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1.
Acta Biomater ; 2021 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-33609743

RESUMEN

Although boron neuron capture therapy (BNCT) has enabled the delivery of stronger radiation dose to glioblastoma multiforme (GBM) cells for precision radiotherapy (RT), patients in need are almost unable to access the treatment due to insufficient operating devices. Therefore, we developed targeted sensitization-enhanced radiotherapy (TSER), a strategy that could achieve precision cell-targeted RT using common linear accelerators. TSER, which involves the combination of GoldenDisk (GD; a spherical radioenhancer), 5-aminolevulinic acid (5-ALA), low-intensity ultrasound (US), and low-dose RT, exhibited synergized radiosensitization effects. Both 5-ALA and hyaluronic-acid-immobilized GD can selectively accumulate in GBM to induce chemical and biological enhancement of radiosensitization, resulting in DNA damage, escalation of reactive oxygen species levels, and cell cycle redistribution, in turn sensitizing GBM cells to radiation under US. TSER showed an enhanced therapeutic effect and survival in the treatment of an orthotropic GBM model with only 20% of the radiation dose compared to that of a 10-Gy RT. The strategy with the potential to inhibit GBM progress and rescue the organ at risk using low-dose RT, thereby improving the quality of life of GBM patients, shedding light on achieving cell-targeted RT using universally available linear accelerators.

2.
J Cell Commun Signal ; 2021 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-33619681

RESUMEN

Podocytes are the key cells involved in protein filtration in the glomerulus. Once proteins appear in the urine when podocytes fail, patients will end with renal failure due to the progression of glomerular damage if no proper treatment is applied. The injury and loss of podocytes can be attributed to diverse factors, such as genetic, immunologic, toxic, or metabolic disorders. Recently, autophagy has emerged as a key mechanism to eliminate the unwanted cytoplasmic materials and to prolong the lifespan of podocytes by alleviating cell damage and stress. Typically, the fundamental function of extracellular vesicles (EVs) is to mediate the intercellular communication. Recent studies have suggested that, EVs, especially exosomes, play a certain role in information transfer by communicating proteins, mRNAs, and microRNAs with recipient cells. Under physiological and pathological conditions, EVs assist in the bioinformation interchange between kidneys and other organs. It is suggested that EVs are related to the pathogenesis of acute kidney injury and chronic kidney disease, including glomerular disease, diabetic nephropathy, renal fibrosis and end-stage renal disease. However, the role of EVs in podocyte autophagy remains unclear so far. Here, this study integrated the existing information about the relevancy, diagnostic value and therapeutic potential of EVs in a variety of podocytes-related diseases. The accumulating evidence highlighted that autophagy played a critical role in the homeostasis of podocytes in glomerular disease.

3.
Artículo en Inglés | MEDLINE | ID: mdl-33620608

RESUMEN

Paracardial cystic lesions (PCLs) are rare, benign lesions and may occur in any part surrounding the heart. It covers a variety of pathological types, including pericardial cysts, thymic cysts, bronchogenic cysts and so on. The aim of this study was to summarize the diagnostic value of echocardiography in different pathological types of the PCLs. Echocardiographic features of 43 consecutive PCL patients treated at the Union Hospital from January 2002 to December 2017 were compared and analyzed with their surgical and pathological findings retrospectively. The PCLs included 19 pericardial cysts, 12 thymic cysts, 7 bronchogenic cysts, 3 cystic teratomas, 1 enteric cyst and 1 lymphangioma. Among them, 29 cases (67.4%) were accurately diagnosed by echocardiography and 14 cases (32.6%) were missed the diagnosis. All diagnosed cysts were showed as thin-walled, monolocular, echo-free structures without blood flow signals in echocardiographic images. 4 patients had compression of the heart and great vessels caused by cysts. In addition, 4 intracardiac lesions were diagnosed by echocardiography and the results were further confirmed in surgery. Echocardiography is of great value in the diagnosis of paracardiac cystic lesions as well as combined intracardiac lesions. Differential diagnosis could be mainly made based on the location of the lesions.

