ABSTRACT
Mitochondria play an important role in the energy production of plant cells through independent genetic systems. This study has aimed to assemble and annotate the functions of the mitochondrial (mt) genome of Luffa cylindrica. The mt genome of L. cylindrica contained two chromosomes with lengths of 380,879 bp and 67,982 bp, respectively. Seventy-seven genes including 39 protein-coding genes, 34 tRNA genes, 3 rRNA genes, and 1 pseudogene, were identified. About 90.63% of the codons ended with A or U bases, and 98.63% of monomers contained A/T, which contributed to the high A/T content (55.91%) of the complete mt genome. Six genes (ATP8, CCMFC, NAD4, RPL10, RPL5 and RPS4) showed positive selection. Phylogenetic analysis indicates that L. cylindrica is closely related to L. acutangula. The present results provide the mt genome of L. cylindrica, which may facilitate possible genetic variation, evolutionary, and molecular breeding studies of L. cylindrica.
Subject(s)
Genome, Mitochondrial , Luffa , Phylogeny , Luffa/genetics , RNA, Transfer/genetics , Genome, Plant , Plant Proteins/genetics , Plant Proteins/metabolismABSTRACT
BACKGROUND: Purple flowering stalk (Brassica rapa var. purpuraria) is a widely cultivated plant with high nutritional and medicinal value and exhibiting strong adaptability during growing. Mitochondrial (mt) play important role in plant cells for energy production, developing with an independent genetic system. Therefore, it is meaningful to assemble and annotate the functions for the mt genome of plants independently. Though there have been several reports referring the mt genome of in Brassica species, the genome of mt in B. rapa var. purpuraria and its functional gene variations when compared to its closely related species has not yet been addressed. RESULTS: The mt genome of B. rapa var. purpuraria was assembled through the Illumina and Nanopore sequencing platforms, which revealed a length of 219,775 bp with a typical circular structure. The base composition of the whole B. rapa var. purpuraria mt genome revealed A (27.45%), T (27.31%), C (22.91%), and G (22.32%). 59 functional genes, composing of 33 protein-coding genes (PCGs), 23 tRNA genes, and 3 rRNA genes, were annotated. The sequence repeats, codon usage, RNA editing, nucleotide diversity and gene transfer between the cp genome and mt genome were examined in the B. rapa var. purpuraria mt genome. Phylogenetic analysis show that B. rapa var. Purpuraria was closely related to B. rapa subsp. Oleifera and B. juncea. Ka/Ks analysis reflected that most of the PCGs in the B. rapa var. Purpuraria were negatively selected, illustrating that those mt genes were conserved during evolution. CONCLUSIONS: The results of our findings provide valuable information on the B.rapa var. Purpuraria genome, which might facilitate molecular breeding, genetic variation and evolutionary researches for Brassica species in the future.
Subject(s)
Brassica rapa , Genome, Mitochondrial , Phylogeny , Brassica rapa/genetics , Molecular Sequence Annotation , Genome, Plant , RNA, Transfer/genetics , Base CompositionABSTRACT
BACKGROUND: Heart failure (HF) is a state of inappropriately sustained inflammation, suggesting the loss of normal immunosuppressive mechanisms. Regulatory T-lymphocytes (Tregs) are considered key suppressors of immune responses; however, their role in HF is unknown. We hypothesized that Tregs are dysfunctional in ischemic cardiomyopathy and HF, and they promote immune activation and left ventricular (LV) remodeling. METHODS: Adult male wild-type C57BL/6 mice, Foxp3-diphtheria toxin receptor transgenic mice, and tumor necrosis factor (TNF) α receptor-1 (TNFR1)-/- mice underwent nonreperfused myocardial infarction to induce HF or sham operation. LV remodeling was assessed by echocardiography as well as histological and molecular phenotyping. Alterations in Treg profile and function were examined by flow cytometry, immunostaining, and in vitro cell assays. RESULTS: Compared with wild-type sham mice, CD4+Foxp3+ Tregs in wild-type HF mice robustly expanded in the heart, circulation, spleen, and lymph nodes in a phasic manner after myocardial infarction, beyond the early phase of