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1.
Front Pharmacol ; 13: 937581, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091763

RESUMO

In this study, three acidic polysaccharides from different plant parts of Codonopsis pilosula var. Modesta (Nannf.) L. T. Shen were obtained by ion exchange chromatography and gel filtration chromatography, and the yields of these three polysaccharides were different. According to the preliminary experimental results, the antioxidant activities of the polysaccharides from rhizomes and fibrous roots (CLFP-1) were poor, and was thus not studied further. Due to this the structural features of polysaccharides from roots (CLRP-1) and aerial parts (CLSP-1) were the object for this study and were structurally characterized, and their antioxidant activities were evaluated. As revealed by the results, the molecular weight of CLRP-1and CLSP-1 were 15.9 kDa and 26.4 kDa, respectively. The monosaccharide composition of CLRP-1 was Ara, Rha, Fuc, Xyl, Man, Gal, GlcA, GalA in a ratio of 3.8: 8.4: 1.0: 0.8: 2.4: 7.4: 7.5: 2.0: 66.7, and Ara, Rha, Gal, GalA in a ratio of 5.8: 8.9: 8.0: 77.0 in for CLSP-1. The results of structural elucidation indicated that both CLRP-1 and CLSP-1 were pectic polysaccharides, mainly composed of 1, 4-linked galacturonic acid with long homogalacturonan regions. Arabinogalactan type I and arabinogalactan type II were presented as side chains. The antioxidant assay in IPEC-J2 cells showed that both CLRP-1 and CLSP-1 promoted cell viability and antioxidant activity, which significantly increase the level of total antioxidant capacity and the activity of superoxide dismutase, catalase, and decrease the content of malondialdehyde. Moreover, CLRP-1 and CLSP-1 also showed powerful antioxidant abilities in Caenorhabditis elegans and might regulate the nuclear localization of DAF-16 transcription factor, induced antioxidant enzymes activities, and further reduced reactive oxygen species and malondialdehyde contents to increase the antioxidant ability of Caenorhabditis elegans. Thus, these finding suggest that CLRP-1 and CLSP-1 could be used as potential antioxidants.

2.
Plant Physiol Biochem ; 190: 47-61, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36099808

RESUMO

In the context of climate change, the magnitude and frequency of temperature extremes (low and high temperatures) are increasing worldwide. Changes to the lower extremes of temperature, known as cold stress (CS), are one of the recurrent stressors in many parts of the world, severely limiting agricultural production. A series of plant reactions to CS could be generalized into morphological, physiological, and biochemical responses based on commonalities among crop plants. However, the differing originality of crops revealed varying degrees of sensitivity to cold and, therefore, exhibited large differences in these responses among the crops. This review discusses the vegetative and reproductive growth effects of CS and highlights the species-specific aspect of each growth stage whereby the reproductive growth CS appears more detrimental in rice and wheat, with marginal yield losses. To mitigate CS negative effects, crop plants have evolved cold-acclimation mechanisms (with differing capability), characterized by specific protein accumulation, membrane modification, regulation of signaling pathways, osmotic regulation, and induction of endogenous hormones. In addition, we reviewed a comprehensive account of management strategies for regulating tolerance mechanisms of crop plants under CS.

3.
Shanghai Kou Qiang Yi Xue ; 31(2): 211-216, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-36110083

RESUMO

PURPOSE: To study the effect of orthodontic treatment with extraction on root resorption and alveolar bone morphology of the central incisor in adult patients. METHODS: Eleven adult patients receiving orthodontic treatment were enrolled, and asked to take cone-beam CT(CBCT) scanning before and after treatment. Root resorption of the upper and lower central incisors after treatment, changes in alveolar bone thickness and height of alveolar bone were measured and compared. Statistical analysis was performed using SPSS 23.0 software package. RESULTS: The length of the tooth and root was reduced to a certain degree. The change in root length of the maxillary incisor was larger than that of the mandibular incisor. The alveolar bone width of the lingual and palatal neck of the central incisor showed some reduction, and alveolar bone width of the palatal neck of the upper central incisor and the middle lingual side of the mandibular central incisor changed to a certain extent. The width of the alveolar bone in the middle labial side of the mandibular central incisor increased, but the alveolar bone on the lingual and palatal side increased after orthodontic treatment, which was more obvious than that of the maxillary central incisor. CONCLUSIONS: Orthodontic treatment with tooth extraction is accompanied by a certain degree of root resorption of the central incisor and alveolar bone on the lingual and palatal side. However it is also accompanied by an increase in the amount of alveolar bone on the labial side. More fenestration and dehiscence are observed in the mandible.


