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1.
Nat Commun ; 12(1): 6450, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750392

RESUMO

The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected EGFR-mutant stage II-IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.

2.
Neurochem Res ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34468932

RESUMO

Further understanding the mechanism for microglia activation is necessary for developing novel anti-inflammatory strategies. Our previous study found that the activation of sigma-1 receptor can effectively inhibit the neuroinflammation, independent of the canonical mechanisms, such as NF-κB, JNK and ERK inflammatory pathways. Thus, it is reasonable that an un-identified, non-canonical pathway contributes to the activation of microglia. In the present study, we found that a sigma-1 receptor agonist of 2-morpholin-4-ylethyl 1-phenylcyclohexane-1-carboxylate (PRE-084) suppressed lipopolysaccharide (LPS) elevated nitric oxide (NO) content in BV-2 microglia culture supernatant and LPS-raised mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS) in BV-2 microglia. Moreover, PRE-084 alleviated LPS-increased Ser 9 de-phosphorylation of glycogen synthase kinase-3 beta (GSK-3ß), LPS-elevated catalytic activity of calcineurin, and LPS-raised percent and frequency of Ca2+ oscillatory BV-2 cells. We further found that the inhibitory effect of PRE-084 was reversed by a calcineurin activator of chlorogenic acid and a GSK-3ß activator of pyrvinium. Moreover, an IP3 receptor inhibitor of 2-aminoethoxydiphenyl borate mimicked the anti-inflammatory activity of PRE-084. Thus, we identified a noncanonical pro-neuroinflammary pathway of Ca2+ oscillation/Calcineurin/GSK-3ß and the inhibition of this pathway is necessary for the anti-inflammatory activity of sigma-1 receptor activation.

3.
Adv Drug Deliv Rev ; 178: 113964, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34499982

RESUMO

Traditional herbal medicine (THM), an ancient science, is a gift from nature. For thousands of years, it has helped humans fight diseases and protect life, health, and reproduction. Nanomedicine, a newer discipline has evolved from exploitation of the unique nanoscale morphology and is widely used in diagnosis, imaging, drug delivery, and other biomedical fields. Although THM and nanomedicine differ greatly in time span and discipline dimensions, they are closely related and are even evolving toward integration and convergence. This review begins with the history and latest research progress of THM and nanomedicine, expounding their respective developmental trajectory. It then discusses the overlapping connectivity and relevance of the two fields, including nanoaggregates generated in herbal medicine decoctions, the application of nanotechnology in the delivery and treatment of natural active ingredients, and the influence of physiological regulatory capability of THM on the in vivo fate of nanoparticles. Finally, future development trends, challenges, and research directions are discussed.

4.
J Nanobiotechnology ; 19(1): 255, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425832

RESUMO

Although nanomedicine have greatly developed and human life span has been extended, we have witnessed the soared incidence of central nervous system (CNS) diseases including neurodegenerative diseases (Alzheimer's disease, Parkinson's disease), ischemic stroke, and brain tumors, which have severely damaged the quality of life and greatly increased the economic and social burdens. Moreover, partial small molecule drugs and almost all large molecule drugs (such as recombinant protein, therapeutic antibody, and nucleic acid) cannot cross the blood-brain barrier. Therefore, it is especially important to develop a drug delivery system that can effectively deliver therapeutic drugs to the central nervous system for the treatment of central nervous system diseases. Cell penetrating peptides (CPPs) provide a potential strategy for the transport of macromolecules through the blood-brain barrier. This study analyzed and summarized the progress of CPPs in CNS diseases from three aspects: CPPs, the conjugates of CPPs and drug, and CPPs modified nanoparticles to provide scientific basis for the application of CPPs for CNS diseases.

5.
J Food Prot ; 84(11): 2020-2036, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34233360

RESUMO

ABSTRACT: Biogenic amines (BAs) are organic compounds with low molecular weight and can be used as indicators of the quality and safety of canned aquatic products during processing and storage. However, excess of these amines can cause foodborne poisoning. Therefore, the determination, analysis, and prevention of BAs are of great importance. This article focuses on the sources, formation, and pretreatment methods, as well as analytical techniques, change tendency, and control techniques of BAs, with the aim of promoting more appropriate analysis of canned aquatic products to provide a reference for the food industries.

