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1.
J Invertebr Pathol ; 204: 108083, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38458350

RESUMO

The abilities to withstand oxidation and assimilate fatty acids are critical for successful infection by many pathogenic fungi. Here, we characterized a Zn(II)2Cys6 transcription factor Bbotf1 in the insect pathogenic fungus Beauveria bassiana, which links oxidative response and fatty acid assimilation via regulating peroxisome proliferation. The null mutant ΔBbotf1 showed impaired resistance to oxidants, accompanied by decreased activities of antioxidant enzymes including CATs, PODs and SODs, and down-regulated expression of many antioxidation-associated genes under oxidative stress condition. Meanwhile, Bbotf1 acts as an activator to regulate fatty acid assimilation, lipid and iron homeostasis as well as peroxisome proliferation and localization, and the expressions of some critical genes related to glyoxylate cycle and peroxins were down-regulated in ΔBbotf1 in presence of oleic acid. In addition, ΔBbotf1 was more sensitive to osmotic stressors, CFW, SDS and LDS. Insect bioassays revealed that insignificant changes in virulence were seen between the null mutant and parent strain when conidia produced on CZP plates were used for topical application. However, propagules recovered from cadavers killed by ΔBbotf1 exhibited impaired virulence as compared with counterparts of the parent strain. These data offer a novel insight into fine-tuned aspects of Bbotf1 concerning multi-stress responses, lipid catabolism and infection cycles.


Assuntos
Beauveria , Ácidos Graxos , Peroxissomos , Fatores de Transcrição , Beauveria/genética , Beauveria/patogenicidade , Animais , Peroxissomos/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ácidos Graxos/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Antioxidantes/metabolismo , Virulência , Estresse Oxidativo
2.
Cell Stress Chaperones ; 28(6): 909-920, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37828395

RESUMO

Oxidative stress is implicated in numerous diseases, with benzo(α)pyrene (BaP) known for causing substantial oxidative damage. Bifidobacterium longum (B. longum) is recognized as an antioxidant bacterium for certain hosts, yet its influence on oxidative damages instigated by BaP remains undetermined. In our study, we introduced various strains of Caenorhabditis elegans (C. elegans) to BaP to trigger oxidative stress, subsequently treating them with different forms of B. longum to evaluate its protective effects. Additionally, we explored the role of daf-16 in this context. Our findings indicated that in wild-type N2 C. elegans, B. longum-even in the form of inactivated bacteria or bacterial ultrasonic lysates (BULs)-significantly extended lifespan. BaP exposure notably decreased lifespan, superoxide dismutase (SOD) activity, and motility, while simultaneously down-regulating the expression of reactive oxygen species (ROS)-associated genes (sod-3, sek-1, cat-1) and daf-16 downstream genes (sod-3, ctl-2). However, it significantly increased the ROS level, malondialdehyde (MDA) content, and lipofuscin accumulation and up-regulated another daf-16 downstream gene (clk-1) (P <0.05). Interestingly, when further treated with B. longum peptide-1 (BLP-1), opposite effects were observed, and all the aforementioned indices changed significantly. In the case of RNAi (daf-16) C. elegans, BaP exposure significantly shortened the lifespan (P <0.05), which was only slightly prolonged upon further treatment with BLP-1. Furthermore, the expression of daf-16 downstream genes showed minor alterations in RNAi C. elegans upon treatment with either BaP or BLP-1. In conclusion, our findings suggest that B. longum acts as a probiotic for C. elegans. BLP-1 was shown to safeguard C. elegans from numerous oxidative damages induced by BaP, but these protective effects were contingent upon the daf-16 gene.


