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1.
J Cell Sci ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34859815

RESUMO

Apoptosis is an important cellular response to viral infection. In current study, we identified activating molecule in Beclin1-regulated autophagy protein 1 (AMBRA1) as a positive regulator of apoptosis triggered by dsRNA. Depletion of AMBRA1 by gene editing significantly reduced dsRNA-induced apoptosis, which was largely restored by trans-complementation of AMBRA1. Mechanistically, AMBRA1 interacts with mitochondrial antiviral-signaling protein (MAVS), a key mitochondrial adaptor in the apoptosis pathway induced by dsRNA and viral infection. Further Co-IP analysis demonstrated that the mitochondrial localization of MAVS was essential for their interaction. The impact of AMBRA1 on dsRNA-induced apoptosis relied on the presence of MAVS and caspase-8. AMBRA1 was involved in the stabilization of MAVS through preventing its proteasomal degradation induced by dsRNA. Consistently, AMBRA1 upregulated the apoptosis induced by Semliki Forest virus infection. Taken together, our work illustrated a role of AMBRA1 in the virus-induced apoptosis through interacting with and stabilizing MAVS.

2.
Int J Biol Macromol ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34822826

RESUMO

In this work, the effect of Inca peanut seed albumin fraction (IPA) on the rheological, thermal and microstructural properties of native corn starch (NCS) was firstly studied. Compared to the NCS, IPA addition could obviously decrease the transparency of NCS, and the transparency of NCS and NCS-IPA suspensions decreased during the storage time. The textural paraments of NCS pastes with or without IPA reached to the maximum at a concentration of 5%. Steady shear rheological tests showed that all systems were non-Newtonian fluid, and the consistency coefficient (K) values reached to the maximum at 5% IPA concentration. The storage and loss modulus values of NCS-IPA pastes were higher than those of NCS pastes, and curves of loss angle (tan δ) indicated that all pastes were typical weak gel. With the increasing addition of IPA, DSC analysis showed that the thermal properties (To, Tp and Tc) of NCS were significantly changed, whereas, there was no distinct difference in the enthalpy. Microscopy illustrated that there were some wrinkle shrinkage and severe folds on the NCS-IPA granules. Fourier-transform infrared (FT-IR) spectroscopy showed that the hydrogen bonding was primarily interaction forces between IPA and NCS molecules.

3.
Org Biomol Chem ; 19(39): 8487-8491, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34545904

RESUMO

An efficient and practical approach for the synthesis of medicinally important acridones was developed from anthranils and commercially available arylboronic acids by a tandem copper(I)-catalyzed electrophilic amination/Ag(I)-mediated oxidative annulation strategy. This new and straightforward protocol displayed a broad substrate scope (25 examples) and high functional group tolerance. What's more, a possible mechanistic proposal was also presented.

4.
Biochem Biophys Res Commun ; 574: 20-26, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34425282

RESUMO

Retinoblastoma is an intraocular malignant tumor and generally occurred in childhood. Here, we intended to appraise the functional influence of microRNA-142-5p (miR-142-5p) in retinoblastoma. MiR-142-5p was declined, and MYCN was upregulated in retinoblastoma tissues and cells. Moreover, miR-142-5p restricted cell proliferation, migration, invasion, and enhanced cell apoptosis in retinoblastoma cells. MYCN was adversely controlled by miR-142-5p. Besides, the inhibition of miR-142-5p-mediated effects on retinoblastoma progression were blocked by MYCN overexpression in retinoblastoma cells. This research illustrated that miR-142-5p restricted retinoblastoma progression via interacting with MYCN.


