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1.
Artigo em Inglês | MEDLINE | ID: mdl-33006532

RESUMO

Elsinoë ampelina is an ascomycetous fungus that causes grape anthracnose, a potentially devastating disease worldwide. In this study, a dual RNA-seq analysis was used to simultaneously monitor the fungal genes related to pathogenesis and grape genes related to defence during the interaction at 2, 3, 4, and 5 days post inoculation (dpi). Consistent with their potential roles in pathogenicity, genes for carbohydrate-active enzymes, secondary metabolites synthesis, pathogen-host interaction and those encoding secreted proteins are upregulated during infection. Based on Agrobacterium tumefaciens-mediated transient assays in Nicotiana benthamiana, we further showed that eight and nine candidate effectors suppressed BAX- and INF1-mediated programmed cell death, respectively. The host response was characterized by the induction multiple defense systems against E. ampelina, including synthesis of phenylpropanoids, stilbenes, and terpenoids biosynthesis, cell wall modifications, regulation by phytohormones, and expression of defense related genes. Together, these findings offer new insights into the molecular mechanisms underlying the grape-E. ampelina interaction.

2.
Ear Nose Throat J ; : 145561320963592, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023339

RESUMO

Reconstruction of auricular deformities and facial scars after burns is a challenging undertaking for surgeons. Excessive scar tissue, a poor blood supply and the paucity of available skin are all substantial difficulties that should be considered before the operation. Expanded neck flaps provide comparatively larger and thinner flaps for the simultaneous treatment of auricular deformities and facial scars in burn patients. In this article, the authors introduced the use of an expanded neck flap as coverage tissue for ear reconstruction and face resurfacing in 2 burn patients. The operation consisted of 3 stages. In the first stage, the expander was implanted subcutaneously under the skin of the neck to create adequate skin and soft tissue. In the second stage, the expander was removed, and the expanded flap was transferred to cover defects on the auricle and face. The third operation to repair the reconstructed ear and thick flap could be performed according the willingness of the patients and surgeons. Esthetically satisfactory results were achieved in both of the patients. The flaps survived completely, and the skin color, texture, and flexibility were well matched to those of the peripheral tissue. Six months postoperatively, the flaps did not shrink, and subsequent contractures did not recur. Both of the patients experienced high satisfaction, and no adverse effects were detected.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33023460

RESUMO

BACKGROUND: Traumatic spinal cord injury (SCI) is a severe condition usually accompanied by an inflammatory process that gives rise to uncontrolled local apoptosis and a subsequent unfavorable prognosis. One reason for this unfavorable outcome could be the activation of the NLRP3 inflammasome. OBJECTIVE: MCC950 is a specific inhibitor of NLRP3 that further inhibits the formation of the NLRP3 inflammasome. The purpose of this study was to determine whether the NLRP3 inflammasome was associated with the severity of local apoptosis and whether MCC950 could prevent neuronal apoptosis following SCI. METHODS: In this study, primary cortical neurons were cultured in vitro. With or without pretreatment/posttreatment with MCC950, neurons were subjected to oxygen-glucose deprivation (OGD) for 2 h and then reperfusion for 20 h. Immunofluorescence was used to determine the expression of NLRP3, ASC and cleaved caspase-1 in neurons. In vivo, SCI model mice were established with a 5 g weight-drop method. MCC950 was intraperitoneally injected at 0, 2, 4, 6, 8, 10, and 12 days after SCI. Basso Mouse Scale (BMS) scores and footprint assays were used to assess motor function. Paw withdrawal threshold and tail flick latency were used to assess somatosensory function. H&E, Nissl and TUNEL staining were used to measure histological changes and apoptosis at 3 days after SCI, and scar formation was observed by Masson staining and GFAP immunohistochemical analysis at 28 days after SCI. RESULTS: Immunofluorescence analysis confirmed that MCC950 inhibited OGD-induced activation of the NLRP3 inflammasome in neurons. Behavioral tests, Masson staining and GFAP immunohistochemical analysis showed that MCC950-treated mice had improved neuronal functional recovery and reduced scar formation at 28 days after SCI. H&E, Nissl and TUNEL staining confirmed that there were more living neurons and fewer apoptotic neurons in MCC950-treated mice than control mice at 3 days after SCI. CONCLUSION: These results reveal that MCC950 exerts neuroprotective effects by reducing neuronal apoptosis, preserving the survival of the remaining neurons, attenuating the severity of the damage, and promoting the recovery of motor function after SCI.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33025380

