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1.
Neural Regen Res ; 18(2): 416-421, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35900439

RESUMO

Radiation therapy is considered the most effective non-surgical treatment for brain tumors. However, there are no available treatments for radiation-induced brain injury. Bisdemethoxycurcumin (BDMC) is a demethoxy derivative of curcumin that has anti-proliferative, anti-inflammatory, and anti-oxidant properties. To determine whether BDMC has the potential to treat radiation-induced brain injury, in this study, we established a rat model of radiation-induced brain injury by administering a single 30-Gy vertical dose of irradiation to the whole brain, followed by intraperitoneal injection of 500 µL of a 100 mg/kg BDMC solution every day for 5 successive weeks. Our results showed that BDMC increased the body weight of rats with radiation-induced brain injury, improved learning and memory, attenuated brain edema, inhibited astrocyte activation, and reduced oxidative stress. These findings suggest that BDMC protects against radiation-induced brain injury.

2.
Biotechnol Bioeng ; 119(3): 743-761, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34936091

RESUMO

For drug products manufactured in mammalian cells, safety assurance practices are needed during production to assure that the final medicinal product is safe from the potential risk of viral contamination. Virus filters provide viral retention for a range of viruses through robust, largely size-based retention mechanism. Therefore, a virus filtration step is commonly utilized in a well-designed recombinant therapeutic protein purification process and is a key component in an overall strategy to minimize the risks of adventitious and endogenous viral particles during the manufacturing of biotechnology products. This study summarizes the history of virus filtration, currently available virus filters and prefilters, and virus filtration integrity test methods and study models. There is also discussion of current understanding and gaps with an eye toward future trends and emerging filtration technologies.


Assuntos
Vírus , Animais , Biotecnologia/métodos , Contaminação de Medicamentos/prevenção & controle , Filtração , Mamíferos , Vírion
3.
Front Cell Dev Biol ; 10: 999547, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36393846

RESUMO

Aim: Bladder outlet obstruction (BOO) leads to bladder wall remodeling accompanying the progression from inflammation to fibrosis where pathological hydrostatic pressure (HP)-induced alteration of bladder smooth muscle cells (BSMCs) hypertrophic and excessive extracellular matrix (ECM) deposition play a pivotal role. Recently, we have predicted survivin (BIRC5) as a potential hub gene that might be critical during bladder fibrosis by bioinformatics analyses from rat BOO bladder, but its function during BOO progression remains unknown. Here, we investigated the role of survivin protein on bladder dysfunction of BOO both in vitro and in vivo. Methods: Sprague-Dawley female rats were divided into three groups: control group, BOO group, and BOO followed by the treatment with YM155 group. Bladder morphology and function were evaluated by Masson staining and urodynamic testing. To elucidate the underlying mechanism, hBSMCs were subjected to pathological HP of 200 cm H2O and co-cultured with the presence or absence of survivin siRNA and/or autophagy inhibitor 3-MA. Autophagy was evaluated by the detection of Beclin1 and LC3B-II expression, proliferation was conducted by the EdU analysis and PCNA expression, and fibrosis was assessed by the examination of Col 1 and Fn expression. Results: BOO led to a gradual alteration of hypertrophy and fibrosis of the bladder, and subsequently induced bladder dysfunction accompanied by increased survivin expression, while these histological and function changes were attenuated by the treatment with YM155. HP significantly increased survivin expression, upregulated Col1 and Fn expression, enhanced proliferation, and downregulated autophagy markers, but these changes were partially abolished by survivin siRNA treatment, which was consistent with the results of the BOO rat experiment. In addition, the anti-fibrotic and anti-proliferative effects of the survivin siRNA treatment on hBSMCs were diminished after the inhibition of autophagy by the treatment with 3-MA. Conclusion: In summary, the upregulation of survivin increased cell proliferation and fibrotic protein expression of hBSMC and drove the onset of bladder remodeling through autophagy during BOO. Targeting survivin in pathological hBSMCs could be a promising way to anti-fibrotic therapeutic approach in bladder remodeling secondary to BOO.

