PMID: 

EXCLI J. 2019 ;18:1019-1036. Epub 2019 Nov 5. PMID: 31762726

Abstract Title: 

Transgenerational influence of parental morphine exposure on pain perception, anxiety-like behavior and passive avoidance memory among male and female offspring of Wistar rats.

Abstract: 

Accumulating evidence suggests that epigenetic mechanisms play an important role in the formation and maintenance of memory within the brain. Moreover, the effect of parental drug-exposure before gestation on behavioral state of offspring has been little studied. The main objective of the current study is to evaluate the effect of parental morphine exposure on avoidance memory, morphine preference and anxiety-like behavior of offspring. The total of 32 males and 32 females were used for mating. The animals were treated with morphine. The offspring according to their parental morphine treatment was divided into four groups (n=16) including paternally treated, maternally treated, both of parents treated and naïve animals. The pain perception, anxiety-like behavior, and avoidance memory were evaluated in the offspring. In the current study, the total of 256 offspring was used for the experiments (4 tasks × 4 groups of offspring × 8 female offspring × 8 male offspring). The finding revealed that the avoidance memory and visceral pain were reduced significantly in male and female offspring with at least one morphine-treated parent. Moreover, anxiety-like behavior was reduced significantly in the male offspring with at least one morphine-treated parent. While anxiety-like behavior was increased significantly in female offspring that were treated by morphine either maternally or both of parents. The data revealed that the endogenous opioid system may be altered in the offspring of morphine-treated parent(s), and epigenetic role could be important. However, analysis of variance signified the important role of maternal inheritance.

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PMID: 

Chemosphere. 2019 Dec 2 ;244:125527. Epub 2019 Dec 2. PMID: 31816550

Abstract Title: 

Developmental exposure to Pbinduces transgenerational changes to zebrafish brain transcriptome.

Abstract: 

Lead (Pb) is a major public health hazard for urban children, with profound and well-characterized developmental and behavioral implications across the lifespan. The ability of early Pbexposure to induce epigenetic changes is well-established, suggesting that Pb-induced neurobehavioral deficits may be heritable across generations. Understanding the long-term and multigenerational repercussions of lead exposure is crucial for clarifying both the genotypic alterations behind these behavioral outcomes and the potential mechanism of heritability. To study this, zebrafish (Danio rerio) embryos (

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PMID: 

Exp Mol Med. 2020 Jan 24. Epub 2020 Jan 24. PMID: 31974504

Abstract Title: 

Preterm birth is associated with epigenetic programming of transgenerational hypertension in mice.

Abstract: 

Renal and cardiovascular complications of prematurity are well established, notably the development of hypertension in adulthood. However, the underlying molecular mechanisms remain poorly understood. Our objective was to investigate the impact of prematurity on the ontogenesis of renal corticosteroid pathways, to evaluate its implication in perinatal renal complications and in the emergence of hypertension in adulthood. Swiss CD1 pregnant mice were injected with lipopolysaccharides at 18 days of gestation (E18) to induce prematurity at E18.5. Pups were sacrificed at birth, 7 days and 6 months of life. Second (F2) and third (F3) generations, established by mating prematurely born adult females with wild-type males, were also analyzed. Former preterm males developed hypertension at M6 (P 

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PMID: 

Free Radic Biol Med. 2019 01 ;130:512-527. Epub 2018 Nov 15. PMID: 30447351

Abstract Title: 

N-acetylcysteine ameliorates cisplatin-induced renal senescence and renal interstitial fibrosis through sirtuin1 activation and p53 deacetylation.

