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1.
J Cell Sci ; 136(15)2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37461827

RESUMO

Protein palmitoylation is a post-translational lipid modification of proteins. Accumulating evidence reveals that palmitoylation functions as a sorting signal to direct proteins to destinations; however, the sorting mechanism remains largely unknown. Here, we show that ARF6 plays a general role in targeting palmitoylated proteins from the Golgi to the plasma membrane (PM). Through shRNA screening, we identified ARF6 as the key small GTPase in targeting CD36, a palmitoylated protein, from the Golgi to the PM. We found that the N-terminal myristoylation of ARF6 is required for its binding with palmitoylated CD36, and the GTP-bound form of ARF6 facilitates the delivery of CD36 to the PM. Analysis of stable isotope labeling by amino acids in cell culture revealed that ARF6 might facilitate the sorting of 359 of the 531 palmitoylated PM proteins, indicating a general role of ARF6. Our study has thus identified a sorting mechanism for targeting palmitoylated proteins from the Golgi to the PM.


Assuntos
Complexo de Golgi , Proteínas de Membrana , Membrana Celular/metabolismo , Complexo de Golgi/metabolismo , Proteínas de Membrana/metabolismo , Transporte Proteico
2.
Nucleic Acids Res ; 51(11): e65, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37194709

RESUMO

Despite the need in various applications, accurate quantification of nucleic acids still remains a challenge. The widely-used qPCR has reduced accuracy at ultralow template concentration and is susceptible to nonspecific amplifications. The more recently developed dPCR is costly and cannot handle high-concentration samples. We combine the strengths of qPCR and dPCR by performing PCR in silicon-based microfluidic chips and demonstrate high quantification accuracy in a large concentration range. Importantly, at low template concentration, we observe on-site PCR (osPCR), where only certain sites of the channel show amplification. The sites have almost identical ct values, showing osPCR is a quasi-single molecule phenomenon. Using osPCR, we can measure both the ct values and the absolute concentration of templates in the same reaction. Additionally, osPCR enables identification of each template molecule, allowing removal of nonspecific amplification during quantification and greatly improving quantification accuracy. We develop sectioning algorithm that improves the signal amplitude and demonstrate improved detection of COVID in patient samples.


Assuntos
Teste para COVID-19 , Reação em Cadeia da Polimerase , Humanos , COVID-19 , DNA/genética , Microfluídica
3.
Nanotechnology ; 35(23)2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38422541

RESUMO

Structural and electrochemical properties of bismuth ferrite nanostructures produced by pulsed laser deposition with various morphologies are reported. The nanostructures are also explored as electrode materials for high-performance supercapacitors. Scanning electron microscopy images revealed that various bismuth ferrite morphologies were produced by varying the background pressure (10-6, 0.01, 0.10, 0.25, 0.50, 1.0, 2.0 and 4.0 Torr) in the deposition chamber and submitting them to a thermal treatment after deposition at 500◦C. The as-deposited bismuth ferrite nanostructures range from very compact thin-film (10-6, 0.01, 0.10 Torr), to clustered nanoparticles (0.25, 0.50, 1.0 Torr), to very dispersed arrangement of nanoparticles (2.0 and 4.0 Torr). The electrochemical characteristic of the electrodes was investigated through cyclic voltammetry process. The increase in the specific surface area of the nanostructures as background pressure in the chamber increases does not lead to an increase in interfacial capacitance. This is likely due to the wakening of electrical contact between nanoparticles with increasing porosity of the nanostructures. The thermal treatment increased the contact between nanoparticles, which caused an increase in the interfacial capacitance of the nanostructure deposited under high background pressure in the chamber.