4.
J Psycholinguist Res ; 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36427114

RESUMO

There is a heated debate on a learning paradigm known as "fast mapping" for its early neocortical dependence and retained memory over time for amnesic patients with hippocampal system damage. Whether the fast mapping allows hippocampus independent learning and induces rapid integration is poorly understood. The present study aims to investigate the effect of fast mapping on very long-term retention, which to our knowledge has not been previously explored. We tested memory retention ranging from 10 min to 1.5 years, for novel word-object associations learned from fast mapping or explicit encoding procedures. The three-alternative forced choice recognition task was employed to assess memory performance. Besides the slight adjustment of the testing schedule, other settings remained the same in Experiment 2 to replicate and verify the findings of Experiment 1. Results showed that overall memory retrieval performance was higher after explicit encoding as compared to fast mapping. However, retrieval performance after explicit encoding dropped after 1.5 years, but remained stable in the fast mapping condition. Furthermore, matching the semantic category of the known and the novel items during the fast mapping paradigm might affect long-term retention. These results suggest that fast mapping creates more stable long-term memory representations as compared to the explicit encoding strategy.

5.
J Int Med Res ; 50(11): 3000605221136679, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36396946

RESUMO

The most commonly used methods for pathogen detection and identification in oral mucosal infectious diseases are DNA or RNA quantitative polymerase chain reaction detection, bacterial or fungal cultures, and immunohistochemical analysis. These traditional methods are time-consuming and can only detect one specific targeted pathogen at a time. An efficient and sensitive method with higher species richness is urgently needed. Metagenomic next-generation sequencing (mNGS) is a new method of pathogen detection with high efficiency and sensitivity. In this case report, mNGS was used to identify the pathogens in oral mucosal tissues of a patient with complex oral mucosal infections and oral leukoplakia. Candida albicans, human gamma herpesvirus 4, and many other pathogens were identified using this method. For complex oral mucosal infections, mNGS is a more efficient and sensitive approach that can replace conventional detection methods.


Assuntos
Doenças Transmissíveis , Metagenômica , Humanos , Sensibilidade e Especificidade , Metagenômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Membrana Mucosa
6.
Adv Clin Exp Med ; 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36413180

RESUMO

BACKGROUND: Hepatic fibrosis (HF) is a common pathological complication of liver cirrhosis which affects human health. It is well established that microRNAs (miRNAs) regulate the proliferation, activation and apoptosis of hepatic stellate cells (HSCs). OBJECTIVES: To determine the function and molecular mechanism of miR-340-5p/secreted phosphoprotein 1 (SPP1) axis in HF and identify potential therapeutic targets. MATERIAL AND METHODS: The HF model in cholestatic rats was induced by ligating the common bile duct. The histological sections of the liver tissues were stained with hematoxylin and eosin (H&E), Masson's trichrome or Sirius Red. The differential expression of mRNAs in the liver tissues was examined using the microarray analysis. The expression levels of miR-340-5p, SPP1, alpha-smooth muscle actin (α-SMA), Collagen I, phosphorylated Smad2 (p-Smad2), and p-Smad3 were determined using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell proliferation was quantified using cell counting kit-8 (CCK-8) assays. The regulatory effect of miR-340-5p on SPP1 was determined with fluorescent reporter assay. RESULTS: The bile duct ligation (BDL) rat model was successfully induced, and SPP1 was upregulated in liver tissue from the BDL group compared to that of the sham group. The expression level of miR-340-5p was decreased in activated human primary normal fibroblasts (NFs) and activated LX-2 cells, and the mRNA and protein expression levels of SPP1 were increased in activated LX-2 cells. The SPP1 was the target of miR-340-5p, and the overexpression of SPP1 increased the proliferation of LX-2 cells, the expression of HF markers α-SMA and Collagen I, and key factors p-Smad2 and p-Smad3 (all p < 0.05). However, reverse results were obtained with the overexpression of miR-340-5p in LX-2 cells. CONCLUSIONS: Our findings provide evidence that SPP1 targeted by miR-340-5p promotes LX-2 cell proliferation and activation through the TGF-ß1/Smads signaling pathway. Therefore, miR-340-5p and SPP1 may be possible therapeutic targets for HF.

