Publications by authors named "Yaping Liu"

242 Publications

Change in circadian preference predicts sustained treatment outcomes in patients with unipolar depression and evening preference.

J Clin Sleep Med 2021 Sep 21. Epub 2021 Sep 21.

Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR.

Study Objectives: Eveningness is associated with worse outcomes in depression. It remained unclear if eveningness could be altered with chronobiological therapy and whether such a change would predict long-term outcomes of depression.

Methods: Data from a randomized controlled trial of 5-week adjunctive bright light therapy with a gradual advance protocol conducted in 91 adult patients with non-seasonal unipolar depression and eveningness (Morningness-Eveningness Questionnaire, MEQ, score ≤ 41) was examined. "Change of eveningness" was defined by MEQ score over 41 at post-treatment week 5 and "persistent change of eveningness" was defined as maintenance of MEQ score >41 throughout the follow-up period from week 5 to post-treatment five months.

Results: Thirty-three subjects (36%) had change of eveningness at week 5. Generalized estimating equations models showed that a change of eveningness at week five predicted a 2-fold increase in remission of depression over the five-month follow up (OR = 2.61 95% CI 1.20-5.71, p=0.016). Twenty-five subjects (75.7%) had a persistent change and were more likely to achieve a remission of depression over the five-month follow up (OR = 3.18, 95% CI: 1.35-7.50, p=0.008).

Conclusions: One-third of the depressed patients changed their evening-preference after 5-week of chronotherapeutic treatment and such change predicted a higher likelihood of depression remission over five months of follow-up.

Clinical Trial Registration: Registry: Chinese Clinical Trial Registry; Identifier: ChiCTR-IOR-15006937.
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http://dx.doi.org/10.5664/jcsm.9648DOI Listing
September 2021

Inhibition effects of long-term calcium-magnesia phosphate fertilizer application on Cd uptake in rice: Regulation of the iron-nitrogen coupling cycle driven by the soil microbial community.

J Hazard Mater 2021 08 19;416:125916. Epub 2021 Apr 19.

Key Laboratory of Original Agro-Environmental Pollution Prevention and Control, Agro-Environmental Protection Institute, Ministry of Agriculture and Rural Affairs, Tianjin 300191, People's Republic of China. Electronic address:

Cadmium (Cd) pollution in paddy soil seriously endangers food safety production. To investigate the effects and microbiological mechanisms of calcium-magnesium-phosphate (CMP) fertilizer application on Cd reduction in rice, field experiments were conducted in Cd-contaminated paddy soil. Compared with conventional compound fertilizer, CMP fertilizer treatments inhibited Cd uptake through plant roots, significantly decreasing Cd content in rice grains from 0.340 to 0.062 mg/kg. Soil pH and total Ca, Mg and P contents increased after CMP fertilizer application, resulting in a further decrease in soil available Cd content from 0.246 to 0.181 mg/kg. Specific extraction analysis recorded a decrease in both available Fe content and the ratio of nitrate to ammonium nitrogen, indicating that the soil Fe-N cycle was affected by the addition of CMP fertilizer. This finding was also recorded using soil bacterial community sequencing, with CMP fertilizer promoting the progress of nitrate-dependent Fe-oxidation driven by Thiobacillus (1.60-2.83%) and subsequent dissimilatory nitrate reduction to ammonium (DNRA) driven by Ignavibacteriae (1.01-1.92%); Fe-reduction driven by Anaeromyxobacter (3.09-2.23%) was also inhibited. Our results indicate that CMP fertilizer application regulates the Fe-N coupling cycle driven by the soil microbial community to benefit remediation of Cd contaminated paddy soil.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125916DOI Listing
August 2021

NMR chemical shift assignments of RNA oligonucleotides to expand the RNA chemical shift database.

Biomol NMR Assign 2021 Aug 27. Epub 2021 Aug 27.

Biophysics Program, University of Michigan, 930 N. University Avenue, Ann Arbor, MI, 48109, USA.

RNAs play myriad functional and regulatory roles in the cell. Despite their significance, three-dimensional structure elucidation of RNA molecules lags significantly behind that of proteins. NMR-based studies are often rate-limited by the assignment of chemical shifts. Automation of the chemical shift assignment process can greatly facilitate structural studies, however, accurate chemical shift predictions rely on a robust and complete chemical shift database for training. We searched the Biological Magnetic Resonance Data Bank (BMRB) to identify sequences that had no (or limited) chemical shift information. Here, we report the chemical shift assignments for 12 RNA hairpins designed specifically to help populate the BMRB.
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http://dx.doi.org/10.1007/s12104-021-10049-0DOI Listing
August 2021

Longitudinal Changes in Parkinson's Disease Symptoms with and Without Rapid Eye Movement Sleep Behavior Disorder: The Oxford Discovery Cohort Study.

Mov Disord 2021 Aug 26. Epub 2021 Aug 26.

Oxford Parkinson's Disease Centre, University of Oxford, Oxford, United Kingdom.

Background: Parkinson's disease (PD) comorbid with rapid eye movement sleep behavior disorder (RBD) may show more severe motor and nonmotor symptoms, suggesting a distinct PD subtype.

Objective: The aim of this study was to investigate the impact of RBD on the longitudinal change of motor and nonmotor symptoms in patients with PD.

Methods: Patients with early PD (diagnosed within 3.5 years) recruited from 2010 to 2019 were followed every 18 months in the Oxford Parkinson's Disease Centre Discovery cohort. At each visit, we used standard questionnaires and measurements to assess demographic features and motor and nonmotor symptoms (including RBD, daytime sleepiness, mood, autonomic symptoms, cognition, and olfaction). Data were analyzed with linear mixed effects and Cox regression models. Possible RBD (pRBD) was longitudinally determined according to RBD Screening Questionnaire scores.

Results: A total of 923 patients were recruited (mean age: 67.1 ± 9.59 years; 35.9% female), and 788 had follow-up assessment(s) (mean: 4.8 ± 1.98 years, range: 1.3-8.3). Among them, 33.3% were identified as pRBD (PD + pRBD). Patients with PD + pRBD had more severe baseline symptoms and showed faster progression on Movement Disorder Society-Unified Parkinson's Disease Rating Scale parts I and III, Purdue Pegboard test, and Beck Depression Inventory scores. Moreover, PD + pRBD was associated with an increased level of risk for mild cognitive impairment (hazard ratio [HR] = 1.36, 95% confidence interval [CI]: 1.01-1.83), freezing of gait (HR = 1.42, 95% CI: 1.10-1.86), and frequent falling (HR = 1.62, 95% CI: 1.02-2.60).

