Nme2 Cas9-mediated therapeutic editing in inhibiting angiogenesis after wet age-related macular degeneration onset.

BACKGROUND: Age-related macular degeneration (AMD), particularly wet AMD characterised by choroidal neovascularization (CNV), is a leading cause of vision loss in the elderly. The hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) pathway contributes to CNV pathogenesis. Previous gene editing research indicated that disrupting these genes in retinal pigment epithelial cells could have a preventive effect on CNV progression. However, no studies have yet been conducted using gene editing to disrupt VEGF signalling after CNV induction for therapeutic validation, which is critical to the clinical application of wet AMD gene editing therapies. METHOD: Here, we employed the single-adeno-associated virus-mediated Nme2 Cas9 to disrupt key molecules in VEGF signalling, Hif1α, Vegfa and Vegfr2 after inducing CNV and estimated their therapeutic effects. RESULTS: We found that Nme2 Cas9 made efficient editing in target genes up to 71.8% post 11 days in vivo. And only Nme2 Cas9-Vegfa treatment during the early stage of CNV development reduced the CNV lesion area by 49.5%, compared to the negative control, while Nme2 Cas9-Hif1α or Nme2 Cas9-Vegfr2 treatment did not show therapeutic effect. Besides, no off-target effects were observed in Nme2 Cas9-mediated gene editing in vivo. CONCLUSIONS: This study provides proof-of-concept possibility of employing Nme2 Cas9 for potential anti-angiogenesis therapy in wet AMD.

Silicate Nanoplatelets Promotes Neuronal Differentiation of Neural Stem Cells and Restoration of Spinal Cord Injury.

Neural stem cell (NSC) transplantation has been suggested as a promising therapeutic strategy to replace lost neurons after spinal cord injury (SCI). However, the low survival rate and neuronal differentiation efficiency of implanted NSCs within the lesion cavity limit the application. Furthermore, it is difficult for transplanted cells to form connections with host cells. Thus, effective and feasible methods to enhance the efficacy of cell transplantation are needed. In this study, the effect of Laponite nanoplatelets, a type of silicate nanoplatelets, on stem cell therapy is explored. Laponite nanoplatelets can induce the neuronal differentiation of NSCs in vitro within five days, and RNA sequencing and protein expression analysis demonstrated that the NF-κB pathway is involved in this process. Moreover, histological results revealed that Laponite nanoplatelets can increase the survival rate of transplanted NSCs and promote NSCs to differentiate into mature neurons. Finally, the formation of connections between transplanted cells and host cells is confirmed by axon tracing. Hence, Laponite nanoplatelets, which drove neuronal differentiation and the maturation of NSCs both in vitro and in vivo, can be considered a convenient and practical biomaterial to promote repair of the injured spinal cord by enhancing the efficacy of NSC transplantation.

Research progress of PBX1 in developmental and regenerative medicine.

Pre-B-cell leukemia transcription factor 1 (PBX1) proteins are a subfamily of evolutionarily conserved atypical homeodomain transcription factors belonging to the superfamily of triple amino acid loop extension homeodomain proteins. PBX family members play crucial roles in the regulation of various pathophysiological processes. This article reviews the research progress on PBX1 in terms of structure, developmental function, and regenerative medicine. The potential mechanisms of development and research targets in regenerative medicine are also summarized. It also suggests a possible link between PBX1 in the two domains, which is expected to open up a new field for future exploration of cell homeostasis, as well as the regulation of endogenous danger signals. This would provide a new target for the study of diseases in various systems.

Transdural Anastomotic Aneurysm in Association with Moyamoya Disease: A Rare and Troublesome Neurosurgical Entity.

