[Retracted] Isopsoralen­mediated suppression of bone marrow adiposity and attenuation of the adipogenic commitment of bone marrow­derived mesenchymal stem cells.

Following the publication of the above article, an interested reader drew to the authors' attention that Figs. 1C and 2 in the paper appeared to contain instances of duplicated data. The authors were able to consult their original data files, and realized that these figures had indeed been assembled incorrectly. Moreover, they identified further errors with a number of the other figures in their published formats (specifically, Figs. 3, 4, 6 and 7), and requested that a corrigendum be published to take account of all the errors that were made during the compilation of these figures. The Editor of International Journal of Molecular Medicine has considered the authors' request to publish a corrigendum, but has declined this request on account of the large number of errors that have been identified, and subsequently determined that this article should be retracted from the Journal on the basis of an overall lack of confidence in the presented data. Upon receiving this decision from the Editor, the authors were in agreement that the article should be retracted. The Editor apologizes to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 39: 527­538, 2017; DOI: 10.3892/ijmm.2017.2880].

Transcriptome analysis reveals the underlying mechanism of heptanal against Aspergillus flavus spore germination.

Methods of controlling Aspergillus flavus contamination in agro-products have attracted attention because of its impact on global food security. We previously reported that the natural cereal volatile heptanal could effectively inhibit A. flavus growth and showed great potential as a bio-preservative agent. In this study, the minimum inhibitory concentration and minimum fungicide concentration of heptanal could change the surface morphology of A. flavus spores, causing them to wrinkle and collapse. Transcriptomic analysis showed that heptanal treatment significantly changed the expression of several genes involved in cell wall and plasma damage, reactive oxygen species (ROS) accumulation, energy metabolism, AMPK-activated protein kinase, biosynthesis of unsaturated fatty acids, RNA degradation, and DNA replication. Heptanal-induced early apoptosis of A. flavus spores was characterized by decreased mitochondrial membrane potential, increased intracellular ROS production, and DNA fragmentation. This study provides new insight into the inhibitory mechanism of heptanal against A. flavus and points to its potential application as a bio-preservative. KEY POINTS: • Heptanal can effectively inhibit A. flavus growth in cereal grains. • The transcriptional changes in A. flavus spores exposed to heptanal were analyzed. • The antifungal mechanism of heptanal against A. flavus was elucidated.

Antifungal mechanism of 1-nonanol against Aspergillus flavus growth revealed by metabolomic analyses.

Chemical control of fungal spoilage of postharvest cereal grains is an important strategy for the management of grain storage. Here, the potential antifungal activity of 1-nonanol, a main component of cereal volatiles, against Aspergillus flavus was studied. The growth of A. flavus was completely inhibited by 0.11 and 0.20 µL/mL 1-nonanol at vapor and liquid contact phases, respectively. Metabolomic analysis identified 135 metabolites whose expression was significantly different between 1-nonanol-treated and untreated A. flavus. These metabolites were involved in the tricarboxylic acid cycle, amino acid biosynthesis, protein degradation and absorption, aminoacyl-tRNA biosynthesis, mineral absorption, and in interactions with ABC transporters. Biochemical validation confirmed the disruptive effect of 1-nonanol on A. flavus growth, as indicated by the leakage of intracellular electrolytes, decreased succinate dehydrogenase, mitochondrial dehydrogenase, and ATPase activity, and the accumulation of reactive oxygen species. We speculated that 1-nonanol could disrupt cell membrane integrity and mitochondrial function and might induce apoptosis of A. flavus mycelia. Simulated grain storage experiments showed that 1-nonanol vapor, at a concentration of 264 µL/L, completely inhibited A. flavus growth in wheat, corn, and paddy grain with an 18% moisture content. This study provides new insights into the antifungal mechanism of 1-nonanol against A. flavus, indicating that it has a promising potential as a bio-preservative to prevent fungal spoilage of postharvest grains. KEY POINTS: • 1-Nonanol showed higher antifungal activity against A. flavus. • The antifungal mechanisms of 1-nonanol against A. flavus were revealed. • 1-Nonanol could damage cell membrane integrity and mitochondrial function.

