ABSTRACT
DNA damage is a key factor affecting gametogenesis and embryo development. The integrity and stability of DNA are fundamental to a woman's successful conception, embryonic development, pregnancy and the production of healthy offspring. Aging, reactive oxygen species, radiation therapy, and chemotherapy often induce oocyte DNA damage, diminished ovarian reserve, and infertility in women. With the increase of infertility population, there is an increasing need to study the relationship between infertility related diseases and DNA damage and repair. Researchers have tried various methods to reduce DNA damage in oocytes and enhance their DNA repair capabilities in an attempt to protect oocytes. In this review, we summarize recent advances in the DNA damage response mechanisms in infertility diseases such as PCOS, endometriosis, diminished ovarian reserve and hydrosalpinx, which has important implications for fertility preservation.
Subject(s)
DNA Damage , DNA Repair , Infertility, Female , Female , Humans , Infertility, Female/genetics , Infertility, Female/therapy , Oocytes , Polycystic Ovary Syndrome/genetics , Endometriosis/genetics , Ovarian Reserve/physiology , Fertility Preservation/methodsABSTRACT
BACKGROUND: The genus Triplostegia contains two recognized species, T. glandulifera and T. grandiflora, but its phylogenetic position and species delimitation remain controversial. In this study, we assembled plastid genomes and nuclear ribosomal DNA (nrDNA) cistrons sampled from 22 wild Triplostegia individuals, each from a separate population, and examined these with 11 recently published Triplostegia plastomes. Morphological traits were measured from herbarium specimens and wild material, and ecological niche models were constructed. RESULTS: Triplostegia is a monophyletic genus within the subfamily Dipsacoideae comprising three monophyletic species, T. glandulifera, T. grandiflora, and an unrecognized species Triplostegia sp. A, which occupies much higher altitude than the other two. The new species had previously been misidentified as T. glandulifera, but differs in taproot, leaf, and other characters. Triplotegia is an old genus, with stem age 39.96 Ma, and within it T. glandulifera diverged 7.94 Ma. Triplostegia grandiflora and sp. A diverged 1.05 Ma, perhaps in response to Quaternary climate fluctuations. Niche overlap between Triplostegia species was positively correlated with their phylogenetic relatedness. CONCLUSIONS: Our results provide new insights into the species delimitation of Triplostegia, and indicate that a taxonomic revision of Triplostegia is needed. We also identified that either rpoB-trnC or ycf1 could serve as a DNA barcode for Triplostegia.
Subject(s)
Caprifoliaceae , Genome, Plastid , Humans , Adult , Phylogeny , Caprifoliaceae/genetics , Genome, Plastid/genetics , Phenotype , DNA, RibosomalABSTRACT
BACKGROUND: MiRNAs can affect the radiosensitization of head and neck squamous cell carcinoma (HNSCC). We aimed to analyze the function of miR-125 family members in HNSCC using The Cancer Genome Atlas (TCGA) and determine their effect on radiation in laryngeal squamous cell cancer (LSCC). METHODS: First, we systematically analyzed the role of the miR-125 family in HNSCC using the TCGA database and found that miR-125a-5p is associated with radiotherapy. We then performed comprehensive enrichment analysis of miR-125a-5p and predicted target genes. Then, we performed transfection, cell proliferation assays, reverse transcription polymerase chain reaction, apoptosis assays, micronucleus tests, and western blotting on hep-2 cells selected with puromycin. RESULTS: MiR-125 family members exhibited significantly different expression in HNSCC. They were significantly associated with tumor-node-metastasis staging, clinical stages, and histological grades. Radiation therapy had a statistically effect on miR-125 family members, except miR-125a-3p. Moreover, miR-125a-5p was related to overall survival in LSCC. Thus, we predicted 110 target genes and seven hub genes of miR-125a-5p. The proliferation rate of cells transfected with lentivirus vector expressing miR-125a-5p was significantly reduced compared to the other groups. The radiation effect was enhanced in cells transfected with miR-125a-5p. The ratio of apoptotic cells transfected and exposed to X-rays (10 Gy) was distinctly higher than that of the Ad-control group. Western blotting analysis revealed that miR-125a-5p upregulated the apoptotic regulators P53 and rH2AX. Thus, miR-125a-5p may increase radiosensitivity in LSCC via upregulation of pro-apoptotic genes. CONCLUSIONS: MiR-125 family members could be prognostic biomarkers of HNSCC and improve HNSCC sensitivity to radiotherapy by activating P53. Upregulating miR-125a-5p via lentivirus vectors may be a novel strategy to strengthen the effect of radiotherapy on LSCC.
