Evaluation of LOXL1 polymorphisms in exfoliation syndrome in a Chinese population

Purpose: To evaluate the association profiles of the lysyl oxidase-like 1 (LOXL1) gene polymorphisms with exfoliation syndrome in a Chinese population. Methods: Fifty unrelated patients with exfoliation syndrome and 125 control subjects were included. Genotypes of the three single nucleotide polymorphisms (SNPs) of LOXL1 (rs1048661, rs3825942, and rs2165241) were analyzed by direct sequencing, and a case-control association study was performed. Results: The three SNPs were significantly associated with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) individually. After controlling for rs3825942 and rs2165241, the association between rs1048661 and XFS/XFG remained significant (p=3.6x10(-7)). At this SNP, the T allele and TT genotype conferred a 7.59-(95% confidence interval [CI]: 3.87-14.89, p=6.95x10(-11)) and 8.69-(95% CI: 4.15-18.20, p<1.00x10(-7)) fold increased risk to the disease. The alleles of T at rs1048661 and C at rs2165241 were found to be risk alleles in Chinese subjects, which were opposite to Caucasian individuals. The haplotypes T-G, defined by SNPs rs1048661 and rs3825942, and T-C by SNPs rs1048661 and rs2165241, were also significantly associated with the disorder. However when the genotypic or allelic frequencies of the three SNPs were compared between XFS and XFG, no significant difference was detected. Conclusions: LOXL1 is a susceptibility gene of XFS/XFG in the Chinese population, and the association is mainly attributed to SNP rs1048661. The risk alleles of rs1048661 and rs2165241 in Chinese subjects were found to be opposite to that of Caucasians. The genotypic and allelic distributions of these SNPs are similar between XFS and XFG.Biochemistry & Molecular BiologyOphthalmologySCI(E)30ARTICLE250-522349-23571

Study on chemical constituents and antioxidant activities of Dianthus caryophyllus L.

ObjectiveCarnation is a plant that holds high value in terms of its edibility, medicinal properties, and ornamental appeal. Creating no sense he aim of this study was to evaluate the antioxidant and antitumor properties of extracts derived from various parts of the carnation plant. Metabolomics technology was employed to identify the primary chemical constituents.MethodsInitially, we measured the total phenolic and total flavonoid contents in carnation roots, stems, leaves, and flowers, followed by assessing the antioxidant and anti-tumor capabilities of each component using diverse experimental methods. Subsequently, UPLC-MS/MS was employed to identify metabolites in different parts of carnation and investigate their roles in antioxidant and anti-tumor activities.ResultsMention numerical value- for better underatnding- Results of the study indicated that the methanol extract obtained from carnation flowers and roots exhibited superior antioxidant capacity compared to that from the stems and leaves. This disparity may be attributed to the abundance of polyphenols, flavonoids, and antioxidants present in the flowers, including methyl ferulate and luteolin-4’-O-glucoside. Furthermore, the significant presence of the anthraquinone compound rhein-8-O-glucoside in carnation roots may contribute to their enhanced antioxidant properties. Ten distinct compounds were isolated and recognized in carnation flowers, with Isoorientin 2”-O-rhamnoside and Kurarinone demonstrating notable antioxidant activity and binding affinity to SOD1 and SOD3, as validated through antioxidant screening and molecular docking.ConclusionOverall, the findings from this study have expanded our knowledge of the phytochemical composition across different anatomical regions of the carnation plant, providing valuable insights for its holistic utilization

Loss of p16Ink4a Function Rescues Cellular Senescence Induced by Telomere Dysfunction

p16Ink4a is a tumor suppressor and a marker for cellular senescence. Previous studies have shown that p16Ink4a plays an important role in the response to DNA damage signals caused by telomere dysfunction. In this study, we crossed Wrn−/− and p16Ink4a−/− mice to knock out the p16Ink4a function in a Wrn null background. Growth curves showed that loss of p16Ink4a could rescue the growth barriers that are observed in Wrn−/− mouse embryonic fibroblasts (MEFs). By challenging the MEFs with the global genotoxin doxorubicin, we showed that loss of p16Ink4a did not dramatically affect the global DNA damage response of Wrn−/− MEFs induced by doxorubicin. However, in response to telomere dysfunction initiated by the telomere damaging protein TRF2ΔBΔM, loss of p16Ink4a could partially overcome the DNA damage response by disabling p16Ink4a up-regulation and reducing the accumulation of γ-H2AX that is observed in Wrn−/− MEFs. Furthermore, in response to TRF2ΔBΔM overexpression, Wrn−/− MEFs senesced within several passages. In contrast, p16Ink4a−/− and p16Ink4a−/−Wrn−/− MEFs could continuously grow and lose expression of the exogenous TRF2ΔBΔM in their late passages. In summary, our data suggest that in the context of telomere dysfunction, loss of p16Ink4a function could prevent cells from senescence. These results shed light on the anti-aging strategy through regulation of p16Ink4a expression

LOS PACIENTES RECUPERADOS DEL COVID-19 PUEDEN SEGUIR CON UNA RESPUESTA HIPERINFLAMATORIA.

