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1.
Mikrochim Acta ; 188(12): 439, 2021 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-34845528

RESUMO

Highly specific novel glycopeptide-based fluorescent molecularly imprinting polymers (g-FMIPs) were constructed to recognize and determine the target glycoprotein in complex biological samples. The glycopeptide of ovalbumin (OVA), with the unique structural characteristics of glycan and peptide, and potential application in improving the specificity recognition of g-FMIPs, was selected as the template molecule. The nitrogen-doped graphene quantum dots (N-GQDs) were introduced for fluorescence response. The obtained g-FMIPs possessed rapid binding kinetics and high adsorption capacity. Notably, the g-FMIPs exhibited remarkable selectivity and sensitivity with a high imprinting factor of 6.57, good linearity of 0.625 - 5.00 µM, and limit of detection of 0.208 µM. After treatment with g-FMIPs, the concentration of OVA in eluted solution was 1.07 µM. The obtained recoveries at 1.43 µM, 2.86 µM, and 4.29 µM spiked concentrations were 97.2%, 93.5%, and 101%, respectively, and the relative standard deviations were 2.6%, 4.2%, and 1.1%, respectively. In summary, the proposed strategy will expand the MIPs construction method and its application prospects in precision recognition and sensitive detection of trace glycoproteins from complex biosamples.

2.
Mar Drugs ; 19(11)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34822470

RESUMO

Actinomycin (Act) V, an analogue of Act D, presented stronger antitumor activity and less hepatorenal toxicity than Act D in our previous studies, which is worthy of further investigation. We hereby report that Act V induces apoptosis via mitochondrial and PI3K/AKT pathways in colorectal cancer (CRC) cells. Act V-induced apoptosis was characterized by mitochondrial dysfunction, with loss of mitochondria membrane potential (MMP) and cytochrome c release, which then activated cleaved caspase-9, cleaved caspase-3, and cleaved PARP, revealing that it was related to the mitochondrial pathway, and the apoptotic trendency can be reversed by caspase inhibitor Z-VAD-FMK. Furthermore, we proved that Act V significantly inhibited PI3K/AKT signalling in HCT-116 cells using cell experiments in vitro, and it also presented a potential targeted PI3Kα inhibition using computer docking models. Further elucidation revealed that it exhibited a 28-fold greater potency than the PI3K inhibitor LY294002 on PI3K inhibition efficacy. Taken together, Act V, as a superior potential replacement of Act D, is a potential candidate for inhibiting the PI3K/AKT pathway and is worthy of more pre-clinical studies in the therapy of CRC.

3.
Sci Rep ; 11(1): 22136, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34764409

RESUMO

Tobacco is be sensitively affected by chilling injury in the vigorous growth period, which can easily lead to tobacco leaf browning during flue-curing and quality loss, however, the physiological response of tobacco in the prosperous period under low temperature stress is unclear. The physiological response parameters of two tobacco varieties to low temperature stress were determined. The main results were as follows: ① For tobacco in the vigorous growing period subjected to low-temperature stress at 4-16 °C, the tissue structure of chloroplast changed and photosynthetic pigments significantly decreased compared with each control with the increase of intensity of low-temperature stress. ② For tobacco in the vigorous growing period at 10-16 °C, antioxidant capacity of the protective enzyme system, osmotic adjustment capacity of the osmotic adjusting system and polyphenol metabolism in plants gradually increased due to induction of low temperature with the increase of intensity of low-temperature stress. ③ Under low-temperature stress at 4 °C, the protective enzyme system, osmotic adjusting system and polyphenol metabolism of the plants played an insignificant role in stress tolerance, which cannot be constantly enhanced based on low-temperature resistance at 10 °C. This study confirmed that under the temperature stress of 10-16 °C, the self-regulation ability of tobacco will be enhanced with the deepening of low temperature stress, but there is a critical temperature between 4 and 10 °C. The self-regulation ability of plants under low temperature stress will be inhibited.

