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OBJECTIVE: To explore the protective effect of Xionggui Decoction against cardiac myopathy in a mouse model of heart failure following myocardial infarction (MI) and explore the underlying mechanism. METHODS: We searched TCMSP, GeneCards, and CTD databases for the targets of active ingredients Xionggui Decoction and heart failure, and the intersecting targets were analyzed with GO and KEGG pathway enrichment analysis using DAVID database. In a mouse model of heart failure following acute MI induced by coronary artery ligation, the cardiac protective effects of 3 g/kg Xionggui Decoction were evaluated by assessing cardiac function, cardiac myopathy and ventricular remodeling of the mice using HE staining, Masson staining, RT-qPCR, and immunohistochemistry. We also tested the effect of Xionggui Decoction at 50 and 100 µg/mL on tertbutylhydrogen peroxide (TBHP)-induced apoptosis of H9C2 cells using CCK8 assay, detection kits for ROS, MDA, SOD, JC-1 and Hoechst 33342/PI staining. RESULTS: Network pharmacological analysis identified 62 potential targets of Xionggui Decoction for treatment of heart failure, and the core targets included PTGS2, ESR1, caspase-3, PPARG, HSP90AA1, BCL2, JUN, and GSK3B, which were involved in cell apoptosis and the AGE-RAGE, P53, PI3K-Akt, and VEGF signaling pathways. In the mouse models of heart failure, treatment with Xionggui Decoction significantly alleviated cardiac myopathy and ventricular remodeling, obviously improved heart function of the mice, lowered myocardial expressions of caspase-3 and BAX, and enhanced the expression of BCL2. In H9C2 cells, Xionggui Decoction significantly alleviated TBHP-induced cell apoptosis by inhibiting oxidative stress in the cells. CONCLUSION: Xionggui Decoction can alleviate myocardial injury and improve cardiac function in mice with heart failure following acute MI possibly by inhibiting cardiomyocyte apoptosis induced by oxidative stress.
Subject(s)
Apoptosis , Disease Models, Animal , Drugs, Chinese Herbal , Heart Failure , Myocardial Infarction , Myocytes, Cardiac , Oxidative Stress , Animals , Mice , Heart Failure/drug therapy , Heart Failure/etiology , Myocardial Infarction/drug therapy , Myocardial Infarction/metabolism , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Apoptosis/drug effects , Oxidative Stress/drug effects , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Ventricular Remodeling/drug effects , Signal Transduction/drug effects , Male , Cell LineABSTRACT
OBJECTIVE: To investigate the protective effect of 5-hydroxy-6,7-dimethoxyflavone (5-HDF), a compound extracted from Elsholtzia blanda Benth., against lung injury induced by H1N1 influenza virus and explore its possible mechanism of action. METHODS: 5-HDF was extracted from Elsholtzia blanda Benth. using ethanol reflux extraction and silica gel chromatography and characterized using NMR and MS analyses. In an A549 cell model of H1N1 influenza virus infection (MOI=0.1), the cytotoxicity of 5-HDF was assessed using MTT assay, and its effect on TRAIL and IL-8 expressions was examined using flow cytometry; Western blotting was used to detect the expression levels of inflammatory, apoptosis, and ferroptosis-related proteins. In a mouse model of H1N1 influenza virus infection established by nasal instillation of 50 µL H1N1 virus at the median lethal dose, the effects of 30 and 60 mg/kg 5-HDF by gavage on body weight, lung index, gross lung anatomy and lung histopathology were observed. RESULTS: 5-HDF exhibited no significant cytotoxicity in A549 cells within the concentration range of 0-200 µg/mL. In H1N1-infected A549 cells, treatment with 5-HDF effectively inhibited the activation of phospho-p38 MAPK and phospho-NF-κB p65, lowered the expressions of IL-8, enhanced the expression of anti-ferroptosis proteins (SLC7A11 and GPX4), and inhibited the expressions of apoptosis markers PARP and caspase-3 and the apoptotic factor TRAIL. In H1N1-infected mice, treatment with 5-HDF for 7 days significantly suppressed body weight loss and increment of lung index and obviously alleviated lung tissue pathologies. CONCLUSION: 5-HDF offers protection against H1N1 influenza virus infection in mice possibly by suppressing H1N1-induced ferroptosis, inflammatory responses, and apoptosis via upregulating SLC7A11 and GPX4, inhibiting the activation of phospho-NF-κB p65 and phospho-p38 MAPK, and decreasing the expression of cleaved caspase3 and cleaved PARP.