Assuntos
MicroRNAs/metabolismo , Proteína Proto-Oncogênica N-Myc/metabolismo , Retinoblastoma/metabolismo , Células Cultivadas , Humanos , MicroRNAs/genética , Proteína Proto-Oncogênica N-Myc/genética , Retinoblastoma/patologia
5.
Neuropsychiatr Dis Treat ; 17: 2451-2463, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335026

RESUMO

Objective: This study aimed to analyze the social-emotional behaviors of Chinese toddlers with cerebral palsy and to identify the risk factors associated with these behaviors. Methods: A total of 300 Chinese toddlers and their parents were recruited in this study. A Chinese version of the Infant-Toddler Social-Emotional Assessment was used to assess the children and basic information and clinical data were collected using an author-designed questionnaire. The patients were also assessed using a coping style questionnaire and the hospital anxiety and depression scale. Multiple logistic regression analysis was performed to identify risk factors. Results: The scores of the externalizing and competence domains for Chinese toddlers with cerebral palsy at different ages were lower compared to healthy children of the same age and gender (p<0.05). For the boys with cerebral palsy aged between 12-17 and 18-23 months, the scores of the internalizing and dysregulation domains were significantly lower compared to the national normal (p<0.01). The effect of perinatal factors on the externalizing and competence domains was more significant compared to other domains, whilst the coping style of the parents significantly affected the dysregulation domain (p=0.001). Multivariate analysis showed that the parental emotional state, education level, coping style and perinatal factors were closely associated with the social-emotional problems of children with cerebral palsy. Conclusion: Children with cerebral palsy are more likely to have behavioral, emotional, and psychiatric issues that are mostly ignored. These children may benefit from early screening and intervention for risk factors to improve rehabilitation and long-term prognosis.

6.
Aging Cell ; 20(8): e13430, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34278704

RESUMO

Dental pulp stem cells (DPSCs) play a vital role in tooth restoration, regeneration, and homeostasis. The link between DPSC senescence and tooth aging has been well-recognized. ROR2 plays an important role in aging-related gene expression. However, the expression and function of ROR2 in DPSC aging remain largely unknown. In this study, we found that ROR2 expression was significantly decreased in aged pulp tissues and DPSCs. The depletion of ROR2 in young DPSCs inhibits their self-renewal capacity, while its overexpression in aged DPSCs restores their self-renewal capacity. Interestingly, we found that sphingomyelin (SM) is involved in the senescence of DPSCs regulated by ROR2. Mechanistically, we confirmed that ROR2 inhibited the phosphorylation of STK4, which promoted the translocation of Forkhead Box O1 (FOXO1) to the nucleus. STK4 inhibition or knockdown of FOXO1 markedly increased the proliferation of DPSCs and upregulated the expression of SMS1, which catalyzed SM biogenesis. Moreover, FOXO1 directly bound to the SMS1 promoter, repressing its transcription. Our findings demonstrated the critical role of the ROR2/STK4-FOXO1/SMS1 axis in the regulation of SM biogenesis and DPSC senescence, providing a novel target for antagonizing tooth aging.

7.
Front Genet ; 12: 688241, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34306029

RESUMO

Background: The low-density lipoprotein receptor-related protein 6 (LRP6) gene is a recently defined gene that is associated with the autosomal-dominant inherited tooth agenesis (TA). In the present study, a family of four generations having TA was recruited and subjected to a series of clinical, genetic, in silico, and in vitro investigations. Methods: After routine clinical evaluation, the proband was subjected to whole-exome sequencing (WES) to detect the diagnostic variant. Next, in silico structural and molecular dynamics (MD) analysis was conducted on the identified novel missense variant for predicting its intramolecular impact. Subsequently, an in vitro study was performed to further explore the effect of this variant on protein maturation and phosphorylation. Results: WES identified a novel variant, designated as LRP6: c.2570G > A (p.R857H), harbored by six members of the concerned family, four of whom exhibited varied TA symptoms. The in silico analysis suggested that this novel variant could probably damage the Wnt bonding function of the LRP6 protein. The experimental study demonstrated that although this novel variant did not affect the LRP6 gene transcription, it caused a impairment in the maturation and phosphorylation of LRP6 protein, suggesting the possibility of the disruption of the Wnt signaling. Conclusion: The present study expanded the mutation spectrum of human TA in the LRP6 gene. The findings of the present study are insightful and conducive to understanding the functional significance of specific LRP6 variants.

