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1.
Ageing Res Rev ; 81: 101707, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35932977

RESUMO

BACKGROUND AND AIMS: Advancing age is the most important risk factor of atrial fibrillation (AF). The shortening of telomere length is a biomarker of biologic aging. There is an increasing body of evidence that leucocyte telomere length (LTL) is associated with the risk of AF development. However, the results in these studies were controversial. The current systematic review and meta-analysis was conducted to examine the role of LTL in predicting the incidence of AF. METHODS AND RESULTS: Observational studies reporting the association between LTL and the risk of AF were retrieved through 25th June, 2022 from PubMed and Embase. A total of twelve studies including 18,293 patients were included in the present analysis. Leucocyte telomere shortening was found to be an independent predictor of AF as a continuous variable in both univariate [OR:2.14; 95%CI(1.48,3.10); P < 0.0001] and multivariate analyses [OR:1.41;95%CI(1.11,1.79); P = 0.005], as well as categorical variable in multivariate analysis [OR:1.53; 95%CI(1.04,2.27); P = 0.03]. Furthermore, leucocyte telomere shortening was significantly associated with recurrent AF [OR:4.32;95%CI(2.42,7.69); P < 0.00001] but not new-onset AF [OR:1.14; 95%CI(0.90,1.45); P = 0.29]. Leucocyte telomere shortening was also associated with an increased risk of persistent AF [OR:14.73;95%CI (3.16,68.67); P = 0.0006] and paroxysmal AF [OR:2.74;95%CI(1.45,5.18); P = 0.002]. Besides, LTL was an independent predictor for progression from paroxysmal AF to persistent AF [OR:3.2;95%CI(1.66,6.18); P = 0.0005]. Differences between males [OR:1.99; 95%CI(1.29,3.06); P = 0.002] and females [OR:0.86; 95%CI (0.29,2.56);P = 0.79] were observed. CONCLUSIONS: Leucocyte telomere shortening predicts the risk of AF, especially recurrent AF. The predictive value is more prominent in males than in females. Shortening in LTL can predict the progression from paroxysmal to persistent AF.

2.
Nat Commun ; 13(1): 4672, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35945250

RESUMO

Linear (Met1-linked) ubiquitination is involved inflammatory and innate immune signaling. Previous studies have characterized enzymes regulating the addition and removal of this modification in mammalian systems. However, only a few plant-derived deubiquitinases targeting Met1-linked ubiquitin chains have been reported and their mechanism of action remains elusive. Here, using a dehydroalanine-bearing Met1-diubiquitin suicide probe, we discover OTUB1 from Oryza sativa (OsOTUB1) as a Met1-linked ubiquitin chain-targeting deubiquitinase. By solving crystal structures of apo OsOTUB1 and an OsOTUB1/Met1-diubiquitin complex, we find that Met1 activity is conferred by Met1-specific motifs in the S1' pocket of OsOTUB1. Large-scale sequence alignments and hydrolysis experiments provide evidence that these motifs are a general determinant of Met1 activity in the OTUB subfamily across species. Analysis of the species distribution of OTUBs capable of hydrolysing Met1-linked ubiquitin chains shows that this activity is conserved in green plants (Viridiplantae) and does not exist in metazoans, providing insights into the evolutionary differentiation between primitive plants and animals.

3.
Medicine (Baltimore) ; 101(31): e30009, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35945773

RESUMO

This is a retrospective study. Our aim was to investigate the risk factors related to dysphagia following anterior surgery treating the multilevel cervical disorder with kyphosis based on a subgroup of follow-up time. Finally, a total of 81 patients suffering from the multilevel cervical disorder with kyphosis following anterior surgery from July 2018 to June 2020 were included in our study. Patients with dysphagia were defined as the dysphagia group and without dysphagia as the no-dysphagia (NG) group based on a subgroup of follow-up time (1-week, 1-month, 3-month, 6-month, and 1-year after surgery). Clinical outcomes and radiological data were performed to compare between dysphagia group and NG. In our study, the rate of dysphagia was 67.9%, 44.4%, 34.6%, 25.9%, and 14.8% at 1-week, 1-month, 3-month, 6-month, and 1-year after surgery, respectively. Our findings showed that change of Cobb angle of C2-7 was associated with dysphagia within 3-month after surgery. Furthermore, postoperative Cobb angle of C2-7 was linked to dysphagia within 6-month after surgery. Interestingly, a history of smoking and lower preoperative SWAL-QOL score were found to be risk factors related with dysphagia at any follow-up. In the present study, many factors were found to be related to dysphagia within 3-month after surgery. Notably, a history of smoking and lower preoperative SWAL-QOL score were associated with dysphagia at any follow-up. We hope this article can provide a reference for spinal surgeons to predict which patients were susceptible to suffering from dysphagia after anterior surgery in the treatment of multilevel cervical disorder with kyphosis.

