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1.
Proc Natl Acad Sci U S A ; 121(20): e2320674121, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38684007

RESUMO

Identifying and protecting hotspots of endemism and species richness is crucial for mitigating the global biodiversity crisis. However, our understanding of spatial diversity patterns is far from complete, which severely limits our ability to conserve biodiversity hotspots. Here, we report a comprehensive analysis of amphibian species diversity in China, one of the most species-rich countries on Earth. Our study combines 20 y of field surveys with new molecular analyses of 521 described species and also identifies 100 potential cryptic species. We identify 10 hotspots of amphibian diversity in China, each with exceptional species richness and endemism and with exceptional phylogenetic diversity and phylogenetic endemism (based on a new time-calibrated, species-level phylogeny for Chinese amphibians). These 10 hotspots encompass 59.6% of China's described amphibian species, 49.0% of cryptic species, and 55.6% of species endemic to China. Only four of these 10 hotspots correspond to previously recognized biodiversity hotspots. The six new hotspots include the Nanling Mountains and other mountain ranges in South China. Among the 186 species in the six new hotspots, only 9.7% are well covered by protected areas and most (88.2%) are exposed to high human impacts. Five of the six new hotspots are under very high human pressure and are in urgent need of protection. We also find that patterns of richness in cryptic species are significantly related to those in described species but are not identical.


Assuntos
Anfíbios , Biodiversidade , Filogenia , Animais , Anfíbios/classificação , China , Conservação dos Recursos Naturais
2.
Brain Behav Immun ; 107: 76-86, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36198341

RESUMO

Current treatments for chronic pain are unsatisfactory, therefore, new therapeutics are urgently needed. Our previous study indicated that KATP channel openers have analgesic effects, but the underlying mechanism has not been elucidated. We speculated that KATP channel openers might increase suppressor of cytokine signaling (SOCS)-3 expression to induce inflammatory tolerance and attenuate chronic pain. Postoperative pain was induced by plantar incision to establish a chronic pain model. Growth arrest-specific 6 (Gas6)-/- and Axl-/- mice were used for signaling studies. The microglia cell line BV-2 was cultured for the in vitro experiments. The KATP channel opener significantly attenuated incision-induced mechanical allodynia in mice associated with the upregulated expression of SOCS3. Opening KATP channels induced the expression of SOCS3 in the Gas6/Axl signaling pathway in microglia, inhibited incision-induced mechanical allodynia by activating the Gas6/Axl-SOCS3 signaling pathway, and induced inflammatory tolerance to relieve neuroinflammation and postoperative pain. We demonstrated that opening of the KATP channel opening activated Gas6/Axl/SOCS3 signaling to induce inflammatory tolerance and relieve chronic pain. We explored a new target for anti-inflammatory and analgesic effects by regulating the innate immune system and provided a theoretical basis for clinical preemptive analgesia.


Assuntos
Dor Crônica , Animais , Camundongos , Dor Crônica/prevenção & controle , Dor Pós-Operatória , Trifosfato de Adenosina
3.
Int J Mol Sci ; 24(5)2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36901721

RESUMO

Pancreatic cancer is projected to be the second leading cause of cancer-related death by 2030 in the US. The benefits of the most common systemic therapy for various pancreatic cancers have been masked by high drug toxicities, adverse reactions, and resistance. The use of nanocarriers such as liposomes to overcome these unwanted effects has become very popular. This study aims to formulate 1,3-bistertrahydrofuran-2yl-5FU (MFU)-loaded liposomal nanoparticles (Zhubech) and to evaluate itsstability, release kinetics, in vitro and in vivo anticancer activities, and biodistribution in different tissues. Particle size and zeta potential were determined using a particle size analyzer, while cellular uptake of rhodamine-entrapped liposomal nanoparticles (Rho-LnPs) was determined by confocal microscopy. Gadolinium hexanoate (Gd-Hex) was synthesized and entrapped into the liposomal nanoparticle (LnP) (Gd-Hex-LnP), as a model contrast agent, to evaluate gadolinium biodistribution and accumulation by LnPs in vivo using inductively coupled plasma mass spectrometry (ICP-MS). The mean hydrodynamic diameters of blank LnPs and Zhubech were 90.0 ± 0.65 nm and 124.9 ± 3.2 nm, respectively. The hydrodynamic diameter of Zhubech was found to be highly stable at 4 °C and 25 °C for 30 days in solution. In vitro drug release of MFU from Zhubech formulation exhibited the Higuchi model (R2 value = 0.95). Both Miapaca-2 and Panc-1 treated with Zhubech showed reduced viability, two- or four-fold lower than that of MFU-treated cells in 3D spheroid (IC50Zhubech = 3.4 ± 1.0 µM vs. IC50MFU = 6.8 ± 1.1 µM) and organoid (IC50Zhubech = 9.8 ± 1.4 µM vs. IC50MFU = 42.3 ± 1.0 µM) culture models. Confocal imaging confirmed a high uptake of rhodamine-entrapped LnP by Panc-1 cells in a time-dependent manner. Tumor-efficacy studies in a PDX bearing mouse model revealed a more than 9-fold decrease in mean tumor volumes in Zhubech-treated (108 ± 13.5 mm3) compared to 5-FU-treated (1107 ± 116.2 mm3) animals, respectively. This study demonstrates that Zhubech may be a potential candidate for delivering drugs for pancreatic cancer treatment.


