Notoginsenoside R1 protects against hypobaric hypoxia-induced high-altitude pulmonary edema by inhibiting apoptosis via ERK1/2-P90rsk-BAD ignaling pathway.

High-altitude pulmonary edema (HAPE) is a potentially fatal disease. Notoginsenoside R1 is a novel phytoestrogen with anti-inflammatory, antioxidant and anti-apoptosis properties. However, its effects and underlying mechanisms in the protection of hypobaric hypoxia-induced HAPE rats remains unclear. This study aimed to explore the protective effects and underlying mechanisms of Notoginsenoside R1 in hypobaric hypoxia-induced HAPE. We found that Notoginsenoside R1 alleviated the lung tissue injury, decreased lung wet/dry ratio, and reduced inflammation and oxidative stress. Additionally, Notoginsenoside R1 ameliorated the changes in arterial blood gas, decreased the total protein concentration in bronchoalveolar lavage fluid, and inhibited the occurrence of apoptosis caused by HAPE. In the process of further exploration of the mechanism, it was found that Notoginsenoside R1 could promote the activation of ERK1/2-P90rsk-BAD signaling pathway, and the effect of Notoginsenoside R1 was attenuated after the use of ERK1/2 inhibitor U0126. Our study indicated that the protective effects of Notoginsenoside R1 against HAPE were mainly related to the inhibition of inflammation, oxidative stress, and apoptosis. Notoginsenoside R1 may be a potential candidate for preventing HAPE.

Rosavidin protects against PM2.5-induced lung toxicity via inhibition of NLRP3 inflammasome-mediated pyroptosis by activating the PI3K/AKT pathway.

Fine particulate matter (PM2.5) contributes to adverse health effects through the promotion of inflammatory cytokine release. Rosavidin (Ro), a phenylpropanoid compound having multiple biological activities, is extracted from Rhodiola crenulata, a medicine and food homology plant. However, the protective role and mechanism of Ro in PM2.5-induced lung toxicity have not been previously studied. This study aimed to investigate the potential protective effect and mechanism of Ro in PM2.5-induced lung toxicity. A lung toxicity rat model was established through trachea drip of PM2.5 suspension after the different dose pretreatment of Ro (50 mg/kg and 100 mg/kg) to evaluate the effect of Ro on PM2.5 caused lung toxicity. The results showed that Ro attenuated the pathological changes, edema, and inflammation response in rats. The PI3K/AKT signaling pathway may be associated with the protective effect of Ro against pulmonary toxicity. Subsequently, we verified the role of PI3K/AKT in the PM2.5 exposure lung tissue. Moreover, expression levels of p-PI3K and p-AKT were lower, and those of NLRP3, ASC, cleaved caspase-1, cleaved IL-1ß, and GSDMD-N were higher in PM2.5 group compared to those in control group. Whereas pre-administration of Ro reversed the expression trends of these proteins in lung tissue. Notably, those protective effects of Ro were not observed after pretreatment with a combination of Ro with nigericin or LY294002. These results indicate that Ro mitigates PM2.5-caused lung toxicity by inhibiting NLRP3 inflammasome-mediated pyroptosis through activation of the PI3K/AKT signaling pathway.

Probiotics ameliorates pulmonary inflammation via modulating gut microbiota and rectifying Th17/Treg imbalance in a rat model of PM2.5 induced lung injury.

The imbalance of intestinal microbiota and inflammatory response is crucial in the development of lung injury induced by PM2.5. In recent years, probiotics have attracted great attention for their health benefits in inflammatory diseases and regulating intestinal balance, but their intricate mechanisms need further experiments to elucidate. In our research, a rat lung damage model induced by PM2.5 exposure in real environment was established to explore the protective properties of probiotics on PM2.5 exposure injury and its related mechanism. The results indicated that compared with the AF control group, rats in the PM2.5 group gained weight slowly, ate less and had yellow hair. The results of pathological and immunohistochemical examinations showed that the inflammatory infiltration of lung tissue was alleviated after probiotic treatment. The Lung function results also showed the improvement effects of probiotics administration. In addition, probiotics could promote the balance of Th17 and Treg cells, inhibit cytokines expression (TNF-α, IL-6, IL-1ß, IL-17A), and increase the concentration of anti-inflammatory factors (IL-10, TGF-ß). In addition, 16 S rRNA sequence analysis showed that probiotic treatment could reduce microbiota abundance and diversity, increase the abundance of possible beneficial bacteria, and decrease the abundance of bacteria associated with inflammation. In general, probiotic intervention was found to have preventive effects on the occurrence of PM2.5 induced pathological injury, and the mechanism was associate with to the inhibition of inflammatory response, regulation of Th17/Treg balance and maintenance of intestinal internal environment stability.