4.
BMC Infect Dis ; 24(1): 414, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641804

RESUMO

BACKGROUND: Lobar pneumonia caused by Mycoplasma pneumoniae is a relatively difficult-to-treat pneumonia in children. The time of radiographic resolution after treatment is variable, a long recovery time can result in several negative effects, and it has attracted our attention. Therefore, exploring factors associated with delayed radiographic resolution will help to identify these children at an early stage and prepare for early intervention. METHODS: The data of 339 children with lobar pneumonia caused by Mycoplasma pneumoniae were collected from the Department of Pediatrics of Fu Yang People's Hospital, China from January 2021 to June 2022. After discharge, the children were regularly followed up in the outpatient department and on the WeChat platform for > 8 weeks. According to whether pulmonary imaging (chest radiography or plain chest computed tomography) returned to normal within 8 weeks, the children were divided into the delayed recovery group (DRG) (n = 69) and the normal recovery group (NRG) (n = 270). The children's general information, laboratory examination findings, bronchoscopy results, and imaging findings were retrospectively analyzed. Single-factor analysis was performed to identify the risk factors for delayed radiographic resolution of lobar pneumonia caused by Mycoplasma pneumoniae, and the factors with statistically significant differences underwent multiple-factor logistic regression analysis. Receiver operating characteristic (ROC) analysis was then performed to calculate the cutoff value of early predictive indicators of delayed radiographic resolution. RESULTS: Single-factor analysis showed that the following were significantly greater in the DRG than NRG: total fever duration, the hospitalization time, C-reactive protein (CRP) level, lactate dehydrogenase (LDH) level, D-dimer level, pulmonary lesions involving two or more lobes, a large amount of pleural effusion, the time to interventional bronchoscopy, and mucus plugs formation. Multivariate logistic regression analysis showed that the hospitalization time, CRP level, LDH level, pulmonary lesions involving two or more lobes, and a large amount of pleural effusion were independent risk factors for delayed radiographic resolution of lobar pneumonia caused by Mycoplasma pneumoniae. The cutoff values on the receiver operating characteristic curve were a hospitalization time of ≥ 10.5 days, CRP level of ≥ 25.92 mg/L, and LDH level of ≥ 378 U/L. CONCLUSION: If patients with lobar pneumonia caused by Mycoplasma pneumoniae have a hospitalization time of ≥ 10.5 days, CRP level of ≥ 25.92 mg/L, and LDH level ≥ 378 U/L, the time of radiographic resolution is highly likely to exceed 8 weeks. Pediatricians must maintain a high level of vigilance for these factors, control the infection as early as possible, strengthen airway management, and follow up closely to avoid complications and sequelae of Mycoplasma pneumoniae pneumonia.


Assuntos
Derrame Pleural , Pneumonia por Mycoplasma , Pneumonia Pneumocócica , Criança , Humanos , Mycoplasma pneumoniae , Estudos Retrospectivos , Pneumonia por Mycoplasma/complicações , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pneumonia Pneumocócica/patologia , Derrame Pleural/complicações
5.
Environ Res ; 252(Pt 2): 118922, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38614202

RESUMO

Grazing is the most extensive land use in grassland worldwide, wherein the soil microbiome is known to support multiple ecosystem functions. Yet, the experimental impact of livestock grazing and dung deposits on the soil microbiome in degraded grassland remains poorly understood. We examined the effects of sheep dung depositions on the bacterial and fungal microbiome of two grasslands: non-degraded and degraded (long-term overgrazing) in northern China. Specifically, sheep dung was experimentally added to the soil and its effects on the soil microbial community were determined 3 months later (corresponding to livestock excreta deposited throughout the entire growing season of grassland, June to September). Our results showed that sheep dung additions showed negative effects on the soil microbiome of already degraded grassland, while with a diminished impact on the non-degraded grassland. In particular, dung deposition decreased soil microbial Shannon index, notably significantly reducing fungal diversity in degraded grassland. Moreover, sheep dung deposition modifies soil bacterial community structure and diminishes bacterial community network complexity. The alteration of soil pH caused by sheep dung deposition partially explains the decline in microbial diversity in degraded grassland. However, sheep dung did not alter the relative abundance and community composition of bacterial and fungal dominant phyla either in the non-degraded or in the degraded grassland. In conclusion, the short-term deposition of sheep dung exerted a detrimental influence on the microbial community in degraded grassland soil. It contributes new experimental evidence regarding the adverse effects of livestock grazing, particularly through dung deposition, on the soil microbiome in degraded grassland. This knowledge is crucial for guiding managers in conserving the soil microbiome in grazed grasslands.


