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1.
Adv Sci (Weinh) ; : e2102741, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34623034

RESUMO

Supramolecular self-assemblies of dendritic peptides with well-organized nanostructures have great potential as multifunctional biomaterials, yet the complex self-assembly mechanism hampers their wide exploration. Herein, a self-stabilized supramolecular assembly (SSA) constructed from a PEGylated dendritic peptide conjugate (PEG-dendritic peptide-pyropheophorbide a, PDPP), for augmenting tumor retention and therapy, is reported. The supramolecular self-assembly process of PDPP is concentration-dependent with multiple morphologies. By tailoring the concentration of PDPP, the supramolecular self-assembly is driven by noncovalent interactions to form a variety of SSAs (unimolecular micelles, oligomeric aggregates, and multi-aggregates) with different sizes from nanometer to micrometer. SSAs at 100 nm with a spherical shape possess extremely high stability to prolong blood circulation about 4.8-fold higher than pyropheophorbide a (Ppa), and enhance tumor retention about eight-fold higher than Ppa on day 5 after injection, which leads to greatly boosting the in vivo photodynamic therapeutic efficiency. RNA-seq demonstrates that these effects of SSAs are related to the inhibition of MET-PI3K-Akt pathway. Overall, the supramolecular self-assembly mechanism for the synthetic PEGylated dendritic peptide conjugate sheds new light on the development of supramolecular assemblies for tumor therapy.

2.
Vet Microbiol ; 262: 109242, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34562786

RESUMO

The ability to form biofilms on surfaces makes Staphylococcus saprophyticus (S. saprophyticus) becomes the main pathogenic factor in nosocomial infections. Previously, we demonstrated that baicalin (Bac) inhibited azithromycin-resistant S. saprophyticus (ARSS) biofilm formation. This investigation aims to explore the influence of baicalin on primary adhesion and aggregation phases of biofilm formation, and the treatment effect of baicalin and azithromycin on ARSS biofilm-associated infection. Crystal violet (CV) staining and scanning electron microscope (SEM) observations clearly showed that sub-inhibitory concentration baicalin inhibited ARSS biofilm formation when baicalin was added before the adhesion and aggregation phases. Baicalin significantly increased the relative adhesion inhibition rate and decreased the rate of bacteria aggregation in a dose-dependent manner. Moreover, CLSM and cell lysis assays revealed that baicalin inhibited the production of surface proteins and cell autolysis in bacteria adhesion and aggregation phases of biofilm formation. Meanwhile, the relative expressions of adhesion-related and autolysis-related genes were down-regulated by baicalin. In vivo, the combination of baicalin and azithromycin succeeded in eradicating ARSS from the mouse cutaneous infection model and decreasing the pathological injuries, the expressions of cytokines in infected tissue, and the number of inflammatory cells in the blood. Simultaneously, baicalin decreased the bacterial burdens in tubes, the level of TNF-α, and the number of monocytes and neutrophils compared with that of the SS and azithromycin groups. Based on these results, baicalin inhibited the adhesion and aggregation phases of biofilm formation by influenced the production of surface proteins and cell autolysis. Baicalin and azithromycin synergetically treated ARSS biofilm-associated infection.

3.
Curr Mol Pharmacol ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34382512

RESUMO

The alterations in vascular homeostasis is deeply involved in the development of numerous diseases, such as coronary heart disease, stroke, and diabetic complications. Changes in blood flow and endothelial permeability caused by vascular dysfunction are the common mechanisms for these three types of diseases. The disorders of glucose and lipid metabolism can result in changes of the energy production patterns in endothelium and surrounding cells which may consequently cause local energy metabolic disorders, oxidative stress and inflammatory responses. Traditional Chinese medicine (TCM) follows the principle of the "treatment by the syndrome differentiation". TCM considers of that coronary heart disease, stroke and diabetes complications all as the type of "Qi deficiency and Blood stasis" syndrome, which mainly happens to the vascular system. Therefore, the common pathogenesis of these three types of diseases suggests the treatment strategy by TCM should be in a close manner and named as "treating different diseases by the same treatment". Qishen Yiqi dripping pills is a modern Chinese herbal medicine which has been widely used for treatment of patients with coronary heart disease characterized as "Qi deficiency and blood stasis" in China. Recently, many clinical reports have demonstrated the potent therapeutic effects of Qishen Yiqi dripping pills on ischemic stroke and diabetic nephropathy. Based on these reports, we will summarize the clinical applications of Qishen Yiqi dripping pills on coronary heart disease, ischemic stroke and diabetic nephropathy, including the involved mechanisms with basic researches.

