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1.
Chem Biodivers ; : e202400977, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38837616

RESUMO

Two previously uncharacterized compounds, an aconitine-type C19-diterpenoid alkaloid (1) and a napelline-type diterpenoid alkaloid C20-diterpenoid alkaloid (2), as well as ten known compounds (3-12), were isolated from Aconitum pendulum. Their structures were elucidated based on spectroscopic data, including 1D and 2D NMR, IR, HR-ESI-MS, and single-crystal X-ray diffraction analysis. The anti-insecticidal activities of these compounds were evaluated by contact toxicity tests against two-spotted spider mites, and compounds 1, 2, and 9 showed moderate contact toxicity, with LC50 values of 0.86±0.09, 0.95±0.23, and 0.89±0.19 mg/mL, respectively. This study highlights the potential use of diterpenoid alkaloids as natural plant-derived pesticides for the management of plant pests.

2.
Int J Womens Health ; 16: 373-384, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482271

RESUMO

Background: Research on the risk factors for cervical cancer in Yunnan Province's four characteristic ethnic groups (Han, Bai, Dai, and Hani) is lacking. Objective: To study the risk factors of cervical cancer in four ethnic women in Yunnan Province, and to provide evidence for its prevention. Methods: The cervical cancer patients of Han, Bai, Dai and Hani ethnic groups in Yunnan Province who were first diagnosed in the Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center) from January 2011 to December 2020 were selected as the research objects. The 1:1 matched case-control study method was used, and single factor and conditional logistic regression were used for statistical analysis. Results: HPV types 16, 18 and 58 are mostly related with cervical cancer, the younger the age of the last pregnancy, the more times of pregnancy, childbirth and abortion, especially the younger the first marriage age of Bai and Dai, are the risk factors of cervical cancer; the infection of genital tract bacteria, mycoplasma and chlamydia is closely related to the incidence of cervical cancer in four ethnicities. Multifactorial analysis showed that demographic characteristics and environment/behavior were not included in the influencing factors of cervical cancer; among Han, Bai, Dai and Hani ethnic minorities, contraception (OR=0.29, OR=0.03, OR=0.09, OR=0.16, P<0.05) was positive factor, HPV infection (OR=64.77, OR=128.71, OR=71.89, OR=40.07, P<0.01) was a causative factor of cervical cancer. Conclusion: Risk of high parity with cervical cancer could be due to a complex interplay of factors, it is very important to formulate prevention strategies and measures in line with the cervical cancer of Han, Bai, Dai and Hani ethnic groups women in Yunnan Province.

3.
Chem Biodivers ; 20(12): e202301454, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37874779

RESUMO

Phytochemical investigation on the anti-inflammatory fraction extracted from the whole plant of Euphorbia helioscopia L. led to the isolation of three new ent-atisane diterpenoids (1-3) and five known analogues (4-8). The structures and absolute configurations of the new compounds were elucidated by comprehensive analysis of the NMR, MS, IR, ECD, and X-ray crystallography. It is worth mentioning that compound 3 belongs to a rare class of ent-atisane diterpenoid featuring a hydroxyl group at C-9. Bioactivity investigation showed that compounds 4, 7, and 8 exhibited significant inhibitory effects on LPS-induced NO production in a dose-dependent manner, which indicates their anti-inflammatory potential.


Assuntos
Diterpenos , Euphorbia , Euphorbia/química , Diterpenos/farmacologia , Diterpenos/química , Espectroscopia de Ressonância Magnética , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Estrutura Molecular
4.
Phytochemistry ; 214: 113825, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37591440

RESUMO

Nine undescribed abietane diterpenoids (1-9) and eleven known abietane analogs (10-20) were isolated from Callicarpa bodinieri. Their structures were characterized by interpreting spectroscopic data, X-ray crystallography, and ECD analysis. The anti-inflammatory activities of these compounds were tested by evaluation of their inhibitory effect on NO production by lipopolysaccharide in RAW 264.7 macrophages, and compounds 3 and 8 exhibited potent anti-inflammatory activities with IC50 values of 36.35 ± 1.12 and 37.21 ± 0.92 µM. The western blotting studies demonstrated that compound 3 inhibited the expression of nitric oxide synthase and p65 that involved in the NF-κB pathway.


