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1.
Bioact Mater ; 19: 251-267, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35510173

RESUMO

Inflammatory bowel disease (IBD) is a chronic, immune-mediated inflammatory disease characterized by the destruction of the structure and function of the intestinal epithelial barrier. Due to the poor remission effect and severe adverse events associated with current clinical medications, IBD remains an incurable disease. Here, we demonstrated a novel treatment strategy with high safety and effective inflammation remission via tissue-adhesive molecular coating. The molecular coating is composed of o-nitrobenzaldehyde (NB)-modified Gelatin (GelNB), which can strongly bond with -NH2 on the intestinal surface of tissue to form a thin biophysical barrier. We found that this molecular coating was able to stay on the surface of the intestine for long periods of time, effectively protecting the damaged intestinal epithelium from irritations of external intestinal metabolites and harmful flora. In addition, our results showed that this coating not only provided a beneficial environment for cell migration and proliferation to promote intestinal repair and regeneration, but also achieved a better outcome of IBD by reducing intestinal inflammation. Moreover, the in vivo experiments showed that the GelNB was better than the classic clinical medication-mesalazine. Therefore, our molecular coating showed potential as a promising strategy for the prevention and treatment of IBD.

2.
Bioact Mater ; 19: 418-428, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35574059

RESUMO

Labeling of mesenchymal stem cells (MSCs) with superparamagnetic iron oxide nanoparticles (SPIONs) has emerged as a potential method for magnetic resonance imaging (MRI) tracking of transplanted cells in tissue repair studies and clinical trials. Labeling of MSCs using clinically approved SPIONs (ferumoxytol) requires the use of transfection reagents or magnetic field, which largely limits their clinical application. To overcome this obstacle, we established a novel and highly effective method for magnetic labeling of MSC spheroids using ferumoxytol. Unlike conventional methods, ferumoxytol labeling was done in the formation of a mechanically tunable biomimetic hydrogel-induced MSC spheroids. Moreover, the labeled MSC spheroids exhibited strong MRI T2 signals and good biosafety. Strikingly, the encapsulated ferumoxytol was localized in the extracellular matrix (ECM) of the spheroids instead of the cytoplasm, minimizing the cytotoxicity of ferumoxytol and maintaining the viability and stemness properties of biomimetic hydrogel-induced MSC spheroids. This demonstrates the potential of this method for post-transplantation MRI tracking in the clinic.

3.
Inhal Toxicol ; : 1-15, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913820

RESUMO

Silicosis, induced by inhaling silica particles in workplaces, is one of the most common occupational diseases. The prognosis of silicosis and its consequent fibrosis is extremely poor due to limited treatment modalities and lack of understanding of the disease mechanisms. In this study, a Wistar rat model for silicosis fibrosis was established by intratracheal instillation of silica (0, 50, 100 and 200 mg/mL, 1 mL) with the evidence of Hematoxylin and Eosin (HE) and Masson staining and the expressions of inflammatory and fibrotic proteins of rats' lung tissues. RNA of lung tissues of rats exposed to 200 mg/mL silica particles and normal saline for 14 d and 28 d was extracted and sequenced to detect differentially expressed genes (DEGs) and to identify silicosis fibrosis-associated modules and hub genes by Weighted gene co-expression network analysis (WGCNA). Predictions of gene functions and signaling pathways were conducted using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. In this study, it has been demonstrated the promising role of the Hippo signaling pathway in silicosis fibrosis, which will be conducive to elucidating the specific mechanism of pulmonary fibrosis induced by silica and to determining molecular initiating event (MIE) and adverse outcome pathway (AOP) of silicosis fibrosis.

