Publications by authors named "Chunlin Wang"

237 Publications

Regional Disparities in Obesity Among a Heterogeneous Population of Chinese Children and Adolescents.

JAMA Netw Open 2021 Oct 1;4(10):e2131040. Epub 2021 Oct 1.

Department of Endocrinology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Importance: Obesity is a public health challenge in China, but the geographical profiles of overweight and obesity among Chinese children are limited.

Objective: To examine regional disparities in the prevalence of obesity among the heterogeneous population of Chinese children and adolescents to provide a more accurate profile of obesity among children in China.

Design, Setting, And Participants: The Prevalence and Risk Factors for Obesity and Diabetes in Youth (PRODY) study was a cross-sectional survey study conducted from January 1, 2017, to December 31, 2019, among 201 098 children aged 3 to 18 years from 11 provinces, autonomous regions, and municipalities that produced a sample of Chinese children with a full range of ages and wide geographical coverage using a multistage, stratified, cluster-sampling design.

Exposures: Five regions geographically representative of China (northern, eastern, southern, western, and central).

Main Outcomes And Measures: The body weights and heights of all participants were measured. Multilevel, multinomial logistic regression models were used to estimate the prevalence of overweight and obesity.

Results: Among 201 098 healthy children (105 875 boys [52.6%]; mean [SD] age, 9.8 [3.8] years) from eastern, southern, northern, central, and western China, the highest obesity prevalence was estimated for children aged 8 to 13 years in northern China (from 18.8% [95% CI, 16.2%-21.7%] to 23.6% [95% CI, 20.5%-26.9%]) and for boys aged 3 to 6 years in western China (from 18.1% [95% CI, 10.4%-29.4%] to 28.6% [95% CI, 14.3%-49.0%]). Boys had a higher prevalence than girls of obesity only in eastern and northern China, with a mean difference in prevalence of 4.6% (95% CI, 3.8%-5.4%) and 7.6% (95% CI, 6.5%-8.6%), respectively.

Conclusions And Relevance: In this survey study, substantial geographic disparities in the prevalence of obesity and overweight were found among the heterogeneous population of Chinese children. The results suggest that special attention should be paid to vulnerable children and that regionally adapted interventions are needed to efficiently mitigate obesity in children.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.31040DOI Listing
October 2021

Propofol mediates pancreatic cancer cell activity through the repression of ADAM8 via SP1.

Oncol Rep 2021 Dec 7;46(6). Epub 2021 Oct 7.

State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China.

Propofol is a commonly used anesthetic with controversial effects on cancer cells. A growing number of studies have demonstrated that low concentrations of propofol are associated with tumor suppression and when used as an intravenous anesthesia improved recurrence‑free survival rates for many cancers, but deeper insights into its underlying mechanism are needed. The study detailed herein focused upon the effect of propofol on pancreatic cancer cells and the mechanism by which propofol reduces A disintegrin and metalloproteinase 8 (ADAM8) expression. The ability of propofol to impact the proliferation, migration and cell cycle of pancreatic cancer cell lines was assessed . This was mechanistically explored following the identification of SP1 binding sites within ADAM8, which enabled the regulatory effects of specificity protein 1 (SP1) on ADAM8 following propofol treatment to be further explored. Ultimately, this study was able to show that propofol significantly inhibited the proliferation, migration and invasion of pancreatic cancer cells and decreased the percentage of cells in S‑phase. Propofol treatment was also shown to repress ADAM8 and SP1 expression, but was unable to affect ADAM8 expression following knockdown of SP1. Moreover, a direct physical interaction between SP1 and ADAM8 was verified using co‑immunoprecipitation and dual‑luciferase reporter assays. Cumulatively, these results suggest that propofol represses pathological biological behaviors associated with pancreatic cancer cells through the suppression of SP1, which in turn results in lower mRNA expression and protein levels.
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http://dx.doi.org/10.3892/or.2021.8200DOI Listing
December 2021

gene variants in familial short stature: a single-center study.

J Pediatr Endocrinol Metab 2021 Sep 27. Epub 2021 Sep 27.

Department of Pediatrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.

Objectives: variants are associated with various short stature and bone dysplasia, such as acromesomelic dysplasia Maroteaux tyoe, individuals with a phenotype similar to Léri-Weill syndrome (LWD), and idiopathic short stature (ISS). However, few studies have reported on the relationship between familial short stature (FSS) and variants. This study aimed to explore the relationship between FSS and variants through the detection and identification of variants in children with FSS, phenotypic description, clear treatment plan, and follow-up of treatment effect.

Methods: Children who met the FSS diagnostic criteria and had informed consent were included in the study. The trio whole-exome sequencing method (trio-WES) was used to detect and evaluate the variants.

Results: A total of 16 children with short stature were included in this study (pretreatment height ≤ -2 standard deviation (SD) in both the patient and the shorter parent, unknown genetic etiology). variants were identified in 12.5%(2/16) of the participants. Patient A was a 6-year-old male and 103.7 cm tall (-3.11SD), while Patient B was a 9-year-old female and 123.2 cm tall (-1.88SD). However, their heights increased after recombinant human growth hormone (rhGH) treatment. The height of patient A increased by 0.36SD six months after treatment while that of patient B increased by 1.22SD after one and a half years of treatment.

Conclusions: variant causes FSS. The growth rate of children significantly improved after rhGH treatment. However, further follow-up study is needed to determine the final height after long-term treatment.
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http://dx.doi.org/10.1515/jpem-2021-0332DOI Listing
September 2021

Dissecting Tumor Antigens and Immune Subtypes of Glioma to Develop mRNA Vaccine.

Front Immunol 2021 27;12:709986. Epub 2021 Aug 27.

Department of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, China.

Background: Nowadays, researchers are leveraging the mRNA-based vaccine technology used to develop personalized immunotherapy for cancer. However, its application against glioma is still in its infancy. In this study, the applicable candidates were excavated for mRNA vaccine treatment in the perspective of immune regulation, and suitable glioma recipients with corresponding immune subtypes were further investigated.

Methods: The RNA-seq data and clinical information of 702 and 325 patients were recruited from TCGA and CGGA, separately. The genetic alteration profile was visualized and compared by cBioPortal. Then, we explored prognostic outcomes and immune correlations of the selected antigens to validate their clinical relevance. The prognostic index was measured GEPIA2, and infiltration of antigen-presenting cells (APCs) was calculated and visualized by TIMER. Based on immune-related gene expression, immune subtypes of glioma were identified using consensus clustering analysis. Moreover, the immune landscape was visualized by graph learning-based dimensionality reduction analysis.

