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Mechanisms of connective tissue formation and blocks of mitogen activated protein kinase

Irina A SHURYGINA, Michael G SHURYGIN, Nataliya I AYUSHINOVA, Galina B GRANINA, Nikolay V ZELENIN

《化学科学与工程前沿（英文）》 2012年第6卷第2期页码 232-237 doi: 10.1007/s11705-012-1286-1

摘要： Ninety male Wistar rats were selected under the “Guide for the Care and Use of Laboratory Animals” for skin-muscle wound models. Three groups of animals were examined respectively for inoculation of inhibitor of p38 MAPK (mitogen activated protein kinase) SB 203580 and JNK inhibitor SP 600125, and a control. Light microscopy, immunohistochemistry, and tensometry revealed that the inhibition of p38 or JNK cascades have modified the formation of the connective tissue scar. The degree of connective tissue growth in the area of surgical wound had been significantly reduced by the end of observation (30 d) as the SB 203580 was applied (% volume of collagen 43.60 (41.05 – 60.15) 73.54 (66.87 – 78.01) in control, = 0.002). Conversely, when we have applied the JNK blocker, the density of collagen in scar tissue increased (78.14 (72.77 – 81.14), = 0.022 control). SB203580 inhibits the expression of p38, c-Jun and c-Fos. When we have used the JNK blocker, the expression of c-Fos and c-Jun decreased, but the expression of p38 increased. This determines the high functional activity of fibroblasts after using SP 600125. Obtained results show the importance of studying regulators of cell differentiation as potential drugs, which significantly affect the outcome of the pathological processes.

关键词： connective tissue mitogen activated protein kinase (MAPK) p38 JNK

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Atypical pituitary hormone–target tissue axis

《医学前沿（英文）》 2023年第17卷第1期页码 1-17 doi: 10.1007/s11684-022-0973-7

摘要： A long-held belief is that pituitary hormones bind to their cognate receptors in classical target glands to actuate their manifold functions. However, a number of studies have shown that multiple types of pituitary hormone receptors are widely expressed in non-classical target organs. Each pituitary gland-derived hormone exhibits a wide range of nonconventional biological effects in these non-classical target organs. Herein, the extra biological functions of pituitary hormones, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotrophic hormone, and prolactin when they act on non-classical organs were summarized, defined by the novel concept of an “atypical pituitary hormone–target tissue axis.” This novel proposal explains the pathomechanisms of abnormal glucose and lipid metabolism, obesity, hypertension, fatty liver, and atherosclerosis while offering a more comprehensive and systematic insights into the coordinated regulation of environmental factors, genetic factors, and neuroendocrine hormones on human biological functions. The continued exploration of the physiology of the “atypical pituitary hormone–target tissue axis” could enable the identification of novel therapeutic targets for metabolic diseases.

关键词： thyroid-stimulating hormone follicle-stimulating hormone luteinizing hormone adrenocorticotrophic hormone prolactin

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Progress and perspectives of neural tissue engineering

null

《医学前沿（英文）》 2015年第9卷第4期页码 401-411 doi: 10.1007/s11684-015-0415-x

摘要：

Traumatic injuries to the nervous system lead to a common clinical problem with a quite high incidence and affect the patient’s quality of life. Based on a major challenge not yet addressed by current therapeutic interventions for these diseases, a novel promising field of neural tissue engineering has emerged, grown, and attracted increasing interest. This review provides a brief summary of the recent progress in the field, especially in combination with the research experience of the author’s group. Several important aspects related to tissue engineered nerves, including the theory on their construction, translation into the clinic, improvements in fabrication technologies, and the formation of a regenerative environment, are delineated and discussed. Furthermore, potential research directions for the future development of neural tissue engineering are suggested.