4.
BMC Med ; 19(1): 247, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34649530

RESUMO

BACKGROUND: We and others have confirmed activation of macrophages plays a critical role in liver injury and fibrogenesis during HBV infection. And we have also proved HBeAg can obviously induce the production of macrophage inflammatory cytokines compared with HBsAg and HBcAg. However, the receptor and functional domain of HBeAg in macrophage activation and its effects and mechanisms on hepatic fibrosis remain elusive. METHODS: The potentially direct binding receptors of HBeAg were screened and verified by Co-IP assay. Meanwhile, the function domain and accessible peptides of HBeAg for macrophage activation were analyzed by prediction of surface accessible peptide, construction, and synthesis of truncated fragments. Furthermore, effects and mechanisms of the activation of hepatic stellate cells induced by HBeAg-treated macrophages were investigated by Transwell, CCK-8, Gel contraction assay, Phospho Explorer antibody microarray, and Luminex assay. Finally, the effect of HBeAg in hepatic inflammation and fibrosis was evaluated in both human and murine tissues by immunohistochemistry, immunofluorescence, ELISA, and detection of liver enzymes. RESULTS: Herein, we verified TLR-2 was the direct binding receptor of HBeAg. Meanwhile, C-terminal peptide (122-143 aa.) of core domain in HBeAg was critical for macrophage activation. But arginine-rich domain of HBcAg hided this function, although HBcAg and HBeAg shared the same core domain. Furthermore, HBeAg promoted the proliferation, motility, and contraction of hepatic stellate cells (HSCs) in a macrophage-dependent manner, but not alone. PI3K-AKT-mTOR and p38 MAPK signaling pathway were responsible for motility phenotype of HSCs, while the Smad-dependent TGF-ß signaling pathway for proliferation and contraction of them. Additionally, multiple chemokines and cytokines, such as CCL2, CCL5, CXCL10, and TNF-α, might be key mediators of HSC activation. Consistently, HBeAg induced transient inflammation response and promoted early fibrogenesis via TLR-2 in mice. Finally, clinical investigations suggested that the level of HBeAg is associated with inflammation and fibrosis degrees in patients infected with HBV. CONCLUSIONS: HBeAg activated macrophages via the TLR-2/NF-κB signal pathway and further exacerbated hepatic fibrosis by facilitating motility, proliferation, and contraction of HSCs with the help of macrophages.


Assuntos
Antígenos E da Hepatite B , Receptor 2 Toll-Like , Animais , Humanos , Cirrose Hepática , Macrófagos , Camundongos , Fosfatidilinositol 3-Quinases
5.
J Asian Nat Prod Res ; : 1-7, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665691

RESUMO

Two new dinor-eudesmane sesquiterpenoids, named multistalin A (1), and multistalin B (2), together with three sesquiterpene glycosides (3-5), and a norlabdane-type diterpene (6) were isolated from the root extract of Chloranthus multistachys Pei. Their structures were elucidated on the basis of spectroscopic analysis including 1D, 2D NMR techniques and HR-ESI-MS. In addition, the cytotoxicity activities of the isolated compounds against selected cancer cells (Hela and A-549) were evaluated by MTT assay.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34688374

