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1.
Front Mol Neurosci ; 17: 1342233, 2024.
Article in English | MEDLINE | ID: mdl-38840775

ABSTRACT

Introduction: Disrupted in schizophrenia-1 (DISC1) is a scaffolding protein whose mutated form has been linked to schizophrenia, bipolar affective disorders, and recurrent major depression. DISC1 regulates multiple signaling pathways involved in neurite outgrowth and cortical development and binds directly to glycogen synthase kinase-3ß (GSK-3ß). Since ketamine activates GSK-3ß, we examined the impact of ketamine on DISC1 and GSK-3ß expression. Methods: Postnatal day 7 rat pups were treated with ketamine with and without the non-specific GSK-3ß antagonist, lithium. Cleaved-caspase-3, GSK-3ß and DISC1 levels were measured by immunoblots and DISC1 co-localization in neurons by immunofluorescence. Binding of DISC1 to GSK-3ß was determined by co-immunoprecipitation. Neurite outgrowth was determined by measuring dendrite and axon length in primary neuronal cell cultures treated with ketamine and lithium. Results: Ketamine decreased DISC1 in a dose and time-dependent manner. This corresponded to decreases in phosphorylated GSK-3ß, which implicates increased GSK-3ß activity. Lithium significantly attenuated ketamine-induced decrease in DISC1 levels. Ketamine decreased co-immunoprecipitation of DISC1 with GSK-3ß and axonal length. Conclusion: These findings confirmed that acute administration of ketamine decreases in DISC1 levels and axonal growth. Lithium reversed this effect. This interaction provides a link between DISC1 and ketamine-induced neurodegeneration.

2.
Cancer Sci ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700108

ABSTRACT

Triple-negative breast cancer (TNBC) has greater infiltration of M2-like macrophages (TAMs), which enhances cancer cell invasion and leads to a poor prognosis. TNBC progression is mediated by both tumor cells and the tumor microenvironment (TME). Here we elucidate the mechanism of the interaction between TNBC cells and TAMs. In this study, we confirmed that CD44v5 is highly expressed in TNBC, which drives TNBC cell metastasis and promotes TAM polarization by co-localizing with IL4Rα and inhibiting its internalization and degradation, thereby promoting activation of the STAT3/IL6 signaling axis. At the same time, TAMs also facilitate TNBC cell metastasis by secreting IL-4, IL-6, and other cytokines, in which the IL-4/IL-4R/STAT3/IL-6 signaling axis plays the same role for TNBC cells responding to TAMs. Moreover, we found that the above progress could be suppressed when the CD44v5 domain was blocked. We demonstrated that the CD44v5/IL-4R/STAT3/IL-6 signaling pathway plays a key role in TNBC cell metastasis, and in TNBC cells inducing TAM polarization and responding to TAMs, promoting metastasis. Collectively, we suggest that the CD44v5 domain may be a promising target for regulating the TME of TNBC as well as treating TNBC.

3.
Sci Rep ; 14(1): 10959, 2024 05 14.
Article in English | MEDLINE | ID: mdl-38745034

ABSTRACT

Molecular hydrogen is an emerging broad-spectrum antioxidant molecule that can be used to treat myocardial infarction (MI). However, with hydrogen inhalation, the concentration that can be reached within target organs is low and the duration of action is short, which makes it difficult to achieve high dose targeted delivery of hydrogen to the heart, seriously limiting the therapeutic potential of hydrogen for MI. As a result of reactions with the internal environment of the body, subcutaneous implantation of magnesium slices leads to continuous endogenous hydrogen production, leading to a higher hydrogen concentration and a longer duration of action in target organs. In this study, we propose magnesium implant-based hydrogen therapy for MI. After subcutaneous implantation of magnesium slices in the dorsum of rats, we measured hydrogen production and efficiency, and evaluated the safety of this approach. Compared with hydrogen inhalation, it significantly improved cardiac function in rats with MI. Magnesium implantation also cleared free radicals that were released as a result of mitochondrial dysfunction, as well as suppressing cardiomyocyte apoptosis.


