Publications by authors named "Yan Sun"

2,582 Publications

  • Page 1 of 1

SLC6A8-mediated intracellular creatine accumulation enhances hypoxic breast cancer cell survival via ameliorating oxidative stress.

J Exp Clin Cancer Res 2021 May 14;40(1):168. Epub 2021 May 14.

Department of Endocrine and Breast Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, #1 You-Yi Rd., Yu-zhong District, Chongqing, 400016, China.

Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with poor prognosis and limited treatment options. Hypoxia is a key hallmark of TNBC. Metabolic adaptation promotes progression of TNBC cells that are located within the hypoxic tumor regions. However, it is not well understood regarding the precise molecular mechanisms underlying the regulation of metabolic adaptions by hypoxia.

Methods: RNA sequencing was performed to analyze the gene expression profiles in MDA-MB-231 cell line (20% O and 1% O). Expressions of Slc6a8, which encodes the creatine transporter protein, were detected in breast cancer cells and tissues by quantitative real-time PCR. Immunohistochemistry was performed to detect SLC6A8 protein abundances in tumor tissues. Clinicopathologic correlation and overall survival were evaluated by chi-square test and Kaplan-Meier analysis, respectively. Cell viability assay and flow cytometry analysis with Annexin V/PI double staining were performed to investigate the impact of SLC6A8-mediated uptake of creatine on viability of hypoxic TNBC cells. TNBC orthotopic mouse model was used to evaluate the effects of creatine in vivo.

Results: SLC6A8 was aberrantly upregulated in TNBC cells in hypoxia. SLC6A8 was drastically overexpressed in TNBC tissues and its level was tightly associated with advanced TNM stage, higher histological grade and worse overall survival of TNBC patients. We found that SLC6A8 was transcriptionally upregulated by p65/NF-κB and mediated accumulation of intracellular creatine in hypoxia. SLC6A8-mediated accumulation of creatine promoted survival and suppressed apoptosis via maintaining redox homeostasis in hypoxic TNBC cells. Furthermore, creatine was required to facilitate tumor growth in xenograft mouse models. Mechanistically, intracellular creatine bolstered cell antioxidant defense by reducing mitochondrial activity and oxygen consumption rates to reduce accumulation of intracellular reactive oxygen species, ultimately activating AKT-ERK signaling, the activation of which protected the viability of hypoxic TNBC cells via mediating the upregulation of Ki-67 and Bcl-2, and the downregulation of Bax and cleaved Caspase-3.

Conclusions: Our study indicates that SLC6A8-mediated creatine accumulation plays an important role in promoting TNBC progression, and may provide a potential therapeutic strategy option for treatment of SLC6A8 high expressed TNBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13046-021-01933-7DOI Listing
May 2021

Biochemical and metabolic responses of the deep-sea mussel Bathymodiolus platifrons to cadmium and copper exposure.

Aquat Toxicol 2021 May 2;236:105845. Epub 2021 May 2.

Center of Deep Sea Research, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China; CAS Key Laboratory of Marine Ecology and Environmental Sciences, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao 266071, China; University of Chinese Academy of Sciences, Beijing 10049, China. Electronic address:

Greater interest in commercial deep-sea mining has been accompanied by mounting environmental concerns, including metal contamination resulting from mining activities. However, little is known about the toxic effects of metal exposure on deep-sea life. Given its ability to accumulate metals from the surrounding environment, its wide distribution at both vents and seeps, and its high abundance, the deep-sea mussel Bathymodiolus platifrons could serve as an ideal model to investigate the toxicological responses of deep-sea organisms to metal exposure. Here, we evaluated metal accumulation, traditional metal-related biomarkers, namely acid phosphatase (ACP), alkaline phosphatase (AKP), superoxide dismutase, catalase, reduced glutathione, metallothioneins, and malondialdehyde, as well as metabolic profiles in the gills of B. platifrons after a 7-day exposure to copper (100 μg/L), cadmium (500 μg/L), or copper-plus-cadmium treatments (100 μg/L Cu and 500 μg/L Cd). Metal exposure concentrations selected in this study can be found in deep-sea hydrothermal environments. Metal exposure resulted in significant metal accumulation in the gills of the mussel, indicating that B. platifrons has promise for use as an indicator of deep-sea metal pollution levels. Traditional biomarkers (AKP, ACP, and measured antioxidants) revealed cellular injury and oxidative stress in mussels following metal exposure. Metabolic responses in the three treatment groups indicated that metal exposure perturbed osmoregulation, energy metabolism, and nucleotide metabolism in mussels, in a response marked by differentially altered levels of amino acids, hypotaurine, betaine, succinate, glucose 6-phosphate, fructose 6-phosphate, guanosine, guanosine 5'-monophosphate, and inosine. Nevertheless, several uniquely altered metabolites were found in each treatment exposure group, suggesting dissimilar modes of toxicity between the two metal types. In the Cd-exposed group, the monosaccharide D-allose, which is involved in suppressing mitochondrial ROS production, was downregulated, a response consistent with oxidative stress in Cd-exposed B. platifrons. In the Cu-exposed group, the detected alterations in dopamine, dopamine-related, and serotonin-related metabolites together suggest disturbed neurotransmission in Cu-exposed B. platifrons. In the Cu-plus-Cd group, we detected a decline in fatty acid levels, implying that exposure to both metals jointly exerted a negative influence on the physiological functioning of the mussel. To the best of our knowledge, this is the first study to investigate changes in metabolite profiles in Bathymodiolus mussels exposed to metal. The findings reported here advance our understanding of the adverse impact of metal exposure on deep-sea life and can inform deep-sea mining assessments through the use of multiple biomarkers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aquatox.2021.105845DOI Listing
May 2021

MicroRNA‑198 suppresses tumour growth and metastasis in oral squamous cell carcinoma by targeting CDK4.

Int J Oncol 2021 Jul 13;59(1). Epub 2021 May 13.

Department of Emergency and Oral Medicine, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning 110002, P.R. China.

