Analysis of the effect of 60Co irradiation sterilization on the chemical composition of volatile organic compounds in Rhizoma Acori Tatarinowii using GC-IMS.

The volatile organic compounds (VOCs) of Rhizoma Acori Tatarinowii were extracted via steam distillation and then irradiated with 60Co-γ rays, in which doses of 60Co-γ 0, 5, and 10 kGy were selected to irradiate the VOCs. Finally, gas chromatography-ion mobility spectrometry (GC-IMS) was used to compare the differences between the VOCs, and then qualitatively analyse the components and contents of each part of the VOCs The results showed that under the three irradiation doses of 60Co-γ 0, 5 and 10 kGy, the VOCs of unirradiated and 5 kGy-irradiated samples were closer, and the samples irradiated at a 10 kGy dose were quite different from the other two components, meaning that when the calamus medicinal materials were sterilised by means of 60Co irradiation, the dose of 5 kGy was closer to the original compound content of the medicinal materials.

[Neuroprotective effect and mechanism of Zuogui Jiangtang Jieyu Formula on diabetes mellitus complicated with depression model rats based on CX3CL1-CX3CR1 axis].

Based on the CX3C chemokine ligand 1(CX3CL1)-CX3C chemokine receptor 1(CX3CR1) axis, this study explored the potential mechanism by which Zuogui Jiangtang Jieyu Formula(ZGJTJY) improved neuroinflammation and enhanced neuroprotective effect in a rat model of diabetes mellitus complicated with depression(DD). The DD rat model was established by feeding a high-fat diet combined with streptozotocin(STZ) intraperitoneal injection for four weeks and chronic unpredictable mild stress(CUMS) combined with isolated cage rearing for five weeks. The rats were divided into a control group, a model group, a positive control group, an inhibitor group, and a ZGJTJY group. The open field test and forced swimming test were used to assess the depression-like behaviors of the rats. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the expression levels of the pro-inflammatory cytokines interleukin-1ß(IL-1ß) and tumor necrosis factor-α(TNF-α) in plasma. Immunofluorescence staining was used to detect the expression of ionized calcium-binding adapter molecule 1(Iba1), postsynaptic density protein-95(PSD95), and synapsin-1(SYN1) in the hippocampus. Hematoxylin-eosin(HE) staining, Nissl staining, and TdT-mediated dUTP nick end labeling(TUNEL) fluorescence staining were performed to assess hippocampal neuronal damage. Western blot was used to measure the expression levels of CX3CL1, CX3CR1, A2A adenosine receptor(A2AR), glutamate receptor 2A(NR2A), glutamate receptor 2B(NR2B), and brain-derived neurotrophic factor(BDNF) in the hippocampus. Compared with the model group, the ZGJTJY group showed improved depression-like behaviors in DD rats, enhanced neuroprotective effect, increased expression of PSD95, SYN1, and BDNF(P<0.01), and decreased expression of Iba1, IL-1ß, and TNF-α(P<0.01), as well as the expression of CX3CL1, CX3CR1, A2AR, NR2A, and NR2B(P<0.01). These results suggest that ZGJTJY may exert its neuroprotective effect by inhibiting the CX3CL1-CX3CR1 axis and activation of hippocampal microglia, thereby improving neuroinflammation and abnormal activation of N-methyl-D-aspartate receptor(NMDAR) subunits, and ultimately enhancing the expression of synaptic-related proteins PSD95, SYN1, and BDNF in the hippocampus.

High-oleic rapeseed oil quality indicators and endogenous antioxidant substances under different processing methods.

This study exposed high-oleic rapeseed oil (HORO) to different pretreatment (microwave or roasting) and processing methods to investigate (cold pressing, hexane extraction, subcritical butane extraction, and aqueous enzymatic extraction) the effects of processing technologies on HORO parameters associated with its physicochemical properties, endogenous antioxidant substances, and antioxidant capacity. The oil yield of various processing technologies was between 35.4% and 59.7%, and the fatty acid composition did not significantly differ. Hierarchical clustering and principal component analyses were used for evaluation. The results revealed that the microwave pretreatment-hexane extraction (M-HE) method resulted in significantly higher levels of tocopherols (688.4 mg/kg), polyphenols (1007.76 mg/kg), and phytosterols (1810.6 mg/kg) in HORO, implying strong free radical scavenging capacity (DPPH-oil: 79.63, DPPH-nonpolar: 71.42, DPPH-polar: 6.65, FRAP: 55.4, ABTS: 3043.7 µmol TE/kg). Hence, M-HE is a promising method for producing HORO with a higher stability and nutritional value.