RESUMO

The original version of this article unfortunately contained a mistake in Fig. 5B. The corrected Fig. 5 is given below. The authors declare that this amendment does not change the result or conclusion of the paper, and apologize for this oversight.

5.
J Ultrasound Med ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33035374

RESUMO

OBJECTIVES: To conduct a quantitative analysis of renal microvascular perfusion in diabetic patients with kidney injury using contrast-enhanced ultrasound (CEUS). METHODS: A total of 172 patients with type 2 diabetes mellitus and kidney injury were recruited from May 2017 to November 2019. After collection of clinical characteristics, a CEUS examination was performed after injection of the contrast agent SonoVue (Bracco SpA, Milan, Italy). Time-intensity curves and renal perfusion parameters were analyzed. Ultrasound-guided renal biopsy was performed. The patients were divided into a diabetic nephropathy (DN) group and a nondiabetic renal disease (NDRD) group according to renal pathologic results. The discrimination of perfusion parameters between the groups was analyzed statistically with SPSS version 19.0 software (IBM Corporation, Armonk, NY). Receiver operating characteristic curves were used to illustrate the diagnostic performance of indicators. RESULTS: Ninety-eight patients, including 45 with DN (29 male; mean age ± SD, 57.76 ± 10.47 years) and 53 with NDRD (40 male; mean age, 48.7 ± 13.88 years) were included in this study. The peak enhancement (PE), wash-in the area under the curve (AUC), wash-in rate, wash-in perfusion index, wash-out AUC, wash-in and wash-out AUC, and wash-out rate were significantly different between the groups (P < .05). There were no differences in time-related parameters between the DN and NDRD groups (P > .05). The receiver operating characteristic curve analysis showed that the AUC for PE was 0.727, and PE lower than 7712.426 had diagnostic potential, with sensitivity of 81% and specificity of 40% in discriminating between NDRD and DN. CONCLUSIONS: The quantification of CEUS parameters can discriminate DN in diabetic patients with kidney injury. The PE and AUC may be feasible parameters.

6.
J Immunol ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998984

RESUMO

BP180 (also termed type XVII collagen) is a hemidesmosomal protein and plays a critical role in cell-cell matrix adhesion in the skin; however, its other biological functions are largely unclear. In this study, we generated a BP180 functional-deficient mouse strain by deleting its extracellular domain of humanized NC16A (termed ΔNC16A mice). We found that BP180 is expressed by bone marrow mesenchymal stem cells (BM-MSC), and its functional deficiency leads to myeloid hyperplasia. Altered granulopoiesis in ΔNC16A mice is through bone marrow stromal cells evidenced by bone marrow transplantation. Furthermore, the level of G-CSF in bone marrow and circulation were significantly increased in ΔNC16A mice as compared with wild-type mice. The increased G-CSF was accompanied by an increased activation of the NF-κB signaling pathway in bone marrow and BM-MSC of ΔNC16A mice. Blockade of G-CSF restored normal granulopoiesis in ΔNC16A mice. Inhibition of NF-κB signaling pathway significantly reduces the release of G-CSF from ΔNC16A BM-MSC in vitro and the level of serum G-CSF in ΔNC16A mice. To our knowledge, these findings provide the first direct evidence that BP180 plays an important role in granulopoiesis through regulating NF-κB signaling pathway in BM-MSC.