Assuntos
Incisivo , Reabsorção da Raiz , Adulto , Tomografia Computadorizada de Feixe Cônico , Humanos , Incisivo/diagnóstico por imagem , Mandíbula , Maxila/diagnóstico por imagem
4.
Fitoterapia ; : 105300, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36116614

RESUMO

Four pairs of undescribed chromane and chromene meroterpenoid scalemic mixtures (1a/1b-4a/4b), together with three pairs of known chromane meroterpenoid ones (5a/5b-7a/7b) were isolated from the twigs and leaves of Rhododendron dauricum L. Among them, 1a/1b-3a/3b and 5a/5b-7a/7b were the chromane ones derived from an intramolecular [2 + 2] cyclic addition of their respective chromene precursors, forming a 6/6/6/4 and 6/6/5/4 ring fused scaffold. The absolute configurations of the chiral center at C-15 of 2a/2b were determined by Snatzke's method, and comparing the experimental and calculated electronic circular dichroism (ECD) data. The inhibitory effects of the isolated compounds were tested against lipopolysaccharide (LPS)-induced nitric oxide production in RAW264.7 macrophage cells to evaluate their anti-inflammatory activity. Compounds 4a, 4b and 6a displayed inhibitory effects on nitric oxide (NO) production, and compound 4b exhibited the obvious anti-inflammatory activity, with an IC50 value of 6.91 ±â€¯0.97 µM, by downregulating nuclear factor kappa B (NF-κB) and reducing the expression of inducible nitric oxide synthase (iNOS) in LPS-induced RAW264.7 cells. These results intimated that 4b could be used as a leading compound to develop anti-inflammatory drugs and is worthy of further investigated.

5.
J Pharmacol Exp Ther ; 2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-36116796

RESUMO

Using synaptosomes purified from the brains of two transgenic mouse models overexpressing mutated human tau (TgP301S and Tg4510) and brains of patients with sporadic Alzheimer's disease, we showed that aggregated and hyperphosphorylated tau was both present in purified synaptosomes and released in a calcium- and SNAP25-dependent manner. In all mouse and human synaptosomal preparations, tau release was inhibited by the selective mGlu2/3 receptor agonist LY379268, an effect prevented by the selective mGlu2/3 antagonist LY341495. LY379268 was also able to block pathological tau propagation between primary neurons in an in vitro microfluidic cellular model. These novel results are transformational for our understanding of the molecular mechanisms mediating tau release and propagation at synaptic terminals in Alzheimer's disease and suggest these processes could be inhibited therapeutically by the selective activation of presynaptic G-protein-coupled receptors. Significance Statement Pathological tau release and propagation is a key neuropathological event underlying cognitive decline in Alzheimer's disease patients. In this paper we describe the role of regulated exocytosis, and the SNARE protein SNAP25, in mediating tau release from rodent and human synaptosomes. We also show that a selective mGluR2/3 agonist is highly effective in blocking tau release from synaptosomes and tau propagation between neurons, opening the way to the discovery of novel therapeutic approaches to this devastating disease.

6.
Diabetes Res Clin Pract ; 191: 110079, 2022 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-36099974

RESUMO

AIMS: To evaluate the longitudinal association of remnant cholesterol with the incidence of diabetic nephropathy using a Chinese diabetes cohort. METHODS: We included 4237 individuals with type 2 diabetes during 2013-2014 from Beijing Health Management Cohort. Remnant cholesterol was defined by Martin-Hopkins equation. Diabetic nephropathy was confirmed by urine albumin/creatinine ratio and estimated glomerular filtration rate. We calculated the hazard ratio (HR) and 95% confidence interval (CI) for incident diabetic nephropathy using adjusted Cox proportional hazards regression. RESULTS: The median [IQR] age was 55 [48, 64] years, and 3 256 (76.8 %) were men. During follow-up, 248 (5.9 %) participants developed diabetic nephropathy. One-SD increase of baseline and average cumulative remnant cholesterol were significantly associated with an increased risk of diabetic nephropathy, and the adjusted HRs were 1.208 (95 % CI: 1.098-1.329) and 1.216 (95 % CI: 1.102-1.341), respectively. Individuals in the highest tertile of baseline and average cumulative remnant cholesterol had a 82.3 % and 87.6 % excess risk of diabetic nephropathy, compared with those in the lowest. CONCLUSION: Remnant cholesterol is independently associated with incident diabetic nephropathy in type 2 diabetes.

