Publications by authors named "J Lin"

27,970 Publications

Rutaecarpine administration inhibits cancer cell growth in allogenic TRAMP-C1 prostate cancer mice correlating with immune balance in vivo.

Biomed Pharmacother 2021 May 1;139:111648. Epub 2021 May 1.

Department of Food Science and Biotechnology, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan.

Background: Rutaecarpine (Rut) is a plant alkaloid abundant in Euodia ruticarpa which is a Chinese herbal medicine used for treating various cancers. However, the Rut administration effect on prostate cancer in vivo remains unclear.

Aim: In the present study we established an allogenic TRAMP-C1 prostate cancer mouse model to evaluate the Rut administration effect and mechanism in vivo.

Methods: To unravel the Rut administration effect on prostate cancer in vivo, C57BL/6J male mice (8 weeks old) were randomly grouped (n = 9), subcutaneously loaded with TRAMP-C1 prostate cancer cells and immediately given daily by gavage with Rut dissolved in soybean oil at 7 mg (low dose), 35 mg (medium dose), and 70 mg/kg b.w./day (high dose) for successive 39 days.

Results: Rut administration significantly and dose-dependently reduced both tumor volume and solid prostate cancer weight in allogenic TRAMP-C1 male mice. Rut administration markedly increased (TNF-α+IFN-γ) (Th1-)/IL-10 (Th2-) cytokine secretion ratios by splenocytes and TNF-α (M1-)/IL-10 (M2-) cytokine secretion ratios by macrophages as compared to those of dietary control group, suggesting that Rut administration in vivo regulates the immune balance toward Th1- and M1-polarized characteristics. Decreased CD19, CD4 and CD8 lymphocytes in the peripheral blood of allogenic TRAMP-C1 mice were significantly elevated by Rut administration. Tumor weights positively correlated with TNF-α secretions by splenocytes, suggesting that there is a tumor cachexia in the tumor-bearing mice. Tumor weights negatively correlated with IgG (Th1-antibody) levels in the sera, suggesting that Th1-polarized immune balance may inhibit prostate cancer cell growth.

Conclusions: Our results evidenced that Rut administration suppresses prostate cancer cell growth in mice subcutaneously loaded with TRAMP-C1 cells and correlated the anti-cancer effects with Th1-polarized immune balance in vivo.
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http://dx.doi.org/10.1016/j.biopha.2021.111648DOI Listing
May 2021

Evaluation of the Genetic Association and Methylation of Immune Response Pathway Genes with the Risk of Chronic Periodontitis in the Uighur Population.

Genet Test Mol Biomarkers 2021 May 4. Epub 2021 May 4.

Department of Endodontics, First Affiliated Hospital of Xinjiang Medical University, and College of Stomatology of Xinjiang Medical University, Urumqi, China.

The aim of this study was to explore the possible associations between single nucleotide polymorphisms (SNPs) and DNA methylation levels of seven genes in the inflammatory response pathway with susceptibility to chronic periodontitis (CP) among the Uighur population of the Xinjiang Autonomous Region of China. A total of 444 eligible subjects (279 CP patients and 165 healthy controls) were enrolled in the study. Genomic DNA was obtained from gingival tissue for genotyping eight SNPs and performing methylation measurements of seven genes. SNP in the formyl peptide receptor 1 () gene achieved statistical significance in the standard allelic association analysis for CP ( = 0.02). The frequency of the minor allele G was higher in the cases than in controls (0.367 vs. 0.291). Additionally, was significantly associated with CP under the dominant genetic model ( = 0.03). Using logistic regression analysis, was found to be consistently associated with CP under the additive dominant model, and this association remained significant after covariates were taken into account [odds ratio (OR) = 1.49 (1.09-2.05),  = 0.014; OR = 1.58 (1.04-2.40),  = 0.031, respectively]. No significant gene-gene interactions were identified. Although we did not find a polymorphism in interleukin 6 () associated with CP in our study, the methylation level of a CpG island region located within the promoter region of was significantly less in CP patients compared with controls ( < 0.05). The genetic polymorphism in and the methylation level of the promoter region of might be associated with CP in the Uighur population of China.
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http://dx.doi.org/10.1089/gtmb.2020.0334DOI Listing
May 2021

Synaptotagmins at the endoplasmic reticulum-plasma membrane contact sites maintain diacylglycerol homeostasis during abiotic stress.

Plant Cell 2021 May 4. Epub 2021 May 4.

Departamento de Biología Molecular y Bioquímica. Instituto de Hortofruticultura Subtropical y Mediterránea "La Mayora", Universidad de Málaga-Consejo Superior de Investigaciones Científicas (IHSM-UMA-CSIC), Universidad de Málaga, 29071, Málaga, Spain.