4.
Artículo en Inglés | MEDLINE | ID: mdl-33620609

RESUMEN

Left atrial (LA) enlargement is present in the majority of adult heart transplant (HT) recipients. We used speckle-tracking echocardiography to investigate whether LA phasic function in HT patients is altered and explored its relationship to HT-related clinical variables. This study evaluated LA function in 112 clinically well HT patients and 40 healthy controls. Clinical data included recipient age at HT, donor age, ischemia time, left ventricular function, and biochemical indicators. Atrial deformation and volume indices were measured with two-dimensional and three-dimensional speckle-tracking echocardiography, respectively. Components of phasic atrial function were calculated and correlations to clinical variables were explored. Compared with controls, HT patients had worse LA reservoir, conduit, and pump function. LA reservoir function of the bicaval group was better than the biatrial group, but differences did not persist after adjustment for potential confounders. Among patients with HT, those with lower LAS-peak had an older recipient age, larger LA volume, as well as worse left ventricular systolic function than those patients with higher LAS-peak. However, E/e', biochemical indicators and donor-related information were similar across the quartiles of LA function. In HT cohort, we observed impairment in all phases of LA function, and LA reservoir function was decreased independent of surgical technique. LAS-peak was associated with worse left ventricular systolic function, which suggested that LA function may play an important role in HT patients.

5.
Clin Cardiol ; 2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33634478

RESUMEN

Primary percutaneous coronary intervention (PPCI), the preferred reperfusion strategy for all acute ST-segment elevation myocardial infarction (STEMI) patients, is not universally available in clinical practice. Pharmacoinvasive strategy has been proposed as a therapeutic option in patients with STEMI when timely PPCI is not feasible. However, pharmacoinvasive strategy has potential delay between clinical patency and complete myocardial perfusion. The optimal reperfusion strategy for STEMI patients with anticipated PPCI delay according to current practice is uncertain. OPTIMAL-REPERFUSION is an investigator-initiated, prospective, multicenter, randomized, open-label, superiority trial with blinded evaluation of outcomes. A total of 632 STEMI patients presenting within 6 hours after symptom onset and with an expected time of first medical contact to percutaneous coronary intervention (PCI) ≥120 minute will be randomized to a reduced-dose facilitated PCI strategy (reduced-dose fibrinolysis combined with simultaneous transfer for immediate invasive therapy with a time interval between fibrinolysis to PCI < 3 hours) or to standard pharmacoinvasive treatment. The primary endpoint is the composite of death, reinfarction, refractory ischemia, congestive heart failure, or cardiogenic shock at 30-days. Enrollment of the first patient is planned in March 2021. The recruitment is anticipated to last for 12 to 18 months and to complete in September 2023 with 1 year follow-up. The OPTIMAL-REPERFUSION trial will help determine whether reduced-dose facilitated PCI strategy improves clinical outcomes in patients with STEMI and anticipated PPCI delay. This study is registered with the ClinicalTrials.gov (NCT04752345).

6.
ACS Nano ; 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33634695

RESUMEN

Biofilm is difficult to thoroughly cure with conventional antibiotics due to the high mechanical stability and antimicrobial barrier resulting from extracellular polymeric substances. Encouraged by the great potential of magnetic micro-/nanorobots in various fields and their enhanced action in swarm form, we designed a magnetic microswarm consisting of porous Fe3O4 mesoparticles (p-Fe3O4 MPs) and explored its application in biofilm disruption. Here, the p-Fe3O4 MPs microswarm (p-Fe3O4 swarm) was generated and actuated by a simple rotating magnetic field, which exhibited the capability of remote actuation, high cargo capacity, and strong localized convections. Notably, the p-Fe3O4 swarm could eliminate biofilms with high efficiency due to synergistic effects of chemical and physical processes: (i) generating bactericidal free radicals (•OH) for killing bacteria cells and degrading the biofilm by p-Fe3O4 MPs; (ii) physically disrupting the biofilm and promoting •OH penetration deep into biofilms by the swarm motion. As a demonstration of targeted treatment, the p-Fe3O4 swarm could be actuated to clear the biofilm along the geometrical route on a 2D surface and sweep away biofilm clogs in a 3D U-shaped tube. This designed microswarm platform holds great potential in treating biofilm occlusions particularly inside the tiny and tortuous cavities of medical and industrial settings.