Assuntos
Nanopartículas , Neoplasias Pancreáticas , Animais , Camundongos , Lipossomos/química , Gadolínio/uso terapêutico , Distribuição Tecidual , Neoplasias Pancreáticas/tratamento farmacológico , Fluoruracila/uso terapêutico , Nanopartículas/química , Neoplasias Pancreáticas
4.
J Food Sci Technol ; 59(10): 4108-4121, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36193355

RESUMO

Dongli, or frozen pear, is a traditional Chinese snack with a unique flavor. This study identified the aroma-active volatile compounds (VOCs) in Dongli using quantitative descriptive analysis (QDA), gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS/MS), and gas chromatography-olfactometry (GC-O). QDA indicated that Dongli of all cultivars presented increased sweet and wine aromas. A total of 21 VOCs were identified by GC-MS/MS. Bidirectional orthogonal partial least square (O2PLS) analysis, GC-O analysis, detection frequency analysis (DFA), and relative odor activity values (ROAV) showed that: estragole and anethole contributing "anise, green" aromas were the key aromatic VOCs of fresh pears, while ethyl butanoate, butyl acetate, heptyl acetate, benzaldehyde, and geranyl acetone contributing "sweet, fruity, green" aromas were the key aromatic VOCs of Dongli. The results revealed that the repeated freezing treatment promoted a unique aroma in pears. This study would contribute to developing new pear products. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05463-8.

5.
J Nanobiotechnology ; 19(1): 210, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261493

RESUMO

BACKGROUND: We investigated the therapeutic effect of targeting extracellular vesicles (EVs) loaded with indocyanine green (ICG) and paclitaxel (PTX) on glioma. METHODS: Raw264.7 cells were harvested to extract EVs for the preparation of ICG/PTX@RGE-EV by electroporation and click chemistry. We evaluated the success of modifying Neuropilin-1 targeting peptide (RGE) on the EV membrane of ICG/PTX@RGE-EV using super-resolution fluorescence microscopy and flow cytometry. Spectrophotometry and high performance liquid chromatography (HPLC) were implemented for qualitative and quantitative analysis of the ICG and PTX loaded in EVs. Photothermal properties of the vesicles were evaluated by exposing to 808-nm laser light. Western blot analysis, cell counting kit 8 (CCK-8), Calcein Acetoxymethyl Ester/propidium iodide (Calcein-AM/PI) staining, and flow cytometry were utilized for assessing effects of vesicle treatment on cellular behaviors. A nude mouse model bearing glioma was established to test the targeting ability and anti-tumor action of ICG/PTX@RGE-EV in vivo. RESULTS: Under exposure to 808-nm laser light, ICG/PTX@RGE-EV showed good photothermal properties and promotion of PTX release from EVs. ICG/PTX@RGE-EV effectively targeted U251 cells, with activation of the Caspase-3 pathway and elevated apoptosis in U251 cells through chemotherapy combined with hyperthermia. The anti-tumor function of ICG/PTX@RGE-EV was confirmed in the glioma mice via increased accumulation of PTX in the ICG/PTX@RGE-EV group and an increased median survival of 48 days in the ICG/PTX@RGE-EV group as compared to 25 days in the PBS group. CONCLUSION: ICG/PTX@RGE-EV might actively target glioma to repress tumor growth by accelerating glioma cell apoptosis through combined chemotherapy-hyperthermia.