Subject(s)
Hydrogen , Magnesium , Myocardial Infarction , Animals , Myocardial Infarction/drug therapy , Myocardial Infarction/metabolism , Magnesium/metabolism , Rats , Male , Rats, Sprague-Dawley , Apoptosis/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/drug effects , Disease Models, Animal
4.
ACS Appl Bio Mater ; 7(5): 2695-2703, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38701372

ABSTRACT

Gold nanoclusters (AuNCs), with customized structures and diverse optical properties, are promising optical materials. Constructing composite systems by the assembly and incorporation of AuNCs can utilize their optical properties to achieve diagnostic and therapeutic applications in the biological field. Therefore, the exploration of the assembly behaviors of AuNCs and the enhancement of their performance has attracted widespread interest. In this review, we introduce multiple interactions and assembly modes that are prevalent in nanocomposites and microcomposites based on AuNCs. Then, the functions of AuNC composites for bioapplications are demonstrated in detail. These composite systems have inherited and enhanced the inherent optical performances of the AuNCs to meet diverse requirements for biological sensing and optical treatments. Finally, we discuss the prospects of AuNC composites and highlight the challenges and opportunities in biomedical applications.


Subject(s)
Biocompatible Materials , Gold , Materials Testing , Metal Nanoparticles , Gold/chemistry , Biocompatible Materials/chemistry , Metal Nanoparticles/chemistry , Humans , Particle Size , Nanocomposites/chemistry , Photochemical Processes
5.
Ultrason Sonochem ; 104: 106844, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38479187

ABSTRACT

An efficient, cost-effective and environmentally friendly ultrasound-assisted hot water method for Imperata cylindrica polysaccharide (ICPs) extraction was developed. According to the response surface results, the optimal ultrasonic time was 85 min, ultrasonic power was 192.75 W, temperature was 90.74 °C, liquid-solid ratio was 26.1, and polysaccharide yield was 28.50 %. The polysaccharide mainly consisted of arabinose (Ara), galactose (Gal), and glucose (Glc), with a molecular weight of 62.3 kDa. Ultrasound-assisted extraction of Imperata cylindrica polysaccharide (UICP) exhibited stronger anti-oxidant activity and ability to ameliorate cellular damage due to uric acid stimulation compared with traditional hot water extraction of Imperata cylindrica polysaccharide (ICPC-b). It also exhibited higher thermal stability, indicating its potential value for applications in the food industry.


Subject(s)
Antioxidants , Uric Acid , Antioxidants/pharmacology , Polysaccharides/pharmacology , Water , Apoptosis
6.
Opt Express ; 32(1): 217-229, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38175050

ABSTRACT

We investigate the capabilities and limitations of quantum-dash mode-locked lasers (QD-MLLDs) as optical frequency comb sources in coherent optical communication systems. We demonstrate that QD-MLLDs are on par with conventional single-wavelength narrow linewidth laser sources and can support high symbol rates and modulation formats. We manage to transmit 64 quadrature amplitude modulation (QAM) signals up to 80 GBd over 80 km of standard single-mode fiber (SSMF), which highlights the distinctive phase noise performance of the QD-MLLD. Using a 38.5 GHz (6 dB bandwidth) silicon photonic (SiP) modulator, we achieve a maximum symbol rate of 104 GBd with 16QAM signaling and a maximum net rate of 416 Gb/s per carrier in a single polarization setup and after 80 km-SSMF transmission. We also compare QD-MLLD performance with commercial narrow-linewidth integrable tunable laser assemblies (ITLAs) and explore their potential for use as local oscillators (LOs) and signal carriers. The QD-MLLD has 45 comb lines usable for transmission at a frequency spacing of 25 GHz, and an RF linewidth of 35 kHz.

7.
Molecules ; 29(1)2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38202838

ABSTRACT

Enzyme biofuel cells (EBFCs) can convert chemical or biochemical energy in fuel into electrical energy, and therefore have received widespread attention. EBFCs have advantages that traditional fuel cells cannot match, such as a wide range of fuel sources, environmental friendliness, and mild reaction conditions. At present, research on EBFCs mainly focuses on two aspects: one is the use of nanomaterials with excellent properties to construct high-performance EBFCs, and the other is self-powered sensors based on EBFCs. This article reviews the applied nanomaterials based on the working principle of EBFCs, analyzes the design ideas of self-powered sensors based on enzyme biofuel cells, and looks forward to their future research directions and application prospects. This article also points out the key properties of nanomaterials in EBFCs, such as electronic conductivity, biocompatibility, and catalytic activity. And the research on EBFCs is classified according to different research goals, such as improving battery efficiency, expanding the fuel range, and achieving self-powered sensors.