Results: Four glioma antigens, namely ANXA5, FKBP10, MSN, and PYGL, associated with superior prognoses and infiltration of APCs were selected. Three immune subtypes IS1-IS3 were identified, which fundamentally differed in molecular, cellular, and clinical signatures. Patients in subtypes IS2 and IS3 carried immunologically cold phenotypes, whereas those in IS1 carried immunologically hot phenotype. Particularly, patients in subtypes IS3 and IS2 demonstrated better outcomes than that in IS1. Expression profiles of immune checkpoints and immunogenic cell death (ICD) modulators showed a difference among IS1-IS3 tumors. Ultimately, the immune landscape of glioma elucidated considerable heterogeneity not only between individual patients but also within the same immune subtype.

Conclusions: ANXA5, FKBP10, MSN, and PYGL are identified as potential antigens for anti-glioma mRNA vaccine production, specifically for patients in immune subtypes 2 and 3. In summary, this study may shed new light on the promising approaches of immunotherapy, such as devising mRNA vaccination tailored to applicable glioma recipients.
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http://dx.doi.org/10.3389/fimmu.2021.709986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429949PMC
August 2021

Single-cell analysis of a tumor-derived exosome signature correlates with prognosis and immunotherapy response.

J Transl Med 2021 09 8;19(1):381. Epub 2021 Sep 8.

Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.

Background: Tumor-derived exosomes (TEXs) are involved in tumor progression and the immune modulation process and mediate intercellular communication in the tumor microenvironment. Although exosomes are considered promising liquid biomarkers for disease diagnosis, it is difficult to discriminate TEXs and to develop TEX-based predictive biomarkers.

Methods: In this study, the gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database, IMvigor210 cohorts, and six independent Gene Expression Omnibus datasets. A TEXs-associated signature named TEXscore was established to predict overall survival in multiple cancer types and in patients undergoing immune checkpoint blockade therapies.

Results: Based on exosome-associated genes, we first constructed a tumor-derived exosome signature named TEXscore using a principal component analysis algorithm. In single-cell RNA-sequencing data analysis, ascending TEXscore was associated with disease progression and poor clinical outcomes. In the TCGA Pan-Cancer cohort, TEXscore was elevated in tumor samples rather than in normal tissues, thereby serving as a reliable biomarker to distinguish cancer from non-cancer sources. Moreover, high TEXscore was associated with shorter overall survival across 12 cancer types. TEXscore showed great potential in predicting immunotherapy response in melanoma, urothelial cancer, and renal cancer. The immunosuppressive microenvironment characterized by macrophages, cancer-associated fibroblasts, and myeloid-derived suppressor cells was associated with high TEXscore in the TCGA and immunotherapy cohorts. Besides, TEXscore-associated miRNAs and gene mutations were also identified. Further experimental research will facilitate the extending of TEXscore in tumor-associated exosomes.

Conclusions: TEXscore capturing tumor-derived exosome features might be a robust biomarker for prognosis and treatment responses in independent cohorts.
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http://dx.doi.org/10.1186/s12967-021-03053-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424990PMC
September 2021

An immunotherapeutic approach to decipher the role of long non-coding RNAs in cancer progression, resistance and epigenetic regulation of immune cells.

J Exp Clin Cancer Res 2021 Jul 24;40(1):242. Epub 2021 Jul 24.

State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, Guizhou Province, People's Republic of China.

Immunotherapeutic treatments are gaining attention due to their effective anti-tumor response. Particularly, the revolution of immune checkpoint inhibitors (ICIs) produces promising outcomes for various cancer types. However, the usage of immunotherapy is limited due to its low response rate, suggesting that tumor cells escape the immune surveillance. Rapid advances in transcriptomic profiling have led to recognize immune-related long non-coding RNAs (LncRNAs), as regulators of immune cell-specific gene expression that mediates immune stimulatory as well as suppression of immune response, indicating LncRNAs as targets to improve the efficacy of immunotherapy against tumours. Moreover, the immune-related LncRNAs acting as epigenetic modifiers are also under deep investigation. Thus, herein, is a summarised knowledge of LncRNAs and their regulation in the adaptive and innate immune system, considering their importance in autophagy and predicting putative immunotherapeutic responses.
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http://dx.doi.org/10.1186/s13046-021-01997-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305593PMC
July 2021

iTRAQ-based quantitative proteomic analysis of the hepatopancreas in Scylla paramamosain during the molting cycle.

Comp Biochem Physiol Part D Genomics Proteomics 2021 Jul 1;40:100870. Epub 2021 Jul 1.

School of Marine Science, Ningbo University, Ningbo, Zhejiang 315832, China. Electronic address:

The hepatopancreas is the key organ involved in energy storage, immune response, and metabolism during crustacean molting, yet the underlying molecular mechanisms in the hepatopancreas that regulate molting remain unknown. In the present study, we conducted a comprehensive proteomic analysis in the hepatopancreas and quantified 1527 proteins, of which 193 changed significantly in abundance among three molting stages (pre-molt: PrM, post-molt: PoM, and inter-molt: InM) of Scylla paramamosain using iTRAQ-coupled LC-MS/MS. Ten exoskeleton and cuticle reconstruction proteins, such as chitinase, cuticle protein and myosin heavy chain, were found change significantly in abundance between PoM and PrM. Six energy metabolism proteins such as mitochondrial cytochrome c oxidase, cytochrome b-c1 and cAMP-dependent protein kinase with positive loadings showed a higher abundance in InM than PoM. In addition, all differentially abundance proteins (DAPs) were annotated for GO function and KEGG pathway analysis. GO analysis demonstrated function subcategories mainly including thiamine metabolism, complement and coagulation cascades, endocrine, shigellosis, salmonella infection, and other factor-regulated calcium reabsorption. The KEGG pathway enrichment analysis indicated that the DAPs were mainly involved in reconstruction of the exoskeleton and cuticle, energy reserves, metabolism, and immune response during the molting process. The results for the proteins and key pathways involved in the molting process provide fundamental molecular evidence that will improve our understanding of morphological and metabolism variation in the molting cycle and will serve as a potential blueprint for future study on molecular mechanism of molting in crustaceans.
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http://dx.doi.org/10.1016/j.cbd.2021.100870DOI Listing
July 2021

Elevated pCO alters the interaction patterns and functional potentials of rearing seawater microbiota.

Environ Pollut 2021 Oct 18;287:117615. Epub 2021 Jun 18.