Assuntos
Biomimética/métodos , Vesículas Extracelulares/efeitos dos fármacos , Glioma/tratamento farmacológico , Hipertermia/tratamento farmacológico , Verde de Indocianina/química , Raios Infravermelhos , Nanopartículas/química , Imagem Óptica/métodos , Paclitaxel/farmacologia , Animais , Caspase 3 , Linhagem Celular Tumoral , Tratamento Farmacológico/métodos , Fluorescência , Glioma/patologia , Humanos , Hipertermia/diagnóstico por imagem , Hipertermia/metabolismo , Hipertermia/patologia , Camundongos , Camundongos Nus , Neuropilina-1 , Células RAW 264.7
6.
Sheng Li Xue Bao ; 73(2): 244-252, 2021 Apr 25.
Artigo em Zh | MEDLINE | ID: mdl-33903886

RESUMO

The aim of this study was to investigate the effects of polarization program on the ability of macrophages to regulate iron metabolism. M1 and M2 macrophages were propagated in vitro from porcine alveolar macrophages 3D4/2 and polarized by cytokines. The 3D4/2 macrophages were treated with 20 ng/mL interferon gamma (IFN-γ) and 10 ng/mL interleukin-4 (IL-4) combined with 10 ng/mL macrophage colony-stimulating factor (M-CSF) to induce polarization to M1 and M2, respectively. After incubation for 24 h, the expression levels of inflammatory factors and iron-metabolism genes were determined using real-time qPCR, Western bot and immunofluorescence. The M1/M2 macrophages culture media supernatant was collected and used to treat porcine intestinal epithelial cells IPEC-J2. The proliferation ability of IPEC-J2 was detected using CCK-8 assay kit. Following exogenous addition of ammonium ferric citrate (FAC) to M1/M2 macrophages, the phagocytic function of macrophages was detected using fluorescein isothiocyanate-dextran (FITC-dextran) and flow cytometry. The results showed that, compared with control, M1 macrophages had higher mRNA levels of iron storage proteins (ferritin heavy and light polypeptide, i.e. FtH and FtL), hepcidin and lipocalin-2, as well as iron content. Moreover, iron enhanced the ability of M1 macrophages to phagocytize FITC-dextran. There was no significant change in these mRNA expression levels in M2 macrophages, but the mRNA expression levels of ferroportin and transferrin receptor were up-regulated. In addition, the conditioned media supernatant from M2 macrophages promoted cell proliferation of IPEC-J2. These findings indicate that M1 macrophages tend to lock iron in the cell and reduce extracellular iron content, thereby inhibiting the proliferation of extracellular bacteria. While M2 macrophages tend to excrete iron, which contributes to the proliferation of surrounding cells and thus promotes tissue repair.


Assuntos
Citocinas , Macrófagos , Animais , Ferritinas , Ferro/metabolismo , Macrófagos/metabolismo , Macrófagos Alveolares/metabolismo , Suínos
7.
Cancer Cell Int ; 20: 518, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33117083

RESUMO

BACKGROUND: Glioma is the most frequent and lethal primary brain malignancy. Amounting evidence has highlighted the importance of exosomal microRNAs (miRNAs or miRs) in this malignancy. This study aimed to investigate the regulatory role of exosomal miR-148a-3p in glioma. METHODS: Bioinformatics analysis was firstly used to predict the target genes of miR-148a-3p. Exosomes were then extracted from normal human astrocytes and glioma cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to determine the expression patterns of miR-148a-3p and ERBB receptor feedback inhibitor 1 (ERRFI1). Dual-luciferase reporter gene assay was applied to verify the direct binding between miR-148a-3p and ERRFI1. Cell counting kit-8 and tube formation assays were further conducted to assess the proliferation and angiogenic properties of human umbilical vein endothelial cells (HUVECs) in the co-culture system with exosomes. Lastly, glioma tumor models were established in BALB/c nude mice to study the role of exosomal miR-148a-3p in vivo. RESULTS: miR-148a-3p was highly expressed, while ERRFI1 was poorly expressed in glioma. miR-148a-3p was found to be enriched in glioma cells-derived exosomes and could be transferred to HUVECs via exosomes to promote their proliferation and angiogenesis. ERRFI1 was identified as a target gene of miR-148a-3p. In addition, miR-148a-3p activated the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling pathway by inhibiting ERRFI1. In the co-culture system, our data demonstrated that glioma cells-derived exosomal miR-148a-3p down-regulated ERRFI1 and activated the EGFR/MAPK signaling pathway, so as to promote cell proliferation and angiogenesis. In vivo experimentation further demonstrated that this mechanism was responsible for the promotive role of exosomal miR-148a-3p in tumorigenesis and angiogenesis. CONCLUSION: Taken together, glioma-derived exosomal miR-148a-3p promoted tumor angiogenesis through activation of the EGFR/MAPK signaling pathway by ERRFI1 inhibition.