Conclusions: Patients with PD + pRBD progress faster on motor, mood, and cognitive symptoms, confirming a more aggressive PD subtype that can be identified at baseline and has major clinical implications. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28763DOI Listing
August 2021

Case report of neurofibromatosis type 1 combined with primary ciliary dyskinesia.

Front Med 2021 Aug 25. Epub 2021 Aug 25.

Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.

Neurofibromatosis (NF) is a genetic disease in which the lungs are rarely involved. However, in NF cases with lung involvement, chest computed tomography may show bilateral basal reticulations, apical bullae, and cysts without bronchiectasis. Herein, we report a patient diagnosed with NF on the basis of the results of genetic testing who presented with early-onset wet cough and bronchiectasis. Considering the differential diagnosis of bronchiectasis combined with his early-onset wet cough, sinusitis, and sperm quality decline, we considered the possibility of primary ciliary dyskinesia (PCD). Further electron microscopy analysis of cilia and identification of homozygous mutations in the RSPH4A gene confirmed the diagnosis of PCD. Therefore, for patients with NF, when an image change exists in the lungs that does not correspond to NF, the possibility of other diagnoses, including PCD, must be considered.
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http://dx.doi.org/10.1007/s11684-021-0860-7DOI Listing
August 2021

Chemical constituents and anti-inflammatory activity of the total alkaloid extract from Melodinus cochinchinensis (Lour.) Merr. and its inhibition of the NF-κB and MAPK signaling pathways.

Phytomedicine 2021 Oct 31;91:153684. Epub 2021 Jul 31.

Faculty of Agriculture and Food, Kunming University of Science and Technology, Kunming 650500, China. Electronic address:

Background: Melodinus cochinchinensis (Lour.) Merr. is a medicinal plant, which is used as a folk medicine for treating meningitis and fractures. However, the anti-inflammatory activity of total alkaloid extract from M. cochinchinensis (MCTA) and its molecular mechanism are still not studied.

Purpose: The aim of this study is to investigate the main chemical constituents of MCTA and explore its anti-inflammatory potential in both in vitro and in vivo assessments.

Methods: UHPLC-ESI-HRMS/MS was applied to analyze the chemical profiling. The anti-inflammatory efficacy of MCTA was evaluated on lipopolysaccharide (LPS) induced RAW 264.7 cells and two common inflammation models in mice. The production of pro-inflammatory mediator and cytokine was tested using the ELISA method. The pathological change was analyzed by histological assessment. The expression of NF-κB, MAPKs and PPAR-γ proteins was evaluated using western blot analysis.

Results: A total of 21 monoterpenoid indole alkaloids (MIAs) were characterized by UHPLC-ESI-HRMS/MS. Aspidospermine- and quinolone-type alkaloids were found to be the major compounds. MCTA significantly decreased the production of NO, IL-1β, IL-6 and TNF-α in LPS-induced RAW 264.7 macrophages. MCTA significantly inhibited the phosphorylation of ERK1/2, JNK and p38 MAPK, suppressed the NF-κB transcriptional activation and improved the PPAR-γ expression. Moreover, the in vivo experiment exhibited that MCTA pretreatment markedly alleviated the xylene-induced ear edema and carrageenan-induced paw edema in mice and decreased the IL-1β, IL-6 and TNF-α expressions.

Conclusion: MCTA is rich in MIAs and exhibited a significant inhibitory effect on the production proinflammatory cytokines. The mechanism might be related to the inhibition of activation of NF-κB and MAPK pathways.
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http://dx.doi.org/10.1016/j.phymed.2021.153684DOI Listing
October 2021

Novel mutation c.1210-3C > G in cis with a poly-T tract of 5T affects CFTR mRNA splicing in a Chinese patient with cystic fibrosis.

Front Med 2021 Jul 24. Epub 2021 Jul 24.

McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China.

Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G > A, p.Gly970Asp in exon 18 and c.1210-3C > G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C > G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C > G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.
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http://dx.doi.org/10.1007/s11684-021-0846-5DOI Listing
July 2021

Clinical characteristics and genetic spectrum of 26 individuals of Chinese origin with primary ciliary dyskinesia.

Orphanet J Rare Dis 2021 07 1;16(1):293. Epub 2021 Jul 1.

McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.

Background: Primary ciliary dyskinesia (PCD) is a rare, highly heterogeneous genetic disorder involving the impairment of motile cilia. With no single gold standard for PCD diagnosis and complicated multiorgan dysfunction, the diagnosis of PCD can be difficult in clinical settings. Some methods for diagnosis, such as nasal nitric oxide measurement and digital high-speed video microscopy with ciliary beat pattern analysis, can be expensive or unavailable. To confirm PCD diagnosis, we used a strategy combining assessment of typical symptoms with whole-exome sequencing (WES) and/or low-pass whole-genome sequencing (WGS) as an unbiased detection tool to identify known pathogenic mutations, novel variations, and copy number variations.

Results: A total of 26 individuals of Chinese origin with a confirmed PCD diagnosis aged 13 to 61 years (median age, 24.5 years) were included. Biallelic pathogenic mutations were identified in 19 of the 26 patients, including 8 recorded HGMD mutations and 24 novel mutations. The detection rate reached 73.1%. DNAH5 was the most frequently mutated gene, and c.8383C > T was the most common mutated variant, but it is relatively rare in PCD patients from other ethnic groups.

Conclusion: This study demonstrates the practical clinical utility of combining WES and low-pass WGS as a no-bias detecting tool in adult patients with PCD, showing a clinical characteristics and genetic spectrum of Chinese PCD patients.
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http://dx.doi.org/10.1186/s13023-021-01840-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252271PMC
July 2021

Activity Guided Isolation of Phenolic Compositions from Wall. and Their Cytoprotective Effect against Hydrogen Peroxide Induced Oxidative Stress in HepG2 Cells.

Molecules 2021 Jun 17;26(12). Epub 2021 Jun 17.