Key Laboratory of Applied Marine Biotechnology, Ningbo University, Chinese Ministry of Education, Ningbo, China. Electronic address:

Mean oceanic CO values have already risen and are expected to rise further on a global scale. Elevated pCO (eCO) changes the bacterial community in seawater. However, the ecological association of seawater microbiota and related geochemical functions are largely unknown. We provide the first evidence that eCO alters the interaction patterns and functional potentials of microbiota in rearing seawater of the swimming crab, Portunus trituberculatus. Network analysis showed that eCO induced a simpler and more modular bacterial network in rearing seawater, with increased negative associations and distinct keystone taxa. Using the quantitative microbial element cycling method, nitrogen (N) and phosphorus (P) cycling genes exhibited the highest increase after one week of eCO stress and were significantly associated with keystone taxa. However, the functional potential of seawater bacteria was decoupled from their taxonomic composition and strongly coupled with eCO levels. The changed functional potential of seawater bacteria contributed to seawater N and P chemistry, which was highlighted by markedly decreased NH, NH-N, and PO-P levels and increased NO-N and NO-N levels. This study suggests that eCO alters the interaction patterns and functional potentials of seawater microbiota, which lead to the changes of seawater chemical parameters. Our findings provide new insights into the mechanisms underlying the effects of eCO on marine animals from the microbial ecological perspective.
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http://dx.doi.org/10.1016/j.envpol.2021.117615DOI Listing
October 2021

ERK activation via A1542/3 limonoids attenuates erythroleukemia through transcriptional stimulation of cholesterol biosynthesis genes.

BMC Cancer 2021 Jun 9;21(1):680. Epub 2021 Jun 9.

State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Province Science City, High Tech Zone, Baiyun District, Guiyang, 550014, Guizhou Province, People's Republic of China.

Background: Cholesterol plays vital roles in human physiology; abnormal levels have deleterious pathological consequences. In cancer, elevated or reduced expression of cholesterol biosynthesis is associated with good or poor prognosis, but the underlying mechanisms are largely unknown. The limonoid compounds A1542 and A1543 stimulate ERK/MAPK by direct binding, leading to leukemic cell death and suppression of leukemia in mouse models. In this study, we investigated the downstream consequences of these ERK/MAPK agonists in leukemic cells.

Methods: We employed RNAseq analysis combined with Q-RT-PCR, western blot and bioinformatics to identify and confirm genes whose expression was altered by A1542 and A1543 in leukemic cells. ShRNA lentiviruses were used to silence gene expression. Cell culture and an animal model (BALB/c) of erythroleukemia induced by Friend virus were utilized to validate effects of cholesterol on leukemia progression.

Results: RNAseq analysis of A1542-treated cells revealed the induction of all 18 genes implicated in cholesterol biosynthesis. Expression of these cholesterol genes was blocked by cedrelone, an ERK inhibitor. The cholesterol inhibitor lovastatin diminished ERK/MAPK activation by A1542, thereby reducing leukemic cell death induced by this ERK1/2 agonist. Growth inhibition by cholesterol was observed both at the intracellular level, and when orally administrated into a leukemic mouse model. Both HDL and LDL also suppressed leukemogenesis, implicating these lipids as important prognostic markers for leukemia progression. Mechanistically, knockdown experiments revealed that the activation of SREBP1/2 by A1542-A1543 was responsible for induction of only a sub-set of cholesterol biosynthesis genes. Induction of other regulatory factors by A1542-A1543 including EGR1, AP1 (FOS + JUN) LDLR, IER2 and others may cooperate with SREBP1/2 to induce cholesterol genes. Indeed, pharmacological inhibition of AP1 significantly inhibited cholesterol gene expression induced by A1542. In addition to leukemia, high expression of cholesterol biosynthesis genes was found to correlate with better prognosis in renal cancer.

Conclusions: This study demonstrates that ERK1/2 agonists suppress leukemia and possibly other types of cancer through transcriptional stimulation of cholesterol biosynthesis genes.
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http://dx.doi.org/10.1186/s12885-021-08402-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191108PMC
June 2021

Live Yeast or Live Yeast Combined with Zinc Oxide Enhanced Growth Performance, Antioxidative Capacity, Immunoglobulins and Gut Health in Nursery Pigs.

Animals (Basel) 2021 May 31;11(6). Epub 2021 May 31.

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.

This study aimed to investigate the effects of dietary LY or LY combined with ZnO supplementation on performance and gut health in nursery pigs. 192 Duroc × Landrace × Yorkshire piglets (weaned on d 32 of the age with 9.2 ± 1.7 kg BW) were allocated into four treatments with eight replicate pens, six piglets per pen. The treatments included a basal diet as control (CTR), an antibiotic plus ZnO diet (CTC-ZnO, basal diet + 75 mg/kg of chlortetracycline + ZnO (2000 mg/kg from d 1 to 14, 160 mg/kg from d 15 to 28)), a LY diet (LY, basal diet + 2 g/kg LY), and a LY plus ZnO diet (LY-ZnO, basal diet + 1 g/kg LY + ZnO). The results showed that pigs fed LY or LY-ZnO had increased ( < 0.05) average daily gain, serum IgA, IgG, superoxide dismutase, fecal butyric acid, and total volatile fatty acid concentrations, as well as decreased ( < 0.05) feed conversion ratio and diarrhea rate compared with CTR. In conclusion, pigs fed diets with LY or LY combined with ZnO had similar improvement to the use of antibiotics and ZnO in performance, antioxidant status, immunoglobulins, and gut health in nursery pigs.
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http://dx.doi.org/10.3390/ani11061626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228624PMC
May 2021

Retraction Note to: Effects of BDNF-Transfected BMSCs on Neural Functional Recovery and Synaptophysin Expression in Rats with Cerebral Infarction.

Mol Neurobiol 2021 Jul;58(7):3602

Department of Neurosurgery, No. 105 Hospital of PLA, No. 424 Changjiang West Road, Hefei, 230031, Anhui, People's Republic of China.

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http://dx.doi.org/10.1007/s12035-021-02416-8DOI Listing
July 2021

Outbreak of vibriosis associated with Vibrio parahaemolyticus in the mud crab Scylla paramamosain cultured in China.

Dis Aquat Organ 2021 May 27;144:187-196. Epub 2021 May 27.

School of Marine Sciences, Ningbo University, Ningbo, Zhejiang Province 315832, PR China.