Abstract: 

The mechanism underlying the development of chronic kidney disease (CKD) after acute kidney injury (AKI) remains unclear. Maladaptive repair has been considered an important mechanism of CKD post AKI. Renal tubular cells under maladaptive repair have characteristics of premature senescence. These premature senescent cells can generate profibrotic factors that promote organ fibrosis. The purpose of this study was to investigate whether cisplatin induces premature renal senescence and the role of premature renal senescence in the progression of CKD post AKI. As oxidative stress is a major cause of senescence, we further evaluated whether antioxidant therapy could protect renal tubular cells from cisplatin-induced premature senescence and retard the progression of CKD post AKI. The molecular mechanism of this protection was also investigated. We found that cisplatin induced premature renal senescence in vitro and in vivo. In a multiple-cisplatin-treatment murine model, renal interstitial fibrosis was accompanied by premature renal senescence. N-acetylcysteine (NAC), an antioxidant, attenuated premature senescence and decreased renal fibrosis, and its effects were dependent on sirtuin1 (SIRT1) activation and p53 deacetylation. These results indicate that cisplatin can induce premature renal senescence, which is associated with the development of CKD post cisplatin-induced AKI. SIRT1 activation and p53 deacetylation might be identified as potential targets for attenuating premature renal senescence and retarding the progression of CKD post AKI.

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PMID: 

Front Aging Neurosci. 2018 ;10:399. Epub 2018 Dec 6. PMID: 30574085

Abstract Title: 

N-Acetylcysteine Prevents the Spatial Memory Deficits and the Redox-Dependent RyR2 Decrease Displayed by an Alzheimer's Disease Rat Model.

Abstract: 

We have previously reported that primary hippocampal neurons exposed to synaptotoxic amyloid beta oligomers (AβOs), which are likely causative agents of Alzheimer's disease (AD), exhibit abnormal Casignals, mitochondrial dysfunction and defective structural plasticity. Additionally, AβOs-exposed neurons exhibit a decrease in the protein content of type-2 ryanodine receptor (RyR2) Cachannels, which exert critical roles in hippocampal synaptic plasticity and spatial memory processes. The antioxidant N-acetylcysteine (NAC) prevents these deleterious effects of AβOs. The main contribution of the present work is to show that AβOs injections directly into the hippocampus, by engaging oxidation-mediated reversible pathways significantly decreased RyR2 protein content but increased single RyR2 channel activation by Caand caused considerable spatial memory deficits. AβOs injections into the CA3 hippocampal region impaired rat performance in the Oasis maze spatial memory task, decreased hippocampal glutathione levels and overall content of plasticity-related proteins (c-Fos, Arc, and RyR2) and increased ERK1/2 phosphorylation. In contrast, in hippocampus-derivedmitochondria-associated membranes (MAM) AβOs injections increased RyR2 levels. Rats fed with NAC for 3-weeks prior to AβOs injections displayed comparable redox potential, RyR2 and Arc protein contents, similar ERK1/2 phosphorylation and RyR2 single channel activation by Caas saline-injected (control) rats. NAC-fed rats subsequently injected with AβOs displayed the same behavior in the spatial memory task as control rats. Based on the presentresults, we propose that redox-sensitive neuronal RyR2 channels partake in the mechanism underlying AβOs-induced memory disruption in rodents.

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PMID: 

J Biochem. 2020 Jan 21. Epub 2020 Jan 21. PMID: 31960917

Abstract Title: 

Quercetin attenuates high glucose induced injury in human retinal pigment epithelial cell line ARPE-19 by up-regulation of miR-29b.

Abstract: 

Quercetin is a kind of distinctive bioactive flavonoid that has potent anti-oxidant, anti-inflammatory and anti-diabetic properties. The present paper was designed to check the effect of quercetin on diabetic retinopathy. ARPE-19 cells were pre-treated with quercetin and then stimulated by high glucose. Cell damage was evaluated by CCK-8 assay, flow cytometer, qRT-PCR, ELISA, DCFH-DA probe and western blot. The association between quercetin and miR-29b expression as well as the downstream pathways was studied by qRT-PCR and western blot. Pre-treating ARPE-19 cells with quercetin clearly attenuated high glucose-induced viability loss, apoptosis, MCP-1 and IL-6 overproduction, and ROS generation. Quercetin down-regulated p53, Bax and cleaved-caspase-3 expression, while up-regulated CyclinD1, CDK4 and Bcl-2. MiR-29b was low-expressed in high glucose-treated cell, but quercetin elevated its expression. Moreover, the protective action of quercetin towards ARPE-19 cells was attenuated when miR-29b was suppressed. Also, quercetin promoted PTEN/AKT pathway while inhibited NF-κB pathway via a miR-29b-dependent way. These data illustrated quercetin possibly possess the anti-diabetic retinopathy potential, as quercetin clearly attenuated high glucose-evoked damage in ARPE-19 cells. The protective action of quercetin may due to its regulation on miR-29b expression as wellas PTEN/AKT and NF-κB pathways.

