Publications by authors named "Qin Xia"

225 Publications

Cloning and identification of a new repressor of 3,17β-Hydroxysteroid dehydrogenase of Comamonas testosteroni.

Mol Biol Rep 2021 Oct 22. Epub 2021 Oct 22.

School of Life Science and Technology, Changchun University of Science and Technology, Changchun, 130022, China.

Background: 3,17β-hydroxysteroid dehydrogenase (3,17β-HSD) is a key enzyme in the metabolic pathway for steroid compounds catabolism in Comamonas testosteroni. Tetracycline repressor (TetR) family, repressors existing in most microorganisms, may play key roles in regulating the expression of 3,17β-HSD. Previous reports showed that three tetR genes are located in the contig58 of C. testosteroni ATCC 11996 (GenBank: AHIL01000049.1), among which the first tetR gene encoded a potential repressor of 3,17β-HSD by sensing environmental signals. However, whether the other proposed tetR genes act as repressors of 3,17β-HSD are still unknown.

Methods And Results: In the present study, we cloned the second tetR gene and analyzed the regulatory mechanism of the protein on 3,17β-HSD using electrophoretic mobility shift assay (EMSA), gold nanoparticles (AuNPs)-based assay, and loss-of-function analysis. The results showed that the second tetR gene was 660-bp, encoding a 26 kD protein, which could regulate the expression of 3,17β-HSD gene via binding to the conserved consensus sequences located 1100-bp upstream of the 3,17β-HSD gene. Furthermore, the mutant strain of C. testosteroni with the second tetR gene knocked-out mutant expresses good biological genetic stability, and the expression of 3,17β-HSD in the mutant strain is slightly higher than that in the wild type under testosterone induction.

Conclusions: The second tetR gene acts as a negative regulator in 3,17β-HSD expression, and the mutant has potential application in bioremediation of steroids contaminated environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11033-021-06566-9DOI Listing
October 2021

High-Quality Genome of the Medicinal Plant Provides Insights Into the Biosynthesis of Indole Alkaloids.

Front Plant Sci 2021 30;12:742420. Epub 2021 Sep 30.

College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.

(Nees) Kuntze is an important plant used to process the traditional Chinese herbal medicines "Qingdai" and "Nanbanlangen". The key active ingredients are indole alkaloids (IAs) that exert antibacterial, antiviral, and antitumor pharmacological activities and serve as natural dyes. We assembled the genome at the chromosome level through combined PacBio circular consensus sequencing (CCS) and Hi-C sequencing data. Hi-C data revealed a draft genome size of 913.74 Mb, with 904.18 Mb contigs anchored into 16 pseudo-chromosomes. Contig N50 and scaffold N50 were 35.59 and 68.44 Mb, respectively. Of the 32,974 predicted protein-coding genes, 96.52% were functionally annotated in public databases. We predicted 675.66 Mb repetitive sequences, 47.08% of sequences were long terminal repeat (LTR) retrotransposons. Moreover, 983 -specific genes (SSGs) were identified for the first time, accounting for ~2.98% of all protein-coding genes. Further, 245 putative centromeric and 29 putative telomeric fragments were identified. The transcriptome analysis identified 2,975 differentially expressed genes (DEGs) enriched in phenylpropanoid, flavonoid, and triterpenoid biosynthesis. This systematic characterization of key enzyme-coding genes associated with the IA pathway and basic helix-loop-helix (bHLH) transcription factor family formed a network from the shikimate pathway to the indole alkaloid synthesis pathway in . The high-quality genome presented herein is an essential resource for the traditional Chinese medicine genomics studies and understanding the genetic underpinning of IA biosynthesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpls.2021.742420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515051PMC
September 2021

Application of Restriction Site-Associated DNA Sequencing (RAD-Seq) for Copy Number Variation and Triploidy Detection in Human.

Cytogenet Genome Res 2021 Oct 15:1-8. Epub 2021 Oct 15.

Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

At present, low-pass whole-genome sequencing (WGS) is frequently used in clinical research and in the screening of copy number variations (CNVs). However, there are still some challenges in the detection of triploids. Restriction site-associated DNA sequencing (RAD-Seq) technology is a reduced-representation genome sequencing technology developed based on next-generation sequencing. Here, we verified whether RAD-Seq could be employed to detect CNVs and triploids. In this study, genomic DNA of 11 samples was extracted employing a routine method and used to build libraries. Five cell lines of known karyotypes and 6 triploid abortion tissue samples were included for RAD-Seq testing. The triploid samples were confirmed by STR analysis and also tested by low-pass WGS. The accuracy and efficiency of detecting CNVs and triploids by RAD-Seq were then assessed, compared with low-pass WGS. In our results, RAD-Seq detected 11 out of 11 (100%) chromosomal abnormalities, including 4 deletions and 1 aneuploidy in the purchased cell lines and all triploid samples. By contrast, these triploids were missed by low-pass WGS. Furthermore, RAD-Seq showed a higher resolution and more accurate allele frequency in the detection of triploids than low-pass WGS. Our study shows that, compared with low-pass WGS, RAD-Seq has relatively higher accuracy in CNV detection at a similar cost and is capable of identifying triploids. Therefore, the application of this technique in medical genetics has a significant potential value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000518930DOI Listing
October 2021

Transcriptome analysis of messenger RNA and long noncoding RNA related to different developmental stages of tail adipose tissues of sunite sheep.

Food Sci Nutr 2021 Oct 25;9(10):5722-5734. Epub 2021 Aug 25.

College of Food Science and Engineering Inner Mongolia Agricultural University Hohhot China.

The tail fat of sheep is the most typical deposited fat, and it can be widely used in human daily life, such as diet, cosmetics, and industrial raw materials. To understand the potential regulatory mechanism of different growth stages of tail fat in Sunite sheep, we performed high-throughput RNA sequencing to characterize the long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles of the sheep tail fat at the age of 6, 18, and 30 months. A total of 223 differentially expressed genes (DEGs) and 148 differentially expressed lncRNAs were found in the tail fat of 6-, 18-, and 30-month-old sheep. Based on functional analysis, we found that fat-related DEGs were mainly expressed at 6 months of age and gradually decreased at 18 and 30 months of age. The target gene prediction analysis shows that most of the lncRNAs target more than 20 mRNAs as their transregulators. Further, we obtained several fat-related differentially expressed target genes; these target genes interact with different differentially expressed lncRNAs at various ages and play an important role in the development of tail fat. Based on the DEGs and differentially expressed lncRNAs, we established three co-expression networks for each comparison group. Finally, we concluded that the development of the sheep tail fat is more active during the early stage of growth and gradually decreases with the increase in age. The mutual regulation of lncRNAs and mRNAs may play a key role in this complex biological process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/fsn3.2537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498062PMC
October 2021

Decorin Induces Cardiac Hypertrophy by Regulating the CaMKII/MEF-2 Signaling Pathway In Vivo.