Faculty of Agriculture and Food, Kunming University of Science and Technology, Kunming 650500, China.

Wall., commonly known as "Pangpo Tea", is traditionally used as a folk medicine and healthy tea for the treatment of liver and intestine diseases. The aim of this study was to purify the antioxidative and cytoprotective polyphenols from leaves. After fractionation with polar and nonpolar organic solvents, the fractions of aqueous ethanol extract were evaluated for their total phenolic (TPC) and flavonoid contents (TFC) and antioxidant activities (DPPH, ABTS, and FRAP assays). The -butanol fraction (BF) showed the highest TPC and TFC with the strongest antioxidant activity. The bio-guided chromatography of BF led to the purification of six flavonoids (-) and one benzoquinolethanoid (). The structures of these compounds were determined by NMR and MS techniques. Compound had the strongest antioxidant capacity, which was followed by and . The protective effect of the isolated compounds on hydrogen peroxide (HO)-induced oxidative stress in HepG2 cells revealed that the compounds and exhibited better protective effects by inhibiting ROS productions, having no significant difference with vitamin C ( > 0.05), whereas showed the best anti-apoptosis activity. The results suggest that could serve as a valuable antioxidant phytochemical source for developing functional food and health nutraceutical products.
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http://dx.doi.org/10.3390/molecules26123690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234824PMC
June 2021

Follicle-stimulating hormone worsens osteoarthritis by causing inflammation and chondrocyte dedifferentiation.

FEBS Open Bio 2021 Jun 27. Epub 2021 Jun 27.

Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Previous studies have found follicle-stimulating hormone (FSH) receptors on chondrocytes (cartilage cells), but the mechanism of FSH action on chondrocytes is not clear. The purpose of this experiment is to study whether FSH affects chondrocytes and how it causes changes in these cells. Our results show that osteoarthritis became worse after FSH injection in the knee joint of mice. After the stimulation of chondrocytes by FSH, a total of 664 up-regulated genes, such as Col12a1 and Col1a1, and 644 down-regulated genes, such as MGP, were screened by transcriptomics. A subset of extracellular matrix (ECM)-related genes and pathways underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the downregulation of MGP, the upregulation of EGR1 and Col1a1, and the increase of IL-6 were verified. It was also observed that FSH can inhibit the cAMP/PKA and MKK4/JNK signaling pathway. In conclusion, we demonstrated that FSH can increase cartilage inflammatory response and promote chondrocyte dedifferentiation by inhibiting the cAMP/PKA and MKK4/JNK signaling pathways.
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http://dx.doi.org/10.1002/2211-5463.13238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329950PMC
June 2021

Edaravone attenuates smoke inhalation injury in rats by the Notch pathway.

Am J Transl Res 2021 15;13(5):4712-4718. Epub 2021 May 15.

Department of Burn and Plastic Surgery, Affiliated Hospital of Chengde Medical University Chengde 067000, Hebei Province, China.

Objective: To explore the protective effect of inhaled edaravone (EDA) on inflammation, oxidative stress (OS), and pulmonary function (PF) in rats after smoke inhalation injury (SII), as well as its mechanisms.

Methods: Twenty-four rats were designated as group A (model group), group B (EBA prevention group), group C (low-dose group) and group D (high-dose group) (n=6 for each group). SII models were induced in all groups. After successful modeling, rats in each group were treated accordingly. After 6 hours of modeling, assessments of PF, oxygenation index (OI), inflammatory cytokine expression, oxidative stress index (OSI), wet/dry weight ratio (W/D), total lung water (TLW), and the expression of Notch markers were carried out.

Results: Compared with group A, the remaining groups had higher peak respiratory velocity (PEF), forced expiratory volume in the first second (FEV1), FEV1/forced vital capacity (FVC) and OI, as well as lower W/D and TLW; levels of serum superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 decreased, and those of serum myeloperoxidase (MPO) and IL-10 increased. Levels of PEF, FEV1, FVC, OI, MPO, and IL-10 were higher in group A than in groups C and D, and those of W/D, TLW, SOD, MDA, TNF-α, and IL-6 were lower. Levels of Notch markers NICD, Hes1 and Hes5 were downregulated in groups B, C, and D, and in group B were lower than those in groups C and D.

Conclusion: Inhaled EDA is able to alleviate inflammation and OS and effectively improve PF in rats after SII, possibly by inhibiting the Notch pathway.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205801PMC
May 2021

Anneslea fragrans Wall. ameliorates ulcerative colitis via inhibiting NF-κB and MAPK activation and mediating intestinal barrier integrity.

J Ethnopharmacol 2021 Oct 8;278:114304. Epub 2021 Jun 8.

Faculty of Agriculture and Food, Kunming University of Science and Technology, Kunming, 650500, China. Electronic address:

Ethnopharmacological Relevance: Anneslea fragrans Wall. is traditionally used as a folk medicine in treating indigestion, fever, dysentery, diarrhea, and liver inflammation in China, Vietnam and Cambodia. However, its anti-inflammatory activity and mechanism under a safety therapeutic dose as well as the main chemical components have not yet been fully investigated.

Aim Of The Study: This study aimed to explore the therapeutic effect and possible molecular mechanisms of aqueous-methanol extract (AFE) of A. fragrans leaves on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) mice and illustrate its potent anti-inflammatory chemical compounds.

Materials And Methods: The AFE was obtained and then analyzed by high performance liquid chromatography (HPLC). Phytochemical investigation on the AFE was carried out to isolate and characterize its major components. The acute toxicity test was performed to provide the safety information of AFE. Subsequently, the protective effect of AFE on DSS-induced UC was evaluated by physiological changes, histopathological and immunohistochemical analysis, and the expressions of antioxidant enzyme, pro-inflammatory cytokines and anti-inflammatory cytokines. The expressions of target proteins in nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) were determined by western blot analysis. The tight junction (TJ) proteins in colon tissue were performed by immunohistochemical technique for evaluating the intestinal barrier integrity.

