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1.
PLoS Comput Biol ; 19(12): e1011330, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38060617

RESUMO

Recent advances in deep learning have significantly improved the ability to infer protein sequences directly from protein structures for the fix-backbone design. The methods have evolved from the early use of multi-layer perceptrons to convolutional neural networks, transformers, and graph neural networks (GNN). However, the conventional approach of constructing K-nearest-neighbors (KNN) graph for GNN has limited the utilization of edge information, which plays a critical role in network performance. Here we introduced SPIN-CGNN based on protein contact maps for nearest neighbors. Together with auxiliary edge updates and selective kernels, we found that SPIN-CGNN provided a comparable performance in refolding ability by AlphaFold2 to the current state-of-the-art techniques but a significant improvement over them in term of sequence recovery, perplexity, deviation from amino-acid compositions of native sequences, conservation of hydrophobic positions, and low complexity regions, according to the test by unseen structures, "hallucinated" structures and diffusion models. Results suggest that low complexity regions in the sequences designed by deep learning, for generated structures in particular, remain to be improved, when compared to the native sequences.


Assuntos
Aminoácidos , Redes Neurais de Computação , Sequência de Aminoácidos , Análise por Conglomerados , Difusão
2.
BMC Pregnancy Childbirth ; 24(1): 9, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166803

RESUMO

BACKGROUND: Intractable postpartum hemorrhage (PPH) during cesarean section has been a significant concern for obstetricians. We aimed to explore the effectiveness and safety of a new type of uterine compression suture, the step-wise surgical technique of knapsack-like sutures for treating intractable PPH caused by uterine atony and placenta factors in cesarean section. METHODS: The step-wise surgical technique of knapsack-like sutures was established on the basis of the artful combination of vertical strap-like sutures and an annular suture-ligation technique. This novel surgical technique was applied to 34 patients diagnosed with PPH during cesarean section due to severe uterine atony and placental factors in our department. The hemostatic effects, clinical outcomes and follow-up visit results were all reviewed and analyzed. RESULTS: This new uterine compression suture successfully stopped bleeding in 33 patients, and the effective rate was 97.06%. Only 1 patient failed and was changed to use bilateral uterine arterial embolization and internal iliac artery embolization. The follow-up visits indicated that 33 patients restored menstruation except for 1 who was diagnosed with amenorrhea. The gynecological ultrasound tests of all the patients suggested good uterine involutions, and they had no obvious complaints such as hypogastralgia. CONCLUSIONS: This step-wise surgical technique of knapsack-like uterine compression sutures can compress the uterus completely. It is a technique that can conserve the uterus and fertility function without special equipment in caesarean section for PPH, with the characteristics of being safe, simple and stable (3 S) with rapid surgery, reliable hemostasis and resident doctor to operation (3R).


Assuntos
Hemorragia Pós-Parto , Inércia Uterina , Feminino , Humanos , Gravidez , Hemorragia Pós-Parto/cirurgia , Hemorragia Pós-Parto/etiologia , Cesárea/efeitos adversos , Inércia Uterina/cirurgia , Hemostasia Cirúrgica/métodos , Placenta/cirurgia , Útero/cirurgia , Útero/irrigação sanguínea , Suturas/efeitos adversos , Técnicas de Sutura/efeitos adversos
3.
Artigo em Inglês | MEDLINE | ID: mdl-38826134

RESUMO

Medial arterial calcification (MAC) accompanying chronic kidney disease (CKD) leads to increased vessel wall stiffness, myocardial ischemia, heart failure, and increased cardiovascular morbidity and mortality. Unfortunately, there are currently no drugs available to treat MAC. The natural polyphenol epigallocatechin-3-gallate (EGCG) has been demonstrated to protect against cardiovascular disease; however, whether EGCG supplementation inhibits MAC in CKD remains unclear. In this study, we utilize a CKD-associated MAC model to investigate the effects of EGCG on vascular calcification and elucidate the underlying mechanisms involved. Our findings demonstrate that EGCG treatment significantly reduces calcium phosphate deposition and osteogenic differentiation of VSMCs in vivo and in vitro in a dose-dependent manner. In addition, through RNA sequencing (RNA-seq) analysis, we show a significant activation of the transcription factor JunB both in CKD mouse arteries and in osteoblast-like VSMCs. Notably, EGCG effectively suppresses CKD-associated MAC by inhibiting the activity of JunB. In addition, overexpression of JunB can abolish while knockdown of JunB can enhance the inhibitory effect of EGCG on the osteogenic differentiation of VSMCs. Furthermore, EGCG supplementation inhibits MAC in CKD via modulation of the JunB-dependent Ras/Raf/MEK/ERK signaling pathway. In conclusion, our study highlights the potential therapeutic value of EGCG for managing CKD-associated MAC, as it mitigates this pathological process through targeted inactivation of JunB.

