Shuliang Lu

Diabetes-impaired wound healing and altered macrophage activation: a possible pathophysiologic correlation.

Macrophages play a critical role in wound healing and can be activated to two distinctive phenotypes in vitro: classical macrophage activation (caM) and alternative macrophage activation (aaM). This study investigated whether the impaired cutaneous repair observed in streptozotocin‐induced diabetic rats was associated with altered macrophage activation. Our results show that macrophage activation phenotypes could be observed in wound healing through double immunostaining. The caM macrophages appeared in the initial stage of wound healing, followed by aaM macrophages, which predominated in normal wounds. However, through examining markers associated with activation by immunoblotting and real‐time polymerase chain reaction (PCR), diabetic wounds demonstrated insufficient caM in the early stage but excessive aaM in the later proliferative phase. Moreover, the macrophage activation markers were correlated with the instructive T helper cell type 1 (Th1)/Th2 cytokines in both groups. It was indicated that changed macrophage activation might contribute to impaired healing in diabetes wounds, and that strategies for reverting this abnormal activation could be useful for enhancing the wound healing process.

Effects of extracellular matrix glycosylation on proliferation and apoptosis of human dermal fibroblasts via the receptor for advanced glycosylated end products.

The balance between proliferation and apoptosis of skin cells is responsible for skin turnover and the success of the wound healing process. Recent reports have shown that advanced glycosylation end product (AGE) formation participates in dermatologic problems in diabetes. However, the effect on proliferation and apoptosis of dermal fibroblasts remains unclear. The aim of this study was to investigate the effects of dermal microenvironment glycosylation on the balance of cellular proliferation and apoptosis. Histology and immunohistochemical staining were performed on type II diabetic and nondiabetic skin tissue specimens to determine the distributions of proliferating cell nuclear antigen, apoptotic cells, AGEs, and receptors for AGEs (RAGEs). Matrix secreted by cultured human fibroblasts was glycosylated by 0.5 M D-ribose. RAGE-blocking antibodies were applied to inhibit the interaction of RAGE and AGEs in this system and then cell viability, cell cycle phase distribution, and apoptosis were measured. Diabetic skin has degenerative, loosely arranged collagen and increased apoptotic cells compared with normal skin. Expression of AGE and RAGE in diabetic skin tissue increased. Glycosylated matrix induced cell cycle arrest and apoptosis of cultured dermal fibroblasts, whereas application of RAGE-blocking antibodies redressed these changes. The accumulation of glycosylated extracellular matrix in diabetic skin tissue is a critical mediator of cellular function. Mediation of RAGE affects the balance of cellular proliferation and apoptosis, which confirms that diabetic wounds possess atypical origin in the repair process.

Optimizing Technology Use for Chronic Lower-Extremity Wound Healing: A Consensus Document.

Innovations in technology are used in managing chronic wounds. Despite the wide range of technologies available, healing of chronic wounds remains variable. In this paper, the authors offer an evidence based approach to the use of technology for diagnosis and management based on the concept of standardised care.

Reduced Dermis Thickness and AGE Accumulation in Diabetic Abdominal Skin

Dermatological problems in diabetes might play an important role in the spontaneous ulcers and impaired wound healing that are seen in diabetic patients. Investigation of the cause of diabetic skin disorders is critical for identifying effective treatment. The abdominal full-thickness skin tissues of 33 patients (14 nondiabetic and 19 diabetic) were analyzed. The cell viability and malondialdehyde (MDA) production of fibroblasts were measured after advanced glycosylation end product (AGE)–bovine serum albumin (BSA) exposure. Cutaneous histological observation showed reduced thickness of the diabetic abdominal dermis with morphological characteristics of obscured multilayer epithelium and shortened, thinned, and disorganized collagen fibrils with focal chronic inflammatory cell infiltration when compared with controls of the same age. Accumulation of AGEs in diabetic skin was prominent. Less hydroxyproline, higher myeloperoxidase activity, and increased MDA content were detected in diabetic skin. In vitro, the time- and dose-dependent inhibitory effects of AGE-BSA on fibroblast viability as well as the fact that AGE-BSA could promote MDA production of fibroblasts were shown. It is shown that the accumulation of AGEs in diabetic skin tissue induces an oxidative damage of fibroblasts and acts as an important contributor to the thinner diabetic abdominal dermis. The authors believe that diabetic cutaneous properties at baseline may increase the susceptibility to injury, and diabetic wounds possess atypical origin in the repair process.

The Relationship Between Inflammation and Impaired Wound Healing in a Diabetic Rat Burn Model.

Inflammation, initiated by polymorphonuclear neutrophil (PMNs) infiltration, is the first step in wound healing. The aim of this study is to investigate the function of neutrophils in a diabetes-impaired wound healing model and to explore the underlying mechanisms leading to neutrophil dysfunction. Superficial second-degree burns were created in the streptozotocin (STZ)-induced diabetic rat model, and the changes in the levels of advanced glycation end products (AGE), receptor of AGE (RAGE), inflammatory cytokines and oxidative markers, as well as cell apoptosis were determined. The effects of AGE on isolated PMNs were also determined in vitro. We found that deposition of AGE in diabetic rat skin activated the neutrophils before injury. However, the dense inflammatory band failed to form in the diabetic rats after injury. Compared with the controls, enhanced expression of RAGE and accelerated cell apoptosis were observed in the burned skin of diabetic rats. The altered expression pattern of inflammatory cytokines (tumor necrosis factor-alpha and interleukin-8) and oxidative markers (glutathione peroxidase, myeloperoxidase, hydrogen peroxide, and malondialdehyde) between burned skin of diabetic and control rats revealed delayed neutrophil chemotaxis and respiratory burst. Furthermore, the results in vitro showed that exposure to AGE inhibited the viability of PMNs, promoted RAGE production and cell apoptosis, and prevented the migration of PMNs, consistent with the findings in vivo. Besides, AGE-treated neutrophils showed increased secretion of inflammatory cytokines and increased oxidative stress. Combined, our results suggest that an interaction between AGE and its receptors inhibits neutrophil viability and function in the diabetic rat burn model.