8.
Sensors (Basel) ; 21(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202463

RESUMO

A seismic data acquisition system based on wireless network transmission is designed to improve the low-frequency response and low sensitivity of the existing acquisition system. The system comprises of a piezoelectric transducer, a high-resolution data acquisition system, and a wireless communication module. A seismic piezoelectric transducer based on a piezoelectric simply supported beam using PMN-PT is proposed. High sensitivity is obtained by using a new piezoelectric material PMN-PT, and a simply supported beam matching with the PMN-PT wafer is designed, which can provide a good low-frequency response. The data acquisition system includes an electronic circuit for charge conversion, filtering, and amplification, an FPGA, and a 24-bit analog-to-digital converter (ADC). The wireless communication was based on the ZigBee modules and the WiFi modules. The experimental results show that the application of the piezoelectric simply supported beam based on PMN-PT can effectively improve the sensitivity of the piezoelectric accelerometer by more than 190%, compared with the traditional PZT material. At low frequencies, the fidelity of the PMN-PT piezoelectric simply supported beam is better than that of a traditional central compressed model, which is an effective expansion of the bandwidth to the low-frequency region. The charge conversion, filtering, amplification, and digitization of the output signal of the piezoelectric transducer are processed and, finally, are wirelessly transmitted to the monitoring centre, achieving the design of a seismic data acquisition system based on wireless transmission.

9.
World J Clin Cases ; 9(17): 4188-4198, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34141781

RESUMO

BACKGROUND: Cervical cancer is the fourth commonest malignancy in women around the world. It represents the second most commonly diagnosed cancer in South East Asian women, and an important cancer death cause in women of developing nations. Data collected in 2018 revealed 5690000 cervical cancer cases worldwide, 85% of which occurred in developing countries. AIM: To assess self-perceived burden (SPB) and related influencing factors in cervical cancer patients undergoing radiotherapy. METHODS: Patients were prospectively included by convenient sampling at The Fifth Affiliated Hospital of Sun Yat-Sen University, China between March 2018 and March 2019. The survey was completed using a self-designed general information questionnaire, the SPB scale for cancer patients, and the self-care self-efficacy scale, Strategies Used by People to Promote Health, which were delivered to patients with cervical cancer undergoing radiotherapy. Measurement data are expressed as the mean ± SD. Enumeration data are expressed as frequencies or percentages. Caregivers were the spouse, offspring, and other in 46.4, 40.9, and 12.7%, respectively, and the majority were male (59.1%). As for pathological type, 90 and 20 cases had squamous and adenocarcinoma/adenosquamous carcinomas, respectively. Stage IV disease was found in 12 (10.9%) patients. RESULTS: A total of 115 questionnaires were released, and five patients were excluded for too long evaluation time (n = 2) and the inability to confirm the questionnaire contents (n = 3). Finally, a total of 110 questionnaires were collected. They were aged 31-79 years, with the 40-59 age group being most represented (65.4% of all cases). Most patients were married (91.8%) and an overwhelming number had no religion (92.7%). Total SPB score was 43.13 ± 16.65. SPB was associated with the place of residence, monthly family income, payment method, transfer status, the presence of radiotherapy complications, and the presence of pain (P < 0.05). The SPB and self-care self-efficacy were negatively correlated (P < 0.01). In multivariate analysis, self-care self-efficacy, place of residence, monthly family income, payment method, degree of radiation dermatitis, and radiation proctitis were influencing factors of SPB (P < 0.05). CONCLUSION: Patients with cervical cancer undergoing radiotherapy often have SPB. Self-care self-efficacy scale, place of residence, monthly family income, payment method, and radiation dermatitis and proctitis are factors independently influencing SPB.

10.
J Int Med Res ; 49(6): 3000605211026117, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34182818

RESUMO

Diquat is a widely used herbicide that is substituted for paraquat. With paraquat off the market, cases of diquat poisoning have been gradually increasing. The kidney is the most frequently impaired organ in diquat poisoning. Few cases of multiple organ failure caused by diquat have been reported.We herein describe a 30-year-old man who orally ingested about 160 mL of enriched diquat. Despite aggressive treatment, the patient's condition progressed to multiple organ failure and death. The pulmonary lesions in this patient were different from those previously reported. This patient did not die of renal failure but of severe respiratory failure. He exhibited three different stages of pulmonary disease.The lung lesions in this case were unique. We hope that doctors will pay more attention to the lung lesions in patients with diquat poisoning in future and find new treatment methods to save the lives of such patients.


