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In diabetes, macrophages and inflammation are increased in the islets, along with ß-cell dysfunction. Here, we demonstrate that galectin-3 (Gal3), mainly produced and secreted by macrophages, is elevated in islets from both high-fat diet (HFD)-fed and diabetic db/db mice. Gal3 acutely reduces glucose-stimulated insulin secretion (GSIS) in ß-cell lines and primary islets in mice and humans. Importantly, Gal3 binds to calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1) and inhibits calcium influx via the cytomembrane and subsequent GSIS. ß-Cell CACNG1 deficiency phenocopies Gal3 treatment. Inhibition of Gal3 through either genetic or pharmacologic loss of function improves GSIS and glucose homeostasis in both HFD-fed and db/db mice. All animal findings are applicable to male mice. Here we show a role of Gal3 in pancreatic ß-cell dysfunction, and Gal3 could be a therapeutic target for the treatment of type 2 diabetes.
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Dieta Hiperlipídica , Galectina 3 , Secreção de Insulina , Células Secretoras de Insulina , Animais , Humanos , Masculino , Camundongos , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Canais de Cálcio/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/genética , Dieta Hiperlipídica/efeitos adversos , Galectina 3/metabolismo , Galectina 3/genética , Glucose/metabolismo , Insulina/metabolismo , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
ß-Cell dysfunction and ß-cell loss are hallmarks of type 2 diabetes (T2D). Here, we found that trimethylamine N-oxide (TMAO) at a similar concentration to that found in diabetes could directly decrease glucose-stimulated insulin secretion (GSIS) in MIN6 cells and primary islets from mice or humans. Elevation of TMAO levels impairs GSIS, ß-cell proportion, and glucose tolerance in male C57BL/6 J mice. TMAO inhibits calcium transients through NLRP3 inflammasome-related cytokines and induced Serca2 loss, and a Serca2 agonist reversed the effect of TMAO on ß-cell function in vitro and in vivo. Additionally, long-term TMAO exposure promotes ß-cell ER stress, dedifferentiation, and apoptosis and inhibits ß-cell transcriptional identity. Inhibition of TMAO production improves ß-cell GSIS, ß-cell proportion, and glucose tolerance in both male db/db and choline diet-fed mice. These observations identify a role for TMAO in ß-cell dysfunction and maintenance, and inhibition of TMAO could be an approach for the treatment of T2D.
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Diabetes Mellitus Tipo 2 , Humanos , Masculino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Glucose/farmacologia , Metilaminas/farmacologia , Transdução de Sinais , Insulina/farmacologiaRESUMO
To reveal the impact of cadmium stress on the physiological mechanism of lettuce, simultaneous determination and correlation analyses of chlorophyll content and photosynthetic function were conducted using lettuce seedlings as the research subject. The changes in relative chlorophyll content, rapid chlorophyll fluorescence induction kinetics curve, and related chlorophyll fluorescence parameters of lettuce seedling leaves under cadmium stress were detected and analyzed. Furthermore, a model for estimating relative chlorophyll content was established. The results showed that cadmium stress at 1 mg/kg and 5 mg/kg had a promoting effect on the relative chlorophyll content, while cadmium stress at 10 mg/kg and 20 mg/kg had an inhibitory effect on the relative chlorophyll content. Moreover, with the extension of time, the inhibitory effect became more pronounced. Cadmium stress affects both the donor and acceptor sides of photosystem II in lettuce seedling leaves, damaging the electron transfer chain and reducing energy transfer in the photosynthetic system. It also inhibits water photolysis and decreases electron transfer efficiency, leading to a decline in photosynthesis. However, lettuce seedling leaves can mitigate photosystem II damage caused by cadmium stress through increased thermal dissipation. The model established based on the energy captured by a reaction center for electron transfer can effectively estimate the relative chlorophyll content of leaves. This study demonstrates that chlorophyll fluorescence techniques have great potential in elucidating the physiological mechanism of cadmium stress in lettuce, as well as in achieving synchronized determination and correlation analyses of chlorophyll content and photosynthetic function.