MicroRNAs (miRNAs/miR) often contribute to the progression of oral squamous cell carcinoma (OSCC) via the regulation of mRNA. The present study aimed to investigate the role of miR‑198 in OSCC pathogenesis and explore the underlying mechanism. Reverse transcription‑quantitative (RT‑q)PCR was performed to determine miR‑198 expression in OSCC tissues and cell lines, and univariate and multivariate analyses were applied to evaluate the survival of patients with OSCC. The effects of miR‑198 on OSCC cell lines were studied and . A set of epithelial‑mesenchymal transition (EMT) markers were detected to determine whether miR‑198 was involved in EMT. Lastly, using luciferase assays, a novel target of miR‑198 was identified and the effect of the new target gene of miR‑198 on cell proliferation and invasion was also studied. It was identified that miR‑198 expression was decreased in OSCC tissues and cell lines, and low expression of miR‑198 was associated with poor overall survival and disease‑free survival. Overexpression of miR‑198 appeared to significantly inhibit the proliferation, invasion and EMT of OSCC cells. Moreover, the luciferase assay results showed that miR‑198 interacted with cyclin‑dependent kinase 4 (CDK4) by directly targeting the miRNA‑binding site in the CDK4 sequence, and RT‑qPCR results showed that CDK4 expression was increased in OSCC tissues and cell lines. In addition, transfection of small interfering RNA against CDK4 in OSCC cells showed similar inhibitory effects on cell proliferation, invasion and EMT, whereas CDK4 overexpression in OSCC cells partially reversed the inhibitory effects of the miR‑198 mimic. The present results indicated that miR‑198 suppressed OSCC tumour growth and metastasis by directly targeting CDK4 expression. Thus, miR‑198 may be a potential therapeutic target in the treatment of OSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ijo.2021.5219DOI Listing
July 2021

Intrauterine Hypoxia Changed the Colonization of the Gut Microbiota in Newborn Rats.

Front Pediatr 2021 26;9:675022. Epub 2021 Apr 26.

Department of Neonatology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Accumulating evidence suggests a connection between the gut microbiota and neonatal diseases. Hypoxia may play an important role in the intestinal lesions in neonates. This study aims to determine whether the gut microbiota differs between intrauterine hypoxic rats and healthy controls and to identify the factors that influence the changes in the gut microbiota. We constructed an intrauterine hypoxia model in rats and collected the intestinal contents of intrauterine hypoxic newborn rats and normal newborn rats within 4 h and on the seventh day after birth. They were divided them into the intrauterine hypoxia first-day group (INH1), intrauterine hypoxia seventh-day group (INH7), normal first-day group (NOR1), and normal seventh-day group (NOR7). The contents of the intestines were sequenced with 16S rRNA sequencing, the sequencing results were analyzed for biological information, and the differences in the diversity, richness, and individual taxa among the groups were analyzed. The abundance of the gut microbiota of neonatal rats with intrauterine hypoxia was higher than that of the control group rats. Intrauterine hypoxia altered the structural composition of the gut microbiota in neonatal rats. The INH1 group showed increased species richness, phylogenetic diversity, and β-diversity, and altered relative abundance in several taxa compared to those in the control group. The differences in the microbiota among the four groups were significantly higher than those within the group, and the differences in the abundance and diversity of the INH7 and NOR7 groups decreased after 7 days of suckling. Functional analysis based on the Cluster of Orthologous Groups (COG) suggested that 23 functional COG categories. There was no significant difference in the functional categories between the hypoxia group and the normal group. Intrauterine hypoxia changed the initial colonization of the gut microbiota in neonatal rats. It could increase the species richness and β-diversity of the gut microbiota, and altered relative abundances of several taxa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2021.675022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107277PMC
April 2021

Effects of oral contraceptive for different responder women before GnRH antagonists: a systematic review and meta-analysis.

Gynecol Endocrinol 2021 May 11:1-10. Epub 2021 May 11.

The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning, PR China.

This analysis aimed to compare the efficacy of oral contraceptive pill (OCP) pretreatment for gonadotropin-releasing hormone antagonist (GnRH-ant) protocol, especially for different responder women. The PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) databases were searched for trials on with and without OCP pretreatment before stimulation with gonadotropins. The standardized mean differences (SMDs) or pooled risk ratios (RRs) with 95% confidence intervals (CIs) were used for statistical analysis. Fifteen studies with 5326 fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were summarized. The clinical pregnancy rate, moderate or severe ovarian hyper-stimulation syndrome (OHSS) rate, and miscarriage rate was not found to be significantly different between patients with and those without OCP pretreatment, even after sensitivity analyses. In addition, there were still no statistically significant differences for the subgroups analyses of hyper-responders, poor responders, and normal responders. No significant differences were detected in the duration of ovarian stimulation, gonadotropin dose consumed, endometrial thickness on day of oocyte collection, or number of oocytes. This meta-analysis did not find an unequivocally beneficial effect of OCP pretreatment for different responder women with using a GnRH-ant protocol. The clinician should weigh the advantages and disadvantages of OCP pretreatment and guide the treatment scheduling considering the patient's own situation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09513590.2021.1918664DOI Listing
May 2021

Automatic Discoid Lateral Meniscus Diagnosis from Radiographs Based on Image Processing Tools and Machine Learning.

J Healthc Eng 2021 20;2021:6662664. Epub 2021 Apr 20.

The Digital ART Lab of School of Software, Shanghai JiaoTong University, Shanghai 200240, China.

The aim of the present study is to build a software implementation of a previous study and to diagnose discoid lateral menisci on knee joint radiograph images. A total of 160 images from normal individuals and patients who were diagnosed with discoid lateral menisci were included. Our software implementation includes two parts: preprocessing and measurement. In the first phase, the whole radiograph image was analyzed to obtain basic information about the patient. Machine learning was used to segment the knee joint from the original radiograph image. Image enhancement and denoising tools were used to strengthen the image and remove noise. In the second phase, edge detection was used to quantify important features in the image. A specific algorithm was designed to build a model of the knee joint and measure the parameters. Of the test images, 99.65% were segmented correctly. Furthermore, 97.5% of the tested images were segmented correctly and their parameters were measured successfully. There was no significant difference between manual and automatic measurements in the discoid (=0.28) and control groups (=0.15). The mean and standard deviations of the ratio of lateral joint space distance to the height of the lateral tibial spine were compared with the results of manual measurement. The software performed well on raw radiographs, showing a satisfying success rate and robustness. Thus, it is possible to diagnose discoid lateral menisci on radiographs with the help of radiograph-image-analyzing software (BM3D, etc.) and artificial intelligence-related tools (YOLOv3). The results of this study can help build a joint database that contains data from patients and thus can play a role in the diagnosis of discoid lateral menisci and other knee joint diseases in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6662664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081628PMC
April 2021

Long-term safety, efficacy, and tolerability of levetiracetam in pediatric patients with epilepsy in Uygur, China: A retrospective analysis.

Epilepsy Behav 2021 May 5;120:108010. Epub 2021 May 5.

Department of Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Province 830001, China; Institute of Clinical Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Province 830001, China. Electronic address:

Purpose: Levetiracetam is approved as an add-on therapy to treat refractory partial seizures in pediatric patients over four years old. The efficacy and safety in pediatric patients with epilepsy in Uygur, China, is unknown. Therefore, the objective of this study was to investigate the safety, efficacy, and tolerability of levetiracetam in pediatric patients with epilepsy in Uygur, China.

Methods: This retrospective study compared the efficacy and safety of levetiracetam monotherapy and in combination with other antiseizure medications (ASMs) in 1055 pediatric patients with epilepsy treated with levetiracetam. The seizure frequencies at 1, 2, and 3 years after starting levetiracetam therapy were recorded and compared with the baseline yearly frequency. Safety variables included the incidence and type of adverse reactions.