wound healing, and exhibited proinflammatory T helper 1-type features with interferon-γ, TNFα, and TNFR1 expression, loss of immunomodulatory capacity, heightened proliferation, and potentiated antiangiogenic and profibrotic properties. Selective Treg ablation in Foxp3-diphtheria toxin receptor mice with ischemic cardiomyopathy reversed LV remodeling and dysfunction, alleviating hypertrophy and fibrosis, while suppressing circulating CD4+ T cells and systemic inflammation and enhancing tissue neovascularization. Tregs reconstituted after ablation exhibited restoration of immunosuppressive capacity and normalized TNFR1 expression. Treg dysfunction was also tightly coupled to Treg-endothelial cell contact- and TNFR1-dependent inhibition of angiogenesis and the mobilization and tissue infiltration of CD34+Flk1+ circulating angiogenic cells in a C-C chemokine ligand 5/C-C chemokine receptor 5-dependent manner. Anti-CD25-mediated Treg depletion in wild-type mice imparted similar benefits on LV remodeling, circulating angiogenic cells, and tissue neovascularization. CONCLUSIONS: Proinflammatory and antiangiogenic Tregs play an essential pathogenetic role in chronic ischemic HF to promote immune activation and pathological LV remodeling. The restoration of normal Treg function may be a viable approach to therapeutic immunomodulation in this disease.
Subject(s)
Cardiomyopathies/immunology , Inflammation Mediators/immunology , Myocardial Infarction/immunology , T-Lymphocytes, Regulatory/immunology , Ventricular Function, Left , Ventricular Remodeling , Angiogenic Proteins/metabolism , Animals , Cardiomyopathies/metabolism , Cardiomyopathies/pathology , Cardiomyopathies/physiopathology , Cells, Cultured , Coculture Techniques , Disease Models, Animal , Endothelial Cells/immunology , Endothelial Cells/metabolism , Fibrosis , Inflammation Mediators/metabolism , Male , Mice, Inbred C57BL , Mice, Knockout , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Myocardium/immunology , Myocardium/metabolism , Myocardium/pathology , Neovascularization, Physiologic , Phenotype , Receptors, Tumor Necrosis Factor, Type I/genetics , Receptors, Tumor Necrosis Factor, Type I/metabolism , Signal Transduction , T-Lymphocytes, Regulatory/metabolismABSTRACT
BACKGROUND: Dietary intervention has been reported to improve intestinal health. The intestinal microbiota of newborn animals plays a fundamental role in the development of intestinal function and the innate immune system. However, little is currently known about dietary interventions in the gut microbiota and barrier function of livestock, especially suckling Bamei piglets. To this end, we studied the effect of early dietary supplementation on intestinal bacterial communities and intestinal barrier function in piglets. RESULTS: 10 purebred Bamei sows were randomly allocated into two groups. In group one, the piglets received a supplementary milk replacer on day 7 of age, whereas the other control group was allowed sow's milk alone. At 21 days, 18 and 17, respectively, piglets in each group of average weight were randomly selected and sacrificed. Tissue and digesta samples were collected from the jejunum to evaluate differences in the microbiome-metabolome and the mRNA expression of inflammatory cytokines (TLR4, TNFα and IL-8) and barrier proteins (ZO-1, Occludin and Claudin-1). Sequencing of 16S rRNA revealed that ES improved the gut microbiome composition of Bamei suckling piglets. The relative abundances of some bacterial species such as Lactobacillales, Romboutsia, Actinobacillus, Bacteroides were significantly reduced in the ES group. Metabolomics analysis indicated that 23 compounds were enriched and 35 compounds decreased in the ES group. And correlation analysis demonstrated that some gut bacterial genera were highly correlated with altered gut microbiota-related metabolites. Meanwhile, ES of Bamei suckling piglets altered the gene expression of inflammatory cytokine and barrier protein in the jejunum. CONCLUSIONS: In summary, these results provide important insights on the relationships between jejunal microbiota and related metabolites, and jejunal barrier function during the early life of Bamei suckling piglets.
