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1.
J Sports Sci Med ; 23(1): 196-208, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38455438

RESUMO

Torsional stiffness of athletic footwear plays a crucial role in preventing injury and improving sports performance. Yet, there is a lack of research focused on the biomechanical effect of torsional stiffness in badminton shoes. This study aimed to comprehensively investigate the influence of three different levels of torsional stiffness in badminton shoes on biomechanical characteristics, sports performance, and injury risk in badminton players. Fifteen male players, aged 22.8 ± 1.96 years, participated in the study, performing badminton-specific tasks, including forehand clear stroke [left foot (FCL) and right foot (FCR)], 45-degree sidestep cutting (45C), and consecutive vertical jumps (CVJ). The tasks were conducted wearing badminton shoes of torsional stiffness measured with Shore D hardness 50, 60, and 70 (referred to as 50D, 60D, and 70D, respectively). The primary biomechanical parameters included ankle, knee, and MTP joint kinematics, ankle and knee joint moments, peak ground reaction forces, joint range of motion (ROM), and stance time. A one-way repeated measures ANOVA was employed for normally distributed data and Friedman tests for non-normally distributed data. The 70D shoe exhibited the highest ankle dorsiflexion and lowest ankle inversion peak angles during 45C task. The 60D shoe showed significantly lower knee abduction angle and coronal motions compared to the 50D and 70D shoes. Increased torsional stiffness reduced stance time in the FCR task. No significant differences were observed in anterior-posterior and medial-lateral ground reaction forces (GRF). However, the 70D shoe demonstrated higher vertical GRF than the 50D shoe while performing the FCR task, particularly during 70% - 75% of stance. Findings from this study revealed the significant role of torsional stiffness in reducing injury risk and optimizing performance during badminton tasks, indicating that shoes with an intermediate level of stiffness (60D) could provide a beneficial balance between flexibility and stability. These findings may provide practical references in guiding future badminton shoe research and development. Further research is necessary to explore the long-term effects of altering stiffness, considering factors such as athletic levels and foot morphology, to understand of the influence of torsional stiffness on motion biomechanics and injury prevalence in badminton-specific tasks.


Assuntos
Extremidade Inferior , Esportes com Raquete , Humanos , Masculino , Fenômenos Biomecânicos , , Joelho
2.
Nutr Neurosci ; 26(1): 11-24, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34927571

RESUMO

OBJECTIVES: Parkinson's disease (PD) is the second most common neurodegenerative disease. Chlorogenic acid (CGA) is a polyphenolic substance derived from various medicinal plants. Although CGA is reported to have potential anti-PD effect, the beneficial effect and the underlying mechanism remain unclear. In this study, we aimed to further investigate the protective effect and clarify the mechanism of action of CGA in Caenorhabditis elegans (C. elegans) models of PD. METHODS: Measurements of a-synuclein aggregation, movement disorders, and lipid, ROS and malondialdehyde (MDA) contents were observed in NL5901 nematodes. Determinations of dopamine (DA) neuron degeneration, food perception, and ROS content were performed in 6-OHDA-exposed BZ555 nematodes. The autophagy activation of CGA was monitored using DA2123 and BC12921 nematodes. Meanwhile, RNAi technology was employed to knockdown the autophagy-related genes and investigate whether the anti-PD effect of CGA was associated with autophagy induction in C. elegans. RESULTS: CGA significantly reduced α-synuclein aggregation, improved motor disorders, restored lipid content, and decreased ROS and MDA contents in NL5901 nematodes. Meanwhile, CGA inhibited DA neuron-degeneration and improved food-sensing behavior in 6-OHDA-exposed BZ555 nematodes. In addition, CGA increased the number of GFP::LGG-1 foci in DA2123 nematodes and degraded p62 protein in BC12921 nematodes. Meanwhile, CGA up-regulated the expression of autophagy-related genes in NL5901 nematodes. Moreover, the anti-PD effect of CGA was closely related to autophagy induction via increasing the expression of autophagy-related genes, including unc-51, bec-1, vps-34, and lgg-1. CONCLUSIONS: The present study indicates that CGA exerts neuroprotective effect in C. elegans via autophagy induction.


Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , Animais , Doença de Parkinson/metabolismo , Caenorhabditis elegans , Ácido Clorogênico/farmacologia , Ácido Clorogênico/metabolismo , Animais Geneticamente Modificados , Doenças Neurodegenerativas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Oxidopamina , Degeneração Neural , Autofagia , Lipídeos , Neurônios Dopaminérgicos , Modelos Animais de Doenças
3.
Molecules ; 28(13)2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37446670

RESUMO

A series of novel macroacyclic Schiff base ligands and their Cu (II) complexes were synthesised via reacting dicarbonyls of varying chain lengths with S-methyl dithiocarbazate (SMDTC) and S-benzyl dithiocarbazate (SBDTC) followed by coordination with Cu (II) ions. X-ray crystal structures were obtained for compound 4, an SBDTC-diacetyl analogue, and Cu7, an SMDTC-hexanedione Cu (II) complex. Anticancer evaluation of the compounds showed that Cu1, an SMDTC-glyoxal complex, demonstrated the highest cytotoxic activity against MCF-7 and MDA-MB-231 breast cancer cells with IC50 values of 1.7 µM and 1.4 µM, respectively. There was no clear pattern observed between the effect of chain length and cytotoxic activity; however, SMDTC-derived analogues were more active than SBDTC-derived analogues against MDA-MB-231 cells. The antibacterial assay showed that K. rhizophila was the most susceptible bacteria to the compounds, followed by S. aureus. Compound 4 and the SMDTC-derived analogues 3, 5, Cu7 and Cu9 possessed the highest antibacterial activity. These active analogues were further assessed, whereby 3 possessed the highest antibacterial activity with an MIC of <24.4 µg/mL against K. rhizophila and S. aureus. Further antibacterial studies showed that at least compounds 4 and 5 were bactericidal. Thus, Cu1 and 3 were the most promising anticancer and antibacterial agents, respectively.


Assuntos
Antineoplásicos , Complexos de Coordenação , Bases de Schiff/química , Staphylococcus aureus , Antibacterianos/química , Bactérias , Complexos de Coordenação/química , Cobre/química , Ligantes , Antineoplásicos/química
4.
Int J Mol Sci ; 23(19)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36232431

RESUMO

The emergence and rapid evolution of human pathogenic viruses, combined with the difficulties in developing effective vaccines, underline the need to develop innovative broad-spectrum antiviral therapeutic agents. The present study aims to determine the in silico antiviral potential of six bacterial antimicrobial peptides (AMPs), two phytochemicals (silvestrol, andrographolide), and two bacterial secondary metabolites (lyngbyabellin A, hapalindole H) against dengue virus, Zika virus, Ebola virus, the major variants of SARS-CoV-2 and monkeypox virus. The comparison of docking scores obtained with natural biomolecules was performed with specific neutralizing antibodies (positive controls for ClusPro) and antiviral drugs (negative controls for Autodock Vina). Glycocin F was the only natural biomolecule tested to show high binding energies to all viral surface proteins and the corresponding viral cell receptors. Lactococcin G and plantaricin ASM1 also achieved high docking scores with all viral surface proteins and most corresponding cell surface receptors. Silvestrol, andrographolide, hapalindole H, and lyngbyabellin A showed variable docking scores depending on the viral surface proteins and cell receptors tested. Three glycocin F mutants with amino acid modifications showed an increase in their docking energy to the spike proteins of SARS-CoV-2 B.1.617.2 Indian variant, and of the SARS-CoV-2 P.1 Japan/Brazil variant, and the dengue DENV envelope protein. All mutant AMPs indicated a frequent occurrence of valine and proline amino acid rotamers. AMPs and glycocin F in particular are the most promising biomolecules for the development of broad-spectrum antiviral treatments targeting the attachment and entry of viruses into their target cell.


