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1.
Sci Total Environ ; 838(Pt 4): 156396, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-35654179

RESUMO

Biodegradable plastics (BPs) have been given high hopes to substitute conventional plastics, but their biodegradation requires strict conditions. BPs can accumulate for a long time in the environment and even derive biodegradable microplastics (BMPs), thus threatening wildlife and ecosystems. However, no efficient method is available for extracting BMPs from organisms' tissues. This study used multi-criteria decision-making (MCDM) methods to comprehensively evaluate and optimize extraction protocols of five BMPs from economic aquatic species. Digestion time, digestion efficiency, mass loss, cost, polymer integrity and size change were selected as evaluating indictors. According to the screening results of MCDM methods, Pepsin+H2O2 was selected as the optimal digestion method of BMPs because of its highest comprehensive score, which has high digestion efficiency (99.56%) and minimum plastic damage. Compared with olive oil, NaI is more suitable for separating BMPs from the digested residues. Furthermore, the combination of Pepsin+H2O2 digestion and NaI density separation was used to extract all five kinds of BMPs from the bivalve, crab, squid, and crayfish tissues, and all the recovery rates exceeded 80%. These results suggest that the optimal protocol is practicable to extract various BMPs from various aquatic organisms.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35682488

RESUMO

Under circumstances of fire, panic usually brings uncertainty and unpredictability to evacuation. Therefore, a deep understanding of panic is desired. This study aims to dig into the underlying mechanism of fire evacuation panic by measuring and analysing psycho- and physiological indicators. In the experiment, participants watched a simulated train station within which three sets of stimuli were triggered separately. Eye movement and brain haemodynamic responses were collected during the watch, while questionnaires and interviews of emotions were conducted after. The analysed physiological indicators include the amplitude of pupil dilation, the time ratios of fixation and saccade, the binned entropy of gaze location, and the brain activation coefficients. The results of this research indicate that fire evacuation panic can be broken down into two elements. (1) Unawareness of situation: less knowledge of the situation leads to a higher level of panic; (2) Intensity of visual stimulation: the panic level is escalated with increased severity of fire that is perceived.


Assuntos
Benchmarking , Incêndios , Movimentos Oculares , Humanos , Pânico , Movimentos Sacádicos
3.
Pharmacol Res ; 182: 106310, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35714824

RESUMO

Non-steroidal anti-inflammatory drugs (NSAIDs) relieve inflammation by suppressing prostaglandin E2/cyclooxygenase 2 (PGE2/COX-2) with cardiovascular and gastrointestinal bleeding risk. Theoretically, suppressing PGE2 through inhibiting the terminal synthase microsomal prostaglandin E2 synthase-1 (mPGES-1) instead of upstream COX-2 is ideal for inflammation. Here, (9S,13R)-12-oxo-phytodienoic acid (AA-24) extracted from Artemisia anomala was first screened as an anti-inflammatory candidate and decreased inducible nitric oxide synthase (iNOS), nitric oxide (NO), mPGES-1, and PGE2 without affecting COX-1/2, thromboxane A2 (TXA2) and prostaglandin I2 (PGI2). Besides, AA-24 suppressed the differentiation of M0 macrophages to M1 phenotype but enhanced it to M2 phenotype, blocked the activation of NF-κB pathway, and increased the activation of Nrf2 and heme oxygenase-1 (HO-1). Moreover, AA-24 selectively inhibited mPGES-1 and reduced inflamed paw edema in carrageenan-induced mice. In conclusion, AA-24 attenuates inflammation by inhibiting mPGES-1 and modulating macrophage polarization via the NF-κB and Nrf2/HO-1 pathways and could be a promising candidate for developing anti-inflammatory drugs.