Assuntos
Herbicidas , Insuficiência Respiratória , Adulto , Diquat , Humanos , Masculino , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Paraquat
11.
Artigo em Inglês | MEDLINE | ID: mdl-33936247

RESUMO

Background: Recurrent spontaneous abortion (RSA) is intractable infertility and can be ameliorated with the use of traditional Chinese medicine preparation, the Wenjing decoction. This study aimed to identify the therapeutic mechanism of Wenjing decoction on specific target proteins involved in RSA. Methods: Wenjing decoction contains Wuzhuyu, Danggui, Chuanxiong, Guizhi, Shengjiang, Banxia, Gancao, Ejiao, Mudanpi, Chishao, Dangshen, and Maidong. Using TCMSP and BATMAN databases, we queried for active ingredients and predicted their target proteins by BATMAN. Using the edgeR package, we analyzed the differentially expressed genes (DEGs) in the GSE121950 database between control samples and RSA (n = 3). The interaction between DEGs and the predicted target proteins was identified by the Venn diagram. Using the Cytoscape software and clusterProfiler package, enrichment analysis was conducted for the intersected target proteins. Additionally, the protein-protein interaction (PPI) network and pharmacological network were generated using the Cytoscape software. Results: In total, 31, 2, 7, 7, 5, 13, 93, 11, 29, and 21 active ingredients were identified from Wuzhuyu, Danggui, Chuanxiong, Guizhi, Shengjiang, Banxia, Gancao, Mudanpi, Chishao, and Dangshen, respectively. Additionally, 100 intersected target proteins were revealed by the Venn diagram. Moreover, 98 functional terms and 24 pathways (including C-type lectin receptor signaling pathway, chemokine signaling pathway, leukocyte transendothelial migration, fluid shear stress, and atherosclerosis, and AGE-RAGE signaling pathway in diabetic complications) were enriched. In the PPI network, 10 proteins involved in these five pathways were identified, namely, TNF-α (tumor necrosis factor-α), IL-10 (interleukin-10), TLR4 (Toll-like receptor 4), JUN (Jun proto-oncogene), IL-1B (interleukin-1-beta), CYBB (cytochrome b558 heavy chain gene), PTGS2 (prostaglandin-endoperoxide synthase 2), APOE (apolipoprotein E), SPI1 (salmonella pathogenicity island 1), and MPO (myeloperoxidase) which showed higher degrees. Conclusion: The abovementioned genes and pathways might be involved in the pharmacological activity of Wenjing decoction in RSA.

12.
Ann Transl Med ; 9(8): 622, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33987320

RESUMO

Background: Macular corneal dystrophy (MCD), a rare autosomal recessive disorder, is caused by pathogenic mutations in the carbohydrate sulfotransferase 6 gene (CHST6) and is characterized by bilateral progressive stromal clouding and vision loss. Corneal transplantation is often necessary. This study aimed to identify disease-causing mutations in a Han-Chinese MCD patient. Methods: A 37-year-old female diagnosed with MCD was recruited. The clinical materials were observed and described, and peripheral blood sample was extracted. Whole exome sequencing (WES) and Sanger sequencing were used to reveal genetic defects. The pathogenicity of identified mutations was assessed using in silico analysis. Results: The patient had typical features of MCD, including decreased vision, multiple irregular gray-white corneal opacities, and corneal thinning. A novel nonsense mutation c.544C>T (p.Gln182Ter) and a validated missense mutation c.631C>G (p.Arg211Gly) were identified in the CHST6 gene coding region, both classified as "pathogenic" following the American College of Medical Genetics and Genomics standards and guidelines. Conclusions: This study reports a Han-Chinese MCD patient with a novel nonsense mutation c.544C>T (p.Gln182Ter) and a recurrent missense mutation c.631C>G (p.Arg211Gly), which expand the spectrum of genetic mutations. The results of this study extend genotype-phenotype correlations between the CHST6 gene mutations and MCD clinical findings, contributing to a more accurate diagnosis and the development of potential gene-targeted MCD therapies. Keywords: Carbohydrate sulfotransferase 6 gene (CHST6); compound heterozygous mutations; Han Chinese family; macular corneal dystrophy (MCD).