Assuntos
Callicarpa , Abietanos/farmacologia , Anti-Inflamatórios/farmacologia , Cristalografia por Raios X , Lipopolissacarídeos/farmacologia
5.
Front Pharmacol ; 14: 1098915, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37397486

RESUMO

Introduction: The incidence of cholangiocarcinoma (CCA) has increased worldwide in recent years. Given the poor prognosis associated with the current management approach of CCA, new therapeutic agents are warranted to improve the prognosis of this patient population. Methods: In this study, we extracted five cardiac glycosides (CGs) from natural plants: digoxin, lanatoside A, lanatoside C, lanatoside B, and gitoxin. Follow-up experiments were performed to assess the effect of these five extracts on cholangiocarcinoma cells and compounds with the best efficacy were selected. Lanatoside C (Lan C) was selected as the most potent natural extract for subsequent experiments. We explored the potential mechanism underlying the anticancer activity of Lan C on cholangiocarcinoma cells by flow cytometry, western blot, immunofluorescence, transcriptomics sequencing, network pharmacology and in vivo experiments. Results: We found that Lan C time-dependently inhibited the growth and induced apoptosis of HuCCT-1 and TFK-1 cholangiocarcinoma cells. Besides Lan C increased the reactive oxygen species (ROS) content in cholangiocarcinoma cells, decreased the mitochondrial membrane potential (MMP) and resulted in apoptosis. Besides, Lan C downregulated the protein expression of STAT3, leading to decreased expression of Bcl-2 and Bcl-xl, increased expression of Bax, activation of caspase-3, and initiation of apoptosis. N-acetyl-L-cysteine (NAC) pretreatment reversed the effect of Lan C. In vivo, we found that Lan C inhibited the growth of cholangiocarcinoma xenografts without toxic effects on normal cells. Tumor immunohistochemistry showed that nude mice transplanted with human cholangiocarcinoma cells treated with Lan C exhibited decreased STAT3 expression and increased caspase-9 and caspase-3 expression in tumors, consistent with the in vitro results. Conclusion: In summary, our results substantiates that cardiac glycosides have strong anti-CCA effects. Interestingly the biological activity of Lan C provides a new anticancer candidate for the treatment of cholangiocarcinoma.

6.
Phytochemistry ; 212: 113723, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37182686

RESUMO

A bioactivity-guided isolation from the aerial parts of Phyllanthus rheophyticus obtained 17 undescribed ent-cleistanthane-type diterpenoids, namely phyllarheophols A-Q, as well as 12 known analogs. Their structures were characterized by a combination of spectroscopic data interpretation, single-crystal X-ray diffraction and ECD analysis. The anti-inflammatory activities of these compounds were evaluated by measuring their inhibitory effects on NO production in LPS-stimulated RAW264.7 macrophages, and their preliminary structure-activity relationships were also discussed. Further study showed that promising compounds phyllarheophol D and phyacioid B significantly suppressed the expressions of cytokines and nitric oxide synthase through the NF-κB signaling pathway.


Assuntos
Anti-Inflamatórios , Diterpenos , Phyllanthus , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Macrófagos/imunologia , Macrófagos/metabolismo , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Phyllanthus/química , Relação Estrutura-Atividade , NF-kappa B/metabolismo , Componentes Aéreos da Planta/química , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/imunologia , Interleucina-6/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Animais , Camundongos
7.
Biosens Bioelectron ; 235: 115398, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37209517