4.
J Oncol ; 2022: 8145129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909905

RESUMO

Objective: This study investigated whether lncRNA NEAT1 could inhibit the proliferation of cutaneous squamous cell carcinoma (CSCC) cells by targeting miR-342-3p/CUL4B, thereby affecting the occurrence and development of CSCC. Methods: Fluorescence quantitative PCR was used to detect the expression of lncRNA NEAT1 and miR-42-3p in skin squamous cell carcinoma and adjacent tissues. Bioinformatics software and luciferase reporter gene assay were used to analyze the association of lncRNA NEAT1 and miR-342-3p. The effect of overexpression or knockdown of miR-342-3p on the proliferation of CSCC cells was examined by MTT and colony formation assays. Western blotting was used to detect the proteins of the miR-342-3p/CUL4B signaling axis. Results: The lncRNA NEAT1 is abnormally overexpressed in CSCC tissues and cell lines. The expression of lncRNA NEAT1 and miR-342-3p in CSCC was negatively correlated. Bioinformatics prediction analysis revealed that lncRNA NEAT1 regulates the expression of miR-342-3p. The results of MTT and plate colony formation experiments showed that the transfection of miR-342-3p mimics significantly inhibited the proliferation and plate colony formation of CSCC cells, while the transfection of miR-342-3p inhibitor significantly promoted the proliferation and plate colony-forming ability of CSCC cells. Western blot results showed that lncRNA NEAT1 affected CSCC cell proliferation through miR-342-3p/CUL4B/PI3K-Akt signaling pathway. Conclusion: The expression of lncRNA NEAT1 and miR-342-3p in CSCC tissues was negatively correlated. This study is the first to demonstrate that the lncRNA NEAT1, as a ceRNA, affects the proliferation of skin squamous cell carcinoma cells through the miR-342-3p/CUL4B/PI3K-Akt signaling pathway. Therefore, lncRNA NEAT1 could be a biological marker or target for CSCC diagnosis or treatment.

5.
Research (Wash D C) ; 2022: 9854904, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909936

RESUMO

Lactic acid acidifies the tumor microenvironment and promotes multiple critical oncogenic processes, including immune evasion. Pyruvate kinase M2 (PKM2) is a dominant form of pyruvate kinase (PK) expressed in cancers that plays essential roles in metabolic reprograming and lactate production, rendering it as an attractive therapeutic target of cancer. However, the mechanism underlying PKM2 regulation remains unclear. Here, we show that long noncoding RNA (lncRNA) HIF-1α inhibitor at transcription level (HITT) inhibits lactate production in a PKM2-dependent manner. Mechanistically, it physically interacts with PKM2 mapped to a region that has been involved in both dimer (less-active) and tetramer (more-active) formation, inhibiting PKM2 oligomerization and leading to dramatic reduction of PK activity. Under glucose starvation, HITT was reduced as a result of miR-106 induction, which subsequently facilitates PKM2 oligomerization and increases vulnerability to apoptosis under glucose starvation stress. In addition, the interaction also reduces lactate secretion from cancer cells, which subsequently polarizes macrophages toward an M2-like anti-inflammatory phenotype and thus possibly contributes to immune escape in vivo. This study highlights an important role of an lncRNA in regulating PKM2 activity and also reveals a metabolic regulatory effect of PKM2 on macrophage polarization.

6.
Front Chem ; 10: 957462, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910740

RESUMO

Pyrite (FeS2) is one of the potential candidates for advanced rechargeable Li-ion batteries (LIBs) owing to its inherent capacity (849 mAh g-1), environmental friendliness, and abundant natural resources. However, the volume expansion of FeS2 and the dissolution of polysulfide in the electrochemical reaction severely limit its application in the field of energy conversion and storage. Herein, FeS2 nanoparticles are encapsulated in S/N co-doped three-dimensional multi-channel structural carbon nanofibers (FeS2@CNFs) through the electrospinning method. As a cathode material for LIBs, FeS2@CNFs demonstrated excellent rate property and cyclic stability. The 3FeS2@CNFs (weight ratio of FeS2 is 30%) present the initial capacity of 1,336.7 mAh g-1 and the remaining 856.5 mAh g-1 at 0.02A g-1 after 100 circles. The favorable electrochemical properties have confirmed that carbon nanofibers can enhance the electroconductivity of electrodes, reduce the volume collapse of FeS2, and remit the dissolution of polysulfide during the Li+ ions insertion/de-insertion process. In addition, co-doped S/N can supply abundant active sites for electrochemical reactions, providing enough space for Li+ ion storage. The results indicate that 3FeS2@CNFs is a cathode with a developmental prospect for LIBs.

