Tight junction biogenesis during early development

The tight junction (TJ) is an essential component of the differentiated epithelial cell required for polarised transport and intercellular integrity and signalling. Whilst much can be learnt about how the TJ is constructed and maintained and how it functions using a wide range of cellular systems, the mechanisms of TJ biogenesis within developmental models must be studied to gain insight into this process as an integral part of epithelial differentiation. Here, we review TJ biogenesis in the early mammalian embryo, mainly considering the mouse but also including the human and other species, and, briefly, within the amphibian embryo. We relate TJ biogenesis to inherent mechanisms of cell differentiation and biosynthesis occurring during cleavage of the egg and the formation of the first epithelium. We also evaluate a wide range of exogenous cues, including cell-cell interactions, protein kinase C signalling, gap junctional communication, Na⁺/K⁺-ATPase and cellular energy status, that may contribute to TJ biogenesis in the embryo and how these may shape the pattern of early morphogenesis.     

Immunohistochemical localization of prostaglandin H synthase in the embryo and uterus of the mouse from ovulation through implantation

Prostaglandins (PGs) in the embryo and endometrium are involved in processes that are important for implantation. Although the presence of PGs (PGE2, PGF2 alpha, PGI2) in decidualized endometrium has been widely reported, less is known about the capacity of the pre-implantation embryo to synthesize PGs. Prostaglandin H (PGH) synthase is necessary for the production of PGs. Using an immunohistochemical method, PGH synthase was localized in the mouse embryo and uterus from superovulation through embryo implantation. No PGH synthase was detected in oocytes at the time of ovulation or in single-cell embryos 1 day post-fertilization (PF). Circular areas of immunostaining became evident in the cytoplasm of blastomeres at the morula stage (day 3 PF). After implantation (day 5 PF), a low level of PGH synthase reactivity was observed in embryonic cells; no PGH synthase was detected in the embryo by day 7 PF. The endometrial glands exhibited maximal immunostaining by day 3 PF, and after implantation, PGH synthase appeared in decidual cells along the border of placentation. Low levels of PGH synthase reactivity were detected in myometrial cells during the period after superovulation through day 7 PF. This is the first demonstration of PGH synthase in the mouse embryo prior to apposition with glandular endometrial epithelium, supporting the hypothesis that the embryo has the potential to produce PGs that may mediate autocrine and/or paracrine responses at the time of nidation.     

听力障碍青少年治疗过程心理干预对患儿语言能力恢复和心境状态的影响

摘要 目的：探讨听力障碍青少年治疗过程心理干预对患儿语言能力恢复和心境状态的影响。方法：选取我院2019年6月到2020年6月共收治的80例7~18岁听力障碍青少年作为研究对象,将患儿随机分为观察组与对照组,每组40例。对所有患儿应用人工耳蜗植入术进行治疗,给予对照组常规言语训练以及健康教育等干预。观察组患儿在常规干预基础上增加全治疗过程的心理干预。对比两组患儿的治疗效果,语言能力恢复,心境状态,ABC评分。结果：观察组患儿治疗的总有效率为92.50%,对照组患儿治疗的总有效率为75.00%,观察组高于对照组（P＜0.05）;两组患儿干预前的言语形成、听觉能力以及听觉感知对比无明显差异（P＞0.05）,两组患儿通过治疗与干预之后,言语形成、听觉能力以及听觉感知明显提升,且观察组评分高于对照组（P＜0.05）;两组患儿干预前的精神、控制、能力、忍受消极情感以及接受变化对比无明显差异（P＞0.05）,两组患儿通过治疗与干预之后,精神、控制、能力、忍受消极情感以及接受变化明显降低,且观察组评分低于对照组（P＜0.05）;两组干预前的兴奋、易激怒、刻板行为以及不恰当语言等评分比较无统计学意义（P＞0.05）,两组患儿干预后,各评分均下降,其中观察组小于对照组,差异有统计学意义（P＜0.05）。结论：对听力障碍青少年在常规治疗与干预基础上增加心理干预,能够提升患儿的治疗效果,提升语言能力恢复情况,减少负面情绪,提升患儿的心境状态,值得临床应用推广。     

N+离子注入对干旱胁迫条件下甘草幼苗的SOD酶和CAT酶活性及丙二醛含量的影响

以低能氮离子束为诱变源,对甘草种进行注入处理后,以萌发的幼苗为材料对其在干旱胁迫条件下保护酶活性及MDA含量变化进行研究.结果表明注入后甘草种的存活率呈现马鞍形曲线变化,其中在4.1×1016N+/cm2剂量处达到鞍点,在剂量4.6×1016N+/cm2处存活率高于对照.在干旱胁迫下,随着胁迫时间的延长,离子束注入后萌发的幼苗MDA含量明显低于对照.酶活结果显示,在干旱胁迫后期,剂量4.6×1016N+/cm2处理后的甘草幼苗SOD和CAT酶活性都高于对照,说明该注入剂量处理甘草种有助于提高甘草幼苗的抗旱性能,SOD同工酶结果也证明该剂量的离子注入对干旱胁迫下同工酶谱带有所影响.     

Inhibition of embryo implantation in mice through vaginal administration of a proprotein convertase 6 inhibitor

Uterine proprotein convertase 6 (PC6) plays a critical role in embryo implantation in both mice and women. It was hypothesized that inhibiting uterine PC6 could prevent pregnancy. Vaginal administration of a PC6 inhibitor presents the ideal route for local drug delivery. A peptide-based PC6 inhibitor, C-30k-PEG Poly R that was previously shown to have properties of increased vaginal absorption and penetration was tested for its contraceptive potential in mice following vaginal administration. The study demonstrated that this approach could inhibit embryo implantation in some mice (24% completely and 47% partially inhibited).     