Subject(s)
Ferroptosis , Flavones , Inflammation , Influenza A Virus, H1N1 Subtype , Influenza A Virus, H1N1 Subtype/drug effects , Humans , A549 Cells , Mice , Animals , Ferroptosis/drug effects , Flavones/pharmacology , Apoptosis/drug effects , Interleukin-8/metabolism , Lung/pathology , Lamiaceae/chemistry , Orthomyxoviridae Infections/drug therapy , Transcription Factor RelA/metabolism , Caspase 3/metabolismABSTRACT
The flower perianth has various, non-mutually exclusive functions, such as visual signalling to pollinators and protecting the reproductive organs from the elements and from florivores, but how different perianth structures and their different sides play a role in these functions is unclear. Intriguingly, in many species there is a clear colour difference between the different sides of the perianth, with colour patterns or pigmentation present on only one side. Any adaptive benefit from such colour asymmetry is unclear, as is how the asymmetry evolved. In this viewpoint paper, we address the phenomenon of flowers with differently coloured inner and outer perianth sides, focusing on petals of erect flowers. Guided by existing literature and our own observations, we delineate three non-mutually exclusive evolutionary hypotheses that may explain the factors underlying differently coloured perianth sides. The pollen-protection hypothesis predicts that the outer side of petals contributes to protect pollen against UV radiation, especially during the bud stage. The herbivore-avoidance hypothesis predicts that the outer side of petals reduces the flower's visibility to herbivores. The signalling-to-pollinators hypothesis predicts that flower colours evolve to increase conspicuousness to pollinators. The pollen-protection hypothesis, the herbivore-avoidance hypothesis, and the signalling-to-pollinators hypothesis generate largely but not entirely overlapping predictions about the colour of the inner and outer side of the petals. Field and laboratory research is necessary to disentangle the main drivers and adaptive significance of inner-outer petal side colour asymmetry.
Subject(s)
Biological Evolution , Flowers , Pigmentation , Pollination , Animals , Color , Flowers/physiology , Flowers/anatomy & histology , Herbivory/physiology , Pigmentation/physiology , Pollen/physiology , Pollination/physiologyABSTRACT
Using the fusion-evaporation reaction ^{106}Cd(^{58}Ni,4n)^{160}Os and the gas-filled recoil separator SHANS, two new isotopes _{76}^{160}Os and _{74}^{156}W have been identified. The α decay of ^{160}Os, measured with an α-particle energy of 7080(26) keV and a half-life of 201_{-37}^{+58} µs, is assigned to originate from the ground state. The daughter nucleus ^{156}W is a ß^{+} emitter with a half-life of 291_{-61}^{+86} ms. The newly measured α-decay data allow us to derive α-decay reduced widths (δ^{2}) for the N=84 isotones up to osmium (Z=76), which are found to decrease with increasing atomic number above Z=68. The reduction of δ^{2} is interpreted as evidence for the strengthening of the N=82 shell closure toward the proton drip line, supported by the increase of the neutron-shell gaps predicted in theoretical models.