关键词： nerve injury tissue engineering nerve grafts

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The stem cell and tissue engineering research in Chinese ophthalmology

GE Jian, LIU Jingbo

《医学前沿（英文）》 2007年第1卷第1期页码 6-10 doi: 10.1007/s11684-007-0002-x

摘要： Much has been considerably developed recently in the ophthalmic research of stem cell (SC) and tissue engineering (TE). They have become closer to the clinical practice, standardized and observable. Leading edge research of SC and TE on the ocular surface reconstruction, neuroregeneration and protection, and natural animal model has become increasingly available. However, challenges remain on the way, especially on the aspects of function reconstruction and specific differentiation. This paper reviews the new developments in this area with an intention of identifying research priorities for the future.

关键词： available observable neuroregeneration protection function reconstruction

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Decellularized extracellular matrix mediates tissue construction and regeneration

《医学前沿（英文）》 2022年第16卷第1期页码 56-82 doi: 10.1007/s11684-021-0900-3

摘要： Contributing to organ formation and tissue regeneration, extracellular matrix (ECM) constituents provide tissue with three-dimensional (3D) structural integrity and cellular-function regulation. Containing the crucial traits of the cellular microenvironment, ECM substitutes mediate cell–matrix interactions to prompt stem-cell proliferation and differentiation for 3D organoid construction in vitro or tissue regeneration in vivo. However, these ECMs are often applied generically and have yet to be extensively developed for specific cell types in 3D cultures. Cultured cells also produce rich ECM, particularly stromal cells. Cellular ECM improves 3D culture development in vitro and tissue remodeling during wound healing after implantation into the host as well. Gaining better insight into ECM derived from either tissue or cells that regulate 3D tissue reconstruction or organ regeneration helps us to select, produce, and implant the most suitable ECM and thus promote 3D organoid culture and tissue remodeling for in vivo regeneration. Overall, the decellularization methodologies and tissue/cell-derived ECM as scaffolds or cellular-growth supplements used in cell propagation and differentiation for 3D tissue culture in vitro are discussed. Moreover, current preclinical applications by which ECM components modulate the wound-healing process are reviewed.

关键词： decellularized extracellular matrix 3D culture organoids tissue repair

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Non-closure of the peritoneum and subcutaneous tissue at radical hysterectomy: A randomized controlled

Zhou-Fang XIONG MD, Wei-Hong DONG MD, Ze-Hua WANG MD,

《医学前沿（英文）》 2010年第4卷第1期页码 112-116 doi: 10.1007/s11684-010-0016-7

摘要： We conducted a trial to assess the influence of closure or nonclosure of the peritoneum and subcutaneous tissue on the clinical outcomes of cervical cancer patients who underwent radical hysterectomy with lower abdominal cross incision. This randomized controlled trial was performed on 158 cervical cancer patients in our hospital between January 2002 and June 2004. Eighty-two patients were allocated to the “closure” group and 76 patients to the “nonclosure” group. Results showed that non-closure of the peritoneum and subcutaneous tissue could shorten operation time and febrile duration, reduce antibiotics requirement, increase the volume of drainage and decrease the incidence of liquefaction of subcutaneous fat (<0.05). There was no difference in blood loss, postoperative complications, bowel function restoration and post-operative stay between the two groups (>0.05). Our study revealed that closure of the peritoneum and subcutaneous tissue provides no immediate postoperative benefits while unnecessarily lengthening surgical time and anesthesia exposure. The practice of closure of the peritoneum and subcutaneous tissue at radical hysterectomy should be questioned.

关键词： cervical cancer radical surgery peritoneum subcutaneous tissue

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Primary cilia in hard tissue development and diseases

