exome sequencing (WES) was performed in 11 patients with liposarcoma. Somatic copy number alterations (SCNAs) were analyzed at the gene level to identify obvious amplification patterns in drug-target genes. The expression and prognostic value of class I histone deacetylases (HDACs) was evaluated in 49 patients with sarcoma in our center and confirmed in 263 sarcoma samples from The Tumor Cancer Genome Atlas (TCGA) database. Q-PCR, flow cytometry and RNA-seq were performed to determine the correlations between class I HDACs, chidamide and PD-L1 in vitro and in vivo. The efficacy of combining chidamide with PD-1 blockade was explored in an immunocompetent murine model and a small cohort of patients with advanced sarcoma. Western blot, ChIP assay and dual luciferase assessment were applied in the mechanistic study. RESULTS: The HDAC gene family was frequently amplified in STS. SCNAs in the HDAC gene family were extensively amplified in 8 of 11 (73%) patients with liposarcoma, based on a drug-target gene set, and we verified amplification in 76.65% (197/257) of cases by analyzing TCGA sarcoma cohort. Class I HDAC expression is associated with a poor prognosis for patients with STS, and its inhibition is responsible for promoting apoptosis and upregulating of programmed cell death ligand 1 (PD-L1). The HDAC class I inhibitor chidamide significantly increases PD-L1 expression, increased the infiltration of CD8+ T cells and reduced the number of MDSCs in the tumor microenvironment. The combination of chidamide with an anti-PD-1 antibody significantly promotes tumor regression and improves survival in a murine model. Moreover, chidamide combined with the anti-PD-1 antibody toripalimab is effective in patients with advanced and metastatic sarcoma, and the side effects are tolerable. Mechanistically, chidamide increases histone acetylation at the PD-L1 gene through the activation of the transcriptional factor STAT1. CONCLUSIONS: The combination of chidamide and anti-programmed cell death 1 (PD-1) therapy represents a potentially important strategy for STS.

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