Assuntos
Tratamento Farmacológico da COVID-19 , Dengue , Doença pelo Vírus Ebola , Zika virus , Aminoácidos , Anticorpos Neutralizantes/uso terapêutico , Antivirais/química , Antivirais/farmacologia , Antivirais/uso terapêutico , Benzofuranos , Dengue/tratamento farmacológico , Diterpenos , Doença pelo Vírus Ebola/tratamento farmacológico , Humanos , Simulação de Acoplamento Molecular , Monkeypox virus/metabolismo , Prolina/uso terapêutico , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Valina/uso terapêutico , Zika virus/genética , Zika virus/metabolismo
5.
Molecules ; 27(13)2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35807365

RESUMO

Roasting is crucial for producing Yuan An yellow tea (YAYT) as it substantially affects sensory quality. However, the effect of roasting time on YAYT flavor quality is not clear. To investigate the effect of roasting time on the sensory qualities, chemical components, odor profiles, and metabolic profile of YAYTs produced with 13 min roasting, 16 min roasting, 19 min roasting, 22 min roasting, and 25 min roasting were determined. The YAYTs roasted for 22 min got higher sensory scores and better chemical qualities, such as the content of gallocatechin (GC), gallocatechin gallate (GCG), free amino acids, solutable sugar, meanwhile the lightness decreased, the hue of tea brew color (b) increased, which meant the tea brew got darker and yellower. YAYTs roasted for 22 min also increased the contents of key odorants, such as benzaldehyde, nonanal, ß-cyclocitral, linalool, nerol, α-cedrol, ß-ionone, limonene, 2-methylfuran, indole, and longiborneol. Moreover, non-targeted metabolomics identified up to 14 differentially expressed metabolites through pair-wise comparisons, such as flavonoids, phenolic acids, sucrose, and critical metabolites, which were the main components corresponding to YAYT roasted for 22 min. In summary, the current results provide scientific guidance for the production of high quality YAYT.


Assuntos
Paladar , Compostos Orgânicos Voláteis , Temperatura Alta , Odorantes/análise , Chá/química , Compostos Orgânicos Voláteis/análise
6.
Nutr Cancer ; 73(3): 473-483, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32270712

RESUMO

Boesenbergia rotunda (L.) Mansf. is an edible herb that is commonly used in the cuisine of several Asian countries. Studies have shown that it possesses high bioactivity against a variety of cancer cells. In this study, we investigated the cytotoxic activity of Boesenbergia rotunda rhizomes and some of its constituents on nasopharyngeal carcinoma cells (HK1). MTT assay results showed that the methanolic and hexane extracts of Boesenbergia rotunda decreased HK1 cell viability with IC50 values of 136 µg/ml and 66 µg/ml, respectively. Cardamonin, a constituent of Boesenbergia rotunda, exhibited the highest cytotoxic activity with an IC50 value of 27 µg/ml. Further studies on cardamonin revealed that it inhibited the migration of HK1 cells, caused G2/M-phase arrest and induced apoptosis. Apoptosis was induced via activating caspase-8 and caspase-3, but independent of caspase-9. This indicated that cardamonin induced extrinsic apoptosis. Western blot analysis further showed that cardamonin caused extrinsic apoptosis, as the expression levels of intrinsic apoptosis-related proteins (Bcl-XL, Bcl-2 and Bax), were not affected. Finally, JC-1 staining of HK1 cells revealed an increase in the mitochondrial membrane potential after treatment, further proving that cardamonin did not induce apoptosis via the intrinsic pathway. These results reflect cardamonin's potential as an anticancer agent.


Assuntos
Antineoplásicos , Neoplasias Nasofaríngeas , Zingiberaceae , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Chalconas , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico
7.
Ann Clin Microbiol Antimicrob ; 20(1): 79, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34856999