6.
Lancet Respir Med ; 9(9): 1021-1029, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34280355

RESUMO

BACKGROUND: Icotinib has provided survival benefits for patients with advanced, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We aimed to compare icotinib with chemotherapy in patients with EGFR-mutant stage II-IIIA NSCLC after complete tumour resection. Here, we report the results from the preplanned interim analysis of the study. METHODS: In this multicentre, randomised, open-label, phase 3 trial done at 29 hospitals in China, eligible patients were aged 18-70 years, had histopathogically confirmed stage II-IIIA NSCLC, had complete resection up to 8 weeks before random assignment, were treatment-naive, and had confirmed activation mutation in exon 19 or exon 21 of the EGFR gene. Participants were randomly assigned (1:1) with an interactive web-based response system to receive either oral icotinib 125 mg thrice daily for 2 years or four 21-day cycles of intravenous chemotherapy (vinorelbine 25 mg/m2 on days 1 and 8 of each cycle plus cisplatin 75 mg/m2 on day 1 of each cycle for adenocarcinoma or squamous carcinoma; or pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 on day 1 every 3 weeks for non-squamous carcinoma). The primary endpoint was disease-free survival assessed in the full analysis set. Secondary endpoints were overall survival assessed in the full analysis set and safety assessed in all participants who received study drug. This trial is registered with ClinicalTrials.gov, NCT02448797. FINDINGS: Between June 8, 2015, and August 2, 2019, 322 patients were randomly assigned to icotinib (n=161) or chemotherapy (n=161); the full analysis set included 151 patients in the icotinib group and 132 in the chemotherapy group. Median follow-up in the full analysis set was 24·9 months (IQR 16·6-36·4). 40 (26%) of 151 patients in the icotinib group and 58 (44%) of 132 patients in the chemotherapy group had disease relapse or death. Median disease-free survival was 47·0 months (95% CI 36·4-not reached) in the icotinib group and 22·1 months (16·8-30·4) in the chemotherapy group (stratified hazard ratio [HR] 0·36 [95% CI 0·24-0·55]; p<0·0001). 3-year disease-free survival was 63·9% (95% CI 51·8-73·7) in the icotinib group and 32·5% (21·3-44·2) in the chemotherapy group. Overall survival data are immature with 14 (9%) deaths in the icotinib group and 14 (11%) deaths in the chemotherapy. The HR for overall survival was 0·91 (95% CI 0·42-1·94) in the full analysis set. Treatment-related serious adverse events occurred in two (1%) of 156 patients in the icotinib group and 19 (14%) of 139 patients in the chemotherapy group. No interstitial pneumonia or treatment-related death was observed in either group. INTERPRETATION: Our results suggest that compared with chemotherapy, icotinib significantly improves disease-free survival and has a better tolerability profile in patients with EGFR-mutant stage II-IIIA NSCLC after complete tumour resection. FUNDING: Betta Pharmaceuticals TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Éteres de Coroa/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , China , Receptores ErbB/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação/genética , Resultado do Tratamento
7.
Exp Gerontol ; 153: 111499, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34329721

RESUMO

We prepared nanostructured lipid carriers (NLC) to promote skin permeation of Corylin so that it can increase its effect on photoaging. Corylin-NLCs were prepared and characterized based on morphology, particle size, zeta potentials, FTIR and DSC. In vitro, we assess the cytotoxicity and lactate dehydrogenase (LDH) of HaCaT cells irradiated by UVB. Expression of antioxidant enzymes was evaluated by commercial kits. The effects of Corylin-NLC on apoptosis were confirmed by flow cytometry and western blotting. In vivo, we use UV irradiated mouse as the oxidative stress model to assess the therapeutic effect of Corylin loaded NLC gel. We identified the Corylin-NLCs can significantly suppress the LDH release, decrease MDA content, increase in CAT, SOD, GSH-Px activity, increase the expression of Bcl-2/Bax protein and reduce the expression of cleaved caspase-3/caspase-3 protein on UVB induced HaCaT cells. The histopathological lesions were significantly improved and observably decreased MDA level, increase in antioxidant enzymes activity in serum of mice by pretreatment of Corylin-NLCs gel. Overall, this study proposes a promising strategy for improving the therapeutic efficacy of photoaging.


