Genomic and transcriptional heterogeneity of multifocal hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) often presents with multiple nodules within the liver, with limited effective interventions. The high genetic heterogeneity of HCC might be the major cause of treatment failure. We aimed to characterize genomic heterogeneity, infer clonal evolution, investigate RNA expression pattern and explore tumour immune microenvironment profile of multifocal HCC. PATIENTS AND METHODS: Whole-exome sequencing and RNA sequencing were carried out in 34 tumours and 6 adjacent normal liver tissue samples from 6 multifocal HCC patients. Protein expression of Ki67, AFP, P53, Survivin and CD8 was detected by immunohistochemistry. Fluorescence in situ hybridization was carried out to validate the amplification status of sorafenib-targeted genes. RESULTS: We deciphered genomic and transcriptional heterogeneity among tumours in each multifocal HCC patient including mutational profiles, copy number alterations, tumour evolutionary trajectory and tumour immune microenvironment profiles. Of note, sorafenib-targeted alterations were identified in the trunk of phylogenetic tree in only one out of the six patients, which may explain the relative low treatment response rate to sorafenib in clinical practice. Moreover, we demonstrated RNA expression patterns and tumour immune microenvironment profiles of all nodules. We found that RNA expression pattern was associated with Edmondson-Steiner grading. Based on the differential expression of 66 reported immune markers, unsupervised hierarchical clustering analysis of 34 nodules identified immune subsets: one low expression cluster with seven nodules and one high expression cluster with 11 nodules. CD8+ T cells were more enriched in nodules of the high expression cluster. CONCLUSIONS: Our study provided a detailed view of genomic and transcriptional heterogeneity, clonal evolution and immune infiltration of multifocal HCC. The heterogeneity of druggable targets and immune landscape might help interpret the clinical responsiveness to targeted drugs and immunotherapy for multifocal HCC patients.

Effects of constant and fluctuating temperature on the development of the oriental fruit moth, Grapholita molesta (Lepidoptera: Tortricidae).

The oriental fruit moth, Grapholita molesta, is an important pest in many commercial orchards including apple, pear and peach orchards, and responsible for substantial economic losses every year. To help in attaining a comprehensive and thorough understanding of the ecological tolerances of G. molesta, we collected life history data of individuals reared on apples under different constant temperature regimes and compared the data with moths reared under a variable outdoor temperature environment. Because G. molesta individuals reared at a constant 25°C had the heaviest pupal weight, the highest survival rate from egg to adult, highest finite rate of increase, and greatest fecundity, 25°C was considered as the optimum developmental temperature. The G. molesta population reared at a constant 31°C had the shortest development time, lowest survival rate and fecundity, resulting in population parameters of r < 0, λ < 1, lead to negative population growth. The population parameters r and λ reared under fluctuating temperature were higher than that reared under constant temperatures, the mean generation time (T) was shorter than it was in all of the constant temperatures treatments. This would imply that the outdoor G. molesta population would have a higher population growth potential and faster growth rate than indoor populations raised at constant temperatures. G. molesta moths reared under fluctuating temperature also had a higher fertility than moths reared under constant temperatures (except at 25°C). Our findings indicated that the population raised under outdoor fluctuating temperature conditions had strong environment adaptiveness.

Molecular cloning and characterization of a chlorophyll degradation regulatory gene (ZjSGR) from Zoysia japonica.