8.
Med Sci Sports Exerc ; 54(12): 2037-2044, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36377051

RESUMO

PURPOSE: Joint deafferentation after post-ankle sprain ligament healing can disrupt sensory input from the ankle and induce maladaptive neuroplasticity, especially in the cerebellum. This study aimed to determine whether the regional homogeneity of intrinsic cerebellar activity differs between patients with ankle instability and healthy controls without a history of ankle injury. METHODS: The current study used a primary data set of 18 patients and 22 healthy controls and an external UK Biobank data set of 16 patients with ankle instability and 69 healthy controls for a cross-database, cross-sectional investigation. All participants underwent resting-state functional magnetic resonance imaging to calculate their regional homogeneity (ReHo) value. Between-group comparisons of the sensorimotor-related subregions of the cerebellum were first performed in the primary data set to identify low cerebellar ReHo in patients with multiple comparison corrections, and the surviving subregions were then externally validated in the UK Biobank data set. Correlation analyses between the ReHo values and clinical features were also performed. RESULTS: The ReHo value of cerebellar lobule VIIIb was significantly lower in the ankle instability group than in the controls (0.170 ± 0.016 vs 0.184 ± 0.019 in the primary data set, 0.157 ± 0.026 vs 0.180 ± 0.042 in the UK Biobank data set). The ReHo values of this subregion showed a significant positive correlation with the Cumberland Ankle Instability Tool scores in the ankle instability group (r = 0.553, P-corrected = 0.0348). CONCLUSIONS: Patients with ankle instability had lower intraregional coherence in cerebellar lobule VIIIb than that of controls, which was also positively correlated with the intensity of self-reported ankle instability.


Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo , Tornozelo , Estudos Transversais , Cerebelo/diagnóstico por imagem
9.
Food Chem ; 405(Pt B): 134854, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36403467

RESUMO

This study aims to present retronasal aroma perception and oral aroma release of Baijiu by progressive profiling and intra-oral solid-phase microextraction (SPME) combined with comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOFMS). Fruity, alcohol, grain, and cellar were the active retronasal aroma attributes of the strong aroma type Baijiu S, and soy sauce, burnt, and roasted were attributes of the soy sauce aroma type Baijiu SS. The dynamic release behaviors of 91 oral aroma compounds of two Baijiu samples were characterized and classified into four or five groups of different oral persistence. Principal component analysis showed that vapor pressure and Henry constant were negatively correlated with the oral persistence of aroma compounds, of which the cumulative interpretation rate was 71.67%. Partial least squares regression analysis showed that aroma compounds, such as ethyl benzeneacetate, ß-phenylethanol, and tetramethylpyrazine, were related to the long-persistence retronasal aroma of Baijiu (Q2 = 0.806).

10.
Int J Biol Sci ; 18(16): 6008-6019, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439874

RESUMO

Cardiac fibrosis is one of the common pathological processes in many cardiovascular diseases characterized by excessive extracellular matrix deposition. SerpinE2 is a kind of protein that inhibits peptidase in extracellular matrix and up-regulated tremendously in mouse model of cardiac fibrosis induced by pressure-overloaded via transverse aortic constriction (TAC) surgery. However, its effect on cardiac fibroblasts (CFs), collagen secretion and the underlying mechanism remains unclear. In this study, DyLight® 488 green fluorescent dye or His-tagged proteins were used to label the exogenous serpinE2 protein. It was showed that extracellular serpinE2 translocated into CFs by low-density lipoprotein receptor-related protein 1 (LRP1) and urokinase plasminogen activator receptor (uPAR) of cell membrane through endocytosis. Knockdown of LRP1 or uPAR reduced the level of serpinE2 in CFs and down-regulated the collagen expression. Inhibition of the endocytosis of serpinE2 could inhibit ERK1/2 and ß-catenin signaling pathways and subsequently attenuated collagen secretion. Knockdown of serpinE2 attenuates cardiac fibrosis in TAC mouse. We conclude that serpinE2 could be translocated into cardiac fibroblasts due to endocytosis through directly interact with the membrane protein LRP1 and uPAR, and this process activated the ERK1/2, ß-catenin signaling pathways, consequently promoting collagen production.


