Stepwise changes in flavonoids in spores/pollen contributed to terrestrial adaptation of plants.

Protecting haploid pollen and spores against UV-B light and high temperature, 2 major stresses inherent to the terrestrial environment, is critical for plant reproduction and dispersal. Here, we show flavonoids play an indispensable role in this process. First, we identified the flavanone naringenin, which serves to defend against UV-B damage, in the sporopollenin wall of all vascular plants tested. Second, we found that flavonols are present in the spore/pollen protoplasm of all euphyllophyte plants tested and that these flavonols scavenge reactive oxygen species to protect against environmental stresses, particularly heat. Genetic and biochemical analyses showed that these flavonoids are sequentially synthesized in both the tapetum and microspores during pollen ontogeny in Arabidopsis (Arabidopsis thaliana). We show that stepwise increases in the complexity of flavonoids in spores/pollen during plant evolution mirror their progressive adaptation to terrestrial environments. The close relationship between flavonoid complexity and phylogeny and its strong association with pollen survival phenotypes suggest that flavonoids played a central role in the progression of plants from aquatic environments into progressively dry land habitats.

Comparison Between Percutaneous Kyphoplasty and Percutaneous Vertebroplasty in Terms of Efficacy in Osteoporotic Vertebral Compression Fractures: A Meta-analysis.

Background and Aim: Osteoporotic vertebral compression fractures (OVCFs) are acknowledged to be common fractures, especially in the elderly population. Minimally invasive percutaneous methods of treatment for these fractures such as kyphoplasty (KP) and vertebroplasty (VP) have been valid and effective tools for decreasing clinical problems, which are associated with more beneficial effects compared with traditional methods such as open surgery or conservative treatment. Hence, we conducted the current meta-analysis in order to gather updated evidence for the systematic assessment of clinical and radiographic outcomes of KP compared with VP. Methods: We searched articles published based on the electronic databases, including PubMed, EMBASE, and Cochrane Library. Publications of studies comparing KP with VP in the treatment of OVCFs were collected. After rigorous and thorough review of study quality, we extracted the data on the basis of eligible trials, which analyzed the summary hazard ratios (HRs) of the end points of interest. Results: Our inclusion criteria involved a total of 6 studies. In total, data from 644 patients, 330 who received VP and 284 who received KP, were included in the review. There was no significant difference in either group in terms of visual analog scale (VAS) scores (MD = 0.17; 95% CI, -0.39 to 0.73; P = .56), risk of cement leakage (odds ratio [OR] = 1.31; 95% CI, 0.62 to 2.74; P = .47) or Oswestry Disability Index (ODI) scores (MD = 0.51; 95% CI, -1.87 to 2.88; P = .68). Nevertheless, the injected cement volume (MD = -0.52; 95% CI, -0.88 to -0.15; P = .005) in the VP group was linked to a markedly lower statistically significant trend compared with the KP group. Conclusion: This meta-analysis evaluated acceptable efficacy levels across the involved trials. VP injected cement volume had several advantages in this meta-analysis. Yet, no significant differences were observed in terms of VAS scores, ODI scores, or cement leakage when KP was compared to VP therapy. Given the combined results of our study, the optimal treatment for patients with OVCFs should be determined by further high-quality multicenter randomized controlled trials with longer follow-up and larger sample sizes.

Delayed callose degradation restores the fertility of multiple P/TGMS lines in Arabidopsis.

Photoperiod/temperature-sensitive genic male sterility (P/TGMS) is widely applied for improving crop production. Previous investigations using the reversible male sterile (rvms) mutant showed that slow development is a general mechanism for restoring fertility to P/TGMS lines in Arabidopsis. In this work, we isolated a restorer of rvms-2 (res3), as the male sterility of rvms-2 was rescued by res3. Phenotype analysis and molecular cloning show that a point mutation in UPEX1 l in res3 leads to delayed secretion of callase A6 from the tapetum to the locule and tetrad callose wall degradation. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis demonstrated that the tapetal transcription factor ABORTED MICROSPORES directly regulates UPEX1 expression, revealing a pathway for tapetum secretory function. Early degradation of the callose wall in the transgenic line eliminated the fertility restoration effect of res3. The fertility of multiple known P/TGMS lines with pollen wall defects was also restored by res3. We propose that the remnant callose wall may broadly compensate for the pollen wall defects of P/TGMS lines by providing protection for pollen formation. A cellular mechanism is proposed to explain how slow development restores the fertility of P/TGMS lines in Arabidopsis.

