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  • 1.

    【2hr】Additional Use of Synovial Mesenchymal Stem Cell Transplantation FollowingSurgical Repair of a Complex Degenerative Tear of the Medial Meniscus of the Knee: A CaseReport

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    机译 滑膜间充质干细胞移植后的其他用途膝内侧半月板的复杂退化性撕裂的外科修复：一例报告
    摘要：Complex degenerative tears of the medial meniscus in the knee are usually treated using meniscectomy. However, this procedure increases the risk of osteoarthritis, while other treatments aimed at meniscal repair remain challenging due to the high possibility of failure. The use of synovial mesenchymal stem cells (MSCs) is an attractive additional approach for meniscal repair, as these cells have high proliferative and chondrogenic potential. In this case report, we surgically repaired a complex degenerative tear of the medial meniscus and then transplanted autologous synovial MSCs. We evaluated clinical outcomes at 2 years and assessed adverse events. We enrolled patients with clinical symptoms that included a feeling of instability in addition to pain caused by their complex degenerative tears of the medial meniscus. Two weeks after surgical repair of the torn meniscus, autologous synovial MSCs were transplanted onto the menisci of five patients. The total Lysholm knee score, the Knee Injury and Osteoarthritis Outcome Scale scores for “pain,” “daily living,” “sports activities,” and the Numerical Rating Scale were significantly increased after 2 years. Three adverse events, an increase in c-reactive protein, joint effusion, and localized warmth of the knee were recorded, although these could have been due to the meniscal repair surgery. This first-in-human study confirmed that the combination of surgical repair and synovial MSC transplantationimproved the clinical symptoms in patients with a complex degenerative tear of the medialmeniscus. No adverse events occurred that necessitated treatment discontinuation. Thesefindings will serve as pilot data for a future prospective study.
  • 2.

    【2hr】Substance Use Disorder, Intravenous Injection, and HIV Infection: AReview

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    机译 物质使用障碍，静脉注射和HIV感染：A评论
    摘要：DSM-V-defined substance use disorder comprises four groups of symptoms: impaired control,social impairment, risky use, and pharmacological reactions. Behavioral patterns ofimpaired control, including impulsivity and risk taking, are associated with HIV riskbehaviors. Substance users with stronger craving symptoms are more likely to use drugs viaintravenous injection than other routes because of the faster drug effect and the higherbioavailability; thus, they are at high risk of HIV infection. HIV risk behaviors such asunprotected sex and intravenous injection facilitate HIV disease spread. Public healthpolicies such as Needle and Syringe Exchange Programs and medication-assisted treatmentare proven to reduce HIV risk behaviors such as the frequency of intravenous injection andeven the incidence of HIV infection, but both of them have limitations. While intravenousinjection is a frequently discussed issue in public policies and the HIV-relatedliterature, it is a much less frequent topic in the addiction literature. We believed thatunderstanding the mental substrate behind impulsivity/risk taking and the possiblebiological mechanism of intravenous injection may help in creating more effectivestrategies to slow down HIV infection.
  • 3.

    【2hr】Preservation Solutions for Kidney Transplantation: History, Advances andMechanisms

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    机译 肾脏移植的保存解决方案：历史，进展和机制
    摘要：Solid organ transplantation was one of the greatest medical advances during the past fewdecades. Organ preservation solutions have been applied to diminish ischemic/hypoxicinjury during cold storage and improve graft survival. In this article, we provide ageneral review of the history and advances of preservation solutions for kidneytransplantation. Key components of commonly used solutions are listed, and effectivesupplementations for current available preservation solutions are discussed. At cellularand molecular levels, further insights were provided into the pathophysiologicalmechanisms of effective ingredients against ischemic/hypoxic renal injury during coldstorage. We pay special attention to the cellular and molecular events duringtransplantation, including ATP depletion, acidosis, mitochondrial dysfunction, oxidativestress, inflammation, and other intracellular mechanisms.
  • 4.