7.
Front Psychol ; 13: 950546, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910964

RESUMO

In recent years, there is the popular phenomenon of "grass planting" marketing. The value co-creation behavior of ordinary consumers KOC (key opinion consumer) in the online community is sometimes out of utilitarian intentions, which is deemed as plain people's "grass planting" advertising in a certain degree. We collected the tourists' data in Chinese Grand Canal National Cultural Park, analyzed the impact of value co-creation behaviors such as tourists' experience sharing, topic discussions, and suggestions in online communities on the value of tourism experience and the quality of brand relationships under the "planting grass" marketing environment and verified the moderating mechanism of tourist altruism in it. According to the results, tourists' online value co-creation behavior has a significant positive impact on the consumer-brand relationship quality, and experience value plays a mediating role. Tourists' online value co-creation behavior has a significant positive impact on experience value, in which altruism plays a moderating role. The greater the tendency of altruism, the higher the impact of tourists' value co-creation behaviors on their experience value, and vice versa. This conclusion is not only of great significance in deepening and improving theories of value co-creation, altruism, experience value and consumer-brand relationship quality, but also has important certain management enlightenment on how to combine the design of merchant value co-creation incentive mechanism with altruism in "grass planting" marketing.

8.
Front Pharmacol ; 13: 941013, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924046

RESUMO

Tibetan medicine is an important part of traditional Chinese medicine and a significant representative of ethnic medicine in China. Tibetan medicine is gradually recognized by the world for its unique curative effects. Wuwei Shexiang pills (WPW) has been widely used to treat "Zhenbu" disease (Also known as rheumatoid arthritis) in Tibetan medicine, however, its potential bioactive ingredients and mechanism for RA treatment remain unclear. In this study, we used a combination of gas chromatography-mass spectrometry (GC-MS), ultra-performance liquid chromatography coupled with quadrupole time-of-fight mass spectrometry (UPLC-Q-TOF/MS), network analysis and experimental validation to elucidate the potential pharmacodynamic substances and mechanisms of WPW in the treatment of rheumatoid arthritis (RA). The results showed that songoramine, cheilanthifoline, saussureanine C, acoric acid, arjunolic acid, peraksine, ellagic acid, arjungenin and other 11 components may be the main activities of WPW in the treatment of RA. PIK3CA, AKT, MAPK, IL-6, TNF, MMP1, MMP3, and CDK1 are considered as core targets. PI3K-AKT, MAPK, apoptosis, cell cycle, and other signaling pathways may be the key pathways for WPW to play a role in the treatment of RA. Furthermore, we validated the underlying molecular mechanism of WPW predicted by network analysis and demonstrated its possible mechanism through in vivo animal experiments. It was found that WPW could significantly improve the degree of paw swelling, and reduce ankle joint diameter and arthritis index. Further histomorphological analysis showed that WPW could reduce the degree of synovial tissue inflammation and ankle joint cartilage damage. Meanwhile, WPW could down-regulate the levels of IL-6, IL-1ß, and IL-17, and increase the levels of IL-10 and IL-4 in the serum of AA rats. TUNEL staining confirmed that WPW could significantly promote the apoptosis of synovial cells. Moreover, the immunohistochemical results showed that WPW decreased the expression of PI3K, AKT, MAPK, MMP1, MMP3, CDK1, and Bcl-2, as well as increased the expression of Bax protein. In conclusion, we successfully combined GC-MS, UPLC-Q-TOF/MS, network analysis, and experimental validation strategies to elucidate the inhibition of inflammation by WPW in AA model rats via PI3K/AKT, MAPK, cell cycle and apoptotic pathways process. This not only provides new evidence for the study of potential pharmacodynamic substances and the mechanism of WPW in the treatment of RA, but also provides ideas for the study of other Tibetan medicine compound preparations.