4.
Planta ; 254(3): 50, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34386845

RESUMO

MAIN CONCLUSION: Overexpression of the leaf color (Lc) gene in Ma bamboo substantially increased the accumulation level of anthocyanin, and improved plant tolerance to cold and drought stresses, probably due to the increased antioxidant capacity. Most bamboos, including Ma bamboo (Dendrocalamus latiflorus Munro), are naturally evergreen and sensitive to cold and drought stresses, while it's nearly impossible to make improvements through conventual breeding due to their long and irregular flowering habit. Moreover, few studies have reported bamboo germplasm innovation through genetic engineering as bamboo genetic transformation remains difficult. In this study, we have upregulated anthocyanin biosynthesis in Ma bamboo, to generate non-green Ma bamboo with increased abiotic stress tolerance. By overexpressing the maize Lc gene, a bHLH transcription activator involved in the anthocyanin biosynthesis in Ma bamboo, we generated purple bamboos with increased anthocyanin levels including cyanidin-3-O-rutinoside, peonidin 3-O-rutinoside, and an unknown cyanidin pentaglycoside derivative. The expression levels of 9 anthocyanin biosynthesis genes were up-regulated. Overexpression of the Lc gene improved the plant tolerance to cold and drought stress, probably due to increased antioxidant capacity. The levels of the cold- and drought-related phytohormone jasmonic acid in the transgenic plants were also enhanced, which may also contribute to the plant stress-tolerant phenotypes. High anthocyanin accumulation level did not affect plant growth. Transcriptomic analysis showed higher expressions of genes involved in the flavonoid pathway in Lc transgenic bamboos compared with those in wild-type ones. The anthocyanin-rich bamboos generated here provide an example of ornamental and multiple agronomic trait improvements by genetic engineering in this important grass species.


Assuntos
Secas , Regulação da Expressão Gênica de Plantas , Antocianinas , Resposta ao Choque Frio , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo
5.
Adv Sci (Weinh) ; 8(17): e2004850, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34240584

RESUMO

Elevated Wnt/ß-catenin signaling has been commonly associated with tumorigenesis especially colorectal cancer (CRC). Here, an MST4-pß-cateninThr40 signaling axis essential for intestinal stem cell (ISC) homeostasis and CRC development is uncovered. In response to Wnt3a stimulation, the kinase MST4 directly phosphorylates ß-catenin at Thr40 to block its Ser33 phosphorylation by GSK3ß. Thus, MST4 mediates an active process that prevents ß-catenin from binding to and being degraded by ß-TrCP, leading to accumulation and full activation of ß-catenin. Depletion of MST4 causes loss of ISCs and inhibits CRC growth. Mice bearing either MST4T178E mutation with constitutive kinase activity or ß-cateninT40D mutation mimicking MST4-mediated phosphorylation show overly increased ISCs/CSCs and exacerbates CRC. Furthermore, the MST4-pß-cateninThr40 axis is upregulated and correlated with poor prognosis of human CRC. Collectively, this work establishes a previously undefined machinery for ß-catenin activation, and further reveals its function in stem cell and tumor biology, opening new opportunities for targeted therapy of CRC.

6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(4): 679-685, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34323049

RESUMO

Objective: To establish a method for simultaneous determination of 12 kinds of perfluorinated compounds (PFCs) in human urine based on ultra performance liquid chromatography tandem quadrupole linear ion trap mass spectrometry (UPLC-QTtrap-MS). Methods: After pH adjustment with 2% formic acid, the urine samples were loaded on a WAX solid phase extraction (SPE) cartridge for extraction, purification and concentration. The eluates were collected, concentrated to dryness under nitrogen, and reconstituted with 10 mmol/L ammonium acetate aqueous solution-methanol ( V water∶ V methanol = 70∶30) before injection. UPLC was performed on a C 18 cartridge, and methanol and 10 mmol/L ammonium acetate aqueous solution was used as mobile phases with gradient elution. QTtrap-MS was operated in multiple reaction monitoring (MRM) mode, and the internal standard calibration curves were applied for quantitative analysis. Results: Good linearity was obtained in the linear range, with the method detection limits and method quantification limits being 0.032 ng/L-6.5 ng/L and 0.10 ng/L-21 ng/L, respectively, for the 12 kinds of PFCs. The spiked recoveries of the 12 kinds of PFCs were 91.5%-114%, with the intra-day precision and the inter-day precision being 0.57%-16.0% and 1.88%-20.1%, respectively. The established method was applied to the determination of 12 kinds of PFCs in the urine samples of primary school students collected in one area. Nine kinds of PFCs were detected in the urine samples in this area. Among the PFCs detected, perfluorobutanesulfonic acid (PFBS) and perfluorooctanoic acid (PFOA) were the main PFCs found in the student urine samples. Conclusion: The method established in this study could be used to simultaneously examine 12 kinds of PFCs in urine. The method combined SPE with isotope internal standard correction and achieved good sensitivity and accuracy.


