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Aging is a growing trend in modern societies, and the incidence of aging-related obesity has been on a steady rise. The key cause of obesity of older adults is identified as the decreased lipolysis of adipocytes, which in turn can be attributed to the decreased expression of key lipases in senescent adipocytes, but effective clinical measures to enhance the lipase expression are currently lacking. In this work, we studied the influence of the total saponins from Panax japonicus (TSPJs) on the expression of key lipases in senescent adipocytes, which can provide an experimental basis for potentially using TSPJs to address aging-related obesity. We found that TSPJs could regulate lipase expression through the ALK7-SMADs signaling pathway, to restore the lipase expression in senescent adipocytes and thus improve lipolysis.

Aging and obesity are closely related. A key change in the adipose tissue during the aging process is the decline of lipolysis. The excitation of the sympathetic nerve system is a key pathway to promote lipolysis, but the underlying mechanism remains unclear. In this work, in vitro and in vivo aging models with and without tyrosine hydroxylase (TH) knockdown were treated with total saponins from Panax japonicus (TSPJs), and the expression of lipolysis-related proteins was examined. It was found that TSPJs could promote the expression of lipolysis-related genes and TH in adipocytes both in vitro and in vivo, and the expression of lipolysis-related genes was downregulated after TH knockdown. It was inferred that TSPJs could promote the excitation of sympathetic nerves by increasing the expression of TH in adipose tissue, which positively regulated the expression of lipases to revitalize lipolysis. The results suggested that TSPJs resisted aging-induced obesity and could be a potential medication for weight management.

Our prophase studies have manifested that the sweet triterpenoid glycoside from the leaves of Cyclocarya paliurus (CPST) effectively improved the disorders of glucolipid metabolism in vitro and in patients. The current purpose was to further detect its mechanisms involved. The results demonstrated that CPST could ameliorate high-fat diet (HFD)-induced insulin resistance (IR), which was linked to reducing HFD-induced mice's body weight, serum glucose (GLUO), triglyceride (TG), total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C), lowering the area under the oral glucose tolerance curve and insulin tolerance, elevating the percentage of brown adipose, high-density lipoprotein cholesterol (HDL-C), reducing fat droplets of adipocytes in interscapular brown adipose tissue (iBAT) and cross-sectional area of adipocytes. Further studies manifested that CPST obviously downregulated TLR4, MyD88, NLRP3, ASC, caspase-1, cleased-caspase-1, IL-18, IL-1β, TXNIP, and GSDMD protein expressions and p-NF-кB/NF-кB ratio in iBAT. These aforementioned findings demonstrated that CPST ameliorated HFD induced IR by regulating TLR4/NF-κB/NLRP3 signaling pathway, which in turn enhancing insulin sensitivity and glucose metabolism.

Long non-coding RNAs (lncRNAs) exhibit a length more than 200 nucleotides and they are characterized by non-coding RNAs (ncRNA) not encoded into proteins. Over the past few years, the role and development of lncRNAs have aroused the rising attention of researchers. To be specific, KCNQ1OT1, the KCNQ1 opposite strand/antisense transcript 1, is clearly classified as a regulatory ncRNA. KCNQ1OT1 is capable of interacting with miRNAs, RNAs and proteins, thereby affecting gene expression and various cell functions (e.g., cell proliferation, migration, epithelial–mesenchymal transition (EMT), apoptosis, viability, autophagy and inflammation). KCNQ1OT1 is dysregulated in a wide range of human diseases (e.g., cardiovascular disease, cancer, diabetes, osteoarthritis, osteoporosis and cataract), and it is speculated to act as a therapeutic target for treating various human diseases. On the whole, this review aims to explore the biological functions, underlying mechanisms and pathogenic roles of KCNQ1OT1 in human diseases.

Among the gynecological cancers, ovarian cancer is the most lethal. Its therapeutic options include a combination of chemotherapy with platinum-based compounds and cytoreductive surgery. Most ovarian cancer patients exhibit an initial response to platinum-based therapy, however, platinum resistance has led to up to 80% of this responsive cohort becoming refractory. Ovarian cancer recurrence and drug resistance to current chemotherapeutic options is a global challenge. Chemo-resistance is a complex phenomenon that involves multiple genes and signal transduction pathways. Therefore, it is important to elucidate on the underlying molecular mechanisms involved in chemo-resistance. This inform decisions regarding therapeutic management and help in the identification of novel and effective drug targets. Studies have documented the individual biomarkers of platinum-resistance in ovarian cancer that are potential therapeutic targets. This review summarizes the molecular mechanisms of platinum resistance in ovarian cancer, novel drug targets, and clinical outcomes.