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AIM: To develop a clinical-radiological model to predict the malignancy of solitary pulmonary nodules (SPNs) and to evaluate the accuracy of chest computed tomography imaging characteristics of SPN in diagnosing pathological type. MATERIALS AND METHODS: The predictive model was developed using a retrospective cohort of 601 SPN patients (Group A) between July 2015 and July 2020. The established model was tested using a second retrospective cohort of 124 patients between August 2020 and August 2021 (Group B). The radiological characteristics of all adenocarcinomas in two groups were analysed to determine the correlation between radiological and pathological characteristics. RESULTS: Malignant nodules were found in 78.87% of cases and benign in 21.13%. Two clinical characteristics (age and gender) and four radiological characteristics (calcification, vascular convergence, pleural retraction sign, and density) were identified as independent predictors of malignancy in patients with SPN using logistic regression analysis. The area under the receiver operating characteristic curve (0.748) of the present model was greater than the other two reported models. Diameter, spiculation, lobulation, vascular convergence, and pleural retraction signs differed significantly among pre-invasive lesions, minimally invasive adenocarcinoma, and invasive adenocarcinoma. Only diameter and density were significantly different among invasive adenocarcinoma subtypes. CONCLUSIONS: Older age, male gender, no calcification, vascular convergence, pleural contraction sign, and lower density were independent malignancy predictors of SPNs. Furthermore, the pathological classification can be clarified based on the radiological characteristics of SPN, providing a new option for the prevention and treatment of early lung cancer.
Subject(s)
Adenocarcinoma , Calcinosis , Lung Neoplasms , Solitary Pulmonary Nodule , Humans , Male , Solitary Pulmonary Nodule/pathology , Retrospective Studies , Radiography , Lung Neoplasms/pathology , Adenocarcinoma/diagnostic imagingABSTRACT
OBJECTIVE: To explore the radiosensitizing effect of icaritin on nasopharyngeal carcinoma (NPC) cells and the underlying mechanism. METHODS: MTT assay and clonal formation assay were used to evaluate the effect of icaritin on proliferation of human NPC HONE1 and HNE1 cells. The effects of icaritin treatment, γ-ray radiation, or both on production of reactive oxygen species (ROS), cell cycle distribution and apoptosis of the NPC cells were assessed using flow cytometry. The expressions of DNA damage markers γ-H2AX, cycle-related proteins CDC25C, p-CDC25C and cyclin B1, and ferroptosis markers ACSL4 and GXP4 were detected using Western blotting. A nude mouse model bearing subcutaneous HONE1 cell xenograft was used to observe the effect of icaritin and radiation on tumor growth. RESULTS: Icaritin dose-dependently inhibited the viability of the NPC cells and enhanced the inhibitory effect of radiation on cell proliferation. Flow cytometry and Western blotting showed that icaritin treatment prior to radiation significantly promoted ROS production and γ-H2AX expression in the NPC cells (P<0.001). Compared with radiation exposure alone, the combined treatment caused cell cycle arrest in G2 phase, down-regulated CDC25C and cyclin B1 expression, and up-regulated p-CDC25C expression in the cells (P<0.01), resulting also in increased cell apoptosis, enhanced expression of ferroptosis protein ACSL4 and lowered expression of GXP4 (P<0.001). In the tumor-bearing mice, icaritin treatment, compared with radiation alone, significantly reduced the tumor growth rate and decreased tumor weight (P<0.001). CONCLUSION: Icaritin can enhance radiosensitivity of NPC cells both in vitro and in nude mice possibly by enhancing ROS production to promote iron death of the cells.