Curr Med Sci 2021 Oct 13. Epub 2021 Oct 13.

Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Objective: Cardiac hypertrophy is an adaptive reaction of the heart against cardiac overloading, but continuous cardiac hypertrophy can lead to cardiac remodeling and heart failure. Cardiac hypertrophy is mostly considered reversible, and recent studies have indicated that decorin not only prevents cardiac fibrosis associated with hypertension, but also achieves therapeutic effects by blocking fibrosis-related signaling pathways. However, the mechanism of action of decorin remains unknown and unconfirmed.

Methods: We determined the degree of myocardial hypertrophy by measuring the ratios of the heart weight/body weight and left ventricular weight/body weight, histological analysis and immunohistochemistry. Western blotting was performed to detect the expression levels of CaMKII, p-CaMKII and MEF-2 in the heart.

Results: Our results confirmed that decorin can regulate the CaMKII/MEF-2 signaling pathway, with inhibition thereof being similar to that of decorin in reducing cardiac hypertrophy.

Conclusion: Taken together, the results of the present study showed that decorin induced cardiac hypertrophy by regulating the CaMKII/MEF-2 signaling pathway in vivo, revealing a new therapeutic approach for the prevention of cardiac hypertrophy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11596-021-2426-yDOI Listing
October 2021

Inducible Sbds Deletion Impairs Bone Marrow Niche Capacity to Engraft Donor Bone Marrow After Transplantation.

Blood Adv 2021 Oct 8. Epub 2021 Oct 8.

University of Pennsylvania, United States.

Bone marrow (BM) niche-derived signals are critical for facilitating engraftment after hematopoietic stem cell (HSC) transplantation (HSCT). HSCT is required for restoration of hematopoiesis in patients with inherited bone marrow failure syndromes (iBMFS). Shwachman-Diamond syndrome (SDS) is a rare iBMFS associated with mutations in SBDS. Previous studies have demonstrated that SBDS deficiency in osteolineage niche cells causes bone marrow dysfunction that promotes leukemia development. However, it is unknown whether BM niche defects caused by SBDS deficiency also impair efficient engraftment of healthy donor HSC following HSCT, a hypothesis that could explain morbidity seen after clinical HSCT for patients with SDS. Here, we report a mouse model with inducible Sbds deletion in hematopoietic and osteolineage cells. Primary and secondary BM transplantation (BMT) studies demonstrated that SBDS deficiency within BM niches caused poor donor hematopoietic recovery and specifically poor HSC engraftment after myeloablative BMT. We have additionally identified multiple molecular and cellular defects within niche populations that are driven by SBDS deficiency and that are accentuated or develop specifically following myeloablative conditioning. These abnormalities include altered frequencies of multiple niche cell subsets including mesenchymal lineage cells, macrophages and endothelial cells; disruption of growth factor signaling, chemokine pathway activation, and adhesion molecule expression; and p53 pathway activation, and signals involved in cell cycle arrest. Taken together, this study demonstrates that SBDS deficiency profoundly impacts recipient hematopoietic niche function in the setting of HSCT, suggesting that novel therapeutic strategies targeting host niches could improve clinical HSCT outcomes for patients with SDS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2021004640DOI Listing
October 2021

Overexpressed Smurf1 is degraded in glioblastoma cells through autophagy in a p62-dependent manner.

FEBS Open Bio 2021 Oct 6. Epub 2021 Oct 6.

School of Life Science, Beijing Institute of Technology, Beijing, China.

HECT-type E3 ubiquitin ligase Smurf1 was originally identified to ubiquitinate Smad protein in the TGF-β/BMP signaling pathway. Recently, Smurf1 has been reported to promote tumorigenesis by regulating multiple biological processes. High expression of Smurf1 plays a vital role in brain tumor progression by mediating aberrant cell signaling pathways. Previous reports have shown that Smurf1 is degraded mainly through the ubiquitin proteasome system, but it remains unclear whether Smurf1 is degraded by autophagy in tumor cells. In this study, we show that autophagy activators promote Smurf1 degradation in glioblastoma cells. The autophagy receptor p62 co-localizes with ubiquitinated substrates to promote sequestration of cytoplasm cargo into the autophagosome. We report that autophagic degradation of Smurf1 is dependent on p62. Moreover, the autophagic degradation of Smurf1 is prevented in the absence of the HECT domain or E3 ubiquitin ligase activity. We further proved that activation of autophagy leads to a decrease of Smurf1 and the inhibition of the PI3K/Akt signaling pathway in glioblastoma cells. Our results suggest that enhancement of autophagic degradation of Smurf1 may be a potential approach to treating glioblastoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/2211-5463.13310DOI Listing
October 2021

Exposure to carbon black nanoparticles during pregnancy aggravates lipopolysaccharide-induced lung injury in offspring: an intergenerational effect.

Am J Physiol Lung Cell Mol Physiol 2021 Sep 29. Epub 2021 Sep 29.

Molecular Biology Laboratory of Respiratory Disease, Institute of Life Sciences, Chongqing Medical University, Chongqing, China.

