Auto/paracrine role of prostaglandins in corpus luteum function

The homeostasis and ephemerality of the corpus luteum (CL) involves an intriguing interplay amongst pituitary, placental and intraovarian regulators. Recent findings have indicated a local pathway of synthesis for the cyclooxygenase-derived prostaglandins (PGs) in luteal cells of all mammalian species investigated. Thus, an autocrine or paracrine role of intraluteal PGs in modulation of luteal Steroidogenesis is implicated. The presence of immune cells in the ovary indicates a constitutive role of these cells and their secretory products, in particular the cytokines, some of which have been demonstrated to greatly influence luteal PG and progesterone production. Despite the plentitude of investigations, a precise role for PGs other than PGF2 in regulation of CL function is still obscure, mainly lacking evidence of cell-specific expression of various classes of PG receptors and their intracellular signaling mechanisms.     

Neuregulin 1 growth factors regulate proliferation but not apoptosis of a CNS neuronal progenitor cell line

Growth factor-dependent proliferation of neuronal progenitors is an essential stage in CNS development. Although several of these growth factors have been identified, high levels of neuregulin 1 (NRG1) mRNA and protein expression in the CNS during the time of neuronal progenitor expansion suggest NRG1 growth factors may also play a key role in their proliferation. No previous studies have examined the expression of multiple NRG1 isoforms and receptors in these progenitors and their role in proliferation or apoptosis. Using a rat CNS clonal cell line with neuronal progenitor properties, we show for the first time these cells coexpress multiple NRG1 isoforms (NRGbeta1, NRGbeta3, CRD-NRGbeta, and SMDF, but not GGF2 or any alpha isoforms) and all three cognate receptors (erbB2-4). We also show for the first time the presence of mRNA for all four variants of the erbB4 receptor in a single CNS cell type. Neutralizing antibody treatments suggest NRG1 isoforms and receptors are involved in proliferation but not apoptosis of these cells. This model system should be useful in future studies of the ligand specificity and function(s) of the erbB4 receptor variants.     

Autocrine and Paracrine Regulation of Neoplastic Cell Growth in Hairy Cell Leukemia

Hairy cell leukemia (HCL), a rare haematological disorder of B-cell origin, mainly presents with bone marrow infiltration, haematopoietic insufficiency, and splenomegaly. In some cases, osteolytic lesions can be observed. Many of these clinical features, especially haematopoietic insufficiency and osteolytic lesions are likely to be caused by soluble factors, such as cytokines. There is evidence that these factors are produced by the malignant hairy cells themselves, suggesting a paracrine pathway. The importance of autocrine as well as paracrine growth loops in growth regulation of HCL-cells is supported by a series of excellent studies, performed within the last few years. It could be clearly shown that cytokines are involved in this autocrine and paracrine regulatory process. The most important cytokines which should be mentioned in this respect are tumor necrosis factor alpha. (TNEa). Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6) and B-cell-growth factor (BCGF). The role of other factors such as viruses and oncogenes remains rather unclear. Nevertheless, recent data suggest that the c-fms, which encodes for the macrophage colony stimulating factor (M-CSF) may be involved in the pathophysiological control of HCL growth.     

Circulating progenitor cells are positively associated with cognitive function among overweight/obese children

Recent evidence has indicated that overweight/obese children may experience cognitive and immune dysfunction, but the underlying mechanisms responsible for the association between overweight/obesity, immune dysfunction, and cognition have yet to be established. The present study aimed to identify a novel link between obesity-induced immune system dysregulation and cognition in preadolescent children. A total of 27 male children (age: 8–10 years) were recruited and separated by body mass index (BMI) into healthy weight (HW: 5th–84.9th percentile, n = 16) and overweight/obese (OW: ⩾85th percentile, n = 11) groups. Adiposity was assessed using dual energy X-ray absorptiometry (DXA), and aspects of executive function were assessed using the Woodcock-Johnson III Tests of Cognitive Abilities. Monocyte populations (CD14⁺CD16⁻, CD14⁺CD16⁺) with and without expression of chemokine receptor type 2 (CCR2), and circulating progenitor cells (CPCs: CD34⁺CD45^dim), in peripheral blood were quantified by flow cytometry. CPCs were isolated by flow sorting and cultured for 24 h for collection of conditioned media (CM) that was applied to SH-SY5Y neuroblastomas to examine the paracrine effects of CPCs on neurogenesis. OW had significantly higher quantities of both populations of monocytes (CD14⁺CD16⁻: 57% increase; CD14⁺CD16⁺: 95% increase, both p < 0.01), monocytes expressing CCR2 (CD14⁺CD16⁻CCR2⁺: 66% increase; CD14⁺CD16⁺CCR2⁺: 168% increase, both p < 0.01), and CPCs (47% increase, p < 0.05) than HW. CPCs were positively correlated with abdominal adiposity in OW, and negatively correlated in HW with a significant difference between correlations (p < 0.05). CPC content was positively correlated with executive processes in OW, and negatively correlated in HW with a significant difference in the strength of the correlations between groups (p < 0.05 for correlation between OW and HW). Finally, CPC-CM from OW trended to increase neuroblast viability in vitro relative to HW (1.79 fold, p = 0.07). These novel findings indicate that increased content of CPCs among OW children may play a role in preventing decrements in cognitive function via paracrine mechanisms.     

