The role of FERMT2 in the tumor microenvironment and immunotherapy in pan-cancer using comprehensive single-cell and bulk sequencing.

FERMT2 has been identified as a participant in integrin-linked kinase signaling pathways, influencing epithelial-mesenchymal transition and thereby affecting tumor initiation, progression, and invasion. While the character of FERMT2 in the tumor microenvironment (TME) as well as its implications for immunotherapy remain unclear. Thus, we conducted a comprehensive analysis to assess the prognostic significance of FERMT2 using Kaplan-Meier analysis. In addition, we employed enrichment analysis to uncover potential underlying molecular mechanisms. Using "Immunedeconv" package, we evaluated the immune characteristics of FERMT2 within TME. Furthermore, we determined the expression levels of FERMT2 in various cell types within TME, based on single-cell sequencing data. To confirm the co-expression of FERMT2 and markers of cancer-associated fibroblasts (CAFs), we performed multiplex immunofluorescence staining on tissue paraffin sections across various cancer types. Our analysis disclosed a significant correlation between elevated FERMT2 expression and unfavorable prognosis in specific cancer types. Furthermore, we identified a strong correlation between FERMT2 expression and diverse immune-related factors, including immune checkpoint molecules, immune cell infiltration, microsatellite instability (MSI), and tumor mutational burden (TMB). Additionally, there was a significant correlation between FERMT2 expression and immune-related pathways, particularly those associated with activating, migrating, and promoting the growth of fibroblasts in diverse cancer types. Interestingly, we observed consistent co-expression of FERMT2 in both malignant tumor cells and stromal cells, particularly within CAFs. Notably, our findings also indicated that FERMT2, in particular, exhibited elevated expression levels within tumor tissues and co-expressed with α-SMA in CAFs based on the multiplex immunofluorescence staining results.

Utility of methylene blue mixed with autologous blood in preoperative localization of pulmonary nodules and masses.

The value of CT-guided puncture with methylene blue mixed with autologous blood in preoperative localization of pulmonary nodules and masses was explored. A total of 113 patients with 146 nodules and masses were treated with methylene blue mixed with autologous blood for preoperative localization and thoracoscopic surgery in the Department of Thoracic Surgery, the First Affiliated Hospital of Fujian Medical University between October 2021 and October 2022. The localization effect, complications, and pathological conditions were observed. The localization success rate was 98.63% (144/146). The localization failed nodules and masses could still be located by looking for needle eyes and reading films. The whole group successfully completed thoracoscopic surgery. The average interval of operation after puncture was 22.16 ± 6.22 h. There was a small amount of suspicious hemothorax after puncture. There was no pneumothorax after puncture in the whole group. There were no hemoptysis, irritating dry cough, and other reactions. The overall complication rate was 2.65%, and no special treatment was given. It is safe and effective to use methylene blue mixed with autologous blood for CT-guided preoperative puncture and localization of small pulmonary nodules and masses.

Polyacetylene Isomers Isolated from Bidens pilosa L. Suppress the Metastasis of Gastric Cancer Cells by Inhibiting Wnt/ß-Catenin and Hippo/YAP Signaling Pathways.

(E)-7-Phenyl-2-hepten-4,6-diyn-1-ol (1) and (Z)-7-Phenyl-2-hepten-4,6-diyn-1-ol (2) are isomeric natural polyacetylenes isolated from the Chinese medicinal plant Bidens pilosa L. This study first revealed the excellent anti-metastasis potential of these two polyacetylenes on human gastric cancer HGC-27 cells and the distinctive molecular mechanisms underlying their activities. Polyacetylenes 1 and 2 significantly inhibited the migration, invasion, and adhesion of HGC-27 cells at their non-toxic concentrations in a dose-dependent manner. The results of a further mechanism investigation showed that polyacetylene 1 inhibited the expressions of Vimentin, Snail, ß-catenin, GSK3ß, MST1, YAP, YAP/TAZ, and their phosphorylation, and upregulated the expression of E-cadherin and p-LATS1. In addition, the expressions of various downstream metastasis-related proteins, such as MMP2/7/9/14, c-Myc, ICAM-1, VCAM-1, MAPK, p-MAPK, Sox2, Cox2, and Cyr61, were also suppressed in a dose-dependent manner. These findings suggested that polyacetylene 1 exhibited its anti-metastasis activities on HGC-27 cells through the reversal of the EMT process and the suppression of the Wnt/ß-catenin and Hippo/YAP signaling pathways.

