Lidocaine, an anesthetic drug, protects Neuro2A cells against cadmium toxicity

Purpose: To investigate the neuroprotective effect of lidocaine in Neuro2A cells Methods: Differentiated N2a cells were used in this study. Cell viability and neuroprotection were assessed using dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and trypan blue assays, while Bax/Bcl-2 expression was assayed by western blotting. Mitochondrial membrane potential, reactive oxygen species and calcium levels were measured using flow cytometry. Results: Lidocaine protected differentiated N2a cells against cadmium-induced toxicity, and also attenuated cadmium toxicity-induced changes in mitochondrial membrane potential (MMP), reactive oxygen species (ROS) and calcium (Ca2+) levels. Furthermore, Bax/Bcl-2 ratio, which was disrupted by cadmium, and cadmium-induced apoptosis, were reversed by lidocaine. Conclusion: Lidocaine protects differentiated N2a cells against cadmium-induced toxicity by reversing apoptosis. Thus, lidocaine is a potential neuroprotective agent

Parameter Estimation of Induction Machine at Standstill Using Two-Stage Recursive Least Squares Method

This paper presents a two-stage recursive least squares (TSRLS) algorithm for the electric parameter estimation of the induction machine (IM) at standstill. The basic idea of this novel algorithm is to decouple an identifying system into two subsystems by using decomposition technique and identify the parameters of each subsystem, respectively. The TSRLS is an effective implementation of the recursive least squares (RLS). Compared with the conventional (RLS) algorithm, the TSRLS reduces the number of arithmetic operations. Experimental results verify the effectiveness of the proposed TSRLS algorithm for parameter estimation of IMs

Combination of curcumin and luteolin synergistically inhibits TNF-α-induced vascular inflammation in human vascular cells and mice

Emerging evidence shows that phytochemicals, the secondary plant metabolites present in a large variety of foods, have the potential ability in reducing the risk of cardiovascular diseases. However, the dosages of phytochemicals in the cellular and animal studies are too high to reach in humans by relevant foods or dietary supplement intake. The aims of this study were to investigate whether and how combined curcumin and luteolin synergistically inhibit tumor necrosis factor-alpha (TNF-α)-induced monocytes adhesion endothelium, a crucial step of the development of endothelial dysfunction, both in human vascular cells and mouse aortic endothelium. Our results show that combined curcumin (1 μM) and luteolin (0.5 μM) synergistically (combination index is 0.60) inhibited TNF-α-induced monocytes adhesion to human EA.hy926 endothelial cells while the individual chemicals did not have such effect at the selected concentrations. We also found that TNF-α-enhanced protein expressions of vascular cell adhesion molecule 1 (VCAM-1), monocyte chemotactic protein-1 (MCP-1) and nuclear factor (NF)-κB translocation were synergistically reduced by the combined curcumin and luteolin in EA.hy 926 cells while the individual chemical did not have this inhibitory effect. Consistently, 2 weeks dietary intake of combined curcumin (500 mg/kg) and luteolin (500 mg/kg) in C57BL/6 mice synergistically prevented TNF-α-stimulated adhesion of mouse monocytes to aortic endothelium ex vivo as well as the TNF-α-increased aortic protein expression of MCP-1 and VCAM-1. Therefore, combined curcumin and luteolin at physiological concentrations synergistically inhibits TNF-α-induced monocytes adhesion to endothelial cells and expressions of MCP-1 and VCAM-1 via suppressing NF-κB translocation into the nucleus

Evaluation of efficacy and safety of gefitinib as monotherapy in Chinese patients with advanced non-small cell lung cancer and very poor performance status