Subject(s)
Carcinoma , Nasopharyngeal Neoplasms , Humans , Animals , Mice , Nasopharyngeal Carcinoma , Cyclin B1 , Carcinoma/metabolism , Nasopharyngeal Neoplasms/genetics , Mice, Nude , Reactive Oxygen Species , Radiation Tolerance , Cell Proliferation , Cell Line, Tumor , ApoptosisABSTRACT
Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage â ¡-â ¢ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage â ¡-â ¢ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage â ¡ and 186 were stage â ¢. Among stage â ¡ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage â ¢ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage â ¢C (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage â ¡ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage â ¢ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage â ¢ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Subject(s)
Melanoma , Skin Neoplasms , Humans , Antibodies, Monoclonal/therapeutic use , Apoptosis , China , Disease-Free Survival , East Asian People , Immunotherapy , Interferon-alpha/therapeutic use , Lymphatic Metastasis , Melanoma/drug therapy , Melanoma/pathology , Programmed Cell Death 1 Receptor/therapeutic use , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Melanoma, Cutaneous MalignantABSTRACT
OBJECTIVE: To investigate the value of bone mineral density (BMD) in predicting postoperative efficacy in patients undergoing total hip arthroplasty (THA), and to analyze the influencing factors of short-term outcomes. PATIENTS AND METHODS: Clinical data, including general data, perioperative indicators, and postoperative follow-up information, were collected from patients undergoing THA from July 2018 to June 2020 at Jiangsu Taizhou People's Hospital for retrospective analysis. Using the Harris Hip Score (HHS) at 12 months after THA as the therapeutic effect evaluation index, the BMD levels of patients with different therapeutic effects were compared, and the correlation of BMD with therapeutic efficacy was analyzed. Furthermore, the influencing factors of postoperative efficacy were discussed by using a logistic regression model. RESULTS: The HHS scores of 194 patients undergoing THA improved markedly at postoperative month 12 compared with the preoperative values (p<0.05), with a treatment excellent and good rate of 79.90% (155/194). The BMD level varied greatly among patients with different curative effects (p<0.05). Pearson correlation analysis identified a significant positive correlation between BMD values and HHS scores in patients undergoing THA. THA patients with different body mass index (BMI), surgical approach, occult blood loss, postoperative complications, length change of the affected limb, postoperative exercise time, and BMD had statistically significant differences in the excellent and good rate of clinical efficacy (p<0.05). According to the multivariate Logistic regression analysis, BMI, surgical approach, length change of the affected limb, and BMD were independent factors influencing the postoperative excellent and good rate of efficacy in THA patients (p<0.05). CONCLUSIONS: Preoperative BMD levels are strongly correlated with postoperative efficacy improvement in patients undergoing THA. BMD is an independent influencing factor of excellent and good postoperative efficacy in patients undergoing THA, and increasing the BMD is conducive to improving outcomes in such patients.
Subject(s)
Arthroplasty, Replacement, Hip , Humans , Retrospective Studies , Bone Density , Treatment Outcome , Body Mass IndexABSTRACT
We propose a dual-resolution scheme to achieve time-efficient autonomous exploration with one or many robots. The scheme maintains a high-resolution local map of the robot's immediate vicinity and a low-resolution global map of the remaining areas of the environment. We believe that the strength of our approach lies in this low- and high-resolution representation of the environment: The high-resolution local map ensures that the robots observe the entire region in detail, and because the local map is bounded, so is the computation burden to process it. The low-resolution global map directs the robot to explore the broad space and only requires lightweight computation and low bandwidth to communicate among the robots. This paper shows the strength of this approach for both single-robot and multirobot exploration. For multirobot exploration, we also introduce a "pursuit" strategy for sharing information among robots with limited communication. This strategy directs the robots to opportunistically approach each other. We found that the scheme could produce exploration paths with a bounded difference in length compared with the theoretical shortest paths. Empirically, for single-robot exploration, our method produced 80% higher time efficiency with 50% lower computational runtimes than state-of-the-art methods in more than 300 simulation and real-world experiments. For multirobot exploration, our pursuit strategy demonstrated higher exploration time efficiency than conventional strategies in more than 3400 simulation runs with up to 20 robots. Last, we discuss how our method was deployed in the DARPA Subterranean Challenge and demonstrated the fastest and most complete exploration among all teams.