8.
Molecules ; 25(7)2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32218351

RESUMO

Lactoferrin (Lf) is a conserved iron-binding glycoprotein with antimicrobial activity, which is present in secretions that recover mucosal sites regarded as portals of invaded pathogens. Although numerous studies have focused on exogenous Lf, little is known about its expression of endogenous Lf upon bacterial infection. In this study, we investigated the distribution of Lf in mice intestine during Escherichia coli (E. coli) K88 infection. PCR and immunohistology staining showed that mRNA levels of Lf significantly increased in duodenum, ileum and colon, but extremely decreased in jejunum at 8 h and 24 h after infection. Meanwhile, endogenous Lf was mostly located in the lamina propria of intestine villi, while Lf receptor (LfR) was in the crypts. It suggested that endogenous Lf-LfR interaction might not be implicated in the antibacterial process. In addition, it was interesting to find that the infiltration of neutrophils into intestine tissues was changed similarly to Lf expression. It indicated that the variations of Lf expression were rather due to an equilibrium between the recruitment of neutrophils and degranulation of activated neutrophils. Thus, this new knowledge will pave the way to a more effective understanding of the role of Lf in intestinal mucosal immunity.


Assuntos
Infecções Bacterianas/metabolismo , Intestinos/microbiologia , Intestinos/patologia , Lactoferrina/metabolismo , Neutrófilos/metabolismo , Animais , Infecções Bacterianas/complicações , Infecções Bacterianas/microbiologia , Modelos Animais de Doenças , Escherichia coli/fisiologia , Inflamação/complicações , Inflamação/patologia , Masculino , Camundongos Endogâmicos C57BL
9.
J Food Sci Technol ; 57(9): 3390-3399, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32728286

RESUMO

Turnip is a vegetable that has many health promoting effects. To diversify the usage and increase the consumption of turnip, the effects of hot air drying, infrared drying, explosion puff drying and freeze drying (FD) on the volatiles of turnip chips were studied. The volatiles of fresh turnip and dried turnip chips were isolated by HS-SPME-GC-MS and a total of 67 volatiles were identified. However, the volatiles in turnip chips dried by different methods are quite different. Based on principal component analysis and hierarchical cluster analysis, the volatiles of fresh turnip were distinguished from those of the dried chips and FD was separated from the other drying methods. As the result of orthogonal projection on latent structure-discriminant analysis (OPLS-DA), isothiocyanato-cyclopropane and (2-isothiocyanatoethyl)-benzene were identified as the characteristic volatiles of fresh turnip. While, 2-azido-2,3,3-trimethyl-butane and hexanal were identified as the characteristic volatiles for FD dried chips.

10.
J Food Sci Technol ; 57(5): 1619-1627, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32327772

RESUMO

Yam soluble protein (YSP) has been reported to have many physiological activities, such as scavenging free radicals, immune activation, and anti-hypertensive activities. Protein solubility and emulsifying activity are important protein-associated functional properties for the application of proteins in food systems. During this study, the factors of protein concentration, pH, temperature and salt concentration that influenced the solubility of YSP were investigated. As a result, the solubility was minimal near its isoelectric point (pH 3.5) and was highest at 45 °C in a temperature range of 40-60 °C. With an increase of protein concentration, the solubility decreased. According to the results of response surface methodology analysis, the interaction between pH and temperature on the solubility of YSP was significant, and the maximum solubility (87.5%) was obtained when the temperature was close to 40 °C, the pH was approximately 7 and the NaCl concentration approached 0.5 mol/L. As the protein concentration increased, the average particle size of the YSP emulsion decreased, and the particle size distribution gradually became balanced. Additionally, the microphotograph of the YSP emulsion reflected its distribution. The results of this study will provide data and a theoretical basis for the understanding of YSP's physicochemical properties and its application in the food industry.

