Detection of Ⅴ,Ⅲ and Ⅰ Type Collagens of Dermal Tissues in Skin Lesions of Patients with Systemic Sclerosis and Its Implication

This study investigated the contents and distribution of collagen Ⅴ （Col Ⅴ） in skin lesions of the patients with systemic sclerosis （SSc） and its roles in the pathogenesis. The contents and distribution for α1 chain of collagen type Ⅰ, Ⅲ and V [α1 （Ⅰ）, α1 （Ⅲ） and α1 （Ⅴ）] in skin lesions of 36 patients with SSc （9 cases of mild fibrosis, 14 moderate, and 13 severe） were detected by using im- munohistochemical SP method. Six cases of normal skin tissues served as controls. The results showed that there was diffuse distribution for three kinds of collagens in dermis. The deep staining α1 （Ⅰ） and α1 （Ⅲ） masses or bands were seen in reticular layer, while α1 （Ⅴ） was distributed more ho- mogeneously. From control to weak, moderate and severe fibrosis stages, α1 （Ⅰ）, α1 （Ⅲ） and α1 （V） showed a gradually increased trend in skin lesions （P〈0.05）. α1 （Ⅴ） was obviously elevated in skin lesions at early stage and persisted in whole fibrotic process and risen in greater contents, while α1 （Ⅰ） and α1 （Ⅲ） were to go higher late and were apparently elevated at moderate and late stages. Com- pared with α1 （Ⅰ）, α1 （Ⅴ） took leading increase at early stage in skin lesions （P〈0.01）, and had more elevated contents than α1 （Ⅲ） at moderate and late stages. The fibrotic changes in dermal reticular layer occurred earlier than those in papillary layer, and the abnormalities of α1 （Ⅴ）/α1 （I） ratio ap- peared before α1 （Ⅲ）/α1 （Ⅰ） ratio. It was concluded that a lot of α1 （Ⅴ） began to deposit in greater contents prior to α1 （Ⅰ） and α1 （Ⅲ） at early stage in SSc and persisted in whole fibrotic process. The changes of α1 （Ⅴ） contents in reticular layer occurred earlier than those in papillary layer, and it sug- gested that the fibrosis in reticular layer appeared earlier.

Clinical efficacy of intradermal type Ⅰ collagen injections in treating skin photoaging in patients from high-altitude areas

BACKGROUND Photoaging,a result of chronic sun exposure,leads to skin damage and pigmentation changes.Traditional treatments may have limitations in high-altitude areas like Yunnan Province.Intradermal Col Ⅰ injections stimulate collagen production,potentially improving skin quality.This study aims to assess the efficacy and safety of this treatment for photoaging.AIM To evaluate the efficacy and safety of intradermal typeΙcollagen(ColΙ)injection for treating photoaging.METHODS This prospective,self-controlled study investigated the impact of intradermal injections of ColΙon skin photodamage in 20 patients from the Yunnan Province.Total six treatment sessions were conducted every 4 wk±3 d.Before and after each treatment,facial skin characteristics were quantified using a VISIA skin detector.Skin thickness data were assessed using the ultrasound probes of the Dermalab skin detector.The Face-Q scale was used for subjective evaluation of the treatment effect by the patients.RESULTS The skin thickness of the right cheek consistently increased after each treatment session compared with baseline.The skin thickness of the left cheek significantly increased after the third through sixth treatment sessions compared with baseline.The skin thickness of the right zygomatic region increased after the second to sixth treatment sessions,whereas that of the left zygomatic region showed a significant increase after the fourth through sixth treatment sessions.The skin thickness of both temporal regions significantly increased after the fifth and sixth treatment sessions compared with baseline(P<0.05).These findings were also supported by skin ultrasound images.The feature count for the red areas and wrinkle feature count decreased following the treatment(P<0.05).VISIA assessments also revealed a decrease in the red areas after treatment.The Face-QSatisfaction with Facial Appearance Overall and Face-Q-Satisfaction with Skin scores significantly increased after each treatment session.The overall appearance of the patients improved after treatment.CONCLUSION Intradermal ColΙinjection improves photoaging,with higher patient satisfaction and fewer adverse reactions,and could be an effective treatment method for populations residing in high-altitude areas.