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Reducing the dietary CP concentration in the formulation of low-protein diets without adverse effects on animal growth performance and meat quality remains challenging. In this study, we investigated the effects of nicotinamide (NAM) on the nitrogen excretion, growth performance, and meat quality of growing-finishing pigs fed low-protein diets. To measure the nitrogen balance, we conducted two trials: in nitrogen balance trial 1, four crossbred (Duroc × Landrace × Large White) barrows (40 ± 0.5 kg BW) were used in a 4 × 4 Latin square design with four diets and periods. The diets consisted of a basal diet + 30 mg/kg NAM (a control dose), basal diet + 90 mg/kg NAM, basal diet + 210 mg/kg NAM, and basal diet + 360 mg/kg NAM. In nitrogen balance trial 2, another four barrows (40 ± 0.5 kg BW) were used in a 4 × 4 Latin square design. The diets consisted of a basal diet + including 30 mg/kg NAM (control), basal diet + 360 mg/kg NAM, low-protein diet + 30 mg/kg NAM, and low-protein diet + 360 mg/kg NAM. To measure growth performance, two trials were conducted. In growth performance trial 1, 40 barrows (37.0 ± 1.0 kg) were randomly allocated to one of four dietary treatments (n = 10 per group), whereas in growth performance trial 2, 300 barrows (41.4 ± 2.0 kg) were randomly allocated to one of four dietary treatments, with each dietary treatment conducted in five repetitions with 15 pigs each. The four diets in the two growth performance trials were similar to those in nitrogen balance trial 2. Supplementing the diet with 210 or 360 mg/kg NAM reduced urinary nitrogen excretion and total nitrogen excretion and increased nitrogen retention comparted with the control diet (P < 0.05). Compared with the control diet, the low-protein diet with 360 mg/kg NAM reduced faecal, urinary, and total nitrogen excretion (P < 0.05) without affecting nitrogen retention and average daily gain (P > 0.05). Pigs fed the low-protein diet with 360 mg/kg NAM showed a decreased intramuscular fat content in the longissimus thoracis muscle when compared with pigs fed the control diet (P > 0.05). Our results suggest NAM as a suitable dietary additive to reduce dietary CP concentration, maximise nitrogen retention and growth performance, and decrease fat deposition in pigs.
Subject(s)
Niacinamide , Nitrogen , Swine , Animals , Niacinamide/pharmacology , Diet/veterinary , Diet, Protein-Restricted/veterinary , Meat/analysis , Animal Feed/analysis , Dietary Supplements , Animal Nutritional Physiological PhenomenaABSTRACT
An epidemiological investigation was conducted on a cluster epidemic of COVID-19 in the vaccinated population in Beijing in 2022, and serum samples were collected from 21 infected cases and 61 close contacts (including 20 cases with positive nucleic acid in the isolation observation period). The results of antibody detection showed that the IgM antibody of two infected persons was positive, and the IgG antibody positive rates of patients who were converted, not converted to positive and infected persons were 36.84% (7/19), 63.41% (26/41) and 71.43% (15/21), respectively. About 98.78% of patients had been vaccinated with the SARS-CoV-2 inactivated vaccine. The positive rate of IgG antibody in patients immunized with three doses of vaccine was 86.00% (43/50), which was higher than that in patients with one or two doses [16.12% (5/31)]. The antibody level of M (Q1, Q3) in patients immunized with three doses was 4.255 (2.303, 7.0375), which was higher than that in patients with one or two doses [0.500 (0.500, 0.500)] (all P values<0.001). The antibody level of patients who were vaccinated less than three months [7.335 (1.909, 7.858)] was higher than that of patients vaccinated more than three months after the last vaccination [2.125 (0.500, 4.418)] (P=0.007). The positive rate and level of IgG antibody in patients who were converted to positive after three doses were 77.78% (7/9) and 4.207 (2.216, 7.099), respectively, which were higher than those in patients who were converted after one or two doses [0 and 0.500 (0.500, 0.500)] (all P values<0.05).
Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Disease Outbreaks , COVID-19 Vaccines , Immunoglobulin G , Antibodies, ViralABSTRACT
In Bragg coherent diffractive imaging, the precise location of the measured crystals in the interior of the sample is usually missing. Obtaining this information would help the study of the spatially dependent behavior of particles in the bulk of inhomogeneous samples, such as extra-thick battery cathodes. This work presents an approach to determine the 3D position of particles by precisely aligning them at the instrument axis of rotation. In the test experiment reported here, with a 60â µm-thick LiNi0.5Mn1.5O4 battery cathode, the particles were located with a precision of 20â µm in the out-of-plane direction, and the in-plane coordinates were determined with a precision of 1â µm.