Regulating the stereoselectivity of medium-chain dehydrogenase/reductase by creating an additional active pocket accommodating prochiral heterocyclic ketones.

Medium chain dehydrogenase/reductase (MDR) is a robust catalyst for the asymmetric synthesis of chiral heterocyclic alcohols, essential building blocks in pharmaceuticals. However, the regulatory mechanism of stereoselective complementary reduction of heterocyclic ketones by carbonyl reductase (CR) is unclear. Structure-guided creation of an additional substrate-binding active pocket inversed the stereoselectivity of SpCR from Spathaspora passalidarum. The mutant m48 showed improved catalytic activity towards the 12 tested heterocyclic ketones (conversion rate >99%, ee value > 99%). Hence, we regulated the stereoselectivity of MDR by creating an active pocket suitable for substrate localisation. This strategy has a guiding significance in addition to the conventional method for stereoselectivity modification of MDR.

[Therapeutic effect and mechanism of Xiaoyao Kangai Jieyu Recipe on mice with breast cancer related depression through regulating COX pathway].

This study aimed to investigate the intervention effect and mechanism of Xiaoyao Kangai Jieyu Recipe(XKJR) on hip-pocampal microglia and neuronal damage in mice with breast cancer related depression. The mouse model of breast cancer related depression was established by inoculation of 4T1 breast cancer cells in axilla and subcutaneous injection of corticosterone(30 mg·kg~(-1)). The successfully modeled mice were randomly divided into a model group, a positive drug group(capecitabine 60 mg·kg~(-1)+fluoxetine 19.5 mg·kg~(-1)), and XKJR group(19.5 mg·kg~(-1) crude drug), with 6 in each group. Another 6 normal mice were taken as a normal group. The administration groups were given corresponding drugs by gavage, while the normal and model groups were given an equal volume of distilled water, once a day for 21 consecutive days. The depressive behavior of mice was assessed by glucose consumption test, open field test and novelty-suppressed feeding test. Hematoxylin and eosin(HE) staining and tumor suppression rate were used to evaluate the changes of axillary tumors. The mRNA expressions and the relative protein expressions of interleukin-1ß(IL-1ß), interleukin-18(IL-18), cyclooxyganese-2(COX-2) and glutamyl-prolyl-tRNA synthetase(EPRs) in the hippocampus of mice were determined by quantitative real-time polymerase chain reaction(qRT-PCR) and immunohistochemistry, respectively. Immunofluorescence was performed to detect the mean fluorescence intensity of CD11b, a marker of hippocampal microglia activation. Nissler staining and transmission electron microscopy were employed to observe the morphological changes and the ultramorphological changes of hippocampal neurons, respectively. The experimental results indicated that compared with the normal group, the model group had reduced glucose consumption and lowered number of total activities in open field test(P<0.05, P<0.01), prolonged first feeding latency in no-velty-suppressed feeding test(P<0.01), and significant depression-like behavior; the contents of IL-1ß, IL-18, COX-2, and EPRs in hippocampus were increased(P<0.05, P<0.01), with hippocampal microglia activation and obvious neuronal damage. Compared with the model group, the positive drug group and the XKJR group presented an improvement in depressive behaviors, a decrease in the contents of IL-1ß, IL-18, COX-2 and EPRs in hippocampus, and an alleviation in the activation of hippocampal microglia and neuronal damage; the tumor suppression rates of positive drug and XKJR were 40.32% and 48.83%, respectively, suggesting a lower tumor growth rate than that of the model group. In summary, XKJR may improve hippocampal microglia activation and neuronal damage in mice with breast cancer related depression through activating COX signaling pathway.

SPATA2 suppresses epithelial-mesenchymal transition to inhibit metastasis and radiotherapy sensitivity in non-small cell lung cancer via impairing DVL1/ß-catenin signaling.