9.
Emerg Microbes Infect ; : 1-22, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35924388

RESUMO

BACKGROUND: Omicron variant was featured with high transmissibility and striking antibody evasion. Shanghai has been experiencing Omicron wave since March 2022. Though several studies have evaluated the risk factors of severe infections, the analyses of BA.2 infection risk and protective factors among geriatric people was much limited. METHODS: This multicenter cohort study described clinical characteristics of geriatric Omicron infections (aged more than 60), and assessed risk and protective factors for severe infections. RESULTS: A total of 1377 patients older than 60 were enrolled, with 75.96% had comorbidities. The median viral shedding time and hospitalization time was 9 and 8 days, respectively. Severe/critical were associated with longer virus clearance time (aOR [95%CI]:0.706(0.533-0.935), P=0.015)), while fully vaccinated/booster and paxlovid use shortened viral shedding time (1.229 [1.076-1.402], P=0.002; 1.140 [.019-1.274], P=0.022, respectively). Older age (>80), cerebrovascular disease, and chronic kidney disease were risk factors of progressing to severe/critical. Fully vaccination was a significant protective factor of severe infections (0.237[0.071-0.793], P=0.019). Further, we found patients with more than two comorbidities were more likely to get serious outcome in all age groups. CONCLUSION: These findings demonstrated that in the elderly older than 60 years old, older age (aged over 80), cerebrovascular disease, and chronic kidney disease were risk factors of severe infection. Patients with more than two comorbidities were more likely to get serious outcome. Fully vaccinated/booster patients were less likely to be severe and vaccinations could shorten viral shedding time. The limitation of lacking overall spectrum of COVID-19 infections among elders could be compensated in other larger scale studies in the future.

10.
Expert Opin Drug Saf ; : 1-6, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35924402

RESUMO

BACKGROUND: Epidermal Growth Factor Receptor/ Anaplastic Lymphoma Kinase Tyrosine kinase inhibitors (EGFR/ALK TKIs) may provoke fatal interstitial pneumonitis (IP). The study was conducted to characterize the main characteristics of EGFR/ALK TKI-induced IP and identify factors associated with death. RESEARCH DESIGN AND METHODS: A disproportionality analysis was conducted using Vigibase, the World Health Organization pharmacovigilance database. Clinical features of patients with EGFR/ALK-TKI-related IP were compared between the fatal and non-fatal groups. RESULTS: A total of 3355 EGFR/ALK-TKI-IP events were identified, over half of them from Asia (57.47%) and mostly the aged (63.21%). Osimertinib appeared the strongest IP association. The median time to onset (TTO) was 40 (interquartile range [IQR] 16-84) days. There were significant differences between the fatal and non-fatal groups in terms of reporting year and TKI regimens (P < 0.05). The fatality rate of erlotinib-induced IP was the highest (35.54%). CONCLUSION: Our study showed that EGFR/ALK TKIs were associated with IP that had a high fatality rate and tended to occur earlier in fatal cases. It is necessary to raise awareness of IP surveillance when EGFR/ALK TKIs were administered.

11.
Nat Mater ; 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927433

RESUMO

Sliding ferroelectricity is a recently observed polarity existing in two-dimensional materials. However, due to the weak polarization and poor electrical insulation in these materials, existing experimental evidences are indirect and mostly based on nanoscale transport properties or piezoresponse force microscopy. We report the direct observation of sliding ferroelectricity, using a high-quality amphidynamic single crystal (15-crown-5)Cd3Cl6, which possesses a large bandgap and so allows direct measurement of polarization-electric field hysteresis. This coordination polymer is a van der Waals material, which is composed of inorganic stators and organic rotators as determined by X-ray diffraction and NMR characterization. From density functional theory calculations, we find that after freezing the rotators, an electric dipole is generated in each layer driven by the geometric mechanism, while a comparable ferroelectric polarization originates from the interlayer sliding. The net polarization of these two components can be directly measured and manipulated. Our finding provides insight into low-dimensional ferroelectrics, especially control of the synchronous dynamics of rotating molecules and sliding layers in solids.

12.
Proteomics Clin Appl ; : e2200031, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35929818

RESUMO

BACKGROUND: While the majority of COVID-19 patients fully recover from the infection and become asymptomatic, a significant proportion of COVID-19 survivors experience a broad spectrum of symptoms lasting weeks to months post-infection, a phenomenon termed "post-acute sequelae of COVID-19 (PASC)". The aim of this study is to determine whether inflammatory proteins are dysregulated and can serve as potential biomarkers for systemic inflammation in COVID-19 survivors. METHODS: We determined the levels of inflammatory proteins in plasma from 22 COVID-19 long haulers (COV-LH), 22 COVID-19 asymptomatic survivors (COV-AS), and 22 healthy subjects (HS) using an Olink proteomics assay and assessed the results by a beads-based multiplex immunoassay. RESULTS: Compared to HS, we found that COVID-19 survivors still exhibited systemic inflammation, as evidenced by significant changes in the levels of multiple inflammatory proteins in plasma from both COV-LH and COV-AS. CXCL10 was the only protein that significantly upregulated in COV-LH compared with COV-AS and HS. CONCLUSIONS: Our results indicate that several inflammatory proteins remain aberrantly dysregulated in COVID-19 survivors and CXCL10 might serve as a potential biomarker to typify COV-LH. Further characterization of these signature inflammatory molecules might improve the understanding of the long-term impacts of COVID-19 and provide new targets for the diagnosis and treatment of COVID-19 survivors with PASC. This article is protected by copyright. All rights reserved.