7.
Infect Drug Resist ; 15: 5401-5409, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119640

RESUMO

Purpose: Acinetobacter baumannii is the most common microorganism in sputum cultures from long-term hospitalized patients and is often the cause of hospital-acquired pneumonia (HAP), which is usually associated with poor prognosis and high mortality. It is sometimes difficult to distinguish between A. baumannii infection and colonization. This study aimed to evaluate factors that differentiate infection from colonization and predict mortality in patients with nosocomial pneumonia caused by A. baumannii. Patients and Methods: The data used in this study were collected in our hospital between January 2018 and December 2020 from patients whose sputum cultures were positive for A. baumannii. Results: A total of 714 patients were included, with 571 in the infection group and 143 in the colonization group. The in-hospital mortality rate in the infection group was 20.5%. Univariate and multivariate logistic regression analyses showed that age, total number of inpatient departments, absolute neutrophil count, and C-reactive protein (CRP) level helped distinguish between infection and colonization. The area under the receiver operating characteristic curve (ROC) of the identification model was 0.694. In the infection group, age, Charlson comorbidity score, neutrophil-to-lymphocyte ratio, blood urea nitrogen/albumin ratio, CRP level, presence of multidrug resistance, and clinical pulmonary infection score (≥6) ratio were associated with in-hospital mortality. The area under the ROC curve for the prediction model was 0.828. The top three drug resistance rates in the infection group were 100% (cefazolin), 98.77% (ceftriaxone), and 71.8% (cefuroxime). Conclusion: The combination of common parameters helps identify A. baumannii respiratory tract infection or colonization. Several novel predictors can be used to predict the risk of death from A. baumannii pneumonia to reduce mortality. The drug resistance of A. baumannii remains high.

8.
Am J Cancer Res ; 12(8): 3729-3744, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119843

RESUMO

Due to the rapid proliferation, cancer cells have increased anabolic biosynthesis, which requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the catalysis of pyruvate carboxylase (PC) and glutaminase (GLS) respectively. In GLS-suppressed cancer cells, the PC-mediated pathway for anaplerosis is crucial to maintain cell growth and proliferation. Here, we investigated the regulatory role and molecular mechanism of N-myc downstream-regulated gene 2 (NDRG2) in PC and PC-mediated anaplerosis. NDRG2 interacted with PC and induced the degradation of PC in glutamine-deprived cells. NDRG2 also inhibited the activity of PC and PC-mediated anaplerosis. As a result, NDRG2 significantly inhibited the malignant growth and proliferation of glioma cells in combination with a glutamine antagonist. In addition, NDRG2 more significantly inhibited the protein level of PC in isocitrate dehydrogenase 1 (R132H)-mutant glioma cells than in wild-type glioma cells. These findings indicate that the molecular mechanism of NDRG2 inhibits PC-mediated anaplerosis and collaborates with glutamine antagonist to inhibit the malignant proliferation of glioma cells, thus providing a theoretical and experimental basis for targeting anaplerosis in glioma therapy.

9.
Asian J Androl ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36124533

RESUMO

Urethral plate (UP)-preserving urethroplasty is simple and has few complications, but it may affect the development of penis in the long term and lead to recurrent chordee. In this study, we used obliquely cut UP to repair hypospadias with mild chordee after degloving (15°-30°) and compared the results with onlay urethroplasty to explore its rationality and feasibility. Between April 2018 and October 2020, 108 hypospadias patients underwent onlay urethroplasty or modified onlay urethroplasty. Clinical data were prospectively collected, and medium-term outcomes were assessed at follow-up. The complications were compared between the two groups. Forty-four patients underwent the modified onlay procedure (Group I), with follow-up time (mean ± standard deviation [s.d.]) of 23.2 ± 4.5 (range: 17-31) months. Sixty-four patients underwent a standard onlay procedure (Group II), with follow-up time (mean ± s.d.) of 39.7 ± 3.9 (range: 32-46) months. There was no difference in age at surgery. The urethral defect length and operative time were longer in Group I. Six cases of fistula and one case each of stricture and diverticulum were reported in Group I. In Group II, 11 cases of fistula and one case each of stricture and diverticulum were reported. The complication rates were 18.2% and 20.3% in Group I and Group II, respectively (P > 0.05). These medium-term follow-up results demonstrate that the modified onlay procedure (oblique cut UP urethroplasty) is a safe and feasible technique for hypospadias with mild chordee after degloving. Compared with standard onlay urethroplasty, this modified procedure is conducive to the complete removal of scar tissue underlying the UP without increasing the risk of surgical complications.