The Association Between Skin Autofluorescence and Vascular Complications in Chinese Patients With Diabetic Foot Ulcer An Observational Study Done in Shanghai

The tissue accumulation of advanced glycation end products (AGEs) can be noninvasively assessed as skin autofluorescence (SAF) by the AGE ReaderTM device. We aimed to detect the association between SAF and diabetes-associated vascular complications in diabetic foot ulcer (DFU) patients engaged in this study. This cross-sectional survey consisted of 118 consecutive hospitalized diabetic foot patients. The diabetic microvascular (retinopathy, nephropathy, and neuropathy) and macrovascular referring to coronary heart disease (CHD), cerebrovascular disease (CVD), or peripheral artery disease (PAD) complications were evaluated, and then they were divided into different subgroups based on the assessment of vascular complications. As seen from the results, the mean SAF value was 2.8 ± 0.2 AU. SAF was significantly associated with diabetes duration and blood urea nitrogen (R2 = 62.8%; P < .01). Moreover, in logistic regression analysis, SAF was significantly associated with retinopathy (odds ratio [OR] = 40.11), nephropathy (OR = 8.44), CHD (OR = 44.31), CVD (OR = 80.73), and PAD (OR = 5.98 × 109). In conclusion, SAF, reflecting tissue accumulation of AGEs, is independently associated with the presence of vascular complications in DFU patients.

Diabetic Foot Infection in the World: - We Need Ways Forward

Impaired wound healing is one of the most important complications of diabetes mellitus. Though infection is not one of the pathogenic triad for development of diabetic foot ulcers, it is an extremely important cause of morbidity and hospitalization, amputation, and impaired healing based on clinical and other evidence from over the world. Approximately 3% to 4% of individuals with diabetes currently have foot ulcers or deep infections. A multicenter survey in China showed that in patients with diabetic foot disease, 67.9% develop foot infections. In the Middle East the prevalence of infection in diabetic patients was reported to be greater than 40%. There have been reports from India that are alarming. It is also thought that this problem is yet undefined in some well-populated parts of the world.

Regenerative medicine in China: main progress in different fields.

Regenerative medicine (RM) is an emerging interdisciplinary field of research and China has developed the research quickly and impressed the world with numerous research findings in stem cells, tissue engineering, active molecules and gene therapy. Important directions are induced differentiation of induced pluripotent stem and embryo stem cells as well as somatic stem cell differentiation potential and their application in trauma, burns, diseases of aging and nerve regeneration. The products ActivSkin and bone repair scaffolds have been approved and are applied in the clinic, and similar products are being studied. About 10 engineered growth-factor drugs for repair and regeneration have been approved and are used in the clinic. Gene therapy, therapeutic cloning and xenotransplantation are some of the strategies being studied. However, China needs to develop standards, regulations and management practices suitable for the healthy development of RM. Aspects that should be strengthened include sound administrative systems, laws, and technical specifications and guidelines; conservation of stem cell resources; emphasis on training and retention of talented stem cell researchers; and reasonable allocation of resources, diversification of investment and breakthroughs in key areas. Finally, broad and deep international cooperation is necessary.

Negative pressure wound therapy applied before and after split-thickness skin graft helps healing of Fournier gangrene: a case report (CARE-Compliant).

AbstractFournier gangrene is a rare but highly infectious disease characterized by fulminant necrotizing fasciitis involving the genital and perineal regions. Negative pressure wound therapy (NPWT; KCI USA Inc, San Antonio, TX) is a widely adopted technique in many clinical settings. Nevertheless, its application and effect in the treatment of Fournier gangrene are unclear.A 47-year-old male patient was admitted with an anal abscess followed by a spread of the infection to the scrotum, which was caused by Pseudomonas aeruginosa. NPWT was applied on the surface of the scrotal area and continued for 10 days. A split-thickness skin graft from the scalp was then grafted to the wound, after which, NPWT utilizing gauze sealed with an occlusive dressing and connected to a wall suction was employed for 7 days to secure the skin graft.At discharge, the percentage of the grafted skin alive on the scrotum was 98%. The wound beside the anus had decreased to 4 × 0.5 cm with a depth of 1 cm. Follow-up at the clinic 1 month later showed that both wounds had healed. The patient did not complain of any pain or bleeding, and was satisfied with the outcome.NPWT before and after split-thickness skin grafts is safe, well tolerated, and efficacious in the treatment of Fournier gangrene.

Regenerative medicine in China: demands, capacity, and regulation.

Regenerative medicine (RM) is an emerging interdisciplinary field of research. Its clinical application focuses on the repair, replacement, and regeneration of cells, tissues, and organs by approaches including cell reprogramming, stem cell transplantation, tissue engineering, activating factors, and clone treatment. RM has become a hot point of research in China and other countries. China’s main and local governments have attached great importance to RM and given strong support in relevant policies and funding. About 3.5 billion RMB has been invested in this field. Since 1999, China has established about 30 RM centers and cooperates with many advanced countries in RM research and benefits from their cooperation. However, China needs to develop standards, regulations, and management practices suitable for the healthy development of RM. In this review, we focus on its great demand, capacity, and relative regulations.