Astragalus and Angelica decoction (A&A) has been clinically used as a classical traditional Chinese medicine (TCM) formula in China for many years for the treatment of kidney diseases, especially renal interstitial fibrosis (RIF). However, the mechanisms underlying the therapeutic effects of A&A on RIF remains poorly understood. In the present study, systematic network pharmacology and effective experimental verification were utilized for the first time to elucidate the pharmacological efficacy and potential mechanism. The outcomes indicated that 22 active components and 87 target genes of A&A were identified and cross-referenced with RIF-associated genes, contributing to confirmation of 74 target genes of A&A for RIF. Pathway and functional enrichment analyses revealed that A&A had substantial effects on MAPK, PI3K-Akt and TNF signaling pathways. In addition, seven core targets with relatively higher betweenness and degree were identified in the constructed Chinese medicine material-chemical component-target-signal pathway network. Moreover, we verified the potential therapeutic effect of A&A in vivo (using a mouse model of RIF), confirming that A&A could effectively protect the kidney by regulating these target genes. The therapeutic effect of A&A on RIF could be attributed to its role in regulating the cell cycle, limiting the apoptosis, and inhibiting the inflammation.

The frequency of human suffering from cancer is increasing annually across the globe. This has fueled numerous investigations aimed at the prevention and cure of various cancers. Long non-coding RNA (lncRNA) are known to play a crucial role in cancer. For instance, cancer susceptibility candidate 11 (CASC11), as one of the long non-coding RNAs, has been reported to be overexpressed in various tumors. This review elucidates the mechanism by which lncRNA CASC11 regulates tumors' biological processes and affirms its value as a therapeutic target for tumors. Through systematic analysis and review of relevant articles in PubMed, we revealed the pathophysiological mechanism of CASC11 on the tumor by regulating the biological processes of tumor such as proliferation, autophagy, apoptosis, thereby promoting tumor metastasis. We also revealed the regulatory pathways of CASC11 in different tumors, for instance by acting on a variety of microRNAs, oncogenic proteins, carcinogens, and transcription factors. Consequently, CASC11 regulates cancer proliferation, apoptosis, and invasion by altering the WNT/β-catenin signaling pathway and epithelial–mesenchymal transition (EMT). Furthermore, CASC11 expression has a high pertinence with clinical prognosis, suggesting that it is a potential marker for malignant tumors or a clinical adjuvant therapy in the future.

In order to explore the regional water–salt balance mechanism in Hetao Irrigation District, field experiments were conducted in 2018 and 2019 in the Heji canal study area. The SWAP model was calibrated and validated based on field experiments' observed data. The SWAP model was used to simulate soil water–salt dynamics in saline wasteland after calibration and validation. The results showed that model simulation results of soil water content and soil salt concentration agreed well with the measured values. Soil water content and soil salt concentration changed obviously under the effect of farmland irrigation in the crop growing period. Soil salt was accumulated in saline wasteland. The soil salt accumulation of each soil layer in saline wasteland was 0.164, 0.092, −0.890 and −1.261 mg/cm3, respectively. Soil water content gradually increased and soil salt concentration gradually decreased in the autumn irrigation period. Soil salt was leached in the saline wasteland. The soil salt accumulation of each soil layer in the saline wasteland was −1.011, −1.242, −1.218 and −1.335 mg/cm3, respectively. The saline wasteland became a drainage and salt drainage region for cultivated land. The saline wastelands had an obvious role in adjusting salt balance and maintaining salt dynamic balance in Hetao Irrigation District. HIGHLIGHTS Soil water–salt transport is concentrated in saline wasteland.; Soil water content and soil salt concentration changed obviously in crop growing period.; Soil salt was accumulated in saline wasteland in crop growing period.; Soil water content gradually increased and soil salt concentration gradually decreased in autumn irrigation period.; Saline wasteland became a drainage and salt drainage region.;

Background: The decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. Methods: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. Results: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p