Results: A total of 680 (64%) pediatric patients responded to levetiracetam therapy with a more than 50% reduction in the frequency of seizures. Seizure-free rates increased over time, 13%, 15%, and 18% at 1, 2, and 3 years, respectively. The number of baseline ASMs and the order of levetiracetam introduction were highly significant, impacting the likelihood of seizure remission during a 3-year follow-up period (p < 0.001). During levetiracetam treatment, 233 pediatric patients (22%) experienced at least one adverse reaction.

Conclusion: These significant findings indicate that levetiracetam is likely to become a widely prescribed ASM for epilepsy in pediatric clinical practice because of its long-term safety, efficacy, and tolerability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2021.108010DOI Listing
May 2021

Meta-analysis: Interleukin 6 gene -174G/C polymorphism associated with type 2 diabetes mellitus and interleukin 6 changes.

J Cell Mol Med 2021 May 7. Epub 2021 May 7.

Department of Biochemistry and Molecular Biology, Qiqihar Medical University, Qiqihar, China.

The gene coding interleukin 6 (IL-6) is a promising candidate in predisposition to type 2 diabetes mellitus (T2DM). This study aimed to meta-analytically examine the association of IL-6 gene -174G/C polymorphism with T2DM and circulating IL-6 changes across -174G/C genotypes. Odds ratio (OR) and standard mean difference (SMD) with 95% confidence interval (CI) were calculated. Twenty-five articles were meta-analysed, with 20 articles for T2DM risk and 9 articles for circulating IL-6 changes. Overall, there was no detectable significance for the association between -174G/C polymorphism and T2DM, and this association was relatively obvious under dominant model (OR: 0.82, 95% CI: 0.56-1.21). Improved heterogeneity was seen in some subgroups, with statistical significance found in studies involving subjects of mixed races (OR: 0.63, 95% CI: 0.46-0.86). Begg's and filled funnel plots, along with Egger's tests revealed week evidence of publication bias. In genotype-phenotype analyses, carriers of -174CC and -174CG genotypes separately had 0.10 and 0.03 lower concentrations (pg/mL) of circulating IL-6 than -174GG carriers. Albeit no detectable significance for the association of -174G/C with T2DM, our findings provided suggestive evidence on a dose-dependent relation between -174G/C mutant alleles and circulating IL-6 concentrations, indicating possible implication of this polymorphism in the pathogenesis of T2DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.16575DOI Listing
May 2021

Systematic Identification of Survival-Associated Alternative Splicing Events in Kidney Renal Clear Cell Carcinoma.

Comput Math Methods Med 2021 19;2021:5576933. Epub 2021 Apr 19.

Laboratory of Tissue and Cell Biology, Experimental Teaching and Management Center, Chongqing Medical University, Chongqing, China.

There is growing evidence that aberrant alternative splicing (AS) is highly correlated with driving tumorigenesis, but its function in kidney renal clear cell carcinoma (KIRC) remains to be discovered. In this study, we obtained the level-3 RNA sequencing and clinical data of KIRC from The Cancer Genome Atlas (TGCA). Combining with the splicing event detail information from TGCA SpliceSeq database, we established the independent prognosis signatures for KIRC with the univariate and multivariate Cox regression analyses. Then, we used the Kaplan-Meier analysis and receiver operating characteristic curves (ROCs) to assess the accuracy of prognosis signatures. We also constructed the regulatory network of splicing factors (SFs) and AS events. Our results showed that a total of 12029 survival-associated AS events of 5761 genes were found in 524 KIRC patients. All types of prognosis signatures displayed a satisfactory ability to reliably predict, especially in exon skip model which the area under curve of ROC was 0.802. Moreover, 18 splicing factors (SFs) highly correlated to AS events were identified. With the construction of the SF-AS interactive network, we found that SF powerfully promotes the occurrence of abnormal AS and may have a profound role in KIRC. Collectively, we screened survival-associated AS events and established prognosis signatures for KIRC, coupling with the SF-AS interactive network, which might provide a key perspective to clarify the potential mechanism of AS in KIRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5576933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075682PMC
April 2021

In situ electrokinetic (EK) remediation of the total and plant available cadmium (Cd) in paddy agricultural soil using low voltage gradients at pilot and full scales.

Sci Total Environ 2021 Apr 23;785:147277. Epub 2021 Apr 23.

Faculty of Biological and Environmental Sciences, Ecosystems and Environment Research Programme, University of Helsinki, Niemenkatu 73, FI-15140 Lahti, Finland; Natural Resources Institute Finland Luke, Itäinen Pitkäkatu 4A, 20520 Turku, Finland. Electronic address:

Electrokinetic (EK) remediation has been widely studied at laboratory scales. However, field-scale research is far less. In this study, a 14-day EK remediation was carried out, in a field pilot (4 m) test and a full-scale (200 m) application for the first time, in a cadmium (Cd) contaminated paddy agricultural field near a mining area. A low voltage of 20 V was applied at both scales; voltage gradient was 20 V m and 4 V m at the pilot and full scales, respectively. Samples were taken from near the anode and cathode, and in the middle of the electric field, in the soil layers 0-10 cm, 10-20 cm, and 40-50 cm. After the EK remediation, a significant portion of the total Cd was removed in all the layers at the pilot scale, by 87%, 72%, and 54% from the top down, but only in the 0-10 cm layer at the full scale by 74%. As for the plant available (exchangeable and soluble) Cd, significant removal (64%) was only observed in the 0-10 cm layer at the pilot scale. The percentage reduction of the electrical conductivity and removal efficiency of the total Cd was higher near the anode than the cathode. The soil pH was elevated near the cathode but stayed below pH 6 due to the sufficient supply of lactic acid. After the EK remediation, the concentration of the total Cd dropped below the hazard threshold, i.e. 0.4 mg (kg dry wt soil) for agricultural paddy fields in China. A total energy of 2 kW·h and 0.6 kW·h was consumed at the pilot and full scales, respectively. This study showed a successful in situ EK remediation of Cd contaminated paddy agricultural soil, especially in the surface layer, with low voltage and energy demand.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.147277DOI Listing
April 2021

Jianpi Jieyu Decoction, An Empirical Herbal Formula, Exerts Psychotropic Effects in Association With Modulation of Gut Microbial Diversity and GABA Activity.

Front Pharmacol 2021 14;12:645638. Epub 2021 Apr 14.

Key Laboratory of Integrative Biomedicine of Brain Diseases, Nanjing University of Chinese Medicine, Nanjing, China.