4.
Int J Med Robot ; : e2452, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35946497

RESUMO

BACKGROUND: This in vitro study aims to evaluate the accuracy of dental implant placement by a novel image-guided hybrid robotic system for dental implant surgery (HRS-DIS). METHODS: The HRS-DIS with a 5 degree of freedom (DOF) serial manipulator and a 6 DOF Stewart platform was developed. To evaluate the accuracy of repeated drilling, the holes were prepared twice with a 2.2 mm drill. To evaluate the accuracy of dental implant placement, the entry, exit and angle deviations of dental implants were measured. RESULTS: Twenty-four holes were prepared twice, and mean (± SD) of diameters were measured as 2.2 ± 0.02 mm. A total of 160 dental implants were placed in 32 phantoms by HRS-DIS. The mean (± SD) of the entry, exit and angle deviation were 0.8 ±0.54 mm, 0.87 ± 0.54 mm and 1.0 1 ± 0.44°, respectively. CONCLUSIONS: The results of the in vitro study preliminarily validated that the HRS-DIS could provide a high accuracy for dental implant surgery. This article is protected by copyright. All rights reserved.

5.
Pharmacol Res ; : 106392, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35940396

RESUMO

This study aimed to investigate the anti-neuropathic pain activity and its underlying molecular mechanism of Ajugarin-I (Aju-I) in a rat model of diabetic neuropathic pain. The rats were given a single injection of 60mg/kg of streptozotocin (STZ) intraperitoneally (i.p.) to induce diabetic neuropathic pain. After two weeks, rats were given Aju-I (1 and 5mg/kg/day) i.p. for four consecutive weeks. The results demonstrated that in diabetic rats, treatment with Aju-I decreased STZ-induced hyperglycemia. It reduced the pain hypersensitivity (mechanical, thermal, and cold nociception) caused by STZ. It effectively restored STZ-associated pathological changes in the pancreas. In the sciatic nerve and spinal cord, it attenuated STZ-associated histopathological alterations and DNA damage. It suppressed oxidative stress by increasing the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2), thioredoxin (Trx), and heme oxygenase (HO-1), but decreasing the immunoreactivity of Kelch-like ECH-associated protein 1 (Keap1). Additionally, TRPV1 (transient receptor potential vanilloid 1) and TRPM8 (transient receptor potential melastatin 8) expression levels were considerably reduced by Aju-I treatment. it enhanced antioxidant levels and suppressed inflammatory cytokines production. Taken together, this research suggests that Aju-I treatment reduces pain behaviors in the STZ model of diabetic neuropathy via modulating Nrf2/Keap-1/HO-1 signaling and TRPV1/TRPM8 nociceptors.