A cellular mechanism underlying the restoration of thermo/photoperiod-sensitive genic male sterility.

During anther development, the transformation of the microspore into mature pollen occurs under the protection of first the tetrad wall and later the pollen wall. Mutations in genes involved in this wall transition often lead to microspore rupture and male sterility; some such mutants, such as the reversible male sterile (rvms) mutant, are thermo/photoperiod-sensitive genic male sterile (P/TGMS) lines. Previous studies have shown that slow development is a general mechanism of P/TGMS fertility restoration. In this study, we identified restorer of rvms-2 (res2), which is an allele of QUARTET 3 (QRT3) encoding a polygalacturonase that shows delayed degradation of the tetrad pectin wall. We found that MS188, a tapetum-specific transcription factor essential for pollen wall formation, can activate QRT3 expression for pectin wall degradation, indicating a non-cell-autonomous pathway involved in the regulation of the cell wall transition. Further assays showed that a delay in degradation of the tetrad pectin wall is responsible for the fertility restoration of rvms and other P/TGMS lines, whereas early expression of QRT3 eliminates low temperature restoration of rvms-2 fertility. Taken together, these results suggest a likely cellular mechanism of fertility restoration in P/TGMS lines, that is, slow development during the cell wall transition of P/TGMS microspores may reduce the requirement for their wall protection and thus support their development into functional pollens, leading to restored fertility.

Discontinuous moving shot technique for conformal thermal ablation in an ex vivo porcine liver model.

PURPOSE: We aimed to determine the ablation characteristics of discontinuous moving shot technique (DMST) in microwave ablation (MWA), radiofrequency ablation (RFA) and laser ablation (LA), and analyze the differences compared with fixed electrode technique (FET) in an ex vivo porcine liver model. METHODS: FET was defined as the ablation needle remaining fixed during ablation. In DMST, ablation needle moved backward for a fixed distance twice along the long axis during ablation. Four moving distances (0.5 cm, 0.75 cm, 1 cm and 2 cm) were used in DMST. Long-axis diameter (LAD) and short-axis diameter (SAD) of ablation zones were measured. The ratio of LAD/SAD was calculated. RESULTS: The shape and size of ablation zones were different between DMST and FET. Compared with FET, DMST could achieve greater LAD when the moving distance became long enough. In MWA with DMST, SAD decreased with the extension of moving distance and finally became smaller than the SAD in FET. While in LA and RFA, the change of moving distance did not affect SAD significantly. CONCLUSION: In MWA, RFA and LA, the characteristics of ablation zone of DMST were different from that of FET. This unique ablation technique may be suitable for conformal thermal ablation.

Modeling of diagnosis for metabolic syndrome by integrating symptoms into physiochemical indexes.

