Publications by authors named "Chen Lin"

4,330 Publications

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Homozygosity for a novel missense variant of causing Joubert syndrome with renal defects in a family of Chinese descent.

Clin Nephrol 2021 Jul 26. Epub 2021 Jul 26.

The retinitis pigmentosa GTPase regulator interacting protein 1-like gene encodes a ciliary protein essential for basic embryonic development. Biallelic variants of cause Joubert syndrome (JS) with renal defects. In addition to characteristic JS features (cerebellar and brain stem malformations, developmental delays, hypotonia, irregular breathing patterns, eye movement abnormalities, ataxia, and intellectual disability), affected individuals typically also exhibit renal disorders, such as cystic kidney disease and nephronophthisis. Here, we describe a 10-year-old female of Chinese descent who was referred to hospital due to lower limb arthralgia. However, the presence of short stature, facial deformities, renal abnormalities, and renal failure suggested a diagnosis of congenital syndrome disorder. Whole-exome sequencing (WES) revealed that the patient was homozygous for a previously unreported variant featuring a missense mutation (NM_015272; c.2180G>A, p.Gly727Asp). A subsequent cranial MRI confirmed the presence of midbrain molar tooth sign and cerebellar Dandy-Walker malformation. However, no significant developmental delays or neurological abnormalities were noted. This study makes a significant contribution to the literature by expanding knowledge of the JS-causing variant spectrum, enhancing understanding of variant-associated JS phenotypes.
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http://dx.doi.org/10.5414/CN110539DOI Listing
July 2021

Differential Metabolomics and Network Pharmacology Analysis of Silkworm Biotransformation between Mulberry Leaves and Silkworm Droppings.

Evid Based Complement Alternat Med 2021 29;2021:8819538. Epub 2021 Jun 29.

Cancer Institute of Integrated Tradition Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, China.

Silkworm droppings are the product of mulberry leaves digested by silkworm intestines, which are an important medicinal resource in traditional Chinese medicine (TCM). The contents of total fat, fat acids, crude protein, amino acids, and secondary metabolites of obtained mulberry leaves and silkworm droppings were analyzed by HPLC, GC-MS, and UHPLC-Q-TOF MS. The target genes and enriched pathways related to significantly changed compositions between mulberry leaves and silkworm droppings were analyzed by network pharmacology. High unsaturated C18 : 3 fatty acids were transformed to low unsaturated C18 : 1 from mulberry leaves to silkworm droppings. Only lysine and 17 mini-peptides had significantly higher content in silkworm droppings than in mulberry leaves. There were 36 common target genes or the different compounds between mulberry leaves and silkworm droppings. The main pathways of mulberry leaf were enriched in antivirus and anticancer properties, while the pathways of silkworm droppings were enriched in hormone regulation and signal transduction.
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http://dx.doi.org/10.1155/2021/8819538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263261PMC
June 2021

Osteogenic and Angiogenic Potency of VEGF165-Transfected Canine Bone Marrow Mesenchymal Cells Combined with Coral Hydroxyapatite in Vitro.

Tissue Eng Regen Med 2021 Jul 24. Epub 2021 Jul 24.

Stomatological Hospital, Southern Medical University, S366 Jiangnan Boulevard, Guangzhou, 510280, China.

Background: To explore the osteogenic and angiogenic potential of human vascular endothelial growth factor 165 (hVEGF165) gene-transfected canine bone marrow mesenchymal stem cells (BMSCs) combined with coral hydroxyapatite (CHA) scaffold.

Methods: We constructed a lentiviral vector and transfected canine BMSCs with the best multiplicity of infection. Osteogenesis was induced in the transfected groups (GFP-BMSCs group and hVEGF-BMSCs group) and non-transfected group (BMSCs group), followed by the evaluation of alkaline phosphatase (ALP) activity and alizarin red S staining. Cells from the three groups were co-cultured with CHA granules, respectively to obtain the tissue-engineered bone. MTT assay and fluorescence microscopy were employed to assess cell proliferation and adhesion. The expression of osteogenic and angiogenic related genes and proteins were evaluated at 7, 14, 21, and 28 days post osteoinduction in cell culture alone and cell co-culture with CHA, respectively using RT-PCR and ELISA.

Results: The hVEGF165 gene was transfected into BMSCs successfully. Higher ALP activity and more calcified nodules were found in the hVEGF-BMSCs group than in the control groups (p < 0.001). Cells attached and proliferated in CHA particles. Both cells cultured alone and cells co-culture with CHA expressed more osteogenic and angiogenic related genes and proteins in the hVEGF-BMSCs group compared to the GFP-BMSCs and BMSCs groups (p < 0.05).

Conclusion: High expression of hVEGF165 in BMSCs potentially promote the osteogenic potential of BMSCs, and synergically drive the expression of other osteogenic and angiogenic factors. hVEGF-BMSCs co-cultured with CHA expressed more osteogenic and angiogenic related factors, creating a favorable microenvironment for osteogenesis and angiogenesis. Also, the findings have allowed for the construction of a CHA-hVEGF-BMSCs tissue-engineered bone.
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http://dx.doi.org/10.1007/s13770-021-00368-7DOI Listing
July 2021

Efficacy and Safety of Homoharringtonine for the Treatment of Acute Myeloid Leukemia: A Meta-analysis.

Clin Lymphoma Myeloma Leuk 2021 Jun 9. Epub 2021 Jun 9.

Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China. Electronic address:

Background: To evaluate the efficacy and safety of homoharringtonine (HHT) in acute myeloid leukemia (AML).

Methods: PubMed, Cochrane Library, Embase, China National Knowledge of Infrastructure, and Wanfang data were systematically searched until October 31, 2020, for AML treatment with and without HHT. Fixed- and random-effect models were used to pool main outcomes, and between-study heterogeneity was assessed.