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Cádmio , Lactuca , Complexo de Proteína do Fotossistema II/metabolismo , Fluorescência , Fotossíntese , Clorofila , Plântula , Folhas de Planta/metabolismoRESUMO
OBJECTIVE: To investigate the effects of low-dose S-ketamine on marker of myocardial injury (BNP, hs-cTnT and HFABP) after thoracoscopic lobectomy in patients aged 70 to 85. METHODS: One hundred patients (four cases excluded) aged 70-85 years, with body mass index 18-24 kg·m-2 and American Society of Anesthesiologists physical status II-III, scheduled for elective lobectomy from April 2022 to April 2023, were selected. The patients were divided into two groups by a random number table method, namely, the low-dose S-ketamine combined with GDFT group (group S) and the control group (group C), with 48 cases in each group. In group S, a low dose of S-ketamine (0.2 mg/kg) was given 1 min before intubation, and the maintenance dose was 0.12 mg·kg-1·h-1. Fluid therapy, guided by cardiac index (CI), changes in stroke volume (â³SV), and other dynamic indicators, was used for rehydration during the operation. Group C was given the same amount of normal saline (0.2 mg/kg) 1 min before intubation, and the same rehydration therapy was adopted during the operation. The mean arterial pressure (MAP) and heart rate (HR) of the two groups were observed and recorded immediately after entering the operating room (T0), immediately after intubation (T1), immediately after the beginning of one-lung ventilation (OLV) (T2), immediately after the beginning of surgery (T3), immediately after the end of OLV (T4), and at the end of surgery (T5). The intraoperative fluid intake and output and the use of vasoactive drugs were recorded. The plasma levels of heart-type fatty acid-binding protein (HFABP), high-sensitivity troponin T (hs-cTnT), brain natriuretic peptide (BNP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were recorded 24 h before operation and 24 and 48 h after operation. Visual analogue scale (VAS) pain scores at rest were recorded at 2 (V1), 6 (V2), 12 (V3), 24 (V4), and 48 h (V5) after operation, and the occurrence of myocardial ischemia during hospitalization was noted. RESULTS: Compared with group C, MAP was significantly higher at T1-T5 in group S (P < 0.05), and the plasma concentrations of IL-6, IL-8, TNF-α, BNP, hs-cTnT, and HFABP were significantly lower at 24 and 48 h after operation (P < 0.05). The VAS pain scores at 2, 6, 12, 24, and 48 h after operation, the number of effective patient-controlled intravenous analgesia (PCIA) compressions, and the total number of PCIA compressions within 48 h after operation were significantly decreased (P < 0.05). Compared with group C, The hospitalization days, and the incidence of postoperative myocardial ischemia in group S were lower (P < 0.05). There were no significant intergroup differences in urine volume, extubation time, the incidence of postoperative atrial fibrillation, bleeding volume, colloid infusion volume, total fluid infusion volume, and the incidence of rescue analgesia. CONCLUSIONS: Low-dose S-ketamine can reduce the levels of hs-cTnT, HFABP, and BNP in older patients after pulmonary lobectomy, which has a positive effect on preventing myocardial injury. TRIAL REGISTRATION: This study was registered on CHICTR (registration No. ChiCTR2300074475). Date of registration: 08/08/2023.
Assuntos
Interleucina-8 , Ketamina , Isquemia Miocárdica , Humanos , Idoso , Interleucina-6 , Fator de Necrose Tumoral alfa , Analgesia Controlada pelo Paciente , Dor , Isquemia Miocárdica/prevenção & controleRESUMO
In order to rapidly and accurately monitor cadmium contamination in lettuce and understand the growth conditions of lettuce under cadmium pollution, lettuce is used as the test material. Under different concentrations of cadmium stress and at different growth stages, relative chlorophyll content of lettuce leaves, the cadmium content in the leaves, and the visible-near infrared reflectance spectra are detected and analyzed. An inversion model of the cadmium content and relative chlorophyll content in the lettuce leaves is established. The results indicate that cadmium concentrations of 1 mg/kg and 5 mg/kg promote relative chlorophyll content, while concentrations of 10 mg/kg and 20 mg/kg inhibit relative chlorophyll content. The cadmium content in the leaves increases with increasing cadmium concentrations. Cadmium stress caused a "blue shift" in the red edge position only during the mature period, while the red valley position underwent a "blue shift" during the seedling and growth periods and a "red shift" during the mature period. The green peak position exhibited a "blue shift". After model validation, it was found that the model constructed using the ratio of red edge area to yellow edge area and the normalized values of red edge area and yellow edge area effectively estimated the cadmium content in lettuce leaves. The model established using the normalized vegetation index of the red edge and the ratio of the peak green value to red shoulder amplitude can effectively estimate the relative chlorophyll content in lettuce leaves. This study demonstrates that the visible-near infrared spectroscopy technique holds great potential for monitoring cadmium contamination and estimating chlorophyll content in lettuce.