7.
Commun Biol ; 4(1): 206, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33589721

RESUMEN

The auxin IAA is a vital plant hormone in controlling growth and development, but our knowledge about its complicated biosynthetic pathways and molecular regulation are still limited and fragmentary. cytokinin induced root waving 2 (ckrw2) was isolated as one of the auxin-deficient mutants in a large-scale forward genetic screen aiming to find more genes functioning in auxin homeostasis and/or its regulation. Here we show that CKRW2 is identical to Histone Monoubiquitination 1 (HUB1), a gene encoding an E3 ligase required for histone H2B monoubiquitination (H2Bub1) in Arabidopsis. In addition to pleiotropic defects in growth and development, loss of CKRW2/HUB1 function also led to typical auxin-deficient phenotypes in roots, which was associated with significantly lower expression levels of several functional auxin synthetic genes, namely TRP2/TSB1, WEI7/ASB1, YUC7 and AMI1. Corresponding defects in H2Bub1 were detected in the coding regions of these genes by chromatin immunoprecipitation (ChIP) analysis, indicating the involvement of H2Bub1 in regulating auxin biosynthesis. Importantly, application of exogenous cytokinin (CK) could stimulate CKRW2/HUB1 expression, providing an epigenetic avenue for CK to regulate the auxin homeostasis. Our results reveal a previously unknown mechanism for regulating auxin biosynthesis via HUB1/2-mediated H2Bub1 at the chromatin level.

8.
J Cereb Blood Flow Metab ; : 271678X21992625, 2021 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-33563078

RESUMEN

Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD+ salvage pathway. Our previous study demonstrated that deletion of NAMPT gene in projection neurons using Thy1-NAMPT-/- conditional knockout (cKO) mice causes neuronal degeneration, muscle atrophy, neuromuscular junction abnormalities, paralysis and eventually death. Here we conducted a combined metabolomic and transcriptional profiling study in vivo in an attempt to further investigate the mechanism of neuronal degeneration at metabolite and mRNA levels after NAMPT deletion. Here using steady-state metabolomics, we demonstrate that deletion of NAMPT causes a significant decrease of NAD+ metabolome and bioenergetics, a buildup of metabolic intermediates upstream of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in glycolysis, and an increase of oxidative stress. RNA-seq shows that NAMPT deletion leads to the increase of mRNA levels of enzymes in NAD metabolism, in particular PARP family of NAD+ consumption enzymes, as well as glycolytic genes Glut1, Hk2 and PFBFK3 before GAPDH. GO, KEGG and GSEA analyses show the activations of apoptosis, inflammation and immune responsive pathways and the inhibition of neuronal/synaptic function in the cKO mice. The current study suggests that increased oxidative stress, apoptosis and neuroinflammation contribute to neurodegeneration and mouse death as a direct consequence of bioenergetic stress after NAMPT deletion.

9.
Biosci Rep ; 41(2)2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33564846

RESUMEN

To develop a screening kit for detecting mutation hotspots of the phenylalanine hydroxylase (PAH) gene. Thirteen exons of the PAH gene were sequenced in 84 cases with phenylketonuria (PKU) diagnosed during neonatal genetic and metabolic disease screening in Shaanxi province, and their mutations were analyzed. We designed and developed a screening kit to detect nine mutation sites covering more than 50% of the PAH mutations found in Shaanxi province (c.728G>A, c.1197A>T, c.331C>T, c.1068C>A, c.611A>G, c.1238G>C, c.721C>T, c.442-1G>A, and c.158G>A) by using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) combined with fluorescent probe technology. Peripheral blood and dried blood samples from PKU families were used for clinical verification of the newly developed kit. PAH gene mutations were detected in 84 children diagnosed with PKU. A total of 159 mutant alleles were identified, consisting of 100 missense mutations, 28 shear mutations, 24 nonsense mutations, and 7 deletion mutations. Exon 7 had the highest mutation frequency (32.08%). Among them, the mutation frequency of p.R243Q was the highest, accounting for 20.13% of all mutations, followed by p.R111X, IVS4-1G>A, EX6-96A>G, and p.R413P; these five loci accounted for 47.17% (75/159) of all mutations. In addition, we identified three previously unreported PAH gene mutations (p.C334X, p.G46D, and p.G256D). Fifteen mutation sites were identified in the 47 PAH carriers identified by next-generation sequencing (NGS), which were verified by the newly developed kit, with an agreement rate of 100%. This newly developed kit based on ARMS-PCR combined with fluorescent probe technology can be used to detect common PAH gene mutations.