ß-Elemene Promotes Apoptosis Induced by Hyperthermia via Inhibiting HSP70.

Thermotherapy has been presented as a promising strategy to be used as an effective nonsurgical technique for colorectal carcinoma. Although this strategy presents several advantages, including low toxicity and high repeatability, thermotherapy often needs to be combined with other therapies because residual tumor cells that survive hyperthermal treatment often lead to relapse. In this study, we evaluated the effects of ß-elemene, which has been proven to have the potential to reverse chemotherapy drug resistance, on promoting the antitumor effects of hyperthermia. ß-elemene treatment significantly promoted apoptosis after 2 hours of hyperthermia treatment and blocked cell cycle phases at G1/G0. ß-elemene also significantly decreased colony formation and tumor formation abilities after hyperthermia treatment. ß-elemene treatment significantly decreased HSP70, but not HSP90 or HSP27, induced by hyperthermia treatment without disturbing HSP70 mRNA. It was also found that ß-elemene decreased phosphorylated ERK1/2 induced by hyperthermia. Regain of HSP70 reversed ß-elemene-mediated apoptosis, indicating that ß-elemene may induce apoptosis by decreasing HSP70. Moreover, ß-elemene treatment significantly decreased invasion capacity by decreasing the EMT, which was induced by hyperthermia treatment. Taken together, our results offer a potential strategy for CRC therapy via the combination of hyperthermia and ß-elemene.

Identification and validation of a major QTL for kernel length in bread wheat based on two F3 biparental populations.

BACKGROUND: High yield and quality are essential goals of wheat (Triticum aestivum L.) breeding. Kernel length (KL), as a main component of kernel size, can indirectly change kernel weight and then affects yield. Identification and utilization of excellent loci in wheat genetic resources is of great significance for cultivating high yield and quality wheat. Genetic identification of loci for KL has been performed mainly through genome-wide association study in natural populations or QTL mapping based on genetic linkage map in high generation populations. RESULTS: In this study, an F3 biparental population derived from the cross between an EMS mutant BLS1 selected from an EMS-induced wheat genotype LJ2135 (derived from the hybrid progeny of a spelt wheat (T. spelta L.) and a common wheat) mutant bank and a local breeding line 99E18 was used to rapidly identify loci controlling KL based on Bulked Segregant Analysis (BSA) and the wheat 660 K single-nucleotide polymorphism (SNP) array. The highest ratio of polymorphic SNPs was located on chromosome 4A. Linkage map analysis showed that 33 Kompetitive Allele Specific PCR markers were linked to the QTL for KL (Qkl.sicau-BLE18-4A) identified in three environments as well as the best linear unbiased prediction (BLUP) dataset. This QTL explained 10.87-19.30% of the phenotypic variation. Its effect was successfully confirmed in another F3 population with the two flanking markers KASP-AX-111536305 and KASP-AX-110174441. Compared with previous studies and given that the of BLS1 has the genetic background of spelt wheat, the major QTL was likely a new one. A few of predicted genes related to regulation of kernel development were identified in the interval of the detected QTL. CONCLUSION: A major, novel and stable QTL (Qkl.sicau-BLE18-4A) for KL was identified and verified in two F3 biparental populations across three environments. Significant relationships among KL, kernel width (KW) and thousand kernel weight (TKW) were identified. Four predicted genes related to kernel growth regulation were detected in the interval of Qkl.sicau-BLE18-4A. Furthermore, this study laid foundation on subsequent fine mapping work and provided a possibility for breeding of elite wheat varieties.

Effect of omega-3 fatty acids on TH1/TH2 polarization in individuals with high exposure to particulate matter ≤ 2.5 µm (PM2.5): a randomized, double-blind, placebo-controlled clinical study.