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Cádmio , Espectroscopia de Luz Próxima ao Infravermelho , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Cádmio/análise , Clorofila/análise , Luz , Folhas de Planta/químicaRESUMO
Background: Serum triglyceride (TG) was an important biomarker for nonalcoholic fatty liver disease (NAFLD), and the association between TG and incident type 2 diabetes mellitus is still under debate with some studies suggesting that elevated TG increase the risk of incident T2DM while others indicative of a negative relationship. These controversial findings may be partially due to the inclusion of the participants with NAFLD. The association between TG and incident type 2 diabetes mellitus in people with NAFLD remained unclear. Therefore, this study aimed to characterize the relationship between the baseline TG levels and incident type 2 diabetes mellitus in a male Japanese cohort with NAFLD. Methods: A total of 1221 males with NAFLD were enrolled from the Nagala (NAFLD in the Gifu Area Longitudinal analysis) study conducted from 2004 to 2015. Cox proportional hazards models were performed to examine the relationship between baseline TG concentration and incident type 2 diabetes mellitus. A two-piecewise linear regression model was explored to evaluate the threshold effect of the baseline TG levels on type 2 diabetes mellitus incidence by using a smoothing function. Results: During a median follow-up of 6.05 years, 39 males with NAFLD at baseline developed type 2 diabetes mellitus. The risk of incident type 2 diabetes mellitus was significantly associated with baseline TG concentration in males with NAFLD after fully adjustment for confounders, with per 10 mg/dl elevation in TG levels increasing the risk of incident diabetes by 8.5% (HR=1.085, CI=1.039-1.132; P<0.001). However, no typical dose-dependent positive association between type 2 diabetes mellitus incidence and the TG levels was observed across the TG tertiles. Interestingly, a U-shaped association between TG concentration and risk of incident type 2 diabetes mellitus was revealed by the two-piecewise linear regression analysis. Baseline TG concentration lower than the threshold values (TG <53mg/dl) were negatively associated with risk of incident type 2 diabetes mellitus. With each 10mg/dl increase in baseline TG levels, the risk of incident type 2 diabetes mellitus decreased by nearly 59% (HR=0.413, 95% CI=0.220-0.778). In contrast, when TG levels were higher than the threshold values (TG>53mg/dl), the risk of incident diabetes increased 9.1% with every 10mg TG elevation (HR=1.091, 95% CI=1.046-1.137). Conclusions: A U-shaped relationship was observed between baseline TG levels and incident type 2 diabetes mellitus in a male normoglycemic Japanese population with NAFLD, although extrapolation of the finding to other populations should be made with caution.
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Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Diabetes Mellitus Tipo 2/complicações , Triglicerídeos , Estudos de Coortes , Incidência , Fatores de RiscoRESUMO
BACKGROUND AND AIMS: NAFLD is the most prevalent chronic liver disease worldwide and has emerged as a serious public health issue with no approved treatment. The development of NAFLD is strongly associated with hepatic lipid content, and patients with NAFLD have significantly higher rates of hepatic de novo lipogenesis (DNL) than lean individuals. Leukotriene B4 (LTB4), a metabolite of arachidonic acid, is dramatically increased in obesity and plays important role in proinflammatory cytokine production and insulin resistance. But the role of liver LTB4/LTB4 receptor 1 (Ltb4r1) in lipid metabolism is unclear. APPROACH AND RESULTS: Hepatocyte-specific knockout (HKO) of Ltb4r1 improved hepatic steatosis and systemic insulin resistance in both diet-induced and genetically induced obese mice. The mRNA level of key enzymes involved in DNL and fatty acid esterification decreased in Ltb4r1 HKO obese mice. LTB4/Ltb4r1 directly promoted lipogenesis in HepG2 cells and primary hepatocytes. Mechanically, LTB4/Ltb4r1 promoted lipogenesis by activating the cAMP-protein kinase A (PKA)-inositol-requiring enzyme 1α (IRE1α)-spliced X-box-binding protein 1 (XBP1s) axis in hepatocytes, which in turn promoted the expression of lipogenesis genes regulated by XBP1s. In addition, Ltb4r1 suppression through the Ltb4r1 inhibitor or lentivirus-short hairpin RNA delivery alleviated the fatty liver phenotype in obese mice. CONCLUSIONS: LTB4/Ltb4r1 promotes hepatocyte lipogenesis directly by activating PKA-IRE1α-XBP1s to promote lipogenic gene expression. Inhibition of hepatocyte Ltb4r1 improved hepatic steatosis and insulin resistance. Ltb4r1 is a potential therapeutic target for NAFLD.
Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores do Leucotrieno B4/metabolismo , Leucotrieno B4/efeitos adversos , Leucotrieno B4/metabolismo , Camundongos Obesos , Endorribonucleases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Obesidade/complicações , Obesidade/genética , Lipogênese/fisiologia , Dieta HiperlipídicaRESUMO
Insulin signaling is essential for glucose metabolism, and insulin decreases insulin receptor (InsR) levels in a dose-dependent and time-dependent manner. However, the regulatory mechanisms of InsR reduction upon insulin stimulation remain poorly understood. Here, we show that Eph receptor B4 (EphB4), a tyrosine kinase receptor that modulates cell adhesion and migration, can bind directly to InsR, and this interaction is markedly enhanced by insulin. Due to the adaptor protein 2 (Ap2) complex binding motif in EphB4, the interaction of EphB4 and InsR facilitates clathrin-mediated InsR endocytosis and degradation in lysosomes. Hepatic overexpression of EphB4 decreases InsR and increases hepatic and systemic insulin resistance in chow-fed mice, whereas genetic or pharmacological inhibition of EphB4 improve insulin resistance and glucose intolerance in obese mice. These observations elucidate a role for EphB4 in insulin signaling, suggesting that EphB4 might represent a therapeutic target for the treatment of insulin resistance and type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Receptor EphB4 , Receptor de Insulina , Animais , Clatrina , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Resistência à Insulina/genética , Fígado/metabolismo , Camundongos , Receptor EphB4/metabolismo , Receptor de Insulina/metabolismoRESUMO
In this study, we investigated the formation and evolution of the corrosion layers in alkali-activated mortar and ordinary Portland cement mortar exposed to sulfuric acid and acetic acid environments with different pH values, and explored the differences in the deterioration mechanisms. The experimental results indicated that ordinary Portland cement (OPC) mortars experienced more severe deterioration in terms of appearance, mass loss, and strength loss as compared with alkali-activated mortars exposed to an acetic acid environment, but their neutralization depths were smaller. Alkali-activated fly ash (AAF) mortar had a the relatively intact appearance but the greatest neutralization depth, which was due to its stable three-dimensional network but highly porous structure. To sum up, alkali-activated fly ash/slag (AFS) mortar had the best resistance to acid attack. In addition, the mortars exposed to acetic acid suffered greater deterioration than those exposed to sulfuric acid with the same pH values, which was mainly due to the highly porous corrosion layer formed in acetic acid, whereas crystallization of gypsum in sulfuric acid had a pore filling effect. However, for alkali-activated slag (AAS) and OPC mortars exposed to a sulfuric acid environment, extensive gypsum resulted in the formation of micro-cracks, and the corrosion layer of OPC mortar was more prone to fall off. OPC mortar also had the greatest resistance difference values of the continuously connected micro-pores before and after acid corrosion, followed by AAS, AAF, and AFS mortars, and these values for all the specimens were smaller in sulfuric acid. Furthermore, the gaps between acetic and sulfuric acid attacks increased with increased calcium content in binders, which were 7%, 13%, 21%, and 29% for AAF, AFS, AAS, and OPC mortars, respectively. Thus, it can be inferred that an appropriate amount of gypsum existed in the corrosion layer which could act as a barrier to some extent ina sulfuric acid environment.
