Rubia cordifolia extract inhibits cell proliferation in A-431 cells

The antiproliferative property of Rubia cordifolia (Rubiaceae) extract has been studied on two different cell types, A-431 cells (epidermal carcinomoid cells) and 3T3 fibroblast cells. It was observed that a fraction of Rubia cordifolia significantly inhibited the incorporation of [³H]-thymidine, induced by fetal bovine serum, in a dose-dependent manner. It also inhibited the PMA (phorbol 12-myristate 13-acetate) induced expression of c-fos genes in A-431 cells. It appears that inhibition of DNA synthesis underlies the mechanism for its antiproliferative properties. © 1998 John Wiley & Sons, Ltd.     

Increased susceptibility of aging gastric mucosa to injury and delayed healing: Clinical implications

In this editorial we comment on the article by Fukushi K et al published in the recent issue of the World Journal of Gastroenterology 2018; 24(34): 3908-3918. We focus specifically on the mechanisms of the anti-thrombotic action of aspirin, gastric mucosal injury and aging-related increased susceptibility of gastric mucosa to injury. Aspirin is widely used not only for the management of acute and chronic pain and arthritis, but also importantly for the primary and secondary prevention of cardiovascular events such as myocardial infarcts and strokes. Clinical trials have consistently shown that antiplatelet therapy with long term, low dose aspirin (LDA) - 75 to 325 mg daily, dramatically reduces the risk of non-fatal myocardial infarcts, stroke and mortality in patients with established arterial diseases. However, such treatment considerably increases the risk of gastrointestinal (GI) ulcerations and serious bleeding by > 2-4 fold, especially in aging individuals. This risk is further increased in patients using LDA together with other antiplatelet agents, other nonsteroidal anti-inflammatory agents (NSAIDs) and/or alcohol, or in patients with Helicobacter pylori (H. pylori) infection. Previous studies by our group and others have demonstrated prominent structural and functional abnormalities in gastric mucosa of aging individuals (which we refer to as aging gastric mucosa or “aging gastropathy”) compared to the gastric mucosa of younger individuals. Aging gastric mucosa has impaired mucosal defense, increased susceptibility to injury by a variety of noxious agents such as aspirin, other NSAIDs and ethanol, and delayed and impaired healing of injury. The mechanism underlying these abnormalities of aging gastric mucosa include reduced mucosal blood flow causing hypoxia, upregulation of PTEN, activation of pro-apoptotic caspase-3 and caspase-9, and reduced survivin (anti-apoptosis protein), importin-α (nuclear transport protein), vascular endothelial growth factor, and nerve growth factor. The decision regarding initiation of a long-term LDA therapy should be made after a careful consideration of both cardiovascular and GI risk factors. The latter include a previous history of GI bleeding and/or ulcers, age ≥ 70, male gender, concurrent use of other NSAIDs, alcohol consumption and H. pylori infection. Furthermore, the incidence of GI ulcers and bleeding can be reduced in patients on long term LDA treatment by several measures. Clinicians treating such patients should test for and eradicate H. pylori, instruct patients to avoid alcohol and non-aspirin NSAIDs, including cyclooxygenase-2-selective NSAIDs, and prescribe proton pump inhibitors in patients on LDA therapy. In the future, clinicians may be able to prescribe one of several potential new drugs, which include aspirin associated with phosphatidylcholine (PL2200), which retains all property of aspirin but reduces by approximately 50% LDA-induced GI ulcerations.     

Spatiotemporal distribution of glia in and around the developing mouse optic tract

In the developing mouse optic tract, retinal ganglion cell (RGC) axon position is organized by topography and laterality (i.e., eye-specific or ipsi- and contralateral segregation). Our lab previously showed that ipsilaterally projecting RGCs are segregated to the lateral aspect of the developing optic tract and found that ipsilateral axons self-fasciculate to a greater extent than contralaterally projecting RGC axons in vitro. However, the full complement of axon-intrinsic and -extrinsic factors mediating eye-specific segregation in the tract remain poorly understood. Glia, which are known to express several guidance cues in the visual system and regulate the navigation of ipsilateral and contralateral RGC axons at the optic chiasm, are natural candidates for contributing to eye-specific pre-target axon organization. Here, we investigate the spatiotemporal expression patterns of both putative astrocytes (Aldh1l1+ cells) and microglia (Iba1+ cells) in the embryonic and neonatal optic tract. We quantified the localization of ipsilateral RGC axons to the lateral two-thirds of the optic tract and analyzed glia position and distribution relative to eye-specific axon organization. While our results indicate that glial segregation patterns do not strictly align with eye-specific RGC axon segregation in the tract, we identify distinct spatiotemporal organization of both Aldh1l1+ cells and microglia in and around the developing optic tract. These findings inform future research into molecular mechanisms of glial involvement in RGC axon growth and organization in the developing retinogeniculate pathway.     