Results: HPLC guided isolation of AFE resulted into two dihydrochalcones, which were elucidated as vacciniifolin (1) and confusoside (2). Acute toxicity evaluation revealed that median lethal dose (LD) of AFE was greater than 5000 mg/kg. Furthermore, AFE significantly attenuated ulcerative colitis symptoms, suppressed myeloperoxidase activity, and increased the expression of superoxide dismutase and glutathione. AFE treatment could also reduce the levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 and increase the levels of interleukin-4 and interleukin-10 in colon tissues and serum of DSS-induced UC mice. In addition, AFE significantly increased the expression of zonula occludens-1, occludin and claudin-1, and inhibited the phosphorylation of target protein of the NF-κB and MAPK signaling pathways in colon tissue.

Conclusion: Dihydrochalcone glycosides are the major chemical constituents in AFE. AFE ameliorated DSS-induced UC in mice by inhibiting the inflammatory response via modulation of NF-κB and MAPK pathways and maintaining the intestinal barrier function, indicating that the plant A. fragrans could be used as a therapeutic candidate for ulcerative colitis.
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http://dx.doi.org/10.1016/j.jep.2021.114304DOI Listing
October 2021

A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial.

NPJ Vaccines 2021 Jun 2;6(1):79. Epub 2021 Jun 2.

Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.

A conditionally replication-defective human cytomegalovirus (HCMV) vaccine, V160, was shown to be safe and immunogenic in a two-part, double-blind, randomized, placebo-controlled phase I clinical trial (NCT01986010). However, the specificities and functional properties of V160-elicited antibodies remain undefined. Here, we characterized 272 monoclonal antibodies (mAbs) isolated from single memory B cells of six V160-vaccinated subjects. The mAbs bind to diverse HCMV antigens, including multiple components of the pentamer, gB, and tegument proteins. The most-potent neutralizing antibodies target the pentamer-UL subunits. The binding sites of the antibodies overlap with those of antibodies responding to natural HCMV infection. The majority of the neutralizing antibodies target the gHgL subunit. The non-neutralizing antibodies predominantly target the gB and pp65 proteins. Sequence analysis indicated that V160 induced a class of gHgL antibodies expressing the HV1-18/KV1-5 germline genes in multiple subjects. This study provides valuable insights into primary targets for anti-HCMV antibodies induced by V160 vaccination.
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http://dx.doi.org/10.1038/s41541-021-00342-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172929PMC
June 2021

Aerosol inhalation of edaravone can improve inflammation, oxidative stress and pulmonary function of rats with smoke inhalation injury by down-regulating miR-320.

Am J Transl Res 2021 15;13(4):2563-2570. Epub 2021 Apr 15.

Department of Burn Plastic Surgery, Affiliated Hospital of Chengde Medical University Chengde 067000, Hebei Province, China.

Objective: To explore the protective effects and related mechanism of aerosol inhalation of edaravone on inflammation, oxidative stress and pulmonary function (PF) in rats with smoke inhalation injury.

Methods: Twenty-four rats were stochastically and equally divided into four groups: group A (edaravone-preventing group), group B (model group), group C (low-dose group) and group D (high-dose group). The serum of rats was collected to determine the expression of miR-320, inflammatory mediators (TNF-α, IL-6, IL-10), oxidative stress indexes (MDA, SOD, MPO) and oxygenation index (OI). Pulmonary tissues of rats were collected to determine the total lung water (TLW), wet-to-dry ratio (W/D) and other parameters. HE staining was adopted for pathological evaluation.

Results: Compared with group B, the levels of miR-320, TNF-α, IL-6, MDA, MPO, TLW and W/D in group A were significantly down-regulated, while IL-10, SOD and OI levels were significantly up-regulated, and the trend of this change was more obvious than that in group C and group D, with notably better improvement degree in group D than group C. In HE staining, the pulmonary tissue structure was basically normal in group A, and was better than that of the other three groups. In group B, the pulmonary tissue was seriously damaged, accompanied by a large number of inflammatory cells infiltration and alveolar wall thickening. The pathological condition of group C was notably ameliorated, the extent of this improvement was more pronounced in group D, and the degree of pathological improvement in group D was superior to that in group C.

Conclusion: Aerosol inhalation of edaravone in advance can reduce the levels of inflammatory factors and oxidative stress indexes in serum of smoke inhalation injury rats, thus protecting PF, which may be related to the down-regulation of miR-320 by edaravone.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129403PMC
April 2021

FSH modulated cartilage ECM metabolism by targeting the PKA/CREB/SOX9 pathway.

J Bone Miner Metab 2021 Sep 14;39(5):769-779. Epub 2021 May 14.

School of Medicine, Shandong University, jinan, 250021, shandong, China.

Introduction: Osteoarthritis (OA) is a common joint disease characterized by articular cartilage degeneration. The prevalence of OA is higher among women than men, and this prevalence is closely related to menopause. The classic view assumes that the underlying mechanism of postmenopausal OA is attributed to declining estrogen levels. Although follicle-stimulating hormone (FSH) levels become elevated in parallel, the effects of FSH on OA have been poorly explored. The present study aimed to study the effect of FSH on cartilage metabolism.

Methods: Chondrocyte-like ATDC5 cells were treated with recombinant FSH protein. Then the cell viability was measured using cell counting kit-8 assay. Expressions of crucial factors involved in the extracellular matrix (ECM) metabolic and PKA-CREB-SOX9 pathway were analyzed by western blot, RT-qPCR, and immunofluorescence staining. Intracellular cAMP levels were assessed by ELISA assay. Experimental OA in mice was induced by destabilization of the medial meniscus (DMM) surgery. Adeno-associated virus expressing shRNA against FSHR (AAV-shFSHR) was intra-articular (IA) injected into the OA model animals to specifically knock down FHSR in cartilage. Histological staining and OARSI scores were used to assess the efficacy of AAV-shFSHR injections.

Results: We found that FSH down-regulated the expression of ECM-related proteins in chondrocyte-like ATDC5 cells. The underlying mechanism is probably associated with regulating PKA/CREB/SOX9 pathway. Besides, blocking FSH signaling via shRNA-mediated downregulation of FSHR in joint tissues effectively delayed the development of posttraumatic OA in mice.

Conclusions: Our results collectively indicated that FSH plays an essential role in the pathogenesis of OA and acts as a crucial mediator.
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http://dx.doi.org/10.1007/s00774-021-01232-3DOI Listing
September 2021

Effects of an evidence-based nursing intervention on neurological function and serum inflammatory cytokines in patients with acute cerebral infarction: A randomized controlled trial.