Assuntos
Síndrome de Fadiga Crônica , beta Catenina , Camundongos , Animais , beta Catenina/metabolismo , Serpina E2/metabolismo , Serpina E2/farmacologia , Inibidores de Proteases/farmacologia , Sistema de Sinalização das MAP Quinases/genética , Fibrose , Transdução de Sinais/genética , Endocitose/genética , Colágeno/metabolismo
11.
iScience ; 25(12): 105563, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36444307

RESUMO

Carbon is one of the most versatile atoms and fosters a wealth of carbon allotropes with superior mechanical and electronic properties. A three-dimensional covalent carbon nanotube, named CCN, with a hexagonal honeycomb-like crystalline structure is proposed theoretically. CCN consists of sp 3 bonded coaxially teamed (6,0) carbon nanotubes, and the tube walls possess intrinsic wrinkles, which trigger miraculous physical properties. The mechanical and thermal dynamic stabilities are confirmed, and molecular dynamics simulations indicate high temperature thermal stability up to 1500 K. CCN has an unusual cork-like zero Poisson's ratio along the axial direction of the nanotubes, and the axial/radial stretching or compression rarely effects the radial/axial dimensions of the nanotubes. CCN is superhard with Vickers hardness of 82.8 GPa, matching that of cubic boron nitride. Substitution B and N atoms for C atoms result in superhard CCN-B12N8 and CCN-C8N12 with quasi-zero Poisson's radio along both axial and radial directions.

12.
Oncol Lett ; 24(6): 458, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36380876

RESUMO

Melanoma is known to be insensitive to radiotherapy; however, the present study reports the case of a patient with vulvar malignant melanoma in which near complete remission of the target area was observed after implementing immune checkpoint inhibitors (ICIs) and hypo-fractionated radiotherapy (HFRT). The patient was treated with an intensity-modulated radiation therapy technique that delivered a hypo-fractionated dose of 3,000 cGy in six fractions. After 3 days, the patient underwent immunotherapy with two cycles of 240 mg triprizumab every 2 weeks. Tumors that underwent radiotherapy had markedly decreased in size and a near complete remission of the melanoma was observed 4 months after radiotherapy. However, the metastases in the liver and lungs continued to grow, new metastases appeared in the abdominal subcutaneous tissue and enlarged lymph nodes were observed in the pelvic area. The results of the present study indicated that ICIs and HFRT exert a marked local effect, but no abscopal effect.

13.
Front Bioeng Biotechnol ; 10: 984166, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36213060

RESUMO

Photothermal therapy (PTT) has attracted extensive attention in cancer treatment due to its non-invasiveness, high efficiency, and repeatability in recent years. Photothermal agents (PTAs) are the key factor for PTT. Recently, although an increasing number of PTAs have been developed, there is still a great demand for optimized photothermal nanoparticles (NPs) with low toxicity, bio-safety and stability. Herein, new indocyanine green (IR820) with near-infrared (NIR:700-1,700 nm) fluorescence emission was selected as a photothermal agent (PTA). To enhance the PTT property, IR820 was encapsulated with another kind of PTA, polydopamine (PDA) under alkaline conditions. Furthermore, to improve the biocompatibility of the NPs, methoxy polyethylene glycol amine (mPEG-NH2) was modified via a Michael addition to form a novel kind of IR820@PDA@PEG NPs. After detailed characterization and analysis, the obtained IR820@PDA@PEG NPs showed a spherical shape with an average diameter of ∼159.6 nm. Meanwhile, the formed IR820@PDA@PEG NPs exhibited better photostability and lower cytotoxicity than free IR820 molecules. The photothermal performance of IR820@PDA@PEG NPs was further analyzed in vitro, and the temperature of IR820@PDA@PEG NPs (100 µg/ml) reached 54.8°C under 793 nm laser irradiation. Afterwards, the cellular uptake of IR820@PDA@PEG NPs was evaluated via confocal laser scanning fluorescence microscopic imaging. Then, PTT experiments on HeLa cells demonstrated that IR820@PDA@PEG NPs can hyperthermal ablate cancer cells (∼49.1%) under 793 nm laser irradiation. Therefore, IR820@PDA@PEG NPs would be a promising PTA for the treatment of cervical cancer HeLa cells.