Results: A total of 37 articles (2846 patients) fitting our criterion were included. The pooled overall response rate for the patients treated with HHT was 82% (CI, 77.9%-85.6%; I = 73.5%), and the complete response rate was 63.4% (CI, 58.8%-68%; I = 67.3%). Our study showed that patients treated with HHT have more overall response and complete response benefits and less cardiotoxicity and relapse rate. Subgroup analysis showed that patients with AML treated with HHT have significant overall response benefits in patients younger than 60 (odds ratio [OR], 1.63; CI, 1.33-2; I = 1.7%; P < .001), the newly diagnosed (OR, 1.59; CI, 1.15-2.21; I = 34.7%; P = .006), and relapsed/refractory patients (OR, 2.13; CI, 1.38-3.29; I = 32.3%; P = .001). Better complete remission benefits were observed in patients younger than 60 (OR, 1.32; CI, 1.1-1.59; I = 7%; P = .004), the newly diagnosed (OR, 1.32; CI, 1.08-1.62; I = 33.5%; P = .006), and relapsed/refractory patients (OR, 1.81; CI, 1.19-2.77; P = .006). For elderly patients, HHT treatment reduced relapse risk by 76.6% (OR, 0.23; CI, 0.09-0.63; I = 0%; P = .004).

Conclusions: HHT can be a reliable choice with less cardiotoxicity for patients with AML, especially for the newly diagnosed or patients younger than 60. For elderly intolerant patients, the use of HHT can reduce relapse.
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http://dx.doi.org/10.1016/j.clml.2021.06.002DOI Listing
June 2021

The Types and Proportions of Commensal Microbiota Have a Predictive Value in Coronary Heart Disease.

J Clin Med 2021 Jul 15;10(14). Epub 2021 Jul 15.

Department of Medical Science and Cardio-Renal Medicine, Graduate School of Medicine, Yokohama City University, Kanagawa 236-0027, Japan.

Previous clinical studies have suggested that commensal microbiota play an important role in atherosclerotic cardiovascular disease; however, a synthetic analysis of coronary heart disease (CHD) has yet to be performed. Therefore, we aimed to investigate the specific types of commensal microbiota associated with CHD by performing a systematic review of prospective observational studies that have assessed associations between commensal microbiota and CHD. Of the 544 published articles identified in the initial search, 16 publications with data from 16 cohort studies (2210 patients) were included in the analysis. The combined data showed that Bacteroides and Prevotella were commonly identified among nine articles ( = 13) in the fecal samples of patients with CHD, while seven articles commonly identified Firmicutes. Moreover, several types of commensal microbiota were common to atherosclerotic plaque and blood or gut samples in 16 cohort studies. For example, Veillonella, Proteobacteria, and Streptococcus were identified among the plaque and fecal samples, whereas Clostridium was commonly identified among blood and fecal samples of patients with CHD. Collectively, our findings suggest that several types of commensal microbiota are associated with CHD, and their presence may correlate with disease markers of CHD.
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http://dx.doi.org/10.3390/jcm10143120DOI Listing
July 2021

Identification and confirmation of 14-3-3 ζ as a novel target of ginsenosides in brain tissues.

J Ginseng Res 2021 Jul 29;45(4):465-472. Epub 2020 Dec 29.

Department of Pathology and Pathophysiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

Background: Ginseng can help regulate brain excitability, promote learning and memory, and resist cerebral ischemia in the central nervous system. Ginsenosides are the major effective compounds of Ginseng, but their protein targets in the brain have not been determined.

Methods: We screened proteins that interact with the main components of ginseng (ginsenosides) by affinity chromatography and identified the 14-3-3 ζ protein as a potential target of ginsenosides in brain tissues.

Results: Biolayer interferometry (BLI) analysis showed that 20(S)-protopanaxadiol (PPD), a ginseng saponin metabolite, exhibited the highest direct interaction to the 14-3-3 ζ protein. Subsequently, BLI kinetics analysis and isothermal titration calorimetry (ITC) assay showed that PPD specifically bound to the 14-3-3 ζ protein. The cocrystal structure of the 14-3-3 ζ protein-PPD complex showed that the main interactions occurred between the residues R56, R127, and Y128 of the 14-3-3 ζ protein and a portion of PPD. Moreover, mutating any of the above residues resulted in a significant decrease of affinity between PPD and the 14-3-3 ζ protein.

Conclusion: Our results indicate the 14-3-3 ζ protein is the target of PPD, a ginsenoside metabolite. Crystallographic and mutagenesis studies suggest a direct interaction between PPD and the 14-3-3 ζ protein. This finding can help in the development of small-molecular compounds that bind to the 14-3-3 ζ protein on the basis of the structure of dammarane-type triterpenoid.
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http://dx.doi.org/10.1016/j.jgr.2020.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282492PMC
July 2021

Chronic Exposure to Hypoxia Inhibits Myelinogenesis and Causes Motor Coordination Deficits in Adult Mice.

Neurosci Bull 2021 Jul 22. Epub 2021 Jul 22.

Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University, Chongqing, 400038, China.

Exposure to chronic hypoxia is considered to be a risk factor for deficits in brain function in adults, but the underlying mechanisms remain largely unknown. Since active myelinogenesis persists in the adult central nervous system, here we aimed to investigate the impact of chronic hypoxia on myelination and the related functional consequences in adult mice. Using a transgenic approach to label newly-generated myelin sheaths (NG2-CreER; Tau-mGFP), we found that myelinogenesis was highly active in most brain regions, such as the motor cortex and corpus callosum. After exposure to hypoxia (10% oxygen) 12 h per day for 4 weeks, myelinogenesis was largely inhibited in the 4-month old brain and the mice displayed motor coordination deficits revealed by the beam-walking test. To determine the relationship between the inhibited myelination and functional impairment, we induced oligodendroglia-specific deletion of the transcription factor Olig2 by tamoxifen (NG2-CreER; Tau-mGFP; Olig2 fl/fl) in adult mice to mimic the decreased myelinogenesis caused by hypoxia. The deletion of Olig2 inhibited myelinogenesis and consequently impaired motor coordination, suggesting that myelinogenesis is required for motor function in adult mice. To understand whether enhancing myelination could protect brain functions against hypoxia, we treated hypoxic mice with the myelination-enhancing drug-clemastine, which resulted in enhanced myelogenesis and improved motor coordination. Taken together, our data indicate that chronic hypoxia inhibits myelinogenesis and causes functional deficits in the brain and that enhancing myelinogenesis protects brain functions against hypoxia-related deficits.
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http://dx.doi.org/10.1007/s12264-021-00745-1DOI Listing
July 2021

The mitochondrial genome of Zhang, Masunaga et Yang, 2009 (Diptera: Dolichopodidae).

Authors:
Chen Lin Ding Yang

Mitochondrial DNA B Resour 2021 6;6(8):2266-2268. Epub 2021 Jul 6.

College of Plant Protection, China Agricultural University, Beijing, PR China.

