BDNF mimetics recover palmitic acid-induced injury in cardiomyocytes by ameliorating Akt-dependent mitochondrial impairments.

Cardiac lipotoxicity is a prevalent consequence of lipid metabolism disorders occurring in cardiomyocytes, which in turn precipitates the onset of heart failure. Mimetics of brain-derived neurotrophic factor (BDNF), such as 7,8-dihydroxyflavone (DHF) and 7,8,3'-trihydroxyflavone (THF), have demonstrated significant cardioprotective effects. However, it remains unclear whether these mimetics can protect cardiomyocytes against lipotoxicity. The aim of this study was to examine the impact of DHF and THF on the lipotoxic effects induced by palmitic acid (PA), as well as the concurrent mitochondrial dysfunction. H9c2 cells were subjected to treatment with PA alone or in conjunction with DHF or THF. Various factors such as cell viability, lactate dehydrogenase (LDH) release, death ratio, and mitochondrial function including mitochondrial membrane potential (MMP), mitochondrial-derived reactive oxygen species (mito-SOX) production, and mitochondrial respiration were assessed. PA dose-dependently reduced cell viability, which was restored by DHF or THF. Additionally, both DHF and THF decreased LDH content, death ratio, and mito-SOX production, while increasing MMP and regulating mitochondrial oxidative phosphorylation in cardiomyocytes. Moreover, DHF and THF specifically activated Akt signaling. The protective effects of DHF and THF were abolished when an Akt inhibitor was used. In conclusion, BDNF mimetics attenuate PA-induced injury in cardiomyocytes by alleviating mitochondrial impairments through the activation of Akt signaling.

Circulating Myokines as Novel Biomarkers for Cardiovascular Diseases.

Myokines are a group of cytokines or polypeptides released from skeletal muscle during exercise. Growing evidence suggests that myokines are associated with the development of cardiovascular disease (CVD). Moreover, several myokines in peripheral blood exhibit dynamic changes in different CVD stages. This review summarizes the potential roles of myokines such as myostatin, irisin, brain-derived neurotrophic factor, mitsugumin 53, meteorin-like, and apelin in various CVD, including myocardial infarction, heart failure, atherosclerosis, hypertension, and diabetes. The association of these myokines with biomarkers currently being used in clinical practice is also discussed. Furthermore, the review considers the emerging role of myokines in CVD and addresses the challenges remaining in translating these discoveries into novel clinical biomarkers for CVD.

[Role of macrophage polarization in hypertension and traditional Chinese medicine intervention: a review].

Hypertension is known to be a chronic inflammatory state and a key risk factor for heart failure, coronary heart disease, and atherosclerosis. Macrophages in the circulatory system are the main cell group that constitutes the immune system and participates in the inflammatory response. Depending on the local microenvironment, macrophages can be polarized into pro-inflammatory(M1) and anti-inflammatory(M2) phenotypes. When blood pressure is elevated, M1 macrophages can release pro-inflammatory cytokines and chemokines to generate an immune response. However, an excessive immune response can lead to tissue damage, and M2 macrophages release anti-inflammatory cytokines to promote the repair of wounds and tissue damage. It is clear that the dynamic balance between M1 and M2 macrophages resembles the traditional Chinese medicine(TCM) theory of Yin and Yang. That is, when Yin and Yang are imbalanced, the human body will exhibit pathological states, e.g., altered blood pressure rhythms. Studies have confirmed that TCM can produce positive therapeutic effects on hypertension by regulating macrophage polarization. Therefore, this study reviews the studies about the TCM regulation of macrophage polarization and summarized the mechanisms of TCM intervention in hypertension, with the aim of providing evidence for clinical treatment and ideas for scientific research design.

Efficient genome editing in cotton using the virus-mediated CRISPR/Cas9 and grafting system.

KEY MESSAGE: The extensive application of CRISPR in cotton was limited due to the labor-intensive transformation process. Thus, we here established a convenient method of CRISPR in cotton by CLCrV-mediated sgRNA delivery.

Isolation and structure elucidation of two new cassane derivatives from the seed kernels of Caesalpinia sinensis.