Collagen typeⅠ在胰腺癌发展中的作用

胰腺癌(PC)是高发病率、高死亡率的恶性肿瘤,尽管目前在胰腺癌的治疗策略中已取得了较大的进展,但胰腺癌的转移、复发及高耐药性仍是大部分患者预后不良的主要原因。Ⅰ型胶原蛋白(Col⁃I)是人体中主要的细胞外基质蛋白,在多种实体肿瘤中表达异常并参与肿瘤的形成。最近研究表明,Col⁃I在胰腺癌中高度表达与胰腺癌的生长、转移、侵袭、耐药以及治疗密切相关,是胰腺癌新的潜在治疗靶点。该文重点介绍了COl⁃I对胰腺癌发生发展的影响,为胰腺癌的诊断和靶向治疗提供新的思路。

维药买朱尼含药血清对IL-1β作用下大鼠软骨细胞MMP-13、Type-ⅡCollagen表达的影响

目的:观察维药买朱尼含药血清对IL-1β作用下体外培养的大鼠关节软骨细胞Type-ⅡCollagen、MMP-1、MMP-13表达的影响,并进一步探讨维药买朱尼防治OA的作用机制。方法:从1周龄SD大鼠关节软骨中分离培养原代软骨细胞,经鉴定后选用第二代细胞随机分为空白对照组、模型组、维药买朱尼组,培养第3d时模型组、维药买朱尼组采用细胞因子IL-1β(10ng/ml)继续培养,分别在培养后第24h、36h、48h采用RealTimePCR方法检测并分析各组软骨细胞中MMP-13、Type-ⅡCollagen的表达情况。结果:在第24h时各组MMP-13表达增加,Type-ⅡCollagen有一定降低,但无统计学差异;而在第36h和48h时空白对照组与模型组MMP-13、Type-ⅡCollagen表达差异均有统计学意义(P<0.05),维药买朱尼组较模型组MMP-13与Type-ⅡCollagen的表达在48h、72h时间点有显著性差异(P<0.05)。结论:维药买朱尼可抑制IL-1β对Type-ⅡCollagen的降解和破坏作用,并能抑制IL-1β对MMP-13的诱导和激活作用。

Collagen type Ⅳ对周围神经中再生轴突及非神经元细胞的作用和影响

本文用抗ｃｏｌｌａｇｅｎｔｙｐｅⅣ对抗体阻断ｃｏｌｌａｇｅｎｔｙｎｅⅣ的方法，研究了ｃｏｌｌａｇｅｎｔｙｐｅⅣ失活的移植神经段（长１０ｍｍ）植入大鼠坐骨神经后对再生轴突和非神经元细胞的作用和影响．实验结果显示：在移植神经段近端距近侧吻合口１ｍｍ处，术后１０ｄ抗ｃｏｌｌａｇｅｎｔｙｐｅⅣ组再生轴突数为对照组的５４％，术后１５ｄ增加到６６％，术后３０ｄ高达９４％．在移植神经段远侧距近侧吻合口９ｍｍ处，术后３０ｄ抗ｃｏｌｌａｇｅｎｔｙｐｅⅣ组再生轴突数为对照组的５８％。表明抗ｃｏｌｌａｇｅｎｔｙｐｅⅣ组再生轴突的生长启动和生长速度明显慢于对照组．巨噬细胞在移植神经段内的滞留数量抗ｃｏｌｌａｇｅｎｔｙｐｅⅣ组明显多于对照组．这些结果揭示ｃｏｌｌａｇｅｎｔｙｐｅⅣ在神经损伤和再生中对促进轴突的生长和维持神经微环境的平衡起着积极的作用．本文对ｃｏｌｌａｇｅｎｔｙｐｅⅣ在神经再生中的作用机制作了初步的分析和探讨。