RESUMO

BACKGROUND: PD-1 blockade is highly effective in patients with mismatch repair-deficient or microsatellite instability-high metastatic colorectal cancer. The role of single-agent PD-1 blockade in the neoadjuvant setting for resectable mismatch repair-deficient or microsatellite instability-high colorectal cancer remains unclear. We investigated the efficacy and safety of PD-1 blockade with toripalimab, with or without the COX-2 inhibitor celecoxib, as neoadjuvant treatment for mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancers. METHODS: The PD-1 Inhibitor in Microsatellite Instability Colorectal Cancer (PICC) trial was a single-centre, open-label, parallel-group, non-comparative, randomised, phase 2 study undertaken at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China). Eligible patients were aged 18-75 years, had histologically confirmed mismatch repair-deficient or microsatellite instability-high colorectal cancer, had clinical stage T3-T4 or any T with lymph node positivity (N+), Eastern Cooperative Oncology Group performance score of 0 or 1, and adequate haematological, hepatic, and renal function. Participants were randomly assigned (1:1), without any stratification or balanced blocking, to receive toripalimab 3 mg/kg intravenously on day 1, with or without celecoxib 200 mg orally twice daily from day 1 to 14 of each 14-day cycle, for six cycles before surgical resection. Adjuvant treatment with toripalimab with or without celecoxib was permitted at the investigators' discretion. The primary endpoint was the proportion of patients with pathological complete response, defined as tumours without any viable tumour cells in the resected primary tumour sample and all sampled regional lymph nodes. All efficacy and safety analyses were assessed in the modified intention-to-treat population, which included all patients who were randomly assigned to treatment and who received at least one dose of toripalimab. This trial is registered with ClinicalTrials.gov, NCT03926338, and is ongoing. FINDINGS: Between May 1, 2019, and April 1, 2021, 53 patients were screened, of whom 34 were randomly assigned to either the toripalimab plus celecoxib group (n=17) or the toripalimab monotherapy group (n=17). As of data cutoff (Aug 10, 2021), median follow-up was 14·9 months (IQR 8·8-17·0). All patients received study treatment and underwent surgical resection; there were no treatment-related surgical delays. All 34 patients had an R0 resection (>1 mm resection margin). 15 of 17 patients (88% [95% CI 64-99]) in the toripalimab plus celecoxib group and 11 of 17 patients (65% [38-86]) in the toripalimab monotherapy group had a pathological complete response. All patients continued to receive adjuvant toripalimab with or without celecoxib for a total perioperative duration of 6 months and were alive and free of recurrence at data cutoff. During neoadjuvant treatment, ten (59%) patients in the toripalimab plus celecoxib group and ten (59%) in the toripalimab monotherapy group had grade 1-2 treatment-related adverse events. Only one (3%) of 34 patients, who was in the toripalimab plus celecoxib group, had a grade 3 or higher treatment-related adverse event during the neoadjuvant phase, which was grade 3 increased aspartate aminotransferase levels. In the adjuvant phase, only one (3%) of 34 patients, who was in the toripalimab monotherapy group, had a grade 3 or higher treatment-related adverse events, which was grade 3 increased aspartate aminotransferase and alanine aminotransferase levels. INTERPRETATION: Neoadjuvant toripalimab with or without celecoxib could be a potential therapeutic option for patients with mismatch repair deficient or microsatellite instability-high, locally advanced, colorectal cancer. This treatment was associated with a high pathological complete response rate and an acceptable safety profile, which did not compromise surgery. Longer term follow-up is needed to assess effects on survival-related endpoints. FUNDING: The National Key R&D Program of China, the National Natural Science Foundation of China, and the Chinese Society of Clinical Oncology-Junshi Biosciences Oncology Immunity Research. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

7.
J Surg Oncol ; 124(8): 1442-1450, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34494280

RESUMO

BACKGROUND AND OBJECTIVES: This study aimed to compare outcomes between neoadjuvant imatinib and upfront surgery in patients with localized rectal gastrointestinal stromal tumors (GIST) patients. METHODS: Eighty-five patients with localized rectal GIST were divided into two groups: upfront surgery ± adjuvant imatinib (Group A, n = 33) and the neoadjuvant imatinib + surgery + adjuvant imatinib (Group B, n = 52). Baseline characteristics between groups were controlled for with inverse probability of treatment weighting (IPTW) adjusted analysis. RESULTS: The response rate to neoadjuvant imatinib was 65.9%. After the IPTW-adjusted analysis, patients who underwent neoadjuvant therapy had better distant recurrence-free survival (DRFS) and disease-specific survival (DSS) compared with those who underwent upfront surgery (5-year DRFS 97.8 vs. 71.9%, hazard ratio [HR], 0.15; 95% CI, 0.03-0.87; p = 0.03; 5-year DSS 100 vs. 77.1%; HR, 0.11; 95% CI, 0.01-0.92; p = 0.04). While no significant association was found between overall survival (OS) and treatment groups (p = 0.07), 5-year OS was higher for the neoadjuvant group than upfront surgery group (97.8% vs. 71.9%; HR, 0.2; 95% CI, 0.03-1.15). CONCLUSIONS: In patients with localized rectal GIST, neoadjuvant imatinib not only shrunk the tumor size but also decreased the risk of metastasis and tumor-related deaths when compared to upfront surgery and adjuvant imatinib alone.