13.
Hepatology ; 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35921500

RESUMO

BACKGROUND & AIMS: Gain-of-function (GOF) mutations of CTNNB1 and loss-of-function (LOF) mutations of AXIN1 are recurrent genetic alterations in hepatocellular carcinoma (HCC). We aim to investigate the functional contribution of Hippo/YAP/TAZ in GOF CTNNB1 or LOF AXIN1 mutant HCCs. APPROACH & RESULTS: The requirement of YAP/TAZ in c-Met/ß-Catenin and c-Met/sgAxin1 driven HCC was analyzed using conditional Yap, Taz, and Yap;Taz knockout (KO) mice. Mechanisms of AXIN1 in regulating YAP/TAZ were investigated using AXIN1 mutated HCC cells. Hepatocyte-specific inducible TTR-CreERT2 KO system was applied to evaluate the role of Yap;Taz during tumor progression. Cabozantinib and G007-LK combinational treatment were tested in vitro and in vivo. Nuclear YAP/TAZ was strongly induced in c-Met/sgAxin1 mouse HCC cells. Activation of Hippo via overexpression of Lats2 or concomitant deletion of Yap and Taz significantly inhibited c-Met/sgAxin1 driven HCC development, whereas the same approaches had mild effects in c-Met/ß-Catenin HCCs. YAP is the major Hippo effector in c-Met/ß-Catenin HCCs, and both YAP and TAZ are required for c-Met/sgAxin1 dependent hepatocarcinogenesis. Mechanistically, AXIN1 binds to YAP/TAZ in human HCC cells and regulates YAP/TAZ stability. Genetic deletion of YAP/TAZ suppresses already formed c-Met/sgAxin1 liver tumors, supporting the requirement of YAP/TAZ during tumor progression. Importantly, tankyrase inhibitor G007-LK, which targets Hippo and Wnt pathways, synergizes with cabozantinib, a c-MET inhibitor, leading to tumor regression in the c-Met/sgAxin1 HCC model. CONCLUSIONS: Our studies demonstrate that YAP/TAZ are major signaling molecules downstream of LOF AXIN1 mutant HCCs, and targeting YAP/TAZ as an effective treatment against AXIN1 mutant human HCCs.

14.
Artigo em Inglês | MEDLINE | ID: mdl-35918265

RESUMO

BACKGROUND AND AIMS: The joint effect of famine exposure and adulthood obesity on risk of dyslipidemia remains unclear. Thus, we aim to explore the joint effect of famine exposure and adulthood obesity on the risk of dyslipidemia, and the potential effect of adult general or abdominal obesity on the association between famine exposure and dyslipidemia. METHODS AND RESULTS: We conducted a community-based cohort study in 8880 subjects aged 40 years or older. Participants were divided into nonexposed, fetal-exposed, childhood-exposed, adolescent-exposed according to birth date. General obesity and abdominal obesity were defined according to body mass index (BMI: overweight≥24.0 kg/m2, obesity≥28.0 kg/m2) and waist-to-hip ratio (WHR, men/women: moderate≥0.90/0.85, high≥0.95/0.90). Dyslipidemia was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. Compared with nonexposed participants, fetal-exposed individuals had significantly increased risk of dyslipidemia (OR:1.24, 95%CI: 1.03-1.50) in the whole study. Significant increased risk of dyslipidemia related to famine exposure was observed in women [ORs (95%CIs) were 1.36 (1.05-1.76) and 1.70 (1.22-2.37) for the fetal and childhood-exposed group, respectively] but not in men. Moreover, both general and central obesity had significant multiplicative interactions with famine exposure for the risk of dyslipidemia (P for interaction = 0.0001 and < 0.0001, respectively). Significant additive interaction was found between famine exposure and WHR on risk of dyslipidemia in women, with the relative excess risk due to interaction (RERI) and 95% CI of 0.43 (0.10-0.76). CONCLUSION: Coexistence of early-life undernutrition and adulthood obesity was associated with a higher risk of dyslipidemia in later life.