14.
Neurochem Res ; 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36243819

RESUMO

3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3 H)-one (3BDO) is a mTOR agonist that inhibits autophagy. The main purpose of this study is to investigate the effects of 3BDO on seizure and cognitive function by autophagy regulation in pentylenetetrazol (PTZ)-kindled epileptic mice model. The PTZ-kindled epileptic mice model was used in study. The behavioral changes and electroencephalogram (EEG) of the mice in each group were observed. The cognitive functions were tested by Morris water maze test. The loss of hippocampal neurons was detected by hematoxylin-eosin (HE) staining and immunofluorescence analysis. Immunohistochemistry, western blot and q-PCR were employed to detect the expression of autophagy-related proteins and mTOR in the hippocampus and cortex. Less seizures, increased hippocampal neurons and reduced astrocytes of hippocampus were observed in the 3BDO-treated epileptic mice than in the PTZ-kindled epileptic mice. Morris water maze test results showed that 3BDO significantly improved the cognitive function of the PTZ-kindled epileptic mice. Western blot analyses and q-PCR revealed that 3BDO inhibited the expression of LC3, Beclin-1, Atg5, Atg7 and p-ULK1/ULK1, but increased that of p-mTOR/mTOR, p-P70S6K/P70S6K in the hippocampus and temporal lobe cortex of epileptic mice. Immunohistochemistry and immunofluorescence also showed 3BDO inhibited the LC3 expression and increased the mTOR expression in the hippocampus of epileptic mice. In addition, the autophagy activator EN6 reversed the decrease in the 3BDO-induced autophagy and aggravated the seizures and cognitive dysfunction in the epileptic mice. 3BDO regulates autophagy by activating the mTOR signaling pathway in PTZ-kindled epileptic mice model, thereby alleviating hippocampus neuronal loss and astrocytes proliferation, reducing seizures and effectively improving cognitive function. Therefore, 3BDO may have potential value in the treatment of epilepsy.

15.
Appl Opt ; 61(28): 8204-8211, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36256132

RESUMO

A time-resolved two-color laser induced fluorescence method is proposed for simultaneous 2D temperature and velocity measurements for complex multi-phase flow. A temperature sensitive dye molecule is used for temperature and velocity tagging at the same time. To effectively eliminate the temperature deviation due to image misalignment, which is commonly seen at the multi-phase boundary, a one-color-camera system is proposed that can decrease the temperature deviation from 30°C-50°C to <10∘C near the two-phase flow boundary with a high contrast ratio (0.41-0.43). Considering the strong influence of the thermal diffusion and convection processes to photo luminescence images' intensities, which can lead to significant velocity calculation deviation, a physically constrained temperature tagging method is introduced. Through both a theoretical model and measurement results, the relative velocity deviation can be decreased from 77.6% to <10% by this method. This work can effectively improve the temperature and velocity measurement accuracy of a temperature sensitive particle/molecule tagging method in multi-phase flow with strong coupling of temperature and velocity.