BACKGROUND: Long-term exposure to high concentrations of PM2.5 may cause immune system dysfunction and damage to the respiratory and cardiovascular systems. PM2.5 may cause CD4 + T helper cells to polarize toward TH1 or TH2 cell types, which may be associated with the onset and progression of many human diseases. Recent studies have shown that omega-3 fatty acids can regulate human immune function and reduce physiological damage caused by air pollution; however, only limited research has examined the therapeutic effects of omega-3 fatty acids on subjects with high exposure to PM2.5 in mass transit systems such as subways. METHODS: This study was designed as a prospective, randomized, double-blinded (to participants and researchers), placebo-controlled clinical trial. The research plan is to randomly select 120 eligible adults based on the difference in PM2.5 exposure in the Chengdu subway station. They should be aged 20-65 years old and work in the subway station more than or equal to 3 times a week, each time greater than or equal to 8 h, and had worked continuously in the subway station for more than 2 years. All participants will receive omega-3 fatty acids or placebo for 8 weeks. The primary outcomes will be changes in the TH1/TH2 cell polarization index and changes in serum cytokine concentrations. Secondary outcomes will be changes in early indicators of atherosclerosis, pulmonary function, COOP/WONCA charts, and scores on the Short-Form 36 Health Survey for quality of life. Results will be analyzed to evaluate differences in clinical efficacy between the two groups. A 6-month follow-up period will be used to assess the long-term value of omega-3 fatty acids for respiratory and cardiovascular disease endpoints. DISCUSSION: We will explore the characteristics of the TH1/TH2 cell polarization index in a population with high exposure to PM2.5. Omega-3 fatty acids and placebo will be compared in many ways to test the effect on people exposed to PM2.5 subway stations. This study is expected to provide reliable evidence to support the promotion of omega-3 fatty acids in clinical practice to protect individuals who are highly exposed to PM2.5. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000038065 . Registered on September 9, 2020.

Astragaloside IV pre-treatment attenuates PM2.5-induced lung injury in rats: Impact on autophagy, apoptosis and inflammation.

BACKGROUND: Fine particulate matter (PM2.5) with an aerodynamic diameter of less than 2.5 µm, exerts serious lung toxicity. At present, effective prevention measures and treatment modalities for pulmonary toxicity caused by PM2.5 are lacking. Astragaloside IV (AS-IV) is a natural product that has received increasing attention from researchers for its unique biological functions. PURPOSE: To investigate the protective effects of AS-IV on PM2.5-induced pulmonary toxicity and identify its potential mechanisms. METHODS: The rat model of PM2.5-induced lung toxicity was created by intratracheal instillation of PM2.5 dust suspension. The investigation was performed with AS-IV or in combination with autophagic flux inhibitor (Chloroquine) or AMP-sensitive protein kinase (AMPK)-specific inhibitor (Compound C). Apoptosis was detected by terminal deoxy-nucleotidyl transferase dUTP nick end labeling (TUNEL) and western blotting. Autophagy was detected by immunofluorescence staining, autophagic flux measurement, western blotting, and transmission electron microscopy. The AMPK/mTOR pathway was analyzed by western blotting. Inflammation was analyzed by western blotting and suspension array. RESULTS: AS-IV prevented histopathological injury, inflammation, autophagy dysfunction, apoptosis, and changes in AMPK levels induced by PM2.5. AS-IV increased autophagic flux and inhibited apoptosis and inflammation by activating the AMPK/ mammalian target of rapamycin (mTOR) pathway. However, AS-IV had no protective effect on PM2.5-induced lung injury following treatment with Compound C or Chloroquine. CONCLUSION: AS-IV prevented PM2.5-induced lung toxicity by restoring the balance among autophagy, apoptosis, and inflammation in rats by activating the AMPK/mTOR signaling pathway.

Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro.

