Signaling Mechanisms of Stem Cell Therapy for Intervertebral Disc Degeneration.

Low back pain is the leading cause of disability worldwide. Intervertebral disc degeneration (IDD) is the primary clinical risk factor for low back pain and the pathological cause of disc herniation, spinal stenosis, and spinal deformity. A possible approach to improve the clinical practice of IDD-related diseases is to incorporate biomarkers in diagnosis, therapeutic intervention, and prognosis prediction. IDD pathology is still unclear. Regarding molecular mechanisms, cellular signaling pathways constitute a complex network of signaling pathways that coordinate cell survival, proliferation, differentiation, and metabolism. Recently, stem cells have shown great potential in clinical applications for IDD. In this review, the roles of multiple signaling pathways and related stem cell treatment in IDD are summarized and described. This review seeks to investigate the mechanisms and potential therapeutic effects of stem cells in IDD and identify new therapeutic treatments for IDD-related disorders.

Bone marrow mesenchymal stem cells alleviate the formation of pathological scars in rats.

Introduction: Although bone marrow-derived mesenchymal stem cells (BMSCs) have attracted increasing attention because of their pivotal functions in the process of wound healing and fibrosis alleviation, the underlying molecular mechanisms have been poorly understood. Moreover, transforming growth factor beta 1 (TGF-ß1) is positively correlated with scar formation, whereas TGF-ß3 inhibits the pathological scar formation process. However, the relation of TGF-ß1, TGF-ß3, and the TGF-ß/Smad signaling pathway with BMSCs is unknown and requires further investigation. Methods: A cell co-culture platform was used to examine the relationship between BMSCs and dermal fibroblasts (DFs). EdU labelling and cell cycle detection were carried out to examine the viability of DF cells. Transwell and wound healing assays were used to test the cell migration of DFs. The expression of TGF-ß pathway components and collagens were determined by RT-qPCR and western blotting. A damaged skin rat model was applied to test the effects of BMSC treatment on skin wound healing. Results: The results showed that BMSC secretion could inhibit the viability and migration of DFs. Moreover, we observed that the TGF-ß-induced expression of TGF-ß1, Smad2, Smad3, COLI and COLIII was attenuated upon BMSC treatment in DFs, while the decrease in TGF-ß3 expression was enhanced by BMSCs. Furthermore, BMSC treatment accelerated wound healing and attenuated skin collagen deposition in a damaged skin rat model, leading to the mitigation of cell proliferation and enhancement of cell apoptosis. In addition, the expression of alpha-smooth muscle actin (α-SMA), COLI, and COLII was alleviated by BMSC treatment. Conclusions: Our results indicate that BMSCs can promote wound healing and inhibit skin collagen deposition, which is associated with the TGF-ß/Smad signaling pathway.

Injection Injury Caused by Disinfectant During COVID-19: A Case Report.

High-pressure injection injury of the hand is a rare but severe emergency, which requires full attention and timely treatment. However, the early symptoms may not be obvious. As the swelling and necrosis progress, the condition gradually worsens, and in severe cases, it may end with amputation. We report a particular case of a hand injection injury, which occurred to a worker who worked overtime to produce disinfectant during the Coronavirus Disease-19 (COVID-19) pandemic. Because of the chemical toxicity of the disinfectant and pressure's damage, although the emergency debridement was promptly performed, we still lost some fingers in the end. In the existing disinfection product manuals, we have not seen any tips on dealing with tissue injection injury. It may reduce workers' attention to injuries, leading to delays in emergency operations.

Restoration of forearm supination by combining pronator teres with allogeneic tendon.

BACKGROUND: Many solutions have been proposed in treating of forearm supination. Comparing with other supination function reconstructions, pronator teres rerouting is believed to be less effective due to its insufficient supination strength. The aim of this study is to introduce a modified procedure, and compare its result with two previous approaches. PATIENTS AND METHODS: From 2015 to 2020, 11 patients have restored forearm supination by rerouting of the pronator teres weave sutured with allogeneic tendons. The average follow-up period was 17.5 months (12 to 24). The range of active supination at the final follow-up was recorded. RESULTS: Almost all patients acquired good supination range. The average active post-operative supination was 72.7° (60° to 80°) at the final follow-up. No complication was observed. All patients retained full range of pronation. CONCLUSIONS: This study provides a modified supination function reconstruction with simple operating, fine results, low risks, and no affecting of pronation function. The use of allogeneic tendon makes up for the muscles with insufficient length, making it valuable to reconsider those rebuilding operations that were once considered unpromising by many.

Modified Bunnell suture expands the surgical indication of the treatment of Haglund's syndrome heel pain with endoscope.

The aim of the present study was to develop a method which can solve the problem of partial tearing of the Achilles tendon insertion caused by the debridement for Haglund's syndrome using endoscopy-assisted percutaneous repair. Seven patients with Haglund's syndrome were prospectively recruited. All 7 patients (3 female, 4 male) had intratendinous calcifications. Preoperative diagnosis was made according to the clinical symptoms and diagnosis, medical examination results, plain film radiographs, and magnetic resonance imaging. The patients whose average age was 35.2 years, had experienced symptoms and were treated by conservative methods for 12-24 months (average 17.1 months). All 7 cases were treated with debridement of Achilles tendon insertion site with a standard 4.0 mm bur and underwent repair treatment with a modified Bunnell suture method under direct visualization using arthroscopy. The American Orthopaedic Foot and Ankle Society (AOFAS) score and the changes of the patient's parallel pitch lines were used to evaluate and assess the results. The follow-up period averaged 22 months. The lateral X-ray film after operation of all the heels of the patients showed that sufficient osseous planning of all the patients was completed. None of the patients converted to conventional open surgery. The average AOFAS scores of the 7 cases were improved significantly at final follow-up compared to pretherapy (P<0.005). The results of 5 of the 7 cases were excellent, 2, were good, and 0 was fair or poor. None of the cases had permanent nerve injuries, wound infections or Achilles tendon avulsion. Our study is a supplement of endoscopic repairing and strengthening of the Achilles tendon. The advantages and clinical significance of endoscopy during the treatment of Haglunds syndrome under the premise of strict control of operation indications were further verified.

