VOZ1 and VOZ2 transcription factors regulate arsenic tolerance and distribution in rice and Arabidopsis.

Rice is the major source of arsenic (As) intake in humans, as this staple crop readily accumulates As in the grain. Identifying the genes and molecular mechanisms underlying As accumulation and tolerance is a crucial step toward developing rice with reduced As levels. We identified 25 rice genes that improve As tolerance in yeast cells by expressing a complementary DNA (cDNA) library generated from As-treated rice roots. Among them, a zinc finger-type transcription factor VASCULAR PLANT ONE- ZINC FINGER 1 (OsVOZ1) (OsVOZ1) conferred the most pronounced As tolerance. OsVOZ1 inhibits As accumulation in yeast via activation of As efflux transporter Acr3p by post-transcriptional modification in yeast. The Arabidopsis voz1 voz2 double-knockout mutant exhibited As hypersensitivity, altered As concentrations in various tissues, and reduced As transport activity via the phloem. Arabidopsis and rice VOZs were highly expressed in phloem cells in various tissues, which are critical for As distribution in plant tissues. The double-knockdown and single-knockout plants of OsVOZ1 and OsVOZ2 reduced As accumulation in their seeds. These findings suggest that rice and Arabidopsis VOZs regulate the translocation of As into tissues by regulating the phloem loading of this element.

Management of uterine cystic adenomyosis by laparoscopic surgery: case report.

BACKGROUND: Endometriosis of the uterine body can be manifested as diffuse solid lesions or cystic lesions. The former is common, while the latter is rare, especially for cystic adenomyosis larger than 5 cm. CASE PRESENTATION: A 30-year-old woman was admitted for severe and worsening dysmenorrhea. Ultrasound examination revealed a rare well-circumscribed cystic lesion about 5.5 × 4 × 5.0 cm. CA-125 level was slightly elevated. She accepted laparoscopic surgery and the adenomyotic tissues were excised. The histopathology of the specimen demonstrated the endometrial glands in the walls of cysts and an area of extensive hemorrhage can be seen in the inner wall of cyst. The patient made a good recovery after surgery and her symptoms complete resoluted. CONCLUSIONS: This is a rare case of a cystic adenomyotic lesion that was treated by laparoscopic surgery.

Synthesis and Evaluation of the Antitumor Activity of Novel 1-(4-Substituted phenyl)-2-ethyl Imidazole Apoptosis Inducers In Vitro.

Novel imidazole derivatives were designed, prepared, and evaluated in vitro for antitumor activity. The majority of the tested derivatives showed improved antiproliferative activity compared to the positive control drugs 5-FU and MTX. Among them, compound 4f exhibited outstanding antiproliferative activity against three cancer cell lines and was considerably more potent than both 5-FU and MTX. In particular, the selectivity index indicated that the tolerance of normal L-02 cells to 4f was 23-46-fold higher than that of tumor cells. This selectivity was significantly higher than that exhibited by the positive control drugs. Furthermore, compound 4f induced cell apoptosis by increasing the protein expression levels of Bax and decreasing those of Bcl-2 in a time-dependent manner. Therefore, 4f could be a potential candidate for the development of a novel antitumor agent.

Synthesis, activity evaluation, and pro-apoptotic properties of novel 1,2,4-triazol-3-amine derivatives as potent anti-lung cancer agents.

In this study, a series of 4,5-bis(substituted phenyl)-4H-1,2,4-triazol-3-amine compounds was designed, synthesised, and evaluated to determine their potential as anti-lung cancer agents. According to the results of screening of lung cancer cell lines A549, NCI-H460, and NCI-H23 in vitro, most of the synthesised compounds have potent cytotoxic activities with IC50 values ranging from 1.02 to 48.01 µM. Particularly, compound 4,5-bis(4-chlorophenyl)-4H-1,2,4-triazol-3-amine (BCTA) was the most potent anti-cancer agent, with IC50 values of 1.09, 2.01, and 3.28 µM against A549, NCI-H460, and NCI-H23 cells, respectively, meaning many-fold stronger anti-lung cancer activity than that of the chemotherapeutic agent 5-fluorouracil. We also explored the effects of BCTA on apoptosis in lung cancer cells by flow cytometry and western blotting. Our results indicated that BCTA induced apoptosis by upregulating proteins BAX, caspase 3, and PARP. Thus, the potential application of compound BCTA as a drug should be further examined.