Subject(s)
Head and Neck Neoplasms , MicroRNAs , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Tumor Suppressor Protein p53/genetics , Cell Line, Tumor , MicroRNAs/genetics , Radiation Tolerance/genetics , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/radiotherapy , Gene Expression Regulation, Neoplastic , Cell Proliferation/geneticsABSTRACT
BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.
Subject(s)
Asthma , Biological Products , Nasal Polyps , Rhinitis , Sinusitis , Humans , Asthma/drug therapy , Biological Products/therapeutic use , Chronic Disease , Consensus , Nasal Polyps/complications , Nasal Polyps/drug therapy , Omalizumab/therapeutic use , Quality of Life , Rhinitis/complications , Rhinitis/drug therapy , Sinusitis/complications , Sinusitis/drug therapy , Steroids/therapeutic useABSTRACT
The impact of COVID-19 is global, and uncertain information will affect product quality and worker efficiency in the complex supply chain network, thus bringing risks. Aiming at individual heterogeneity, a partial mapping double-layer hypernetwork model is constructed to study the supply chain risk diffusion under uncertain information. Here, we explore the risk diffusion dynamics, drawing on epidemiology, and establish an SPIR (Susceptible-Potential-Infected-Recovered) model to simulate the risk diffusion process. The node represents the enterprise, and hyperedge represents the cooperation among enterprises. The microscopic Markov chain approach (MMCA) is used to prove the theory. Network dynamic evolution includes two removal strategies: (i) removing aging nodes; (ii) removing key nodes. Using Matlab to simulate the model, we found that it is more conducive to market stability to eliminate outdated enterprises than to control key enterprises during risk diffusion. The risk diffusion scale is related to interlayer mapping. Increasing the upper layer mapping rate to strengthen the efforts of official media to issue authoritative information will reduce the infected enterprise number. Reducing the lower layer mapping rate will reduce the misled enterprise number, thereby weakening the efficiency of risk infection. The model is helpful for understanding the risk diffusion characteristics and the importance of online information, and it has guiding significance for supply chain management.
ABSTRACT
Anacardic acid (AA) is a phenolic acid extract found in a number of plants, crops, and fruits. It exhibits a wide range of biological activities. This study displayed that AA effectively alleviated EAE, a classical mouse model of multiple sclerosis. AA administered to the EAE greatly decreased inflammatory cell infiltration to the CNS and protected the myelin integrity in the white matter of the spinal cord. AA could block lipopolysaccharide-induced DC activation. inhibited the polarization of 2D2 mice-derived T cells by inhibiting the DCs activity. Immunoblot results indicated that the phosphorylation of NF-κB is significantly suppressed in AA-treated DCs. This work displayed that AA possessed a potential anti-inflammatory therapeutic effect for the treatment of autoimmune disease.
Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Anacardic Acids , Animals , Dendritic Cells , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Mice , Mice, Inbred C57BL , Neuroinflammatory Diseases , Spinal CordABSTRACT
Myopia has become a global public health problem due to high prevalence. Although the etiological factors of myopia have been gradually recognized, the underlying mechanism remains largely elusive. Choroidal vascular dysfunction is recognized as a critical vision-threatening complication in myopia. Circular RNAs (circRNAs) are shown as the critical regulators in many biological processes and human diseases. In this study, we investigated the role of circRNAs in choroidal vascular dysfunction in myopia. The level of circFoxO1 was significantly upregulated in myopic choroid. circFoxO1 silencing suppressed choroidal endothelial cell viability, proliferation, migration, and tube formation in vitro and alleviated choroidal vascular dysfunction in vivo and ex vivo. circFoxO1 silencing retarded the progression of myopia as shown by reduced extracellular matrix remodeling and improved refractive error and axial elongation. Mechanistically, circFoxO1 acted as the sponge of miR-145 to sequester and inhibit miR-145 activity, thereby inducing VEGFA or ANGPT2 expression. miR-145 could mimic the effects of circFoxO1 silencing on choroidal endothelial phenotypes. Collectively, intervention of choroidal vascular dysfunction via regulating circFoxO1 level is a potential strategy for the prevention and management of myopia.