The stay-green gene (SGR) is a key regulatory factor for chlorophyll degradation and senescence. However, to date, little is known about SGR in Zoysia japonica. In this study, ZjSGR was cloned, using rapid amplification of cDNA ends-polymerase chain reaction (PCR). The target sequence is 831 bp in length, corresponding to 276 amino acids. Protein BLAST results showed that ZjSGR belongs to the stay-green superfamily. A phylogenetic analysis implied that ZjSGR is most closely related to ZmSGR1. The subcellular localization of ZjSGR was investigated, using an Agrobacterium-mediated transient expression assay in Nicotiana benthamiana. Our results demonstrated that ZjSGR protein is localized in the chloroplasts. Quantitative real time PCR was carried out to investigate the expression characteristics of ZjSGR. The expression level of ZjSGR was found to be highest in leaves, and could be strongly induced by natural senescence, darkness, abscisic acid (ABA), and methyl jasmonate treatment. Moreover, an in vivo function analysis indicated that transient overexpression of ZjSGR could accelerate chlorophyll degradation, up-regulate the expression of SAG113, and activate ABA biosynthesis. Taken together, these results provide evidence that ZjSGR could play an important regulatory role in leaf chlorophyll degradation and senescence in plants at the molecular level.

Photoperiod regulates the differential expression of KiSS-1 and GPR54 in various tissues and sexes of striped hamster.

In order to investigate how photoperiod affects the expression of KiSS-1/G-protein-coupled receptor 54 (GPR54), the hypothalamus, the ovaries and testicles of the striped hamster were studied following photoperiod treatment and melatonin injection. We found that the melatonin concentration in the blood of the striped hamster was consistent with the treated photoperiods and that the photoperiod had significant effects on KiSS-1 expression, but the effect of photoperiod on GPR54 expression differed among tissues and sexes. The relative expression of KiSS-1 in the gonads of the male and female striped hamster was significantly higher than that in the hypothalamus, while the difference in GPR54 between the gonads and hypothalamus was inconsistent between the male and female striped hamster. In the striped hamster injected with melatonin, the expression level of KiSS-1 in the gonads and hypothalamus of the male and female striped hamster was significantly decreased; the expression level of GnRH in the gonads was also significantly decreased; the expression of GPR54 in the hypothalamus was increased. In the hypothalamus, a significant positive correlation existed between KiSS-1 and GnRH expression, while a negative correlation was observed between GPR54 and GnRH expression. These results suggest that the photoperiod-melatonin-KiSS-1-GnRH pathway plays an important role in the seasonal reproduction mechanism of the striped hamster. Additionally, photoperiod or melatonin may not be a direct regulatory factor of GPR54 expression.

Relationship between vitamin D (1,25-dihydroxyvitamin D3) receptor gene polymorphisms and primary biliary cirrhosis risk: a meta-analysis.

The vitamin D (1,25-dihydroxyvitamin D3) receptor (VDR) gene encodes a protein that functions in the transcriptional regulation of vitamin D-responsive genes and plays a role in innate immunity and adaptive immune responses. In this study, we investigated the relationship between VDR polymorphisms (BsmI, ApaI, and TaqI) and primary biliary cirrhosis (PBC) risk. We conducted an overall meta-analysis and subgroup meta-analysis based on ethnicity that included a total of 6 eligible studies (672 cases and 1148 controls). We detected no significant PBC risk variation for all genetic models in the overall analysis and in the subgroup analysis based on ethnicity for the BsmI polymorphism. For the ApaI polymorphism, significant associations were observed in the overall analysis as well as in the Asian subgroup. Furthermore, in the subgroup analysis based on ethnicity, a significant association was observed in the Caucasian subgroup but not in the Asian subgroup for the TaqI polymorphism. Based on the results of our meta-analysis, the VDR BsmI polymorphism may not be associated with PBC risk, while the VDR ApaI polymorphism is likely associated with PBC risk, particularly in Asians. The VDR TaqI polymorphism may be associated with PBC risk in Caucasians.

Association between alcohol dehydrogenase 1C gene *1/*2 polymorphism and pancreatitis risk: a meta-analysis.

