Comparison of anaesthesia-related outcomes in patients monitored by newly recruited nurse anaesthetists and anaesthesiologists: An observational study.

AIMS: To compare anaesthesia-related outcomes between patients monitored by newly recruited nurse anaesthetists and those monitored by newly recruited anaesthesiologists. DESIGN: This was a retrospective study. METHODS: We conducted a retrospective study that collected demographic information on newly recruited nurse anaesthetists and anaesthesiologists between 2017 and 2022 and recorded information on patients within 6 months of monitoring. Postoperative pain, emergency agitation, nausea, and vomiting were designated anaesthesia-related outcomes. Propensity score matching was used to adjust for covariates. The study adhered to the STROBE guidelines. RESULTS: The study's statistical analysis included 4483 patients monitored by 22 newly recruited nurse anaesthetists and 4959 patients monitored by 23 newly recruited anaesthesiologists. Compared with patients monitored by newly trained anaesthesiologists, the patients monitored by nurse anaesthetists were younger (42.07 ± 20.00 vs. 47.39 ± 18.45 years, p < 0.001) and had a lower body mass index (23.56 ± 4.46 vs. 24.19 ± 4.25, p < 0.001). Patients monitored by anaesthesiologists had a greater proportion of women (61.62% vs. 59.25%, p < 0.001), a high proportion of ASA III and ASA IV (17.1% vs. 8.88%, p < 0.001), and a longer mean surgery duration (78.65 ± 59.01 vs. 70.70 ± 60.65 min, p < 0.001). After propensity score matching was used to adjust for covariates, no statistically significant differences were found in the prevalence of postoperative pain, emergency agitation, or postoperative nausea and vomiting between the two groups (p < 0.05). CONCLUSION: Nurse anaesthetists monitoring alone during anaesthesia maintenance is feasible and safe. The two groups had no significant differences in the incidence of postoperative pain, emergency agitation, or postoperative nausea and vomiting. RELEVANCE TO CLINICAL PRACTICE: The shortage of anaesthesiologists leads to heavy work burden and high incidence of occupational burnout among anaesthesiologists. The study found that it was safe for nurse anaesthetists to perform anaesthetic monitoring alone in the operating room under the supervision of the attending anaesthesiologist and did reduce the burden of anaesthesiologists' work. The results of the current study contribute to the expansion of occupational categories for nurse anaesthetists in countries where anaesthesiologists are in short supply. It provides new ideas for hospital administrators and policy-makers to formulate medical and nursing service policies.

Unplanned Post-Anesthesia Care Unit to ICU Transfer Following Cerebral Surgery: A Retrospective Study.

Background: Unplanned transfer to intensive care unit (ICU) lead to reduced trust of patients and their families in medical staff and challenge medical staff to allocate scarce ICU resources. This study aimed to explore the incidence and risk factors of unplanned transfer to ICU during emergence from general anesthesia after cerebral surgery, and to provide guidelines for preventing unplanned transfer from post-anesthesia care unit (PACU) to ICU following cerebral surgery. Methods: This was a retrospective case-control study and included patients with unplanned transfer from PACU to ICU following cerebral surgery between January 2016 and December 2020. The control group comprised patients matched (2:1) for age (±5 years), sex, and operation date (±48 hours) as those in the case group. Stata14.0 was used for statistical analysis, and p < .05 indicated statistical significance. Results: A total of 11,807 patients following cerebral surgery operations were cared in PACU during the study period. Of the 11,807 operations, 81 unscheduled ICU transfer occurred (0.686%). Finally, 76 patients were included in the case group, and 152 in the control group. The following factors were identified as independent risk factors for unplanned ICU admission after neurosurgery: low mean blood oxygen (OR = 1.57, 95%CI: 1.20-2.04), low mean albumin (OR = 1.14, 95%CI: 1.03-1.25), slow mean heart rate (OR = 1.04, 95%CI: 1.00-1.08), blood transfusion (OR = 2.78, 95%CI: 1.02-7.58), emergency surgery (OR = 3.08, 95%CI: 1.07-8.87), lung disease (OR = 2.64, 95%CI: 1.06-6.60), and high mean blood glucose (OR = 1.71, 95%CI: 1.21-2.41). Conclusion: We identified independent risk factors for unplanned transfer from PACU to ICU after cerebral surgery based on electronic medical records. Early identification of patients who may undergo unplanned ICU transfer after cerebral surgery is important to provide guidance for accurately implementing a patient's level of care.