4.
Ecotoxicol Environ Saf ; 280: 116520, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38833985

RESUMO

Early studies have shown that the gut microbiota is a critical target during cadmium exposure. The prebiotic activity of epigallocatechin-3-gallate (EGCG) plays an essential role in treating intestinal inflammation and damage. However, the exact intestinal barrier protection mechanism of EGCG against cadmium exposure remains unclear. In this experiment, four-week-old mice were exposed to cadmium (5 mg kg-1) for four weeks. Through 16 S rDNA analysis, we found that cadmium disrupted the gut microbiota and inhibited the indole metabolism pathway of tryptophan (TRP), which serves as the principal microbial production route for endogenous ligands to activate the aryl hydrocarbon receptor (AhR). Additionally, cadmium downregulated the intestinal AhR signaling pathway and harmed the intestinal barrier function. Treatment with EGCG (20 mg kg-1) and the AhR agonist 6-Formylindolo[3,2-b] carbazole (FICZ) (1 µg/d) significantly activated the AhR pathway and alleviated intestinal barrier injury. Notably, EGCG partially restored the gut microbiota and upregulated the TRP-indole metabolism pathway to increase the level of indole-related AhR agonists. Our findings demonstrate that cadmium dysregulates common gut microbiota to disrupt TRP metabolism, impairing the AhR signaling pathway and intestinal barrier. EGCG reduces cadmium-induced intestinal functional impairment by intervening in the intestinal microbiota to metabolize AhR agonists. This study offers insights into the toxic mechanisms of environmental cadmium and a potential mechanism to protect the intestinal barrier with EGCG.


Assuntos
Cádmio , Catequina , Microbioma Gastrointestinal , Receptores de Hidrocarboneto Arílico , Transdução de Sinais , Triptofano , Animais , Catequina/análogos & derivados , Catequina/farmacologia , Receptores de Hidrocarboneto Arílico/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Triptofano/metabolismo , Triptofano/análogos & derivados , Cádmio/toxicidade , Transdução de Sinais/efeitos dos fármacos , Masculino , Intestinos/efeitos dos fármacos , Intestinos/patologia , Camundongos Endogâmicos C57BL , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Indóis/farmacologia , Carbazóis/farmacologia
5.
Molecules ; 29(2)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38257381

RESUMO

Agarwood (Aquilaria malaccensis Lam.) is a resinous material from different geographical locations. The current evaluation of agarwood quality is usually based on its physical properties and chemical compounds, yet only a few studies have linked agarwood quality with its anxiolytic effect, as indicated by characteristic compounds. In this study, using solid-phase microextraction/gas chromatography-time-of-flight mass spectrometry (SPME/GC-TOFMS) and multivariate analysis, we found 116 significantly different compounds in agarwood samples from four locations in Southeast Asia with regard to their quality. Brunei and Nha Trang agarwood had abundant sesquiterpenoids, exhibiting notable pharmacological efficacy in relieving anxiety. Malaysian and Irian agarwood had abundant alcohols and aldehydes, qualifying them as high-quality spices. Compound-target-disease network and pathway enrichment analysis were further employed to predict 79 gene targets and 20 pathways associated with the anxiolytic effects based on the 62 sesquiterpenoids. The correlated relationships among the sesquiterpenoids and targets suggest that agarwood treats anxiety via multiple compounds acting on multiple targets. Varying levels of sesquiterpenes across agarwood groups might lead to differences in the anxiolytic effects via signaling pathways, such as neurotransmitter- and hormone-regulated pathways. Our study originally evaluates agarwood quality and its anxiolytic effect by linking the characteristic compounds to potential gene targets and pathways.