Numerous studies have focused on the relationship be-tween alcohol dehydrogenase 1C gene (ADH1C) *1/*2 polymorphism (Ile350Val, rs698, also known as ADH1C *1/*2) and pancreatitis risk, but the results have been inconsistent. Thus, we conducted a meta-anal-ysis to more precisely estimate this association. Relevant publications were searched in several widely used databases and 9 eligible studies were included in the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Significant associations between ADH1C *1/*2 poly-morphism and pancreatitis risk were observed in both overall meta-analysis for 12 vs 22 (OR = 1.53, 95%CI = 1.12-2.10) and 11 + 12 vs 22 (OR = 1.44, 95%CI = 1.07-1.95), and the chronic alcoholic pancre-atitis subgroup for 12 vs 22 (OR = 1.64, 95%CI = 1.17-2.29) and 11 + 12 vs 22 (OR = 1.53, 95%CI = 1.11-2.11). Significant pancreatitis risk variation was also detected in Caucasians for 11 + 12 vs 22 (OR = 1.45, 95%CI = 1.07-1.98). In conclusion, the ADH1C *1/*2 polymorphism is likely associated with pancreatitis risk, particularly chronic alcoholic pancreatitis risk, with the *1 allele functioning as a risk factor.

Toxicokinetics of T-2 toxin and its major metabolites in broiler chickens after intravenous and oral administration.

T-2 toxin, one of the most toxic trichothecene mycotoxins, causes economic losses in animal production. Little information is available on the toxicokinetic parameters of T-2 toxin and its major metabolites (i.e., HT-2 toxin and T-2 triol) in broiler chickens. In this study, toxicokinetics of T-2 toxin and its major metabolites were evaluated in broiler chickens after a single intravenous (0.5 mg/kg b.w.) and multiple oral administrations (2.0 mg/kg b.w., every 12 h for 2 days). Plasma concentration profiles of T-2 toxin and its metabolites were analyzed by a noncompartmental model method. Following intravenous administration, the terminal elimination half-lives (t(1/2λz)) of T-2 toxin, HT-2 toxin, and T-2 triol were 17.33 ± 1.07 min, 33.62 ± 3.08 min, and 9.60 ± 0.50 min, respectively. Following multiple oral administrations, no plasma levels above the limit of quantification were observed for HT-2 toxin. The t(1/2λz) of T-2 toxin and T-2 triol was 23.40 ± 2.94 min and 87.60 ± 29.40 min, respectively. Peak plasma concentrations (Cmax ) of 53.10 ± 10.42 ng/mL (T-2 toxin) and 47.64 ± 9.19 ng/mL (T-2 triol) were observed at Tmax of 13.20 ± 4.80 min and 38.40 ± 15.00 min, respectively. T-2 toxin had a low absolute oral bioavailability (17.07%). Results showed that the T-2 toxin was rapidly absorbed and most of the T-2 toxin was extensively transformed to metabolites in broiler chickens.

Refolding of recombinant human interferon alpha-2a from Escherichia coli by urea gradient size exclusion chromatography.

Protein refolding is still a puzzle in the production of recombinant proteins expressed as inclusion bodies (IBs) in Escherichia coli. Gradient size exclusion chromatography (SEC) is a recently developed method for refolding of recombinant proteins in IBs. In this study, we used a decreasing urea gradient SEC for the refolding of recombinant human interferon alpha-2a (rhLFNalpha-2a) which was overexpressed as IBs in E. coli. In chromatographic process, the denatured rhLFNalpha-2a would pass along the 8.0-3.0 M urea gradient and refold gradually. Several operating conditions, such as final concentration of urea along the column, gradient length, the ratio of reduced to oxidized glutathione and flow rate were investigated, respectively. Under the optimum conditions, 1.2 x 10(8) IU/mg of specific activity and 82% mass recovery were obtained from the loaded 10 ml of 1.75 mg/ml denatured protein, and rhLFNalpha-2a was also purified during this process with the purity of higher than 92%. Compared with dilution method, urea gradient SEC was more efficient for the rhl FNalpha-2a refolding in terms of specific activity and mass recovery.

Association between serum asprosin and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus in the community.