Assuntos
Bifidobacterium longum , Proteínas de Caenorhabditis elegans , Animais , Caenorhabditis elegans/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Benzo(a)pireno/toxicidade , Benzo(a)pireno/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Bifidobacterium longum/metabolismo , Estresse Oxidativo , Peptídeos/metabolismo , Superóxido Dismutase/metabolismo , Longevidade , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/farmacologia
3.
Nucleic Acids Res ; 51(15): 8283-8292, 2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37486765

RESUMO

As an enabling technique of synthetic biology, the scale of DNA assembly largely determines the scale of genetic manipulation. However, large DNA assembly technologies are generally cumbersome and inefficient. Here, we developed a YLC (yeast life cycle)-assembly method that enables in vivo iterative assembly of large DNA by nesting cell-cell transfer of assembled DNA in the cycle of yeast mating and sporulation. Using this method, we successfully assembled a hundred-kilobase (kb)-sized endogenous yeast DNA and a megabase (Mb)-sized exogenous DNA. For each round, over 104 positive colonies per 107 cells could be obtained, with an accuracy ranging from 67% to 100%. Compared with other Mb-sized DNA assembly methods, this method exhibits a higher success rate with an easy-to-operate workflow that avoid in vitro operations of large DNA. YLC-assembly lowers the technical difficulty of Mb-sized DNA assembly and could be a valuable tool for large-scale genome engineering and synthetic genomics.


Assuntos
Técnicas Genéticas , Saccharomyces cerevisiae , Biologia Sintética , Estágios do Ciclo de Vida , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Biologia Sintética/métodos
4.
Microb Pathog ; 180: 106132, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37201638

RESUMO

The ability of zinc oxide nanoparticles (ZnONPs) to induce bacteriostasis in Mycobacterium tuberculosis (M. tb) and their roles in regulating the pathogenic activities of immune cells have been reported previously, but the specific mechanisms underlying these regulatory functions remain unclear. This work aimed to determine how ZnONPs play the antibacterial role against M. tb. In vitro activity assays were employed to determine the minimum inhibitory concentrations (MICs) of the ZnONPs against various strains of M. tb (BCG, H37Rv, and clinical susceptible MDR and XDR strains). The ZnONPs had MICs of 0.5-2 mg/L against all tested isolates. In addition, changes in the expression levels of autophagy and ferroptosis-related markers in BCG-infected macrophages exposed to ZnONPs were measured. BCG-infected mice that were administered ZnONPs were used to determine the ZnONPs functions in vivo. ZnONPs decreased the number of bacteria engulfed by the macrophages in a dose-dependent manner, while different doses of ZnONPs also affected inflammation in different directions. Although ZnONPs enhanced the BCG-induced autophagy of macrophages in a dose-dependent manner, only low doses of ZnONPs activated autophagy mechanisms by increasing the levels of pro-inflammatory factors. The ZnONPs also enhanced BCG-induced ferroptosis of macrophages at high doses. Co-administration of a ferroptosis inhibitor with the ZnONPs improved the anti-Mycobacterium activity of ZnONPs in an in vivo mouse model and alleviated acute lung injury caused by ZnONPs. Based on the above findings, we conclude that ZnONPs may act as potential antibacterial agents in future animal and clinical studies.


Assuntos
Ferroptose , Mycobacterium tuberculosis , Nanopartículas , Óxido de Zinco , Camundongos , Animais , Óxido de Zinco/farmacologia , Vacina BCG , Autofagia , Antibacterianos/farmacologia , Inflamação
5.
J Psychiatr Res ; 163: 127-134, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37209618