Carbon black nanoparticles (CBNPs) are one of the most frequently used nanoparticles. Exposure to CBNPs during pregnancy (PrE to CBNPs) can directly induce inflammation, lung injury and genotoxicity in dams, and results in abnormalities in offspring. However, whether exposure to CBNPs during pregnancy enhances the susceptibility of offspring to environmental stimuli remains unknown. To address this issue, in this study, we intranasally treated pregnant mice with mock or CBNPs from gestational day (GD) 9 to GD18, and F1 and F2 offspring were normally obtained. By intratracheal instillation of mice with lipopolysaccharide (LPS) to trigger a classic animal model for acute lung injury, we intriguingly found that after LPS treatment, F1 and F2 offspring after exposure during pregnancy to CBNPs both exhibited more pronounced lung injury symptoms, including more degenerative histopathological changes, vascular leakage, elevated MPO activity and activation of inflammation-related signaling transduction, compared to F1 and F2 offspring in the mock treatment group, suggesting PrE to CBNPs would aggravate LPS-induced lung injury in offspring, and this effect is intergenerational. We also observed that PrE to CBNPs upregulated the mRNA expression of DNA methyltransferases (Dnmt) 1/3a/3b and DNA hypermethylation in both F1 and F2 offspring, which might partially account for the intergenerational effect. Together, our study demonstrates for the first time that PrE to CBNPs can enhance sensitivity to LPS in both F1 and F2 offspring, and this intergenerational effect may be related to DNA hypermethylation caused by CBNPs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajplung.00545.2020DOI Listing
September 2021

miR-24 and its target gene Prdx6 regulate viability and senescence of myogenic progenitors during aging.

Aging Cell 2021 Oct 24;20(10):e13475. Epub 2021 Sep 24.

Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.

Satellite cell-dependent skeletal muscle regeneration declines during aging. Disruptions within the satellite cells and their niche, together with alterations in the myofibrillar environment, contribute to age-related dysfunction and defective muscle regeneration. In this study, we demonstrated an age-related decline in satellite cell viability and myogenic potential and an increase in ROS and cellular senescence. We detected a transient upregulation of miR-24 in regenerating muscle from adult mice and downregulation of miR-24 during muscle regeneration in old mice. FACS-sorted satellite cells were characterized by decreased levels of miR-24 and a concomitant increase in expression of its target: Prdx6. Using GFP reporter constructs, we demonstrated that miR-24 directly binds to its predicted site within Prdx6 mRNA. Subtle changes in Prdx6 levels following changes in miR-24 expression indicate miR-24 plays a role in fine-tuning Prdx6 expression. Changes in miR-24 and Prdx6 levels were associated with altered mitochondrial ROS generation, increase in the DNA damage marker: phosphorylated-H2Ax and changes in viability, senescence, and myogenic potential of myogenic progenitors from mice and humans. The effects of miR-24 were more pronounced in myogenic progenitors from old mice, suggesting a context-dependent role of miR-24 in these cells, with miR-24 downregulation likely a part of a compensatory response to declining satellite cell function during aging. We propose that downregulation of miR-24 and subsequent upregulation of Prdx6 in muscle of old mice following injury are an adaptive response to aging, to maintain satellite cell viability and myogenic potential through regulation of mitochondrial ROS and DNA damage pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acel.13475DOI Listing
October 2021

Early life stress induces anxiety-like behavior during adulthood through dysregulation of neuronal plasticity in the basolateral amygdala.

Life Sci 2021 Sep 15;285:119959. Epub 2021 Sep 15.

Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang 330031, China. Electronic address:

Aims: Early life stress (ELS) increases the risk of psychiatric diseases such as anxiety disorders and depression in later life. Hyperactivation of the basolateral amygdala (BLA) neurons plays a pivotal role in the pathogenesis of stress-related diseases. However, the functional roles of BLA neurons in ELS-induced anxiety disorders are not completely understood.

Main Methods: Mice were subjected to maternal separation (MS) during postnatal days 3 to 21 to mimic ELS. Anxiety-like behavior was tested by open field test (OFT), elevated plus maze (EPM), and novelty suppressed feeding (NSF). Then, c-fos expression, a proxy for neuronal activity, was evaluated by immunofluorescence. Finally, synaptic transmission and intrinsic excitability were measured by whole-cell patch-clamp recordings.

Key Findings: MS significantly increased anxiety-like behavior in adulthood, as indicated by less time spent in the center area of the OFT, less time spent in and fewer entries to the open arms of the EPM, and increased latency to feed in NSF. Mechanistically, MS increased the expression of c-fos in BLA. MS enhanced the excitatory, but not inhibitory, synaptic transmission onto BLA projection neurons (PNs), which was caused by enhanced presynaptic glutamate release. Moreover, MS also markedly increased the intrinsic neuronal excitability of BLA PNs, probably due to the reduced medium afterhyperpolarization (mAHP) in BLA PNs.

Significance: Our results suggest that the changes of neuronal activity and synaptic transmission in the BLA PNs may play a crucial role in ELS-induced anxiety-like behavior, and these findings provide new insights into the pathological mechanisms of stress-related anxiety disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2021.119959DOI Listing
September 2021

Association of Increased Amygdala Activity with Stress-Induced Anxiety but not Social Avoidance Behavior in Mice.

Neurosci Bull 2021 Sep 7. Epub 2021 Sep 7.

Laboratory of Fear and Anxiety Disorders, Institutes of Life Science, Nanchang University, Nanchang, 330031, China.

Chronic stress leads to many psychiatric disorders, including social and anxiety disorders that are associated with over-activation of neurons in the basolateral amygdala (BLA). However, not all individuals develop psychiatric diseases, many showing considerable resilience against stress exposure. Whether BLA neuronal activity is involved in regulating an individual's vulnerability to stress remains elusive. In this study, using a mouse model of chronic social defeat stress (CSDS), we divided the mice into susceptible and resilient subgroups based on their social interaction behavior. Using in vivo fiber photometry and in vitro patch-clamp recording, we showed that CSDS persistently (after 20 days of recovery from stress) increased BLA neuronal activity in all the mice regardless of their susceptible or resilient nature, although impaired social interaction behavior was only observed in susceptible mice. Increased anxiety-like behavior, on the other hand, was evident in both groups. Notably, the CSDS-induced increase of BLA neuronal activity correlated well with the heightened anxiety-like but not the social avoidance behavior in mice. These findings provide new insight to our understanding of the role of neuronal activity in the amygdala in mediating stress-related psychiatric disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12264-021-00762-0DOI Listing
September 2021

Optimization of heterogeneous Fenton-like process with [email protected] as catalyst for degradation of organic matter in leachate concentrate and degradation mechanism research.

Waste Manag 2021 Oct 25;134:220-230. Epub 2021 Aug 25.

College of Environmental and Energy Engineering, Beijing University of Technology, Beijing 100124, China.