Assuntos
Fezes , Pradaria , Microbiota , Microbiologia do Solo , Animais , Ovinos/microbiologia , Fezes/microbiologia , China , Fungos , Bactérias/classificação , Bactérias/metabolismo , Solo/química
6.
Blood ; 138(13): 1182-1193, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-33945603

RESUMO

Events mediated by the P-selectin/PSGL-1 pathway play a critical role in the initiation and propagation of venous thrombosis by facilitating the accumulation of leukocytes and platelets within the growing thrombus. Activated platelets and endothelium express P-selectin, which binds P-selectin glycoprotein ligand-1 (PSGL-1) that is expressed on the surface of all leukocytes. We developed a pegylated glycomimetic of the N terminus of PSGL-1, PEG40-GSnP-6 (P-G6), which proved to be a highly potent P-selectin inhibitor with a favorable pharmacokinetic profile for clinical translation. P-G6 inhibits human and mouse platelet-monocyte and platelet-neutrophil aggregation in vitro and blocks microcirculatory platelet-leukocyte interactions in vivo. Administration of P-G6 reduces thrombus formation in a nonocclusive model of deep vein thrombosis with a commensurate reduction in leukocyte accumulation, but without disruption of hemostasis. P-G6 potently inhibits the P-selectin/PSGL-1 pathway and represents a promising drug candidate for the prevention of venous thrombosis without increased bleeding risk.


Assuntos
Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/uso terapêutico , Selectina-P/antagonistas & inibidores , Trombose/tratamento farmacológico , Animais , Hemostasia/efeitos dos fármacos , Humanos , Glicoproteínas de Membrana/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Microcirculação/efeitos dos fármacos , Selectina-P/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polietilenoglicóis/uso terapêutico , Trombose/metabolismo
7.
Virol J ; 20(1): 4, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624458

RESUMO

BACKGROUND: Under the pressure of non-pharmaceutical interventions (NPIs) targeting severe acute respiratory syndrome coronavirus 2, the prevalence of human adenovirus (HAdV) was monitored before and after NPIs launched on Jan 24, 2020 in pediatric patients in Beijing, China. METHODS: Respiratory samples collected from children hospitalized with acute respiratory infections from Jan 2015 to Dec 2021 were screened by direct immunofluorescence test or capillary electrophoresis-based multiplex PCR assay. The hexon, penton base, and fiber genes were amplified from HAdV positive specimens, then sequenced. For HAdV typing, phylogenetic trees were built by MEGA X. Then clinical data of HAdV positive cases were collected. All data were evaluated using SPSS Statistics 22.0 software. RESULTS: A total of 16,097 children were enrolled and 466 (2.89%, 466/16,097) were HAdV-positive. The positive rates of HAdV varied, ranging from 4.39% (151/3,438) in 2018 to1.25% (26/2,081) in 2021, dropped from 3.19% (428/13,408) to 1.41% (38/2,689) from before to after NPIs launched (P < 0.001). There were 350 cases typed into nine types of species B, C, or E and 34 recorded as undetermined. Among them, HAdV-B3 (51.56%, 198/384) was the most prevalent types from 2015 to 2017, and HAdV-B7 (29.17%, 112/384) co-circulated with HAdV-B3 from 2018 to 2019. After NPIs launched, HAdV-B3 and B7 decreased sharply with HAdV-B7 undetected in 2021, while HAdV-C1 became the dominant one and the undetermined were more. CONCLUSIONS: The endemic pattern of HAdV changed in Beijing because of the NPIs launched for COVID-19. Especially, the dominant types changed from HAdV-B to HAdV-C.


Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , COVID-19 , Infecções Respiratórias , Criança , Humanos , Pequim/epidemiologia , Adenovírus Humanos/genética , Filogenia , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/prevenção & controle , COVID-19/epidemiologia , COVID-19/prevenção & controle , China/epidemiologia , Infecções Respiratórias/epidemiologia , Reação em Cadeia da Polimerase Multiplex
8.
Org Biomol Chem ; 21(35): 7129-7135, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37602718

RESUMO

We report a palladium-catalyzed Heck-carbonylation of alkene-tethered carbamoyl chlorides by utilizing aryl formates as convenient CO surrogates. One C-O and two C-C bonds are constructed to give diversiform esterified oxindoles/γ-lactams bearing an all-carbon quaternary stereocenter under gas-free conditions. This transformation features a wide substrate scope and good functional group tolerance and can be easily applied to late-stage functionalization.

9.
Arch Virol ; 168(10): 257, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37755543

RESUMO

Our previous surveillance revealed that t203-like G9 (tentatively designated subtype G9-VI) rotaviruses re-emerged in 2010 in Beijing and rapidly prevailed over the G9-III subtype (the most common G9 subtype globally) and previously predominant G genotypes over the following two years. G9-VI belongs to the VP7 evolutionary lineage VI, which includes unusual and sporadic human rotaviruses from China (t203) and Japan. To obtain insight into the epidemiology, evolution, and transmission advantages of G9-VI rotavirus, we performed follow-up surveillance (2014-2017) and whole-genome analysis of 12 representative G9 strains. The results showed that the G9 genotype was predominant (77.4%), with a marked increase in prevalence (previously 43.5%). Within the G9 genotype, subtype G9-VI accounted for the majority (98.3%) of cases. The most prevalent P-genotype was P[8] (93.7%), within which subtype P[8]b was rare (0.7%). Phylogenetically, the G9-VI subtype strains in this study clustered closely with contemporary emerging human rotaviruses from many other countries in VP7 lineage VI, indicating that this subtype is capable of spreading globally. These currently emerging G9-VI rotaviruses formed a distinct monophyletic subcluster when compared to early G9-VI rotaviruses. Furthermore, four specific amino acid substitutions and synonymous codon substitutions were observed in the VP7 genes between the current G9-VI and globally common G9-III rotaviruses. The remaining nine genes of all of the analyzed representative G9 strains, whether G9-VI or G9-III, combined with the P[8]a, P[8]b, or P[6] genotype and exhibited the same Wa-like backbone constellation.

10.
Eur J Pediatr ; 182(12): 5385-5397, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37740042

RESUMO

The emerging field of nutritional psychiatry offers proof that diet quality can be changed to reduce one's risk of developing mental illness. What you eat has a big impact on teenage mental health, and the quality and frequency of breakfast, as well as the different food groups, can affect adolescent mental health. In this study, regression models were employed to analyze four indicators (self-rated health, body satisfaction, life satisfaction, and eight symptoms) of mental health problems as well as demographic factors (gender, age, body mass index, affluence class, physical activity), with forest plots displaying the regression connections. This study, a descriptive cross-sectional survey of 3480 adolescents aged 11 to 15 years, chosen data from the 2018 Greek Health Behaviour in School-aged Children (HBSC) International Study for secondary analysis. The data revealed that high levels of four indicators of mental health (self-rated health, body satisfaction, life satisfaction, and eight symptoms) were significantly related to breakfast quality, total dietary patterns. Students reporting poor total food quality, for example, were more predictive of self-assessment when unhealthy (2.286 95% CI 1.851-2.824), and the largest connections with eating a "bad" breakfast were discovered when the eight symptoms of mental status were the worst (- 0.869 95% CI: - 1.300, - 0.439); physical activity may enhance the positive relationship of diet quality on mental health, while obesity weakens this positive relationship; and age patterns varied by gender, with girls and older individuals showing a higher risk of diet quality and mental health.   Conclusions: The findings revealed that each of the four indices of general mental health was correlated with teenage breakfast and overall diet quality. Physical activity and weight were shown to be moderating factors, and obesity had the biggest impact on psychological risk. Gender, age, and family economic inequality were potential explanations for the rise in psychological symptoms. Researchers are urged to focus more on nutritional psychiatry research and look into psychological perception disparities in the future. What is Known: • There is a potential correlation between adolescent dietary patterns or quality and mental health. • Factors such as age, gender, socio-economic status, body weight and physical activity all have an impact on diet and mental health outcomes. What is New: • There have been no studies of the ability to simultaneously predict breakfast quality and overall diet quality for broadly defined mental health complaints [positive (life satisfaction), neutral (body satisfaction, self-rated health) and negative (eight symptoms: depressed mood, irritability, nervousness, difficulty sleeping, dizziness, headache, stomachache and backache)]. • Differences in overall diet quality trends between demographic subgroups remain unclear.