RESUMO

BACKGROUND: Inhibitory control impairment in alcohol use disorder (AUD) may indicate detrimental effects of chronic alcohol use on different functional systems in the brain, but the current studies lack consistency. This study aims to identify the most consistent response inhibition-related brain dysfunction based on existing data. METHODS: We performed systematic searches of the PubMed, Embase, Web of Science, and PsychINFO databases for available studies. Anisotropic effect-size signed differential mapping was used to quantitatively analyze the differences in response inhibition-related brain activation between AUD patients and HCs. Meta regression was used to explore the relationship between brain alterations and clinical variables. RESULTS: The brain hypoactivation or hyperactivation in AUD patients compared with HCs during the response inhibition tasks was mainly located in the prefrontal cortex including the superior frontal gyrus, inferior frontal gyrus, and middle frontal gyrus, anterior cingulate gyrus (ACC), superior temporal gyrus, occipital gyrus, and somatosensory areas including postcentral gyrus and supramarginal gyrus. The meta-regression revealed that older patients were more likely to present activation in the left superior frontal gyrus when performing the response inhibition tasks. CONCLUSIONS: The response inhibitive dysfunctions in a distinct prefrontal-cingulate cortices may presumably reflect the core impairment in cognitive control abilities. Dysfunction in the occipital gyrus and somatosensory areas may indicate an abnormal motor-sensory and visual function in AUD. Such functional abnormalities may represent neurophysiological correlates of the executive deficits observed in AUD patients. This study has been registered in PROSPERO (number CRD42022339384).


Assuntos
Alcoolismo , Humanos , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Lobo Frontal , Imageamento por Ressonância Magnética
6.
Front Immunol ; 13: 973993, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341438

RESUMO

Objective: Hepatocellular carcinoma (HCC) is the sixth most commonly occurring cancer and ranks third in mortality among all malignant tumors; as a result, HCC represents a major human health issue. Although aberrant glycosylation is clearly implicated in HCC, changes in serum immunoglobulin (Ig)G and IgM glycosylation have not been comprehensively characterized. In this study, we used lectin microarrays to evaluate differences in serum IgG and IgM glycosylation among patients with HCC, hepatitis B cirrhosis (HBC), or chronic hepatitis B (CHB), and healthy normal controls (NC) and aimed to establish a model to improve the diagnostic accuracy of HCC. Methods: In total, 207 serum samples collected in 2019-2020 were used for lectin microarray analyses, including 97 cases of HCC, 50 cases of HBC, 30 cases of CHB, and 30 cases of NC. Samples were randomly divided into training and validation groups at a 2:1 ratio. Training group data were used to investigate the diagnostic value of the relative signal intensity for the lectin probe combined with alpha-fetoprotein (AFP). The efficacy of models for HCC diagnosis were analyzed by receiver operating characteristic (ROC) curves. Results: In terms of IgG, a model combining three lectins and AFP had good diagnostic accuracy for HCC. The area under the ROC curve was 0.96 (P < 0.05), the sensitivity was 82.54%, and the specificity was 100%. In terms of IgM, a model including one lectin combined with AFP had an area under the curve of 0.90 (P < 0.05), sensitivity of 75.41%, and specificity of 100%. Conclusion: Estimation of serum IgG and IgM glycosylation could act as complementary techniques to improve diagnosis and shed light on the occurrence and development of the HCC.


Assuntos
Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , alfa-Fetoproteínas , Neoplasias Hepáticas/patologia , Lectinas , Biomarcadores Tumorais , Cirrose Hepática , Imunoglobulina M , Imunoglobulina G
7.
Int Immunopharmacol ; 112: 109255, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36152539

RESUMO

Probiotics are living bacteria that provide health benefits to the host when consumed in sufficient quantities. However, the protective effect of the bioactive peptides isolated from the probiotics against benzo(α)pyrene (BaP) induced gastrointestinal injury has never been investigated. The current work used a bio-assay guided technique to identify-four new cyclic peptides in BaP-induced Caco-2 cell culture and mouse colitis model. Lactobacillus rhamnosus cycle (Thr-His-Ala-Trp) peptide-1 (LRCP-1) effectively inhibited BaP-induced epithelial cytokine over-release and intracellular ROS over-production. Simultaneously, LRCP-1 attenuated BaP-induced NAD (P)H: oxidases (NOXs), Matrix metalloproteinases (MMPs) over-expression, respectively. Furthermore, increased NAD (P)H: quinone oxidoreductase 1 (NQO1)/heme oxygenase-1 (HO-1)/nuclear factor E2-related factor 2 (Nrf2) expression and aryl hydrocarbon receptor (AhR) pathway activation induced by the BaP-exposure were also inhibited after the LRCP-1 treatment. Notably, LRCP-1 is a promising agent protecting gastrointestinal epithelial cells from BaP-induced inflammatory and oxidative damages.


