The effects of Penicillium digitatum and Fusarium oxysporum rots on nutritional content of pawpaw (Carica papaya L.)

Investigations were carried out on the effects of Penicillium digitatum and Fusarium oxysporum on the nutritional value of pawpaw (Carica papaya). Decreases were observed in ash content, phosphorus, sodium, reducing sugars and ascorbic acid levels of fruits infected with P. digitatum, but increases in calcium and potassium content. In fruits infected by F. oxysporium, there were decreases in phosphorus, calcium, sodium ascorbic acid and reducing sugar levels; but the levels of ash content increased. The total protein level increased in the fruits infected with both fungi. These results revealed a reduction in fruit quality.     

Fusion protein of Δ27LFn and EFn has the potential as a novel anthrax toxin inhibitor

PA-binding domain of LF (LFn) or PA-binding domain of EF (EFn) is the anthrax protective antigen (PA) binding domain of anthrax lethal factor (LF) or edema factor (EF). Here we show the development of a novel anthrax toxin inhibitor, fusion protein of N-terminal 27 amino acids deletion of LFn (Δ27LFn) and EFn. In a cell model of intoxication, fusion protein of Δ27LFn and EFn (Δ27LFn-EFn) was a 62-fold more potent toxin inhibitor than LFn or EFn, and this increased activity corresponded to a 39-fold higher PA-binding affinity by Biacore analysis. More importantly, Δ27LFn-EFn could protect the highly susceptible Fischer 344 rats from anthrax lethal toxin challenge. This work suggested that Δ27LFn-EFn has the potential as a candidate therapeutic agent against anthrax.

Structured summary

MINT-7014735, MINT-7014747, MINT-7014761: PA63 (uniprotkb:P13423) and LF (uniprotkb:P15917) bind (MI:0407) by surface plasmon resonance (MI:0107)     

Current status and prospects of basic research and clinical application of mesenchymal stem cells in acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a common and clinically devastating disease that causes respiratory failure. Morbidity and mortality of patients in intensive care units are stubbornly high, and various complications severely affect the quality of life of survivors. The pathophysiology of ARDS includes increased alveolar–capillary membrane permeability, an influx of protein-rich pulmonary edema fluid, and surfactant dysfunction leading to severe hypoxemia. At present, the main treatment for ARDS is mechanical treatment combined with diuretics to reduce pulmonary edema, which primarily improves symptoms, but the prognosis of patients with ARDS is still very poor. Mesenchymal stem cells (MSCs) are stromal cells that possess the capacity to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as the umbilical cord, endometrial polyps, menstrual blood, bone marrow, and adipose tissues. Studies have confirmed the critical healing and immunomodulatory properties of MSCs in the treatment of a variety of diseases. Recently, the potential of stem cells in treating ARDS has been explored via basic research and clinical trials. The efficacy of MSCs has been shown in a variety of in vivo models of ARDS, reducing bacterial pneumonia and ischemia-reperfusion injury while promoting the repair of ventilator-induced lung injury. This article reviews the current basic research findings and clinical applications of MSCs in the treatment of ARDS in order to emphasize the clinical prospects of MSCs.     

Synthesis and pharmacological evaluation of some dual-acting amino-alcohol ester derivatives of flurbiprofen and 2-[1,1'-biphenyl-4-yl]acetic acid: a potential approach to reduce local gastrointestinal toxicity

The search for safer non-steroidal anti-inflammatory drugs (NSAIDs) continues with the failure of anticipated 'ideal' anti-inflammatory agents, the coxibs, on long-term usage. Increased gastric motility and acidity due to the free carboxy group are involved in the etiology of gastric toxicity, common to conventional NSAIDs. Keeping this fact in mind, it was planned to modify some of the conventional NSAIDs to amino-alcohol ester derivatives, which satisfied the structural requirements for these compounds to possess anticholinergic activity in the intact form. Besides blocking the acidic carboxylic group, incorporation of anticholinergic acivity in these molecules was expected to reduce the gastric toxicity by decreasing gastric acid secretion and motility. Synthesis and pharmacological evaluation of six different N,N-disubstituted amino-ethyl ester derivatives, structurally resembling the amino-alcohol ester class of anticholinergic agents, each for [1,1'-biphenyl]-4-acetic acid (3) and flurbiprofen (10), have been reported as potential substitutes for these NSAIDs, with improved therapeutic profile. All the ester derivatives were found to have sufficient chemical stability in buffers (pH 2.0 and 7.4), ensuring them to be absorbed as intact moieties from the gastrointestinal tract. A significant reduction in ulcerogenic potency in comparison to the parent drugs with a slightly higher anti-inflammatory potency suggests that the majority of these candidates have an improved therapeutic profile over their parent drugs. Hence, a promising novel approach, different from the conventional prodrug concept, has been successfully worked out to overcome the local gastric toxicity, yielding therapeutically better compounds for long-term oral anti-inflammatory therapy.     

Superoxide Dismutases and Anti-Oxidants Protected Mice from no-Reflow and Necrotic Damage Induced by Ischemia

A simple method in mice was established to screen anti-ischemic compounds. Thirteen times binding of rubber ring (1 × 1 mm, d = 42 mm) for 4.5 hrs, swelled the paws of 60% mice applied and 14 times binding swelled only of 5% mice. Critically reversible limit lay between these conditions. “All or none” rule dominated the paw swelling perhap due to different endogenous anti-oxidants' levels of individual mice. Determination of paw reversibility at 90 min of recirculation, was proved to be suitable. Swollen paws at this time returned normal and the paws with no-reflow dropped out by muscle necrosis after several days. Intravenous (i.v.) bovine Cu, Zn-SOD and bacterial Mn-SOD (3 - 10 × 10⁴ U/kg) or liposomal Cu, Zn-SOD (0.3 - 3 × 10⁴ U/kg) were protective (35-50%) by 14 times binding. Allopurinol (10-100 mg/kg) and D-mannitol (3-30mg/kg) was effective (25-55%). Catalase (i.v., up to 10⁵ U/kg) showed little protection, but local injection of 100 U/kg resulted in 50% protection. Glutathione (30 mg/kg) was suppressive only by local injection suggesting the importance of administration route. Desferal, heparin and nitric oxide synthesis inhibitor showed some protection, but indomethacin, mepyramine, ascorbate, vitamin E and dexamethasone were without effect. Excess dosing of all anti-oxidants tested, dramatically decreased their effects demanding caution for therapeutic trials.     