Recent studies suggest that gut microbiota was associated with the bidirectional gut-brain axis which could modulate neuropsychological functions of the central nervous system. Gut microbiota could produce gamma aminobutyric acid (GABA) that could modulate the gut-brain axis response Jianpi Jieyu (JPJY) decoction, a traditional Chinese formula, is mainly composed of and Radix . Although the JPJY decoction has been used to treat the depression in China, the potential action of its antidepressant has not been well understood. Thus this study was aim to investigate the role of JPJY improve gut microbiota homeostasis in the chronic stress induced depressive mice. The antidepressant effect of JPJY on chronic unpredictable mild stress (CUMS) mice was evaluated by using sucrose preference test, tail suspension test and forced swim test. Fatigue-like behaviors were evaluated using degree of redness, grip strength test, and exhaustive swimming test. The new object recognition test was used to evaluate cognition performance. Fecal samples were collected and taxonomical analysis of intestinal microbial distribution was conducted with 16S rDNA. Serum level of GABA was measured using high performance liquid chromatography (HPLC). The expression of GluR1 and p-Tau protein in the hippocampus was determined using Western blotting. The dose of 9.2 g/kg JPJY produced antidepressant-like effects. JPJY and its major components also modulated gut microbiota diversity in the CUMS mice. Serum level of GABA and the expressions of hippocampal GluR1 and p-Tau were reversed after the administration of JPJY in CUMS mice. JPJY regulates gut microbiota to produce antidepressant-like effect and improve cognition deficit in depressive mice while its molecular mechanism possibly be enhanced NR1 and Tau expression in hippocampus and increased GABA in serum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.645638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079981PMC
April 2021

Physiological characterization of chitin synthase A responsible for the biosynthesis of cuticle chitin in Culex pipiens pallens (Diptera: Culicidae).

Parasit Vectors 2021 May 1;14(1):234. Epub 2021 May 1.

Department of Pathogen Biology, Nanjing Medical University, Nanjing, China.

Background: The pathogens transmitted by mosquitoes to humans and animals cause several emerging and resurgent infectious diseases. Increasing insecticide resistance requires rational action to control the target vector population. Chitin is indispensable for insect growth and development and absent from vertebrates and higher plants. Chitin synthase A (CHSA) is a crucial enzyme in chitin synthesis; therefore, identifying and characterizing how CHSA determines chitin content may contribute to the development of novel vector control strategies.

Results: The injection of small interfering RNA targeting CHSA (siCHSA) to knockdown CHSA transcripts in larval, pupal and adult stages of Culex pipiens pallens resulted in the appearance of different lethal phenotypes. When larval and pupal stages were injected with siCHSA, CHSA knockdown prevented larval molting, pupation and adult eclosion, and affected the production of chitin and chitin degradation, which resulted in an ecdysis defect phenotype of mosquitoes. When siCHSA was injected into mosquitoes in the adult stage, CHSA knockdown also affected the laminar organization of the mesoderm and the formation of pseudo-orthogonal patterns of the large fibers of the endoderm.

Conclusion: We provide a systematic and comprehensive description of the effects of CHSA on morphogenesis and metamorphosis. The results show that CHSA not only affects chitin synthesis during molting, but also might be involved in chitin degradation. Our results further show that CHSA is important for the structural integrity of the adult mosquito cuticle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13071-021-04741-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088658PMC
May 2021

Four new polyacetylenes from the roots of .

Nat Prod Res 2021 Jan 10:1-8. Epub 2021 Jan 10.

Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, P.R. China.

Four new polyacetylene substances, sadivaethynes A-D, were isolated from the ethanol extract of the roots of (Turcz.) Schischk using repeated column chromatography. Structural elucidation of compounds was established by 1D and 2D NMR spectra referring to the literature, together with high-resolution mass spectrometric analysis. All compounds were evaluated for cytotoxicity against two human cancer cell lines (MGC-803, Ishikawa) .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14786419.2020.1869973DOI Listing
January 2021

Enhancing Hydrodeoxygenation of Bio-oil via Bimetallic Ni-V Catalysts Modified by Cross-Surface Migrated-Carbon from Biochar.

ACS Appl Mater Interfaces 2021 May 30;13(18):21482-21498. Epub 2021 Apr 30.

College of Materials and Energy, South China Agricultural University, Guangzhou 510640, China.

Aromatics from selective hydrodeoxygenation (HDO) of biomass-derived bio-oil are an ideal feedstock for replacing industrial fossil products. In this study, biochar-modified Hβ/Ni-V catalysts were prepared and tested in the atmospheric HDO of guaiacol and bio-oil to produce aromatics. Compared with unmodified Hβ/Ni-V, higher HDO activity was achieved in catalysts with all kinds of biochar modifications. Especially, the pine nut shell biochar (PB)-modified PB-Hβ-8/Ni-V showed the highest selectivity to aromatics (69.17%), mainly including benzene and toluene. Besides, under the conditions of 380 °C and weight hourly space velocity (WHSV) of 0.5 h, the cleavage of C-OH (C means the carbon in the benzene ring) was promoted to form more aromatics. Moreover, great recyclability (58.77% aromatics for the reactivated run-3 test) and efficient HDO of bio-oil (44.9% aromatic yield) were also achieved. Based on the characterization results, the enhanced aromatic selectivity of PB-Hβ-8/Ni-V was attributed to the synergetic effect between PB and Hβ/Ni-V. In detail, a stable surface migrated-carbon layer was formed on Hβ/Ni-V via the metal catalytic chemical vapor deposition (CVD) process of the pyrolysis PB volatiles. Simultaneously, a carbothermal reduction driven by the migrated-carbon took place to decorate the surface metals, obtaining more Ni and V active sites. With this synergism, increased Ni sites promoted H adsorption and dissociation, which improved the hydrogenation activity. Furthermore, the higher affinity of the reactant and increased oxygen vacancies both contributed to enhancing the selective surface adsorption of oxygenous groups and the cleavage of the C-OH bond, thus improving the deoxygenation activity. Therefore, the HDO activity was improved to form more target aromatics over biochar-modified catalysts. This work highlighted a potential avenue to develop economic and environmental catalysts for the upgrading of bio-oil.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c05350DOI Listing
May 2021

Clinical Efficacy and Safety of Zoledronic Acid Combined with PVP/PKP in the Treatment of Osteoporotic Vertebral Compression Fracture: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Biomed Res Int 2021 8;2021:6650358. Epub 2021 Apr 8.

Department of Orthopaedics, China-Japan Friendship Hospital, Beijing 100029, China.

Objective: We conducted this meta-analysis to provide better evidence of the efficacy and safety of zoledronic acid (ZA) combined with percutaneous vertebroplasty/kyphoplasty (PVP/PKP) on osteoporotic vertebral compression fracture (OVCF) and proposed a protocol for its application in clinical practice.

Methods: All randomized controlled trials (RCTs) of ZA combined with PVP or PKP compared to individual PVP/PKP for the management of patients with OVCFs were included in this study. Electronic database searches were conducted from database inception to November 2020, including the Cochrane Library, PubMed, Web of Science, and Embase. The pooled data were analyzed using RevMan 5.3 software.