Assuntos
Antineoplásicos/uso terapêutico , Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/patologia , Mesilato de Imatinib/uso terapêutico , Terapia Neoadjuvante/mortalidade , Idoso , Estudos de Casos e Controles , Terapia Combinada , Feminino , Seguimentos , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
8.
Talanta ; 234: 122631, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364440

RESUMO

Some metabolites have been found to play key roles in inflammation and immunity events that are associated with diseases such as cancer, diabetes and cytokine release syndrome. Characterization upon the inflammation and immunity-related metabolites (IIMs) will be helpful to the assessment of related pathological states. Although these metabolites have been partially reported in previous studies, the methods for specific measurement of them remain lacking. In the present study, a liquid chromatography - mass spectrometry based method was developed for the targeted analyses of 45 IIMs including amino acids, organic acids, phosphatidylcholines (PCs), polyunsaturated fatty acids and hormones selected based on the literature knowledge. Direct extraction with dansyl-chloride in acetonitrile was proved to be the most efficient and time-saving strategy, in which precipitation, extraction and derivatization were integrated. IIMs derivatized for 4 min and quenched for 2 min revealed the most comprehensive abundance. Based on the defined conditions, all the IIMs had a low limit of detection smaller than 1 ng/mL with the linear range greater than three orders of magnitude. The relative standard derivations of intra-day and inter-day precisions were ranged from 2.2% to 13.4% and 1.7% to 19.5%, respectively. The recovery rates and accuracy in low concentration were 98.9% ± 5.6% and 106.7% ± 11.6%, in medium concentration were 97.1% ± 6.8% and 106.9% ± 9.5%, and in high concentration were 98.4% ± 8.9% and 98.1% ± 8.1%, respectively. Matrix effect and stability were ranged from -37.8% to 35.6% and 2.9% to 14.2%, respectively. To show the usefulness of the method, serum IIMs in hepatitis B virus (HBV) infected patients and healthy subjects were determined and compared. Bile acids, lipoxygenase-mediated lipid mediators and non-enzymatic products showed global increases, whereas most of LysoPCs and cyclooxygenase-mediated prostaglandin D2 decreased in HBV serum samples. This study provided a robust approach for the characterization of IIMs.


Assuntos
Soro , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Humanos , Inflamação
9.
Artigo em Inglês | MEDLINE | ID: mdl-34334298

RESUMO

PURPOSE: To evaluate the predictive implications and prognosis of mucinous adenocarcinoma (MAC) in locally advanced rectal cancer (LARC) with intensified neoadjuvant treatment. METHODS: Individual patient data of LARC patients from 3 prospective clinical trials was analyzed. Neoadjuvant treatment regimens comprised chemoradiotherapy (CRT) with fluorouracil (5-FU) or mFOLFOX6, neoadjuvant chemotherapy alone with mFOLFOX6 or mFOLFOXIRI. The postoperative pathological result, local recurrence and disease-free survival (DFS) were retrospectively analyzed in patients with MAC and adenocarcinoma (AC) with neoadjuvant treatment. RESULTS: Totally, 743 patients were recruited, with 620 patients eligible for analysis. Fifty-three (8.5%) patients were MAC. The pathological complete response (pCR) rate and tumor downstaging rate (ypStage 0-I) between MAC and AC patients was 7.5% vs. 22.0% (P = .01) and 20.8% vs. 48.7% (P < .001), respectively. Among patients receiving preoperative CRT with 5FU or mFOLFOX6, the pCR rate and tumor downstaging rate between MAC and AC patients was 11.1% vs. 27.3% (P = .03) and 23.7% vs. 52.6% (P = .001), respectively. Regarding neoadjuvant chemotherapy alone with mFOLFOX6 or mFOLFOXIRI, the pCR rate and tumor downstaging rate was 0 vs.13.2% (P = .11) and 11.8% vs. 42.5% (P = .03) between MAC and AC group, respectively. With the median follow-up time of 38.9 months, the 3-year DFS and 3-year locoregional recurrence rate was 58.4% vs. 77.6% (P = .02) and 26.0% vs. 5.7% (P = .001) in the MAC and AC group, respectively. MAC (hazard ratio [HR] 1.85, 95% confidence interval [CI], 1.15-2.98), PNI (HR 3.23, 95% CI, 1.85-5.72) and LVI (HR 2.04, 95% CI, 1.02-4.08) were independent prognosis factors and were associated with worse DFS. CONCLUSIONS: Patients with MAC of the rectum are associated with a lower pCR rate and tumor downstaging rate, higher incidence of local recurrence, and poorer DFS with neoadjuvant treatment.