RESUMO

BACKGROUND AND OBJECTIVES: The chemotherapeutic management of infections has become challenging due to the global emergence of antibiotic resistant pathogenic bacteria. The recent expansion of studies on plant-derived natural products has lead to the discovery of a plethora of phytochemicals with the potential to combat bacterial drug resistance via various mechanisms of action. This review paper summarizes the primary antibiotic resistance mechanisms of bacteria and also discusses the antibiotic-potentiating ability of phytoextracts and various classes of isolated phytochemicals in reversing antibiotic resistance in anthrax agent Bacillus anthracis and emerging superbug bacteria. METHODS: Growth inhibitory indices and fractional inhibitory concentration index were applied to evaluate the in vitro synergistic activity of phytoextract-antibiotic combinations in general. FINDINGS: A number of studies have indicated that plant-derived natural compounds are capable of significantly reducing the minimum inhibitory concentration of standard antibiotics by altering drug-resistance mechanisms of B. anthracis and other superbug infection causing bacteria. Phytochemical compounds allicin, oleanolic acid, epigallocatechin gallate and curcumin and Jatropha curcas extracts were exceptional synergistic potentiators of various standard antibiotics. CONCLUSION: Considering these facts, phytochemicals represents a valuable and novel source of bioactive compounds with potent antibiotic synergism to modulate bacterial drug-resistance.


Assuntos
Antraz/tratamento farmacológico , Antibacterianos/farmacologia , Bacillus anthracis/química , Sinergismo Farmacológico , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/farmacologia , Fatores Biológicos , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Compostos Fitoquímicos/farmacologia
8.
Phytother Res ; 35(2): 954-973, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32893437

RESUMO

Blood-brain barrier (BBB) dysfunction has been implicated in Alzheimer's disease (AD) and is closely linked to the release of proinflammatory cytokines in brain capillary endothelial cells. We have previously reported that lychee seed polyphenols (LSP) exerted anti-neuroinflammatory effect. In this study, we aimed to explore the protective effect of LSP on BBB integrity. The monolayer permeability of bEnd.3 cells, and the mRNA level and protein expression of tight junction proteins (TJs), including Claudin 5, Occludin, and ZO-1, were examined. In addition, the inhibition of Aß(25-35)-induced NLRP3 inflammasome activation, and the autophagy induced by LSP were investigated by detecting the expression of NLRP3, caspase-1, ASC, LC3, AMPK, mTOR, and ULK1. Furthermore, the cognitive function and the expression of TJs, NLRP3, caspase-1, IL-1ß, and p62 were determined in APP/PS1 mice. The results showed that LSP significantly decreased the monolayer permeability and inhibited the NLRP3 inflammasome in Aß(25-35)-induced bEnd3 cells. In addition, LSP induced autophagy via the AMPK/mTOR/ULK1 pathway in bEnd.3 cells, and improved the spatial learning and memory function, increased the TJs expression, and inhibited the expression of NLRP3, caspase-1, IL-1ß, and p62 in APP/PS1 mice. Therefore, LSP protects BBB integrity in AD through inhibiting Aß(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Doença de Alzheimer/tratamento farmacológico , Autofagia/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Inflamassomos/efeitos dos fármacos , Litchi/química , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Polifenóis/uso terapêutico , Sementes/química , Animais , Masculino , Camundongos , Camundongos Transgênicos , Polifenóis/farmacologia , Transfecção
9.
Molecules ; 26(21)2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34771147

RESUMO

This study aimed to compare the effect of hot roller (HR) drying and hot air (HA) drying on the sensory evaluation, chemical quality, antioxidant activity, and metabolic profile of Yihong Congou black tea processed from E'cha NO1. The Yihong Congou black tea dried with HA obtained higher sensory scores and better chemical qualities such as the hue of tea brew color (a and b), content of theaflavins, thearubigins, water extract, free amino acids, tea polyphenol, and the ratio of polyphenol to amino acids as well as higher antioxidant capacities compared to that dried with HR. The HA drying tea increased the contents of volatile compounds that had positive correlation with sweet and flowery flavor, while the HR drying tea increased the contents of volatile compounds related to fruity flavor. Moreover, non-targeted metabolomics data indicated that the levels of most free amino acids significantly increased, while the levels of most soluble sugars reduced in the HA drying method compared to the HR drying method. The metabolic analysis was also consistent with the above results and revealed that D-ribose and gallic acid were the main characteristic metabolites of HA drying. Our results could provide a technical reference and theoretical guide to processing a high quality of Yihong Congou black tea.