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BACKGROUND: Cardiogenic embolism caused by patent foramen ovale (PFO) is a common etiology of cryptogenic stroke (CS), particularly in young and middle-aged patients. Studies about right-to-left shunt (RLS) detection using contrast-enhanced transcranial Doppler (c-TCD) are numerous. According to the time phase and number of microbubbles detected on c-TCD, RLS can be classified and graded. We hypothesized that the characteristics of an infarction lesion on diffusion-weighted imaging differs when combining the type and grade of RLS on c-TCD in patients with PFO-related CS. AIM: To explore the characteristics of infarction lesions on diffusion-weighted imaging when combining the RLS type and grade determined by c-TCD. METHODS: We retrospectively evaluated CS patients from August 2015 to December 2019 at a tertiary hospital. In total, 111 PFO-related CS patients were divided according to whether RLS was permanent (microbubbles detected both at resting state and after the Valsalva maneuver) or latent (microbubbles detected only after the Valsalva maneuver) on c-TCD. Each group was subdivided into small, mild and large RLS according to the grade of shunt on c-TCD. A normal control group was composed of 33 patients who suffered from simple dizziness. Intragroup and intergroup differences were analyzed in terms of clinical, laboratory and diffusion-weighted imaging lesion characteristics. The correlation between RLS grade evaluated by c-TCD and size of PFO determined by transesophageal echocardiography were also analyzed. RESULTS: In 111 patients with PFO-related CS, 68 had permanent RLS and 43 had latent RLS. Clinical characteristics and laboratory tests were not significantly different among the permanent RLS, latent RLS and normal control groups. The proportion of patients with multiple territory lesions in the permanent RLS group (50%) was larger than that in the latent RLS group (27.91%; P = 0.021). Posterior circulation was more likely to be affected in the latent RLS group than in the permanent RLS group (30.23% vs 8.82%, P = 0.004). Permanent-large and latent-large RLS were both more likely to be related to multiple (P trend = 0.017 and 0.009, respectively), small (P trend = 0.035 and 0.006, respectively) and cortical (P trend = 0.031 and 0.033, respectively) lesions. The grade of RLS evaluated by c-TCD was correlated to the size of PFO determined by transesophageal echocardiography (r = 0.758, P < 0.001). CONCLUSION: Distribution of the infarct suggested the possible type of RLS. Multiple, small and cortical infarcts suggest large RLS induced by a large PFO.
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We report the development of a compact near-infrared (NIR) laser-based trace methane (CH4) detection system. This detection system relied on a 2334 nm distributed feedback (DFB) fiber laser as the light source. A parallel dense light-spot pattern multipass gas cell (MGC) with 41.5 m effective absorption path length was utilized to improve the system sensitivity. A self-calibration approach based on direct absorption spectroscopy (DAS) calibrated wavelength modulation spectroscopy (WMS) technique was employed to solve the problem of extra concentration calibration requirement in traditional WMS technique, and to improve the accuracy and stability of the system. According to the Allan deviation analysis, 1-s measurement precision of 0.61 ppmv for DAS and 0.16 ppmv for WMS was obtained, which could be further reduced to 0.11 ppmv for DAS and 0.03 ppmv for WMS by averaging up to 80 s and 50 s, respectively. A week-long continuous atmospheric CH4 concentration measurement was also carried out to demonstrate the long-term performance of our CH4 detection system. With a fast dynamic response characteristics, high-accuracy and high-sensitivity, the proposed detection system is suitable for CH4 measurement in many fields such as atmospheric chemistry analyzation, industrial safety monitoring, agricultural information acquisition, etc.
Assuntos
Lasers , MetanoRESUMO
Several members of the FGF family have been identified as potential regulators of glucose homeostasis. We previously reported that a low threshold of FGF-induced FGF receptor 1c (FGFR1c) dimerization and activity is sufficient to evoke a glucose lowering activity. We therefore reasoned that ligand identity may not matter, and that besides paracrine FGF1 and endocrine FGF21, other cognate paracrine FGFs of FGFR1c might possess such activity. Indeed, via a side-by-side testing of multiple cognate FGFs of FGFR1c in diabetic mice we identified the paracrine FGF4 as a potent anti-hyperglycemic FGF. Importantly, we found that like FGF1, the paracrine FGF4 is also more efficacious than endocrine FGF21 in lowering blood glucose. We show that paracrine FGF4 and FGF1 exert their superior glycemic control by targeting skeletal muscle, which expresses copious FGFR1c but lacks ß-klotho (KLB), an obligatory FGF21 co-receptor. Mechanistically, both FGF4 and FGF1 upregulate GLUT4 cell surface abundance in skeletal muscle in an AMPKα-dependent but insulin-independent manner. Chronic treatment with rFGF4 improves insulin resistance and suppresses adipose macrophage infiltration and inflammation. Notably, unlike FGF1 (a pan-FGFR ligand), FGF4, which has more restricted FGFR1c binding specificity, has no apparent effect on food intake. The potent anti-hyperglycemic and anti-inflammatory properties of FGF4 testify to its promising potential for use in the treatment of T2D and related metabolic disorders.
