Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation.

In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with Stat3 in the nucleus to deacetylate and deacetyliminate Stat3 on multiple acetyl-lysine sites. Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity. Loxl3-mediated deacetylation/deacetylimination disrupts Stat3 dimerization, abolishes Stat3 transcription activity, and restricts cell proliferation. In Loxl3-/- mice, Stat3 is constitutively acetylated and naive CD4+ T cells are potentiated in Th17/Treg cell differentiation. When overexpressed, the SRCR repeats from other LOX family members can catalyze protein deacetylation/deacetylimination. Thus, our findings delineate a hitherto-unknown mechanism of protein deacetylation and deacetylimination catalyzed by lysyl oxidases.

Ampicillin exacerbates acetaminophen-induced acute liver injury by inducing intestinal microbiota imbalance and butyrate reduction.

BACKGROUND AND AIMS: Antibiotics (ATBx) and acetaminophen (APAP) are widely used worldwide. APAP is the most common cause of acute liver injury (ALI) and might be used in combination with ATBx in clinics. However, the impact of ATBx on APAP-induced ALI has rarely been studied. METHODS: First, we compared the effects of seven ATBx on APAP-induced ALI. Then, we analysed faecal, serum and liver samples to investigate the impact of the gut microbiota on this process. Finally, we assessed the role of short-chain fatty acids in this process. RESULTS: In this work, we found that the ALI was significantly aggravated in the mice treated with ampicillin (Amp) instead of other ATBx. Amp exposure reduced the diversity and altered the composition of gut microbiota. The altered gut microbiota aggravated APAP-induced ALF, which was proven by faecal microbiota transplantation from ATBx-treated mice. Metagenomic analysis showed a significantly decreased Lactobacillus abundance in Amp-treated mice. Gavage with Lactobacillus, especially Lactobacillus rhamnosus, significantly reversed the severer ALF induced by APAP and Amp. Moreover, Lactobacillus supplementation increased butyrate-producing clostridia and lowered butyrate levels in Amp-treated mice. In accordance, butyrate supplementation could also alleviate Amp-aggravated ALI. In addition, inhibition of nuclear factor erythroid 2-related factor 2 counteracted the protective effect of butyrate on aggravated ALI induced by Amp and APAP. CONCLUSION: Together, this study revealed a potential health impact of Amp that may exacerbate liver damage when co-exposed to excess APAP.

Host ALDH2 deficiency aggravates nonalcoholic steatohepatitis through gut-liver axis.

Nonalcoholic steatohepatitis (NASH) is the major cause of liver dysfunction. Animal and population studies have shown that mitochondrial aldehyde dehydrogenase (ALDH2) is implicated in fatty liver disease. However, the role of ALDH2 in NASH and the underlying mechanisms remains unclear. To address this issue, ALDH2 knockout (ALDH2-/-) mice and wild-type littermate mice were fed a methionine-and choline-deficient (MCD) diet to induce a NASH model. Fecal, serum, and liver samples were collected and analyzed to investigate the impact of the gut microbiota and bile acids on this process. We found that MCD-fed ALDH2-/- mice exhibited increased serum pro-inflammation cytokines, hepatic inflammation and fat accumulation than their wild-type littermates. MCD-fed ALDH2-/- mice exhibited worsened MCD-induced intestinal inflammation and barrier damage, and gut microbiota disorder. Furthermore, mice receiving microbiota from MCD-fed ALDH2-/- mice had increased severity of NASH compared to those receiving microbiota from MCD-fed wild-type mice. Notably, the intestinal Lactobacillus was significantly reduced in MCD-fed ALDH2-/- mice, and gavage with Lactobacillus cocktail significantly improved MCD-induced NASH. Finally, we found that ALDH2-/- mice had reduced levels of bile salt hydrolase and specific bile acids, especially lithocholic acid (LCA), accompanied by downregulated expression of the intestinal FXR-FGF15 pathway. Supplementation of LCA in ALDH2-/- mice upregulated intestinal FXR-FGF15 pathway and alleviated NASH. In summary, ALDH2 plays a critical role in the development of NASH through modulation of gut microbiota and bile acid. The findings suggest that supplementing with Lactobacillus or LCA could be a promising therapeutic approach for treating NASH exacerbated by ALDH2 deficiency.

