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1.
Front Genet ; 13: 824495, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092938

RESUMO

Alzheimer's disease (AD) is a degenerative disease of central nervous system with unclear pathogenesis, accounting for 60%-70% of dementia cases. Long noncoding RNAs (LncRNAs) play an important function in the development of AD. This study aims to explore the role of differentially expressed lncRNAs in AD patients' serum in the pathogenesis of AD. Microarray analysis was performed in the serum of AD patients and healthy controls to establish lncRNAs and mRNAs expression profiles. GO analysis and KEGG pathway analysis revealed that G1/S transition of mitotic cell cycle might be involved in the development of AD. The result showed that RP11-59J16.2 was up-regulated and MCM2 was down-regulated in serum of AD patients. SH-SY5Y cells were treated with Aß 1-42 to establish AD cell model. Dual luciferase reporter gene analysis verified that RP11-59J16.2 could directly interact with 3'UTR of MCM2 and further regulate the expression of MCM2. Inhibition of RP11-59J16.2 or overexpression of MCM2, CCK-8 assay and Annexin V FITC/PI apoptosis assay kit results showed that RP11-59J16.2 could reduce cell viability, aggravate apoptosis and increase Tau phosphorylation in AD cell model by inhibiting MCM2. In short, our study revealed a novel lncRNA RP11-59J16.2 that could promote neuronal apoptosis and increase Tau phosphorylation by regulating MCM2 in AD model, and indicated that lncRNA RP11-59J16.2 might be a potential target molecule for AD development.

2.
Chem Sci ; 13(32): 9256-9264, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36093013

RESUMO

Hydrogen production technology by water splitting has been heralded as an effective means to alleviate the envisioned energy crisis. However, the overall efficiency of water splitting is limited by the effectiveness of the anodic oxygen evolution reaction (OER) due to the high energy barrier of the 4e- process. The key to addressing this challenge is the development of high-performing catalysts. Transition-metal hydroxides with high intrinsic activity and stability have been widely studied for this purpose. Herein, we report a gelatin-induced structure-directing strategy for the preparation of a butterfly-like FeNi/Ni heterostructure (FeNi/Ni HS) with excellent catalytic performance. The electronic interactions between Ni2+ and Fe3+ are evident both in the mixed-metal "torso" region and at the "torso/wing" interface with increasing Ni3+ as a result of electron transfer from Ni2+ to Fe3+ mediated by the oxo bridge. The amount of Ni3+ also increases in the "wings", which is believed to be a consequence of charge balancing between Ni and O ions due to the presence of Ni vacancies upon formation of the heterostructure. The high-valence Ni3+ with enhanced Lewis acidity helps strengthen the binding with OH- to afford oxygen-containing intermediates, thus accelerating the OER process. Direct evidence of FeNi/Ni HS facilitating the formation of the Ni-OOH intermediate was provided by in situ Raman studies; the intermediate was produced at lower oxidation potentials than when Ni2(CO3)(OH)2 was used as the reference. The Co congener (FeCo/Co HS), prepared in a similar fashion, also showed excellent catalytic performance.

3.
J Nanobiotechnology ; 20(1): 411, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109732

RESUMO

The major challenge to controlling the COVID pandemic is the rapid mutation rate of the SARS-CoV-2 virus, leading to the escape of the protection of vaccines and most of the neutralizing antibodies to date. Thus, it is essential to develop neutralizing antibodies with broad-spectrum activity targeting multiple SARS-CoV-2 variants. Here, we report a synthetic nanobody (named C5G2) obtained by phage display and subsequent antibody engineering. C5G2 has a single-digit nanomolar binding affinity to the RBD domain and inhibits its binding to ACE2 with an IC50 of 3.7 nM. Pseudovirus assays indicated that monovalent C5G2 could protect the cells from infection with SARS-CoV-2 wild-type virus and most of the viruses of concern, i.e., Alpha, Beta, Gamma and Omicron variants. Strikingly, C5G2 has the highest potency against Omicron BA.1 among all the variants, with an IC50 of 4.9 ng/mL. The cryo-EM structure of C5G2 in complex with the spike trimer showed that C5G2 binds to RBD mainly through its CDR3 at a conserved region that does not overlap with the ACE2 binding surface. Additionally, C5G2 binds simultaneously to the neighboring NTD domain of the spike trimer through the same CDR3 loop, which may further increase its potency against viral infection. Third, the steric hindrance caused by FR2 of C5G2 could inhibit the binding of ACE2 to RBD as well. Thus, this triple-function nanobody may serve as an effective drug for prophylaxis and therapy against Omicron as well as future variants.