氧化苦参碱对皮肤创面愈合中PCNA、α-SMA及Type Ⅰ collagen的影响

目的探讨氧化苦参碱对小鼠皮肤创面愈合中血清增殖细胞核抗原(PCNA)、α-平滑肌肌动蛋白(α-SMA)及细胞Ⅰ型胶原蛋白(Type Ⅰ collagen)的影响。方法昆明小鼠背部手术制备1.5 cm×1.5 cm全层皮肤缺损创面模型。自第1 d始,除对照组给予等量生理盐水外,余各组分别按20、40、80 mg/kg给予氧化苦参碱。Van Gieson纤维胶原染色法观察小鼠背部皮肤创面组织胶原纤维的表达;免疫组学法评价创面组织中PCNA、α-SMA及Type Ⅰ collagen的表达。结果Van Gieson纤维胶原染色显示,氧化苦参碱可促进新生肉芽组织、毛细血管及新生纤维胶原生长。免疫组学研究显示,在第7 d时,氧化苦参碱20、40、80 mg/kg使小鼠皮肤创面组织中PCNA表达明显升高(P<0.05);在第9 d、11 d时,氧化苦参碱20 mg/kg使小鼠皮肤创面组织中α-SMA显著增加;氧化苦参碱20 mg/kg在第3 d、11 d,氧化苦参碱40 mg/kg在第3 d,氧化苦参碱80 mg/kg在第3 d、7 d引起Type Ⅰ collagen的表达显著升高(P<0.05)。结论氧化苦参碱能增加皮肤创面愈合中PCNA、α-SMA及Type Ⅰ collagen的表达。

基于上皮细胞-间充质细胞转分化(EMT)理论的艾灸配合化纤Ⅳ号方对实验大鼠Collagen Type Ⅲ和PDGF干预作用实验研究

目的:基于上皮细胞-间充质细胞转分化(EMT)学说观察化纤Ⅳ号方、艾灸以及二者相配合治疗肺纤维化大鼠Collagen TypeⅢ(Ⅲ-C)和PDGF的变化,探讨其治疗效应及生物学机制。方法:将鼠龄约为6周的SD大鼠随机分为空白组、模型组、化纤Ⅳ号方组、艾灸组、化纤Ⅳ号方与艾灸配合治疗组(简称为"灸药组"),治疗30 d后处死观察其肺组织病理改变,并检测其Collagen TypeⅢ、PDGF的基因和蛋白表达情况。结果:实时荧光定量结果显示:与空白组相比,各组Ⅲ-C和PDGF m RNA表达增高(P<0.05)。与模型组相比,各组的Ⅲ-C和PDGF m RNA表达有明显降低(P<0.01)。而各组中,灸药组疗效最明显,Ⅲ-C和PDGF的表达最低。蛋白免疫印迹法检测结果显示:与模型组相比各组的Ⅲ-C蛋白表达有差异。结论:1艾灸、化纤Ⅳ号方均可减轻博莱霉素诱导肺纤维化大鼠的肺纤维化程度。2艾灸配合化纤Ⅳ号方可减轻博莱霉素诱导肺纤维化大鼠的肺纤维化程度,且其效果优于单用艾灸或单用化纤Ⅳ号方。3艾灸、化纤Ⅳ号方及其二者配合使用不同程度阻抑博莱霉素诱导肺纤维化大鼠肺纤维化进程的效应机制,可能与通过调控其EMT过程中的Ⅲ-C和PDGF表达环节紧密相关。

TGF-β_1、BMP-2和TypeⅡ Collagen在黄韧带中的表达及意义

目的研究TGF-1β、BM P-2和typeⅡco llagen在退行性腰椎滑脱(degenerative lum bar spondy lo listhes is,DLS)和腰椎间盘突出症(lum bar d isc hern iation,LDH)黄韧带中的表达及其意义。方法37例手术切除的腰椎椎板间部黄韧带标本分为3组,第1组为退行性腰椎滑脱组(DLS)10例;第2组为腰椎间盘突出症组(LDH)17例,第3组为正常对照组10例,其中7例取自腰椎骨折手术病人,3例取自意外死亡者。应用EnV is ion二步免疫组化的方法检测其TGF-1β、BM P-2和typeⅡco llagen的表达情况,普通光镜观察,计算出各标本的表达阳性率和表达强度,数据以x-±s标准差及表达强度表示,结果分别用Spss统计软件和R id it进行分析。结果TGF-1β、BM P-2和typeⅡco llagen的阳性表达产物见于成纤维细胞、成软骨细胞和软骨细胞中,而Ⅱ型胶原染色还可同时见于基质。TGF-1β、BM P-2和typeⅡco llagen在DLS组中的表达明显高于LDH组和正常组(P<0.01或P<0.05),Ⅱ型胶原基质染色明显深于LDH组和对照组。LDH组的TGF-1β和typeⅡco llagen的表达阳性率和表达强度与正常组之间差异无显著性(P>0.05),而BM P-2的表达阳性率和表达强度在LDH组与正常组之间具有统计学意义(P<0.01)。结论黄韧带所受到的异常机械牵张力可以增加TGF-1β在黄韧带细胞中的合成,而TGF-1β则促进退行性腰椎滑脱黄韧带中的Ⅱ型胶原合成,导致黄韧带的退变和肥厚。BM P-2在退变黄韧带中的表达异常增高,可能与黄韧带的软骨化倾向有关。

