Chemoprevention of rat liver toxicity and carcinogenesis by Spirulina

Spirulina platensis (SP) is a filamentous cyanobacterium microalgae with potent dietary phyto-antioxidant, anti-inflammatory and anti-cancerous properties. The present study aimed to investigate the chemopreventive effect of SP against rat liver toxicity and carcinogenesis induced by dibutyl nitrosamine (DBN) precursors, and further characterized its underlying mechanisms of action in HepG2 cell line. Investigation by light and electron microscopy showed that DBN treatment induced severe liver injury and histopathological abnormalities, which were prevented by SP supplementation. The incidence of liver tumors was significantly reduced from 80 to 20% by SP. Immunohistochemical results indicated that both PCNA and p53 were highly expressed in the liver of DBN-treated rats, but were significantly reduced by SP supplementation. Molecular analysis indicated that SP treatment inhibited cell proliferation, which was accompanied by increased p21 and decreased Rb expression levels at 48hrs post-treatment. In addition, SP increased Bax and decreased Bcl-2 expression, indicating induction of apoptosis by 48hrs. This is the first report of the in vivo chemopreventive effect of SP against DBN-induced rat liver cytotoxicity and carcinogenesis, suggesting its potential use in chemoprevention of cancer.     

The approximate entropy of the electromyographic signals of tremor correlates with the osmotic fragility of human erythrocytes

Background  

The main problem of tremor is the damage caused to the quality of the life of patients, especially those at more advanced ages. There is not a consensus yet about the origins of this disorder, but it can be examined in the correlations between the biological signs of aging and the tremor characteristics.     

Comparative neuroanatomy suggests repeated reduction of neuroarchitectural complexity in Annelida

Background

Paired mushroom bodies, an unpaired central complex, and bilaterally arranged clusters of olfactory glomeruli are among the most distinctive components of arthropod neuroarchitecture. Mushroom body neuropils, unpaired midline neuropils, and olfactory glomeruli also occur in the brains of some polychaete annelids, showing varying degrees of morphological similarity to their arthropod counterparts. Attempts to elucidate the evolutionary origin of these neuropils and to deduce an ancestral ground pattern of annelid cerebral complexity are impeded by the incomplete knowledge of annelid phylogeny and by a lack of comparative neuroanatomical data for this group. The present account aims to provide new morphological data for a broad range of annelid taxa in order to trace the occurrence and variability of higher brain centers in segmented worms.

Results

Immunohistochemically stained preparations provide comparative neuroanatomical data for representatives from 22 annelid species. The most prominent neuropil structures to be encountered in the annelid brain are the paired mushroom bodies that occur in a number of polychaete taxa. Mushroom bodies can in some cases be demonstrated to be closely associated with clusters of spheroid neuropils reminiscent of arthropod olfactory glomeruli. Less distinctive subcompartments of the annelid brain are unpaired midline neuropils that bear a remote resemblance to similar components in the arthropod brain. The occurrence of higher brain centers such as mushroom bodies, olfactory glomeruli, and unpaired midline neuropils seems to be restricted to errant polychaetes.

Conclusions

The implications of an assumed homology between annelid and arthropod mushroom bodies are discussed in light of the 'new animal phylogeny'. It is concluded that the apparent homology of mushroom bodies in distantly related groups has to be interpreted as a plesiomorphy, pointing towards a considerably complex neuroarchitecture inherited from the last common ancestor, Urbilateria. Within the annelid radiation, the lack of mushroom bodies in certain groups is explained by widespread secondary reductions owing to selective pressures unfavorable for the differentiation of elaborate brains. Evolutionary pathways of mushroom body neuropils in errant polychaetes remain enigmatic.     

Symptomatic relief precedes improvement of myocardial blood flow in patients under spinal cord stimulation

Background

Spinal cord electrical stimulation (SCS) has shown to be a treatment option for patients suffering from angina pectoris CCS III-IV although being on optimal medication and not suitable for conventional treatment strategies, e.g. CABG or PTCA. Although many studies demonstrated a clear symptomatic relief under SCS therapy, there are only a few short-term studies that investigated alterations in cardiac ischemia. Therefore doubts remain whether SCS has a direct effect on myocardial perfusion.

Methods

A prospective study to investigate the short- and long-term effect of spinal cord stimulation (SCS) on myocardial ischemia in patients with refractory angina pectoris and coronary multivessel disease was designed. Myocardial ischemia was measured by MIBI-SPECT scintigraphy 3 months and 12 months after the beginning of neurostimulation. To further examine the relation between cardiac perfusion and functional status of the patients we measured exercise capacity (bicycle ergometry and 6-minute walk test), symptoms and quality of life (Seattle Angina Questionnaire [SAQ]), as well.