    【2hr】Research Status of Mesenchymal Stem Cells in LiverTransplantation

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    机译 肝间充质干细胞的研究现状移植
    摘要：Liver transplantation has been deemed the best choice for end-stage liver diseasepatients but immune rejection after surgery is still a serious problem. Patients have totake immunosuppressive drugs for a long time after liver transplantation, and this oftenleads to many side effects. Mesenchymal stem cells (MSCs) gradually became of interest toresearchers because of their powerful immunomodulatory effects. In the past, a largenumber of in vitro and in vivo studies have demonstrated the great potential of MSCs forparticipation in posttransplant immunomodulation. In addition, MSCs also have propertiesthat may potentially benefit patients undergoing liver transplantation. This article aimsto provide an overview of the current understanding of the immunomodulation achieved bythe application of MSCs in liver transplantation, to discuss the problems that may beencountered when using MSCs in clinical practice, and to describe some of the underlyingcapabilities of MSCs in liver transplantation. Cell–cell contact, soluble molecules, andexosomes have been suggested to be critical approaches to MSCs’ immunoregulation in vitro;however, the exact mechanism, especially in vivo, is still unclear. In recent years, theclinical safety of MSCs has been proven by a series of clinical trials. The obstacles tothe clinical application of MSCs are decreasing, but large sample clinical trialsinvolving MSCs are still needed to further study their clinical effects.
  • 5.

    【2hr】The Gut Microbiota in Multiple Sclerosis: An Overview of ClinicalTrials

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    机译 多发性硬化症的肠道菌群：临床概述试用版
    摘要：Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, anddegenerative disease that affects the central nervous system. A recent studyshowed that interaction between the immune system and the gut microbiota plays acrucial role in the development of MS. This review reports the clinical studiescarried out in recent years that aimed to evaluate the composition of themicrobiota in patients with relapsing–remitting MS (RR-MS). We also report whatis available in the literature regarding the effectiveness of fecal microbiotatransplantation and the role of the diet in restoring the intestinal bacterialpopulation. Studies report that patients with RR-MS have a microbiota that,compared with healthy controls, has higher amounts of , , , , , , , , and . Incontrast, MS patients have a microbiota with impoverished microbial populationsof , , , , , , , , , and . In conclusion, the restoration of themicrobial population in patients with RR-MS appears to reduce inflammatoryevents and the reactivation of the immune system.
  • 6.

    【2hr】Measuring the Antimicrobial Activity of Lauric Acid against Various Bacteriain Human Gut Microbiota Using a New Method

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    机译 测量月桂酸对各种细菌的抗菌活性新方法研究人类肠道菌群
    摘要：Lauric acid (LA) has a broad spectrum of anti-microbiological activities againstenveloped viruses and various bacteria, and might be useful to protect against microbialinfection and control the balance and distribution of bacteria in human gut microbiota. Itis not necessarily more difficult to measure antimicrobial activity the traditional way,but it is, however, more laborious. In the present study, we developed a new method tomeasure the antimicrobial activity of LA in multiple samples with a microplate reader. A“test complex” (TC) was produced consisting of 100 μL of agar medium with LA in the bottomlayer and 300 μL of broth in the top layer in 96-well deep-well microplates. Afterward,analysis of the broth in the top layer showed that the antimicrobial activity was the sameas that of the “control complex,” (CC) which consisted of 100 μL of agar medium in thebottom layer and 300 μL of broth with LA in the top layer. Furthermore, evaluation of theantimicrobial effect of the TC when using a microplate reader was the same as that withthe use of the colony counting method. The colony counting method has confirmed that theantimicrobial activity of LA when bacteria are inoculated into the broth was equivalentbetween CC and TC, and we validated this by correlating the number of bacteria withabsorbance. In addition, the broth itself in TC was transparent enough that the turbidityof broth can be used as an index of the number of bacteria, which enabled the use of amicroplate reader for multiple samples. For human gut microbes, LA was shown to have lowantimicrobial activity against commensal lactic acid bacteria, but high antimicrobialactivity against pathogenic and ,suggesting that LA might modulate intestinal health, as confirmed by the proposedmethod.
  • 7.