Traumatic brain injury (TBI) is the major cause of high mortality and disability rates worldwide. Pioglitazone is an activator of peroxisome proliferator-activated receptor-gamma (PPARγ) that can reduce inflammation following TBI. Clinically, neuroinflammation after TBI lacks effective treatment. Although there are many studies on PPARγ in TBI animals, only few could be converted into clinical, since TBI mechanisms in humans and animals are not completely consistent. The present study, provided a potential theoretical basis and therapeutic target for neuroinflammation treatment after TBI. First, we detected interleukin-6 (IL-6), nitric oxide (NO) and Caspase-3 in TBI clinical specimens, confirming a presence of a high expression of inflammatory factors. Western blot (WB), quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were used to detect PPARγ, IL-6, and p-NF-κB to identify the mechanisms of neuroinflammation. Then, in the rat TBI model, neurobehavioral and cerebral edema levels were investigated after intervention with pioglitazone (PPARγ activator) or T0070907 (PPARγ inhibitor), and PPARγ, IL-6 and p-NF-κB were detected again by qRT-PCR, WB and immunofluorescence (IF). The obtained results revealed that: 1) increased expression of IL-6, NO and Caspase-3 in serum and cerebrospinal fluid in patients after TBI, and decreased PPARγ in brain tissue; 2) pioglitazone could improve neurobehavioral and reduce brain edema in rats after TBI; 3) the protective effect of pioglitazone was achieved by activating PPARγ and reducing NF-κB and IL-6. The neuroprotective effect of pioglitazone on TBI was mediated through the PPARγ/NF-κB/IL-6 pathway. Keywords: Traumatic brain injury, IL-6, Pioglitazone, PPARγ, p-NF-κB

MicroRNAs (miRNAs) are an evolutionarily conserved class of small regulatory noncoding RNAs, binding to complementary target mRNAs and resulting in mRNA translational inhibition or degradation, and they play an important role in regulating many aspects of physiologic and pathologic processes in mammalian cells. Thus, efficient manipulations of miRNA functions may be exploited as promising therapeutics for human diseases. Two commonly used strategies to inhibit miRNA functions include direct transfection of chemically synthesized miRNA inhibitors and delivery of a gene vector that instructs intracellular transcription of miRNA inhibitors. While most miRNA inhibitors are based on antisense molecules to bind and sequester miRNAs from their natural targets, it is challenging to achieve effective and stable miRNA inhibition. Here we develop a user-friendly system to express circular inhibitors of miRNA (CimiRs) by exploiting the noncanonical head-to-tail backsplicing mechanism for generating endogenous circular RNA sponges. In our proof-of-principle experiments, we demonstrate that the circular forms of the hsa-miR223-binding site of human β-arrestin1 (ARRB1) 3′ UTR sponge RNA (BUTR), the bulged anti-miR223 (cirBulg223) and bulged anti-miR21 (cirBulg21), exhibit more potent suppression of miRNA functions than their linear counterparts. Therefore, the engineered CimiR expression system should be a valuable tool to target miRNAs for basic and translational research. Keywords: microRNA, miRNA, miRNA sponge, circular RNA, miRNA inhibitor, competing endogenous RNA, miRNA decoy, noncoding RNA, oncomiR

We aimed to investigate the effects of total saponins from Panax japonicus (TSPJ) on adipocyte inflammation and insulin resistance induced by a high-fat diet (HFD). Moreover, its underlying mechanism was further explored. In vivo, we found that TSPJ inhibited the activation of NF-κB and increase the transcription of p-AKT, leading to reduced inflammation and improved sensitivity of adipocytes to insulin. In vitro evaluation revealed that palmitic acid (PA) induced inflammation by activating the NF-κB pathway, and triggered insulin resistance by affecting the expression of p-AKT in adipocytes. Treatment with 30 mg/kg and 90 mg/kg TSJP in animals and pre-treatment with 25 μg/mL and 50 μg/mL TSJP in 3T3-L1 could inhibit inflammation and insulin resistance induced by HFD and PA. Our study showed that TSPJ inhibited adipocyte inflammation by inhibiting the NF-κB pathway. Besides, TSPJ could also affect the expression of p-AKT to increase insulin sensitivity in adipocytes via targeting AMPK.

