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1.
Neural Regen Res ; 18(1): 207-212, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35799544

RESUMO

Currently available commercial nerve guidance conduits have been applied in the repair of peripheral nerve defects. However, a conduit exhibiting good biocompatibility remains to be developed. In this work, a series of chitosan/graphene oxide (GO) films with concentrations of GO varying from 0-1 wt% (collectively referred to as CHGF-n) were prepared by an electrodeposition technique. The effects of CHGF-n on proliferation and adhesion abilities of Schwann cells were evaluated. The results showed that Schwann cells exhibited elongated spindle shapes and upregulated expression of nerve regeneration-related factors such as Krox20 (a key myelination factor), Zeb2 (essential for Schwann cell differentiation, myelination, and nerve repair), and transforming growth factor ß (a cytokine with regenerative functions). In addition, a nerve guidance conduit with a GO content of 0.25% (CHGFC-0.25) was implanted to repair a 10-mm sciatic nerve defect in rats. The results indicated improvements in sciatic functional index, electrophysiology, and sciatic nerve and gastrocnemius muscle histology compared with the CHGFC-0 group, and similar outcomes to the autograft group. In conclusion, we provide a candidate method for the repair of peripheral nerve defects using free-standing chitosan/GO nerve conduits produced by electrodeposition.

2.
Chem Eng J ; 451: 138822, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36060034

RESUMO

The novel mutations attributed by the high mutagenicity of the SARS-CoV-2 makes its prevention and treatment challenging. Developing an ultra-fast, point-of-care-test (POCT) protocol is critical for responding to large-scale spread of SARS-CoV-2 in public places and in resource-poor remote areas. Here, we developed a nanoplasmonic enhanced isothermal amplification (NanoPEIA) strategy that combines a nanoplasmonic sensor with isothermal amplification. The novel strategy provides an ideal easy-to operate detection platform for obtaining accurate, ultra-fast and high-throughput (96 samples can be tested together) data. For clinical samples with viral detection at Ct value <25, the entire process (including sample preparation, virus lysis, detection, and data analysis) can be completed within six minutes. The method is also appropriate for detection of SARS-CoV-2 γ-coronavirus mutants. The NanoPEIA method was validated using clinical samples from 21 patients with SARS-CoV-2 infection and 31 healthy individuals. The detection result on the 52 clinical samples for SARS-CoV-2 showed that the NanoPEIA platform had a 100% sensitivity for N and orf1ab genes, which was higher than those obtained using RT-qPCR (88.9% and 90.0%, respectively). The specificities of 31 clinical negative samples were 92.3% and 91.7% for the N gene and the orf1ab gene, respectively. The limits of detection (LoD) of the clinical samples were 28.3 copies/mL and 23.3 copies/mL for the N gene and the orf1ab gene, respectively. The efficient NanoPEIA detection strategy facilitates real-time detection and visualization within ultrashort durations and can be applied for POCT diagnosis in resource-poor and highly populated areas.

3.
Mol Cell ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36108631

RESUMO

Human mixed-lineage leukemia (MLL) family methyltransferases methylate histone H3 lysine 4 to different methylation states (me1/me2/me3) with distinct functional outputs, but the mechanism underlying the different product specificities of MLL proteins remains unclear. Here, we develop methodologies to quantitatively measure the methylation rate difference between mono-, di-, and tri-methylation steps and demonstrate that MLL proteins possess distinct product specificities in the context of the minimum MLL-RBBP5-ASH2L complex. Comparative structural analyses of MLL complexes by X-ray crystal structures, fluorine-19 nuclear magnetic resonance, and molecular dynamics simulations reveal that the dynamics of two conserved tyrosine residues at the "F/Y (phenylalanine/tyrosine) switch" positions fine-tune the product specificity. The variation in the intramolecular interaction between SET-N and SET-C affects the F/Y switch dynamics, thus determining the product specificities of MLL proteins. These results indicate a modified F/Y switch rule applicable for most SET domain methyltransferases and implicate the functional divergence of MLL proteins.