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Objective: To investigate the infection sources and the transmission chains of three outbreaks caused by 2019-nCoV Omicron variant possibly spread through cross-border logistics in Beijing. Methods: Epidemiological investigation and big data were used to identify the exposure points of the cases. Close contacts were traced from the exposure points, and the cases' and environmental samples were collected for nucleic acid tests. Positive samples were analyzed by gene sequencing. Results: The Omicron variant causing 3 outbreaks in Beijing from January to April, 2022 belonged to BA.1, BA.1.1 and BA.2. The outbreaks lasted for 8, 12 and 8 days respectively, and 6, 42 and 32 cases infected with 2019-nCoV were reported respectively. International mail might be the infection source for 1 outbreak, and imported clothes might be the infection sources for another 2 outbreaks. The interval between the shipment start time of the imported goods and the infection time of the index case was 3-4 days. The mean incubation period (Q1, Q3) was 3 (2,4) days and the mean serial interval (Q1, Q3) was 3 (2,4)days. Conclusions: The 3 outbreaks highlighted the risk of infection by Omicron variant from international logistics-related imported goods at normal temperature. Omicron variant has stronger transmissibility, indicating that rapid epidemiological investigation and strict management are needed.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Beijing , Disease Outbreaks , China/epidemiologyABSTRACT
The development of high mobility emissive organic semiconductors is of great significance for the fabrication of miniaturized optoelectronic devices, such as organic light emitting transistors. However, great challenge exists in designing key materials, especially those who integrates triplet exciton utilization ability. Herein, dinaphthylanthracene diimides (DNADIs), with 2,6-extended anthracene donor, and 3'- or 4'-substituted naphthalene monoimide acceptors were designed and synthesized. By introducing acceptor-donor-acceptor structure, both materials show high electron mobility. Moreover, by fine-tuning of substitution sites, good integration with high solid state photoluminescence quantum yield of 26 %, high electron mobility of 0.02â cm2 â V-1 s-1 , and the feature of hot-exciton induced delayed fluorescence were obtained in 4'-DNADI. This work opens a new avenue for developing high electron mobility emissive organic semiconductors with efficient utilization of triplet excitons.
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Low temperatures limit the geographic distribution and yield of plants. Hormones play an important role in coordinating the growth and development of plants and their tolerance to low temperatures. However, the mechanisms by which hormones affect plant resistance to extreme cold stress in the natural environment are still unclear. In this study, two winter wheat varieties with different cold resistances, Dn1 and J22, were used to conduct targeted plant hormone metabolome analysis on the tillering nodes of winter wheat at 5 °C, -10 °C and -25 °C using an LC-ESI-MS/MS system. We screened 39 hormones from 88 plant hormone metabolites and constructed a partial regulatory network of auxin, jasmonic acid and cytokinin. GO analysis and enrichment of KEGG pathways in different metabolites showed that the 'plant hormone signal transduction' pathway was the most common. Our study showed that extreme low temperature increased the most levels of auxin, cytokinin and salicylic acid, and decreased levels of jasmonic acid and abscisic acid, and that levels of auxin, jasmonic acid and cytokinin in Dn1 were higher than those in J22. These changes in hormone levels were associated with changes in gene expression in synthesis, catabolism, transport and signal transduction pathways. These results differ from the previous hormone regulation mechanisms, which were mostly obtained at 4 °C. Our results provide a basis for further understanding the molecular mechanisms by which plant endogenous hormones regulate plant freezing stress tolerance.