The heterogeneous Fenton-like process with bimetallic chelated magnetic chitosan aerogel ([email protected]) as catalyst was applied to treat pre-coagulated leachate nanofiltration concentrate. The process conditions were optimized by Box-Behnken Design (BBD) and the maximum UV removal reached 96.06% under the conditions of temperature 87.62 °C, oxidant dosage 0.2395 mol/L and catalyst dosage 1 g/L. The TOC concentration was reduced from 847.5 to 99.7 mg/L and COD concentration was reduced from 1625 to 464 mg/L. The three-dimensional (3D) fluorescence analysis showed that most of Fulvic acid-like (FA-like) was removed. The adsorption experiment showed that the catalyst reached the adsorption balanced after 60 min and the corresponding FA adsorption removal reached 14.1%. The addition of Tert-butanol (TBA) reduced the FA removal by 59.4%, indicating that the hydroxyl radicals (OH) was the main active species. Experiments of the OH capture at different pH showed that the Fenton-like system produced more OH at pH of 4, at which the maximum FA removal was 96.61%, while the FA removal still reached 94.26% at pH of 7. The OH capture at different temperature showed that the Fenton-like system produced more OH at 90 °C. KI and TBA shielding experiments showed that OH was produced on the catalyst surface rather than being produced by catalysis of free metal ions in the solution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wasman.2021.08.021DOI Listing
October 2021

Impacts of depression subcase and case on all-cause mortality in older people: The findings from the multi-centre community-based cohort study in China.

Int J Geriatr Psychiatry 2021 Aug 13. Epub 2021 Aug 13.

Institute of Psychology, Health and Society, University of Liverpool, Liverpool, UK.

Objectives: It is unclear whether and to what extent depression subcases and cases in older age were associated with all-cause mortality. Little is known about gender differences in the associations. We assess these in older Chinese.

Methods: We examined a random sample of 6124 participants aged ≥60 years across five provinces in China. They were interviewed using a standard method of the GMS-AGECAT to diagnose depression subcase and case and record sociodemographic and disease risk factors at baseline, and to follow up their vital status. We employed Cox regression models to determine all-cause mortality in relation to depression subcases and cases, with adjustment for important variables, including social support and co-morbidities.

Results: Over the 10-year follow-up, 928 deaths occurred. Compared to those without depression at baseline, participants with depression subcase (n = 196) and case (n = 264) had increased risk of mortality; adjusted hazard ratios (HRs) were 1.46 (95% CI 1.07-2.00) and 1.45 (1.10-1.91). The adjusted HRs in men were 1.15 (0.72-1.81) and 1.85 (1.22-2.81), and in women 1.87 (1.22-2.87) and 1.22 (0.83-1.77) respectively. In participants aged ≥65 years, the adjusted HRs were 1.12 (0.68-1.84) and 1.99 (1.28-3.10) in men, and 2.06 (1.32-2.24) and 1.41 (0.94-2.10) in women. Increased HR in depression subcases was higher in women than man (ratio of HRs was 1.84, p = 0.034).

Conclusions: Older people with depression subcase could have increased all-cause mortality to a similar extent to those with depression case. More attention should be paid to subcases of depression in women to tackle gender inequalities and improve survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/gps.5611DOI Listing
August 2021

The construction of the structural equation model of burden, benefit finding, and anxiety-depression of esophageal cancer caregivers based on Lazarus stress and coping theory.

Ann Palliat Med 2021 Jul;10(7):7644-7652

Department of Nursing, Affiliated Hospital of Jiangnan University, Wuxi, China.

Background: A large number of studies have shown that the assignment of long-term care duties brings great pressure and negative emotions to caregivers of cancer patients, and also affects the quality of care. Lazarus and Folkman's stress and coping theory holds that the process of cognition and evaluation of stress is key to the stress response when a stressor acts on individuals. This study is to explore the mediating effect of benefit finding between caregiver burden and anxiety-depression of esophageal cancer caregivers, according to a model hypothesis constructed based on stress and coping theory. The design of this study involved correlation and theoretical testing using a structural equation model.

Methods: A total of 228 pairs of esophageal cancer patients from 2 tertiary hospitals and their family caregivers were recruited in this study from May 2020 to January 2021. A questionnaire survey was conducted using the general information questionnaire, the caregiver burden inventory (CBI), the benefit finding scale (BFS), and the hospital anxiety and depression scale (HADS).

Results: A good fitting model [chi-square (χ2)/degrees of freedom (df) =2.212, root mean square error of approximation (RMSEA) =0.07, comparative fit index (CFI) =0.976, Tucker-Lewis index (TLI) =0.964, goodness of fit (GFI) =0.954, normed fit index (NFI) =0.957] indicated the mediating effect of benefit finding between caregiver burden and anxiety-depression of esophageal cancer caregivers. A higher level of benefit finding had a negative effect on caregiver burden and anxiety-depression, which reduced the burden and psychological distress of caregivers. The theoretical hypothesis was validated.

Conclusions: Clinical nurses should pay attention to the benefit finding level of caregivers. For caregivers with low-level of benefit finding, intervention measures should be taken to improve the psychological cognitive level of caregivers, which can ultimately improve the quality of life of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-21-1466DOI Listing
July 2021

Identification of the Prognostic Signatures of Glioma With Different Status.

Front Oncol 2021 14;11:633357. Epub 2021 Jul 14.

School of Life Science, Beijing Institute of Technology, Beijing, China.

The high-grade glioma is characterized by cell heterogeneity, gene mutations, and poor prognosis. The deletions and mutations of the tumor suppressor gene (5%-40%) in glioma patients are associated with worse survival and therapeutic resistance. Characterization of unique prognosis molecular signatures by status in glioma is still unclear. This study established a novel risk model, screened optimal prognostic signatures, and calculated the risk score for the individual glioma patients with different status. Screening results revealed fourteen independent prognostic gene signatures in PTEN-wt and three in the -50PTEN-mut subgroup. Moreover, we verified risk score as an independent prognostic factor significantly correlated with tumor malignancy. Due to the higher malignancy of the PTEN-mut gliomas, we explored the independent prognostic signatures (, , and ) for a potential therapeutic target in PTEN-mut glioma. We further separated IDH wild-type glioma patients into GBM and LGG to verify the therapeutic target along with PTEN status, notably, the above screened therapeutic targets are also significant prognostic genes in both IDH-wt/PTEN-mut GBM and LGG patients. We further identified the small molecule compound (+)-JQ1 binds to all three targets, indicating a potential therapy for PTEN-mut glioma. In sum, gene signatures and risk scores in the novel risk model facilitate glioma diagnosis, prognosis prediction, and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.633357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317988PMC
July 2021

Glioblastoma Therapy: Rationale for a Mesenchymal Stem Cell-based Vehicle to Carry Recombinant Viruses.