7.
Singapore Med J ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-33047141

RESUMO

INTRODUCTION: Selective fetoscopic laser photocoagulation (SFLP) for twin-to-twin transfusion syndrome (TTTS) is challenging for new surgeons at the start of their learning curve. We described an approach utilising telementoring and team-based training to facilitate rapid attainment of the skills required for safe and efficient practice with a limited caseload. METHODS: We conducted a prospective observational study of SFLP performed by the novice primary surgical team in three stages: under direct on-site supervision from an expert mentor (Group 1), with remote tele-guidance from that mentor (Group 2) and independently (Group 3), at an academic tertiary hospital in Singapore. The primary team undertook regular training on high-fidelity tissue models to accelerate skills acquisition and complement the surgical performance. RESULTS: Nine patients diagnosed with Stage 2 TTTS were assessed for procedural characteristics, surgical outcomes and perinatal survival following SFLP. There were no significant differences in operative duration, anastomoses ablated, gestational age or birth weight at delivery. The complications observed were: recurrent TTTS (22.2% of pregnancies), twin anaemia polycythaemia sequence (33.3%), preterm prelabour membrane rupture (22.2%) and delivery at < 32 weeks (44.4%). At least one twin was live-born in 88.9% of cases, while postnatal survival to six months of at least one twin occurred in 77.8%. CONCLUSION: Systematic mentoring and specialised skills training are useful in aiding new surgeons to negotiate the steep learning curve and achieve good outcomes at the start of a new practice, particularly in the setting of low patient numbers. This is best paired with dedicated model training to achieve and maintain surgical dexterity for this complex procedure.

8.
Shanghai Kou Qiang Yi Xue ; 29(3): 267-274, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-33043343

RESUMO

PURPOSE: To investigate the molecular mechanism of LncRNA NEAT1 regulating proliferation, migration and invasion of tongue squamous cell carcinoma cells by regulating miR-339-5p/ITGA3 axis. METHODS: qRT-PCR and Western blot were used to detect the expression of NEAT1, miR-339-5p, ITGA3 mRNA and ITGA3 protein in 25 cases of human tongue squamous cell carcinoma, its corresponding adjacent tissues, human normal oral mucosal cell line HOK and human tongue squamous cell carcinoma cell lines TSCCA, CAL27, SCC15 and HN13. CAL27 cell lines that inhibited NEAT1 and overexpressed miR-339-5p were constructed, respectively. Cell viability was detected by MTT assay, cell numbers of migration and invasion were detected by Transwell assay, and the expression of Cyclin D1 and MMP-9 proteins were detected by Western blotting. The dual luciferase reporter gene was used to verify the targeting relationship of NEAT1, miR-339-5p and ITGA3, and the regulatory relationship was detected by Western blotting and qRT-PCR. SPSS 17.0 software package was used for statistical analysis of the data. RESULTS: Compared with normal human oral mucosal cell line HOK, the expression of NEAT1 and ITGA3 was up-regulated, while the expression of miR-339-5p was down-regulated in human tongue squamous cell carcinoma cell lines. Inhibition of NEAT1 or over-expression of miR-339-5p significantly inhibited proliferation, migration and invasion of CAL27 cells, and significantly inhibited expression of Cyclin D1 and MMP-9 proteins. Dual luciferase reporter gene assay confirmed that NEAT1 directly interacted with miR-339-5p and suppressed its expression. miR-339-5p negatively regulated ITGA3 expression. Inhibition of NEAT1 reversed the inhibitory effect of the inhibition of miR-339-5p on proliferation, migration and invasion of CAL27 cells. CONCLUSIONS: LncRNA NEAT1 promotes proliferation, migration and invasion of tongue squamous cell carcinoma cells by down-regulating miR-339-5p/ITGA3 axis.