The long-legged fly Zhang, Masunaga et Yang, 2009 belongs to the subfamily Dolichopodinae of Dolichopodidae. The newly sequenced mitogenome of is a new representative of the subfamily. The nearly complete mitogenome is 15,124 bp in length, consisting of 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), and 22 transfer RNA genes (tRNAs). All genes have similar locations and encoding directions with that of other published mitogenomes of Dolichopodidae. The nucleotide composition biases toward A and T with the overall A + T % is 73.9%. All protein-coding genes initiate with standard start codon ATN except and , and TAA/TAG are conventionally used as stop codons. All tRNAs, ranging from 62 to 71 bp, have a clover-leaf structure. Based on the result of the phylogenetic analysis, Dolichopodidae and Empididae were monophyletic, and the relationships among subfamilies of Dolichopodidae were Diaphorinae + (Peloropeodinae + (Xanthochlorinae + (Medeterinae + Dolichopodinae))). The monophyly of the subfamily Dolichopodinae and the sister relationship between and were also strongly supported.
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http://dx.doi.org/10.1080/23802359.2021.1948369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266247PMC
July 2021

Characterization of two closely related citrus cultivars using UPLC-ESI-MS/MS-based widely targeted metabolomics.

PLoS One 2021 20;16(7):e0254759. Epub 2021 Jul 20.

Department of Pharmacy, Standardization Education Ministry Key Laboratory of Traditional Chinese Medicine, Chengdu University of TCM, Chengdu, Sichuan, China.

Citrus cultivars are widely spread worldwide, and some of them only differ by specific mutations along the genome. It is difficult to distinguish them by traditional morphological identification. To accurately identify such similar cultivars, the subtle differences between them must be detected. In this study, UPLC-ESI-MS/MS-based widely targeted metabolomics analysis was conducted to study the chemical differences between two closely related citrus cultivars, Citrus reticulata 'DHP' and C. reticulata 'BZH'. Totally 352 metabolites including 11 terpenoids, 35 alkaloids, 80 phenolic acids, 25 coumarins, 7 lignans, 184 flavonoids and 10 other compounds were detected and identified; Among them, 15 metabolites are unique to DHP and 16 metabolites are unique to BZH. Hierarchical cluster analysis (HCA), principal component analysis (PCA), and orthogonal signal correction and partial least squares-discriminant analysis (OPLS-DA) can be used to clearly discriminate between DHP and BZH. 93 metabolites including 36 down-regulated and 57 up-regulated are significantly different in DHP and BZH. They are mainly involved in the biosynthesis of flavonoids, flavones, flavonols, and isoflavonoids. In addition, the relative content levels of flavonoids, alkaloids, and terpenoids are much higher in the peel of DHP than that of BZH, the presence of which may correlate with the quality difference of the peels. The results reported herein indicate that metabolite analysis based on UPLC-ESI-MS/MS is an effective means of identifying cultivars with different genotypes, especially those that cannot be distinguished based on traditional identification methods.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254759PLOS
July 2021

Targeting local lymphatics to ameliorate heterotopic ossification via FGFR3-BMPR1a pathway.

Nat Commun 2021 07 19;12(1):4391. Epub 2021 Jul 19.

Department of Wound Repair and Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China.

Acquired heterotopic ossification (HO) is the extraskeletal bone formation after trauma. Various mesenchymal progenitors are reported to participate in ectopic bone formation. Here we induce acquired HO in mice by Achilles tenotomy and observe that conditional knockout (cKO) of fibroblast growth factor receptor 3 (FGFR3) in Col2 cells promote acquired HO development. Lineage tracing studies reveal that Col2 cells adopt fate of lymphatic endothelial cells (LECs) instead of chondrocytes or osteoblasts during HO development. FGFR3 cKO in Prox1 LECs causes even more aggravated HO formation. We further demonstrate that FGFR3 deficiency in LECs leads to decreased local lymphatic formation in a BMPR1a-pSmad1/5-dependent manner, which exacerbates inflammatory levels in the repaired tendon. Local administration of FGF9 in Matrigel inhibits heterotopic bone formation, which is dependent on FGFR3 expression in LECs. Here we uncover Col2 lineage cells as an origin of lymphatic endothelium, which regulates local inflammatory microenvironment after trauma and thus influences HO development via FGFR3-BMPR1a pathway. Activation of FGFR3 in LECs may be a therapeutic strategy to inhibit acquired HO formation via increasing local lymphangiogenesis.
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http://dx.doi.org/10.1038/s41467-021-24643-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289847PMC
July 2021

Gait Flexibility among Older Persons Significantly More Impaired in Fallers Than Non-Fallers-A Longitudinal Study.

Int J Environ Res Public Health 2021 Jul 2;18(13). Epub 2021 Jul 2.

Department of Clinical Sciences in Lund/ENT, Lund University, 22185 Lund, Sweden.

Gait disorders are a relevant factor for falls and possible to measure with wearable devices. If a wearable sensor can detect differences in gait parameters between fallers and non-fallers has not yet been studied. The aim of this study was to measure and compare gait parameters, vestibular function, and balance performance between fallers and non-fallers among a group of older persons. Participants were senior members ( = 101) of a Swedish non-profit gymnastic association. Gait parameters were obtained using an inertial measurement unit (IMU) that the participants wore on the leg while walking an obstacle course and on an even surface. Vestibular function was assessed by the Head-shake test, the Head impulse test, and the Dix-Hallpike maneuver. Balance was assessed by the Timed Up and Go, the Timed Up and Go manual, and the Timed Up and Go cognitive tests. Falls during the 12-month follow-up period were monitored using fall diaries. Forty-two persons (41%) had fallen during the 12-month follow-up. Fallers had more limited ability to vary their gait (gait flexibility) than non-fallers ( < 0.001). No other differences between fallers and non-fallers were found. The use of gait flexibility, captured by an IMU, seems better for identifying future fallers among healthy older persons than Timed Up and Go or Timed Up and Go combined with a cognitive or manual task.
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http://dx.doi.org/10.3390/ijerph18137074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297078PMC
July 2021

Preliminary results in anterior cervical discectomy and fusion with the uncovertebral joint fusion cage in a goat model.

BMC Musculoskelet Disord 2021 Jul 17;22(1):628. Epub 2021 Jul 17.

Department of Operation Room and Anesthesia Center, West China Hospital, Sichuan University, No. 37 Guo Xue Rd, Chengdu, 610041, China.