Subject(s)
Choroid/drug effects , Endothelium, Vascular/drug effects , Forkhead Box Protein O1/genetics , Gene Expression Regulation , Myopia/prevention & control , RNA, Circular/administration & dosage , Angiopoietin-2/genetics , Angiopoietin-2/metabolism , Animals , Apoptosis , Cell Movement , Cell Proliferation , Cells, Cultured , Choroid/metabolism , Choroid/pathology , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Humans , Male , Mice , Mice, Inbred C57BL , MicroRNAs/genetics , Myopia/etiology , Myopia/pathology , RNA, Circular/antagonists & inhibitors , RNA, Circular/genetics , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Hyperlipidemia-induced retinal vascular dysfunction is a complex pathological process. circRNAs are important regulators of biological processes and disease progression. However, the expression pattern of circRNAs in hyperlipidemia-induced retinal vascular dysfunction remains unclear. Herein, we used a murine model of hyperlipidemia and identified 317 differentially expressed circRNAs between hyperlipidemic retinas and normolipidemic retinas by circRNA microarrays. GO analysis indicated that the host genes of dysregulated circRNAs were targeted to cell differentiation (ontology: biological process), cytoplasm (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis revealed that circRNAs-mediated network was mostly enriched in focal adhesion signaling. Notably, circLDB1 was significantly up-regulated in the serum of coronary artery disease patients and aqueous humor of age-related macular degeneration patients. circLDB1 regulated endothelial cell viability, proliferation, and apoptosis in vitro. Thus, circRNAs are the promising targets for the prediction and diagnosis of hyperlipidemia-induced vascular diseases.
Subject(s)
Diabetic Retinopathy/genetics , Hyperlipidemias/genetics , RNA, Circular/genetics , Retinal Vessels/metabolism , Animals , Diabetic Retinopathy/metabolism , Female , Gene Regulatory Networks , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Hyperlipidemias/metabolism , Male , Mice , Mice, Inbred C57BL , RNA, Circular/metabolism , Retinal Vessels/pathologyABSTRACT
Age-associated loss of skeletal muscle mass and function is one of the main causes of the loss of independence and physical incapacitation in the geriatric population. This study used the D-galactose-induced C2C12 myoblast aging model to explore whether nobiletin (Nob) could delay skeletal muscle aging and determine the associated mechanism. The results showed that Nob intervention improved mitochondrial function, increased ATP production, reduced reactive oxygen species (ROS) production, inhibited inflammation, and prevented apoptosis as well as aging. In addition, Nob improved autophagy function, removed misfolded proteins and damaged organelles, cleared ROS, reduced mitochondrial damage, and improved skeletal muscle atrophy. Moreover, our results illustrated that Nob can not only enhance mitochondrial function, but can also enhance autophagy function and the protein synthesis pathway to inhibit skeletal muscle atrophy. Therefore, Nob may be a potential candidate for the prevention and treatment of age-related muscle decline.
Subject(s)
Galactose , Mitochondria , Adenosine Triphosphate/metabolism , Aged , Aging/metabolism , Cellular Senescence , Flavones , Galactose/adverse effects , Galactose/metabolism , Humans , Mitochondria/metabolism , Muscle, Skeletal/metabolism , Muscular Atrophy/chemically induced , Muscular Atrophy/drug therapy , Reactive Oxygen Species/metabolismABSTRACT
Epigenetic alterations occur in many physiological and pathological processes. N6-methyladenosine (m6A) modification is the most prevalent modification in eukaryotic mRNAs. However, the role of m6A modification in pathological angiogenesis remains elusive. In this study, we showed that the level of m6A modification was significantly upregulated in endothelial cells and mouse retinas following hypoxic stress, which was caused by increased METTL3 levels. METTL3 silencing or METTL3 overexpression altered endothelial cell viability, proliferation, migration, and tube formation in vitro. METTL3 knockout in vivo decreased avascular area and pathological neovascular tufts in an oxygen-induced retinopathy model and inhibited alkali burn-induced corneal neovascularization. Mechanistically, METTL3 exerted its angiogenic role by regulating Wnt signaling through the m6A modification of target genes (e.g., LRP6 and dishevelled 1 [DVL1]). METTL3 enhanced the translation of LRP6 and DVL1 in an YTH m6A RNA-binding protein 1 (YTHDF1)-dependent manner. Collectively, this study suggests that METTL3-mediated m6A modification is an important hypoxic stress-response mechanism. The targeting of m6A through its writer enzyme METTL3 is a promising strategy for the treatment of angiogenic diseases.