Subject(s)
Bacteria/classification , Cytokines/genetics , Jejunum/microbiology , Metabolomics/methods , Sequence Analysis, DNA/methods , Animal Feed , Animals , Animals, Newborn , Bacteria/genetics , Bacteria/isolation & purification , Chromatography, Liquid , Dietary Supplements , Gene Expression Regulation , Immunity, Innate , Jejunum/immunology , Mass Spectrometry , RNA, Ribosomal, 16S/genetics , Random Allocation , SwineABSTRACT
Recent outbreaks of Ebola-virus infections in several countries demand a rapid point-of-care (POC)-detection strategy. This paper reports on an innovative pathway founded on electronic-resonance-frequency modulation to detect Ebola glycoprotein (GP), on the basis of a carrier-injection-trapping-release-transfer mechanism and the standard antibody-antigen-interaction principle within a dielectric-gated reduced graphene oxide (rGO) field-effect transistor (GFET). The sensitivity of Ebola detection can be significantly enhanced by monitoring the device's electronic-resonance frequency, such as its inflection frequency ( fi), where the phase angle reaches a maximum (θmax). In addition to excellent selectivity, a sensitivity of â¼36-160% and â¼17-40% for 0.001-3.401 mg/L Ebola GP can be achieved at high and low inflection-resonance frequencies, respectively, which are several orders of magnitude higher than the sensitivity from other electronic parameters (e.g., resistance-based sensitivity). Using equivalent circuit modeling for contributions from channel and contact, analytical equations for resonance shifts have been generalized. When matching with the incoming ac-measurement signal, electronic resonance from the phase-angle spectrum evolves from various relaxation processes (e.g., trap and release of injected charges at surface-trap sites of the channel-gate oxide and channel-source or drain interfaces) that are associated with a characteristic emission frequency. Using charge-relaxation dynamics, a high-performance bio-FET sensing platform for healthcare and bioelectronic applications is realized through resonance shifting.
Subject(s)
Ebolavirus/metabolism , Graphite/chemistry , Point-of-Care Systems , Transistors, Electronic , Viral Proteins/immunology , Antibodies, Immobilized/chemistry , Antibodies, Immobilized/immunology , Antibodies, Viral/chemistry , Antibodies, Viral/immunology , Antigen-Antibody Reactions , Gold/chemistry , Hemorrhagic Fever, Ebola/diagnosis , Humans , Metal Nanoparticles/chemistry , Recombinant Proteins/biosynthesis , Recombinant Proteins/immunology , Recombinant Proteins/isolation & purification , Surface Plasmon Resonance , Viral Proteins/genetics , Viral Proteins/metabolismABSTRACT
Stimuli-responsive field-effect transistors (FETs) based on 2D nanomaterials have been considered as attractive candidates for sensing applications due to their rapid response, high sensitivity, and real-time monitoring capabilities. Here we report on an impedance spectroscopy technique for FET sensor applications with ultra-high sensitivity and good reproducibility. An alumina-gated FET, using an ultra-thin black phosphorus flake as the channel material, shows significantly improved stability and ultra-high sensitivity to lead ions in water. In addition, the phase angle in the low frequency region was found to change significantly in the presence of lead ion solutions, whereas it was almost unchanged in the high frequency region. The dominant sensing performance was found at low frequency phase spectrum around 50 Hz and a systematic change in the phase angle in different lead ion concentrations was found. Applying the impedance spectroscopy technique to insulator-gated FET sensors could open a new avenue for real-world sensor applications.