Objective: To preliminarily evaluate the safety and efficacy of the uncovertebral joint fusion cage in a goat model of cervical spine interbody fusion.

Methods: Twenty-four healthy adult goats were randomly assigned to one of the two following groups: Group A, goats were implanted with an uncovertebral joint fusion cage combined with a local autograft and Group B, goats were implanted with a non-profile cage filled with a local autograft. The goats were prospectively evaluated for 24 weeks and then were sacrificed for evaluation. X-rays, CT and micro-CT scanning, and undecalcified bone histological analysis were used for the evaluation of fusion.

Results: 75.0% (9/12) of the goats in Group A were evaluated as having fusion at 12 weeks, compared to 41.7% (5/12) in Group B. 83.3% (10/12) of the goats in Group A were evaluated as having fusion at 24 weeks compared to 58.3% (7/12) in Group B. The fusion grading scores in Group A were significantly higher than that in Group B both at 12 weeks and 24 weeks (P < 0.05). Micro-CT scanning and undecalcified bone histological analysis showed that new bone formation can be obviously found in the bilateral uncovertebral joint. The bone volume fraction (BV/ TV) in Group A (23.59 ± 4.43%) was significantly higher than Group B (16.16 ± 4.21%), with P < 0.05.

Conclusions: Preliminary results of this study demonstrated that uncovertebral joint fusion cage is effective for achieving early bone formation and fusion without increase of serious complications.
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http://dx.doi.org/10.1186/s12891-021-04412-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286593PMC
July 2021

Diterpenoid alkaloids from the whole herb of Delphinium grandiflorum L.

Phytochemistry 2021 Jul 14;190:112866. Epub 2021 Jul 14.

School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, Sichuan, PR China; Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, 610031, Sichuan, PR China. Electronic address:

Seven previously undescribed diterpenoid alkaloids, eight reaction products and thirteen known compounds were isolated from the whole plant of Delphinium grandiflorum L. (Ranunculaceae). Grandiflonines A and B have an unprecedented C-diterpenoid alkaloid skeleton, which features inversion of the configuration of C-18. Their structures were determined by comprehensive analyses of spectroscopic data, X-ray diffraction and Mosher's method. The probable biosynthetic pathway of grandiflonine A was discussed. Additionally, the analgesic activity and anti-inflammatory activity by inhibition of NO production were evaluated. Among them, deoxylappaconitine (ED = 0.35 mg/kg, TI = 46.22) showed significant analgesic activity that was superior to the reference drug lappaconitine (ED = 3.5 mg/kg, TI = 3.34).
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http://dx.doi.org/10.1016/j.phytochem.2021.112866DOI Listing
July 2021

Genome-wide DNA methylation profiles provide insight into epigenetic regulation of red and white muscle development in Chinese perch Siniperca chuatsi.

Comp Biochem Physiol B Biochem Mol Biol 2021 Jul 14;256:110647. Epub 2021 Jul 14.

Hunan Provincial Key Laboratory of Nutrition and Quality Control of Aquatic Animals, College of Biological and Environmental Engineering, Changsha University, Changsha, China. Electronic address:

Fish skeletal muscles are composed of spatially well-separated fiber types, namely, red and white muscles with different physiological functions and metabolism. To compare the DNA methylation profiles of the two types of muscle tissues and identify potential candidate genes for the muscle growth and development under epigenetic regulation, genome-wide DNA methylation of the red and white muscle in Chinese perch Siniperca chuatsi were comparatively analyzed using bisulfate sequencing methods. An average of 0.9 billion 150-bp paired-end reads were obtained, of which 86% were uniquely mapped to the genome. Methylation mostly occurred at CG sites at a ratio of 94.43% in the red muscle and 93.16% in the white muscle. The mean methylation levels at C-sites were 5.95% in red muscle and 5.83% in white muscle, whereas the mean methylation levels of CG, CHG, and CHH were 73.23%, 0.62%, and 0.67% in red muscle, and 71.01%, 0.62%, and 0.67% in white muscle, respectively. A total of 4192 differentially methylated genes (DMGs) were identified significantly enriched in cell signaling pathways related to skeletal muscle differentiation and growth. Various muscle-related genes, including myosin gene isoforms and regulatory factors, are differentially methylated in the promoter region between the red and white muscles. Further analysis of the transcriptional expression of these genes showed that the muscle regulatory factors (myf5, myog, pax3, pax7, and twitst2) and myosin genes (myh10, myh16, myo18a, myo7a, myo9a, and myl3) were differentially expressed between the two kinds of muscles, consistent with the DNA methylation analysis results. ELISA assays confirmed that the level of 5mC in red muscle was significantly higher than in white muscle (P < 0.05). The RT-qPCR assays revealed that the expression levels of the three DNA methylation transferase (dnmt) subtypes, dnmt1, dnmt3ab, and dnmt3bb1, were significantly higher in red muscle than in white muscle. The higher DNA methylation levels in the red muscle may result from higher DNA methylation transferase expression in the red muscles. Thus, this study might provide a theoretical foundation to better understand epigenetic regulation in the growth and development of red and white muscles in animals, at least in Chinese perch fish.
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http://dx.doi.org/10.1016/j.cbpb.2021.110647DOI Listing
July 2021

Ultrafast Excited-State Dynamics of Photoluminescent Pt(II) Dimers Probed by a Coherent Vibrational Wavepacket.

J Phys Chem Lett 2021 Jul 16:6794-6803. Epub 2021 Jul 16.

Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.

Intricate potential energy surfaces (PESs) of some transition metal complexes (TMCs) pose challenges in mapping out initial excited-state pathways that could influence photochemical outcomes. Ultrafast intersystem crossing (ISC) dynamics of four structurally related platinum(II) dimer complexes were examined by detecting their coherent vibrational wavepacket (CVWP) motions of Pt-Pt stretching mode in the metal-metal-to-ligand-charge-transfer excited states. Structurally dependent CVWP behaviors (frequency, dephasing time, and oscillation amplitudes) were captured by femtosecond transient absorption spectroscopy, analyzed by short-time Fourier transformation, and rationalized by quantum mechanical calculations, revealing dual ISC pathways. The results suggest that the ligands could fine-tune the PESs to influence the proximity of the conical intersections of the excited states with the Franck-Condon state and thus to control the branching ratio of the dual ISC pathways. This comparative study presents future opportunities in control excited-state trajectories of TMCs via ligand structures.
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http://dx.doi.org/10.1021/acs.jpclett.1c01289DOI Listing
July 2021

Anti-hyperlipidemic effects of the compound Danshen tablet: roles of antioxidation, anti-inflammation, anticoagulation, and anti-apoptosis.