Metastasis is the major cause of cancer-related death of cancer patients. Epithelial-mesenchymal transition (EMT) is one critical process during the cascade of tumor metastasis. EMT is a developmental program exploited by cancer cells to transition from epithelial state to mesenchymal state and confers metastatic properties as well as treatment resistance. Finding factors to inhibit EMT will greatly improve the prognosis patients. Spermatogenesis associated 2 (SPATA2) was originally isolated from human testis and proved playing a role in spermatogenesis. To date, however, the role of SPATA2 in oncogenesis is unknown. In the current study, by mining the public database and validating in a cohort of collected non-small cell lung cancer (NSCLC) specimens, we uncovered that the expression of SPATA2 positively correlated with the prognosis of patients and was an independent prognosis marker in NSCLC. Functional studies proved that ectopic overexpression of SPATA2 inhibited EMT resulting in impaired motility and invasiveness properties in vitro and metastasis in vivo, and increased radiosensitivity in NSCLC. Mechanistic investigation showed that SPATA2 could suppress the ß-catenin signaling via attenuating DVL1 ubiquitination to achieve the functions. Taken together, the current study revealed an inhibitory role of SPATA2 on EMT and that SPATA2 could be a potential target for therapy of NSCLC.

A methylation-related signature for predicting prognosis and sensitivity to first-line therapies in gastric cancer.

Background: Methylation modification patterns play a crucial role in human cancer progression, especially in gastrointestinal cancers. We aimed to use methylation regulators to classify patients with gastric adenocarcinoma and build a model to predict prognosis, promoting the application of precision medicine. Methods: We obtained RNA sequencing data and clinical data from The Cancer Genome Atlas (TCGA) database (n=335) and Gene Expression Omnibus (GEO) database (n=865). Unsupervised consensus clustering was used to identify subtypes of gastric adenocarcinoma. We performed functional enrichment analysis, immune infiltration analysis, drug sensitivity analysis, and molecular feature analysis to determine the clinical application for different subtypes. The univariate Cox regression analysis and the LASSO regression analysis were subsequently used to identify prognosis-related methylation regulators and construct a risk model. Results: Through unsupervised consensus clustering, patients were divided into two subtypes (cluster A and cluster B) with different clinical outcomes. Cluster B included patients with a better prognosis outcome and who were more likely to respond to immunotherapy. We then successfully built a predictive model and found five methylation-related genes (CHAF1A, CPNE8, PHLDA3, SPARC, and EHF) potentially significant to the prognosis of patients. The 1-, 3-, and 5-year areas under the curve of the risk model were 0.712, 0.696, and 0.759, respectively. The risk score was an independent prognostic factor and had the highest concordance index among common clinical indicators. Meanwhile, the tumor microenvironment, sensitivity of chemotherapeutic drugs, molecular features, and oncogenic dedifferentiation differed significantly across the risk groups and subtypes. Conclusions: We classified patients with gastric adenocarcinoma based on methylation regulators, which has positive implications for first-line clinical treatment. The prognostic model could predict the prognosis of patients and help to promote the development of precision medicine.

Case report: Application of non-VKA oral anticoagulants in patient of idiopathic hypereosinophilic syndrome with intracardiac thrombus.

Idiopathic hypereosinophilic syndrome (IHES) is a rare but life-threatening disease related to a group of myeloproliferative disorders characterized by prolonged eosinophilia of unknown cause and inflammatory damage to multiple organs. Here, we present a 44-year-old female patient complaining of shortness of breath and palpitations for 1 month. Her history and presentation were unremarkable, except for a 3-years history of rheumatoid arthritis treated with ibuprofen (0.3 g per day). Initial examination showed heart rate (HR) 120 bpm, respiratory rate (RR) 20 bpm, temperature (T) 36°C, blood pressure (BP) 130/70 mmHg, ventricular gallop rhythm, rales at the lung bases, soft abdomen, nonpalpable liver and spleen, and slight edema in both lower extremities. Bone marrow aspirate and biopsy confirmed the diagnosis of IHES, while cardiac MRI showed intracardiac thrombus. The symptoms of shortness of breath and palpitation disappeared, the eosinophil counts in routine blood tests were normal, and the thrombus in the cardiac cavity gradually disappeared after combined therapy of anti-hypereosinophilic, anti-coagulant and anti-heart failure treatments.