6.
J Cancer ; 13(9): 2912-2921, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912009

RESUMO

Background: Deficient mismatch repair (dMMR) or the microsatellite instability (MSI) phenotype occupied approximately 15-18% of CRC patients. Previous studies showed that dMMR/MSI status is a favorable prognostic factor for stage II/III CRC patients. For metastatic colorectal cancer (mCRC) patients, only 5% of patients have the dMMR/MSI-H phenotype. The relationship between dMMR/MSI, chemosensitivity and survival in mCRC patients of real-world is still not clear. Materials and methods: In this study, we enrolled 77 dMMR/MSI-H mCRC patients and compared their clinicopathological characteristics with those of 510 proficient MMR (pMMR) or microsatellite stable (MSS) mCRC patients. With propensity score matching (PSM) analysis, we further compared the chemosensitivity and survival of dMMR/MSI-H mCRC patients with pMMR/MSS patients. We also analyzed the efficacy of different chemotherapy and target therapy in the dMMR/MSI-H population. Results: In PSM cohort, the objective response rate (ORR) of mCRC patients with dMMR/MSI-H undergoing first-line palliative chemotherapy was 35.2%, which was similar with patients with pMMR/MSS (35.4%, p = 1.00). The median progression-free survival (PFS) of first-line chemotherapy was significantly different (dMMR/MSI-H vs pMMR/MSS = 7.4 months vs 10.2 months; HR = 0.74; 95%CI, 0.57-0.98; p = 0.03). Overall survival (OS) of patients did not significantly differ by status (dMMR/MSI-H vs pMMR/MSS = 40.0 months vs 41.3 months; HR = 1.09; 95%CI, 0.74-1.59; p = 0.68). For second-line palliative chemotherapy, there was no difference in ORR (p = 0.53) or in PFS (HR = 0.88; 95%CI, 0.59-1.33; p = 0.56) between dMMR/MSI-H and pMMR/MSS tumors. We also found that in the overall cohort, the ORR of patients who received oxaliplatin-based and irinotecan-based chemotherapy were 28.8% and 54.5%, respectively, which were not significantly different (p = 0.16). Our results also showed that the use of bevacizumab could lead to a significantly higher ORR in dMMR/MSI-H mCRC patients compared to chemotherapy alone (55.0% vs 22.2%; p = 0.02), whereas cetuximab could not. Conclusion: The dMMR/MSI-H is not a prognostic factor for mCRC patients but is correlated with shorter PFS to first-line palliative chemotherapy.

7.
Opt Lett ; 47(15): 3904-3907, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913343

RESUMO

Based on a photonics-aided scheme, we achieve an experimental demonstration of a, to the best of our knowledge, record-breaking 200-m terahertz (THz)-wave wireless delivery at 335 GHz with the aid of a pair of high-gain polytetrafluoroethylene (PTFE) lenses. By using a 10-GBaud probabilistically shaped 64-ary quadrature amplitude modulation (PS-64QAM) signal and advanced digital signal processing (DSP) including a likelihood-based selection radius-directed equalizer (LBS-RDE), the single-carrier net bit rate of the wireless delivery reaches 44 Gbit/s. High-speed THz-wave communication with up to 200-m wireless distance is successfully realized based on a photonics-aided scheme for the first time.

8.
ChemSusChem ; 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35916074

RESUMO

Photocatalysis is a promising technology for conversion of the glycerol into formic acid, but photocatalytic oxidation of C-C bonds in glycerol exhibits poor selectivity towards formic acid because the photogenerated radicals (e.g., hydroxyl radicals) further oxidize formic acid to CO 2 . In this work, we revealed a synergy of photogenerated holes and superoxide radicals that achieved the selective oxidation of glycerol into formic acid over the TiO 2 catalyst. The charge separation of pristine TiO 2 was improved with the aid of oxygen, which resulted in efficient hole oxidation of the C-C bonds in glycerol to formic acid. Surface active species was controlled to prevent being converted to hydroxyl radicals on TiO 2 via controlling the oxygen and water contents , which solved the problem of formic acid peroxidation without sophisticated catalyst modifications. Mechanism studies suggested that glyceraldehyde and glycolaldehyde were the intermediates to generate formic acid. This work provides a green and efficient approach to produce formic acid as a liquid hydrogen carrier from bio-based alcohols.

9.
Histol Histopathol ; : 18505, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35916204

RESUMO

BACKGROUND: Long noncoding RNA ubiquitin-conjugating enzyme E2 R2 antisense RNA 1 (UBE2R2-AS1) has been recently reported to participate in the progression of tumors, including glioma and liver cancer. However, the roles of UBE2R2-AS1 in prostate cancer (PC) remained poorly understood. METHODS: The expression of UBE2R2-AS1 was determined in tumor tissues and paired adjacent tissues from PC patients using quantitative reverse transcription PCR analysis. Correlation between UBE2R2-AS1 expression and clinicopathological parameters and overall survival were investigated by Chi-square test and Kaplan-Meier method analysis. The in vitro experiments, including CCK-8 assay, colony formation, flow cytometry and transwell assay were performed to investigate the functional role of UBE2R2-AS1 knockdown or overexpression on PC cell lines (PC-3 and DU145). Related protein expression levels were measured by western blot analysis. RESULTS: Our data showed that UBE2R2-AS1 expression was significantly upregulated in PC tissues compared with that in adjacent tissues. The high levels of UBE2R2-AS1 were associated with high Gleason score, advanced clinical T stage, lymph node metastasis and poor prognosis. Knockdown of UBE2R2-AS1 suppressed cell proliferation, migration and invasion, induced cell cycle G0/G1 arrest and apoptosis in PC cells, along with decreased expression of PCNA, CDK4, Cyclin D1, Bcl-2, N-cadherin and Vimentin, and increased E-cadherin expression. Overexpression of UBE12R2-AS1 obtained the opposite results in PC cells. CONCLUSIONS: Our findings suggest that UBE2R2-AS1 might be a potential diagnostic and/or therapeutic target in PC.