    【2hr】Non-Invasive Cell Tracking with Brighter and Red-Transferred Luciferase forPotential Application in Stem Cell Therapy

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    机译 使用更明亮和红色转移的萤光素酶进行无创细胞追踪在干细胞治疗中的潜在应用
    摘要：This study investigated the safety of a novel cell-labeling technology with mKATE and luciferase (mKATE-renLUC) and assessed the efficacyon tracking implanted human placental stromal cells (PSC) in an erectile dysfunction (ED)animal model. Human PSC were labeled with mKATE-renLUC using a lentivirus. Cell viability,apoptosis, proliferation, migration, surface marker expression and differentiationpotential of the labeled PSC were evaluated and compared with non-labeled PSC. Theparacrine profile of labeled cells was examined using an angiogenesis protein array. Thebrightness and duration of labeled cells with different densities were evaluated. An EDrat model was established and labeled PSC were injected into cavernosal tissue of thepenis. The migration and distribution of transplanted PSC were monitored using an IVISimaging system in real time. Implanted PSC were identified in isolated tissues viadetection of mKATE fluorescence. The cell viability, morphology, proliferation, migration,surface marker expression and differentiation potential of mKATE-renLUC-labeled PSC weresimilar to those of non-labeled cells in vitro (no statistical difference >0.05). Similar expressions of trophic factors were found betweenlabeled and non-labeled PSC. The migration and distribution of PSC expressing renLUC weretracked in vivo using IVIS imaging system. mKATE-positive PSC were detected in penile,kidney, prostate and hepatic tissues using histological methods. This labeling technologyprovides a safe and effective cell-tracking approach with a brighter fluorophore andcodon-optimized luciferase.
  • 8.

    【2hr】hUC-MSCs Exert a Neuroprotective Effect via Anti-apoptotic Mechanisms in aNeonatal HIE Rat Model

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    机译 hUC-MSC通过抗凋亡机制发挥神经保护作用新生儿HIE大鼠模型
    摘要：In this study, we investigated how human umbilical cord mesenchymal stem cells exerted aneuroprotective effect via antiapoptotic mechanisms in a neonatal hypoxic-ischemicencephalopathy rat model. A total of 78 10-day old (P10) rats were used. After humanumbilical cord mesenchymal stem cells were collected from human umbilical cords andamplified in culture, they were administered to rat subjects 1 h after inducedhypoxic-ischemic encephalopathy treatment. The short-term (48 h) and long-term (28 day)outcomes were evaluated after human umbilical cord mesenchymal stem cells treatment usingneurobehavioral function assessment. Triphenyltetrazolium chloride monohydrate stainingwas performed at 48 h. Beclin-2 and caspase-3 levels were evaluated with Western blot andreal time polymerase chain reaction at 48 h. Human umbilical cord mesenchymal stem cellswere collected and administrated to hypoxic-ischemic encephalopathy pups byintracerebroventricular injection. Hypoxic-ischemic encephalopathy typically inducedsignificant delay in development and caused impairment in both cognitive and motorfunctions in rat subjects. Human umbilical cord mesenchymal stem cells were shown toameliorate hypoxic-ischemic encephalopathy-induced damage and improve both cognitive andmotor functions. Although hypoxic-ischemic encephalopathy induced significant expressionof caspase-3 and Beclin-2, human umbilical cord mesenchymal stem cells decreased theexpression of both of them. Human umbilical cord mesenchymal stem cells may serve as apotential treatment to ameliorate brain injury in hypoxic-ischemic encephalopathypatients.
  • 9.

    【2hr】Topical Application of Human Wharton’s Jelly Mesenchymal Stem CellsAccelerates Mouse Sciatic Nerve Recovery and is Associated with Upregulated NeurotrophicFactor Expression

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    机译 沃顿商学院的果冻间充质干细胞的局部应用加速小鼠坐骨神经恢复，并与神经营养上调相关因子表达
    摘要：Peripheral nerve regeneration following injury is often slow and impaired, which resultsin weakened and denervated muscle with subsequent atrophy. Human Wharton’s jellymesenchymal stem cells (hWJ-MSC) have potential regenerative properties which, however,remain unknown in mouse nerve recovery. This study investigated the effect of the topicalapplication of hWJ-MSC onto repairing transected sciatic nerves in a mouse model. Humanadipocyte-derived stem cells (hADSC) were used as a positive control. The sciatic nerve ofBALB/c mice was transected at a fixed point and repaired under the microscope using 10-0sutures. hWJ-MSC and hADSC were applied to the site of repair and mice were followed upfor 1 year. The hWJ-MSC group had significantly better functional recovery of five-toespread and gait angles compared with the negative control and hADSC groups. hWJ-MSCimproved sciatic nerve regeneration in a dose-dependent fashion. The hWJ-MSC group had abetter quality of regenerated nerve with an increased number of myelinated axonsthroughout. hWJ-MSC appear to be safe in mice after 1 year of follow-up. hWJ-MSC alsoexpressed higher levels of neurotrophic factor-3, brain-derived neurotrophic factor, andglial-derived neurotrophic factor than hADSC. hWJ-MSC may promote better nerve recoverythan hADSC because of this upregulation of neurotrophic factors.
  • 10.