10.
Front Immunol ; 12: 691766, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456908

RESUMO

About 250 million people worldwide are chronically infected with Hepatitis B virus (HBV), contributing to a large burden on public health. Despite the existence of vaccines and antiviral drugs to prevent infection and suppress viral replication respectively, chronic hepatitis B (CHB) cure remains a remote treatment goal. The viral persistence caused by HBV is account for the chronic infection which increases the risk for developing liver cirrhosis and hepatocellular carcinoma (HCC). HBV virion utilizes various strategies to escape surveillance of host immune system therefore enhancing its replication, while the precise mechanisms involved remain elusive. Accumulating evidence suggests that the proteins encoded by HBV (hepatitis B surface antigen, hepatitis B core antigen, hepatitis B envelope antigen, HBx and polymerase) play an important role in viral persistence and liver pathogenesis. This review summarizes the major findings in functions of HBV encoding proteins, illustrating how these proteins affect hepatocytes and the immune system, which may open new venues for CHB therapies.


Assuntos
Antígenos da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Proteínas Virais/imunologia , Animais , DNA Polimerase Dirigida por DNA/imunologia , Hepatite B/complicações , Hepatite B/imunologia , Vírus da Hepatite B/patogenicidade , Humanos , Fígado/patologia , Hepatopatias/etiologia
11.
Am J Physiol Gastrointest Liver Physiol ; 321(4): G436-G447, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34405716

RESUMO

Chronic constipation (CC) is a gastrointestinal disorder that adversely affects the quality of life. MicroRNAs are involved in the pathogenesis of functional gastrointestinal disorders. This study aims to investigate the molecular mechanism of microRNA-128 in CC. Here, we successfully constructed a murine model of CC based on morphine and rhubarb. The expression of stem cell factor (SCF) and neuron-specific enolase (NSE) was low in the models. Using miRNA array and bioinformatic analysis, we predicted and confirmed the expression of miR-128 and its downstream target genes in CC model. Compared with the control group, CC group showed a significant downregulation of miR-128 and upregulation of p38α and macrophage colony-stimulating factors (M-CSFs). Moreover, we observed elevated inflammatory cytokine and decreased anti-inflammatory cytokine levels in colonic tissues. Furthermore, coculture assays indicated that regulating expression of miR-128 in colonic epithelial cells induced the secretion of IL-6 and TNF-α by macrophages. In conclusion, our study demonstrated that miR-128 regulated the p38α/M-CSF signaling pathway to promote chronic inflammatory responses and changes in the immune microenvironment of the colon, thereby offering potential insights into the pathogenesis of CC and therapeutic targets for its treatment.NEW & NOTEWORTHY In this study, we constructed a murine model and identified a novel signaling mechanism involved in the chronic constipation progression. Our findings on the role of miR-128/p38α/M-CSF axis provide new insights into the treatment of chronic constipation.