BACKGROUND: Metabolic syndrome (MS) is a major global health concern comprising a cluster of co-occurring conditions that increase the risk of heart disease, stroke and type 2 diabetes. MS is usually diagnosed using a combination of physiochemical indexes (such as BMI, abdominal circumference and blood pressure) but largely ignores clinical symptoms when investigating prevention and treatment of the disease. Exploring predictors of MS using multiple diagnostic indicators may improve early diagnosis and treatment of MS. Traditional Chinese medicine (TCM) attaches importance to the etiology of disease symptoms and indications using four diagnostic methods, which have long been used to treat metabolic disease. Therefore, in this study, we aimed to develop predictive indicators for MS using both physiochemical indexes and TCM methods. METHODS: Clinical information (including both physiochemical and TCM indexes) was obtained from a cohort of 586 individuals across 4 hospitals in China, comprising 136 healthy controls and 450 MS cases. Using this cohort, we compared three classic machine learning methods: decision tree (DT), support vector machine (SVM) and random forest (RF) towards MS diagnosis using physiochemical and TCM indexes, with the best model selected by comparing the accuracy, specificity and sensitivity of the three models. In parallel, the best proportional partition of the training data to the test data was confirmed by observing the changes in evaluation indexes using each model. Next, three subsets containing different categories of variables (including both TCM and physicochemical indexes combined - termed the "fused indexes", only physicochemical indexes, and TCM indexes only) were compared and analyzed using the best performing model and optimum training to test data proportion. Next, the best subset was selected through comprehensive comparative analysis, and then the important prediction variables were selected according to their weight. RESULTS: When comparing the three models, we found that the RF model had the highest average accuracy (average 0.942, 95%CI [0.925, 0.958]) and sensitivity (average 0.993, 95%CI [0.990, 0.996]). Besides, when the training set accounted for 80% of the cohort data, the specificity got the best value and the accuracy and sensitivity were also very high in RF model. In view of the performance of the three different subsets, the prediction accuracy and sensitivity of models analyzing the fused indexes and only physicochemical indexes remained at a high level. Further, the mean value of specificity of the model using fused indexes was 0.916, which was significantly higher than the model with only physicochemical indexes (average 0.822) and the model with only TCM indexes (average 0.403). Based on the RF model and data allocation ratio (8:2), we further extracted the top 20 most significant variables from the fused indexes, which included 14 physicochemical indexes and 6 TCM indexes including wiry pulse, chest tightness, spontaneous perspiration, greasy tongue coating etc. CONCLUSION: Compared with SVM and DT models, the RF model showed the best performance, especially when the ratio of the training set to test set is 8:2. Compared with single predictive indexes, the model constructed by combining physiochemical indexes with TCM indexes (i.e. the fused indexes) exhibited better predictive ability. In addition to common physicochemical indexes, some TCM indexes, such as wiry pulse, chest tightness, spontaneous perspiration, greasy tongue coating, can also improve diagnosis of MS.

Epigallocatechin gallate inhibits dimethylhydrazine-induced colorectal cancer in rats.

BACKGROUND: Epigallocatechin gallate (EGCG) is a polyhydroxy phenolic compound extracted from tea and its antitumor effect has received widespread attention. We explored the inhibitory effect of EGCG on dimethylhydrazine (DMH)-induced colorectal cancer (CRC) using a rat model, predicted the interaction between EGCG and CRC target genes using a database, and explained the EGCG associated target pathways and mechanisms in CRC. AIM: To understand the inhibitory mechanisms of EGCG on CRC cell proliferation and identify its pharmacological targets by network pharmacology analysis. METHODS: DMH (40 mg/kg, s.c., twice weekly for eight weeks) was used to induce CRC in rats. After model establishment, the rats were administered with EGCG (50, 100, or 200 mg/kg, p.o., once daily for eight weeks) and killed 12 and 20 wk after the start of the experiment. Formation of aberrant crypt foci and tumor was studied by histological analysis. Using network pharmacology analysis, candidate and collective targets of EGCG and CRC were identified, and Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were used to predict the pathways altered by EGCG. RESULTS: At week 12, high-dose EGCG treatment significantly reduced the tumor formation rate, total number of tumors, cancerous and non-cancerous tumors, tumor volume, ascites formation, and aberrant crypt foci count. At week 20, all three doses of EGCG were effective. Seventy-eight collective targets of EGCG and CRC were identified, of which 28 genes were dysregulated in CRC. Kyoto Encyclopedia of Genes and Genomes and GO analyses showed that the dysregulated genes were enriched in hsa05210 (CRC), hsa04115 (p53 signaling pathway), and hsa04151 (PI3K-Akt signaling pathway), GO:0043124 (negative regulation of I-kappaB kinase/NF-kappaB signaling pathway), GO:0043409 (negative regulation of mitogen-activated protein kinase cascade), and GO:2001244 (positive regulation of intrinsic apoptotic signaling pathway) respectively. CONCLUSION: EGCG inhibits the formation of DMH-induced CRC by regulating key pathways involved in tumorigenesis.

Slowing development restores the fertility of thermo-sensitive male-sterile plant lines.

Temperature-sensitive genic male sterility (TGMS) lines are widely used in the breeding of hybrid crops1,2, but by what means temperature as a general environmental factor reverses the fertility of different TGMS lines remains unknown. Here, we identified an Arabidopsis TGMS line named reversible male sterile (rvms) that is fertile at low temperature (17 °C) and encodes a GDSL lipase. Cytological observations and statistical analysis showed that low temperature slows pollen development. Further screening of restorers of rvms, as well as crossing with a slow-growth line at normal temperature (24 °C), demonstrate that slowing of development overcomes the defects of rvms microspores and allows them to develop into functional pollen. Several other Arabidopsis TGMS lines were identified, and their fertility was also restored by slowing of development. Given that male reproductive development is conserved3, we propose that slowing of development is a general mechanism applicable to the sterility-fertility conversion of TGMS lines from different plant species.