    【2hr】Rat Facial Nerve Regeneration with Human Immature Dental Pulp StemCells

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    机译 人牙髓未成熟的大鼠面神经再生细胞
    摘要：Facial paralysis can result in severe implications for the patients. However, stem cellbiology has become an important field in regenerative medicine since the discovery andcharacterization of mesenchymal stem cells. Our aim was to evaluate the regeneration afterfacial nerve crush injury and application of human immature dental pulp stem cells(iDPSC). For this study 70 Wistar rats underwent a unilateral facial nerve crush injuryand were divided into two groups: Group I (GI): Crushed; Group II (GII): Crushed andiDPSC, and distributed into study periods of 3, 7, 14, 21, and 42 postoperative days.Facial nerve regeneration was analyzed via functional recovery of whisker movement,histomorphometric analysis, and immunoblotting assay. The results show that GII hadcomplete functional recovery at 14 days, while GI recovered after 42 days. Also, regardingthe facial nerve trunk, GII presented histological improvement, evidencing better axonaland structural organization of the myelin sheath, and exhibited statistically highervalues for the outer and inner perimeters and g-ratio. Nevertheless, GI exhibitedstatistically higher values for the thickness of myelin sheath. In the buccal branch, nodifferences were observed for all parameters between groups. At 42 days, both groups GIand GII were close to the levels observed for the control group. Concerning nerve growthfactor expression, GII exhibited statistically greater values ( <0.05) compared with the control group at 7 days. In summary, a single injection of humaniDPSC promoted a positive effect on regeneration of the facial nerve trunk after 14 daysand provided an alternative to support regeneration following peripheral nerve injury.
  • 11.

    【2hr】Intravenous transplantation of olfactory bulb ensheathing cells for a spinalcord hemisection injury rat model

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    机译 嗅球鞘细胞的静脉移植脊髓半截损伤大鼠模型
    摘要：Cellular transplantation strategies utilizing intraspinal or intrathecal olfactoryensheathing cells (OECs) have been reported as beneficial for spinal cord injury (SCI).However, there are many disadvantages of these methods, including additional trauma to thespinal cord parenchyma and technical challenges. Therefore, we investigated thefeasibility and potential benefits of intravenous transplantation of OECs in a rathemisection SCI model. OECs derived from olfactory bulb tissue were labeled with quantumdots (QDs), and their biodistribution after intravenous transplantation was tracked usinga fluorescence imaging system. Accumulation of the transplanted OECs was observed in theinjured spinal cord within 10 min, peaked at seven days after cell transplantation, anddecreased gradually thereafter. This time window corresponded to the blood–spinal cordbarrier (BSCB) opening time, which was quantitated with the Evans blue leakage assay.Using immunohistochemistry, we examined neuronal growth (GAP-43), remyelination (MBP), andmicroglia (Iba-1) reactions at the lesion site. Motor function recovery was also measuredusing a classic open field test (Basso, Beattie and Bresnahan score). Compared with thegroup injected only with QDs, the rats that received OEC transplantation exhibited aprominent reduction in inflammatory responses, increased neurogenesis and remyelination,and significant improvement in motor function. We suggest that intravenous injection couldalso be an effective method for delivering OECs and improving functional outcomes afterSCI. Moreover, the time course of BSCB disruption provides a clinically relevanttherapeutic window for cell-based intervention.
  • 12.