ABSTRACT
PURPOSE: Continuous positive airway pressure (CPAP) therapy may decrease the risk of mortality and cardiovascular events in patients with obstructive sleep apnea. However, these benefits are not completely clear. METHODS: We undertook a meta-analysis of randomized clinical trials identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database. RESULTS: Eighteen studies (4146 patients) were included. Overall, CPAP therapy did not significantly decrease the risk of cardiovascular events compared with the control group (odds ratio (OR), 0.84; 95 % confidence intervals (CI), 0.62-1.13; p = 0.25; I (2) = 0 %). CPAP was associated with a nonsignificant trend of lower rate of death and stroke (for death: OR, 0.85; 95 % CI, 0.35-2.06; p = 0.72; I (2) = 0.0 %; for stroke: OR, 0.56; 95 % CI, 0.18-1.73; p = 0.32; I (2) = 12.0 %), a significantly lower Epworth sleepiness score (ESS) (mean difference (MD), -1.78; 95 % CI, -2.31 to -1.24; p < 0.00001; I (2) = 76 %), and a significantly lower 24 h systolic and diastolic blood pressure (BP) (for 24 h systolic BP: MD, -2.03 mmHg; 95 % CI, -3.64 to -0.42; p = 0.01; I (2) = 0 %; for diastolic BP: MD, -1.79 mmHg; 95 % CI, -2.89 to -0.68; p = 0.001; I (2) = 0 %). Daytime systolic BP and body mass index were comparable between the CPAP and control groups. Subgroup analysis did not show any significant difference between short- and mediate-to-long-term follow-up groups with regard to cardiovascular events, death, and stroke. CONCLUSIONS: CPAP therapy was associated with a trend of decreased risk of cardiovascular events. Furthermore, ESS and BP were significantly lower in the CPAP group. Larger randomized studies are needed to confirm these findings.
Subject(s)
Cardiovascular Diseases/complications , Cardiovascular Diseases/therapy , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/therapy , Blood Pressure , Body Mass Index , Cardiovascular Diseases/mortality , Cause of Death , Comorbidity , Continuous Positive Airway Pressure , Follow-Up Studies , Humans , Incidence , Randomized Controlled Trials as Topic , Risk , Sleep Apnea, Obstructive/mortalitySubject(s)
Cardiomyopathies , Myocardial Ischemia , Heart , Humans , T-Lymphocytes, Regulatory , Ventricular RemodelingABSTRACT
Water contaminants, e.g., inorganic chemicals and microorganisms, are critical metrics for water quality monitoring and have significant impacts on human health and plants/organisms living in water. The scope and focus of this review is nanomaterial-based optical, electronic, and electrochemical sensors for rapid detection of water contaminants, e.g., heavy metals, anions, and bacteria. These contaminants are commonly found in different water systems. The importance of water quality monitoring and control demands significant advancement in the detection of contaminants in water because current sensing technologies for water contaminants have limitations. The advantages of nanomaterial-based sensing technologies are highlighted and recent progress on nanomaterial-based sensors for rapid water contaminant detection is discussed. An outlook for future research into this rapidly growing field is also provided.
Subject(s)
Metals, Heavy/analysis , Water Pollutants, Chemical/analysis , Nanostructures/chemistryABSTRACT
Graphene (G) is attracting significant attention because of its unique physical and electronic properties. The production of graphene through the reduction of graphene oxide (GO) is a low-cost method. The reduction of GO can further lead to electrically conductive reduced GO. These graphene-based nanomaterials are attractive for high-performance water sensors due to their unique properties, such as high specific surface areas, high electron mobilities, and exceptionally low electronic noise. Because of potential risks to the environment and human health arising from heavy-metal pollution in water, G-/GO-based water sensors are being developed for rapid and sensitive detection of heavy-metal ions. In this review, a general introduction to graphene and GO properties, as well as their syntheses, is provided. Recent advances in optical, electrochemical, and electrical detection of heavy-metal ions using graphene or GO are then highlighted. Finally, challenges facing G/GO-based water sensor development and outlook for future research are discussed.