Assuntos
Constipação Intestinal/metabolismo , Fator Estimulador de Colônias de Macrófagos/metabolismo , MicroRNAs/metabolismo , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Linhagem Celular Tumoral , Colo/metabolismo , Constipação Intestinal/genética , Feminino , Interleucina-6/metabolismo , Mucosa Intestinal/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , MicroRNAs/genética , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo
12.
Environ Sci Pollut Res Int ; 28(45): 64552-64560, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34312749

RESUMO

Petroleum hydrocarbons are important characteristic pollutants in the process of oil exploitation in the Yellow River Delta (China), and they cause a potential hazard to the surrounding ecological environment. The research on eco-toxicological effects of petroleum-derived products still needs to be studied in depth. This paper describes the physiological indices of wheat (Triticum aestivum L.) seeds and seedlings under independent stresses of acetone, 2-pentanone, and 2-hexanone to determine the toxicological effects of ketones derived from petroleum products on typical crops. The experimental results indicated that ketones with concentrations lower than 0.4 mg·cm-2 and 800 mg·kg-1 the germination of wheat seeds and the growth of seedlings were promoted to 113.32-127.27% and 105.41-126.39%, respectively, thus exhibiting low-dose excitatory effects. However, when the concentration was higher than 0.4 mg·cm-2 and 800 mg·kg-1, germination and seedlings' growth were significantly reduced to 7.14-2.12% and 35.09-13.33%, respectively. At the same time, acetone had a greater impact on the growth of wheat seed roots, the malondialdehyde (MDA), and chlorophyll contents in leaf tissues. The low concentration of acetone had a significant promoting effect on the activity of α-amylase in wheat seeds. 2-Pentanone reduced the electrical conductivity of wheat seed extract, and it significantly promoted the catalase (CAT) activity at low concentrations. 2-Hexanone had a strong inhibitory effect on wheat germination and growth. This study provided new research results to determine the toxic effects of petroleum-derived products and provided a basis for the environmental management of such substances.


Assuntos
Germinação , Plântula , Acetona/toxicidade , Metil n-Butil Cetona , Pentanonas , Sementes , Triticum
13.
J Med Chem ; 64(12): 7879-7899, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34128674

RESUMO

Hepatocellular carcinoma (HCC) has high associated morbidity and mortality rates. Although chemical medication represents a primary HCC treatment strategy, low response rates and therapeutic resistance serve to reduce its efficacy. Hence, identifying novel effective drugs is urgently needed, and many researchers have sought to identify new anti-cancer drugs from marine organisms. The marine population is considered a "blue drug bank" of unique anti-cancer compounds with diverse groups of chemical structures. Here, we discuss marine-derived compounds, including PM060184 and bryostatin-1, with demonstrated anti-cancer activity in vitro or in vivo. Based on the marine source (sponges, algae, coral, bacteria, and fungi), we introduce pharmacological parameters, compound-induced cytotoxicity, effects on apoptosis and metastasis, and potential molecular mechanisms. Cumulatively, this review provides insights into anti-HCC research conducted to date in the field of marine natural products and marine-derived compounds, as well as the potential pharmacological mechanisms of these compounds and their status in drug development.


Assuntos
Antineoplásicos/uso terapêutico , Organismos Aquáticos/química , Produtos Biológicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Bactérias/química , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Linhagem Celular Tumoral , Fungos/química , Humanos
14.
Anal Chem ; 93(22): 7898-7907, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34038073

RESUMO

Biomimetic cell membrane-coated nanoparticles have been broadly applied because of their superior biochemical properties. The right-side-out cell membrane coating manner provides nanoparticles with an immune-evasive stealth function in vivo. However, this acts as a drag for drug discovery when the drug targets are the intracellular domain of transmembrane receptors. Herein, inside-out-oriented cell membrane-coated nanoparticles were prepared for screening tyrosine kinase inhibitors, which specifically interacted with the intracellular kinase domain of the epidermal growth factor receptor. Biotinylated human lung adenocarcinoma epithelial cell membranes specifically interacted with streptavidin-immobilized Fe3O4 magnetic nanoparticles and then formed inside-out-oriented cell membrane-coated magnetic nanoparticles (IOCMMNPs). The cell membrane orientation of the IOCMMNPs was successfully confirmed by immunogold electron microscopy, fluorescently labeled confocal microscopy, sialic acid quantification assay, and the adsorption capacity assay. Moreover, IOCMMNPs possessed satisfactory binding capacity, selectivity, and high sensitivity (limit of detection = 0.4 × 10-3 µg mL-1). Ultimately, IOCMMNPs successfully targeted two main compounds from Strychnos nux-vomica whose potential antitumor activities were further validated by pharmacological studies. The application of the inside-out cell membrane coating strategy further enhances the drug screening efficiency and broadens the insight and methodologies for drug lead discovery. This inside-out cell membrane coating concept also provides a method for the future development of engineered cell membrane-coated nanotechnology.