    【2hr】Comparing the Effects of the mTOR Inhibitors Azithromycin and Rapamycin on InVitro Expanded Regulatory T Cells

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    机译 比较mTOR抑制剂阿奇霉素和雷帕霉素对In的影响体外扩增调节性T细胞
    摘要：Adoptive transfer of autologous polyclonal regulatory T cells (Tregs) is a promisingoption for reducing graft rejection in allogeneic transplantation. To gain therapeuticlevels of Tregs there is a need to expand obtained cells ex vivo, usually in the presenceof the mTOR inhibitor Rapamycin due to its ability to suppress proliferation of non-Treg Tcells, thus promoting a purer Treg yield. Azithromycin is a bacteriostatic macrolide withmTOR inhibitory activity that has been shown to exert immunomodulatory effects on severaltypes of immune cells. In this study we investigated the effects of Azithromycin, comparedwith Rapamycin, on Treg phenotype, growth, and function when expanding bulk, naïve, andmemory Tregs. Furthermore, the intracellular concentration of Rapamycin in CD4+ T cells aswell as in the culture medium was measured for up to 48 h after supplemented. Tregphenotype was assessed by flow cytometry and Treg function was measured as inhibition ofresponder T-cell expansion in a suppression assay. The concentration of Rapamycin wasquantified with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS).Azithromycin and Rapamycin both promoted a FoxP3-positive Treg phenotype in bulk Tregs,while Rapamycin also increased FoxP3 and FoxP3+Helios positivity in naïve and memoryTregs. Furthermore, Rapamycin inhibited the expansion of naïve Tregs, but also increasedtheir suppressive effect. Rapamycin was quickly degraded in 37°C medium, yet was retainedintracellularly. While both compounds may benefit expansion of FoxP3+ Tregs in vitro,further studies elucidating the effects of Azithromycin treatment on Tregs are needed todetermine its potential use.
  • 13.

    【2hr】A circular RNA derived from MMP9 facilitates oral squamous cell carcinomametastasis through regulation of MMP9 mRNA stability

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    机译 源自MMP9的环状RNA促进口腔鳞状细胞癌通过调节MMP9 mRNA的稳定性进行转移
    摘要：Emerging evidence demonstrates that dysregulation of circular RNA is linked totumorigenesis and aggressive progression. However, its role in oral squamous cellcarcinoma remains largely uncharacterized. In this study, we identified a novelmetastasis-associated circular RNA, circular matrix metalloproteinase 9 (hsa_circ_0001162,a circular RNA derived from matrix metalloproteinase 9), which was remarkably upregulatedin oral squamous cell carcinoma and positively correlated with matrix metalloproteinase 9expression. Patients with high circular matrix metalloproteinase 9 expression were proneto lymph node metastasis and an advanced TNM stage. Importantly, circular matrixmetalloproteinase 9 was identified as an efficacious diagnostic and prognostic biomarkerfor oral squamous cell carcinoma patients. Functional experiments showed that depletion ofcircular matrix metalloproteinase 9 weakened the migratory and invasive capabilities oforal squamous cell carcinoma cells in vitro as well as inhibited lung metastasis in vivo.Regarding the mechanism, circular matrix metalloproteinase 9 could simultaneously interactwith AUF1 and miR-149 to block the inhibitory effect of AUF1 and miR-149 on matrixmetalloproteinase 9 3′-untranslated region, resulting in enhanced matrix metalloproteinase9 messenger RNA stability, thereby facilitating oral squamous cell carcinoma metastasis.Collectively, our data indicate that circular matrix metalloproteinase 9 acts as ametastasis-promoting gene in oral squamous cell carcinoma through regulating the messengerRNA stability of its parental gene. Therapeutic targeting of circular matrixmetalloproteinase 9 may be a promising treatment intervention for metastatic oral squamouscell carcinoma patients.
  • 14.