Subject(s)
Plant Growth Regulators , Triticum , Plant Growth Regulators/metabolism , Freezing , Triticum/metabolism , Cold-Shock Response , Tandem Mass Spectrometry , Cold Temperature , Cytokinins/metabolism , Plants/metabolism , Indoleacetic Acids/metabolism , Hormones/metabolism , Gene Expression Regulation, PlantABSTRACT
Objective: To explore the effect of growth arrest-specific5 (GAS5) inhibition on the proliferation, colony formation, invasion, migration andepithelial-mesenchymal transition(EMT), cancer cell stem of HCT-116 and its mechanism. Methods: The colorectal carcinoma (CRC) cell HCT116 was divided into blank control, negative control (NC), si-GAS5 and si-GAS5+ miR-21 inhibitor groups. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to test the expressions of miR-21 and GAS5 at 48 h after transfection. The binding site of GAS5 and miR-21 was determined by luciferase reporter array. Cell proliferation ability was detected by CCK-8 assay. Cell colony ability was detected by colony formation assay. Cell invasion and migration abilities were detected by Transwell assay. Cell cycle and apoptosis were examined by flow cytometer (FCM). The protein levels of EMT associated factors including Snail, N-cadherin, vimentin, E-cadherin, stem cell related factors including CD44, SOX2, Oct2, and PTEN/Akt signal pathway associated factors were examined by western blotting. Results: The expression levels of miR-21 in blank, NC, si-GAS5 group were 1.00±0.10, 1.00±0.10, 1.80±0.20, the absorbance values were 0.51±0.02, 0.50±0.01 and 0.65±0.01, the cell clones were 90±4, 91±5, 200±8, the invaded cells were 118±3, 119±3, 150±4, the migrated cells were 110±2, 108±2, 127±2, the cell ratios in G(1) phase were (49.3±2.1)%, (50.1±2.0)% and (42.2±1.1)%, the cell ratios in S phase were (19.2±1.2)%, (20.2±1.1)% and (28.3±2.2)%, the cell apoptotic ratios were (14.4±2.2)%, (14.5±2.1)% and (7.2±1.3)%. These results indicated that inhibition of GAS5 up regulated the expression level of miR-21, promoted cell proliferation, invasion and migration, decreased G(1)-phase cells and increased S-phase cells, and suppressed cell apoptosis (P<0.05). Moreover, inhibition of GAS5 up regulated the expressions of Snail, N-cadherin, vimentin, Sox2, CD44, Oct2 and p-Akt in HCT-116 cells (P<0.05), while down regulated the expressions of E-cadherin and PTEN (P<0.05). Inhibition of miR-21 reversed the impact of GAS5 knockdown on PTEN/Akt signaling pathway (P<0.05). Conclusion: GAS5 can act as a competing endogenous RNA for miR-21, and down regulation of GAS5 can promote the development of CRC by activating the miR-21/PTEN/Akt signaling pathway and promoting the acquisition of EMT and tumor cell stemness.
Subject(s)
Colorectal Neoplasms , MicroRNAs , Humans , Cadherins/genetics , Cadherins/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , MicroRNAs/metabolism , Proto-Oncogene Proteins c-akt/metabolism , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Vimentin/metabolismABSTRACT
Human corneal endothelial cells (HCECs) are the prerequisite for maintaining corneal transparency, but HCECs remain arrested at the G1 phase after embryonic development and can not proliferate and regenerate. Thus, the density of HCECs decreases spontaneously with corneal development. Systemic factors, primary corneal disease, refractive factors, glaucoma, inflammation, and trauma all can cause a massive loss of HCECs, lead to corneal edema and turbidity, and ultimately induce blindness. Currently, keratoplasty is the only effective treatment, but the scarcity of donor corneas and the limitation of corneal preservation technology restrict the availability of keratoplasty. Therefore, the most appealing way to tackle the tissue shortage problem is corneal endothelial cell regeneration. In recent years, not only the endogenous regeneration of HCECs mediated by surgery, drugs and gene therapy but also the exogenous regeneration of HCECs mediated by cell therapy have made fruitful progress. Although a number of regeneration strategies have entered the clinical trial stage, the wide clinical application of corneal endothelial regeneration is still far away. This review elaborates the basic research, clinical application and limitation of current strategies of corneal endothelial cell regeneration.