Two new cassane-type derivatives (1-2), together with three known compounds (3-5), were isolated from the seed kernels of Caesalpinia sinensis. Their structures were elucidated on the basis of interpretation of comprehensive spectroscopic data, including HRESIMS and 1D/2D NMR spectroscopy, and the absolute configuration were established by means of ECD calculation. Compound 2, possessing a 16-degradative cassane skeleton, was rarely encountered in cassane diterpenoids isolated from the genus Caesalpinia. All compounds were evaluated for their anti-inflammatory activities against the overproduction of NO in LPS-stimulated RAW 264.7 macrophages, and compounds 1-5 could inhibit production of NO at the concentration of 50 µM.

Identification of NHXs in Gossypium species and the positive role of GhNHX1 in salt tolerance.

BACKGROUND: Plant Na+/H+ antiporters (NHXs) are membrane-localized proteins that maintain cellular Na+/K+ and pH homeostasis. Considerable evidence highlighted the critical roles of NHX family in plant development and salt response; however, NHXs in cotton are rarely studied. RESULTS: The comprehensive and systematic comparative study of NHXs in three Gossypium species was performed. We identified 12, 12, and 23 putative NHX proteins from G. arboreum, G. raimondii, and G. hirsutum, respectively. Phylogenetic study revealed that repeated polyploidization of Gossypium spp. contributed to the expansion of NHX family. Gene structure analysis showed that cotton NHXs contain many introns, which will lead to alternative splicing and help plants to adapt to high salt concentrations in soil. The expression changes of NHXs indicate the possible differences in the roles of distinct NHXs in salt response. GhNHX1 was proved to be located in the vacuolar system and intensively induced by salt stress in cotton. Silencing of GhNHX1 resulted in enhanced sensitivity of cotton seedlings to high salt concentrations, which suggests that GhNHX1 positively regulates cotton tolerance to salt stress. CONCLUSION: We characterized the gene structure, phylogenetic relationship, chromosomal location, and expression pattern of NHX genes from G. arboreum, G. raimondii, and G. hirsutum. Our findings indicated that the cotton NHX genes are regulated meticulously and differently at the transcription level with possible alternative splicing. The tolerance of plants to salt stress may rely on the expression level of a particular NHX, rather than the number of NHXs in the genome. This study could provide significant insights into the function of plant NHXs, as well as propose promising candidate genes for breeding salt-resistant cotton cultivars.

[Multiple subcutaneous nodules for 46 days in an infant aged 66 days].

A boy, aged 66 days, was admitted to the hospital due to subcutaneous nodules for 46 days and abdominal distension for 10 days. The main clinical manifestations were loss of adipose tissue, subcutaneous nodules, insulin-resistant diabetes, hypertriglyceridemia, and hepatic steatosis. The boy was diagnosed with congenital generalized lipodystrophy type 1 (CGL1). His condition was improved after administration of middle-chain fatty acid formula milk and insulin injection or oral metformin. Gene testing revealed a homozygous mutation, c.646A>T, in the AGPAT2 gene, and both his parents were carriers of this mutation. This case of CGL1 has the youngest age of onset ever reported in China and multiple subcutaneous nodules as the initial symptom.

Ladder chain Cd-based polymer as a highly effective adsorbent for removal of Congo red.

Developing of high effective and fast-rate adsorbent materials has been recently attracted intensive attentions all over the world due to organic dye polluted water treatment. However, few studies have been reported on the ultrahigh-capacity and fast-rate removal of Congo red. In this work, a new stable Cd-based coordination polymer exhibits excellent adsorption performance towards Congo Red. This ladder chain [Cd4(H2L)4(H2O)8(NDS)]n·3n(NDS) (I) (H2L = N1,N2-bis(pyridin-3-ylmethyl) ethane-1,2-diamine, 1,5-H2NDS = 1,5-naphthalene disulfonic acid) has been successfully synthesized by the hydrothermal reaction. At room temperature, the experimental adsorption capacity of coordination polymer (I) towards Congo red can reach up to 16,880 mg g-1 in 20 min (pH = 2.0-3.2), and its higher capacity and faster rate are all better than those in reported inorganic and metal-organic frameworks absorbents. The adsorption process is spontaneous and endothermic reaction, and fits well with the second-order kinetics, Langmuir and Scatchard isotherm adsorption models. The excellent adsorption performance of (I) towards Congo red is related to the strong electrostatic, various hydrogen bonding and π-π stacking interactions under acidic conditions.