10.
Gen Psychiatr ; 35(4): e100532, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118417

RESUMO

Background: The management of modifiable risk factors and comorbidities may impact the future trajectory of cognitive impairment, but easy-to-implement management methods are lacking. Aims: This study investigated the effects of simple but comprehensive cognitive health management practices on the cognitive function of older adults in the community with normal cognition (NC) and mild cognitive impairment (MCI). Methods: The comprehensive cognitive health management programme included a psychiatric assessment of the cognitive risk factors for those in the intervention groups and individualised recommendations for reducing the risks through self-management supported by regular medical professional follow-up. The intervention groups for this study included 84 elderly participants with NC and 43 elderly participants with MCI who received comprehensive cognitive health management. The control groups included 84 elderly participants with NC and 43 elderly participants with MCI who matched the intervention group's general characteristics and scale scores using the propensity matching score analysis. The Montreal Cognitive Assessment (MoCA) scale and Geriatric Depression Scale (GDS) scores were compared after a 1-year follow-up. Results: For older adults with MCI in the intervention group, MoCA scores were higher at the 1-year follow-up than at baseline (24.07 (3.674) vs 22.21 (3.052), p=0.002). For the MoCA subscales, the intervention group's abstract and delayed memory scores had significantly increased during the 1-year follow-up. Furthermore, in a generalised linear mixed model analysis, the interaction effect of group×follow-up was statistically significant for the MCI group (F=6.61, p=0.011; coefficients=5.83). Conclusions: After the comprehensive cognitive health management intervention, the older adults with MCI in the community showed improvement at the 1-year follow-up. This preliminary study was the first to demonstrate an easy-to-implement strategy for modifying the cognitive risk factors of elderly individuals with MCI in the community, providing new insight into early-stage intervention for dementia.

11.
Ann Transl Med ; 10(16): 851, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36111021

RESUMO

Background: A high seropositive rate of thyroid autoantibodies is often reported in patients with type 1 diabetes mellitus (T1DM), latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus (T2DM). However, the positive rate of thyroid autoantibodies in latent autoimmune diabetes in youth (LADY) patients has not been reported in China. Thus, the purpose of the current study was to clarify the thyroid autoantibody distribution in patients with LADY to provide evidence for the clinical screening of autoimmune thyroid diseases (AITD). Methods: This nationwide, multicenter and cross-sectional study included 1,723 younger patients (<30 years old) and 2,000 older patients (≥30 years old) aged 15 to 79 years. The patients were grouped into younger T1DM (n=281), LADY (n=130), younger T2DM (n=200), older T1DM (n=287), LADA (n=129), and older T2DM (n=200) groups. Autoantibodies against thyroid peroxidase (TPOA) and thyroglobulin (TGA) prevalence were analyzed in each group. Results: The prevalence of TGA or TPOA in LADY patients was similar to that in younger T1DM patients. The seropositive rate of TPOA in LADY patients was higher than that in LADA patients (36.2% vs. 23.3%, respectively; P=0.023); the risk of TPOA was higher in LADY patients than in LADA patients, even after adjusting for sex, glutamic acid decarboxylase (GADA)- and insulinoma-associated-2 (IA-2A)-positivity (OR =1.94, P=0.023). LADY patients with high GADA titers exhibited a higher frequency of thyroid autoantibodies than patients with low GADA titers did (TPOA, P=0.005; TGA, P=0.023; TPOA or TGA, P=0.004). Further analysis showed that only male patients showed a strong association between high GADA titers and thyroid autoantibodies positivity, and the association remained significant after adjustment for age (OR =11.14, P=0.025 for TGA; OR =4.99, P=0.011 for TPOA; OR =5.52, P=0.007 for TPOA or TGA). Conclusions: Routine screening for thyroid autoantibodies is recommended in LADY patients, and special clinical attention should be paid to the thyroid autoantibodies status of male patients of LADY with high GADA titers to identify patients at high risk of developing AITD.