INTRODUCTION: Prolonged exposure to air polluted with airborne fine particulate matter (PM2.5) can increase respiratory disease risk. Astragaloside IV (AS-IV) is one of the main bioactive substances in the traditional Chinese medicinal herb, Astragalus membranaceus Bunge. AS-IV has numerous pharmacological properties; whereas there are few reports on the prevention of PM2.5-induced lung injury by AS-IV through modulation of the autophagic pathway. This study aimed to investigate the protective effects and the underlying mechanisms of AS-IV in PM2.5-induced lung injury rats and rat alveolar macrophages (NR8383 cells). METHODS: The pneumotoxicity model was established by intratracheal injection of PM2.5 in rats, and PM2.5 challenge in NR8383 cells. The severity of lung injury was evaluated by wet weight to dry weight ratio and McGuigan pathology scoring. Inflammatory factors and oxidative stress were detected through ELISA. The expressions of p-PI3K, p-Akt, and p-mTOR proteins were analyzed by immunohistochemistry. Immunofluorescence and transmission electron microscopy were used to detect autophagosomes. The expressions of autophagy marker protein (LC3B and p62), PI3K/Akt/mTOR signaling and NF-κB translocation were detected by Western blot in lung tissue and NR8383 cells. RESULTS: After PM2.5 stimulation, rats showed severe inflammation and oxidative stress, along with inhibition of autophagy in lung tissue. AS-IV not only decreased pulmonary inflammation and oxidative stress by inhibiting nuclear factor kappa B translocation, but also regulated autophagy by inhibiting PI3K/Akt/mTOR signaling. After treatment with 3-methyladenine (a classic PI3K inhibitor, blocking the formation of autophagosomes), the protective effect of AS-IV on PM2.5-induced lung injury was further strengthened. In parallel, using Western blot, immunohistochemistry, and transmission electron microscopy, we demonstrated that AS-IV restore autophagic flux mainly through regulating the degradation of autophagosomes rather than suppressing the formation in vivo and in vitro. CONCLUSION: Our data indicated that AS-IV protects from PM2.5-induced lung injury in vivo and in vitro by inhibiting the PI3K/Akt/mTOR pathway to regulate autophagy and inflammation.

Ginsenosides for the treatment of metabolic syndrome and cardiovascular diseases: Pharmacology and mechanisms.

Epidemiological studies showed that the metabolic syndromes (MetS) and cardiovascular diseases (CVDs) are responsible for a serious threat to human health worldwide. MetS is a syndromes characterized by fat metabolism disorder, obesity, diabetes, insulin resistance and other risk factors, which increases the risk of CVDs initiation and development. Although certain drugs play a role in lowering blood sugar and lipid, some side effects also occur. Considering the multiple pathogenesis, a great deal of natural products have been attempted to treat metabolic syndromes. Ginsenosides, as the active components isolated from Panax ginseng C.A.Mey, have been reported to have therapeutic effects on MetS and CVDs, of which pharmacological mechanisms were further studied as well. This review aims to systematically summarize current pharmacological effects of ginsenosides on MetS and CVDs, potential mechanisms and clinic trials, which will greatly contribute to the development of potential agents for related disease treatment.

Effect of uremic serum on Th17/Treg cell balance and endoplasmic reticulum stress in rats.

BACKGROUND/AIMS: The imbalance of T helper 17 (Th17) and regulatory T (Treg) cells exists in the occurrence and development of various diseases. Endoplasmic reticulum stress (ERS) is an important self-protective cellular response to harmful stimuli, such as uremic environment. The objective of this study was to investigate the Th17/Treg cell balance and ERS in a uremic environment and analyze the relationship between them. METHODS: (1) The rat spleen lymphocytes were extracted and treated with thapsigargin (inducer of ERS) and sodium citrate. The proportion of Th17 and Treg cells were then detected. (2) The uremic serum-cultured lymphocytes were used and divided into three groups: non-uremic serum group, uremic serum group, and uremic serum + sodium citrate group. Afterward, the proportion of Th17/Treg cells and the expression of ERS-related proteins (GRP78 and CHOP) were detected. RESULTS: Thapsigargin had no significant effect on the proportion of Th17 cells within a limited concentration range, but it could reduce the proportion of Treg cells, sodium citrate had a negative influence on the deviation of Th17/Treg cells treated with thapsigargin. Uremic serum treatment reduced the proportion of Treg cells, resulting in an increase of the Th17/Treg ratio. However, sodium citrate had no influence on the deviation of Th17/Treg cells treated by uremic serum. Sodium citrate reduced the elevation of ERS-related proteins induced by uremic serum. CONCLUSIONS: Uremic serum can lead to the imbalance of Th17/Treg cells as well as ERS, suggesting that ERS is one of the mechanisms of the imbalance of Th17/Treg cells induced by uremic serum. Sodium citrate can inhibit ERS induced by uremic serum.