Assuntos
Materiais Biomiméticos , Nanopartículas de Magnetita , Nanopartículas , Preparações Farmacêuticas , Biomimética , Membrana Celular , Humanos , Chumbo
15.
Cancer Invest ; 39(9): 696-710, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33938344

RESUMO

5-Fluorouracil (5-FU) resistance is an urgent problem of colorectal cancer (CRC) chemotherapy that needs to be resolved. To investigate 5-FU-associated lncRNAs for CRC might be of great significant. LncRNA ENSG00000254615 was detected by RNA-sequencing. ENSG00000254615 were detected highly expressed in 5-FU-sensitive CRC cells and tissue specimens, and inhibited cell proliferation and attenuated 5-FU resistance in vitro and in vivo. Furthermore, ENSG00000254615 participated in the regulation of p21 and Cyclin D1. Taken together, we proposed that ENSG00000254615 inhibits proliferation and attenuates 5-FU resistance of CRC by regulating p21 and Cyclin D1 expression.


Assuntos
Proliferação de Células/genética , Neoplasias Colorretais/genética , Ciclina D1/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Resistencia a Medicamentos Antineoplásicos/genética , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Animais , Antimetabólitos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Células HCT116 , Células HEK293 , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
16.
Org Lett ; 23(9): 3530-3535, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33881322

RESUMO

A novel visible-light-induced 1,4-hydroxysulfonylation of vinyl enynes with sulfonyl chlorides has been established, providing a highly efficient protocol to access multisubstituted sulfonyl allenic alcohols. Control experiments and mechanistic studies disclose that the target products result from sequential reactions of hydroxyl and tosyl radicals, among which chloride anion plays a key role to generate the requisite •OH, thus bridging water and enynes. Moreover, the vinyl pendant is believed to decisively affect the site-selectivity of hydroxyl radical.

17.
Front Behav Neurosci ; 15: 646528, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33927600

RESUMO

Objective: Postoperative cognitive dysfunction (POCD) is a common and severe complication of cardiovascular surgery. Lymphocyte-to-monocyte ratio (LMR) has been reported to be an independent predictor of lots of diseases associated with inflammation, but the association between the LMR and POCD is not clear. The present study aimed to investigate the potential value of LMR level to predict POCD in patients undergoing cardiovascular surgery. Methods: A prospective observational study was performed on the patients diagnosed with heart diseases undergoing cardiovascular surgeries with cardiopulmonary bypass. The leukocyte counts were measured by blood routine examination preoperatively. Then we calculated the LMR by dividing the lymphocyte count by the monocyte count. Neurocognitive functions were assessed 1 day before and 7 days after surgery. Perioperative factors were recorded to explore the relationship between LMR and POCD. Results: In total, 75 patients finished the whole study, while 34 patients developed POCD. The preoperative LMR level in the POCD group was higher than that in the non-POCD group. A cutoff value of 4.855 was identified to predict POCD occurrence according to ROC curve. The perioperative dynamic change of LMR level in the POCD group was higher than those in the non-POCD group. A cutoff value of 2.255 was identified to predict POCD occurrence according to ROC curve and the dynamic LMR change had similar varying trend with preoperative LMR level. Conclusions: The dynamic change of LMR level in the peripheral blood is associated with occurrence of POCD, and preoperative LMR level seems to be a prognostic biomarker of postoperative cognitive dysfunction in patients after cardiovascular surgery.