Subject(s)
Adenosine/analogs & derivatives , Epigenesis, Genetic , Gene Expression Regulation , Methyltransferases/metabolism , Neovascularization, Pathologic/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Adenosine/metabolism , Animals , Biomarkers , Disease Susceptibility , Gene Silencing , Humans , Hypoxia/complications , Hypoxia/metabolism , Mice , Mice, Knockout , Neovascularization, Pathologic/metabolism , Retinal Diseases/etiology , Retinal Diseases/metabolism , Retinal Diseases/pathology , Wnt Signaling PathwayABSTRACT
INTRODUCTION: Laryngeal squamous cell carcinoma (LSCC) is diverse in its natural history and responsiveness to treatments. There is an urgent need to generate candidate biomarkers for the stratification and individualization of treatment to avoid overtreatment or inadequate treatment. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been identified as an oncogenic gene in multiple human tumors entitles, and dysregulation of NEAT1 was tightly linked to carcinogenesis and cancer progression. METHODS: One hundred two paraffin samples of LSCC patients were collected. Furthermore, in situ hybridization (ISH), Kaplan-Meier, and MTT were used to analyze the relationship between NEAT1 and the progress of LSCC. RESULTS: In this study, ISH revealed that NEAT1 was strongly expressed in the nucleus. The increased expression of NEAT1 was correlated with T grade, neck nodal metastasis, clinical stage, drinking history, or smoking history of LSCC. The Kaplan-Meier analysis indicated that patients with higher NEAT1 expression had a worse overall survival in LSCC patients. In addition, NEAT1 knockdown significantly inhibited the growth of LSCC cells. CONCLUSION: Together, these results suggested that NEAT1 involved in the progress of LSCC and might act as a tumor oncogenic gene. This study provides a potential new marker and target for gene therapy in the treatment of LSCC.
Subject(s)
Laryngeal Neoplasms , RNA, Long Noncoding , Squamous Cell Carcinoma of Head and Neck , Biomarkers, Tumor/genetics , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Laryngeal Neoplasms/pathology , Prognosis , RNA, Long Noncoding/genetics , Squamous Cell Carcinoma of Head and Neck/geneticsABSTRACT
Two new ß-dihydroagarofuran-type sesquiterpenes 1ß,2α,6α,8ß,15- pentaacetoxy- 9α-benzoyloxy- ß-dihydroagarofuran (1) and 1ß,2ß,6α,15-tetraacetoxy-9ß-benzoyloxy- ß-dihydroagarofuran (2), together with five known abietane diterpenoids (3-7) were isolated from ethyl acetate extract of stems of Tripterygium wilfordii. Their structures were elucidated on the basis of detailed spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against A549, HOS and MCF-7. Among them, compounds 4 and 5 exhibited manifest inhibition on A549, HOS and MCF-7 cancer cell lines.