Ann Transl Med 2021 May;9(9):744

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Background: Hyperlipidemia could cause some serious harm to human health diseases, such as atherosclerosis, coronary heart disease. This study sought to investigate the effects of the compound Danshen tablet (CDT) on hyperlipidemia induced by a high-fat diet in ApoE mice and related antioxidation, anti-inflammation, anticoagulation, and anti-apoptosis mechanisms.

Methods: The control group (Group 1) comprised 15 male C57BL/6N mice, and the other 5 groups (Groups 2-6) comprised 75 male ApoE mice. These 75 mice were randomly divided into 1 of the following 5 groups: Group 2, a model group; Groups 3-5, the CDT groups, each of which was administered 375, 750, or 1,500 mg/kg of CDT; and Group 6, an atorvastatin group, which was administered 5.2 mg/kg of atorvastatin. All the mice were fed a high-fat diet for 16 weeks and intragastrically administered with CDT or atorvastatin once a day according to their body weight. After 16 weeks, serum was collected, the aorta was isolated, and blood lipid levels were detected. An enzyme-linked immunosorbent assay was used to detect the serum levels of 4-hydroxynonenal (4-HNE), 8-hydroxy-2'-deoxyguanosine (8-OHdG), intercellular adhesion molecule 1 (ICAM-1), monocyte chemoattractant protein 1 (MCP-1), thromboxane B2 (TXB2), tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1). The thickness of the aortic wall was measured by ultrasonography. Atherosclerotic plaque and endothelial cell apoptosis in the aortic root were evaluated using oil red O staining and terminal dUTP nick-end labeling (TUNEL) assays, respectively.

Results: A comparison of mice in the CDT group and mice in the model group showed that CDT significantly inhibited mice's weight gain. CDT reduced the levels of the inflammatory factor ICAM-1 and the oxidative damage molecule 4-HNE. In the coagulation system, CDT significantly increased tPA levels and reduced TXB2 and PAI-1 levels. Ultrasonography showed that CDT increased the thickness of the aortic wall. The oil red O staining results revealed that CDT significantly ameliorated lipid accumulation in the aortic valve. TUNEL assays indicated that CDT reduced the number of TUNEL-positive cells in the aortic valve.

Conclusions: CDT has a certain protective effect on hyperlipidemia. The mechanism of CDT may be related to antioxidation, anti-inflammation, anticoagulation, and anti-apoptosis.
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http://dx.doi.org/10.21037/atm-20-7915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246178PMC
May 2021

Death-Associated Protein Kinase 1 Promotes Alveolar Epithelial Cell Apoptosis and Ventilator-Induced Lung Injury Through P53 Pathway.

Shock 2021 Jul 8. Epub 2021 Jul 8.

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Ave, Wuhan, 430022, Hubei, China Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Ave, Wuhan, 430022, Hubei, China.

Objectives: Mechanical stretch induced alveolar epithelial cell (AEC) apoptosis participates in the onset of ventilator induced lung injury (VILI). In this study, we explored whether death associated protein kinase 1 (DAPK1) mediated cyclic stretch (CS) induced AEC apoptosis and VILI though P53 pathway.

Materials And Methods: AEC apoptosis was induced by CS using the FX-5000T Flexercell Tension Plus system. C57BL/6 mouse received high tidal volume ventilation to build VILI model. DAPK1 inhibitor, P53 inhibitor or DAPK1 plasmid was used to regulate the expression of DAPK1 and P53, respectively. Flow cytometery was performed to assay cell apoptosis and the changes of mitochondrial membrane potential (MMP); Immunoblotting was adopted to analyse related protein expression; The binding of related proteins was detected by coimmunoprecipitation; AEC apoptosis in vivo was determined by immunohistochemistry assay.

Results: CS promoted AEC apoptosis, increased DAPK1 and P53 expression and induced the binding of DAPK1 and P53; inhibition of DAPK1 or P53 reduced CS induced AEC apoptosis, suppressed the expression of Bax, increased Bcl-2 level and stabilized MMP; AEC apoptosis and the level of P53 were both increased after overexpressing of DAPK1. Moreover, DAPK1 plasmid transfection also promoted the expression of Bax and the change of MMP, but decreased the level of Bcl-2. Inhibition of DAPK1 or P53 in vivo alleviated high tidal volume ventilation induced AEC apoptosis and lung injury.

Conclusions: DAPK1 contributes to AEC apoptosis and the onset of VILI though P53 and its intrinsic pro-apoptotic pathway. Inhibition of DAPK1 or P53 alleviates high tidal volume ventilation induced lung injury and AEC apoptosis.
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http://dx.doi.org/10.1097/SHK.0000000000001831DOI Listing
July 2021

Virulence and community dynamics of fungal species with vertical and horizontal transmission on a plant with multiple infections.

PLoS Pathog 2021 Jul 15;17(7):e1009769. Epub 2021 Jul 15.

State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, China.

The virulence evolution of multiple infections of parasites from the same species has been modeled widely in evolution theory. However, experimental studies on this topic remain scarce, particularly regarding multiple infections by different parasite species. Here, we characterized the virulence and community dynamics of fungal pathogens on the invasive plant Ageratina adenophora to verify the predictions made by the model. We observed that A. adenophora was highly susceptible to diverse foliar pathogens with mixed vertical and horizontal transmission within leaf spots. The transmission mode mainly determined the pathogen community structure at the leaf spot level. Over time, the pathogen community within a leaf spot showed decreased Shannon diversity; moreover, the vertically transmitted pathogens exhibited decreased virulence to the host A. adenophora, but the horizontally transmitted pathogens exhibited increased virulence to the host. Our results demonstrate that the predictions of classical models for the virulence evolution of multiple infections are still valid in a complex realistic environment and highlight the impact of transmission mode on disease epidemics of foliar fungal pathogens. We also propose that seedborne fungi play an important role in structuring the foliar pathogen community from multiple infections within a leaf spot.
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http://dx.doi.org/10.1371/journal.ppat.1009769DOI Listing
July 2021

Proteomics provides individualized options of precision medicine for patients with gastric cancer.

Sci China Life Sci 2021 Jul 9. Epub 2021 Jul 9.