10.
Ann Palliat Med ; 10(1): 404-414, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33545772

RESUMEN

BACKGROUND: Continuous epidural infusion (CEI) can provide analgesia during labor. The dural puncture epidural (DPE) technique is used to accelerate the onset of neuraxia anesthesia. The primary objective of this study was to compare the percentage of patients that received adequate labor analgesia following an injection of 0.08% epidural ropivacaine via the DPE and CEI techniques combined with the PIEB mode of maintenance. METHODS: Patients who were laboring were randomly allocated to receive either CEI + PIEB or DPE + PIEB. Subjects indicated a VAS score immediately prior to epidural placement, and parturients with a VAS score of ≤50 mm were excluded. A 25-gauge needle was used for dural puncture. Analgesia was provided with 10 mL of 0.08% ropivacaine and 0.4 µg/mL of sufentanil, and was maintained at 10 mL/h in both groups with the same solution. All pumps were programmed for patient-controlled epidural analgesia (PCEA) boluses of 5 mL with a 20-minute lockout. VAS measurements were collected at 2-minute intervals for up to 20 minutes after initiation of the epidural bolus. The median time to adequate analgesia was analyzed using Kaplan-Meier curves and Cox proportional hazard models. RESULTS: Data were collected and analyzed from 200 participants (n=100 per group). Adequate analgesia at 10 minutes was higher in the DPE + PIEB group compared to the CEI + PIEB group (DPE + PIEB =58.4% vs. CEI + PIEB =41.6%; P=0.007). The DPE + PIEB group also had a shorter median time to adequate analgesia [median (95% confidence interval (CI), 8 minutes (7-9 minutes) vs. 12 minutes (10-14 minutes)] compared to the CEI + PIEB group [hazard ratio (HR) =1.488; 95% CI, 1.105-2.002; P=0.002]. CONCLUSIONS: The percentage of parturients with adequate analgesia at 10 minutes was higher with DPE + PIEB compared to CEI + PIEB. Furthermore, the DPE + PIEB mode was associated with a faster time to a VAS score ≤30 mm.

11.
Ann Palliat Med ; 2021 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-33549029

RESUMEN

BACKGROUND: Use of anticoagulant as lock solutions is an important method to maintain the function of haemodialysis (HD) central venous catheters (CVCs), and the common anticoagulants heparin and citrate are not suitable for some patients. Argatroban can inhibit thrombin directly, has a definite anticoagulant effect, and is expected to be a new anticoagulant for CVC lock solutions. METHODS: A total of 60 HD patients with non-tunnelled or tunnelled CVCs will be randomly assigned to two groups: an argatroban group and a control group. The participants will be given argatroban 0.5 mg/mL or unfractionated heparin (UFH) 1,000 U/mL locked post-dialysis instilled into the CVC lumens and followed up for 2 weeks. Data on demographic and general clinical information, laboratory examination, adverse events, adverse reactions and serious adverse events in the two groups will be collected. The differences in coagulation indexes at 30 min following catheter lock will be compared. The thrombosis rate, infection rate and percentage of catheter-days in the two groups will be observed. The primary outcomes include: efficacy assessments of combined outcome events: (I) rates of cumulative catheter survival in the 2-week HD session (the standard of catheter survival was catheter mean blood flow ≥250 mL/min); (II) rates of cumulative survival free of catheter thrombosis in the 2-week HD session. The second outcomes include: catheter dysfunction, the variation value (seconds) in activated partial thromboplastin time (aPTT) at 30 min following catheter locking and aPTT before next dialysis, catheter-associated bleeding, and catheterassociated infections. DISCUSSION: At present, there is no clinical study of argatroban as a CVC lock solution. This study will explore the efficacy and safety of the argatroban as locking solution in the prevention of the dysfunction of HD CVCs to provide evidence for further research. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800017105. Registered 12 July, 2018 (prospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=29054).

12.
Int J Early Child ; : 1-18, 2021 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-33518791

RESUMEN

The rapid spread of the coronavirus virus (COVID-19) has been responsible for massive global impacts on the lives of children, families and communities. It is important to document these effects for the Early Childhood Education and Care (ECEC) sector. This report focuses on the Asia-Pacific region and ECEC sector, given limited regional studies on the impact of COVID-19 on early childhood education. It draws attention to the effects of the pandemic across five member countries of the Organisation Mondiale pour l' Education Préscolaire (OMEP)-Australia, China, Japan, Korea and Thailand. The authors describe initial responses to control the spread of the pandemic in each national context and identify socio-political factors that enable broad understandings of national responses to COVID-19. In relation to the ECEC sector, responses are discussed in terms of cultural differences, economic issues, educational and professional concerns and educator wellbeing. While important government actions have rightly focused on virus suppression, it also remains important to maintain attention on the rights of children to ensure that the health crisis does not also become a child's rights crisis and that sufficient attention is given to children's safety and wellbeing.