Results: Seven RCTs with 929 subjects were finally included. All included studies reported visual analog scores (VAS), and no statistically significant differences were identified at follow-ups of 3 d and 1 w ( > 0.05). In contrast, significant differences were observed at the 1 mo, 3 mo, 6 mo, and 12 mo follow-ups ( < 0.05). Two trials reported the Cobb angle and vertebral body height (VBH), including 182 subjects without significant differences at the 12 mo follow-up ( > 0.05). In addition, significant differences in the bone mineral density (BMD), -isomerized C-terminal telopeptide of type I collagen (-CTX), N-terminal propeptide of type I collagen (PINP), and N-terminal molecular fragment (N-MID) levels were observed between the two groups ( < 0.05). All trials reported side effects. Significant differences in recurrent fractures, fever, flu-like symptoms, and arthralgia or myalgia were identified ( < 0.05); however, no significant difference in postoperative leakage was detected ( > 0.05).

Conclusion: Compared to PVP/PKP alone, an additional ZA injection had advantages of long-term analgesic effects with improved bone metabolism indexes. Moreover, combination therapy significantly prevented complications and drug reactions were well tolerated. Overall, this systematic review revealed that ZA combined with PVP/PKP was an effective, safe, and comprehensive therapy for patients with OVCFs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6650358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049795PMC
April 2021

Silencing of CD147 inhibits hepatic stellate cells activation related to suppressing aerobic glycolysis via hedgehog signaling.

Cytotechnology 2021 Apr 18;73(2):233-242. Epub 2021 Feb 18.

Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Medical University, Xi'an, 710077 Shaanxi China.

Hepatic stellate cells (HSCs) activation is a key step that promotes hepatic fibrosis. Emerging evidence suggests that aerobic glycolysis is one of its important metabolic characteristics. Our previous study has reported that CD147, a glycosylated transmembrane protein, contributes significantly to the activation of HSCs. However, whether and how it is involved in the aerobic glycolysis of HSCs activation is unknown. The objective of the present study was to validate the effect of CD147 in HSCs activation and the underlying molecular mechanism. Our results showed that the silencing of CD147 decreased the expression of α-smooth muscle-actin (α-SMA) and collagen I at both mRNA and protein levels. Furthermore, CD147 silencing decreased the glucose uptake, lactate production in HSCs, and repressed the lactate dehydrogenase (LDH) activity, the expression of hexokinase 2 (HK2), glucose transporter 1 (Glut1). The effect of galloflavin, a well-defined glycolysis inhibitor, was similar to CD147 siRNA. Mechanistically, CD147 silencing suppressed glycolysis-associated HSCs activation through inhibiting the hedgehog signaling. Moreover, the hedgehog signaling agonist SAG could rescue the above effect of CD147 silencing. In conclusion, CD147 silencing blockade of aerobic glycolysis via suppression of hedgehog signaling inhibited HSCs activation, suggesting CD147 as a novel therapeutic target for hepatic fibrosis.

Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-021-00460-9.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10616-021-00460-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035397PMC
April 2021

Alantolactone inhibits cervical cancer progression by downregulating BMI1.

Sci Rep 2021 Apr 29;11(1):9251. Epub 2021 Apr 29.

Hubei Clinical Research Center for Parkinson's Disease at Xiangyang No. 1 People's Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, 442000, People's Republic of China.

Cervical cancer is the second most common cancer in women. Despite advances in cervical cancer therapy, tumor recurrence and metastasis remain the leading causes of mortality. High expression of BMI1 is significantly associated with poor tumor differentiation, high clinical grade, and poor prognosis of cervical cancer, and is an independent prognostic factor in cervical carcinoma. Alantolactone (AL), a sesquiterpene lactone, exhibits potent anti-inflammatory and anticancer activities. In this paper, we investigated the mechanism of AL in reducing the proliferation, migration, and invasion of HeLa and SiHa cervical cancer cells as well as its promotion of mitochondrial damage and autophagy. BMI1 silencing decreased epithelial-mesenchymal transformation-associated proteins and increased autophagy-associated proteins in HeLa cells. These effects were reversed by overexpression of BMI1 in HeLa cells. Thus, BMI1 expression is positively correlated with invasion and negatively correlated with autophagy in HeLa cells. Importantly, AL decreased the weight, volume, and BMI1 expression in HeLa xenograft tumors. Furthermore, the structure of BMI1 and target interaction of AL were virtually screened using the molecular docking program Autodock Vina; AL decreased the expression of N-cadherin, vimentin, and P62 and increased the expression of LC3B and Beclin-1 in xenograft tumors. Finally, expression of BMI1 increased the phosphorylation of STAT3, which is important for cell proliferation, survival, migration, and invasion. Therefore, we suggest that AL plays a pivotal role in inhibiting BMI1 in the tumorigenesis of cervical cancer and is a potential therapeutic agent for cervical cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-87781-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085045PMC
April 2021

New insights into hallux valgus by whole exome sequencing study.

Exp Biol Med (Maywood) 2021 Apr 29:15353702211008641. Epub 2021 Apr 29.

Department of Cell Biology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.

The traditional view is that the occurrence and development of hallux valgus (HV) are mainly due to environmental factors. Recent studies have suggested the large contribution of genetic heritability to HV, but it remains elusive about the genetic variants underlying the development of HV. To gain knowledge about the molecular mechanisms of HV pathogenesis by genetic approach, whole exome sequencing studies were performed in 10 individuals (7 affected by HV and 3 unaffected) from three independent families. Specific mutations were found to be related to the pathogenesis of HV and conform to the laws of inheritance. A total of 36 genes with functional candidate single nucleotide variants were identified. Genetic predisposition plays an important role in the development of HV. Interestingly, some of these genes are related to chronic arthritis, such as the complement encoding gene , or are related to long toe or long fingers, such as , , , , and . This study identified rare potentially pathogenic mutations represented by genes related to digital anomalies and chronic arthritis underlying the familial types of HV, which acquired new insights into the genetic and physiological foundations of HV, thereby might improve accurate prevention and drug development for HV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/15353702211008641DOI Listing
April 2021

Associations between Genetically Predicted Circulating Protein Concentrations and Endometrial Cancer Risk.

Cancers (Basel) 2021 Apr 26;13(9). Epub 2021 Apr 26.

Population Sciences in the Pacific Program, Cancer Epidemiology Division, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI 96813, USA.