An Energy-Restricted Diet Including Yogurt, Fruit, and Vegetables Alleviates High-Fat Diet-Induced Metabolic Syndrome in Mice by Modulating the Gut Microbiota.

BACKGROUND: The importance of the composition of an energy-restricted diet in the treatment of metabolic syndrome (MetS) is unknown. OBJECTIVES: In this study we aimed to investigate the benefits of a novel dietary treatment (50% calorie restriction diet composed of yogurt, fruit, and vegetables [CR-YD]) in mice with MetS. METHODS: Forty 7-wk-old male C57BL/6 J mice were randomly assigned to 4 groups (n = 10/group) that were fed for 14 wk ad libitum with a normal diet (ND; 10%:70%:20% energy from fat: carbohydrate: protein) or for 12 wk with a high-fat diet (HFD; 60:20:20) or the HFD followed by 2 wk of feeding with a 50% calorie-restricted HFD (CR-HFD) or YD (CR-YD, 21.2%:65.4%:13.4% energy). Body weight, fat deposition, hepatic steatosis, serum concentrations of inflammatory biomarkers, and glucose homeostasis were assessed. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in MetS. RESULTS: The HFD group had 50% greater body weight and 475% greater fat deposition than the ND group (P < 0.05). Compared with the HFD group, the CR-HFD and CR-YD groups had 22% and 31% lower body weight and 49% and 75% less fat deposition, respectively (P < 0.05). Compared with the CR-HFD group, the CR-YD group had 11% lower body weight, 96% less fat deposition, 500% less hepatic steatosis, 75% lower glucose, and 450% more hepatic Akkermansia bacteria (P < 0.05). The CR-YD group also had 50% lower histopathology scores and 1.35-fold higher levels of Claudin4 than the CR-HFD group (P < 0.05). The HFD + CR-YD fecal group had 10.6% lower body weight, 119% lower steatosis, and 17.9% lower glucose (P < 0.05) than the HFD + CR-HFD fecal group. CONCLUSIONS: Compared with CR alone, the CR-YD diet has a better therapeutic effect in mice with HFD-induced MetS.

Fatty liver is a sensitive early warning for hypertension and its complication in the Chinese population.

OBJECTIVE: The patient of hypertension and its complication increase fast in the past years. Obesity is thought to be a risk factor for hypertension, and BMI (body mass index) is widely used to evaluate the obesity and hypertension risk. However, the abdominal obesity and visceral fat accumulation are more obvious in the East Asian population. The aim of this study was to evaluate the predictive value of fatty liver for hypertension in the Chinese population. METHOD: We compared the predictive value of BMI and fatty liver for the hypertension and its complication in 1386 patients with hypertension in Shanghai China. RESULTS: In the analysis of 1386 patients with hypertension in Shanghai China, we found that the prevalence and risk of hypertension and its complications were higher in the fatty liver group than that in the group of BMI≥24. Furthermore, the areas under the ROC curve of fatty liver for hypertension and its complications were superior to that of BMI. CONCLUSION: These results suggested that fatty liver is a more sensitive early warning for hypertension and its complication than BMI in Chinese population.

Calorie restriction conferred improvement effect on long-term rehabilitation of ischemic stroke via gut microbiota.

Calorie restriction can modulate the gut microbiota and protect against many diseases including ischemic stroke. However, the role of calorie-restriction-induced microbiota alteration remained unknown in ischemic stroke rehabilitation. Here we conducted 30% reduction of caloric intake on mice for four weeks, to evaluate its role on ischemic stroke rehabilitation. Significantly, this calorie restriction led to better long-term rehabilitation in comparison of normal control. Notably, the transplantation of gut microbiome from calorie-restriction-treated mice to post-stroke mice was eligible to obtain better long-term rehabilitation of stroke mice. Bifidobacterium identified by 16 S ribosomal RNA sequencing were enriched in those of calorie-restriction mice. Then we administrated Bifidobacterium to stroke mice and found Bifidobacterium treatment could successfully improve the long-term rehabilitation of cerebral ischemia mice. Furthermore, the metabolomics analysis revealed a panel of upshifting metabolites, suggesting that calorie restriction greatly altered the gut microbiota composition and its metabolism. Hence, we discovered the novel effect of CR on long-term rehabilitation of ischemic stroke and the underlying role of gut microbiota, which might provide novel thoughts for the clinical post-stroke rehabilitation.