4.
J Clin Med ; 11(18)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36143087

RESUMO

Objective: To investigate the maternal-neonatal outcomes of obstetric deliveries performed in negative pressure isolated delivery rooms (NPIDRs) during the coronavirus disease 2019 (COVID-19) omicron variant pandemic period in a single tertiary center in northern Taiwan. Methods: Confirmed positive and suspected-positive COVID-19 cases delivered in NPIDRs and COVID-19-negative mothers delivered in conventional delivery rooms (CDRs) in the period of 1 May 2022 to 31 May 2022 during the COVID-19 omicron variant pandemic stage were reviewed. The maternal-neonatal outcomes between the two groups of mothers were analyzed. All deliveries were performed following the obstetric and neonatologic protocols conforming to the epidemic prevention regulations promulgated by the Taiwan Centers for Disease Control (T-CDC). Multiple gestations, deliveries at gestational age below 34 weeks, and major fetal anomalies were excluded from this study. Results: A total of 213 obstetric deliveries were included. Forty-five deliveries were performed in NPIDRs due to a positive COVID-19 polymerase chain reaction (PCR) test (n = 41) or suspected COVID-19 positive status (n = 4). One hundred and sixty-eight deliveries with negative COVID-19 PCR tests were performed in CDRs. There was no statistical difference in maternal characteristics between the two groups of pregnant women. All COVID-19-confirmed cases either presented with mild upper-airway symptoms (78%) or were asymptomatic (22%); none of these cases developed severe acute respiratory syndrome. The total rate of cesarean section was not statistically different between obstetric deliveries in NPIDRs and in CDRs (38.1% vs. 40.0%, p = 0.82, respectively). Regardless of delivery modes, poorer short-term perinatal outcomes were observed in obstetric deliveries in NPIDRs: there were significant higher rates of neonatal respiratory distress (37.8% vs. 10.7%, p < 0.001, respectively), meconium-stained amniotic fluid (22.2% vs. 4.2%, p < 0.001, respectively) and newborn intensive care unit admission (55.6% vs. 8.3%, p < 0.001, respectively) in obstetric deliveries performed in NPIDRs than in CDRs. Maternal surgical outcomes were not significantly different between the two groups of patients. There was no vertical transmission or nosocomial infection observed in COVID-19 confirmed cases in this study period. Conclusions: Our study demonstrates that obstetric deliveries for positive and suspected COVID-19 omicron-variant cases performed in NPIDRs are associated with poorer short-term perinatal outcomes. Reasonable use of personal protective equipment in NPIDRs could effectively prevent nosocomial infection during obstetric deliveries for pregnant women infected with the COVID-19 omicron variant.

5.
Obesity (Silver Spring) ; 30(10): 2044-2054, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36046944

RESUMO

OBJECTIVE: The study aimed to identify BMI-related lipids and to explore the role of lipids linking BMI and gestational diabetes mellitus (GDM). METHODS: Plasma lipidome, height, and weight were measured in early pregnancy among 1008 women. Pearson correlation analyses and least absolute shrinkage and selection operator regression (LASSO) were performed to identify BMI-associated lipids. Based on these lipids, a lipid score was created using LASSO, and its association with GDM risk was evaluated by conditional logistic regression. The causal relationships between BMI and lipids were tested by Mendelian randomization analysis with genotyping data. Mediation analysis was conducted to evaluate the mediating effect of lipids on the association of BMI with GDM. RESULTS: Of 366 measured lipids, BMI was correlated with 28 lipids, which mainly belong to glycerophospholipids and glycerolipids. A total of 10 lipid species were associated with BMI, and a lipid score was established. A causal relationship between BMI and lysophosphatidylcholine 14:0 was observed. The lipid score was associated with a 1.69-fold increased risk of GDM per 1-point increment (95% CI: 1.33-2.15). Furthermore, BMI-associated lipids might explain 66.4% of the relationship between BMI and GDM. CONCLUSIONS: Higher BMI in early pregnancy was associated with altered lipid metabolism that may contribute to the increased risk of GDM.