4.
Artigo em Inglês | MEDLINE | ID: mdl-35750239

RESUMO

OBJECTIVES: Although subchondral bone marrow lesions (BMLs) and synovitis have been well acknowledged as important sources of pain in knee osteoarthritis (KOA), it is unclear if synovitis plays the mediating role in the relationship between BMLs and knee pain. METHODS: We analyzed 600 subjects with magnetic resonance imaging (MRI) in the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium (FNIH) cohort at baseline and 24-month. BMLs and synovitis were measured according to the MRI Osteoarthritis Knee Score (MOAKS) scoring system. BMLs were scored in five subregions. A summary synovitis score of effusion and Hoffa-synovitis was calculated. Knee pain was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Linear regression models were applied to analyze the natural direct effect (NDE) of BMLs and synovitis with knee pain, respectively, and natural indirect effect (NIE) mediated by synovitis. RESULTS: 590 participants (58.8% females, with a mean age of 61.5) were included in the present analyses. For NDE, knee pain was cross-sectionally associated with medial femorotibial BMLs (ß= 0.23, 95% CI: 0.09, 0.38) and synovitis (ß= 0.40, 95% CI: 0.20, 0.60). Longitudinal associations retained significant [medial femorotibial BMLs (ß=0.37, 95% CI: 0.21, 0.53); synovitis (0.72, 95% CI: 0.45, 0.99)]. In the NIE analyses, synovitis mediated the association between medial femorotibial BML and knee pain at baseline (ß=0.051, 95% CI: 0.01, 0.09) and over 24 months (ß= 0.079, 95% CI: 0.023, 0.15), with the mediating proportion of 17.8% and 22.4%, respectively. CONCLUSION: Synovitis partially mediates the association between medial femorotibial BMLs and knee pain.

5.
Chin J Nat Med ; 20(6): 458-472, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35750385

RESUMO

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. It is known that aucubin (AU) exerts anti-inflammatory activity, but its effects and mechanisms in RA are unclear. This study investigated the anti-inflammatory effects and mechanisms of AU in vivo and in vitro. Human fibroblast-like synoviocyte cells from patients with RA (HFLS-RA), RAW264.7 cells, and MC3T3-E1 cells were used to evaluate the effects of AU on migration, invasion, apoptosis, osteoclast differentiation and production. Immunofluorescence was used to observe nuclear translocation of nuclear factor (NF)-κB, the double luciferase reporter gene method was used to observe NF-κB-p65 activity in AU-treated MC3T3-E1 cells. RT-qPCR was used to measure expression of bone metabolism and inflammation-related genes, and western blot was used to measure bone metabolism and NF-κB protein expression levels. Collagen-induced arthritis (CIA) rat model was used for pharmacodynamics study. Arthritis indexes were measured in the ankle and knee, histological staining and Micro-computed tomography were performed on the ankle joints. Also, inflammatory factor gene expression and the levels of NF-κB-related proteins were detected as in vitro. AU effectively inhibited HFLS-RA cell migration and invasion, promoted apoptosis, and inhibited RAW264.7 cell differentiation into osteoclasts, as well as inhibited NF-κB-p65 activity in MC3T3-E1 cells. Notably, AU significantly reduced the gene expression levels of three cell-related inflammatory factors and bone metabolism factors, effectively inhibited the expression of p-Iκκα ß, p-IκBα, and p-p65 proteins. In vivo, AU relieved joint inflammation, reduced related inflammatory factors, and inhibited NF-κB signaling. It could be used to treat RA-related synovial inflammation and bone destruction through the NF-κB pathway.

6.
Mol Ecol Resour ; 2022 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-35751596

RESUMO

Inulin is an important reserve polysaccharide in Asteraceae plants, and is also widely used as sweetener, dietary fiber, and prebiotics. Nevertheless, lack of genomic resources for inulin-producing plants hinders extensive studies on inulin metabolism and regulation. Here, we present chromosome-level reference genomes for four inulin-producing plants: chicory (Cichorium intybus), endive (Cichorium endivia), great burdock (Arctium lappa) and yacon (Smallanthus sonchifolius), with assembled genome size 1.28, 0.89, 1.73, and 2.72 Gigabases (Gb), respectively. We found chicory, endive, and great burdock genomes were shaped by whole genome triplication (WGT-1), and yacon genome was shaped by WGT-1 and two subsequent whole genome duplications (WGD-2 and WGD-3). A yacon unique whole genome duplication (WGD-3) occurred at 5.6-5.8 million years ago. Our results also showed the genome size difference between chicory and endive is largely due to LTR retrotransposons, and rejected a previous hypothesis that chicory is one ancestor of endive. Furthermore, we identified fructan-active-enzyme and transcription-factor genes, and found there is one copy in chicory, endive and great burdock but two copies in yacon for most of these genes, except for 1-FEH II gene which is significantly expanded in chicory. Interestingly, inulin synthesis genes 1-SST and 1-FFT locate nearby each other, and the same for degradation genes 1-FEH I and 1-FEH II. Finally, we predicted protein structures for 1-FFT genes to explore the determining mechanism of inulin chain length.