Assuntos
Ansiolíticos , Sesquiterpenos , Humanos , Ansiolíticos/farmacologia , Farmacologia em Rede , Microextração em Fase Sólida , Transtornos de Ansiedade , Cromatografia Gasosa-Espectrometria de Massas , Sesquiterpenos/farmacologia
6.
Ecotoxicol Environ Saf ; 263: 115292, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37494733

RESUMO

Chlorantraniliprole (CAP) is a presentative diamide pesticide utilized in agricultural area and as well as rice-fish co-culture system for pest control. However, the understanding of toxic effects of CAP on fish species is still incomplete. In the present study, we performed an integrated study of the acute toxicity and bioaccumulation of CAP on the crucian carp, Carassius carassius, a fish species widely distributed in freshwater area in China and commonly farmed in the rice-fish co-culture systems. Besides, biochemical changes, transcriptional responses and gut microbiota of fish were investigated upon sub-chronic CAP exposure. The results showed that CAP is low toxic to crucian carp with a 96 h LC50 of 74.824 mg/L, but has considerable accumulation in the fish muscles when exposed to 3 mg/L of CAP for 14 d and still detectable after 18 d recovery in fresh water. For sub-chronic test, fish were exposed to CAP at 0, 0.3, 3 and 30 mg/L respectively for 14 d. CAP induced oxidative stress and detoxification inhibition in the liver of fish by decreasing antioxidative and detoxicated enzymes activities and downregulating relevant genes expression. In addition, disrupted gut flora composition was found in all experimental groups by the 16 S rRNA sequencing data, indicating the gut microbiota dysbiosis in crucian carp and potential adverse host effect. All the results suggest that CAP at sublethal concentrations has prominent toxic effect on crucian carp and more attentions should be paid especially using directly in an integrated aquaculture system.


Assuntos
Carpas , Microbioma Gastrointestinal , Praguicidas , Animais , Praguicidas/toxicidade , ortoaminobenzoatos/toxicidade
7.
Molecules ; 28(16)2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37630374

RESUMO

The energy band structure, density of states, and optical properties of monolayers of MoS2 doped with alkaline earth metals (Be/Mg/Ca/Sr/Ba) are systematically studied based on first principles. The results indicate that all the doped systems have a great potential to be formed and structurally stable. In comparison to monolayer MoS2, doping alkaline earth metals results in lattice distortions in the doped system. Therefore, the recombination of photogenerated hole-electron pairs is suppressed effectively. Simultaneously, the introduction of dopants reduces the band gap of the systems while creating impurity levels. Hence, the likelihood of electron transfer from the valence to the conduction band is enhanced, which means a reduction in the energy required for such a transfer. Moreover, doping monolayer MoS2 with alkaline earth metals increases the static dielectric constant and enhances its polarizability. Notably, the Sr-MoS2 system exhibits the highest value of static permittivity, demonstrating the strongest polarization capability. The doped systems exhibit a red-shifted absorption spectrum in the low-energy region. Consequently, the Be/Mg/Ca-MoS2 systems demonstrate superior visible absorption properties and a favorable band gap, indicating their potential as photo-catalysts for water splitting.

8.
Molecules ; 28(13)2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37446920

RESUMO

The main purpose of this study was to reveal the nutritional value and antioxidant activity of 34 edible flowers that grew in Yunnan Province, China, through a comprehensive assessment of their nutritional composition and antioxidant indices. The results showed that sample A3 of Asteraceae flowers had the highest total flavonoid content, with a value of 8.53%, and the maximum contents of vitamin C and reducing sugars were from Rosaceae sample R1 and Gentianaceae sample G3, with values of 143.80 mg/100 g and 7.82%, respectively. Samples R2 and R3 of Rosaceae were the top two flowers in terms of comprehensive nutritional quality. In addition, the antioxidant capacity of Rosaceae samples was evidently better than that of three others, in which Sample R1 had the maximum values in hydroxyl radical (·OH) scavenging and superoxide anion radical (·O2-) scavenging rates, and samples R2 and R3 showed a high total antioxidant capacity and 2,2-diphenyl-1-pyridylhydrazine (DPPH) scavenging rate, respectively. Taken together, there were significant differences in the nutrient contents and antioxidant properties of these 34 flowers, and the comprehensive quality of Rosaceae samples was generally better than the other three families. This study provides references for 34 edible flowers to be used as dietary supplements and important sources of natural antioxidants.