Assuntos
Carcinoma de Células Escamosas , MicroRNAs , RNA Longo não Codificante/fisiologia , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Integrina alfa3 , MicroRNAs/genética , RNA Longo não Codificante/genética
9.
Org Lett ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064005

RESUMO

A robust six-membered rhodamine spirocyclic probe 1 containing a versatile 2-aminoimidazolyl moiety was elaborately designed and synthesized via an attractive C-C and C-N coupling strategy to improve the performance in the detection of ultralow transition metal ions. Probe 1 allowed the highly hypersensitive detection of Cu2+ with a superior picomolar limit of detection (35 pM) and nanomolar naked-eye performance (80 nM) via the switching of C-C and C-N cleavage by a catalytic hydrolysis mode.

10.
Sci Adv ; 6(40)2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32998884

RESUMO

Immune checkpoint blockade therapy (ICT) has shown potential in the treatment of multiple tumors, but suffers poor response rate in clinic. We found that even combining ICT with chemotherapy, which was wildly used in clinical trials, failed to achieve satisfactory tumor inhibition in the B16F10 model. Thus, we further constructed a previously unexplored immune cocktail therapy and realized multiple boosting of the cancer-immunity cycle. Cocktail therapy consisted of two kinds of tumor microenvironment-responsive drug and gene delivery nanoparticles to achieve specific delivery of doxorubicin and codelivery of plasmids expressed small hairpin RNA of PD-L1 (pshPD-L1) and hyaluronidase (pSpam1) in the tumor area. Experimental evidences proved that any component in the cocktail therapy was indispensable, and the cocktail therapy exhibited excellent antitumor effects against different types of tumors. The cocktail therapy presented here offers a searching strategy for more synergistic units with ICT and is meaningful for developing more efficient antitumor immunotherapy.

11.
Neoplasma ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33030956

RESUMO

Ovarian cancer is the most lethal gynecological cancer. In spite of recent advances, clinical outcomes remain poor, urgently needing novel therapeutic approaches. Growing evidence indicates that microRNAs play crucial roles in ovarian carcinogenesis and progression and that ferroptosis serves as a novel tumor suppressor. However, the molecular mechanisms of miRNA-mediated ferroptosis regulation in ovarian cancer are still largely unknown. In the present study, we show that miR-424-5p negatively regulates ferroptosis by directly targeting ACSL4 in ovarian cancer cells. Upregulation of miR-424-5p suppressed ACSL4 by directly binding to its 3'-UTR, which subsequently reduced erastin- and RSL3-induced ferroptosis. Meanwhile, knockdown of miR-424-5p increased the sensitivity of ovarian cancer cells to erastin and RSL3. Furthermore, ACSL4 was upregulated in ovarian cancer tissues, and high ACSL4 expression predicted worse prognosis and sensitized ovarian cancer cells to erastin- and RSL3-induced ferroptosis. Importantly, decreases in lipid peroxides and ferroptotic cell death mediated by miR-424-5p could be abrogated by ACSL4 overexpression. Taken together, our findings demonstrate that miR-424-5p regulates ferroptosis by targeting ACSL4 in ovarian cancer cells and suggest a potential therapeutic approach for ovarian cancer.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33057710

RESUMO

OBJECTIVES: To determine the dissemination and molecular characteristics of NDM-producing Escherichia coli strains from duck farms in south-east coastal China and their threats to human health. METHODS: A total of 232 NDM-producing E. coli were recovered from 1505 samples collected from 25 duck farms and their surrounding environments in five provinces in China. Resistance genes were confirmed using PCR. Genomic characteristics of the carbapenemase-producing isolates were determined by WGS and bioinformatic analysis. RESULTS: The rate of NDM-positive E. coli detected in samples from the five provinces ranged from 3.7% to 28.5%. There was substantial variation in the prevalence of NDM-positive E. coli from different duck farms in each province studied. Three variants (blaNDM-1, blaNDM-4 and blaNDM-5) were found in 232 NDM-positive E. coli; blaNDM-5 (94.8%, 220/232) was the most prevalent. WGS analysis indicated that ST746, ST48, ST1011 and ST167 E. coli isolates were prevalent in the current study and poultry was likely the primary reservoir for NDM-positive ST746 and ST48 E. coli in China. Phylogenomic analysis showed that NDM-positive E. coli isolates from ducks were closely related to those of human origin. In addition, WGS analysis further revealed that blaNDM co-existed with other antibiotic resistance genes, conferring resistance to nine classes of antimicrobials. CONCLUSIONS: This study revealed that ducks farm in China are an important reservoir for NDM-positive E. coli and STs of the isolates showed obvious distinctive diversities in geographical distribution. The distribution and spread of NDM-positive E. coli in duck farms poses a threat to public health.