    【2hr】A Phase 1 Study of Intravenous Busulfan as a Conditioning Regimen forMultiple Myeloma

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    机译 静脉白硫素作为调理方案的一期研究。多发性骨髓瘤
    摘要：The efficacy of melphalan (MEL) 140 mg/m pre-transplant conditioning versusMEL 200 mg/m for the elderly is still debated. We hypothesized thatsingle-agent intravenous busulfan (BU) would show significant anti-myeloma efficacy and bebetter tolerated by elderly patients. A prospective 3+3 dose escalation study enrolledsymptomatic multiple myeloma (MM) patients 65 years or older with SWOG performance 0–2 fortreatment with intravenous BU pre-transplant at different administration levels. Theprimary objective was to determine the maximum tolerated dose (MTD) of BU that could besafely given over the least number of days. All patients, except one, received maintenancetreatment post-transplant, mostly for 2 years. We enrolled 13 patients, mean age of 73years (range 68–80). Pharmacokinetic analysis showed no greater than 2% accumulation inthe 13 patients, confirming a lack of accumulation in the multi-dose regimen. No deathsoccurred in the peri-transplant period. Grade 3/4 adverse effects were hematological, nodose-limiting toxicity was observed and MTD was not reached. Three patients developedgrade 3 mucositis but none developed veno-occlusive disease. Ten (77%) patients achieved acomplete remission (CR) post-transplant with a remarkably long average time to bestresponse of 6.7 months (range: 6–14 m), and two attained a partial response. Medianoverall survival was 84 months (95% CI, 21–104) and the median progression-free survivalwas 60 months (95% CI, 9–93). Our results suggest that IV BU could be an alternativeconditioning regimen to MEL 140 in elderly patients with MM, and supports futurerandomized trials.
  • 15.

    【2hr】Combination treatment of autologous bone marrow stem cell transplantation andhyperbaric oxygen therapy for type 2 diabetes mellitus: A randomized controlledtrial

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    机译 自体骨髓干细胞移植联合治疗2型糖尿病高压氧治疗：随机对照试用
    摘要：The objective of this study was to compare standard treatment versus the combination ofintrapancreatic autologous stem cell (ASC) infusion and hyperbaric oxygen treatment (HBOT)before and after ASC in the metabolic control of patients with type 2 diabetes mellitus(T2DM). This study was a prospective, randomized controlled trial. The combinedintervention consisted of 10 sessions of HBOT before the intrapancreatic infusion of ASCand 10 sessions afterwards. ASCs were infused into the main arterial supply of thepancreas to maximize the presence of the stem cells where the therapeutic effect is mostdesired. A total of 23 patients were included (control group = 10, intervention group =13). Age, gender, diabetes duration, number of medications taken, body weight and height,and insulin requirements were recorded at baseline and every three months. Also, body massindex, fasting plasma glucose, C-peptide, and HbA1c, C-peptide/glucose ratio (CPGR) weremeasured every three months for one year. HbA1c was significantly lower in theintervention group compared with control throughout follow-up. Overall, 77% of patients inthe intervention group and 30% of patients in the control group demonstrated a decrease ofHbA1c at 180 days (compared with baseline) of at least 1 unit. Glucose levels weresignificantly lower in the intervention group at all timepoints during follow-up.C-peptide levels were significantly higher in the intervention group during follow-up andat one year: 1.9 ± 1.0 ng/mL versus 0.7 ± 0.4 ng/mL in intervention versus control groups,respectively, = 0.0021. CPGR was higher in the intervention group atall controls during follow-up. The requirement for insulin was significantly lower in theintervention group at 90, 180, 270, and 365 days. Combined therapy of intrapancreatic ASCinfusion and HBOT showed increased metabolic control and reduced insulin requirements inpatients with T2DM compared with standard treatment.
  • 16.

    【2hr】Production, Characterization, and Function of Pseudoislets from PerinatalCanine Pancreas

