Indian medicinal mushrooms as a source of antioxidant and antitumor agents

Medicinal mushrooms occurring in South India namely Ganoderma lucidum, Phellinus rimosus, Pleurotus florida and Pleurotus pulmonaris possessed profound antioxidant and antitumor activities. This indicated that these mushrooms would be valuable sources of antioxidant and antitumor compounds. Investigations also revealed that they had significant antimutagenic and anticarcinogenic activities. Thus, Indian medicinal mushrooms are potential sources of antioxidant and anticancer compounds. However, intensive and extensive investigations are needed to exploit their valuable therapeutic use.     

0～3岁婴幼儿母亲育教能力评定标准

目的:研究秦巴山区0~3岁婴幼儿母亲育儿、教儿能力评估标准。方法:按婴幼儿年龄进行分层抽样,选取秦巴山区试验点0~3岁婴幼儿母亲797人,依据用"秦巴山区0~3岁婴幼儿母亲育教能力评定表"调查的结果建立区域常模。结果:①1岁以内婴幼儿母亲育教能力的评定标准分为5个等级:总分≤16分为优秀,总分在17~19分为良好,总分在20~27分为一般,总分在28~30分为较差,总分≥31分为很差;②1~3岁婴幼儿母亲育教能力的评定标准也被划分为5个等级:总分≤21分为优秀,总分在22~26分为良好,总分在27~35分为一般,总分在36~40分为较差,总分≥41分为很差;③用评定量表对62名婴幼儿母亲相隔约2月后重测信度为0.87,效度检验亦符合测量要求。结论:编制的评定表在对秦巴山区0~3岁婴幼儿母亲育教能力、教育措施实施的评估中具有一定的应用价值。     

Sleep- and wake-dependent changes in neuronal activity and reactivity demonstrated in fly neurons using in vivo calcium imaging

Sleep in Drosophila shares many features with mammalian sleep, but it remains unknown whether spontaneous and evoked activity of individual neurons change with the sleep/wake cycle in flies as they do in mammals. Here we used calcium imaging to assess how the Kenyon cells in the fly mushroom bodies change their activity and reactivity to stimuli during sleep, wake, and after short or long sleep deprivation. As before, sleep was defined as a period of immobility of >5 min associated with a reduced behavioral response to a stimulus. We found that calcium levels in Kenyon cells decline when flies fall asleep and increase when they wake up. Moreover, calcium transients in response to two different stimuli are larger in awake flies than in sleeping flies. The activity of Kenyon cells is also affected by sleep/wake history: in awake flies, more cells are spontaneously active and responding to stimuli if the last several hours (5–8 h) before imaging were spent awake rather than asleep. By contrast, long wake (≥29 h) reduces both baseline and evoked neural activity and decreases the ability of neurons to respond consistently to the same repeated stimulus. The latter finding may underlie some of the negative effects of sleep deprivation on cognitive performance and is consistent with the occurrence of local sleep during wake as described in behaving rats. Thus, calcium imaging uncovers new similarities between fly and mammalian sleep: fly neurons are more active and reactive in wake than in sleep, and their activity tracks sleep/wake history.The fundamental features that characterize mammalian sleep also define Drosophila melanogaster sleep (1–3). Most crucially, in both flies and mammals, sleep is distinguished from simple rest (quiet wake) by an increased arousal threshold, i.e., a reduced ability to respond to external stimuli. Moreover, in flies and mammals sleep is controlled homeostatically by the duration as well by the intensity of prior wake, suggesting basic similarities in the mechanisms of sleep regulation across species. Thus, in flies both sleep deprivation and a rich learning experience lead to a sleep rebound characterized by overall increased sleep time, increased arousal threshold, and longer sleep episodes (4–6). As in mammals, overall neuronal activity in flies is also high during wake and low during sleep (6–8). Specifically, a seminal study using local field potential (LFP) recordings from the Drosophila medial protocerebrum found high spike-like potentials that disappeared after the block of synaptic transmission in the mushroom bodies (MBs) (7). This high spike activity was present when flies were moving or had been quiescent for only a few seconds, but disappeared with sleep (i.e., after periods of immobility >5 min), when the overall LFP power in all frequencies also decreased by ∼60% (7). The study concluded that neural activity in the sleeping fly brain, or at least in a central region spanning the MBs, resembles that seen in mammals in several brainstem cell groups including noradrenergic neurons, whose firing strongly declines or stops completely during sleep (9). A more recent study in tethered flies able to walk on an air-suspended ball also found that periods of immobility >5 min are associated with increased arousal thresholds and with “flat” LFPs (6). LFPs, however, reflect the activity of thousands of cells (10), and the use of modified stereotrodes to resolve single-unit activity in flies is still in its infancy (11). Glass or tungsten microelectrodes, on the other hand, have recorded one neuron at a time in flies (e.g., refs. 12–14) and, to our knowledge, have not measured changes across sleep and wake.Our goal was to study many fly neurons simultaneously while preserving single-cell resolution, to determine how sleep and wake affect spontaneous activity and the ability of neurons to react to stimuli. It was recently shown in rats that during sleep deprivation single cortical neurons may go unpredictably “offline,” as they normally do during sleep, with negative effects on performance (15). Thus, we also asked whether this phenomenon occurs in flies. We focused on the MBs, large areas of the Drosophila brain involved in olfactory learning (16, 17) and sleep regulation (18, 19), and used in vivo calcium imaging (20, 21) to measure spontaneous and evoked neuronal activity in the MB principal neurons, the Kenyon cells, during sleep, wake, and in response to different periods of sleep deprivation.     