Subject(s)
Drugs, Chinese Herbal , Sesquiterpenes , Drugs, Chinese Herbal/pharmacology , Molecular Structure , Sesquiterpenes/pharmacology , TripterygiumABSTRACT
BACKGROUND: Ectopic fat accumulation in skeletal muscle results in dysfunction and atrophy, but the underlying molecular mechanisms remain unclear. OBJECTIVE: The aim of this study was to investigate the effects of a high-fat diet (HFD) in modulating the structure and energy metabolism of skeletal muscle and the underlying mechanisms in mice. METHODS: Four-week-old male C57BL/6 J mice (n = 30) were allowed 1 wk for acclimatization. After 6 mice with low body weight were removed from the study, the remaining 24 mice were fed with a normal-fat diet (NFD; 10% energy from fat, n = 12) or an HFD (60% energy from fat, n = 12) for 24 wk. At the end of the experiment, serum glucose and lipid concentrations were measured, and skeletal muscle was collected for atrophy analysis, inflammation measurements, and phosphoproteomic analysis. RESULTS: Compared with the NFD, the HFD increased (P < 0.05) body weight (35.8%), serum glucose (64.5%), and lipid (27.3%) concentrations, along with elevated (P < 0.05) expressions of the atrophy-related proteins muscle ring finger 1 (MURF1; 27.6%) and muscle atrophy F-box (MAFBX; 44.5%) in skeletal muscle. Phosphoproteomic analysis illustrated 64 proteins with differential degrees of phosphorylation between the HFD and NFD groups. These proteins were mainly involved in modulating cytoskeleton [adenylyl cyclase-associated protein 2 (CAP2) and actin-α skeletal muscle (ACTA1)], inflammation [NF-κB-activating protein (NKAP) and serine/threonine-protein kinase RIO3 (RIOK3)], glucose metabolism [Cdc42-interacting protein 4 (TRIP10); protein kinase C, and casein kinase II substrate protein 3 (PACSIN3)], and protein degradation [heat shock protein 90 kDa (HSP90AA1)]. The HFD-induced inhibitions of the insulin signaling pathway and activations of inflammation in skeletal muscle were verified by Western blot analysis. CONCLUSIONS: Quantitative phosphoproteomic analysis in C57BL/6 J mice fed an NFD or HFD for 24 wk revealed that the phosphorylation of inflammatory proteins and proteins associated with glucose metabolism at specific serine residues may play critical roles in the regulation of skeletal muscle atrophy induced by an HFD. This work provides information regarding underlying molecular mechanisms for inflammation-induced dysfunction and atrophy in skeletal muscle.
Subject(s)
Diet, High-Fat , Inflammation/metabolism , Muscle, Skeletal/metabolism , Muscular Atrophy/metabolism , Phosphoproteins/metabolism , Proteomics , Animals , Male , Mice , Mice, Inbred C57BL , Obesity/metabolism , Phosphorylation , Proteolysis , Signal TransductionABSTRACT
Pathological ocular angiogenesis commonly results in visual impairment or even blindness. Unveiling the mechanisms of pathological angiogenesis is critical to identify the regulators and develop effective targeted therapies. Here, we used corneal neovascularization (CNV) model to investigate the mechanism of pathological ocular angiogenesis. We show that N6-methyladenosine (m6A) mRNA demethylation mediated by fat mass- and obesity-associated protein (FTO) could regulate endothelial cell (EC) function and pathological angiogenesis during CNV. FTO levels are increased in neovascularized corneas and ECs under pathological conditions. In vitro silencing of FTO in ECs results in reduced cellular proliferation, migration, and tube formation under both basal and pathological conditions. Furthermore, FTO silencing attenuates suture-induced CNV in vivo. Mechanically, FTO silencing in ECs could increase m6A methylation levels in critical pro-angiogenic genes, such as FAK, leading to decreased RNA stability and increased RNA decay through m6A reader YTHDF2. Our study demonstrates that FTO regulates pathological ocular angiogenesis by controlling EC function in an m6A-YTHDF2-dependent manner.
Subject(s)
Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Corneal Neovascularization/genetics , Gene Expression Regulation , Membrane Glycoproteins/genetics , Nerve Tissue Proteins/genetics , RNA, Messenger/genetics , RNA-Binding Proteins/genetics , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism , Animals , Cell Proliferation , Cells, Cultured , Corneal Neovascularization/metabolism , Corneal Neovascularization/pathology , Disease Models, Animal , Membrane Glycoproteins/metabolism , Mice , Mice, Inbred C57BL , Nerve Tissue Proteins/metabolism , RNA Stability , RNA, Messenger/metabolism , RNA-Binding Proteins/metabolismABSTRACT
Lithium-sulfur batteries are considered as the next generation of energy storage systems because of their high theoretical specific capacity and energy density. Unfortunately, the sluggish reaction kinetics, weak adsorption toward to lithium polysulfides, and slow lithium ion diffusion impede the smooth electrochemical process, resulting in the lithium-sulfur batteries with the unsatisfactory cycling stability and rate performance. Since it is recognized that polar metal oxides and doped nitrogen in carbon materials have chemical interaction with lithium polysulfides, a nanostructured nitrogen-doped porous carbon/MoO2 composite is synthesized through a simple hydrothermal method by using graphene oxide nanoribbon and phosphomolybdic acid hydrate as precursors. The porous nanostructure promotes the charge and mass transport, while MoO2 nanoparticles immobilize lithium polysulfides via strong chemisorption and enhance the redox kinetics of polysulfides owing to the efficient catalytic activity in liquid-solid boundary. Consequently, the as-obtained nanostructured porous carbon/MoO2-based sulfur cathode exhibits low polarization, high initial discharge capacity (1403 mAh g-1 at 0.1 C), good rate capabilities (584 mAh g-1 at 4 C), and impressive cycling performance at 1 C (503 mAh g-1 after 500 cycles with capacity fade rate of 0.07% per cycle).