Moyamoya disease (MMD) is an idiopathic progressive steno-occlusive disease in the internal carotid artery (ICA) bifurcation. In rare circumstances, transdural anastomotic aneurysm (TAA) could develop during the progression of MMD. We present an illustrative case of TAA in association with MMD. To further explore this rare entity, a comprehensive literature review was also conducted. Our illustrative patient experienced spontaneous remission of the aneurysm during follow-up. By literature review, 12 patients with 13 TAAs, including our case, were identified. The patients aged from 10 to 74 years (46.3 ± 17.4). Eleven (92%) of the patients presented with intracranial hemorrhage, and 1 TAA (8%) was incidentally found. The responsible transdural collaterals were from the middle meningeal artery, occipital artery, internal maxillary artery, and ophthalmic artery in 8 (66.7%), 2 (16.7%), 1 (8%), and 2 (17%) patients, respectively. The anastomosed cerebral arteries were middle cerebral artery, anterior cerebral artery, posterior cerebral artery, and ICA in 5 (42%), 3 (25%), 3 (25%), and 1 (8%) patient, respectively. Eight (67%) patients underwent open surgeries. Two (17%) patients underwent transarterial embolization (TAE) only. Two (17%) patients experienced spontaneous remission of the aneurysm. Seven (58%) patients died or had neurologic deficits. TAAs rarely occur in the progression of MMD, which often presents with intracranial bleeding. Invasive management through open surgery or endovascular treatment is warranted to prevent catastrophic rebleeding. As some individuals might experience spontaneous aneurysm remission, conservative treatment and close imaging follow-up could be considered as an alternative when invasive treatment is risky.

PBX1 Attenuates Hair Follicle-Derived Mesenchymal Stem Cell Senescence and Apoptosis by Alleviating Reactive Oxygen Species-Mediated DNA Damage Instead of Enhancing DNA Damage Repair.

Tissues and organs undergo structural deterioration and functional decline during aging. DNA damage is considered a major cause of stem cell senescence. Although stem cells develop sophisticated DNA repair systems, when the intrinsic and extrinsic insults exceed the DNA repair capacity, cellular senescence, and age-related diseases inevitably occur. Therefore, the prevention and alleviation of DNA damage is an alternative to DNA repair in attenuating stem cell senescence and preventing age-related diseases. Pre-B-cell leukaemia homeobox 1 (PBX1) participates in maintaining the pluripotency of human embryonic and haematopoietic stem cells. Our recent studies showed that PBX1 promotes hair follicle-derived mesenchymal stem cell (HF-MSC) proliferation, decreases cellular senescence and apoptosis, and enhances induced pluripotent stem cell generation. Whether PBX1 attenuates HF-MSC senescence and apoptosis by alleviating DNA damage or by enhancing DNA repair remains unknown. In this study, we aimed to determine the effects of PBX1 on the intrinsic ROS or extrinsic H2O2-induced cellular senescence of HF-MSCs. To this end, we generated HF-MSCs overexpressing either PBX1, or poly (ADP-ribose) polymerase 1, or both. Our results showed that PBX1 overexpression attenuates HF-MSC senescence and apoptosis by alleviating reactive oxygen species (ROS)-mediated DNA damage instead of enhancing DNA repair. This is the first study to report that PBX1 attenuates stem cell senescence and apoptosis by alleviating DNA damage. It provides new insight into the mechanism of stem cell senescence and lays the foundation for the development of strategies for age-related disease prevention and treatment, and in particular, hair follicle repair and regeneration.

Mechanism underlying circularRNA_014301-mediated regulation of neuronal cell inflammation and apoptosis.

Spinal cord injury (SCI) causes damage to the spinal cord owing to trauma or disease and myelinated fiber tracts that transmit sensation and motor signals to and from the brain. Circular RNAs (circRNAs) are a recently discovered class of regulatory molecules, and their roles in SCI are still unknown. circRNA_014301 was indicated to be differentially expressed in the spinal cord at the site of SCI in a rat model. To analyze the role of circRNA_014301 in SCI, we exposed rat adrenal pheochromocytoma PC12 cells were exposed to increasing concentrations of lipopolysaccharide (LPS) and to construct a PC12 cell inflammatory model. Cell Counting Kit-8 assay was used to analyze cell viability. Reverse transcription-quantitative PCR and ELISA were used to detect the expression of inflammatory factors (IL-1ß, IL-6 and TNF-α). Annexin V-FITC/PI double staining was employed to detect cell apoptosis, and western blotting was performed to detect the expression of apoptotic proteins (Bax/Bcl-2/cleaved caspase-3) and NF-κB. The results demonstrated that LPS induced inflammation in PC12 cells as evidenced by the reduced cell proliferation and enhanced expression of inflammatory and apoptotic factors under increasing LPS concentrations. Western blotting analyses indicated that circRNA_014301 induced the expression of p-NF-κB/NF-κB, Bax and cleaved caspase-3, and decreased the expression of Bcl-2 following LPS-induced inflammation, and this apoptosis-promoting effect was relieved by small interfering-RNA-mediated knockdown of circRNA_014301. Thus, circRNA_014301 silencing alleviated apoptosis and inflammation in PC12 cells. SCI is invariably associated with spinal cord inflammation, and LPS was used to stimulate apoptosis and inflammatory injury in PC12 cells, and create a cell model of SCI. By promoting PC12 cell apoptosis under inflammatory conditions, it was indicated that circRNA_014301 may suppress SCI. Therefore, circRNA_014301 may represent a potential target for SCI diagnosis and therapy.