7.
Talanta ; 249: 123612, 2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35688080

RESUMO

The development of facile, rapid and cost-effective strategies for sensitive detection of cancer biomarkers in human samples is of great significance for early diagnosis of malignant tumors related diseases. In this work, we develop a high-performance electrochemical biosensor based on highly active dual nanozyme amplified system, i.e., ultrathin two-dimension (2D) conductive metal-organic framework (C-MOF) nanosheets (NSs) decorated with high-density ultrafine gold nanoparticles (Au-NPs), and explore its application in sensitive detection of cancer biomarker H2O2 in live cells. The C-MOF NSs {i.e., Cu-HHTP (HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene)-NSs} provide large surface area and abundant active open metal sites (Cu-O4), which could improve the catalytic activity of Cu-HHTP-NSs towards H2O2. Moreover, abundant exposed O atoms also serve as anchor sites for the deposition of high-density ultrafine Au-NPs (∼3 nm) without agglomeration. Owing to the synergistic contributions of high catalytic activity of Cu-HHTP-NSs and Au-NPs as well as their unique structural and electrical properties, the as-prepared nanohybrid modified electrode exhibits good sensing performances to H2O2 with an extremely low detection limit of 5.6 nM (3σ rules) and a high sensitivity of 188.1 µA cm-2 mM-1. Furthermore, the proposed nanozymatic electrochemical biosensor has been applied in real-time tracking H2O2 released from different human colon cells to identify colon cancer cells from normal colon epithelial cell, which demonstrates its great prospect for early diagnosis and management of various cancer diseases.

8.
J Med Virol ; 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35656887

RESUMO

Human metapneumovirus (HMPV) plays an important role in acute respiratory tract infections (ARTIs), especially in children. We investigated the epidemiology of HMPV associated with ARTIs among pediatric inpatients and identified HMPV genetic variations in Qingdao, China, from January 2018 to June 2019. HMPV-positive samples were identified from throat swabs by multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR). The G gene sequences of HMPV were obtained, followed by phylogenetic analysis. As a result, 71 out of 1051 (6.76%) patients were HMPV positive, and the HMPV-positive rate in children under 5 years of age was three times higher than that in those aged 5-17 years. The epidemic season of HMPV was in spring, with a peak mainly in March. Thirty-two nucleotide sequences of the HMPV G gene successfully obtained were clustered into three genotypes, A2c (25/32, 78.13%), B1 (3/32, 9.38%) and B2 (4/32, 12.50%). In addition, 76% (19/25) of A2c viruses were identified as the emerging A2c111nt-dup variants, which were predominantly circulating among pediatric inpatients with ARTIs between January 2018 and June 2019 in Qingdao. The emerging A2c111nt-dup variants have spread between countries and cities and might spread more widely in the future. Further prevalence monitoring of this duplication variant is needed to clarify the potentially expanding transmission and to provide a scientific basis for disease control and vaccine development.

9.
Eur J Med Chem ; 238: 114482, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35671593

RESUMO

The activation of stimulator of interferon genes (STING) signaling pathways plays an important role in the innate immune response. Although several STING agonists have been developed recently, the majority of clinical CDN STING agonists are administered by intratumoral (IT) injection. Therefore, there remains a need to develop diverse non-CDN small-molecule STING agonists with systemic administration. Herein, by using a scaffold hopping strategy, we designed a series of thieno [2,3-d]imidazole derivatives as novel STING agonists. Further structure-activity relationship study and optimization led to the discovery of compound 45 as a highly potent human STING agonist with an EC50 value of 1.2 nM. Compound 45 was found to bind to multiple human STING isoforms and accordingly activated the downstream TBK1/IRF3 and NF-κB signaling pathways in the reporter cells bearing with different STING isoforms. The activation on STING signaling pathway was abolished in the STING knock-out cells, indicating that it is a specific STING agonist. Compound 45 significantly inhibited the tumor growth in allograft 4T1 and CT26 tumor models by systemic administration, and more significantly, 45 was able to induce tumor regression in CT26 tumor model without inducing weight loss, suggesting that compound 45 is a highly promising candidate worthy for further development.