15.
RSC Adv ; 12(33): 21026-21040, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35919837

RESUMO

Magnetic graphene oxide (MGO) was prepared and used as a catalyst to activate peroxymonosulfate (PMS) for degradation of Coomassie brilliant blue G250 (CBB). The effects of operation conditions including MGO dosage, PMS dosage and initial concentration of CBB were studied. CBB removal could reach 99.5% under optimum conditions, and high removals of 98.4-99.9% were also achieved for other organic dyes with varied structures, verifying the high efficiency and wide applicability of the MGO/PMS catalytic system. The effects of environmental factors including solution pH, inorganic ions and water matrices were also investigated. Reusability test showed that CBB removals maintained above 90% in five consecutive runs, indicating the acceptable recyclability of MGO. Based on quenching experiments, solvent exchange (H2O to D2O) and in situ open circuit potential (OCP) test, it was found that ˙OH, SO4˙- and high-valent iron species were responsible for the efficient degradation of CBB in the MGO/PMS system, while the contributions of O2˙-, 1O2 and the non-radical electron-transfer pathway were limited. Furthermore, the plausible degradation pathway of CBB was proposed based on density functional theory (DFT) calculations and liquid chromatography-mass spectrometry (LC-MS) results, and toxicity variation in the degradation process was evaluated by computerized structure-activity relationships (SARs) using green algae, daphnia, and fish as indicator species.

16.
Front Plant Sci ; 13: 892630, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937318

RESUMO

Callose synthase plays an essential role in plant growth and development and in response to all sorts of stresses through regulating callose formation. However, few research about the function and mechanism of the insect resistance of callose synthase genes have been reported in cotton. In this study, a cotton callose synthase gene GhCalS5 was cloned, and its function and mechanism of resistance to cotton aphids were analyzed. The expression of GhCalS5 was significantly upregulated in both, leaves and stems of cotton plants at 48 h after cotton aphid infestation and in the leaves of cotton plants at 24 h after salicylic acid treatment. The overexpression of GhCalS5 enhanced cotton resistance to cotton aphids. Expectedly silencing of GhCalS5 reduced cotton resistance to cotton aphids. Overexpression of GhCalS5 enhanced callose formation in cotton leaves. Our results suggest that GhCalS5 is involved in cotton resistance against cotton aphids by influencing callose formation.

17.
Front Endocrinol (Lausanne) ; 13: 882840, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937794

RESUMO

Introduction: The relationship between the characteristics of puberty growth and the stature (height and overweight and obesity) in late adolescence was not clear. We aimed to explore the effects of puberty growth patterns on the stature in late adolescence. Methods: A total of 13,143 children from a longitudinal cohort from 2006 to 2016 in Zhongshan city of China were included. The Preece-Baines growth curve was fitted for each individual child, and the age at peak height velocity (APHV), peak height velocity (PHV), and age at take-off (TOA) were obtained from the Preece-Baines model. To compare the difference in height in late adolescence (at 18 years old) at different pubertal height growth patterns (height spurt timing, intensity, and duration), the height at baseline was matched by using the propensity score matching. The log-binomial model was applied to assess the association between the three pubertal height growth patterns (timing, intensity, and duration) and overweight and obesity status in late adolescence, controlling the urbanity and body mass index (BMI) at baseline. Results: After matching the baseline height, boys and girls in three pubertal patterns with early timing (P < 0.01), small intensity (P < 0.01), and short duration (P < 0.01) of height spurt had the lowest final height in the late adolescence. A 16% increase and 45% increase of risk for overweight and obesity were significantly associated with the early APHV in boys and girls, respectively, relative risk (RR) in boys, 1.16(95% confidence interval, CI: 1.03-1.30), P = 0.011; RR in girls, 1.45(1.21-1.75), P < 0.001. A 21% increase and 59% increase of risk for overweight and obesity were significantly associated with small PHV in boys and girls, respectively, RR in boys, 1.21(1.07-1.36), P < 0.001; RR in girls, 1.59(1.30-1.95), P < 0.001; and an 80% increase of risk for overweight and obesity with small spurt duration in girls (RR = 1.80; 95% CI: 1.49, 2.18; P < 0.001). Conclusion: Pubertal growth patterns, including earlier puberty onset timing, smaller puberty intensity, and shorter puberty spurt duration, had a positive association with lower height risks and higher overweight and obesity risks in late adolescence.