6.
Environ Pollut ; 312: 120089, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36058315

RESUMO

Cell phone use and radio-frequency electromagnetic radiation (RF-EMF) are rapidly increasing and may be associated with lower semen quality, yet results from epidemiological studies are inconclusive. Information on electronic devices use was collected through standard questionnaires from 1454 men aged 22-45 years old. Semen volume, sperm concentration, total sperm count, total motility, progressive motility, and normal morphology in repeated specimens were determined by trained clinical technicians. Percent changes [95% confidence intervals (CIs)] were estimated as (10ß-1) × 100 for electronic devices use associated with repeated sperm quality parameters in the linear mixed-effect models. After adjusting for multiple confounders, we found significant inverse associations of total duration of electronic devices use with sperm progressive motility and total motility, duration of cell phone and computer use with sperm concentration, progressive motility, and total motility (all P < 0.05). No significant association was found between cell phone/computer use alone and sperm quality parameters. Moreover, per hour increase of time spent on cell phone talking was associated with decreased sperm concentration and total count by an average of -8.0% (95% CI: -15.2%, -0.2%) and -12.7% (95% CI: -21.3%, -3.1%), respectively. Besides, daily calling time was associated with lower sperm progressive motility and total motility among those who used headsets during a call (P for interaction <0.05). In conclusion, our study suggested that more time spent on electronic devices use had a modest reduction effect on semen quality. Daily calling time was significantly associated with lower sperm concentration and total count, and using headsets during a call appeared to aggravate the negative association between daily calling time and sperm motility. Additional studies are needed to confirm these findings.

7.
J Biol Chem ; : 102442, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36055405

RESUMO

Leukocyte cell-derived chemotaxin 2 (LECT2) acts as a tumor suppressor in hepatocellular carcinoma (HCC). However, the anti-neoplastic mechanism of LECT2, especially its influence on hepatic cancer stem cells (CSCs), remains largely unknown. In The Cancer Genome Atlas (TCGA) cohort, LECT2 mRNA expression was shown to be associated with stage, grade, recurrence, and overall survival in human HCC patients, and LECT2 expression was downregulated in hepatoma tissues compared with the adjacent non-tumoral liver. Here, we show by immunofluorescence and immunoblot analyses that LECT2 was expressed at lower levels in tumors and in poorly differentiated HCC cell lines. Using functional assays, we also found LECT2 was capable of suppressing oncogenic behaviors such as cell proliferation, anchorage-independent growth, migration, invasiveness, and epithelial-mesenchymal transition (EMT) in hepatoma cells. Moreover, we show exogenous LECT2 treatment inhibited CSC functions such as tumor sphere formation and drug efflux. Simultaneously, hepatic CSC marker expression was also downregulated, including expression of CD133 and CD44. This was supported by infection with adenovirus encoding LECT2 (Ad-LECT2) in HCC cells. Furthermore, in animal experiments, Ad-LECT2 gene therapy showed potent efficacy in treating HCC. We demonstrate LECT2 overexpression significantly promoted cell apoptosis and reduced neovascularization/CSC expansion in rat hepatoma tissues. Mechanistically, we showed using immunoblot and immunofluorescence analyses that LECT2 inhibited ß-catenin signaling via the suppression of the hepatocyte growth factor (HGF)/c-MET axis to diminish CSC properties in HCC cells. In summary, we reveal novel functions of LECT2 in the suppression of hepatic CSCs, suggesting a potential alternative strategy for HCC therapy.