Assuntos
Probióticos , Receptores de Hidrocarboneto Arílico , Humanos , Camundongos , Animais , Receptores de Hidrocarboneto Arílico/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Benzo(a)pireno/toxicidade , Heme Oxigenase-1 , Enterócitos , Espécies Reativas de Oxigênio/metabolismo , Células CACO-2 , NAD , Citocinas/metabolismo , Modelos Animais de Doenças , Probióticos/uso terapêutico , Peptídeos Cíclicos , Quinonas
8.
J Adv Prosthodont ; 14(4): 236-249, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36105881

RESUMO

PURPOSE: The present study compared the accuracy between digital and conventional implant impressions. MATERIALS AND METHODS: The experimental models were divided into six groups depending on the implant location and the scanning span. Digital impressions were captured using the intraoral optical scanner TRIOS (3Shape, Copenhagen, Denmark). Conventional impressions were taken with the monophase impression material based on addition-cured silicones, Honigum-Mono (DMG, Hamburg, Germany). A high-precision laboratory scanner D900 (3Shape, Copenhagen, Denmark) was used to obtain digital data of resin models and stone casts. Surface tessellation language (STL) datasets from scanner were imported into the analysis software Geomagic Qualify 14 (3D Systems, Rock Hill, SC, USA), and scan body deviations were determined through two-dimensional and three-dimensional analyses. Each scan body was measured five times. The Sidak t test was used to analyze the experimental data. RESULTS: Implant position and scanning distance affected the impression accuracy. For a unilateral arch implant and the mandible models with two implants, no significant difference was observed in the accuracy between the digital and conventional implant impressions on scan bodies; however, the corresponding differences for trans-arch implants and mandible with six implants were extremely significant (P<.001). CONCLUSION: For short-span scanning, the accuracy of digital and conventional implant impressions did not differ significantly. For long-span scanning, the precision of digital impressions was significantly inferior to that of the traditional impressions.

9.
Transl Psychiatry ; 12(1): 300, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35902559

RESUMO

Although altered reward sensitivity has been observed in individuals with bipolar disorder (BD), the brain function findings related to reward processing remain unexplored and inconsistent. This meta-analysis aimed to identify brain activation alterations underlying reward anticipation in BD. A systematic literature research was conducted to identify fMRI studies of reward-relevant tasks performed by BD individuals. Using Anisotropic Effect Size Signed Differential Mapping, whole-brain and ROI of the ventral striatum (VS) coordinate-based meta-analyses were performed to explore brain regions showing anomalous activation in individuals with BD compared to healthy controls (HC), respectively. A total of 21 studies were identified in the meta-analysis, 15 of which were included in the whole-brain meta-analysis and 17 in the ROI meta-analysis. The whole-brain meta-analysis revealed hypoactivation in the bilateral angular gyrus and right inferior frontal gyrus during reward anticipation in individuals with BD compared to HC. No significant activation differences were observed in bilateral VS between two groups by whole-brain or ROI-based meta-analysis. Individuals with BD type I and individuals with euthymic BD showed altered activation in prefrontal, angular, fusiform, middle occipital gyrus, and striatum. Hypoactivation in the right angular gyrus was positively correlated with the illness duration of BD. The present study reveals the potential neural mechanism underlying impairment in reward anticipation in BD. Some clinical features such as clinical subtype, mood state, and duration of illness confound the underlying neurobiological abnormality reward anticipation in BD. These findings may have implications for identifying clinically relevant biomarkers to guide intervention strategies for BD.