En un estudio reciente se caracterizó de manera integral los cambiostranscripcionales en las células mononucleares de sangre periférica durante la etapa de recuperación de COVID-19 mediante la técnica de secuenciación de ARN de células individuales. Los resultados obtenidos indican que las células T disminuyeron notablemente, mientras que los monocitos con alta expresión de genes proinflamatorios aumentaron en pacientes en la etapa de recuperación temprana (ERS) de COVID-19. Este estudio proporciona la primera evidencia de una firme respuesta inmune inflamatoria durante laERS, lo que sugiere que los pacientes con COVID-19 siguen siendo vulnerables después del alta hospitalaria

The Gain of Function of p53 Mutant p53S in Promoting Tumorigenesis by Cross-talking with H-RasV12

The loss of wild type p53 tumor suppressive function and oncogenic gain-of-function of p53 mutants have been showing important implications in tumorigenesis. The p53N236S (p53N239S in human, p53S) mutation has been shown to lose wild type p53 function by yeast assay. However, its gain of function is still not clear. By gel shift assay, we showed that mutant p53S had lost its DNA binding ability to its target promoters. Further real-time PCR data confirmed that p53S had lost the function of regulating the transcription of p21 Cip1/Waf1, cyclin G, PUMA, and Bax in response to 10Gy irradiation. These data confirmed the loss of function of p53S in mammalian cells. By xenograft assay, we showed that the p53S per se was not oncogenic enough to form tumor, however, cooperating with H-RasV12, p53S could dramatically promote tumorigenesis in p53 null MEFs. Further study showed that co-expression of p53S and H-RasV12 could increase the expression level of H-RasV12 and partially eliminate the elevation of stress response proteins such as Chk2, &#947;-H2AX, Hsp70, Rb, p16Ink4a caused by either p53S or H-RasV12. These data suggested that p53S cross-talked with H-RasV12 and reduced the cellular stress response to oncogenic signals, which facilitated the cell growth and tumorigenesis. Together these data provided the molecular basis for the cooperation of p53S and H-RasV12 and revealed the gain of function of p53S in cross-talking with H-RasV12. This study revealed an important aspect of gain of function for p53 mutant, therefore might shed light on the clinical strategy in targeting p53 mutant.</p

Pu-erh Tea Inhibits Tumor Cell Growth by Down-Regulating Mutant p53

Abstract: Pu-erh tea is a kind of fermented tea with the incorporation of microorganisms’ metabolites. Unlike green tea, the chemical characteristics and bioactivities of Pu-erh tea are still not well understood. Using water extracts of Pu-erh tea, we analyzed the tumor cell growth inhibition activities on several genetically engineered mouse tumor cell lines. We found that at the concentration that did not affect wild type mouse embryo fibroblasts (MEFs) growth, Pu-erh tea extracts could inhibit tumor cell growth by down-regulated S phase and cause G1 or G2 arrest. Further study showed that Pu-erh tea extracts down-regulated the expression of mutant p53 in tumor cells at the protein level as well as mRNA level. The same concentration of Pu-erh tea solution did not cause p53 stabilization or activation of its downstream pathways in wild type cells. We also found that Pu-erh tea treatment could slightly down-regulate both HSP70 and HSP90 protein levels in tumor cells. These data revealed the action of Pu-erh tea on tumor cells and provided the possible mechanism for Pu-erh tea action, which explained its selectivity in inhibiting tumor cells without affecting wild type cells. Our data sheds light on the application of Pu-erh tea as a

Influence of TP53 Codon 72 Polymorphism Alone or in Combination with HDM2 SNP309 on Human Infertility and IVF Outcome.

To evaluate the association of the TP53 codon 72 (rs 1042522) alone or in combination with HDM2 SNP309 (rs 2279744) polymorphisms with human infertility and IVF outcome, we collected 1450 infertility women undergoing their first controlled ovarian stimulation for IVF treatment and 250 fertile controls in the case-control study. Frequencies, distribution, interaction of genes, and correlation with infertility and IVF outcome of clinical pregnancy were analyzed. We found a statistically significant association between TP53 codon 72 polymorphism and IVF outcome (52.10% vs. 47.40%, OR = 0.83, 95%CI:0.71-0.96, p = 0.01). No significant difference was shown between TP53 codon 72, HDM2 SNP309 polymorphisms, human infertility, and between the combination of two genes polymorphisms and the clinical pregnancy outcome of IVF. The data support C allele as a protective factor for IVF pregnancy outcome. Further researches should be focused on the mechanism of these associations