Dietary fructose-induced gut dysbiosis promotes mouse hippocampal neuroinflammation: a benefit of short-chain fatty acids.

BACKGROUND: Western-style diets arouse neuroinflammation and impair emotional and cognitive behavior in humans and animals. Our previous study showed that a high-fructose diet caused the hippocampal neuroinflammatory response and neuronal loss in animals, but the underlying mechanisms remained elusive. Here, alterations in the gut microbiota and intestinal epithelial barrier were investigated as the causes of hippocampal neuroinflammation induced by high-fructose diet. RESULTS: A high-fructose diet caused the hippocampal neuroinflammatory response, reactive gliosis, and neuronal loss in C57BL/6N mice. Depletion of the gut microbiota using broad-spectrum antibiotics suppressed the hippocampal neuroinflammatory response in fructose-fed mice, but these animals still exhibited neuronal loss. Gut microbiota compositional alteration, short-chain fatty acids (SCFAs) reduction, intestinal epithelial barrier impairment, NOD-like receptor family pyrin domain-containing 6 (NLRP6) inflammasome dysfunction, high levels of serum endotoxin, and FITC-dextran were observed in fructose-fed mice. Of note, SCFAs, as well as pioglitazone (a selective peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist), shaped the gut microbiota and ameliorated intestinal epithelial barrier impairment and NLRP6 inflammasome dysfunction in fructose-fed mice. Moreover, SCFAs-mediated NLRP6 inflammasome activation was inhibited by histamine (a bacterial metabolite) in ex vivo colonic explants and suppressed in murine CT26 colon carcinoma cells transfected with NLRP6 siRNA. However, pioglitazone and GW9662 (a PPAR-γ antagonist) exerted no impact on SCFAs-mediated NLRP6 inflammasome activation in ex vivo colonic explants, suggesting that SCFAs may stimulate NLRP6 inflammasome independently of PPAR-γ activation. SCFAs and pioglitazone prevented fructose-induced hippocampal neuroinflammatory response and neuronal loss in mice. Additionally, SCFAs activated colonic NLRP6 inflammasome and increased DCX+ newborn neurons in the hippocampal DG of control mice. CONCLUSIONS: Our findings reveal that gut dysbiosis is a critical factor for a high-fructose diet-induced hippocampal neuroinflammation in C57BL/6N mice possibly mediated by impairing intestinal epithelial barrier. Mechanistically, the defective colonic NLRP6 inflammasome is responsible for intestinal epithelial barrier impairment. SCFAs can stimulate NLRP6 inflammasome and ameliorate the impairment of intestinal epithelial barrier, resulting in the protection against a high-fructose diet-induced hippocampal neuroinflammation and neuronal loss. This study addresses a gap in the understanding of neuronal injury associated with Western-style diets. A new intervention strategy for reducing the risk of neurodegenerative diseases through SCFAs supplementation or dietary fiber consumption is emphasized.

Effect of traditional Chinese medicine compounds on rumen fermentation, methanogenesis and microbial flora in vitro.

This study was conducted to investigate the effects of traditional Chinese medicine compounds (TCMC) on rumen fermentation, methane emission and populations of ruminal microbes using an in vitro gas production technique. Cablin patchouli herb (CPH), Atractylodes rhizome (AR), Amur Cork-tree (AC) and Cypsum were mixed with the weight ratios of 1:1:1:0.5 and 1:1:1:1 to make up TCMC1 and TCMC2, respectively. Both TCMC were added at level of 25 g/kg of substrate dry matter. In vitro gas production was recorded and methane concentration was determined at 12 and 24 h of incubation. After 24 h, the incubation was terminated and the inoculants were measured for pH, ammonia nitrogen, volatile fatty acids (VFA). Total deoxyribonucleic acid of ruminal microbes was extracted from the inocula, and populations were determined by a real-time quantitative polymerase chain reaction. Populations of total rumen methanogens, protozoa, total fungi, Ruminococcus albus, Fibrobacter succinogenes and Ruminococcus flavefaciens were expressed as a proportion of total rumen bacterial 16S ribosomal deoxyribonucleic acid. Compared with the control, the 2 TCMC decreased (P ≤ 0.05) total VFA concentration, acetate molar proportion, acetate to propionate ratio, gas and methane productions at 12 and 24 h, hydrogen (H) produced and consumed, and methanogens and total fungi populations, while the 2 TCMC increased (P ≤ 0.05) propionate molar proportion. Traditional Chinese medicine compound 1 also decreased (P ≤ 0.05) R. flavefaciens population. From the present study, it is inferred that there is an effect of the TCMC in suppressing methanogenesis, probably mediated via indirect mode by channeling H2 utilized for methanogenesis to synthesis of propionate and direct action against the rumen microbes involved in methane formation. In addition, the relative methane reduction potential (RMRP) of TCMC2 was superior to that of TCMC1.