RESUMO

Nowadays, lung cancer is one of the most dangerous cancers threatening human life all over the world. As a crucial biomarker, cytokeratin 19 fragment 21-1 (CYFRA 21-1) is extraordinary important for diagnosis of non-small cell lung cancer (NSCLC). In this work, we synthesized hollow SnO2/CdS QDs/CdCO3 heterostructured nanocubes with high and stable photocurrents, which applied to construction of a sandwich-typed photoelectrochemical (PEC) immunosensor for detection of CYFRA 21-1, integrated by in-situ catalytic precipitation strategy with home-built PtPd alloy anchored MnCo-CeO2 (PtPd/MnCo-CeO2) nanozyme for synergistic amplification. The interfacial electron transfer mechanism upon visible-light irradiation was investigated in details. Further, the PEC responses were seriously quenched by the specific immunoreaction and precipitation catalyzed by the PtPd/MnCo-CeO2 nanozyme. The established biosensor showed a wider linear range of 0.001-200 ng mL-1 and a lower limit of detection (LOD = 0.2 pg mL-1, S/N = 3), coupled by exploring such analysis even in diluted human serum sample. This work opens a constructive avenue to develop ultrasensitive PEC sensing platforms for detecting diverse cancer biomarkers in clinic.


Assuntos
Técnicas Biossensoriais , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Biomarcadores Tumorais , Técnicas Eletroquímicas , Neoplasias Pulmonares/diagnóstico , Limite de Detecção , Imunoensaio , Pulmão
8.
Talanta ; 260: 124631, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37163924

RESUMO

Vascular endothelial growth factor 165 (VEGF165) is a crucial regulator of angiogenesis and works as a major protein biomarker of cancer metastasis. Therefore, its quantitative detection is pivotal in clinic. In this work, CuS/ZnIn2S4 flower-like heterojunctions had strong and stable photocurrents, which behaved as photoactive material to construct a photoelectrochemical (PEC) aptasensor for detecting VEGF165, combined by home-prepared (MnCo)Fe2O4 nanozyme-mediated signal amplification. The interfacial photo-induced electron transfer mechanism was chiefly discussed by UV-vis diffuse reflectance spectroscopy in details. Specifically, the (MnCo)Fe2O4 modified VEGF165 aptamer was released from the PEC aptasensing platform for its highly specific affinity to target VEGF165, which terminated the color precipitation reaction, ultimately recovering the PEC signals. The developed sensor displayed a wider linear range from 1 × 10-2 to 1 × 104 pg mL-1 with a smaller limit of detection (LOD) of 0.1 fg mL-1. This study provides some valuable insights for building other ultrasensitive aptasensors for clinical assays of cancer biomarkers in practice.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Neoplasias , Humanos , Biomarcadores Tumorais , Fator A de Crescimento do Endotélio Vascular , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Neoplasias/diagnóstico , Aptâmeros de Nucleotídeos/química , Limite de Detecção
9.
Biosens Bioelectron ; 230: 115293, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37028001

RESUMO

Fumonisin B1 (FB1), the most prevalent and highest toxicity mycotoxins among fumonisins family, poses threats to human especially children and infants even at a trace level. Therefore, its facile and sensitive detection is of importance. Herein, Z-scheme Cu2MoS4/CdS/In2S3 nanocage-like heterojunctions (labeled Cu2MoS4/CdS/In2S3) were synthesized, whose photoelectrochemical (PEC) property and electron transfer mechanism were strictly investigated. The Cu2MoS4/CdS/In2S3 behaved as photoactive substrate for building a PEC sensing platform for detection of FB1, integrated with PtPd alloy modified hollow CoSnO3 nanoboxes (labeled PtPd-CoSnO3) nanozyme. By virtue of the stronger affinity between the target FB1 and its aptamer (FB1-Apt), the photocurrent was recovered by releasing the CoSnO3-PtPd3 modified FB1-Apt (FB1-Apt/PtPd-CoSnO3) from the photoanode, which can terminate the catalytic precipitation reaction for its peroxidase-like property. The resultant PEC aptasensor exhibited a wider dynamic linear range from 1 × 10-4 to 1 × 102 ng mL-1 with a lower limit of detection (0.0723 pg mL-1). Thus, this research provides a feasible PEC sensing platform for routine analysis of other mycotoxins in practice.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Fumonisinas , Criança , Humanos , Técnicas Eletroquímicas , Fumonisinas/química , Aptâmeros de Nucleotídeos/química , Limite de Detecção
10.
J Nat Prod ; 86(4): 1003-1009, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-36858948