12.
Front Mol Biosci ; 9: 940290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111133

RESUMO

Background: Rotator cuff tears (RCT) is the most common cause of shoulder dysfunction, however, its molecular mechanisms remain unclear. Non-coding RNAs(ncRNAs), such as long ncRNA (lncRNA), microRNA (miRNA) and circular RNA (circRNA), are involved in a variety of diseases, but little is known about their roles in RCT. Therefore, the purpose of this study is to identify dysregulated ncRNAs and understand how they influence RCT. Methods: We performed RNA sequencing and miRNA sequencing on five pairs of torn supraspinatus muscles and matched unharmed subscapularis muscles to identify RNAs dysregulated in RCT patients. To better comprehend the fundamental biological processes, we carried out enrichment analysis of these dysregulated mRNAs or the co-expressed genes of dysregulated ncRNAs. According to the competing endogenous RNA (ceRNA) theory, we finally established ceRNA networks to explore the relationship among dysregulated RNAs in RCT. Results: A total of 151 mRNAs, 38 miRNAs, 20 lncRNAs and 90 circRNAs were differentially expressed between torn supraspinatus muscles and matched unharmed subscapularis muscles, respectively. We found that these dysregulated mRNAs, the target mRNAs of these dysregulated miRNAs or the co-expressed mRNAs of these dysregulated ncRNAs were enriched in muscle structure development, actin-mediated cell contraction and actin binding. Then we constructed and analyzed the ceRNA network and found that the largest module in the ceRNA network was associated with vasculature development. Based on the topological properties of the largest module, we identified several important ncRNAs including hsa_circ_0000722, hsa-miR-129-5p and hsa-miR-30c-5p, whose interacting mRNAs related to muscle diseases, fat and inflammation. Conclusion: This study presented a systematic dissection of the expression profile of mRNAs and ncRNAs in RCT patients and revealed some important ncRNAs which may contribute to the development of RCT. Such results could provide new insights for further research on RCT.

13.
Clin Chem Lab Med ; 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36113983

RESUMO

OBJECTIVES: Hepatocellular carcinoma (HCC) is difficult to diagnose early and progresses rapidly, making it one of the most deadly malignancies worldwide. This study aimed to evaluate whether salivary glycopattern changes combined with machine learning algorithms could help in the accurate diagnosis of HCC. METHODS: Firstly, we detected the alteration of salivary glycopatterns by lectin microarrays in 118 saliva samples. Subsequently, we constructed diagnostic models for hepatic cirrhosis (HC) and HCC using three machine learning algorithms: Least Absolute Shrinkage and Selector Operation, Support Vector Machine (SVM), and Random Forest (RF). Finally, the performance of the diagnostic models was assessed in an independent validation cohort of 85 saliva samples by a series of evaluation metrics, including area under the receiver operator curve (AUC), accuracy, specificity, and sensitivity. RESULTS: We identified alterations in the expression levels of salivary glycopatterns in patients with HC and HCC. The results revealed that the glycopatterns recognized by 22 lectins showed significant differences in the saliva of HC and HCC patients and healthy volunteers. In addition, after Boruta feature selection, the best predictive performance was obtained with the RF algorithm for the construction of models for HC and HCC. The AUCs of the RF-HC model and RF-HCC model in the validation cohort were 0.857 (95% confidence interval [CI]: 0.780-0.935) and 0.886 (95% CI: 0.814-0.957), respectively. CONCLUSIONS: Detecting alterations in salivary protein glycopatterns with lectin microarrays combined with machine learning algorithms could be an effective strategy for diagnosing HCC in the future.