Stem Cell Rev Rep 2021 Jul 28. Epub 2021 Jul 28.

School of Life Science, Beijing Institute of Technology, Beijing, 100811, China.

Evasion of growth suppression is among the prominent hallmarks of cancer. Phosphatase and tensin homolog (PTEN) and p53 tumor-suppressive pathways are compromised in most human cancers, including glioblastoma (GB). Hence, these signaling pathways are an ideal point of focus for novel cancer therapeutics. Recombinant viruses can selectivity kill cancer cells and carry therapeutic genes to tumors. Specifically, oncolytic viruses (OV) have been successfully employed for gene delivery in GB animal models and showed potential to neutralize immunosuppression at the tumor site. However, the associated systemic immunogenicity, inefficient transduction of GB cells, and inadequate distribution to metastatic tumors have been the major bottlenecks in clinical studies. Mesenchymal stem cells (MSCs), with tumor-tropic properties and immune privilege, can improve OVs targeting. Remarkably, combining the two approaches can address their individual issues. Herein, we summarize findings to advocate the reactivation of tumor suppressors p53 and PTEN in GB treatment and use MSCs as a "Trojan horse" to carry oncolytic viral cargo to disseminated tumor beds. The integration of MSCs and OVs can emerge as the new paradigm in cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12015-021-10207-wDOI Listing
July 2021

Therapeutic Perspective of Temozolomide Resistance in Glioblastoma Treatment.

Cancer Invest 2021 Sep 19;39(8):627-644. Epub 2021 Jul 19.

School of Life Science, Beijing Institute of Technology, Beijing, China.

Glioblastoma (GB) is the most lethal form of primary brain neoplasm. TMZ is the first-line standard treatment, but the strong resistance constrains the efficacy in clinical use. GB contains glioma stem cells (GSCs), which contribute to TMZ resistance, promote cell survival evolvement, and repopulate the tumor mass. This review summarizes the TMZ-resistance mechanisms and discusses several potential therapies from the conservative opinion of GSC-targeted therapy orientation to the current view of TMZ resistance-aimed efficacy, which will provide an understanding of the role of heterogeneity in drug resistance and improve therapeutic efficacy in general.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07357907.2021.1952595DOI Listing
September 2021

Identification of Novel Environmental Substances Relevant to Pediatric Graves' Disease.

Front Endocrinol (Lausanne) 2021 23;12:691326. Epub 2021 Jun 23.

Department of Endocrinology, Genetics and Metabolism, Children's Hospital of Soochow University, Suzhou, China.

Graves' disease (GD) is the most common cause of hyperthyroidism, yet a relatively rare disease in the pediatric population. GD is a complex disorder influenced by both genetic and environmental factors. In this study, we aimed to find new environmental factors influencing the pathogenesis of GD. We investigated serum substances in 30 newly diagnosed GD children and 30 age- and gender-matched healthy controls. We measured total iodine by inductively coupled plasma-mass spectrometry (ICP-MS), analyzed perfluorinated compounds ultra-high-performance liquid chromatography coupled with multiple reaction monitoring mass spectrometry (UHPLC-MRM-MS), and explored other environmental substances using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) analysis. Twenty-nine single-nucleotide polymorphisms (SNPs) in eight genes related to GD were analyzed by SNaPshot. The serum total iodine was significantly higher in GD group, but its association with GD onset was weak, only with Exp(B) value near 1. The perfluorinated compound levels were not different between the two groups. More importantly, we found 16 environmental substances significantly different between GD and control groups, among which ponasterone A is a risk factor ( = 0.007 and Exp(B) = 14.14), while confertifoline is a protective factor against GD onset ( = 0.002 and Exp(B) = 0.001). We also identified 10 substances correlated significantly with thyroid indices in GD patients, among which seven associated with levels of the thyroid autoantibody TPOAb. No known SNPs were found predisposing GD. In this study, we explored a broad variety of environmental substances and identified novel factors that are potentially involved in the pediatric GD pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2021.691326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261246PMC
June 2021

Postoperative pain treatment with transmuscular quadratus lumborum block and fascia iliaca compartment block in patients undergoing total hip arthroplasty: a randomized controlled trial.

BMC Anesthesiol 2021 07 10;21(1):188. Epub 2021 Jul 10.

Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, No.99, Huaihai West Road, Quanshan District, Jiangsu Province, 221000, China.

Background: Patients often suffer moderate or even severe pain after total hip arthroplasty; such pain seriously affects early postoperative recovery. This study aimed to investigate the analgesic efficacy of ultrasound-guided transmuscular quadratus lumborum block combined with fascia iliaca compartment block for elderly patients undergoing total hip arthroplasty.

Methods: Fifty-four patients scheduled for total hip arthroplasty were included in this randomized controlled study. The patients were randomly assigned to receive only transmuscular quadratus lumborum block (group Q) or transmuscular quadratus lumborum block combined with fascia iliaca compartment block (group QF) with ultrasound guidance. Postoperatively in both groups, paracetamol 1 g was regularly administered at 6 h intervals and patient-controlled intravenous analgesia was administered. The primary outcome was cumulative sufentanil consumption via patient-controlled intravenous analgesia 24 h postoperatively. The secondary outcomes included pain degree, time to the first analgesic requirement, joint range of motion, quality of recovery, and the incidence of postoperative complications.

Results: Fifty patients were included, and their data were analyzed. The cumulative sufentanil consumption in group QF was significantly lower during the first 24 h after surgery than that in group Q, and the cumulative sufentanil consumption in group QF was reduced at 6-12 and 12-18 h after surgery. The postoperative pain intensity was lower in group QF than in group Q (linear mixed-effects model, the main effect of treatment: P < 0.001). Compared with group Q, group QF had higher quality of recovery and joint range of movement. The time to the first analgesic requirement was longer in group QF than in group Q (log-rank, P < 0.001). There was no statistically significant difference in complications postoperatively between the two groups.