18.
Front Genet ; 13: 952667, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937999

RESUMO

As a critical layer of epigenetics, RNA modifications demonstrate various molecular functions and participate in numerous biological processes. RNA modifications have been shown to be essential for embryogenesis and stem cell fate. As high-throughput sequencing and antibody technologies advanced by leaps and bounds, the association of RNA modifications with multiple human diseases sparked research enthusiasm; in addition, aberrant RNA modification leads to tumor angiogenesis by regulating angiogenesis-related factors. This review collected recent cutting-edge studies focused on RNA modifications (N6-methyladenosine (m6A), N5-methylcytosine (m5C), N7-methylguanosine (m7G), N1-methyladenosine (m1A), and pseudopuridine (Ψ)), and their related regulators in tumor angiogenesis to emphasize the role and impact of RNA modifications.

19.
Front Med (Lausanne) ; 9: 944547, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911415

RESUMO

Background: A critical and controversial issue is whether antiviral therapy should be recommended in chronic hepatitis B virus (HBV) infection patients with persistently normal alanine aminotransferase (PNALT) and detectable HBV DNA. The study aimed to develop a non-invasive model for predicting significant liver histological changes (SLHC), which is the histological indication for antiviral therapy in chronic hepatitis B (CHB) patients with PNALT and detectable HBV DNA. Methods: 398 chronic HBV infection patients with PNALT and detectable HBV DNA who underwent liver biopsy were divided into the estimation set (n = 256) and validation set (n = 142). A multivariate logistic regression model was developed to predict SLHC in the estimation set, and the diagnostic performance was further validated in the validation set. Results: 132 patients (33.2%) with PNALT and detectable HBV DNA had SLHC. Aspartate aminotransferase (AST), cholinesterase (ChE), and liver stiffness measurement (LSM) were identified as the independent predictors of SLHC. The AUROC of the SLHC index, which combined AST, ChE, and LSM, was 0.824 and 0.816 in the estimation and validation set, respectively, for the prediction of SLHC. Applying the SLHC index ≤ 0.15, the presence of SLHC could be excluded with high negative predictive value in the estimation set (93.2%) and in the validation set (90.2%). Applying the SLHC index ≥ 0.55, the presence of SLHC could be considered with high positive predictive value in the estimation set (79.2%) and in the validation set (76.5%). Conclusion: The SLHC index provides a high accuracy in predicting liver histological indication for antiviral therapy in CHB patients with PNALT and detectable HBV DNA.

20.
Front Aging Neurosci ; 14: 926485, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912073

RESUMO

Small extracellular vesicles (sEVs) mediate cell-cell communication by transferring their cargo biological materials into recipient cells. Diabetes mellitus (DM) induces cerebral vascular dysfunction and neurogenesis impairment, which are associated with cognitive decline and an increased risk of developing dementia. Whether the sEVs are involved in DM-induced cerebral vascular disease, is unknown. Therefore, we studied sEVs derived from cerebral endothelial cells (CEC-sEVs) of aged DM rats (DM-CEC-sEVs) and found that DM-CEC-sEVs robustly inhibited neural stem cell (NSC) generation of new neuroblasts and damaged cerebral endothelial function. Treatment of aged DM-rats with CEC-sEVs derived from adult healthy normal rats (N-CEC-sEVs) ameliorated cognitive deficits and improved cerebral vascular function and enhanced neurogenesis. Intravenously administered N-CEC-sEVs crossed the blood brain barrier and were internalized by neural stem cells in the neurogenic region, which were associated with augmentation of miR-1 and -146a and reduction of myeloid differentiation primary response gene 88 and thrombospondin 1 proteins. In addition, uptake of N-CEC-sEVs by the recipient cells was mediated by clathrin and caveolin dependent endocytosis signaling pathways. The present study provides ex vivo and in vivo evidence that DM-CEC-sEVs induce cerebral vascular dysfunction and neurogenesis impairment and that N-CEC-sEVs have a therapeutic effect on improvement of cognitive function by ameliorating dysfunction of cerebral vessels and increasing neurogenesis in aged DM rats, respectively.

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