Hexanal induces early apoptosis of Aspergillus flavus conidia by disrupting mitochondrial function and expression of key genes.

Aspergillus flavus is a notorious saprophytic fungus that compromises the quantity and quality of postharvest grains and produces carcinogenic aflatoxins. The natural compound hexanal disrupts cell membrane synthesis and mitochondrial function and induces apoptosis in A. flavus; here, we investigated the molecular mechanisms underlying these effects. The minimum inhibition and fungicidal concentration (MIC and MFC) of hexanal against A. flavus spores were 3.2 and 9.6 µL/mL, respectively. Hexanal exposure resulted in abnormal spore morphology and early spore apoptosis. These changes were accompanied by increased reactive oxygen species production, reduced mitochondrial membrane potential, and DNA fragmentation. Transcriptomic analysis revealed that hexanal treatment greatly altered the metabolism of A. flavus spores, including membrane permeability, mitochondrial function, energy metabolism, DNA replication, oxidative stress, and autophagy. This study provides novel insights into the mechanism underlying the antifungal activity of hexanal, suggesting that hexanal can be used an anti-A. flavus agent for agricultural applications. KEY POINTS: • Hexanal exposure resulted in abnormal spore morphology. • The apoptotic characteristics of A. flavus were induced after hexanal treatment. • Hexanal could change the expression of key A. flavus growth-related genes.

Metabolomic analyses revealed multifaceted effects of hexanal on Aspergillus flavus growth.

Hexanal, a natural volatile organic compound, exerts antifungal activity against Aspergillus flavus; however, the mechanisms underlying these effects are unclear. In this study, we found that the growth of A. flavus mycelium was completely inhibited following exposure to 0.4 µL/mL hexanal (minimal inhibitory concentration). A detailed metabolomics survey was performed to identify changes in metabolite production by A. flavus cells after exposure to 1/2 the minimal inhibitory concentration of hexanal for 6 h, which revealed significant differences in 70 metabolites, including 20 upregulated and 50 downregulated metabolites. Among them, levels of L-malic acid, α-linolenic acid, phosphatidylcholine, D-ribose, riboflavin, D-mannitol, D-sorbitol, and deoxyinosine were significantly reduced. The metabolomics results suggest that the metabolites are mainly involved in the tricarboxylic acid cycle (TCA), ABC transport system, and membrane synthesis in A. flavus cells. Hexanal treatment reduced succinate dehydrogenase and mitochondrial dehydrogenase activity and stimulated superoxide anion and hydrogen peroxide accumulation in A. flavus mycelia. Increases in the electric conductivity and A260nm of the culture supernatant indicated cell membrane leakage. Therefore, hexanal appears to disrupt cell membrane synthesis, induce mitochondrial dysfunction, and increase oxidative stress in A. flavus mycelia. KEY POINTS: • Metabolite changes of A. flavus mycelia were identified after hexanal treatment. • Most differential metabolites were downregulated in hexanal-treated A. flavus. • An antifungal model of hexanal against A. flavus was proposed.

[Non-structural carbohydrate content of trees and its influencing factors at multiple spatial-temporal scales: A review]. / æ ‘æœ¨éžç»“æž„æ€§ç¢³æ°´åŒ–åˆç‰©å«é‡å¤šæ—¶ç©ºå°ºåº¦å˜åŒ–ç‰¹å¾åŠå ¶å½±å“å› ç´ ç ”ç©¶è¿›å±•.

Non-structural carbohydrates (NSC) are essential substances for the tree growth and metabolism, and play an important role in environmental adaptation of trees. At temporal scale, NSC contents in trees have limited inter-annual variation, which could be attributed to the strategy of tree growth and carbon storage. Different factors influence NSC contents of trees in various climatic regions, which change substantially at the seasonal scale. At spatial scale, the variations of NSC content in trees show an insignificantly decreasing trend with the decreases of latitude at global and continental scales, which are mainly related to the hydrothermal gradients. The trend at regional scale is opposite because of the decrease of hydrothermal gradients and lower sample frequency. More sophisticated relations exist between the variations of NSC content in trees and altitudes, which are caused by species-specific characteristics and the variations of micro-habitat conditions. The variations of NSC content in trees at multiple spatial-temporal scales are generally determined by both biotic and abiotic factors, which are mainly dependent on the tradeoff among photosynthate production, respiratory depletion, and tree growth. Furthermore, the methods used for the determination of NSC content are different, which results in great uncertainties in comparing conclusions from different studies. The methods used for sample collection and measurement of NSC should be improved and unified to enhance the comparison among different studies. The NSC contents of trees in different age classes should be measured with all organs collected at multiple spatial-temporal scales. The underlying mechanisms, significance of NSC storage, transformation and allocation on tree growth and survival should be further discussed.