Conclusions: Our study provides a multimodal, opioid-sparing analgesic regimen for elderly patients undergoing total hip arthroplasty. The combination of transmuscular quadratus lumborum block and fascia iliaca compartment block provides a significant advantage for early postoperative functional recovery. Further studies are required to confirm the minimum effective dose.

Trial Registration: The study was registered on the 21st December 2020 (retrospectively registered) on the Chinese Clinical Trial Registry: ChiCTR2000038686 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12871-021-01413-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272275PMC
July 2021

Optimization of catalytic wet oxidating fulvic acid with zero-valent copper chitosan activated carbon ball as the catalyst.

Sci Rep 2021 07 7;11(1):13998. Epub 2021 Jul 7.

Faculty of Environment and Life, Beijing University of Technology, Beijing, 100124, China.

The degradation efficiency of fulvic acid (FA) was investigated in the catalytic wet oxidation process (CWPO) by zero-valent copper chitosan activated carbon ball (ZVC/CTS-ACB). Characterization of ZVC/CTS-ACB shows that zero-valent copper was loaded successfully on the chitosan activated carbon. Plackett-Buiman (PB) design and response surface methodology (RSM) were employed to determine the influence factors and the optimum processing parameters. The model was well fitted to the actual data and the correlation coefficients of R and R-adj were 0.9359 and 0.9039, respectively. Under the obtained optimum conditions for FA degradation: temperature = 94 °C and pH 3.8, the average FA removal by three replicate experiments was 93.02%, which has a high consistency to the RSM optimal target response of 93.86%. The comparison of catalytic performance showed that the addition of catalyst ZVC/CTS-ACS could increase the removal rate of FA, color number (CN) and TOC by 93.6%, 83.5% and 81.9% respectively. The high TOC removal rate indicated the good performance of the catalyst to FA mineralization. Additionally, the ICP analysis of copper ion leaching was only 0.08 mg/l after 5 repeated recycles of the catalyst, demonstrating the high stability of ZVC/CTS-ACB that is beneficial for the actual application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-92789-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263760PMC
July 2021

Propofol Mediated Protection of the Brain From Ischemia/Reperfusion Injury Through the Regulation of Microglial Connexin 43.

Front Cell Dev Biol 2021 8;9:637233. Epub 2021 Jun 8.

Department of Anesthesiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Cerebral ischemia/reperfusion (I/R) injury is a serious condition that leads to increased apoptosis of microglial and neurons in the brain. In this study, we identified that Cx43 expression level is significantly increased in the microglial cells during I/R injury. Using an model (hypoxia/reoxygenation-H/R injury), we observed that H/R injury leads to an increase in activation of microglial cells and increase in levels of pro-inflammatory markers such as IL-1β, IL-6, and TNF-α. Additionally, we could also observe significant increase in phosphorylation of Cx43 and Cav3.2 levels. To assess the role of H/R injured microglial cells on neuronal population, we cultured the neurons with conditioned media (MCS) from H/R injured microglial cells. Interestingly, we observed that microglial H/R injury significantly decreased Map2 expression and affected neuronal morphology. Further, we aimed to assess the effects of propofol on cerebral H/R injury, and observed that 40 μM propofol significantly decreased Cx43, Cx43 phosphorylation, and CaV3.2 levels. Additionally, propofol decreased apoptosis and increased Map2 expression levels in H/R injured neurons. Using silencing experiments, we confirmed that siCx43 could significantly improve the propofol's rescue after H/R injury in both microglia and neurons. We further developed an MCAO (middle cerebral artery occlusion) rat model to understand the effect of propofol in I/R injury. Interestingly, propofol treatment and downregulation of Cx43 significantly decreased the infract volume and apoptosis in these MCAO rats. Thus, this study clearly establishes that propofol protects the brain against I/R injury through the downregulation of Cx43 in microglial cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.637233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217990PMC
June 2021

Silicon dioxide nanoparticles induced neurobehavioral impairments by disrupting microbiota-gut-brain axis.

J Nanobiotechnology 2021 Jun 10;19(1):174. Epub 2021 Jun 10.

Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, People's Republic of China.

Background: Silicon dioxide nanoparticles (SiONPs) are widely used as additive in the food industry with controversial health risk. Gut microbiota is a new and hot topic in the field of nanotoxicity. It also contributes a novel and insightful view to understand the potential health risk of food-grade SiONPs in children, who are susceptible to the toxic effects of nanoparticles.

Methods: In current study, the young mice were orally administrated with vehicle or SiONPs solution for 28 days. The effects of SiONPs on the gut microbiota were detected by 16S ribosomal RNA (rRNA) gene sequencing, and the neurobehavioral functions were evaluated by open field test and Morris water maze. The level of inflammation, tissue integrity of gut and the classical indicators involved in gut-brain, gut-liver and gut-lung axis were all assessed.

Results: Our results demonstrated that SiONPs significantly caused the spatial learning and memory impairments and locomotor inhibition. Although SiONPs did not trigger evident intestinal or neuronal inflammation, they remarkably damaged the tissue integrity. The microbial diversity within the gut was unexpectedly enhanced in SiONPs-treated mice, mainly manifested by the increased abundances of Firmicutes and Patescibacteria. Intriguingly, we demonstrated for the first time that the neurobehavioral impairments and brain damages induced by SiONPs might be distinctively associated with the disruption of gut-brain axis by specific chemical substances originated from gut, such as Vipr1 and Sstr2. Unapparent changes in liver or lung tissues further suggested the absence of gut-liver axis or gut-lung axis regulation upon oral SiONPs exposure.

Conclusion: This study provides a novel idea that the SiONPs induced neurotoxic effects may occur through distinctive gut-brain axis, showing no significant impact on either gut-lung axis or gut-liver axis. These findings raise the exciting prospect that maintenance and coordination of gastrointestinal functions may be critical for protection against the neurotoxicity of infant foodborne SiONPs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12951-021-00916-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194163PMC
June 2021

Autophagy deficiency exacerbates acute lung injury induced by copper oxide nanoparticles.

J Nanobiotechnology 2021 May 31;19(1):162. Epub 2021 May 31.

Molecular Biology Laboratory of Respiratory Diseases, Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, People's Republic of China.