释放膜微粒：间充质干细胞治疗的新机制

间充质干细胞（Mesenchymalstemcells,MSC）是一类具有自我更新和多向分化潜能的成体干细胞,具有取材方便、体外扩增能力强和免疫原性低等特点,已成为细胞治疗和组织工程的重要种子细胞。MSC治疗已经进入临床试验阶段,部分疾病已经完成Ⅲ期临床试验,证实了这种新型疗法的安全性和有效性。然而．关于MSC治疗的机制并未阐明。近几年的研究发现,间充质干细胞的分化及其旁分泌作用,可能不是其组织修复及治疗多种疾病的主要原因．而来源于间充质干细胞的膜微粒,可能是治疗过程中的主要参与者。本文就MSC膜微粒的生物学特性、作用机制及临床应用的可能性等问题进行综述。     

Suppression of ATP-induced excitability in rat small-diameter trigeminal ganglion neurons by activation of GABAB receptor

The aim of the present study was to investigate whether a GABA_B receptor agonist could modulate ATP-activated neuronal excitability of nociceptive TRG neurons using perforated whole-cell patch-clamp and immunohistochemical techniques. Immunohistochemical analysis revealed that 86% of P₂X₃ receptor-immunoreactive, small-diameter TRG neurons co-expressed GABA_B receptor. Under voltage-clamp conditions (V_h = −60 mV), application of ATP activated the inward current in acutely isolated rat TRG neurons in a dose-dependent manner (10–50 μM) and this current could be blocked by pyridoxal-phosphate-6-azophenyl-27,47-disulfonic acid (PPADS) (10 μM), a selective P₂ purinoreceptor antagonist. The peak amplitude of ATP-activated currents was significantly inhibited after application of GABA_B receptor agonist, baclofen (10–50 μM), in a concentration-dependent and reversible manner. The baclofen-induced inhibition of ATP-activated current was abolished by co-application of 3-amino-2 (4-chlorophenyl)-2hydroxypropysufonic acid) saclofen, a GABA_B receptor antagonist (50 μM). Under current-clamp conditions, application of 20 μM ATP significantly depolarized the membrane potential resulting in increased mean action potential frequencies, and these ATP-induced effects were significantly inhibited by baclofen and these effects were antagonized by co-application of saclofen. Together, the results suggested that GABA_B receptor activation could inhibit the ATP-induced excitability of small-diameter TRG neurons activated through the P₂X₃ receptor. Thus, the interaction between P₂X₃ and GABA_B receptors of small-diameter TRG neuronal cell bodies is a potential therapeutic target for the treatment of trigeminal nociception.     

人脐带间充质干细胞旁分泌物质的作用及对肝功能衰竭的影响

脐带间充质干细胞(umbilical cord mesenchymalstem cell, UC-MSC)是从人脐带华尔通胶(Wharton jelly)中分离出的细胞,它可以表达间充质干细胞的表面标志,其生物学特性与骨髓间充质干细胞相似,可以诱导分化为多种细胞.最近国内外学者对UC-MSC的移植及诱导分化治疗进行了大量研究,如在心肌梗死、肾脏及血液系统疾病中的研究.但对UC-MSC旁分泌物质的研究却不多见.此文就UC-MSC的分泌、分化及免疫调节作用、旁分泌物质的作用及对肝功能衰竭的影响和应用前景作一综述.     

Adult stem cells as a tool for kidney regeneration

Kidney regeneration is a challenging but promising strategy aimed at reducing the progression to end-stage renal disease (ESRD) and improving the quality of life of patients with ESRD. Adult stem cells are multipotent stem cells that reside in various tissues, such as bone marrow and adipose tissue. Although intensive studies to isolate kidney stem/progenitor cells from the adult kidney have been performed, it remains controversial whether stem/progenitor cells actually exist in the mammalian adult kidney. The efficacy of mesenchymal stem cells (MSCs) in the recovery of kidney function has been demonstrated in animal nephropathy models, such as acute tubular injury, glomerulonephritis, renal artery stenosis, and remnant kidney. However, their beneficial effects seem to be mediated largely via their paracrine effects rather than their direct differentiation into renal parenchymal cells. MSCs not only secrete bioactive molecules directly into the circulation, but they also release various molecules, such as proteins, mRNA, and microRNA, in membrane-covered vesicles. A detailed analysis of these molecules and an exploration of the optimal combination of these molecules will enable the treatment of patients with kidney disease without using stem cells. Another option for the treatment of patients with kidney disease using adult somatic cells is a direct/indirect reprogramming of adult somatic cells into kidney stem/progenitor cells. Although many hurdles still need to be overcome, this strategy will enable bona fide kidney regeneration rather than kidney repair using remnant renal parenchymal cells.