Subject(s)
Corneal Transplantation , Endothelial Cells , Cells, Cultured , Endothelium, Corneal , Humans , RegenerationABSTRACT
OBJECTIVE: Extracellular vesicles released by mesenchymal stem cells (MSC-EVs) can be applied to alleviate intervertebral disc degeneration (IVDD) by curbing apoptosis of nucleus pulposus cells (NPCs). The current study aims to evaluate the effect of MSC-EVs on NPC apoptosis and IVDD and the related regulatory mechanisms involving microRNA (miR)-217. METHOD: Expression of miR-217 was examined in tumor necrosis factor-α (TNF-α)-induced NPCs and MSC-EVs, followed by identification in the relationship between miR-217, enhancer of zeste homolog 2 (EZH2) and forkhead box O-3 (FOXO3). After isolation of EVs from MSCs and subsequent co-culture with NPCs, we assessed effects of miR-217 on NPC viability, autophagy, senescence and apoptosis along with extracellular matrix (ECM) degradation. Further in vivo experiments were conducted in rat models of IVDD to substantiate the effect of miR-217 on IVDD. RESULTS: Poor miR-217 expression was found in TNF-α-induced NPCs, while high miR-217 expression was identified in MSC-EVs (P < 0.05). MSC-EVs transferred miR-217 to NPCs and increased its expression, thus attenuating NPC apoptosis and ECM degradation (elevated collagen II and aggrecan but reduced MMP13 and ADAMTS5) (P < 0.05). miR-217 targeted EZH2, and EZH2 bound to the FOXO3 promoter and consequently downregulated its expression. FOXO3 restrained NPC apoptosis and ECM degradation by stimulating cell autophagy (P < 0.05). Furthermore, in vivo experimental results confirmed the suppressive role of miR-217 shuttled by MSC-EVs in IVDD. CONCLUSION: Overall, the delivery of miR-217 may be a novel mechanism underlying the effect of MSC-EVs on NPC apoptosis and ECM degradation following IVDD.
Subject(s)
Extracellular Vesicles , Intervertebral Disc Degeneration , Mesenchymal Stem Cells , MicroRNAs , Nucleus Pulposus , Animals , Rats , Aggrecans/metabolism , Apoptosis , Collagen/metabolism , Enhancer of Zeste Homolog 2 Protein/metabolism , Extracellular Vesicles/metabolism , Extracellular Vesicles/pathology , Intervertebral Disc Degeneration/pathology , Intervertebral Disc Degeneration/prevention & control , Matrix Metalloproteinase 13/metabolism , Mesenchymal Stem Cells/metabolism , MicroRNAs/metabolism , Nucleus Pulposus/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Objective: To investigate the source and the transmission chain of a cold-chain product associated COVID-19 epidemic caused by 2019-nCoV Delta variant in Beijing. Methods: Epidemiological investigation were used to verify the exposure points of the cases. Close contacts were traced from the exposure points, and human and environmental samples were collected for nucleic acid tests. Positive samples were analyzed by gene sequencing. Results: A total of 112 cases of COVID-19 were reported in the epidemic from January 18 to February 6, 2022 in Beijing. Except for 1 case was uncertain, there were epidemiological links among 111 cases. The source of infection was the packages of imported cold-chain products from Southeast Asia, which were harvested and stored in a local cold-storage in January 2021, and packaged and sent to the cold-storage A in A district in June 2021, and then sold in batches in cold-storage B in B district from January 2022. The first case was infected in the handling of positive frozen products, and then 77 cases occurred due to working, eating and living together with the index case in the cold-storage B, cold-storage C and restaurant D. Besides the cold-storage B, C and the restaurant D, there were 16 sub-transmission chains, resulting in additional 35 cases. Conclusion: The epidemic indicated that the risk of 2019-nCoV infection from imported cold-chain products contaminated by package and highlighted the importance to strengthen the management of cold-chain industry in future.