13.
Int J Cancer ; 2021 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-33533501

RESUMEN

We conducted a study to document the impact of COVID-19 pandemic on cancer screening continuum in selected low- and middle-income countries (LMICs). LMICs having an operational cancer control plan committed to screen eligible individuals were selected. Managers/supervisors of cancer screening programs were invited to participate in an online survey and subsequent in-depth interview. Managers/supervisors from 18 programs in 17 countries participated. Lockdown was imposed in all countries except Brazil. Screening was suspended for at least 30 days in 13 countries, while diagnostic-services for screen-positives were suspended in 9 countries. All countries except Cameroon, Bangladesh, India, Honduras and China managed to continue with cancer treatment throughout the outbreak. The participants rated service availability compared to pre-COVID days on a scale of 0 (no activities) to 100 (same as before). A rating of ≤50 was given for screening services by 61.1%, diagnostic services by 44.4% and treatment services by 22.2% participants. At least 70% participants strongly agreed that increased noncompliance of screen-positive individuals and staff being overloaded or overwhelmed with backlogs would deeply impact screening programs in the next 6 months at least. Although many of the LMICs were deficient in following the "best practices" to minimize service disruptions, at least some of them made significant efforts to improve screening participation, treatment compliance and program organization. A well-coordinated effort is needed to reinitiate screening services in the LMICs, starting with a situational analysis. Innovative strategies adopted by the programs to keep services on-track should be mutually shared.

14.
Medicine (Baltimore) ; 100(4): e23898, 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33530186

RESUMEN

INTRODUCTION: Mechanical ventilation is a powerful tool for the treatment of various critical emergencies. However, surviving critically ill patients often have poor psychological and physiological outcomes. Prevention of various complications and adverse outcomes of mechanical ventilation is a priority and a challenge in the intensive care unit (ICU). Early intervention is the key to reducing complications and improving outcomes of mechanical ventilation in the ICU. As an auxiliary rehabilitation treatment, the improved sitting Wuqinxi intervention has recognized unique advantages. It has achieved beneficial therapeutic effects during early intervention in clinical practice. It can reduce the incidence of delirium, shorten the duration of mechanical ventilation, and prevent complications and secondary damages related to mechanical ventilation in the ICU. Therefore, the purpose of this study will be to explore the effect of improved sitting Wuqinxi on the clinical outcomes of mechanically ventilated ICU patients. METHODS: This prospective, multicenter, randomized, single-blinded, parallel controlled clinical study will involve 160 patients who met the inclusion criteria. The patients will be randomly divided into the experimental and control groups. Both groups will be given standardized comprehensive western medicine treatment (including mechanical ventilation) and routine care in the ICU. Management of the experimental group will also include "improved sitting Wuqinxi," with the treatment objective to observe the effect of the improved sitting Wuqinxi intervention on the clinical outcomes in mechanically ventilated ICU patients. The outcome measures will include the incidence of complications, duration of mechanical ventilation, length of ICU stay, and cost of hospitalization. In addition, the effect of the improved sitting Wuqinxi intervention on the safety indexes of mechanically ventilated ICU patients will be assessed and the clinical effects of the improved sitting Wuqinxi intervention will be comprehensively evaluated. DISCUSSION: The purpose of this study will be to evaluate the effect of the improved sitting Wuqinxi intervention on the incidence of complications, duration of mechanical ventilation, length of ICU stay, cost of hospitalization, and safety indicators. If successful, it will provide a reliable, simple, and feasible auxiliary rehabilitation treatment scheme for mechanically ventilated ICU patients.