[Tree seedling distribution, regeneration mechanism and response to climate change in alpine treeline ecotone]. / é«˜å±±æž—çº¿ç”Ÿæ€äº¤é”™åŒºæœ¨æœ¬æ¤ç‰©å¹¼è‹—åˆ†å¸ƒç‰¹å¾ã€æ›´æ–°æœºåˆ¶åŠå ¶å¯¹æ°”å€™å˜åŒ–çš„å“åº”.

Tree seedlings are one of the important components in alpine treeline ecotone, whose regeneration is crucial to treeline migration in response to climate change. We analyzed the spatial distribution, regeneration of tree seedlings and their responses to climate change in treeline ecotone in recent decades. The spatial distribution of tree seedlings in treeline ecotone is dominated by diffuse and clustered forms, with different indicative significance for spatial dynamics of treeline. At global scale, the altitude distribution limits of tree seedlings are usually related to the length and average temperature of growing season, along with the species characteristics. However, precipita-tion plays an important role at regional scale. The initial stage of seedling recruitment is restricted by seed source, which determines seed distribution and germination to a great extent. Microenvironment facilitates seedling regeneration by providing shelter for establishment and improving their survival rate. The regeneration process is more relevant to multiple biotic, abiotic factors and their interactions. With global warming, rising temperature in treeline ecotone and more precipitation are more suitable for seedling regeneration of treeline species. The expansion of seedlings to higher elevations could be considered as the portent of timberline upwards migration. Due to species-specific adaption strategy, however, some trees only increase seedling density and timberline location is constant. In the future, it is necessary to take precise dating techniques, such as tree-ring and 14C dating, and conduct long-term in-situ monitoring and indoor simulation experiments. To provide scientific basis for mountain ecosystem restoration and conservation, we should strengthen the studies on spatial patterns and regeneration mechanism of seedlings in treeline ecotone at multiple spatio-temporal scales, the adaptation strategies of tree seedlings in different types of treeline ecotone and treeline dynamics prediction.

N-(3-methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide promotes bone formation via the canonical Wnt/ß-catenin signaling pathway.

Osteoporosis is characterized by low bone mineral density and microarchitectural deterioration of bone tissue. N-(3-methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide (MBOC) is one of the macamides isolated from Maca (Lepidium meyenii Walp.), a cruciferous plant from the Andes of Peru. In this study, C3H/10T1/2 mesenchymal stem cells were treated with MBOC in osteogenic induction medium. An ovariectomized (OVX) mouse model was used to investigate the effect of 1-month MBOC treatment on the prevention of postmenopausal osteoporosis. Remarkably, trabecular thickness, trabecular number, and bone volume/tissue volume of the distal femoral metaphysis were significantly increased in OVX + MBOC mice compared with OVX mice, as revealed by microcomputed tomography analysis. Trabecular separation was decreased in OVX + MBOC mice compared with OVX mice. Consistently, MBOC increased the levels of osteocalcin and runt-related transcription factor 2 in OVX mice, as well as the expression of runt-related transcription factor 2, osterix, and alkaline phosphatase in C3H/10T1/2 cells. Mechanistically, MBOC activates the canonical Wnt/ß-catenin signaling pathway via inhibiting phosphorylation of GSK-3ß at Tyr216 and maintaining ß-catenin expression. Collectively, the current study demonstrates the robustness of MBOC in the induction of mesenchymal stem cells osteogenic differentiation and consequent bone formation, suggesting that MBOC may be a potentially effective drug to treat postmenopausal osteoporosis.

Relationship between Renalase Expression and Kidney Disease: an Observational Study in 72 Patients Undergoing Renal Biopsy.