Angiotensin-converting enzyme inhibitor reduces scar formation by inhibiting both canonical and noncanonical TGF-ß1 pathways.

Angiotensin-converting enzyme inhibitors (ACEIs) can improve the fibrotic processes in many internal organs. Recent studies have shown a relationship between ACEI with cutaneous scar formation, although it has not been confirmed, and the underlying mechanism is unclear. In this study, we cultured mouse NIH 3T3 fibroblasts with different concentrations of ACEI. We measured cell proliferation with a Cell Counting Kit-8 and collagen expression with a Sirius Red Collagen Detection Kit. Flow cytometry and western blotting were used to detect transforming growth factor ß1 (TGF-ß1) signaling. We also confirmed the potential antifibrotic activity of ACEI in a rat scar model. ACEI reduced fibroblast proliferation, suppressed collagen and TGF-ß1 expression, and downregulated the phosphorylation of SMAD2/3 and TAK1, both in vitro and in vivo. A microscopic examination showed that rat scars treated with ramipril or losartan were not only narrower than in the controls, but also displayed enhanced re-epithelialization and neovascularization, and the formation of organized granulation tissue. These data indicate that ACEI inhibits scar formation by suppressing both TGF-ß1/SMAD2/3 and TGF-ß1/TAK1 pathways, and may have clinical utility in the future.

Effect of Calcium Alginate Microsphere Loaded With Vascular Endothelial Growth Factor on Adipose Tissue Transplantation.

Revascularization in the early period after transplantation is the key to improving adipocyte survival. Vascular endothelial growth factor (VEGF) is known as the master regulator of angiogenesis. However, consensus is lacking regarding safe and efficient methods for applying VEGF in free fat transplantation in the clinical setting. We constructed calcium alginate (CA) microspheres loaded with VEGF to increase the survival of implanted adipocytes. BALB/c nude mice were used as adipose tissue transplantation receptors. Adipocytes were mixed with CA microspheres loaded with VEGF and implanted subcutaneously into the dorsum of mice. Grafts were harvested at week 3, 6, and 12 after transplantation. We found that the mass and microvascular density of grafts in the VEGF+CA group (CA microspheres loaded with VEGF) were statistically higher than that of other groups in a time-dependent manner. We demonstrated that CA microspheres loaded with VEGF can significantly promote the fat graft neovascularization, thus improving adipocyte survival.

Effect of chitosan nanospheres loaded with VEGF on adipose tissue transplantation: a preliminary report.

Neovascularization plays an important role in adipose tissue transplantation, because survival of implanted cells strongly relies on sufficient oxygen and nutrient supply. Vascular endothelial growth factor (VEGF) is known as the master regulator of angiogenesis. It is capable of starting the complex cascade of events leading to endothelial cell activation, assembly of new vascular structures, mural cell recruitment, and vessel stabilization. However, consensus is lacking regarding safe and efficient methods for applying VEGF in free fat transplantation in the clinical setting. We investigated whether chitosan nanospheres, a biocompatible high-molecular-weight material, safely improve the efficiency of VEGF application in free fat transplantation. Immunologically compromised nude mice were used as adipose tissue transplantation receptors. Nanospheres loaded with VEGF were mixed with adipocytes and injected subcutaneously to the dorsa of mice. Grafts were harvested at weeks 3, 6, and 12. We found that treated-graft weight and vascularization were significantly higher than controls in a time-dependent manner. We demonstrated that chitosan nanospheres loaded with VEGF significantly promote the fat graft neovascularization and improve adipocyte survival.

Construction of a double eyelid: an uncut strip of orbicularis removed through three mini-incisions.

BACKGROUND: In recent years, many mini-incisional techniques for double-eyelid plasty have been developed. However, the removal of pretarsal tissue has not been satisfactory because only small pockets of soft tissue just inferior to the skin have been removed to place the suture. The formed double eyelid may therefore not be durable. This report introduces a modified mini-incisional method that involves removing a long uncut strip of orbicularis through three mini-incisions. METHODS: A strip of orbicularis uncut from the inner canthus to the outer canthus was removed through three mini-incisions made on the upper eyelid, quite similar to that of a full incisional procedure. The left orbicularis then was pruned in three directions: left, right, and down (toward the palpebral margin). Finally, the incisions were sutured, and a vivid fold was created. RESULTS: From 2008 to 2012, the authors applied this technique to 90 patients (174 eyes). Although the trauma may have been more severe due to a large amount of orbicularis removed, including an uncut strip of orbicularis, bleeding during the operation was easy to control and usually very limited. The edema period for most patients ended within 3 weeks, mainly because of the skin bridge between each incision. The scars became unnoticeable after 3-6 months. Disappearance of the fold was not found in any case at either the 3- or 12-month (average, 9-month) follow-up evaluation or during the 4-year follow-up period. CONCLUSION: The described technique combines the advantages of both full incisional and the usual mini-incisional techniques in developing a long-lasting suprapalpebral fold with inconspicuous scars and a short recovery period. LEVEL OF EVIDENCE V: Opinions of respected authorities, based on clinical experience,descriptive studies, or reports of expert committees.