Endometrial cancer (EC) is the leading female reproductive tract malignancy in developed countries. Currently, genome-wide association studies (GWAS) have identified 17 risk loci for EC. To identify novel EC-associated proteins, we used previously reported protein quantitative trait loci for 1434 plasma proteins as instruments to evaluate associations between genetically predicted circulating protein concentrations and EC risk. We studied 12,906 cases and 108,979 controls of European descent included in the Endometrial Cancer Association Consortium, the Epidemiology of Endometrial Cancer Consortium, and the UK Biobank. We observed associations between genetically predicted concentrations of nine proteins and EC risk at a false discovery rate of <0.05 (-values range from 1.14 × 10 to 3.04 × 10). Except for vascular cell adhesion protein 1, all other identified proteins were independent from known EC risk variants identified in EC GWAS. The respective odds ratios (95% confidence intervals) per one standard deviation increase in genetically predicted circulating protein concentrations were 1.21 (1.13, 1.30) for DNA repair protein RAD51 homolog 4, 1.27 (1.14, 1.42) for desmoglein-2, 1.14 (1.07, 1.22) for MHC class I polypeptide-related sequence B, 1.05 (1.02, 1.08) for histo-blood group ABO system transferase, 0.77 (0.68, 0.89) for intestinal-type alkaline phosphatase, 0.82 (0.74, 0.91) for carbohydrate sulfotransferase 15, 1.07 (1.03, 1.11) for D-glucuronyl C5-epimerase, and 1.07 (1.03, 1.10) for CD209 antigen. In conclusion, we identified nine potential EC-associated proteins. If validated by additional studies, our findings may contribute to understanding the pathogenesis of endometrial tumor development and identifying women at high risk of EC along with other EC risk factors and biomarkers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13092088DOI Listing
April 2021

Influence of psychological nursing and health education on depression, anxiety and life quality of elderly patients with lung cancer.

Psychogeriatrics 2021 Apr 29. Epub 2021 Apr 29.

Nursing Department, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: To explore and analyze the influence of psychological nursing and health education on depression, anxiety and life quality of elderly patients with lung cancer.

Methods: There were 84 elderly patients with lung cancer who were admitted and treated in our hospital since July 2018 till July 2019, serving as the objects of observation. The selected patients were divided into the control group (n = 42) and the observation group in principle of random allocation by computer numbers. Routine care was conducted to the control group, while psychological nursing and health education were implemented to the observation group, so as to compare the improvement effect of depression, anxiety, life quality and compliance on the two groups of patients before/after the two different nursing methods were adopted for intervention.

Results: Hamilton Depression Scale and Hamilton Anxiety Scale scores in the observation group were lower than those in the control group, and the levels of various pulmonary function indicators including degree of blood oxygen saturation, forced expiratory volume in 1 second, forced vital capacity and maximum ventilatory capacity and quality of life scores were significantly improved; compared with the control group, the total compliance of the observation group was significantly increased, and the difference between the two groups was statistically significant (P < 0.05).

Conclusion: The psychological nursing and health education implemented for elderly patients with lung cancer will improve patients' bad mood effectively, enhance life quality and perfect prognosis for patients, maintaining significant value in clinical application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/psyg.12700DOI Listing
April 2021

A preclinical study: correlation between PD-L1 PET imaging and the prediction of therapy efficacy of MC38 tumor with Ga-labeled PD-L1 targeted nanobody.

Aging (Albany NY) 2021 Apr 27;13. Epub 2021 Apr 27.

Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250017, P.R. China.

Although immunotherapy has achieved great clinical success in clinical outcomes, especially the anti-PD-1 or anti-PD-L1 antibodies, not all patients respond to anti-PD-1 immunotherapy. It is urgently required for a clinical diagnosis to develop non-invasive imaging meditated strategy for assessing the expression level of PD-L1 in tumors. In this work, a Ga-labeled single-domain antibody tracer, Ga-NOTA-Nb109, was designed for specific and noninvasive imaging of PD-L1 expression in an MC38 tumor-bearing mouse model. Comprehensive studies including Positron Emission Tomography (PET), biodistribution, blocking studies, immunohistochemistry, and immunotherapy, have been performed in differences PD-L1 expression tumor-bearing models. These results revealed that Ga-NOTA-Nb109 specifically accumulated in the MC38-hPD-L1 tumor. The content of this nanobody in MC38 hPD-L1 tumor and MC38 Mixed tumor was 8.2 ± 1.3, 7.3 ± 1.2, 3.7 ± 1.5, 2.3 ± 1.2%ID/g and 7.5 ± 1.4, 3.6 ± 1.7, 1.7 ± 0.6, 1.2 ± 0.5%ID/g at 0.5, 1, 1.5, 2 hours post-injection, respectively. Ga-NOTA-Nb109 has the potential to further noninvasive PET imaging and therapy effectiveness assessments based on the PD-L1 status in tumors. To explore the possible synergistic effects of immunotherapy combined with chemotherapy, MC38 xenografts with different sensitivity to PD-L1 blockade were established. In addition, we found that PD-1 blockade also had efficacy on the PD-L1 knockout tumors. RT-PCR and immunofluorescence analysis were used to detect the expression of PD-L1. It was observed that both mouse and human PD-L1 expressed among three types of MC38 tumors. These results suggest that PD-L1 on tumor cells affect the efficacy, but it on host myeloid cells might be essential for checkpoint blockade. Moreover, anti-PD-1 treatment activates tumor-reactive CD103 CD39 CD8+T cells (TILs) in tumor microenvironment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202981DOI Listing
April 2021

Attitude change after a curriculum on the science and philosophy of well-being and happiness for high school students: A classroom-randomized trial.

Br J Educ Psychol 2021 Apr 24:e12419. Epub 2021 Apr 24.

Department of Psychology, Beijing High School #19, Beijing, China.

Background: Multiple interventions have been tested to promote well-being in high school students, often focusing on depression prevention.

Aims: To test the impact of a one-semester active learning curriculum covering the modern science and philosophy of well-being and happiness on attitudinal measures related to the curriculum and standard measures of depression and well-being.

Sample: Subjects were first-year students in an urban high school in Beijing, China (equivalent to US tenth grade).

Methods: Nine classrooms were randomly assigned to the intervention curriculum (n = 252), and nine classrooms were randomly assigned to a traditional psychology curriculum (n = 263). Students completed questionnaires pre- and post-semester including a Positive Attitude Scale (PAS, concerning Relatedness, Competence, Autonomy, Gratitude, Calmness, Mindfulness, and Hope), Positive and Negative Affect Scale (PANAS), Centers for Epidemiological Studies Depression Scale (CES-D), Life Satisfaction Scale (LS), Subjective Happiness Scale (SHS), Meaning in Life Questionnaire (MLQ), and a test of knowledge about well-being (Knowledge Test, KT).

Results: In a hierarchical linear model, there were statistically significant intervention effects on six of the seven subscales of the PAS, on PANAS balance, and on the KT. CES-D, LS, SHS, and MLQ were improved but not significantly so. Notable overall secular trends in measures of well-being were observed, with a peak in September and nadir in April.

Conclusions: A one-semester course for high school students regarding well-being and happiness demonstrated significant changes in positive attitudes, affective balance, and knowledge about happiness. Circannual trends in well-being measures over the academic year have implications for those designing school intervention studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjep.12419DOI Listing
April 2021

DNA Methylation, Preterm Birth and Blood Pressure in African American Children: The DPREG Study.