Expressions of type I collagen, α2 integrin and β1 integrin in sclera of guinea pig with defocus myopia and inhibitory effects of bFGF on the formation of myopia

AIM:To investigate the expressions of type I collagen, α2 integrin and β1 integrin in the posterior sclera of guinea pigs with defocus myopia and whether basic fibroblast growth factor (bFGF) injection inhibits the formation and development of myopia by upregulating the expression of type I collagen, α2 integrin and β1 integrin. METHODS:After 14 days of treatment, the refractive state and axial length were measured and the levels of type I collagen, α2 integrin and β1 integrin were assayed in the posterior sclerae of groups of guinea pigs that wore a monocular-7D polymethylmethacrylate (PMMA) lens or had -7D lens wear followed by the peribulbar injection of Phosphate Buffer Solution (PBS) or bFGF. The untreated fellow eye served as a control. Guinea pigs with no treatment served as normal group. ·RESULTS:The results showed that 14 days of monocular defocus increased axial eye length and refraction, while bFGF delivery inhibited them markedly. Further, it was also found that the monocular-7D lens could decrease the levels of type I collagen, α2 integrin and β1 integrin expressions, while, unlike PBS, bFGF increased them significantly in comparison to contralateral control eyes and normal eyes. CONCLUSION:bFGF can prevent the formation anddevelopment of defocus myopia by upregulating the expressions of type I collagen, α2 integrin and β1 integrin. Taken together, our results demonstrate that bFGF promotes sclera remodeling to prevent myopia in guinea pigs.

Serum hyaluronic acid, procollagen type Ⅲ and Ⅳ in histological diagnosis of liver fibrosis

OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), proeollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis. METHODS: The concentrations of serum HA, PCⅢ, CⅣ in 253 patients with chronic liver diseases were measured by radioimmunoassay. Liver biopsies were performed in all patients at the same time. The liver was pathologically evaluated by a pathologist according to a scoring system. Combined with the results of liver pathological diagnosis, the accuracy of serum HA, PCⅢ, CⅣ in diagnosing patients with hepatic fibrosis (staging≥S_2) or cirrhosis (S_4) was assessed using the receiver operating curve (ROC). RESULTS: The cutoff values of serum HA, PCⅢ and CⅣ for identifying patients with hepatic fibrosis (≥S_2) or cirrhosis (S_4) were determined. The cutoff values of serum HA, PCⅢ and CⅣ for detecting patients with fibrosis (stage≥S_2) were 90μg/L, 90μg/L, 75μg/L, respectively; their sensitivity (Se) was 80.4%, 82%, 63.1%; their specificity (Spe) was 70.2%, 60.8%, 83.8%; their positive predictive values (PPV) were 86.7%, 83.5%, 90.4%; their negative predictive values (NPV) were 59.8%, 58.4%, 48.4%, respectively. The cutoff values for detecting patients with liver cirrhosis were 210μg/L for HA, 96.2% for Se, 85.3% for Spe, 65.4% for PPV, 98.8% for NPV; 150μg/L for PCⅢ, 76.4% for Se, 68.7% for Spe, 40.4% for PPV, 91.3% for NPV; 90μg/L for CⅣ, 80% for Se, 75.8% for Spe, 47.8% for PPV, 93.2% for NPV, respectively. CONCLUSIONS: Serum HA, PCⅢ and CⅣ can be determined for an accurate diagnosis of hepatic fibrosis in various stages. HA is the best for screening liver cirrhosis.