13.
BMC Infect Dis ; 21(1): 398, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926377

RESUMO

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors. METHOD: Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data. RESULTS: In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as "suspected sHLH positive". Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P < 0.05). Multivariable logistic regression revealed that high ferritin (>1922.58 ng/mL), low platelets (<101 × 109/L) and high triglycerides (>2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19. CONCLUSIONS: HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.


Assuntos
COVID-19/complicações , Linfo-Histiocitose Hemofagocítica/etiologia , Adulto , Idoso , Aspartato Aminotransferases/sangue , COVID-19/epidemiologia , COVID-19/terapia , China/epidemiologia , Comorbidade , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/virologia , Feminino , Ferritinas/sangue , Humanos , Incidência , Contagem de Linfócitos , Linfo-Histiocitose Hemofagocítica/epidemiologia , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Pessoa de Meia-Idade , Mortalidade , Estudos Retrospectivos , Fatores de Risco
14.
Front Cell Infect Microbiol ; 11: 638785, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33842388

RESUMO

Background: Dengue fever is a mosquito-borne febrile illness. Southeast Asia experienced severe dengue outbreaks in 2019, and over 1000 cases had been reported in Jiangxi, a previously known low-epidemic region in China. However, the emergence of a dengue virus epidemic in a non-epidemic region remains unclear. Methods: We enrolled 154 dengue fever patients from four hospitals in Jiangxi, from April 2019 to September 2019. Real-time PCR, NS1 antigen rapid test, and IgM, IgG tests were performed, and 14 samples were outsourced to be sequenced metagenomically. Results: Among the 154 cases, 42 were identified as imported and most of them returned from Cambodia. A total of 113 blood samples were obtained and 106 were identified as DENV-1, two as DENV-2, and five were negative through RT-PCR. All DENV-1 strains sequenced in this study were all classified to one cluster and owned a high similarity with a Cambodia strain isolated in 2019. The evolutionary relationships of amino acid were consistent with that of nucleotide genome result. The sequence-based findings of Jiangxi strains were consistent with epidemiological investigation. Conclusion: Epidemiological analysis demonstrated that the emergence of dengue cases led to autochthonous transmission in several cities in Jiangxi, a low-epidemic region before. This study emphasized future prevention and control of dengue fever in both epidemic and non-epidemic regions.


Assuntos
Vírus da Dengue , Dengue , Epidemias , Animais , China , Dengue/epidemiologia , Surtos de Doenças , Humanos , Filogenia
15.
Front Cell Dev Biol ; 9: 634690, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33748119

RESUMO

Over the past few years, the field of regulated cell death continues to expand and novel mechanisms that orchestrate multiple regulated cell death pathways are being unveiled. Meanwhile, researchers are focused on targeting these regulated pathways which are closely associated with various diseases for diagnosis, treatment, and prognosis. However, the complexity of the mechanisms and the difficulties of distinguishing among various regulated types of cell death make it harder to carry out the work and delay its progression. Here, we provide a systematic guideline for the fundamental detection and distinction of the major regulated cell death pathways following morphological, biochemical, and functional perspectives. Moreover, a comprehensive evaluation of different assay methods is critically reviewed, helping researchers to make a reliable selection from among the cell death assays. Also, we highlight the recent events that have demonstrated some novel regulated cell death processes, including newly reported biomarkers (e.g., non-coding RNA, exosomes, and proteins) and detection techniques.