Conversion of one-anastomosis gastric bypass to Roux-en-Y gastric bypass: short-term results from a tertiary referral center

BackgroundOne-anastomosis gastric bypass (OAGB), also known as minigastric bypass, is an increasingly popular bariatric surgery option worldwide. While OAGB offers advantage in terms of procedure time and technical ease, revisional operations to correct complications may be necessary.ObjectivesWe aimed to describe the indications and perioperative outcomes for OAGB conversions to Roux-en-Y gastric bypass (RYGB) at a single-referral center.SettingAcademic hospital, Abu Dhabi, United Arab Emirates.MethodsAll patients undergoing conversion from OAGB to RYGB from February 2016 through September 2018 were retrospectively identified from a prospectively maintained database of revisional bariatric surgeries.ResultsSixteen patients underwent conversion from previous OAGB to RYGB during the study period. The cohort was 62.5% female (n = 10) with a mean age of 40.2 years and median body mass index of 30.7 kg/m². Indications for conversion included intractable nausea/vomiting (n = 8, 50.0%), biliary reflux (n = 3, 18.8%), weight recidivism (n = 3, 18.8%), and protein-calorie malnutrition (n = 2, 12.5%). Twelve cases (75.0%) were successfully completed with a laparoscopic approach, with 4 cases (25.0%) converted to open. The median length of stay was 5.5 days. Six patients (37.5%) experienced minor and major complications within 30 days of discharge. Fourteen patients (87.5%) were available for follow-up at 6 months, with 100% of these patients reporting resolution of their preoperative symptoms. There were no mortalities.ConclusionsData from this largest reported single-center experience demonstrates that conversion of OAGB to RYGB is safe and technically feasible. Further studies and longer-term follow-up are needed to definitively describe outcomes after this revisional bariatric surgery.     

Cytotoxicity Assessment of Six Different Extracts of Abelia triflora leaves on A-549 Human Lung Adenocarcinoma Cells

The present investigation was designed to assess the anticancer activity of six different leaf extracts (ethylacetate, methanol, chloroform, petroleum ether, n-butanol, and water soluble) of Abelia triflora on A-549 humanlung adenocarcinoma epithelial cells. A-549 cells were exposed to 10-1000 μg/ml concentrations of the leaf extractsof A. triflorafor 24 h and then percentage cell viability was assessed by 3-(4,5-dimethylthiazol-2yl)-2,5-biphenyltetrazolium bromide (MTT) assay. The results showed that leaf extracts of A. triflora significantly reduced theviability of A-549 cells in a concentration-dependent manner. Decrease was recorded as 31% with ethyl acetate,36% with methanol, 46% with chloroform, 54% with petroleum ether, 62% with n-butanol, and 63% withwater soluble extracts at 1000 μg/ml each. Among the various plant extracts, ethyl acetate extract showed thehighest decrease in the percentage cell viability, followed by methanol, chloroform, petroleum ether, n-butanol,and water soluble extracts. Our results demonstrated preliminary screening of anticancer activity of differentsoluble extracts of A. triflora extracts against A-549 cells, which can be further used for the development of apotential therapeutic anticancer agents.     

Suppressing inflammation by inhibiting the NF-κB pathway contributes to the neuroprotective effect of angiotensin-(1-7) in rats with permanent cerebral ischaemia

BACKGROUND AND PURPOSE

Angiotensin-(1-7) [Ang-(1-7)] has anti-inflammatory effects in peripheral organs, but its effects in ischaemic stroke are unclear as yet. We investigated whether its anti-inflammatory effect contributes to the neuroprotection induced by Ang-(1-7) in a rat model of permanent middle cerebral artery occlusion (pMCAO).