Restor Neurol Neurosci 2021 ;39(2):129-137

Department of Neurology, Cangzhou Central Hospital, Cangzhou, Hebei, China.

Background: Acute cerebral infarction is a clinically common and critical disease which seriously endangers the life and safety of elderly patients. Evidence-based nursing is an effective way of nursing and has great significance in improving the neurological function and quality of life of patients. In China, evidence-based nursing has been highlighted and highly developed in recent decades.

Objectives: This research aimed to investigate the effect of evidence-based nursing on the recovery of neurological function and serum inflammatory cytokines in patients with acute cerebral infarction.

Methods: A total of 116 patients with acute cerebral infarction were randomly divided into two groups: the control group patients (n = 58) received conventional nursing, while the intervention group patients (n = 58) received evidence-based nursing intervention. National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer assessment (FMA) and activities of daily living (ADL) scores, as well as serum TNF-α and IL-6 levels were evaluated and compared between the two groups.

Results: NIHSS scores in the intervention group were significantly lower than the control group. FMA and ADL scores in the intervention group were significantly higher than the control group. TNF-α and IL-6 levels in the serum of the intervention group were significantly lower than the control group.

Conclusions: In conclusion, evidence-based nursing has a positive effect on the treatment of patients with acute cerebral infarction, which decreases the level of serum inflammatory cytokines and contributes to the recovery of neurological function, motor function and activities of daily living.
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http://dx.doi.org/10.3233/RNN-201080DOI Listing
January 2021

The influence of VDR polymorphisms on the type 2 diabetes susceptibility in Chinese: an interaction with hypertriglyceridemia.

Mol Genet Genomics 2021 Jul 20;296(4):837-844. Epub 2021 Apr 20.

Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China.

Evidence shows that mutations in vitamin D receptor (VDR) have been linked with an increased risk of type 2 diabetes (T2D). However, the interaction effect between VDR variants and environmental factors on the T2D susceptibility remained unclear. Therefore, the current study was conducted to explore the joint effect of VDR polymorphisms and serum triglyceride level on T2D. A total of 2017 participants were included in the cross-sectional study. Taqman probe assays were applied to rs3847987 and rs739837 genotyping. Multiple logistic regression and general linear model were used to examine the effect of interaction between VDR variants and TG on T2D susceptibility and fasting serum glucose, respectively. The results showed that rs739837 polymorphism was significantly associated with an increased risk of T2D under the dominant model (OR = 1.30, 95% CI 1.02-1.66), after adjusting for potential risk factors. Meanwhile, there was a significant additive interaction between rs3847987 and hypertriglyceridemia (synergy index [SI]: 2.98, 95% CI: 1.23-7.23) and between rs739837 and hypertriglyceridemia (SI: 2.36, 95% CI: 1.05-5.31) on T2D susceptibility. Additionally, a significant linear association between fasting glucose and rs3847987 had been found at high triglyceride level (> 1.90 mmol/L) with an inversely concentration-dependent manner. The study provided further evidence that rs739837 and high level of triglyceride were both associated with higher T2D susceptibility in Chinese population. Additionally, the detrimental effect of VDR variants on T2D could be modified by hypertriglyceridemia status.
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http://dx.doi.org/10.1007/s00438-021-01784-zDOI Listing
July 2021

Causal associations of short and long sleep durations with 12 cardiovascular diseases: linear and nonlinear Mendelian randomization analyses in UK Biobank.

Eur Heart J 2021 Sep;42(34):3349-3357

Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, 33 A Kung Kok Street, Sha Tin District, Hong Kong SAR 000000, China.

Aims: Observational studies have suggested strong associations between sleep duration and many cardiovascular diseases (CVDs), but causal inferences have not been confirmed. We aimed to determine the causal associations between genetically predicted sleep duration and 12 CVDs using both linear and nonlinear Mendelian randomization (MR) designs.

Methods And Results: Genetic variants associated with continuous, short (≤6 h) and long (≥9 h) sleep durations were used to examine the causal associations with 12 CVDs among 404 044 UK Biobank participants of White British ancestry. Linear MR analyses showed that genetically predicted sleep duration was negatively associated with arterial hypertension, atrial fibrillation, pulmonary embolism, and chronic ischaemic heart disease after correcting for multiple tests (P < 0.001). Nonlinear MR analyses demonstrated nonlinearity (L-shaped associations) between genetically predicted sleep duration and four CVDs, including arterial hypertension, chronic ischaemic heart disease, coronary artery disease, and myocardial infarction. Complementary analyses provided confirmative evidence of the adverse effects of genetically predicted short sleep duration on the risks of 5 out of the 12 CVDs, including arterial hypertension, pulmonary embolism, coronary artery disease, myocardial infarction, and chronic ischaemic heart disease (P < 0.001), and suggestive evidence for atrial fibrillation (P < 0.05). However, genetically predicted long sleep duration was not associated with any CVD.

Conclusion: This study suggests that genetically predicted short sleep duration is a potential causal risk factor of several CVDs, while genetically predicted long sleep duration is unlikely to be a causal risk factor for most CVDs.
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http://dx.doi.org/10.1093/eurheartj/ehab170DOI Listing
September 2021

Identification of Imprinted Genes Based on Homology: An Example of .

Genes (Basel) 2021 03 8;12(3). Epub 2021 Mar 8.

Laboratory of Fruit Crop Biotechnology, College of Horticulture, Nanjing Agricultural University, No. 1 Weigang, Nanjing 210095, China.

Genomic imprinting has drawn increasing attention in plant biology in recent years. At present, hundreds of imprinted genes have been identified in various plants, and some of them have been reported to be evolutionarily conserved in plant species. In this research, 17 candidate genes in were obtained based on the homologous imprinted genes in and other species. We further constructed reciprocal crosses of diploid strawberry () using the varieties 10-41 and 18-86 as the parents to investigate the conservation of these imprinted genes. Potentially informative single nucleotide polymorphisms (SNPs) were used as molecular markers of two parents obtained from candidate imprinted genes which have been cloned and sequenced. Meanwhile, we analyzed the SNP site variation ratios and parent-of-origin expression patterns of candidate imprinted genes at 10 days after pollination (DAP) endosperm and embryo for the hybrids of reciprocal cross, respectively. A total of five maternally expressed genes (MEGs), i.e., , -2, , , and , were identified in the endosperm, which did not show imprinting in the embryo. Finally, tissues expression analysis indicated that the five imprinted genes excluding mainly expressed in the endosperm. This is the first report on imprinted genes of , and we provide a simple and rapid method based on homologous conservation to screen imprinted genes. The present study will provide a basis for further study of function and mechanism of genomic imprinting in .
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http://dx.doi.org/10.3390/genes12030380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999015PMC
March 2021

Dual role (promotion and inhibition) of transglutaminase in mediating myofibrillar protein gelation under malondialdehyde-induced oxidative stress.