Assuntos
Extração em Fase Sólida , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Humanos
7.
Biomed Pharmacother ; 138: 111531, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311530

RESUMO

Heart failure (HF) is the advanced heart disease with high morbidity and mortality. Compound DanShen Dripping Pill (CDDP) is a widely used Traditional Chinese Medicine for cardiovascular disease treatment. Herein, we investigated if CDDP can protect mice against doxorubicin (DOX) or isoprenaline (ISO)-induced HF. After 3 days feeding of normal chow containing CDDP, mice were started DOX or ISO treatment for 4 weeks or 18 days. At the end of treatment, mice were conducted electrocardiogram and echocardiographic test. Blood and heart samples were determined biochemical parameters, myocardial structure and expression of the related molecules. CDDP normalized DOX/ISO-induced heart weight changes, HF parameters and fibrogenesis. The DOX/ISO-impaired left ventricular ejection fraction and fractional shortening were restored by CDDP. Mechanistically, CDDP blocked DOX/ISO-inhibited expression of antioxidant enzymes and DOX/ISO-induced expression of pro-fibrotic molecules, inflammation and cell apoptosis. Additional DOX/ISO-impaired targets in cardiac function but protected by CDDP were identified by RNAseq, qRT-PCR and Western blot. In addition, CDDP protected cardiomyocytes against oxygen-glucose deprivation-induced injuries. Taken together, our study shows that CDDP can protect against myocardial injuries in different models, suggesting its potential application for HF treatment.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Cardiopatias/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Cardiotoxicidade , Linhagem Celular , Modelos Animais de Doenças , Doxorrubicina , Fibrose , Cardiopatias/induzido quimicamente , Cardiopatias/metabolismo , Cardiopatias/patologia , Mediadores da Inflamação/metabolismo , Isoproterenol , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
8.
Plant J ; 107(5): 1513-1532, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34181801

RESUMO

De novo shoot organogenesis is an important biotechnological tool for fundamental studies in plant. However, it is difficult in most bamboo species, and the genetic control of this highly dynamic and complicated regeneration process remains unclear. In this study, based on an in-depth analysis at the cellular level, the shoot organogenesis from calli of Ma bamboo (Dendrocalamus latiflorus Munro) was divided into five stages. Subsequently, single-molecule long-read isoform sequencing of tissue samples pooled from all five stages was performed to generate a full-length transcript landscape. A total of 83 971 transcripts, including 73 209 high-quality full-length transcripts, were captured, which served as an annotation reference for the subsequent RNA sequencing analysis. Time-course transcriptome analysis of samples at the abovementioned five stages was conducted to investigate the global gene expression atlas showing genome-wide expression of transcripts during the course of bamboo shoot organogenesis. K-means clustering analysis and stage-specific transcript identification revealed important dynamically expressed transcription regulators that function in bamboo shoot organogenesis. The majority of abiotic stress-responsive genes altered their expression levels during this process, and further experiments demonstrated that exogenous application of moderate but not severe abiotic stress increased the shoot regeneration efficiency. In summary, our study provides an overview of the genetic flow dynamics during bamboo shoot organogenesis. Full-length cDNA sequences generated in this study can serve as a valuable resource for fundamental and applied research in bamboo in the future.