EXPERIMENTAL APPROACH

We infused Ang-(1-7), Mas receptor antagonist A-779, angiotensin II type 2 receptor antagonist PD123319 or artificial CSF into the right lateral ventricle of male Sprague-Dawley rats from 48 h before onset of pMCAO until the rats were killed. Twenty-four hours after pMCAO, the neuroprotective effect of Ang-(1-7) was analysed by evaluating infarct volume and neurological deficits. The levels of oxidative stress were detected by spectrophotometric assay. The activation of NF-κB was assessed by Western blot and immunohistochemistry analysis. The level of COX-2 was tested by Western blot analysis and concentrations of pro-inflammatory cytokines were measured by elisa.

KEY RESULTS

Infusion of Ang-(1-7), i.c.v., significantly reduced infarct volume and improved neurological deficits. It decreased the levels of oxidative stress and suppressed NF-κB activity, which was accompanied by a reduction of pro-inflammatory cytokines and COX-2 in the peri-infarct regions. These effects of Ang-(1-7) were reversed by A-779 but not by PD123319. Additionally, infusion of A-779 alone increased oxidative stress levels and enhanced NF-κB activity, which was accompanied by an up-regulation of pro-inflammatory cytokines and COX-2.

CONCLUSION AND IMPLICATIONS

Our findings indicate that suppressing NF-κB dependent pathway via Mas receptor may represent one mechanism that contributes to the anti-inflammatory effects of Ang-(1-7) in rats with pMCAO.     

DWI在颅内囊性病变诊断中的应用价值

目的探讨MR弥散加权成像（DWI）在诊断颅内囊性病变中的价值。方法回顾性分析69例经手术病理或临床随访证实的颅内囊性病变DWI信号特征,定量测量不同类型病变囊变区的ADC值,进行统计学分析。结果DWI上15例脑脓肿和8例表皮样囊肿均呈高信号;8例蛛网膜囊肿均为低信号;38例脑肿瘤患者中除3例胶质瘤呈高信号外,其余均为低信号。脑脓肿与脑肿瘤的囊变坏死区ADC值比较,差异有统计学意义（P〈0．01）;胶质瘤与听神经瘤、转移瘤与听神经瘤的囊变坏死区ADC值比较,差异均无统计学意义（P〉0．05）;而蛛网膜囊肿与表皮样囊肿ADC值比较,二者之间的差异有统计学意义（P〈0．01）。结论DWI及ADC值对鉴别脑脓肿和囊性或坏死性及肿瘤有重要价值,对鉴别蛛网膜囊肿和表皮样囊肿有明显优势,DWI表现为低信号的颅内囊性病变可除外脑脓肿和表皮样囊肿。     

Autoantibodies to apolipoprotein A-1 as a biomarker of cardiovascular autoimmunity

Immune-driven inflammation plays an important part inatherogenesis and is therefore believed to be key to thedevelopment of cardiovascular disease(CVD), whichis currently the leading cause of death in the Westernworld. By fulfilling some of the Koch postulates, athero-genesis has even been proposed to be considered as anautoimmune disease, raising the hope that CVD couldbe prevented by immunomodulation. Nevertheless,the role of the immune system and autoimmune reac-tions in atherosclerosis appear to be a double edged-sword, with both pro-atherogenic and anti-atherogenicattributes. Hence, if immunomodulation is to becomea therapeutic option for atherosclerosis and CVD, it willbe crucial to correctly identify patients who might ben-efit from targeted suppression of deleterious autoim-mune responses. This could be achieved, for example, by the detection of disease-associated autoantibodies. In this work, we will review the currently available clini-cal, in vitro, and animal studies dedicated to autoan-tibodies against apolipoprotein A-1(anti-apoA-1 IgG), the major proteic fraction of high density lipoprotein. Current clinical studies indicate that high levels of anti-apoA-1 IgG are associated with a worse cardiovascular prognosis. In addition, in vitro and animal studies indi-cate a pro-inflammatory and pro-atherogenic role, sup-porting the hypothesis that these autoantibodies may play a direct causal role in CVD, and furthermore that they could potentially represent a therapeutic target for CVD in the future.     

From Rapa Nui to rapamycin: targeting PI3K/Akt/mTOR for cancer therapy

One of the most prominent pathways explored in the area of targeted therapy is the PI3K/Akt/mTOR pathway, which plays a central role in cell survival and proliferation. Deregulation of this pathway has been implicated in the promotion of cancer cell growth and survival. Inhibition of several steps of this pathway has been shown to confer favorable antitumor activity in a variety of cancer types. This article provides a brief analysis of the PI3K/Akt/mTOR pathway, its importance in tumor pathogenesis and the current status of preclinical and clinical studies targeting signaling components of this pathway.