10.
Br J Cancer ; 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927310

RESUMO

BACKGROUND: The aim of this study was to gain an increased understanding of the aetiology of breast cancer, by investigating possible associations between serum lipoprotein subfractions and metabolites and the long-term risk of developing the disease. METHODS: From a cohort of 65,200 participants within the Trøndelag Health Study (HUNT study), we identified all women who developed breast cancer within a 22-year follow-up period. Using nuclear magnetic resonance (NMR) spectroscopy, 28 metabolites and 89 lipoprotein subfractions were quantified from prediagnostic serum samples of future breast cancer patients and matching controls (n = 1199 case-control pairs). RESULTS: Among premenopausal women (554 cases) 14 lipoprotein subfractions were associated with long-term breast cancer risk. In specific, different subfractions of VLDL particles (in particular VLDL-2, VLDL-3 and VLDL-4) were inversely associated with breast cancer. In addition, inverse associations were detected for total serum triglyceride levels and HDL-4 triglycerides. No significant association was found in postmenopausal women. CONCLUSIONS: We identified several associations between lipoprotein subfractions and long-term risk of breast cancer in premenopausal women. Inverse associations between several VLDL subfractions and breast cancer risk were found, revealing an altered metabolism in the endogenous lipid pathway many years prior to a breast cancer diagnosis.

11.
Clin Cancer Res ; 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35929990

RESUMO

PURPOSE: To compare the efficacy and safety of high-dose vitamin C plus FOLFOX +/- bevacizumab versus FOLFOX +/- bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Between 2017 and 2019, histologically confirmed mCRC patients (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (1:1) into a control (FOLFOX +/- bevacizumab) and an experimental (high-dose vitamin C [1.5 g/kg/d, intravenously for 3 hours from D1 to D3] plus FOLFOX +/- bevacizumab) group. Randomization was based on the primary tumor location and bevacizumab prescription. RESULTS: The progression-free survival (PFS) of the experimental group was not superior to the control group (median PFS, 8.6 vs 8.3 months; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.70-1.05; P = 0.1). The objective response rate (ORR) and overall survival (OS) of the experimental and control group were similar (ORR, 44.3% vs 42.1%; P = 0.9; median OS, 20.7 vs 19.7 months; P = 0.7). Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control group, respectively. In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs 7.8 months; HR, 0.67; 95% CI, 0.50-0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only. CONCLUSIONS: High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in mCRC patients as first-line treatment but may be beneficial in mCRC patients harboring RAS mutation.

12.
Discov Oncol ; 13(1): 68, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35916979

RESUMO

The aim is to describe a simple and feasible model for the diagnosis of insulinoma. This retrospective study enrolled 37 patients with insulinoma and 44 patients with hypoglycemia not due to insulinoma at the First Affiliated Hospital of Guangxi Medical University. General demographic and clinical characteristics; hemoglobin A1c (HbA1c), insulin and C-peptide concentrations; and the results of 2-h oral glucose tolerance tests (OGTT) were recorded, and a logistic regression model predictive of insulinoma was determined. Body mass index (BMI), HbA1c concentration, 0-h C-peptide concentration, and 0-h and 1-h plasma glucose concentrations (P < 0.05 each) were independently associated with insulinoma. A regression prediction model was established through multivariate logistics regression analysis: Logit p = 7.399+(0.310 × BMI) - (1.851 × HbA1c) - (1.467 × 0-h plasma glucose) + (1.963 × 0-h C-peptide) - (0.612 × 1-h plasma glucose). Using this index to draw a receiver operating characteristic (ROC) curve, the area under the curve (AUC) was found to be 0.957. The optimal cut-off value was - 0.17, which had a sensitivity of 89.2% and a specificity of 86.4%. Logit P ≥ - 0.17 can be used as a diagnostic marker for predicting insulinoma in patients with hypoglycemia.