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PMID: 

Biochem Biophys Res Commun. 2020 Jan 18. Epub 2020 Jan 18. PMID: 31964531

Abstract Title: 

Quercetin pretreatment enhances the radiosensitivity of colon cancer cells by targeting Notch-1 pathway.

Abstract: 

Cancer stem-like cells are rare immortal cells within tumor, which are thought to play important roles in ionizing radiation (IR) therapy-resistance. Quercetin is a natural flavonoid with potential anti-cancer properties without significant cytotoxicity in normal tissues. In this study, we demonstrated that quercetin-IR combination treatment exhibited more dramatic anti-cancer effect than either quercetin or IR treatment alone via targeting colon cancer stem cells (CSCs) and inhibiting the Notch-1 signaling. These effects were further verified by in vivo studies which showed remarkable decrease of the CSCs markers and the expression of Notch-1 signaling proteins in human colon cancer xenografts in nude mice. Co-treatment with quercetin and low dose of radiation significantly reduced the expressions of all five proteins of γ-secretase complexin HT-29 and DLD-1 cells. In addition, ectopic expression of the Notch intracellular domain (NICD) partly reversed the inhibition effects by the combination therapy. In conclusion, our results indicated that the combination of quercetin (20 μM) and IR (5Gy) might be a promising therapeutic strategy for colon cancer treatment by targeting colon cancer stem-like cells and inhibiting the Notch-1 signaling. In future studies, we intend to further explore the potential therapeutic efficacy of the quercetin-radiation combination treatment in clinical trials.

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PMID: 

Int J Biol Macromol. 2019 Nov 9. Epub 2019 Nov 9. PMID: 31712153

Abstract Title: 

Intake of Ganoderma lucidum polysaccharides reverses the disturbed gut microbiota and metabolism in type 2 diabetic rats.

Abstract: 

Ganoderma lucidum polysaccharides (GLP), a kind of medicinal mushrooms, were widely used in southeastern countries with putative anti-diabetic effects. In order to unravel the underlying mechanism of its anti-diabetic effect, this study examines the effects of GLP on gut microbiota composition and functions in type 2 diabetes mellitus (T2DM) status. In this study, the effects of GLP on the gut microbiota and fecal metabolites in high-fat diet and streptozotocin-induced T2DM rats were examined by 16S rDNA sequencing andH NMR profiling. As a result, administration of GLP led to significant decreases in the levels of fasting blood glucose and insulin. Moreover, GLP treatment reduced the abundance of harmful bacteria, such as Aerococcus, Ruminococcus, Corynebactrium and Proteus, and increased the level of Blautia, Dehalobacterium, Parabacteroides and Bacteroides. The PICRUSt analysis indicated that GLP could restore the disturbed amino acids metabolism, carbohydrates metabolism, inflammatory substances metabolism and nucleic acid metabolism of gut bacterial community in T2DM rats and most metabolic changes observed by metabolomics analysis were consistent with these consequences. Taken collectively, GLP can restore the disordered gut microbiota of T2DM rats to a normal level and modify metabolites of the host to realize its antidiabetic effects.

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PMID: 

Anticancer Agents Med Chem. 2019 Oct 14. Epub 2019 Oct 14. PMID: 31749435

Abstract Title: 

Anti-Cancer Effects of a Neutral Triterpene Fraction from Ganoderma lucidum and its Active Constituents on SW620 Human Colorectal Cancer Cells.