Calcium-dependent protein kinases in cotton: insights into early plant responses to salt stress.

BACKGROUND: Soil salinization is one of the major environmental constraints to plant growth and agricultural production worldwide. Signaling components involving calcium (Ca2+) and the downstream calcium-dependent protein kinases (CPKs) play key roles in the perception and transduction of stress signals. However, the study of CPKs in cotton and their functions in response to salt stress remain unexplored. RESULTS: A total of 98 predicted CPKs were identified from upland cotton (Gossypium hirsutum L. 'TM-1'), and phylogenetic analyses classified them into four groups. Gene family distribution studies have revealed the substantial impacts of the genome duplication events to the total number of GhCPKs. Transcriptome analyses showed a wide distribution of CPKs' expression among different organs. A total of 19 CPKs were selected for their rapid responses to salt stress at the transcriptional level, most of which were also incduced by the thylene-releasing chemical ethephon, suggesting a partal overlap of the salinity and ethylene responses. Silencing of 4 of the 19 CPKs (GhCPK8, GhCPK38, GhCPK54, and GhCPK55) severely compromised the basal cotton resistance to salt stress. CONCLUSIONS: Our genome-wide expression analysis of CPK genes from up-land cotton suggests that CPKs are involved in multiple developmental responses as well as the response to different abiotic stresses. A cluster of the cotton CPKs was shown to participate in the early signaling events in cotton responses to salt stress. Our results provide significant insights on functional analysis of CPKs in cotton, especially in the context of cotton adaptions to salt stress.

[Effect of traditional Chinese medicine in inhibiting obesity and inflammatory diseases by regulating gut microbiota].

Traditional Chinese medicine(TCM) has been increasingly used in the prevention and treatment of obesity and obesity-related diseases. However, its mechanism of action is not yet clear. In recent years, with the development of high-throughput sequencing technology, scientific researches have found that the disorder of gut microbiota is associated with obesity and other diseases. Furthermore, it has been found that TCM can improve the structure of gut microbiota by increasing probiotics and reducing pathogens, which play an importent role in preventing the development and progression of obesity and other diseases. This article first explores the possible association between intestinal microbiota and obesity. Then, it reviews the traditional Chinese medicine and its role in regulating intestinal microbiota for the prevention and treatment of diseases, including obesity and inflammation, insulin resistance, type 2 diabetes, non-alcoholic fatty liver disease, inflammatory bowel disease and other diseases, in theexpectation of new strategies and research direction for treating obesity and relevant diseases, and providing important guidance for further studies in this field in the future.

Comparative expression and regulation of duplicated fibroblast growth factor 1 genes in grass carp (Ctenopharyngodon idella).

Fibroblast growth factor 1 (Fgf1) is known as a mitogenic factor involved in the regulation of cell growth, proliferation, and differentiation in vertebrates. Here, we report the isolation and characterization of two fgf1 genes in grass carp (Ctenopharyngodon idella). Grass carp fgf1a and fgf1b cDNAs are highly divergent, sharing a relatively low amino acid sequence identity of 50%, probably due to fish-specific gene duplication. fgf1a and fgf1b mRNAs were detected in the zygote and expressed throughout embryogenesis. Both fgf1a and fgf1b mRNAs were primarily detectable in the notochord at 12 hpf. At 24 hpf, fgf1a mRNA was mainly expressed in the gut and somites, while fgf1b transcript persisted in the notochord and was detected in the tailbud. At 36 hpf, both fgf1a and fgf1b transcripts were detected in the brain, somites, and tailbud. In addition, the fgf1a mRNA was detected at the base of the yolk sac, whereas the fgf1b mRNA was expressed in the pectoral fin. In adult fish, duplicated fgf1a and fgf1b mRNAs were distributed in most tissues. After 2-6days of starvation, both fgf1a and fgf1b mRNAs were upregulated in the muscle and liver. In the brain, fgf1a mRNA was upregulated, while fgf1b mRNA was significantly downregulated at 6days. Furthermore, both fgf1a and fgf1b mRNA levels were significantly decreased in the brain and muscle after administration of 10 or 50µg of the human growth hormone (hGH),while their mRNA levels were no significant difference in the liver. These results suggest that duplicated fgf1s may play important but divergent roles in the grass carp development.