Subject(s)
Electrochemical Techniques/methods , Graphite/chemistry , Metals, Heavy/analysis , Water Pollutants, Chemical/analysisABSTRACT
Pomegranate peel is the by-product of pomegranate processing, which contains a lot of triterpene compounds. In this study, the total triterpenes of pomegranate peel (TPP) were extracted using an ultrasonic-assisted ethanol extraction method under optimal conditions, purified using D-101 macroporous resin to obtain a purity of 75.28%. The triterpenes in TPP were mainly pentacyclic triterpenes determined by LC-MS/MS. Network pharmacological analysis predicted that the anticancer targets were closely related to the MAPK pathway. The in vitro results showed that TPP could inhibit cell proliferation, promote apoptosis, reduce mitochondrial membrane potential and increase ROS levels. The western blot results indicated that the expression levels of the apoptotic proteins Bax, Bcl-2, cytochrome C, cleaved caspase-3 and cleaved caspase-9 were increased. In addition, the protein expression of the MAPK pathway predicted by network pharmacology also changed significantly. These results provided that TPP has potential for adjuvant therapy of tumors.
Subject(s)
Apoptosis , Cell Proliferation , Plant Extracts , Pomegranate , Triterpenes , Triterpenes/pharmacology , Triterpenes/chemistry , Triterpenes/isolation & purification , Humans , Pomegranate/chemistry , Apoptosis/drug effects , Cell Proliferation/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Cell Line, Tumor , Membrane Potential, Mitochondrial/drug effects , Fruit/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Reactive Oxygen Species/metabolism , Tandem Mass SpectrometryABSTRACT
Fidelity of wound healing after myocardial infarction (MI) is an important determinant of subsequent adverse cardiac remodeling and failure. Macrophages derived from infiltrating Ly6C hi blood monocytes are a key component of this healing response; however, the importance of other macrophage populations is unclear. Here, using a variety of in vivo murine models and orthogonal approaches, including surgical myocardial infarction, splenectomy, parabiosis, cell adoptive transfer, lineage tracing and cell tracking, RNA sequencing, and functional characterization, we establish in mice an essential role for splenic CD169 + Tim4 + marginal metallophilic macrophages (MMMs) in post-MI wound healing. Splenic CD169 + Tim4 + MMMs circulate in blood as Ly6C low cells expressing macrophage markers and help populate CD169 + Tim4 + CCR2 - LYVE1 low macrophages in the naïve heart. After acute MI, splenic MMMs augment phagocytosis, CCR3 and CCR4 expression, and robustly mobilize to the heart, resulting in marked expansion of cardiac CD169 + Tim4 + LyVE1 low macrophages with an immunomodulatory and pro-resolving gene signature. These macrophages are obligatory for apoptotic neutrophil clearance, suppression of inflammation, and induction of a reparative macrophage phenotype in the infarcted heart. Splenic MMMs are both necessary and sufficient for post-MI wound healing, and limit late pathological remodeling. Liver X receptor-α agonist-induced expansion of the splenic marginal zone and MMMs during acute MI alleviates inflammation and improves short- and long-term cardiac remodeling. Finally, humans with acute ST-elevation MI also exhibit expansion of circulating CD169 + Tim4 + macrophages. We conclude that splenic CD169 + Tim4 + MMMs are required for pro-resolving and reparative responses after MI and can be manipulated for therapeutic benefit to limit long-term heart failure. CLINICAL PERSPECTIVE: What is new?: We establish for the first time that metallophilic marginal macrophages (MMMs) from the spleen, expressing the markers CD169 and Tim4, circulate in blood and traffic to the heart to help maintain the CD169 + Tim4 + CCR2 - LYVE1 low macrophage population in the heart. After acute myocardial infarction, splenic MMMs augment cardiac trafficking in response to chemotactic signals, resulting in expansion of CD169 + Tim4 + macrophages in the heart that play an essential role in post-MI efferocytosis, wound healing and repair while limiting longer term adverse cardiac remodeling. Analogous to mice, humans also exhibit circulating CD169 + Tim4 + macrophages in the blood that expand after acute ST segment elevation MI. What are the clinical implications?: This study highlights the importance of the cardiosplenic axis in acute MI, and the splenic marginal zone, in determining the course and outcome of post-MI LV remodeling.Pharmacological expansion of splenic marginal zone macrophages alleviated post-MI adverse LV remodeling and inflammation, suggesting that splenic modulation is a potential translational therapeutic approach for limiting post-MI inflammation and improving heart repair.