Abstract: 

BACKGROUND: Ganoderma lucidum (Leyss. ex Fr.) Karst. (G. lucidum, GL) belongs to the family of Ganodermataceae (Basidiomycetes), and possesses activities including antitumor, antimicrobial, antiviral, and antiaging activities. Triterpenoids are typical chemical constituents in G. lucidum, and play an important role in the anti-cancer effects. According to the substituent group at carbon 26 position, GL total triterpenes fraction can be divided into two types, a Neutral Triterpene Fraction (NTF) and an Acidic Triterpene Fraction (ATF). The anti-cancer effects of total triterpenes fraction and total acidic triterpene fraction extracted from G. lucidum have been widely known in vivo and in vitro, whereas few have focused on total neutral triterpene fraction.OBJECTIVE: The aim of this study was to evaluate the anti-cancer effects of NTF extracted from G. lucidum in vitro and in vivo and explore its anti-cancer active constituents on SW620 human colorectal cancer cells.METHODS: NTF and ATF were extracted from the dry fruiting body of G. lucidum by impregnation method with 90% ethanol, and further isolated by using alkaline extraction and acid precipitation method. The total triterpenoids content of NTF and ATF were determined by using ultraviolet-visible spectrophotometry. The cytotoxic effects on human colon cancer cells SW480, SW620, SW1116, and mouse embryonic fibroblast cell line NIH3T3 were evaluated by using MTT method. Anti-cancer activity of NTF in vivo was evaluated in Athymic nude mice against SW620 cells. An activity-guided separation and purification process was used to identify the anti-cancer active constituents of NTF by column and preparative high performance liquid chromatography. Structures of the constituents were confirmed by 1H-NMR, 13C-NMR and MS. Protein expression was performed by Western blotting.RESULTS: The percentage of total triterpenoids was 46.7% and 57.6% in ATF and NTF, respectively. Both fractions could reduce the viability of SW480, SW620, and SW1116 cells in vitro, whereby NTF exhibited a stronger effect than ATF. NTF markedly inhibited the growth of SW620 cell xenografts in mice at doses (250, 500mg/kg) during the treatment. Furthermore, a new garnoderic alcohol, named as ethyl ganoderate A and eight known ganoderic alcohols were isolated and identified from NTF by a bioassay-guided separation process. All of these compounds possessed anti-cancer activities against SW620 cells in vitro. As a representative ganoderma alcohol, ganodermanondiol significantly reduced the viability of SW620 cells through the induction of apoptosis, which was associated with the upregulated the levels of cleaved-poly (ADP-ribose) polymerase (PARP), cleaved-caspase-3, and -9. In addition, ganodermanondiol showed low cytotoxic activity against normal NIH3T3 cells.CONCLUSION: NTF are potential anti-cancer agents against colon cancer and the active constituents may be ganoderic alcohols whose inhibitory mechanism of anti-cancer action may be related to the activation of a mitochondrial-dependent pathway.

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PMID: 

Adv Exp Med Biol. 2019 ;1182:243-262. PMID: 31777022

Abstract Title: 

Preventive and Therapeutic Effect of Ganoderma (Lingzhi) on Renal Diseases and Clinical Applications.

Abstract: 

The mechanisms of kidney diseases, such as acute kidney injury (AKI) and chronic kidney disease (CKD), have been intensively studied. Nonetheless, the morbidity and mortality of AKI and CKD increased in recent years. Recently, natural products have been increasingly recognized as an alternative source for treating renal diseases on account of the conventional experience and the multi-target characteristics. Ganoderma lucidum (G. lucidum, Lingzhi) has been used for centuries as nutraceuticals and alternative medicine to improve health and to treat numerous diseases. Benefiting from various biological activities, such as anti-oxidation, anti-inflammation, anti-tumor growth and metastasis, etc., G. lucidum has been proved to exhibit significant role in preventing and treating various kidney diseases. In this chapter, we review certain researches and provide comprehensive insights into the renoprotective effects of G. lucidum.

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