RESUMO

Three unreported ent-abietane-type norditerpene lactones, euphohelides A-C (1-3), and 11 known analogs (4-14) were isolated from the whole plants of Euphorbia helioscopia L. Euphohelide A (1) is an unprecedented 2-nor-ent-abietane lactone bearing a unique 5/6/6/5 tetracyclic system. Euphohelides B (2) and C (3) possess 2-nor-6/6/6/5 and 2,3-dinor-5/6/6/5 dilactone tetracyclic moieties, respectively. Their structures were established by spectroscopic methods, computational ECD, and X-ray crystallographic analyses. A biomimetic synthesis of 1 was achieved from precursor 4 based on the speculative biogenetic pathway. Compounds 1 and 5 significantly alleviated the release of LPS-induced NO with IC50 values of 32.98 ± 1.13 and 33.82 ± 3.25 µM, which might be related to the regulation of the NF-κB signaling pathway.


Assuntos
Diterpenos , Euphorbia , Abietanos/farmacologia , Euphorbia/química , Lactonas/farmacologia , Lactonas/química , Diterpenos/farmacologia , Diterpenos/química , Anti-Inflamatórios/farmacologia , Estrutura Molecular
11.
Chem Biodivers ; 19(11): e202200762, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36177989

RESUMO

Two new eremophilane-type sesquiterpenoids, sagittacins F and G (1 and 2), together with one known isomer of sagittacin F (3) were isolated from the leaves and stems of Ligularia sagitta. Their structures were elucidated by interpretation of spectroscopic data and the absolute configurations of 1 and 3 were determined by X-ray spectroscopy. Compound 1 belongs to a rare class of eremophilane-type sesquiterpenoid featuring an α-oriented hydroxy group at C-1. A nitric oxide (NO) production inhibitory assay was applied to evaluate their anti-inflammatory activities by using LPS-induced RAW 264.7 cells. Compounds 2 and 3 exhibited modest NO production inhibitions with IC50 values of 45.15±2.72 and 49.83±2.34 µM, respectively.


Assuntos
Ligularia , Sesquiterpenos , Camundongos , Animais , Sesquiterpenos Policíclicos , Estrutura Molecular , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Células RAW 264.7 , Óxido Nítrico
12.
RSC Adv ; 12(36): 23240-23251, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36090389

RESUMO

Cardiac glycosides (CGs) are good candidates as drug leads in the treatment of cancer because of their structural diversities and potent biological activities. In this study, fifteen CGs including three new ones (1-3) were isolated from Digitalis lanata Ehrh. Their structures were elucidated by HRESIMS, NMR spectroscopic methods, including homonuclear and heteronuclear coupling constant analysis, and acid-catalyzed hydrolysis and derivatization analysis of the sugar chain. The cytotoxic activities of these CGs were evaluated against three human cancer cell lines (A549, HeLa and MCF-7 cell lines), and all of them showed strong activities at nanomolar scale. The flow cytometric analysis indicated that compound 1 induced cell cycle arrest in the G2/M phase. Transcriptome analysis revealed a panel of possible targets for compound 1. RT-PCR and western blot experiments showed that 1 significantly inhibited the expression of vasohibin-2 (VASH2). Moreover, compound 1 restrained angiogenesis in a concentration-dependent manner in the chick embryo chorioallantoic membrane (CAM) model.