The role of angiotensin-(1-7) on acquired platinum resistance-induced angiogenesis in non-small cell lung cancer in vitro and in vivo.

Renin-angiotensin system (RAS) signaling has been implicated in the development of cancer. The new RAS ACE2/Ang-(1-7)/Mas axis antagonizes the classical ACE/Ang II/AT1R axis. Ang-(1-7) has pleiotropic roles in lung cancer including suppressing proliferation, angiogenesis, and metastasis. This research was designed to investigate the effect of Ang-(1-7) on tumor-associated angiogenesis in DDP-resistant lung cancer cell lines. We first established acquired DDP-resistant cell lines A549 (A549-DDP) and LLC (LLC-DDP). We next performed RT-qPCR, western blot, ELISA, tube formation, microvessel density detection, immunohistochemistry, and tumor formation assays. The results showed that the mRNA and protein levels of RAS components and vascular endothelial growth factor A (VEGFa) were lessened in the A549/LLC-DDP+Ang-(1-7) group compared with the A549/LLC-DDP group. This effect could be blocked by the MAS receptor antagonist A779. The data revealed that Ang-(1-7) could perform its antiangiogenic function by PI3K/AKT and MAPK pathways. Furthermore, the impact of Ang-(1-7) on tumor-associated angiogenesis has been confirmed in lung cancer xenograft model with acquired DDP resistance. These results provide a theoretical basis for designing therapeutic strategies for targeting Ang-(1-7) in the treatment of NSCLC.

Anlotinib-containing regimen for advanced small-cell lung cancer: A protocol of meta-analysis.

BACKGROUND: Small cell lung cancer (SCLC) is a highly malignant lung cancer with a very poor prognosis. Clinical treatment options for SCLC are still limited, especially for patients who have failed first or second line therapy. Anlotinib is a potentially beneficial new treatment option for SCLC. The aim of this meta-analysis is to evaluate the efficacy and safety of anlotinib-containing regimen for the treatment of SCLC. METHODS: We will search SinoMed, Wanfang Database, China National Knowledge Infrastructure, Embase, Cochrane Library, and PubMed for relevant articles that may meet the criteria published before March 31, 2021. We will perform a meta-analysis to evaluate the efficacy and safety of anlotinib-containing regimen for the treatment of SCLC. Clinical randomized controlled trials comparing anlotinib-containing regimens with other treatment regimens for advanced SCLC will be included in this study. The risk of bias will be evaluated for each included study using the Cochrane Handbook for Systematic Reviews of Interventions. We will use RevMan 5.3 software for statistical analysis of the data. RESULTS: The results of this study will provide evidence of anlotinib-containing regimens for advanced SCLC, and provide clinicians and patients with another convenient and effective treatment regimen for SCLC. This meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This meta-analysis will provide clinical evidence of anlotinib-containing regimens for advanced SCLC, which may or may not be found for anlotinib use. SYSTEMATIC REVIEW REGISTRATION: INPLASY202110034.

In situ suturing of a post-meatal segment of the anterior inferior cerebellar artery dissected by an aneurysm: A technical note.

Aneurysms originating along the peripheral portion of the anterior inferior cerebellar artery (AICA) are rare entities. As a result of the small diameter of the AICA, it is very challenging to preserve the parent artery during endovascular treatment for a peripheral AICA aneurysm. In this report, we present a rare case of aneurysm in the a2 segment of the right AICA. During surgery, the aneurysm was found to be a dissecting aneurysm. As the tissue of the aneurysm neck had a similar thickness to that of the adjacent normal vessel, interrupted suturing of the vessel was performed after partial removal and trimming of the aneurysm wall. The patient experienced an uneventful postoperative recovery. No other neurological deficit was noted. Magnetic resonance imaging three days after surgery revealed no acute ischaemia in the brainstem and cerebellum. Catheter angiography nine months later showed no recurrence of the aneurysm or stenosis of the AICA. The a2 segment of the AICA runs tortuously along the subarachnoid space of the cerebellopontine angle, which permits higher vascular mobility. In selected cases, in situ suturing or re-anastomosis could be considered for a2 segment aneurysms.

