Artemisinin ameliorates cognitive decline by inhibiting hippocampal neuronal ferroptosis via Nrf2 activation in T2DM mice.

BACKGROUND: Neuronal ferroptosis plays a critical role in the pathogenesis of cognitive deficits. The present study explored whether artemisinin protected type 2 diabetes mellitus (T2DM) mice from cognitive impairments by attenuating neuronal ferroptosis in the hippocampal CA1 region. METHODS: STZ-induced T2DM mice were treated with artemisinin (40 mg/kg, i.p.), or cotreated with artemisinin and Nrf2 inhibitor MEL385 or ferroptosis inducer erastin for 4 weeks. Cognitive performance was determined by the Morris water maze and Y maze tests. Hippocampal ROS, MDA, GSH, and Fe2+ contents were detected by assay kits. Nrf2, p-Nrf2, HO-1, and GPX4 proteins in hippocampal CA1 were assessed by Western blotting. Hippocampal neuron injury and mitochondrial morphology were observed using H&E staining and a transmission electron microscope, respectively. RESULTS: Artemisinin reversed diabetic cognitive impairments, decreased the concentrations of ROS, MDA and Fe2+, and increased the levels of p-Nr2, HO-1, GPX4 and GSH. Moreover, artemisinin alleviated neuronal loss and ferroptosis in the hippocampal CA1 region. However, these neuroprotective effects of artemisinin were abolished by Nrf2 inhibitor ML385 and ferroptosis inducer erastin. CONCLUSION: Artemisinin effectively ameliorates neuropathological changes and learning and memory decline in T2DM mice; the underlying mechanism involves the activation of Nrf2 to inhibit neuronal ferroptosis in the hippocampus.

2D multifunctional SiAs2/GeAs2van der Waals heterostructure.

The structural and electronic properties of two-dimensional (2D) SiAs2/GeAs2van der Waals heterostructure (vdWH) and its applications are investigated by combing first-principles calculations and Silvaco Atlas simulations. The stable SiAs2/GeAs2vdWH exhibits an indirect bandgap of 0.99 eV in type II band alignment for light detection and energy harvesting. The vdWH can exhibit a direct bandgap up to 0.66 eV by applying an appropriate electric field (Eext). Due to theEextinduced charge redistribution, its band alignment can be transformed from type II to type I for light-emitting. Further simulation shows that the band alignment of SiAs2/GeAs2vdWH can be tuned back and forth between type II and type I by gate voltage in a single field-effect transistor for multiple functional applications. These results may be useful for applications of the SiAs2/GeAs2heterostructure in future electronic and optoelectronic devices.

Dihydroartemisinin improves hypercholesterolemia in ovariectomized mice via enhancing vectorial transport of cholesterol and bile acids from blood to bile.

The increase of concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the serum of postmenopausal women is the important risk factor of the high morbidity of cardiovascular diseases of old women worldwide. To test the anti-hypercholesterolemia function of dihydroartemisinin (DHA) in postmenopausal women, ovariectomized (OVX) mice were generated, and DHA were administrated to OVX mice for 4 weeks. The blood and liver tissues were collected for biochemical and histological tests respectively. The mRNA and protein expression levels of genes related to metabolism and transport of cholesterol, bile acid and fatty acid in the liver or ileum were checked through qPCR and western blot. DHA could significantly reduce the high concentrations of TC and LDL-C in the serum and the lipid accumulation in the liver of ovariectomized mice. The expression of ABCG5/8 was reduced in liver of OVX mice, and DHA could up-regulate the expression of them. Genes of transport proteins for bile salt transport from blood to bile, including Slc10a1, Slco1b2 and Abcb11, were also significantly up-regulated by DHA. DHA also down-regulated the expression of Slc10a2 in the ileum of OVX mice to reduce the absorption of bile salts. Genes required for fatty acid synthesis and uptake, such as Fasn and CD36, were reduced in the liver of OVX mice, and DHA administration could significantly up-regulate the expression of them. These results demonstrated that DHA could improve hypercholesterolemia in OVX mice through enhancing the vectorial transport of cholesterol and bile acid from blood to bile.

BiOCl/group-IV Xene bilayer heterojunctions: stability and electronic and photocatalytic properties.