Adipose-derived stem cells with miR-150-5p inhibition laden in hydroxyapatite/tricalcium phosphate ceramic powders promote osteogenesis via regulating Notch3 and activating FAK/ERK and RhoA.

Adipose-derived mesenchymal stem cells (ADSCs) are multipotent stromal cells and play huge role in forming and repairing bone tissues. Emerging evidence shows that MicroRNAs (miRNAs) are involved in ADSCs differentiation. Here, we explored the role of miR-150-5p and its related mechanisms in ADSCs osteogenesis. Real-time PCR was used to determine miR-150-5p expression during ADSCs osteogenesis. miR-150-5p inhibitors, miR-150-5p ADV or short hairpin RNA (shRNA) of Notch3 were transfected to ADSCs for analyzing the effects on osteogenesis. The mixture of hydroxyapatite/tricalcium phosphate (HA/TCP) ceramic powders and transfected ADSCs was implanted into BALB/C nude mice. Micro-CT and histological methods were performed to evaluate the new bone formation. Compared with negative control (NC) and miR-150-5p overexpression, inhibition of miR-150-5p increased ADSCs osteogenesis by regulating Notch3. MiR-150-5p overexpression decreased the expression of pFAK, pERK1/2, and RhoA, while these were up-regulated when miR-150-5p was inhibited, or notch3 was silenced. Furthermore, miR-150-5p inhibition partially reversed the suppression effect of notch3 knockdown on osteogenesis in vitro and in vivo. This study demonstrated the critical function of miR-150-5p during osteogenesis. The combination of ADSCs with miR-150-5p inhibition and HA/TCP might be a promising strategy for bone damage repair. STATEMENT OF SIGNIFICANCE: Osteoporosis is a common chronic metabolic bone disease in humans. Bone tissue engineering based on mesenchymal stem cells, biomaterials, and growth factors, provides a promising way to treat osteoporosis and bone defects. ADSCs commonly differentiate into adipose cells, they can also differentiate into osteogenic cell lineages. Nucleic acids and protein have usually been considered as regulators of ADSCs osteogenic differentiation. In the current study, we demonstrated the combination of ADSCs with miR-150-5p inhibition and hydroxyapatite/tricalcium phosphate ceramic powders enhanced bone regeneration. Furthermore, miR-150-5p/Notch3 axis regulating osteogenesis via the FAK/ERK1/2 and RhoA pathway was assessed. The current study showed the application of ADSCs in bone regeneration might be a promising strategy for osteoporosis and bone damage repairing.

Emerging Potential of Exosomes on Adipogenic Differentiation of Mesenchymal Stem Cells.

The mesenchymal stem cells have multidirectional differentiation potential and can differentiate into adipocytes, osteoblasts, cartilage tissue, muscle cells and so on. The adipogenic differentiation of mesenchymal stem cells is of great significance for the construction of tissue-engineered fat and the treatment of soft tissue defects. Exosomes are nanoscale vesicles secreted by cells and widely exist in body fluids. They are mainly involved in cell communication processes and transferring cargo contents to recipient cells. In addition, exosomes can also promote tissue and organ regeneration. Recent studies have shown that various exosomes can influence the adipogenic differentiation of stem cells. In this review, the effects of exosomes on stem cell differentiation, especially on adipogenic differentiation, will be discussed, and the mechanisms and conclusions will be drawn. The main purpose of studying the role of these exosomes is to understand more comprehensively the influencing factors existing in the process of stem cell differentiation into adipocytes and provide a new idea in adipose tissue engineering research.

Risk factors of role stress and professional burnout among nurse anesthetists: A multicenter cross-sectional study.