Elevated Type II Secretory Phospholipase A2 Increases the Risk of Early Atherosclerosis in Patients with Newly Diagnosed Metabolic Syndrome.

A critical association between type II secretory phospholipase A2 (sPLA2-IIa) and established atherosclerotic cardiovascular disease has been demonstrated. However, the contribution of sPLA2-IIa to early atherosclerosis remains unknown. This study investigated the association between early-stage atherosclerosis and sPLA2-IIa in metabolic syndrome (MetS) patients. One hundred and thirty-six MetS patients and 120 age- and gender-matched subjects without MetS were included. Serum sPLA2-IIa protein levels and activity were measured using commercial kits. Circulating endothelial activation molecules (vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, and P-selectin), and carotid intima-media thickness (cIMT), were measured as parameters of vascular endothelial dysfunction and early atherosclerosis. MetS patients exhibited significantly higher sPLA2-IIa protein and activity levels than the controls. Both correlated positively with fasting blood glucose and waist circumference in MetS patients. Additionally, MetS patients exhibited strikingly higher levels of endothelial activation molecules and increased cIMT than controls. These levels correlated positively with serum sPLA2-IIa protein levels and activity. Moreover, multivariate analysis showed that high sPLA2-IIa protein and activity levels were independent risk factors of early atherosclerosis in MetS patients. This study demonstrates an independent association between early-stage atherosclerosis and increased levels of sPLA2-IIa, implying that increased sPLA2-IIa may predict early-stage atherosclerosis in MetS patients.

Microbiota prevents cholesterol loss from the body by regulating host gene expression in mice.

We have previously observed that knockout of Niemann-Pick C1-Like 1 (NPC1L1), a cholesterol transporter essential for intestinal cholesterol absorption, reduces the output of dry stool in mice. As the food intake remains unaltered in NPC1L1-knockout (L1-KO) mice, we hypothesized that NPC1L1 deficiency may alter the gut microbiome to reduce stool output. Consistently, here we demonstrate that the phyla of fecal microbiota differ substantially between L1-KO mice and their wild-type controls. Germ-free (GF) mice have reduced stool output. Inhibition of NPC1L1 by its inhibitor ezetimibe reduces stool output in specific pathogen-free (SPF), but not GF mice. In addition, we show that GF versus SPF mice have reduced intestinal absorption and increased fecal excretion of cholesterol, particularly after treatment with ezetimibe. This negative balance of cholesterol in GF mice is associated with reduced plasma and hepatic cholesterol, and likely caused by reduced expression of NPC1L1 and increased expression of ABCG5 and ABCG8 in small intestine. Expression levels of other genes in intestine and liver largely reflect a state of cholesterol depletion and a decrease in intestinal sensing of bile acids. Altogether, our findings reveal a broad role of microbiota in regulating whole-body cholesterol homeostasis and its response to a cholesterol-lowering drug, ezetimibe.

Value of a virtual hepatic segment model in assisting in the ultrasonic localization of intrahepatic lesions.

BACKGROUND: During scanning of the right hypochondrium and right intercostal regions with an ultrasonic transducer, several ultrasonic images of oblique sections are obtained. It is still a challenge for ultrasonography to divide these non-conventional sections into an accurate hepatic segmentation pattern. The aim of this research was to investigate the value of the virtual hepatic segment model (VHSM) in assisting the ultrasonic localization of space-occupying hepatic lesions. METHODS: VHSM was constructed via 3D reconstruction according to the first Chinese visible human dataset. Preoperative ultrasonography, contrast-enhanced CT scan and VHSM techniques were performed in 100 patients with space-occupying focal lesions in the liver parenchyma for segmental localization. The results of these three techniques were compared with the operative findings. RESULTS: VHSM was successfully detected on 2D sectional images by 3D reconstruction through surface rendering and volume rendering. The model could simulate ultrasonic directions to conduct a virtual dissection on any section plane, and fine liver segmentation could be displayed in any virtual plane. In 100 patients, there were 112 liver space-occupying focal lesions distributed in 148 liver segmentations. Regarding the positioning accuracies for lesions of different sizes and the lesion segmental distribution accuracies estimated using the three methods mentioned above, ultrasonography exhibited a significantly lower accuracy than VHSM for the segmental localization of lesions (P < 0.05), and contrast-enhanced CT was not significantly different from ultrasonography plus VHSM (P > 0.05). CONCLUSION: VHSM increased the accuracy of ultrasonic localization of space-occupying hepatic lesions, particularly in hepatic hypovascular regions.

