CircPHKB decreases the sensitivity of liver cancer cells to sorafenib via miR-1234-3p/CYP2W1 axis.

Sorafenib is currently the first-line treatment for patients with advanced liver cancer, but its therapeutic efficacy declines significantly after a few months of treatment. Therefore, it is of great importance to investigate the regulatory mechanisms of sorafenib sensitivity in liver cancer cells. In this study, we provided initial evidence demonstrating that circPHKB, a novel circRNA markedly overexpressed in sorafenib-treated liver cancer cells, attenuated the sensitivity of liver cancer cells to sorafenib.

ETS1 acts as a regulator of human healthy aging via decreasing ribosomal activity.

Adaptation to reduced energy production during aging is a fundamental issue for maintaining healthspan or prolonging life span. Currently, however, the underlying mechanism in long-lived people remains poorly understood. Here, we analyzed transcriptomes of 185 long-lived individuals (LLIs) and 86 spouses of their children from two independent Chinese longevity cohorts and found that the ribosome pathway was significantly down-regulated in LLIs.

Activation of AKT/AP1/FoxM1 signaling confers sorafenib resistance to liver cancer cells.

Sorafenib is the first‑line drug used in the treatment of liver cancer; however, drug resistance seriously limits the clinical response to sorafenib. The present study investigated the molecular mechanisms of sorafenib resistance in liver cancer cells. The data indicated that forkhead box M1 (FoxM1) was significantly overexpressed in sorafenib‑resistant cells, at the mRNA and protein levels.

Carrying the T Allele of the SNP rs574344, an eQTL of GSTM1, Contributes to Longevity in the Han Chinese Population.

Background: There has been recent recognition that the GSTM1 gene is associated with successful aging and longevity. It has been hypothesized that individuals with a GSTM1 deletion are at a greater risk for developing a plethora of diseases. This study was carried out to investigate the association between the rs574344 single nucleotide polymorphism, an expression quantitative trait locus of GSTM1, and longevity in the Han Chinese population.

Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians.

Centenarians (CENs) are excellent subjects to study the mechanisms of human longevity and healthy aging. Here, we analyzed the transcriptomes of 76 centenarians, 54 centenarian-children, and 41 spouses of centenarian-children by RNA sequencing and found that, among the significantly differentially expressed genes (SDEGs) exhibited by CENs, the autophagy-lysosomal pathway is significantly up-regulated. Overexpression of several genes from this pathway, , , , and , could promote autophagy and delay senescence in cultured IMR-90 cells, while overexpression of the homolog of , , extended the life span in transgenic flies.

Genetic Association Analysis of Common Variants in FOXO3 Related to Longevity in a Chinese Population.

Recent studies suggested that forkhead box class O3 (FOXO3) functions as a key regulator for the insulin/insulin-like growth factor-1signaling pathway that influence aging and longevity. This study aimed to comprehensively elucidate the association of common genetic variants in FOXO3 with human longevity in a Chinese population. Eighteen single-nucleotide polymorphisms (SNPs) in FOXO3 were successfully genotyped in 616 unrelated long-lived individuals and 846 younger controls.

Familial longevity study reveals a significant association of mitochondrial DNA copy number between centenarians and their offspring.

Reduced mitochondrial function is an important cause of aging and age-related diseases. We previously revealed a relatively higher level of mitochondrial DNA (mtDNA) content in centenarians. However, it is still unknown whether such an mtDNA content pattern of centenarians could be passed on to their offspring and how it was regulated.

Mitochondrial DNA plays an equal role in influencing female and male longevity in centenarians.

The mitochondrion is a double membrane-bound organelle which plays important functional roles in aging and many other complex phenotypes. Transmission of the mitochondrial genome in the matrilineal line causes the evolutionary selection sieve only in females. Theoretically, beneficial or neutral variations are more likely to accumulate and be retained in the female mitochondrial genome during evolution, which may be an initial trigger of gender dimorphism in aging.

Common variants in SIRT1 and human longevity in a Chinese population.

Background: The silent information regulator SIR2/SIRT1gene has been demonstrated as regulating lifespan in many model organisms, including yeast, worms, fruit flies and rodents. SIRT1, the human homolog of SIR2, is considered a candidate gene as a modifier of human life expectancy.

Methods: In the current study we included 616 long-lived individuals and 846 matched younger controls to investigate associations between 8 common single nucleotide polymorphisms (SNPs) (i.

Gas Chromatography/Mass Spectrometry-Based Metabolomic Profiling Reveals Alterations in Mouse Plasma and Liver in Response to Fava Beans.