A meta-analysis showing the quantitative evidence base of perineural nalbuphine for wound pain from upper-limb orthopaedic trauma surgery.

The adjuvant effectiveness of nalbuphine in context of brachial plexus block (BPB) in patients undergoing upper-limb orthopaedic trauma surgery has remained uncertain. The purpose of this meta-analysis was to evaluate the analgesic benefit of mixing nalbuphine into local anaesthetics in BPB for wound pain from upper-limb trauma surgery. Primary outcome was the duration of analgesia. Seventeen trials (1104 patients) were analysed. Patients receiving nalbuphine have an increased weighted mean difference (WMD) 95% confidence interval of the duration of analgesia by 186.91 minutes (133.67 to 240.16) (P < 0.001). Compared to placebo, nalbuphine shorten the onset time of sensory and motor block by WMD of 2.59 (1.27 to 3.92) and 3.06 minutes (1.65 to 4.48) (P < 0.001), respectively. Meanwhile, nalbuphine prolonged the durations of sensory and motor block (P < 0.001). Qualitative and quantitative synthesis revealed no differences with regard to the outcomes related to side-effects. There is moderate-quality evidence that the addition of nalbuphine to local anaesthetics for BPB in patients undergoing upper-limb orthopaedic trauma surgery significantly prolongs the duration of analgesia, while preserving a similar safety-profile compared with local anaesthetics alone. However, these benefits should be further weighed against nalbuphine-related neurological safety in future studies.

Nigrosporins B, a Potential Anti-Cervical Cancer Agent, Induces Apoptosis and Protective Autophagy in Human Cervical Cancer Ca Ski Cells Mediated by PI3K/AKT/mTOR Signaling Pathway.

Nigrosporins B, an anthraquinone derivative obtained from the secondary metabolites of marine fungus Nigrospora oryzae. In this study, we characterized the distinctive anti-cancer potential of Nigrosporins B in vitro and underlying molecular mechanisms in human cervical cancer Ca Ski cells for the first time. The results of MTT assay showed that Nigrosporins B significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner, especially for the Ca Ski cells with an IC50 of 1.24 µM. Nigrosporins B exerted an apoptosis induction effect on Ca Ski cells as confirmed by flow cytometry, AO/EB dual fluorescence staining, mitochondrial membrane potential analysis and western blot assay. In addition, Nigrosporins B induced obvious autophagy accompanied with the increase of autophagic vacuoles and the acceleration of autophagic flux as indicated by Cyto-ID staining, mRFP-GFP-LC3 adenovirus transfection and western blot analysis. Interestingly, the combination of Nigrosporins B with the three autophagy inhibitors all significantly enhanced the cytotoxicity of Nigrosporins B on Ca Ski cells, indicating that the autophagy induced by Nigrosporins B might protect Ca Ski cells from death. Furthermore, we found that Nigrosporins B inhibited the phosphorylation of PI3K, AKT, mTOR molecules and increased the protein expression levels of PTEN and p-AMPKα in a dose-dependent manner, suggesting that Nigrosporins B induced apoptosis and protective autophagy through the suppression of the PI3K/AKT/mTOR signaling pathway. Together, these findings revealed the anti-cervical cancer effect of Nigrosporins B and the underlying mechanism of action in Ca Ski cells, it might be as a promising alternative therapeutic agent for human cervical cancer.

Efficacy and safety of long-term transcutaneous electroacupuncture versus sham transcutaneous electroacupuncture for delayed gastric emptying after distal gastrectomy: study protocol for a randomized, patient-assessor blinded, controlled trial.

BACKGROUND: Delayed gastric emptying (DGE) after distal gastrectomy impacts patients' nutritional status and quality of life. The current treatments of DGE seem unsatisfactory or need invasive interventions. It is unknown whether transcutaneous electroacupuncture (TEA) is effective in treating DGE. METHODS: A total of 90 eligible participants who underwent distal gastrectomy will be randomly allocated to either the TEA group (n = 60) or the sham transcutaneous electroacupuncture (sham-TEA) group (n = 30). Each participant will receive TEA on the bilateral acupoints of Zusanli (ST36) and Neiguan (PC6) for 4 weeks. The primary outcomes will be the residual rates of radioactivity in the stomach by gastric scintigraphy and total response rates. The secondary outcomes will be endoscopic features, autonomic function, nutritional and psychological status, serum examination, and quality of life (QoL). The adverse events will also be reported. The patients will be followed up 1 year after the treatment. DISCUSSION: The findings of this randomized trial will provide high-quality evidence regarding the efficacy and safety of long-term TEA for treating DGE after distal gastrectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033965. Registered on 20 June 2020.