In this study, a Gram-negative bacterium was isolated from diseased Scylla paramamosain and tentatively named strain QX17. The bacterial isolate was identified as Vibrio parahaemolyticus based on morphological and biochemical characteristics and molecular identification with the 16S rRNA and HSP60 genes. In the challenge experiment, S. paramamosain injected intramuscularly with the V. parahaemolyticus isolate developed pathological signs similar to the naturally diseased mud crabs. The infection experiment also showed that the median lethal dosage (LD50) for QX17 was 4.79 × 102 CFU g-1 (crab weight). Histopathological analysis of the diseased mud crabs infected with V. parahaemolyticus showed deformation and basement membrane rupture of hepatopancreatic tubules in the hepatopancreas, and disordered and broken muscle fiber in the muscle. Antimicrobial susceptibility tests revealed that QX17 was highly sensitive to most of the tested aminoglycosides, tetracyclines, and quinolones. To the best of our knowledge, this is the first study reporting isolation and antibiotic sensitivities of V. parahaemolyticus from cultured mud crabs. The discovery of V. parahaemolyticus in cultured mud crabs not only adds to the growing list of emerging pathogens in crab aquaculture in China, but also highlights the necessity of developing early detection strategies and appropriate interventions to reduce the damage caused by V. parahaemolyticus in mud crab aquaculture.
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http://dx.doi.org/10.3354/dao03587DOI Listing
May 2021

Serum-Derived Small Extracellular Vesicles From Diabetic Mice Impair Angiogenic Property of Microvascular Endothelial Cells: Role of EZH2.

J Am Heart Assoc 2021 05 14;10(10):e019755. Epub 2021 May 14.

Center for Translational Medicine Lewis Katz School of Medicine Temple University Philadelphia PA.

Background Impaired angiogenic abilities of the microvascular endothelial cell (MVEC) play a crucial role in diabetes mellitus-impaired ischemic tissue repair. However, the underlying mechanisms of diabetes mellitus-impaired MVEC function remain unclear. We studied the role of serum-derived small extracellular vesicles (ssEVs) in diabetes mellitus-impaired MVEC function. Methods and Results ssEVs were isolated from 8-week-old male db/db and db/+ mice by ultracentrifugation and size/number were determined by the Nano-sight tracking system. Diabetic ssEVs significantly impaired tube formation and migration abilities of human MVECs. Furthermore, local transplantation of diabetic ssEVs strikingly reduced blood perfusion and capillary/arteriole density in ischemic hind limb of wildtype C57BL/6J mice. Diabetic ssEVs decreased secretion/expression of several pro-angiogenic factors in human MVECs. Mechanistically, expression of enhancer of zest homolog 2 (EZH2), the major methyltransferase responsible for catalyzing H3K27me3 (a transcription repressive maker), and H3K27me3 was increased in MVECs from db/db mice. Diabetic ssEVs increased EZH2 and H3K27me3 expression/activity in human MVECs. Expression of EZH2 mRNA was increased in diabetic ssEVs. EZH2-specific inhibitor significantly reversed diabetic ssEVs-enhanced expression of EZH2 and H3K27me3, impaired expression of angiogenic factors, and improved blood perfusion and vessel density in ischemic hind limb of C57BL/6J mice. Finally, EZH2 inactivation repressed diabetic ssEVs-induced H3K27me3 expression at promoter of pro-angiogenic genes. Conclusions Diabetic ssEVs impair the angiogenic property of MVECs via, at least partially, transferring EZH2 mRNA to MVECs, thus inducing the epigenetic mechanism involving EZH2-enhanced expression of H3K27me3 and consequent silencing of pro-angiogenic genes. Our findings unravel the cellular mechanism and expand the scope of bloodborne substances that impair MVEC function in diabetes mellitus.
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http://dx.doi.org/10.1161/JAHA.120.019755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200714PMC
May 2021

Integrated metabolomics and transcriptomics reveal the anti-aging effect of melanin from ink (MSMI) on D-galactose-induced aging mice.

Aging (Albany NY) 2021 04 21;13(8):11889-11906. Epub 2021 Apr 21.

Key Laboratory of Applied Marine Biotechnology, Ministry of Education, Ningbo University, Ningbo 315211, China.

ink, a flavoring and coloring agent in food, has attracted considerable attention due to its various pharmacological activities. Our previous study showed that the melanin of ink (MSMI) can alleviate oxidative damage and delay aging in D-galactose(D-gal)-induced aging mice. This study aimed to reveal the possible mechanisms of the anti-aging effect of MSMI. In this article, a comprehensive analysis of gas chromatography-mass spectrometry (GC-MS)-based metabolomics and microarray-based transcriptomics revealed that 221 mRNAs were differentially expressed and 46 metabolites were significantly changed in the anti-aging progress of MSMI. Integrated analysis of transcript and metabolic profiles indicated that MSMI mainly altered carbohydrate metabolism, lipid metabolism, and insulin signaling pathway. MSMI achieved anti-aging effects not only by reducing oxidative damage and sorbitol toxicity but also by regulating lipid metabolism, improving insulin sensitivity, and reducing the formation of advanced glycation end products (AGEs). Moreover, our findings firstly demonstrated that MSMI could increase the expression of interferon-induced proteins and might be a potential antiviral compound.
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http://dx.doi.org/10.18632/aging.202890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109126PMC
April 2021

Preterm Birth and Birth Weight and the Risk of Type 1 Diabetes in Chinese Children.

Front Endocrinol (Lausanne) 2021 14;12:603277. Epub 2021 Apr 14.

Department of Endocrinology, National Clinical Research Center for Child Health, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Aims: Findings from previous studies about the association of preterm birth as well as birth weight with the risk of T1DM were still inconsistent. We aimed to further clarify these associations based on Chinese children and explore the role of gender therein.

Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in China from 2017 to 2019. Children aged between 3 and 18 years old with complete information were included in this analysis. Multiple Poisson regression models were used for evaluating the associations of birth weight as well as preterm birth with T1DM in children.

Results: Out of 181,786 children, 82 childhood T1DM cases were identified from questionnaire survey. Children with preterm birth (<37 weeks) had higher risk of type 1 diabetes (OR: 3.17, 95%CI: 1.76-5.71). Children born with high birth weight (≥4,000g) had no statistically significant risk of T1DM (OR:1.71, 95%CI: 0.90-3.22). However, children's gender might modify the effect of high birth weight on T1DM (girls: OR: 3.15, 95%CI: 1.33-7.47; boys: OR: 0.99, 95%CI: 0.38-2.55, for interaction=0.065). In addition, children with low birth weight were not associated with T1DM (OR: 0.70, 95%CI: 0.24-2.08). The findings from matched data had the similar trend.

Conclusions: In China mainland, preterm birth increased the risk of childhood T1DM, but high birth weight only affected girls. Therefore, early prevention of T1DM may start with prenatal care to avoid adverse birth outcomes and more attention should be paid to children with preterm birth and girls with high birth weight after birth.
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http://dx.doi.org/10.3389/fendo.2021.603277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079970PMC
April 2021

A Modified Tumor-Node-Metastasis Staging System for Colon Cancer Patients with Fewer than Twelve Lymph Nodes Examined.