Subject(s)
Bioelectric Energy Sources , Nanostructures , Electricity , Electric Conductivity , Electronics
8.
Appl Opt ; 62(32): 8696-8701, 2023 Nov 10.
Article in English | MEDLINE | ID: mdl-38037987

ABSTRACT

We demonstrate photonic beamforming using a quantum-dash (QD) optical frequency comb (OFC) source. Thanks to the 25 GHz free spectral range (FSR) and up to 40 comb lines available from the QD OFC, we can implement phased antenna arrays (PAAs) with directional radiation and scanning. We consider two types of PAAs: a uniform linear array (ULA) and a uniform planar array (UPA). By selecting different comb lines with a programmable optical filter, we can tune the FSR of the OFC source and realize a discrete scanning function. We evaluate the beam squint of the ULAs, and the results show that we can achieve broadband operation. Finally, we show that we can achieve both directional radiation and scanning simultaneously using the UPA.

9.
Micromachines (Basel) ; 14(12)2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38138398

ABSTRACT

We present here a performance comparison of quantum-dash (Qdash) semiconductor amplifiers (SOAs) with three, five, eight, and twelve InAs dash layers grown on InP substrates. Other than the number of Qdash layers, the structures were identical. The eight-layer Qdash SOA gave the highest amplified spontaneous emission power (4.3 dBm) and chip gain (26.4 dB) at 1550 nm, with a 300 mA CW bias current and at 25 °C temperature, while SOAs with fewer Qdash layers (for example, three-layer Qdash SOA), had a wider ASE bandwidth (90 nm) and larger 3 dB gain saturated output power (18.2 dBm) in a shorter wavelength range. The noise figure (NF) of the SOAs increased nearly linearly with the number of Qdash layers. The longest gain peak wavelength of 1570 nm was observed for the 12-layer Qdash SOA. The most balanced performance was obtained with a five-layer Qdash SOA, with a 25.4 dB small-signal chip gain, 15.2 dBm 3 dB output saturated power, and 5.7 dB NF at 1532 nm, 300 mA and 25 °C. These results are better than those of quantum well SOAs reported in a recent review paper. The high performance of InAs/InP Qdash SOAs with different Qdash layers shown in this paper could be important for many applications with distinct requirements under uncooled scenarios.

10.
Carbohydr Polym ; 317: 121064, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37364951

ABSTRACT

ICPC-a was from the Imperata cylindrica with a molecular weight of 45 kDa, which was composed of α-D-1,3-Glcp and α-D-1,6-Glcp. The ICPC-a showed thermal stability, maintaining its structural integrity up to 220°C. X-ray diffraction analysis confirmed its amorphous nature, while scanning electron microscopy revealed a layered morphology. ICPC-a significantly ameliorated uric acid stimulation-induced HK-2 cell injury and apoptosis and reduced uric acid levels in mice with hyperuricemic nephropathy. ICPC-a protected against renal injury by inhibiting lipid peroxidation levels, increasing antioxidant damage and defense levels, inhibiting secretion of pro-inflammatory factors, regulating purine metabolism, PI3K-Akt signaling pathway, NF-κB signaling pathway, inflammatory bowel disease, mTOR signaling pathway, and MAPK signaling pathway. These findings indicate that ICPC-a is a promising natural substance with multiple targets, multiple pathways of action, and without toxicity, making it a valuable subject for further research and development.


Subject(s)
Dextrans , Uric Acid , Mice , Animals , Dextrans/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Poaceae/metabolism , Kidney/metabolism , NF-kappa B/metabolism
11.
Sci Rep ; 13(1): 2357, 2023 02 09.
Article in English | MEDLINE | ID: mdl-36759519