BACKGROUND: In China, there is no unified standard for the responsibilities and authority of nurse anesthetists, resulting in different professional expectations from anesthesiologists and nursing managers, which may result in high levels of role stress and burnout in nurse anesthetists. Additional factors such as high occupational risk and heavy work may also contribute to role stress and burnout. METHODS: In this multicenter cross-sectional study, an online questionnaire survey was conducted among 198 nurses from six tertiary hospitals in Shandong Province. The t test, analysis of variance, linear regression, and logistic regression were used to analyze the risk factors for role stress and professional burnout. RESULTS: The scores of role conflict and role ambiguity in role stress were 30.61 ± 9.53 and 31.89 ± 9.56, respectively; satisfaction with income and the working environment, the hospital's attention, years of experience as a nurse, clarity concerning the nurse anesthetist's occupational scope, and attitude to career prospects were independent risk factors for role stress. The burnout data were non-normally distributed and were expressed as medians and quartiles. The scores of emotional exhaustion, depersonalization, and personal achievement in professional burnout were 30 (26-34), 11 (8-14), and 23 (20-26) respectively. The number of working hours per week, attitude to career prospects, satisfaction with the working environment and income, physical health, gender, and education were independent risk factors for burnout. CONCLUSIONS: Chinese nurse anesthetists were found to be in danger of high role stress and professional burnout, a situation requiring the attention of managers.

Lithium chloride represses abdominal aortic aneurysm via regulating GSK3ß/SIRT1/NF-κB signaling pathway.

Lithium chloride (LiCl), a pharmacological compound, was effective in reducing inflammation, but whether it can protect against abdominal aortic aneurysm (AAA) is largely unknown. This study is designed to investigate therapeutic effects of LiCl on AAA and the potential mechanism. Rat AAA models were induced by periaortic application of CaCl2. AAA rats were treated by daily intraperitoneal injection of LiCl or vehicle alone to study the protection effects of LiCl in vivo. Rat primary vascular smooth muscle cells (VSMCs) stimulated with tumor necrosis factor (TNF)-α served as an in vitro model. LiCl treatment prevented the development of AAA through inhibiting the inflammatory cells infiltration and inflammatory cytokines overproduction, as well as attenuating superoxide production and elastin degradation in aorta of AAA rats. Additionally, the downregulation of p-GSK3ß(Ser9) and SIRT1, upregulation of NF-κB(p-65), MMP-2 and MMP-9 in AAA were abolished by LiCl treatment. In vitro by upregulating p-GSK3ß(Ser9), LiCl significantly induced SIRT1 expression, along with inhibition of the NF-κB activation and decreased elastin level elicited in VSMCs by TNF-α stimulation. SIRT1 activator SRT1720 achieved similar repressive effects as LiCl on TNF-α-induced NF-κB activation and decreased elastin in VSMCs. Moreover, administration of LiCl also caused regression of established rats AAA. This study provided the first evidence that LiCl prevented the development of AAA through inhibiting inflammation, MMPs, and superoxide production, and facilitating the biosynthesis of elastin. The beneficial effect of LiCl may be mediated by regulation GSK3ß/SIRT1/NF-κB cascade.

Surface modification of small intestine submucosa in tissue engineering.

With the development of tissue engineering, the required biomaterials need to have the ability to promote cell adhesion and proliferation in vitro and in vivo. Especially, surface modification of the scaffold material has a great influence on biocompatibility and functionality of materials. The small intestine submucosa (SIS) is an extracellular matrix isolated from the submucosal layer of porcine jejunum, which has good tissue mechanical properties and regenerative activity, and is suitable for cell adhesion, proliferation and differentiation. In recent years, SIS is widely used in different areas of tissue reconstruction, such as blood vessels, bone, cartilage, bladder and ureter, etc. This paper discusses the main methods for surface modification of SIS to improve and optimize the performance of SIS bioscaffolds, including functional group bonding, protein adsorption, mineral coating, topography and formatting modification and drug combination. In addition, the reasonable combination of these methods also offers great improvement on SIS surface modification. This article makes a shallow review of the surface modification of SIS and its application in tissue engineering.

MicroRNA-150 Modulates Adipogenic Differentiation of Adipose-Derived Stem Cells by Targeting Notch3.