Subsequent cooling-circulation after radiofrequency and microwave ablation avoids secondary indirect damage induced by residual thermal energy.

PURPOSE: We aimed to investigate the exact role of residual thermal energy following microwave ablation (MWA) and radiofrequency ablation (RFA) at the final ablation and transition zones and determine whether residual thermal energy could be dissipated by subsequent cooling-circulation. METHODS: In an ex vivo study, MWA and RFA were performed on fresh porcine liver, and central and border temperatures were compared. In an in vivo study, MWA and RFA were performed to the livers of New Zealand white rabbits. Tissue samples were stained with α-NADH-diaphorase. The coagulation zones (NADH-negative) and transition zones (lightly NADH-stained) of different groups were compared at different time points. RESULTS: In the ex vivo model, the residual thermal energy after MWA and RFA could be dispersed by subsequent cooling-circulation due to the temperature decreasing rapidly. In the in vivo study, the coagulation volume in the ablation group was larger than that in the cooling-circulation group (P < 0.05) 2 days after ablation. In the ablation group, the damaged zone (the transition zone plus the coagulation zone) on α-NADH-diaphorase-stained images increased rapidly within 2 hours after ablation and slowly reached the maximum on day 2. However, the damaged zones did not change significantly at the three time points observed in the cooling-circulation group. CONCLUSION: The residual thermal energy in MWA and RFA induced secondary damage beyond the direct coagulation zone, and it could be dissipated by subsequent cooling-circulation, contributing to smaller ablation and transition zones.

Chaihu-shugan san inhibits inflammatory response to improve insulin signaling in liver and prefrontal cortex of CUMS rats with glucose intolerance.

Depression is a mental illness comorbid risk factor for glucose intolerance worldwide. Chaihu-shugan san, a 'Shu-Gan' formula in traditional Chinese medicine, is clinically used in the treatment of depression. The aim of this study was to investigate whether Chaihu-shugan san improved glucose tolerance with its antidepressant activity in rat model of depression and explore the mechanisms underlying its action on liver-brain inflammation axis. After 6 weeks of chronic unpredictable mild stress (CUMS) procedure, male Wistar rats were given Chaihu-shugan san water extract (925 and 1850 mg/kg) by gavage for the next 6 consecutive weeks. Sucrose consumption test was used to assess animal depressive-like behaviors. Oral glucose tolerance test (OGTT) was employed to define the status of glucose tolerance in rats. Serum alanine aminotransferase (ALT) and interleukin-1 beta (IL-1ß) were measured by commercial kits, respectively. Western blot was used to detect the expression of key proteins in inflammatory signaling cascades including toll-like receptor 4 (TLR4), myeloid differentiation protein 88 (MyD88), nuclear factor-kappa B (NF-κB), Nod-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), cysteinyl aspartate specific proteinase-1 (Caspase-1) and IL-1ß, as well as insulin signaling in liver and prefrontal cortex of rats. Immunohistochemical staining or immunofluorescence staining of NF-κB, and nuclear/cytoplasmic ratio of NF-κB by Western blot were used to describe its nuclear entry in liver and prefrontal cortex of rats. RT-qPCR and Western blot analysis, as well as microRNA-155 (miR-155) mimic or inhibitor transfection were used to explore possible association of MyD88 and miR-155. In this study, Chaihu-shugan san increased sucrose consumption and reduced serum glucose levels in CUMS rats, showing its antidepressant activity with glucose tolerance improvement. Chaihu-shugan san reduced serum levels of ALT and IL-1ß in this animal model. Furthermore, this formula inhibited hepatic and prefrontal cortical inflammatory response by suppressing TLR4/MyD88/NF-κB pathway and NLRP3 inflammasome activation, and improved insulin signaling in CUMS rats. More importantly, Chaihu-shugan san up-regulated miR-155 expression in liver and prefrontal cortex of CUMS rats. These results provide direct evidence that Chaihushugan San can ameliorate depressive-like behaviors by inhibiting liver-brain inflammation axis.