《医学前沿（英文）》 2021年第15卷第5期页码 657-678 doi: 10.1007/s11684-021-0829-6

摘要： Bone and teeth are hard tissues. Hard tissue diseases have a serious effect on human survival and quality of life. Primary cilia are protrusions on the surfaces of cells. As antennas, they are distributed on the membrane surfaces of almost all mammalian cell types and participate in the development of organs and the maintenance of homeostasis. Mutations in cilium-related genes result in a variety of developmental and even lethal diseases. Patients with multiple ciliary gene mutations present overt changes in the skeletal system, suggesting that primary cilia are involved in hard tissue development and reconstruction. Furthermore, primary cilia act as sensors of external stimuli and regulate bone homeostasis. Specifically, substances are trafficked through primary cilia by intraflagellar transport, which affects key signaling pathways during hard tissue development. In this review, we summarize the roles of primary cilia in long bone development and remodeling from two perspectives: primary cilia signaling and sensory mechanisms. In addition, the cilium-related diseases of hard tissue and the manifestations of mutant cilia in the skeleton and teeth are described. We believe that all the findings will help with the intervention and treatment of related hard tissue genetic diseases.

关键词： primary cilia bone mechanical sensing hard tissue cilium-related bone disease tooth

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Stem cell niches and endogenous electric fields in tissue repair

null

《医学前沿（英文）》 2011年第5卷第1期页码 40-44 doi: 10.1007/s11684-011-0108-z

摘要：

Adult stem cells are responsible for homeostasis and repair of many tissues. Endogenous adult stem cells reside in certain regions of organs, known as the stem cell niche, which is recognized to have an important role in regulating tissue maintenance and repair. In wound healing and tissue repair, stem cells are mobilized and recruited to the site of wound, and participate in the repair process. Many regulatory factors are involved in the stem cell-based repair process, including stem cell niches and endogenous wound electric fields, which are present at wound tissues and proved to be important in guiding wound healing. Here we briefly review the role of stem cell niches and endogenous electric fields in tissue repair, and hypothesize that endogenous electric fields become part of stem cell niche in the wound site.

关键词： stem cell stem cell niche electric field tissue repair

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Microorganism-derived biological macromolecules for tissue engineering

《医学前沿（英文）》 2022年第16卷第3期页码 358-377 doi: 10.1007/s11684-021-0903-0

摘要： According to literature, certain microorganism productions mediate biological effects. However, their beneficial characteristics remain unclear. Nowadays, scientists concentrate on obtaining natural materials from live creatures as new sources to produce innovative smart biomaterials for increasing tissue reconstruction in tissue engineering and regenerative medicine. The present review aims to introduce microorganism-derived biological macromolecules, such as pullulan, alginate, dextran, curdlan, and hyaluronic acid, and their available sources for tissue engineering. Growing evidence indicates that these materials can be used as biological material in scaffolds to enhance regeneration in damaged tissues and contribute to cosmetic and dermatological applications. These natural-based materials are attractive in pharmaceutical, regenerative medicine, and biomedical applications. This study provides a detailed overview of natural-based biomaterials, their chemical and physical properties, and new directions for future research and therapeutic applications.

关键词： biological macromolecules regenerative medicine tissue engineering exopolysaccharide carbohydrate

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Adenovirus-mediated tissue inhibitor of metalloproteinase-3 gene transfection inhibits rabbit intervertebral

Xudong YU MM, Zengwu SHAO MD, Liming XIONG MD, Weiwei XU MM, Hezhong WANG MM, Huifa XU MM,