Assuntos
Nanoestruturas , Envelhecimento da Pele , Animais , Portadores de Fármacos , Flavonoides , Lipídeos , Camundongos
8.
Front Pharmacol ; 12: 671708, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34326769

RESUMO

Metabolic syndrome (MetS) is a pathological state of many abnormal metabolic sections. These abnormalities are closely related to diabetes, heart pathologies and other vascular diseases. Danggui-Shaoyao-San (DSS) is a traditional Chinese medicine formula that has been used as a therapy for Alzheimer's disease. DSS has rarely been reported in the application of MetS and its mechanism of how it improves gut microbia dysbiosis and hepatic lipid homeostasis. In this study, three extracts of DSS were obtained using water, 50% methanol in water and methanol as extracting solvents. Their chemical substances were analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass (UPLC-Q/TOF-MS). Pharmacodynamic effect of the extracts were evaluated by comparison of biochemical factors, 16S rRNA sequencing test for gut microbiota analysis, as well as metabonomic and transcriptomic assessments on liver tissues from fructose-fed rats. This study aimed at investigating DSS's mechanism of regulating blood lipid, anti-inflammation and reducing blood glucose. The results showed that the 50% methanol extract (HME) was more effective. It was worth noting that hydroxysteroid 17ß-dehydrogenase 13 (HSD17ß13) as a critical element of increasing blood lipid biomarker-triglyceride (TG), was decreased markedly by DSS. The influence from upgraded hydroxysteroid 17ß-dehydrogenase 7 (HSD17ß7) may be stronger than that from downgraded Lactobacillus in the aspect of regulating back blood lipid biomarker-total cholesterol (TC). The differential down-regulation of tumornecrosis factor alpha (TNF-α) and the significant up-regulation of Akkermansia showed the effective effect of anti-inflammation by DSS. The declining glycine and alanine induced the lowering glucose and lactate. It demonstrated that DSS slowed down the reaction of gluconeogenesis to reduce the blood glucose. The results demonstrated that DSS improved pathological symptoms of MetS and some special biochemical factors in three aspects by better regulating intestinal floras and improving hepatic gene expressions and metabolites.

9.
Mitochondrial DNA B Resour ; 6(8): 2240-2245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34286088

RESUMO

Pampus chinensis is a commercially important fishery species in the Indo-West Pacific region. In the present study, the genetic variation of P. chinensis among 10 sampling localities along the China coast and one from the Indonesia region was evaluated using mitochondrial DNA control region sequences. As a result, a total of 30 variable sites were detected in the 458 bp segment of the control region among 330 individuals from 11 localities, and 41 haplotypes were defined. Samples in the China coast present a high level of genetic diversity, with the values of haplotype diversity ranged from 0.674 to 0.860, and nucleotide diversity from 0.820% to 1.502%. Pairwise FST statistics showed a moderate genetic divergence (-0.027 to 0.384) among samples from different geographical locations. Median-joining network analysis revealed a similar pattern of phylogeographic structure in samples from Ningbo and Dongxing although they were far apart. Therefore, joint influences of dispersal capability, spatial distance, ocean current and geographic segregation on the formation of the present population structure in P. chinensis was proposed. The results of the present study would be helpful for the sustainable utilization and management of this species.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34287767

RESUMO

Psoriasis, an autoimmune inflammatory skin disorder, is one of the commonest immune-mediated disease conditions affecting individuals globally. At the moment, the conventional methods applied against psoriasis treatment have various drawbacks involving limited efficacy, skin irritation, immunosuppression, etc. Therefore, it is important for scientists to find a more potent and alternative drug approach towards psoriasis therapeutics. Natural medicine still remains an important source for new drug discovery due to its therapeutical significance in various drug administration routes. However, the traditional formulation of topical therapies for psoriasis is limited in efficacy, which limits the use of natural medicine. Based on the aforementioned limitations, the use of nanocarriers in preparation of these topical herbal products could be tremendously beneficial in enhancing the efficacy of topical medications. Growing pieces of evidence have proposed that the utilization of nanocarriers in transdermal preparation as a prospective technique, with regards to better potency, directs drug absorption to site of action, and minimum toxicity effect respectively. In the course of this review, we emphasized the pathological mechanism of psoriasis, natural medicine formula, active components of natural medicine, and nanopreparations used in the treatment of psoriasis.