Vertical van der Waals heterojunctions (HJs) composed of a photocatalytic star material BiOCl monolayer and group-IV Xene monolayer (silicene, germanene etc.) were studied by using first-principles calculations. Formation energy analysis and molecular dynamics simulation show that the BiOCl/Xene bilayer HJs can exist stably up to room temperature. Owing to evident charge redistribution and accumulation occurring between the bilayers, electron-hole puddles form and charge carrier transfer and separation occur in the HJs, which are beneficial to the improvement of photocatalytic performance. The HJ energy bands maintain the Dirac cones with almost linear dispersion curves, suggesting low effective mass and high mobility of carriers, and can be effectively tuned by strain. Our results show that the BiOCl/Xene bilayer HJs with high separation efficiency and high mobility of carriers and strain-adjustable bandgaps provide varieties in the functionalities of 2D van der Waals HJs and show great potentials in photocatalytic applications.

Histone Modifications Regulate the Developmental Expression of Human Hepatic UDP-Glucuronosyltransferase 1A1.

Human UDP-glucuronosyltransferase 1A1 (UGT1A1) is a unique enzyme involved in bilirubin conjugation. We previously characterized the hepatic expression of transcription factors affecting UGT1A1 expression during development. Accordingly, in this study, we characterized the ontogenetic expression of hepatic UGT1A1 from the perspective of epigenetic regulation. We observed significant histone-3-lysine-4 dimethylation (H3K4me2) enrichment in the adult liver and histone-3-lysine-27 trimethylation (H3K27me3) enrichment in the fetal liver, indicating that dynamic alterations of histone methylation were associated with ontogenetic UGT1A1 expression. We further showed that the transcription factor hepatocyte nuclear factor 1α (HNF1A) affects histone modifications around the UGT1A1 locus. In particular, we demonstrated that by recruiting HNF1A the cofactors mixed-lineage leukemia 1, the transcriptional coactivator p300, and nuclear receptor coactivator 6 aggregate at the UGT1A1 promoter, thereby regulating histone modifications and subsequent UGT1A1 expression. In this study, we proposed new ideas for the developmental regulation of metabolic enzymes via histone modifications, and our findings will potentially contribute to the development of age-specific therapies.

Hepatic expression of transcription factors affecting developmental regulation of UGT1A1 in the Han Chinese population.

PURPOSE: Complete or partial inactivity of UGT1A1, the unique enzyme responsible for bilirubin glucuronidation, is commonly associated with hyperbilirubinemia. We investigated the dynamic expression of UGT1A1, and that of the transcription factors (TFs) involved in its developmental regulation, during human hepatic growth in Han Chinese individuals. METHODS: Eighty-eight prenatal, pediatric, and adult liver samples were obtained from Han Chinese individuals. Quantitative real-time polymerase chain reaction was used to evaluate mRNA expression of UGT1A1 and TFs including PXR, CAR, HNF1A, HNF4A, PPARA, etc. UGT1A1 protein levels and metabolic activity were determined by western blotting and high-performance liquid chromatography. Direct sequencing was employed to genotype UGT1A1*6 (211G˃A) and UGT1A1*28 (TA6˃TA7) polymorphisms. RESULTS: UGT1A1 expression was minimal in prenatal samples, but significantly elevated during pediatric and adult stages. mRNA and protein levels and metabolic activity were prominently increased (120-, 20-, and 10-fold, respectively) in pediatric and adult livers compared to prenatal samples. Furthermore, expression did not differ appreciably between pediatric and adult periods. Dynamic expression of TFs, including PXR, CAR, HNF1A, HNF4A, and PPARA, was consistent with UGT1A1 levels at each developmental stage. A pronounced correlation between expression of these TFs and that of UGT1A1 (P < 0.001) was observed. Moreover, UGT1A1*6 and UGT1A1*28 polymorphisms reduced levels of UGT1A1 by up to 40-60 %. CONCLUSIONS: Hepatic expression of transcription factors is associated with developmental regulation of UGT1A1 in the Han Chinese population. Moreover, UGT1A1 polymorphisms are associated with reduced expression of UGT1A1 mRNA and protein, as well as enzyme activity.