Assuntos
Proteínas de Membrana , Neoplasias , Inibidores de 14-alfa Desmetilase , Humanos , Imidazóis/farmacologia , Imunidade Inata , Imunoterapia , Proteínas de Membrana/metabolismo , Neoplasias/tratamento farmacológico
10.
Front Nutr ; 9: 925846, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719162

RESUMO

Over the latest decade, lipidomics has been extensively developed to give robust strength to the qualitative and quantitative information of lipid molecules derived from physiological animal tissues and edible muscle foods. The main lipidomics analytical platforms include mass spectrometry (MS) and nuclear magnetic resonance (NMR), where MS-based approaches [e.g., "shotgun lipidomics," ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF-MS)] have been widely used due to their good sensitivity, high availability, and accuracy in identification/quantification of basal lipid profiles in complex biological point of view. However, each method has limitations for lipid-species [e.g., fatty acids, triglycerides (TGs), and phospholipids (PLs)] analysis, and necessitating the extension of effective chemometric-resolved modeling and novel bioinformatic strategies toward molecular insights into alterations in the metabolic pathway. This review summarized the latest research advances regarding the application of advanced lipidomics in muscle origin and meat processing. We concisely highlighted and presented how the biosynthesis and decomposition of muscle-derived lipid molecules can be tailored by intrinsic characteristics during meat production (i.e., muscle type, breed, feeding, and freshness). Meanwhile, the consequences of some crucial hurdle techniques from both thermal/non-thermal perspectives were also discussed, as well as the role of salting/fermentation behaviors in postmortem lipid biotransformation. Finally, we proposed the inter-relationship between potential/putative lipid biomarkers in representative physiological muscles and processed meats, their metabolism accessibility, general nutritional uptake, and potency on human health.

11.
Front Nutr ; 9: 913297, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719170

RESUMO

Thermal treatment of lipids rich in fatty acids contributes to the formation of lipid oxidation products (LOPs), which have potentially harmful effects on human health. This study included soybean oil (SO), palm oil (PO), olive oil (OO), and lard oil (LO) as the research objects, with an aim to investigate the impact of heating temperature and fatty acid type on the generation of LOPs (α-dicarbonyl compounds, malondialdehyde (MDA), α,ß-unsaturated aldehydes, and 16 volatile aldehydes). Results showed that LOPs increased significantly (p < 0.05) with the increase in temperature (100 ~ 200°C). Furthermore, the amount of 2,3-butanedione (159.53 µg/g), MDA (3.15 µg/g), 4-hydroxy-hexenal (3.03 µg/g), 2-butenal (292.18%), 2-pentenal (102.26%), hexanal (898.72%), and 2,4-heptadienal (E, E) (2182.05%) were more at 200°C in SO rich in polyunsaturated fatty acids (PUFAs) than other oils. Results from heat map analysis indicated that the 2, 4-heptadienal, and glyoxal related to the myristic acid of oil. Moreover, the MDA was in close association with PUFAs. Based on the effect of temperature and fatty acid type on the generation of LOPs, this study could serve as a control method to reduce harmful LOPs.