<p>Abstract</p> <p>Background</p> <p>This paper reports the outcome of gefitinib for Chinese advanced NSCLC patients with poor performance status (PS) at the Peking Union Medical College Hospital.</p> <p>Methods</p> <p>From Oct 2002 to Apr. 2006, 42 advanced NSCLC patients with PS 3/4 received gefitinib 250 mg/day treatment. Median survival (MS) were calculated using the Kaplan-Meier method and a Cox regression model was used to find main factors affecting MS.</p> <p>Results</p> <p>Adverse events (AEs) were generally mild (grade 1 and 2) and reversible. The most frequent AEs were rash 72.2% (26/42) and diarrhea 44.4% (26/42). The objective tumor response rate and stable disease rate were 40.5% and 26.2% respectively, and median survival(MS) of all patients was 10.1 months (95% confidential interval CI, 3.4 ~ 16.8), and progression-free survival(PFS) was 5.7 months (95% CI, 4.5 ~ 6.9). The MS were significantly related with objective response of gefitinib. Objective responses was significantly related with rashes induced with gefitinib.</p> <p>Conclusion</p> <p>Our study suggest that treatment with gefitinib may be well tolerated and beneficial for Chinese patients with poor PS, and the safety and efficacy were similar to patients with good PS.</p

Dietary epicatechin improves survival and delays skeletal muscle degeneration in aged mice

We recently reported that epicatechin, a bioactive compound that occurs naturally in various common foods, promoted general health and survival of obese diabetic mice. It remains to be determined whether epicatechin extends health span and delays the process of aging. In the present study, epicatechin or its analogue epigallocatechin gallate (EGCG) (0.25% w/v in drinking water) was administered to 20-mo-old male C57BL mice fed a standard chow. The goal was to determine the antiaging effect. The results showed that supplementation with epicatechin for 37 wk strikingly increased the survival rate from 39 to 69%, whereas EGCG had no significant effect. Consistently, epicatechin improved physical activity, delayed degeneration of skeletal muscle (quadriceps), and shifted the profiles of the serum metabolites and skeletal muscle general mRNA expressions in aging mice toward the profiles observed in young mice. In particular, we found that dietary epicatechin significantly reversed age-altered mRNA and protein expressions of extracellular matrix and peroxisome proliferator–activated receptor pathways in skeletal muscle, and reversed the age-induced declines of the nicotinate and nicotinamide pathway both in serum and skeletal muscle. The present study provides evidence that epicatechin supplementation can exert an antiaging effect, including an increase in survival, an attenuation of the aging-related deterioration of skeletal muscles, and a protection against the aging-related decline in nicotinate and nicotinamide metabolism.—Si, H., Wang, X., Zhang, L., Parnell, L. D., Ahmed, B., LeRoith, T., Ansah, T.-A., Zhang, L., Li, J., Ordovás, J. M., Si, H., Liu, D., Lai, C.-Q. Dietary epicatechin improves survival and delays skeletal muscle degeneration in aged mice. FASEB J. 33, 965–977 (2019)

Cervical HPV infection in Yueyang, China: a cross-sectional study of 125,604 women from 2019 to 2022

ObjectiveHuman papillomavirus (HPV) infection is currently the main cause of cervical cancer and precancerous lesions in women. The aim of this study was to investigate the epidemiological characteristics of HPV genotypes among women in Yueyang city and to provide a basis for the prevention and treatment of cervical cancer in this city.MethodsA cross-sectional study was conducted on 125,604 women who had received treatment from eight hospitals in Yueyang city from September 2019 to September 2022. Analysis of the prevalence of HPV in patients.ResultsThe prevalence of HPV was 20.5% (95%CI: 20.2–20.7%), of which the high-risk type (HR-HPV) accounted for 17.5% (95%CI: 17.3–17.7%) and the low-risk type (LR-HPV) accounted for 5.0% (95%CI: 4.9–5.1%). Among the HR-HPV subtypes, the top five in prevalence, from the highest to the lowest, were HPV52 (5.1%), HPV16(2.7%), HPV58 (2.6%), HPV53 (2.4%), and HPV51 (1.7%). The main LR-HPV infection types were HPV81 (2,676 cases, OR = 2.1%; 95%CI, 2.0–2.1%). Among the infected patients, 19,203 cases (OR = 74.3%; 95%CI, 73.8–74.9%) had a single subtype, 4,673 cases (OR = 18.1%; 95%CI, 17.6–18.6%) had two subtypes, and 1957 cases (OR = 7.6%; 95%CI, 7.3–7.9%) had three or more subtypes. HPV prevalence is highest among women &lt;25 years, 55–64 years and ≥ 65 years of age.ConclusionThe prevalence of HPV in women in Yueyang city was 20.5%, with HR-HPV being dominant. As women aged &lt;25 years, 55–64 years, and ≥ 65 years are at a relatively higher risk, more attention should be paid to them for prevention and control of HPV infections