Assuntos
Aminoácidos/metabolismo , Aromatizantes/metabolismo , Metabolômica , Polifenóis/metabolismo , Chá/metabolismo , Temperatura , Aminoácidos/química , Aromatizantes/química , Conservação de Alimentos , Polifenóis/química , Chá/química
10.
Molecules ; 26(8)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918814

RESUMO

Cardamonin is a polyphenolic natural product that has been shown to possess cytotoxic activity against a variety of cancer cell lines. We previously reported the semi-synthesis of a novel Cu (II)-cardamonin complex (19) that demonstrated potent antitumour activity. In this study, we further investigated the bioactivity of 19 against MDA-MB-468 and PANC-1 cancer cells in an attempt to discover an effective treatment for triple-negative breast cancer (TNBC) and pancreatic cancer, respectively. Results revealed that 19 abolished the formation of MDA-MB-468 and PANC-1 colonies, exerted growth-inhibitory activity, and inhibited cancer cell migration. Further mechanistic studies showed that 19 induced DNA damage resulting in gap 2 (G2)/mitosis (M) phase arrest and microtubule network disruption. Moreover, 19 generated reactive oxygen species (ROS) that may contribute to induction of apoptosis, corroborated by activation of caspase-3/7, PARP cleavage, and downregulation of Mcl-1. Complex 19 also decreased the expression levels of p-Akt and p-4EBP1, which indicates that the compound exerts its activity, at least in part, via inhibition of Akt signalling. Furthermore, 19 decreased the expression of c-Myc in PANC-1 cells only, which suggests that it may exert its bioactivity via multiple mechanisms of action. These results demonstrate the potential of 19 as a therapeutic agent for TNBC and pancreatic cancer.


Assuntos
Antineoplásicos/farmacologia , Chalconas/farmacologia , Complexos de Coordenação/farmacologia , Cobre/farmacologia , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Transdução de Sinais , Neoplasias de Mama Triplo Negativas/patologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Chalconas/química , Complexos de Coordenação/química , Cobre/química , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Citoesqueleto/patologia , Dano ao DNA , Regulação para Baixo/efeitos dos fármacos , Histonas/metabolismo , Humanos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
11.
Angew Chem Int Ed Engl ; 60(44): 23619-23624, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34490710

RESUMO

A strategy of chiral donor-acceptor copolymerization is proposed to develop chiral nonconjugated polymers with thermally activated delayed fluorescence (TADF). Based on this strategy, two pairs of chiral polymers (R,R)-/(S,S)-pTpAcDPS and (R,R)-/(S,S)-pTpAcBP were synthesized. The alternating copolymerization of the chiral donors and acceptors could effectively separate the frontier molecular orbitals, which made the polymers show small ΔEST of 0.01-0.03 eV and efficient TADF properties. Moreover, the polymers also showed the quantum yield of up to 92 % and the circularly polarized luminescence. The solution-processed circularly polarized organic light-emitting diodes showed circularly polarized electroluminescence signals with high external quantum efficiencies of up to 22.1 % and maximum luminance of up to 34350 cd m-2 . This is the first report of CP-OLEDs based on chiral TADF polymer, which provides a useful and valuable guidance for the development of high-efficiency CPEL polymers.

12.
Future Oncol ; 16(12): 749-762, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32228198

RESUMO

Aim: Evaluate quality of life (QoL) in patients with advanced non-small cell lung cancer treated with second or third line nab-paclitaxel ± durvalumab. Patients & methods: Longitudinal QoL was assessed using Lung Cancer Symptom Scale, EuroQoL Five-Dimensions Five-Levels and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core. Results: QoL was generally stable through eight treatment cycles (both arms). Clinically meaningful improvement from baseline was noted in Lung Cancer Symptom Scale (overall constitutional score and three-item index [nab-paclitaxel + durvalumab]) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core (global health status/QoL and emotional functioning [both arms] and pain [nab-paclitaxel + durvalumab]) analyses. EuroQoL Five-Dimensions Five-Levels domains were stable/improved or completely resolved at least once in 19-56% and 9-51% of patients, respectively. Conclusion: While QoL trends were promising, additional data are required to support these regimens in this setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Retratamento , Resultado do Tratamento
13.
Cancer ; 125(14): 2394-2399, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30933354