Physicochemical properties of rice bran blended oil in deep frying by principal component analysis.

This study aimed to obtain a rice bran blended oil with good quality in deep frying. The thermal stability, nutrients and harmful substances of rice bran oil (RBO) and other four oils (palm oil, PO; cottonseed oil, CO; sunflower oil, SuO; soybean oil, SO) were analyzed. Besides, the blended oil formulas were established by the principal component analysis method, and their physicochemical properties, frying characteristic indicators, nutrients, and harmful substances were compared. The results provided that two suitable blended oil formulas (F1: 50% RBO + 40% PO + 10% CO; F2: 60% RBO + 35% PO + 5% CO) of good frying performance were attained by principal component analysis. The acid value (1.19 mg/g), peroxide value (0.09 meq/kg), residual oil rate (8.07%), 3-MCPD ester reduction content (2.33 mg/kg), benzopyrene concentration content (0.95 µg/kg) and vitamin E consumption rate (67.86%) in F2 were lower than that in F1. Moreover, the oryzanol retention rate (87.84%) of F2 was higher than that of F1. In summary, F2 was more conducive to human health and more suitable than F1 in deep-frying. This information had an important directive on the industrial production of rice bran blend oil. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05472-7.

Sleep deprivation leads to further impairment of hippocampal synaptic plasticity by suppressing melatonin secretion in the pineal gland of chronically unpredictable stress rats.

There has been ample research showing that insomnia is a potential trigger of depression as well as a symptom of depression. These two factors contribute to behavioural problems and are closely related to the plasticity of hippocampal synapses. Although depression and insomnia impair hippocampal synaptic plasticity, the mechanism by which this happens remains a mystery. This study aimed to investigate the pathogenesis of insomnia comorbidity in depression and the regulatory effect of venlafaxine combined with melatonin on hippocampal synaptic plasticity in chronic unpredictable mild stress (CUMS) with sleep deprivation (SD) rats. Thus, rats were subjected to 14 days of chronic mild unpredictable stress, gradually acclimated to sleep deprivation on days 12-14. Followed by 21 consecutive days of sleep deprivation, 18 h per day, with daily gavage of venlafaxine (13.5 mg/kg) + melatonin (72 mg/kg) on days 15-36. Venlafaxine + melatonin treatment improves depression-like behaviour, pentobarbital sodium experimental sleep latency, and sleep duration in CUMS +SD rats. In addition to improving depressive-like behaviors, sleep deprivation also upregulates the expression of caspase-specific cysteine protein 3 (Caspase 3) in the pineal glial cells of chronic mild rats, as well as in hippocampal microglia. Expression of ionic calcium-binding adaptor 1 (iba-1), downregulates the secretion of several synaptic plasticity-related proteins, notably cAMP response element binding protein (CREB), glial cell line-derived neurotrophic factor (GDNF), and the synaptic scaffolding protein Spinophiline (Spinophiline). Hematoxylin-eosin staining showed that the structure of the pineal gland and hippocampus was damaged, and Golgi staining showed that the dendrites and spines in the DG area of the hippocampus were destroyed, vaguely aggregated or even disappeared, and the connection network could not be established. Western blot analysis further revealed a positive correlation between low melatonin levels and reduced Spinophiline protein. Interestingly, venlafaxine + melatonin reversed these events by promoting hippocampal synaptic plasticity by regulating melatonin secretion from the pineal gland. Therefore, it exerted an antidepressant effect in sleep deprivation combined with CUMS model rats. Overall, the results of this study suggest that the pathophysiology of depressive insomnia comorbidity is mediated by impaired pineal melatonin secretion and impaired hippocampal synaptic plasticity. In addition, these responses are associated with melatonin secretion from the pineal gland.

Antidepressant actions of melatonin and melatonin receptor agonist: Focus on pathophysiology and treatment.