Immediate pneumothorax after neurosurgical procedures.

OBJECTIVE: Pneumothorax after neurosurgical procedures is very rare and incompletely understood. This study was performed to explore the clinical characteristics and pathogenesis of pneumothorax after neurosurgery. METHODS: We retrospectively evaluated patients admitted from December 2016 to April 2019 for treatment of spontaneous intracranial hemorrhage. The inclusion criteria were neurosurgical procedures (open surgeries or endovascular intervention) performed under general anesthesia, no performance of central venous puncture during surgery, and occurrence of pneumothorax immediately after the neurosurgical procedure. RESULTS: Eight patients developed pneumothorax after neurosurgical procedures for spontaneous intracranial hemorrhage under general anesthesia. Of the eight patients, seven had aneurysmal subarachnoid hemorrhage and one had left temporal-parietal hemorrhage. The lung injury prediction score (LIPS) was 3, 4, 5, 6, and 9.5 in three, one, two, one, and one patient, respectively. During the operation, volume-controlled ventilation (tidal volume, 8-10 mL/kg) was selected for all patients. CONCLUSIONS: Neurogenic pulmonary edema, inappropriate mechanical ventilation, and stimulation by endotracheal intubation might conjointly contribute to postoperative pneumothorax. To avoid this rare entity, mechanical ventilation with a low tidal volume or low pressure during general anesthesia should be adopted for patients with hemorrhagic cerebrovascular diseases involving the temporal lobe and a LIPS of >3.

Intracranial Dural Arteriovenous Fistulas With Brainstem Engorgement: An Under-Recognized Entity in Diagnosis and Treatment.

Background: In rare circumstances, patients with intracranial (dural arteriovenous fistulas) DAVFs could be complicated with brainstem engorgement, which might lead to delayed or false diagnosis and subsequent improper management. Methods: On July 2th, 2019, a systematic search was conducted in the PubMed database for patients with intracranial DAVFs complicated with brainstem engorgement. Results: Sixty-eight articles reporting of 86 patients were included for final analysis. The patients were aged from 20 to 76 years (57.10 ± 12.90, n = 82). The female to male ratio was 0.68 (35:51). Thirty-three (40.2%, 33/82) patients were initially misdiagnosed as other diseases. The specific location distributions were cranio-cervical junction, cavernous sinus, superior petrosal sinus, transverse and/or sigmoid sinus, tentorium, and other sites in 27 (32.5%), 11 (13.2%), 9 (10.8%), 10 (12.0%), 21 (25.3%), and 5 (6.0%) patients, respectively. The Cognard classification of DAVFs were II, III, IV, and V in 9 (10.7%, 9/84), 1 (1.2%, 1/84), 1 (1.2%, 1/84), and 73 (86.9%, 73/84) patients. Eighteen (22%, 18/82) patients were demonstrated to have stenosis or occlusion of the draining system distal to the fistula points. The mean follow-up period was 7.86 (n = 74, range 0-60 months) months. Fifty-four (70.1%, 54/77) patients experienced a good recovery according to the mRS score. Conclusions: Intracranial DAVFs complicated with brainstem engorgement are rare entities. Initial misdiagnosis and delayed definite diagnosis are common in the past three decades. The treatment outcome is still unsatisfactory at present. Early awareness of this rare entity and efficiently utilizing the up to date investigations are of utmost importance.

Adoptive transfer of bone marrow-derived dendritic cells (BMDCs) alleviates OVA-induced allergic airway inflammation in asthmatic mice.