Assuntos
COVID-19 , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2 , Animais , Anticorpos Neutralizantes , Camundongos , Camundongos Endogâmicos BALB C , Glicoproteína da Espícula de Coronavírus
4.
Food Chem ; 401: 134078, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36113215

RESUMO

Melamine, a nitrogen-containing organic molecule, has received widespread attention as it had been illegally added in dairy products to increase the content of nitrogen, leading to kidney stones in healthy people after long-term ingestion. Based on SERS technology and Covalent Organic Framework (COF) materials, we developed carboxyl-functionalized Ag-COF-COOH materials as SERS substrates for the detection of melamine adulteration. Using COF material as a ligand can effectively reduce the influence of interferents in milk. In addition, we investigated two causes of melamine SERS enhancement: the ordered arrangement of Ag NPs and the strong interaction between the substrate and the melamine. The linear range was 1-20 µg/L and the limit of detection (LOD) was 0.68 µg/L in liquid milk due to the high sensitivity and reliability of this method. The results show that this new SERS substrate has great potential for applications in the food surveillance industry.

6.
Phys Med Biol ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36126658

RESUMO

OBJECTIVE: To develop a simultaneous PET-Optical (OPET) breast imaging dual-head PET subsystem, called DH-Mammo PET, for accurate, early diagnosis and efficacy assessment of breast cancer with high resolution and sensitivity. APPROACH: We developed a breast-dedicated PET based on LYSO crystal, silicon photomultiplier array and multi-voltage threshold sampling technique. It consists of two detector heads, each with a detection area of 216 mm × 145.5 mm. The distance between the detector heads is fixed at 120 mm. In order to extract coincidences and correct data, GPU-based software coincidence processing, random, scatter, normalization, gap-filling and attenuation corrections were applied in turn. The images were reconstructed using maximum likelihood expectation maximization with depth of interaction (DOI) modeling. The performance of DH-Mammo PET was evaluated referring to NEMA NU 4-2008, NU 2-2007 and Chinese industry recommended standard YY/T 1835-2022. Besides, several clinical patient images of DH-Mammo PET were compared with those of a whole-body PET/CT. MAIN RESULTS: The energy resolution was 14.5%, and time resolution was < 1.31 ns. Indicated by the 22Na point source imaging, its spatial resolution was 2.60 mm (5.40 mm), 1.00 mm (1.04 mm), and 0.96 mm (0.93 mm) in the X, Y and Z directions, respectively, using the system response matrix with (without) DOI modeling. Indicated by the Derenzo phantom imaging, the spatial resolution was ~3.0 mm, <1.2 mm, and <1.2 mm in the X, Y and Z directions. The system sensitivity was 6.87%, 4.89% and 3.37% with an energy window of 100-800, 250-750 and 350-650 keV, respectively. The scatter fraction was 26.43%, and the peak NECR was 162.6 kcps at 24.1 MBq for the modified rat-like phantom. As for the recovery coefficients, they ranged from 0.15 to 1.04 for rods between 1 mm and 5 mm obtained with a NEMA image quality phantom. The spill-over ratio for the air-filled and water-filled chamber was 0.05 and 0.11, respectively. DH-Mammo PET can provide more image details in clinical experiments and fulfil a fast scan with 60s-120 s acquisition time. SIGNIFICANCE: Good spatial resolution and high sensitivity of DH-Mammo PET would enable fast and accurate PET imaging of the breast. Besides, combining the DH-Mammo PET with the diffuse optical tomography would make full use of tumor metabolic imaging and tissue endogenous optical imaging, which would improve the accuracy of early clinical diagnosis of small lesions of breast cancers.