Characterization of duplicated heme oxygenase-1 genes and their responses to hypoxic stress in blunt snout bream (Megalobrama amblycephala).

The heme oxygenase (HO)-1 is a cytoprotective enzyme that can be involved in cytoprotection against hypoxia stress. In this study, we cloned duplicated HO-1a and HO-1b cDNAs in hypoxia-sensitive blunt snout bream (Megalobrama amblycephala). HO-1a and HO-1b encode peptides with 272 amino acids and 246 amino acids, respectively, and they share a low sequence identity of 55%. HO-1a and HO-1b mRNAs were maternally deposited in the zygote, and the mRNAs decreased to the lowest levels at 8 hpf. Both mRNAs were significantly (p < 0.01) expressed from 12 hpf and fluctuated but maintained a high level after 16 hpf. Using in situ hybridization, HO-1a and HO-1b mRNAs were ubiquitously expressed in embryos at 12 hpf. At 24 and 36 hpf, HO-1b transcripts were detected in the mid- and hindbrain, respectively, whereas HO-1a was mainly transcribed in the eyes and endoderm at 24 hpf and in the brain at 36 hpf. In adult fish, HO-1a was abundantly expressed in the heart, liver, gill, kidney, spleen, and brain, while HO-1b mRNA was detected mainly in the kidney. After exposure to hypoxic stress, both HO-1a and HO-1b mRNAs were upregulated significantly in the gill and liver but downregulated significantly in the brain (p < 0.01). These findings suggest that duplicated HO genes have evolved divergently and yet play overlapping biological roles in regulating the response to hypoxia in M. amblycephala.

[Clinical study on compound prescription with Valerianae Jatamansi Rhizoma et Radix in treatment of generalized anxiety disorder].

This study was aimed to observe the clinical efficacy of anxiolytic compound prescription with Valerianae Jatamansi Rhizoma et Radix (ACPV) in treating liver Qi stagnation and feel ill at ease type generalized anxiety disorder (GAD). Sixty-seven patients diagnosed as GAD with stagnation of liver Qi and feel ill at ease were randomly divided into treatment group and control group. Patients in treatment group (n=34) was treated with ACPV decoction, and patients in control group (n=33) were treated with deanxit. Both groups were treated with respective drugs for 4 weeks. HAMA scale, traditional Chinese medicine (TCM) symptom scale (liver Qi stagnation and feel ill at ease type) and salivary cortisol levels were measured before and 2 weeks and 4 weeks after drug treatment. The life events scale (LES) and drug safety evaluation were performed before and after 4 weeks treatment. Two patients were excluded according to LES, and 5 patients were discontinued. Sixty patients were enrolled in the study finally (30 cases in each group). As compared with baseline, HAMA scores in both groups were significantly decreased at 2 weeks and 4 weeks (P<0.05, P<0.01). After 2 weeks and 4 weeks treatment, the TCM syndrome score in both group was also significantly improved (P<0.01). Moreover, the salivary cortisol levels in both groups were also decreased at 2 weeks and 4 weeks (P<0.05, P<0.01). The total efficiency between two groups had no statistically significant difference after 2 weeks treatment and 4 weeks treatment; moreover, no statistically significant differences were observed between two groups in HAMA scores, TCM syndrome scale scores and salivary cortisol levels between two groups. The incidence of adverse reactions in the treatment group was significantly lower than that in the control group (P<0.01), and there were no obvious side effects in general physical examination during the period of treatment. Thus, anxiolytic compound prescription with Valerianae Jatamansi Rhizoma et Radix is effective for GAD (stagnation of liver Qi and feel ill at ease type).

[Inhibitory effect of oleanolic acid on inflammatory response in IL-1ß-stimulated human synovial sarcoma SW982 cells].