Assuntos
Desjejum , Saúde Mental , Criança , Feminino , Humanos , Adolescente , Estudos Transversais , Grécia/epidemiologia , Dieta , Obesidade , Comportamento Alimentar
11.
Int J Mol Sci ; 24(11)2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37298121

RESUMO

Spinel ferrites are versatile, low-cost, and abundant metal oxides with remarkable electronic and magnetic properties, which find several applications. Among them, they have been considered part of the next generation of electrochemical energy storage materials due to their variable oxidation states, low environmental toxicity, and possible synthesis through simple green chemical processing. However, most traditional procedures lead to the formation of poorly controlled materials (in terms of size, shape, composition, and/or crystalline structure). Thus, we report herein a cellulose nanofibers-mediated green procedure to prepare controlled highly porous nanocorals comprised of spinel Zn-ferrites. Then, they presented remarkable applications as electrodes in supercapacitors, which were thoroughly and critically discussed. The spinel Zn-ferrites nanocorals supercapacitor showed a much higher maximum specific capacitance (2031.81 F g-1 at a current density of 1 A g-1) than Fe2O3 and ZnO counterparts prepared by a similar approach (189.74 and 24.39 F g-1 at a current density of 1 A g-1). Its cyclic stability was also scrutinized via galvanostatic charging/discharging and electrochemical impedance spectroscopy, indicating excellent long-term stability. In addition, we manufactured an asymmetric supercapacitor device, which offered a high energy density value of 18.1 Wh kg-1 at a power density of 2609.2 W kg-1 (at 1 A g-1 in 2.0 mol L-1 KOH electrolyte). Based on our findings, we believe that higher performances observed for spinel Zn-ferrites nanocorals could be explained by their unique crystal structure and electronic configuration based on crystal field stabilization energy, which provides an electrostatic repulsion between the d electrons and the p orbitals of the surrounding oxygen anions, creating a level of energy that determines their final supercapacitance then evidenced, which is a very interesting property that could be explored for the production of clean energy storage devices.


Assuntos
Nanofibras , Celulose , Zinco
12.
Molecules ; 28(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38138553

RESUMO

With the development of social economy, using lithium-ion batteries in energy storage in industries such as large-scale electrochemical energy storage systems will cause lithium resources to no longer meet demand. As such, sodium ion batteries have become one of the effective alternatives to LIBs. Many attempts have been carried out by researchers to achieve this, among which F-doping is widely used to enhance the electrochemical performance of SIBs. In this paper, we reviewed several types of transition metal oxide cathode materials, and found their electrochemical properties were significantly improved by F-doping. Moreover, the modification mechanism of F-doping has also been summed up. Therefore, the application and commercialization of SIBs in the future is summarized in the ending of the review.

13.
Molecules ; 28(17)2023 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-37687103

RESUMO

Developing efficient and sensitive MOF-based luminescence sensors for bioactive molecule detection is of great significance and remains a challenge. Benefiting from favorable chemical and thermal stability, as well as excellent luminescence performance, a porous Zn(II)Ho(III) heterometallic-organic framework (ZnHoMOF) was selected here as a bifunctional luminescence sensor for the early diagnosis of a toluene exposure biomarker of hippuric acid (HA) through "turn-on" luminescence enhancing response and the daily monitoring of NFT/NFZ antibiotics through "turn-off" quenching effects in aqueous media with high sensitivity, acceptable selectivity, good anti-interference, exceptional recyclability performance, and low detection limits (LODs) of 0.7 ppm for HA, 0.04 ppm for NFT, and 0.05 ppm for NFZ. Moreover, the developed sensor was employed to quantify HA in diluted urine samples and NFT/NFZ in natural river water with satisfactory results. In addition, the sensing mechanisms of ZnHoMOF as a dual-response chemosensor in efficient detection of HA and NFT/NFZ antibiotics were conducted from the view of photo-induced electron transfer (PET), as well as inner filter effects (IFEs), with the help of time-dependent density functional theory (TD-DFT) and spectral overlap experiments.