13.
Theor Appl Genet ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068118

RESUMO

KEY MESSAGE: A minor QTL for grain weight in rice, qTGW1.2b, was fine-mapped. Its casual gene OsVQ4 was confirmed through CRISPR/Cas9-targeted mutagenesis, exhibiting an effect that was larger than the original QTL effect. The CRISPR/Cas system exhibits a great potential for rice improvement, but the application was severely hindered due to insufficient target genes, especial the lack of validated genes underlying quantitative trait loci having small effects. In this study, a minor QTL for grain weight, qTGW1.2b, was fine-mapped into a 44.0 kb region using seven sets of near isogenic lines (NILs) developed from the indica rice cross (Zhenshan 97)3/Milyang 46, followed by validation of the causal gene using CRISPR/Cas9-targeted mutagenesis. In the NIL populations, 1000-grain weight of the Zhenshan 97 homozygous lines decreased by 0.9-2.0% compared with the Milyang 46 homozygous lines. A gene encoding VQ-motif protein, OsVQ4, was identified as the candidate gene based on parental sequence differences. The effect of OsVQ4 was confirmed by creating CRISPR/Cas9 knockout lines, whose 1000-grain weight decreased by 2.8-9.8% compared with the wild-type transgenic line and the recipient. These results indicate that applying genome editing system could create novel alleles with large phenotypic variation at minor QTLs, which is an effective way to validate causal genes of minor QTLs. Our study establishes a strategy for cloning minor QTLs, which could also be used to identify a large number of potential target genes for the application of CRISPR/Cas system.

14.
Eur Radiol ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068187

RESUMO

OBJECTIVES: To evaluate carotid stiffening in participants without conventional cardiovascular risk factors (CVRFs) by using ultrafast pulse wave velocity (ufPWV). METHODS: The present study enrolled 517 participants without conventional CVRFs (CVRF-Free total population). Subjects in this population were defined as current non-smokers with untreated blood pressure < 140/90 mmHg, fasting blood glucose (FBG) < 7.0 mmol/L, total cholesterol (TC) < 6.2 mmol/L, low-density lipoprotein cholesterol < 4.1 mmol/L, and high-density lipoprotein cholesterol ≥ 1.0 mmol/L. Participants in the subgroup with optimal CVRFs (CVRF-Optimal subgroup; n = 188) were defined as having blood pressure < 120/80 mmHg, TC < 5.2 mmol/L, and FBG < 5.6 mmol/L. Clinical interviews, physical examinations, serum draw, carotid intima-media thickness (cIMT), and ufPWV were evaluated. Adjusted odds ratios (ORs) with 95% confidence intervals and ordinal logistic regression models were used. RESULTS: Carotid stiffening was present in 46.2-54.5% of CVRF-Free subjects. Age, male sex, and body mass index (BMI) were independently associated with carotid stiffening in both the CVRF-Free total population and CVRF-Optimal subgroup (OR for age = 1.10-1.11, OR for male sex = 2.65-7.19, OR for BMI = 1.34-1.62; p < 0.05). Carotid stiffening was associated with TC only in the CVRF-Free total population (OR for TC = 1.84; p = 0.034). CONCLUSIONS: Many CVRF-Free individuals have carotid stiffening. ufPWV for atherosclerotic stiffening aids the assessment of early atherogenesis and may further clarify the true status of healthy adults without CVRFs. KEY POINTS: • CVRF-Optimal individuals have a lower carotid stiffness than CVRF-Free populations. • ufPWV is a quantitative predictor for the early assessment of AS. • Absent major CVRFs cannot be considered low risk for carotid stiffening and atherosclerosis.