RESUMO

BACKGROUND: A partial response according to the Response Evaluation Criteria in Solid Tumors includes a wide range of changes in tumor size. This study evaluated whether further specification of tumor reduction based on the depth of response (DpR) would provide a more precise association with outcomes for patients with non-small cell lung cancer (NSCLC) treated with first-line platinum-based chemotherapy. METHODS: A retrospective analysis was performed for the randomized phase 3 CA031 trial in patients with NSCLC treated with carboplatin in combination with nab-paclitaxel or solvent-based paclitaxel. Quartiles according to the maximum tumor reduction from the baseline were defined (quartile 1 [Q1], >0% to 25%; quartile 2 [Q2], >25% to 50%; quartile 3 [Q3], >50% to 75%; and quartile 4 [Q4], >75%) and were compared with those patients with no tumor reduction (NTR). The primary objective was to evaluate the association between DpR and overall survival (OS). RESULTS: Of the 1052 patients enrolled in the CA031 trial, 959 (91%) were evaluable, and they included 365 (38.1%) who were classified as Q1, 327 (34.1%) who were classified as Q2, 131 (13.7%) who were classified as Q3, and 34 (3.5%) who were classified as Q4; 102 had NTR (10.6%). The median OS values for patients in the NTR, Q1, Q2, Q3, and Q4 groups were 4.8, 10.4, 14.5, 19.3, and 23.5 months, respectively. The maximum DpR on treatment was an independent predictor of improved OS in comparison with patients with NTR; the hazard ratio decreased from 0.43 in Q1 to 0.16 in Q4. CONCLUSIONS: DpR was strongly associated with OS in patients with NSCLC receiving first-line platinum-based therapy. Additional studies may help to define the role of DpR in solid tumors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Critérios de Avaliação de Resposta em Tumores Sólidos , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/uso terapêutico , Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Paclitaxel/uso terapêutico , Intervalo Livre de Progressão , Estudos Retrospectivos , Carga Tumoral/efeitos dos fármacos , Adulto Jovem
14.
Pharmacol Res ; 147: 104396, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31404628

RESUMO

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Our previous studies have proven that Trillium tschonoskii Maxim. (TTM), a traditional Chinese medicine, possesses potent anti-tumor effect. However, the detailed components and molecular mechanism of TTM in anti-NSCLC are still unknown. In the present experiment, polyphyllin VI (PPVI) was successfully isolated from TTM with guidance of the anti-proliferative effect in A549 cells, and the cell death of PPVI treated A549 and H1299 cells was closely linked with the increased intracellular ROS levels. In addition, PPVI induced apoptosis by promoting the protein expression of Bax/Bcl2, caspase-3 and caspase-9, and activated autophagy by improving LC3 II conversion and GFP-LC3 puncta formation in A549 and H1299 cells. The mechanism study found that the activity of mTOR which regulates cell growth, proliferation and autophagy was significantly suppressed by PPVI. Accordingly, the PI3K/AKT and MEK/ERK pathways positively regulating mTOR were inhibited, and AMPK negatively regulating mTOR was activated. In addition, the downstream of mTOR, ULK1 at Ser 757 which downregulates autophagy was inhibited by PPVI. The apoptotic cell death induced by PPVI was confirmed, and it was significantly suppressed by the overexpression of AKT, ERK and mTOR, and the induced autophagic cell death which was depended on the Atg7 was decreased by the inhibitors, such as LY294002 (LY), Bafilomycin A1 (Baf), Compound C (CC) and SBI-0206965 (SBI). Furthermore, the mTOR signaling pathway was regulated by the increased ROS as the initial signal in A549 and H1299 cells. Finally, the anti-tumor growth activity of PPVI in vivo was validated in A549 bearing athymic nude mice. Taken together, our data have firstly demonstrated that PPVI is the main component in TTM that exerts the anti-proliferative effect by inducing apoptotic and autophagic cell death in NSCLC via the ROS-triggered mTOR signaling pathway, and PPVI may be a promising candidate for the treatment of NSCLC in future.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Saponinas/farmacologia , Saponinas/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Morte Celular Autofágica/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos Nus , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Trillium
15.
BMC Complement Altern Med ; 19(1): 169, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291936