Assuntos
Antioxidantes , Fenóis , Humanos , Antioxidantes/química , Fenóis/química , China , Flores/química , Flavonoides/química , Extratos Vegetais/química
9.
Phys Rev Lett ; 128(19): 197801, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35622042

RESUMO

Double-helix structures, such as DNA, are formed in nature to realize many unique functions. Inspired by this, researchers are pursuing strategies to design such structures from polymers. A key question is whether the double helix can be formed from the self-folding of a single polymer chain without specific interactions. Here, using Langevin dynamics simulation and theoretical analysis, we find that a stable double-helix phase can be achieved by the self-folding of single semiflexible polymers as a result of the cooperation between local structure and nonlocal attraction. The critical temperature of double-helix formation approximately follows T^{cri}∼ln(k_{θ}) and T^{cri}∼ln(k_{τ}), where k_{θ} and k_{τ} are the polymer bending and torsion stiffness, respectively. Furthermore, the double helix can exhibit major and minor grooves due to symmetric break for better packing. Our results provide a novel guide to the experimental design of the double helix.


Assuntos
DNA , Polímeros , Polímeros/química , Temperatura
10.
Antimicrob Agents Chemother ; 65(7): e0010021, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-33875436

RESUMO

Candida glabrata is currently the first or second most commonly encountered non-albicans Candida species worldwide. The potential severity of Candida resistance mandates the discovery of novel antifungal agents, including those that can be used in combination therapies. In this study, we evaluated the in vitro interactions of pyrogallol (PG) and azole drugs against 22 clinical C. glabrata isolates. The potential mechanism underlying the synergism between PG and fluconazole (FLC) was investigated by the rhodamine 6G efflux method and quantitative reverse transcription (qRT)-PCR analysis. In susceptibility tests, PG showed strong synergism with FLC, itraconazole (ITC), and voriconazole (VRC), with fractional inhibitory concentration index values of 0.18 to 0.375 for PG+FLC, 0.250 to 0.750 for PG+ITC, and 0.141 to 0.750 for PG+VRC. Cells grown in the presence of PG+FLC exhibited reduced rhodamine 6G extrusion and significantly downregulated expression of the efflux-related genes CgCDR1, CgCDR2, and CgPDR1 compared with cells grown in the presence of PG or FLC alone. PG did not potentiate FLC when tested against a ΔCgpdr1 strain. Restoration of a functional CgPDR1 allele also restored the synergism. These results indicate that PG is an antifungal agent that synergistically potentiates the activity of azoles. Furthermore, PG appears to exert its effects by inhibiting efflux pumps and downregulating CgCDR1, CgCDR2, and CgPDR1, with CgPDR1 probably playing a crucial role in this process.


Assuntos
Candida glabrata , Fluconazol , Antifúngicos/farmacologia , Candida glabrata/genética , Farmacorresistência Fúngica/genética , Fluconazol/farmacologia , Testes de Sensibilidade Microbiana , Pirogalol/farmacologia
11.
J Clin Lab Anal ; 35(12): e24085, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34773716