The relationship between the levels of renalase and changes in proteinuria, hypertension, renal function, renal tubular epithelial cell apoptosis and B-cell lymphoma-2 (Bcl-2) expression was investigated in patients (chronic nephritis, primary nephrotic syndrome or other kidney disease) that underwent renal biopsy. The study group comprised 72 patients undergoing renal biopsy. Patient profiles and renal function were collected. Concentrations of renalase and Bcl-2 were measured by immunohistochemistry. Tubular injury was detected by periodic acid Schiff staining (PAS) and renal tubular epithelial cell apoptosis was assessed by TUNEL assay. The expression of renalase was significantly lower in renal biopsy specimens than in normal kidney tissues. There was a positive linear relationship between renalase and some serum and cardiac indices; a negative correlation was found between age, eGFR, Ccr and 24-h urinary protein. Renal tubule injury index and tubular epithelial cell apoptosis index showed a negative linear correlation with renalase. The results showed that renalase probably increased the expression of Bcl-2. By two independent samples t-test, renalase levels were significantly increased in the non-hypertension group than in the hypertension group. One-way ANOVA showed that renalase expression was higher in samples with Lee's grade III than in those with Lee's grade V. The expression of renalase was significantly decreased in patients who underwent renal biopsy, and was also associated with blood and renal function. The research proved that renalase may reduce renal tubular injury and apoptosis of renal tubular epithelial cells through the mitochondrial apoptosis pathway, finally achieving the purpose of delaying the progress of renal failure.

Risk factors for osteoporosis in liver cirrhosis patients measured by transient elastography.

Osteoporosis or osteopenia is a common complication in patients with cirrhosis, but little is known about the risk factors for the occurrence of osteoporosis.Patients with liver cirrhosis due to chronic virus infection and alcoholic abuse were enrolled. Bone mineral density (BMD) was determined using dual-energy x-ray absorptiometry (DXA). Osteoporosis was diagnosed according to WHO criteria. The severity of liver stiffness was measured by Fibroscan. Demographic data, such as age, gender, weight, height, and body mass index (BMI), were collected. Logistic regression analysis was used to recognize the risk factors of osteoporosis in patients with cirrhosis.A total of 446 patients were included in this study: 217 had liver cirrhosis (male, 74.2%; mean age, 57.2 ±â€Š10.27) and 229 were matched controls (male, 69%, mean age, 56.69 ±â€Š9.37). Osteoporosis was found in 44 patients (44/217, 20.3%). The spine and hip BMD in cirrhotic patients were significantly lower than that in controls. When the cirrhotic and control subjects were stratified by age, gender, and BMI, the significant difference was also observed in women patients, patients older than 60, and patients with BMI < 18. Multivariate analysis showed that the older age [odds ratio (OR) = 1.78, P = .046], lower BMI (OR = 0.63, P = .049), greater fibroscan score (OR = 1.15, P = .009), and liver cirrhosis induced by alcohol liver disease (OR = 3.42, P < .001) were independently associated with osteoporosis in cirrhotic patients.Osteoporosis occurred in about one-fifth of patients with liver cirrhosis, which was associated with age, BMI, Fibroscan score, and alcohol liver disease related liver cirrhosis.

Leptocarpin Suppresses Proliferation, Migration, and Invasion of Human Osteosarcoma by Targeting Type-1 Insulin-Like Growth Factor Receptor (IGF-1R).