Assuntos
Transtorno Bipolar , Estriado Ventral , Antecipação Psicológica/fisiologia , Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Recompensa , Estriado Ventral/diagnóstico por imagem
10.
Front Med (Lausanne) ; 9: 1066870, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36590968

RESUMO

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular tumor of endothelial origin with low- to intermediate-grade malignant potentials. Since there is no characteristic clinical or biological marker available for PEH, most cases require a surgical lung biopsy for diagnosis. To date, although some patients with PEH reported in the literature were diagnosed through bronchoscopic biopsy, most of the patients still underwent surgical lung biopsy for confirmation. In this case report, we present a rare case diagnosed as PEH through endobronchial biopsies due to the presence of an intraluminal mass that blocked the trachea and caused atelectasis in the right upper lobe. Moreover, since surgery was not appropriate for this patient with unresectable bilateral multiple nodules, we adopted genetic analysis using NGS to provide a guide for personalized treatment. Then, based on the NGS results, the patient was treated with anti-PD-1 mAb and sirolimus for 1 year and has been stable in a 1-year follow-up examination.

11.
Front Psychiatry ; 12: 707622, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803753

RESUMO

Objective: This study aims to investigate the significant alterations in brain white matter integrity in individuals with bipolar disorder (BD) who had attempted suicide by applying a tract-based spatial statistics (TBSS) approach with tensor-based spatial normalization. Methods: A TBSS approach with novel tensor-based registration was used to compare the white matter fractional anisotropy (FA) between 51 individuals with BD, of whom 19 had attempted suicide, and 43 healthy controls (HC). The suicide attempt was assessed with the Columbia-Suicide Severity Rating Scale (C-SSRS). In addition, we also investigated the correlations of FA values with clinical measures in BD, including illness duration, and the severity of depression and anxiety measured by the Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA), respectively. Results: A significant reduction of FA value in the hippocampal cingulum was observed in BD individuals who had attempted suicide compared with those who had not. For the genu/body of the corpus callosum, inferior fronto-occipital fasciculus, uncinate fasciculus, and anterior thalamic radiation, the reductions in FA values were significantly greater in both BD subgroups who attempted suicide and who did not, compared to HC. The correlation analysis showed that the illness duration of attempters was correlated to the FA value of the genu of the corpus callosum, while the HAMD and HAMA scores of non-attempters were relevant to the FA of the superior longitudinal fasciculus. Conclusion: The observation that white matter integrity was altered in the hippocampal cingulum in BD individuals who attempted suicide suggested that this brain area may be the neurobiological basis of suicide attempts. Our findings also support the involvement of white matter (WM) microstructure of frontal-subcortical circuits in the neurobiological mechanism of BD. In addition, the illness duration of patients with attempted suicide may have an effect on the altered integrity of the corpus callosum.

12.
Cancer Manag Res ; 13: 6239-6248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393516

RESUMO

BACKGROUND: We aimed to explore the efficacy and tolerance of drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) treatment in relapsed/refractory small cell lung cancer (SCLC) patients. METHODS: Eleven relapsed/refractory SCLC patients were enrolled and treated with DEB-BACE. Then, treatment response and tumor marker levels were assessed at the first, second and sixth month post treatment. Quality of life was assessed by the EORTC QLQ-C30 scale. Progression-free survival (PFS) and overall survival (OS) were also evaluated. RESULTS: At the first, second and sixth month post treatment, the objective response rates were 63.6%, 54.5%, and 36.4%, respectively; and the disease control rates were 90.9%, 90.9% and 54.5%, respectively. In addition, the neuron-specific enolase (NSE) and progastrin-releasing peptide levels were reduced at the second and sixth month. Quality of life assessed by EORTC QLQ-C30 scale, which included subscales of general health status, functional domains, symptom domains, and single domains except for financial difficulty, was markedly improved at second month post treatment. Median values of PFS and OS were 5.1 (95% CI: 4.1-5.9) months and 9.0 (95% CI: 6.0-12.0) months, respectively. The ECOG score and preoperative NSE level were independent predictive factors for PFS, and age as well as lesion location were independent predictive factors for OS. Adverse events were all mild and manageable with chest pain and chest stuffiness the most common ones. CONCLUSION: DEB-BACE could be a therapeutic option for relapsed/refractory SCLC patients regarding its favorable treatment response, quality of life, survival benefit and safety profile.