ABSTRACT
Liver injury is an important cause of serious liver disease. This study aims to explore the effects of miR-217 targeting NAT2 on hepatocyte proliferation, apoptosis, and autophagy following carbon tetrachloride (CCL4)-induced liver injury. Rat models of CCL4-induced liver injury were established. Healthy Wistar rats were randomized into the normal, blank, negative control (NC), microRNA-217 (miR-217) mimic, miR-217 inhibitor, small interfering RNA (siRNA)-N-acetyltransferase 2 (NAT2), and miR-217 inhibitor + siRNA-NAT2 groups. NAT2 activity was evaluated with reversed-phase high-performance liquid chromatographic method. Immunohistochemistry was used to detect NAT2 protein positive rate. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to examine expressions of miR-217, NAT2, Bcl-2, Bax, p35, LC3-II, Becline-1, and the ratio of caspase-3/cleaved caspase-3. Autophagy, proliferation, and cell cycle distribution were determined by electron microscope, CCK-8, and flow cytometry. NAT2 protein positive rate and miR-217, NAT2, Bcl-2, and p35 expressions were higher and Bax, LC3-II, and Becline-1 expressions and the ratio of caspase-3/cleaved caspase-3 lower in the normal group than the other six groups. Compared with the blank and NC groups, in the miR-217 mimic and siRNA-NAT2 groups, Bax, LC3-II, and Becline-1 expressions and the ratio of caspase-3/cleaved caspase-3, and hepatocyte apoptosis and autophagy increased, while NAT2, Bcl-2, and p35 expressions and hepatocyte proliferation decreased; opposite results were observed in the miR-217 inhibitor group. Collectively, miR-217 targeting NAT2 inhibits proliferation and promotes apoptosis and autophagy of hepatocytes in CCL4-induced liver injury.
Subject(s)
Apoptosis , Arylamine N-Acetyltransferase/metabolism , Autophagy , Cell Proliferation , Chemical and Drug Induced Liver Injury/enzymology , Hepatocytes/enzymology , Liver/enzymology , MicroRNAs/metabolism , Animals , Apoptosis Regulatory Proteins/metabolism , Arylamine N-Acetyltransferase/genetics , Autophagosomes/metabolism , Autophagosomes/pathology , Autophagy-Related Proteins/metabolism , Carbon Tetrachloride , Cell Cycle Proteins/metabolism , Chemical and Drug Induced Liver Injury/genetics , Chemical and Drug Induced Liver Injury/pathology , Disease Models, Animal , Hepatocytes/pathology , Liver/pathology , Male , MicroRNAs/genetics , Rats, Wistar , Signal TransductionABSTRACT
Adsorption behaviors of methylene blue (MB) from aqueous solution using sunflower stem pith (SSP) as adsorbent were investigated. The effects of adsorption conditions such as adsorption time, initial concentration of MB and dosage of SSP on the detoxification of MB were examined. The equilibrium adsorption data were analyzed using three well-known isotherms: Langmuir, Freundlich and Temkin. The results indicated that the Langmuir isotherm fitted well to the data as compared with another isotherm model. The maximum adsorption capacity calculated by the Langmuir isotherm model was 277 mg/g at 338 K. Kinetic analyses were conducted using pseudo first order, pseudo second order and the Elovich model. The regression results showed that the MB adsorption was described by the pseudo second order model. Different thermodynamic parameters such as Gibb's free energy (ΔGo), standard enthalpy change (ΔHo) and standard entropy change (ΔSo) were also evaluated. The results showed that the detoxification of MB using SSP as adsorbent was feasible, non-spontaneous and exothermic under experimental conditions.