Food Chem 2021 Aug 3;353:129453. Epub 2021 Mar 3.

College of Food Science and Engineering, Northwest A&F University, No. 22 Xinong Road, Yangling, Shaanxi 712100, China. Electronic address:

This study investigated the effects of transglutaminase (TGase) on the properties of myofibrillar protein (MP) and its heat-induced gels under malondialdehyde (MDA)-induced oxidation. The physicochemical characteristics, protein aggregation and rheological properties of MP were assessed. The gelling behaviours of MP were analysed with measurements of gel strength, cooking loss, microstructure and secondary structure. Under varying degrees of MDA oxidation, the addition of TGase always led to changes in the tertiary structure, loss of free amine and thiol groups, crosslinking of the myosin heavy chain, and decreasing solubility. However, the effect of TGase on MP gel quality differed. At 6 mmol/L MDA, the addition of TGase reduced the quality of MP gels by increasing cooking loss. However, at 12 mmol/L MDA, TGase reduced both the cooking loss and gel strength.
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http://dx.doi.org/10.1016/j.foodchem.2021.129453DOI Listing
August 2021

Associations of sleep phenotypes with severe intentional self-harm: a prospective analysis of the UK Biobank cohort.

Sleep 2021 Aug;44(8)

Li Chiu Kong Family Sleep assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.

Study Objectives: We aimed to investigate the prospective associations of sleep phenotypes with severe intentional self-harm (ISH) in middle-aged and older adults.

Methods: A total of 499,159 participants (mean age: 56.55 ± 8.09 years; female: 54.4%) were recruited from the UK Biobank between 2006 and 2010 with follow-up until February 2016 in this population-based prospective study. Severe ISH was based on hospital inpatient records or a death cause of ICD-10 codes X60-X84. Patients with hospitalized diagnosis of severe ISH before the initial assessment were excluded. Sleep phenotypes, including sleep duration, chronotype, insomnia, sleepiness, and napping, were assessed at the initial assessments. Cox regression analysis was used to estimate temporal associations between sleep phenotypes and future risk of severe ISH.

Results: During a follow-up period of 7.04 years (SD: 0.88), 1,219 participants experienced the first hospitalization or death related to severe ISH. After adjusting for demographics, substance use, medical diseases, mental disorders, and other sleep phenotypes, short sleep duration (HR: 1.50, 95% CI: 1.23-1.83, p < .001), long sleep duration (HR: 1.56, 95% CI: 1.15-2.12, p = .004), and insomnia (usually: HR: 1.57, 95% CI: 1.31-1.89, p < .001) were significantly associated with severe ISH. Sensitivity analyses excluding participants with mental disorders preceding severe ISH yielded similar results.

Conclusion: The current study provides the empirical evidence of the independent prediction of sleep phenotypes, mainly insomnia, short- and long-sleep duration, for the future risk of severe ISH among middle-aged and older adults.
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http://dx.doi.org/10.1093/sleep/zsab053DOI Listing
August 2021

Reelin promotes oligodendrocyte precursors migration via the Wnt/β-catenin signaling pathway.

Neurol Res 2021 Jul 21;43(7):543-552. Epub 2021 Feb 21.

Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu, PRC.

: The extracellular matrix glycoprotein Reelin plays an important role in the development of the central nervous system and is involved in neurogenesis, neuronal polarization and migration. Although it has been reported that Reelin and its receptor are expressed in oligodendrocyte precursors (OPCs), the main functions and possible mechanism of Reelin in OPCs remain unclear.: In this study, immunofluorescence staining was used to detect the expressions of A2B5, PDGFRα, Reelin, VLDLR and Dab1 in OPCs. The expression of p-Dab1 in OPCs which was treated with Reelin at different concentrations was assayed by western blot. Effects of Reelin on the proliferation of OPCs was measured by EdU and CCK-8. Annexin V-FITC/PI assayed the effect of Reelin on the apoptosis of OPCs. Effects of Reelin on the migration ability of OPCs were detected by the scratch test and transwell experiments. Immunoblotting was used to measure the activation of Wnt/β-catenin signaling with Reelin, while transwell experiments were performed to verify the migration of OPCs under the activation of Wnt/β-catenin signaling.: Results showed that the receptor of Reelin, very-low-density lipoprotein receptor (VLDLR), and its adaptor protein, Dab1, are highly expressed in A2B5/PDGFRα double-positive OPCs. Recombinant Reelin protein promoted OPCs migration in vitro but had no obvious effects on proliferation or apoptosis. Reelin also promoted the phosphorylation of Dab1 and increased the expression of β-catenin in OPCs. WIKI4, an inhibitor of Wnt/β-catenin signaling, suppressed the migration of OPCs induced by Reelin.: The present study indicated that Reelin promotes OPCs migration via the Wnt/β-catenin pathway.
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http://dx.doi.org/10.1080/01616412.2021.1888604DOI Listing
July 2021

A Bibliometric Analysis of Advanced Healthcare Materials: Research Trends of Biomaterials in Healthcare Application.

Adv Healthc Mater 2021 05 17;10(10):e2002222. Epub 2021 Feb 17.

The First Affiliated Hospital of University of Science and Technology of China, 17 Lujiang Road, Hefei, 230001, China.