11.
Ecotoxicol Environ Saf ; 169: 325-334, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30458399

RESUMO

Polybrominated diphenyl ethers (PBDEs) are organic pollutants (POPs) with the characteristics of environmental persistence, long-distance transmission in nature, biological accumulation and toxic effects on human health. To investigate the level of contamination due to PBDEs in typical indoor public places in Hangzhou, dust samples were collected from ten supermarkets, three electronic markets and five different areas throughout one commodity market. Based on sample pretreatment and GC-ECD instrumental analysis, the contamination characteristics, sources and the influencing factors of 14 PBDE congeners were analyzed. The results revealed that the mean of ∑14PBDEs in dust in the supermarkets and electronic markets was 546.13 ng/g and 1140.05 ng/g, respectively, while in the commodity market the mean was 1005.42 ng/g and varied in the five different areas as follows: shoe areas (1367.22 ng/g) > parking lot (1001.05 ng/g) > waiting halls (970.31 ng/g) > packet areas (933.23 ng/g) > curtain areas (755.28 ng/g). The high levels of PBDE were attributed to the quantity of electrical appliances in the supermarkets (r = 0.708*, p < 0.05) and the electronic markets (r = 0.799**, p < 0.05) through Spearman correlation coefficient analysis. BDE-209 was the dominant congener, accounting for 53.72% in supermarkets and 64.25% in electronic markets. The calculated inhalation exposure revealed that the exposure level of PBDEs varied in supermarkets, electronic markets and commodity markets, with values of 0.476 ng/day/kg, 0.993 ng/day/kg and 0.876 ng/day/kg, respectively. Moreover, BDE-209's contribution to the total intake of PBDEs was the highest, with a value of 0.072-0.970 ng/day/kg, while the value of BDE-183 was the lowest, with a value of 0-0.020 ng/day/kg. The exposure level of PBDEs in the studied indoor public places was lower than the reference dose of EPA.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Poeira/análise , Monitoramento Ambiental/métodos , Éteres Difenil Halogenados/análise , Exposição por Inalação/análise , China , Humanos
12.
J Comput Aided Mol Des ; 32(11): 1217-1227, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30392073

RESUMO

Genetics experiments have identified six mutations located in the subdomain IA (A17V, R23H, G32D, G32S, R34K, V372I) of Ssa1 that influence propagation of the yeast [PSI+] prion. However, the underlining molecular mechanisms of these mutations are still unclear. The six mutation sites are present in the IA subdomain of the nucleotide-binding domain (NBD). The ATPase subdomain IA is a critical mediator of inter-domain allostery in Hsp70 molecular chaperones, so the mutation and changes in this subdomain may influence the function of the substrate-binding domain. In addition, ADP release is a rate-limiting step of the ATPase cycle and dysregulation of the ATPase cycle influences the propagation of the yeast [PSI+] prion. In this work, steered molecular dynamics (SMD) simulations were performed to explore the interaction between ADP and NBD. Results suggest that during the SMD simulations, hydrophobic interactions are predominant and variations in the binding state of ADP within the mutants is a potential reason for in vivo effects on yeast [PSI+] prion propagation. Additionally, we identify the primary residues in the ATPase domain that directly constitute the main hydrophobic interaction network and directly influence the ADP interaction state with the NBD of Ssa1. Furthermore, this in silico analysis reaffirms the importance of previously experimentally-determined residues in the Hsp70 ATPase domain involved in ADP binding and also identifies new residues potentially involved in this process.