RESUMO

BACKGROUND: Metabolic abnormalities in patients with gastric adenocarcinoma lead to drug resistance and poor prognosis. Therefore, this study aimed to explore biomarkers that can predict the prognostic risk of gastric adenocarcinoma by analyzing drug metabolism-related genes. METHODS: The RNA-seq and clinical information on gastric adenocarcinoma were downloaded from the UCSC and gene expression omnibus databases. Univariate and least absolute shrinkage and selection operator regression analyses were used to identify the prognostic gene signature of gastric adenocarcinoma. The relationships between gastric adenocarcinoma prognostic risk and tumor microenvironment were assessed using CIBERSORT, EPIC, QUANTISEQ, MCPCounter, xCell, and TIMER algorithms. The potential drugs that could target the gene signatures were predicted in WebGestalt, and molecular docking analysis verified their binding stabilities. RESULTS: Combined with clinical information, an eight-gene signature, including GPX3, ABCA1, NNMT, NOS3, SLCO4A1, ADH4, DHRS7, and TAP1, was identified from the drug metabolism-related gene set. Based on their expressions, risk scores were calculated, and patients were divided into high- and low-risk groups, which had significant differences in survival status and immune infiltrations. Risk group was also identified as an independent prognostic factor of gastric adenocarcinoma, and the established prognostic and nomogram models exhibited excellent capacities for predicting prognosis. Finally, miconazole and niacin were predicted as potential therapeutic drugs for gastric adenocarcinoma that bond stably with NOS3 and NNMT through hydrogen interactions. CONCLUSIONS: This study proposed a drug metabolism-related eight-gene signature as a potential biomarker to predict the gastric adenocarcinoma prognosis risks.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Inativação Metabólica/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Adenocarcinoma/tratamento farmacológico , Adulto , Idoso , Biomarcadores Tumorais/genética , Glibureto/química , Glibureto/metabolismo , Glibureto/farmacocinética , Humanos , Miconazol/química , Miconazol/farmacocinética , Pessoa de Meia-Idade , Simulação de Acoplamento Molecular , Nomogramas , Prognóstico , Mapas de Interação de Proteínas/genética , Proteínas/química , Proteínas/genética , Reprodutibilidade dos Testes , Fatores de Risco , Neoplasias Gástricas/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
12.
Environ Toxicol ; 36(1): 16-23, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32757256

RESUMO

Pyrethroid pesticides are applied to both agricultural and aquacultural industries for pest control. However, information of their impact on the commercial important freshwater crayfish, Procambarus clarkii is scarce. Therefore, the present study aimed to characterize to effects of a commonly used pyrethroid pesticide, deltamethrin on DNA damage, immune response, and neurotoxicity in P. clarkii. Animals were exposed to 7, 14, and 28 ng/L of deltamethrin, which correspond to 1/8, 1/4, and 1/2 of the LC50 (96 hours) of this pyrethroid to P. clarkii. Significant increase of olive tail moment (OTM) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) was found after deltamethrin exposure in a dose-dependent way. Total hemocyte counts (THC) and activities of immune-related enzymes including acid phosphatase (ACP), lysozyme (LZM), and phenoloxidase (PO) were all decreased and significantly lower than control at concentration of 28 ng/L after 96 hours exposure. Acetylcholinesterase (AChE) activity, an indicator of neurotoxic effect was investigated and it was decreased significantly in muscles at 14 and 28 ng/L after 24 hours exposure. The level of intracellular reactive oxygen species (ROS) in hemocytes was also measured and the significant increase of ROS was found at 14 and 28 ng/L concentrations. The results revealed that deltamethrin induced DNA damage, immunotoxicity, and neurotoxicity in P. clarkii by excessive generation of ROS. Because of the dose-dependent responses of all parameters under exposure of deltamethrin at environmentally realistic concentrations, these parameters could be used as sensitive biomarkers for risk assessment of deltamethrin in aquaculture area.

13.
Ecotoxicol Environ Saf ; 188: 109889, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31704331

RESUMO

It is known that abamectin (ABM) inflicts oxidative damage on aquatic animals; however, knowledge about the immune response under pesticide-induced oxidative stress is incomplete. In the present study, several cellular and humoral immune parameters, including total haemocyte counts (THC), lysosomal membrane stability (LMS), activities of acid phosphatase (ACP), alkaline phosphatase (AKP) and lysozyme (LZM) were investigated to reveal the effects of ABM exposure on the immune defence mechanisms of the important freshwater crab, Erocheir sinensis. According to the results, a significant increase of THC was found in low concentration groups (0.03 and 0.06 mg/L), while dramatic decreases occurred in high concentration groups (0.12 and 0.24 mg/L) after 96 h of exposure. We also detected significant increases of reactive oxygen species (ROS) in haemocytes at 0.12 and 0.24 mg/L, and there was a dose- and time-dependent decrease of lysosomal membrane stability. These results suggest that the excessive generation of ROS induced by ABM may be leading the massive collapse of lysosomal membrane, which in turn may be causing the sharp drop of haemocyte counts in E. sinensis. The increase of hydrolytic enzymes ACP and AKP at low concentrations and the decrease at high concentrations also indicate an immune response associated with haemocytes status under stress. However, activities of LZM decreased significantly. After injection of Aeromonas hydrophil, mortalities increased under exposure to ABM and were positively related to ABM concentration. These results confirm that ABM exposure has the ability to impair immune defence and result in the host's susceptibility to pathogens.