In the field of biomaterials for healthcare applications, Advanced Healthcare Materials (AHM) has become one of the leading journals. Since 2011, AHM keeps bringing the latest research results in biomaterial science aimed at promoting human health. Nowadays, bibliometrics, of which methodological approaches can quantitively and qualitatively analyze the research performance of journals or subject fields, has attracted considerable attention among the scientific community. A general bibliometric overview of the research performance of AHM is presented. With the aid of Web of Science Core Collection database and VOSviewer software, the annual publication, the most prolific and influential authors/countries from AHM is identified. In addition, the most cited documents and keyword cooccurrence network analysis allow to recognize the major research topics in AHM. At last, the summary of current research trends based on AHM bibliometric analysis, several considerations for the clinical translation of biomaterials, and prospects to advance the field are also proposed. This editorial presents major research trends in the field of engineered materials for healthcare applications.
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http://dx.doi.org/10.1002/adhm.202002222DOI Listing
May 2021

The mediating roles of coping styles and resilience in the relationship between perceived social support and posttraumatic growth among primary caregivers of schizophrenic patients: a cross-sectional study.

BMC Psychiatry 2021 01 26;21(1):58. Epub 2021 Jan 26.

Department of Pathogenic Biology, Binzhou Medical University, No.346 Guanhai Road, Yantai, Shandong Province, China.

Background: Despite the substantial burden of caring schizophrenic patients, primary caregivers can also experience posttraumatic growth (PTG) which may buffer their negative experience. Influencing factors of PTG and their functional pathways among primary caregivers of schizophrenic patients remain unclear. This study is designed to test the simple and serial mediating roles of coping styles and resilience in the relationship between perceived social support and PTG among those primary caregivers.

Methods: A cross-sectional study was conducted from October 2018 to January 2019, and 365 primary caregivers (self-reported) of schizophrenic patients were analyzed. Measures used to assess their perceived social support, coping styles, resilience, and PTG were the Perceived Social Support Scale, the Simplified Coping Style Questionnaire, the Connor-Davidson Resilience Scale, and the Posttraumatic Growth Inventory, respectively. Structural equation modeling was used to run the analysis.

Results: The average scores of PTG (range: 0-5), perceived social support (range: 1-7), positive coping style (range: 0-3), negative coping style (range: 0-3), resilience (range: 0-4) reported by primary caregivers was (2.91 ± 0.99), (4.80 ± 1.26), (1.79 ± 0.65), (1.49 ± 0.56), and (2.46 ± 0.66), respectively. The fitness indices of measurement and structural models were satisfactory. Three indirect pathways totally explained 55.56% variance of the PTG. The indirect effect of positive coping style between perceived social support and PTG was 0.20 [95% confidence interval (CI) 0.05 to 0.37], and this simple mediation pathway explained 27.78% variance of PTG. The indirect effect of resilience between perceived social support and PTG was 0.11 [95% CI 0.01 to 0.20], and this simple mediation pathway explained 15.28% variance of PTG. The indirect effect of positive coping style and then resilience between perceived social support and PTG was 0.09 [95% CI 0.01 to 0.17], and this serial mediation pathway explained 12.50% variance of PTG.

Conclusions: Both simple and serial mediation roles of positive coping style and resilience are established in the relationship between perceived social support and PTG among primary caregivers of schizophrenic patients. Positive coping style and resilience are two important targets for future interventional studies, and interventions on them may bring the synergistic effect on improving PTG.
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http://dx.doi.org/10.1186/s12888-021-03058-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836590PMC
January 2021

The Bioavailability, Extraction, Biosynthesis and Distribution of Natural Dihydrochalcone: Phloridzin.

Int J Mol Sci 2021 Jan 19;22(2). Epub 2021 Jan 19.

Faculty of Agriculture and Food, Kunming University of Science and Technology, Kunming 650500, China.

Phloridzin is an important phytochemical which was first isolated from the bark of apple trees. It is a member of the dihydrochalcones and mainly distributed in the plants of the genus, therefore, the extraction method of phloridzin was similar to those of other phenolic substances. High-speed countercurrent chromatography (HSCCC), resin adsorption technology and preparative high-performance liquid chromatography (HPLC) were used to separate and purify phloridzin. Many studies showed that phloridzin had multiple pharmacological effects, such as antidiabetic, anti-inflammatory, antihyperglycaemic, anticancer and antibacterial activities. Besides, the physiological activities of phloridzin are cardioprotective, neuroprotective, hepatoprotective, immunomodulatory, antiobesity, antioxidant and so on. The present review summarizes the biosynthesis, distribution, extraction and bioavailability of the natural compound phloridzin and discusses its applications in food and medicine.
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http://dx.doi.org/10.3390/ijms22020962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835879PMC
January 2021

Type I interferonopathies with novel compound heterozygous TREX1 mutations in two siblings with different symptoms responded to tofacitinib.

Pediatr Rheumatol Online J 2021 Jan 6;19(1). Epub 2021 Jan 6.

Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.

Background: Type I interferonopathies are a group of rare autoimmune diseases characterised by excessive activation of type I interferon that leads to disturbances in immune function. Three prime repair exonuclease 1 (TREX1) is an important exonuclease and plays an important role in DNA damage repair. TREX1 mutations are associated with many type I interferonopathies. Studies have been published on the effectiveness of tofacitinib in the treatment of type I interferonopathies. The aim of this study is to identify the pathogenic variation in a Chinese family with type I interferonopathies and to observe the therapeutic effects of tofacitinib.

Methods: A Chinese family with two members with type I interferonopathies was investigated. Whole exome sequencing and Sanger sequencing were applied for mutation screening using peripheral blood DNA of the patient and her family members. Sequencing results were analysed using bioinformatics software tools including VarCards and PolyPhen-2. Close clinical follow-up and observation were used to record changes in the disease before and after treatment with tofacitinib.

Results: Compound heterozygous variants of TREX1 were observed in the patient's genome. One was a missense variant (NM_016381; c.C227T; p.Ala76Val) from the patient's father, and the other was a frameshift variant (NM_016381; c.458dupA; p.Gln153Glnfs*3) from the patient's mother. One of the proband's elder brothers with similar skin lesions also carried these two variants. This brother of the proband had more serious cutaneous involvement with the comorbidity of cerebral palsy. These TREX1 variants have not been reported in previous studies and are predicted to be highly pathogenic. The proband was given tofacitinib that led to a marked improvement.

Conclusions: We identified two novel complex heterozygous variants in the TREX1 gene, which may underlie the molecular pathogenesis of the type I interferonopathies observed in members of this family. Tofacitinib could be an alternative treatment for this disease.
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http://dx.doi.org/10.1186/s12969-020-00490-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789551PMC
January 2021

Generalized Hailey-Hailey disease: Novel splice-site mutations of ATP2C1 gene in Chinese population and a literature review.