BACKGROUND Leptocarpin (LTC) has drawn much attention for suppressing tumor growth or reducing inflammation. However, the effect of LTC on osteosarcoma has rarely been reported. Our object was to determine whether LTC suppresses MG63 cell proliferation, migration, and invasion, and whether type-1 insulin-like growth factor receptor (IGF-1R) is one of the targets in LTC suppressing osteosarcoma. MATERIAL AND METHODS Cytotoxicity of LTC was performed by use of a cell-counting kit-8 (CCK-8). RNA interference (RNAi) or pEABE-bleo IGF-1R plasmid were used for silencing or overexpressing IGF-1R, Western blot (WB) analysis was used for IGF-1R expression, CCK-8 for proliferation, and transwell assay for migration and invasion. RESULTS LTC (23.533 µM) treatment for 48 h was taken as the 50% inhibiting concentration (IC50), which significantly (P<0.05) suppressed MG63 cells proliferation, migration, and invasion. LTC (IC50) obviously inhibited IGF-1R expression in MG63 cells, with similar effect to small interfering RNA (siRNA), while pEABE-bleo IGF-1R transfection overexpressed IGF-1R. siRNA silencing IGF-1R suppressed MG63 cells proliferation, migration, and invasion, while pEABE-bleo IGF-1R transfection was significantly (P<0.05) promoted. With or without siRNA or pEABE-bleo IGF-1R transfection, LTC (IC50) suppressed MG63 cells proliferation, migration, and invasion. The effect of LTC (IC50) combined with siRNA on suppressing MG63 cells proliferation, migration, and invasion was more obvious, while the effect of LTC (IC50) combined with pEABE-bleo IGF-1R transfection was less significant (P<0.05). CONCLUSIONS LTC suppressed osteosarcoma proliferation, migration, and invasion by inhibiting IGF-1R expression. IGF-1R is one of the targets in LTC suppressing osteosarcoma.

Isopsoralen-mediated suppression of bone marrow adiposity and attenuation of the adipogenic commitment of bone marrow-derived mesenchymal stem cells.

Osteoporosis (OP) increases the risk of bone fractures and other complications, and is thus a major clinical problem. In this study, we examined the effect of isopsoralen on the differentiation of bone-derived marrow mesenchymal stem cells (BMSCs) into osteoblasts and adipocytes, as well as bone formation under osteoporotic conditions. Primary femoral BMSCs isolated from C57BL/6 mice were used to evaluate the isopsoralen-mediated regulation of the expression of alkaline phosphatase (ALP), osteocalcin (OCN) and runt-related transcription factor 2 (RUNX2) during osteogenesis 2 weeks. We also examined the expression of peroxisome proliferator-activated receptor Î³ (PPARγ) and CCAAT/enhancer binding protein ß (C/EBPß) under adipogenic conditions for 1 and 2 weeks. In addition, ovariectomized (OVX) mice were used to examine the effects of isopsoralen on bone formation for 2 months. Finally, mammalian target of rapamycin complex 1 (mTORC1) signaling was examined under osteogenic and adipogenic conditions. We found that following treatment with isopsoralen, the expression levels of ALP, OCN and RUNX2 were upregulated, whereas those of PPARγ and C/EBPß were downregulated. mTORC1 signaling was also inhibited in vitro and in vivo. In the OVX mice that were intragastrically administered isopsoralen, bone parameters (trabecular thickness, bone volume/total volume and trabecular number) in the distal femoral metaphysis were significantly increased and the adipocyte number was decreased. On the whole, our findings demonstrate that isopsoralen promoted BMSC differentiation into osteoblasts and suppressed differentiation into adipocytes.

Tenuigenin promotes the osteogenic differentiation of bone mesenchymal stem cells in vitro and in vivo.

Osteoporosis, which is a systemic skeletal disease characterized by low bone mineral density and microarchitectural deterioration of bone quality, is a global and increasing public health problem. Recent studies have suggested that Tenuigenin (TEN), a class of native compounds with numerous biological activities such as anti-resorptive properties, exerts protective effects against postmenopausal bone loss. The present study aims to investigate the osteogenic effects of TEN on bone mesenchymal stem cells (BMSCs) in vitro and in vivo. Alkaline phosphatase (ALP) activity/staining, Alizarin red staining and the expression of osteogenic markers, including runt-related transcription factor 2, osterix, osteocalcin, collagen Iα1, ß-catenin and glycogen synthase kinase-3ß were investigated in primary femoral BMSCs from C57/BL6 mice cultured under osteogenic conditions for 2 weeks to examine the effects of TEN. An ovariectomized (OVX) mouse model was used to investigate the effect of TEN treatment for 3 months in vivo. We found that ALP activity, mineralized nodules and the expression of osteogenic markers were increased and WNT/ß-catenin signaling was enhanced in vitro and in vivo. Bone parameters, including trabecular thickness, trabecular number and bone mineral density were higher in the OVX+TEN group than in control OVX mice. Our results suggest the therapeutic potential of TEN for the treatment of patients with postmenopausal osteoporosis.