12.
Front Neurol ; 13: 902474, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720075

RESUMO

Background and Purposes: The risk factors of poor postoperative angiogenesis in moyamoya disease (MMD) patients remain unknown. We aimed to investigate the association between hyperhomocysteinemia (HHcy) and postoperative angiogenesis of adult patients with MMD. Methods: A total of 138 adult patients with MMD were prospectively recruited from July 1 to December 31, 2019. After excluding 10 patients accepting conservative therapy and 77 individuals without postoperative digital subtraction angiography (DSA), all 51 MMD patients were enrolled, and 28 patients received bilateral operations separately. Patients were grouped according to postoperative angiogenesis and HHcy presentation, respectively. Clinical data and laboratory examinations were compared. Potential risk factors were evaluated by univariate and multivariate logistic regression analysis. Nomogram was further performed. The biological functions of homocysteine (Hcy) were explored in vitro. Results: Comparing to the normal, patients with poor postoperative angiogenesis were higher in serum Hcy (p = 0.004), HHcy ratio (p = 0.011), creatinine (Cr) (p < 0.001), uric acid (UA) (p = 0.036), Triglyceride (p = 0.001), high-density lipoprotein cholesterol (HDL-C) (p = 0.001), low-density lipoprotein cholesterol (LDL-C) (p = 0.009), ApoA (p = 0.022), apolipoprotein B (ApoB) (p = 0.013). Furthermore, HHcy was more common in men (p = 0.003) than women. Logistic analysis results showed that Hcy (OR = 0.817, 95% CI = 0.707-0.944, p = 0.006) was an independent risk factor. HHcy and Cr were significantly associated with poor postoperative angiogenesis in MMD patients. Further, Hcy could inhibit the proliferation, migration, and tube formation of human brain microvascular endothelial cells (HBMECs), which can be reversed by vascular endothelial growth factor (VEGF). Conclusion: The HHcy was significantly correlated with poor postoperative angiogenesis in adult patients with MMD. Hcy significantly inhibits HBMECs proliferation, migration, and tube formation. Furthermore, VEGF could reverse the inhibition effect induced by Hcy. Lowering the level of Hcy may be beneficial for postoperative MMD patients. Focusing on the pathophysiology and mechanism of HHcy might help to guide postoperative clinical management.

13.
SAGE Open Med Case Rep ; 10: 2050313X221104034, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720249

RESUMO

Rudimentary uterine horn pregnancy is a rare and serious type of ectopic pregnancy and is hard to diagnose due to a lack of typical clinical symptoms at the early stage. A 35-year-old woman who was17 weeks pregnant and had a complicated history of infertility came to our hospital complaining of abdominal pain without vaginal bleeding. Computed tomography scan after 12 hours showed that her pregnancy was in the small cavity of a rudimentary uterine horn, which had ruptured. Noncommunicating rudimentary uterine horn pregnancy is an extremely rare form of ectopic gestation, and its diagnosis and management remain challenging. Nevertheless, physician awareness of various forms of unicornuate uteri and rudimentary uterine horn can save lives.

14.
Front Plant Sci ; 13: 896436, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720567

RESUMO

Selection and utilization of salt-tolerant crops are essential strategies for mitigating salinity damage to crop productivity with increasing soil salinization worldwide. This study was conducted to identify salt-tolerant white clover (Trifolium repens) genotypes among 37 materials based on a comprehensive evaluation of five physiological parameters, namely, chlorophyll (Chl) content, photochemical efficiency of PS II (Fv/Fm), performance index on an absorption basis (PIABS), and leaf relative water content (RWC), and to further analyze the potential mechanism of salt tolerance associated with changes in growth, photosynthetic performance, endogenous polyamine metabolism, and Na+/K+ uptake and transport. The results showed that significant variations in salt tolerance were identified among 37 genotypes, as PI237292 and Tr005 were the top two genotypes with the highest salt tolerance, and PI251432 and Korla were the most salt-sensitive genotypes compared to other materials. The salt-tolerant PI237292 and Tr005 not only maintained significantly lower EL but also showed significantly better photosynthetic performance, higher leaf RWC, underground dry weight, and the root to shoot ratio than the salt-sensitive PI251432 and Korla under salt stress. Increases in endogenous PAs, putrescine (Put), and spermidine (Spd) contents could be key adaptive responses to salt stress in the PI237292 and the Tr005 through upregulating genes encoding Put and Spd biosynthesis (NCA, ADC, SAMDC, and SPDS2). For Na+ and K+ accumulation and transport, higher salt tolerance of the PI237292 could be associated with the maintenance of Na+ and Ca+ homeostasis associated with upregulations of NCLX and BTB/POZ. The K+ homeostasis-related genes (KEA2, HAK25, SKOR, POT2/8/11, TPK3/5, and AKT1/5) are differentially expressed among four genotypes under salt stress. However, the K+ level and K+/Na+ ratio were not completely consistent with the salt tolerance of the four genotypes. The regulatory function of these differentially expressed genes (DEGs) on salt tolerance in the white clover and other leguminous plants needs to be investigated further. The current findings also provide basic genotypes for molecular-based breeding for salt tolerance in white clover species.