Assuntos
Braquiúros/imunologia , Inseticidas/toxicidade , Ivermectina/análogos & derivados , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Braquiúros/efeitos dos fármacos , Braquiúros/metabolismo , Hemócitos/efeitos dos fármacos , Hemócitos/metabolismo , Hemócitos/patologia , Imunidade Inata/efeitos dos fármacos , Ivermectina/toxicidade , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Espécies Reativas de Oxigênio/metabolismo
14.
J Cell Biochem ; 120(4): 5232-5243, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30378152

RESUMO

TRIM32 is a member of the tripartite motif (TRIM) family, which has been associated with tumorigenesis. However, its expression and potential functional role(s) in lung cancer progression have not been fully understood. To evaluate the relationship between the expression of TRIM32 and the prognosis of patients with lung cancer, an independent data set (The Human Protein Atlas website) was introduced. The expression and function analysis of TRIM32 in lung cancer cell lines were also performed by using cell counting kit-8, flow cytometry, transwell, real-time polymerase chain reaction and Western blot analysis. Our data showed that TRIM32 was overexpressed in lung cancer tissues and cell lines and was associated with a poor prognosis. TRIM32 silencing inhibited cell proliferation, migration, invasion, adhesion, and the activation of janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling. The results showed knockdown of TRIM32 in NCI-H446 cells also inhibited cell growth in nude mice in the xenograft model. Additionally, TRIM32 overexpression promoted lung cancer cell proliferation and motility and mediated the expression of Bax, Bcl-2, cleaved caspase-3, matrix metalloproteinase-2 (MMP-2) and MMP-9 were inhibited by JAK2/STAT3 signaling inhibitor (AG490). Taken together, our findings suggest that TRIM32 may regulate lung cancer cell proliferation, apoptosis, and motility through activating the JAK2/STAT3-signaling pathway and may be a novel and promising target for lung cancer.


Assuntos
Carcinogênese/genética , Neoplasias Pulmonares/genética , Fatores de Transcrição/genética , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Adesão Celular/efeitos dos fármacos , Adesão Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Humanos , Janus Quinase 2/metabolismo , Neoplasias Pulmonares/patologia , Camundongos Nus , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismo , Prognóstico , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Tirfostinas/farmacologia , Ubiquitina-Proteína Ligases/metabolismo
15.
Pathobiology ; 86(2-3): 102-110, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30404093

RESUMO

OBJECTIVE: To evaluate the potential beneficial effects of hawthorn leaf flavonoids (HLF) against polycystic ovary syndrome (PCOS) in a rat model of disease and elucidate the underlying molecular mechanism. METHODS: The PCOS model was established by subcutaneous injection of dehydroepiandrosterone (DHEA, 60 mg/kg/day) for 21 consecutive days. HLF (200 mg/kg/day) were orally administered simultaneously or after the injection. The body weight was regularly monitored and recorded. The ovaries were weighed and histologically examined via hematoxylin and eosin staining. The number of follicular cysts was counted under a light microscope. The serous hormones were measured using enzyme-linked immunosorbent assay kits. Insulin resistance (IR) was calculated as HOMA-IR = fasting insulin (µU/L) × fasting glucose (mM)/22.5. The estrous cycle was determined by vaginal smear. The relative expression of tumor necrosis factor-α and interleukin-6 was measured by real-time polymerase chain reaction. The superoxide dismutase activity and malondialdehyde content was determined using commercially available kits. RESULTS: DHEA induced a significant increase of body weight, ovary weight, number of follicular cysts, serous hormones, IR, inflammatory cytokines, and oxidative stress, and it also impaired the estrous cycle. Oral administration of HLF greatly alleviated these complications. Little toxicity of HLF was observed in our rat model. CONCLUSION: HLF manifest protective effects against PCOS progression in the animal model, which may hold great promise for future clinical applications.