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    机译 围产期假胰岛的产生，表征和功能犬胰腺
    摘要：We evaluated the cell composition and function of canine pancreatic pseudoislets (PIs)produced from 42- to 55-day-old fetuses, 1- to 21-day-old pups, and an adult dog pancreas.After mild collagenase treatment, partially digested tissues were cultured for 2–3 weeks.PI production started on culture day 3, was marked for 6 to 9 days, and then stopped. PIproduction was greatest with the neonatal specimens, reaching about 12 million aggregatesper litter (55-day-old fetus) or per pancreas (1-day-old pup). Cell composition at allstages was similar to that in adult pancreatic islets, with predominant β cells, scant αcells and, most importantly, presence of δ cells. Among pancreatic markers assessed byquantitative real-time PCR (qRT-PCR) mRNA assay, insulin showed the highest expressionlevels in PIs from newborn and adult pancreas, although these were more than 1000 timeslower than in adult islets. Pdx1 mRNA expression was high in PIs from 55-day-oldpancreases and was lower at later stages. Consistent with the qRT-PCR results, the insulincontent was far lower than reported in adult dog pancreatic islets. However, insulinrelease by PIs from 1-day-old pups was demonstrated and was stimulated by a high-glucosemedium. PIs were transplanted into euglycemic and diabetic SCID mice. In euglycemicanimals, the transplant cell composition underwent maturation and transplants were stillviable after 6 months. In diabetic mice, the PI transplants produced insulin and partiallycontrolled the hyperglycemia. These data indicate that PIs can be produced ex vivo fromcanine fetal or postnatal pancreases. Although functional PIs can be obtained, theproduction yield is most likely insufficient to meet the requirements for diabetic dogtransplantation without further innovation in cell culture amplification.
  • 17.

    【2hr】Pretreatment of Diabetic Adipose-derived Stem Cells with mitoTEMPO Reversestheir Defective Proangiogenic Function in Diabetic Mice with Critical LimbIschemia

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    机译 mitoTEMPO逆转预处理糖尿病性脂肪干细胞对其具有严重肢体的糖尿病小鼠的促血管生成功能的破坏缺血
    摘要：Adipose-derived stem cells (ADSCs) have the ability to migrate to injury sites andfacilitate tissue repair by promoting angiogenesis. However, the therapeutic effect ofADSCs from patients with diabetes is impaired due to oxidative stress. Given that diabetesis a group of metabolic disorders and mitochondria are a major source of reactive oxygenspecies (ROS), it is possible that mitochondrial ROS plays an important role in theinduction of diabetic ADSC (dADSC) dysfunction. ADSCs isolated from diabetic mice weretreated with mitoTEMPO, a mitochondrial ROS scavenger, or TEMPO, a universal ROSscavenger, for three passages. The results showed that pretreatment with mitoTEMPOincreased the proliferation, multidifferentiation potential, and the migration andproangiogenic capacities of dADSCs to levels similar to those of ADSCs from control mice,whereas pretreatment with TEMPO showed only minor effects. Mechanistically, mitoTEMPOpretreatment enhanced the mitochondrial antioxidant capacity of dADSCs, and knockdown ofsuperoxide dismutase reduced the restored mitochondrial antioxidant capacity andattenuated the proangiogenic effects induced by mitoTEMPO pretreatment. In addition,mitoTEMPO pretreatment improved the survival of dADSCs in diabetic mice with critical limbischemia, showing protective effects similar to those of control ADSCs. Pretreatment ofdADSCs with mitoTEMPO decreased limb injury and improved angiogenesis in diabetic micewith critical limb ischemia. These findings suggested that short-term pretreatment ofdADSCs with a mitochondrial ROS scavenger restored their normal functions, which may be aneffective strategy for improving the therapeutic effects of ADSC-based therapies inpatients with diabetes.
  • 18.

    【2hr】PRMT5 Promotes Human Lung Cancer Cell Apoptosis via Akt/Gsk3β SignalingInduced by Resveratrol

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    机译 PRMT5通过Akt /Gsk3β信号促进人类肺癌细胞凋亡白藜芦醇诱导
    摘要：Protein arginine methyltransferase 5 (PRMT5) is implicated in various types of humancancer and tumor development, especially in lung cancer. Nevertheless, it is still unclearwhether suppression of PRMT5 could promote lung cancer cell apoptosis and chemosensitivityinduced by resveratrol, and the underlying molecular mechanism remains completely unknown.Here, we showed that PRMT5 was overexpressed in human lung cancer tissues and differenttypes of lung cancer cell lines. Moreover, we constructed PRMT5 stable knockdown celllines (A549 and ASCT-a-1) and investigated the roles of PRMT5 and the related signalingpathway in lung cancer cell apoptosis induced by resveratrol. Our results indicated thatinhibition or down-regulation of PRMT5 by GSK591, a PRMT5-specific inhibitor, or shRNAsmarkedly enhanced cell apoptosis and chemosensitivity stimulated by resveratrol. Furtherinvestigation showed that inhibition or down-regulation of PRMT5 further reduced Akt/GSK3βphosphorylation and the downstream targets cyclin D1 and E1 expression upon resveratroltreatment. Our findings suggest that PRMT5 is a pivotal mediator for human lung cancercell death induced by resveratrol, which also reveals that PRMT5 may serve as a newtherapeutic target for the treatment of human lung cancer.
  • 19.