13.
Hum Brain Mapp ; 42(16): 5458-5476, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34431584

RESUMO

Working memory (WM) impairments are common features of psychiatric disorders. A systematic meta-analysis was performed to determine common and disorder-specific brain fMRI response during performance of WM tasks in patients with SZ and patients with MDD relative to healthy controls (HC). Thirty-four published fMRI studies of WM in patients with SZ and 18 published fMRI studies of WM in patients with MDD, including relevant HC, were included in the meta-analysis. In both SZ and MDD there was common stronger fMRI response in right medial prefrontal cortex (MPFC) and bilateral anterior cingulate cortex (ACC), which are part of the default mode network (DMN). The effects were of greater magnitude in SZ than MDD, especially in prefrontal-temporal-cingulate-striatal-cerebellar regions. In addition, a disorder-specific weaker fMRI response was observed in right middle frontal gyrus (MFG) in MDD, relative to HC. For both SZ and MDD a significant correlation was observed between the severity of clinical symptoms and lateralized fMRI response relative to HC. These findings indicate that there may be common and distinct anomalies in brain function underlying deficits in WM in SZ and MDD, which may serve as a potential functional neuroimaging-based diagnostic biomarker with value in supporting clinical diagnosis, measuring illness severity and assessing the efficacy of treatments for SZ and MDD at the brain level.


Assuntos
Mapeamento Encefálico , Encéfalo/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Imageamento por Ressonância Magnética , Memória de Curto Prazo/fisiologia , Rede Nervosa/fisiopatologia , Esquizofrenia/fisiopatologia , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico por imagem , Humanos , Rede Nervosa/diagnóstico por imagem , Esquizofrenia/complicações , Esquizofrenia/diagnóstico por imagem
14.
J Thorac Dis ; 13(4): 2339-2350, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34012583

RESUMO

BACKGROUND: The study aimed to explore the efficacy and safety of drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) plus intercostals arterial infusion chemotherapy in non-small cell lung cancer (NSCLC) patients with refractory malignant pleural effusion (MPE). METHODS: 17 NSCLC patients with refractory MPE treated by DEB-BACE plus the intercostals arterial infusion chemotherapy (DEB-BACE group) were recruited. Their treatment response [complete remission (CR), partial remission (PR), overall efficacy, failure] for MPE was assessed at 1 month after therapy; adverse effects were recorded; MPE progression-free survival and overall survival (OS) were calculated. Moreover, 19 NSCLC patients with refractory MPE treated by conventional chemotherapy were reviewed as control (chemotherapy group), then their medical records were collected. RESULTS: With respect to MPE response, DEB-BACE group exhibited increased CR (82.4% vs. 10.5%, P<0.001) and overall efficacy (100.0% vs. 52.6%, P=0.001), similar PR (17.6% vs. 42.1%, P=0.112) while less failure (0.0% vs. 47.4%, P=0.001) compared to chemotherapy group. Furthermore, OS was prolonged in DEB-BACE group (median: 13.4; 95% CI: 11.0-15.8 months) than chemotherapy group (median: 7.0; 95% CI: 4.4-9.6 months) (P=0.002). Further analyses displayed that in DEB-BACE group, CR was associated with improved ECOG score and longer MPE progression-free survival, and adverse events mainly included fever, chest distress/pain, gastrointestinal side effects, myelosuppression, rash and hemoptysis, which were all mild and tolerable. CONCLUSIONS: DEB-BACE plus intercostals arterial infusion chemotherapy could serve as a salvage treatment option for NSCLC patients with refractory MPE.