To study the role of oleanolic acid on interleukin (IL)-1ß-stimulated expression of inflammatory cytokines, and to explore its anti-inflammatory mechanism in SW982 cells, the toxicity of oleanolic acid on SW982 cells was detected by MTT; effects of different concentrations of oleanolic acid(5, 10, 20 µmol·L(-1)) on the expression of inflammatory factors IL-6, IL-8 and matrix metalloproteinase-1 (MMP-1) was tested at protein and m RNA levels. The study was performed in IL-1ß-stimulated SW982 cells together with enzyme-linked immunosorbent assay (ELISA) and real-time fluorescence quantitative PCR (real-time PCR) methods; the influence of oleanolic acid on the phosphorylation of mitogen-activated protein kinase (MAPK), phosphatidyl inositol-3-kinase/Akt (PI3K/Akt) and nuclear transcription factor-κB (NF-κB) signaling pathways related protein was analyzed by Western blot. Results showed that different concentrations of oleanolic acid(≤40 µmol·L(-1)) were almost non-toxicity to SW982 cells; oleanolic acid significantly inhibited the expression of inflammatory factors in a dose-dependent manner; oleanolic acid restrained extracellular signal-related kinase (ERK), p38, c-jun N-terminal kinase (JNK) and Akt protein phosphorylation and IκB-α protein degradation obviously. The inhibition effect of oleanolic acid on inflammatory factors stimulated by IL-1ß may be worked through MAPK, PI3K/Akt and NF-κB signaling pathways.

[Research advances in gene polymorphisms in biological pathways of drugs for asthma].

The studies on gene polymorphisms in biological pathways of the drugs for the treatment of asthma refer to the studies in which pharmacogenetic methods, such as genome-wide association studies, candidate gene studies, genome sequencing, admixture mapping analysis, and linkage disequilibrium, are used to identify, determine, and repeatedly validate the effect of one or more single nucleotide polymorphisms on the efficacy of drugs. This can provide therapeutic strategies with optimal benefits, least side effects, and lowest costs to patients with asthma, and thus realize individualized medicine. The common drugs for asthma are ß2 receptor agonists, glucocorticoids, and leukotriene modifiers. This article reviews the research achievements in polymorphisms in biological pathways of the common drugs for asthma, hoping to provide guidance for pharmacogenetic studies on asthma in future and realize individualized medicine for patients with asthma soon.

Expression of ATP synthase CF1 alpha subunit gene (CTL-spn) as screened by the cDNA-SRAP approach is correlated with spininess in Carthamus tinctorius L.

The safflower floret is a traditional Chinese medicine used to promote blood circulation and remove obstruction in the channels. The spines on its bracts are considered a handicap when manual harvest is involved. In this study, cDNA-SRAP was used to systematically investigate which genes are associated with the spines. Sixty pairs of possible primer combinations were used on two cDNA pools representing spininess and spinelessness. Six transcript-derived fragments were identified, of which two with low recombination were sequenced successfully and named as GPY-1 and GPY-2. By using the RACE method, the full-length cDNA of GPY-2 is cloned and named as CTL-spn. The full-length cDNA of CTL-spn was 1 679 bp long with a 1 524 bp ORF encoding a 508 aminoacid protein. The deduced amino acid sequence of the CTL-spn gene shared a high homology (97%) with other known ATP synthase CF1 alpha subunits. Semiquantitative RT-PCR analysis revealed that the mRNA of GPY-1 and GPY-2 accumulated in only spiny lines. Considering the important role of ATP synthase CF1 alpha subunit in plants, it may directly take part in the formation process of spininess and enhancing resistance reaction of spiny safflower. Also, our results provide the important insights for breeding spineless cultivars of safflower.

Interactions between Beta-Amyloid and Pericytes in Alzheimer's Disease.

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder characterized by aberrant amyloid precursor protein (APP) cleavage, pathological aggregations of beta-amyloid (Aß) that make up Aß plaques and hyperphosphorylation of Tau that makes up neurofibrillary tangles (NFTs). Although progress has been made in research on AD, the fundamental causes of this disease have not been fully elucidated. Recent studies have shown that vascular dysfunction especially the loss of pericytes plays a significant role in the onset of AD. Pericytes play a variety of important roles in the nervous system including the regulation of the cerebral blood flow (CBF), the formation and maintenance of the blood-brain barrier (BBB), angiogenesis, and the clearance of toxic substances from the brain. Pericytes participate in the transport of Aß through various receptors, and Aß acts on pericytes to cause them to constrict, detach, and die. The loss of pericytes elevates the levels of Aß1-40 and Aß1-42 by disrupting the integrity of the BBB and reducing the clearance of soluble Aß from the brain interstitial fluid. The aggravated deposition of Aß further exacerbates pericyte dysfunction, forming a vicious cycle. The combined influence of these factors eventually results in the loss of neurons and cognitive decline. Further exploration of the interactions between pericytes and Aß is beneficial for understanding AD and could lead to the identification of new therapeutic targets for the prevention and treatment of AD. In this review, we explore the characterization of pericytes, interactions between pericytes and other cells in the neurovascular unit (NVU), and the physiological functions of pericytes and dysfunctions in AD. This review discusses the interactions between pericytes and Aß, as well as current and further strategies for preventing or treating AD targeting pericytes.