Assuntos
Antibacterianos , Nitrofuranos , Luminescência , Biomarcadores
14.
J Cell Mol Med ; 26(18): 4837-4846, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36000536

RESUMO

SERPINA5 belongs to the serine protease inhibitor superfamily and has been reported to be lowly expressed in a variety of malignancies. However, few report of SERPINA5 in gastric cancer has been found. The purpose of this study was to determine the role of SERPINA5 in GC and to investigate potential tumorigenic mechanisms. We performed qPCR to determine the level of SERPINA5 expression in GC. We used public databases to evaluate whether SERPINA5 could be utilized to predict overall survival and disease-free survival in GC patients. We also knocked down the expression of SERPINA5 and evaluated its effect on cell proliferation and migration. Furthermore, we explored the signal pathways and regulatory mechanisms related to SERPINA5 functions. According to our findings, SERPINA5 was shown to exhibit high expression in GC. Notably, SERPINA5 was prognostic in GC with high expression being unfavourable. SERPINA5 was further observed to promote GC tumorigenesis by modulating GC cell proliferation ability. Mechanically, SERPINA5 could inhibit CBL to regulate the PI3K/AKT/mTOR signalling pathway, thereby promoting GC carcinogenesis progression. These results highlight the important role of SERPINA5 in GC cell proliferation and suggest that SERPINA5 could be a novel target for GC treatment and a predictor for GC prognosis.


Assuntos
Neoplasias Gástricas , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Inibidor da Proteína C/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Neoplasias Gástricas/patologia , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
15.
J Cell Mol Med ; 26(2): 354-363, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34894202

RESUMO

Stress is one of the leading causes of male infertility, but its exact function in testosterone synthesis has scarcely been reported. We found that adult male rats show a decrease in bodyweight, genital index and serum testosterone level after continual chronic stress for 21 days. Two-dimensional gel electrophoresis (2-DE) and MALDI-TOF-MS analysis identified 10 differentially expressed proteins in stressed rats compared with controls. A strong protein interaction network was found to be centred on Atp5a1 among these proteins. Atp5a1 expression significantly decreased in Leydig cells after chronic stress. Transfection of Atp5a1 siRNAs decreased StAR, CYP11A1, and 17ß-HSD expression by damaging the structure of mitochondria in TM3 cells. This study confirmed that chronic stress plays an important role in testosterone synthesis by regulating Atp5a1 expression in Leydig cells.


Assuntos
Células Intersticiais do Testículo , Testosterona , Animais , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Células Intersticiais do Testículo/metabolismo , Masculino , Mitocôndrias/metabolismo , ATPases Mitocondriais Próton-Translocadoras , Ratos
16.
Lab Invest ; 102(4): 411-421, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34775495