Crystal Structure of the Engineered Neutralizing Antibody M18 Complexed to Domain 4 of the Anthrax Protective Antigen

The virulence of Bacillus anthracis is critically dependent on the cytotoxic components of the anthrax toxin, lethal factor (LF) and edema factor (EF). LF and EF gain entry into host cells through interactions with the protective antigen (PA), which binds to host cellular receptors such as CMG2. Antibodies that neutralize PA have been shown to confer protection in animal models and are undergoing intense clinical development. A murine monoclonal antibody, 14B7, has been reported to interact with domain 4 of PA (PAD4) and block its binding to CMG2. More recently, the 14B7 antibody was used as the platform for the selection of very high affinity, single-chain antibodies that have tremendous potential as a combination anthrax prophylactic and treatment. Here, we report the high-resolution X-ray structures of three high-affinity, single-chain antibodies in the 14B7 family; 14B7 and two high-affinity variants 1H and M18. In addition, we present the first neutralizing antibody-PA structure, M18 in complex with PAD4 at 3.8 Å resolution. These structures provide insights into the mechanism of neutralization, and the effect of various mutations on antibody affinity, and enable a comparison between the binding of the M18 antibody and CMG2 with PAD4.     

The effect of streptococcus on the persistence of Brugia malayi and on the production of elephantiasis in cats

Cats were exposed to 200 Brugia malayi larvae on one hind foot over a 3 week period. Six weeks after the initial exposure to B. malayi, 10 of the cats were challenged on both hind legs with a Group G streptococcus. The remaining 10 cats were not exposed to the streptococcus. Following bacterial challenge, the B. malayi-infected leg of 9 of 10 cats displayed sequelae including erysipelas and abscesses. In addition, 5 of the affected legs had an elephantoid appearance, both by gross observation and as seen at necropsy 10 weeks after the initial B. malayi infection. The contralateral, uninfected leg of each cat remained normal in appearance. Histologic processing and examination of the elephantoid tissue showed it to be collagen; eosinophils and mast cells were plentiful in the collagen matrix. In the controls, only 1 animal displayed erysipelas and no abscesses were seen. Lymphedema seen in the B. malayi-infected leg of 5 control cats was less extensive than in uninfected cats challenged with streptococci and at necropsy no significant collagen matrix was evident. The location and number of worms in the lymphatics were noted. This study demonstrated that secondary microbial infections can contribute to the causation of elephantiasis under certain circumstances and that developing B. malayi were in some way adversely affected by the streptococcal involvement of the filaria-infected lymphatics.     

双丹胶囊对大鼠脑缺血再灌注损伤保护作用研究

目的：观察双丹胶囊对大鼠局灶性脑缺血再灌注损伤的脑梗死体积、自由基变化的影响,探讨双丹胶囊对脑缺血损伤的保护作用。方法：复制大鼠中动脉缺血再灌注模型,分别给药干预,在给药后观察行为学、脑梗死率、脑指数、脑含水量、SOD、MAD等指标。结果：双丹胶囊可改善动物的神经行为学评分,明显降低动物的脑梗死率、脑指数、脑含水量、提高脑组织SOD活性、降低MDA含量,并成剂量依赖。结论：双丹胶囊对脑缺血再灌注损伤具有保护作用。     

Akkermansia与高原牛肺水肿病相关性研究

【目的】本文通过对高原牛胃肠道菌群结构组成的分析,从微生物学角度探讨Akkermansia与高原牛肺水肿病的关系。【方法】本研究以沈阳地区健康娟姗牛为对照,以引进入拉萨半年的健康娟姗牛、拉萨本地健康黄牛以及引进入拉萨半年患肺水肿病的娟姗牛的粪便作为分析样本,采用Illumina MiSeq高通量测序技术测定样本中微生物16S rRNA基因V3–V4区序列,通过比较4种粪便样本菌群组成及丰度的差异,探讨Akkermansia与高原牛肺水肿病的相关性。【结果】Verrucomicrobia中Akkermansia在拉萨本地健康黄牛的胃肠道中的含量显著高于引进入拉萨半年的健康娟姗牛,在引进入拉萨半年患肺水肿病的娟姗牛胃肠道中的含量显著高于引进入拉萨半年的健康娟姗牛。在属水平上,沈阳地区健康娟姗牛胃肠道菌群中Akkermansia丰度占比为0.07%;引进入拉萨半年的健康娟姗牛胃肠道菌群中Akkermansia丰度占比为0.09%;拉萨本地黄牛胃肠道菌群中Akkermansia丰度占比为6.62%,是优势菌属;引进入拉萨半年的患肺水肿病的娟姗牛胃肠道菌群中Akkermansia丰度占比为11.85%,且是第一优势菌属。【结论】首次从微生物学角度探讨Akkermansia与高原牛肺水肿病的关系,为将Akkermansia丰度作为诊断肺水肿病的监测指标提供参考,但具体丰度值还有待进一步研究。