Cost-benefit analysis of hepatic resection, radiofrequency ablation and liver transplantation in small hepatocellular carcinoma.

OBJECTIVE: The aim of the present study was to evaluate the cost-effectiveness ratio of surgical treatment options for small hepatocellular carcinoma (SHC) by using the decision tree model and providing a reference for the clinical therapeutic decisions for SHC. METHODS: The data of 719 cases with SHC in the BCLC 0-A who were treated in the past were collected. The survival duration and treatment cost of patients in each experimental group after hepatic resection (HR), radiofrequency ablation (RFA), and orthotopic liver transplantation (OLT) were statistically analyzed. RESULTS: For SHC with a diameter of less than 3.0 cm, HR, RFA, and OLT had similar cost-effectiveness ratios. OLT could achieve a longer life expectancy, but it was greatly affected by the dropout rate while waiting for the liver donor. RFA was preferred when the willingness to pay (WTP) < 2,5000 RMB/QALY, OLT was preferred when WTP > 75,000 RMB/QALY, and HR was preferred when WTP was between the two. EXPERT OPINION: HR in SHC with OLT had the longest life expectancy, but due to the limitations of organ sources, OLT was the preferred treatment option when the WTP was large enough.

ATG 4B Serves a Crucial Role in RCE-4-Induced Inhibition of the Bcl-2-Beclin 1 Complex in Cervical Cancer Ca Ski Cells.

RCE-4, a steroidal saponin isolated from Reineckia carnea, has been studied previously and has exhibited promising anti-cervical cancer properties by inducing programmed cell death (PCD) of Ca Ski cells. Considering the cancer cells developed various pathways to evade chemotherapy-induced PCD, there is, therefore, an urgent need to further explore the potential mechanisms underlying its actions. The present study focused on targeting the Bcl-2-Beclin 1 complex, which is known as the key regulator of PCD, to deeply elucidate the molecular mechanism of RCE-4 against cervical cancer. The effects of RCE-4 on the Bcl-2-Beclin 1 complex were investigated by using the co-immunoprecipitation assay. In addition, autophagy-related genes (ATG) were also analyzed due to their special roles in PCD. The results demonstrated that RCE-4 inhibited the formation of the Bcl-2-Beclin 1 complex in Ca Ski cells via various pathways, and ATG 4B proteins involved in this process served as a key co-factor. Furthermore, based on the above, the sensitivity of RCE-4 to Ca Ski cells was significantly enhanced by inhibiting the expression of the ATG 4B by applying the ATG 4B siRNA plasmid.

[Integrin activation, focal adhesion maturation and tumor metastasis].

Integrins are a large family of heterodimeric cell adhesion molecules composed of α and ß subunits. Through interaction with their specific ligands, integrins mediate cell-cell and cell-extracellular matrix interactions. Via outside-in signaling, integrins can recruit cytoplasmic proteins to their intracellular domains and then cluster into supramolecular structures and trigger downstream signaling. Integrin activation is associated with a global conformation rearrangement from bent to extended in ectodomains and the separation of α and ß subunit cytoplasmic domains. During cell migration, integrins regulate the focal adhesion dynamics and transmit forces between the extracellular matrix and the cell cytoskeleton. In tumor microenvironment, integrins on multiple kinds of cells could be activated, which modulates cell migration into tumor and contributes to angiogenesis and tumor metastasis. Here, we review the mechanism of integrin activation, dynamics of focal adhesions during cell migration and tumor metastasis.

Conductive Skeleton-Heterostructure Composites Based on Chrome Shavings for Enhanced Electromagnetic Interference Shielding.