Pre-hepatectomy type Ⅳ collagen 7S predicts post-hepatectomy liver failure and recovery

BACKGROUND Liver resection is an effective treatment for benign and malignant liver tumors.However,a method for preoperative evaluation of hepatic reserve has not yet been established.Previously reported assessments of preoperative hepatic reserve focused only on liver failure in the early postoperative period and did not consider the long-term recovery of hepatic reserve.When determining eligibility for hepatectomy,the underlying pathophysiology needs to be considered to determine if the functional hepatic reserve can withstand both surgery and any postoperative therapy.AIM To identify pre-hepatectomy factors associated with both early postoperative liver failure and long-term postoperative liver function recovery.METHODS This study was a retrospective cohort study.We retrospectively investigated 215 patients who underwent hepatectomy at our hospital between May 2013 and December 2016.Early post-hepatectomy liver failure(PHLF)was defined using the International Study Group of Liver Surgery’s definition of PHLF.Long-term postoperative recovery of liver function was defined as the time taken for serum total bilirubin and albumin levels to return to levels of<2 mg/dL and>2.8 g/dL,respectively,and the time taken for Child-Pugh score to return to Child-Pugh class A.RESULTS Preoperative type IV collagen 7S was identified as a significant independent factor associated with both PHLF and postoperative long-term recovery of liver function.Further analysis revealed that the time taken for the recovery of Child-Pugh scores and serum total bilirubin and albumin levels was significantly shorter in patients with type IV collagen 7S≤6 ng/mL than in those with type IV collagen 7S>6 ng/mL.In additional analyses,similar results were observed in patients without chronic viral hepatitis associated with fibrosis.CONCLUSION Preoperative type IV collagen 7S is a preoperative predictor of PHLF and longterm postoperative liver function recovery.It can also be used in patients without chronic hepatitis virus.

Effects of Icariin on Expression of OPN mRNA and Type ⅠCollagen in Rat Osteoblasts in Vitro

To study the effects of Icariin on expression of osteopontin （OPN） mRNA and type Ⅰ collagen in rat osteoblasts in vitro and to explore its possible mechanisms in preventing osteoporosis. OB was isolated from calvaria of new-born new-born fetal Sprague-Dawley （SD） rats by means of modified sequential collagenase digestion and incubated in MEM medium and the cell morphology was observed under inverted phase contrast microscope, OB was identified by alkaline phosphatase （ALP） staining. Different concentration （0.1μg/mL, 1.0 μg/mL, 10 μ/mL） of Icariin was added to the OB and incubated. The effect of Icariin on the proliferation and osteogenesis of OB was monitored by MTT analysis. The expression of type l collagen was estimated with immunohistochemistry techniques. The expression levels of mRNA of OPN in the cells in every group were examined by reverse-transcriptase ploymerase chain reaction （RT-PCR）. The expression of OPN mRNA and type Ⅰ collagen was strengthened gradually with the increase of Icariin concentration and peaked with 10 μg/mL Icariin on the 5th day. Icariin could significantly promote the expression of OPN mRNA and type Ⅰ collagen in rat osteoblasts in vitro. The levels of expression of OPN mRNA and type Ⅰ collagen were changed with different concentration of Icariin. Icariin could effectively prevent and treat osteoporosis and promote the bone formation.

Is type Ⅰ alpha 2 collagen gene responsible for intracranial aneurysm in Northeast China?

In this study, we investigated whether a single nucleotide polymorphism （rs42524 G 〉 C） in the type I alpha 2 collagen gene was associated with sporadic ruptured intracranial aneurysm or its clinical characteristics in patients from Northeast China. Genotyping of the rs42524 G 〉 C polymorphism was carried out using a polymerase chain reaction-restriction fragment length polymorphism assay. The data showed that the frequency of the rs42524 GC ＋ CC genotype was significantly higher than the GG genotype among intracranial aneurysm patients whose Hunt and Hess grading scale was 〉 3. In addition, the rs42524 G 〉 C genotype was found to have a statistically significant association with intracranial aneurysm risk. These findings indicate that the type I alpha 2 collagen gene gene may be involved in a predisposition to intracranial aneurysm in the Northeast Chinese population. Crucially, the rs42524 C allele may be an important risk factor for increased severity of the condition in patients with ruptured intracranial aneurysms.

