Sweroside Alleviated Aconitine-Induced Cardiac Toxicity in H9c2 Cardiomyoblast Cell Line

Aconitine is the main bioactive ingredient of Aconitum plants, which are well-known botanical herbs in China. Aconitine is also notorious for its high cardiotoxicity, as it can induce life-threatening ventricular arrhythmias. Unfortunately, there are few effective antidotes to aconitine toxicity. This study aimed to evaluate the potent protective effects of the ingredients from V. baillonii on aconitine toxicity on H9c2 cell line. Cell viability was assessed by methylthiazoltetrazolium bromide (MTT). Intracellular Ca2+ concentration alteration and reactive oxygen species (ROS) generation were observed by confocal microscopy and flow cytometry, respectively. Cellular oxidative stress was analyzed by measuring malondialdehyde (MDA) and superoxide dismutase (SOD) levels. Mitochondrial membrane potential (ΔΨ) was determined using JC-1 kit. RT-PCR and Hoechst staining techniques were conducted to determine the levels of autophagy/apoptosis. The mRNA levels of dihydropyridine receptor (DHPR), ryanodine receptors (RyR2) and sarcoplasmic reticulum Ca2+-ATPase (SERCA) were measured by RT-PCR. We screened six components from V. baillonii, among which, sweroside exhibited the strongest protective effects on aconitine-induced cardiac toxicity. Sweroside suppressed the aconitine-induced mRNA expressions of NaV1.5 (encoded by SCN5A), RyR2 and DHPR, and reversed the aconitine-induced decrease in mRNA level of SERCA, thus preventing the aconitine-induced persistent intracellular Ca2+ accumulation and avoiding intracellular Ca2+ overload. We further found that sweroside restabilized the aconitine-disrupted mitochondrial membrane potential (ΔΨ) and reversed the aconitine-induced increase in the mRNA levels of cell autophagy-related factors (Beclin-1, Caspase-3, and LC3- II) in H9c2 cells. In the whole-animal experiments, we observed that sweroside (50 mg/kg) alleviated effectively aconitine-induced arrhythmias by analysis of electrocardiogram (ECG) recording in rats. Our results demonstrate that sweroside may protect cardiomyocytes from aconitine toxicity by maintaining intracellular Ca2+ homeostasis, restabilizing mitochondrial membrane potential (ΔΨ) and avoiding cell autophagy/apoptosis

catena-Poly[[chloridocadmium(II)]bis­{μ-1-[(2-ethyl-1H-imidazol-1-yl)meth­yl]-1H-benzotriazole}[chloridocadmium(II)]di-μ-chlorido]

In the polymeric title complex, [CdCl2(C12H13N5)]n, the CdII atom is five-coordinated by two N atoms from two bridging 1-[(2-ethyl-1H-imidazol-1-yl)meth­yl]-1H-benzotriazole (bmei) ligands, two bridging Cl atoms and one terminal Cl atom in a distorted trigonal–bipyramidal geometry. The CdII atoms are connected alternately by the Cl atoms and bmei ligands, leading to a zigzag chain extending parallel to [011]. π–π inter­actions, with a centroid–centroid distance of 3.3016 (3) Å, help to stabilize the crystal packing

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Paper architectures are 3D paper buildings created by folding and cutting. The creation process of paper architecture is often labor-intensive and highly skill-demanding, even with the aid of existing computer-aided design tools. We propose an automatic algorithm for generating paper architectures given a user-specified 3D model. The algorithm is grounded on geometric formulation of planar layout for paper architectures that can be popped-up in a rigid and stable manner, and sufficient conditions for a 3D surface to be popped-up from such a planar layout. Based on these conditions, our algorithm computes a class of paper architectures containing two sets of parallel patches that approximate the input geometry while guaranteed to be physically realizable. The method is demonstrated on a number of architectural examples, and physically engineered results are presented

Laparoscopic resection for gastric GISTs: surgical and long-term outcomes of 133 cases