11.
Am J Chin Med ; 49(5): 1093-1114, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34107859

RESUMO

Idiopathic pulmonary fibrosis (IPF), a tumor-like disease, is a serious and fatal pulmonary inflammatory condition usually characterized by irreversible destruction of the lung parenchyma, excessive matrix accumulation, and decline in lung function. IPF still remains a great burden to the universe. At the moment, the available therapeutic regimens utilized for IPF such as non-pharmacological therapies (lung transplantation) and pharmacological therapies (drugs, nintedanib, pirfenidone, etc.) are normally accompanied by significant limitations, such as adverse reactions, low bioavailability, poor selectivity, low-tissue distribution, in vivo instability, systemic toxicity, inconveniency and unsafe usage. There is a need for the exploration and discovery of new novel remedies by researchers and scientists globally. Recent numerous preliminary studies have laid significant emphasis and demonstrated the antifibrotic importance, good curative actions (little or no adverse reactions), and multiple target sites of the active components from traditional herbal medicine (THM) against IPF, which could serve as a modern, alternative and potential therapeutics or drug candidates in treating IPF. This paper extensively summarizes the pharmacological actions and signaling pathways or mechanisms of active components obtained from THM for treating IPF. Moreover, the sources and modernization, markets, relevant FDA and CFDA studies (the USA and China), preclinical analysis, and various compositions of THM currently under clinical trials are also highlighted. Additionally, this present analytical data would be instrumental towards further drug progression or advancement of active components from THM for the potential therapeutics of IPF in the future.


Assuntos
Medicina Herbária/métodos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Medicina Tradicional/métodos , Fitoterapia/métodos , Humanos , Plantas Medicinais
12.
ACS Appl Mater Interfaces ; 13(24): 28164-28170, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34102060

RESUMO

The classical AlCl3/imidazole-chloride-salt ionic liquid electrolytes are expensive, corrosive, and environmentally sensitive, which limit the large-scale application of aluminum-ion batteries. Herein, a gel polymer electrolyte is prepared through a facile process using a low-cost AlCl3/Et3NHCl ionic liquid as the plasticizer and polyamide as the polymer matrix. The gel polymer electrolyte achieves a decent ionic conductivity of 3.86 × 10-3 S cm-1, a wide electrochemical stability window of 2.6 V (vs Al), and long-term interfacial stability at room temperature. The assembled Al//graphite battery delivers considerable rate capability and excellent cycling performance. Besides, the gel polymer electrolyte can alleviate both moisture sensitivity and leakage corrosion issues owing to the full encapsulation of the ionic liquid by polyamide polymeric matrix. The gel polymer electrolyte should offer great potential for aluminum-ion battery applications.

13.
Zhongguo Fei Ai Za Zhi ; 24(6): 420-425, 2021 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-34024062

RESUMO

BACKGROUND: Preliminary researches conformed that neoadjuvant immunotherapy combined with chemotherapy had a significant short-term effect in resectable non-small cell lung cancer (NSCLC), but there were few clinical trials about neoadjuvant chemoimmunotherapy in China. We aimed to assess retrospectively the antitumour activity and safety of neoadjuvant chemoimmunotherapy for resectable stage Ib-IIIb NSCLC. METHODS: Twenty patients who had been diagnosed as stage Ib-IIIb NSCLC and received chemoimmunotherapy as neoadjuvant treatment between November 2019 and December 2020, in Beijing Chest Hospital, Capital Medical University were recruited. These patients received neoadjuvant treatment for 21 days as a cycle and antitumour activity and safety were evaluated every two cycles. RESULTS: Of 20 patients received neoadjuvant chemoimmunotherapy, 17 patients underwent surgical resection. 16 patients had R0 resection (no residual tumor resection) and 1 patient had R1 resection (microscopic residual tumor resection). Radiographic objective response rate (ORR) was 85.0% (4 complete response, 13 partial response). 5.0% (1/20) of patients had stable disease, and 10.0% (2/20) of patients had progression disease. The major pathologic response (MPR) was 47.1% (8/17), and complete pathologic response (CPR) was 29.4% (5/17). 1 case developed grade IV immune-related pneumonia (IRP) and 9 (45.0%) cases had grade III hematologic toxicity. CONCLUSIONS: Immunotherapy combined with chemotherapy as neoadjuvant therapy has a better efficiency and tolerable adverse effects for patients with resectable NSCLC in stage Ib-IIIb.