Serum type Ⅳ collagen level is predictive for esophageal varices in patients with severe alcoholic disease

AIM: To determine factors predictive for esophageal varices in severe alcoholic disease (SAD). METHODS: Abdominal ultrasonography (US) was performed on 444 patients suffering from alcoholism. Forty-four patients found to have splenomegaly and/ or withering of the right liver lobe were defined as those with SAD. SAD patients were examined by upper gastrointestinal (UGI) endoscopy for the presence of esophageal varices. The existence of esophageal varices was then related to clinical variables. RESULTS: Twenty-five patients (56.8%) had esophageal varices. A univariate analysis revealed a significant difference in age and type Ⅳ collagen levels between patients with and without esophageal varices. A logistic regression analysis identified type Ⅳ collagen as the only independent variable predictive for esophageal varices (P = 0.017). The area under the curve (AUC) for type Ⅳ collagen as determined by the receiver operating characteristic (ROC) for predicting esophageal varices was 0.78. CONCLUSION: This study suggests that the level of type Ⅳ collagen has a high diagnostic accuracy for the detection of esophageal varices in SAD.

Enrichment of putative human epidermal stem cells based on cell size and collagen type IV adhesiveness

人的表皮的干细胞(EpSCs ) 的丰富和鉴定具有为基本研究和临床的申请的首要的重要性。尽管为 EpSCs 的丰富的几条途径被建立了，充实可行 EpSCs 的一张纯人口仍然是一项挑战性的任务。一条改进途径值得发展提高 EpSCs 的纯净和生存能力。这里，我们报导那种房间尺寸与骨胶原类型 IV 粘着性结合了能在一条改进途径被使用充实纯、可行的人的 EpSCs。我们分开了很快支持者 keratinocytes 进从 5-7 microm (人口 A )在尺寸 的三张人口到 7-9 microm (人口 B )，到>或在直径的 =9 microm (人口 C )，并且发现人的通常认为的 EpSCs 能进一步与最小的尺寸在人口 A 被充实。在三张人口之中，人口 A 显示了 beta1-integrin 受体的最高的密度，在 G0/G1 阶段包含了房间的最高的百分比，显示出最高的原子核到细胞质比率，并且拥有了最高的殖民地形成效率(CFE ) 。当注入了鼠科的胚囊时，这些房间参予了多织物形成。与根据 beta1-integrin 抗体染色排序通常认为的 EpSCs 的一条以前的途径相比，更显著地， EpSCs 的生存能力由改进途径充实显著地被提高。我们的结果为人的 EpSCs 的丰富提供通常认为的策略，并且在干细胞生物学鼓励进一步的学习进房间尺寸的角色。

Novel electrospun poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits for repair of peripheral nerve injury

Recent studies have shown the potential of artificially synthesized conduits in the repair of peripheral nerve injury.Natural biopolymers have received much attention because of their biocompatibility.To investigate the effects of novel electrospun absorbable poly(ε-caprolactone)/type I collagen nanofiber conduits(biopolymer nanofiber conduits)on the repair of peripheral nerve injury,we bridged 10-mm-long sciatic nerve defects with electrospun absorbable biopolymer nanofiber conduits,poly(ε-caprolactone)or silicone conduits in Sprague-Dawley rats.Rat neurologica1 function was weekly evaluated using sciatic function index within 8 weeks after repair.Eight weeks after repair,sciatic nerve myelin sheaths and axon morphology were observed by osmium tetroxide staining,hematoxylin-eosin staining,and transmission electron microscopy.S-100(Schwann cell marker)and CD4(inflammatory marker)immunoreactivities in sciatic nerve were detected by immunohistochemistry.In rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits,no serious inflammatory reactions were observed in rat hind limbs,the morphology of myelin sheaths in the injured sciatic nerve was close to normal.CD4 immunoreactivity was obviously weaker in rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits than in those subjected to repair with poly(ε-caprolactone)or silicone.Rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits tended to have greater sciatic nerve function recovery than those receiving poly(ε-caprolactone)or silicone repair.These results suggest that electrospun absorbable poly(ε-caprolactone)/type I collagen nanofiber conduits have the potential of repairing sciatic nerve defects and exhibit good biocompatibility.All experimental procedures were approved by Institutional Animal Care and Use Committee of Taichung Veteran General Hospital,Taiwan,China(La-1031218)on October 2,2014.