8.
Front Immunol ; 13: 939873, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090986

RESUMO

Lung cancer is a malignant tumor with the highest morbidity and mortality rate worldwide, and it seriously endangers human health. In recent years, immunotherapy has been widely used in lung cancer and has achieved great benefits, especially the application of promoting antitumor immune defense. However, immune-related adverse events (irAEs) caused by immune checkpoint inhibitors have received increasing attention, which largely limits their use. We report the first case of new acute mastitis caused by anti-PD1 inhibitors due to lung adenocarcinoma. A 65-year-old female patient came to our hospital for treatment with cough and shortness of breath for one month. Chest CT showed that the malignant tumor in the lower lobe of the right lung with pleural effusion had metastasized to many places, and then pleural effusion was taken for pathological examination. Pathological examination indicated that the pleural fluid originated from lung adenocarcinoma. Subsequently, the patient received platinum-containing dual-agent chemotherapy (carboplatin and pemetrexed disodium) combined with immunotherapy (camrelizumab). During treatment, the patient developed known adverse events and unreported acute mastitis. After stopping camrelizumab, the patient's mastitis gradually improved. Our case shows that acute mastitis might be a new adverse event after the use of camrelizumab. Since this new adverse event has not been reported, we hope that oncology medical workers can obtain insight from our case and use it as a reference for the identification and management of irAEs.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Mastite , Derrame Pleural , Adenocarcinoma de Pulmão/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados , Proliferação de Células , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico
9.
Heliyon ; 8(8): e10216, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36060988

RESUMO

In recent decades, researchers have conducted in-depth studies of the design and synthesis of colorimetric/fluorometric probes and the application of such probes to biological and practical samples. The multifunctional colorimetric and fluorescent azo benzene-based probe (4'-hydroxyl-2,4-diaminoazobenzene, MP) was designed to detect Al3+, Fe3+, Cu2+ and F¯. Based on the distinct redshift of the absorption band and a significant color change (yellow → purple), MP was utilized for both naked-eyed and quantitative detection of Al3+ and Fe3+ after formation of the 1:1 complex. Test paper coated with MP and used in conjunction with a cell phone was used for colorimetric detection of Al3+ and Fe3+ ions (20 µM-2.0 mM) in water samples through naked-eye and digital image colorimetry. The "MP-Fe3+" coordination shift that occurs in the presence of the competitive ligand F¯ was used in the colorimetric measurement of F¯ in toothpaste. In the presence of Cu2+ ion, the non-emissive MP has transformed into fluorescent benzotriazole product PMP (Φ = 0.53) through the bimolecular rate-limiting step, and the second-order rate constant k is calculated as 31 ± 2 M-1 s-1. MP exhibits a "turn-on" fluorescence response in the presence of Cu2+ that is greater than its response in the presence of competitive species such as Fe3+, Al3+, Co2+, Fe2+, Zn2+, Cd2+, Mg2+, Mn2+, Ni2+ and Ag+. MP was shown to have low toxicity to living HeLa cells and to present good imaging characteristics for tracking of Cu2+ in vivo.

10.
Mar Biotechnol (NY) ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36083384

RESUMO

The development and growth of fish skeletal muscles require myoblast fusion to generate multinucleated myofibers. While zebrafish fast-twitch muscle can fuse to generate multinucleated fibers, the slow-twitch muscle fibers remain mononucleated in zebrafish embryos and larvae. The mechanism underlying the fiber-type-specific control of fusion remains elusive. Recent genetic studies using mice identified a long-sought fusion factor named Myomixer. To understand whether Myomixer is involved in the fiber-type specific fusion, we analyzed the transcriptional regulation of myomixer expression and characterized the muscle growth phenotype upon genetic deletion of myomixer in zebrafish. The data revealed that overexpression of Sonic Hedgehog (Shh) drastically inhibited myomixer expression and blocked myoblast fusion, recapitulating the phenotype upon direct genetic deletion of myomixer from zebrafish. The fusion defect in myomixer mutant embryos could be faithfully rescued upon re-expression of zebrafish myomixer gene or its orthologs from shark or human. Interestingly, myomixer mutant fish survived to adult stage though were notably smaller than wildtype siblings. Severe myopathy accompanied by the uncontrolled adipose infiltration was observed in both fast and slow muscle tissues of adult myomixer mutants. Collectively, our data highlight an indispensable role of myomixer gene for cell fusion during both embryonic muscle development and post-larval muscle growth.