Renewable bio-based electromagnetic interference (EMI) shielding materials receive increasing attention undoubtedly. However, there is still a challenge to use raw biomass materials to construct a significant structure through an effortless and environmental route for EMI shielding applications. Herein, for the first time, we demonstrated a hybrid composite of multi-walled carbon nanotube/polypyrrole/chrome-tanned collagen fiber (MWCNT/PPy/CF), which utilized waste chrome shavings as a matrix. X-ray photoelectron spectroscopy reveals that the chromium on the CF has a binding effect on the PPy layer, which endows the tight integration between the CF and PPy layer. After the MWCNT network was loaded on the PPy layer, this ternary structure could provide stable conductive paths and a rich number of polarized interfaces. The MWCNT/PPy/CF composite exhibits superior electrical conductivity (354 ± 52 S/m), higher than PPy/CF (222 ± 38 S/m) and MWCNT/CF (104 ± 11 S/m), owing to the synergy of dual conductive structures. Notably, the shielding effectiveness (SE) value of the MWCNT/PPy/CF composite reaches 30 dB in the X band at a thickness of 0.48 mm. The shielding effectiveness of reflection (SER) (9.1 dB) is similar to that of PPy/CF (8.2 dB), while the shielding effectiveness of absorption (SEA) is significantly improved from 15.3 dB (PPy/CF) to 20.4 dB (MWCNT/PPy/CF) due to the additional coverage of the MWCNT network. This indicates the synergy between the MWCNT network and conductive PPy/CF skeleton. This work provided a method to prepare sustainable and low-cost renewable EMI shielding materials using chrome shavings. Meanwhile, this novel structure combining a conductive skeleton and heterostructure can be considered as a potential application in relevant fields.

Can Masks Be Reused After Hot Water Decontamination During the COVID-19 Pandemic?

Masks have become one of the most indispensable pieces of personal protective equipment and are important strategic products during the coronavirus disease 2019 (COVID-19) pandemic. Due to the huge mask demand-supply gap all over the world, the development of user-friendly technologies and methods is urgently needed to effectively extend the service time of masks. In this article, we report a very simple approach for the decontamination of masks for multiple reuse during the COVID-19 pandemic. Used masks were soaked in hot water at a temperature greater than 56 °C for 30 min, based on a recommended method to kill COVID-19 virus by the National Health Commission of the People's Republic of China. The masks were then dried using an ordinary household hair dryer to recharge the masks with electrostatic charge to recover their filtration function (the so-called "hot water decontamination + charge regeneration" method). Three kinds of typical masks (disposable medical masks, surgical masks, and KN95-grade masks) were treated and tested. The filtration efficiencies of the regenerated masks were almost maintained and met the requirements of the respective standards. These findings should have important implications for the reuse of polypropylene masks during the COVID-19 pandemic. The performance evolution of masks during human wear was further studied, and a company (Zhejiang Runtu Co., Ltd.) applied this method to enable their workers to extend the use of masks. Mask use at the company was reduced from one mask per day per person to one mask every three days per person, and 122 500 masks were saved during the period from 20 February to 30 March 2020. Furthermore, a new method for detection of faulty masks based on the penetrant inspection of fluorescent nanoparticles was established, which may provide scientific guidance and technical methods for the future development of reusable masks, structural optimization, and the formulation of comprehensive performance evaluation standards.

Enhanced O-linked Glcnacylation in Crohn's disease promotes intestinal inflammation.

BACKGROUND: Treatment of Crohn's disease (CD) remains to be a challenge due to limited insights for its pathogenesis. We aimed to determine the role of O-Linked ß-N-acetylglucosamine (O-GlcNAc) in the development of CD and evaluate therapeutic effects of O-GlcNAc inhibitors on CD. METHODS: O-GlcNAc in intestinal epithelial tissues of CD, adherent-invasive Escherichia coli (AIEC) LF82-infected cells and mice was determined by immunoblot and immunohistochemistry. AIEC LF82 and dextran sulfate sodium were administrated into C57BL/6 mice for estabolishing inflammatory bowel disease model and for therapeutic study. FINDINGS: O-GlcNAc was increased in intestinal epithelial tissues of CD patients and AIEC LF82-infected mice. Infection of AIEC LF82 up-regulated the level of UDP-GlcNAc and increased O-GlcNAc in human colon epithelial HCT116 and HT-29 cells. We identified that IKKß and NF-κB were O-Glycosylated in AIEC LF82-treated cells. Mutations of IKKß (S733A) and p65 (T352A) abrogated the O-GlcNAc in IKKß and NF-κB and inhibited AIEC LF82-induced activation of NF-κB. Application of 6-diazO-5-oxO-L-norleucine, an agent that blocks the production of UDP-GlcNAc and inhibits O-GlcNAc, inactivated NF-κB in AIEC LF82-infected cells, enhanced the formation of autophagy, promoted the removal of cell-associated AIEC LF82, alleviated intestinal epithelial inflammation, and improved the survival of the colitis mice. INTERPRETATION: Intestinal inflammation in CD is associated with increased O-GlcNAc modification, which is required for NF-κB activation and suppression of autophagy. Targeting O-GlcNAc could be an effective therapy for inflammatory bowel disease. FUNDING: National Natural Science Foundation of China (Nos. 81573087 and 81772924) and International Cooperation Foundation of Jilin Province (20190701006GH).