Assuntos
Fator 4 de Crescimento de Fibroblastos/farmacologia , Hipoglicemiantes/farmacologia , Músculo Esquelético/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Fator 4 de Crescimento de Fibroblastos/administração & dosagem , Fator 4 de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/administração & dosagem , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/farmacologia , Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/metabolismo , Inflamação , Resistência à Insulina , Ligantes , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Músculo Esquelético/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Comunicação Parácrina , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
In this study, the feasibility of classifying soybean frogeye leaf spot (FLS) is investigated. Leaf images and hyperspectral reflectance data of healthy and FLS diseased soybean leaves were acquired. First, image processing was used to classify FLS to create a reference for subsequent analysis of hyperspectral data. Then, dimensionality reduction methods of hyperspectral data were used to obtain the relevant information pertaining to FLS. Three single methods, namely spectral index (SI), principal component analysis (PCA), and competitive adaptive reweighted sampling (CARS), along with a PCA and SI combined method, were included. PCA was used to select the effective principal components (PCs), and evaluate SIs. Characteristic wavelengths (CWs) were selected using CARS. Finally, the full wavelengths, CWs, effective PCs, SIs, and significant SIs were divided into 14 datasets (DS1-DS14) and used as inputs to build the classification models. Models' performances were evaluated based on the classification accuracy for both the overall and individual classes. Our results suggest that the FLS comprised of five classes based on the proportion of total leaf surface covered with FLS. In the PCA and SI combination model, 5 PCs and 20 SIs with higher weight coefficient of each PC were extracted. For hyperspectral data, 20 CWs and 26 effective PCs were also selected. Out of the 14 datasets, the model input variables provided by five datasets (DS2, DS3, DS4, DS10, and DS11) were more superior than those of full wavelengths (DS1) both in support vector machine (SVM) and least squares support vector machine (LS-SVM) classifiers. The models developed using these five datasets achieved overall accuracies ranging from 91.8% to 94.5% in SVM, and 94.5% to 97.3% in LS-SVM. In addition, they improved the classification accuracies by 0.9% to 3.6% (SVM) and 0.9% to 3.7% (LS-SVM).
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Glycine max/ultraestrutura , Processamento de Imagem Assistida por Computador/métodos , Micoses/microbiologia , Doenças das Plantas/microbiologia , Folhas de Planta , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Cercospora , Folhas de Planta/microbiologia , Folhas de Planta/ultraestrutura , Glycine max/microbiologia , Máquina de Vetores de SuporteRESUMO
The aim of this work was to enrich the knowledge on the potential applications of Elaeagnus mollis leaf extracts. For this purpose, the bioactive compounds (phenolic, flavonoid, alkaloid, proanthocyanidin, chlorophyll and carotene content), antioxidant activity, anti-HepG2 cell proliferation, and cholinesterase inhibitory potential (AChE and BChE) of E. mollis leaves which obtained from different habitats were quantitatively analyzed using various solvents (water, methanol, ethanol, and n-hexane). The results showed that the methanol extracts exhibited the strongest 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity and the water extracts showed the best antioxidant activity in the 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) free radical scavenging activity, ferric reducing antioxidant power (FRAP), and reducing power (RP) assays. Moreover, the methanol extracts showed the best inhibitory activity against cholinesterase and HepG2 cancer cells. Correlation analysis revealed that the high antioxidant and anti-HepG2 cell proliferation activities were mainly attributed to the total phenolics, flavonoids, and proanthocyanidins while AChE inhibition was attributed to the total alkaloid and carotene content. The statistical results showed that the effect of habitats was lower than that of different solvents used. Additionally, the metabolic profiles of E. mollis leaves were evaluated using HPLC-ESI-Q TRAP-MS/MS, and a total of 1,017 chemical components were detected and classified into 23 classes. The organic acids and derivatives ranked the first, followed by flavone, amino acid and derivatives, and so on. In conclusion, the effects of different solvents were more significant than the effects of different habitats and the methanol extracts of E. mollis leaves could be used as an effective source of functional active components, provide benefits to physical health care and be applied to the food and pharmaceutical industries.