Airway dendritic cells (DCs) are recognized as important factors in the mechanisms of allergic inflammatory diseases. Suppressor of cytokine signaling 3 (SOCS3) is involved in regulating the functions of T cells and macrophages, but the roles of SOCS3-expressing DCs in the pathogeneses of allergic inflammatory diseases are still controversial. We compared the effects of adoptively transferred SOCS3-/- and SOCS3+/+ bone marrow-derived DCs (BMDCs) on airway inflammation in ovalbumin (OVA)-sensitized asthmatic mice. Adoptive transfer of mature DCs (lipopolysaccharide [LPS]-induced DCs, DClps) with or without SOCS3 gene expression significantly ameliorated allergic airway inflammation. SOCS3-/- DCs slightly attenuated BMDC-induced immunogenic tolerance. DClps migrated to OVA-sensitized lungs with higher efficiency than immature DCs (DCim). DClps with or without SOCS3 greatly improved lung pathology scores and alleviated airway inflammatory cell infiltration after adoptive transfer into mice; they also increased interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß) production and inhibited signal transducer and activator of transcription (STAT) 4 and STAT6 signaling in the lungs after OVA sensitization. In conclusion, the BMDC adoptive transfer-induced immunogenic tolerance in OVA-sensitized mice might not be due to SOCS3 gene depletion. BMDC adoptive transfer may be developed into a new approach that alleviates asthma by modulating the balance between immune tolerance and inflammation.

Duraplasty of PHBV/PLA/Col membranes promotes axonal regeneration by inhibiting NLRP3 complex and M1 macrophage polarization in rats with spinal cord injury.

Duraplasty after decompression decreases the lesion size and scar formation, promoting better functional recovery, but the underlying mechanism has not been clarified. Here, we fabricated a series of poly(hydroxybutyrate-co-hydroxyvalerate)/polylactic acid/collagen (PHBV/PLA/Col) membranes and cultured them with VSC4.1 motor neurons. The material characteristics and in vitro biological characteristics were evaluated. In the subcutaneous implantation test, PHBV/PLA/COl scaffolds supported the cellular infiltration, microvasculature formation, and decreased CD86-positive macrophage aggregation. Following contusion spinal cord injury at T10 in Sprague-Dawley rats, durotomy was performed with allograft dura mater or PHBV/PLA or PHBV/PLA/Col membranes. At 3 days post-injury, Western blot assay showed decreased the expression of the NLRP3, ASC, cleaved-caspase-1, IL-1ß, TNF-α, and CD86 expression but increased the expression of CD206. Immunofluorescence demonstrated that duraplasty with PHBV/PLA/Col membranes reduced the infiltration of CD86-positive macrophages in the lesion site, decreased the glial fibrillary acidic protein expression, and increased the expression of NF-200. Moreover, duraplasty with PHBV/PLA/Col membranes improved locomotor functional recovery at 8 weeks post-injury. Thus, duraplasty with PHBV/PLA/Col membranes decreased the glial scar formation and promoted axon growth by inhibiting inflammasome activation and modulating macrophage polarization in acute spinal cord injury.

Endovascular treatment of the cavernous sinus dural arteriovenous fistula: current status and considerations.

A cavernous sinus dural arteriovenous fistula (CS-DAVF) is an abnormal arteriovenous communication involving the dura mater within or near the CS wall. The dural arteries from the internal carotid artery and external carotid artery supply the CS-DAVF, and the superior ophthalmic vein (SOV) and inferior petrous sinus (IPS) are frequent venous drainers. In CS-DAVF cases, high-risk lesions require treatment. Endovascular treatment (EVT) has been the first-line option for CS-DAVFs. To our knowledge, a review of the EVT of CS-DAVFs is lacking. Therefore, in this paper, we review the available literature on this issue. In addition, some illustrative cases are also provided to more concisely expound the EVT of CS-DAVFs. According to the recent literature, transvenous embolization via the IPS is considered the most effective method for EVT of CS-DAVFs. In addition, the transorbital approach is another reasonable choice. Other venous approaches can also be tried. Because of the low cure rate, transarterial embolization for CS-DAVFs is limited to only highly selected patients. In the EVT of CS-DAVFs, various agents have been used, including coil, Onyx, and n-butyl cyanoacrylate, with coil being the preferred one. In addition, when EVT cannot obliterate the CS-DAVF, stereotactic radiotherapy may be considered. In general, despite various complications, EVT is a feasible and effective method to manage CS-DAVFs by way of various access routes and can yield a good prognosis.

Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway.