Depression has become one of the most commonly prevalent neuropsychiatric disorders, and the main characteristics of depression are sleep disorders and melatonin secretion disorders caused by circadian rhythm disorders. Abnormal endogenous melatonin alterations can contribute to the occurrence and development of depression. However, molecular mechanisms underlying this abnormality remain ambiguous. The present review summarizes the mechanisms underlying the antidepressant effects of melatonin, which is related to its functions in the regulation of the hypothalamic-pituitary-adrenal axis, inhibition of neuroinflammation, inhibition of oxidative stress, alleviation of autophagy, and upregulation of neurotrophic, promotion of neuroplasticity and upregulation of the levels of neurotransmitters, etc. Also, melatonin receptor agonists, such as agomelatine, ramelteon, piromelatine, tasimelteon, and GW117, have received considerable critical attention and are highly implicated in treating depression and comorbid disorders. This review focuses on melatonin and various melatonin receptor agonists in the pathophysiology and treatment of depression, aiming to provide further insight into the pathogenesis of depression and explore potential targets for novel agent development.

A comparison of the modified Broström procedure and modified Karlsson procedure in treating chronic lateral ankle instability: a systematic review and meta-analysis.

BACKGROUND: This study sought to compare the efficacy and surgery complications of the modified Broström procedure and the modified Karlsson procedure in treating patients with chronic lateral ankle instability (CLAI). METHODS: Full-text publications on the clinical efficacy of Broström's and Karlsson's procedures were retrieved from multiple databases. Review Manager 5.0 was adopted for the meta-analysis, sensitivity analysis, and bias analysis. RESULTS: Nine studies comprising a total of 643 patients were identified. The meta-analysis suggested that the American Orthopedic Foot and Ankle Society (AOFAS) scores of patients in the Karlsson group were higher than those of patients in the Broström group [mean deviation (MD) =6.31, 95% confidence interval (CI): 2.31-10.30, P=0.002; P for heterogeneity <0.00001, I2=58%]. The Tegner scores of patients in the Karlsson group were higher than those of patients in the Broström group (MD =0.72, 95% CI: 0.48-0.95, P=0.24; P for heterogeneity <0.00001, I2=23%). Operation times in the Broström group were higher than those in the Karlsson group (MD =-15.50, 95% CI: -19.98--11.02, P<0.00001; P for heterogeneity <0.00001, I2=63%). Patients in the Karlsson group had higher levels of satisfaction than those in the Broström group (MD =0.63, 95% CI: 0.47-0.79, P<0.00001; P for heterogeneity =0.91, I2=0%). No significant difference was observed in surgery complications between the Karlsson and Broström groups [odds ratio (OR) =1.71, 95% CI: 0.79-3.71, P=0.18; P for heterogeneity =0.99, I2=0%]. DISCUSSION: Based on the heterogeneity analysis results, this study showed that Karlsson's procedure was more efficient and safer than Broström's treatment in the treatment of CLAI patients.

Retraction: Nanozyme-Initiated In Situ Cascade Reactions for Self-Amplified Biocatalytic Immunotherapy.

Adv. Mater. 2021, 33, 2006363 DOI: 10.1002/adma.202006363 The above article, published online on December 6, 2020, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief Jos Lenders, and Wiley-VCH GmbH. The authors asked to retract this article as subsequent experiments revealed that the conclusions of this manuscript are invalid. The generation of hydroxyl radicals by the artificial cascade enzyme-drug conjugate could not be confirmed.

Nanozyme-Initiated In Situ Cascade Reactions for Self-Amplified Biocatalytic Immunotherapy.

Biocatalytic nanomaterials have been verified to modulate the immunosuppressive state of an extensive range of solid tumors and directly induce antitumor immune response, which effectively combats the holdbacks in cancer immunotherapy. Herein, biomimetic cascade enzyme-initiated toxic-radical-generating devices (GHZD NCs) are fabricated by enveloping glucose oxidase (GOx), artificial nanozyme hemin, and sesquiterpene lactone endoperoxide derived dihydroartemisinin (DHA) into zeolitic imidazolate framework (ZIF-8) for enhanced biocatalytic immunotherapy. The GHZD NCs exhibit amplified multienzyme-mimic (glucose oxidase, peroxidase, and glutathione peroxidase) cascade reactions in artificial nanoscale proximity. Concurrently, a glutathione (GSH)-stimulated labile iron-current amplifier boosts C-centered free radicals, which endows the GHZD NCs with tumor-specific and self-circulating generation ability of vicious C-centered free radicals. Irreversible free radicals (·C and ·OH) and sustainable H2 O2 from sequential catalytic processes logically and selectively elevate the oxidative stress in the tumor, which further triggers an efficient immunogenic cell death (ICD) progress. In addition, the in situ nanozyme-based immunotherapy employed for tumor suppression successfully elicits the long-lasting immunological memory effect, which hinders the growth of distant tumors and lung metastasis.

circRNA-miRNA-mRNA regulatory network in human lung cancer: an update.