14.
JCI Insight ; 6(11)2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-33905377

RESUMO

BACKGROUNDEarly diagnosis and treatment are key to the long-term survival of lung cancer patients. Although CT has significantly contributed to the early diagnosis of lung cancer, there are still consequences of excessive or delayed treatment. By improving the sensitivity and specificity of circulating tumor cell (CTC) detection, a solution was proposed for differentiating benign from malignant pulmonary nodules.METHODSIn this study, we used telomerase reverse transcriptase-based (TERT-based) CTC detection (TBCD) to distinguish benign from malignant pulmonary nodules < 2 cm and compared this method with the pathological diagnosis as the gold standard. FlowSight and FISH were used to confirm the CTCs detected by TBCD.RESULTSOur results suggest that CTCs based on TBCD can be used as independent biomarkers to distinguish benign from malignant nodules and are significantly superior to serum tumor markers. When the detection threshold was 1, the detection sensitivity and specificity of CTC diagnosis were 0.854 and 0.839, respectively. For pulmonary nodules ≤ 1 cm and 1-2 cm, the sensitivity and specificity of CTCs were both higher than 77%. Additionally, the diagnostic ability of CTC-assisted CT was compared by CT detection. The results show that CT combined with CTCs could significantly improve the differentiation ability of benign and malignant nodules in lung nodules < 2 cm and that the sensitivity and specificity could reach 0.899 and 0.839, respectively.CONCLUSIONTBCD can effectively diagnose pulmonary nodules and be used as an effective auxiliary diagnostic scheme for CT diagnosis.FUNDINGNational Key Research and Development Project grant nos. 2019YFC1315700 and 2017YFC1308702, CAMS Initiative for Innovative Medicine grant no. 2017-I2M-1-005, and National Natural Science Foundation of China grant no. 81472013.

15.
Toxicol Lett ; 345: 12-23, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33857584

RESUMO

We previously determined that specific microRNAs (miRNAs) are involved in renal pathophysiological occurrences induced by cadmium (Cd) in rats. This study expands our studies on miRNAs, determining their role in Cd-induced nephrotoxicity in occupational workers. We performed miRNA microarray analyses of blood and urine samples from patients diagnosed as occupational chronic Cd poisoning (OCCP) with abnormally elevated concentrations of urinary beta-2-microglobulin (U-ß2-MG), an indicator of tubular proteinuria. We also performed in vitro bioinformatics-based investigations of apoptosis-related genes targeted by miRNAs involved in the biological response to Cd exposure. We tested five differentially expressed miRNAs and determined a significant increase of sera miR-363-3p. Also, we determined that miR-363-3p increase is associated with phosphoinositide 3-kinase (PI3K) down-regulation and the suppressed proliferation and enhanced apoptosis of renal tubule epithelial cells. The obtained results suggest miR-363-3p involvement in the pathophysiology of Cd-induced renal injury in humans and maybe considered for possible interventional therapeutic strategies for Cd-associated kidney damage.


Assuntos
Apoptose/efeitos dos fármacos , Cádmio/efeitos adversos , Nefropatias/induzido quimicamente , Túbulos Renais Proximais/efeitos dos fármacos , MicroRNAs/metabolismo , Exposição Ocupacional/efeitos adversos , Fosfatidilinositol 3-Quinase/metabolismo , Adulto , Animais , Estudos de Casos e Controles , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Feminino , Regulação Enzimológica da Expressão Gênica , Humanos , Nefropatias/enzimologia , Nefropatias/genética , Nefropatias/patologia , Túbulos Renais Proximais/enzimologia , Túbulos Renais Proximais/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Saúde do Trabalhador , Fosfatidilinositol 3-Quinase/genética , Ratos , Transdução de Sinais
16.
Ann Transl Med ; 9(6): 478, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33850875