BACKGROUND: Mesenchymal stem cells (MSCs) are suspected to exert neuroprotective effects in brain injury, in part through the secretion of extracellular vesicles like exosomes containing bioactive compounds. We now investigate the mechanism by which bone marrow MSCs (BMSCs)-derived exosomes harboring the small non-coding RNA miR-29b-3p protect against hypoxic-ischemic brain injury in rats. METHODS: We established a rat model of middle cerebral artery occlusion (MCAO) and primary cortical neuron or brain microvascular endothelial cell (BMEC) models of oxygen and glucose deprivation (OGD). Exosomes were isolated from the culture medium of BMSCs. We treated the MCAO rats with BMSC-derived exosomes in vivo, and likewise the OGD-treated neurons and BMECs in vitro. We then measured apoptosis- and angiogenesis-related features using TUNEL and CD31 immunohistochemical staining and in vitro Matrigel angiogenesis assays. RESULTS: The dual luciferase reporter gene assay showed that miR-29b-3p targeted the protein phosphatase and tensin homolog (PTEN). miR-29b-3p was downregulated and PTEN was upregulated in the brain of MCAO rats and in OGD-treated cultured neurons. MCAO rats and OGD-treated neurons showed promoted apoptosis and decreased angiogenesis, but overexpression of miR-29b-3p or silencing of PTEN could reverse these alterations. Furthermore, miR-29b-3p could negatively regulate PTEN and activate the Akt signaling pathway. BMSCs-derived exosomes also exerted protective effects against apoptosis of OGD neurons and cell apoptosis in the brain samples from MCAO rats, where we also observed promotion of angiogenesis. CONCLUSION: BMSC-derived exosomal miR-29b-3p ameliorates ischemic brain injury by promoting angiogenesis and suppressing neuronal apoptosis, a finding which may be of great significance in the treatment of hypoxic-ischemic brain injury.

Single-Stage Clipping of Seven Intracranial Aneurysms in the Anterior Circulation via Unilateral Pterional Approach: A Case Report and Literature Review.

The occurrence of multiple intracranial aneurysms (MIAs) is not rare, with a reported incidence of 15 to 35%. However, patients harboring seven or more intracranial aneurysms are so uncommon that only sporadic cases have ever been reported. We present a rare case with seven intracranial aneurysms (two anterior communicating artery aneurysms, two right middle cerebral artery aneurysms, two left ophthalmic artery aneurysms, and one right ophthalmic artery aneurysm) in the anterior circulation that were simultaneously clipped via the extended right pterional approach. The surgery was uneventful. The patient experienced a rapid postoperative recovery with no neurologic deficits. To our knowledge, this is the first case of seven bilateral intracranial aneurysms that were surgically clipped via unilateral craniotomy. This case showed that in properly selected patients with anterior circulation MIAs, even as many as seven, one-stage clipping can be achieved. Successful clipping of the contralateral ophthalmic aneurysms was the key step in the operation.

Gelatin Methacrylate (GelMA)-Based Hydrogels for Cell Transplantation: an Effective Strategy for Tissue Engineering.

Gelatin methacrylate (GelMA)-based hydrogels are gaining a great deal of attention as potentially implantable materials in tissue engineering applications because of their biofunctionality and mechanical tenability. Since different natural tissues respond differently to mechanical stresses, an ideal implanted material would closely match the mechanical properties of the target tissue. In this regard, applications employing GelMA hydrogels are currently limited by the low mechanical strength and biocompatibility of GelMA. Therefore, this review focuses on modifications made to GelMA hydrogels to make them more suitable for tissue engineering applications. A large number of reports detail rational synthetic processes for GelMA or describe the incorporation of various biomaterials into GelMA hydrogels to tune their various properties, e.g., physical strength, chemical properties, conductivity, and porosity, and to promote cell loading and accelerate tissue repair. A novel strategy for repairing tissue injuries, based on the transplantation of cell-loaded GelMA scaffolds, is examined and its advantages and challenges are summarized. GelMA-cell combinations play a critical and pioneering role in this process and could potentially accelerate the development of clinically relevant applications.

Glucagon like peptide 2 has a positive impact on osteoporosis in ovariectomized rats.