ABSTRACT

Straw returning is an effective management measure to improve or maintain soil fertility in agricultural ecosystems. This study investigated the effects of straw returning combined with compound fertilizer on the bacterial community, enzyme activities, and soil nutrients' contents in a rape-rice rotation soil aggregates. To do so, a 5-year field trial (November 2016 to October 2021) was carried out in a paddy soil with three treatments: no straw + no fertilization (CK), compound fertilizer (F), and straw returning + compound fertilizer (SF). Soil aggregates were classified into mega-aggregates (> 2 mm), macro-aggregates (0.25-2 mm), micro-aggregates (0.053-0.25 mm), and silt-clay (< 0.053 mm) using the wet sieve method. High-throughput sequencing was employed to characterize the bacterial community, and Pearson correlation coefficient was used to identify the relationships among bacterial community, organic carbon, nitrogen, phosphorus, and enzyme activities in soil aggregates. Compared with F, the results showed that straw returning increased the content of > 2 mm aggregates by 3.17% and significantly decreased the content of 0.053-0.25 mm aggregates by 20.27%. The contents of organic carbon and total nitrogen in > 0.053 mm straw amended aggregates increased by 15.29 and 18.25%, respectively. Straw returning significantly increased the urease activity of > 0.053 mm aggregates with an average of 43.08%, while it decreased the phosphatase and invertase activities of soil aggregates by 7.71-40.66%. The Shannon indices of the bacterial community in each particle sizes soil aggregates decreased by an average of 1.16% and the Chao indices of the bacterial community in < 2 mm aggregates increased by an average of 3.90% in straw amended soils. Nevertheless, the relative abundances of Chloroflexi and Nitrospirotain in all soil aggregates increased by 6.17-71.77% in straw amended soils. Altogether, our findings suggest that straw returning is an efficient approach to enhance soil structure, carbon and nitrogen contents, and the richness of soil bacterial diversity.


Subject(s)
Oryza , Rape , Soil/chemistry , Fertilizers , Ecosystem , Agriculture , Carbon , Bacteria/genetics , Nitrogen/analysis , Soil Microbiology
12.
Article in English | MEDLINE | ID: mdl-36212967

ABSTRACT

To further determine how BHE affected the growth of HCC cells, the proportion of each cell cycle phase was explored in HCC cells by flow cytometry. Blue honeysuckle (Lonicera caerulea L.) is a species of bush that grows in eastern Russia. Blue honeysuckle extract (BHE) is rich in bioactive phytochemicals which can inhibit the proliferation of tumor cells. The mechanism underlying the anticancer activity of BHE in primary liver cancer is poorly understood. The purpose of this study was to evaluate the growth inhibition mechanism of bioactive substances from blue honeysuckle on hepatocellular carcinoma (HCC) cells and to explore its protein and gene targets. The compounds in BHE were determined by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). Cell counting kit-8 (CCK8) assay was used to evaluate the effects of BHE on HCC cell proliferation, and flow cytometry assay (FCA) was used to determine how BHE arrested the proportion of each cell cycle phase in HCC cells. Western blot (WB) was performed to determine the expression of cell cycle-related proteins in HCC cells treated with different concentrations of BHE. The xenograft tumor animal models were established by HCC cell implantation. The results showed that cyanidin-3-o-glucoside and cyanidin-3-o-sophoroside which are the main biologically active components were detected in BHE. BHE is highly effective in inhibiting the proliferation of HCC cells by arresting the HCC cell cycle in the G2/M phase. BHE also downregulated the expression of conventional or classical dendritic cells-2 (cDC2) and cyclin B1 by promoting the expression of myelin transcription factor 1 (MyT1) in HCC cells. The weight and volume of xenografts were significantly decreased in the BHE treated groups when compared to the control group. BHE increased the expression of MyT1 in xenograft tissues. These findings showed that blue honeysuckle extract inhibits proliferation in vivo and in vitro by downregulating the expression of cDC2 and cyclin B1 and upregulating the expression of MyT1 in HCC cells.