1,25-Dihydroxy vitamin D prevents tumorigenesis by inhibiting oxidative stress and inducing tumor cellular senescence in mice.

Human epidemiological studies suggest that 1,25(OH)2 D3 deficiency might increase cancer incidence, but no spontaneous tumors have been reported in mice lacking 1,25(OH)2 D3 or deficient in its receptor. In our study, we detected, for the first time, diverse types of spontaneous tumors in l,25(OH)2 D3 deficient mice more than 1 year of age. This was associated with increased oxidative stress, cellular senescence and senescence-associated secretory phenotype molecules, such as hepatocyte growth factor, mediated via its receptor c-Met. Furthermore, 1,25(OH)2 D3 prevented spontaneous tumor development. We also demonstrated that l,25(OH)2 D3 deficiency accelerates allograft tumor initiation and growth by increasing oxidative stress and DNA damage, activating oncogenes, inactivating tumor suppressor genes, stimulating malignant cell proliferation and inhibiting their senescence; in contrast, supplementation with exogenous l,25(OH)2 D3 or antioxidant, or knock-down of the Bmi1 or c-Met oncogene, largely rescued the phenotypes of allograft tumors. Results from our study suggest that 1,25(OH)2 D3 deficiency enhances tumorigenesis by increasing malignant cell oxidative stress and DNA damage, stimulating microenvironmental cell senescence and a senescence-associated secretory phenotype, and activating oncogenes and inactivating tumor suppressor genes, thus increasing malignant cell proliferation. Our study provides direct evidence supporting the role of vitamin D deficiency in increasing cancer incidence. Conversely, 1,25(OH)2 D3 prevented spontaneous tumor development, suggesting that this inhibitory effect prevents the initiation and progression of tumorigenesis, thus provides a mechanistic basis for 1,25(OH)2 D3 to prevent tumorigenesis in an aging organism.

Histidine Regulates Seed Oil Deposition through Abscisic Acid Biosynthesis and ß-Oxidation.

The storage compounds are deposited into plant seeds during maturation. As the model oilseed species, Arabidopsis (Arabidopsis thaliana) has long been studied for seed oil deposition. However, the regulation of this process remains unclear. Through genetic screen with a seed oil body-specific reporter, we isolated low oil1 (loo1) mutant. LOO1 was mapped to HISTIDINE BIOSYNTHESIS NUMBER 1A (HISN1A). HISN1A catalyzes the first step of His biosynthesis. Oil significantly decreased, and conversely proteins markedly increased in hisn1a mutants, indicating that HISN1A regulates both oil accumulation and the oil-protein balance. HISN1A was predominantly expressed in embryos and root tips. Accordingly, the hisn1a mutants exhibited developmental phenotype especially of seeds and roots. Transcriptional profiling displayed that ß-oxidation was the major metabolic pathway downstream of HISN1A ß-Oxidation was induced in hisn1a mutants, whereas it was reduced in 35S:HISN1A-transgenic plants. In plants, seed storage oil is broken-down by ß-oxidation, which is controlled by abscisic acid (ABA). We found that His activated genes of ABA biosynthesis and correspondingly advanced ABA accumulation. Exogenous ABA rescued the defects of hisn1a mutants, whereas mutation of ABA DEFICIENT2, a key enzyme in ABA biosynthesis, blocked the effect of His on ß-oxidation, indicating that ABA mediates His regulation in ß-oxidation. Intriguingly, structural analysis showed that a potential His-binding domain was present in the general amino acid sensors GENERAL CONTROL NON-DEREPRESSIBLE2 and PII, suggesting that His may serve as a signal molecule. Taken together, our study reveals that His promotes plant seed oil deposition through ABA biosynthesis and ß-oxidation.

Aromatase expression increases the survival and malignancy of estrogen receptor positive breast cancer cells.