ABSTRACT
The chloroplast (cp) genome holds immense potential for a variety of applications including species identification, phylogenetic analysis, and evolutionary studies. In this study, we utilized Illumina NovaSeq 6000 to sequence the DNA of Camellia sinensis L. cultivar 'Zhuyeqi', followed by the assembly of its chloroplast genome using SPAdes v3.10.1, with subsequent analysis of its features and phylogenetic placement. The results showed that the cp genome of 'Zhuyeqi' was 157,072 bp, with a large single-copy region (LSC, 86,628 bp), a small single-copy region (SSC,18,282 bp), and two inverted repeat regions (IR, 26,081 bp). The total AT and GC contents of the cp genome of 'Zhuyeqi' were observed to be 62.21% and 37.29%, respectively. The cp genome encoded 135 unique genes, including 90 protein-coding genes (CDS), 37 tRNA genes, and 8 rRNA genes. Moreover, 31 codons and 247 simple sequence repeats (SSRs) were identified. The cp genomes of 'Zhuyeqi' were found to be relatively conserved, with conservation observed in the IR region, which showed no evidence of inversions or rearrangements. The five regions with the largest variations were identified, with four regions (rps12, rps19, rps16, and rpl33) located in the LSC region and one divergent region (trnI-GAU) in the IR region. Phylogenetic analysis revealed that Camellia sinensis (KJ996106.1) was closely related to 'Zhuyeqi', indicating a close phylogenetic relationship between these two species. These findings could provide important genetic information for further research into breeding of tea tree, phylogeny, and evolution of Camellia sinensis.
Subject(s)
Camellia sinensis , Genome, Chloroplast , Phylogeny , Camellia sinensis/genetics , Evolution, Molecular , Plant BreedingABSTRACT
Risk management for drinking water often requires continuous monitoring of various toxins in flowing water. While they can be readily integrated with existing water infrastructure, two-dimensional (2D) electronic sensors often suffer from device-to-device variations due to the lack of an effective strategy for identifying faulty devices from preselected uniform devices based on electronic properties alone, resulting in sensor inaccuracy and thus slowing down their real-world applications. Here, we report the combination of wet transfer, impedance and noise measurements, and machine learning to facilitate the scalable nanofabrication of graphene-based field-effect transistor (GFET) sensor arrays and the efficient identification of faulty devices. Our sensors were able to perform real-time detection of heavy-metal ions (lead and mercury) and E. coli bacteria simultaneously in flowing tap water. This study offers a reliable quality control protocol to increase the potential of electronic sensors for monitoring pollutants in flowing water.
Subject(s)
Drinking Water , Graphite , Mercury , Metals, Heavy , Water Pollutants , Graphite/chemistry , Escherichia coli , Drinking Water/analysisABSTRACT
Heart failure (HF) is characterized by progressive fibrosis. Both fibroblasts and mesenchymal stem cells (MSCs) can differentiate into pro-fibrotic myofibroblasts. MSCs secrete and express platelet-derived growth factor (PDGF) and its receptors. We hypothesized that PDGF signaling in cardiac MSCs (cMSCs) promotes their myofibroblast differentiation and aggravates post-myocardial infarction left ventricular remodeling and fibrosis. We show that cMSCs from failing hearts post-myocardial infarction exhibit an altered phenotype. Inhibition of PDGF signaling in vitro inhibited cMSC-myofibroblast differentiation, whereas in vivo inhibition during established ischemic HF alleviated left ventricular remodeling and function, and decreased myocardial fibrosis, hypertrophy, and inflammation. Modulating cMSC PDGF receptor expression may thus represent a novel approach to limit pathologic cardiac fibrosis in HF.