Tumor volume of resectable adenocarcinoma of the esophagogastric junction at multidetector CT: association with regional lymph node metastasis and N stage.

PURPOSE: To determine whether the volume of resectable adenocarcinoma of the esophagogastric junction (AEG) measured at multidetector computed tomography (CT) is associated with regional lymph node metastasis and N stage. MATERIALS AND METHODS: The study was approved by the institutional ethics committee, and written informed consent was obtained from each participant. Two hundred sixteen patients with resectable AEG prospectively underwent contrast material-enhanced thoracoabdominal multidetector CT less than 2 weeks before curative resection. Gross tumor volume was retrospectively measured on CT scans. Univariate and multivariate analyses were performed to identify whether gross tumor volume is associated with regional lymph node metastasis. The Mann-Whitney U test was performed to compare gross tumor volume among N stages, with Bonferroni correction for multigroup comparisons. Receiver operating characteristic analysis was performed to determine if gross tumor volume could help classify N stage. RESULTS: Univariate analysis showed that gross tumor volume is associated with regional lymph node metastasis (P < .0001). Multivariate analysis revealed that gross tumor volume is an independent risk factor of lymph node metastasis (P = .023, odds ratio = 2.791). The Mann-Whitney U test showed that gross tumor volume could help differentiate between stage N0 and stages N1-N2 or N1-N3 disease and between stages N1-N2 and stage N3 disease (P < .0001 for all). In patients with stage T1-T3 AEG, gross tumor volume could help differentiate between stage N0 and stages N1-N2 (cutoff, 15.23 cm(3)) or N1-N3 (cutoff, 17.16 cm(3)) disease and between stages N1-N2 and stage N3 disease (cutoff, 33.96 cm(3)). In patients with stage T3 AEG, gross tumor volume could help differentiate stage N0 from stages N1-N2 (cutoff, 18.41 cm(3)) or N1-N3 (cutoff, 19.30 cm(3)) disease and stages N1-N2 from stage N3 disease (cutoff, 33.96 cm(3)). CONCLUSION: Gross tumor volume of AEG measured with multidetector CT is associated with regional lymph node metastasis and N stage.

Sublingual immunotherapy for experimental allergic conjunctivitis in a murine model induced by Dermatophagoides farinae allergen.

BACKGROUND: Sublingual immunotherapy (SLIT) is a clinically effective treatment in allergic conjunctivitis (AC); however, the mechanism of the underlying pharmacodynamics remains unclear. Here, we investigate the efficacy and the mechanism of a sublingually administered Dermatophagoides farinae (Der f) vaccine in a murine AC model. METHODS: A murine model of AC caused by Der f extract was developed in BALB/c mice by repeated application of allergen. Sensitized mice were SLIT treated by Der f drops and subsequently analyzed for AC symptoms, histopathological and immunological parameters. RESULTS: In this study, Der f extract successfully induced the symptoms of AC in BALB/c mice. In these sensitized mice, clinical symptoms (scratching behavior, lacrimation, conjunctival hyperemia and edema), immunological and histopathological findings (inflammatory cell infiltration) were very similar to those in human AC. SLIT treatment of sensitized mice markedly reduced the clinical and histopathological symptoms and decreased the expression levels of total immunoglobulin E (IgE), Der f-specific IgE and T helper cell 2 (Th2) cytokine interleukin-4, with a significant increase in Der f-specific IgG4 and Th1 cytokine interferon-γ. CONCLUSIONS: SLIT with Der f drops is a potentially effective means of immunotherapy for Der f-induced AC by modulating the Th2-biased allergic immune response.