Assuntos
Difosfato de Adenosina/química , Adenosina Trifosfatases/química , Proteínas de Choque Térmico HSP70/química , Simulação de Dinâmica Molecular , Proteínas de Saccharomyces cerevisiae/química , Adenosina Trifosfatases/genética , Sítios de Ligação , Simulação por Computador , Proteínas de Choque Térmico HSP70/genética , Mutação , Fatores de Terminação de Peptídeos/química , Ligação Proteica , Conformação Proteica , Domínios Proteicos , Proteínas de Saccharomyces cerevisiae/genética
13.
J Food Sci Technol ; 55(1): 381-388, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29358831

RESUMO

In this study, yam soluble protein (YSP) was extracted from Chinese yam (Dioscorea opposita Thunb. cv. Baiyu) and the functional properties were investigated under the influence of pH and ionic strength. As results, YSP was highly soluble and had better emulsifying activity over a wide range of pH. The solubility of YSP decreased in 0.5 and 1.0 M NaCl solution. An increment in NaCl concentration reduced the emulsion activity index and emulsion stability index of YSP. The oil absorption capacity of YSP was 3.2 ml/g protein. With the increase of pH, the foam capacity (FC) and stability (FS) decreased and then increased. FS of YSP increased as the salt concentration increased from 0 to 0.5 M, and then decreased. The minimal gelation concentration of YSP was 8% (w/v) and 10% YSP gel (w/v) had maximum gel strength in 0.1 M NaCl. These results suggested that YSP produced by acid precipitation may be used as a protein source with remarkable functional properties.

14.
J Neuroinflammation ; 14(1): 228, 2017 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-29178967

RESUMO

BACKGROUND: Long-term use of morphine induces analgesic tolerance, which limits its clinical efficacy. Evidence indicated morphine-evoked neuroinflammation mediated by toll-like receptor 4 (TLR4) - NOD-like receptor protein 3 (NLRP3) inflammasome was important for morphine tolerance. In our study, we investigated whether other existing alternative pathways caused morphine-induced activation of TLR4 in microglia. We focused on heat shock protein 70 (HSP70), a damage-associated molecular pattern (DAMP), which was released from various cells upon stimulations under the control of KATP channel and bound with TLR4-inducing inflammation. Glibenclamide, a classic KATP channel blocker, can improve neuroinflammation by inhibiting the activation of NLRP3 inflammasome. Our present study investigated the effect and possible mechanism of glibenclamide in improving morphine tolerance via its specific inhibition on the release of HSP70 and activation of NLRP3 inflammasome induced by morphine. METHODS: CD-1 mice were used for tail-flick test to evaluate morphine tolerance. The microglial cell line BV-2 and neural cell line SH-SY5Y were used to investigate the pharmacological effects and the mechanism of glibenclamide on morphine-induced neuroinflammation. The activation of microglia was accessed by immunofluorescence staining. Neuroinflammation-related cytokines were measured by western blot and real-time PCR. The level of HSP70 and related signaling pathway were evaluated by western blot and immunofluorescence staining. RESULTS: Morphine induced the release of HSP70 from neurons. The released HSP70 activated microglia and triggered TLR4-mediated inflammatory response, leading to the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) p65 and the activation of NLRP3 inflammasome. Moreover, anti-HSP70 neutralizing antibody partly attenuated chronic morphine tolerance. The secretion of HSP70 was under the control of MOR/AKT/KATP/ERK signal pathway. Glibenclamide as a classic KATP channel blocker markedly inhibited the release of HSP70 induced by morphine and suppressed HSP70-TLR4-NLRP3 inflammasome-mediated neuroinflammation, which consequently attenuated morphine tolerance. CONCLUSIONS: Our study indicated that morphine-induced extracellular HSP70 was an alternative way for the activation of TLR4-NLRP3 in analgesic tolerance. The release of HSP70 was regulated by MOR/AKT/KATP/ERK pathway. Our study suggested a promising target, KATP channel and a new leading compound, glibenclamide, for treating morphine tolerance.


Assuntos
Tolerância a Medicamentos/fisiologia , Proteínas de Choque Térmico HSP70/metabolismo , Canais KATP/antagonistas & inibidores , Morfina , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptor 4 Toll-Like/imunologia , Animais , Glibureto/farmacologia , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Canais KATP/efeitos dos fármacos , Camundongos , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo
15.
Acta Chim Slov ; 64(3): 633-637, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28862301

RESUMO

Two CuI complexes based on the π-conjugated tetrathiafulvalene-annulated phenanthroline ligands (TTF-Phen, L1 and L2), [CuI(Xantphos)(L1)]BF4 (1, Xantphos = 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene) and [CuI(Binap)(L2)]BF4 (2, Binap = 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl), have been synthesized. They have been fully characterized, and their photophysical and electrochemical properties are reported together with those of L1 and L2 for comparison. Both CuI complexes show metal-to-ligand charge transfer (MLCT) absorption bands, whereas the 3MLCT luminescence is strongly quenched.