In postmenopausal women, local estrogen produced by adipose stromal cells in the breast is believed to support estrogen receptor alpha (ERα) positive breast cancer cell survival and growth. This raises the question of how the ERα positive metastatic breast cancer cells survive after they enter blood and lymph circulation, where estrogen level is very low in postmenopausal women. In this study, we show that the aromatase expression increased when ERα positive breast cancer cells were cultured in suspension. Furthermore, treatment with the aromatase substrate, testosterone, inhibited suspension culture-induced apoptosis whereas an aromatase inhibitor attenuated the effect of testosterone suggesting that suspended circulating ERα positive breast cancer cells may up-regulate intracrine estrogen activity for survival. Consistent with this notion, a moderate level of ectopic aromatase expression rendered a non-tumorigenic ERα positive breast cancer cell line not only tumorigenic but also metastatic in female nude mice without exogenous estrogen supplementation. The increased malignant phenotype was confirmed to be due to aromatase expression as the growth of orthotopic tumors regressed with systemic administration of an aromatase inhibitor. Thus, our study provides experimental evidence that aromatase plays an important role in the survival of metastatic ERα breast cancer cells by suppressing anoikis.

[Effect of Paidu Baoshen Pill on renal fibrosis in 5/6 nephrectomized rats].

OBJECTIVE: To observe the anti-renal fibrosis effect of Paidu Baoshen Pill (PBP) on 5/6 nephrectomized rats and to explore its mechanism. METHODS: Totally 50 SD male healthy rats were randomly divided into the normal control group (n = 10), the sham-operation group (n = 10), and the nephrectomy model group (n = 30) according to the proportion of 1:1:3. Rats in the sham-operation group had their renal capsule isolated without nephrectomy. Rats in the nephrectomy model group had their kidneys 5/6 nephrectomized. Then 24 h urine was collected and 24 h urinary protein (24 h UP) detected. Serum blood urea nitrogen (BUN) and serum creatitine (SCr) were also tested. According to the SCr level 30 rats of the model group were further randomly divided into the model group, the PBP group, and the Niaoduqing Granule (NG) group, 10 in each group. Rats in the PBP group and the NG group were respectively administered with PBP (at the daily dose of 1.0 g/kg) and NG (at the daily dose of 3.33 g/kg) by gastrogavage (they were dissolved in distilled water). At the same time, 2 mL distilled water was administered by gastrogavage to rats in the normal control group, the sham-operation group, and the nephrectomy model group, once daily for 4 successive weeks. Mental conditions, activities, hair color, shape of stool, and the body weight were observed during administration. After 4 weeks, urine was collected to detect 24 h UP. Blood was sampled to detect SCr, BUN, transforming growth factor ß1 (TGF-ß1), type III procollagen (PC III), collagen type IV (Col IV), laminin (LN), and fibronectin (FN). After rats were killed, their left remnant renal tissues were collected for pathological examinations. The protein expression quantity of TGF-ß1 and FN was detected by immunohistochemical method. mRNA expression levels of TGF-ß1 and FN were detected using real time fluorescent quantitative PCR. RESULTS: There was no statistical difference in the above indices between the normal control group and the sham-operation group (P > 0.05). Compared with the sham-operation group, rats' general condition was poorer in the model group, their body weight grew slower, and 24 h UP increased; serum levels of BUN, SCr, TGF-ß1, PC III, Col IV, LN, and FN increased; the residual renal pathological lesion was serious; expression levels of TGF-ß1, TGF-ß1, mRNA, FN, and FN mRNA increased in the renal tissue (all P < 0.01). Compared with the model group, rats' general condition was better, their body weight grew faster, 24 h UP reduced (P < 0.05), blood levels of BUN and SCr decreased significantly (P < 0.01), serum levels of TGF-ß1, PC III, CoL IV, LN, and FN decreased (P < 0.05, P < 0.01); the residual renal pathological lesion was attenuated in the PBP group and the NG group; expression levels of TGF-ß1, TGF-ß1, mRNA, FN, and FN mRNA decreased (P < 0.01). Compared with the NG group, blood levels of SCr and FN, and expression levels of FN and FN mRNA decreased more in the PBP group (P < 0.05). CONCLUSIONS: PBP had the effect of anti-renal fibro- sis in 5/6 nephrectomized rats. Down-regulating expression levels of TGF-ß1, and FN from gene transcription and protein translation levels might be one of its mechanisms.