A real-world study of socioeconomic factors with survival in adults aged 18-64 years with renal cell carcinoma.

Aim: To evaluate the impact of socioeconomic factors (SEFs) on survival of renal cell carcinoma (RCC) patients. Materials & methods: RCC patients diagnosed between 2007 and 2015 were collected from the SEER database. The crude and multivariate Cox regression analysis was used to identify the independent prognostic factors and quantity the mortality risks for overall survival (OS). Results: Three SEFs including marital status, insurance status and median household income were identified as prognostic factors for OS. SEF-stage was built based on the three SEFs. Moreover, the SEF-stage 1 had superior OS than SEF-stage 2 within the respective American Joint Committee on Cancer stages. Conclusion: The SEF-stage was an independently prognostic factor for OS in RCC. Incorporation of SEF-stage into the American Joint Committee on Cancer staging system might be beneficial for better survival prediction and clinical management. However, further studies were needed to validate these findings in other populations.

Annonaceous acetogenin mimic AA005 suppresses human colon cancer cell growth in vivo through downregulation of Mcl-1.

Annonaceous acetogenins are a well-established family of natural products with significant bioactivities, especially high cytotoxic and antitumor activities. AA005 is an annonaceous acetogenin mimic that has shown significant cytotoxicity against a variety of cancer cell lines, but its in vivo antitumor effects have not been demonstrated so far, and its anticancer mechanisms remain ambiguous. In this study, we investigated the effects of AA005 on human colon cancer cell lines in vivo. Human colon carcinoma cell line SW620 xenograft nude mice were treated with AA005 (5 mg/kg/day, i.p.) for 21 days. AA005 administration markedly inhibited the tumor growth via promoting nuclear translocation of apoptosis-inducing factor (AIF) and inducing AIF-dependent cell death. Subsequent studies in human colon carcinoma cell lines SW620 and RKO in vitro revealed that after the colon cancer cells exposed to AA005, downregulation of a B-cell lymphoma 2 family protein, myeloid cell leukemia-1 (Mcl-1), was an early event due to the inhibition of Mcl-1 mRNA level and protein synthesis in a time-dependent manner. Intriguingly, knockdown of Mcl-1 using small interfering RNA markedly accelerated the nuclear translocation of AIF and upregulation of receptor interacting protein-1, and enhanced AA005-mediated lethality, whereas ectopic expression of Mcl-1 substantially attenuated AA005-mediated lethality in the colon cancer cells. Finally, silencing Mcl-1 expression markedly enhanced AA005-induced lethality in SW620 xenograft nude mice, demonstrating a pivotal role of Mcl-1 downregulation in mediating the in vivo antitumor effects of AA005. Taken together, this study demonstrates for the first time the anticancer effects of AA005 against human colon cancer cell lines in vivo, which is mediated through the downregulation of Mcl-1.

Longevity-Associated Forkhead Box O3 (FOXO3) Single Nucleotide Polymorphisms are Associated with Type 2 Diabetes Mellitus in Chinese Elderly Women.

BACKGROUND This study aimed to investigate the association of single nucleotide polymorphisms (SNPs) of Forkhead box O3 (FOXO3) gene with type 2 diabetes mellitus (T2D). MATERIAL AND METHODS A total of 843 elderly residents from east China were enrolled in this study, which included 426 patients with type 2 diabetes and 417 controls. Four SNPs were analyzed by qPCR. Genotype frequencies of the 4 SNPs in FOXO3 of the patients and controls were analyzed using logistic regression analysis. The association between each SNP and clinical indicators was analyzed by linear regression analysis. RESULTS None of the 4 FOXO3 variants, rs13217795, rs2764264, rs2802292, and rs13220810, were associated with the risk of type 2 diabetes compared to controls. However, rs13217795, rs2764264, and rs2802292 were associated with lower blood glucose levels. Notably, further subgroup analysis indicated that the longevity-associated alleles of FOXO3 SNP (rs13217795, rs2764264, and rs2802292) were associated with lower blood glucose levels in women (TC versus TT, -0.724 mmol/L, P=0.005; CC versus TT, -1.093 mmol/L, P=0.03; TC versus TT, -0.801 mmol/L, P=0.002; CC versus TT, -1.212 mmol/L, P=0.001; TG versus TT, -0.754 mmol/L, P=0.004; and GG versus TT, -1.150 mmol/L, P=0.001) but not in men. CONCLUSIONS The results indicated that longevity-associated FOXO3 variants were correlated with lower blood glucose levels in elderly women with type 2 diabetes in east China.