14.
Liver Int ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069651

RESUMO

BACKGROUND AND AIMS: Epidemiological evidence regarding the association of air pollution with the risk of non-alcoholic fatty liver disease (NAFLD) is limited. This study was to examine the associations of long-term exposure to various air pollutants and overall air pollution with risk of incident NAFLD as well as cirrhosis, a major liver-related morbidity for NAFLD. METHODS: Included were 456 687 UK residents. Air pollution data included PM2.5 , PM2.5-10 , PM10 , NO2 and NOx . A weighted air pollution score was also generated from PM10 and NOx . Cox proportional hazard models were employed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We identified 4978 cases of NAFLD and 1575 cases of incident cirrhosis, over a median follow-up of 11.9 years. PM2.5 , PM10 , NO2 and NOx exposures contributed to the excess risk of NAFLD associated with air pollution score; and the corresponding adjusted HRs (95% CI) were 1.10 (1.05, 1.14), 1.14 (1.09, 1.20), 1.19 (1.13, 1.24) and 1.11 (1.07, 1.15), respectively, for each interquartile range increase in the above specific air pollutants. Similar patterns were also indicated for cirrhosis risk. Alcohol consumption was an effect modifier for the association between air pollution score and NAFLD risk, whereas body mass index modified the association for cirrhosis risk. CONCLUSION: Long-term exposure to air pollution was associated with risks of NAFLD and cirrhosis among the UK population.

15.
Nucleic Acids Res ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36099422

RESUMO

Cancer-related epitopes can engage the immune system against tumor cells, thus exploring epitopes derived from non-coding regions is emerging as a fascinating field in cancer immunotherapies. Here, we described a database, IEAtlas (http://bio-bigdata.hrbmu.edu.cn/IEAtlas), which aims to provide and visualize the comprehensive atlas of human leukocyte antigen (HLA)-presented immunogenic epitopes derived from non-coding regions. IEAtlas reanalyzed publicly available mass spectrometry-based HLA immunopeptidome datasets against our integrated benchmarked non-canonical open reading frame information. The current IEAtlas identified 245 870 non-canonical epitopes binding to HLA-I/II allotypes across 15 cancer types and 30 non-cancerous tissues, greatly expanding the cancer immunopeptidome. IEAtlas further evaluates the immunogenicity via several commonly used immunogenic features, including HLA binding affinity, stability and T-cell receptor recognition. In addition, IEAtlas provides the biochemical properties of epitopes as well as the clinical relevance of corresponding genes across major cancer types and normal tissues. Several flexible tools were also developed to aid retrieval and to analyze the epitopes derived from non-coding regions. Overall, IEAtlas will serve as a valuable resource for investigating the immunogenic capacity of non-canonical epitopes and the potential as therapeutic cancer vaccines.

16.
J Cell Mol Med ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36106529

RESUMO

Disturbances or defects in the process of wound repair can disrupt the delicate balance of cells and molecules necessary for complete wound healing, thus leading to chronic wounds or fibrotic scars. Myofibroblasts are one of the most important cells involved in fibrotic scars, and reprogramming provides a potential avenue to increase myofibroblast clearance. Although myofibroblasts have long been recognized as terminally differentiated cells, recent studies have shown that myofibroblasts have the capacity to be reprogrammed into adipocytes. This review intends to summarize the potential of reprogramming myofibroblasts into adipocytes. We will discuss myofibroblast lineage tracing, as well as the known mechanisms underlying adipocyte regeneration from myofibroblasts. In addition, we investigated different changes in myofibroblast gene expression, transcriptional regulators, signalling pathways and epigenetic regulators during skin wound healing. In the future, myofibroblast reprogramming in wound healing will be better understood and appreciated, which may provide new ideas for the treatment of scarless wound healing.