Assuntos
Crataegus/química , Flavonoides/farmacologia , Ovário/efeitos dos fármacos , Extratos Vegetais/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Administração Oral , Animais , Desidroepiandrosterona , Modelos Animais de Doenças , Feminino , Ovário/patologia , Folhas de Planta/química , Síndrome do Ovário Policístico/induzido quimicamente , Ratos , Ratos Sprague-Dawley
16.
Environ Sci Technol ; 52(22): 13457-13468, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30351035

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs) are predominant pollutants normally coexisting at electronic waste dumping sites or in agricultural soils irrigated with wastewater. The accumulation of PAHs and HMs in food crops has become a major concern for food security. This study explored the hydroponic uptake of 16 priority PAHs and 5 HMs (Cd, Cr, Cu, Pb, and Zn) by pak choi ( Brassica chinensis L.). PAHs exhibited stronger inhibition on pak choi growth and physiological features than HMs. Five HMs were categorized into high-impact HMs (Cr, Cu, and Pb) and low-impact HMs (Cd and Zn) with distinct behavior under the coexposure with PAHs, and low-impact HMs showed synergistic toxicity effects with PAHs. Coexposure to PAHs and HMs slightly decreased the uptake and translocation of PAHs by pak choi, possibly attributing to the commutative hindering effects on root adsorption or cation-π interactions. The bioconcentration factors in PAHs + HMs treatments were independent of the octanol-water partition coefficient ( Kow), owing to the cation-π interaction associated change of Kow and induced defective root system. This study provides new insights into the mechanisms and influential factors of PAHs uptake in Brassica chinensis L. and gives clues for reassessing the environmental risks of PAHs in food crops.


Assuntos
Brassica , Metais Pesados , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Poluentes Químicos da Água
17.
J Chem Phys ; 149(23): 234903, 2018 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-30579311

RESUMO

Motivated by loop closure during protein folding and DNA packing, we systemically studied the effects of the solvent quality and chain stiffness on the thermodynamics and kinetics of the end-to-end contact formation for semiflexible polymer chains with reactive ends by Langevin dynamics simulations. In thermodynamics, a rich variety of products of the end-to-end contact have been discovered, such as loop, hairpin, toroid, and rodlike bundle, the populations of which are dependent on the solvent quality and chain stiffness. In kinetics, the overall pathways to form the end-to-end contact have been identified. The change of solvent quality and chain stiffness can tune the roughness of energy landscape and modulate the kinetic partitioning of the end-to-end contact formation pathways, leading to differing kinetic behaviors. In good or poor solvents, the first end-to-end contact rate k c decreases with increasing the strength of bending stiffness k θ monotonically. In very poor solvents, however, the dependence of the logarithm of the first end-to-end contact rate ln k c on k θ exhibits erratic behavior, which stems from more rugged energy landscape due to the polymer chain getting trapped into the intermediate state composed of the rodlike bundles with two ends in separation. For semiflexible chains, with increasing chain length N, the rate k c increases initially and then decreases: in good solvents, the rate k c exhibits a power-law relationship to chain length N with an exponent of ∼-1.50 in the region of long chains, which is in good agreement with the value derived from the experiment in the asymptotic limit of large N; and in poor solvents, the rate k c exhibits a significantly stronger chain length dependence than those observed in good solvents in the region of long chains due to frustration to form the end-to-end contact along a specific path, especially the scaling exponent between the rate k c and chain length N is ∼-3.62 for the case of polymer chains with k θ = 4 at the solvent quality ε ij = 1, in accord with the value obtained from the experiments.