15.
Front Plant Sci ; 13: 787852, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720576

RESUMO

Counting wheat heads is a time-consuming process in agricultural production, which is currently primarily carried out by humans. Manually identifying wheat heads and statistically analyzing the findings has a rigorous requirement for the workforce and is prone to error. With the advancement of machine vision technology, computer vision detection algorithms have made wheat head detection and counting feasible. To accomplish this traditional labor-intensive task and tackle various tricky matters in wheat images, a high-precision wheat head detection model with strong generalizability was presented based on a one-stage network structure. The model's structure was referred to as that of the YOLO network; meanwhile, several modules were added and adjusted in the backbone network. The one-stage backbone network received an attention module and a feature fusion module, and the Loss function was improved. When compared to various other mainstream object detection networks, our model outperforms them, with a mAP of 0.688. In addition, an iOS-based intelligent wheat head counting mobile app was created, which could calculate the number of wheat heads in images shot in an agricultural environment in less than a second.

16.
Exp Ther Med ; 24(1): 445, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35720624

RESUMO

[This corrects the article DOI: 10.3892/etm.2015.2220.].

17.
Front Aging Neurosci ; 14: 788661, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35721027

RESUMO

Objective: Ischemic moyamoya (MMD) disease could alter the cerebral structure, but little is known about the topological organization of the structural covariance network (SCN). This study employed structural magnetic resonance imaging and graph theory to evaluate SCN reorganization in ischemic MMD patients. Method: Forty-nine stroke-free ischemic MMD patients and 49 well-matched healthy controls (HCs) were examined by T1-MPRAGE imaging. Structural images were pre-processed using the Computational Anatomy Toolbox 12 (CAT 12) based on the diffeomorphic anatomical registration through exponentiated lie (DARTEL) algorithm and both the global and regional SCN parameters were calculated and compared using the Graph Analysis Toolbox (GAT). Results: Most of the important metrics of global network organization, including characteristic path length (Lp), clustering coefficient (Cp), assortativity, local efficiency, and transitivity, were significantly reduced in MMD patients compared with HCs. In addition, the regional betweenness centrality (BC) values of the bilateral medial orbitofrontal cortices were significantly lower in MMD patients than in HCs after false discovery rate (FDR) correction for multiple comparisons. The BC was also reduced in the left medial superior frontal gyrus and hippocampus, and increased in the bilateral middle cingulate gyri of patients, but these differences were not significant after FDR correlation. No differences in network resilience were detected by targeted attack analysis or random failure analysis. Conclusions: Both global and regional properties of the SCN are altered in MMD, even in the absence of major stroke or hemorrhagic damage. Patients exhibit a less optimal and more randomized SCN than HCs, and the nodal BC of the bilateral medial orbitofrontal cortices is severely reduced. These changes may account for the cognitive impairments in MMD patients.

18.
Front Pharmacol ; 13: 877709, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35721185

RESUMO

The immune system of centenarians remains active and young to prevent cancer and infections. Aging is associated with inflammaging, a persistent low-grade inflammatory state in which CD4+ T cells play a role. However, there are few studies that have been done on the CD4+ T cell subsets in centenarians. Herein, the changes in CD4+ T cell subsets were investigated in centenarians. It was found that with aging, the old adults had higher levels of proinflammatory cytokines and lower levels of anti-inflammatory cytokines in plasma. The levels of CRP, IL-12, TNF-α, IFN-γ, IL-6 and IL-10 were further increased in centenarians compared to old adults. While the levels of IL-17A, IL-1ß, IL-23 and TGF-ß in centenarians were closer to those in young adults. The total CD4+, CD8+, Th17 and Treg cells from peripheral blood mononuclear cells (PBMCs) were similar among the three groups. It was observed that the ratio of Th17/Treg cells was elevated in old adults compared to young adults. The ratio was not further elevated in centenarians but rather decreased. In addition, the ex vivo PBMCs differentiation assay showed that increased Th17 cells in centenarians tended to secrete fewer proinflammatory cytokines, while decreased Treg cells in centenarians were prone to secrete more anti-inflammatory cytokines. These observations suggested centenarians alleviated inflammaging by decreasing the ratio of Th17/Treg cells and changing them into anti-inflammatory secretory phenotypes, which provided a novel mechanism for anti-aging research.