Transareolar single-port endoscopic thoracic sympathectomy with a flexible endoscope for primary palmar hyperhidrosis: a prospective randomized controlled trial.

BACKGROUND: Transareolar single-port endoscopic thoracic sympathectomy (ETS) with a flexible endoscope has rarely been reported. This study assessed the performance of this novel minimally invasive technique for primary palmar hyperhidrosis (PPH). METHODS: From January 2019 to September 2019, 118 males with severe PPH requiring single-port and bilateral ETS were randomly allocated to undergo transareolar ETS using a flexible endoscope (group A, n=58) or transaxillary ETS using a 5 mm thoracoscope (group B, n=60). RESULTS: Both groups had similar patient characteristics. All procedures were performed successfully, with no mortality or conversion to open surgery. All patients had dry and warm palms immediately after surgery. Compared with group B, group A had a significantly shorter median incision length [5.1 (5.0-5.2) vs. 10.9 (10.8-11.9) mm; P<0.001], and significantly lower median postoperative pain score [1 (1.0-2.0) vs. 3 (3.0-4.0); P<0.001]. There were no differences between the two groups in operative time, palmar temperature increase, and transient postoperative sweating. After complete follow-up, group A had a significantly higher median cosmetic score than group B [4.0 (3.0-4.0) vs. 3.0 (3.0-3.0); P<0.001]. There were no differences between the two groups regarding symptom resolution, compensatory hyperhidrosis, and satisfaction score. No patient reported residual pain or symptom recurrence. CONCLUSIONS: Transareolar single-port ETS with a flexible endoscope is safe, effective, and minimally invasive with a small incision, minimal pain, and excellent cosmetic results. This novel procedure is suitable for routine treatment of PPH in males.

RCE­4, a potential anti­cervical cancer drug isolated from Reineckia carnea, induces autophagy via the dual blockade of PI3K and ERK pathways in cervical cancer CaSki cells.

The steroidal saponin RCE­4 (1ß, 3ß, 5ß, 25S)­spirostan­1, 3­diol 1­[α­L­rhamnopyranosyl­(1→2)­ß­D­xylopyranoside], isolated from Reineckia carnea, exerts significant anti­cervical cancer activity by inducing apoptosis. The potential effect of RCE­4 on proliferation inhibition and autophagy induction has rarely been studied. Therefore, the focus of the present study was to investigate the effects of RCE­4 on proliferation, and to elucidate the detailed mechanisms involved in autophagy induction in cervical cancer cells. CaSki cells were treated with RCE­4 or/and autophagy inhibitors, and the effect of RCE­4 on cellular proliferation was assessed by MTT assay. The pro­autophagic properties of RCE­4 were subsequently confirmed using monomeric red fluorescent protein­green fluorescent protein­microtubule­associated proteins 1A/1B light chain 3B (LC3) adenoviruses and CYTO­ID autophagy assays, and by assessing the accumulation of lipid­modified LC3 (LC3II). The mechanisms of RCE­4­induced autophagy were investigated by western blot analysis. The results demonstrated that inhibiting autophagy significantly promoted RCE­4­induced cell death, indicating that autophagy served a protective role following RCE­4 treatment. In addition, RCE­4­induced autophagy was reflected by increased expression levels of the serine/threonine­protein kinase ULK1, phosphorylated (p)­ULK1, p­Beclin­1 and LC3II, the formation of autophagosomes and autolysosomes, and sequestosome 1 (p62) degradation. Subsequent analysis indicated that RCE­4 activated the AMP­activated protein kinase (AMPK) pathway by upregulating AMPK and p­AMPK, and also inhibited the PI3K and extracellular signal­regulated kinase (ERK) signaling pathways by downregulating p­PI3K, p­Akt, p­mTOR, Ras, c­Raf, p­c­Raf, dual specificity mitogen­activated protein kinase kinase (MEK)1/2, p­MEK1/2 and p­Erk1/2. Additionally, with increased treatment times RCE­4 may impair lysosomal cathepsin activity and inhibit autophagy flux by suppressing the expression of AMPK, p­AMPK, ULK1, p­ULK1 and p­Beclin­1, and upregulating that of p62. These results indicated that the dual RCE­4­induced inhibition of the PI3K and ERK pathways may result in a more significant anti­tumor effect and prevent chemoresistance, compared with the inhibition of either single pathway; furthermore, dual blockade of PI3K and ERK, and the AMPK pathway may be involved in the regulation of autophagy caused by RCE­4. Taken together, RCE­4 induced autophagy to protect cancer cells against apoptosis, but AMPK­mediated autophagy was inhibited in the later stages of RCE­4 treatment. In addition, autophagy inhibition improved the therapeutic effect of RCE­4. These data highlight RCE­4 as a potential candidate for cervical cancer treatment.