7.
Sci Total Environ ; : 158874, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36126710

RESUMO

Aerosol volatility has a substantial impact on gas-particle partitioning, aging process and hence brown carbon (BrC) absorption. Here we analyzed single-particle volatility in winter in Beijing using a thermodenuder coupled with a single particle aerosol mass spectrometer along with a suite of collocated measurements. Our results showed that elemental carbon, metals, organic nitrogen (ON) were the dominant low-volatility components. The ON-containing particles accounting for 50 % of the total low-volatility particles comprised mainly ON-organic carbon (ON-OC) particles which were associated with biomass burning and significantly enhanced during polluted periods with high relative humidity and nitrogen oxides (NOx) levels. By analyzing the relationship between single-particle volatility and BrC, we found that semi-volatile particles related to fossil fuel combustion contributed dominantly to the light absorption of BrC (~50 %). Comparatively, the low-volatility and semi-volatile particles related to biomass burning contributed 21-35 % and 10-15 %, respectively to the BrC light absorption. Our results demonstrated that single particles from different sources with different volatility showed different impacts on BrC absorption. Although low-volatility organic aerosol accounted only for ~16 % of the total ambient organics, they can contribute as much as ~30-40 % to BrC light absorption in winter in Beijing.

9.
Antiviral Res ; : 105418, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36122620

RESUMO

REV-ERBα is a member of the nuclear receptor superfamily of transcription factors that aids in the regulation of many diseases. However, the prospect of using REV-ERBα for anti-influenza virus treatment remains poorly described, and there is an urgent need to develop effective anti-influenza agents due to the emergence of drug-resistant influenza viruses. In this study, eight SR9009 analogues were designed, synthesized, and evaluated for their biological activities against multiple influenza virus strains (H1N1, H3N2, adamantane- and oseltamivir-resistant H1N1 and influenza B virus), using ribavirin as the positive control. SR9009 and its analogues showed low micromolar or submicromolar EC50 values and exhibited modestly improved antiviral potency compared to that of ribavirin. In particular, compound 5a possessed the most potent inhibitory activity (EC50 = 0.471, 0.644, 1.644, 0.712 and 0.661 µM for A/PR/8/34, A/WSN/33, A/Wisconsin/67/2005, B/Yamagata/16/88 and Hebei/SWL1/2006, respectively). Cotransfection assays showed that all synthesized derivatives efficaciously suppressed transcription driven by the Bmal1 promoter. Mechanistic study results indicated that 5a efficiently inhibited IAV replication and interfered with the ealry stage of influenza virus life cycle. In addition, we found that 5a upregulated the key antiviral interferon-stimulated genes MxA, OAS2 and CH25H. Further in-depth transcriptome analysis revealed a series of upregulated genes that may contribute to the antiviral activities of 5a. These findings may provide an important direction for the development of new host-targeted broad-spectrum antiviral agents.

10.
J Virol ; : e0134422, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36125302

RESUMO

Subtype H7 avian influenza A viruses (IAVs) are enzootic in wild aquatic birds and have caused sporadic spillovers into domestic poultry and humans. Here, we determined the distribution of fucosylated α2,3 sialoglycan (i.e., sialyl Lewis X [SLeX]) in chickens and five common dabbling duck species and the association between SLeX and cell/tissue/host tropisms of H7 IAVs. Receptor binding analyses showed that H7 IAVs bind to both α2,3-linked (SA2,3Gal) and α2,6-linked sialic acids (SA2,6Gal), but with a higher preference for SLeX; H7 IAVs replicated more efficiently in SLeX-overexpressed than SLeX-deficient MDCK cells. While chickens and all tested dabbling ducks expressed abundant SA2,3Gal and SA2,6Gal, SLeX was detected in both respiratory and gastrointestinal tissues of chickens and mallard ducks and in only the respiratory tissues of gadwall, green-wing teal, and northern shoveler but not in wood ducks. Viral-tissue binding assays showed that H7 IAVs bind to chicken colon crypt cells that express SLeX but fewer bind to mallard colon crypt cells, which do not express SLeX; H7 IAVs bind efficiently to epithelial cells of all tissues expressing SA2,3Gal. High viral replication was identified in both chickens and mallards infected with an H7 virus, regardless of SLeX expression, and viruses were detected in all cells to the same degree as viruses detected in the viral-tissue binding assays. In summary, this study suggests that SLeX facilitates infection of H7 viruses, but other types of SA2,3Gal glycan receptors shape the tissue/host tropisms of H7 IAVs. IMPORTANCE In addition to causing outbreaks in domestic poultry, subtype H7 IAVs can cause sporadic spillover infections in lower mammals and humans. In this study, we showed that SLeX expression varies among wild dabbling ducks. Although it facilitated virus binding and affected infection of H7 IAV in cells, SLeX expression is not the only determinant of viral replication at either the tissue or host level. This study suggested that access to heterologous SA2,3Gal glycan receptors, including fucosylated α2,3-linked sialoglycans, shape tissue and host tropism of H7 IAVs in aquatic wild birds.