Does the dysregulation of matrix metalloproteinases contribute to recurrent implantation failure?

Introduction: The progress in in vitro fertilization (IVF) techniques for infertility management has led to the investigation of embryo implantation site proteins such as Matrix metalloproteinases (MMPs), which may have a key role in embryo-endometrium crosstalk and in the molecular mechanisms of the embryo implantation.

Areas covered: Numerous studies have generated much information concerning the relation between the different proteins at the site of implantation such as cytokines, growth factors, adhesion molecules and MMPs. However, the exact role of the MMPs in embryo implantation and the impact of their dysregulation in recurrent implantation failure have yet to be characterized.

Expert commentary: The proteomic investigation of the MMPs and their molecular pathways may enable scientists and clinicians to correct this dysregulation (via appropriate means of prevention and treatment), better manage embryo transfer during IVF cycles, and thus increase the ongoing pregnancy rate.     

恶性胆道梗阻患者所行经皮穿刺肝内胆管引流术中成功置入金属支架的术前影响因素分析

目的:探讨恶性胆道梗阻患者行PTBD(Percutaneous Transhepatic Biliary Drainage)术中金属支架置入成功率的影响因素。方法:回顾性搜集2010年10月-2017年1月上海市第一人民医院收治的因患有近端恶性胆道梗阻行PTBD术患者的相关临床资料。比较不同原发病因患者支架置入情况。根据患者支架置入是否成功将其分为支架组和非支架组,比较患者的一般临床特征。结果:胰腺癌、胃癌和胆囊癌为本研究中数量上前3位的肿瘤,将以上3组分别按照支架置入数行x~2检验,其中胰腺癌(n=18,支架=6)和胃癌(n=14,支架=11)有统计学意义。将50例患者分为支架组(n=28)和非支架组(n=22),组间比较差异有统计学意义的因素包括:白细胞计数(支架组=6.40±3.40×10~9/L,非支架组=10.74±6.41×10~9/L),中性粒细胞计数(支架组=4.90±3.06×10~9/L,非支架组=8.92±6.25×10~9/L),胆道感染(支架组=9,非支架组=15)。进一步将该50例患者分为6组:胰腺癌-胆道感染组、胃癌-胆道感染组、其他肿瘤-胆道感染组、胰腺癌+胆道感染组、胃癌+胆道感染组、其他肿瘤+胆道感染组。将以上6组分别按照支架置入数行x~2检验,胰腺癌+胆道感染组(n=11,支架=1,P=0.001)有统计学意义。结论:PTBD术对于恶性胆道梗阻是一种有效的姑息治疗手段。胆道感染是PTBD术中支架置入成功的不利因素,胰腺癌合并胆道感染会显著降低PTBD术中支架置入成功率。     

Derivation of Human Trophoblast Stem Cells

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Insulin and branched-chain amino acid depletion during mouse preimplantation embryo culture programmes body weight gain and raised blood pressure during early postnatal life

Mouse maternal low protein diet exclusively during preimplantation development (Emb-LPD) is sufficient to programme altered growth and cardiovascular dysfunction in offspring. Here, we use an in vitro model comprising preimplantation culture in medium depleted in insulin and branched-chain amino acids (BCAA), two proposed embryo programming inductive factors from Emb-LPD studies, to examine the consequences for blastocyst organisation and, after embryo transfer (ET), postnatal disease origin. Two-cell embryos were cultured to blastocyst stage in defined KSOM medium supplemented with four combinations of insulin and BCAA concentrations. Control medium contained serum insulin and uterine luminal fluid amino acid concentrations (including BCAA) found in control mothers from the maternal diet model (N-insulin + N-bcaa). Experimental medium (three groups) contained 50% reduction in insulin and/or BCAA (L-insulin + N-bcaa, N-insulin + L-bcaa, and L-insulin + N-bcaa). Lineage-specific cell numbers of resultant blastocysts were not affected by treatment. Following ET, a combined depletion of insulin and BCAA during embryo culture induced a non sex-specific increase in birth weight and weight gain during early postnatal life. Furthermore, male offspring displayed relative hypertension and female offspring reduced heart/body weight, both characteristics of Emb-LPD offspring. Combined depletion of metabolites also resulted in a strong positive correlation between body weight and glucose metabolism that was absent in the control group. Our results support the notion that composition of preimplantation culture medium can programme development and associate with disease origin affecting postnatal growth and cardiovascular phenotypes and implicate two important nutritional mediators in the inductive mechanism. Our data also have implications for human assisted reproductive treatment (ART) practice.     

Fetal loss in mice exposed to magnetic fields during early pregnancy

The effects of low-frequency magnetic fields (MFs) on early pregnancy were studied in CBA/S mice. The magnetic field was a 20 kHz, 15 μT sawtooth. Pregnant females were divided into four groups, two control groups and two exposed groups. One group was exposed to MFs continuously from day 1 postconception (pc) until day 5.5 pc, and the other group was exposed continuously until day 7 pc. All animals were sacrificed on day 19 pc, the day before partus, and their uterine contents were analyzed. No significant increase in the resorption (early fetal death) rate was found in the exposed animals compared to the sham controls. In the group exposed during days 1.0–5.5 pc, the body weight and length of the living fetuses were significantly decreased. Except on day 3 pc (progesterone) and day 13 pc (calcium) in the treated groups, there were no significant differences in progesterone and calcium levels in peripheral blood. Implantation occurred on the same day in MF-treated and control animals. © 1995 Wiley-Liss, Inc.