Ergosterol purified from medicinal mushroom Amauroderma rude inhibits cancer growth in vitro and in vivo by up-regulating multiple tumor suppressors

We have previously screened thirteen medicinal mushrooms for their potential anti-cancer activities in eleven different cell lines and found that the extract of Amauroderma rude exerted the highest capacity in inducing cancer cell death. The current study aimed to purify molecules mediating the anti-cancer cell activity. The extract of Amauroderma rude was subject to fractionation, silica gel chromatography, and HPLC. We purified a compound and identified it as ergosterol by EI-MS and NMR, which was expressed at the highest level in Amauroderma rude compared with other medicinal mushrooms tested. We found that ergosterol induced cancer cell death, which was time and concentration dependent. In the in vivo experiment, normal mice were injected with murine cancer cell line B16 that is very aggressive and caused mouse death severely. We found that treatment with ergosterol prolonged mouse survival. We found that ergosterol-mediated suppression of breast cancer cell viability occurred through apoptosis and that ergosterol up-regulated expression of the tumor suppressor Foxo3. In addition, the Foxo3 down-stream signaling molecules Fas, FasL, BimL, and BimS were up-regulated leading to apoptosis in human breast cancer cells MDA-MB-231. Our results suggest that ergosterol is the main anti-cancer ingredient in Amauroderma rude, which activated the apoptotic signal pathway. Ergosterol may serve as a potential lead for cancer therapy.     

Fermented mushroom milk-supplemented dietary fibre prevents the onset of obesity and hypertriglyceridaemia in Otsuka Long-Evans Tokushima fatty rats