[Effect of litchi seed aqueous extracts on learning and memory obstacles induced by D-galactose in mice and its mechanism].

OBJECTIVE: To investigate the improving effect of Litchi Seed Aqueous Extracts on learning and memory obstacles model and its mechanism. METHODS: The learning and memory obstacles model was incluced by subcutoneous injection of D-galactose (500 mg/kg) for 8 weeks. The model group and treatment groups were given huperzine A (0.4 mg/kg) and Litchi Seed Aqueous Extracts (15,60 g/kg) respectively for 4 weeks by ig at the 5th week. After huperzine A and Litchi Seed Aqueous Extracts treatment for 4 weeks, water maze test was used to determine the ability of mice's spatial learning and memory. The contents of advanced glycation end products (AGEs) in serum, the content of nitric oxide (NO) and acetylcholine (Ach), the activity of nitric oxide synthase (NOS) and acetylcholinesterase (AchE) in the brain tissue were detected. RESULTS: Litchi Seed Aqueous Extracts significantly ameliorated the learning and memory ability in mice, decreased the level of AGEs in serum, and reduced the content of NO and activity of NOS in brain tissues. No significantly influence was observed for the Ach and Ach-E in brain tissues. CONCLUSION: Litchi Seed Aqueous Extracts possesses improving the learning and memory effects on the model mice induced by D-galactose, which may be related to inhibiting too much AGEs and NO formation and reducing damage in the brain cells.

Ameliorative effect of berberine on renal damage in rats with diabetes induced by high-fat diet and streptozotocin.

Berberine (BBR) is one of the main constituents in Rhizoma coptidis and it has widely been used for the treatment of diabetic nephropathy. The aims of the study were to investigate the effects and mechanism of action of berberine on renal damage in diabetic rats. Diabetes and hyperglycaemia were induced in rats by a high-fat diet and intraperitoneal injection of 40 mg/kg streptozotocin (STZ). Rats were randomly divided into 5 groups, such as i) control rats, ii) untreated diabetic rats iii) 250 mg/kg metformin-treated, iv and v) 100 and 200 mg/kg berberine-treated diabetic rats and treated separately for 8 weeks. The fasting blood glucose, insulin, total cholesterol, triglyceride, glycosylated hemoglobin were measured in rats. Kidneys were isolated at the end of the treatment for histology, Western blot analysis and estimation of malonaldehyde (MDA), superoxide dismutase (SOD) and renal advanced glycation endproducts (AGEs). The results revealed that berberine significantly decreased fasting blood glucose, insulin levels, total cholesterol, triglyceride levels, urinary protein excretion, serum creatinine (Scr) and blood urea nitrogen (BUN) in diabetic rats. The histological examinations revealed amelioration of diabetes-induced glomerular pathological changes following treatment with berberine. In addition, the protein expressions of nephrin and podocin were significantly increased. It seems likely that in rats berberine exerts an ameliorative effect on renal damage in diabetes induced by high-fat diet and streptozotocin. The possible mechanisms for the renoprotective effects of berberine may be related to inhibition of glycosylation and improvement of antioxidation that in turn upregulate the expressions of renal nephrin and podocin.

Enhancement of TAT cell membrane penetration efficiency by dimethyl sulphoxide.

Cell penetrating peptides (CPPs) are promising tools for transducing presynthesized therapeutic molecules which possess low membrane permeability. The poor efficiency of cellular uptake and unexpected cellular localization are still the main obstacles to the development of drug delivery by using CPPs. In this study, we investigated the effect of a penetration enhancer, dimethylsulfoxide (DMSO), on the penetrating efficiency of a synthetic TAT peptide or the TAT fusion protein. FITC-labeled TAT and TAT-GFP were added to 10% DMSO or 100 microM chloroquine pretreated cells, fluorescence uptake into culturing cells was observed using fluorescence microscopy, FACS or quantitatively analyzed by a fluorescence spectrum. 10% DMSO treatment markedly increased internalization of TAT into cells and appeared in a well-distributed pattern throughout the cytosol and nucleus without membrane perforating or detectable cytotoxicity, the enhancement effect by 10% DMSO was reduced by endocytosis inhibitors including ammonium chloride and sodium azide. 10% DMSO also enhanced TAT-Apoptin induced apoptosis of carcinoma cells. These findings implicated that DMSO can be a novel delivery enhancer appropriate for CPP penetration.