13.
Zhongguo Zhong Yao Za Zhi ; 47(12): 3348-3360, 2022 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-35851129

RESUMO

This study aimed to explore the action targets and mechanisms of Polygala tenuifolia and Acorus tatarinowii in treating Alzheimer's disease(AD) based on network pharmacology, molecular docking, and animal tests. The AD-related targets were collec-ted from GeneCard and the main active ingredients and targets of P. tenuifolia and A. tatarinowii from the TCMSP. Cytoscape was applied to construct the "Chinese herb-active ingredient-target-disease" network, followed by the construction of protein-protein interaction(PPI) network using STRING. GO biological function and KEGG pathway enrichment analysis was performed by DAVID and Metascape. The main active components of P. tenuifolia and A. tatarinowii and their potential core targets were docking using AutoDock Vina. The effects of P. tenuifolia and A. tatarinowii on the cognitive function were verified in mice with scopolamine(SCOP)-induced cognitive impairment. A total of seven active ingredients including kaempferol, onjixanthone Ⅰ, and marmesin and 56 potential targets of P. tenuifolia and A. tatarinowii were screened out, with the core targets covering AKT1, PTGS2, TNF, and NF-κB inflammation pathway mainly involved. The results of molecular docking also showed that the main active components of P. tenuifolia and A. tatarinowii stably bond to the core targets predicted by network pharmacology. The new object recognition experiment suggested that P. tenuifolia and A. tatarinowii improved the learning and memory abilities of mice after SCOP induction. As revealed by pathological section observation and relevant kit assay, P. tenuifolia and A. tatarinowii reduced the damage of central cholinergic neurons and enhanced the antioxidant ability of SCOP-induced mice. Western blot confirmed that P. tenuifolia and A. tatarinowii down-regulated the protein expression levels of TLR4, NF-κB, and related inflammatory factors(TNF-α, IL-1ß, and IL-6). All these have suggested that P. tenuifolia and A. tatarinowii inhibits AD via multiple components, multiple targets, and multiple pathways, which has provided an experimental basis for the clinical application of P. tenuifolia and A. tatarinowii for the treatment of AD.


Assuntos
Doença de Alzheimer , Medicamentos de Ervas Chinesas , Doença de Alzheimer/tratamento farmacológico , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Camundongos , Simulação de Acoplamento Molecular , NF-kappa B/genética , Farmacologia em Rede
14.
Molecules ; 27(11)2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35684476

RESUMO

Two new neolignans jatrolignans, C (1) and D (2), a pair of epimers, were isolated from the whole plants of Jatropha curcas L. (Euphorbiaceae). Their structures were determined with HRESIMS, IR, and NMR data analysis, and electronic circular dichroism (ECD) experiments via a comparison of the experimental and the calculated ECD spectra. Their antichlamydial activity was evaluated in Chlamydia abortus. They both showed dose-dependent antichlamydial effects. Significant growth inhibitory effects were observed at a minimum concentration of 40 µM.


Assuntos
Euphorbiaceae , Jatropha , Lignanas , Jatropha/química , Lignanas/química , Lignanas/farmacologia
15.
Water Res ; 209: 117890, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34856430

RESUMO

Traditional methods of cyanides' (CN-) mineralization cannot overcome the contradiction between the high alkalinity required for the inhibition of hydrogen cyanide evolution and the low alkalinity required for the efficient hydrolysis of cyanate (CNO-) intermediates. Thus, in this study, a novel Electro-Fenton system was constructed, in which the free cyanides released from ferricyanide photolysis can be efficiently mineralized by the synergy of •OH and •O2-. The complex bonds in ferricyanide (100 mL, 0.25 mM) were completely broken within 80 min under ultraviolet radiation, releasing free cyanides. Subsequently, in combination with the heterogeneous Electro-Fenton process, •OH and •O2- were simultaneously generated and 92.9% of free cyanides were transformed into NO3- within 120 min. No low-toxic CNO- intermediates were accumulated during the Electro-Fenton process. A new conversion mechanism was proposed that CN- was activated into electron-deficient cyanide radical (•CN) by •OH, and then the •CN intermediates reacted with •O2- via nucleophilic addition to quickly form NO3-, preventing the formation of CNO- and promoting the mineralization of cyanide. Furthermore, this new strategy was used to treat the actual cyanide residue eluent, achieving rapid recovery of irons and efficient mineralization of cyanides. In conclusion, this study proposes a new approach for the mineralization treatment of cyanide-containing wastewater.