13.
BMC Microbiol ; 22(1): 203, 2022 08 20.
Article in English | MEDLINE | ID: mdl-35987607

ABSTRACT

PURPOSE: The objective of this study was to investigate the molecular characteristics and potential resistance mechanisms of linezolid-resistant (LZR) Staphylococcus capitis isolates from a tertiary hospital in China. METHODS: S. capitis isolates were obtained from clinical patient specimens; three of the isolates came from blood cultures and one from the hydrothorax. The agar dilution and E-test methods were used to identify antibiotic resistance. The chloramphenicol-florfenicol resistance (cfr) gene carrier status of the strains was determined by PCR. Whole-genome sequencing (WGS) was used to identify point mutations and L3, L4, and L22 mutations and to study the genetic environment of the cfr gene and the relationships between strains. RESULTS: The 4 isolates obtained in this study were all linezolid-resistant Staphylococcus strains. A similar of susceptibility profile pattern was observed in all four S. capitis strains, each of which exhibited a multidrug-resistant phenotype. A potentially novel mutation, C2128T, was identified, and the cfr genes of S. capitis strains were all positive. Additionally, the same mutations (C2128T and G2600T) were identified in all 23S rRNA sequences of the isolates, whereas mutations were lacking in the L3, L4, and L22 ribosomal proteins. The genetic environments surrounding cfr were identical in all four isolates. A schematic diagram of the phylogenetic tree showed that they were closely related to AYP1020, CR01, and TW2795, and a total of seven drug resistance genes were identified in these strains. CONCLUSIONS: The study indicated that the resistance of the Staphylococcus capitis strains to linezolid was caused by multiple mechanisms, and a potential novel mutation, C2128T, that may have an impact on bacterial resistance was identified.


Subject(s)
Drug Resistance, Bacterial , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Staphylococcus capitis , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/genetics , Genes, rRNA , Humans , Linezolid/pharmacology , Methicillin-Resistant Staphylococcus aureus/genetics , Microbial Sensitivity Tests , Mutation , Phylogeny , RNA, Ribosomal, 23S/genetics , Staphylococcal Infections/microbiology , Staphylococcus capitis/genetics
14.
Opt Lett ; 47(5): 1133-1136, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35230309

ABSTRACT

We demonstrate a reconfigurable microwave photonic (MWP) filter using a quantum dash (QDash) mode-locked laser (MLL) that can generate an optical frequency comb (OFC) with ∼50 comb lines and a free spectral range of 25 GHz. Thanks to the large number of comb lines, the MWP filter responses can be easily programmed by tailoring the OFC spectrum. We implement MWP filter responses with Gaussian, sinc, flat-top, and multiple peaks, as well as demonstrate that tuning of the central frequency. We achieve a minimum 3 dB bandwidth of ∼100 MHz for a sinc-shaped MWP filter, while the maximum out-of-band rejection can be up to ∼30 dB with Gaussian apodization. Our results show that the QDash-MLL is a promising OFC source for developing integrated and reconfigurable MWP filters.

15.
Free Radic Biol Med ; 183: 35-50, 2022 04.
Article in English | MEDLINE | ID: mdl-35304269

ABSTRACT

Hydrogen is a novel medical gas with several properties, including anti-oxidative, anti-inflammatory, anti-apoptotic, anti-allergic, and energy metabolism stimulating properties. Hydrogen therapy has been proven effective in the treatment of myocardial ischemia, myocardial infarction, and ischemia-reperfusion injury. Diabetic cardiomyopathy (DCM) is a serious cardiovascular complication of long-term chronic diabetes that is linked to increased heart failure and arrhythmia morbidity. The effect of hydrogen on the pathogenesis of DCM is yet to be determined. Metformin is a well-known pharmacological agent for the treatment of diabetes; however, the application of large doses of the drug is limited by its side effects. Therefore, this highlights the importance of developing novel therapies against DCM. In this regard, we investigated the effect of hydrogen on DCM and the mechanisms that underlie it. Furthermore, we also assessed the efficacy of co-administration of metformin and hydrogen. In this study, we found that hydrogen improved cardiac dysfunction and abnormal morphological structure in streptozotocin-induced diabetic mice. As a mechanism, it was confirmed that hydrogen mediated its action by reducing pyroptosis via inhibition of the AMPK/mTOR/NLRP3 signaling pathway and ameliorating fibrosis via inhibition of the TGF-ß1/Smad signaling pathway. Furthermore, our findings suggested that co-administration of hydrogen and metformin shows potent protective effects, as evidenced by increased survival rates, reduced fasting blood glucose, and decreased cell injury when compared to a single application of metformin. In conclusion, our study demonstrated that hydrogen inhalation attenuates DCM by reducing pyroptosis and fibrosis and that hydrogen can be combined with metformin to exhibit a more potent cardioprotective effect in DCM.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Cardiomyopathies , Metformin , Animals , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetic Cardiomyopathies/drug therapy , Diabetic Cardiomyopathies/metabolism , Fibrosis , Hydrogen/pharmacology , Metformin/pharmacology , Metformin/therapeutic use , Mice , Myocardium/metabolism , Pyroptosis
16.
Eur J Pharmacol ; 922: 174917, 2022 May 05.
Article in English | MEDLINE | ID: mdl-35341785