AIMS: In this study, we evaluate the effects of glucagon-like peptide 2 (GLP-2) on bone microarchitecture, bone turnover markers (BTMs) and inflammation markers in ovariectomized (OVX) rats. MATERIAL AND METHODS: In total, 31 Sprague-Dawley rats were divided into the following three groups: sham (control sham-operated with vehicle, n = 7), OV (OVX with vehicle, n = 12), and GLP-2 (OVX with GLP-2, n = 12). Intervention began at the 12th week after surgery and lasted for 4 weeks. The dosage of the GLP-2 was 160 µg/kg/d through subcutaneous injections, and normal saline was used as the vehicle agent. After 4 weeks of treatment, serum BTM and inflammation marker levels were measured by ELISA, and femora samples were analyzed by qRT-PCR, micro-CT, histology and histomorphometry. KEY FINDINGS: After 4 weeks of treatment, serum TRAcP-5b and RANKL levels as well as the CTX-1/P1NP ratio in the GLP-2 group decreased, and ALP activity, P1NP level, and OPG/RANKL ratio increased significantly; qRT-PCR analysis showed that mRNA levels of RANKL decreased, and Runx2, ALP, and Col-1 levels as well as the OPG/RANKL ratio increased significantly in the GLP-2 group compared with the OV group. In bone histology analysis, GLP-2 significantly decreased the AV/MV, Oc.N and Oc.S but increased the Ob.N, BFR and MAR. Analysis with µ-CT showed that the BMD, BV/TV, Tb.N and Conn.D increased significantly in the GLP-2 group compared with the OV group. The levels of serum inflammation markers TNF-α, IL-1ß and IL-6 decreased, and TGF-ß levels increased in the GLP-2 group compared with the OV group. SIGNIFICANCE: GLP-2 may have a positive impact on osteoporosis by promoting bone formation, inhibiting bone resorption and decreasing circulatory inflammation in ovariectomized rats.

Integration of mesenchymal stem cell sheet and bFGF-loaded fibrin gel in knitted PLGA scaffolds favorable for tendon repair.

Tendon injuries are common and require a long time to heal, and are particularly associated with some adverse problems such as adhesion and rupture. Herein, we aim to develop new bioactive scaffolds endowed with stem cell sheets and growth factors to enable cell migration and proliferation favorable for tendon regeneration in situ. An exogenous basic fibroblast growth factor (bFGF)-loaded fibrin gel was firstly incorporated into the porous network of knitted poly(lactide-co-glycolide) (PLGA) scaffolds and then sheets of mesenchymal stem cells (MSCs) were also integrated into the scaffolds. It was shown that the pores in the knitted PLGA scaffold were readily filled with a complex network of fibrin fiber gel and the fibrin fibers were beneficial for the controlled release of bFGF over a long time period. After transplantation in a critical-size Achilles tendon defect model (7 mm) in the rat right hindlimb, gross observation revealed no immunologic incompatibility or rejection derived from the scaffold systems. It was observed that the MSC sheets contributed directly to tendon regeneration, and exerted an environment-modifying effect on the injuries in situ, consistent with the beneficial effect of bFGF. It was interesting that the knitted PLGA-fibrin gel scaffolds loaded with MSC sheets and bFGF showed the highest expression of tendon-related gene markers and outstanding repair efficacy, including appreciable biomechanical strength and native-like histological microstructures. Therefore, the integration of MSC sheets and bFGF into PLGA/bFGF-fibrin gel scaffolds may stimulate the proliferation and tenogenic differentiation of MSCs in situ and synergistically enhance the injured tendon reconstruction.

Current status of endovascular treatment for dural arteriovenous fistula of the transverse-sigmoid sinus: A literature review.

Most intracranial dural arteriovenous fistulae (DAVFs) involve the transverse-sigmoid sinus (TSS), and various types of endovascular treatment (EVT) have been involved in managing TSS DAVFs. A current, comprehensive review of the EVT of TSS DAVFs is lacking. This study used the PubMed database to perform a literature review on TSS DAVFs to increase the current understanding of this condition. For high-grade TSS DAVFs such as Borden type 3, the goal of EVT is curative treatment. However, for low-grade TSS DAVFs such as Borden type 1 and some Borden type 2 TSS DAVFs, symptom relief or elimination of cortical reflux may be sufficient. Currently, EVT has become the first-line treatment for TSS DAVFs, including transarterial embolization (TAE), transvenous embolization (TVE) or both. TAE alone and TSS balloon-assisted TAE are also commonly used. However, TVE for TSS DAVFs is recognized as the most effective treatment, including coil direct packing TSS, Onyx® (ethylene vinyl alcohol copolymer) TVE, and balloon-assisted Onyx® TVE, which are commonly applied. In addition, TSS reconstructive treatment can be an effective procedure to treat TSS DAVFs. EVT is accompanied with complications, including technique- and treatment-related complications. Although complications may occur, TSS DAVFs have an acceptable prognosis after EVT.