AIM: Fermented milk product containing edible mushroom water extracts (mushroom yogurt; MY) has been reported to have glycaemic control and triglyceride-lowering effects in streptozotocin (STZ)-induced diabetic rats and Zucker diabetic fatty (ZDF) rats. Here, we investigated how MY-supplemented dietary fibre (10 and 20%, v/w) influences the onset of obesity and hypertriglyceridaemia in Otsuka Long-Evans Tokushima fatty (OLETF) rats. METHODS: The OLETF rats were fed a powdered chow diet supplemented with MY at the levels of 10 (v/w) and 20% for 6 weeks from 10 weeks of age, but the OLETF control rats were not supplemented. Their weight, fat distribution and lipid profile have been determined. RESULTS: The body weights in MY-fed rats were reduced compared with the control rats. The perirenal fat was decreased in both MY groups, but the visceral and epididymal fats reduced only in the MY 20% group. The concentrations of serum triglyceride and non-esterified fatty acid in MY-fed rats were decreased in a dose-dependent manner. However, the levels of other serum lipid profiles [total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol] were comparable among all rats. CONCLUSION: Anti-obesity and triglyceride lowering by MY-supplemented dietary fibre in OLETF rats might have resulted from the synergistic effect of components in the fermented mushroom-milk product.     

不同血液净化方式治疗急性毒蕈中毒患者多脏器功能衰竭的疗效观察

目的对比血流灌流(HP)联合血液透析(HD)与HP联合血浆置换(PE)两种血液净化方式治疗急性毒蕈中毒患者多脏器功能衰竭(MSOF)的临床效果。方法前瞻性分析2018年6月至2020年11月攀枝花市中心医院收治的46例急性毒蕈中毒合并MSOF患者的临床资料。采用随机入院序列号分组法将其均为两组,每组各23例。对照组给予HP联合HD治疗,观察组给予HP联合PE治疗。比较两组治疗期后血浆蛋白结合毒素、血清趋化因子和肝、肾、心肌、凝血功能指标变化情况。结果两组治疗后血浆蛋白结合毒素、血清趋化因子水平和肝、肾、心肌、凝血功能指标较治疗前均明显改善,差异均有统计学意义(P<0.05)。观察组治疗后血浆蛋白结合毒素芳香氨基酸、内毒素、血氨水平明显低于对照组[(1.02±0.25)mg/dLvs.(2.23±0.59)mg/dL、(0.23±0.07)EU/mLvs.(0.69±0.22)EU/mL、(100.28±33.14)μg/Lvs.(197.87±15.98)μg/L],差异均有统计学意义(P<0.05);观察组血清趋化因子配体16(CXCL-16)、诱导蛋白-10(IP-10)、CC亚族趋化因子配体20(CCL20)水平均明显低于对照组[(1.99±0.40)ng/mL vs.(3.04±1.00)ng/mL、(48.49±12.09)pg/mLvs.(62.75±21.29)pg/mL、(56.12±11.48)pg/mLvs.(76.58±16.87)pg/mL],差异均有统计学意义(P<0.05)。观察组肝功能指标天冬氨酸氨基转移酶(AST)、终末期肝病模型(MELD)评分和心肌指标肌酸激酶(CK)、心肌蛋白水平明显低于对照组[(187.74±64.05)U/Lvs.(338.57±117.02)U/L、(6.22±2.08)分vs.(8.18±2.24)分、(95.90±23.73)U/Lvs.(121.96±40.49)U/L、(47.12±12.99)μg/Lvs.(69.30±16.75)μg/L],凝血指标活化部分凝血活酶时间(APTT)和凝血酶原时间(PT)明显短于对照组[(33.74±2.12)svs.(36.52±2.50)s、(8.18±2.24)svs.(14.48±2.00)s],差异均有统计学意义(P<0.05);但肾功能指标尿素、尿肌酐(Cre)与对照组比[(7.75±2.38)μmol/Lvs.(8.57±2.53)μmol/L、(159.60±59.14)μmol/Lvs.(163.80±56.90)μmol/L],差异无统计学意义(P>0.05)。结论急性毒蕈中毒患者MSOF血液净化治疗中选用HP联合PE疗效确切,能有效清除体内毒素,降低机体炎症反应,改善患者心、肝、肾和凝血功能。     

蕈中毒机理和治疗探讨(附16例分析)

本文对16例蕈中毒进行了分析,指出不同类型的毒蕈含有不同的毒素,一种毒蕈可含多类毒素,不同种类毒蕈也可含同一类毒素,各类毒素有特殊的靶器官,所致临床表现不同,蕈中毒最严重的并发症是急性呼吸衰竭和急性肾功能衰竭。对蕈中毒机理和治疗作了讨论。     