Favism is a life-threatening hemolytic anemia resulting from the intake of fava beans by susceptible individuals with low erythrocytic glucose 6-phosphate dehydrogenase (G6PD) activity. However, little is known about the metabolomic changes in plasma and liver after the intake of fava beans in G6PD normal and deficient states. In this study, gas chromatography/mass spectrometry was used to analyze the plasma and liver metabolic alterations underlying the effects of fava beans in C3H- and G6PD-deficient (G6PDx) mice, and to find potential biomarkers and metabolic changes associated with favism.

Improved lipids, diastolic pressure and kidney function are potential contributors to familial longevity: a study on 60 Chinese centenarian families.

Centenarians are a good healthy aging model. Interestingly, centenarians' offspring are prone to achieve longevity. Here we recruited 60 longevity families and investigated the blood biochemical indexes of family members to seek candidate factors associated with familial longevity.

Lack of association between polymorphisms in the SIRT6 gene and longevity in a Chinese population.

Sirtuin 6 (SIRT6) has recently been demonstrated to play an important role in the regulation of longevity in mammals. We therefore aimed to determine whether common variations in the SIRT6 gene are associated with human longevity. Five tag single nucleotide polymorphisms (SNPs) across the SIRT6 gene and its 5 kb up-/downstream region, including rs350852, rs350844, rs352493, rs4807546 and rs3760905, have been successfully determined in 616 unrelated Chinese long-lived individuals (LLIs) (mean age: 102.

Association of common variants in TOMM40/APOE/APOC1 region with human longevity in a Chinese population.

Apolipoprotein E (APOE), translocase of outer mitochondrial membrane 40 homolog (TOMM40) and apolipoprotein C-I (APOC1) may extend lifespan by marked delay or escape from age-related diseases. This study aimed to elucidate the association of human longevity with genetic variations in TOMM40/APOE/APOC1 region in a Chinese population. Ten tag single-nucleotide polymorphisms (SNPs) in the TOMM40/APOE/APOC1 region were successfully genotyped in 616 unrelated long-lived individuals and 846 younger controls.

The Soybean Peptide Vglycin Preserves the Diabetic β-cells through Improvement of Proliferation and Inhibition of Apoptosis.

Replenishment of insulin-producing pancreatic β-cells would be beneficial in diabetes. The number of β-cells is maintained primarily by self-neogenesis to compensate for β-cell failure, loss or dedifferentiation. We present here a polypeptide vglycin, which was isolated and purified from germinating pea seeds.

Role of AIF-1 in the regulation of inflammatory activation and diverse disease processes.

Allograft Inflammatory Factor-1 (AIF-1) is a 17kDa cytoplasmic, calcium-binding, inflammation-responsive scaffold protein that is mainly expressed in immunocytes. AIF-1 influences the immune system at several key points and thus modulates inflammatory diseases. AIF-1 boosts the expression of inflammatory mediators such as cytokines, chemokines, inducible nitric oxide synthase (iNOS) and promotes inflammatory cell proliferation and migration.

Daintain/AIF-1 plays roles in coronary heart disease via affecting the blood composition and promoting macrophage uptake and foam cell formation.

Background: Daintain/AIF-1 is an inflammatory polypeptide factor/allograft inflammatory factor 1 derived from macrophages. It is characterized in APOE(-/-) mice as a novel inflammatory factor associated with atherosclerosis. The purpose of this study was to characterize its function in human atherosclerosis.

Daintain/AIF-1 (allograft inflammatory factor-1) promotes erythrocyte lysis and heme release probably via binding to hemoglobin.

Free heme is potentially cytotoxic, particularly in the presence of oxidants or activated phagocytes. Daintain/AIF-1 (allograft inflammatory factor-1) is a macrophage factor that has been implicated in the regulation of inflammation. In the present study, daintain/AIF-1 was found to induce cytolysis of erythrocytes, resulting in heme release in vitro.

Effects of daintain/AIF-1 on β cell dysfunction in INS-1 cells.

We investigated the effects of daintain/AIF-1, a novel inflammatory cytokine, on INS-1β cells. Cells incubated with daintain/AIF-1 showed decreased cell viability and glucose-stimulated insulin secretion, as well as upregulated apoptosis and NO production. These deleterious effects of daintain/AIF-1 indicate that daintain/AIF-1 plays important roles in the dysfunction of pancreatic β cells in type-1 diabetes.

17β-Estradiol increased the expression of daintain/AIF-1 in RAW264.7 macrophages.

We investigated the effect of 17β-estradiol (E2) on the expression of daintain/AIF-1, a marker of activated macrophages, in RAW264.7. E2 upregulated the protein and mRNA levels of daintain/AIF-1 in similar manners under physiological concentrations of 10(-11) M to 10(-7) M.