OBJECTIVE: This study aimed to investigate the relationship between serum asprosin level and diabetic peripheral neuropathy (DPN) in community patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: A total of 498 patients with T2DM were recruited from Zhuoma Community Health Service Station and Chengbei West Street Community Health Service Center in Changzhi City of Shanxi Province between November 2019 and July 2021. Their height, weight, and body mass index (BMI), as well as fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), triglyceride (TG), and serum asprosin levels, were analyzed. Patients were divided into the DPN group (n = 329) and the non-DPN group (n = 169) according to the presence or absence of DPN. The t-test, Mann-Whitney U test, and χ² test were used to compare the indicators between the two groups. Pearson or Spearman correlation analysis was used to evaluate the correlation between serum asprosin and other clinical data. Multivariate logistic regression analysis was used to analyze the influencing factors of DPN. RESULTS: Compared with the non-DPN group, the DPN group had higher serum asprosin (p < 0.05). The prevalence of DPN gradually increased according to the tertiles of asprosin (56%, 67%, and 75%; p < 0.05). Multivariate logistic regression analysis showed that after adjustment for covariates, patients with asprosin concentrations between 295.4-367.0 pg/ml and concentrations > 367.0 pg/ml had a higher risk of diabetic neuropathy compared than those with asprosin levels < 295.4 pg/ml (p < 0.05). CONCLUSIONS: Serum asprosin was found to be positively correlated with DPN, and it resulted as an influencing factor for DPN in patients with T2DM in the community. With the increase of asprosin, the risk of DPN also increased.

Relationship between dietary patterns and diabetic microvascular complications in patients with type 2 diabetes mellitus.

OBJECTIVE: This study aimed to investigate the relationship between different dietary patterns and diabetic microvascular complications in patients with type 2 diabetes mellitus. PATIENTS AND METHODS: This study was conducted based on the Chinese Chronic Disease and its Risk Factor Surveillance System. A multi-stage stratified sampling method was used to randomly select two districts (Henghualing District, Taiyuan City, and Yuzi District, Jinzhong City) and two counties (Huguan County, Changzhi City, and Jiang County, Yuncheng City) from the chronic disease surveillance sites in Shanxi Province to collect general information, dietary records, physical measurements, and laboratory tests. In total, 1,227 patients were enrolled according to the study criteria. Factor analysis was performed to construct six dietary patterns, and the relationship between dietary pattern scores and type 2 diabetic microvascular complications was analysed using binary logistic regression after correcting for confounders. RESULTS: (1) Regarding the prevalence of type 2 diabetic microvascular complications and dietary characteristics, the prevalence of microvascular complications in patients with type 2 diabetes mellitus was 55.3% and was higher in urban than in rural areas. The prevalence of diabetic kidney disease (DKD), diabetic retinopathy, and diabetic peripheral neuropathy (DPN) were 21.4%, 12.7%, and 38.0%, respectively. (2) Six dietary patterns were constructed, namely, 'animal protein', 'coarse grains and plant protein', 'nuts and fruits', 'refined grains and vegetables', 'dairy', and 'added sugars', with factor contributions of 15.42%, 9.99%, 8.23%, 8.16%, 7.56%, and 7.28% respectively, explaining 56.64% of the total dietary variation. (3) After adjusting for confounding variables, the results of binary logistic regression indicated that patients in the highest quartile of dietary pattern scores for 'nuts and fruits' experienced a 43.3% lower risk of DKD compared to those in the lowest quartile [odds ratio (OR) = 0.567; 95% confidence interval (CI), 0.359-0.894; p < 0.001]. Similarly, patients in the highest quartile of dietary pattern scores for 'animal protein' had a 42.8% lower risk of DPN compared with those in the lowest quartile (OR = 0.572; 95% CI, 0.388-0.843; p < 0.05). CONCLUSIONS: The results of this study suggest that in patients with type 2 diabetes mellitus, a 'nuts and fruits' dietary pattern reduces the risk of DKD and an 'animal protein' dietary pattern reduces the risk of DPN.

Heterologous expression of dammarenediol synthase gene in an engineered Saccharomyces cerevisiae.