Comparative transcriptome analysis of fruiting body and sporulating mycelia of Villosiclava virens reveals genes with putative functions in sexual reproduction.

Sexual reproduction of heterothallic clavicipitaceous fungus Villosiclava virens (anamorph: Ustilaginoidea virens) generates ascospores, which is considered as primary infection source of rice false smut disease. However, little is known about the molecular underpinnings of sexual reproduction in V. virens. In this study, transcriptomes of V. virens in fruiting body (FB) and sporulating mycelia (SM) were compared using Illumina paired-end sequencing technology. A total of 33,384,588 and 23,765,275 clean reads of FB and SM transcriptome profiles could be used to map cDNA of V. virens, respectively. We evaluated the gene expression variations between FB and SM, a total of 488 genes therein were significantly higher expressed in FB than SM, and 342 genes were significantly higher expressed genes in SM than FB. These differentially expressed genes were annotated using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases. Several genes were found to specifically function in sexual reproduction, involving in mating type, pheromone synthesis, signaling transduction, transcription factors, and meiosis; additionally, a few of genes were presumed to function in conidia sporulation and infection. Comparative transcriptome analysis of V. virens during FB and SM provided an overview of gene expression profiles at the transcriptional level and provided hints to better understand the molecular mechanisms of sexual development. Additionally, the data presented here also proved benefit for mining of essential genes contributing to sexual conidiation and infection.

Effects of UGT1A1*6, UGT1A1*28, and ABCB1-3435C>T polymorphisms on irinotecan induced toxicity in Chinese cancer patients.

OBJECT: The aim of this study was to investigate whether UGT1A1*6/*28 or ABCB1-3435C>T polymorphisms affect irinotecan-induced severe diarrhea and neutropenia in Chinese cancer patients. METHODS: A total of 157 cancer patients was enrolled in this study and the genotypes of UGT1A1*6/*28 and ABCB1-3435C>T polymorphisms were analyzed by PCRSanger sequence. The relationship between UGT1A1*6/*28 and ABCB1-3435C>T polymorphisms and irinotecan induced severe diarrhea and neutropenia were analyzed. RESULTS AND CONCLUSION: UGT1A1*6 and UGT1A1*28 polymorphisms were associated with severe neutropenia (p = 0.025, p = 0.022, respectively) but not diarrhea (p = 0.343, p = 0.185, respectively), and ABCB1- 3435C>T polymorphism was not associated with irinotecan induced severe toxicities (p = 0.457, p = 0.161, respectively).

Achieving highly efficient 2D SnC monolayer-based photocatalyst for water splitting via a synergistic strategy of S-scheme heterostructure construction and silicon doping.

Owing to its stable graphene-like honeycomb structure, suitable band gap, and nontoxicity, SnC monolayer (ML) has attracted increasing attention in photocatalytic applications. One pertinent obstacle inherent to SnC ML-based photocatalysts has been the high energy barrier in hydrogen evolution reaction (HER) that always requires external energy input and/or strongly acidic conditions. Herein, we propose a two-dimensional (2D) SnC/ZrS2 van der Waals heterostructure (vdWHS) for highly efficient photocatalytic water splitting using first-principles calculations. The results show that the pristine vdWHS is an S-scheme heterostructure that works in acidic conditions for water splitting owing to the high energy barrier in HER. Notably, detailed further investigations show that doping Si in the SnC ML of the vdWHS can solve this high barrier problem, leading to a high-performance low-cost photocatalyst. Our work offers a convenient strategy to solve the notorious high barrier problem in HER that often troubles the SnC ML and other 2D materials such as transition metal dichalcogenide MLs for the design and fabrication of highly efficient photocatalysts.

Sodium sulphate ameliorates hypercholesterolemia via the upregulation of Cyp7a1 in hepatocytes and alleviates hepatic insulin resistance via the downregulation of Trib3 in mice with high cholesterol diets.