9.
Carbohydr Polym ; 267: 118160, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34119134

RESUMO

To achieve target delivery of anti-tumor drugs with great biocompatibility into tumor tissues, a stimuli-responsive dendronized hyaluronic acid (HA)-docetaxel conjugate (HA-DTX-Dendron, HADD) was designed and prepared. The incorporation of HA in HADD improved the delivery of DTX to tumor cells with rich CD44 receptors. Enhanced biocompatibility and therapeutic outcomes were achieved using glyodendrons-modified HA and tumor microenvironment-responsive linkers in HADD. The glycodendron was connected with HA via GSH-responsive disulfide bonds, and the drug DTX was linked to the carrier via a cathepsin B-responsive tetrapeptide GFLG. This design resulted in self-assembly nanostructures for facilitating uptake of HADD by tumor cells and rapid release of DTX to exert its therapeutic effect. Compared to free DTX, HADD showed much higher tumor growth inhibition in the MDA-MB-231 tumor-bearing mice model (up to 99.71%), and no toxicity was observed. Therefore, HADD could be employed as an efficacious nano-agent for treating triple negative breast cancer (TNBC).

10.
Sci Rep ; 11(1): 9541, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953309

RESUMO

Research on direct targets of traditional Chinese medicine (TCM) is the key to study the mechanism and material basis of it, but there is still no effective methods at present. We took Compound Danshen dropping pills (CDDP) as a study case to establish a strategy to identify significant direct targets of TCM. As a result, thirty potential active kinase targets of CDDP were identified. Nine of them had potential dose-dependent effects. In addition, the direct inhibitory effect of CDDP on three kinases, AURKB, MET and PIM1 were observed both on biochemical level and cellular level, which could not only shed light on the mechanisms of action involved in CDDP, but also suggesting the potency of drug repositioning of CDDP. Our results indicated that the research strategy including both in silico models and experimental validation that we built, were relatively efficient and reliable for direct targets identification for TCM prescription, which will help elucidating the mechanisms of TCM and promoting the modernization of TCM.

11.
J Psychiatr Res ; 139: 106-112, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34058648

RESUMO

BACKGROUND: In patients with schizophrenia, clinical symptoms and cognitive impairment are its core features, both of which have a significant impact on the prognosis and functional outcome. Empathy, as an important social cognition, has been found to be associated with the clinical symptoms in schizophrenia, but the conclusions on this issue are inconsistent. Therefore, this study will continue to explore it through a large sample of inpatients with chronic schizophrenia in the Chinese Han population. METHODS: We obtained the sociodemographic characteristics of 987 inpatients, measured their clinical symptoms using the Positive and Negative Syndrome Scale (PANSS), and assessed their self-reported empathy using the Interpersonal Reactivity Index (IRI). The factor score for negative symptoms (FSNS) of PANSS was additionally calculated. RESULTS: Correlation and linear regression analysis showed that patients' PANSS scores were widely correlated with their IRI scores. In particular, the negative symptoms of patients were significantly correlated to IRI total score (r = -0.131, p < .001) and subscales such as Perspective Taking (PT) (r = -0.233, p < .001). FSNS had close relationships with empathy as well. There are also many significant associations between other dimensions, such as general psychopathology and Perspective Taking (PT) or Fantasy (FS) (all p < .05). CONCLUSIONS: Our results indicated that clinical symptoms, especially negative symptoms, were closely related to their current empathy in patients with schizophrenia, suggesting that the severity of clinical symptoms may be a powerful factor in predicting social cognition such as empathy of schizophrenia.


Assuntos
Esquizofrenia , China , Empatia , Humanos , Psicologia do Esquizofrênico , Autorrelato
12.
Biomater Sci ; 9(12): 4473-4483, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34002187

RESUMO

Photodynamic therapy (PDT) can be defined as a kind of intracellular photocatalysis. Inspired by the design of photocatalysts, the construction of the heterojunction also is expected to improve the production of reactive oxygen species (ROS) for PDT. Herein, the Cu2-xSe/Bi2Se3@PEG (CB3@PEG) nano-heterostructure has been prepared by a cation-exchange process, where the interaction between the host and exchange agent is vital. CB3@PEG exhibits the near-infrared (NIR)-triggered hydroxyl radical and singlet oxygen (˙OH and 1O2) generation, which is more than 6 times in contrast with that of pure Cu2-xSe@PEG, attributed to the Z-scheme charge transfer mechanism with the high redox ability and great charge separation. Moreover, with the narrower band gap of Bi2Se3, CB3@PEG exhibits enhanced NIR harvest as well as high photothermal conversion efficiency (60.4%). Due to the Fenton reaction caused by the Cu ion, CB3@PEG is endowed with the chemodynamic therapy (CDT) and signal-enhanced T1-weight magnetic resonance imaging (MRI) capacity. In addition, the great photothermal ability and X-ray absorption coefficient provide outstanding contrast in photothermal imaging (PTI) and computerized tomography (CT) imaging. Finally, the multi-imaging combined with the synergistic treatment (PTT/CDT/PDT) makes CB3@PEG achieve enhanced efficiency in anticancer therapy.