MicroRNAs (miRNAs) influence stem cell functions, including mobilization, proliferation, and differentiation. miR-150 is abundantly expressed in monocytes. Knockdown of miR-150 promotes bone marrow stem cell migration. The role of miR-150 in adipose-derived stem cells (ADSCs) is unclear. In this study, the effects of miR-150 on adipogenic differentiation and proliferation of ADSCs were investigated. ADSCs were isolated from the inguinal adipose tissue of wild-type (WT) and miR-150 knockout (KO) mice and were induced for adipogenic differentiation. The miR-150 level was detected by real-time PCR. ADSCs were transfected by miR-150 or small-interfering RNA (siRNA) of Notch3. MTT assay and colony formation assay were performed in miR-150 knockdown and control ADSCs. Real-time PCR showed that miR-150 was expressed in ADSCs. miR-150 knockdown significantly decreased the capacity of adipogenic differentiation of ADSCs, as compared with their counterparts from WT mice. It is intriguing that the overexpression of miR-150 significantly increased C/EBPα and PPAR-γ expression and lipid formation in ADSCs with adipogenic induction. Overexpression of miR-150 significantly decreased Notch3 expression in ADSCs compared with the control groups. Furthermore, Notch3 inhibition promoted the adipogenic differentiation in ADSCs. miR-150 also suppressed proliferation potential and the expression of Nanog in ADSCs. In summary, this study demonstrates, for the first time, that miR-150 promotes adipogenic differentiation and inhibits proliferation of ADSCs. miR-150 regulates adipogenic differentiation of ADSCs, likely mediated by the downregulation of Notch3.

Biocompatibility of injectable hydrogel from decellularized human adipose tissue in vitro and in vivo.

Adipose tissue engineering is considered as a promising treatment for repairing soft tissue defects. The decellularized extracellular matrix (ECM) is becoming the research focus in tissue engineering for its tissue specificity. In this study, the human adipose tissue liposucted from healthy people were decellularized by a series of mechanical, chemical, and enzymatic methods. The components of cell and lipid were effectively removed, whereas the collagens and other ingredients in adipose tissue were retained in the human decellularized adipose tissue (hDAT). Then the extracted hDAT was further fabricated into injectable hydrogel, which could be self-assembled to form gel under certain condition. The hDAT hydrogel was nontoxic to human adipose-derived stem cells (ADSCs) and could spontaneously induce adipogenic differentiation in vitro. It was highly biocompatible and could not cause inflammation and rejection after being implanted subcutaneously. The hDAT hydrogel developed in this study will be one of the available choices for soft tissue enlargement and cosmetic fillers because of its noninvasive in collection and implantation process. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1684-1694, 2019.

Modulation of Immune-Inflammatory Responses in Abdominal Aortic Aneurysm: Emerging Molecular Targets.

Abdominal aortic aneurysm (AAA), a deadly vascular disease in human, is a chronic degenerative process of the abdominal aorta. In this process, inflammatory responses and immune system work efficiently by inflammatory cell attraction, proinflammatory factor secretion and subsequently MMP upregulation. Previous studies have demonstrated various inflammatory cell types in AAA of human and animals. The majority of cells, such as macrophages, CD4+ T cells, and B cells, play an important role in the diseased aortic wall through phenotypic modulation. Furthermore, immunoglobulins also greatly affect the functions and differentiation of immune cells in AAA. Recent evidence suggests that innate immune system, especially Toll-like receptors, chemokine receptors, and complements are involved in the progression of AAAs. We discussed the innate immune system, inflammatory cells, immunoglobulins, immune-mediated mechanisms, and key cytokines in the pathogenesis of AAA and particularly emphasis on a further trend and application of these interventions. This current understanding may offer new insights into the role of inflammation and immune response in AAA.

p62 is linked to mitophagy in oleic acid-induced adipogenesis in human adipose-derived stromal cells.