13.
Artigo em Inglês | MEDLINE | ID: mdl-35918849

RESUMO

Immunomodulation has made remarkable achievements in fighting against infectious disease and cancer. Conventionally, immunomodulation largely relied on chemical/biochemical agents which, unfortunately, suffer from sever off-target adverse effects. Recent understandings on nano-bio interactions suggest that nanomaterials per se can directly participate in immunomodulation. A range of physical and chemical cues at nano-bio interface have been harnessed to regulate diverse immuno-signaling for disease control and treatment. In this Minireview, we summarize recent studies of the physical and chemical cues enabled by intrinsic nanomaterials that trigger immunological signaling. Firstly, we discuss physical cues mediated by surface topography, hydrophobicity, charge and heat at nano-bio interface for immunomodulation. Secondly, various chemical cues, such as metal species and oxidative species are outlined. Finally, our perspectives on the challenge and possible future directions are provided.

14.
Front Microbiol ; 13: 950402, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935186

RESUMO

Since porcine reproductive and respiratory syndrome virus (PRRSV) was first described in China in 1996, several genetically distinct strains of PRRSV have emerged with varying pathogenicity and severity, thereby making the prevention and control of PRRS more difficult in China and worldwide. Between 2017 and 2021, the detection rate of NADC34-like strain in China increased. To date, NADC34-like strains have spread to 10 Chinese provinces and have thus developed different degrees of pathogenicity and mortality. In this review, we summarize the history of NADC34-like strains in China and clarify the prevalence, genomic characteristics, restriction fragment length polymorphisms, recombination, pathogenicity, and vaccine status of this strain in China. In so doing, this study aims to provide a basis for the further development of prevention and control measures targeting the NADC34-like strain.

16.
Blood Cancer Discov ; 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35926182

RESUMO

SF3B1 mutations, which occur in 20% of patients with myelodysplastic syndromes (MDS), are the hallmarks of a specific MDS subtype, MDS with ringed sideroblasts (MDS-RS), which is characterized by the accumulation of erythroid precursors in the bone marrow and primarily affects the elderly population. Here, using single-cell technologies and functional validation studies of primary SF3B1-mutant MDS-RS samples, we show that SF3B1 mutations lead to the activation of the EIF2AK1 pathway in response to heme deficiency and that targeting this pathway rescues aberrant erythroid differentiation and enables the red blood cell maturation of MDS-RS erythroblasts. These data support the development of EIF2AK1 inhibitors to overcome transfusion dependency in patients with SF3B1-mutant MDS-RS with impaired red blood cell production.

17.
J Biol Chem ; : 102288, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35926713

RESUMO

Mechanistic target of rapamycin complex 2 (mTORC2) is a multi-subunit kinase complex, central to multiple essential signaling pathways. Two core subunits, Rictor and mSin1, distinguish it from the related mTORC1 and support context-dependent phosphorylation of its substrates. mTORC2 structures have been determined previously, however, important questions remain, particularly regarding the structural determinants mediating substrate specificity and context-dependent activity. Here, we used cryo-EM to obtain high-resolution structures of the human mTORC2 apo-complex in the presence of substrates Akt and SGK1. Using functional assays, we then tested predictions suggested by substrate-induced structural changes in mTORC2. For the first time, we visualized in the apo-state the side chain interactions between Rictor and mTOR that sterically occlude recruitment of mTORC1 substrates and confer resistance to the mTORC1 inhibitor rapamycin. Also in the apo-state, we observed that mSin1 formed extensive contacts with Rictor via a pair of short α-helices nestled between two Rictor helical repeat clusters, as well as by an extended strand that makes multiple weak contacts with Rictor helical cluster 1. In co-complex structures, we found that SGK1, but not Akt, markedly altered the conformation of the mSin1 N-terminal extended strand, disrupting multiple weak interactions while inducing a large rotation of mSin1 residue Arg-83, which then interacts with a patch of negatively charged residues within Rictor. Finally, we demonstrate mutation of Arg-83 to Ala selectively disrupts mTORC2-dependent phosphorylation of SGK1, but not of Akt, supporting context-dependent substrate selection. These findings provide new structural and functional insights into mTORC2 specificity and context-dependent activity.