State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China.

While precision medicine driven by genome sequencing has revolutionized cancer care, such as lung cancer, its impact on gastric cancer (GC) has been minimal. GC patients are routinely treated with chemotherapy, but only a fraction of them receive the clinical benefit. There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy. Here, we carried out retrospective analyses of 1,020 formalin-fixed, paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC. We identified two proteomic subtypes: the chemo-sensitive group (CSG) and the chemo-insensitive group (CIG) in the discovery set. The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (64.2% vs. 49.6%; Cox P-value=0.002), whereas no such improvement was observed in CIG (50.0% vs. 58.6%; Cox P-value=0.495). We validated these results in an independent validation set. Further, differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC. A prospective study is warranted to test these findings for future GC patient care.
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http://dx.doi.org/10.1007/s11427-021-1966-4DOI Listing
July 2021

Dietary chenodeoxycholic acid improves growth performance and intestinal health by altering serum metabolic profiles and gut bacteria in weaned piglets.

Anim Nutr 2021 Jun 19;7(2):365-375. Epub 2021 Apr 19.

Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.

Nutritional diarrhea and subsequent performance degradation in weaned piglets are major challenges for the pig industry. Bile acids (BA) can be added to the diet as emulsifiers. This experiment was conducted to investigate the effects of chenodeoxycholic acid (CDCA), a major primary BA, on growth performance, serum metabolic profiles and gut health in weaned piglets. A total of 72 healthy weaned piglets were randomly assigned to the control (CON) and the CDCA groups, which were feed a basal diet and the basal diet supplemented with 200 mg/kg CDCA for 30 d, respectively. Our results demonstrated that CDCA significantly increased final BW and average daily gain (ADG), decreased feed-to-gain (F:G) ratio and tended to reduce diarrhea incidence. In addition, CDCA increased the villus height-to-crypt depth (V:C) ratio, elevated goblet cell numbers and the expression of tight junction proteins, suggesting the enhancement of intestinal barrier function. As an emulsifier, CDCA increased jejunal lipase activity and the mRNA expression of pancreatic lipases. CDCA supplementation also altered the serum metabolic profiles, including increasing the levels of indole 3-acetic acid, N'-formylkynurenine and theobromine that were beneficial for gut health. Moreover, the relative abundance of 2 beneficial gut bacteria, and , were increased, whereas the relative abundance of a harmful bacteria, , was decreased in the gut of weaned piglets supplemented with CDCA. Importantly, the altered serum metabolic profiles showed a strong correlation with the changed gut bacteria. In conclusion, CDCA improved the growth performance of weaned piglets by improving intestinal morphology and barrier function, and enhancing lipid digestion, accompanied by alterations of serum metabolic profiles, and changes in relative abundance of certain gut bacteria.
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http://dx.doi.org/10.1016/j.aninu.2020.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245770PMC
June 2021

Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial.

Lancet Oncol 2021 Jul 9. Epub 2021 Jul 9.

Department of General Surgery, The First Hospital Affiliated to Army Medical University, Chongqing, China.

Background: The optimal perioperative chemotherapeutic regimen for locally advanced gastric cancer remains undefined. We evaluated the efficacy and safety of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in patients with locally advanced gastric cancer undergoing D2 gastrectomy.

Methods: We did this open-label, phase 3, superiority and non-inferiority, randomised trial at 27 hospitals in China. We recruited antitumour treatment-naive patients aged 18 years or older with historically confirmed cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma, with Karnofsky performance score of 70 or more. Patients undergoing D2 gastrectomy were randomly assigned (1:1:1) via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m on day one of each 21 day cycle plus oral capecitabine 1000 mg/m twice a day), adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m on day one of each 21 day cycle plus oral S-1 40-60 mg twice a day), or perioperative SOX (intravenous oxaliplatin 130 mg/m on day one of each 21 day plus oral S-1 40-60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy). The primary endpoint, assessed in the modified intention-to-treat population, 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-SOX and the non-inferiority (hazard ratio non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx. Safety analysis were done in patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT01534546.

Findings: Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were screened and 1022 (93%) were included in the modified intention-to-treat population, of whom 345 (34%) patients were assigned to the adjuvant-CapOx, 340 (33%) patients to the adjuvant-SOX group, and 337 (33%) patients to the perioperative-SOX group. 3-year disease-free survival was 51·1% (95% CI 45·5-56·3) in the adjuvant-CapOx group, 56·5% (51·0-61·7) in the adjuvant-SOX group, and 59·4% (53·8-64·6) in the perioperative-SOX group. The hazard ratio (HR) was 0·77 (95% CI 0·61-0·97; Wald p=0·028) for the perioperative-SOX group compared with the adjuvant-CapOx group and 0·86 (0·68-1·07; Wald p=0·17) for the adjuvant-SOX group compared with the adjuvant-CapOx group. The most common grade 3-4 adverse events was neutropenia (32 [12%] of 258 patients in the adjuvant-CapOx group, 21 [8%] of 249 patients in the adjuvant-SOX group, and 30 [10%] of 310 patients in the perioperative-SOX group). Serious adverse events were reported in seven (3%) of 258 patients in adjuvant-CapOx group, two of which were related to treatment; eight (3%) of 249 patients in adjuvant-SOX group, two of which were related to treatment; and seven (2%) of 310 patients in perioperative-SOX group, four of which were related to treatment. No treatment-related deaths were reported.

Interpretation: Perioperative-SOX showed a clinically meaningful improvement compared with adjuvant-CapOx in patients with locally advanced gastric cancer who had D2 gastrectomy; adjuvant-SOX was non-inferior to adjuvant-CapOx in these patients. Perioperative-SOX could be considered a new treatment option for patients with locally advanced gastric cancer.

Funding: National Key Research and Development Program of China, Beijing Scholars Program 2018-2024, Peking University Clinical Scientist Program, Taiho, Sanofi-Aventis, and Hengrui Pharmaceutical.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1470-2045(21)00297-7DOI Listing
July 2021

Association of heart failure subtypes and atrial fibrillation: Data from the Atherosclerosis Risk in Communities (ARIC) study.

Int J Cardiol 2021 Jul 8. Epub 2021 Jul 8.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA. Electronic address:

Aims: To determine the prevalence and incidence of AF among HF subtypes in a biracial community-based cohort.