Evaluation of the therapeutic efficacy of sequential therapy involving percutaneous microwave ablation in combination with 131I-hypericin using the VX2 rabbit breast solid tumor model.

PURPOSE: Combination of percutaneous microwave ablation (PMWA) and intravenous injection of 131I-hypericin(IIIH) may bear potential as a mini-invasive treatment for tumor. The objective of this study was to assess the effect of PMWA and IIIH in breast tumor growth. METHODS: Ten New Zealand White rabbits bearing VX2 breast carcinomas were randomly divided into two groups (each 5 examples) and processed using PMWA followed by IIIH and IIIH alone. The IIIH activity was evaluated using planar scintigraphy, autoradiography and biodistribution analysis. The maximum effective safe dose of IIIH was found through 48 rabbits with VX2 breast tumor, which were randomized into six groups (n=8 per group). Subsequently, a further 75 rabbits bearing VX2 breast solid tumors were randomly divided into five groups (each 15 examples) and treated as follows: A, no treatment group; B, PMWA alone; C, IIIH alone; D, PMWA+IIIH×1 (at 8 h post-PMWA); and E, PMWA+IIIH×2 (at 8 h and at 8 days post-PMWA). The therapeutic effect was assessed by measurement of tumor size and performation of positron emission tomography/computed tomograph (PET/CT) scans, liver and renal function tests and Kaplan-Meier survival analysis. RESULTS: The planar scintigraphy findings suggested a significant uptake of 131I in necrotic tumor tissue. The autoradiography gray scales indicated higher selective uptake of IIIH by necrotic tissue, with significant differences between the groups with and those without necrotic tumor tissue (P<0.05). The maximum effective safe dose of IIIH was 1 mCi/kg. The PET/CT scans and tumor size measurement suggested improvements in treatment groups at all time points (P<0.01). Significant differences were detected among Groups A, B, D and E (P<0.05). Lower levels of lung metastasis were detected in Groups D and E (P<0.05). There were no abnormalities in liver and renal functions tests or other reported side effects. CONCLUSION: IIIH exhibited selective uptake by necrotic tumor tissue. Sequential therapy involving PMWA+IIIH was successfully inhibiting tumor growth and prolonging survival.

Image and pathological changes after microwave ablation of breast cancer: a pilot study.

PURPOSE: To prospectively assess MR imaging evaluation of the ablation zone and pathological changes after microwave ablation (MWA) in breast cancer. MATERIALS AND METHODS: Twelve enrolled patients, diagnosed with non-operable locally advanced breast cancer (LABC), were treated by MWA and then neoadjuvant chemotherapy, followed by surgery. MR imaging was applied to evaluate the effect of MWA. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were applied to analyze the ablated area. RESULTS: All MWA procedures were performed successfully under local anesthesia. For a mean duration of 2.15 min, the mean largest, middle and smallest diameters in the ablated zone 24-h post-ablation in MR imaging were 2.98 cm ± 0.53, 2.51 cm ± 0.41 and 2.23 cm ± 0.41, respectively. The general shape of the ablation zone was close to a sphere. The ablated area became gradually smaller in MR imaging. No adverse effects related to MWA were noted in all 12 patients during and after MWA. HE staining could confirm the effect about 3 months after MWA, which was confirmed by TEM. CONCLUSIONS: 2 min MWA can cause an ablation zone with three diameters larger than 2 cm in breast cancer, which may be suitable for the local treatment of breast cancer up to 2 cm in largest diameter. However, the long-term effect of MWA in the treatment of small breast cancer should be determined in the future.

AduoLa Fuzhenglin down-regulates microwave-induced expression of ß1-adrenergic receptor and muscarinic type 2 acetylcholine receptor in myocardial cells of rats.

This paper is aimed to study the effect of ADL on expression of ß1-AR and M2-AchR in myocardial cells of rats exposed to microwave radiation. Immunohistochemistry, Western blot and image analysis were used to detect the expression of ß1-AR and M2-AchR in myocardial cells at 7 and 14 d after microwave exposure. The results show that the expression level was higher in microwave exposure group and 0.75 g/(kg•d) ADL group than in sham operation group and significantly lower in 1.5 and 3.0 g/(kg•d) ADL groups than in microwave group. So we have a conclusion that the expression of ß1-AR and M2-AchR is down-regulated in myocardial cells of rats exposed to microwave radiation. ADL can protect rats against microwave-induced heart tissue injury.