ABSTRACT

Cardiac hypertrophy occurs as a result of high levels of thyroid hormone, which may contribute to heart failure and is closely related to oxidative stress. Hydrogen is a good antioxidant. In this study, we found that intragastric levothyroxine administration for two weeks caused obvious cardiac hypertrophy without reduced systolic function. Additionally, hydrogen inhalation ameliorated the levothyroxine-induced metabolic increase and cardiac hypertrophy in rats. Serum brain natriuretic peptide expression was also attenuated by hydrogen treatment. However, hydrogen had no significant effect on levothyroxine -induced serum troponin I and serum thyroid hormone changes. Hydrogen treatment also reduced the levothyroxine-induced increase in cardiac malondialdehyde, 8-hydroxy-2-deoxyguanosine and serum hydrogen peroxide levels and upregulated superoxide dismutase and glutathione peroxidase activity. Additionally, western blotting results showed that hydrogen inhalation inhibited the expression of cardiac nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), angiotensin II type 1 receptor, sarcoplasmic reticulum Ca2+-ATPase (SERCA2), phospho-phospholamban and α-myosin heavy chain proteins. In conclusion, the present study revealed a protective effect of hydrogen on levothyroxine -induced cardiac hypertrophy by regulating angiotensin II type 1 receptors and NOX2-mediated oxidative stress in rats.


Subject(s)
Hydrogen , Receptor, Angiotensin, Type 1 , Angiotensin II/pharmacology , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Cardiomegaly/chemically induced , Cardiomegaly/drug therapy , Cardiomegaly/metabolism , Hydrogen/pharmacology , Hydrogen/therapeutic use , NADPH Oxidase 2/metabolism , NADPH Oxidases/metabolism , Oxidative Stress , Rats , Receptor, Angiotensin, Type 1/metabolism , Thyroid Hormones/metabolism , Thyroxine/pharmacology
17.
Opt Express ; 30(3): 3205-3214, 2022 Jan 31.
Article in English | MEDLINE | ID: mdl-35209585

ABSTRACT

Chip-scale optical frequency comb sources are ideal compact solutions to generate high speed optical pulses for applications in wavelength division multiplexing (WDM) and high-speed optical signal processing. Our previous studies have concentrated on the use of quantum dash based lasers, but here we present results from an InAs/InP quantum dot (QDot) C-band passively mode-locked laser (MLL) for frequency comb generation. By using this single-section QDot-MLL we demonstrate an aggregate line rate of 12.544 Tbit/s 16QAM data transmission capacity for both back-to-back (B2B) and over 100-km of standard single mode fiber (SSMF). This finding highlights the viability for InAs/InP QDot lasers to be used as a low-cost optical source for large-scale networks.

18.
Front Genet ; 12: 765400, 2021.
Article in English | MEDLINE | ID: mdl-34759961

ABSTRACT

Rationale: Severe asthma is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of asthmatic bronchial epithelial cells have provided biological insights and underscored possible pathological mechanisms; however, the molecular basis in severe asthma is still poorly understood. Objective: The objective of this study was to identify the features of asthma and uncover the molecular basis of severe asthma in distinct molecular phenotype. Methods: The k-means clustering and differentially expressed genes (DEGs) were performed in 129 asthma individuals in the Severe Asthma Research Program. The DEG profiles were analyzed by weighted gene co-expression network analysis (WGCNA), and the expression value of each gene module in each individual was annotated by gene set variation analysis (GSVA). Results: Expression analysis defined five stable asthma subtype (AS): 1) Phagocytosis-Th2, 2) Normal-like, 3) Neutrophils, 4) Mucin-Th2, and 5) Interferon-Th1 and 15 co-expressed gene modules. "Phagocytosis-Th2" enriched for receptor-mediated endocytosis, upregulation of Toll-like receptor signal, and myeloid leukocyte activation. "Normal-like" is most similar to normal samples. "Mucin-Th2" preferentially expressed genes involved in O-glycan biosynthesis and unfolded protein response. "Interferon-Th1" displayed upregulation of genes that regulate networks involved in cell cycle, IFN gamma response, and CD8 TCR. The dysregulation of neural signal, REDOX, apoptosis, and O-glycan process were related to the severity of asthma. In non-TH2 subtype (Neutrophils and Interferon-Th1) with severe asthma individuals, the neural signals and IL26-related co-expression module were dysregulated more significantly compared to that in non-severe asthma. These data infer differences in the molecular evolution of asthma subtypes and identify opportunities for therapeutic development. Conclusions: Asthma is a heterogeneous disease. The co-expression analysis provides new insights into the biological mechanisms related to its phenotypes and the severity.