Increasing evidence has demonstrated that hypoxia was an aggressive feature in endometrial cancer (EC), which is significantly associated with the tumor grade, lymph node metastasis, and tumor resistance to chemotherapy. However, the relationship between hypoxia and the immune microenvironment in EC is not very clear. Exosomes are small membrane vesicles secreted from a variety of cell types which mediate cell-to-cell communication through transported biomolecules. Here, we investigated whether exosomes can play an immunomodulatory role in intercellular communication between EC cells and macrophages. EC KEL cells were cultured under hypoxia or normoxic condition to collect exosomes. After identification, the exosomes derived from hypoxic or normoxic KEL cells were cultured with the monocyte cell line THP-1 to study the immunoregulation function of KEL cells. The results showed that the total number of exosomes produced by hypoxic KEL cells was significantly higher than that in normoxic condition. In addition, hypoxia markedly stimulated the increase in miRNA-21 expression in the exosomes. After coculture, we found that exosomal miRNA-21 could be horizontally transferred into THP-1 cells. And then, the notably enhanced mRNA expression levels of IL-10 and CD206 in THP-1 cells were observed, suggestive of M2 polarization. To further study the effect of miRNA-21-containing exosomes, we transfected miRNA-21 mimics or inhibitor into THP-1 cells. The results showed that miRNA-21 mimics promoted IL-10 and CD206 mRNA expression levels, and the miRNA-21 inhibitor significantly prevented the alteration induced by intake of hypoxic KEL cell-derived exosomes. In summary, we found that endometrial cancer KEL cells in hypoxic condition promoted monocyte THP-1 cell transformation to M2-like polarization macrophages through delivering exosomal miRNA-21, which may be a potential mechanism of the formation of the immune microenvironment in EC progression.

Mesenchymal stem cells (MSCs) are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic, chondrogenic and adipogenic lineages. We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood. Here, we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs. Using two different siRNA bioinformatic prediction programs, we design five siRNAs targeting mouse BMP9 (or simB9), which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors. We demonstrate that two of the five siRNAs, simB9-4 and simB9-7, exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs. Furthermore, simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers, matrix mineralization and ectopic bone formation from MSCs. Thus, our findings demonstrate the important role of BMP9 in osteogenic differentiation of MSCs. The characterized simB9 siRNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic signaling. Our results also indicate that recombinant adenovirus-mediated expression of siRNAs is efficient and sustained, and thus may be used as an effective delivery vehicle of siRNA therapeutics. Keywords: BMP9, Bone formation, Mesenchymal stem cells, Osteogenic differentiation, RNA interference, Recombinant adenovirus, siRNA

As the most commonly occurring cancer in women worldwide, breast cancer poses a formidable public health challenge on a global scale. Breast cancer consists of a group of biologically and molecularly heterogeneous diseases originated from the breast. While the risk factors associated with this cancer varies with respect to other cancers, genetic predisposition, most notably mutations in BRCA1 or BRCA2 gene, is an important causative factor for this malignancy. Breast cancers can begin in different areas of the breast, such as the ducts, the lobules, or the tissue in between. Within the large group of diverse breast carcinomas, there are various denoted types of breast cancer based on their invasiveness relative to the primary tumor sites. It is important to distinguish between the various subtypes because they have different prognoses and treatment implications. As there are remarkable parallels between normal development and breast cancer progression at the molecular level, it has been postulated that breast cancer may be derived from mammary cancer stem cells. Normal breast development and mammary stem cells are regulated by several signaling pathways, such as estrogen receptors (ERs), HER2, and Wnt/β-catenin signaling pathways, which control stem cell proliferation, cell death, cell differentiation, and cell motility. Furthermore, emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer, especially for triple-negative breast cancer. This review provides a comprehensive survey of the molecular, cellular and genetic aspects of breast cancer. Keywords: BRCA1/2, Breast cancer, Cancer stem cells, Estrogen receptors, HER2, Noncoding RNAs, Triple-negative breast cancer, Tumor heterogeneity