Autophagy Promotes Peripheral Nerve Regeneration and Motor Recovery Following Sciatic Nerve Crush Injury in Rats.

Autophagy maintains cellular homeostasis by stimulating the lysosomal degradation of cytoplasmic structures, including damaged organelles and dysfunctional proteins. The role of autophagy in the renewal and regeneration of injured peripheral nerves remains poorly understood. The current study investigated the role of autophagy in peripheral nerve regeneration and motor function recovery following sciatic nerve crush injury in rats by stimulating or suppressing autophagy and detecting the presence of autophagosomes and LC3-II expression by electron microscopy and Western blotting, respectively. Neurobehavioral function was tested by CatWalk gait analysis 1, 2, 3, and 6 weeks after injury, and the expression of neurofilament (NF)-200 and myelin basic protein (MBP) at the injury site was examined by immunocytochemistry. Apoptosis at the lesion site was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Treatment of injured rats with the autophagy inducer rapamycin increased the number of autophagosomes and LC3-II expression while reducing the number of apoptotic cells at the lesion; this was associated with an upregulation of MBP and NF-200 expression and increased motor function recovery as compared to sham-operated rats and those that were subjected to crush injury but untreated. The opposite effects were observed in rats treated with the autophagy inhibitor 3-methyladenine. These data indicate that the modulation of autophagy in peripheral nerve injury could be an effective pharmacological approach to promote nerve regeneration and reestablish motor function.

[Feeding habits of Solenocera melantho in the northern East China Sea.] / 东海北部大管鞭虾的食性.

The feeding habits of the mud shrimp Solenocera melantho were determined based on the analysis of 720 stomach contents sampled in the northern East China Sea during June 2009 and May 2010. The diet of the specimens was studied in relation to the season, sex, size class and reproductive condition. The diet of S. melantho consisted of 43 different prey categories, which belonged to small crustaceans, protozoa, polychaetes, algae, fishes and molluscs. Among these, crustaceans, foraminifera and polychaetes made up the main diet of S. melantho with 34.7%, 29.4% and 12.4% in abundance, respectively. Diet composition showed seasonal fluctuation and ontogenetic change. The predominant prey was foraminifera, algae and invertebrate eggs in spring, foraminifera, fishes and polychaetes in summer and autumn, and polychaetes and foraminifera in winter. The feeding intensity was high in spring and summer, and low in autumn. The small size group (<24 mm CL) tended to like foraminifera and algae, while the large size group (≥24 mm CL) preferred polychaetes and crustaceans. Females with advanced ovaries also displayed low stomach fullness, suggesting that feeding activity was affected by the reproductive cycle. S. melantho displayed a high food niche in both sexes and each season, which could be attributed to the fluctuations in available resources. The average trophic level of the S. melantho in four seasons was 2.67, indicating that the species in the northern East China Sea was of low-level carnivores.

Regulation of bone formation by baicalein via the mTORC1 pathway.

Osteoporosis is a systemic skeletal disease that is characterized by low bone density and microarchitectural deterioration of bone tissue. The increasing prevalence of osteoporosis has attracted much attention. In this study, MC3T3-E1 pre-osteoblasts were treated with the natural compound, baicalein (0.1 µmol/L, 1 µmol/L, 10 µmol/L), to stimulate differentiation over a 14-day period. In addition, a canonical ovariectomized (OVX) mouse model was used to investigate the effect of 3-month baicalein treatment (10 mg/kg per day) in preventing postmenopausal osteoporosis. In vitro, we found that baicalein induced activation of alkaline phosphatase, stimulated the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, and induced expression of osteoblast differentiation markers, ie, osteocalcin, osterix, collagen Iα1, and runt-related transcription factor 2 (RUNX2), in osteoblasts. In vivo, several bone parameters, including trabecular thickness, trabecular bone mineral density, and trabecular number, in the distal femoral metaphysis were significantly increased in OVX mice treated intragastrically with baicalein for 3 months compared with OVX mice that were not treated with baicalein. We also found that expression of osteocalcin and RUNX2 was decreased in primary ossified tissue from the OVX group, and baicalein increased the levels of osteocalcin and RUNX2 in OVX mice. These data suggest that baicalein can stimulate MC3T3-E1 cells to differentiate into osteoblasts via activation of the mTORC1 signaling pathway, which includes protein kinases and transcription factors such as P-4E/BP1 and P-S6K1.