《医学前沿（英文）》 2009年第3卷第4期页码 415-420 doi: 10.1007/s11684-009-0072-z

摘要： The aim of this study was to investigate the inhibitory effects of recombinant adenovirus vector carrying tissue inhibitor of metalloproteinase-3 (RAdTIMP-3) against degeneration of rabbit intervertebral disc. Thirty Japanese white rabbits of 4 months old were randomly divided into 5 groups. Mild or moderate rabbit lumbar disc degeneration model was constructed with the controllable axial loading device by imposing 98N pressure at the discs for 2 weeks. Various doses of virus were injected into the degenerated discs as follows: 20μL of normal saline in group 1; 20μL of RAd66 (an empty adenovirus vector, 1.0×10OPU/mL) in group 2; and 20, 10, and 5μL of RAdTIMP-3 (1.0×10OPU/mL) in groups 3, 4, and 5, respectively. Two weeks after the injection, the discs were collected for investigations, including assessment of degeneration degrees according to the Thompson’s grading system, reverse-transcription polymerase chain reaction (RT-PCR) assay for TIMP-3 gene, Safranin O-Fast green staining, and immunohistochemical staining for TIMP-3 and type II collagen. According to Thompson’s criteria, the degeneration of groups 3, 4, and 5, especially group 3, was alleviated as compared with groups 1 and 2. RT-PCR revealed that the expression of TIMP-3 in groups 3, 4, and 5, especially in group 3, was significantly enhanced as compared with group 1 (<0.01). Both Safranin O-Fast green staining and type II collagen staining demonstrated better reserved integrity of disc matrix in groups 3, 4, and 5 than in groups 1 and 2. TIMP-3 staining exhibited an obvious increase of positive-staining rate in groups 3, 4, and 5 as compared with group 1. The positive-staining rate in group 3 (79.42%±1.35%) was about 3times that of group 1 (25.47%±5.46%, <0.01). RAdTIMP-3 can effectively protect the matrix of rabbit intervertebral disc against overloading-induced degeneration in a dose-dependent manner, resulting in the alleviation of disc degeneration.

关键词： tissue inhibitor of metalloproteinase-3 intervertebral disc rabbit gene therapy

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Advances in tissue state recognition in spinal surgery: a review

Hao Qu, Yu Zhao

《医学前沿（英文）》 2021年第15卷第4期页码 575-584 doi: 10.1007/s11684-020-0816-3

摘要： Spinal disease is an important cause of cervical discomfort, low back pain, radiating pain in the limbs, and neurogenic intermittent claudication, and its incidence is increasing annually. From the etiological viewpoint, these symptoms are directly caused by the compression of the spinal cord, nerve roots, and blood vessels and are most effectively treated with surgery. Spinal surgeries are primarily performed using two different techniques: spinal canal decompression and internal fixation. In the past, tactile sensation was the primary method used by surgeons to understand the state of the tissue within the operating area. However, this method has several disadvantages because of its subjectivity. Therefore, it has become the focus of spinal surgery research so as to strengthen the objectivity of tissue state recognition, improve the accuracy of safe area location, and avoid surgical injury to tissues. Aside from traditional imaging methods, surgical sensing techniques based on force, bioelectrical impedance, and other methods have been gradually developed and tested in the clinical setting. This article reviews the progress of different tissue state recognition methods in spinal surgery and summarizes their advantages and disadvantages.

关键词： spinal surgery tissue state recognition image force sensing bioelectrical impedance

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Risk stratification system for skin and soft tissue infections after allogeneic hematopoietic stem cell

《医学前沿（英文）》 2022年第16卷第6期页码 957-968 doi: 10.1007/s11684-021-0910-1

摘要： Skin and soft tissue infections (SSTIs) refer to infections involving the skin, subcutaneous tissue, fascia, and muscle. In transplant populations with hematological malignancies, an immunocompromised status and the routine use of immunosuppressants increase the risk of SSTIs greatly. However, to date, the profiles and clinical outcomes of SSTIs in hematopoietic stem cell transplantation (HSCT) patients remain unclear. This study included 228 patients (3.67%) who developed SSTIs within 180 days after allogeneic HSCT from January 2004 to December 2019 in Peking University People’s Hospital. The overall annual survival rate was 71.5%. We compared the differences between survivors and non-survivors a year after transplant and found that primary platelet graft failure (PPGF), comorbidities of acute kidney injury (AKI), and hospital-acquired pneumonia (HAP) were independent risk factors for death in the study population. A PPGF–AKI–HAP risk stratification system was established with a mortality risk score of 1×PPGF+1×AKI+1×HAP. The areas under the curves of internal and external validation were 0.833 (95% CI 0.760–0.906) and 0.826 (95% CI 0.715–0.937), respectively. The calibration plot revealed the high consistency of the estimated risks, and decision curve analysis showed considerable net benefits for patients.