Glomerular podocytes are highly specialized epithelial cells and play an essential role in establishing the selective permeability of the glomerular filtration barrier of kidney. Maintaining the viability and structural integrity of podocytes is critical to the clinical management of glomerular diseases, which requires a thorough understanding of podocyte cell biology. As mature podocytes lose proliferative capacity, a conditionally SV40 mutant tsA58-immortalized mouse podocyte line (designated as tsPC) was established from the Immortomouse over 20 years ago. However, the utility of the tsPC cells is hampered by the practical inconvenience of culturing these cells. In this study, we establish a user-friendly and reversibly-immortalized mouse podocyte line (designated as imPOD), on the basis of the tsPC cells by stably expressing the wildtype SV40 T-antigen, which is flanked with FRT sites. We show the imPOD cells exhibit long-term high proliferative activity, which can be effectively reversed by FLP recombinase. The imPOD cells express most podocyte-related markers, including WT-1, Nephrin, Tubulin and Vinculin, but not differentiation marker Synaptopodin. The imPOD cells do not form tumor-like masses in vivo. We further demonstrate that TGFβ1 induces a podocyte injury-like response in the FLP-reverted imPOD cells by suppressing the expression of slit diaphragm-associated proteins P-Cadherin and ZO-1 and upregulating the expression of mesenchymal markers, α-SMA, Vimentin and Nestin, as well as fibrogenic factors CTGF and Col1a1. Collectively, our results strongly demonstrate that the newly engineered imPOD cells should be a valuable tool to study podocyte biology both under normal and under pathological conditions. Keywords: Chronic kidney disease, FLP recombinase, Glomerular disease, Glomerulus, Immortalization, Nephropathy, Podocyte, SV40 T antigen

Background/Aims: As the most lethal urological cancers, renal cell carcinoma (RCC) comprises a heterogeneous group of cancer with diverse genetic and molecular alterations. There is an unmet clinical need to develop efficacious therapeutics for advanced, metastatic and/or relapsed RCC. Here, we investigate whether anthelmintic drug Niclosamide exhibits anticancer activity and synergizes with targeted therapy Sorafenib in suppressing RCC cell proliferation. Methods: Cell proliferation and migration were assessed by Crystal violet staining, WST-1 assay, cell wounding and cell cycle analysis. Gene expression was assessed by qPCR. In vivo anticancer activity was assessed in xenograft tumor model. Results: We find that Niclosamide effectively inhibits cell proliferation, cell migration and cell cycle progression, and induces apoptosis in human renal cancer cells. Mechanistically, Niclosamide inhibits the expression of C-MYC and E2F1 while inducing the expression of PTEN in RCC cells. Niclosamide is further shown to synergize with Sorafenib in suppressing RCC cell proliferation and survival. In the xenograft tumor model, Niclosamide is shown to effectively inhibit tumor growth and suppress RCC cell proliferation. Conclusions: Niclosamide may be repurposed as a potent anticancer agent, which can potentiate the anticancer activity of the other agents targeting different signaling pathways in the treatment of human RCC.

In order to explore the rule of groundwater salt dynamic in Hetao Irrigation District, a typical monitoring area was selected as the research area in Yongji Irrigation Area of Hetao Irrigation District. The groundwater level and groundwater salinity were analyzed during the year and inter-annual variation in 2008-2013. The groundwater level showed an obvious seasonal change trend during the year variation. The groundwater level was at the peak value after spring irrigation and autumn irrigation. The groundwater level was at the low value before melting and autumn irrigation. The groundwater level had an obvious periodicity during the inter-annual variation. The groundwater level could keep a relatively stable for many years. The groundwater salinity showed an obvious seasonal change trend during the year variation. The groundwater salinity was greatly affected by irrigation and had a decreased trend after irrigation. The groundwater salinity had an obvious periodicity during the inter-annual variation and could keep a relatively stable for many years in cultivated land. The groundwater salinity had an increased trend during the inter-annual variation in wasteland. The wasteland was the drainage area for cultivated land. The wasteland had an obvious role in adjusting salt dynamic balance in Hetao Irrigation District.