Enhancement of the synthesis of n-3 PUFAs in fat-1 transgenic mice inhibits mTORC1 signalling and delays surgically induced osteoarthritis in comparison with wild-type mice.

BACKGROUND: An exogenous supplement of n-3 polyunsaturated fatty acids (PUFAs) has been reported to prevent osteoarthritis (OA) through undefined mechanisms. OBJECTIVE: This study investigated the effect of alterations in the composition of endogenous PUFAs on OA, and associations of PUFAs with mammalian target of rapamycin complex 1 (mTORC1) signalling, a critical autophagy pathway in fat-1 transgenic (TG) mice. METHODS: fat-1 TG and wild-type mice were used to create an OA model by resecting the medial meniscus. The composition of the endogenous PUFAs in mouse tissues was analysed by gas chromatography, and the incidence of OA was evaluated by micro-computed tomography (micro-CT), scanning electron microscopy and histological methods. Additionally, primary chondrocytes were isolated and cultured. The effect of exogenous and endogenous PUFAs on mTORC1 activity and autophagy in chondrocytes was assessed. RESULTS: The composition of endogenous PUFAs of TG mice was optimised both by increased n-3 PUFAs and decreased n-6 PUFAs, which significantly alleviated the articular cartilage destruction and osteophytosis in the OA model (p<0.01), decreased protein expression of matrix metalloproteinase-13 (MMP-13) and ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs) in the articular cartilage (p<0.01) and reduced chondrocyte number and loss of cartilage extracellular matrix. Both exogenous and endogenous n-3 PUFAs downregulated mTORC1 activity and promoted autophagy in articular chondrocytes. Conversely, mTORC1 pathway activation suppressed autophagy in articular chondrocytes. CONCLUSIONS: Enhancement of the synthesis of endogenous n-3 PUFAs from n-6 PUFAs can delay the incidence of OA, probably through inhibition of mTORC1, promotion of autophagy and cell survival in cartilage chondrocytes. Future investigation into the role of the endogenous n-6/n-3 PUFAs composition in OA prevention and treatment is warranted.

[Utilization and management of Trichiurus japonicus resources in East China Sea based on Beverton-Holt model].

In this paper, the population structure of Trichiurus japonicus in East China Sea was analyzed based on the data of its age composition and anus length in 2002-2004, and the rational utilization of T. japonicus resources in the Sea was approached by using the catch (in mass) per recruit theory of Beverton-Holt model. The results revealed that: (1) there was a miniaturization trend of the T. japonicus population in East China Sea. The range of age composition changed from 0-6 year in the late 1950's to 0-4 year in the early 21st century, and the population was dominated by the group of 0-1 year now. The percentage of 2-year old T. japonicus decreased from 12.84% in the late 1950s' to 6.91% in the early 21st century, and that of 3-year old T. japonicus decreased from 4.92% in the late 1950s' to 0.57% in the early 21st century; (2) the exploitation rate of T. japonicus in the period of 2000-2003 was 0.864, which was beyond of the optimum exploitation rate of 0.51, suggesting that the T. japonicus in East China Sea was under over-fishing; and (3) to enhance the age value at first capture (t(c)) was the best measure of increasing the catch (in mass) per recruit of T. japonicus. The age at recruitment (t(r)) and the t(c) of T. japonicus in East China Sea was 0. 25 and 0.5 at present, respectively. If the t(c) changed from 0.5 to 1, the unit catch would be increased by 55.38%, and if the t(c) changed to 1.5, 2 or 2.75, it would be increased by 100.81%, 130.52% or 145.23%, respectively. It was suggested that due to the difficulties in greatly reducing catching intensity, it could be available to properly increase the to value while decrease the catching intensity to protect the T. japonicus resources in East China Sea and realize their sustainable use.