Results

31 patients (65 ± 11 SEM years; 25 male, 6 female) were included into the study. The average consumption of short acting nitrates (SAN) decreased rapidly from 12 ± 1.6 times to 3 ± 1 times per week. The walking distance and the maximum workload increased from 143 ± 22 to 225 ± 24 meters and 68 ± 7 to 96 ± 12 watt after 3 months. Quality of life increased (SAQ) significantly after 3 month compared to baseline, as well. No further improvement was observed after one year of treament. Despite the symptomatic relief and the improvement in maximal workload computer based analysis (Emory Cardiac Toolbox) of the MIBI-SPECT studies after 3 months of treatment did not show significant alterations of myocardial ischemia compared to baseline (16 patients idem, 7 with increase and 6 with decrease of ischemia, 2 patients dropped out during initial test phase). Interestingly, in the long-term follow up after one year 16 patients (of 27 who completed the one year follow up) showed a clear decrease of myocardial ischemia and only one patient still had an increase of ischemia compared to baseline.

Conclusion

Thus, spinal cord stimulation not only relieves symptoms, but reduces myocardial ischemia as well. However, since improvement in symptoms and exercise capacity starts much earlier, decreased myocardial ischemia might not be a direct effect of neurostimulation but rather be due to a better coronary collateralisation because of an enhanced physical activity of the patients.     

Increasing Negativity of Age Stereotypes across 200 Years: Evidence from a Database of 400 Million Words

Scholars argue about whether age stereotypes (beliefs about old people) are becoming more negative or positive over time. No previous study has systematically tested the trend of age stereotypes over more than 20 years, due to lack of suitable data. Our aim was to fill this gap by investigating whether age stereotypes have changed over the last two centuries and, if so, what may be associated with this change. We hypothesized that age stereotypes have increased in negativity due, in part, to the increasing medicalization of aging. This study applied computational linguistics to the recently compiled Corpus of Historical American English (COHA), a database of 400 million words that includes a range of printed sources from 1810 to 2009. After generating a comprehensive list of synonyms for the term elderly for these years from two historical thesauri, we identified 100 collocates (words that co-occurred most frequently with these synonyms) for each of the 20 decades. Inclusion criteria for the collocates were: (1) appeared within four words of the elderly synonym, (2) referred to an old person, and (3) had a stronger association with the elderly synonym than other words appearing in the database for that decade. This yielded 13,100 collocates that were rated for negativity and medicalization. We found that age stereotypes have become more negative in a linear way over 200 years. In 1880, age stereotypes switched from being positive to being negative. In addition, support was found for two potential explanations. Medicalization of aging and the growing proportion of the population over the age of 65 were both significantly associated with the increase in negative age stereotypes. The upward trajectory of age-stereotype negativity makes a case for remedial action on a societal level.     

Poliomyelitis in MuLV-infected ICR-SCID mice after injection of basement membrane matrix contaminated with lactate dehydrogenase-elevating virus

The arterivirus lactate dehydrogenase-elevating virus (LDV) causes life-long viremia in mice. Although LDV infection generally does not cause disease, infected mice that are homozygous for the Fv1(n) allele are prone to develop poliomyelitis when immunosuppressed, a condition known as age-dependent poliomyelitis. The development of age-dependent poliomyelitis requires coinfection with endogenous murine leukemia virus. Even though LDV is a common contaminant of transplantable tumors, clinical signs of poliomyelitis after inadvertent exposure to LDV have not been described in recent literature. In addition, LDV-induced poliomyelitis has not been reported in SCID or ICR mice. Here we describe the occurrence of poliomyelitis in ICR-SCID mice resulting from injection of LDV-contaminated basement membrane matrix. After exposure to LDV, a subset of mice presented with clinical signs including paresis, which was associated with atrophy of the hindlimb musculature, and tachypnea; in addition, some mice died suddenly with or without premonitory signs. Mice presenting within the first 6 mo after infection had regions of spongiosis, neuronal necrosis and astrocytosis of the ventral spinal cord, and less commonly, brainstem. Axonal degeneration of ventral roots prevailed in more chronically infected mice. LDV was identified by RT-PCR in 12 of 15 mice with typical neuropathology; positive antiLDV immunolabeling was identified in all PCR-positive animals (n = 7) tested. Three of 8 mice with neuropathology but no clinical signs were LDV negative by RT-PCR. RT-PCR yielded murine leukemia virus in spinal cords of all mice tested, regardless of clinical presentation or neuropathology.     

MicroRNAs in cancer drug resistance: Basic evidence and clinical applications

Development of drug resistance has considerably limited the efficacy of cancer treatments, including chemotherapy and targeted therapies. Hence, understanding the molecular mechanisms underpinning the innate or the acquired resistance to these therapies is critical to improve drug efficiency and clinical outcomes. Several studies have implicated microRNAs (miRNA) in this process. MiRNAs repress gene expression by specific binding to complementary sequences in the 3' region of target messenger RNAs (mRNAs), followed by target mRNA degradation or blocked translation. By targeting molecules specific to a particular pathway within tumor cells, the new generation of cancer treatment strategies has shown significant advantages over conventional chemotherapy. However, the long-term efficacy of targeted therapies often remains poor, because tumor cells develop resistance to such therapeutics. Targeted therapies often involve monoclonal antibodies (mAbs), such as those blocking the ErB/HER tyrosine kinases, epidermal growth factor receptor (cetuximab) and HER2 (trastuzumab), and those inhibiting vascular endothelial growth factor receptor signaling (e.g., bevacizumab). Even though these are among the most used agents in tumor medicine, clinical response to these drugs is reduced due to the emergence of drug resistance as a result of toxic effects in the tumor microenvironment. Research on different types of human cancers has revealed that aberrant expression of miRNAs promotes resistance to the aforementioned drugs. In this study, we review the mechanisms of tumor cell resistance to mAb therapies and the role of miRNAs therein. Emerging treatment strategies combine therapies using innovative miRNA mimics or antagonizers with conventional approaches to maximize outcomes of patients with cancer.     