World J Surg 2021 08 29;45(8):2601-2609. Epub 2021 Apr 29.

Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, 157 Baojian Road, Harbin, Heilongjiang, China.

Background: To construct a modified tumor-node-metastasis (TNM) staging system for stage I-III colon cancer patients with lymph nodes examined (LNE) < 12.

Methods: The clinicopathological and survival data of 3870 stage I-III colon cancer patients with LNE < 12 from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 (development cohort) and 126 stage I-III patients with LNE < 12 from the Second Affiliated Hospital of Harbin Medical University between 2011 and 2015 (validation cohort) were identified. The optimal stratification of LNR for cancer-specific survival (CSS) was achieved using X-tile software. The predictive accuracy of the modified stage (mStage) was determined by the concordance index (C-index).

Results: The modified N stage (mN stage) was built based on the LNR (mN0: LNR = 0, mN1: 0 < LNR < 0.4 or cancer nodule formation and mN2: 0.4 ≤ LNR ≤ 1). Preferable C-indices could be found for mStage compared with TNM stage in both development (0.750 vs 0.727) and validation cohorts (0.682 vs 0.646). Besides, patients with mStage A and B diseases could not benefit from adjuvant chemotherapy, while in patients with mStage C-F diseases, those receiving radical surgery plus adjuvant chemotherapy presented better CSS than those with radical surgery alone.

Conclusions: The mStage system could predict the prognosis of colon cancer patients with LNE < 12 accurately and showed superior predictive power compared with conventional TNM staging system. Moreover, adjuvant chemotherapy might play inequable roles in patients with different mStage diseases.
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http://dx.doi.org/10.1007/s00268-021-06141-0DOI Listing
August 2021

β-1,3-Glucan from Euglena gracilis as an immunostimulant mediates the antiparasitic effect against Mesanophrys sp. on hemocytes in marine swimming crab (Portunus trituberculatus).

Fish Shellfish Immunol 2021 Jul 10;114:28-35. Epub 2021 Apr 10.

Key Laboratory of Applied Marine Biotechnology, Ministry of Education; Collaborative Innovation Center for Zhejiang Marine High-efficiency and Healthy Aquaculture; School of Marine Sciences, Ningbo University, 818 Fenghua Road, Ningbo, 315211, PR China. Electronic address:

β-1,3-glucans, natural polysaccharide groups, exert immunomodulatory effects to improve the innate response and disease resistance in aquatic species and mammals. However, this β-glucan stimulant is yet to be assayed in swimming crab (Portunus trituberculatus) hemocytes. In this study, we explored the immunomodulatory effect of β-1,3-glucans (derived from Euglena gracilis) via in vitro 24 h stimulation assays in swimming crab hemocytes. We found that this algal β-1,3-glucans in crab hemocytes significantly elevated cellular enzymes related parameters, including phenoloxidase (PO), lysozyme, acid phosphatase (ACP) activities, and superoxide anion generation (O) rate both at intracellular (P < 0.05) and extracellular (P < 0.05) levels. Besides, alkaline phosphatase (AKP) in hemocytes exhibited no significant differences across the groups (P > 0.05). β-glucan significantly influenced (P < 0.05) the activities of the antioxidant enzyme, superoxide dismutase (SOD) in hemocytes. Moreover, the relative mRNA expression of numerous immune-related genes, including proPO, TLR-2, Alf-1, NOX, Lysozyme, Crustin-1, and Cuznsod, was significantly higher stimulated hemocytes than in control (P < 0.05). We also reported the dose-dependent antiparasitic activity against Mesanophyrs sp., in stimulated hemocytes than in the control (P < 0.05). The present study collectively demonstrated that β-glucan potentially stimulates innate immunity by elevating cellular enzyme responses and up-regulating the mRNA expression of genes associated with crab innate immunity. Thus, β-glucan is a promising immunostimulant for swimming crab farming in crustaceans aquaculture.
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http://dx.doi.org/10.1016/j.fsi.2021.04.005DOI Listing
July 2021

FLI1 Induces Megakaryopoiesis Gene Expression Through WAS/WIP-Dependent and Independent Mechanisms; Implications for Wiskott-Aldrich Syndrome.

Front Immunol 2021 26;12:607836. Epub 2021 Feb 26.

State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.

Wiskott-Aldrich Syndrome, WAS/WAVE, is a rare, X-linked immune-deficiency disease caused by mutations in the gene, which together with its homolog, N-, regulates actin cytoskeleton remodeling and cell motility. WAS patients suffer from microthrombocytopenia, characterized by a diminished number and size of platelets, though the underlying mechanism is not fully understood. Here, we identified FLI1 as a direct transcriptional regulator of and its binding partner . Depletion of either or in human erythroleukemic cells accelerated cell proliferation, suggesting tumor suppressor function of both genes in leukemia. Depletion of also led to a significant reduction in the percentage of CD41 and CD61 positive cells, which mark committed megakaryocytes. RNAseq analysis revealed common changes in megakaryocytic gene expression following FLI1 or WASP knockdown. However, in contrast to FLI1, WASP depletion did not alter expression of late-stage platelet-inducing genes. N-WASP was not regulated by FLI1, yet its silencing also reduced the percentage of CD41+ and CD61+ megakaryocytes. Moreover, combined knockdown of WASP and N-WASP further suppressed megakaryocyte differentiation, indicating a major cooperation of these related genes in controlling megakaryocytic cell fate. However, unlike WASP/WIP, N-WASP loss suppressed leukemic cell proliferation. WASP, WIP and N-WASP depletion led to induction of FLI1 expression, mediated by GATA1, and this may mitigate the severity of platelet deficiency in WAS patients. Together, these results uncover a crucial role for FLI1 in megakaryocyte differentiation, implicating this transcription factor in regulating microthrombocytopenia associated with Wiskott-Aldrich syndrome.
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http://dx.doi.org/10.3389/fimmu.2021.607836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953068PMC
July 2021

Global analysis of shared T cell specificities in human non-small cell lung cancer enables HLA inference and antigen discovery.

Immunity 2021 03;54(3):586-602.e8

Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA.