Assuntos
Fotoquimioterapia , Medicina de Precisão , Terapia Fototérmica , Espécies Reativas de Oxigênio , Nanomedicina Teranóstica , Tomografia Computadorizada por Raios X
13.
Int J Psychiatry Clin Pract ; 25(3): 292-298, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33879034

RESUMO

OBJECTIVE: Cognitive impairment is an essential feature of schizophrenia; however, the relationship between clinical psychiatric symptoms with cognitive impairment is still unclear. Therefore, we aimed to assess cognitive deficits and the relationship between clinical symptoms and cognitive function in patients with chronic schizophrenia, which provide a reference guide for psychiatrists. METHODS: We compared the cognitive function in 312 schizophrenia inpatients and 397 healthy controls by using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The positive and negative symptom scale (PANSS) was used to assess the clinical symptoms of the patients. RESULTS: Analysis of covariance showed that the RBANS total and four index scores (all p < 0.001) were significantly lower in patients than healthy controls. After Bonferroni correction, Pearson correlation analysis showed that there was a significant negative association between PANSS negative symptom subscale and RBANS total score and all 5 domain scores (all p < 0.01). Further regression analysis showed that negative symptoms, age, age of onset, and antipsychotic dose were important independent predictors of cognitive deficits. CONCLUSIONS: Our findings suggest that patients with chronic schizophrenia exhibit cognitive deficits compared with healthy people. Negative symptoms and some clinical variables are associated with cognitive impairment in patients with schizophrenia.KEYPOINTSThis study indicates that patients with chronic schizophrenia have extensive cognitive impairment shown on RBANS except for the visuospatial/constructional domain.Cognitive impairment in patients is associated with age, negative symptoms, age of onset, and antipsychotic dose.There is a significant negative association between cognitive deficits and negative symptoms in patients with chronic schizophrenia.The results of this study need to be confirmed in future studies with longitudinal designs with a large and sex-balanced sample in first-episode drug naïve patients with schizophrenia.

14.
Med Drug Discov ; : 100090, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33817623

RESUMO

The COVID-19 disease caused by the SARS-CoV-2 virus is a health crisis worldwide. While developing novel drugs and vaccines is long, repurposing existing drugs against COVID-19 can yield treatments with known preclinical, pharmacokinetic, pharmacodynamic, and toxicity profiles, which can rapidly enter clinical trials. In this study, we present a novel network-based drug repurposing platform to identify candidates for the treatment of COVID-19. At the time of the initial outbreak, knowledge about SARS-CoV-2 was lacking, but based on its similarity with other viruses, we sought to identify repurposing candidates to be tested rapidly at the clinical or preclinical levels. We first analyzed the genome sequence of SARS-CoV-2 and confirmed SARS as the closest virus by genome similarity, followed by MERS and other human coronaviruses. Using text mining and database searches, we obtained 34 COVID-19-related genes to seed the construction of a molecular network where our module detection and drug prioritization algorithms identified 24 disease-related human pathways, five modules, and 78 drugs to repurpose. Based on clinical knowledge, we re-prioritized 30 potentially repurposable drugs against COVID-19 (including pseudoephedrine, andrographolide, chloroquine, abacavir, and thalidomide). Our work shows how in silico repurposing analyses can yield testable candidates to accelerate the response to novel disease outbreaks.

15.
Macromol Rapid Commun ; 42(9): e2100013, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33759304

RESUMO

Photodynamic therapy (PDT) has shown its promise in the treatment of cancer. Herein, a dendron-functionalized polyglutamic acid (PGA) polymer (PG-L8G-Ppa-Dendron, PGPD) is synthesized and it is conjugated with pyropheophorbide-a (Ppa) for the first time to treat triple negative breast cancer (TNBC), whereas a linear polyglutamate-Ppa conjugate (PGP) is synthesized as a control. Compared to the linear counterpart, the glycosylated polymer-based PGPD with a dendritic structure has excellent solubility and it self-assembles to form uniform-sized nanoparticles. PGPD displays a highly effective PDT effect in the animal model, evidenced with effective induction of reactive oxygen species (ROS) production and cell apoptosis. This may be due to an enhanced efficiency in delivery and accumulation of Ppa by this glycosylated dendritic polymer at tumor sites. Therefore, PGPD can be a highly effective and biosafe nanoagent for PDT of TNBC.