11.
Rev Sci Instrum ; 93(8): 084501, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050105

RESUMO

We report on a holoscope axion search experiment near 19.6 µeV from the Taiwan Axion Search Experiment with Haloscope collaboration. This experiment is carried out via a frequency-tunable cavity detector with a volume V = 0.234 liter in a magnetic field B0 = 8 T. With a signal receiver that has a system noise temperature Tsys ≅ 2.2 K and an experiment time of about one month, the search excludes values of the axion-photon coupling constant gaγγ ≳ 8.1 × 10-14 GeV-1, a factor of 11 above the Kim-Shifman-Vainshtein-Zakharov benchmark model, at the 95% confidence level in the mass range of 19.4687-19.8436 µeV. We present the experimental setup and procedures to accomplish this search.

12.
BMC Public Health ; 22(1): 1692, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068522

RESUMO

BACKGROUND: The COVID-19 crisis poses considerable threats to public health, and exploring the key configuration conditions of the public behavior response is very important for emergency risk management. OBJECTIVE: This study attempts to reveal differences in the conditional configuration and mechanism of public behavior based on the proposed framework, further make up for the deficiencies of existing research in explaining such issues as "How to promote the public's protective behavior or reduce the public's excessive behavior?" and finally provide new evidence and ideas for the government to improve the emergency management system. METHODS: A total of 735 valid cases were obtained using an online survey and revealed the conditional configuration and mechanism of public behavior differences through a fuzzy set qualitative comparative analysis based on the proposed public behavioral framework. RESULTS: The results show that critical factors including risk communication, trust, risk perception, and negative emotions alone did not constitute a necessary condition for public protective or excessive behavior. The different configurations of influencing factors reveal the complexity of public behavioral risk management, and taking adequate measures to increase public trust and reduce negative public emotions constitute the core path of risk management to enhance positive public behavior. CONCLUSIONS: The configurations of various influencing factors reveal the complexity of public behavioral risk management. For behavioral risk management, governments should focus on adapting to multiple conditions according to their situations and, under the "overall perspective," formulate policies based on local conditions and further form a differentiated risk management path. Practically speaking, for the government, taking adequate measures to increase public trust and reduce negative public emotions is the core path of risk management to enhance positive public behavior.


Assuntos
COVID-19 , Governo , Humanos , Pandemias/prevenção & controle , Saúde Pública , Confiança
13.
Front Oncol ; 12: 947055, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992861

RESUMO

Of all the thoracic surgical procedures, chest wall surgery is probably the lowest-risk type. In fact, it is not so. Clinical work also often has the trap of chest wall surgery. An operation to remove a mass in the axilla may result in upper limb disability on the affected side. Here, we report the case of a 47-year-old female patient with a left chest wall adjacent axillary mass, which was considered an abnormal structural lymph node on color ultrasound examination and chest CT. Otherwise, she felt no discomfort. The left upper limb moved freely without being affected by the mass. A routine resection of the tumor was performed after the preoperative examination was completed. After the operation, the incision recovered well. However, the day after the surgery, she developed numbness and pain in her left little finger and ring finger, pain that often kept her from sleeping. The mass was confirmed to be a schwannoma with cystic degeneration by pathology slicing after the operation. By this time, doctors were alerted to the fact that the removal of the chest wall mass had nearly disabled the left upper limb of the patient, which was a great warning to the thoracic surgeon. In this case report, we hope that all surgeons will be cautious and careful and will not trust the imaging diagnosis too much. It is also hoped that the patient understands that some procedures may lead to unexpected complications.