16.
Tumour Biol ; 36(1): 421-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25266804

RESUMO

Rho-associated protein kinase 1 (ROCK1), a serine/threonine protein kinase, affects cell invasion and migration by changing the status of the cytoskeleton. In recent years, ROCK1 was found to be overexpressed in a variety of tumors. However, the information of ROCK1 in glioma still remains elusive. In our study, the expression of ROCK1 in glioma tissues was examined by real-time PCR and the relationship between ROCK1 expression and clinical characteristics of patients with glioma was also analyzed. With the inhibition of ROCK1 expression by RNAi, the effects of ROCK1 on biological behaviors of glioma cells including cell viability, cell cycle, and cell invasion were probed in the U251 cell line by methyl thiazolyl tetrazolium (MTT) assay, flow cytometer analysis, and Transwell invasion experiment. In addition, the effects of ROCK1 on the regulation of Ki67, cyclin D1, matrix metalloproteinases 9 (MMP9), and E-cadherin were also investigated. The results indicated that ROCK1 messenger RNA (mRNA) was increased significantly compared to that in the adjacent normal tissue (P < 0.05) and the expression level of ROCK1 mRNA in high-grade malignant glioma tissue was significantly higher than that in low-grade malignant glioma tissue (P < 0.05). MTT assay and flow cytometer analysis revealed that the cell viability and cell proliferation in the ROCK1 small interfering RNA (siRNA) transfection group were markedly lower than those in the blank or negative control group (P < 0.05), and no obvious differences were found between the blank group and negative control group. The Transwell invasion experiments showed that the invasive ability of U251 cells in the ROCK1 siRNA transfection group was obviously lower than that in the blank or negative control group (P < 0.05), and there were no visible differences between the blank group and negative control group. Western blot demonstrated that the protein levels of Ki67, cyclin D1, and MMP9 in the ROCK1 siRNA transfection group were distinctly lower than those in the blank or negative control group (P < 0.05) and that the protein level of E-cadherin displayed an opposite variation (P < 0.05). In summary, the expressions of ROCK1 in glioma tissue were visibly upregulated and the increase of ROCK1 had a positive correlation with the malignant grade of glioma. The results implied that the proliferation and metastasis of the glioma cell could be inhibited by suppressing the expression of ROCK1, and our findings would provide a new target for intervention and treatment of glioma.


Assuntos
Neoplasias Encefálicas/enzimologia , Glioma/enzimologia , Quinases Associadas a rho/genética , Adulto , Antígenos CD , Neoplasias Encefálicas/patologia , Caderinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/metabolismo , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Glioma/patologia , Humanos , Antígeno Ki-67/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Gradação de Tumores , Invasividade Neoplásica , Quinases Associadas a rho/metabolismo
17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 46(2): 301-4, 2015 Mar.
Artigo em Zh | MEDLINE | ID: mdl-25924451

RESUMO

OBJECTIVE: To seek a simple and effective approach through probing method about primary culture and purification of neonatal rat cardiac myocytes. METHODS: Twenty neonatal rats were randomly divided into 2 groups. Group A: the cardiac myocytes were gained by means of enzymic digestion and tubularis-blowing; Group B: the cardiac myocytes were gained by means of enzymic digestion and rotator-stirring. The cardiac myocytes in both groups were purified by means of differential attachment technique and BrdU inhibition and were identified with immunofluorescence staining. Viability was assessed with trypan blue staining and pulsation was assessed under microscope. RESULTS: The rates of cardiac myocyte's viability, pulsation and purity in group A were (89.90 +/- 2.92)%, (91.30 +/- 2.00)% and (94.90 +/- 1.79)% respectively; The corresponding rates in group B were (94.70 +/- 2.31)%, (95.00 +/- 1.24)% and (95.60 +/- 1.43)% respectively. The rates of cardiac myocyte's viability, pulsation in group B were significantly higher than that of group A, which was statistically different (P>0.05). The rate of cardiac myocytes purity in group B was a bit higher than group A, but which wasn't statistically different (P<0.05). Fibroblasts cultured with BrdU grew weaker and less than those without BrdU. CONCLUSION: The method of rotator-stirring and enzymic digestion was better than that of tubularis-blowing and enzymic digestion, which helped to gain cardiac myocyte effectively. BrdU helped to purify cardiac myocytes.