To identify disease-relevant T cell receptors (TCRs) with shared antigen specificity, we analyzed 778,938 TCRβ chain sequences from 178 non-small cell lung cancer patients using the GLIPH2 (grouping of lymphocyte interactions with paratope hotspots 2) algorithm. We identified over 66,000 shared specificity groups, of which 435 were clonally expanded and enriched in tumors compared to adjacent lung. The antigenic epitopes of one such tumor-enriched specificity group were identified using a yeast peptide-HLA A02:01 display library. These included a peptide from the epithelial protein TMEM161A, which is overexpressed in tumors and cross-reactive epitopes from Epstein-Barr virus and E. coli. Our findings suggest that this cross-reactivity may underlie the presence of virus-specific T cells in tumor infiltrates and that pathogen cross-reactivity may be a feature of multiple cancers. The approach and analytical pipelines generated in this work, as well as the specificity groups defined here, present a resource for understanding the T cell response in cancer.
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http://dx.doi.org/10.1016/j.immuni.2021.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960510PMC
March 2021

Trilineage Sequencing Reveals Complex TCRβ Transcriptomes in Neutrophils and Monocytes Alongside T Cells.

Genomics Proteomics Bioinformatics 2021 Mar 1. Epub 2021 Mar 1.

Institute for Clinical Chemistry, University of Heidelberg Medical Faculty Mannheim, D- 68167 Mannheim, Germany; Ingenium digital diagnostics, D-87662 Kaltental, Germany. Electronic address:

Recent findings indicate the presence of T cell receptor-based combinatorial immune receptors beyond T cells in neutrophils and monocytes/macrophages. Using a semiquantitative trilineage immune repertoire sequencing approach, we identify under rigorous bioinformatic conditions highly complex TCRβ transcriptomes in circulating human neutrophils and monocytes which encode repertoire diversities that are one and two orders of magnitudes, respectively, smaller than that of T cells. Intraindividual transcriptomic analyses reveal that neutrophils, monocytes and T cells express distinct TCRβ repertoires with less than 0.1% overall trilineage repertoire sharing. Interindividual comparison shows that in all three leukocyte lineages the vast majority of the expressed TCRβ variants are private. We also find that differentiation of monocytes into macrophages induces dramatic individual-specific repertoire shifts revealing a surprising degree of immune repertoire plasticity in the monocytic lineage. These results uncover the remarkable complexity of the two phagocyte-based flexible immune systems which until now has been hidden in the shadow of T cells.
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http://dx.doi.org/10.1016/j.gpb.2019.02.004DOI Listing
March 2021

Ubash3b promotes TPA-mediated suppression of leukemogenesis through accelerated downregulation of PKCδ protein.

Biochimie 2021 May 5;184:8-17. Epub 2021 Feb 5.

State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, Guizhou, 550014, PR China. Electronic address:

Acquired drug-resistance, often involving downregulation or mutations in the target protein, is a major caveat in precision medicine. Understanding mechanisms of resistance to therapeutic drugs may unravel strategies to overcome or prevent them. We previously identified phorbol ester (PE) compounds such as TPA that induce Protein Kinase δ (PKCδ), thereby suppressing leukemogenesis. Here we identified erythroleukemia cell lines that resist PEs and showed that reduced PKCδ protein expression underlies drug resistance. Reduced level of PKCδ in resistant cell lines was due to its phosphorylation followed by protein degradation. Indeed, proteasome inhibition prevented PE-induced loss of PKCδ. Accordingly, a combination of TPA and the proteasome inhibitor ALLN significantly suppressed leukemia in a mouse model of leukemia. PKCδ downregulation by TPA was independent of the downstream MAPK/ERK/P38/JNK pathway. Instead, expression of ubiquitin-associated and SH3 domain-containing protein b (Ubash3b) was induced by TPA, which leads to PKCδ protein dephosphorylation and degradation. This specific degradation was blocked by RNAi-mediated depletion of Ubash3b. In drug-sensitive leukemic cells, TPA did not induce Ubash3b, and consequently, PKCδ levels remained high. A PE-resistant cell line derived from PE-treated sensitive cells exhibited very low PKCδ expression. In these drug resistance cells, a Ubash3b independent mechanism led to PKCδ degradation. Thus, PE compounds in combination with proteasome or specific inhibitors for Ubash3b, or other factors can overcome resistance to TPA, leading to durable suppression of leukemic growth. These results identify Ubash3b as a potential target for drug development.
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http://dx.doi.org/10.1016/j.biochi.2021.02.001DOI Listing
May 2021

Compound hemizygous variants in SERPINA7 gene cause thyroxine-binding globulin deficiency.

Mol Genet Genomic Med 2021 02 7;9(2):e1571. Epub 2021 Feb 7.

Pediatric Department, The 1st Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Sub-heading: Compound hemizygous variants in SERPINA7 gene.

Background: Thyroxine-binding globulin (TBG) is encoded by SERPINA7 (OMIM. 314200) which is located on Xq22.3. SERPINA7 variants caused TBG deficiency which does not require treatment, but the decreased thyroxine may be misdiagnosed as hypothyroidism. We discovered some variants of TBG caused by alterations that differ from previously reported.

Materials And Methods: In this study, we enrolled 32 subjects from 10 families and sequenced the SERPINA7 genes of TBG-deficient subjects. Then, variants were analyzed to assess their effect on TBG expression and secretion. Bioinformatics database, protein structure, and dynamics simulation were used to evaluate the deleterious effects. Finally, we identified 2 novel and 4 known variants, and found 26 of 30 subjects carried the p.L303F. The DynaMut predictions indicated the variants (p.E91K, p.I92T, p.R294C, and p.L303F) exhibited decreased stability.

Conclusion: Analyses revealed the p.L303F change the protein stability and flexibility, and it had an impact on the function of TBG, but when coexisted with other variants it might change the conformational structure of the protein and aggravate the damage to the protein. We speculated that the existence of a higher number of variants resulted in lower TBG secretion.
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http://dx.doi.org/10.1002/mgg3.1571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077092PMC
February 2021

L20, a Calothrixin B analog, induces intrinsic apoptosis on HEL cells through ROS/γ-H2AX/p38 MAPK pathway.

Biomed Pharmacother 2021 May 5;137:111336. Epub 2021 Feb 5.