RESUMO

Background: The butyrophilin (BTN) family has many members with diverse functions related to immunomodulation, initiation and progression of tumors. BTN3A3 belongs to the BTN family, and exploring its expression and correlation with the prognosis of non-small cell lung cancer (NSCLC) patients has great clinical significance. Methods: Clinical specimens were used to detect BTN3A3 expression. Small interfering RNA (siRNA) was used to knock down BTN3A3 and analyze the proliferative, migratory and invading ability of the transfected NSCLC cells. Multiplex immunofluorescence staining was used to detect the expression of BTN3A3 protein in the tumor microenvironment (TME). We analyzed the relationship between the expression of BTN3A3 and the clinicopathological features and prognosis of NSCLC patients. Results: The expression of BTN3A3 in NSCLC tissues was significantly lower than in adjacent tissues, and patients with low expression of BTN3A3 had late clinical stages and lower degree of tumor differentiation. Knocking down BTN3A3 promoted the proliferation, migration and invasion of NSCLC. In the TME, the density of BTN3A3+ tumor cells positively correlated with the density of CD8+ T cells, and the patients with low expression of BTN3A3 had poor overall survival (OS). Conclusions: Changes in the BTN3A3 expression level may play a potential key role in the carcinogenesis and development of NSCLC. Patients with low expression of BTN3A3 showed a more aggressive and invasive phenotype and a lower level of CD8+ T-cell infiltration, which may be an important factor affecting the OS of NSCLC patients.

17.
Pharmaceutics ; 13(5)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33921919

RESUMO

The poor ability of recognition and penetration of chemotherapeutic agents to tumor cells are still great challenges for targeted breast cancer treatment. Herein, we established a tumor-targeted nanostructured lipid carrier encapsulating gambogic acid (GA) and paclitaxel (PTX), which was co-modified with acid-cleavable folic acid (cFA) and a human-derived cell penetrating peptide dNP2 (CKIKKVKKKGRKKIKKVKKKGRK). The multi-functional nano-platform exhibited an enhanced targeting and penetrability to tumor tissues, which was accomplished by the combined action of cFA and dNP2. After intravenous injection, firstly, cFA could actively target the breast cancer tissues by the selective recognition of folate receptor (FR); then, upon arrival at the tumor microenvironment, the acid-cleavable FA and dNP2 dual modified nanostructured lipid carrier (cFA/dNP2-GA/PTX-NLC) exhibited sensitive cleavage of folic acid (FA), which could reduce the hindrance effect of FA to maximize the dNP2 cell-penetrating properties. The effect of different modification on cellular uptake, in vivo bio-distribution, and anticancer activity of NLCs proved our hypothesis that compared with NLCs modified by non-cleavable FA or a single ligand, cFA/dNP2-GA/PTX-NLC displayed more efficient intracellular delivery, stronger targeting ability in vivo, improved cytotoxicity on 4T1 cells, and produced the better therapeutic efficacy of GA and PTX. The strategy affords a feasible way to overcome the poor recognition and permeability of medicines in cancer treatment.

18.
Chin J Nat Med ; 19(3): 231-240, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33781457

RESUMO

Salidroside (SAL) is a phenolic substance with high solubility and low permeability, which make it easy to cause the efflux effect of P-glycoprotein and degradation of intestinal flora, resulting in lower bioavailability. The aim of this study was to develop and optimize a water-in-oil nanoemulsion of SAL (w/o SAL-N) to explore its suitability in oral drug delivery systems. In this work, SAL-N was successfully prepared by water titration method at Km = 1 to construct the pseudo-ternary phase diagrams. Physical characterization including the average viscosity, pH, refractive index, particle size, PDI, TEM, DSC, the content of SAL, and stability study were performed. It was evaluated for drug release in vitro and pharmacokinetic studies in vivo. The optimized nanoemulsion formulation consisted of Labrafil M 1944CS (63%), Span-80/Tween-80/EtOH (27%) and 200 mg∙mL-1 SAL solution (SAL-SOL) (10%). Low viscosity and suitable pH were expected for the nanoemulsion. The spherical morphology and nanoscale size of SAL-N enhanced the stability of the nanoemulsion system. In vitro drug release showed that SAL-N had a better controlled release property than SAL-SOL at earlier time points. The pharmacokinetic studies exhibited that SAL-N had significantly higher in t1/2 (2.11-fold), AUC0-48 h (1.75-fold) and MRT0-48 h (2.63-fold) than SAL-SOL (P < 0.01). The w/o SAL-N prepared in this work can be effectively delivered via the oral route. It can be seen w/o nanoemulsion is a strategy for the drug with polyphenols to delay the release, enhance oral absorption and reduce metabolic rate.