19.
J Cardiovasc Pharmacol ; 78(6): 819-825, 2021 12 01.
Article in English | MEDLINE | ID: mdl-34524259

ABSTRACT

ABSTRACT: The energy used by the heart is generated mainly by the metabolism of fatty acids and glucose. Trimetazidine (TMZ) inhibits fatty acid metabolism and is used for the treatment of heart diseases such as heart failure. 3-Bromopyruvate (3-BrPA) can suppress glucose metabolism, and it is considered a promising candidate agent for tumor therapy. Because TMZ and 3-BrPA can separately inhibit the 2 main cardiac energy sources, it is necessary to investigate the effects of 3-BrPA combined with TMZ on the heart. Forty male Wistar rats were randomly divided into 4 groups: a control group, a TMZ group, a 3-BrPA group, and a 3-BrPA + TMZ group. Weight was recorded every day, and echocardiography was performed 14 days later. Heart function, the levels of adenosine triphosphate, oxidative stress-related factors (ROS, glutathione, oxidized glutathione, malondialdehyde, superoxide dismutase and total antioxidant capacity), and apoptosis in heart tissues were assessed to evaluate the effects of 3-BrPA and TMZ on the heart. In our study, no obvious changes occurred in the 3-BrPA group or the TMZ group compared with the control group. The combination of 3-BrPA and TMZ worsened heart function, decreased adenosine triphosphate levels, and increased oxidative stress and myocardial apoptosis. In conclusion, 3-BrPA and TMZ are not recommended for concurrent use.


Subject(s)
Apoptosis/drug effects , Cardiovascular Agents/toxicity , Enzyme Inhibitors/toxicity , Heart Diseases/chemically induced , Myocytes, Cardiac/drug effects , Oxidative Stress/drug effects , Pyruvates/toxicity , Trimetazidine/toxicity , Adenosine Triphosphate/metabolism , Animals , Cardiotoxicity , Energy Metabolism/drug effects , Heart Diseases/metabolism , Heart Diseases/pathology , Heart Diseases/physiopathology , Male , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Rats, Wistar , Signal Transduction , Ventricular Function, Left/drug effects
20.
Dis Markers ; 2021: 4572282, 2021.
Article in English | MEDLINE | ID: mdl-34306253

ABSTRACT

Heart failure (HF) is the typical terminal stage of cardiac diseases involving inflammatory states. The function of microRNAs (miRNAs) in the progress of HF remains poorly understood. In this study, real-time PCR results showed a decreased expression of miRNA-181b (miR-181b) in HF patients compared with healthy individuals. Besides, miR-181b expressions were negatively correlated with hypersensitive C-reactive protein (hsCRP) levels in the serum of HF patients. Receiver operator characteristic (ROC) curve analysis showed that miR-181b was a diagnostic predictor of HF, and the area under the curve was 0.970 (DCM-induced HF group) and 0.962 (ICM-induced HF group). Strikingly, in HF rats induced by isoproterenol (ISO), the expression of miR-181b of heart tissue was suppressed before tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) increase, as revealed by western blot and real-time PCR. Besides, the overexpression of miR-181b also decreased the expression of TNF-α, IL-1ß, and IL-6 in lipopolysaccharide- (LPS-) induced neonatal cardiomyocytes. In conclusion, our results revealed that miR-181b might be a potential biomarker for HF and provided a novel target for anti-inflammatory therapy.


Subject(s)
Heart Failure/diagnosis , Inflammation/prevention & control , MicroRNAs/blood , Adult , Animals , Biomarkers/blood , Blotting, Western , Cytokines/blood , Female , Heart Failure/blood , Heart Failure/complications , Humans , Inflammation/blood , Inflammation/complications , Inflammation Mediators/blood , Male , Middle Aged , Rats , Rats, Wistar , Real-Time Polymerase Chain Reaction
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