19.
Front Mol Neurosci ; 15: 916249, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35721316

RESUMO

Objective: Intracerebral hemorrhage (ICH) is the most lethal subtype of stroke, without effective treatment. Necrosulfonamide (NSA), a specific inhibitor for mixed lineage kinase domain-like protein, has been reported to exert neuroprotective effects in neurological diseases by ameliorating neuroinflammation and necroptosis. We hypothesized that NSA would alleviate acute brain injury and improve behavioral outcomes after ICH. Materials and Methods: Male adult C57BL/6 mice were assigned randomly into three groups. In vehicle and treatment groups, animals were injected with collagenase VII to induce ICH. The solvent (0.25% DMSO) and NSA (5 mg/kg) were administrated intraperitoneally twice a day, respectively. The sham group was injected with saline and administrated with DMSO. The brain hematoma volume, inflammatory factors, and blood-brain barrier permeability were measured on day 3 after the operation. Fluorescent double immunostaining was performed to evaluate the neuronal death. Neurological functions were assessed. Results: In the NSA group, the hematoma size was significantly reduced, inflammatory cells and cytokines were suppressed, and the blood-brain barrier was protected compared to vehicle controls. NSA dramatically reduced the death of neurons and improved the performance of neurological functions after ICH. Conclusion: Necrosulfonamide has a neuroprotective role in alleviating acute brain injury in a mouse ICH model, and this is associated with reduced neuroinflammation and necroptosis.

20.
Cancer Cell Int ; 22(1): 202, 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35642041

RESUMO

BACKGROUND: Breast cancer is the most common malignancy affecting women, yet effective targets and related candidate compounds for breast cancer treatment are still lacking. The lipogenic enzyme, stearoyl-CoA desaturase-1 (SCD1), has been considered a potential target for breast cancer treatment. Icaritin (ICT), a prenylflavonoid derivative from the Traditional Chinese Medicine Epimedii Herba, has been reported to exert anticancer effects in various types of cancer. The purpose of the present study was to explore the effect of the new ICT derivative, IC2, targeting SCD1 on breast cancer cells and to explore the specific mechanism. METHODS: Immunohistochemistry and semiquantitative evaluation were performed to detect the expression level of SCD1 in normal and tumor samples. Computer-aided drug design (CADD) technology was used to target SCD1 by molecular docking simulation, and several new ICT derivatives were prepared by conventional chemical synthesis. Cell viability was evaluated by an MTT assay and dead cell staining. SCD1 expression in cancer cells was determined by Western blot and qRT-PCR analyses. The enzymatic activity of SCD1 was evaluated by detecting the conversion rate of [d31] palmitic acid (PA) using Gas chromatography-mass spectrometry (GC-MS). DAPI staining, flow cytometry and Western blot were used to detect cell apoptosis. Mitochondrial membrane potential and reactive oxygen species (ROS) assays were used to determine cell mitochondrial function. Lentiviral transduction was utilized to generate SCD1-overexpressing cell lines. RESULTS: We found that SCD1 was overexpressed and correlated with poor prognosis in breast cancer patients. Among a series of ICT derivatives, in vitro data showed that IC2 potentially inhibited the viability of breast cancer cells, and the mechanistic study revealed that IC2 treatment resulted in ROS activation and cellular apoptosis. We demonstrated that IC2 inhibited SCD1 activity and expression in breast cancer cells in a dose-dependent manner. Moreover, SCD1 overexpression alleviated IC2-induced cytotoxicity and apoptosis in breast cancer cells. CONCLUSIONS: The new ICT derivative, IC2, was developed to induce breast cancer cell apoptosis by inhibiting SCD1, which provides a basis for the development of IC2 as a potential clinical compound for breast cancer treatment.

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