Circular RNAs, as hopeful diagnosis markers and therapeutic molecules, have been studied, probed and applied into several diseases, such as cardiovascular diseases, systemic lupus erythematosus, leukemia, pulmonary tuberculosis, and cancer especially. Recently, mounting evidence has supported that circRNAs play a key role in the tumorigenesis, progress, invasion and metastasis in lung cancer. Its special structure-3'-5' covalent loop-allow it to execute several special functions in both normal eukaryotic cells and cancer cells. Our review summaries the latest studies on characteristics and biogenesis of circRNAs, and highlight the regulatory functions about miRNA sponge of lung-cancer-related circRNAs. In addition, the interaction of the circRNA-miRNA-mRNA regulatory network will also be elaborated in detail in this review. Therefore, this review can provide a new idea or strategy for further development and application in clinical setting in terms of early-diagnosis and better treatment.

AFP-producing hepatoid adenocarcinoma (HAC) of peritoneum and omentum: a case report and literature review.

Hepatoid adenocarcinoma (HAC) is a group of neoplasms with features resembling hepatocellular carcinoma. The stomach is the most commonly affected organ among the reported primary sites. We report the case of a 28-year-old man with chronic hepatitis B and a complaint of abdominal distension. The patient was examined by PET-CT and magnetic resonance imaging (MRI), which showed diffuse thickening of the peritoneum and omentum but no mass was found in the liver. Pathological examination of a biopsy of the omental nodules was consistent with moderately differentiated hepatocellular carcinoma (HCC); thus, a diagnosis of HAC of the peritoneum and omentum was established. The patient received a chemotherapy regimen consisting of oxaliplatin and capecitabine and gained remarkable effects as the AFP level dropped significantly, and the tumour nearly disappeared. When the patient shifted to the standard multikinase inhibitors, Sorafenib or Lenvatinib, both treatments were ineffective. HAC is a heterogeneous group of prognostically unfavourable tumours mimicking the histological appearance of HCC, and the treatment outcomes are still unclear.

G-Protein-Coupled Estrogen Receptor Antagonist G15 Decreases Estrogen-Induced Development of Non-Small Cell Lung Cancer.

G-protein-coupled estrogen receptor (GPER) was found to promote non-small cell lung cancer (NSCLC) by estrogen, indicating the potential necessity of inhibiting GPER by a selective antagonist. This study was performed to elucidate the function of GPER-selective inhibitor G15 in NSCLC development. Cytoplasmic GPER (cGPER) and nuclear GPER (nGPER) were detected by immunohistochemical analysis in NSCLC samples. The relation of GPER and estrogen receptor ß (ERß) expression and correlation between GPER, ERß, and clinical factors were analyzed. The effects of activating GPER and function of G15 were analyzed in the proliferation of A549 and H1793 cell lines and development of urethane-induced adenocarcinoma. Overexpression of cGPER and nGPER was detected in 80.49% (120/150) and 52.00% (78/150) of the NSCLC samples. High expression of GPER was related with higher stages, poorer differentiation, and high expression of ERß. The protein level of GPER in the A549 and H1793 cell lines was increased by treatment with E2, G1 (GPER agonist), or fulvestrant (Ful; ERß antagonist) and decreased by G15. Administration with G15 reversed the E2- or G1-induced cell growth by inhibiting GPER. In urethane-induced adenocarcinoma mice, the number of tumor nodules and tumor index increased in the E2 or G1 group and decreased by treatment with G15. These findings demonstrate that using G15 to block GPER signaling may be considered as a new therapeutic target in NSCLC.

FGFR2 Promotes Gastric Cancer Progression by Inhibiting the Expression of Thrombospondin4 via PI3K-Akt-Mtor Pathway.