Asunto(s)
Cuidados Críticos/métodos , Medicina China Tradicional/métodos , Respiración Artificial , Delirio/prevención & control , Humanos , Estudios Prospectivos , Respiración Artificial/efectos adversos , Método Simple Ciego , Sedestación , Factores de Tiempo , Desconexión del Ventilador
15.
Int J Mol Med ; 47(3): 1, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33537831

RESUMEN

Diabetic nephropathy (DN) is the primary cause of end­stage renal disease, which is closely associated with dysfunction of the podocytes, the main component of the glomerular filtration membrane; however, the exact underlying mechanism is unknown. Polyamines, including spermine, spermidine and putrescine, have antioxidant and anti­aging properties that are involved in the progression of numerous diseases, but their role in DN has not yet been reported. The present study aimed to explore the role of polyamines in DN, particularly in podocyte injury, and to reveal the molecular mechanism underlying the protective effect of exogenous spermine. Streptozotocin intraperitoneal injection­induced type 1 diabetic (T1D) rat models and high glucose (HG)­stimulated podocyte injury models were established. It was found that in T1D rat kidneys and HG­induced podocytes, ornithine decarboxylase (a key enzyme for polyamine synthesis) was downregulated, while spermidine/spermine N1­acetyltransferase (a key enzyme for polyamines degradation) was upregulated, which suggested that reduction of the polyamine metabolic pool particularly decreased spermine content, is a major factor in DN progression. In addition, hyperglycemia can induce an increased rat kidney weight ratio, serum creatinine, urea, urinary albumin excretion and glomerular cell matrix levels, and promote mesangial thickening and loss or fusion of podocytes. The expression levels of podocyte marker proteins (nephrin, CD2­associated protein and podocin) and autophagy­related proteins [autophagy protein 5, microtube­associated proteins 1A/1B light chain 3 (LC3)II/LC3I, Beclin 1 and phosphorylated (p)­AMPK] were downregulated, while cleaved caspase­3, P62 and p­mTOR were increased. These changes could be improved by pretreatment with exogenous spermine or rapamycin (autophagic agonist). In conclusion, spermine may have the potential to prevent diabetic kidney injury in rats by promoting autophagy via regulating the AMPK/mTOR signaling pathway.

16.
Clin Sci (Lond) ; 135(4): 629-649, 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33538300

RESUMEN

Tumor microenvironment (TME) exerts key roles in pancreatic ductal adenocarcinoma (PDAC) development. However, the factors regulating the cross-talk between PDAC cells and TME are largely unknown. In the present study, we identified a long noncoding RNA (lncRNA) KLHDC7B divergent transcript (KLHDC7B-DT), which was up-regulated in PDAC and correlated with poor survival of PDAC patients. Functional assays demonstrated that KLHDC7B-DT enhanced PDAC cell proliferation, migration, and invasion. Mechanistically, KLHDC7B-DT was found to directly bind IL-6 promoter, induce open chromatin structure at IL-6 promoter region, activate IL-6 transcription, and up-regulate IL-6 expression and secretion. The expression of KLHDC7B-DT was positively correlated with IL-6 in PDAC tissues. Via inducing IL-6 secretion, KLHDC7B-DT activated STAT3 signaling in PDAC cells in an autocrine manner. Furthermore, KLHDC7B-DT also activated STAT3 signaling in macrophages in a paracrine manner, which induced macrophage M2 polarization. KLHDC7B-DT overexpressed PDAC cells-primed macrophages promoted PDAC cell proliferation, migration, and invasion. Blocking IL-6/STAT3 signaling reversed the effects of KLHDC7B-DT on macrophage M2 polarization and PDAC cell proliferation, migration, and invasion. In conclusion, KLHDC7B-DT enhanced malignant behaviors of PDAC cells via IL-6-induced macrophage M2 polarization and IL-6-activated STAT3 signaling in PDAC cells. The cross-talk between PDAC cells and macrophages induced by KLHDC7B-DT represents potential therapeutic target for PDAC.

17.
Mol Med Rep ; 23(4): 1, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33576465

RESUMEN

During embryonic cortical development, radial glial cells (RGCs) are the major source of neurons, and these also serve as a supportive scaffold to guide neuronal migration. Similar to Vimentin, glial fibrillary acidic protein (GFAP) is one of the major intermediate filament proteins present in glial cells. Previous studies confirmed that prenatal ethanol exposure (PEE) significantly affected the levels of GFAP and increased the disassembly of radial glial fibers. GFAPδ is a variant of GFAP that is specifically expressed in RGCs; however, to the best of our knowledge, there are no reports regarding how PEE influences its expression during cortical development. In the present study, the effects of PEE on the expression and distribution of GFAPδ during early cortical development were assessed. It was found that PEE significantly decreased the expression levels of GFAP and GFAPδ. Using double immunostaining, GFAPδ was identified to be specifically expressed in apical and basal RGCs, and was co­localized with other intermediate filament proteins, such as GFAP, Nestin and Vimentin. Additionally, PEE significantly affected the morphology of radial glial fibers and altered the behavior of RGCs. The loss of GFAPδ accelerated the transformation of RGCs into astrocytes. Using co­immunostaining with Ki67 or phospho­histone H3, GFAPδ+ cells were observed to be proliferative or mitotic cells, and ethanol treatment significantly decreased the proliferative or mitotic activities of GFAPδ+ RGCs. Taken together, the results suggested that PEE altered the expression patterns of GFAPδ and impaired the development of radial glial fibers and RGC behavior. The results of the present study provided evidence that GFAPδ may be a promising target to rescue the damage induced by PEE.