15.
Life Sci ; 263: 118549, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33039385

RESUMO

AIMS: Estrogen can induce inhibition of colonic smooth muscle contraction in male and female mice, which may lead to constipation; however, the mechanisms of inhibition are poorly understood. Hence, this study investigated the effect of estrogen on rat colonic smooth muscle contraction and role of small-conductance Ca2+-activated K+ 3 (SK3) and transcription factors (Sp1 and Sp3) in the underlying mechanisms. MAIN METHODS: The experiment included 24 female Sprague-Dawley (SD) rats divided into 4 groups. The rats were oophorectomized surgically, and a silicone tube containing blank solvent, 0.3 mg/mL estrogen (E2), equal-concentration of estrogen and estrogen receptor antagonist (EI), and bovine serum albumin-E2 (BSA-E2) was implanted. The rats were sacrificed on day 14. The molecular insights were confirmed using real-time quantitative reverse transcription PCR (qRT-PCR) and western blot analyses to determine the effect of estrogenic stimulation on gene and protein expression analyses, respectively. KEY FINDINGS: The E2 group showed significantly greater SK3 expression (P < .005) compared with other groups and significantly lowers smooth muscle cell (SMC) contractility (P < .005). Estrogen stimulation and SK3 overexpression resulted in a significant decrease (P < .05) in Ca2+ mobilization in the E2 group versus the control group. Further, the E2 group showed significantly higher Sp1 mRNA (P < .05) but lower Sp3 mRNA expression (P < .05) and protein expression (P < .001) compared with other groups. SIGNIFICANCE: E2 may promote SK3 expression by its genomic effect and inhibit colonic contraction by affecting SK3 expression via an interaction between Sp1 and Sp3.

16.
Neoplasma ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33038905

RESUMO

Ovarian cancer is the most lethal gynecological cancer. In spite of recent advances, clinical outcomes remain poor, urgently needing novel therapeutic approaches. Growing evidence indicates that microRNAs play crucial roles in ovarian carcinogenesis and progression and that ferroptosis serves as a novel tumor suppressor. However, the molecular mechanisms of miRNA-mediated ferroptosis regulation in ovarian cancer are still largely unknown. In the present study, we show that miR-424-5p negatively regulates ferroptosis by directly targeting ACSL4 in ovarian cancer cells. Upregulation of miR-424-5p suppressed ACSL4 by directly binding to its 3'-UTR, which subsequently reduced erastin- and RSL3-induced ferroptosis. Meanwhile, knockdown of miR-424-5p increased the sensitivity of ovarian cancer cells to erastin and RSL3. Furthermore, ACSL4 was upregulated in ovarian cancer tissues, and high ACSL4 expression predicted worse prognosis and sensitized ovarian cancer cells to erastin- and RSL3-induced ferroptosis. Importantly, decreases in lipid peroxides and ferroptotic cell death mediated by miR-424-5p could be abrogated by ACSL4 overexpression. Taken together, our findings demonstrate that miR-424-5p regulates ferroptosis by targeting ACSL4 in ovarian cancer cells and suggest a potential therapeutic approach for ovarian cancer.