BACKGROUND/AIMS: Fibroblast growth factor receptor 2 (FGFR2) has attracted considerable interest as a therapeutic target in gastric cancer (GC). There is growing evidence to suggest that the bioavailability of the potent pro-tumor function of FGFR2 is associated with thrombospondins (TSPs). As a follow-on from our previous study, here we evaluated the potential clinical significance and mechanism of the relationship between FGFR2 and TSP4 in GC. METHODS: Expression levels of FGFR2 and TSP4 were detected by immunohistochemistry in GC tissue microarray slides. SGC7901 and MKN28 cell lines were used to confirm the relationship between FGFR2 and TSP4. In vitro cell viability, colony formation, and invasion and migration assays were performed to evaluate the effect of FGFR2-TSP4 axis on tumor cell activities. The mechanism of TSP4 regulated by FGFG2 was explored via small molecular inhibitors in vitro and a xenograft model. RESULTS: FGFR2 was shown to be markedly overexpressed in GC tissues and was correlated with a high risk of lymph node metastasis, late clinical stage, and poor prognosis. Low TSP4 expression was associated with shorter overall survival (OS) and advanced stage in GC patients. Interestingly, correlation analysis indicated that FGFR2 was negatively associated with TSP4. Indeed, in vitro and in vivo experiments suggested FGFR2 activation could downregulate TSP4 expression, which played an important role in the proliferation, invasion and migration of GC cells. We also found involvement of the PI3K-AKT-mTOR pathway in the FGFR2-TSP4 axis. CONCLUSION: The FGFR2 signal promotes human GC progression through the downregulation of TSP4 via PI3K-AKT-mTOR pathway. Our findings provide a foundation for further investigating promising therapeutic strategies for GC overexpressing FGFR2.

AMPK blunts chronic heart failure by inhibiting autophagy.

AMP-activated protein kinase (AMPK), a serine/threonine protein kinase, has been shown to exert a protective effect against cardiac hypertrophy and heart failure. Our previous reports have demonstrated that AMPK can inhibit cardiac hypertrophy and block the development of heart failure by promoting autophagy. However, other investigators have demonstrated that overactive and dysregulated autophagy may also contribute to the onset and exacerbation of heart failure. Thus, a major goal of the present investigation is to explore how AMPK regulates autophagy in heart failure. First, heart failure was induced in mice by 4 weeks of pressure overload; AMPK activation was subsequently induced by injecting 5-aminoimidazole-4-carboxamide 1-ß-d-ribonucleotide (AICAR) after the establishment of chronic heart failure. We showed that AMPK activation significantly attenuated the progression of heart failure and improved cardiac function, which was accompanied by decreased autophagy levels in the failing hearts. Additionally, we demonstrated that the treatment with AICAR inhibited phosphorylation of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) downstream effectors 4E-binding protein1 (4EBP1), and ribosomal protein S6 kinase (p70S6K). A major action of AICAR was significantly to activate AKT (Ser473), the downstream substrate of mTOR complex 2 (mTORC2). In conclusion, the data suggest that AMPK improved cardiac function during the development of chronic heart failure by attenuating autophagy, potentially via mTORC2 activation and the downstream effects.

Immunomodulatory acidic polysaccharides from Zizyphus jujuba cv. Huizao: Insights into their chemical characteristics and modes of action.

Chinese jujube is commonly used in folklore medicine. This study aimed to examine the in vivo immunomodulatory activity of two acidic polysaccharides, HP1 and HP2, extracted and purified from Zizyphus jujuba cv. Huizao (which remains extensively unexplored). HP1 and HP2 had the same monosaccharide species and manganese contents, but differed in their molar rhamnose, arabinose, mannose, glucose, galactose and uronic acid contents (7.32 and 35.9%, as galacturonic acid), Mw (68.7 and 111 kDa, respectively), and contents of K, Cr, Cu, Zn, Pb and Ca. Both HP1 and HP2 could significantly (P < 0.05) increase spleen and thymus indices, promote serum hemolysin formation, enhance the phagocytic activity of macrophages and inhibit footpad edema of mice, with HP2 likely being a more consistent and potent immunomodulator. This study clearly demonstrates the potential of Z. jujuba cv. Huizao polysaccharides as immunomodulators and their associated chemical characteristics and working mechanisms.