18.
Biomed Res Int ; 2021: 6635963, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33928154

RESUMO

Background: Baveno VI criteria, based on liver stiffness (LS) measured by transient elastography and platelet counts (PLT), have been proposed to avoid unnecessary endoscopy screening for high-risk varices (HRVs). However, the cut-off value of LS measured by 2D-SWE and PLT to predict HRVs in compensated hepatitis B-related cirrhotic patients remains unknown. Aims: To prospectively analyze the cut-off of the combination of LS measured by 2D-SWE and PLT in predicting HRVs and the influence of antiviral therapies in its efficacy. Methods: Serum parameters, LS, and endoscopy results were obtained from 160 compensated hepatitis B-related cirrhotic patients. The accuracy of the combined algorithm was assessed in the whole cohort and subgroups with or without consecutive antiviral therapies in the past 6 months. Results: In the whole cohort, the optimal cut-off value of LS for HRVs was 14.5 kPa. Patients with a LS value < 14.5 kPa with a PLT value > 110 × 109/L can be excluded from HRVs (NPV = 0.99, endoscopy saved rates = 0.68). Conversely, a LS value of ≥14.5 kPa and a PLT value of ≤110 × 109/L indicated HRVs, with accurate rates of 82.35%, and 10.63% of patients can avoid additional endoscopy screening. Moreover, antiviral therapy had no significant effect on the accuracy and rates saved from further endoscopy screening, when comparing patients with or without antiviral therapies (all p values > 0.05). Conclusions: The combination of LS (14.5 kPa) measured by 2D-SWE and PLT (110 × 109/L) can predict HRVs accurately in compensated hepatitis B-related cirrhotic patients without significant interference of antiviral therapy histories.


Assuntos
Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas/sangue , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Hepatite B/sangue , Hepatite B/complicações , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Resistência ao Cisalhamento , Algoritmos , Antivirais/farmacologia , Antivirais/uso terapêutico , Varizes Esofágicas e Gástricas/fisiopatologia , Feminino , Hepatite B/diagnóstico por imagem , Hepatite B/fisiopatologia , Humanos , Fígado/fisiopatologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Fatores de Risco
19.
Nat Chem ; 13(6): 559-567, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33833447

RESUMO

Singlet fission (SF) can potentially boost the efficiency of solar energy conversion by converting a singlet exciton (S1) into two free triplets (T1 + T1) through an intermediate state of a correlated triplet pair (TT). Although efficient TT generation has been recently realized in many intramolecular SF materials, their potential applications have been hindered by the poor efficiency of TT dissociation. Here we demonstrate that this can be overcome by employing a spatially separated 1(T…T) state with weak intertriplet coupling in tetracene oligomers with three or more chromophores. By using transient magneto-optical spectroscopic methods, we show that free-triplet generation can be markedly enhanced through the SF pathway that involves the spatially separated 1(T…T) state rather than the pathway mediated by the spatially adjacent TT state, leading to a marked improvement in free-triplet generation with an efficiency increase from 21% for the dimer to 85% (124%) for the trimer (tetramer).

20.
Metabolites ; 11(3)2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33668385

RESUMO

Potassium (K) reduces the deleterious effects of drought stress on plants. However, this mitigation has been studied mainly in the aboveground plant pathways, while the effect of K on root-soil interactions in the underground part is still underexplored. Here, we conducted the experiments to investigate how K enhances plant resistance and tolerance to drought by controlling rhizosphere processes. Three culture methods (sand, water, and soil) evaluated two rapeseed cultivars' root morphology, root exudates, soil nutrients, and microbial community structure under different K supply levels and water conditions to construct a defensive network of the underground part. We found that K supply increased the root length and density and the organic acids secretion. The organic acids were significantly associated with the available potassium decomposition, in order of formic acid > malonic acid > lactic acid > oxalic acid > citric acid. However, the mitigation had the hormesis effect, as the appropriate range of K facilitated the morphological characteristic and physiological function of the root system with increases of supply levels, while the excessive input of K could hinder the plant growth. The positive effect of K-fertilizer on soil pH, available phosphorus and available potassium content, and microbial diversity index was more significant under the water stress. The rhizosphere nutrients and pH further promoted the microbial community development by the structural equation modeling, while the non-rhizosphere nutrients had an indirect negative effect on microbes. In short, K application could alleviate drought stress on the growth and development of plants by regulating the morphology and secretion of roots and soil ecosystems.

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