Phenotype-dependent alteration of pathways and networks reveals a pure synergistic mechanism for compounds treating mouse cerebral ischemia

Aim:

Our previous studies have showed that ursodeoxycholic acid (UA) and jasminoidin (JA) effectively reduce cerebral infarct volume in mice. In this study we explored the pure synergistic mechanism of these compounds in treatment of mouse cerebral ischemia, which was defined as synergistic actions specific for phenotype variations after excluding interference from ineffective compounds.

Methods:

Mice with focal cerebral ischemia were treated with UA, JA or a combination JA and UA (JU). Concha margaritifera (CM) was taken as ineffective compound. Cerebral infarct volume of the mice was determined, and the hippocampi were taken for microarray analysis. Particular signaling pathways and biological functions were enriched based on differentially expressed genes, and corresponding networks were constructed through Ingenuity Pathway Analysis.

Results:

In phenotype analysis, UA, JA, and JU significantly reduced the ischemic infarct volume with JU being superior to UA or JA alone, while CM was ineffective. As a result, 4 pathways enriched in CM were excluded. Core pathways in the phenotype-positive groups (UA or JA) were involved in neuronal homeostasis and neuropathology. JU-contributing pathways included all UA-contributing and the majority (71.7%) of JA-contributing pathways, and 10 new core pathways whose effects included inflammatory immunity, apoptosis and nervous system development. The functions of JU group included all functions of JA group, the majority (93.1%) of UA-contributing functions, and 3 new core functions, which focused on physiological system development and function.

Conclusion:

The pure synergism between UA and JA underlies 10 new core pathways and 3 new core functions, which are involved in inflammation, immune responses, apoptosis and nervous system development.     

“Mucosal maps” of the canine nasal cavity: Micro-computed tomography and histology

Nasal turbinals, delicate and complex bones of the nasal cavity that support respiratory or olfactory mucosa (OM), are now easily studied using high resolution micro-computed tomography (μ-CT). Standard μ-CT currently lacks the capacity to identify OM or other mucosa types without additional radio-opaque staining techniques. However, even unstained mucosa is more radio-opaque than air, and thus mucosal thickness can be discerned. Here, we assess mucosal thickness of the nasal fossa using the cranium of a cadaveric adult dog that was μ-CT scanned with an isotropic resolution of 30 μm, and subsequently histologically sectioned and stained. After co-alignment of μ-CT slice planes to that of histology, mucosal thickness was estimated at four locations. Results based on either μ-CT or histology indicate olfactory mucosa is thicker on average compared with non-olfactory mucosa (non-OM). In addition, olfactory mucosa has a lesser degree of variability than the non-OM. Variability in the latter appears to relate mostly to the varying degree of vascularity of the lamina propria. Because of this, in structures with both specialized vascular respiratory mucosa and OM, such as the first ethmoturbinal (ET I), the range of thickness of OM and non-OM may overlap. Future work should assess the utility of diffusible iodine-based contrast enhanced CT techniques, which can differentiate epithelium from the lamina propria, to enhance our ability to differentiate mucosa types on more rostral ethmoturbinals. This is especially critical for structures such as ET I, which have mixed functional roles in many mammals.     

Assessment the long-term effects of septoplasty surgery on olfactory function

Objectives: This research aimed to evaluate pre-operatively and post-operatively the olfactory function of patients who had undergone surgery in our clinic for chronic nasal blockage via the Connecticut Chemosensory Clinical Research Center (CCCRC) smell test.

Method: Thirty-seven patients (24 females, 13 males) were enrolled in this study. All had undergone surgery in our clinic due to chronic nasal blockage (not for smell dysfunction), having been diagnosed with septal deviation in conjunction with concha bullosa and/or inferior turbinate hypertrophy. This is a prospective study without a control group. The mean age was 33.74?±?8.98 (range =19–54). All of the operations were performed under general anesthesia. CCCRC smell tests were performed on every patient before the operation and at post-operative 1st week, 6th week, 6th month, and 1st year.

Results: In this study, we found that septoplasty, in conjunction with middle concha surgery and/or inferior concha radiofrequency, did not affect the olfactory function negatively.

Conclusion: Although nasal surgery has the potential to affect the smell function negatively, it was found that olfactory function was not affected after the surgery during a considerably long follow-up period. Moreover, an improvement in smell function was detected at post-operative 6th month and 1st year.     

Middle Turbinate Headache Syndrome

The middle turbinate and nasal septum are innervated by the anterior ethmoidal nerve, a branch of the ophthalmic division of the trigeminal nerve. As reported in the classical work of Wolff (1948), stimulation of these regions causes pain in the medial canthus of the supraorbital region. Periorbital pain due to middle turbinate compression against the septum or the lateral wall of the nose may be due to congestion of the nasal mucosa or to pneumatization of the middle turbinate (concha bullosa). The diagnosis is made by exclusion and requires a high index of suspicion, anterior rhinoscopy, computerized tomography (CT), and confirmation by the lidocaine test. We present five cases of middle turbinate headache syndrome, all with contha bullosa. Four were treated surgically by partial middle turbinectomy and septoplasty more than 1 year ago, with excellent results. One patient refused surgical treatment which was suggested after failure of medical treatment with antihistamines, decongestants, and a topical corticosteroid, and continues to be symptomatic. Despite the small number of cases studied, the authors conclude that the procedure used was effective for the resolution of headache.     