State Key Laboratory for Functions and Applications of Medicinal Plants/Department of Immunology, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang 550014, PR China. Electronic address:

Erythroleukemia is a malignant disease in the blood system. Quinones consists of a class of antitumor agents. Calothrixin B is a carbazole-1,4-quinone alkaloid isolated from Calothrix cyanobacteria with a unique indolo[3,2-j] phenanthridine framework. This study aimed to investigate the anti-leukemic effect of the new Calothrixin B derivative, L20, and to dig up the underlying mechanisms. Cytotoxicity analysis of L20 has revealed that it shows significant IC concentrations in HEL cells at low doses (1.10 ± 0.05 µM) than in K562, and KG-1a (5.46 ± 3.09, and 1.82 ± 1.08 µM respectively). The study even revealed that the L20 could induce a dose and time-dependent cellular death in HEL cells. The L20 increased expression of phospho-γ-H2A.X and phospho-p38 in HEL cells, causing DNA damage and nuclear alterations due to the G/M phase cell cycle arrest. The HEL cells even lost the mitochondrial membrane potential (MMP) and resulted in the release of reactive oxygen species (ROS). Additionally, L20 inhibited the proliferation of HEL cells by inducing apoptosis through the mitochondrial pathway, depending on the caspase family. The study even established this may be due to the upregulation of the p-P38MAPK and downregulation of p-ERK. Pretreatment with P38/ERK inhibitors, SB203580, and U0126, decreased L20-induced apoptosis. These findings indicated that L20 induced mitochondrial mediated-apoptosis and G/M arrest through DNA damage and modulation of p38 MAPK pathways. Thus, the study suggests L20, a chemical analog of Calothrixin B, as a novel chemotherapeutic agent against erythroleukemia.
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http://dx.doi.org/10.1016/j.biopha.2021.111336DOI Listing
May 2021

Integrative bioinformatics approaches for identifying potential biomarkers and pathways involved in non-obstructive azoospermia.

Transl Androl Urol 2021 Jan;10(1):243-257

Department of Infertility and Sexual Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Non-obstructive azoospermia (NOA) is a disease related to spermatogenic disorders. Currently, the specific etiological mechanism of NOA is unclear. This study aimed to use integrated bioinformatics to screen biomarkers and pathways involved in NOA and reveal their potential molecular mechanisms.

Methods: GSE145467 and GSE108886 gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between NOA tissues and matched obstructive azoospermia (OA) tissues were identified using the GEO2R tool. Common DEGs in the two datasets were screened out by the VennDiagram package. For the functional annotation of common DEGs, DAVID v.6.8 was used to perform Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. In accordance with data collected from the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, a protein-protein interaction (PPI) network was constructed by Cytoscape. Cytohubba in Cytoscape was used to screen the hub genes. Furthermore, the hub genes were validated based on a separate dataset, GSE9210. Finally, potential micro RNAs (miRNAs) of hub genes were predicted by miRWalk 3.0.

Results: A total of 816 common DEGs, including 52 common upregulated and 764 common downregulated genes in two datasets, were screened out. Some of the more important of these pathways, including focal adhesion, PI3K-Akt signaling pathway, cell cycle, oocyte meiosis, AMP-activated protein kinase (AMPK) signaling pathway, FoxO signaling pathway, and Huntington disease, were involved in spermatogenesis. We further identified the top 20 hub genes from the PPI network, including , , , , , , , , , , , , , , , , , , , and , which were all downregulated genes. In addition, potential miRNAs of hub genes, including hsa-miR-3666, hsa-miR-130b-3p, hsa-miR-15b-5p, hsa-miR-6838-5p, and hsa-miR-195-5p, were screened out.

Conclusions: Taken together, the identification of the above hub genes, miRNAs and pathways will help us better understand the mechanisms associated with NOA, and provide potential biomarkers and therapeutic targets for NOA.
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http://dx.doi.org/10.21037/tau-20-1029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844508PMC
January 2021

CTLA-4 expression by B-1a B cells is essential for immune tolerance.

Nat Commun 2021 01 22;12(1):525. Epub 2021 Jan 22.

Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.

CTLA-4 is an important regulator of T-cell function. Here, we report that expression of this immune-regulator in mouse B-1a cells has a critical function in maintaining self-tolerance by regulating these early-developing B cells that express a repertoire enriched for auto-reactivity. Selective deletion of CTLA-4 from B cells results in mice that spontaneously develop autoantibodies, T follicular helper (Tfh) cells and germinal centers (GCs) in the spleen, and autoimmune pathology later in life. This impaired immune homeostasis results from B-1a cell dysfunction upon loss of CTLA-4. Therefore, CTLA-4-deficient B-1a cells up-regulate epigenetic and transcriptional activation programs and show increased self-replenishment. These activated cells further internalize surface IgM, differentiate into antigen-presenting cells and, when reconstituted in normal IgH-allotype congenic recipient mice, induce GCs and Tfh cells expressing a highly selected repertoire. These findings show that CTLA-4 regulation of B-1a cells is a crucial immune-regulatory mechanism.
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http://dx.doi.org/10.1038/s41467-020-20874-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822855PMC
January 2021

Association of Vitamin D Receptor Gene Polymorphisms with Metabolic Syndrome in Chinese Children.

Int J Gen Med 2021 12;14:57-66. Epub 2021 Jan 12.

Department of Pediatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.

Purpose: To investigate the association between vitamin D receptor (VDR) gene polymorphisms and vitamin D deficiency, overweightness/obesity, and metabolic syndrome (MetS) in a cohort of Han children residing in Hangzhou, China.

Patients And Methods: This study assessed 106 overweight/obese and 86 healthy (control) children. Five single-nucleotide polymorphisms (SNPs) in the VDR gene, namely, TaqI (rs731236 T > C), ApaI (rs7975232 C > A), BsmI (rs1544410 G > A), FokI (rs2228570 G >A), and Cdx2 (rs11568820 G > A), were genotyped by sequencing the total polymerase chain reaction products. The distributions of different genotypes and alleles were compared among different groups.

Results: The serum 25-hydroxyvitamin D (25(OH)D) concentration was significantly lower in overweight/obese children, while the AA genotype of ApaI SNP exhibited higher frequencies in the overweight/obese group than in the control. Furthermore, children with the ApaI AA genotype showed higher levels of Glu-60min, Glu-90min, Glu-120min and triglyceride. The AA genotype of FokI SNP was significantly associated with MetS. However, no association was observed between the five VDR SNPs and the risk of vitamin D deficiency.

Conclusion: VDR ApaI polymorphisms appear to be correlated with overweightness/obesity and glucose intolerance. FokI polymorphisms may be linked to a higher susceptibility toward MetS in Chinese children.
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http://dx.doi.org/10.2147/IJGM.S287205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812523PMC
January 2021

A C21-steroidal derivative suppresses T-cell lymphoma in mice by inhibiting SIRT3 via SAP18-SIN3.

Commun Biol 2020 12 3;3(1):732. Epub 2020 Dec 3.

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, China.