Assuntos
Sistemas de Liberação de Medicamentos , Emulsões , Glucosídeos/administração & dosagem , Nanopartículas , Fenóis/administração & dosagem , Disponibilidade Biológica , Estabilidade de Medicamentos , Tamanho da Partícula , Solubilidade , Água
19.
Medicine (Baltimore) ; 100(12): e24574, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761635

RESUMO

BACKGROUND: Metabolic syndrome (MS) is a common chronic disease in modern society, and the etiology and pathogenesis of it is still unknown. For its main symptoms: disorder of glucose and lipid metabolism, the usual treatment is applying statin and hypoglycemic drugs. Comparing to the long-term application of these drugs which may cost great side effects, Dendrobium Nobile Lindl (DN) has been proved for its hypoglycemic and lipid-lowering effects without obvious side effects. So this trial is aim to evaluate the efficacy and safety of DN-powder in intervention of MS, and to explore the mechanism of action of DN through multi-group correlation analysis. METHODS: This clinical trial is a single-arm, non-randomized, open, exploratory trial. A total of 30 participants who are suffering from MS will be assigned into therapy group (n = 30). The treatment course will last for 8 weeks, and a follow-up period for 4 weeks. The participants will receive DN-powder for 6 g, twice a day during the study period. The primary outcome will be the change of lipid and glucose metabolism. Other outcomes will be the body weight and body mass index (BMI) which will be assessments record in every 2 weeks. Participants who quit the trial due to untolerable reactions or uncontrollable conditions will enter into a follow-up period after the last treatment. All participants will enter into a follow-up period for 4 weeks after the last treatment. Adverse events will be recorded during the whole study. DISCUSSION: The results of the trial are aim to provide evidence of the safety and efficacy of DN-powder in intervention of MS which may be potential to become an important alternative therapy for certain patients. TRIAL REGISTRATION: It has been registered at http://www.chictr.org.cn/showprojen.aspx?proj=55914. (Identifier: ChiCTR2000034550), Registered 9 July 2020.


Assuntos
Dendrobium/química , Medicamentos de Ervas Chinesas/efeitos adversos , Hipoglicemiantes/efeitos adversos , Hipolipemiantes/efeitos adversos , Síndrome Metabólica/tratamento farmacológico , Adolescente , Adulto , Idoso , Glicemia/análise , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Seguimentos , Humanos , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Adulto Jovem
20.
Sci Rep ; 11(1): 2201, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33500426

RESUMO

This study aims to develop an artificial intelligence (AI)-based model to assist radiologists in pneumoconiosis screening and staging using chest radiographs. The model, based on chest radiographs, was developed using a training cohort and validated using an independent test cohort. Every image in the training and test datasets were labeled by experienced radiologists in a double-blinded fashion. The computational model started by segmenting the lung field into six subregions. Then, convolutional neural network classification model was used to predict the opacity level for each subregion respectively. Finally, the diagnosis for each subject (normal, stage I, II, or III pneumoconiosis) was determined by summarizing the subregion-based prediction results. For the independent test cohort, pneumoconiosis screening accuracy was 0.973, with both sensitivity and specificity greater than 0.97. The accuracy for pneumoconiosis staging was 0.927, better than that achieved by two groups of radiologists (0.87 and 0.84, respectively). This study develops a deep learning-based model for screening and staging of pneumoconiosis using man-annotated chest radiographs. The model outperformed two groups of radiologists in the accuracy of pneumoconiosis staging. This pioneer work demonstrates the feasibility and efficiency of AI-assisted radiography screening and diagnosis in occupational lung diseases.


Assuntos
Aprendizado Profundo , Programas de Rastreamento , Modelos Biológicos , Pneumoconiose/diagnóstico , Bases de Dados como Assunto , Humanos , Pneumoconiose/diagnóstico por imagem , Pneumoconiose/patologia , Radiologistas , Reprodutibilidade dos Testes
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