17.
Cell Biosci ; 12(1): 154, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088389

RESUMO

BACKGROUND: Sepsis is a fatal condition commonly caused by Methicillin-resistant Staphylococcus aureus (MRSA) with a high death rate. Macrophages can protect the host from various microbial pathogens by recognizing and eliminating them. Earlier we found that Quaking (QKI), an RNA binding protein (RBP), was involved in differentiation and polarization of macrophages. However, the role of QKI in sepsis caused by pathogenic microbes, specifically MRSA, is unclear. This study aimed to investigate the role of QKI in regulation of host-pathogen interaction in MRSA-induced sepsis and explored the underlying mechanisms. METHODS: Transmission electron microscope and immunofluorescence were used to observe the autophagy level in macrophages. Real-time PCR and western blot were used to analyzed the expression of mRNA and protein respectively. The potential protein interaction was analyzed by iTRAQ mass spectrometry and Immunoprecipitation. RNA fluorescence in situ hybridization, dual-luciferase reporter assay and RNA immunoprecipitation were used to explore the mechanism of QKI regulating mRNA of PI3K-p110ß. RESULTS: The mRNA level of QKI was aberrantly decreased in monocytes and PBMCs of septic patients with the increasing level of plasma procalcitonin (PCT). Then the mice with myeloid specific knockout of QKI was challenged with MRSA or Cecal Ligation and Puncture (CLP). Mice in these two models displayed higher survival rates and lower bacterial loads. Mechanistically, QKI deletion promoted phagocytosis and autophagic degradation of MRSA via activating p110ß (a member of Class IA phosphoinositide 3-kinases) mediated autophagic response. QKI expression in macrophages led to the sequestration of p110ß in mRNA processing (P) bodies and translational repression. Upon infection, the direct interaction of RNF6, a RING-type E3 ligase, mediated QKI ubiquitination degradation and facilitated PI3K-p110ß related autophagic removal of pathogen. The administration of nanoparticles with QKI specific siRNA significantly protected mice from MRSA infection. CONCLUSIONS: This study disclosed the novel function of QKI in the P body mRNA regulation during infection. QKI degradation in macrophage by RNF6 protects mice from MRSA infection via enhancing PI3K-p110ß dependent autophagy. It suggested that QKI may serve as a potential theranostic marker in MRSA-induced sepsis.

18.
Curr Vasc Pharmacol ; 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36045517

RESUMO

BACKGROUND: Atrial arrhythmias are associated with increased risk of stroke and death in the elderly. The risk and predictive factors of recurrent atrial arrhythmias in elderly patients after coronary stenting are not well known. OBJECTIVE: This research sought to investigate the roles of pro- and anti-inflammatory cytokine imbalances in different types of recurrent atrial arrhythmias in elderly patients defined as individuals aged 65 years or older after sirolimus eluting stent (Cordis, Warren, New Jersey) implantation. METHODS: We measured interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17 (IL-17), interleukin-13 (IL-13) and interleukin-37 (IL-37) in elderly patients with recurrent atrial arrhythmias and assessed the impact of pro- and anti-inflammatory cytokine imbalances on recurrent atrial arrhythmias in elderly patients after coronary stenting. RESULTS: Levels of IL-1 ß, IL-6, IL-8, TNF-α were remarkably increased (p<0.001) and IL-10, IL-17, IL-13, and IL-37 were remarkably lowered (p<0.001) in elderly patients with recurrent atrial arrhythmias after coronary stent implantation. Imbalance of pro- and anti-inflammatory cytokines induced recurrent atrial arrhythmias after coronary stenting. Pro- and anti-inflammatory cytokine imbalances may be used to identify elderly patients who have an increased risk of developing recurrent atrial arrhythmias after coronary stenting. CONCLUSION: Imbalance of pro- and anti-inflammatory cytokines was associated with recurrent atrial arrhythmias in elderly patients after coronary stenting. Pro- and anti-inflammatory cytokines may be clinically useful biomarkers for predicting recurrent atrial arrhythmias in elderly patients after coronary stent implantation.

20.
Mol Genet Genomic Med ; : e2042, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069346

RESUMO

BACKGROUND: Distal arthrogryposis (DA) is a group of congenital autosomal-dominant disorders secondary to defects in joint and muscle function, characterized by multiple joint contractures of the hands and feet. DA can be divided into 10 types according to clinical features. DA has been confirmed to be caused by mutations in genes encoding components of the contractile apparatus of skeletal muscle fibers, such as troponin I2 (TNNI2). METHODS: In this study, we report a three-generation DA family belonging to the DA2B type. The clinical characteristics of affected members are genetically stable and consistent, with severe deformities in hands and feet, and two affected adults had short stature. None exhibited facial abnormalities. Blood from three affected and three healthy members were collected for whole-exome sequencing and Sanger sequencing. RESULTS: A missense variant in TNNI2 (NM_003282.4: c.525G>T: p.K175N) was successfully identified, which resulted in the substitution of amino acid at position 175 of TNNI2 from lysine to asparagines. CONCLUSION: The variant c.525G>T in TNNI2 explains the cause of DA in the family. This variant was identified in Chinese people for the first time, and the same variant had been reported in another study but no description of clinical symptoms. Our study comprehensively characterized the c.525G>T variant in TNNI2.

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