Mol Genet Genomic Med 2021 02 20;9(2):e1580. Epub 2020 Dec 20.

Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Hailey-Hailey disease (HHD; OMIM: 169600) is an autosomal dominate genodermatosis, characterized by recurrent blisters and erosions clinically and remarkable acantholysis pathologically. The underlying pathogenic factor is the mutation of ATP2C1 gene (OMIM: 604384), which encodes secretory pathway Ca /Mn -ATPase (SPCA1). Skin folds are the predilection site of HHD. Atypical cases with a generalized pattern have rarely been reported, making it prone to misdiagnosis.

Methods: In this study, we presented three Chinese pedigrees of Hailey-Hailey disease with generalized skin lesions. ATP2C1 mutations were screened by DNA sequencing and their transcripts were further confirmed by minigene assay. We also performed a literature review of previously published generalized HHD over past two decades together with our cases.

Results: Three splice-site mutations were identified: c.2487+1G>A, c.2126+1G>A, and c.1891-2A>G, which resulted in an exon 25-truncated transcript, two exon 22-truncated transcripts, and two exon 21-truncated transcripts, respectively. The c.2487+1G>A and the c.1891-2A>G mutations are novel mutations which have not been reported before. No clustered mutations of ATP2C1 gene were found in generalized HHD patients in literature along with our novel mutations.

Conclusion: We found no hot spot mutations in ATP2C1 correlated with the generalized pattern of HHD. Our study expanded the spectrum of ATP2C1 mutations, which would be useful for disease diagnosis and genetic counseling.
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http://dx.doi.org/10.1002/mgg3.1580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077163PMC
February 2021

Metformin protects chondrocytes against IL-1β induced injury by regulation of the AMPK/NF-κ B signaling pathway.

Pharmazie 2020 12;75(12):632-636

Osteoarthritis (OA) is a common joint disorder characterized by degeneration and inflammation of the articular cartilage. The etiology of OA is complex, and there is no effective drug for the treatment currently. Metformin, the first-line drug for type 2 diabetes mellitus, has been reported to play an essential role in a variety of diseases; however, whether it could be used in OA therapy remains unclear. In this study, we used interleukin-1β (IL-1β) to mimic the pathophysiology of OA to explore the function and the underlying mechanism of metformin on OA. In our study, cell viability was measured using cell counting kit-8 assay, expressions of crucial factors involved in the extracellular matrix (ECM) metabolic, proinflammatory response, cell apoptosis, and nuclear factor κ B(NF-κ B) pathway were analyzed using western blot analysis and immunofluorescence staining. We found that metformin increased the proliferation of the cells, alleviated IL-1β-induced ECM metabolic imbalance and proinflammatory cytokine production, and exerted anti-apoptosis activity in ATDC5 cells. Furthermore, the results showed that metformin blocked the NF-κ B pathway in IL-1β-induced ATDC5 cells activation of AMP-activated protein kinase (AMPK). These results indicated that metformin protected chondrocytes against IL-1β-induced injury, possibly by regulation of the AMPK/NF-κ B signaling pathway. It may have the potential as a novel drug for OA treatment.
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http://dx.doi.org/10.1691/ph.2020.0762DOI Listing
December 2020

FinaleDB: a browser and database of cell-free DNA fragmentation patterns.

Bioinformatics 2021 08;37(16):2502-2503

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Summary: Circulating cell-free DNA (cfDNA) is a promising biomarker for the diagnosis and prognosis of many diseases, including cancer. The genome-wide non-random fragmentation patterns of cfDNA are associated with the nucleosomal protection, epigenetic environment and gene expression in the cell types that contributed to cfDNA. However, current progress on the development of computational methods and understanding of molecular mechanisms behind cfDNA fragmentation patterns is significantly limited by the controlled-access of cfDNA whole-genome sequencing (WGS) dataset. Here, we present FinaleDB (FragmentatIoN AnaLysis of cEll-free DNA DataBase), a comprehensive database to host thousands of uniformly processed and curated de-identified cfDNA WGS datasets across different pathological conditions. Furthermore, FinaleDB comes with a fragmentation genome browser, from which users can seamlessly integrate thousands of other omics data in different cell types to experience a comprehensive view of both gene-regulatory landscape and cfDNA fragmentation patterns.

Availability And Implementation: FinaleDB service: http://finaledb.research.cchmc.org/. FinaleDB source code: https://github.com/epifluidlab/finaledb_portal, https://github.com/epifluidlab/finaledb_workflow.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388032PMC
August 2021

Broad-complex transcription factor mediates opposing hormonal regulation of two phylogenetically distant arginine kinase genes in Tribolium castaneum.

Commun Biol 2020 10 30;3(1):631. Epub 2020 Oct 30.

College of Horticulture and Plant Protection, Yangzhou University, 225009, Yangzhou, China.

The phosphoarginine-arginine kinase shuttle system plays a critical role in maintaining insect cellular energy homeostasis. Insect molting and metamorphosis are coordinated by fluctuations of the ecdysteroid and juvenile hormone. However, the hormonal regulation of insect arginine kinases remain largely elusive. In this report, we comparatively characterized two arginine kinase genes, TcAK1 and TcAK2, in Tribolium castaneum. Functional analysis using RNAi showed that TcAK1 and TcAK2 play similar roles in adult fertility and stress response. TcAK1 was detected in cytoplasm including mitochondria, whereas TcAK2 was detected in cytoplasm excluding mitochondria. Interestingly, TcAK1 expression was negatively regulated by 20-hydroxyecdysone and positively by juvenile hormone, whereas TcAK2 was regulated by the opposite pattern. RNAi, dual-luciferase reporter assays and electrophoretic mobility shift assay further revealed that the opposite hormonal regulation of TcAK1 and TcAK2 was mediated by transcription factor Broad-Complex. Finally, relatively stable AK activities were observed during larval-pupal metamorphosis, which was generally consistent with the constant ATP levels. These results provide new insights into the mechanisms underlying the ATP homeostasis in insects by revealing opposite hormonal regulation of two phylogenetically distant arginine kinase genes.
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http://dx.doi.org/10.1038/s42003-020-01354-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603314PMC
October 2020
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