J Immigr Minor Health 2021 Apr 22. Epub 2021 Apr 22.

Center for Research on People of Color, Columbia University School of Nursing, 560 W 168th St, New York, NY, 10032, USA.

Preterm birth (< 37 weeks) has been associated with high blood pressure (BP) and cardiovascular disease in adulthood. Epigenetic mechanisms may explain how preterm birth influences later BP. In this study, we examined the association between DNA methylation (DNAm), preterm birth and BP in African American children. We recruited 100 children and collected clinical and birth history data. DNA was extracted from saliva and the Illumina EPIC BeadChip was used for epigenetic analyses. Preterm birth was not associated with systolic or diastolic BP. No significant DNAm sites were associated with preterm birth in candidate gene methylation analyses. Body mass index was associated with systolic BP (p = 0.01). We did not observe an effect of preterm birth on DNAm or BP in early childhood. Our study is one of the few, however, to examine these associations among African Americans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10903-021-01201-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060901PMC
April 2021

Experimental and theoretical assessment of protonated Hoogsteen 9-methylguanine-1-methylcytosine base-pair dissociation: kinetics within a statistical reaction framework.

Phys Chem Chem Phys 2021 Apr;23(15):9365-9380

Department of Chemistry and Biochemistry, Queens College of the City University of New York, 65-30 Kissena Blvd., Queens, NY 11367, USA. and Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, 365 5th Ave., New York, NY 10016, USA.

We investigated the collision-induced dissociation (CID) reactions of a protonated Hoogsteen 9-methylguanine-1-methylcytosine base pair (HG-[9MG·1MC + H]+), which aims to address the mystery of the literature reported "anomaly" in product ion distributions and compare the kinetics of a Hoogsteen base pair with its Watson-Crick isomer WC-[9MG·1MC + H]+ (reported recently by Sun et al.; Phys. Chem. Chem. Phys., 2020, 22, 24986). Product ion cross sections and branching ratios were measured as a function of center-of-mass collision energy using guided-ion beam tandem mass spectrometry, from which base-pair dissociation energies were determined. Product structures and energetics were assessed using various theories, of which the composite DLPNO-CCSD(T)/aug-cc-pVTZ//ωB97XD/6-311++G(d,p) was adopted as the best-performing method for constructing a reaction potential energy surface. The statistical Rice-Ramsperger-Kassel-Marcus theory was found to provide a useful framework for rationalizing the dominating abundance of [1MC + H]+ over [9MG + H]+ in the fragment ions of HG-[9MG·1MC + H]+. The kinetics analysis proved the necessity for incorporating into kinetics modeling not only the static properties of reaction minima and transition states but more importantly, the kinetics of individual base-pair conformers that have formed in collisional activation. The analysis also pinpointed the origin of the statistical kinetics of HG-[9MG·1MC + H]+vs. the non-statistical behavior of WC-[9MG·1MC + H]+ in terms of their distinctively different intra-base-pair hydrogen-bonds and consequently the absence of proton transfer between the N1 position of 9MG and the N3' of 1MC in the Hoogsteen base pair. Finally, the Hoogsteen base pair was examined in the presence of a water ligand, i.e., HG-[9MG·1MC + H]+·H2O. Besides the same type of base-pair dissociation as detected in dry HG-[9MG·1MC + H]+, secondary methanol elimination was observed via the SN2 reaction of water with nucleobase methyl groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cp06682fDOI Listing
April 2021

UNC13B variants associated with partial epilepsy with favourable outcome.

Brain 2021 Apr 20. Epub 2021 Apr 20.

Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

The unc-13 homolog B (UNC13B) gene encodes a presynaptic protein, mammalian uncoordinated 13-2 (Munc13-2), that is highly expressed in the brain-predominantly in the cerebral cortex-and plays an essential role in synaptic vesicle priming and fusion, potentially affecting neuronal excitability. However, the functional significance of UNC13B mutation in human disease is not known. In this study we screened for novel genetic variants in a cohort of 446 unrelated cases (families) with partial epilepsy without acquired causes by trio-based whole-exome sequencing. UNC13B variants were identified in 12 individuals affected by partial epilepsy and/or febrile seizures from eight unrelated families. The eight probands all had focal seizures and focal discharges in EEG recordings, including two patients who experienced frequent daily seizures and one who showed abnormalities in the hippocampus by brain MRI; however, all of the patients showed favorable outcome without intellectual or developmental abnormalities. The identified UNC13B variants included one nonsense variant, two variants at or around a splice site, one compound heterozygous missense variant, and four missense variants that cosegregated in the families. The frequency of UNC13B variants identified in the present study was significantly higher than that in a control cohort of Han Chinese and controls of the East Asian and all populations in the Genome Aggregation Database. Computational modeling, including hydrogen bond and docking analyses, suggested that the variants lead to functional impairment. In Drosophila, seizure rate and duration were increased by Unc13b knockdown compared to wild-type flies, but these effects were less pronounced than in sodium voltage-gated channel alpha subunit 1 (Scn1a) knockdown Drosophila. Electrophysiologic recordings showed that excitatory neurons in Unc13b-deficient flies exhibited increased excitability. These results suggest that UNC13B is potentially associated with epilepsy. The frequent daily seizures and hippocampal abnormalities but ultimately favorable outcome under antiepileptic therapy in our patients indicate that partial epilepsy caused by UNC13B variant is a clinically manageable condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/awab164DOI Listing
April 2021

Induced pluripotent stem cells from subjects with Lesch-Nyhan disease.

Sci Rep 2021 Apr 19;11(1):8523. Epub 2021 Apr 19.

Department of Neurology, Emory University School of Medicine, 101 Woodruff Circle, 6305 Woodruff Memorial Building, Atlanta, GA, 30322, USA.

Lesch-Nyhan disease (LND) is an inherited disorder caused by pathogenic variants in the HPRT1 gene, which encodes the purine recycling enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt). We generated 6 induced pluripotent stem cell (iPSC) lines from 3 individuals with LND, along with 6 control lines from 3 normal individuals. All 12 lines had the characteristics of pluripotent stem cells, as assessed by immunostaining for pluripotency markers, expression of pluripotency genes, and differentiation into the 3 primary germ cell layers. Gene expression profiling with RNAseq demonstrated significant heterogeneity among the lines. Despite this heterogeneity, several anticipated abnormalities were readily detectable across all LND lines, including reduced HPRT1 mRNA. Several unexpected abnormalities were also consistently detectable across the LND lines, including decreases in FAR2P1 and increases in RNF39. Shotgun proteomics also demonstrated several expected abnormalities in the LND lines, such as absence of HGprt protein. The proteomics study also revealed several unexpected abnormalities across the LND lines, including increases in GNAO1 decreases in NSE4A. There was a good but partial correlation between abnormalities revealed by the RNAseq and proteomics methods. Finally, functional studies demonstrated LND lines had no HGprt enzyme activity and resistance to the toxic pro-drug 6-thioguanine. Intracellular purines in the LND lines were normal, but they did not recycle hypoxanthine. These cells provide a novel resource to reveal insights into the relevance of heterogeneity among iPSC lines and applications for modeling LND.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-87955-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055678PMC
April 2021

Sex-disparities in risk factors and atherosclerosis cardiovascular disease in diabetic patients.