New eremophilane-type sesquiterpenes and maleimide-bearing compounds from Carpesium abrotanoides L.

Two new eremophilane-type sesquiterpenes, carperemophilanes A and B (1-2), three new maleimide-bearing compounds, carpesiumaleimides A-C (3-5), along with a known sesquiterpene, carabrol (6), were isolated from the ethanol extract of Carpesium abrotanoides L. Their structures were elucidated by analysis of their NMR and MS data as well as by comparison with the literature. The absolute configuration of carperemophilane A (1) was determined by single-crystal X-ray diffraction analysis. All isolated compounds (1-6) were evaluated in vitro for cytotoxicity against two human cancer cell lines MDA-MB-231 and HGC-27 using the MTT method. Compounds 1, 2 and 6 showed cytotoxic activities with IC50 values ranging from 7.45 to 37.35 µM.

Simplified synchronous disconnection of pulmonary arteries and veins for right upper lobectomy.

BACKGROUND: Video-assisted thoracoscopic lobectomy with lymphadenectomy is considered one of the most effective treatments for early non-small cell lung cancer. We developed a novel approach for lobectomy in patients with right upper lung cancer through simplified synchronous disconnection of pulmonary arteries and veins. This study aimed to evaluate the feasibility, efficacy, safety, and cost-effectiveness of this minimally invasive technique in managing right upper lobectomy. PATIENTS AND METHODS: From March 2016 to September 2017, 62 patients with right upper lung cancer underwent lobectomy via simplified synchronous disconnection of pulmonary arteriovenous by video-assisted thoracoscopic surgery. All patients were followed up for 6-12 months after the procedure through clinic visits or telephone/e-mail interviews. RESULTS: Of the 62 patients (mean age, 57.2 ± 8.7 years), 28 were men (45.2%) and 34 (54.8%) were women. All procedures were successfully performed by thoracoscopy, with a mean operating time of 66.2 ± 9.0 min. The mean blood loss was 40.3 ± 19.5 mL. Only 1 (1.61%) patient required blood transfusion. The mean number of endoscopic linear stapling devices used was 2.6 ± 0.7. The mean number of lymph nodes harvested was 16.0 ± 1.6. Postoperative pneumonia was encountered in 4 (6.45%) patients. There was no postoperative mortality. The mean length of hospital stay was 5.3 ± 1.3 days. Six-month follow-up revealed an excellent clinical result and degree of satisfaction. CONCLUSIONS: Simplified synchronous disconnection of pulmonary arteries and veins is a feasible, economical, safe, and effective therapeutic procedure for right upper lung carcinoma. This novel procedure shows promise as a viable surgical approach for right upper lobectomy.

Nuclear magnetic resonance-based metabolomics approach to evaluate preventive and therapeutic effects of Gastrodia elata Blume on chronic atrophic gastritis.

Chronic atrophic gastritis (CAG) is one of the most common digestive system diseases worldwide which defined by WHO as initial step of cancer. Gastrodia elata Blume (GEB) is a traditional herbal with multiple pharmacological activities which was widely used in Asian countries. This study aims to explore the preventive and therapeutical effects of Gastrodia elata Blume on auto-immune induced CAG in rats. Tissues of stomachs were collected and submitted to 1H NMR-based metabolomics analysis and histopathological inspection. The biochemical indexes of MDA, SOD, GSH, NO and XOD were measured. Gastrodia elata Blume could apparently ameliorate the damaged gastric glands and the biochemical parameters, enhance gastric acid secretion, and significantly relieve the inflammation of the stomach. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles and correlation network analysis revealed that Gastrodia elata Blume could effectively treat CAG via regulating energy and purine metabolisms, and by anti-oxidation and anti-inflammation effects.