16.
J Innate Immun ; 13(3): 179-193, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33626545

RESUMO

Expression of host noncoding RNAs and coding mRNAs is significantly altered by viral infection. In the current study, we screened the transcriptional profile of human lung epithelial A549 cells infected with Zika virus (ZIKV) by microarray assay. Seventy-nine long noncoding RNAs (lncRNAs) and 140 mRNAs were differentially expressed (DE). The bioinformatics analysis revealed that the mRNAs adjacent to the DE lncRNAs were closely related to the host responses to viral infection. We selected 7 lncRNAs from the top 50 hits for validation. The quantitative real-time PCR data confirmed that expression of selected lncRNAs was induced by ZIKV infection. Moreover, the expression of 7 lncRNAs was induced by infection of dengue virus, Japanese encephalitis virus, or vesicular stomatitis virus, or by treatment of poly(I:C) and IFN-ß. Furthermore, loss of innate immune adaptor IPS-1 or receptor IFNAR1 resulted in lower induction levels of several lncRNAs by ZIKV. Overexpression of 3 lncRNAs (RPL27-OT1, OASL-IT1, and REC8-OT3) reduced the virus yields of ZIKV. Knockout of OASL-IT1 significantly enhanced ZIKV replication. In OASL-IT1 knockout cells, the levels of interferons (IFNs) and the activation of 3 innate immune signaling pathways triggered by ZIKV were dramatically reduced. Collectively, our work found a positive feedback loop in the IFN system, in which IFNs and OASL-IT1 regulate each other, thereby promoting establishment of antiviral defense.


Assuntos
RNA Longo não Codificante/genética , Mucosa Respiratória/imunologia , Viroses/imunologia , Infecção por Zika virus/imunologia , Zika virus/fisiologia , Células A549 , Biologia Computacional , Retroalimentação Fisiológica , Técnicas de Silenciamento de Genes , Humanos , Imunidade Inata , Interferon beta/metabolismo , Poli I-C/imunologia , Transdução de Sinais/imunologia , Replicação Viral
17.
Ann Anat ; 235: 151672, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33434657

RESUMO

Cellular FLICE-inhibitory protein (c-FLIP), an anti-apoptotic regulator, shows remarkable similarities to caspase-8, which plays a key role in the cleavage of gasdermin D (GSDMD). It has been reported that the oxygen-glucose deprivation/recovery (OGD/R) model and lipopolysaccharide (LPS)/adenosine triphosphate (ATP) treatment could induce inflammation and pyroptosis. However, the regulatory role of c-FLIP in the pyroptotic death of retinal neurons is unclear. In this study, we hypothesized that c-FLIP might regulate retinal neuronal pyroptosis by GSDMD cleavage. To investigate this hypothesis, we induced retinal neuronal damage in vitro (OGD/R and LPS/ATP) and in vivo (acute high intraocular pressure [aHIOP]). Our results demonstrated that the three injuries triggered the up-regulation of pyroptosis-related proteins, and c-FLIP could cleave GSDMD to generate a functional N-terminal (NT) domain of GSDMD, causing retinal neuronal pyroptosis. In addition, c-FLIP knockdown in vivo ameliorated the already established visual impairment mediated by acute IOP elevation. Taken together, these findings revealed that decreased c-FLIP expression protected against pyroptotic death of retinal neurons possibly by inhibiting GSDMD-NT generation. Therefore, c-FLIP might provide new insights into the pathogenesis of pyroptosis-related diseases and help to elucidate new therapeutic targets and potential treatment strategies.


Assuntos
Piroptose , Neurônios Retinianos , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD , Glucose , Oxigênio , Proteínas de Ligação a Fosfato
18.
Int J Biol Macromol ; 166: 108-116, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33098897

RESUMO

In this work, the physicochemical properties of native waxy rice starch (WRS) and alcohol-alkali-treated waxy rice starch (AAT-WRS) were studied in the presence of sucrose. The results indicated that the addition of sucrose improved the transparency and freeze-thaw stability of WRS pastes and AAT-WRS pastes. Differential scanning calorimetry showed that the gelatinization temperatures of WRS increased with increased sucrose concentration, but the gelatinization enthalpy increased at low concentration of sucrose and decreased at high concentration. Rheological measurements indicated that sucrose addition had no significant effect on the pseudoplastic shear-thinning behaviors of WRS pastes and AAT-WRS pastes, but changed the apparent viscosity. Dynamic moduli (G' and G″) values of WRS pastes and AAT-WRS pastes with or without sucrose showed frequency dependency and sucrose addition dependency. The elastic behavior was dominant over viscous in the WRS-sucrose mixed pastes, while the AAT-WRS-sucrose mixed pastes was the opposite. The textural paraments of WRS and AAT-WRS before or after retrogradation increased with the increasing concentration of sucrose. These results suggested that sucrose potentially changed the physicochemical properties of WRS and AAT-WRS.