11.
J Sci Food Agric ; 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36054707

RESUMO

BACKGROUND: Polygonatum cyrtonema Hua is cultivated for its edible and medical value. The steam-processed rhizome of P. cyrtonema is the main form for daily consumption and it has been used traditionally in tonics for treating various age-related disorders. The aim of our study was to compare the physicochemical properties and antioxidant activity of polysaccharides respectively extracted from crude P. Cyrtonema (PCPC), and steam-processed P. cyrtonema (PCPS), and to explore a possible underlying antioxidant mechanism. RESULTS: The PCPC with a molecular weight of 4.35 × 103 Da mainly consisted of fructose and trace amounts of glucose, whereas PCPS with 4.24 × 104 Da was composed of fructose, arabinose, glucose, xylose, mannose, galacturonic acid and glucuronic acid. The PCPC had a triple-helical conformation whereas PCPS was a random coil. Both exhibited free radicals- scavenging activity in vitro. In a mouse model of oxidative damage, PCPC or PCPS treatment significantly reversed histopathological alterations, reactive oxygen species (ROS) accumulation and the reduction of antioxidant enzyme activity. They both also promoted Nrf2 nuclear transport by decreasing Keap-1 expression and increasing HO-1 expression. Both in vitro and in vivo, PCPS exhibited more potent antioxidant activity than PCPC. CONCLUSION: Overall, the results suggest that PCPS has a stronger effect on the prevention of oxidative damage by activating Nrf2/HO-1 antioxidant signaling. This study demonstrates the role of steam-processed P. cyrtonema rhizome and provides valuable perspective for PCPS as a functional agent. © 2022 Society of Chemical Industry.

12.
Bioorg Chem ; 128: 106116, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36063753

RESUMO

Carnosic acid could disrupt the ß-catenin/BCL9 protein-protein interaction and inhibit ß-catenin dependent transcription, thereby reduce the incidence of colorectal cancer induced by abnormal activation of Wnt/ß-catenin signalling pathway. However, its activity was weak (IC50 for SW480: 28.2 ± 2.05 µM) and total synthesis was difficult. During the structural simplification of natural products, S0 was revealed to be the basic pharmacophore of carnosic acid. Subsequent structural optimization of S0 led to the discovery of S11 as a possible anticancer agent with prominent proliferation inhibition effect (IC50 for SW480: 9.56 ± 0.91 µM) and best selectivity index (SI = 3.0) against Wnt hyperactive cancer cells. Futher mechanism investigation through TOP/FOP dual luciferase reporter assay, immunofluorescence, co-immunoprecipitation, microscale thermophoresis, downstream oncoprotein expression and cell apoptosis showed that compound S11 could significantly inhibit the proliferation of SW480 cells via obvioudsly decreasing the nucleus translocation of ß-catenin and effectively disrupting ß-catenin/BCL9 protein-protein interaction. Additionally, cell migration, molecule docking, in vitro stability and solubility assays were also conducted. Overall, S11 was worthy of in-depth study as a potential inhibitor for the Wnt/ß-catenin pathway and its discovery also proved that the structural simplification of natural products was still one of the effective methods to find new lead compounds or candidate drugs.


Assuntos
Produtos Biológicos , beta Catenina , Androstenóis , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Hidroxibenzoatos , Via de Sinalização Wnt , beta Catenina/metabolismo
13.
Org Lett ; 24(36): 6647-6652, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36053175

RESUMO

A visible-light-promoted three component reaction of diazo compounds, nitriles, and carboxylic acids is reported. The reaction utilizes acceptor-only diazo compounds as carbene precursors and nitriles as carbene-trapping reagents to form the key nitrile ylides. Under the optimal reaction conditions, a wide range of imide products were obtained in good to excellent yields. The gram-scale synthesis and synthetic application of the imide products to form isoquinoline-1,3(2H,4H)-dione derivatives further proved the value of this method.