16.
World J Gastrointest Oncol ; 14(10): 1981-2003, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36310708

RESUMO

BACKGROUND: Cuproptosis has recently been considered a novel form of programmed cell death. To date, long-chain non-coding RNAs (lncRNAs) crucial to the regulation of this process remain unelucidated. AIM: To identify lncRNAs linked to cuproptosis in order to estimate patients' prognoses for hepatocellular carcinoma (HCC). METHODS: Using RNA sequence data from The Cancer Genome Atlas Live Hepatocellular Carcinoma (TCGA-LIHC), a co-expression network of cuproptosis-related genes and lncRNAs was constructed. For HCC prognosis, we developed a cuproptosis-related lncRNA signature (CupRLSig) using univariate Cox, lasso, and multivariate Cox regression analyses. Kaplan-Meier analysis was used to compare overall survival among high- and low-risk groups stratified by median CupRLSig risk score. Furthermore, comparisons of functional annotation, immune infiltration, somatic mutation, tumor mutation burden (TMB), and pharmacologic options were made between high- and low-risk groups. RESULTS: Three hundred and forty-three patients with complete follow-up data were recruited in the analysis. Pearson correlation analysis identified 157 cuproptosis-related lncRNAs related to 14 cuproptosis genes. Next, we divided the TCGA-LIHC sample into a training set and a validation set. In univariate Cox regression analysis, 27 LncRNAs with prognostic value were identified in the training set. After lasso regression, the multivariate Cox regression model determined the identified risk equation as follows: Risk score = (0.2659 × PICSAR expression) + (0.4374 × FOXD2-AS1 expression) + (-0.3467 × AP001065.1 expression). The CupRLSig high-risk group was associated with poor overall survival (hazard ratio = 1.162, 95%CI = 1.063-1.270; P < 0.001) after the patients were divided into two groups depending upon their median risk score. Model accuracy was further supported by receiver operating characteristic and principal component analysis as well as the validation set. The area under the curve of 0.741 was found to be a better predictor of HCC prognosis as compared to other clinicopathological variables. Mutation analysis revealed that high-risk combinations with high TMB carried worse prognoses (median survival of 30 mo vs 102 mo of low-risk combinations with low TMB group). The low-risk group had more activated natural killer cells (NK cells, P = 0.032 by Wilcoxon rank sum test) and fewer regulatory T cells (Tregs, P = 0.021) infiltration than the high-risk group. This finding could explain why the low-risk group has a better prognosis. Interestingly, when checkpoint gene expression (CD276, CTLA-4, and PDCD-1) and tumor immune dysfunction and rejection (TIDE) scores are considered, high-risk patients may respond better to immunotherapy. Finally, most drugs commonly used in preclinical and clinical systemic therapy for HCC, such as 5-fluorouracil, gemcitabine, paclitaxel, imatinib, sunitinib, rapamycin, and XL-184 (cabozantinib), were found to be more efficacious in the low-risk group; erlotinib, an exception, was more efficacious in the high-risk group. CONCLUSION: The lncRNA signature, CupRLSig, constructed in this study is valuable in prognostic estimation of HCC. Importantly, CupRLSig also predicts the level of immune infiltration and potential efficacy of tumor immunotherapy.

17.
Ecotoxicol Environ Saf ; 247: 114223, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36306624

RESUMO

Gambierdiscus spp. is mainly responsible for the ciguatera fish poisoning (CFP) around the world. The gambiertoxin produced by Gambierdiscus can be passed through the food chain to form ciguatoxins (CTXs) that cause ciguatoxins poisoning. However, the toxic effects of Gambierdiscus on fish through the food chain and related mechanism remains unclear. In this study, the toxicity of Gambierdiscus caribaeus on the marine medaka (Oryzias melastigma) was investigated, where the simulated food chain toxic algae-food organism-fish (G. caribaeus-Artemia metanauplii-O. melastigma) was set. The results showed that direct or indirect exposure through the food chain of G. caribaeus could affect the swimming behaviour of O. melastigma, manifested as decreased swimming performance and spontaneous abnormal swimming behaviours. Histological observation showed that direct or indirect exposure of G. caribaeus caused different degrees of pathological damage to the gills, intestine and liver tissues of O. melastigma. Transcriptome sequencing and RT-qPCR demonstrated that G. caribaeus exposure could trigger a series of physiological and biochemical responses, mainly reflected in energy metabolism, reproductive system, neural activity, immune stress and drug metabolism in marine medaka. Our finding may provide novel insight into the toxicity of Gambierdiscus on fish.


Assuntos
Intoxicação por Ciguatera , Ciguatoxinas , Dinoflagelados , Oryzias , Animais , Ciguatoxinas/toxicidade , Dinoflagelados/genética
18.
Nanomedicine ; 47: 102615, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36265558

RESUMO

Cervical diseases such as lymph node disease and tubal obstruction have threatened women's health. However, the traditional diagnostic methods still have shortcomings. NIR-II fluorescence imaging with advantages of low scattering, negligible autofluorescence, and high spatial resolution could be an ideal option. To obtain high quality NIR-II fluorescence imaging, selecting appropriate nanoprobes becomes the important issue. As a small molecular photothermal agent, extensive applications of ICG are rather limited because of its drawbacks. Herein, natural silk fibroin (SF) was synthesized and encapsulated ICG molecules to form SF@ICG nanoparticles (NPs). After detailed analysis, SF@ICG NPs showed excellent stability and long circulation time, as well as strong NIR-II fluorescence emission, well photo-stability, biocompatibility and well photothermal property under 808 nm laser irradiation. Furthermore, SF@ICG NPs were utilized for NIR-II fluorescence imaging of lymph node/lymphangiography and angiography of fallopian tubes. The process of fallopian tubes could be detected with high resolution and high sensitivity.