RESUMO

BACKGROUND: Garcinia species contain bioactive compounds such as flavonoids, xanthones, triterpernoids, and benzophenones with antibacterial, antifungal, anti-inflammatory, and antioxidant activities. In addition, many of these compounds show interesting biological properties such as anti-human immunodeficiency virus activity. Garcinia parvifolia is used in traditional medicine. Currently, the antiviral activity of G. parvifolia is not known. METHODS: This study was conducted to determine the effects of ethyl acetate (45 L Ea), ethanol (45 L Et), and hexane (45 L H) leaf extracts of G. parvifolia on the infectivity of pseudorabies virus (PrV) in Vero cells. The antiviral effects of the extracts were determined by cytopathic effect (CPE), inhibition, attachment, and virucidal assays. RESULTS: The 50% cytotoxicity concentration (CC50) values obtained were 237.5, 555.0, and < 1.25 µg/mL for 45 L Ea, 45 L Et, and 45 L H, respectively. The 45 L Ea showed the greatest viral inhibition potency of 75% at 125 µg/mL. Both 45 L Ea and 45 l Et caused 100% residual viral inhibition at 250 µg/mL. The selectivity index values for 45 L Ea, 45 L Et, and 45 L H were 2.65, 1.75, and 0.10 showing that 45 L Ea had the greatest antiviral activity among the three extracts. CONCLUSION: This study showed that ethyl acetate is the best solvent to be used to obtain extract from G. parvifolia leaves with potent antiviral activities.


Assuntos
Antivirais/farmacologia , Garcinia/química , Herpesvirus Suídeo 1/efeitos dos fármacos , Extratos Vegetais/farmacologia , Acetatos , Animais , Antivirais/isolamento & purificação , Antivirais/toxicidade , Chlorocebus aethiops , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Células Vero , Ensaio de Placa Viral
16.
Arch Virol ; 163(8): 2121-2131, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29633078

RESUMO

Viral respiratory infections are raising serious concern globally. Asian medicinal plants could be useful in improving the current treatment strategies for influenza. The present study examines the activity of five plants from Bangladesh against influenza virus. MDCK cells infected with influenza virus A/Puerto Rico/8/34 (H1N1) were treated with increasing concentrations of ethyl acetate extracts, and their cytotoxicity (CC50), virus-inhibiting activity (IC50), and selectivity index (SI) were calculated. The ethyl acetate extract of fruits of Embelia ribes Burm. f. (Myrsinaceae) had the highest antiviral activity, with an IC50 of 0.2 µg/mL and a SI of 32. Its major constituent, embelin, was further isolated and tested against the same virus. Embelin demonstrated antiviral activity, with an IC50 of 0.3 µM and an SI of 10. Time-of-addition experiments revealed that embelin was most effective when added at early stages of the viral life cycle (0-1 h postinfection). Embelin was further evaluated against a panel of influenza viruses including influenza A and B viruses that were susceptible or resistant to rimantadine and oseltamivir. Among the viruses tested, avian influenza virus A/mallard/Pennsylvania/10218/84 (H5N2) was the most susceptible to embelin (SI = 31), while A/Aichi/2/68 (H3N2) virus was the most resistant (SI = 5). In silico molecular docking showed that the binding site for embelin is located in the receptor-binding domain of the viral hemagglutinin. The results of this study provide evidence that E. ribes can be used for development of a novel alternative anti-influenza plant-based agent.


Assuntos
Antivirais/farmacologia , Embelia/química , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza B/efeitos dos fármacos , Influenza Humana/virologia , Extratos Vegetais/farmacologia , Antivirais/química , Benzoquinonas/química , Benzoquinonas/farmacologia , Humanos , Vírus da Influenza A/fisiologia , Vírus da Influenza B/fisiologia , Extratos Vegetais/química
17.
Int J Mol Sci ; 19(7)2018 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-30036972