16.
Neuropsychol Rev ; 31(4): 703-720, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33582965

RESUMO

Gray matter atrophy in multiple sclerosis (MS) is thought to be associated with disability and cognitive impairment, but previous studies have sometimes had discordant results, and the atrophy patterns of relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS) remain to be clarified. We conducted a meta-analysis using anisotropic effect-size-based algorithms (AES-SDM) to identify consistent findings from whole-brain voxel-based morphometry (VBM) studies of gray matter volume (GMV) in 924 RRMS patients and 204 PPMS patients. This study is registered with PROSPERO (number CRD42019121319). Compared with healthy controls, RRMS and PPMS patients showed gray matter atrophy in the cortico-striatal-thalamic network, sensorimotor network, and bilateral insula. RRMS patients had a larger GMV in the left insula, cerebellum, right precentral gyrus, and bilateral putamen as well as a smaller GMV in the bilateral cingulate, caudate nucleus, right thalamus, superior temporal gyrus and left postcentral gyrus than PPMS patients. The disease duration, Expanded Disability Status Scale score, Paced Auditory Serial Addition Test z-score, and T2-weighted lesion load were associated with specific gray matter regions in RRMS or PPMS. Alterations in the cortico-striatal-thalamic networks, sensorimotor network, and insula may be involved in the common pathogenesis of RRMS and PPMS. The deficits in the cingulate gyrus and caudate nucleus are more apparent in RRMS than in PPMS. The more severe cerebellum atrophy in PPMS may be a brain feature associated with its neurological manifestations. These imaging biomarkers provide morphological evidence for the pathophysiology of MS and should be verified in future research.


Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Esclerose Múltipla Crônica Progressiva/patologia , Tálamo/diagnóstico por imagem
17.
Quant Imaging Med Surg ; 11(1): 95-106, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33392014

RESUMO

BACKGROUND: Background activity on fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is often used as a reference to assess a patient's response to tumor treatment. To produce a suitable background activity reference, we examined the variations in standardized uptake values (SUVs) in the blood pool and liver of a large multi-aged population. METHODS: A total of 2,526 subjects underwent 18F-FDG PET/CT examinations and were divided into 12 age groups. Pearson's partial correlation and multivariate regression analyses were performed to assess the associations between individual factors and SUVs of the blood pool and liver and to identify the factor that most influenced the SUVs. The mean SUVs across the age groups were also determined. RESULTS: Positive correlations were found between individual factors and SUVs. Age appeared to be the most important predictor of SUVs and was significantly associated with the blood pool SUVmax (ß=0.466, P=0.000), blood pool SUVmean (ß=0.393, P=0.000), liver SUVmax (ß=0.347, P=0.000), and liver SUVmean (ß=0.354, P=0.000). Blood pool and liver SUVs rose rapidly until the age of 20 and then showed a slow upward trend without reaching a plateau. CONCLUSIONS: Age is an important factor that influences variations in the blood pool and liver SUVs. Our study clarified this understanding of age-related variations in SUVs and provided a normal range of blood pool and liver SUVs that may aid clinicians in evaluating tumors with greater accuracy.

18.
Acta Histochem ; 122(5): 151553, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32381365

RESUMO

Neuroinflammation plays a key role in perioperative neurocognitive disorders (PND). Increased evidences indicate that triggering receptor expressed on myeloid cells 2 (TREM2) can mitigate inflammatory response in the brain, and the aim of this study is to investigate whether TREM2 is involved in surgery-induced cognitive dysfunction in adult mice. We used adult C57BL/6 mice subjected to intramedullary fixation surgery, and found that surgery did not impair the motor ability of mice, but worsened the learning and memory function, and reduced the expression of TREM2. Meanwhile, up-regulated TREM2 expression in the brain of mice, induced by selective TREM2 agonist HSP60, significantly improved the learning and memory, alleviated the neuroinflammation, and decreased the neuronal cell apoptosis in mice. Meanwhile, TREM2-siRNA abolished the increased expression of TREM2 induced by HSP60, and reversed all the HSP60-induced beneficial effects. Therefore, our study indicated that up-regulation of TREM2 alleviated neuroinflammation and improved learning and memory function after surgery in mice.