Alcohol and HBV synergistically promote hepatic steatosis.

BACKGROUND AND AIMS: Hepatitis virus and alcohol are the main factors leading to liver damage. Synergy between hepatitis B virus (HBV) and alcohol in promoting liver cell damage and disease progression has been reported. However, the interaction of HBV and ethanol in hepatic steatosis development has not been fully elucidated. METHODS: Eight-week-old male C57BL/6 mice were treated with or without HBV, ethanol, or the combination of HBV and ethanol (HBV+EtOH), followed by a three-week high-fat diet (HFD) regimen. Liver histology, serum biomarkers, and liver triglyceride levels were analysed. Furthermore, a meta-analysis of the effects of alcohol and HBV on hepatic steatosis in populations was performed. RESULTS: Hepatic steatosis was significantly more severe in the HBV+EtOH group than in the other groups. The serum alanine aminotransferase, aspartate aminotransferase and liver triglyceride levels in the HBV+EtOH group were also significantly higher than those in the other groups. The HBeAg and HBsAg levels in the HBV+EtOH group were significantly higher than those in the pair-fed HBV-infected mice. In addition, the meta-analysis showed that alcohol consumption increased the risk of hepatic steatosis by 43% in HBV-infected patients (pooled risk ratio (RR)=1.43, P<0.01). CONCLUSIONS: Alcohol and HBV synergistically promote high-fat diet-induced hepatic steatosis in mice. In addition, alcohol consumption increases the risk of hepatic steatosis in HBV-infected patients.

ALDH2 and Cancer Therapy.

Aldehyde dehydrogenase 2 (ALDH2) is a member of ALDH family. ALDH1 has been widely recognized for its roles in carcinogenesis and cancer therapy; however, investigation for ALDH2 in cancer is seldom mentioned. The ALDH2 point mutation ALDH2*2 is the most frequent human gene variant, and it is present in approximately 560 million East Asians. ALDH2*2 demonstrates its effect on alcohol consumption limiting and alcoholism developing protection, and this variant is recently found to have an important impact on human health. This chapter focuses on its potential effect on cancer therapy, especially for chemotherapeutics with anthracyclines.

Polymorphism of the DNA methyltransferase 1 gene is associated with the susceptibility to essential hypertension in male.

Essential hypertension is a leading global public health issue, billions of people suffered from it every year. Recently, multiple evidence suggests that DNA methylation play an important role in regulating blood pressure. Here, we tested the risk for essential hypertension conferred by single nucleotide polymorphisms (SNPs) within DNA methyltransferase 1 (DNMT1). Three loci (rs2228611, rs2228612, and rs16999593) were selected to be analyzed in 3410 cases and 1307 normal controls in southern Chinese aged 60 or above. No significant association with essential hypertension was observed for rs2228612 and rs16999593. A higher risk of essential hypertension was found in the minor A allele of rs2228611 in the codominant and recessive model (P < 0.05). After stratified by sex, this association was found in male but not female. Furthermore, this difference was abolished after BMI adjustment in the whole population and reduced in male. In addition, the mutation rate of rs2228611 was higher in the obesity group compared with the normal weight group of male. Intriguingly, rs2228611 was also a risk factor of essential hypertension in normal weight male. These findings indicated that rs2228611 might contribute to male hypertension via BMI-dependent mechanisms in obesity male and BMI-independent mechanisms in normal weight male.

The ALDH2 gene rs671 polymorphism is not associated with essential hypertension.

Essential hypertension (EH) is a worldwide problem. Acetaldehyde dehydrogenase 2 (ALDH2) gene has been suggested to be correlated with EH. However, the results are inconsistent. This study aimed to investigate the associations of ALDH2 rs671 polymorphism with EH in a Chinese Han population in Shanghai. Genotype of ALDH2 rs671 was analyzed in 1923 EH patients and 1115 control subjects. We found no association between ALDH2 rs671 and EH risk or EH-related quantitative blood chemistry values. Furthermore, a meta-analysis was performed and the summary results from 11220 patients and 8339 control subjects were consistent with our findings. These results indicated that rs671 of ALDH2 may not associate with the risk of EH.