Methods: We studied 6496 participants in the Atherosclerosis Risk in Community study (mean age, 75.8 ± 5.3, 59% women, 23% black) who attended the 2011-2013 visit. HF was identified from physician adjudicated diagnosis, hospital discharges, and self-report. HF subtypes were based on echocardiography. A left ventricular ejection fraction <40% represents HF with reduced ejection fraction (HFrEF), 40%-49% for HF with midrange ejection fraction (HFmEF), and ≥ 50% for HF with preserved ejection fraction (HFpEF). AF was ascertained through 2017 from study electrocardiograms, hospital discharges, and death certificates. Confounder-adjusted logistic regression and Cox models were used to estimate associations of HF subtype with prevalent and incident AF.

Results: Among eligible participants, 393 had HF (HFpEF = 232, HFmEF = 41, HFrEF = 35 and unclassified HF = 85) and 735 had AF. Compared to those without HF, all HF subtypes were more likely to have prevalent AF [odds ratio (95% confidence interval (CI)) 7.4 (5.6-9.9) for HFpEF, 8.1 (4.3-15.3) for HFmEF, 10.0 (5.0-20.2) for HFrEF, 8.8 (5.6-14.0) for unclassified HF]. Among participants without AF at baseline (n = 5761), 610 of them developed AF. Prevalent HF was associated with increased risk of AF [hazard ratio (95%CI) 2.3 (1.6-3.2) for HFpEF, 5.0 (2.7-9.3) for HFmEF, 3.5 (1.7-7.6) for HFrEF, 1.9 (0.9-3.7) for unclassified HF].

Conclusion: AF and HF frequently co-occur, with small differences by HF subtype, underscoring the importance of understanding the interplay of these two epidemics and evaluating shared preventive and therapeutic strategies.
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http://dx.doi.org/10.1016/j.ijcard.2021.07.006DOI Listing
July 2021

Detection of high-valent iron species in alloyed oxidic cobaltates for catalysing the oxygen evolution reaction.

Nat Commun 2021 Jul 9;12(1):4218. Epub 2021 Jul 9.

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.

Iron alloying of oxidic cobaltate catalysts results in catalytic activity for oxygen evolution on par with Ni-Fe oxides in base but at much higher alloying compositions. Zero-field Fe Mössbauer spectroscopy and X-ray absorption spectroscopy (XAS) are able to clearly identify Fe in mixed-metal Co-Fe oxides. The highest Fe population is obtained in the 40-60% Fe alloying range, and XAS identifies the ion residing in an octahedral oxide ligand field. The oxygen evolution reaction (OER) activity, as reflected in Tafel analysis of CoFeO films in 1 M KOH, tracks the absolute concentration of Fe. The results reported herein suggest an important role for the formation of the Fe redox state in activating cobaltate OER catalysts at high iron loadings.
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http://dx.doi.org/10.1038/s41467-021-24453-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270959PMC
July 2021

A new diterpenoid alkaloid from C. Marquand & Airy Shaw.

Nat Prod Res 2021 Jul 9:1-6. Epub 2021 Jul 9.

School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, P.R. China.

A new C-diterpenoid alkaloid named gyalanutine A () and fourteen known compounds - were isolated from the plant of C. Marquand & Airy Shaw. Compound displayed an unusual lycoctonine-type C-diterpenoid alkaloid skeleton with the cleavage of -C and C-C bonds, and the construction of the -C bond. Structures were identified by multiple spectroscopic analyses including 1 D, 2 D NMR, IR and HR-ESI-MS. Compounds were tested for acetylcholinesterase inhibitory and anti-inflammatory activity.
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http://dx.doi.org/10.1080/14786419.2021.1948043DOI Listing
July 2021

Tracing anti-osteoporosis components from raw and salt-processed semen of Cuscuta chinensis by employing a biochemometrics strategy that integrates ultrasonic-assisted extraction, quantitation, efficacy assessment in zebrafish, and grey relationship analysis.

J Sep Sci 2021 Jul 9. Epub 2021 Jul 9.

College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, P. R. China.

Semen of Cuscuta chinensis has been reported to have an anti-osteoporosis effect, however, the components which account for the anti-osteoporosis effect have not been clarified. In this work we propose a biochemometrics strategy that integrates quantitation, anti-osteoporosis evaluation in zebrafish, and grey relationship analysis for the identification of anti-osteoporosis components from the semen of Cuscuta chinensis. In the beginning, a precise and accurate liquid chromatography-tandem mass spectrometry method was established for simultaneous quantitation of seven major components in crude and salt-processed Cuscuta chinensis. The mode of multiple reaction monitoring was used. Chloramphenicol was selected as the internal standard. The method showed good linearity and repeatability. The recovery rates of each component ranged from 95.4 to 103.9%. The precisions of intra-day and inter-day were all within 5.0%. The method was then applied for quantitation of the seven major components in 11 batches of crude and salt-processed Cuscuta chinensis. Subsequently, the anti-osteoporosis effects of crude and salt-processed Cuscuta chinensis were evaluated in zebrafish. Principle component analysis, grey relationship analysis, and partial least squares regression were applied for deciphering the relationship between the contents of seven major components and the anti-osteoporosis effects. Hyperin, p-hydroxycinnamic acid, and astragalin were found to be the major anti-osteoporosis components.
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http://dx.doi.org/10.1002/jssc.202100272DOI Listing
July 2021

Discovery of 8,9-seco--Kaurane Diterpenoids as Potential Leads for the Treatment of Triple-Negative Breast Cancer.

J Med Chem 2021 Jul 8;64(14):9926-9942. Epub 2021 Jul 8.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China.

Triple-negative breast cancer (TNBC) is a lethal malignancy without safe and effective therapeutic drugs. In this study, the anti-TNBC bioassay-guided isolation of the medicinal plant followed by the structural modification led to the construction of a small -kaurane diterpenoid library (-). With subsequent biological screening, 20 highly potent compounds (ICs < 3 μM) were identified. Among them, 8,9-seco--kaurane displayed comparable activity (ICs ∼ 80 nM) to doxorubicin but with better selectivity. The analysis of structure-activity relationships suggested that the cleavage of the C8-C9 bond and the presence of α,β-unsaturated ketone moiety were essential for the activity. The mechanistic study revealed that induced apoptosis, autophagy, and metastasis suppression in TNBC cells via inhibition of Akt. , significantly suppressed the TNBC tumor growth without causing side effects. All these results suggested that may serve as a promising lead for the development of novel anti-TNBC agents in the future.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00166DOI Listing
July 2021

Electrochemical-induced hydroxylation of aryl halides in the presence of EtN in water.