18.
FASEB J ; 36(9): e22467, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35929417

RESUMO

Although long non-coding RNAs (lncRNAs) are reported to regulate follicular development and reproductive disease pathogenesis, the underlying mechanisms have not been elucidated. In this study, lncRNA expression profiling of different-sized healthy follicles from Hu sheep with different prolificacy revealed 50 613 lncRNAs. Numerous lncRNAs were differentially expressed among different comparison groups. This study characterized one novel transcript, lncRNA-412.25 (from healthy follicles with a diameter of >5 mm), which was predominantly expressed in the high prolificacy group and localized to the cytoplasm of granulosa cells (GCs). LncRNA-412.25 knockdown promoted and inhibited Hu sheep GC apoptosis and proliferation, respectively. Interestingly, lncRNA-412.25 could directly bind to miR-346, which can target the gene of leukemia inhibitory factor (LIF). Knockdown of lncRNA-412.25 promoted GC apoptosis by downregulating LIF expression, where this effect was attenuated by miR-346. Moreover, the miR-346 inhibitor mitigated the lncRNA-412.25 knockdown-induced downregulation of phosphorylated protein of signal transducer and activator of transcription 3 (STAT3), which was validated using immunofluorescence analysis. Our results demonstrated that lncRNA-412.25 regulates GC proliferation and apoptosis in Hu sheep by binding to miR-346 and then activating the LIF/STAT3 pathway. These findings provide novel insights into the mechanisms underlying prolificacy in sheep.


Assuntos
MicroRNAs , RNA Longo não Codificante , Animais , Apoptose/genética , Proliferação de Células/fisiologia , Feminino , Células da Granulosa/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Ovinos , Transdução de Sinais
19.
Front Pharmacol ; 13: 918292, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935822

RESUMO

In recent years, studies have shown a close relationship between cardiomyocyte death and ferroptosis. Clioquinol (CQ) can inhibit ferroptosis. Porous lipid-poly (lactic-co-glycolic acid) (PLGA) microbubbles (MBs) were prepared by double emulsification (W1/O/W2) using 1,2-dioctadecanoyl-sn-glycero-3-phophocholine and PLGA as raw materials. Porous lipid-PLGA MBs were used as carriers to prepare CQ/PLGA MBs containing CQ. CQ/PLGA had the advantages of high drug loading, good biocompatibility, and sustained release. Our results showed that CQ/PLGA improved the effect of CQ and reduced its cytotoxicity. Under low-frequency ultrasound with certain parameters, CQ/PLGA showed steady-state cavitation, which increased the membrane permeability of mouse cardiomyocyte HL-1 to a certain extent and further prevented the process of ferroptosis in mouse cardiomyocyte HL-1.

20.
Int J Clin Pract ; 2022: 4593443, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936064

RESUMO

Methods: Sixteen male mice were randomly divided into 4 groups: control (ordinary feeding), D-gal (D-galactose) group, D-gal + MSC (human umbilical cord Wharton jelly cells), and D-gal + MSC-TNFα groups. Except for the control group (fed with same amount of saline solution), other mice received gastric feeding of 250 mg/kg D-galactose every day for 8 weeks. TNFα (10 ng/mL for 24 h) cocultured or noncocultured HUCWJCs (5 × 105) were suspended in 0.1 ml of sterile PBS and injected into tail veins every other week in D-gal + MSC-TNFα and D-gal + MSC groups, respectively, and only 0.1 ml of sterile PBS for control and D-gal groups. The bone mass was detected by qPCR, ELISA, microcomputed tomography (µCT), and hematoxylin-eosin staining. Proliferation, apoptosis, and differentiation of periosteal-derived osteoblasts (POB) were assessed. Transwell assay and scratch healing were performed to detect POB migration and invasion ability. The effect of HUCWJCs on POB signaling pathway expression was evaluated by immunoblotting. Results: The malondialdehyde (MDA) in serum was higher and superoxide dismutase (SOD) was lower in the D-gal group compared to the other groups (p < 0.05). Mice in D-gal group showed significantly decreased bone mass when compared to the control group, while HUCWJCs treatment partially rescued the phenotype, as demonstrated by µCT and histology (p < 0.05). Mechanically, HUCWJCs treatment partially promoted proliferation and migration and decreased apoptosis of POB induced by oxidative stress via activating the mitogen-activated protein kinase (MAPK) signaling pathway. Conclusion: HUCWJCs can prevent the progression of osteoporosis by inhibiting oxidative stress, which may act by regulating osteoblasts fate through the MAPK signaling pathway.


Assuntos
Células-Tronco Mesenquimais , Osteoporose , Animais , Galactose/metabolismo , Galactose/farmacologia , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Estresse Oxidativo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Cordão Umbilical/metabolismo , Microtomografia por Raio-X
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