Effect of myrtol on chronic bronchitis or chronic obstructive pulmonary disease: A protocol for systematic review and meta-analysis.

BACKGROUND: The key to the management of chronic obstructive (CB) and chronic obstructive pulmonary disease (COPD) is to control symptoms of the disease and to prevent deterioration in the health of affected patients. Myrtol has been proved to be effective in treating the symptoms of patients with CB and COPD and preventing the deterioration in their health. However, there has been no systematic review of the efficacy and safety of myrtol in the treatment of CB or COPD. The purpose of this study is going to evaluate the effects of myrtol on the management of CB or COPD based on randomized controlled trials. METHODS: Electronic literature and other ongoing studies will be searched before November 31, 2019. Randomized controlled trials that report the use of myrtol in the treatment of CB or COPD (in the absence and presence of concurrent treatments) will be selected for inclusion regardless of language. Primary outcomes will include cumulative numbers of exacerbation events and the number of days of disability including days in bed, days off work due to breathing complications, and days on which the participant was unable to undertake normal activities due to breathing complications. Study selection, data extraction, and deviation the derivation risk assessment will be carried out by 2 independent investigators. Meta-analysis will be carried out by the RevMan5.3 software. RESULTS: The study will provide summary results for estimating the efficacy and safety of myrtol for future treatments of CB or COPD. CONCLUSIONS: This systematic review will determine if myrtol is an effective and a safe intervention on the symptoms and the prevention of exacerbation of CB or COPD. ETHICS AND DISSEMINATION: Ethical approval will not be required for this study because no identifying patient data will be used. The review will be published as an article or a conference presentation in a peer-reviewed journal. REGISTRATION: OSF registration number: DOI 10.17605/OSF.IO/PXRBV.

Gelomyrtol for acute or chronic sinusitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Sinusitis is a common condition worldwide, significantly affecting the quality of life of patients. Due to the limitations of conventional medicines, such as serious side effects and low efficacies, Gelomyrtol may be a promising treatment for sinusitis. As no related systematic review has been published, the purpose of this study will be to evaluate the safety and efficacy of Gelomyrtol for acute or chronic sinusitis. METHODS: PubMed, EMBASE, the Cochrane Library, the Web of Science, the Chinese National Knowledge Infrastructure Database, the Chinese Biomedical Literature Database, the Wan Fang Database, and the Chongqing VIP Chinese Science, and Technology Periodical Database will be searched from their commencement until July 2020. Randomized controlled trials of Gelomyrtol for acute or chronic sinusitis will be selected in any language. Primary outcomes will include the Sino-Nasal Outcome Test-22 (SNOT-22) score, quality of life score as measured by SF-36, and the change in computed tomography (CT) score. Study selection, data extraction, and deviation risk assessment will be carried out by 2 investigators independently. RevMan V.5.3 software will be used to analyze the study data. RESULTS: The study will provide high-quality evidence for estimating the efficacy and safety of Gelomyrtol in the treatment of acute or chronic sinusitis. CONCLUSIONS: This systematic review will explore whether Gelomyrtol is an effective and safe intervention in the treatment of acute or chronic sinusitis. ETHICS AND DISSEMINATION: As no patient data will be used in this study, ethical approval will not be required. The review will be published as an article or a conference presentation in a peer-reviewed journal. REGISTRATION: OSF registration number: DOI 10.17605/OSF.IO/MTEU2.

Flag leaf size and posture of bread wheat: genetic dissection, QTL validation and their relationships with yield-related traits.