Genetic heterogeneity in primary and relapsed mantle cell lymphomas : impact of recurrent CARD11 mutations

The genetic mechanisms underlying disease progression, relapse and therapy resistance in mantle cell lymphoma (MCL) remain largely unknown. Whole-exome sequencing was performed in 27 MCL samples from 13 patients, representing the largest analyzed series of consecutive biopsies obtained at diagnosis and/or relapse for this type of lymphoma. Eighteen genes were found to be recurrently mutated in these samples, including known (ATM, MEF2B and MLL2) and novel mutation targets (S1PR1 and CARD11). CARD11, a scaffold protein required for B-cell receptor (BCR)-induced NF-κB activation, was subsequently screened in an additional 173 MCL samples and mutations were observed in 5.5% of cases. Based on in vitro cell line-based experiments, overexpression of CARD11 mutants were demonstrated to confer resistance to the BCR-inhibitor ibrutinib and NF-κB-inhibitor lenalidomide. Genetic alterations acquired in the relapse samples were found to be largely non-recurrent, in line with the branched evolutionary pattern of clonal evolution observed in most cases. In summary, this study highlights the genetic heterogeneity in MCL, in particular at relapse, and provides for the first time genetic evidence of BCR/NF-κB activation in a subset of MCL

Genomic heterogeneity of multiple synchronous lung cancer

Multiple synchronous lung cancers (MSLCs) present a clinical dilemma as to whether individual tumours represent intrapulmonary metastases or independent tumours. In this study we analyse genomic profiles of 15 lung adenocarcinomas and one regional lymph node metastasis from 6 patients with MSLC. All 15 lung tumours demonstrate distinct genomic profiles, suggesting all are independent primary tumours, which are consistent with comprehensive histopathological assessment in 5 of the 6 patients. Lung tumours of the same individuals are no more similar to each other than are lung adenocarcinomas of different patients from TCGA cohort matched for tumour size and smoking status. Several known cancer-associated genes have different mutations in different tumours from the same patients. These findings suggest that in the context of identical constitutional genetic background and environmental exposure, different lung cancers in the same individual may have distinct genomic profiles and can be driven by distinct molecular events

The Invasion and Metastasis Promotion Role of CD97 Small Isoform in Gastric Carcinoma

CD97 is over-expressed in the majority of gastric adenocarcinomas and is associated with its dedifferentiation and aggressiveness. Our previous results demonstrated that out of three CD97 isoforms tested, only the small one was able to promote increased invasiveness in vitro. Based on these data we further aimed to investigate the role of CD97 small isoform in gastric cancer progression in vivo by employing the cells with a stable CD97 small isoform knock-down and an orthotopic gastric cancer mouse model. We could demonstrate that the knock down of CD97/EGF1,2,5, led to a significant decrease in the number of cells penetrating the gelatin coated membrane as compared with control cells. In the gastric cancer mouse model, both the hypodermic and the orthotopic yielded tumor masses of the CD97/EGF1,2,5kd group and were significantly smaller than the control. Metastatic tumor cell number in early metastatic regional lymph nodes on post-operative day 42 was distinctly decreased in the CD97/EGF1,2,5kd group as compared with the SGC-NS group, and was accompanied with the downregulation of CD44, VEGFR, CD31 and CD97. We concluded in this study that CD97 small isoform not only supported gastric cancer local growth, but also promoted metastatic spread in orthotopically implanted mouse model suggesting involvement of the CD97 small isoform in the preparation of (pre)metastatic niche