Background It aims to evaluate the surgical efficacy and long-term survival of different laparoscopic surgeries for gastric GISTs. Methods From a prospectively collected database, 133 patients with primary gastric GISTs undergoing laparoscopic surgery were selected from January 2008 to December 2014. They were divided into three groups according to the different operations that were performed, including laparoscopic gastric wedge resection (LWR Group, n=103), laparoscopic subtotal gastrectomy (LSG Group, n=18) and laparoscopic total gastrectomy (LTG group, n=12). Clinicopathological features and short- and long-term outcomes were analyzed retrospectively. Results All patients had received R0 resection. There were no differences among the three groups in age, BMI or NIH risk classification. Compared with the LSG group and LTG group, the LWR group had a shorter operative time, less blood loss, fewer operative complications and shorter time to ground activities, semi-liquid diet and hospital stay (P<0.05). There was no statistically significant difference in time to first flatus and liquid diet or in the rate of postoperative complications (P<0.05). In the patients with a large tumor (size≥5 cm), LWR was significantly associated with shorter operative time, less blood loss and shorter hospital stay compared with the laparoscopic gastric non-wedge resection (N-LWR) (P<0.05). The median follow-up was 30 months, with 4 cases of recurrence and 3 deaths. The 5-year cumulative survival rate was similar among the three groups (P>0.05). Conclusions Compared with LSG and LTG, more favorable minimally invasive results can be achieved from LWR for gastric GISTs, which may be the optimal surgical procedure

Long-term proton pump inhibitor use and the incidence of gastric cancer: A systematic review and meta-analysis

Background: There are controverted whether the long-term use of proton pump inhibitors (PPI) will increase the risk of gastric cancer. We performed a meta-analysis to assess the risk of gastric cancer in PPI users compared with non-PPI users. Methods: The main inclusion criteria were original studies reporting the incidence of gastric cancer in PPI users compared with non-PPI users. Key outcomes were the risk ratios (RR) for gastric cancer in association with PPI users or non-PPI users. Results: We analyzed data from 8 studies, comprising more than 927,684 patients. The risk of gastric cancer in PPI users was significantly higher than in non-PPI users [RR= 2.10, 95% CI (1.17-3.97)]. The risk of gastric cancer was similar between the 2 groups when the duration was ≤1 year [RR= 2.18, 95% CI (0.66-7.11)]. While the risk of gastric cancer for PPI users was higher than in non-PPI users when the duration was between 1-3 years, ≥1 year, ≥3 years and ≥5 years. The risk of non-cardiac gastric cancer for PPI users was higher than for non-PPI users [RR= 2.66, 95% CI (1.66 -4.27)], and the risk of non-cardiac gastric cancer for PPI users was higher than for non-PPI users when the duration ≥1 year [RR= 1.99, 95% CI (1.03-3.83)], but the risk for cardiac gastric cancer was similar between the 2 groups [RR= 1.86, 95% CI (0.71-4.89)]. Conclusions: We found the long-term use of PPI (duration ≥1 year) was significantly associated with a higher risk of non-cardiac gastric cancer

Effects of Veratrilla baillonii Extract on Hepatic Gene Expression Profiles in Response to Aconitum brachypodum-Induced Liver Toxicity in Mice

This manuscript was aimed to explore the hepato-protective effect of water extract of Veratrilla baillonii Franch. (Gentianaceae) (WVBF) on serious hepatic toxicity induced in mice treated with Aconitum brachypodum Diels (Ranunculaceae) at transcriptome level. The physiological and pathological symptoms were evaluated as the markers for hepato toxicity induced by A. brachypodum Diels (CFA) extracted compounds. Moreover, gene chip method was used to compare and investigate the gene expression level of WVBF on CFA induced-liver toxicity to identify the potential target of WVBF and CFA on liver. The results showed that WVBF had a significant detoxification effect on CFA-induced acute hepatic toxicity. There were 130 genes with lower expression and 124 genes expressed at higher rate in CFA treated group as compared with normal control group, while there are 67 genes down-regulated and 74 genes up-regulated in WVBF treated group in comparison with CFA treated group. WVBF could attenuate CFA-induced liver damage in mice through regulating oxidative stress, inflammatory injury and cell apoptosis/necrosis pathways. On the other hand, WVBF and CFA may have potential synergetic effects on the target genes of certain diseases such as inflammation, cancer and diabetes

ETHANOLIC EXTRACT OF ACONITI BRACHYPODI RADIX ATTENUATES NOCICEPTIVE PAIN PROBABLY VIA INHIBITION OF VOLTAGE-DEPENDENT NA+ CHANNEL