Assuntos
Neoplasias da Mama , Dendrímeros , Fotoquimioterapia , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Humanos , Nanomedicina , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Ácido Poliglutâmico
16.
Artigo em Inglês | MEDLINE | ID: mdl-33593833

RESUMO

Two novel ISCR1-associated dfr genes, dfrA42 and dfrA43, were identified from trimethoprim (TMP)-resistant Proteus strains and were shown to confer high level TMP resistance (MIC ≥ 1024 mg/L) when cloned into Escherichia coli These genes were hosted by complex class 1 integrons suggesting their potentials for dissemination. Analysis of enzymatic parameters and TMP affinity were performed, suggesting that the mechanism of TMP resistance for these novel DHFRs is the reduction of binding with TMP.

17.
J Affect Disord ; 282: 1203-1209, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33601697

RESUMO

BACKGROUND: The prevalence of depression increase with the outbreaks of epidemic disease. The prevalence of depression during the outbreak of Corona Virus Disease 2019 (COVID-19) in prenatal and postnatal women was examined in China. METHODS: 2201 prenatal and postnatal women in mainland China were recruited in this cross-sectional study from February 28th to April 26th, 2020. The Patient Health Questionnaire (PHQ-9) was used to assess depression in prenatal and postnatal women. RESULTS: The prevalence rate of depression was 35.4%. The risk factors for depression included drinking (p = 0.04; adjusted OR = 2.81, 95%CI: 1.26~6.24), nausea and vomiting during pregnancy (p < 0.001; adjusted OR = 3.54, 95%CI: 1.10~11.44), pregnancy's influence on mobility (p = 0.02; adjusted OR = 1.42, 95%CI: 1.11~1.83), anxiety (p < 0.001; adjusted OR = 1.66, 95%CI: 1.57~1.75), insomnia (p < 0.001; adjusted OR = 1.17, 95%CI: 1.14~1.21) and daily attention to fetal movement (p < 0.001; adjusted OR = 0.41, 95%CI: 0.31~0.56). LIMITATIONS: This study used a cross-sectional design, and cannot compare changes in the incidence of depression before and after the COVID-19 outbreak. CONCLUSIONS: During the COVID-19 outbreak, the prevalence rate of depression among Chinese prenatal and postnatal women was 35.4%. Moreover, anxiety, insomnia, drinking, nausea and vomiting during pregnancy, as well as the impaired movement and less daily monitoring of fetal movement were risk factors for depression.


Assuntos
COVID-19 , Depressão , Ansiedade , China/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Surtos de Doenças , Feminino , Humanos , Saúde Mental , Gravidez , Prevalência , Fatores de Risco , SARS-CoV-2 , Inquéritos e Questionários
18.
Stem Cell Res Ther ; 12(1): 128, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579360

RESUMO

BACKGROUND: Recently, growing evidence has indicated an important role of the complement system, a crucial component of immunity, in mediating neuroinflammation and promoting neuronal apoptosis following closed head injury (CHI). We previously reported that transplanted induced neural stem cells (iNSCs) pre-treated with CHI mouse serum could enhance complement receptor type 1-related protein y (Crry) expression and ameliorate complement-mediated damage in mouse CHI models. However, the mechanism underlying the elevated levels of Crry expression remains elusive. METHODS: CHI models were established using a standardized weight-drop device. We collected CHI mouse serum at 12 h post-trauma. RT-QPCR assay, western blot analysis, complement deposition assay, Akt inhibition assay, flow cytometry, cell transplantation, and functional assay were utilized to clarify the mechanism of Crry expression in iNSCs receiving CHI mouse serum treatment. RESULTS: We observed dramatic increases in the levels of Crry expression and Akt activation in iNSCs receiving CHI mouse serum treatment. Remarkably, Akt inhibition led to the reduction of Crry expression in iNSCs. Intriguingly, the treatment of iNSC-derived neurons with recombinant complement receptor 2-conjugated Crry (CR2-Crry), which inhibits all complement pathways, substantially enhanced Crry expression and Akt activation in neurons after CHI mouse serum treatment. In subsequent in vitro experiments of pre-treatment of iNSCs with CR2-Crry, we observed significant increases in the levels of Crry expression and Akt activation in iNSCs and iNSC-derived astrocytes and neurons post-treatment with CHI mouse serum. Additionally, an in vivo study showed that intracerebral-transplanted iNSCs pre-treated with CR2-Crry markedly enhanced Crry expression in neurons and protected neurons from complement-dependent damage in the brains of CHI mice. CONCLUSION: INSCs receiving CR2-Crry pre-treatment increased the levels of Crry expression in iNSCs and iNSC-derived astrocytes and neurons and attenuated complement-mediated injury following CHI.