ABSTRACT
BACKGROUND: Heme oxygenase-1 (HO-1) is an inducible stress-response protein that imparts antioxidant and antiapoptotic effects. However, its pathophysiological role in cardiac remodeling and chronic heart failure (HF) is unknown. We hypothesized that induction of HO-1 in HF alleviates pathological remodeling. METHODS AND RESULTS: Adult male nontransgenic and myocyte-restricted HO-1 transgenic mice underwent either sham operation or coronary ligation to induce HF. Four weeks after ligation, nontransgenic HF mice exhibited postinfarction left ventricular (LV) remodeling and dysfunction, hypertrophy, fibrosis, oxidative stress, apoptosis, and reduced capillary density, associated with a 2-fold increase in HO-1 expression in noninfarcted myocardium. Compared with nontransgenic mice, HO-1 transgenic HF mice exhibited significantly (P<0.05) improved postinfarction survival (94% versus 57%) and less LV dilatation (end-diastolic volume, 46+/-8 versus 85+/-32 microL), mechanical dysfunction (ejection fraction, 65+/-9% versus 49+/-16%), hypertrophy (LV/tibia length 4.4+/-0.4 versus 5.2+/-0.6 mg/mm), interstitial fibrosis (11.2+/-3.1% versus 18.5+/-3.5%), and oxidative stress (3-fold reduction in tissue malondialdehyde). Moreover, myocyte-specific HO-1 overexpression in HF promoted tissue neovascularization and ameliorated myocardial p53 expression (2-fold reduction) and apoptosis. In isolated mitochondria, mitochondrial permeability transition was inhibited by HO-1 in a carbon monoxide (CO)-dependent manner and was recapitulated by the CO donor tricarbonylchloro(glycinato)ruthenium(II) (CORM-3). HO-1-derived CO also prevented H2O2-induced cardiomyocyte apoptosis and cell death. Finally, in vivo treatment with CORM-3 alleviated postinfarction LV remodeling, p53 expression, and apoptosis. CONCLUSIONS: HO-1 induction in the failing heart is an important cardioprotective adaptation that opposes pathological LV remodeling, and this effect is mediated, at least in part, by CO-dependent inhibition of mitochondrial permeability transition and apoptosis. Augmentation of HO-1 or its product, CO, may represent a novel therapeutic strategy for ameliorating HF.
Subject(s)
Apoptosis/physiology , Heart Failure/pathology , Heart Failure/physiopathology , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , Animals , Carbon Monoxide/metabolism , Cardiotonic Agents/pharmacology , Chronic Disease , Fibrosis , Gene Expression/physiology , Heart Failure/drug therapy , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Mitochondria/physiology , Myocardial Infarction/drug therapy , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Myocardium/metabolism , Myocardium/pathology , Neovascularization, Physiologic/physiology , Organometallic Compounds/pharmacology , Oxidative Stress/physiology , Stroke Volume/physiology , Up-Regulation/physiology , Ventricular Dysfunction, Left/drug therapy , Ventricular Dysfunction, Left/pathology , Ventricular Dysfunction, Left/physiopathology , Ventricular Remodeling/physiologyABSTRACT
Hyperglycemia induces p38 MAPK-mediated renal proximal tubular cell (RPTC) apoptosis. The current study hypothesized that alteration of the Akt signaling pathway by hyperglycemia may contribute to p38 MAPK activation and development of diabetic nephropathy. Immunoblot analysis demonstrated a hyperglycemia-induced increase in Akt phosphorylation in diabetic kidneys at 1 mo, peaking at 3 mo, and dropping back to baseline by 6 mo. Immunohistochemical staining with anti-pAkt antisera localized Akt phosphorylation to renal tubules. Maximal p38 MAPK phosphorylation was detected concomitant with increase in terminal uridine deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells and caspase-3 activity in 6-mo diabetic kidneys. Exposure of cultured RPTCs to high glucose (HG; 22.5 mM) significantly increased Akt phosphorylation at 3, 6, and 9 h, and decreased thereafter. In contrast, p38 MAPK phosphorylation was detected between 9 and 48 h of HG treatment. Increased p38 MAPK activation at 24 and 48 h coincided with increased apoptosis, demonstrated by increased caspase-3 activity at 24 h and increased TUNEL-positive cells at 48 h of HG exposure. Blockade of p38 cascade with SB203850 inhibited HG-induced caspase-3 activation and TUNEL-positive cells. Overexpression of constitutively active Akt abrogated HG-induced p38 MAPK phosphorylation and RPTC apoptosis. In addition, blockade of the phosphatidylinositol-3 kinase/Akt pathway with LY294002 and silencing of Akt expression with Akt small interfering RNA induced p38 MAPK phosphorylation in the absence of HG. These results collectively suggest that downregulation of Akt activation during long-term hyperglycemia contributes to enhanced p38 MAPK activation and RPTC apoptosis. Mechanism of downregulation of Akt activation in 6-mo streptozotocin diabetic kidneys was attributed to decreased Akt-heat shock protein (Hsp) 25, Akt-p38 interaction, and decreased PTEN activity. Thus PTEN or Hsp25 could serve as potential therapeutic targets to modulate Akt activation and control p38 MAPK-mediated diabetic complications.