14.
Nano Lett ; 22(17): 7212-7219, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36054509

RESUMO

The ongoing coronavirus (COVID-19) pandemic requires enormous production of facemasks and related personal protection materials, thereby increasing the amount of nondegradable plastic waste. The core material for facemasks is melt-blown polypropylene (PP) fiber. Each disposable facemask consumes ∼0.7 g of PP fibers, resulting in annual global consumption and disposal of more than 1 150 000 tons of PP fibers annually. Herein, we developed a laser-assisted melt-blown (LAMB) technique to manufacture PP nanofibers with a quality factor of 0.17 Pa-1 and significantly reduced the filter's weight. We demonstrated that a standard surgical facemask could be made with only 0.13 g of PP nanofibers, saving approximately 80% of the PP materials used in commercial facemasks. Theoretical analysis and modeling were also conducted to understand the LAMB process. Importantly, nanofibers can be easily scaled up for mass production by upgrading traditional melt blown line with scanning laser-assisted melt-blown (SLAMB).


Assuntos
COVID-19 , Nanofibras , COVID-19/prevenção & controle , Humanos , Lasers , Máscaras , Polipropilenos
15.
Front Endocrinol (Lausanne) ; 13: 950326, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060966

RESUMO

Neuroblastoma breakpoint family, member 1 (NBPF1), appears to be a double-edged sword with regard to its role in carcinogenesis. On the one hand, the tumor-suppressing functions of NBPF1 have been definitively observed in neuroblastoma, prostate cancer, cutaneous squamous cell carcinoma, and cervical cancer. On the other hand, there is evidence that NBPF1 regulates the colony formation, invasion, and maintenance of liver cancer cells and hence functions as an oncogene. The roles of NBPF1 are strictly dependent on the biological context and type of organization. However, a systematic pan-cancer analysis has thus far not been undertaken, and the significance of NBPF1 in the occurrence and progression of many malignancies is uncertain. In this paper, bioinformatics techniques were employed to analyze NBPF1 expression across different cancers and investigate the relationship between NBPF1 and clinical features, prognosis, genetic alteration, and tumor immune microenvironment, respectively. Our results show that NBPF1 is variably expressed in distinct tumor tissues and is also closely linked to clinical outcomes. In particular, compared to other tumor types, there was a strong negative correlation between NBPF1 expression and various components of the tumor microenvironment in adrenocortical carcinoma (ACC). We thus developed an NBPF1-derived immune risk model based on NBPF1-related immune genes; ACC patients with a high-risk score tended to have a poorer prognosis, accompanied by immune hyporesponsiveness. NBPF1 can be used as a prognostic biomarker for multiple cancers. Moreover, anti-NBPF1 immunotherapy may be suitable for treating ACC patients.


Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Genes Supressores de Tumor , Oncogenes , Microambiente Tumoral , Neoplasias do Córtex Suprarrenal/genética , Carcinoma Adrenocortical/genética , Carcinoma de Células Escamosas/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Genes Supressores de Tumor/fisiologia , Humanos , Neuroblastoma/genética , Oncogenes/genética , Neoplasias Cutâneas/genética , Microambiente Tumoral/genética
16.
J Biomed Opt ; 27(9)2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36088528

RESUMO

SIGNIFICANCE: Optical imaging of responses in fluorescently labeled neurons has progressed significantly in recent years. However, there is still a need to monitor neural activities at divergent spatial scales and at depths beyond the optical diffusion limit. AIM: To meet these needs, we aim to develop multiscale photoacoustic tomography (PAT) to image neural activities across spatial scales with a genetically encoded calcium indicator GCaMP. APPROACH: First, using photoacoustic microscopy, we show that depth-resolved GCaMP signals can be monitored in vivo from a fly brain in response to odor stimulation without depth scanning and even with the cuticle intact. In vivo monitoring of GCaMP signals was also demonstrated in mouse brains. Next, using photoacoustic computed tomography, we imaged neural responses of a mouse brain slice at depths beyond the optical diffusion limit. RESULTS: We provide the first unambiguous demonstration that multiscale PAT can be used to record neural activities in transgenic flies and mice with select neurons expressing GCaMP. CONCLUSIONS: Our results indicate that the combination of multiscale PAT and fluorescent neural activity indicators provides a methodology for imaging targeted neurons at various scales.