CCAAT/enhancer-binding protein CEBP-2 controls fat consumption and fatty acid desaturation in Caenorhabditis elegans.

Mammalian CCAAT/enhancer-binding proteins (C/EBPs) are generally known as regulators in adipocyte differentiation. However, more understanding of the role of C/EBPs in lipid and glucose metabolism remains to be discovered. In this study, we verified the effect of CEBP-2, the homolog of CEBPs, on fat storage in Caenorhabditis elegans. Expressions of 85 genes that encode the major enzymes in energy metabolic pathways were then screened in cebp-2-deficient worms using a quantitative real-time polymerase chain reaction (QRT-PCR). Our data implied that loss of function of CEBP-2 displayed a low-fat phenotype in C. elegans owing to increased expression of ech-1.1 and decreased expression of fat-5. Our findings indicated that cebp-2 controls total body fat content by governing fatty acid mitochondrial ß-oxidation and desaturation in C. elegans. These data provide insights into how C/EBPs may affect lipid metabolism in mammals in addition to regulating adipocyte differentiation.

Nuclear hormone receptor regulation of microRNAs controls innate immune responses in C. elegans.

Nuclear hormone receptors respond to small molecules such as retinoids or steroids and regulate development. Signaling in the conserved p38/PMK-1 MAP kinase pathway regulates innate immunity. In this study, we show that the Caenorhabditis elegans nuclear receptor DAF-12 negatively regulates the defense against pathogens via the downstream let-7 family of microRNAs, which directly target SKN-1, a gene downstream of PMK-1. These findings identify nuclear hormone receptors as components of innate immunity that crosstalk with the p38/PMK-1 MAP kinase pathway.

Annonaceous acetogenin mimic AA005 induces cancer cell death via apoptosis inducing factor through a caspase-3-independent mechanism.

BACKGROUND: Annonaceous acetogenins are a family of natural products with antitumor activities. Annonaceous acetogenin mimic AA005 reportedly inhibits mammalian mitochondrial NADH-ubiquinone reductase (Complex I) and induces gastric cancer cell death. However, the mechanisms underlying its cell-death-inducing activity are unclear. METHODS: We used SW620 colorectal adenocarcinoma cells to study AA005 cytotoxic activity. Cell deaths were determined by Trypan blue assay and flow cytometry, and related proteins were characterized by western blot. Immunofluorescence and subcellular fractionation were used to evaluate AIF nuclear translocation. Reactive oxygen species were assessed by using redox-sensitive dye DCFDA. RESULTS: AA005 induces a unique type of cell death in colorectal adenocarcinoma cells, characterized by lack of caspase-3 activation or apoptotic body formation, sensitivity to poly (ADP-ribose) polymerase inhibitor Olaparib (AZD2281) but not pan-caspase inhibitor Z-VAD.fmk, and dependence on apoptosis-inducing factor (AIF). AA005 treatment also reduced expression of mitochondrial Complex I components, and leads to accumulation of intracellular reactive oxygen species (ROS) at the early stage. Blocking ROS formation significantly suppresses AA005-induced cell death in SW620 cells. Moreover, blocking activation of RIP-1 by necroptosis inhibitor necrotatin-1 inhibits AIF translocation and partially suppresses AA005-induced cell death in SW620 cells demonstrating that RIP-1 protein may be essential for cell death. CONCLUSIONS: AA005 may trigger the cell death via mediated by AIF through caspase-3 independent pathway. Our work provided new mechanisms for AA005-induced cancer cell death and novel clues for cancer treatment via AIF dependent cell death.

Freeze-thaw Caenorhabditis elegans freeze-thaw stress response is regulated by the insulin/IGF-1 receptor daf-2.

BACKGROUND: Adaption to cold temperatures, especially those below freezing, is essential for animal survival in cold environments. Freezing is also used for many medical, scientific, and industrial purposes. Natural freezing survival in animals has been extensively studied. However, the underlying mechanisms remain unclear. Previous studies demonstrated that animals survive in extremely cold weather by avoiding freezing or controlling the rate of ice-crystal formation in their bodies, which indicates that freezing survival is a passive thermodynamic process. RESULTS: Here, we showed that genetic programming actively promotes freezing survival in Caenorhabditis elegans. We found that daf-2, an insulin/IGF-1 receptor homologue, and loss-of-function enhanced survival during freeze-thaw stress, which required the transcription factor daf-16/FOXO and age-independent target genes. In particular, the freeze-thaw resistance of daf-2(rf) is highly allele-specific and has no correlation with lifespan, dauer formation, or hypoxia stress resistance. CONCLUSIONS: Our results reveal a new function for daf-2 signaling, and, most importantly, demonstrate that genetic programming contributes to freezing survival.

Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells.

Peroxiredoxins (Prxs) are potential therapeutic targets for major diseases such as cancers. However, isotype-specific inhibitors remain to be developed. We report that adenanthin, a diterpenoid isolated from the leaves of Rabdosia adenantha, induces differentiation of acute promyelocytic leukemia (APL) cells. We show that adenanthin directly targets the conserved resolving cysteines of Prx I and Prx II and inhibits their peroxidase activities. Consequently, cellular H(2)O(2) is elevated, leading to the activation of extracellular signal-regulated kinases and increased transcription of CCAAT/enhancer-binding protein ß, which contributes to adenanthin-induced differentiation. Adenanthin induces APL-like cell differentiation, represses tumor growth in vivo and prolongs the survival of mouse APL models that are sensitive and resistant to retinoic acid. Thus, adenanthin can serve as what is to our knowledge the first lead natural compound for the development of Prx I- and Prx II-targeted therapeutic agents, which may represent a promising approach to inducing differentiation of APL cells.

Two-dimensional fluorescence in-gel electrophoresis of coronary restenosis tissues in minipigs: increased adipocyte fatty acid binding protein induces reactive oxygen species-mediated growth and migration in smooth muscle cells.

OBJECTIVE: We aimed to uncover the protein changes of coronary artery in-stent restenosis (ISR) tissue in minipigs with and without streptozotocin-induced diabetes mellitus by quantitative 2-dimensional fluorescence in-gel electrophoresis (2D-DIGE), and to investigate the influences of crucial proteins identified, particularly adipocyte fatty acid binding protein (AFABP), in human arterial smooth muscle cells. METHODS AND RESULTS: Sirolimus-eluting stents were implanted in the coronary arteries of 15 diabetic and 26 nondiabetic minipigs, and angiography was repeated after 6 months. The intima tissue of significant ISR and non-ISR segments in both diabetic and nondiabetic minipigs was analyzed by 2D-DIGE and MALDI-TOF/TOF mass spectrometry. AFABP level was significantly increased in ISR tissue than in non-ISR tissue in both diabetic and nondiabetic minipigs, with level being higher in diabetic ISR than in nondiabetic ISR tissue. In human arterial smooth muscle cells, overexpression of AFABP significantly altered phenotype and promoted growth and migration, with effects more prominent in high-glucose than in low-glucose medium, whereas AFABP knockdown inhibited these effects. AFABP overexpression increased reactive oxygen species production by upregulating the expression of NADPH oxidase subunits Nox1, Nox4, and P22 through multiple pathways, with elevation of downstream gene cyclin D1, matrix metalloproteinase-2, and monocyte chemoattractant protein-1. However, AFABP-induced effects were inhibited by diphenyleneiodonium, pathway inhibitors, and small interfering RNA. In addition, the supernatant from AFABP-expressing human arterial smooth muscle cells and recombinant AFABP also promoted cellular growth and migration. CONCLUSIONS: This study has demonstrated that AFABP is significantly increased in coronary artery ISR segments of both diabetic and nondiabetic minipigs. Increased AFABP expression and secretory AFABP of human arterial smooth muscle cells promote growth and migration via reactive oxygen species-mediated activation.

Impact of the gut microbiome on atherosclerosis.

Atherosclerosis is a chronic inflammatory metabolic disease with a complex pathogenesis. However, the exact details of its pathogenesis are still unclear, which limits effective clinical treatment of atherosclerosis. Recently, multiple studies have demonstrated that the gut microbiota plays a pivotal role in the onset and progression of atherosclerosis. This review discusses possible treatments for atherosclerosis using the gut microbiome as an intervention target and summarizes the role of the gut microbiome and its metabolites in the development of atherosclerosis. New strategies for the treatment of atherosclerosis are needed. This review provides clues for further research on the mechanisms of the relationship between the gut microbiota and atherosclerosis.