    【2hr】Endothelial Progenitor Cells Attenuate Ventilator-Induced Lung Injury withLarge-Volume Ventilation

    包量

    机译 内皮祖细胞可减轻呼吸机所致的肺损伤大容量通风
    摘要：Ventilator-induced lung injury (VILI) is a common complication that results fromtreatment with mechanical ventilation (MV) in acute respiratory distress syndrome (ARDS)patients. The present study investigated the effect of endothelial progenitor cell (EPC)transplantation on VILI. Wistar rats were divided into three groups ( =8): sham (S), VILI model (V) induced by tidal volume ventilation (17 mL/kg), and VILI plusEPC transplantation (VE) groups. The lung PaO /FiO ratio, pulmonarywet-to-dry (W/D) weight ratio, number of neutrophils, total protein, neutrophil elastaselevel, and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum wereexamined. Furthermore, the histological and apoptotic analysis, and lung tissue proteinexpression analysis of Bax, Bcl-2, cleaved caspase-3, matrix metalloproteinase (MMP)-9,total nuclear factor kappa B (total-NF-κB), phosphorylated NF-κB (phospho-NF-κB) andmyosin light chain (MLC) were performed. The ventilation-induced decrease inPaO /FiO ratio, and the increase in W/D ratio and total proteinconcentration were prevented by the EPC transplantation. The EPC transplantation (VEgroup) significantly attenuated the VILI-induced increased expression of tumor necrosisfactor (TNF)-α, interleukin (IL)-1β, IL-8, MMP-9, phospho-NF-κB and MLC, neutrophilelastase levels and neutrophil counts in BALF. In addition, the anti-inflammatory factorIL-10 increased in the VE group. Furthermore, pulmonary histological injury and apoptosis(TUNEL-positive cells, increase in Bax and cleaved caspase-3) were considerably diminishedby the EPC transplantation. The EPC transplantation ameliorated the VILI. The mechanismmay be primarily through the improvement of epithelial permeability, inhibition of localand systemic inflammation, and reduction in apoptosis.
  • 20.

    【2hr】HBO Promotes the Differentiation of Neural Stem Cells via InteractionsBetween the Wnt3/β-Catenin and BMP2 Signaling Pathways

    包量

    机译 HBO通过相互作用促进神经干细胞的分化在Wnt3 /β-Catenin和BMP2信号通路之间
    摘要：Hyperbaric oxygen (HBO) therapy may promote neurological recovery from hypoxic-ischemicencephalopathy (HIE). However, the therapeutic effects of HBO and its associatedmechanisms remain unknown. The canonical Wnt/β-catenin signaling pathways and bonemorphogenetic protein (BMP) play important roles in mammalian nervous system development.The present study examined whether HBO stimulates the differentiation of neural stem cells(NSCs) and its effect on Wnt3/β-catenin and BMP2 signaling pathways. We showed HBOtreatment (2 ATA, 60 min) promoted differentiation of NSCs into neurons andoligodendrocytes in vitro. In addition, rat hypoxic-ischemic brain damage (HIBD) tissueextracts also promoted the differentiation of NSCs into neurons and oligodendrocytes, withthe advantage of reducing the number of astrocytes. These effects were most pronouncedwhen these two were combined together. In addition, the expression of Wnt3a, BMP2, andβ-catenin nuclear proteins were increased after HBO treatment. However, blockade ofWnt/β-catenin or BMP signaling inhibited NSC differentiation and reduced the expression ofWnt3a, BMP2, and β-catenin nuclear proteins. In conclusion, HBO promotes differentiationof NSCs into neurons and oligodendrocytes and reduced the number of astrocytes in vitropossibly through regulation of Wnt3/β-catenin and BMP2 signaling pathways. HBO may serveas a potential therapeutic strategy for treating HIE.
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