Characterization of the in vitro metabolites of idelalisib in liver microsomes and interspecies comparison.

Idelalisib acts as a phosphoinositide 3 kinase inhibitor, which has been approved by the US FDA for the treatment of certain hematological malignancies. The aim of this study is to profile the metabolites of idelalisib in the liver microsomes of mouse, rat, rabbit, dog, monkey and human. Idelalisib at the concentration of 20 µM was incubated with the liver microsomes in the presence of NADPH, GSH and UDPGA. The incubation samples were analyzed by ultra-high performance liquid chromatography coupled with diode array detector and linear ion trap-orbitrap tandem mass spectrometer (UHPLC-DAD-LTQ-Orbitrap-MS), and the post-acquisition data was processed by Metworks software. Under the current experimental conditions, a total of 14 metabolites were detected. The structures of the metabolites were characterized based on their accurate masses, fragmental ions and retention times. Our results suggested the following: 1) idelalisib was prone to oxidative defluorination to give rise to desfluoroidelalisib (M13). This metabolite was reactive in nature as its corresponding GSH conjugate was detected (M4). Except GSH conjugation, this metabolite can further undergo oxygenation (M7 and M14), and glucuronidation (M3); 2) oxygenation was the major metabolic pathway in liver microsomes, leading to the metabolite M10 in all test species; 3) idelalisib can be directly conjugated with glucuronide to form N+-glucuronide (M1). Species-specific metabolic difference was observed between animals and human and rat and dog have closer metabolic profiles to human compared with other animal species.

Adrenomedullin Reduces Secondary Injury and Improves Outcome in Rats with Fluid Percussion Brain Injury.

OBJECTIVE: Traumatic brain injury (TBI) is a devastating neurologic injury and remains a major cause of death in the world. Secondary injury after TBI is associated with long-term disability in patients with TBI. This study evaluated adrenomedullin (AM) on secondary injury and neurologic functional outcome in rats after TBI. METHODS: Forty-eight Sprague Dawley rats were randomly assigned into 3 groups: sham, TBI, and TBI with AM groups. TBI was induced by fluid percussion injury, and AM was intravenously injected. Neurologic function was examined at 2, 3, and 7 days after TBI. Enzyme-linked immunosorbent assay was used to test tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-8 levels in the brain. Brain edema and blood-brain barrier (BBB) permeability in brain tissue were tested. Western blot was used to examine the expression of aquaporin-4, phosphorylated myosin light-chain, and cleaved caspase-3. Terminal deoxynucleotidyl transferase dUTP nick end labeling was used to test the apoptosis. RESULTS: Compared with the sham group, TNF-α, IL-1ß, and IL-6 levels, brain edema, BBB permeability, neurologic examination scores, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, and expression of aquaporin-4, phosphorylated myosin light-chain, and cleaved caspase-3 significantly increased in the TBI group. AM treatment significantly inhibited TBI-induced effects. CONCLUSIONS: AM can improve neurologic function and ameliorate brain injury in rats with TBI. AM exerts its neuroprotective effect via its anti-inflammatory and antiapoptotic effect.

Anti-Cancer Effects of Emodin on HepG2 Cells as Revealed by 1H NMR Based Metabolic Profiling.

Hepatic carcinoma is one of the most common cancers in the world, with a high incidence. Emodin is an anthraquinone derived from Polygonum multiflorum Thunb, possessing anti-cancer activity. The purpose of this study is to investigate the anti-cancer effect of different dosages of emodin on HepG2 cells using a 1H NMR based metabolic approach complemented with qRT-PCR and flow cytometry to identify potential markers and discover the targets to explore the underlying mechanism. Emodin can dose-dependently inhibit the growth of HepG2 cells, perturb cell cycle progression, down-regulate the expression of genes and proteins related to glycolysis, and trigger intracellular ROS generation. Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) and correlation network analysis of the 1H NMR data showed significant changes in many endogenous metabolites after emodin exposure concerning oxidative stress and disturbances in amino acid and energy metabolism. These findings are helpful to understand the anti-cancer mechanism of emodin and provide a theoretical basis for its future application and development.