Aconiti Brachypodi Radix, belonging to the genus of Aconitum (Family Ranunculaceae), are used clinically as anti-rheumatic, anti-inflammatory and anti-nociceptive in traditional medicine of China. However, its mechanism and influence on nociceptive threshold are unknown and need further investigation. The analgesic effects of ethanolic extract of Aconiti Brachypodi Radix (EABR) were thus studied in vivo and in vitro. Three pain models in mice were used to assess the effect of EABR on nociceptive threshold. In vitro study was conducted to clarify the modulation of the extract on the tetrodotoxin-sensitive (TTX-S) sodium currents in rat’s dorsal root ganglion (DRG) neurons using whole-cell patch clamp technique. The results showed that EABR (5-20 mg/kg, i.g.) could produce dose-dependent analgesic effect on hot-plate tests as well as writhing response induced by acetic acid. In addition, administration of 2.5-10 mg/kg EABR (i.g.) caused significant decrease in pain responses in the first and second phases of formalin test without altering the PGE2 production in the hind paw of the mice. Moreover, EABR (10 μg/ml -1 mg/ml) could suppress TTX-S voltage-gated sodium currents in a dose-dependent way, indicating the underlying electrophysiological mechanism of the analgesic effect of the folk plant medicine. Collectively, our results indicated that EABR has analgesic property in three pain models and useful influence on TTX-S sodium currents in DRG neurons, suggesting that the interference with pain messages caused by the modulation of EABR on TTX-S sodium currents in DRG neurones may explain some of its analgesic effect

Body composition parameters for predicting the efficacy of neoadjuvant chemotherapy with immunotherapy for gastric cancer

BackgroundImmune checkpoint inhibitors are increasingly used in neoadjuvant therapy for locally advanced gastric cancer. However, the effect of body composition on the efficacy of neoadjuvant therapy has not been reported.MethodsThe computed tomography (CT) images and clinicopathological data of 101 patients with locally advanced gastric cancer who received neoadjuvant chemotherapy combined with immunotherapy (NCI) from 2019 to 2021 were collected. The CT image of L3 vertebral body section was selected, and the body composition before and after the neoadjuvant treatment was calculated using the SliceOmatic software, mainly including skeletal muscle index (SMI), subcutaneous adipose index (SAI), and visceral adipose index (VAI). The relationship between body composition and the efficacy and adverse events of NCI was analyzed.ResultsOf the 101 patients, 81 with evaluable data were included in the analysis. Of the included patients, 77.8% were male; the median age of all the patients was 62 years, and the median neoadjuvant therapy cycle was three. After the neoadjuvant therapy, 62.9% of the tumors were in remission (residual tumor cells ≤ 50%), and 37.1% of the tumors had no remission (residual tumor cells>50%). Moreover, 61.7% of the patients had treatment-related adverse events (TRAEs), and 18.5% had immune-related adverse events (irAEs). After neoadjuvant therapy, the body mass index (from 23 to 22.6 cm2/m2, p=0.042), SAI (from 34.7 to 32.9 cm2/m2, p=0.01) and VAI (from 32.4 to 26.8 cm2/m2, p=0.005) were significantly lower than those before treatment, while the SMI had no significant change (44.7 vs 42.5 cm2/m2, p=0.278). The multivariate logistics regression analysis revealed that low SMI (odds ratio [OR]: 3.23,95% confidence interval [CI]: 1.06–9.81, p=0.047), SMI attenuation (△SMI) ≥ 1.8(OR: 1.45,95%CI: 1.20–3.48, p=0.048), and clinical node positivity (OR: 6.99,95%CI: 2.35–20.82, p=0.001) were independent risk factors for non-remission. Additionally, high SAI is an independent risk factor for irAEs (OR: 14, 95%CI: 1.73–112.7, p=0.013).ConclusionLow SMI and △SMI≥1.8 are independent risk factors for poor tumor regression in patients with advanced gastric cancer receiving NCI. Patients with a high SAI are more likely to develop irAEs

Psoriasis Regression Analysis of MHC Loci Identifies Shared Genetic Variants with Vitiligo

Psoriasis is a common inflammatory skin disease with genetic components of both immune system and the epidermis. PSOR1 locus (6q21) has been strongly associated with psoriasis; however, it is difficult to identify additional independent association due to strong linkage disequilibrium in the MHC region. We performed stepwise regression analyses of more than 3,000 SNPs in the MHC region genotyped using Human 610-Quad (Illumina) in 1,139 cases with psoriasis and 1,132 controls of Han Chinese population to search for additional independent association. With four regression models obtained, two SNPs rs9468925 in HLA-C/HLA-B and rs2858881 in HLA-DQA2 were repeatedly selected in all models, suggesting that multiple loci outside PSOR1 locus were associated with psoriasis. More importantly we find that rs9468925 in HLA-C/HLA-B is associated with both psoriasis and vitiligo, providing first important evidence that two major skin diseases share a common genetic locus in the MHC, and a basis for elucidating the molecular mechanism of skin disorders