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Elaeagnaceae/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , China , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Ecossistema , Células Hep G2 , Humanos , Folhas de Planta/química , Plantas Medicinais/química , SolventesRESUMO
Zanthoxylum bungeanum, a spice and medicinal plant, is cultivated in many parts of China and some countries in Southeast Asia; however, data on its genome are lacking. In the present study, we performed a whole-genome survey and developed novel genomic-SSR markers of Z. bungeanum. Clean data (â¼197.16 Gb) were obtained and assembled into 11185221 scaffolds with an N50 of 183 bp. K-mer analysis revealed that Z. bungeanum has an estimated genome size of 3971.92 Mb, and the GC content, heterozygous rate, and repeat sequence rate are 37.21%, 1.73%, and 86.04%, respectively. These results indicate that the genome of Z. bungeanum is complex. Furthermore, 27153 simple sequence repeat (SSR) loci were identified from 57288 scaffolds with a minimum length > 1 kb. Mononucleotide repeats (19706) were the most abundant type, followed by dinucleotide repeats (5154). The most common motifs were A/T, followed by AT/AT; these SSRs accounted for 71.42% and 11.84% of all repeats, respectively. A total of 21243 non-repeating primer pairs were designed, and 100 were randomly selected and validated by PCR analysis using DNA from 10 Z. bungeanum individuals and 5 Zanthoxylum armatum individuals. Finally, 36 polymorphic SSR markers were developed with polymorphism information content (PIC) values ranging from 0.16 to 0.75. Cluster analysis revealed that Z. bungeanum and Z. armatum could be divided into two major clusters, suggesting that these newly developed SSR markers are useful for genetic diversity and germplasm resource identification in Z. bungeanum and Z. armatum.
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Genes de Plantas , Genoma de Planta , Repetições de Microssatélites , Sequenciamento Completo do Genoma , Zanthoxylum/genética , Composição de Bases , Marcadores Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Filogenia , Zanthoxylum/classificaçãoRESUMO
Plants can accumulate a large amount of reactive oxygen species under adverse conditions such as drought and high temperature, which seriously affect the normal growth and development of plants. The antioxidant system can scavenge the reactive oxygen species produced under drought conditions and so mitigate oxidative damage. However, the regulation patterns of many miRNAs under drought stress are still unclear. The content of antioxidant enzymes and the expression patterns of miRNAs and their target genes related to antioxidant systems were studied under drought stress in Zanthoxylum bungeanum. The results indicate that under drought stress, POD, CAT, APX, proline, MDA and related genes all show positive responses to drought, while SOD and its genes showed a negative response. It is indicated that in the antioxidant process of Z. bungeanum, POD, CAT, and APX play a major role, and SOD plays a supporting role. In addition, GUS histochemical and RT-qPCR experimental results show that the expression levels of miRNAs and their target genes are basically negatively correlated, indicating that miRNAs can inhibit the expression of related genes and are also important regulators in the antioxidant system of Z. bungeanum. According to the expression patterns of antioxidant enzymes, miRNA and its target genes under drought stress, combined with previous research results, a model of plant antioxidant mechanism was constructed to provide a reference for further understanding of plant antioxidant mechanism.
Assuntos
Secas , MicroRNAs , Oxirredutases , Estresse Fisiológico , Zanthoxylum , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , MicroRNAs/metabolismo , Oxirredutases/genética , Oxirredutases/metabolismo , Estresse Fisiológico/genética , Zanthoxylum/genética , Zanthoxylum/metabolismoRESUMO
Most of our knowledge about translation regulatory mechanisms comes from studies on lower organisms. However, the translation control system of higher organisms is less understood. Here we find that in 5' untranslated region (5'UTR) of human Annexin II receptor (AXIIR) mRNA, there are two upstream open reading frames (uORFs) acting in a fail-safe manner to inhibit the translation from the main AUG. These uORFs are unfavorable for re-initiation after termination of uORF translation. Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), hnRNPA0 and ELAV like RNA binding protein 1 (ELAVL1) bind to the 5'UTR of AXIIR mRNA. They focus the translation of uORFs on uORF1 and attenuate leaky scanning that bypasses uORFs. The cooperation between the two uORFs and the three proteins formed a multiple fail-safe system that tightly inhibits the translation of downstream AXIIR. Such cooperation between multiple molecules and elements reflects that higher organism develops a complex translation regulatory system to achieve accurate and flexible gene expression control.