Subject(s)
Helianthus/chemistry , Methylene Blue/chemistry , Water Pollutants, Chemical/chemistry , Adsorption , Hydrogen-Ion Concentration , Kinetics , ThermodynamicsABSTRACT
BACKGROUNDS/AIMS: MicroRNAs (miRs) often contribute to the progression of non-small cell lung cancer (NSCLC) via regulation of mRNAs that are involved in lung homeostasis. We conducted a study aimed at exploring the roles of miR-183 in the proliferation, epithelial-mesenchymal transition (EMT), invasion and migration of human NSCLC cells via targeting MTA1. METHODS: NSCLC and adjacent normal tissues were collected from 194 patients with NSCLC. Positive expression of MTA1 protein was detected by immunohistochemistry. The highest levels of expression of miR-183 were detected using RT-qPCR in SPC-A-1 cells, which were selected and assigned to the following groups: blank, negative control (NC), miR-183 mimic, miR-183 inhibitor, siRNA-MTA1, and miR-183 inhibitor + siRNA-MTA1. The expression of miR-183 and the mRNA and protein expression of MTA1, E-cadherin, Vimentin, Snail, PCNA, Bax and Bcl-2 in tissues and transfected cells were measured using RT-qPCR and western blot analysis. Cell proliferation, apoptosis, migration and invasion were evaluated by CCK-8, flow cytometry, scratch tests and Transwell assays. Tumor xenografts were conducted in nude mice to determine tumor growth. RESULTS: SPC-A-1 cells with the highest levels of miR-183 expression were selected. Compared with adjacent normal tissues, the expression of miR-183 and the mRNA and protein expression of E-cadherin and Bax were decreased in NSCLC tissues, while mRNA and protein expression of MTA1, Vimentin, snail, PCNA and Bcl-2 were increased. MiR-183 was over-expressed in the miR-183 mimic group and under-expressed in the miR-183 inhibitor and miR-183 inhibitor + siRNA-MTA1 groups. In the miR-183 mimic and siRNA-MTA1 groups, the mRNA and protein expression of E-cadherin and Bax, as well as cell apoptosis, were enhanced, while the expression levels of MTA1, Vimentin, snail, PCNA and Bcl-2 mRNA and protein, cell proliferation, migration, invasion and tumor growth were reduced relative to the blank and NC groups. The miR-183 inhibitor group exhibited an opposite trend. CONCLUSION: Our study indicates that miR-183 down-regulates MTA1 to inhibit the proliferation, EMT, migration and invasion of human NSCLC cells.
Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Histone Deacetylases/metabolism , Lung Neoplasms/pathology , MicroRNAs/metabolism , Repressor Proteins/metabolism , Animals , Antagomirs/metabolism , Cadherins/genetics , Cadherins/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Down-Regulation , Histone Deacetylases/genetics , Humans , Lung Neoplasms/genetics , Mice , Mice, Nude , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , Proliferating Cell Nuclear Antigen/genetics , Proliferating Cell Nuclear Antigen/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA Interference , Repressor Proteins/antagonists & inhibitors , Repressor Proteins/genetics , Snail Family Transcription Factors/genetics , Snail Family Transcription Factors/metabolism , Trans-Activators , Transplantation, Heterologous , Vimentin/genetics , Vimentin/metabolism , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolismABSTRACT
In this work, a series of highly porous sulfur-doped carbons are prepared through physical activation methods by using polythiophene as a precursor. The morphology, structure, and physicochemical properties are revealed by a variety of characterization methods, such as scanning electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, and nitrogen sorption measurement. Their porosity parameters and chemical compositions can be well-tuned by changing the activating agents (steam and carbon dioxide) and reaction temperature. These sulfur-doped porous carbons possess specific surface area of 670-2210 m2 g-1, total pore volume of 0.31-1.26 cm3 g-1, and sulfur content of 0.6-4.9 atom %. The effect of porosity parameters and surface chemistry on carbon dioxide adsorption in sulfur-doped porous carbons is studied in detail. After a careful analysis of carbon dioxide uptake at different temperatures (273 and 293 K), pore volumes from small pore size (less than 1 nm) play an important role in carbon dioxide adsorption at 273 K, whereas surface chemistry is the key factor at a higher adsorption temperature or lower relative pressure. Furthermore, sulfur-doped porous carbons also possess good gas adsorption selectivity and excellent recyclability for regeneration.