AIMS: Dammarenediol production by an engineered yeast Saccharomyces cerevisiae was investigated. METHODS AND RESULTS: A dammarenediol-producing engineered yeast was constructed by heterologous expression of the dammarenediol synthase gene from Panax ginseng hairy roots through RT-PCR. Fermentation was carried out in a 5-L GRJY-bioreactor with an inoculum size of 1% v/v at 30°C. Dammarenediol detection was performed with silica gel chromatography and HPLC. Determination of dammarenediol synthase activity subcellular distribution was carried out by surveying the enzyme activity in microsomes, lipid particles and total yeast homogenate. When cultured under aerobic conditions, the engineered yeast could produce dammarenediol up to 250µgl(-1). However, when an anaerobic shift strategy was employed, dammarenediol accumulated at a level as twice as that under aerobic condition. The dammarenediol synthase and dammarenediol were mainly localized in lipid particles. CONCLUSIONS: Dammarenediol could be heterologously produced in engineered yeast. The heterologously expressed dammarenediol synthase is mainly localized in lipid particles. Anaerobic shift strategy could enhance the dammarenediol level in the engineered yeast. SIGNIFICANCE AND IMPACT OF THE STUDY: This study showed that the high-value plant product dammarenediol could be produced by heterologous expression of the according gene in yeast. Furthermore, the anaerobic shift strategy could be potentially applied in oxidosqualene-derived compounds production in yeast. Here, the information about subcellular distribution of heterologously expressed dammarenediol synthase in the engineered yeast was also provided.

Genetic diversity and population structure of Chinese pony breeds using microsatellite markers.

China is one of the principal origins of ponies in the world. We made a comprehensive analysis of genetic diversity and population structure of Chinese ponies based on 174 animals of five indigenous Chinese pony breeds from five provinces using 13 microsatellite markers. One hundred and forty-four alleles were detected; the mean number of effective alleles among the pony breeds ranged from 5.38 (Guizhou) to 6.78 (Sichuan); the expected heterozygosity ranged from 0.82 (Guizhou) to 0.85 (Debao, Sichuan). Although abundant genetic variation was found, the genetic differentiation was low between the ponies, with 6% total genetic variance among the different breeds. All the pairwise F(ST) values were significant; they varied from 0.0424 for the Sichuan-Yunnan pair to 0.0833 for the Guizhou-Sichuan pair. All five pony breeds deviated from Hardy-Weinberg equilibrium, except the Yunnan pony. Phylogenetic trees of the five pony breeds based on genetic distances were constructed using a neighbor-joining method. The Sichuan and Yunnan ponies were grouped into the same branch, with a high bootstrap support value (97%). Guizhou and Ningqiang ponies were clustered into the same branch with a bootstrap value of 56%, whereas the Debao pony was placed in a separate group, with a bootstrap value of 56%. This grouping pattern was supported by genetic structure analysis.

Biological observations on the crocodile shark Pseudocarcharias kamoharai.

Sex ratios and gravid characteristics were analysed for the crocodile shark Pseudocarcharias kamoharai from the tropical eastern Pacific Ocean. Gravid females ranged from 80 to 102 cm fork length (L(F) ). The mode litter size was four (two embryos per uterus), mean embryo length was linearly correlated with maternal length (r = 0·465, n = 32); there was no significant difference in L(F) between female and male embryos.

The effect of cytoplasmic dynein on the development and functional maintenance of retinal photoreceptor cells.

Cytoplasmic dynein is a multi-subunit complex that includes cytoplasmic dynein-1 (dynein1) and cytoplasmic dynein-2 (dynein2). It participates in various basic cellular processes, including nuclear migration, mitotic spindle organization, chromosome separation during mitosis, and the location and function of numerous intracellular organelles. Retinal photoreceptor cells are terminally differentiated neurons that cannot regenerate and cannot be replaced once lost. It is thus crucial to study their development to facilitate the generation and improvement of photoreceptor disease treatments. The outer segment (OS) of photoreceptor cells is a specific sensory cilium. An increasing number of studies have shown that cytoplasmic dynein plays an essential role in the development of retinal photoreceptor cells. To date, people have done a lot of studies on the various functions of dynein in cells and have a very detailed understanding. However, the role of dynein in retinal photoreceptor cells has not been summarized in detail. This article summarizes the currently available knowledge relating to the effects and mechanisms of cytoplasmic dynein on the development and functional maintenance of retinal photoreceptor cells.