Alkyl- and aryl-substituted salicyl phosphates as detection reagents in enzyme-amplified fluorescence DNA hybridization assays on solid support.

Nine salicyl phosphate esters with hydrophobic substituents (5-phenyl, 5-(2,4-difluorophenyl), 5-tert-octyl, 5-cumyl, 5-(4-tert-butylphenyl, 5-(1-adamantyl), 5-(n-dodecyl), 5-(1,1-diphenylethyl, and 5-trityl) were synthesized and found to be good substrates for calf intestinal alkaline phosphatase. The enzymatic hydrolysis produced the corresponding salicylates, which were strongly fluorescent when excited by ultraviolet light around 300 nm with maximum emission at 420-435 nm. The salicylates were less soluble and/or more adhesive than the nonfluorescent salicyl phosphate substrates, resulting in localization of fluorescence signal, which is a requirement for membrane-based assays. The salicyl phosphates bearing 8-14 carbon substitutents were found to be suitable detection reagents for dot-blot DNA hybridization assays on nylon membrane using a biotinylated probe, allowing the detection of 125 pg of target pBR322 plasmid DNA using a simple apparatus consisting of a transilluminator, a camera. and a 455-nm cutoff optical filter.     

粘虫(Pseudaletia separata(Walker))生殖系统的解剖

本文内容是研究粘虫(Pseudaletia separata(Walker)生殖系统的形态构造。全文分为雄性内部生殖器、雄性外部生殖器、雌性内部生殖器及雌性外部生殖器四部分。 粘虫的雄性内生殖器中, 有睾丸一对, 左右并列, 呈扁椭圆形, 外被紫红色睾丸膜; 输精管一对, 基部膨大成二对贮精囊; 射精管分成复射精管及单射精管两部分。雄性外生殖器的构造极为复杂, 第9腹节的背、腹板分别形成马鞍状的背兜及基腹弧; 第10腹节仅有其附肢特化成钩形突、颚形突和背兜侧突等; 抱握器占雄性外生殖器中的大部分, 其顶上角具长约1毫米的端刺一枚, 此为本种特征之一, 可以此与近似种区别; 阳茎由基部球状的阳茎囊和端部柄状的阳茎端组成, 内具内阳茎及角状器:雄性外生殖器中有关器官的肌肉来源亦作了叙述。 精液是以贮存于精球的方式授入雌体, 精球分为精球体、精球柄及系带三部分。 雌性内生殖器中, 卵巢为多滋式, 一对, 各由四个卵巢管组成, 两组卵巢管再与一对侧输卵管相连, 后者通入中输卵管中, 中输卵管后端连有外生殖腔, 其外方的开口是为产卵孔; 受精囊为长形梨状物, 分成主囊及副囊两部分, 两者在顶部愈合, 并由此发出受精管与外生殖腔相通, 在主囊顶端有受精囊腺; 附腺一对, 与附腺囊相连, 后者通入附腺主囊, 并由此开口入外生殖腔。雌性外生殖器是由交配囊和产卵器组成, 前者复可分成囊导管、囊体及囊颈三部分, 其外方的开口为交配囊孔, 有导精管从囊颈连于外生殖腔; 产卵器由第8、9腹节组成, 非呈特殊构造。     

Ginger and alpha lipoic acid ameliorate age-related ultrastructural changes in rat liver

Because of the important role that oxidative stress is thought to play in the aging process, antioxidants could be candidates for preventing its related pathologies. We investigated the ameliorative effects of two antioxidant supplements, ginger and alpha lipoic acid (ALA), on hepatic ultrastructural alterations in old rats. Livers of young (4 months) and old (24 months) Wistar rats were studied using transmission electron microscopy. Livers of old rats showed sinusoidal collapse and congestion, endothelial thickening and defenestration, and inconsistent perisinusoidal extracellular matrix deposition. Aged hepatocytes were characterized by hypertrophy, cytoplasmic vacuolization and a significant increase in the volume densities of the nuclei, mitochondria and dense bodies. Lipofuscin accumulation and decreased microvilli in bile canaliculi and space of Disse also were observed. The adverse alterations were ameliorated significantly by both ginger and ALA supplementation; ALA was more effective than ginger. Ginger and ALA appear to be promising anti-aging agents based on their amelioration of ultrastructural alterations in livers of old rats.