Amelioration of hypercholesterolemia is essential for the treatment of atherosclerotic cardiovascular disease. Sodium sulphate is the effective component of mirabilite, which has been used in traditional Chinese medicine for the treatment of various diseases. In the present study, C57BL/6 mice were fed with a high-cholesterol diet (HCD) for 7 weeks and were treated with sodium sulphate in the last three of those weeks. Sodium sulphate significantly reduced the total cholesterol level and the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio in the serum of mice fed the HCD. In addition, cytochrome P450 7a1 and 39a1 were significantly upregulated in the livers of mice treated with sodium sulphate. Furthermore, tribbles pseudokinase 3 expression was significantly increased in the livers of mice fed the HCD, but was significantly reduced by sodium sulphate treatment. In terms of the insulin signaling pathway, the ratio of phosphorylated AKT to total AKT in the livers of mice fed the HCD was significantly lower compared with that of control mice fed a normal diet, but was significantly increased by sodium sulphate treatment. Sodium sulphate treatment also reduced the levels of fibroblast growth factor (FGF)15 in the ileum and inhibited the FGF15/FGF receptor 4-Klotho ß/c-Jun N-terminal kinase/c-Jun signaling pathway in the livers of mice fed the HCD. In addition, sodium sulphate changed the composition of the gut microbiota of mice fed the HCD. In conclusion, sodium sulphate may mitigate hypercholesterolemia and hepatic insulin resistance in mice fed an HCD.

Mn-X (X = F, Cl, Br, I) Co-Doped GeSe Monolayers: Stabilities and Electronic, Spintronic and Optical Properties.

GeSe monolayer (ML) has recently attracted much interest due to its unique structure and excellent physical properties that can be effectively tuned through single doping of various elements. However, the co-doping effects on GeSe ML are rarely studied. In this study, the structures and physical properties of Mn-X (X = F, Cl, Br, I) co-doped GeSe MLs are investigated by using first-principle calculations. The formation energy and phonon disspersion analyses reveal the stability of Mn-Cl and Mn-Br co-doped GeSe MLs and instability of Mn-F and Mn-I co-doped GeSe MLs. The stable Mn-X (X = Cl, Br) co-doped GeSe MLs exhibit complex bonding structures with respect to Mn-doped GeSe ML. More importantly, Mn-Cl and Mn-Br co-doping can not only tune magnetic properties, but also change the electronic properties of GeSe MLs, which makes Mn-X co-doped GeSe MLs indirect band semiconductors with anisotropic large carrier mobility and asymmetric spin-dependent band structures. Furthermore, Mn-X (X = Cl, Br) co-doped GeSe MLs show weakened in-plane optical absorption and reflection in the visible band. Our results may be useful for electronic, spintronic and optical applications based on Mn-X co-doped GeSe MLs.

Synthesis and high-temperature ferromagnetism of Fe-doped SiGe diluted magnetic semiconductor thin films.

Fe-doped SiGe (Si0.25Ge0.75:Fex, x = 0.01, 0.025, and 0.05) thin films were prepared by radio frequency magnetron sputtering and subsequent rapid thermal annealing on a Ge (100) substrate and their structural, magnetic and magneto-transport properties were investigated. Structural characterization using AFM, SEM, XRD, and HRTEM shows that the obtained samples are polycrystalline and their lattice constants increase with the Fe concentration. Analysis of their electronic and spintronic states using XPS and XMCD reveals that Fe dopants mainly exist as substitutional Fe2+ ions in the SiGe lattice, providing both local magnetic moments and hole carriers. Furthermore, magnetization measurements indicate that all the samples exhibit ferromagnetism, and their Curie temperature increases with the Fe concentration up to 294 K; meanwhile, magneto-transport measurements reveal a giant magnetoresistance (GMR) effect of over 800% and an anomalous Hall effect (AHE), as well as semiconducting behaviors, in the samples. Further analysis suggests that the ferromagnetism comes from a hole-mediated process originating from substitutional Fe dopants in the SiGe matrix and this is enhanced by the tensile strain in the films. The synthesis and high-temperature ferromagnetism of Fe-doped SiGe thin films may play a key role in group IV-based spintronic applications.

The intratumor mycobiome promotes lung cancer progression via myeloid-derived suppressor cells.