RESUMO
In obesity, macrophages and other immune cells accumulate in insulin target tissues, promoting a chronic inflammatory state and insulin resistance. Galectin-3 (Gal3), a lectin mainly secreted by macrophages, is elevated in both obese subjects and mice. Administration of Gal3 to mice causes insulin resistance and glucose intolerance, whereas inhibition of Gal3, through either genetic or pharmacologic loss of function, improved insulin sensitivity in obese mice. In vitro treatment with Gal3 directly enhanced macrophage chemotaxis, reduced insulin-stimulated glucose uptake in myocytes and 3T3-L1 adipocytes and impaired insulin-mediated suppression of glucose output in primary mouse hepatocytes. Importantly, we found that Gal3 can bind directly to the insulin receptor (IR) and inhibit downstream IR signaling. These observations elucidate a novel role for Gal3 in hepatocyte, adipocyte, and myocyte insulin resistance, suggesting that Gal3 can link inflammation to decreased insulin sensitivity. Inhibition of Gal3 could be a new approach to treat insulin resistance.
Assuntos
Galectina 3/sangue , Galectina 3/metabolismo , Adipócitos/metabolismo , Adipócitos/patologia , Animais , Quimiotaxia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Galectina 3/antagonistas & inibidores , Galectina 3/genética , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Insulina/sangue , Resistência à Insulina , Macrófagos/imunologia , Macrófagos/patologia , Camundongos , Camundongos Knockout , Células Musculares/metabolismo , Células Musculares/patologia , Obesidade/imunologia , Obesidade/metabolismo , Obesidade/patologiaRESUMO
OBJECTIVE: To investigate the role of TXNDC5 in serum starvation-induced proliferation inhibition of HeLa cell. METHODS: TXNDC5 was either over-expressed or knocked down by small interfering RNA (siRNA) in HeLa cells which were then cultured in conventional medium or serum starvation medium. The protein level of TXNDC5 was evaluated by Western blot analysis. The mRNA level of TXNDC5 was measured by quantitative real-time PCR. Cell growth rate was determined by cell proliferation assay kit (MTS method). Cell cycle distribution and apoptosis were detected by flow cytometry. RESULTS: Serum starvation mildly reduced the mRNA level of TXNDC5 (P<0.05), but dramatically increased the protein level of TXNDC5 in HeLa cells. The stability of TXNDC5 mRNA remained unchanged. Cycloheximide abolished the serum starvation-induced up-regulation of TXNDC5 protein. Over-expression of TXNDC5 had no effect on cell proliferation. However, suppression of TXNDC5 attenuated the proliferation inhibition of HeLa cell induced by serum starvation (P<0.05), increased the proportion of cells in S phase (P<0.05), but had no effect on cell apoptosis. CONCLUSION: TXNDC5 mediates serum starvation-induced proliferation inhibition of HeLa cell.
Assuntos
Proliferação de Células , Isomerases de Dissulfetos de Proteínas/metabolismo , Apoptose , Ciclo Celular , Meios de Cultura/química , Técnicas de Silenciamento de Genes , Células HeLa , Humanos , Isomerases de Dissulfetos de Proteínas/genética , Soro/químicaRESUMO
Annexin II receptor (AXIIR) is also known as chromosome 5 open reading frame 39 (C5orf39), it was originally identified as a cell surface receptor for Annexin II. AXIIR gene is peculiar to human. So far, the only known function about AXIIR is mediating Annexin II signal. In this study, we find that over-expression of AXIIR induces apoptosis, and this phenomenon is found in multiple human cell types. AXIIR is located in cytoplasm, binds to and activates pro-Caspase-8, which subsequently activates Caspase-3/7. AXIIR also down-regulates BCL2, BCL-XL, and activates Caspase-9, which finally activates Caspase-3/7 as well. Over-expression of BCL-XL does not affect AXIIR-induced apoptosis, whereas inhibition of Caspase-8 partially abolished AXIIR-induced apoptosis. AXIIR induces apoptosis independent of Annexin II and FADD. AXIIR is neither required for TRAIL-induced Caspase-8 activation. Although the transcriptional level of AXIIR in multiple cell types is considerably high, the translational level of AXIIR can hardly be detected. And inhibition of protein degradation pathways does not elevate AXIIR expression. Taken together, our observations reveal that besides being a cell surface receptor of Annexin II, AXIIR can also be located in cytoplasm and act as a novel inducer of apoptosis in human cells, partially through activating Caspase-8 in a manner that is different from conventional apoptotic pathways. The translation of AXIIR is generally tightly inhibited in cells. The physiological significance of such inhibition might be to prevent cells from apoptosis.