KEY MESSAGE: Major and environmentally stable QTL for flag leaf-related traits in wheat were identified and validated across ten environments using six populations with different genetic backgrounds. Flag leaf size and posture are two important factors of "ideotype" in wheat. Despite numerous studies on genetic analysis of flag leaf size including flag leaf length (FLL), width (FLW), area (FLA) and the ratio of length/width (FLR), few have focused on flag leaf posture including flag leaf angle (FLANG), opening angle (FLOA) and bend angle (FLBA). Further, the numbers of major, environmentally stable and verified genetic loci for flag leaf-related traits are limited. In this study, QTL for FLL, FLW, FLA, FLR, FLANG, FLOA and FLBA were identified based on a recombinant inbred line population together with values from up to ten different environments. Totally, eight major and stably expressed QTL were identified. Three co-located chromosomal intervals for seven major QTL were identified. The five major QTL QFll.sicau-5B.3 and QFll.sicau-2D.3 for FLL, QFlr.sicau-5B for FLR, QFlw.sicau-2D for FLW and QFla.sicau-2D for FLA were successfully validated by the tightly linked Kompetitive Allele Specific PCR (KASP) markers in the other five populations with different genetic backgrounds. A few genes related to leaf growth and development in intervals for these major QTL were predicated. Significant relationships between flag leaf- and yield-related traits were evidenced by analyses of Pearson correlations, conditional QTL and genetic mapping. Taken together, these results provide valuable information for understanding flag leaf size and posture of "ideotype" as well as fine mapping and breeding utilization of promising loci in bread wheat.

Therapeutic effect of methylprednisolone combined with high frequency electrotherapy on acute spinal cord injury in rats.

Acute spinal cord injury (SCI) has a high rate of disability and mortality. Although secondary SCI results in local tissue hypoxia and the release of inflammatory mediators, it is both controllable and reversible. Therefore, timely rehabilitation treatment is beneficial for the partial recovery of patients with SCI. The present study aimed to investigate the use of methylprednisolone combined with high-frequency electrotherapy as a method of rehabilitation treatment in rats with SCI. The rat SCI model was prepared using the modified Allen's method with the animals randomly divided into the following 4 groups (n=10 for each group): SCI; methylprednisolone (300 mg/kg); high-frequency electrotherapy; and combination treatment with electrotherapy combined with methylprednisolone (300 mg/kg). The Basso, Beattie and Bresnahan (BBB) score, somatosensory evoked potential (SEP) and motor evoked potential (MEP) were used to assess spinal function. Brain-derived neurotrophic factor (BDNF) and NF-κB expression levels were detected using reverse transcription-quantitative PCR and western blotting. Tumor necrosis factor (TNF)-α and IL-2 expression levels were determined by ELISA, and caspase 3 activity was also assessed. In all treatment groups, BDNF mRNA and protein expression levels were significantly increased, whilst those of NF-κB were reduced. Additionally, an elevated BBB score, improved SEPs and MEPs, inhibited caspase 3 activity and downregulated TNF-α and IL-2 expression levels were observed, compared with the SCI group (P<0.05). However, the combination group exhibited more significant effects on SCI. In conclusion, methylprednisolone combined with high frequency electrotherapy may improve the symptoms of SCI by increasing the expression level of BDNF, reducing that of NF-κB, and suppressing the secretion of inflammatory factors.

Identification of quantitative trait loci for kernel traits in a wheat cultivar Chuannong16.

BACKGROUND: Kernel length (KL), kernel width (KW) and thousand-kernel weight (TKW) are key agronomic traits in wheat breeding. Chuannong16 ('CN16') is a commercial cultivar with significantly longer kernels than the line '20828'. To identify and characterize potential alleles from CN16 controlling KL, the previously developed recombinant inbred line (RIL) population derived from the cross '20828' × 'CN16' and the genetic map constructed by the Wheat55K SNP array and SSR markers were used to perform quantitative trait locus/loci (QTL) analyses for kernel traits. RESULTS: A total of 11 putative QTL associated with kernel traits were identified and they were located on chromosomes 1A (2 QTL), 2B (2 QTL), 2D (3 QTL), 3D, 4A, 6A, and 7A, respectively. Among them, three major QTL, QKL.sicau-2D, QKW.sicau-2D and QTKW.sicau-2D, controlling KL, KW and TKW, respectively, were detected in three different environments. Respectively, they explained 10.88-18.85%, 17.21-21.49% and 10.01-23.20% of the phenotypic variance. Further, they were genetically mapped in the same interval on chromosome 2DS. A previously developed kompetitive allele-specific PCR (KASP) marker KASP-AX-94721936 was integrated in the genetic map and QTL re-mapping finally located the three major QTL in a 1- cM region flanked by AX-111096297 and KASP-AX-94721936. Another two co-located QTL intervals for KL and TKW were also identified. A few predicted genes involved in regulation of kernel growth and development were identified in the intervals of these identified QTL. Significant relationships between kernel traits and spikelet number per spike and anthesis date were detected and discussed. CONCLUSIONS: Three major and stably expressed QTL associated with KL, KW, and TKW were identified. A KASP marker tightly linked to these three major QTL was integrated. These findings provide information for subsequent fine mapping and cloning the three co-localized major QTL for kernel traits.