The SIN3 repressor complex and the NAD-dependent deacetylase SIRT3 control cell growth, and development as well as malignant transformation. Even then, a little known about cross-talks between these two chromatin modifiers or whether their interaction explored therapeutically. Here we describe the identification of a C-steroidal derivative compound, 3-O-chloroacetyl-gagamine, A671, which potently suppresses the growth of mouse and human T-cell lymphoma and erythroleukemia in vitro and preclinical models. A671 exerts its anti-neoplastic effects by direct interaction with Histone deacetylase complex subunit SAP18, a component of the SIN3 suppressor complex. This interaction stabilizes and activates SAP18, leading to transcriptional suppression of SIRT3, consequently to inhibition of proliferation and cell death. The resistance of cancer cells to A671 correlated with diminished SAP18 activation and sustained SIRT3 expression. These results uncover the SAP18-SIN3-SIRT3 axis that can be pharmacologically targeted by a C-steroidal agent to suppress T-cell lymphoma and other malignancies.
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http://dx.doi.org/10.1038/s42003-020-01458-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713351PMC
December 2020

Transcriptome analysis of genes and pathways associated with metabolism in Scylla paramamosain under different light intensities during indoor overwintering.

BMC Genomics 2020 Nov 10;21(1):775. Epub 2020 Nov 10.

School of Marine Science, Ningbo University, Ningbo, 315211, Zhejiang, China.

Background: Scylla paramamosain is one of the commercially crucial marine crustaceans belonging to the genus Scylla, which is commonly distributed along the coasts of China, Vietnam, and Japan. Genomic and transcriptomic data are scarce for the mud crab. Light intensity is one of the ecological factors that affect S. paramamosain during indoor overwintering. To understand the energy metabolism mechanism adapted to light intensity, we analyzed the transcriptome of S. paramamosain hepatopancreas in response to different light intensities (0, 1.43, 40.31 μmol·m·s).

Results: A total of 5052 differentially expressed genes were identified in low light group (LL group, 3104 genes were up-regulated and 1948 genes were down-regulated). A total of 7403 differentially expressed genes were identified in high light group (HL group, 5262 genes were up-regulated and 2141 genes were down-regulated). S. paramamosain adapts to different light intensity environments through the regulation of amino acids, fatty acids, carbon and energy metabolism. Different light intensities had a strong impact on the energy generation of S. paramamosain by influencing oxygen consumption rate, aerobic respiration, glycolysis/gluconeogenesis pathway, the citrate cycle (TCA cycle) and fatty acid degradation.

Conclusion: Low light is more conducive to the survival of S. paramamosain, which needs to produce and consume relatively less energy to sustain physiological activities. In contrast, S. paramamosain produced more energy to adapt to the pressure of high light intensities. The findings of the study add to the knowledge of regulatory mechanisms related to S. paramamosain metabolism under different light intensities.
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http://dx.doi.org/10.1186/s12864-020-07190-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654585PMC
November 2020

Effect of environmental factors on survival and population growth of ciliated parasite, sp. (Ciliophora: Scuticociliatia) infecting .

Parasitology 2021 04 4;148(4):477-485. Epub 2020 Nov 4.

Key Laboratory of Applied Marine Biotechnology, Ministry of Education; Collaborative Innovation Center for Zhejiang Marine High-efficiency and Healthy Aquaculture; School of Marine Sciences, Ningbo University, 818 Fenghua Road, Ningbo315211, P. R. China.

Mesanophrys sp. is a newly identified parasitic ciliate infecting farmed swimming crab. To demonstrate the correlation between parasite development and environmental conditions, this study aimed to investigate the effect of temperature, salinity, pH and frequency of passage of parasite on survival, growth and body size of Mesanophrys sp. in vitro. The results revealed that survival, population density and growth rate of the parasite were highest at 12°C and decreased with increasing temperature from 16 to 26°C. In addition, the survival, population density and growth rate of Mesanophrys sp. were high at 20‰. When salinity was adjusted to levels lower (0-10‰) and higher (40-60‰) than 20‰, the parasite's survival and growth rate gradually declined. The optimal pH for parasite survival was 8.0, whereas its survival was inhibited at <4.5 or >9.5. Our result also showed that parasite body proportions (length:width) were significantly smaller at the highest temperature compared to the lower temperature, whereas different salinities had no significant effect. Furthermore, we introduced dynamic parasite culture systems in vitro where Mesanophrys sp. was cultured in medium-containing culture plates through continually reducing and halving the old medium into fresh. Application of this optimized dilution timing technique with fresh medium and sub-cultured enabled a continuous culture of parasites. Under this optimized condition, the highest population density and exponential growth rate of the parasite were achieved than that of a control group. This study will help to understand the ciliated parasite infection dynamics and provides new possibilities for in vitro parasite-associated studies.
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http://dx.doi.org/10.1017/S0031182020002127DOI Listing
April 2021

HLA-A Locus is Associated With Sepsis and Septic Shock After Traumatic Injury.

Ann Surg 2020 May 19. Epub 2020 May 19.

*University of Washington, Seattle, Washington †Stanford University, Stanford, California ‡Immucor, Peachtree Corners, Georgia §University of California, San Francisco, California.

Objective: Determine whether variation in the HLA region is associated with the development of post-traumatic sepsis and septic shock.

Background: Sepsis-related deaths remain a major source of mortality after traumatic injury. Genetic characteristics may contribute to susceptibility to adverse outcomes including sepsis and septic shock. Recent advances in next-generation sequencing technology now allow comprehensive genotyping of the HLA region.

Methods: White adult trauma patients requiring more than 2 days of mechanical ventilation underwent HLA genotyping, and were followed for the development of sepsis and septic shock. Odds ratios (OR) for the associations between our outcomes and HLA variants were estimated, a correction for multiple comparisons was applied, and significant variants were included in regression models adjusting for potential confounders.

Results: A total of 1184 patients were included. Patients were severely injured (median injury severity score 33); 33% developed sepsis, 6% septic shock, and in-hospital mortality was 14%. An amino acid variant (156Q) within the HLA-A peptide-binding groove was associated with greater odds of sepsis [OR 1.50, (1.18-1.89)]. HLA-A02:01 was associated with lower odds of septic shock [OR 0.52, (0.32-0.82)]. These associations remained significant after adjusting for potential confounders.

Conclusions: This is the first study to apply next-generation sequencing techniques to evaluate associations between immunogenetic factors and post-traumatic sepsis and septic shock. Associations with class I HLA variants are novel as they implicate adaptive immunity in post-traumatic sepsis. These findings are a step towards developing a panel of genetic markers assessing risk of infection-related complications as we move towards more personalized medicine.
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http://dx.doi.org/10.1097/SLA.0000000000003932DOI Listing
May 2020
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