Postgrad Med 2021 Apr 26:1-5. Epub 2021 Apr 26.

Department of Endocrinology, Third People's Hospital of Huizhou, Huizhou, China.

: The current study was to evaluate risk factors and atherosclerotic cardiovascular disease (ASCVD) among diabetic patients by sex.: Patients with type 2 diabetes mellitus were enrolled, and baseline characteristics and prevalent ASCVD (including coronary heart disease [CHD], ischemic stroke [IS], and peripheral vascular disease [PVD]) were collected and compared by sex.: Females accounted for 48.5% (n = 284) of the current study. Compared to males, females had a longer duration of diabetes mellitus (9.1 ± 4.0 vs 8.0 ± 3.7 years), and were more likely to be obese (38% vs 34.4%), have hypertension (49.3% vs 45.7%) and have a lower estimated glomerular filtration rate (75.0 ± 20.6 vs 77.4 ± 19.2 ml/min/1.73 m). Females were less likely to smoke (2.8% vs 31.1%), and receive anti-platelets (53.5% vs 56%), angiotensin converting enzyme inhibitor/angiotensin receptor blocker (31.7% vs 35.1%), and metformin (81.7% vs 85.4%). Females had a higher prevalence of CHD (9.9% vs 8.6%) and composite ASCVD (21.8% vs 18.9%). After adjustment for potential covariates, female sex remained independently associated with composite ASCVD (odds ratio [OR]: 1.21 and 95% confidence interval [CI]: 1.05-1.57) and CHD (OR: 1.13 and 95% CI: 1.01-1.38).: Among diabetic people, compared to males, females had a higher comorbid burden but received less optimal treatment, which might partly explain their higher prevalence of composite ASCVD and CHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00325481.2021.1917930DOI Listing
April 2021

HMGB1 Promotes the Release of Sonic Hedgehog From Astrocytes.

Front Immunol 2021 1;12:584097. Epub 2021 Apr 1.

Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

High mobility group box 1 protein (HMGB1) is known to be a trigger of inflammation in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, it may play a different role in some way. Here we investigated the effect of HMGB1 on promoting sonic hedgehog (shh) release from astrocytes as well as the possible signal pathway involved in it. Firstly, shh increased in astrocytes after administration of recombinant HMGB1 or decreased after HMGB1 was blocked when stimulated by homogenate of the onset stage of EAE. Moreover, the expression of HMGB1 receptors, toll-like receptor (TLR) 2 and receptor for advanced glycation end products (RAGE) increased after HMGB1 administration in primary astrocytes. However, the enhancing effect of HMGB1 on shh release from astrocytes was suppressed only after RAGE was knocked out or blocked. Mechanistically, HMGB1 functioned by activating RAGE-mediated JNK, p38, stat3 phosphorylation. Moreover, HMGB1 could induce shh release in EAE. Additionally, intracerebroventricular injection of recombinant shh protein on the onset stage of EAE alleviated the progress of disease and decreased demylination, compared to the mice with normal saline treatment. Overall, HMGB1 promoted the release of shh from astrocytes through signal pathway JNK, p38 and stat3 mediated by receptor RAGE, which may provide new insights of HMGB1 function in EAE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.584097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047406PMC
April 2021

Asthma does not influence the severity of COVID-19: a meta-analysis.

J Asthma 2021 Apr 23:1-7. Epub 2021 Apr 23.

Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.

Objective: Previous studies have reported a correlation between coronavirus disease-2019 (COVID-19) and asthma. However, data on whether asthma constitutes a risk factor for COVID-19 and the prevalence of asthma in COVID-19 cases still remains scant. Here, we interrogated and analyzed the association between COVID-19 and asthma.

Methods: In this study, we systematically searched PubMed, Embase, and Web of Science databases for studies published between January 1, to August 28, 2020. We included studies that reported the epidemiological and clinical features of COVID-19 and its prevalence in asthma patients. We excluded reviews, animal trails, single case reports, small case series and studies evaluating other coronavirus-related illnesses. Raw data from the studies were pooled into a meta-analysis.

Results: We analyzed findings from 18 studies, including asthma patients with COVID-19. The pooled prevalence of asthma in COVID-19 cases was 0.08 (95% CI, 0.06-0.11), with an overall I of 99.07%,  < 0.005 . The data indicated that asthma did not increase the risk of developing severe COVID-19 (odds ratio [OR] 1.04 (95% CI, 0.75-1.46)  = 0.28; I=20%). In addition, there was no significant difference in the incidence of asthma with analyze age in COVID-19 infections [OR] 0.77(95% CI, 0.59-1.00)  = 0.24; I=29%).

Conclusion: Taken together, our data suggested that asthma is not a significant risk factor for the development of severe COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02770903.2021.1917603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074647PMC
April 2021

The Inhibitory Effects of Ficin on Biofilm Formation.

Biomed Res Int 2021 23;2021:6692328. Epub 2021 Mar 23.

School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, China.

To investigate the effects of ficin on biofilm formation of conditionally cariogenic (). Biomass and metabolic activity of biofilm were assessed using crystal violet assay, colony-forming unit (CFU) counting, and MTT assay. Extracellular polysaccharide (EPS) synthesis was displayed by SEM imaging, bacteria/EPS staining, and anthrone method while acid production was revealed by lactic acid assay. Growth curve and live/dead bacterial staining were conducted to monitor bacterial growth state in both planktonic and biofilm form. Total protein and extracellular proteins of biofilm were analyzed by protein/bacterial staining and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), severally. qRT-PCR was conducted to detect acid production, acid tolerance, and biofilm formation associated genes. Crystal violet assay, CFU counting, and MTT assay showed that the suppression effect of ficin on biofilm formation was concentration dependent. 4 mg/mL ficin had significant inhibitory effect on biofilm formation including biomass, metabolic activity, EPS synthesis, and lactic acid production ( < 0.05). The growth curves from 0 mg/mL to 4 mg/mL ficin were aligned with each other. There was no significant difference among different ficin groups in terms of live/dead bacterial staining result ( > 0.05). Protein/bacterial staining outcome indicated that ficin inhibit both total protein and biofilm formation during the biofilm development. There were more relatively small molecular weight protein bands in extracellular proteins of 4 mg/mL ficin group when compared with the control. Generally, ficin could inhibit biofilm formation and reduce cariogenic virulence of effectively in vitro; thus, it could be a potential anticaries agent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6692328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009705PMC
March 2021