Although polymorphic microbiomes have emerged as hallmarks of cancer, far less is known about the role of the intratumor mycobiome as living microorganisms in cancer progression. Here, using fungi-enriched DNA extraction and deep shotgun metagenomic sequencing, we have identified enriched tumor-resident Aspergillus sydowii in patients with lung adenocarcinoma (LUAD). By three different syngeneic lung cancer mice models, we find that A. sydowii promotes lung tumor progression via IL-1ß-mediated expansion and activation of MDSCs, resulting in suppressed activity of cytotoxic T lymphocyte cells and accumulation of PD-1+ CD8+ T cells. This is mediated by IL-1ß secretion via ß-glucan/Dectin-1/CARD9 pathway. Analysis of human samples confirms that enriched A. sydowii is associated with immunosuppression and poor patient outcome. Our findings suggest that intratumor mycobiome, albeit at low biomass, promotes lung cancer progression and could be targeted at the strain level to improve patients with LUAD outcome.

Clinical Observation of Alternative Wave Electroacupuncture Combined with Lee's Naprapathy in Treating Knee Osteoarthritis (Blood Stasis due to Qi Stagnation).

Objective: We aim to explore the clinical therapeutic effect of alternative wave electroacupuncture combined with Lee's naprapathy therapy on knee osteoarthritis (KOA) (blood stasis due to qi stagnation). Method: 122 patients with KOA treated in our hospital from January 2018 to October 2021 were randomly grouped into a combined group (n = 61) and a control group (n = 61). The combined group was treated with alternative wave electroacupuncture combined with Lee's naprapathy, while the control group was treated with alternative wave electroacupuncture alone. Clinical efficacy of the two groups was observed. The Visual Analogue Scale (VAS), Lysholm Scale, Indexes of Severity for Osteoarthritis (ISOA), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were compared before and after treatment, followed up for 3 months and 6 months. The adverse reactions of the two groups were observed. Result: The overall response rate of the combined group (96.72%) was higher than that of the control group (81.97%), and the difference was statistically significant (P < 0.05). After treatment and follow-up for 3 months and 6 months, the Lysholm score of the combined group was higher than that of the control group, while the VAS, ISOA, and WOMAC scores were lower than those of the control group, and the difference between the two was statistically significant (P < 0.05). There were no serious adverse reactions in both groups (P > 0.05). Conclusion: The alternative wave electroacupuncture combined with Lee's naprapathy is effective and safe in treating KOA (blood stasis due to qi stagnation).

Loperamide induces excessive accumulation of bile acids in the liver of mice with different diets.

Loperamide is a non-prescription medicine normally used for the treatment of diarrhea. The abuse and misuse of loperamide have been demonstrated to have toxic effects on heart. It is still unclear whether the abuse of loperamide can cause hepatic toxicity. The C57BL/6 mice fed with high fat diet (HFD) or normal food diet (NFD) were administrated with loperamide (5 mg/kg/day) intragastrically once a day for two weeks, after that, the feces, blood, hepatic tissues and intestines were harvested for biochemical and histological detection, and the expression of genes related with lipid metabolism was further checked by qRT-PCR (quantitative real-time polymerase chain reaction) and Western blot. The administration of loperamide caused the constipation in mice fed with NFD or HFD. The content of bile acids was significantly reduced in the feces of mice treated with loperamide, but the content of bile acids was significantly increased in the liver of these mice. The results of H&E staining showed that loperamide administration caused the damage of hepatic tissues, especially for mice fed with HFD. The expression of genes related with the biosynthesis of cholesterol and bile acids, including Hmgcr, Lss, Sqle, Fdps, Idi1, Mvk, Cyp7a1 and Ch25h, was all upregulated in the liver of mice treated with loperamide. Conversely, the expression of Abcg5, Abcb11 and Abcc2, which encode genes for transporting cholesterols and bile acids from hepatocytes to bile respectively, was downregulated in the liver of mice treated with loperamide. At the same time, the expression of Fabp6 and Slc51a, which transport bile acids from intestinal lumen into the blood, was all upregulated in the ileum of mice treated with loperamide. The expression of SHP, which inhibits the transcription of Cyp7a1 in hepatocytes, was significantly downregulated in the hepatic tissues of mice treated with loperamide. These results demonstrated that administration of loperamide caused excessive accumulation of bile acids in the liver of mice via upregulating genes for biosynthesis of cholesterol and bile acid and downregulating genes for discharging cholesterol and bile acids in hepatocytes of mice, moreover, the downregulation of SHP in hepatic tissues might be one of the mechanisms of it, especially for mice fed with HFD.