中药不同组分对小鼠缺血脑组织蛋白表达谱的影响

目的 运用蛋白质组学技术分析中药不同组分对小鼠缺血脑组织蛋白表达谱的影响.方法 黄芩苷、栀子苷、胆酸、珍珠母分别干预缺血再灌小鼠3h后,断头取脑,提取蛋白,用蛋白质芯片比较分析以上组分对小鼠缺血脑组织蛋白表达谱影响的差异.结果 黄芩苷、栀子苷、胆酸、珍珠母可影响5373Da,5707Da,15103Da 3个靶点蛋白的表达,中药对蛋白表达具有多靶点性和差异性.结论 蛋白质芯片技术是探索中药药理机制的有效手段.     

Ontogeny and Microanatomy of the Nasal Turbinals in Lemuriformes

The nasal cavity of strepsirrhine primates (lemurs and lorises) has the most primitive arrangement of extant primates. In nocturnal species, the numerous turbinals of the ethmoid bear a large surface area of olfactory mucosa (OM). In this study, we examine turbinal development in four genera of diurnal or cathemeral lemuriformes. In addition, we examined an age series of each genus to detect whether structures bearing OM as opposed to respiratory mucosa (RM) develop differently, as has been observed in nocturnal strepsirrhines. In adults, the maxilloturbinal is covered by highly vascular respiratory mucosa throughout its entire length, with large sinusoidal vessels in the lamina propria; any parts of other turbinals that closely borders the maxilloturbinal has a similar mucosa. Posteriorly, the most vascular RM is restricted in the nasopharyngeal duct, which becomes partitioned from the dorsal olfactory region. A comparison of newborns to adults reveals that the first ethmoturbinal increases more in length in the parts that are covered with RM than OM, which supports the idea that ethmoturbinals can specialize in more than one function. Finally, we observe that the regions of turbinals that are ultimately covered with RM develop more accessory lamellae or additional surface area of existing scrolls compared to the regions covered with OM. Because such outgrowths of bone develop postnatally and without cartilaginous precursors, we hypothesize that the complexity of olfactory lamellae within the ethmoturbinal complex is primarily established at birth, while respiratory lamellae become elaborated due to the epigenetic influence of respiratory physiology. Anat Rec, 299:1492–1510, 2016. © 2016 Wiley Periodicals, Inc.     

耳针调节内脏功能的作用机制研究

目的研究耳针调节内脏功能的形态学基础,寻找耳穴与内脏之间的神经联系。方法将辣根过氧化物酶(HRP)注射于耳穴皮下,HRP颗粒将通过神经末梢的吸收经轴浆逆行运输到神经元胞体。结果在迷走神经下节和交感干神经节上发现HRP酶标细胞。结论本实验揭示在耳甲(耳内脏穴分布的区域)和支配内脏的交感神经节之间可能存在一条神经通路。     

The activity of N-acetyl-β-d-hexosaminidase A and B and β-glucuronidase in nasal polyps and hypertrophic nasal concha

Nasal polyps and hypertrophic lower nasal conchae are common disorders of nasal cavity. The majority of etiopathogenetic theories indicate inflammatory background of polyps and hypertrophic concha. N-acetyl-β-d-hexosaminidase and β-glucuronidase are lysosomal exoglycosidases revealing accelerated activity in inflammatory processes. Aim: The aim of the study was to evaluate the catabolism of glycoconjugates in nasal polyps and hypertrophic nasal concha basing on the activity of N-acetyl-β-d-hexosaminidase (HEX) and β-glucuronidase (GLU). Material and methods: Material consisted of nasal polyps taken from 40 patients during polypectomy in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and hypertrophic lower nasal conchae taken from 20 patients during mucotomy. The activity of HEX, HEX A, HEX B and GLU in supernatant of homogenates of nasal polyps and hypertrophic lower nasal concha tissues has been estimated using colorimetric method. Results: Statistically significant decrease has been observed in concentration of the activity (per 1 mg of tissue) of HEX (p < 0.05), HEX B (p < 0.001) and specific activity (per 1 mg of protein) of HEX B (p < 0.001) in nasal polyps tissue in comparison to hypertrophic lower nasal conchae tissue. Conclusions: Decrease in the activity and specific activity concentration of the majority of examined lysosomal exoglycosidases (increasing in inflammations) in comparison to hypertrophic lower nasal conchae suggests electrolytes disorders and questions the inflammatory background of nasal polyps.     

下鼻甲成形术加骨折外移术治疗肥厚性鼻炎的疗效观察

目的探讨在鼻内镜下保留鼻腔正常形态完成下鼻甲手术,保留鼻腔的解剖及生理功能,以达到治疗吧厚I性鼻炎的目的。方法对符合肥厚性鼻炎诊断的患者,在鼻内镜下切除部分下鼻甲骨及部分外侧黏膜,把保留的黏膜瓣覆盖在下鼻甲创面上,形成结构正常的新下鼻甲,并将下鼻甲向外侧骨折移位。结果本组130例（184N）全部病例鼻塞症状全部消失,创面光滑平整,无干痂及粘连。经随访1-2年,全部病例均无其他不适症状。结论鼻内镜下应用电动微型吸切器完成下鼻甲成形术加骨折外移术,是治疗慢性肥厚性鼻炎实用有效的方法。     

Primary cutaneous amyloidosis of the auricular concha: case report and review of published work

A 70-year-old Japanese female developed tiny papules on her bilateral ears 2 years previously. A histological study of a biopsy specimen revealed that amorphous materials were present in the widened dermal papillae. Because these materials were positive for both Congo red and Dylon, we diagnosed the lesion as primary cutaneous amyloidosis of the auricular concha. Immunohistochemically, the amyloid substance stained positively with 34betaE12 (cytokeratin 1/5/10/14), suggesting that it had an epidermal origin. Seven reported cases of this unique disorder were also reviewed.