16.
Phytochemistry ; 192: 112951, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34563976

RESUMO

Sixteen cardiac glycosides, including five previously undescribed compounds, were extracted and purified from whole plants of Calotropis gigantea (L.). Spectroscopic data and electronic circular dichroism (ECD) analyses were used to determine their structures. Calogiganin C is the first naturally occurring example of a cardenolide containing a 7-membered lactone in ring A. The cytotoxic activities of these compounds against A172, U251, AGS, PANC-1, HepG2, HCT116 and NCI-H226 cell lines were evaluated. Four of them exhibited the most potent growth inhibitory activity against a panel of human cancer cell lines, including A172, U251, AGS, PANC-1 and HCT116. Notably, uscharidin and calotropin showed pronounced cytotoxicities at low nanomolar concentrations against A172 and U251 cells, and possible cell death mechanism studies manifested that these two compounds induced G2/M cell cycle arrest, which demonstrated promising anticancer potential.


Assuntos
Antineoplásicos Fitogênicos , Antineoplásicos , Calotropis , Glicosídeos Cardíacos , Antineoplásicos Fitogênicos/farmacologia , Cardenolídeos/farmacologia , Linhagem Celular Tumoral
17.
Front Mol Biosci ; 8: 710676, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485384

RESUMO

Natural products frequently have unique physiological activities and new action mechanisms due to their structural diversity and novelty, and are an important source for innovative drugs and lead compounds. We present herein that natural product santamarine targeted thioredoxin reductase (TrxR) to weaken its antioxidative function in cells, accompanied by accumulation of high levels of reactive oxygen species (ROS), and finally induced a new mechanism of tumor cell oxidative stress-mediated apoptosis. TrxR knockdown or overexpression cell lines were employed to further evaluate the cytotoxicity of santamarine regulated by TrxR, demonstrated that TrxR played a key role in the physiological effect of santamarine on cells. Santamarine targeting TrxR reveals its previously unrecognized mechanism of antitumor and provides a basis for the further development of santamarine as a potential cancer therapeutic agent.

18.
J Nat Prod ; 84(8): 2094-2103, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34292737

RESUMO

Nonsmall cell lung cancer (NSCLC) has been a fatal and refractory disease worldwide. Novel therapeutic developments based on fundamental investigations of anticancer mechanisms underlie substantial foundations to win the fight against cancer diseases. In this study, we isolated a natural product fusaricide (FCD) from an endophytic fungus of Lycium barbarum, identified as Epicoccum sp. For the first time, we discovered that FCD potently inhibited proliferation in a variety of human NSCLC cell lines, with relatively less toxicity to normal cells. Our study exhibited that FCD induced apoptosis, caused DNA damage and cell cycle arrest in G0/G1 phase, and activated caspase-3 as well as other apoptosis-related factors in human NSCLC NCI-H460 cells. FCD was proven to be an iron chelator that actively decreased levels of cellular labile iron pool in NCI-H460 cells in our study. FeCl3 supplement reversed FCD-induced apoptosis. The upregulation of transferrin receptor 1 (TfR1) and downregulation of ferritin heavy chain (FTH) expression were observed after FCD treatment. In summary, our study highlighted the potential anticancer effects of FCD against human NSCLCs and demonstrated that the FCD-mediated apoptosis depended on binding to intracellular iron.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Benzopiranos/farmacologia , Caspase 3/metabolismo , Quelantes de Ferro/farmacologia , Piridonas/farmacologia , Antígenos CD/metabolismo , Apoferritinas/metabolismo , Ascomicetos/química , Carcinoma Pulmonar de Células não Pequenas , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , China , Endófitos/química , Humanos , Neoplasias Pulmonares , Lycium/microbiologia , Estrutura Molecular , Receptores da Transferrina/metabolismo
19.
JAMA Oncol ; 7(3): 361-369, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33443541

