Expression of CYP1B1 but not CYP1A1 by primary cultured human mammary stromal fibroblasts constitutively and in response to dioxin exposure: role of the Ah receptor

The expression of CYP1B1 in human mammary fibroblasts (HMFs) was characterized as a potential modulator of their individual function as well as effects on adjacent mammary epithelia. We have used these characteristics to explore the diversity of fibroblast cells isolated from reduction mammoplasty patients and from different breast locations in breast cancer patients (tumors, peripheral to tumor and skin). These parameters have also been used to examine differences between two donors. The results have shown that while none of these HMFs expressed a detectable CYP1A1 protein basally or in response to TCDD, they all expressed CYP1B1 constitutively at similar levels (0.5-0.9 pmol/mg microsomal proteins) and they were induced by TCDD (up to 5-fold) consistent with mediation by the Ah receptor (AhR). DMBA metabolism by HMFs exhibited high proportions of 5,6-, 10,11- and 3,4-dihydrodiols, a profile that is typical of human CYP1B1 regioselectivity. RT-PCR followed by Southern blot analyses demonstrated that CYP1B1 mRNA expression in HMFs parallels levels of respective microsomal proteins. The AhR is expressed in these HMFs as two cytosolic forms (approximately 106 and 104 kDa) and a substantial proportion of the 104 kDa form was localized to the nucleus even prior to TCDD treatment. In all HMFs isolated directly from collagenase digested breast tissues the AhR is expressed at levels 10-fold lower than in breast epithelial cells. However, HMFs that were isolated after serial passaging of mammary epithelial cultures had shown much higher levels of the AhR expression and more dramatic TCDD-induced down-regulation (>80% in 24 h) associated with more efficient nuclear translocation. These differences suggested the presence of two functionally distinct subtypes of HMFs: interstitial stromal fibroblasts that are readily released by collagenase digestion of breast tissues, and lobular stromal fibroblasts which are more tightly associated with the breast epithelia.      

Bioengineering strategies for regeneration of craniofacial bone: a review of emerging technologies

Oral Diseases (2010) 16 , 709–716 Although advances in surgical techniques and bone grafting have significantly improved the functional and cosmetic restoration of craniofacial structures lost because of trauma or disease, there are still significant limitations in our ability to regenerate these tissues. The regeneration of oral and craniofacial tissues presents a formidable challenge that requires synthesis of basic science, clinical science, and engineering technology. Tissue engineering is an interdisciplinary field of study that addresses this challenge by applying the principles of engineering to biology and medicine toward the development of biological substitutes that restore, maintain, and improve normal function. This review will explore the impact of biomaterials design, stem cell biology and gene therapy on craniofacial tissue engineering.     

Brain-IL-1β induces local inflammation but systemic anti-inflammatory response through stimulation of both hypothalamic–pituitary–adrenal axis and sympathetic nervous system

It is well established that systemic inflammation induces a counter-regulatory anti-inflammatory response particularly resulting in deactivation of monocytes/macrophages. However, recently we demonstrated a systemic anti-inflammatory response without preceding signs of systemic inflammation in patients with brain injury/surgery and release of cytokines into the cerebrospinal fluid (CSF). In order to analyze the mechanisms and pathways of systemic immunodepression resulting from sterile cerebral inflammation we established an animal model using continuous intra-cerebroventricular (i.c.v.) or intra-hypothalamic (i.h.) infusion of rat recombinant (rr) tumor necrosis factor (TNF)-α and interleukin (IL)-1β for 48 h. Controls received intra-venous (i.v.) cytokine administration. Interestingly, i.c.v. and i.h. infusion of IL-1β but not TNF-α produced distinct signs of central nervous system (CNS) inflammation. Correspondingly, i.c.v. infusion of IL-1β particularly diminished the TNF-α but increased the IL-10 concentration in whole blood cultures after endotoxin stimulation. All parameters normalized within 48 h after termination of the infusion. Blocking the hypothalamic–pituitary–adrenal (HPA) axis by hypophysectomy (HPX) led to complete recovery of the diminished TNF-α concentration and temporarily inhibited the IL-10 increase. Blocking the sympathetic nervous system (SNS) transmission by application of the β₂-adrenoreceptor antagonist propranolol not only inhibited the increase but further downregulated the endotoxin induced IL-10 concentration in the media of whole blood cell cultures, whereas the TNF-α decrease was only partially prevented. Interestingly, HPX and propranolol also diminished the cell invasion into the CSF. In summary, activation of both the HPA axis and the SNS plays an important role in systemic anti-inflammatory response resulting from cytokines in brain and cerebral inflammation.     

散偏汤联合针刺治疗偏头痛的临床疗效

目的 观察散偏汤联合针刺治疗偏头痛的临床疗效.方法 选取2019年8月至2020年11月沈阳市中医院收治的100例偏头痛患者作为为研究对象,根据随机数字表分为观察组与对照组,每组各50例,对照组采用口服盐酸氟桂利嗪胶囊进行治疗,观察组采用针刺联合口服散偏汤治疗,4周为1个疗程,治疗1个疗程后,比较两组视觉模拟量表(VA...