BACKGROUND: Obesity is closely related to the abnormal differentiation of adipocytes, which are subjected to high plasma levels of free fatty acids (FFAs). As the most abundant FFA in the bloodstream, oleic acid (OA) has the ability to induce adipogenic differentiation in human adipose-derived stromal cells (hADSCs). Recently, p62, an autophagy mediator, has been shown to play a role in obesity and adipose tissue metabolism. Therefore, the aim of this study was to investigate the roles of autophagy and mitochondrial function at different stages of OA (in combination with insulin and dexamethasone)-induced adipogenesis in hADSCs. METHODS: The hADSCs were incubated with OA, insulin, and dexamethasone after pretreatment with autophagy inhibitors or knockdown of p62 with shRNA. The adiposeness level was then analyzed by oil red O staining in the cells. The related proteins or mRNA levels were detected by western blot analysis or quantitative real-time polymerase chain reaction (PCR). RESULTS: Treatment with 80 µM OA (substituted for isobutylmethylxantine; IBMX) for 10 days successfully induced hADSCs to adipocytes. During OA-induced adipogenesis, autophagy was induced, with an increased LC3II/I ratio on day 3 and a decreased protein level of p62 on and after day 3. Inhibition of autophagy with 3-methyladenine (3MA) at the early stage (day 0 to day 3) of differentiation, but not at the middle or late stage, significantly decreased OA-induced adipogenesis; while knockdown of p62 with shRNA significantly promoted adipogenesis in hADSCs. Moreover, the copy number of mtDNA (the ND1 gene) and the protein level of TOM20, a mitochondrial membrane protein, were increased following OA treatment, which was related to the stability of mitochondria. Interestingly, knockdown of p62 increased the mito-LC3II/I and cyto-LC3II/I ratios by 110.1% and 73.3%, respectively. The increase in the ratio of mito-LC3II/I was higher than that of cyto-LC3II/I. Furthermore, p62 knockdown-enhanced adipogenesis in hADSCs was abolished by inhibiting mitophagy with cyclosporine A. CONCLUSIONS: These results suggested that p62 plays a protective role in adipogenesis of hADSCs through regulating mitophagy.

Curcumin attenuates the development of thoracic aortic aneurysm by inhibiting VEGF expression and inflammation.

Angiogenesis is an important process in the pathogenesis of aortic aneurysm. The aim of the present study was to investigate the angiogenic balance and the expression of vascular endothelial growth factor (VEGF) in thoracic aortic aneurysm (TAA). A previous study demonstrated that curcumin exerts a marked effect on aortic aneurysm development. Therefore, the present study determined whether curcumin is able to modulate angiogenesis and inflammatory signaling in TAA by collecting human TAA samples and establishing a rat TAA model using periaortic application of CaCl2. TAA rats were treated with curcumin or 1% carboxymethyl cellulose and were sacrificed 4 weeks after the operation. All tissue specimens were analyzed by histological staining, immunohistochemistry and western blotting. Human TAA samples exhibited increased neovascularization and VEGF expression when compared with normal aortic walls. In rat tissues, treatment with curcumin resulted in reduced aneurysm size and restored the wavy structure of the elastic lamellae. In addition, curcumin decreased neovascularization and the expression of VEGF. Immunohistochemical analysis indicated that curcumin significantly inhibited infiltration of cluster of differentiation (CD)3+ and CD68+ cells in TAA. Furthermore, curcumin treatment decreased the expression of vascular cell adhesion molecule­1, intracellular adhesion molecule­1, monocyte chemoattractant protein­1 and tumor necrosis factor­α. Collectively, the results demonstrated that angiogenesis and VEGF expression were increased in the aortic wall in TAA. Treatment with curcumin inhibited TAA development in rats, which was associated with suppression of VEGF expression. In addition, curcumin attenuated inflammatory cell infiltration and suppressed inflammatory factor expression in the periaortic tissue of TAA.

Gelatin-Based Hydrogels for Organ 3D Bioprinting.

Three-dimensional (3D) bioprinting is a family of enabling technologies that can be used to manufacture human organs with predefined hierarchical structures, material constituents and physiological functions. The main objective of these technologies is to produce high-throughput and/or customized organ substitutes (or bioartificial organs) with heterogeneous cell types or stem cells along with other biomaterials that are able to repair, replace or restore the defect/failure counterparts. Gelatin-based hydrogels, such as gelatin/fibrinogen, gelatin/hyaluronan and gelatin/alginate/fibrinogen, have unique features in organ 3D bioprinting technologies. This article is an overview of the intrinsic/extrinsic properties of the gelatin-based hydrogels in organ 3D bioprinting areas with advanced technologies, theories and principles. The state of the art of the physical/chemical crosslinking methods of the gelatin-based hydrogels being used to overcome the weak mechanical properties is highlighted. A multicellular model made from adipose-derived stem cell proliferation and differentiation in the predefined 3D constructs is emphasized. Multi-nozzle extrusion-based organ 3D bioprinting technologies have the distinguished potential to eventually manufacture implantable bioartificial organs for purposes such as customized organ restoration, high-throughput drug screening and metabolic syndrome model establishment.