19.
Biochem Pharmacol ; 206: 115265, 2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36183803

RESUMO

Heart failure patients have elevated arginine vasopressin (AVP) levels, which are involved in inducing peripheral vasoconstriction and cardiac hypertrophy. This hypertrophy, along with cardiomyocyte apoptosis, results from oxidative stress. Therefore, the antioxidant drug, melatonin (Mel), is commonly used to treat cardiac hypertrophy and apoptosis; however, whether it could alleviate AVP-induced myocardialinjury remains to be addressed. In this study, high AVP doses were found to induce H9c2 cardiomyoblast apoptosis, demonstrated by increased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, pro-apoptotic B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax) up-regulation, and anti-apoptotic Bcl-2 downregulation. This AVP-induced apoptotic increase, along with lowered cell viability, was also associated with higher reactive oxygen species (ROS) levels and lowered mitochondrial membrane potentials (MMP), which were all reversed upon Mel administration. Further investigations found that apoptosis, ROS, and MMP outcomes under high AVP were associated with Mst1-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway suppression, yielding mitochondrial dysfunction, and Mel reversed them via promoting Mst1 phosphorylation, which then activated Nrf2 to increase anti-oxidative enzyme production. These findings were supported by siRNA gene suppression, where knocking down either Nrf2 or Mst1 abrogated the anti-apoptotic effects of Mel in cardiomyoblasts. Therefore, Mel could reduce cardiomyoblast apoptosis under high AVP levels, via Mst1-Nrf2 pathway re-activation, to enhance anti-oxidative responses.

20.
Quant Imaging Med Surg ; 12(10): 4823-4836, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36185052

RESUMO

Background: To investigate the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) features for predicting hypoxia-inducible factor 1-alpha (HIF-1α) expression and patient outcomes in soft tissue sarcoma (STS). Methods: We enrolled 71 patients with STS who underwent 3.0 Tesla (3.0T) MRI, including conventional MRI and DCE-MRI sequencing. The location, maximum tumor diameter, envelope, T2-weighted tumor heterogeneity, peritumoral edema, peritumoral enhancement, necrosis, configuration, tail-like pattern, bone invasion, and vessel/nerve invasion and/or encasement of the STSs were determined using conventional MRI images. The DCE-MRI parameters, including the volume transfer constant (Ktrans ), reflux rate (Kep ), volume fraction of extravascular extracellular matrix (Ve ), and time-signal intensity curve (TIC) type, of each lesion were independently analyzed by two observers. Independent samples t-test, chi-square test, and Mann-Whitney U-test were performed to evaluate the differences in the MRI features between the two groups. The relationships between the DCE-MRI parameters and HIF-1α expression were analyzed using Spearman's correlation analysis. The Cox proportional hazards model and Kaplan-Meier method were used for survival analysis. Results: Of the conventional MRI features, high heterogeneity, peritumoral enhancement, necrosis, and multilobulation of the T2-weighted tumor were prone to occur in the high-expression group. Of the DCE-MRI parameters, the high-expression group showed significantly higher Ktrans (0.311±0.091 vs. 0.210±0.058 min-1), and Kep values (0.896±0.656 vs. 0.444±0.300 min-1) than the low-expression group. No significant differences in TIC types and Ve values were observed between the low- and high-expression groups (P>0.05). There were positive correlations between Ktrans and Kep values with HIF-1α expression (r=0.705, P<0.001; r=0.123, P<0.001, respectively). Receiver operating characteristic (ROC) analysis indicated high specificity (93.9%) of the Ktrans value for predicting high expression of HIF-1α. The Kep value provided the best performance in diagnostic sensitivity (84.2%). Survival analyses revealed that more than 50% necrosis, multilobulation, and Ktrans values greater than 0.262 min-1 were strongly associated with a higher risk of death. Conclusions: Conventional MRI features and DCE-MRI parameters were significantly helpful in determining HIF-1α expression levels and predicting the overall survival (OS) of patients with STS.

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