RESUMO

IMPORTANCE: There is no current consensus on the role of chemotherapy in addition to radiation for postoperative adjuvant treatment of patients with early-stage cervical cancer with adverse pathological factors. OBJECTIVE: To evaluate the clinical benefits of sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT) compared with radiation alone (RT) as a postoperative adjuvant treatment in early-stage cervical cancer. DESIGN, SETTING, AND PARTICIPANTS: After radical hysterectomy at 1 of 8 participating hospitals in China, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological factors were randomized 1:1:1 to receive adjuvant RT, CCRT, or SCRT. Data were collected from February 2008 to December 2018. INTERVENTIONS: Patients received adjuvant RT (total dose, 45-50 Gy), CCRT (weekly cisplatin, 30-40 mg/m2), or SCRT (cisplatin, 60-75 mg/m2, plus paclitaxel, 135-175 mg/m2) in a 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy, respectively. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of disease-free survival (DFS) at 3 years. RESULTS: A total of 1048 women (median [range] age, 48 [23-65] years) were included in the analysis (350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group). Baseline demographic and disease characteristics were balanced among the treatment groups except that the rate of lymph node involvement was lowest in the RT group (18.3%). In the intention-to-treat population, SCRT was associated with a higher rate of DFS than RT (3-year rate, 90.0% vs 82.0%; hazard ratio [HR], 0.52; 95% CI, 0.35-0.76) and CCRT (90.0% vs 85.0%; HR, 0.65; 95% CI, 0.44-0.96). Treatment with SCRT also decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95) after adjustment for lymph node involvement. However, neither DFS nor cancer death risk was different among patients treated with CCRT or RT. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, conducted in a postoperative adjuvant treatment setting, SCRT, rather than CCRT, resulted in a higher DFS and lower risk of cancer death than RT among women with early-stage cervical cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00806117.


Assuntos
Neoplasias do Colo do Útero , Quimiorradioterapia/métodos , Quimioterapia Adjuvante , Cisplatino/uso terapêutico , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
20.
Front Microbiol ; 11: 1773, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849397

RESUMO

In arsenopyrite bioleaching, the interfacial reaction between mineral and cells is one of the most important factors. The energy of the interface is influenced by the mineralogical and microbiological characteristics. In this paper, the interfacial energy was calculated, and the surface of arsenopyrite during the bioleaching process was characterized by 3D laser microscopy, scanning electron microscopy with energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy, in order to assess the dissolution and oxidation behavior of arsenopyrite during bioleaching. The results showed that the contact angles of arsenopyrite were 22 ± 2° when covered with biofilms, but the reaction surface of arsenopyrite turned 103 ± 2°. However, the angle was 45-50° when covered by passive layer, which was half as that of arsenopyrite surface. The interfacial energy of arsenopyrite without biofilms increased from 45 to 62 mJ/m2, while it decreased to 5 ± 1 mJ/m2 when covered by biofilms during the leaching process. The surface was separated into fresh surface, oxidized surface, and (corrosion) pits. The interfacial energy was influenced by the fresh and oxidized surfaces. Surface roughness increased from 0.03 ± 0.01 to 5.89 ± 1.97 µm, and dissolution volume increased from 6.31 ± 0.47 × 104 to 2.72 ± 0.49 × 106 µm3. The dissolution kinetics of arsenopyrite followed the model of Kt = lnX, and the dissolution mechanisms were mixed controlled: surface reaction control and diffusion through sulfur layer. On the surface of arsenopyrite crystal, the oxidation steps of each element can be described as: for Fe, Fe(II)-(AsS)→Fe(III)-(AsS)→Fe(III)-OH or Fe(III)-SO; for S, As-S(-1) or Fe-S(-1)→polysulfide S→intermediate S-O→sulfate; and for As, As-1-S→As0→As+1-O→As+3-O→As+5-O.

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