Observation of topological superconductivity in a stoichiometric transition metal dichalcogenide 2M-WS2.

Topological superconductors (TSCs) are unconventional superconductors with bulk superconducting gap and in-gap Majorana states on the boundary that may be used as topological qubits for quantum computation. Despite their importance in both fundamental research and applications, natural TSCs are very rare. Here, combining state of the art synchrotron and laser-based angle-resolved photoemission spectroscopy, we investigated a stoichiometric transition metal dichalcogenide (TMD), 2M-WS2 with a superconducting transition temperature of 8.8 K (the highest among all TMDs in the natural form up to date) and observed distinctive topological surface states (TSSs). Furthermore, in the superconducting state, we found that the TSSs acquired a nodeless superconducting gap with similar magnitude as that of the bulk states. These discoveries not only evidence 2M-WS2 as an intrinsic TSC without the need of sensitive composition tuning or sophisticated heterostructures fabrication, but also provide an ideal platform for device applications thanks to its van der Waals layered structure.

Activity of alpha2,6-sialyltransferase and its gene expression in peripheral B lymphocytes in patients with IgA nephropathy.

It is known that aberrant sialylation of IgA1 is involved in the pathogenesis of IgA nephropathy (IgAN). We hypothesize that aberrant sialylation of serum IgA1 may result from changes in the activity of alpha2,6-sialyltransferase (alpha2,6-ST) or expression of its coding gene ST6GALNAC2 in peripheral B lymphocytes. Sixty patients with IgAN and 20 healthy controls were enrolled. Peripheral B lymphocytes were isolated by CD-19-positive magnetic beads. The expression level of ST6GALNAC2 was quantitatively analysed by real-time reverse-transcriptase polymerase chain reaction (PCR). Serum IgA1 and sialylation levels were detected by enzyme-linked immunosorbent assay (ELISA) and specific lectin-binding ELISA. Activity of alpha2,6-ST was measured by specific lectin-binding ELISA. Expression of ST6GALNAC2 in B peripheral lymphocytes was significantly lower in patients with IgAN than that in normal controls (3.7 +/- 2.2 versus 6.3 +/- 2.3, P = 0.016); alpha2,6-ST activity in B lymphocytes was correlated positively with the level of alpha2,6-sialic acid in serum IgA1 in patients (n = 42) and controls (n = 12) (r = 0.37, P = 0.007). However, alpha2,6-ST activity did not differ between patients with IgAN and controls (1.19 +/- 1.43 versus 1.06 +/- 1.17, P > 0.05). These data suggested that reduced sialylation of serum IgA1 may result from decreased expression of ST6GALNAC2. The factors affecting activity of alpha2,6-ST in the sialylation of IgA1 need to be further investigated.

Efficacy of intracarotid propofol infusion and impact of cerebral blood flow alteration.