Urinary type IV collagen excretion predicts an increased urinary albumin-to-creatinine ratio in normoalbuminuric patients with diabetes

Aims: We evaluated whether urinary excretion of type IV collagen (U-COL) may predict an increase in the urinary albumin-to-creatinine ratio (ACR) and what factors regulate U-COL in 145 normoalbuminuric patients with type 2 diabetes. Methods: We measured HbA1c, systolic blood pressure (SBP), urinary 8-hydroxydeoxyguanosine (8-OHdG) and monocyte chemoattractant protein (MCP)-1 at start of this study (Baseline), ACR and U-COL in addition to these measurements at one year later (Evaluation-1), and ACR and SBP after two years of the Evaluation-1 (Evaluation-2). The relationships were investigated between the increase of ACR and the U-COL. The effect of angiotensin receptor blockers (ARB) treatment on the correlations between U-COL and ACR at Evaluation-2 on one hand, and between U-COL and percent change of ACR on the other, was also analyzed. Furthermore, we investigated whether the increase in 8-OHdG and in MCP-1 in a year prior to the Evaluation-1 were risk factors of the rise in U-COL levels. Results: Both U-COL and SBP at Evaluation-1, but not ARB treatment, were independent risk factors for an increased ACR after 2 years. ARB treatment significantly suppressed the increase in ACR after 2 years in patients with higher U-COL excretion. The percentage changes in 8-OHdG (%8-OHdG) and MCP-1 (%MCP-1) in one year prior to Evaluation-1 measurements are independent risk factors for U-COL. HbA1c and SBP values one year prior to Evaluation-1 are independent risk factors not only for %8-OHdG but also, for baseline U-COL. The %8-OHdG is an independent risk factor for %MCP-1. Conclusions: U-COL may predict an increase in the ACR. The U-COL seems to be increased with oxidative stress and inflammation induced by past hyperglycemia.

Cell therapy of a patient with type Ⅲ Osteogenesis imperfecta caused by mutation in COL1A2 gene and unstable collagen type I

The allogenic bone marrow derived mesenchymal stem cells transplantation was given to the newborn girl diagnosed with osteogenesis imperfecta type III, with multiple bone fractures, extreme shortness and limbs deformities. The treatment was performed at the age of 4 and 6 weeks. The clinical diagnosis was supported by biochemical analysis of collagen type I recovered from culture medium of cultivated patient’s skin fibroblast, which revealed its triple helix instability at temperature about 2?C lower than normal. Sequencing of both genes encoding procollagen type I revealed heterozygous substitution G23569Ain COL1A2 gene causing change of glycine at position 517 to aspartate. The donor of mesenchymal stem cells was the girl’s father. She received two intravenous infusions of suspended cultured mesenchymal cells in 16 days apart without any side effects. An analysis of procollagen type I secreted to the culture medium by bone marrow-derived mesenchymal stem cells obtained from the patient, 3 months following transplantation revealed its normal triple helix stability. During the subsequent two years of follow up two new bone fractures were noted. Currently a two-year-old girl’s presents extreme growth and weight deficiency. The motoric development is also retarded, but the patient constantly improves and makes progresses.

Collagen type Ⅲ is an important linking molecule between generated renal tubules and an artificial polyester interstitium--Reticulin as a linker between generated tubules and the interstitium

在再生医学领域,已经有很多人考虑在将来用干/祖细胞治疗急慢性肾功能衰竭。但是,要使这种治疗方案行之有效,需要了解关于患病肾脏肾小管发育的细胞生物学信息。与干/祖细胞治疗急慢性肾功能衰竭相关尚待明晰的细胞生物学问题包括:①干/祖细胞的整合。②干/祖细胞的定向分化类型。③新形成肾小管的空间构成。为了更好的了解这项技术的相关机制,文章应用了先进的培养技术在人工非细胞外基质材料界面条件下构建肾小管。将新生兔肾来源的干/祖细胞用多层聚酯纤维网覆盖,放置在灌注培养器中,用含1×10-7mol/L醛固酮的新鲜合成的在DMEM基础上改良的IMDM培养基诱导培养13d。扫描电镜下,在大豆凝集素、银染和抗Ⅲ型胶原或层粘连蛋白γ1单克隆抗体标记的全标本包埋爬片或冰冻切片上观察肾小管的生长情况。扫描电镜观察结果显示,新生成的肾小管完全被基底膜覆盖,纤维网状板有大量的纤维与生成的肾小管基底面和周围人工聚酯材料相互交联。抗Ⅲ型胶原染色和银染结果表明,在新生成的肾小管的基底膜和邻近的人工聚酯材料间有大量的纤维交织,在发育成熟的肾小管中有与新生成肾小管相同排列形式的Ⅲ型胶原纤维。以上实验结果说明,Ⅲ胶原是联系新生成的肾小管基底面和人工基质聚酯纤维的分子纽带。