Assuntos
Encéfalo/metabolismo , Disfunção Cognitiva/cirurgia , Microglia/metabolismo , Células Mieloides/metabolismo , Animais , Encéfalo/patologia , Encéfalo/cirurgia , Disfunção Cognitiva/complicações , Disfunção Cognitiva/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Microglia/patologia , Células Mieloides/patologia , Regulação para Cima
19.
J Sex Med ; 17(7): 1254-1267, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32312660

RESUMO

BACKGROUND: The differences and relationships between stimulus-related brain activation for sexually preferred stimuli and sexually nonpreferred stimuli are still unclear. AIM: This study aimed to identify brain regions that were mostly associated with sexual stimuli. METHODS: We used the activation likelihood estimation, meta-analytic connectivity modelling, and behavioral domain metadata in the BrainMap database to perform this analysis. OUTCOMES: We found convergent activation foci and created a model for the extended brain network involved in responses to sexual stimuli and also assessed the functional properties of these regions. RESULTS: A total of 34 experiments from 15 studies including 368 subjects and 343 foci were analyzed. The results showed that sexual stimuli are related to the extensive activation of the occipital-temporal-limbic system and less extensive activation of the basal ganglia. Sexually preferred stimuli activated mainly the anterior cingulate cortex and right fusiform gyrus, while sexually nonpreferred stimuli activated the limbic system, occipital gyrus, and thalamus. CLINICAL IMPLICATIONS: To have a further understanding of the central mechanisms of human sexuality. STRENGTHS & LIMITATIONS: Patient characteristics and analysis techniques in the included studies were heterogeneous. CONCLUSIONS: These findings suggest that the anterior cingulate cortex is an important cognitive control area for both sexually preferred and nonpreferred stimuli. Meta-analytic connectivity modelling analysis revealed a network of the core brain areas involved in response to sexual stimuli, and behavioral domain analysis indicated that these areas have both common and discrete functional properties. Long X, Tian F, Zhou Y, et al. Different Neural Correlates of Sexually Preferred and Sexually Nonpreferred Stimuli. J Sex Med 2020;17:1254-1267.


Assuntos
Nível de Alerta , Imageamento por Ressonância Magnética , Encéfalo , Mapeamento Encefálico , Humanos , Comportamento Sexual
20.
ACS Synth Biol ; 9(5): 1181-1189, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32268063

RESUMO

Genome-scale gene knockout is an important approach to the study of global genetic interactions. SCRaMbLEing of synthetic yeast chromosomes provides an efficient way to generate random deletion mutants. Here, we demonstrate the use of SCRaMbLE to explore synthetic lethal interactions. First, all essential genes of yeast chromosome III (chrIII) were clustered in a centromeric plasmid. We found that three types of reorganized clustered chrIII essential genes had similar transcriptional levels. Further, SCRaMbLEing of synthetic chromosome III (synIII) with supplementary clustered essential genes enables deletion of large chromosomal regions. Investigation of 141 SCRaMbLEd strains revealed varied deletion frequencies of synIII chromosomal regions. Among the no deletion detected regions, a hidden synthetic lethal interaction was revealed in the region of synIII 82-88 kb. This study shows that SCRaMbLE with clustered essential genes enhances streamlining of synthetic yeast chromosome and provides a novel strategy to uncover complex genetic interactions.


Assuntos
Cromossomos Fúngicos , Engenharia Genética/métodos , Saccharomyces cerevisiae/genética , Genes Essenciais , Plasmídeos/genética , Plasmídeos/metabolismo , Deleção de Sequência
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