RESUMO

Amyloid-ß (Aß) is commonly recognized as the most important factor that results in neuronal cell death and accelerates the progression of Alzheimer's disease (AD). Increasing evidence suggests that microglia activated by Aß release an amount of neurotoxic inflammatory cytokines that contribute to neuron death and aggravate AD pathology. In our previous studies, we found that lychee seed fraction (LSF), an active fraction derived from the lychee seed, could significantly improve the cognitive function of AD rats and inhibit Aß-induced neuroinflammation in vitro, and decrease neuronal injuries in vivo and in vitro. In the current study, we aimed to isolate and identify the specific components in LSF that were responsible for the anti-neuroinflammation effect using preparative high performance liquid chromatography (pre-HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) methods. To this end, we confirmed two polyphenols including catechin and procyanidin A2 that could improve the morphological status of BV-2 cells and suppress the release, mRNA levels, and protein expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) through downregulating the nuclear factor-κB (NF-κB) signaling pathway using ELISA, RT-PCR, and Western blotting methods. Furthermore, catechin and procyanidin A2 could inhibit Aß-induced apoptosis in BV-2 cells by upregulating Bcl-2 and downregulating Bax protein expression. Therefore, the current study illustrated the active substances in lychee seed, and first reported that catechin and procyanidin A2 could suppress neuroinflammation in Aß-induced BV-2 cells, which provides detailed insights into the molecular mechanism of catechin and procyanidin A2 in the neuroprotective effect, and their further validations of anti-neuroinflammation in vivo is also essential in future research.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Inflamação/tratamento farmacológico , Litchi/química , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Polifenóis/química , Polifenóis/uso terapêutico , Sementes/química , Animais , Apoptose/efeitos dos fármacos , Catequina/metabolismo , Linhagem Celular , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Camundongos , NF-kappa B/metabolismo , Neurônios/imunologia , Proantocianidinas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
18.
Pharm Biol ; 56(1): 201-208, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29529970

RESUMO

CONTEXT: The resistance of bacteria to antibiotics is raising serious concern globally. Asian medicinal plants could improve the current treatment strategies for bacterial infections. The antibacterial properties of medicinal plants used by the Khyang tribe in Bangladesh have not been investigated. OBJECTIVE: The present study examines the antibacterial properties of 18 medicinal plants used by the Khyang tribe in day-to-day practice against human pathogenic bacteria. MATERIALS AND METHODS: Leaves, bark, fruits, seeds, roots and rhizomes from collected plants were successively extracted with hexane, ethyl acetate and ethanol. The corresponding 54 extracts were tested against six human pathogenic bacteria by broth microdilution assay. The antibacterial mode of actions of phytoconstituents and their synergistic effect with vancomycin and cefotaxime towards MRSA was determined by time-killing assay and synergistic interaction assay, respectively. RESULTS AND DISCUSSION: Hexane extract of bark of Cinnamomum cassia (L.) J. Presl. (Lauraceae) inhibited the growth of MRSA, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii with MIC values below 100 µg/mL. From this plant, cinnamaldehyde evoked at 4 × MIC in 1 h an irreversible decrease of MRSA count Log10 (CFU/mL) from 6 to 0, and was synergistic with vancomycin for MRSA with fractional inhibitory concentration index of 0.3. CONCLUSIONS: Our study provides evidence that the medicinal plants in Bangladesh have high potential to improve the current treatment strategies for bacterial infection.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Medicina Tradicional , Extratos Vegetais/farmacologia , Antibacterianos/isolamento & purificação , Bactérias/crescimento & desenvolvimento , Bangladesh , Cefotaxima/farmacologia , Farmacorresistência Bacteriana , Sinergismo Farmacológico , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Fatores de Tempo , Vancomicina/farmacologia
20.
Acta Crystallogr Sect E Struct Rep Online ; 69(Pt 2): o178, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23424463

RESUMO

The title compound, C(12)H(16)N(2)S(3), was obtained by the condensation reaction of S-benzyl dithio-carbazate and 3-mercaptobutan-2-one. The phenyl ring and thiol (SH) group are approximately perpendicular [S-C-C-C and N-C-C-S torsion angles = 67.8 (3) and 116.9 (2)°, respectively] to the rest of the mol-ecule. In the crystal, mol-ecules are linked by weak S-H⋯S and N-H⋯S hydrogen bonds, π-π inter-actions between the benzene rings [centroid-centroid distance = 3.823 (2) Å] and C-H⋯π inter-actions.

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