Correlation of increased Th17/Treg cell ratio with endoplasmic reticulum stress in chronic kidney disease.

To investigate the relationship between the regulatory immune network and endoplasmic reticulum stress (ERS) in patients with different stages of chronic kidney disease (CKD).A total of 91 patients diagnosed with CKD were divided into different groups according to the stage of disease and treatment with hemodialysis (HD) or peritoneal dialysis (PD). Routine blood and biochemical tests were performed in patients in the different CKD groups and in healthy controls (n = 20). The frequencies of T helper type 17 (Th17) and regulatory T (Treg) cells in the overall T cell population were measured by flow cytometric analysis. Levels of Th17 cell (IL-17) and Treg cell (IL-10) cytokines and the ERS markers CCAAT-enhancer-binding protein homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) were measured by enzyme-linked immunosorbent assay in serum samples collected from controls and patients. Correlations between each parameter and serum creatinine were analyzed by Spearman rank correlation and regression test.CKD stage showed a positive correlation with serum creatinine level, and increased and decreased percentages of Th17 and Treg cells, respectively, reflected in an increased Th17/Treg cell ratio. Consistent with this, CKD stage was positively correlated with serum concentrations of IL-17 and negatively correlated with serum IL-10 levels. Moreover, serum levels of CHOP and GRP78 increased with advancing CKD stage. These correlations were most pronounced in patients in the CKD5 group, who also had the poorest response to HD and PD treatment, compared with CKD5 patients in the nondialysis group. Correlation analysis showed that serum levels of CHOP and GRP78 were independently and positively correlated with the ratio of Th17/Treg cells.We have found that an increased Th17/Treg cell ratio and increased serum levels of ERS markers correlate with the progression of CKD. Our results indicate that the interplay between regulation of the immune network and management of ERS is closely associated with the pathogenesis of CKD. Although HD and PD treatment manage chronic kidney conditions and prevent further deterioration of renal function, they have limited effects on improving the immune disorder and relieving ERS. Our study suggests a potential new direction for development of therapeutic strategies in CKD.

A meta-analysis: The diagnostic values of long non-coding RNA as a biomarker for gastric cancer.

Long non-coding RNAs (lncRNAs) have been identified as novel biomarkers for the diagnosis, staging and prognosis for gastric cancer. However, various studies have reported a series of significances based on different diagnostic values. Therefore, the current study performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of lncRNAs for gastric cancer, and to discuss lncRNA types and sources of heterogeneity. The Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, EMBASE, the Chinese Biomedical Literature Database, the China Academic Journals Full-text Database and the Chinese Scientific Journals Database were systematically searched for potential studies. Studies were included if they were associated with lncRNAs, gastric cancer and reported diagnostic outcomes. Analysis of diagnostic values was used to summarize the overall test performance of lncRNAs. Ten studies were included in this meta-analysis. The ranges of the diagnostic value of lncRNAs for gastric cancer were as follows: Sensitivity was 0.45-0.83, and pooled sensitivity was 0.63; specificity was 0.60-0.93, and pooled specificity was 0.75; positive likelihood ratio was 1.80-6.92, and pooled positive likelihood ratio was 2.51; negative likelihood ratio was 0.23-0.67, and pooled negative likelihood ratio was 0.50; diagnostic odds ratio was 3.33-13.75, and pooled diagnostic odds ratio was 5.47. An overall area under the curve value of the summary receiver operating characteristic curve was 0.7550. LncRNAs did not have a high accuracy for identifying gastric cancer at present, but may be a useful screening tool for diagnosing gastric cancer due to their correlation with gastric cancer biological features. LncRNAs are potential biomarkers for gastric cancer if the screening strategy is altered, or they are combined with other biomarkers to diagnose gastric cancer.