18.
Biomed Pharmacother ; 137: 111376, 2021 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-33588266

RESUMEN

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide, especially in developing countries. To date, several approaches have been proposed for the prevention and treatment of CVDs. However, the increased risk of developing cardiovascular events that result in hospitalization has become a growing public health concern. The pathogenesis of CVDs has been analyzed from various perspectives. Recent data suggest that regulatory RNAs play a multidimensional role in the development of CVDs. Studies have identified several mRNA modifications that have contributed to the functional characterization of various cardiac diseases. RNA methylation, such as N6-methyladenosine, N1-methyladenosine, 5-methylcytosine, N7-methylguanosine, N4-acetylcytidine, and 2'-O-methylation are novel epigenetic modifications that affect the regulation of cell growth, immunity, DNA damage, calcium signaling, apoptosis, and aging in cardiomyocytes. In this review, we summarize the role of RNA methylation in the pathophysiology of CVDs and the potential of using epigenetics to treat such disorders.

19.
Arch Microbiol ; 2021 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-33611635

RESUMEN

Enterococcus faecalis (E. faecalis) is an indigenous intestinal bacterium and has potential to be applied as probiotic supplement. Low pH is one of the main stresses that E. faecalis has to deal with to colonize in the gastrointestinal tract. Previous study indicated low concentration of flavonoids may enhance the tolerance of probiotic to environmental stress. In the present research, transcriptome analysis was employed to investigate the influence of Cyclocarya paliurus flavonoids (CPF) on E. faecalis exposed to low pH environment. The results revealed that under the stress of low pH, genes related to cell wall and membrane, transmembrane transport, metabolism process, energy production, and conversion stress proteins were significantly differentially expressed. And certain undesired changes of which (such as genes for MFS transporter were downregulated) could be partially mitigated by CPF intervention, indicating their capacity to improve the low pH tolerance of E. faecalis. Results from this study deepened our understanding of the beneficial role of CPF on the probiotic in the gastrointestinal environment.

20.
Artículo en Inglés | MEDLINE | ID: mdl-33611692

RESUMEN

BACKGROUND: Abnormal ion channel currents caused by myocardial electrical remodeling is one of the main causes of malignant arrhythmias. Glycogen synthase kinase 3ß (GSK-3ß) is the main therapeutic target following ischemia as it regulates nerve cell channels. However, few studies have investigated its role in myocardial electrical remodeling. The present study aimed to investigate the role of GSK-3ß in a rat myocardial infarction (MI)-induced electrical remodeling and potential effects on cardiac ionic channels including KCNJ2/Kir2.1/IK1. METHODS: Ligation of the left anterior descending artery in rats was performed to establish a MI model. The rats were randomly divided into three groups, the sham, MI, and MI + SB group. The animals in the latter group were administered SB216763 (GSK-3ß inhibitor) at a dose of 0.6 mg·kg-1·day-1. The ventricular function was assessed by echocardiography, electrocardiography, and histological analysis 7 days post-surgery. Serum was collected to measure lactate dehydrogenase and cardiac troponin I levels, and the mRNA and protein levels of the KCNJ2/Kir2.1/IK1 channel in the heart tissues were assessed. H9c2 cells were cultured to examine the effects of SB216763 on the protein expression of Kir2.1 channel under hypoxic conditions. RESULTS: The results revealed that SB216763 ameliorated acute cardiac injury and improved myocardial dysfunction. Moreover, SB216763 increased the mRNA and protein expression of Kir2.1 during MI. Furthermore, SB216763 treatment abrogated the decreased expression of Kir2.1 in H9c2 cells under hypoxic conditions. CONCLUSIONS: GSK-3ß inhibition upregulates Kir2.1 expression in a rat model of MI.

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