EpCAM Is Essential to Maintaining the Immune Homeostasis of Intestines via Keeping the Expression of pIgR in the Intestinal Epithelium of Mice.

EpCAM deficiency causes congenital tufting enteropathy (CTE) which is considered as one kinds of very early onset inflammatory bowel disease (IBD). However, functions of EpCAM on regulating the immunity of intestines are still unclear. To study the mechanism of EpCAM on maintaining the intestinal immune homeostasis, the intestines of WT and EpCAM-/- mice at E18.5, P0 and P3 stages were collected for morphological, histological and gene expression tests. Serious inflammation was detected in the small intestines of P3 EpCAM-/- mice. Compared to WT mice, genes related to inflammatory factors and immunity cells, including TNFα, IL-1ß, IL-6, IL-8rb, MIP2, MCP1, Ly6d and Ly6g, were all significantly upregulated and the expression of intestinal abundance matrix metalloproteinases (MMPs) was also significantly increased in the intestines of EpCAM-/- mice at E18.5, P0 and P3 stages. Signals of p38, ERK1/2 and JNK were hyper-activated in the intestines of EpCAM-/- mice. The expression of pIgR was significantly decreased and the expression and activation of transcriptional factors which promote the expression of pIgR were also reduced in the intestines of EpCAM-/- mice compared to WT controls. In conclusion, EpCAM could maintain the immune homeostasis of intestines via keeping the expression of pIgR in the intestinal epithelium.

Ginsenoside Rb1 improves intestinal aging via regulating the expression of sirtuins in the intestinal epithelium and modulating the gut microbiota of mice.

Intestinal aging seriously affects the absorption of nutrients of the aged people. Ginsenoside Rb1 (GRb1) which has multiple functions on treating gastrointestinal disorders is one of the important ingredients from Ginseng, the famous herb in tradition Chinese medicine. However, it is still unclear if GRb1 could improve intestinal aging. To investigate the function and mechanism of GRb1 on improving intestinal aging, GRb1 was administrated to 104-week-old C57BL/6 mice for 6 weeks. The jejunum, colon and feces were collected for morphology, histology, gene expression and gut microbiota tests using H&E staining, X-gal staining, qPCR, Western blot, immunofluorescence staining, and 16S rDNA sequencing technologies. The numbers of cells reduced and the accumulation of senescent cells increased in the intestinal crypts of old mice, and administration of GRb1 could reverse them. The protein levels of CLDN 2, 3, 7, and 15 were all decreased in the jejunum of old mice, and administration of GRb1 could significantly increase them. The expression levels of Tert, Lgr5, mKi67, and c-Myc were all significantly reduced in the small intestines of old mice, and GRb1 significantly increased them at transcriptional or posttranscriptional levels. The protein levels of SIRT1, SIRT3, and SIRT6 were all reduced in the jejunum of old mice, and GRb1 could increase the protein levels of them. The 16S rDNA sequencing results demonstrated the dysbiosis of the gut microbiota of old mice, and GRb1 changed the composition and functions of the gut microbiota in the old mice. In conclusion, GRb1 could improve the intestinal aging via regulating the expression of Sirtuins family and modulating the gut microbiota in the aged mice.

Quercetin protects islet ß-cells from oxidation-induced apoptosis via Sirt3 in T2DM.