Subject(s)
Apoptosis/physiology , Diabetes Mellitus, Experimental/metabolism , Diabetic Nephropathies/metabolism , Kidney Tubules/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/physiology , p38 Mitogen-Activated Protein Kinases/metabolism , Animals , Caspase 3/metabolism , Cells, Cultured , Diabetes Mellitus, Experimental/complications , Diabetic Nephropathies/etiology , Diabetic Nephropathies/pathology , Disease Models, Animal , Humans , Hyperglycemia/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Kidney Tubules/pathology , Male , Mice , Mice, Inbred Strains , PTEN Phosphohydrolase/metabolism , Protein Serine-Threonine Kinases/metabolism , StreptozocinABSTRACT
Atomically thin black phosphorus (BP) field-effect transistors have excellent potential for sensing applications. However, commercial scaling of PFET sensors is still in the early stage due to various technical challenges, such as tedious fabrication, low response% caused by rapid oxidation, non-ideal response output (spike/bidirectional), and large device variation due to poor control over layer thickness among devices. Attempts have been made to address these issues. First, a theoretical model for response% dependence on the number of layers is developed to show the role of atomically thin BP for better responses. A position-tracked, selected-area-exfoliation method has been developed to rapidly produce thin BP layers with a narrow distribution (â¼1-7 layers), which can harness excellent gate control over the PFET channel. The typical current on/off ratio is in the range of â¼300-500. The cysteine-modified Al2O3-gated PFET sensors show high responses (â¼30-900%) toward a wide detection range (â¼1-400 ppb) of lead ions in water with a typical response time of â¼10-30 s. A strategy to minimize device variation is proposed by correlating PFETs' on/off ratio with sensitivity parameters. The thickness variation of the gate oxide is investigated to explain non-ideal and ideal response transient kinetics.
ABSTRACT
The jejunum is the primary organ for digestion and nutrient absorption in mammals. The development of the jejunum in suckling piglets directly affects their growth performance post-weaning. The jejunum microbiome plays an important role in proliferation, metabolism, apoptosis, immune, and homeostasis of the epithelial cells within the organ. The composition and diversity of the gut microbiome is susceptible to the protein composition of the diet. Therefore, the effects of maternal low-protein diets on piglets' intestinal microbial structure and function have become a hot topic of study. Herein, a maternal low-protein diet was formulated to explore the effects on jejunum microbiome composition and metabolic profiles in Bamei suckling piglets. Using 16S ribosomal RNA (16S rRNA) sequencing in conjunction with bioinformatics analysis, 21 phyla and 297 genera were identified within the gut microflora. The top 10 phyla and 10 genera are within the gut bacteria. Next, KEGG analysis showed that the low-protein diet significantly increased the gut microbial composition, transport and catabolism, immune system, global and overview maps, amino acid metabolism, metabolism of cofactors and vitamins, endocrine system, biosynthesis of other secondary metabolites, signal transduction, environmental adaptation, and cell motility. Taken together, low-protein diets do not appear to affect the reproductive performance of Bamei sows but improved the gut microbiome of the suckling piglets as well as reduced the probability of diarrhea. The data presented here provide new insights on the dietary protein requirements to support the Huzhu Bamei pig industry.