14.
Diabetes Res Clin Pract ; 191: 110039, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35985429

RESUMO

AIMS: To examine the associations of serum concentrations of adiponectin and leptin and leptin/adiponectin ratio (LAR) in early pregnancy with risk of gestational diabetes mellitus (GDM) in Chinese women. The predictive ability of those biomarkers for GDM was also assessed. METHODS: Within the Tongji-Shuangliu Birth Cohort, a nested case-control study was established with 332 GDM cases and 664 matched controls at 1:2 ratio on age (±3 years) and gestational age (±4 weeks). Serum adiponectin and leptin levels were measured in early pregnancy (median gestational week, 11; range, 6-15). Conditional logistic regression models with adjustment for potential covariates were used to evaluate the associations. RESULTS: Multivariable-adjusted odds ratios (ORs) comparing extreme quartiles of adiponectin, leptin and LAR were 0.55 (95 % CI, 0.35, 0.85), 1.96 (95 % CI, 1.19, 3.24), and 2.72 (95 % CI, 1.63, 4.54) for GDM, respectively (All P-trend < 0.02). Adding adiponectin and leptin to a conventional prediction model (including traditional risk factors and fasting glucose) increased the C-statistics from 0.708 (95 % CI, 0.674, 0.741) to 0.728 (95 % CI, 0.695, 0.760), and achieved a net reclassification improvement of 0.292. CONCLUSIONS: Our findings indicate that adiponectin is inversely associated with GDM, while leptin and LAR are positively associated with GDM in Chinese pregnant women.

15.
Basic Res Cardiol ; 117(1): 42, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-36008727

RESUMO

Sympathetic nerve denervation after myocardial infarction (MI) predicts risk of sudden cardiac death. Therefore, therapeutic approaches limit infarct size, improving adverse remodeling and restores sympathetic innervation have a great clinical potential. Remote ischemic perconditioning (RIPerc) could markedly attenuate MI-reperfusion (MIR) injury. In this study, we aimed to assess its effects on cardiac sympathetic innervation and metabolism. Transient myocardial ischemia is induced by ligature of the left anterior descending coronary artery (LAD) in male Sprague-Dawley rats, and in vivo cardiac 2-[18F]FDG and [11C]mHED PET scans were performed at 14-15 days after ischemia. RIPerc was induced by three cycles of 5-min-long unilateral hind limb ischemia and intermittent 5 min of reperfusion during LAD occlusion period. The PET quantitative parameters were quantified in parametric polar maps. This standardized format facilitates the regional radioactive quantification in deficit regions to remote areas. The ex vivo radionuclide distribution was additionally identified using autoradiography. Myocardial neuron density (tyrosine hydroxylase positive staining) and chondroitin sulfate proteoglycans (CSPG, inhibiting neuron regeneration) expression were assessed by immunohistochemistry. There was no significant difference in the mean hypometabolism 2-[18F]FDG uptake ratio (44.6 ± 4.8% vs. 45.4 ± 4.4%) between MIR rats and MIR + RIPerc rats (P > 0.05). However, the mean [11C]mHED nervous activity of denervated myocardium was significantly elevated in MIR + RIPerc rats compared to the MIR rats (35.9 ± 7.1% vs. 28.9 ± 2.3%, P < 0.05), coupled with reduced denervated myocardium area (19.5 ± 5.3% vs. 27.8 ± 6.6%, P < 0.05), which were associated with preserved left-ventricular systolic function, a less reduction in neuron density, and a significant reduction in CSPG and CD68 expression in the myocardium. RIPerc presented a positive effect on cardiac sympathetic-nerve innervation following ischemia, but showed no significant effect on myocardial metabolism.


Assuntos
Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Animais , Fluordesoxiglucose F18 , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley
16.
Int Immunopharmacol ; 111: 109129, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35961266

RESUMO

Osteoarthritis (OA) is the most common arthritis, and is characterized by inflammation and cartilage degradation. Chicoric acid (CA), a bioactive caffeic acid derivative isolated from the root of Taraxacum mongolicumHand. - Mazz., has been reported to have anti-inflammatory effects. However, the therapeutic effects of CA on chondrocyte inflammation remain unknown. Our study aimed to explore the effect of CA on OA both in vivo and in vitro. In vitro, CA treatment significantly suppressed the overproduction of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), and IL-12 in tumor necrosis factor alpha (TNF-α)-induced human C28/I2 chondrocytes. Moreover, CA attenuated TNF-α induced degradation of the extracellular matrix (ECM) by upregulating the expression of collagen Ⅱ and aggrecan, and downregulating ADAMTS-5 and matrix metalloproteinases (MMPs). Additionally, CA treatment inhibited apoptosis in C28/I2 cells by upregulating of Bcl-2 levels, downregulating Bax and ROS levels, and activating the Nrf2/HO-1 pathway. Mechanistically, CA exerted an anti-inflammatory effect by inhibiting the PI3K/AKT and NF-κB signaling pathways, enhancing Nrf-2/HO-1 to limit the activation of NF-κB. In vivo experiments also proved the therapeutic effects of CA on OA in rats. These findings indicate that CA may become a new drug for the treatment of OA.