The assembly and maintenance of cilia depend on intraflagellar transport (IFT) proteins, which play an important role in development and homeostasis. IFT80 is a newly defined IFT protein and partial mutation of IFT80 in humans causes diseases such as Jeune asphyxiating thoracic dystrophy (JATD) and short rib polydactyly (SRP) type III, both characterized by abnormal skeletal development. However, the role and mechanism of IFT80 in the invasion of gastric cancer is unknown. We established SGC-7901 and MKN-45 gastric cancer cell lines that stably overexpressed IFT80, as verified by quantitative reverse transcription-PCR, Western blot, and immunofluorescence. Matrix metalloproteinase-9 (MMP9) plays an important role in tumor invasion, and its expression was assessed by quantitative reverse transcription-PCR, Western blotting, and immunofluorescence. The invasion ability of IFT80 on SGC-7901 and MKN-45 cells was examined by the Matrigel invasion assay. The relationship between p75NGFR, and the p75NGFR antagonists, PD90780 and IFT80, were detected by quantitative reverse transcription-PCR and Western blotting. We first detected an IFT80 expression pattern, and found that IFT80 was highly expressed in gastric cancer clinical samples. Overexpression of IFT80 in the gastric cancer cell lines, SGC-7901 and MKN-45, led to lengthening cilia. Additionally, overexpression of IFT80 significantly improved proliferation and invasion, but inhibited apoptosis, in gastric cancer cells. We further found that overexpression of IFT80 increased p75NGFR and MMP9 mRNA and protein expression. Treatment with the p75NGFR antagonist PD90780 inhibited the increased invasion ability resulting from overexpression of IFT80 in SGC-7901 and MKN-45 gastric cancer cells. Thus, these results suggest that IFT80 plays an important role in invasion of gastric cancer through regulating the ift80/p75NGFR/MMP9 signal pathways.

Both selenium (Se) and polysaccharides from Pyracantha fortuneana (Maxim.) Li (PFPs) (P. fortuneana) have been reported to possess antioxidative and immuno-protective activities. Whether or not Se-containing polysaccharides (Se-PFPs) have synergistic effect of Se and polysaccharides on enhancing the antioxidant and immune activities remains to be determined. We previously reported that polysaccharides isolated from Se-enriched P. fortuneana (Se-PFPs) possessed hepatoprotective effects. However, it is not clear whether or not they have anti-mutagenic effects. In the present study, we compared and evaluated anti-mutagenic effects of Se-PFPs at three concentrations (1.35, 2.7 and 5.4 g/kg body weight) with those of PFPs, Se alone or Se + PFPs in mice using micronucleus assay in bone marrow and peripheral blood as well as mitomycin C-induced chromosomal aberrations in mouse testicular cells. We also elucidated the underlying mechanism. Our results demonstrated that Se-PFPs inhibited cyclophosphamide (CP)-induced micronucleus formation in both bone marrow and peripheral blood, enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in mouse liver, and reduced the activity and expression of cytochrome P450 1A (CYP4501A) in mouse liver in a dose-dependent manner. In addition, we found that the anti-mutagenic potential of Se-PFPs was higher than those of PFPs, Se alone or Se + PFPs at the same level. These results suggest that the anti-mutagenic potential of Se-PFPs may be mediated through the inhibition of the activity and expression of CYP4501A. This study indicates that application of Se-PFPs may provide an alternative strategy for cancer therapy by targeting CYP1A family.

Selenium-enriched polysaccharides from Pyracantha fortuneana (SePFP) has many beneficial physiological activities, but how it improves the aging associated abnormal lipid metabolism is still unclear. Therefore, we explored the mechanisms of the regulatory role of SePFP on liver lipid accumulation in aging mice. Methods: 60 naturally aged C57BL/6J male mice were divided into 6 groups: adult group, aging group (21-month-old mice), aging mice treated with low-, medium- and high-doses of SePFP (SePFP-L, SePFP-M, SePFP-H), and aging mice treated with resveratrol (RSV). SePFP and RSV were administrated daily via oral gavage from 16 to 21 months old. The parameters of energy metabolism were measured in all mice before sacrifice, and liver tissues were collected to determine the levels of metabolism-related enzymes by real-time PCR and Western blot. Results: We found that SePFP significantly reduced the body weight, liver to bodyweight ratio, and white fat to body weight ratio in aging mice. SePFP also down-regulated the triglycerides and cholesterol levels in liver and serum, and decreased respiratory quotient in aging mice. The mechanism of SePFP regulating lipid metabolism was mainly through promoting fatty acid transportation to mitochondria and enhancing mitochondrial β-oxidation and ketone body production. Conclusion: SePFP attenuates liver lipid deposition in aging mice by enhancing hepatic mitochondrial β- oxidation. [ABSTRACT FROM AUTHOR]