双孢菇清除·OH自由基作用及对胸腺嘧啶核苷酸（5＇－TMP）辐射防护作用的ESR研究

本实验利用ＥＳＲ技术研究了双孢菇提取物中大、小分子化合物的清除·ＯＨ作用及辐射对胸腺嘧啶核苷酸间接损伤的防护作用。结果表明，双孢菇提取物中大、小分子均有较好的清除·ＯＨ作用，且呈明显量效关系。通过清除·ＯＨ，双孢菇对辐射导致的胸腺嘧啶核苷酸（５＇－ＴＭＰ）的间接损伤有显著防护作用。     

The Nitric Oxide/Cyclic GMP Messenger System in Olfactory Pathways of the Locust Brain

Nitric oxide is generated by a Ca²⁺/calmodulin-stimulated nitric oxide synthase and activates soluble guanylyl cyclase. Using NADPH diaphorase (NADPHd) staining as a marker for the enzyme nitric oxide synthase and an antiserum against cGMP, we investigated the cellular organization of nitric oxide donor and target cells in olfactory pathways of the brain of the locust ( Schistocerca gregaria ). A small subset of neuronal and glial cells expressed cGMP immunoreactivity after incubation of tissue in a nitric oxide donor. Nitric oxide-induced increases in cGMP immunoreactivity were quantified in a tissue preparation of the antennal lobe and in primary mushroom body cell cultures. The mushroom body neuropil is a potential target of a transcellular nitric oxide/ cGMP messenger system since it is innervated by extrinsic NADPHd-positive neurons. The mushroom body-intrinsic Kenyon cells do not stain for NADPHd but can be induced to express cGMP immunoreactivity. The colocalization of NADPHd and cGMP immunoreactivity in a cluster of interneurons of the antennal lobe, the principal olfactory neuropil of the insect brain, suggests a role of the nitric oxide/cGMP system in olfactory sensory processing. Colocalization of NADPHd staining and cGMP immunoreactivity was also found in certain glial cells. The cellular organization of the nitric oxide/cGMP system in neurons and glia raises the possibility that nitric oxide acts not only as an intercellular but also as an intracellular messenger molecule in the insect brain.     

Early Molecular Adsorbents Recirculating System Treatment of Amanita Mushroom Poisoning

Acute poisoning due to ingestion of hepatotoxic Amanita sp. mushrooms can result in a spectrum of symptoms, from mild gastrointestinal discomfort to life‐threatening acute liver failure. With conventional treatment, Amanita phalloides mushroom poisoning carries a substantial risk of mortality and many patients require liver transplantation. The molecular adsorbent recirculating system (MARS) is an artificial liver support system that can partly compensate for the detoxifying function of the liver by removing albumin‐bound and water‐soluble toxins from blood. This treatment has been used in acute liver failure to enable native liver recovery and as a bridging treatment to liver transplantation. The aim of the study is to evaluate the outcome of 10 patients with Amanita mushroom poisoning who were treated with MARS. The study was a retrospectively analyzed case series. Ten adult patients with accidental Amanita poisoning of varying severity were treated in a liver disease specialized intensive care unit from 2001 to 2007. All patients received MARS treatment and standard medical therapy for mushroom poisoning. The demographic, laboratory, and clinical data from each patient were recorded upon admission. The one‐year survival and need for liver transplantation were documented. The median times from mushroom ingestion to first‐aid at a local hospital and to MARS treatment were 18 h (range 14–36 h) and 48 h (range 26–78 h), respectively. All 10 patients survived longer than one year. One patient underwent a successful liver transplantation. No serious adverse side‐effects were observed with the MARS treatment. In conclusion, MARS treatment seems to offer a safe and effective treatment option in Amanita mushroom poisoning.