17.
Pediatr Infect Dis J ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33044433

RESUMO

BACKGROUND: There are limit studies about pediatric brain abscess in China. The aim of this study was to analyze clinical characteristics and outcomes of pediatric brain abscess in recent years in China. METHODS: The clinical information of children with brain abscess hospitalized in Beijing Children's Hospital between January 1, 2007 and December 31, 2016 were retrospectively reviewed. RESULTS: Ninety-four children were enrolled in this study. A Streptococcus milleri group (13.8%) was identified as the most common causative organisms, followed by Staphylococcus aureus (6.4%). The overall mortality was 21.6%, with 50.0% of deaths happening in the first week after diagnosis. Long-term outcomes of 74 patients were assessed with Glasgow Outcome Scale-Extended Pediatric Reversion: 50 patients with a score of 1-2 (favorable outcome) and 24 patients with a score of 3-8 (unfavorable outcome). Patients with multiple abscesses (P = 0.029) and intraventricular rupture of brain abscess/hydrocephalus (P = 0.024) had higher risk of unfavorable outcomes. CONCLUSIONS: Brain abscess is a serious disease with high mortality in children; more aggressive treatments should be considered in the first week of diagnosis because of high risk of death, and for patients with multiple brain abscesses and intraventricular rupture of brain abscess/hydrocephalus because of their higher risk of unfavorable.

18.
Arch Virol ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044625

RESUMO

We have determined the complete genomic sequence of a potyvirus from Achyranthes bidentata in Zhejiang, China, using reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) PCR. The genomic RNA is 9482 nucleotides (nt) long excluding the 3'-terminal poly(A) tail and encodes a putative large polyprotein with 3073 amino acids (aa). It has 75.4-53.5% nt sequence identity and 84.0-49.1% polyprotein sequence identity to other potyviruses and is probably a distantly related isolate of the same species as the recently reported achyranthes virus A isolate from South Korea (AcVA-SK). This is the first report of the occurrence of a potyvirus infecting A. bidentata in China.

19.
Pharmacol Res ; : 105111, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065284

RESUMO

Macrophages, a type of myeloid immune cell, play essential roles in fighting against pathogenic invasion and activating T cell-mediated adaptive immune responses. As a major constituent of the tumor microenvironment (TME), macrophages play a complex role in tumorigenesis and tumor progression. They can inhibit tumor growth by releasing proinflammatory cytokines and exerting cytotoxic activities but principally contribute to tumor progression by promoting tumor proliferation, angiogenesis, and metastasis. The tumor-promoting hallmarks of macrophages have aroused widespread interest in targeting tumor-associated macrophages (TAMs) for cancer immunotherapy. Increasing preclinical and clinical studies suggest that TAMs are a promising target for cancer immunotherapy. To date, TAM-targeted therapeutic strategies have mainly been divided into two kinds: inhibiting pro-tumor TAMs and activating anti-tumor TAMs. We reviewed the heterogeneous and plastic characteristics of macrophages in the TME and the feasible strategies to target TAMs in cancer immunotherapy and summarized the complementary effect of TAM-targeted therapy with traditional treatments or other immunotherapies.

20.
Eur J Med Chem ; : 112922, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33069436

RESUMO

Magnolol and honokiol are the two major active ingredients with similar structure and anticancer activity from traditional Chinese medicine Magnolia officinalis, and honokiol is now in a phase I clinical trial (CTR20170822) for advanced non-small cell lung cancer (NSCLC). In search of potent lead compounds with better activity, our previous study has demonstrated that magnolol derivative C2, 3-(4-aminopiperidin-1-yl)methyl magnolol, has better activity than honokiol. Here, based on the core of 3-(4-aminopiperidin-1-yl)methyl magnolol, we synthesized fifty-one magnolol derivatives. Among them, compound 30 exhibited the most potent antiproliferative activities on H460, HCC827, H1975 cell lines with the IC50 values of 0.63-0.93 µM, which were approximately 10- and 100-fold more potent than those of C2 and magnolol, respectively. Besides, oral administration of 30 and C2 on an H460 xenograft model also demonstrated that 30 has better activity than C2. Mechanism study revealed that 30 induced G0/G1 phase cell cycle arrest, apoptosis and autophagy in cancer cells. Moreover, blocking autophagy by the autophagic inhibitor enhanced the anticancer activity of 30in vitro and in vivo, suggesting autophagy played a cytoprotective role on 30-induced cancer cell death. Taken together, our study implied that compound 30 combined with autophagic inhibitor could be another choice for NSCLC treatment in further investigation.

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