Assuntos
Miócitos Cardíacos/citologia , Cultura Primária de Células , Animais , Animais Recém-Nascidos , Bromodesoxiuridina , Células Cultivadas , Fibroblastos , Ratos
18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(2): 498-504, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24822428

RESUMO

Fast Fourier transforms (FFT) is a basic approach to remote sensing image processing. With the improvement of capacity of remote sensing image capture with the features of hyperspectrum, high spatial resolution and high temporal resolution, how to use FFT technology to efficiently process huge remote sensing image becomes the critical step and research hot spot of current image processing technology. FFT algorithm, one of the basic algorithms of image processing, can be used for stripe noise removal, image compression, image registration, etc. in processing remote sensing image. CUFFT function library is the FFT algorithm library based on CPU and FFTW. FFTW is a FFT algorithm developed based on CPU in PC platform, and is currently the fastest CPU based FFT algorithm function library. However there is a common problem that once the available memory or memory is less than the capacity of image, there will be out of memory or memory overflow when using the above two methods to realize image FFT arithmetic. To address this problem, a CPU and partitioning technology based Huge Remote Fast Fourier Transform (HRFFT) algorithm is proposed in this paper. By improving the FFT algorithm in CUFFT function library, the problem of out of memory and memory overflow is solved. Moreover, this method is proved rational by experiment combined with the CCD image of HJ-1A satellite. When applied to practical image processing, it improves effect of the image processing, speeds up the processing, which saves the time of computation and achieves sound result.

19.
PLoS One ; 19(3): e0299392, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38512922

RESUMO

Skin cancer is one of the most common malignant tumors worldwide, and early detection is crucial for improving its cure rate. In the field of medical imaging, accurate segmentation of lesion areas within skin images is essential for precise diagnosis and effective treatment. Due to the capacity of deep learning models to conduct adaptive feature learning through end-to-end training, they have been widely applied in medical image segmentation tasks. However, challenges such as boundary ambiguity between normal skin and lesion areas, significant variations in the size and shape of lesion areas, and different types of lesions in different samples pose significant obstacles to skin lesion segmentation. Therefore, this study introduces a novel network model called HDS-Net (Hybrid Dynamic Sparse Network), aiming to address the challenges of boundary ambiguity and variations in lesion areas in skin image segmentation. Specifically, the proposed hybrid encoder can effectively extract local feature information and integrate it with global features. Additionally, a dynamic sparse attention mechanism is introduced, mitigating the impact of irrelevant redundancies on segmentation performance by precisely controlling the sparsity ratio. Experimental results on multiple public datasets demonstrate a significant improvement in Dice coefficients, reaching 0.914, 0.857, and 0.898, respectively.


Assuntos
Dermatopatias , Neoplasias Cutâneas , Humanos , Dermatopatias/diagnóstico por imagem , Pele/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Processamento de Imagem Assistida por Computador
20.
Food Chem ; 453: 139581, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-38754354

RESUMO

This study investigated the impact of ultrasound treatment on dioscorin, the primary storage protein found in yam tubers. Three key factors, namely ultrasound power, duration, and frequency, were focused on. The research revealed that ultrasound-induced cavitation effects disrupted non-covalent bonds, resulting in a reduction in α-helix and ß-sheet contents, decreased thermal stability, and a decrease in the apparent hydrodynamic diameter (Dh) of dioscorin. Additionally, previously hidden amino acid groups within the molecule became exposed on its surface, resulting in increased surface hydrophobicity (Ho) and zeta-potential. Under specific ultrasound conditions (200 W, 25 kHz, 30 min), Dh decreased while Ho increased, facilitating the adsorption of dioscorin molecules onto the oil-water interface. Molecular dynamics (MD) simulations showed that at lower frequencies and pressures, the structural flexibility of dioscorin's main chain atoms increased, leading to more significant fluctuations between amino acid residues. This transformation improved dioscorin's emulsifying properties and its oil-water interface affinity.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Dioscorea/química , Emulsões/química , Proteínas de Plantas/química , Ondas Ultrassônicas
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