Copper oxide nanoparticles (CuONPs) are one of the widely used metal nanoparticles in the industrial and commercial fields. Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome and has been linked to nanoparticles-induced toxicity. In particular, the roles of autophagy in response to CuONPs have been explored in vitro, although the conclusions are controversial. To clarify the role of autophagy in CuONPs-induced acute lung injury, microtubule-associated protein 1 light chain 3 beta (Map1lc3b or lc3b) knockout mice and their corresponding wild type mice are applied. Our results showed that single-dose intratracheal instillation of CuONPs with dosages of 1.25, 2.5 or 5 mg/kg caused acute lung injury 3 days after treatment in a dose-dependent manner, as evidenced by deteriorative lung histopathology, more infiltration of macrophage cells, increased oxidative stress and copper ions. Loss of lc3b resulted in aggravated lung injury induced by CuONPs, which was probably due to the blockade of mitophagy and consequently the accumulation of aberrant mitochondria with overloaded copper ions. Our study provides the first in vivo evidence that autophagy deficiency exacerbates CuONPs-induced acute lung injury, and highlights that targeting autophagy is a meaningful strategy against CuONPs-associated respiratory toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12951-021-00909-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166141PMC
May 2021

Optimizing conditioning regimen with low-dose irradiation or busulfan enables the outcome of transplantation from a 6-7/8 HLA-matched donor comparable to that from an 8/8 HLA-matched unrelated donor in severe aplastic anemia patients under 40 years.

Ann Hematol 2021 Sep 14;100(9):2363-2373. Epub 2021 May 14.

Department of Hematology and Oncology, National Children's Medical Center, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai, 200127, China.

With the dramatic improvements in outcomes following alternative donor hematopoietic stem cell transplantation (HSCT), interest in the use of alternative donors in severe aplastic anemia (SAA) is increasing. We conducted a multicenter prospective study to explore the efficiency and safety of upfront HSCT from a 6-8/8 HLA-matched unrelated donor (MUD) or 6-7/8 HLA-matched related donor (MRD) in acquired SAA patients under 40 years. Between August 2014 and July 2017, 115 patients were enrolled, including 48 (41.7%) patients receiving grafts from an 8/8 MUD, 25 (21.7%) from a 6-7/8 MRD, and 42 (36.5%) from a 6-7/8 MUD. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was higher in the 6-7/8 MUD group than in the 8/8 MUD group (42.9% vs. 12.8%, P=0.001). The corresponding incidence in the 6-7/8 MRD group was comparable to that in the 8/8 MUD group (21.7% vs. 12.8%, P=0.332). There was no significant difference in the incidence of chronic GVHD (24.3%, 13.6%, and 17.9%, P=0.676), graft failure (2.4%, 8.0%, and 6.3%, P=0.551), overall survival (85.7%, 96.0%, and 87.5%, P=0.424), and failure-free survival (83.3%, 88.0%, and 83.3%, P=0.885) among the three groups (6-7/8 MUD, 6-7/8 MRD, and 8/8 MUD). In multivariate analysis, conditioning regimen without low-dose irradiation or busulfan was associated with an inferior failure-free survival (HR=2.973, P=0.042). In conclusion, after an intensified conditioning regimen with additional low-dose irradiation or busulfan, the outcome of HSCT from a 6-7/8 MRD or 6-7/8 MUD is comparable to that from an 8/8 MUD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-021-04540-wDOI Listing
September 2021

Stabilization of Nrf2 leading to HO-1 activation protects against zinc oxide nanoparticles-induced endothelial cell death.

Nanotoxicology 2021 08 10;15(6):779-797. Epub 2021 May 10.

Institute of Life Sciences, Chongqing Medical University, Chongqing, People's Republic of China.

With the abundant production and wide application of zinc oxide nanoparticles (ZnONPs), the potential health risks of ZnONPs have raised serious concerns. Oxidative stress is recognized as the most important outcome of the toxicity induced by ZnONPs. The Nrf2-Keap1 system and its downstream antioxidative genes are the fundamental protective mechanisms for redox hemeostasis. However, the detailed mechanisms of Nrf2 activation in ZnONPs-treated endothelial cells and murine blood vessels have yet to be elucidated. Herein, we show that Nrf2 was activated and played a negative role in cell death induced by ZnONPs. Moreover, we demonstrate that HO-1 was the most extensively upregulated antioxidative gene-activated by Nrf2. Forced overexpression of HO-1, pharmacological activation of HO-1 with the agonists RTA-408 (omaveloxolone, an FDA-approved drug) and RTA-402 repressed cell death, and treatment with HO-1 antagonist SnPP exacerbated the cell death. Importantly, loss of HO-1 diminished the cytoprotective role induced by Nrf2 in ZnONPs-treated HUVEC cells, indicating that the Nrf2-HO-1 axis was the crucial regulatory mechanism for the antioxidative response in the context of ZnONPs-induced endothelial damage. Mechanistically, we demonstrate that the p62-Keap1 axis was not involved in the activation of Nrf2. Intriguingly, the degradation half-life of Nrf2 in HUVEC cells was increased from less than 1 h under quiescent conditions to approximately 6 h under ZnONPs treatment condition; moreover, ZnONPs treatment induced activation of Nrf2/HO-1 and accumulation of ubiquitin in the aorta ventralis of mouse, suggesting that the ubiquitin-proteasome system had been perturbed, which subsequently led to the stabilization of Nrf2 and activation of HO-1. This study might contribute to a better understanding of ZnONPs-associated toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17435390.2021.1919330DOI Listing
August 2021

miR-4456/CCL3/CCR5 Pathway in the Pathogenesis of Tight Junction Impairment in Chronic Obstructive Pulmonary Disease.

Front Pharmacol 2021 19;12:551839. Epub 2021 Apr 19.

Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Cigarette smoke exposure (CSE) is a major cause of chronic obstructive pulmonary disease (COPD). The smoke disrupts cell-cell adhesion by inducing epithelial barrier damage to the tight junction (TJ) proteins. Even though the inflammatory mechanism of chemokine (C-C motif) ligand 3 (CCL3) in COPD has gained increasing attention in the research community, however, the underlying signaling pathway, remains unknown. To identify the relationship of CCL3 in the pathogenesis of tight junction impairment in COPD and the pathway through which CSE causes damage to TJ in COPD via CCL3, both and . We screened the inflammatory factors in the peripheral blood mononuclear cells (PBMCs) from healthy controls and patients at each GOLD 1-4 stage of chronic obstructive pulmonary disease. RT-PCR, western blot, and ELISA were used to detect the levels of CCL3, ZO-1, and occludin after Cigarette smoke exposure. Immunofluorescence was applied to examine the impairment of the TJs in 16-HBE and A549 cells. The reverse assay was used to detect the effect of a CCR5 antagonist (DAPTA) in COPD. In the CSE-induced COPD mouse model, H&E staining and lung function tests were used to evaluate the pathological and physical states in each group. Immunofluorescence was used to assess the impairment of TJs in each group. ELISA and RT-PCR were used to examine the mRNA or protein expression of CCL3 or miR-4456 in each group. The and results showed that CCL3 expression was increased in COPD compared with healthy controls. CCL3 caused significant injury to TJs through its C-C chemokine receptor type 5 (CCR5), while miR-4456 could suppress the effect of CCL3 on TJs by binding to the 3'-UTR of CCL3. miR-4456/CCL3/CCR5 pathway may be a potential target pathway for the treatment of COPD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.551839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089484PMC
April 2021

The Expression of Three Negative Co-Stimulatory B7 Family Molecules in Small Cell Lung Cancer and Their Effect on Prognosis.

Front Oncol 2021 15;11:600238. Epub 2021 Apr 15.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: In recent years, immune checkpoint inhibitors have shown significant effects in a variety of solid tumors. However, due to the low incidence of small cell lung cancer (SCLC) and its unclear mechanism, immune checkpoints in SCLC have not been fully studied.

Methods: We evaluated the expression of PD-L1, B7-H3, and B7-H4 in 115 SCLC tissue specimens using immunohistochemistry. The clinical data of patients with SCLC were retrospectively reviewed to investigate three negative co-stimulatory B7 family molecules' ability to affect the prognosis of SCLC.

Results: Among the SCLC patients with complete follow-up data (n = 107), sixty-nine (64.49%) expressed moderate to high B7-H3 levels, which correlated positively with tumor sizes ( < 0.001). Eighty (74.77%) patients expressed moderate to high B7-H4 levels, which correlated positively with metastases ( = 0.049). The positive expression of B7-H3 and B7-H4 correlated significantly with shortened overall survival (OS) (B7-H3, = 0.006; B7-H4, = 0.019). PD-L1 was positively expressed only in 13.08% of cancer tissues, and there was no significant correlation with prognosis. The Cox proportional hazards regression showed that B7-H3 was an independent prognostic indicator of OS ( = 0.028; HR = 2.125 [95% CI = 0.985-4.462]).

Conclusions: Our results suggest that B7-H3 has a negative predictive effect on SCLC. This outcome provides a theoretical basis for the subsequent research on immune checkpoint inhibitors targeting B7-H3.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.600238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082063PMC
April 2021

Corrigendum to "Cannabidiol inhibits febrile seizure by modulating AMPA receptor kinetics through its interaction with the N-terminal domain of GluA1/GluA2" [Pharmacol. Res. 161 (2020) 105128 1-14].

Pharmacol Res 2021 Jun 21;168:105468. Epub 2021 Apr 21.

Department of Pharmacology of Chinese Materia Medica, Institution of Chinese Integrative Medicine, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei Province, 050017, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2021.105468DOI Listing
June 2021

Measurement of expansion factor and distortion for expansion microscopy using isolated renal glomeruli as landmarks.

J Biophotonics 2021 07 27;14(7):e202100001. Epub 2021 Apr 27.

Institute for Advanced Study, Soochow University, Suzhou, China.

Expansion microscopy has enabled super resolution imaging of biological samples. The accurate measurement of expansion factor and distortion typically requires locating and imaging the same region of interest in the sample before and after expansion, which is often time-consuming to achieve. Here we introduce a convenient method for relocation by utilizing isolated porcine glomeruli as landmarks during expansion. Following heat denaturation and proteinase K digestion protocols, the glomeruli exhibit expansion factor of 3.5 to 4 (only 7%-16% less expanded than the hydrogel), and 1% to 2% of relative distortion. Due to its appropriate size of 100 to 300 μm, the location of the glomerulus in the sample are visible to eyes, while its detailed shape only requires bright field microscopy. For expansion factors ranging from 3 to 10, the region in the vicinity of the glomerulus can be easily re-identified, and sometimes allows quantification of expansion factor and distortion under bright field without fluorescent labels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbio.202100001DOI Listing
July 2021

Ferritinophagy is involved in the zinc oxide nanoparticles-induced ferroptosis of vascular endothelial cells.

Autophagy 2021 Apr 12:1-20. Epub 2021 Apr 12.

College of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China.

Zinc oxide nanoparticles (ZnONPs) hold great promise for biomedical applications. Previous studies have revealed that ZnONPs exposure can induce toxicity in endothelial cells, but the underlying mechanisms have not been fully elucidated. In this study, we report that ZnONPs can induce ferroptosis of both HUVECs and EA.hy926 cells, as evidenced by the elevation of intracellular iron levels, lipid peroxidation and cell death in a dose- and time-dependent manner. In addition, both the lipid reactive oxygen species (ROS) scavenger ferrostatin-1 and the iron chelator deferiprone attenuated ZnONPs-induced cell death. Intriguingly, we found that ZnONPs-induced ferroptosis is macroautophagy/autophagy-dependent, because the inhibition of autophagy with a pharmacological inhibitor or by gene knockout profoundly mitigated ZnONPs-induced ferroptosis. We further demonstrated that NCOA4 (nuclear receptor coactivator 4)-mediated ferritinophagy (autophagic degradation of the major intracellular iron storage protein ferritin) was required for the ferroptosis induced by ZnONPs, by showing that knockdown can reduce the intracellular iron level and lipid peroxidation, and subsequently alleviate ZnONPs-induced cell death. Furthermore, we showed that ROS originating from mitochondria (mtROS) probably activated the AMPK-ULK1 axis to trigger ferritinophagy. Most importantly, pulmonary ZnONPs exposure caused vascular inflammation and ferritinophagy in mice, and ferrostatin-1 supplementation significantly reversed the vascular injury induced by pulmonary ZnONPs exposure. Overall, our study indicates that ferroptosis is a novel mechanism for ZnONPs-induced endothelial cytotoxicity, and that NCOA4-mediated ferritinophagy is required for ZnONPs-induced ferroptotic cell death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15548627.2021.1911016DOI Listing
April 2021
-->