Quantitative and correlation analysis of the DNA methylation and expression of DAPK in breast cancer.

BACKGROUND: Death-associated protein kinase 1 (DAPK) is an important tumor suppressor kinase involved in the regulation of multiple cellular activities such as apoptosis and autophagy. DNA methylation of DAPK gene was found in various types of cancers and often correlated with the clinicopathological characteristics. However, the mRNA and protein expression of DAPK in the same sample was rarely measured. Thus, it was unclear if the correlation between DAPK gene methylation and clinicopathological parameters was due to the loss of DAPK expression. METHODS: In this study, the DNA methylation rate, mRNA and protein expression of DAPK was quantitatively detected in 15 pairs of breast cancer patient samples including tumor (T) and adjacent non-tumor (N) tissues. RESULTS: The correlation between DNA methylation rate and mRNA expression, together with the correlation between mRNA and protein expression, was calculated. No correlation was observed between any levels using either the measurement value of each sample or the T/N ratio of each pair. DISCUSSION: These data suggested that the DNA methylation status of DAPK did not correlate well with its mRNA or protein expression. Extra caution is needed when interpreting the DNA methylation data of DAPK gene in clinical studies.

Citrate attenuates vascular calcification in chronic renal failure rats.

Vascular calcification (VC) is a major contributor of cardiovascular dysfunction in chronic renal failure (CRF). Citrate binds calcium and inhibits the growth of calcium crystals. This present study intends to evaluate the effect of citrate on VC in adenine-induced CRF rats. The rats were randomly divided into five groups: the control group, the citrate control group, model group, model rats with low-dose treatment of citrate (216 mg/kg) and model rats with high-dose treatment of citrate (746 mg/kg). The rats were euthanized at 5 weeks with their blood and aorta in detection. The results showed that serum level of blood urea nitrogen, serum creatinine, phosphorus, calcium, and related renal failure function marker were elevated in the model group. Furthermore, the aortic calcium accumulation and alkaline phosphatase activity were significantly increased in the model group compared with control groups. Additionally, hematoxylin-eosin staining results demonstrated that the vascular calcification in aorta is significantly increased in the model group. Finally, the expression of VC-related proteins including bone morphogenetic protein and osteocalcin were increased in the model group, whereas alpha-smooth muscle actin was decreased in the model group compared with the control group. However, treatment with citrate caused a reversal effect of all the above events in a dose-dependent manner. In conclusion, citrate may attenuate vascular calcification in adenine-induced CRF rats.

17ß­Estradiol treatment drives Sp1 to upregulate MALAT­1 expression and epigenetically affects physiological processes in U2OS cells.

Osteosarcoma is the most common primary bone tumor characterized by high risk of metastasis, thus presents with an overall survival rate of 60%, despite the use of chemotherapy and surgery. Metastasis­associated lung adenocarcinoma transcript 1 (MALAT­1) has been reported to upregulated and epigenetically regulate the metastasis in osteosarcoma; however, the regulatory mechanisms of MALAT­1 expression remain unclear. In the current study, significant upregulation of MALAT­1 was observed subsequent to exposure to low concentrations of 17ß­estradiol (E2) in U2OS cells. Using chromatin immunoprecipitation assays, E2­activated estrogen receptor α (ERα) was identified to promote the binding of specificity protein 1 (Sp1) to the MALAT­1 promoter. Electrophoretic mobility shift assay and immunoprecipitation results demonstrate that ERα binds indirectly to the MALAT­1 promoter by binding directly to Sp1 protein. Notably, without E2 stimulation, overexpressed ERα results in no significant promotion of the Sp1/MALAT­1 promoter, indicating that the translocation of ERα to nuclei stimulated by E2 is necessary. The immunofluorescence assay confirmed that E2 stimulation promotes the translocation of Sp1 to the nuclei in an ERα­dependent manner. Subsequently, the effects of E2 on osteosarcoma physiological processes were further analyzed. Consistently, E2 treatment was observed to promote proliferation, colony formation, migration and invasion in U2OS cells. Taken together, the results indicate a role for E2 in regulating the physiological processes of osteosarcoma cells by regulating MALAT­1 expression levels.