RESUMO

Acute lymphoblastic leukemia (ALL) is a common malignancy in children. In this study, we aimed to explore putative mechanisms of microRNA-155-5p (miR-155-5p) involvement in childhood ALL (cALL) via interactions with casitas B-lineage lymphoma (CBL), interferon regulatory factor 4 (IRF4), and cyclin-dependent kinase 6 (CDK6). Bioinformatic analysis was performed initially to identify differentially expressed genes in cALL. The expression levels of miR-155-5p, CBL, IRF4, and CDK6 in peripheral blood lymphocytes from clinical ALL samples were determined using RT-qPCR and Western blot assays. A dual-luciferase reporter gene assay was used to ascertain a possible targeting relationship between miR-155-5p and CBL, CCK-8 assay and flow cytometry were used to measure cell activity and apoptosis of ALL cells. Co-IP was performed to investigate the interaction between CBL and IRF4 and the ubiquitination level of IRF4. Furthermore, in vivo validation was performed inducing xenograft tumor models with ALL cells in nude mice. As indicated by bioinformatic analysis, miR-155-5p and CDK6 were upregulated and CBL was downregulated in ALL. miR-155-5p was found to target CBL to inhibit CBL expression. miR-155-5p promoted the proliferation of ALL cells and inhibited their apoptosis by inhibiting the expression of CBL, which otherwise degraded IRF4 protein through ubiquitination, leading to inhibited CDK6 expression. Collectively, the results show that miR-155-5p can promote the development of cALL via the regulation on CBL-mediated IRF4/CDK6 axis.


Assuntos
MicroRNAs , Leucemia-Linfoma Linfoblástico de Células Precursoras , Animais , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Quinase 6 Dependente de Ciclina/genética , Quinase 6 Dependente de Ciclina/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores Reguladores de Interferon/genética , Camundongos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
17.
Biochem Biophys Res Commun ; 606: 68-74, 2022 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-35339754

RESUMO

Cyclophosphamide is an alkylating agent used to treat a variety of cancers, including leukemia. Here, we show a previously unrecognized role of cyclophosphamide in triggering the protein degradation of glutathione peroxidase 4 (GPX4), a phospholipid hydroperoxidase that protects cells from oxidative damage. Mechanistically, we found that the ubiquitin-proteasome system, but not autophagy, mediates cyclophosphamide-induced degradation of GPX4 in human leukemia cell lines. Surprisingly, cyclophosphamide-induced degradation of GPX4 leads to caspase-independent parthanatos, but not lipid peroxidation-mediated ferroptosis, through the nuclear translocation of apoptosis-inducing factor mitochondria-associated 1 (AIFM1). Consequently, the overexpression of GPX4 or the knockdown of AIFM1 limits the anticancer activity of cyclophosphamide in vitro and in xenograft tumor models. These findings establish a new framework for understanding the central role of GPX4 in blocking oxidative cell death.


Assuntos
Fator de Indução de Apoptose , Ferroptose , Leucemia , Parthanatos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Fator de Indução de Apoptose/metabolismo , Linhagem Celular Tumoral , Ciclofosfamida/farmacologia , Humanos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo
18.
Cell Mol Biol (Noisy-le-grand) ; 67(5): 174-180, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35818256

RESUMO

This study aimed to explore the secretion of sex hormones in peripheral blood of women with common hematological tumors before and after chemotherapy. From January 2019 to April 2021, 100 female patients with common hematological tumors in our hospital were selected as the observation group, and 50 healthy women in our hospital during the same period were selected as the control group. The serum levels of follicle-stimulating hormone (FSH), estradiol (E2) and luteinizing hormone (LH) were detected and compared between the observation group and the control group before chemotherapy, patients with different disease types in the observation group, postmenopausal patients in the observation group, and postmenopausal patients in the observation group. Results showed that the serum FSH, E2 and LH levels of the observation group had no significant changes before chemotherapy (P > 0.05). Compared with before chemotherapy, the levels of serum FSH and LH in patients with different disease types in the observation group after chemotherapy were significantly higher, while E2 was significantly lower (P < 0.05), and the serum FSH, E2 and LH levels of postmenopausal patients in the observation group did not change significantly after chemotherapy (P > 0.05). The levels of FSH and LH in the observation group after chemotherapy were significantly higher, and E2 was significantly lower (P < 0.05). In general, the levels of sex hormone secretion in peripheral blood of women with common hematological tumors before and after chemotherapy can change significantly, especially in postmenopausal patients, but not in postmenopausal patients, which has a certain reference value for clinical practice.