Assuntos
Traumatismos Cranianos Fechados , Células-Tronco Neurais , Animais , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/transplante , Neuroproteção , Proteínas Proto-Oncogênicas c-akt/genética , Receptores de Complemento 3b , Proteínas Recombinantes de Fusão
19.
Clin Res Hepatol Gastroenterol ; 45(3): 101543, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33554864

RESUMO

OBJECTIVES: Endoscopic resection (ER) has been rapidly adopted in the treatment of early-stage esophageal cancer. We aimed to compare the outcomes of ER with esophagectomy for patients with small-sized (≤2 cm) stage T1a and T1b esophageal cancer in a population-based cohort. METHODS: We queried the Surveillance, Epidemiology, and End Results database for patients with T1N0M0 esophageal cancer who underwent ER or esophagectomy and generated a balanced cohort with 217 matched pairs using propensity score matching (PSM). Kaplan-Meier method and multivariable Cox regression analysis were employed to investigate the matched cohort. Subgroup analyses of T stage were also performed. RESULTS: We identified 702 patients; 309 (44.0 %) underwent ER, and 393 (56.0 %) underwent esophagectomy. In the unmatched cohort, patients who underwent ER were older, more likely to have a T1a stage, and less likely to receive lymph node sampling. In the entire matched cohort, multivariate analysis found esophagectomy were associated with better overall survival (OS) (HR: 0.62, 95 % CI: 0.40-0.96, p = 0.032) than ER, but no significant difference in esophageal cancer-specific survival (ECSS) (HR: 1.37, 95 % CI: 0.64-2.96, p = 0.420) between the two procedures. The results were similar for subgroup analyses of stage T1b patients. However, ER and esophagectomy were associated with similar OS (HR: 0.74, 95 % CI: 0.41-1.36; p = 0.334) and ECSS (HR: 3.69, 95 % CI: 0.95-14.39; p = 0.060) in patients with stage T1a disease. CONCLUSIONS: In patients with stage T1 esophageal cancer, ER was similar to esophagectomy in terms of oncologic outcomes. More prospective studies should be implemented to determine the optimal treatment for T1b esophageal cancer patients with risk factors.

20.
Carbohydr Polym ; 255: 117490, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33436250

RESUMO

To deliver photosensitizers with PEGylated heparin (HP) into tumor cells for photodynamic therapy, we prepared two polyethylene glycol (PEG)-functionalized HP-based polymers conjugated with pyropheophorbide-a (Ppa): a non-GSH-responsive nanoagent (HP-Ppa-mPEG) with the mPEG moiety chemically attached to HP directly; and a GSH-responsive nanoagent (HP-Ppa-SS-mPEG) with the mPEG moiety conjugated to HP via a disulfide linkage. The Ppa-functionalized HP without PEGylation (HP-Ppa) was designed as another control. These amphiphilic polymers could aggregate into nanoparticles. Cellular uptake of three nanoparticles by 4T1 cells led to abundant production of reactive oxygen species after irradiation by a 660 nm laser, inducing cell apoptosis. HP-Ppa-SS-mPEG was found to achieve the highest tumor accumulation, the longest retention time and the best penetration into tumor tissues, resulting in the highest in vivo anticancer efficacy with 94.3 % tumor growth inhibition rate, suggesting that tumor microenvironment-responsive PEGylated HP-based nanomedicines may act as efficient anticancer agents.


Assuntos
Antineoplásicos/farmacologia , Clorofila/análogos & derivados , Heparina/química , Neoplasias Mamárias Experimentais/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Clorofila/química , Feminino , Lasers , Luz , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Nanoconjugados/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/síntese química , Polietilenoglicóis/química , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
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