[RESEARCH PROGRESS OF ADIPOSE-DERIVED STEM CELLS COMPOUND WITH THREE DIMENSIONAL PRINTING SCAFFOLD FOR ENGINEERED TISSUE].

OBJECTIVE: To review the research progress of adipose-derived stem cells (ADSCs) compound with three dimensional (3D) printing scaffold in tissue engineering of fat, bone, cartilage, blood vessel, hepatocyte, and so on. METHODS: The recently published literature about ADSCs compound with 3D printing scaffold in tissue engineering at home and abroad was reviewed, analyzed, and summarized. RESULTS: A large number of basic researches showed that ADSCs could differentiate into a variety of tissues on 3D printing scaffold and involve in tissue repair and regeneration. But there is still a long way between the basic theory and the clinical practice at the early stages of development. CONCLUSION: It can effectively improve and restore the structure and function of the damaged tissue and organ to use ADSCs and 3D printing scaffold.

Zinc Prevents Abdominal Aortic Aneurysm Formation by Induction of A20-Mediated Suppression of NF-κB Pathway.

Chronic inflammation and degradation of elastin are the main processes in the development of abdominal aortic aneurysm (AAA). Recent studies show that zinc has an anti-inflammatory effect. Based on these, zinc may render effective therapy for the treatment of the AAA. Currently, we want to investigate the effects of zinc on AAA progression and its related molecular mechanism. Rat AAA models were induced by periaortic application of CaCl2. AAA rats were treated by daily intraperitoneal injection of ZnSO4 or vehicle alone. The aorta segments were collected at 4 weeks after surgery. The primary rat aortic vascular smooth muscle cells (VSMCs) were stimulated with TNF-α alone or with ZnSO4 for 3 weeks. The results showed that zinc supplementation significantly suppressed the CaCl2-induced expansion of the abdominal aortic diameter, as well as a preservation of medial elastin fibers in the aortas. Zinc supplementation also obviously attenuated infiltration of the macrophages and lymphocytes in the aortas. In addition, zinc reduced MMP-2 and MMP-9 production in the aortas. Most importantly, zinc treatment significantly induced A20 expression, along with inhibition of the NF-κB canonical signaling pathway in vitro in VSMCs and in vivo in rat AAA. This study demonstrated, for the first time, that zinc supplementation could prevent the development of rat experimental AAA by induction of A20-mediated inhibition of the NF-κB canonical signaling pathway.

Sodium orthovanadate induces the apoptosis of SH-SY5Y cells by inhibiting PIWIL2.

PIWIs have been shown to be abnormally expressed in a variety of cancers and may be important in the maintenance and invasion of cancer cells. The high expression of PIWIL2 contributed to the resistance effect of cisplatin in colon cancer cells, and the knockout of the PIWIL2 gene reduced the aggressive nature and malignant degree of colon cancer cells. Sodium orthovanadate (SOV) is a vanadium compound, and exhibited antineoplastic activity in certain types of human cancer cells, including lung, kidney and prostate cancer cells. However, its effects in human neuroblastoma (NB) cells have not yet been reported. The objective of this study was to investigate the effect of SOV on the apoptosis of NB cells and to explore how PIWIL2 is involved in the mechanism underlying this effect. In the present study, SH­SY5Y cells were treated with SOV and the optimal concentration was determined for further assays. Cell apoptosis, cell count, viability, the cell cycle, and the expression of PIWIL2 mRNA and protein were then determined. The results showed that SOV could induce cell apoptosis, reduce the percentage of viable cells, induce accumulation of SH­SY5Y cells at the G2/M and S phase of the cell cycle, and inhibit the expression of PIWIL2 and Bcl­2 mRNA and protein. The results suggested that the underlying mechanisms may be, at least in part, due to SOV inhibiting the expression of PIWIL2. These findings demonstrated the effect of SOV and supported its further evaluation as a treatment for human NB.

3D Bioprinting Technologies for Hard Tissue and Organ Engineering.