Assuntos
Neoplasias Hematológicas , Hormônio Luteinizante , Estradiol , Feminino , Hormônio Foliculoestimulante , Hormônios Esteroides Gonadais , Neoplasias Hematológicas/tratamento farmacológico , Humanos
19.
Pain Med ; 23(5): 902-911, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-34314503

RESUMO

OBJECTIVE: Recent neuroimaging studies have found that brain function is abnormal in primary dysmenorrhea (PDM). The present study aimed to explore frequency-specific brain alterations and their occurrence in the PDM. METHODS: Forty-seven patients with PDM and 36 matched healthy controls were enrolled in the study and underwent resting-state functional magnetic resonance imaging. The alterations in brain function in patients with PDM were assessed with different frequency filter bands (Slow5, Slow4, Slow3, and full low frequency) and a functional connectivity density (FCD) approach. The clinical significance of the altered FCD was then explored. Additionally, mediation analysis was used to detect the altered FCD-mediated clinical relationships in PDM. RESULTS: Frequency-specific FCD alterations have been observed in patients with PDM, especially in the central executive, default mode, and sensorimotor networks and in the hippocampus. The altered full low-frequency FCD in the hippocampus was associated with the duration of disease and pain severity scores. The altered Slow5 FCD in the second somatosensory area (S2) was associated with the severity of pain in PDM. Furthermore, the FCD in S2 mediated the duration associated with pain symptoms in PDM. CONCLUSION: The present study identified frequency-specific FCD alterations in PDM and suggested that the S2 area is a potential treatment target for PDM.


Assuntos
Mapeamento Encefálico , Dismenorreia , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Medição da Dor
20.
BMC Vet Res ; 18(1): 437, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36514049

RESUMO

BACKGROUND: Salmonella enterica, serovar Enteritidis (SE) is a food-borne pathogen, which can cause great threat to human health through consumption of the contaminated poultry products. Chicken is the main host of SE. The mRNA and microRNA (miRNA) expression profiles were analyzed on cecum of Shouguang chicken via next-generation sequencing and bioinformatics approaches. The treated group was inoculated SE, and the control group was inoculated with phosphate buffer saline (PBS). RESULTS: There were 1760 differentially expressed mRNAs in the SE-infected group, of which 1046 were up-regulated mRNA, and 714 were down-regulated mRNA. In addition, a total of 821 miRNAs were identified, and 174 miRNAs were differentially expressed, of which 100 were up-regulated and 74 were down-regulated. Functional enrichment of differentially expressed mRNAs was similar to miRNA target genes. The functional analysis results of differentially expressed mRNAs and miRNAs were performed. Immune-related processes and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were enriched by up-regulated mRNA. The down-regulated mRNAs were enriched in tissue development and metabolic-related KEGG pathways. The functional analysis of up-regulated miRNA target genes was similar to the down-regulated mRNAs. The down-regulated miRNA target genes were enriched in metabolic-related GO (Gene Ontology) -BP (Biological process) terms and KEGG pathways. The overlap of the up-regulated mRNA and the up-regulated miRNA target genes (class I) was 325, and the overlap of the down-regulated miRNA target genes (class II) was 169. The class I enriched in the immune-related GO-BP terms and KEGG pathways. The class II mainly enriched in metabolic-related GO-BP terms and KEGG pathways. Then we detected the expression of mRNA and miRNA through qRT-PCR. The results shown that the expression of HHIP, PGM1, HTR2B, ITGB5, RELN, SFRP1, TCF7L2, SCNN1A, NEK7, miR-20b-5p, miR-1662, miR-15a, miR-16-1-3p was significantly different between two groups. Dual-luciferase reporter assay was used to detect the relationship between miR-20b-5p and SCNN1A. The result indicated that miR-20b-5p regulate immune or metabolic responses after SE infection in Shouguang chickens by directly targeting SCNN1A. CONCLUSIONS: The findings here contribute to the further analysis of the mechanism of mRNA and miRNA defense against SE infection, and provide a theoretical foundation for the molecular disease-resistant breeding of chickens.


Assuntos
Galinhas , MicroRNAs , Animais , Ceco/metabolismo , Galinhas/genética , Perfilação da Expressão Gênica/veterinária , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , Salmonella enteritidis/genética
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