BACKGROUND: Intracarotid propofol infusion was studied in canines as an experimental basis for application of propofol in the Wada test. METHODS: First, efficacy and side-effects of propofol anaesthesia were studied in eight mongrel dogs that received intracarotid and i.v. propofol infusions for 30 min according to a cross-over design. Auditory evoked potentials were used to guide anaesthesia. Secondly, eight mongrel dogs received intracarotid propofol infusion during both normal and cerebral hyperperfusion states using nicardipine. Haemodynamics and clinical endpoints were compared between the two infusion conditions. RESULTS: We required 33 (7.6) mg propofol intracarotically vs 113 (17) mg propofol i.v. to achieve an anaesthetic state. The mean arterial pressure (MAP) decreased about 15-27% from the baseline during i.v. infusion. However, no obvious decrease of MAP was observed after intracarotid infusion. Administration of nicardipine increased the blood flow in the internal carotid artery by 17%. Then, the propofol dosage for achieving the anaesthetic effect increased from 7.7 (0.9) mg in the normal control to 11.3 (0.8) mg in the nicardipine group. The onset time of anaesthetic effect was prolonged and the recovery time was shortened during intracarotid infusion during cerebral hyperperfusion. CONCLUSIONS: Compared with i.v. propofol infusion, intracarotid infusion could reach and maintain the target anaesthetic depth with less dosage and without affecting MAP. In addition, increase of cerebral blood flow requires a higher propofol dose, prolongs onset, and shortens recovery time during intracarotid propofol anaesthesia, indicating that patients with a cerebral hyperperfusion state may need higher dose of anaesthetics during the Wada test.

MOTS-c improves osteoporosis by promoting the synthesis of type I collagen in osteoblasts via TGF-ß/SMAD signaling pathway.

OBJECTIVE: To investigate whether MOTS-c can regulate the synthesis of type I collagen in osteoblasts by regulating TGF-ß/SMAD pathway, thereby improving osteoporosis. MATERIALS AND METHODS: Viability of hFOB1.19 cells treated with MOTS-c was detected by CCK-8 assay. The mRNA and protein levels of TGF-ß, SMAD7, COL1A1 and COL1A2 in hFOB1.19 cells were detected by quantitative Real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. We then changed expressions of TGF-ß and SMAD7 by plasmids transfection to detect levels of COL1A1 and COL1A2 in hFOB1.19 cells by qRT-PCR and Western blot, respectively. RESULTS: Cell viability was significantly increased after treatment of 1.0 µM MOTS-c for 24 h or 0.5 µM MOTS-c for 48 h in a time-dependent manner. The mRNA and protein expressions of TGF-ß, SMAD7, COL1A1 and COL1A2 in hFOB1.19 cells were dependent on the concentration of MOTS-c. In addition, MOTS-c increased the expressions of COL1A1 and COL1A2, which were partially reversed by knockdown of TGF-ß or SMAD7. CONCLUSIONS: MOTS-c could promote osteoblasts to synthesize type I collagen via TGF-ß/SMAD pathway.

Therapeutic effect of hyperoxygenated solution on acute lung injury induced by oleic acid.

BACKGROUND/AIMS: Hyperoxygenated solution (HOS) has been shown to protect the myocardium, spinal cord and brain from ischemic injury. In this study, we evaluated the effect of HOS on acute lung injury (ALI) induced by oleic acid in rabbits. METHODS: 24 rabbits were randomized into four groups: control (C), oleic acid (OA), inhaled oxygen (OX), and HOS treatment (HOS). The ALI model was produced by administrating oleic acid intravenously. Half an hour after oleic acid infusion, animals received inhaled oxygen at 30% FiO2 or 20 ml/kg HOS intravenously. Various parameters were measured during the 2 h after oleic acid treatment. RESULTS: After treatment with oleic acid, mean arterial pressure and PaO2 decreased significantly compared to group C (p < 0.01), while lung/body ratio, lung water content, and the levels of myeloperoxidase (MPO) and TNF-alpha in the serum and BALF increased significantly (p < 0.01). Histologically, interstitial edema, alveoli exudation and massive inflammatory cell infiltration were observed in the lung. However, when treated with 20 ml/kg HOS, PaO2 significantly increased compared to group OA (p < 0.05). The MPO and TNF-alpha levels in the serum and BALF were decreased (p < 0.01), pulmonary edema was reduced (p < 0.01). Improved pathological manifestations were observed. CONCLUSION: HOS at 20 ml/kg has therapeutic effects to ameliorate the biological and morphological changes to the lung induced by oleic acid. HOS is a safe, simple and effective measure to protect animals from ALI.