关键词： skin and soft tissue infections hematopoietic stem cell transplantation risk stratification system mortality

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Current advances for bone regeneration based on tissue engineering strategies

Rui Shi, Yuelong Huang, Chi Ma, Chengai Wu, Wei Tian

《医学前沿（英文）》 2019年第13卷第2期页码 160-188 doi: 10.1007/s11684-018-0629-9

摘要： Bone tissue engineering (BTE) is a rapidly developing strategy for repairing critical-sized bone defects to address the unmet need for bone augmentation and skeletal repair. Effective therapies for bone regeneration primarily require the coordinated combination of innovative scaffolds, seed cells, and biological factors. However, current techniques in bone tissue engineering have not yet reached valid translation into clinical applications because of several limitations, such as weaker osteogenic differentiation, inadequate vascularization of scaffolds, and inefficient growth factor delivery. Therefore, further standardized protocols and innovative measures are required to overcome these shortcomings and facilitate the clinical application of these techniques to enhance bone regeneration. Given the deficiency of comprehensive studies in the development in BTE, our review systematically introduces the new types of biomimetic and bifunctional scaffolds. We describe the cell sources, biology of seed cells, growth factors, vascular development, and the interactions of relevant molecules. Furthermore, we discuss the challenges and perspectives that may propel the direction of future clinical delivery in bone regeneration.

关键词： bone tissue engineering stem cell bone scaffold growth factor bone regeneration

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Fabrication of scaffolds in tissue engineering: A review

Peng ZHAO, Haibing GU, Haoyang MI, Chengchen RAO, Jianzhong FU, Lih-sheng TURNG

《机械工程前沿（英文）》 2018年第13卷第1期页码 107-119 doi: 10.1007/s11465-018-0496-8

摘要：

Tissue engineering (TE) is an integrated discipline that involves engineering and natural science in the development of biological materials to replace, repair, and improve the function of diseased or missing tissues. Traditional medical and surgical treatments have been reported to have side effects on patients caused by organ necrosis and tissue loss. However, engineered tissues and organs provide a new way to cure specific diseases. Scaffold fabrication is an important step in the TE process. This paper summarizes and reviews the widely used scaffold fabrication methods, including conventional methods, electrospinning, three-dimensional printing, and a combination of molding techniques. Furthermore, the differences among the properties of tissues, such as pore size and distribution, porosity, structure, and mechanical properties, are elucidated and critically reviewed. Some studies that combine two or more methods are also reviewed. Finally, this paper provides some guidance and suggestions for the future of scaffold fabrication.

关键词： tissue engineering scaffolds electrospinning 3D printing molding techniques conventional methods

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Copper and zinc interaction on water clearance and tissue metal distribution in the freshwater mussel

Tianxiang XIA, Xuehua LIU

《环境科学与工程前沿（英文）》 2011年第5卷第2期页码 236-242 doi: 10.1007/s11783-010-0218-8

摘要： Copper and zinc interaction on clearance from water and distribution in different tissues was investigated for the freshwater mussel, , under laboratory conditions. Clearance rate of Cu or Zn from water was highly dependent on exposure concentration. Interaction effect was most evident at 300 μg·L Cu exposure and depressed the Zn clearance rate significantly ( <0.05). However, the presence of 100 μg·L and 300 μg·L Zn hardly affected the Cu clearance rate. The 300 μg·L Cu presence enhanced Cu accumulation in each tissue most significantly ( <0.01), but caused Zn content to decrease in the gills by 62% ( <0.05), viscera by 49% ( <0.05) and foot by 31% ( <0.05), and increase in the mantle by 97% ( <0.05) and the muscles by 243% ( <0.05) for different Zn exposure treatments. The response of metal accumulation in various tissues of the test mussels indicated that Zn transferred from the gills, viscera and foot to the mantle and muscles might be one of the important characteristics of the Zn regulatory mechanism by leading to a narrow range of Zn concentration in the different tissues.

关键词： interaction mussel copper zinc clearance distribution