Org Biomol Chem 2021 Jul 8. Epub 2021 Jul 8.

Faculty of Material and Chemical Engineering, Yibin University, Yibin 644000, China and Institute of Materia Medica, School of Pharmacy, Fujian Provincial Key Laboratory of Natural Medicine Pharmacology, Fujian Medical University, Fuzhou 350122, China.

A thorough study of mild and environmentally friendly electrochemical-induced hydroxylation of aryl halides without a catalyst is presented. The best protocol consists of hydroxylation of different aryl iodides and aryl bromides by water solution in the presence of Et3N under air, affording the target phenols in good isolated yields. Moreover, aryl chlorides were successfully employed as substrates. This methodology also provides a direct pathway for the formation of deoxyphomalone, which displayed a significant anti-proliferation effect.
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http://dx.doi.org/10.1039/d1ob00931aDOI Listing
July 2021

[Exosomes derived from PMN-MDSCs preconditioned by hypoxia attenuate arthropathy of collagen-induced arthritis mice].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Aug;37(8):728-735

Department of Laboratory Medicine, Nanjing Second Hospital, Nanjing University of Chinese Medicine, Nanjing 210009, China . *Corresponding author, E-mail:

Objective To investigate the role of the exosomes (EX) derived from polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) preconditioned by hypoxia in the treatment of the collagen-induced arthritis (CIA) mouse model. Methods CIA mouse model was induced by bovine type II collagen(Col2) and Freund's adjuvant. PMN-MDSCs were isolated from CIA mouse spleen by magnetic beads. PMN-MDSC-derived exosomes (PMN-MDSC-EXs) were extracted from the supernatant of PMN-MDSCs under normal (210 mL/L O) and hypoxia (10 mL/L O) conditions. PMN-MDSC-EXs were identified by transmission electron microscopy and flow cytometry. The surface-specific markers of PMN-MDSC-EXs were detected by Western blotting, including CD9, CD63, heat shock protein 70 (HSP70), and calnexin. PMN-MDSC-EXs were added to the CD4 T cell proliferation system in vitro to detect immunosuppressive ability. PMN-MDSC-EXs were injected into the CIA mouse model through the tail vein. The clinic scores of joints were recorded every three days, and the joint structures were observed by HE staining. The levels of total IgG, Col2 antibody, interferon γ (IFN-γ), interleukin 17 (IL-17) in the serum were detected by ELISA. The content of miR-29a-3p and miR-93-5p in PMN-MDSC-EXs under normal and hypoxia conditions was detected by real-time quantitative PCR. Results PMN-MDSCs were successfully isolated from the spleens of CIA mice and PMN-MDSC-EXs was prepared under normal and hypoxia conditions. Compared with normal PMN-MDSC-EXs, hypoxia-treated PMN-MDSC-EXs could inhibit the proliferation of CD4 T cells more effectively. The swelling degree of toes, clinical scores, and joint damage in the group of hypoxia-treated PMN-MDSC-EXs were significantly reduced. The levels of total IgG, Col2 antibody, IFN-γ and IL-17 in the serum decreased after the treatment with hypoxia-treated PMN-MDSC-EXs. The content of miR-29a-3p and miR-93-5p in hypoxia-treated PMN-MDSC-EXs was much higher than that in normal PMN-MDSC-EXs. Conclusion Under hypoxia condition, the immunosuppressive ability of PMN-MDSC-EXs is stronger, which can alleviate the arthropathy of CIA mice more effectively.
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August 2021

Analysis of Long Noncoding RNAs in Aila-Induced Non-Small Cell Lung Cancer Inhibition.

Front Oncol 2021 21;11:652567. Epub 2021 Jun 21.

College of Clinical Medicine, College of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, China.

Non-small cell lung cancer (NSCLC) has the highest morbidity and mortality among all carcinomas. However, it is difficult to diagnose in the early stage, and current therapeutic efficacy is not ideal. Although numerous studies have revealed that Ailanthone (Aila), a natural product, can inhibit multiple cancers by reducing cell proliferation and invasion and inducing apoptosis, the mechanism by which Aila represses NSCLC progression in a time-dependent manner remains unclear. In this study, we observed that most long noncoding RNAs (lncRNAs) were either notably up- or downregulated in NSCLC cells after treatment with Aila. Moreover, alterations in lncRNA expression induced by Aila were crucial for the initiation and metastasis of NSCLC. Furthermore, in our research, expression of was significantly downregulated in NSCLC cells after treatment with Aila and regulated expression levels of . In conclusion, our findings demonstrate that Aila is a potent natural suppressor of NSCLC by modulating expression of and .
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http://dx.doi.org/10.3389/fonc.2021.652567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255921PMC
June 2021

Evaluation of Reliable Reference Genes for Erythrocyte Generation from Cord Blood CD34 Cells.

DNA Cell Biol 2021 Jul 2. Epub 2021 Jul 2.

Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing, China.

generation of red blood cells has the potential to circumvent shortfalls in the global demand for blood for transfusion applications. However, cell differentiation and proliferation are often regulated by precise changes in gene expression, but the underlying mechanisms and molecular changes remain unclear. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) can be used to evaluate multiple target genes. To make the results more reliable, suitable reference genes should be used to calibrate the error associated with qRT-PCR. In this study, we utilized bioinformatics to screen 3 novel candidate reference genes (calcium and integrin binding family member 2 [], olfactory receptor family 8 subfamily B member 8 [], and zinc finger protein 425 []) along with eight traditional reference genes (glyceraldehyde-3-phosphate dehydrogenase [], β-actin [], , β2-microglobulin [], peptidylprolyl isomerase A [], TATA box-binding protein [], hydroxymethylbilane synthase [], and hypoxanthine phosphoribosyltransferase 1 []). Two software algorithms (geNorm and NormFinder) were used to evaluate the stability of expression of the 11 genes at different stages of erythrocyte development. Comprehensive analysis showed that expression of and was the most stable, whereas and were the least suitable candidate genes. These results suggest that appropriate reference genes should be selected before performing gene expression analysis during erythroid differentiation and that and are suitable reference genes for gene expression studies on erythropoiesis.
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http://dx.doi.org/10.1089/dna.2021.0185DOI Listing
July 2021
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