Assuntos
Cálcio , Tomografia Computadorizada por Raios X , Animais , Encéfalo/diagnóstico por imagem , Camundongos , Neurônios , Imagem Óptica/métodos
17.
J Control Release ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36108811

RESUMO

Transdermal administration of chemotherapeutics into tumor tissues may be an effective treatment to reduce toxic side effects and improve patient compliance for melanoma. Herein, we report a multistage transdermal drug delivery system for chemotherapy of melanoma. In this system, dendritic lipopeptide (DLP) modified multistage targeted liposomes (Mtlip) were incorporated into the hydrogel matrix to achieve localized and sustained drug release; Ultra-deformability of Mtlip can pass through dense stratum corneum to the epidermis where melanoma is located; Virus-mimicking Mtlip enhances the payload in tumor tissues by high permeability; The positive charged Mtlip can improve cell uptake efficiency and selectively accumulate into mitochondria to increases toxic. The efficacy of this type of multistage targeted liposomes loaded hydrogel in treating melanoma was systematically evaluated both in vitro and in vivo.

18.
Magn Reson Med ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36111354

RESUMO

PURPOSE: To investigate the effects of gadolinium (Gd) retention of macrocyclic (gadobutrol) or linear (gadopentetate) Gd-based contrast agents (GBCAs) on neuron loss, neurological deficits, and sensory behavior in mice with or without stroke. METHODS: Ninety C57BL/6 mice underwent sham (n = 36) or transient middle cerebral artery occlusion (tMCAO) (n = 54) surgery and then received intraperitoneal injections of 5.0 mmol/kg gadobutrol, 5.0 mmol/kg gadopentetate or saline (10 ml/kg/administration) per day for 3 consecutive days. The Gd concentration in the ischemic cerebrum was quantified by inductively coupled plasma mass spectrometry on Day 1 and Day 28 after the last injection (post-injection, p. i.). Neuron loss, glia activation and neurological deficits were assessed on Day 1 and 28 p. i. Sensory behavior was also assessed on Day 28 p. i. RESULTS: Gd concentrations were higher in the brains of tMCAO mice than in those of sham mice on Days 1 p. i. of both GBCAs (gadobutrol, p < 0.05; gadopentetate, p < 0.001) and 28 p. i of gadopentetate. (p < 0.001). Sham or tMCAO mice injected with GBCAs showed no significant difference in neuron loss, glia activation, neurological deficits, brain atrophy, or hippocampus-dependent memory (all p > 0.05). Both gadobutrol and gadopentetate induced mechanical and heat hyperalgesia in sham mice (all p < 0.05). However, mechanical hyperalgesia but rather heat hyperalgesia was found in tMCAO mice with the highest force tested (1.0 g) and statistically significant in both paws (right and left) with gadopentetate only (p < 0.05). CONCLUSIONS: Neither gadobutrol nor gadopentetate worsened neuron loss, glia activation, brain atrophy, neurological deficits, or hippocampus-dependent memory after tMCAO. However, GBCA administration induced mechanical hyperalgesia in sham and tMCAO mice although in the same level, which may be an important consideration for patients with central post-stroke pain and those who are sensitive to pain and about to receive multiple GBCA administrations.

20.
Int J Mol Sci ; 23(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36077405

RESUMO

Brown adipose tissue (BAT) is functionally linked to skeletal muscle because both tissues originate from a common progenitor cell, but the precise mechanism controlling muscle-to-brown-fat communication is insufficiently understood. This report demonstrates that the immunoglobulin superfamily containing leucine-rich repeat (Islr), a marker of mesenchymal stromal/stem cells, is critical for the control of BAT mitochondrial function and whole-body energy homeostasis. The mice loss of Islr in BAT after cardiotoxin injury resulted in improved mitochondrial function, increased energy expenditure, and enhanced thermogenesis. Importantly, it was found that interleukin-6 (IL-6), as a myokine, participates in this process. Mechanistically, Islr interacts with NADH: Ubiquinone Oxidoreductase Core Subunit S2 (Ndufs2) to regulate IL-6 signaling; consequently, Islr functions as a brake that prevents IL-6 from promoting BAT activity. Together, these findings reveal a previously unrecognized mechanism for muscle-BAT cross talk driven by Islr, Ndufs2, and IL-6 to regulate energy homeostasis, which may be used as a potential therapeutic target in obesity.


Assuntos
Tecido Adiposo Marrom , Interleucina-6 , Tecido Adiposo Marrom/metabolismo , Animais , Diferenciação Celular , Metabolismo Energético , Homeostase , Imunoglobulinas/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Leucina/metabolismo , Camundongos , Músculo Esquelético/metabolismo , NADH Desidrogenase/metabolismo , Termogênese
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