Assuntos
Amido/análogos & derivados , Sacarose/química , Viscosidade , Álcoois/química , Álcalis/química , Géis/química , Oryza/química , Transição de Fase , Reologia
19.
Eur J Clin Microbiol Infect Dis ; 40(1): 103-110, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32797320

RESUMO

This study analyzed the epidemiological and clinical features of dengue fever in Zhangshu, Jiangxi Province, in 2019 and provided evidence for the diagnosis, treatment, prevention, and control of dengue fever. A total of 718 dengue fever patients in Zhangshu in 2019 were involved. ELISA and qRT-PCR were used for pathogenic detection of dengue virus. Multiple adjuvant therapies were applied, and the condition of patients after treatment was examined. Patients were between the ages of 0.75 and 92 years old, and all of them had a fever. A total of 519 cases had fatigue, and 413 cases had generalized myalgia and bone ache; 356 cases had dry mouth, 289 cases had bitter taste, and 167 cases felt dry and bitter taste; 279 cases had rash, and 93 cases had pruritus; 587 cases had decreased leukocyte, among which, 7 cases had leukocyte lower than 1 × 10 [9]/L; 380 cases had a low platelet count, and the platelet count of 29 cases was lower than 50 × 10 [9]/L; 488 cases had increased aspartic transaminase, and 460 cases had increased alanine aminotransferase; 5 cases had a severe disease. It proved that the majority of dengue fever sufferers were adults, with the main clinical features being fever and rash and the chief injured organs being the blood system, liver, heart, and gastrointestinal tract. Besides, over 40% of patients had dry and bitter taste, and 12 cases had alopecia after discharge. It indicates that the incidence of dengue fever in Zhangshu is closely related to the sudden population flow and imported cases.


Assuntos
Dengue/epidemiologia , Surtos de Doenças , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Dengue/sangue , Dengue/etiologia , Vírus da Dengue/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores Sexuais , Adulto Jovem
20.
Cancer Med ; 10(8): 2787-2801, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33314711

RESUMO

The exostosin (EXT) protein family is involved in diverse human diseases. However, the expression and prognostic value of EXT genes in human lung squamous cell carcinoma (LUSC) is not well understood. In this study, we analyzed the association between expression of EXT1 and EXT2 genes and survival in patients with LUSC using bioinformatics resources such as Oncomine and The Cancer Genome Atlas (TCGA) databases, the Gene Expression Profiling Interactive Analysis (GEPIA) server and Kaplan-Meier plotter. Furthermore, regulatory microRNAs (miRNAs) were predicted for EXT1 and used to establish a potential miRNA-messenger RNA (mRNA) regulation network for LUSC using the ENCORI platform. We observed that EXT1 and EXT2 expression levels were higher in LUSC than those in normal tissues. However, only EXT1 expression was significantly associated with poor overall survival (OS) in LUSC patients. Functional annotation enrichment analysis showed that genes co-expressed with the EXT1 gene were enriched in biological processes such as cell adhesion and migration, and KEGG pathways such as extracellular matrix receptor interactions, complement and coagulation cascades, and cell death. Furthermore, three miRNAs, hsa-mir-190a-5p, hsa-mir-195-5p, and hsa-mir-490-3p, were identified to be potentially involved in the regulation of EXT1. In summary, we identified EXT1 expression as a novel potential prognostic marker for human LUSC and the regulatory miRNAs that could possibly contribute to the prognosis of the disease.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , N-Acetilglucosaminiltransferases/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/mortalidade , Linhagem Celular Tumoral , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , MicroRNAs/genética , N-Acetilglucosaminiltransferases/metabolismo , Prognóstico , Mapas de Interação de Proteínas/genética
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