Assuntos
NF-kappa B , Osteoartrite , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Apoptose , Ácidos Cafeicos , Condrócitos , Humanos , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Osteoartrite/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais , Succinatos , Fator de Necrose Tumoral alfa/metabolismo
17.
Front Pharmacol ; 13: 919898, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003507

RESUMO

Allyl methyl trisulfide (AMTS) is one major lipid-soluble organosulfur compound of garlic. Previous studies have reported the potential therapeutic effect of garlic on acute lung injury (ALI) or its severe condition acute respiratory distress syndrome (ARDS), but the specific substances that exert the regulatory effects are still unclear. In this study, we investigate the protective effects of AMTS on lipopolysaccharide (LPS)-induced ALI mice and explored the underlying mechanisms. In vivo experiments, ICR mice were pretreated with 25-100 mg/kg AMTS for 7 days and followed by intratracheal instillation of LPS (1.5 mg/kg). The results showed that AMTS significantly attenuated LPS-induced deterioration of lung pathology, demonstrated by ameliorative edema and protein leakage, and improved pulmonary histopathological morphology. Meanwhile, the expression of inflammatory mediators and the infiltration of inflammation-regulation cells induced by LPS were also inhibited. In vitro experiments also revealed that AMTS could alleviate inflammation response and inhibit the exaggeration of macrophage M1 polarization in LPS-induced RAW264.7 cells. Mechanistically, we identified that AMTS treatment could attenuate the LPS-induced elevation of protein expression of p-IκBα, nuclear NF-κB-p65, COX2, iNOS, p-P38, p-ERK1/2, and p-JNK. Collectively, these data suggest that AMTS could attenuate LPS-induced ALI and the molecular mechanisms should be related to the suppression of the NF-κB and MAPKs pathways.

20.
Nutr Metab (Lond) ; 19(1): 56, 2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-35996181

RESUMO

OBJECTIVE: To examine the association of early-pregnancy serum C-peptide with incident gestational diabetes mellitus (GDM) and the predictive ability of maternal C-peptide for GDM. METHODS: A nested case-control study of 332 GDM cases and 664 controls was established based on the Tongji-Shuangliu Birth Cohort. The GDM cases and controls were matched at 1:2 on maternal age (± 3 years) and gestational age (± 4 weeks). Multivariable conditional logistic regression was applied to assess the association of C-peptide with risk of GDM. Partial Spearman's correlation coefficients were estimated for the correlations between C-peptide and multiple metabolic biomarkers. C-statistics were calculated to assess the predictive ability of early-pregnancy C-peptide for GDM. RESULTS: Of 996 pregnant women, median maternal age was 28.0 years old and median gestational age was 11.0 weeks. After adjustment for potential confounders, the odds ratio of GDM comparing the extreme quartiles of C-peptide was 2.28 (95% confidence interval, 1.43, 3.62; P for trend < 0.001). Partial correlation coefficients ranged between 0.07 and 0.77 for the correlations of C-peptide with fasting insulin, homeostatic model of insulin resistance, leptin, fasting blood glucose, triglycerides, glycosylated hemoglobin, waist-hip ratio, systolic blood pressure, and low-density lipoprotein cholesterol (P ≤ 0.025), and were - 0.11 and - 0.17 for high-density lipoprotein cholesterol and adiponectin (P < 0.001). Serum C-peptide slightly improved the predictive performance of the model with conventional predictive factors (0.66 vs. 0.63; P = 0.008). CONCLUSION: While the predictive value for subsequent GDM should be validated, early-pregnancy serum C-peptide may be positively associated with risk of GDM.

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