OBJECTIVES: Sirt3 may regulate ROS production and might be involved in ß-cell apoptosis, which plays an important role in the progression of type 2 diabetes mellitus (T2DM). Quercetin is a potent anti-oxidative bioflavonoid, but its effects on T2DM remain to be explored. This study aimed to investigate the effects of quercetin on ß-cell apoptosis and explore its mechanisms. MATERIALS AND METHODS: The effects of quercetin were conducted on db/db mice and INS1 cells. Fasting blood glucose was determined by the colorimetric method, serum insulin was measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, Sirt3 in INS1 cells was knocked down by plasmid transfection. The antioxidant proteins (SOD2 and CAT), apoptosis proteins (cleaved Caspase-3, Bax, and BCL-2), and Sirt3 protein in pancreases and INS1 cells were determined by western blotting. RESULTS: When INS1 cells and diabetic mice were treated with quercetin, the levels of SOD2, CAT, and Sirt3 proteins were increased, the levels of cleaved Caspase-3 and the ratio of Bax to BCL-2 were decreased at different degrees, along with reduced blood glucose levels and elevated insulin levels in diabetic mice. When Sirt3 was knocked down in INS1 cells, increase of two antioxidants and decrease of cell apoptosis generated by quercetin could not occur. CONCLUSION: Quercetin protected islet ß-cells from oxidation-induced apoptosis via Sirt3 in T2DM, which would be beneficial to develop new strategies for preventing ß-cell failure in T2DM.

Cigarette smoking exposure breaks the homeostasis of cholesterol and bile acid metabolism and induces gut microbiota dysbiosis in mice with different diets.

Exposure of humans to second-hand smoking (SHS) increases glucose and lipid metabolic disorders. The link of hepatic metabolic dysfunction to environmental cigarette smoking has been noticed, but the related mechanism is still unclear. C57BL/6 mice with normal food diet (NFD) or high fat diet (HFD) were exposed to 15 min cigarette smoking twice a day in a 0.038 m3 box for 4 weeks, and the concentration of nicotine in the air of the box was 21.05 mg/m3 during the smoke exposure. Liver tissues and serum were collected for gene expression and biochemistry test. The fecal microbiota was also checked through 16S rDNA sequences. Cigarette smoking exposure increased the accumulation of total cholesterol (TC) in liver, and the expression of cholesterol synthesis-related genes was upregulated. The expression of CYP8B1 protein was significantly down-regulated, and the ratio of cholic acid (CA) to chenodeoxycholic acid (CDCA) was significantly reduced in the liver of mice exposed to cigarette smoking especially for HFD group. Cigarette smoking exposure caused insulin resistance in the liver of mice with HFD. The composition of the gut microbiota was altered with the exposure of cigarette smoking, and the change of the distribution of primary bile acids might be one of the reasons. It was concluded that cigarette smoking would break the homeostasis of cholesterol and bile acids metabolism and changed the composition of gut microbiota. Our discoveries confirmed that smoking bans are important for the public health.

Ovariectomy Impaired Hepatic Glucose and Lipid Homeostasis and Altered the Gut Microbiota in Mice With Different Diets.

The lower incidence of metabolic diseases of women than men and the increasing morbidity of metabolic disorders of menopausal women indicated that hormones produced by ovaries may affect homeostasis of glucose and lipid metabolism, but the underlying mechanisms remain unclear. To explore the functions of ovaries on regulating glucose and lipid metabolism in females, 8 weeks old C57BL/6 mice were preformed ovariectomy and administrated with normal food diet (NFD) or high fat diet (HFD). Six weeks after ovariectomy, blood biochemical indexes were tested and the morphology and histology of livers were checked. The expression levels of genes related to glucose and lipid metabolism in liver were detected through transcriptome analysis, qPCR and western blot assays. 16S rDNA sequence was conducted to analyze the gut microbiota of mice with ovariectomy and different diets. The serum total cholesterol (TC) was significantly increased in ovariectomized (OVX) mice fed with NFD (OVXN), and serum low density lipoprotein-cholesterol (LDL-C) was significantly increased in both OVXN mice and OVX mice fed with HFD (OVXH). The excessive glycogen storage was found in livers of 37.5% mice from OVXN group, and lipid accumulation was detected in livers of the other 62.5% OVXN mice. The OVXN group was further divided into OVXN-Gly and OVXN-TG subgroups depending on histological results of the liver. Lipid drops in livers of OVXH mice were more and larger than other groups. The expression level of genes related with lipogenesis was significantly increased and the expression level of genes related with ß-oxidation was significantly downregulated in the liver of OVXN mice. Ovariectomy also caused the dysbiosis of intestinal flora of OVXN and OVXH mice. These results demonstrated that hormones generated by ovaries played important roles in regulating hepatic glucose and lipid metabolism and communicating with the gut microbiota in females.