Hard tissues and organs, including the bones, teeth and cartilage, are the most extensively exploited and rapidly developed areas in regenerative medicine field. One prominent character of hard tissues and organs is that their extracellular matrices mineralize to withstand weight and pressure. Over the last two decades, a wide variety of 3D printing technologies have been adapted to hard tissue and organ engineering. These 3D printing technologies have been defined as 3D bioprinting. Especially for hard organ regeneration, a series of new theories, strategies and protocols have been proposed. Some of the technologies have been applied in medical therapies with some successes. Each of the technologies has pros and cons in hard tissue and organ engineering. In this review, we summarize the advantages and disadvantages of the historical available innovative 3D bioprinting technologies for used as special tools for hard tissue and organ engineering.

Adipose stem cells promote smooth muscle cells to secrete elastin in rat abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a life-threatening disease and its prevalence rate increases with social aging. The degradation of elastic is an important factor in the formation of AAA. METHODS: Adipose derived stem cells (ADSCs) and bone marrow mesenchymal stem cells (BMSCs) were isolated from rats, and identified by Oil red O and alizarin red staining after adipogenesis and osteogenesis induction. In addition, ADSCs were also identified by flow cytometry with CD markers. AAA model in rats was established, and smooth muscle cells (SMCs) were isolated from AAA aortic wall and identified by immunohistochemistry. ADSCs or BMSCs were co-cultured with AAA aortic wall for in vitro experiment, and ADSCs were injected into AAA model for in vivo test. Then orcein staining was used for observing the morphology of elastic fiber, Western blot and real-time PCR were used respectively to detect the protein and gene expression of elastin, gelatinases spectrum analysis was used to detect the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9. RESULTS: Lots of red lipid droplets were visible by Oil red O staining after adipogenesis induction, and black calcium nodules appeared by alizarin red staining after osteogenesis induction. The results of flow cytometry showed that ADSCs expressed CD44 and CD105, but exhibited negligible expression of CD31 and CD45. SMCs exhibited spindle-like morphology and α-actin protein was positive in cytoplasm. After co-cultured with ADSCs or BMSCs, the elastic fiber recovered normal winding shape, both the gene and protein expression of elastin increased, and the activity of MMP-2 decreased. The in vivo result was similar to that of in vitro. CONCLUSIONS: ADSCs promote the expression of elastin in SMCs and contribute to the reconstruction of elastic fiber, which may provide new ideas for treating AAA.

XAV939 promotes apoptosis in a neuroblastoma cell line via telomere shortening.

Telomeres, telomerase and tankyrase (TNKS) have an extremely important and special association with human cell aging and cancer. Telomerase activity is abnormally high in cancer cells and is accompanied by the overexpression of tankyrase 1 (TNKS1). TNKS1 is a positive regulator of telomerase activation and telomere extension in the human body, indicating that TNKS1 may be a possible therapeutic target for cancer. XAV939 is a small-molecule inhibitor of TNKS1. The objective of the present study was to investigate the apoptotic effect of XAV939 on the neuroblastoma (NB) SH-SY5Y cell line, as well as the change in telomere length and telomerase activity and elucidate the mechanism from this perspective. In the present study, we initially treated SH-SY5Y cells with XAV939 and RNA interference (RNAi)-TNKS1, and subsequently chose the optimal sequence for RNAi-TNKS1. We then measured the telomere length using quantitative real-time polymerase chain reaction (qPCR) assay, detected the telomerase activity using the ELISA kit, observed apoptotic morphology by transmission electron microscopy, and detected the percentages of apoptotic cells using flow cytometry and Hoechst 33342 staining. We also determined the invasive ability by a cell invasion assay. The results showed that short hairpin RNA-2 (shRNA-2) was the optimal sequence for RNAi-TNKS1. Treatment with both XAV939 and RNAi-TNKS1 shortened the telomere length, promoted apoptosis and reduced the invasive ability of the SH-SY5Y cells, yet had no effect on telomerase activity. XAV939 promoted apoptosis and reduced the invasiveness of SH-SY5Y cells dependent on telomere shortening, and further research should be conducted to clarify the exact mechanisms. This research may contribute to the cure of malignant NB using multi-targeted therapy with small-molecule agents.