18.
Zhongguo Zhong Yao Za Zhi ; 43(15): 3140-3144, 2018 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30200709

RESUMO

To develop a rapid resolution liquid chromatography (RRLC) method for the simultaneous determination of epimedoside A, epimedin A1, epimedin A, epimedin B, epimedin C, icariin, baohuosideⅡ, icarisideⅠ, sagittatoside B, 2"-O-rhamnosyl icarisideⅡ, and baohuosideⅠin epimedium total flavone capsule. At the same time, the effects of the above 11 compounds on osteogenic differentiation of MC3T3-E1 cells were investigated by detecting the content of alkaline phosphatase (AKP). The results showed that baohuoside Ⅱ had the highest activities, and both the activities of baohuoside Ⅱ and icariside Ⅰ were stronger than those of icariin.In this study, the content determination method of flavonoid glycosides was established, and the anti-osteoporosis effect of monomers was compared, providing technical support for the study of the pharmacodynamic and mechanism of Epimedium total flavone capsule.


Assuntos
Epimedium/química , Flavonas/análise , Flavonoides/análise , Osteogênese/efeitos dos fármacos , Células 3T3 , Animais , Camundongos , Osteoporose , Compostos Fitoquímicos/análise
19.
Int Wound J ; 14(1): 46-52, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26695819

RESUMO

To perform a meta-analysis of published literature to assess the role of high-concentration inspired oxygen in reducing the incidence of surgical site infections (SSIs) following all types of surgery, a comprehensive search for published randomized controlled trials (RCTs) comparing high- with low-concentration inspired oxygen for SSIs was performed. The related data were extracted by two independent authors. The fixed and random effects methods were used to combine data. Twelve RCTs involving 6750 patients were included. Our pooled result found that no significant difference in the incidence of SSIs was observed between the two groups, but there was high statistic heterogeneity across the studies [risk ratio (RR): 0·91; 95% confidence interval (CI): 0·72-1·14; P = 0·40; I2 = 54%]. The sensitivity analysis revealed the superiority of high-concentration oxygen in decreasing the SSI rate (RR: 0·86; 95% CI: 0·75-0·98; P = 0·02). Moreover, a subgroup analysis of studies with intestinal tract surgery showed that patients experienced less SSI when high-concentration inspired oxygen was administrated (RR: 0·53; 95% CI: 0·37-0·74; P = 0·0003). Our study provided no direct support for high-concentration inspired oxygen in reducing the incidence of SSIs in patients undergoing all types of surgery.


Assuntos
Oxigênio/administração & dosagem , Medição de Risco/estatística & dados numéricos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade
20.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(3): 317-21, 2016 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-27236889

RESUMO

OBJECTIVE: To assess the effect of Qingfei Quyu Decoction (QQD) in preventing radiation pneumonitis in esophageal carcinoma patients by concurrent using it with chemoradiotherapy. METHODS: A total of 120 patients with mid-late stage esophageal carcinoma were randomly assigned to the treatment group (60 cases) and the control group (60 cases). All patients received concurrent radiochemotherapy. Patients in the treatment group additionally took QQD, one dose per day for 8 successive weeks. The incidence of radiation pneunonitis was compared between the two groups. The improvement rates of short-term benefit rate, Karnofsky performance scale (KPS), and body weight (BW) improvement rate were calculated between the two groups. The 1-and 2-year overall survival rates were compared between the two groups. RESULTS: The incidence of radiation pneunonitis was 8.93% (15/56) in the treatment group and 18.64% (11/59) in the control group (P < 0.05). The short-term benefit rate was 92.86% (52/56) in the treatment group and 69.49% (41/59) in the control group (P < 0.05). Besides, the KPS and BW improvement rate were higher in the treatment group [89.29% (50/56) and 83.05% (49/59) ] than in the control group [80.36% (45/56) and 66.10% (39/59)] (P < 0.05). The 1-and 2-year overall survival rate were 66.07% and 35.71% in the treatment group, higher than those of the control group (61.02% and 30.51%; P > 0.05). CONCLUSION: Concurrent using QQD with chemoradiotherapy for treating esophageal carcinoma patients could lower the incidence of radiation pneumonitis, attenuate the degree of radiation induced lung injury, improve clinical benefit rate, and elevate their QOL.


Assuntos
Quimiorradioterapia/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Pneumonite por Radiação/prevenção & controle , Carcinoma de Células Escamosas , Humanos , Taxa de Sobrevida
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