Endoplasmic reticulum-plasma membrane contact sites (ER-PM CS) play fundamental roles in all eukaryotic cells. Arabidopsis thaliana mutants lacking the ER-PM protein tether synaptotagmin1 (SYT1) exhibit decreased plasma membrane (PM) integrity under multiple abiotic stresses such as freezing, high salt, osmotic stress and mechanical damage. Here, we show that, together with SYT1, the stress-induced SYT3 is an ER-PM tether that also functions in maintaining PM integrity. The ER-PM CS localization of SYT1 and SYT3 is dependent on PM phosphatidylinositol-4-phosphate and is regulated by abiotic stress. Lipidomic analysis revealed that cold stress increased the accumulation of diacylglycerol at the PM in a syt1/3 double mutant relative to wild type while the levels of most glycerolipid species remain unchanged. Additionally, the SYT1-green fluorescent protein (GFP) fusion preferentially binds diacylglycerol in vivo with little affinity for polar glycerolipids. Our work uncovers a SYT-dependent mechanism of stress adaptation counteracting the detrimental accumulation of diacylglycerol at the PM produced during episodes of abiotic stress.
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http://dx.doi.org/10.1093/plcell/koab122DOI Listing
May 2021

Clinical and molecular genetic analysis of a Chinese family with hereditary elliptocytosis caused by a novel mutation in the EPB41 gene.

J Clin Lab Anal 2021 May 4:e23781. Epub 2021 May 4.

Department of Laboratory Medicine, the First Affiliated Hospital of Shantou University Medical College, Shantou, P.R. China.

Background: Hereditary elliptocytosis (HE) is a heterogeneous red blood cell membrane disorder characterized by the presence of elliptocytes on a peripheral blood smear. Clinical manifestations of HE vary widely from asymptomatic carriers to patients with severe transfusion-dependent anemia. Most patients are asymptomatic or have mild anemia, which hinders diagnosis. The proband in this case had mild anemia and jaundice over a period of 4 years, the etiology of which was unclear. Hence, he was admitted to our hospital for further diagnosis.

Methods: Peripheral blood smears and routine blood tests were performed and biochemical parameters of the proband, and his family members were determined. To confirm the diagnosis, gene mutations were screened in the proband using next-generation sequencing (NGS) and verified by Sanger sequencing in other family members.

Results: A novel mutation (c.1294delA, p.Ser432 fs) in exon 15 of the EPB41 gene was detected in the proband and his family members. This mutation results in a frameshift and a premature stop codon at position 455, encoding a truncated protein. The variant was likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics. SWISS-MODEL protein structure prediction indicated partial loss of the spectrin and actin binding and C-terminal domains.

Conclusion: A heterozygous mutation 1294delA in exon 15 of the EPB41 gene was identified using NGS and Sanger sequencing in members of a Chinese family. This identification expands the spectrum of EPB41 mutations and contributes to the genetic diagnosis of families with HE.
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http://dx.doi.org/10.1002/jcla.23781DOI Listing
May 2021

Evolution of delayed resistance to immunotherapy in a melanoma responder.

Nat Med 2021 May 3. Epub 2021 May 3.

Department of Pathology, Harvard Medical School, Brigham and Woman's Hospital, Boston, MA, USA.

Despite initial responses, most melanoma patients develop resistance to immune checkpoint blockade (ICB). To understand the evolution of resistance, we studied 37 tumor samples over 9 years from a patient with metastatic melanoma with complete clinical response to ICB followed by delayed recurrence and death. Phylogenetic analysis revealed co-evolution of seven lineages with multiple convergent, but independent resistance-associated alterations. All recurrent tumors emerged from a lineage characterized by loss of chromosome 15q, with post-treatment clones acquiring additional genomic driver events. Deconvolution of bulk RNA sequencing and highly multiplexed immunofluorescence (t-CyCIF) revealed differences in immune composition among different lineages. Imaging revealed a vasculogenic mimicry phenotype in NGFR tumor cells with high PD-L1 expression in close proximity to immune cells. Rapid autopsy demonstrated two distinct NGFR spatial patterns with high polarity and proximity to immune cells in subcutaneous tumors versus a diffuse spatial pattern in lung tumors, suggesting different roles of this neural-crest-like program in different tumor microenvironments. Broadly, this study establishes a high-resolution map of the evolutionary dynamics of resistance to ICB, characterizes a de-differentiated neural-crest tumor population in melanoma immunotherapy resistance and describes site-specific differences in tumor-immune interactions via longitudinal analysis of a patient with melanoma with an unusual clinical course.
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http://dx.doi.org/10.1038/s41591-021-01331-8DOI Listing
May 2021