Adipose tissue-derived mesenchymal stem cells (AT-MSCs) offer potential as a therapeutic option for chronic discogenic low back pain (LBP) because of their immunomodulatory functions and capacity for ...cartilage differentiation. The goal of this study was to assess the safety and tolerability of a single intradiscal implantation of combined AT-MSCs and hyaluronic acid (HA) derivative in patients with chronic discogenic LBP.
We performed a single-arm phase I clinical trial with a 12-month follow-up and enrolled 10 eligible chronic LBP patients. Chronic LBP had lasted for more than 3 months with a minimum intensity of 4/10 on a visual analogue scale (VAS) and disability level ≥ 30% on the Oswestry Disability Index (ODI). The 10 patients underwent a single intradiscal injection of combined HA derivative and AT-MSCs at a dose of 2 × 10
cells/disc (n = 5) or 4 × 10
cells/disc (n = 5). Safety and treatment outcomes were evaluated by assessing VAS, ODI, Short Form-36 (SF-36), and imaging (lumbar spine X-ray imaging and MRI) at regular intervals over 1 year.
No patients were lost at any point during the 1-year clinical study. We observed no procedure or stem cell-related adverse events or serious adverse events during the 1-year follow-up period. VAS, ODI, and SF-36 scores significantly improved in both groups receiving both low (cases 2, 4, and 5) and high (cases 7, 8, and 9) cell doses, and did not differ significantly between the two groups. Among six patients who achieved significant improvement in VAS, ODI, and SF-36, three patients (cases 4, 8, and 9) were determined to have increased water content based on an increased apparent diffusion coefficient on diffusion MRI.
Combined implantation of AT-MSCs and HA derivative in chronic discogenic LBP is safe and tolerable. However, the efficacy of combined AT-MSCs and HA should be investigated in a randomized controlled trial in a larger population.
ClinicalTrials.gov NCT02338271 . Registered 7 January 2015.
Hydrogels are physically and chemically cross-linked, 3D, porous, hydrated molecular structures that mimic the native tissue microenvironment. Hydrogels fabricated with environmentally sensitive ...polymers can possess additional properties such as thermoresponsiveness. This property originates from its phase transition from gel to solution and vice versa with temperature variation. Phase transition mechanisms also depend on the interaction between the polymers and surrounding environment. Their thermoresponsiveness makes hydrogels attractive for drug delivery, gene therapy, cell culture, and tissue engineering approaches. The resemblance to living tissue of such thermoresponsive hydrogels produced by crosslinking of natural polymers opens up many biomedical application opportunities for human use. The most intensively studied natural thermoresponsive polymer is poly(
N
-isopropyl-acrylamide) (PNIPAM). This review focuses on the phase transition mechanism in thermoresponsive PNIPAM, the factors affecting the behavior of the gel, its specific properties, and, in particular, the role of PNIPAM’s phase transition in drug delivery, cell culture, and tissue engineering.
Induced pluripotent stem cells (iPSCs) are pivotal to the advancement of regenerative medicine. However, the low efficacy of iPSC generation and insufficient knowledge about the reprogramming ...mechanisms involved in somatic cell/adult stem cell reversion to a pluripotent phenotype remain critical hurdles to the therapeutic application of iPSCs. The present study investigated whether the concentration of fetal bovine serum (FBS), a widely employed cell culture additive, can influence the cellular reprogramming efficacy (RE) of human adipose-derived stem cells (hADSCs) to generate iPSCs. Compared with the typically employed concentration of FBS (10%), high concentrations (20% and 30%) increased the RE of hADSCs by approximately twofold, whereas a low concentration (5%) decreased the RE by the same extent. Furthermore, cell counting kit-8 (CCK-8), bromodeoxyuridine (BrdU) incorporation, and fluorescence-activated cell sorting (FACS) assays showed that hADSC proliferation during reprogramming was significantly enhanced by FBS at 20% and 30%, whereas quantitative polymerase chain reaction (qPCR) and Western blotting assays revealed a concomitant decrease in p53, p51, and p21 expression. In addition, the efficacy of retrovirus-mediated transduction into hADSCs was increased by approximately 10% at high concentrations of FBS. It was confirmed that platelet-derived growth factor in the FBS enhanced proliferation and reprogramming efficacy. Finally, the generated iPSCs showed a normal karyotype, the same fingerprinting pattern as parental hADSCs, a genome-wide transcriptome pattern similar to that of human embryonic stem cells (hESCs), and in vivo pluripotency. In conclusion, the current investigation demonstrated that high concentrations of FBS can modulate molecular and cellular mechanisms underlying the reprogramming process in hADSCs, thereby augmenting the cellular RE for iPSC generation.
We discuss the theoretical approaches for various electrochemical capacitor systems via performance-potential estimation in regard to specific energy and power densities. Typical energy storage ...systems, such as symmetric capacitor system and asymmetric capacitor system, are classified with the symmetry of the electrodes (symmetric/asymmetric), and the types of electrolytes (aqueous/organic). Energy and power densities of each system are theoretically calculated using various factors and coefficients for performance comparison. Then, theoretical modeling for the BatCap system is conducted to indicate the electrochemical performance of this new concept device followed by consideration of ideal structure of the BatCap electrode material. Conclusively, this study successively indicates the performance of each energy storage system depending on the specified conditions of the electrodes and electrolyte which consist of the energy storage systems.
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•We discuss the theoretical guidelines to designing high performance energy storage device.•We derive performance-potential estimation in regard to specific energy and power densities.•Symmetry of electrodes and the types of electrolytes are essential on the electrochemical performances of the devices.•Introduction of asymmetric electrodes with organic electrolyte enhances the performance of the electrochemical devices.•Theoretical modeling of a new concept device, BatCap, is conducted with consideration of ideal structure.
Stretchable electronics have recently been extensively investigated for the development of highly advanced human‐interactive devices. Here, a highly stretchable and sensitive strain sensor is ...fabricated based on the composite of fragmentized graphene foam (FGF) and polydimethylsiloxane (PDMS). A graphene foam (GF) is disintegrated into 200–300 μm sized fragments while maintaining its 3D structure by using a vortex mixer, forming a percolation network of the FGFs. The strain sensor shows high sensitivity with a gauge factor of 15 to 29, which is much higher compared to the GF/PDMS strain sensor with a gauge factor of 2.2. It is attributed to the great change in the contact resistance between FGFs over the large contact area, when stretched. In addition to the high sensitivity, the FGF/PDMS strain sensor exhibits high stretchability over 70% and high durability over 10 000 stretching‐releasing cycles. When the sensor is attached to the human body, it functions as a health‐monitoring device by detecting various human motions such as the bending of elbows and fingers in addition to the pulse of radial artery. Finally, by using the FGF, PDMS, and μ‐LEDs, a stretchable touch sensor array is fabricated, thus demonstrating its potential application as an artificial skin.
A highly stretchable and sensitive strain sensor based on a composite of fragmentized graphene foam (FGF) and polydimethylsiloxane (PDMS) is fabricated in a facile process. The FGF/PDMS sensor demonstrates high stretchability up to 70% and high durability over 10 000 stretching cycles with gauge factor in the range of 15–29 depending on the maximum strain applied and the FGF content.
Background
Ruminococcus gnavus (R. gnavus) are mucin‐degrading gut bacteria that play a key role in the early colonization of the gut by serving as endogenous sources of nutrients. They can also ...influence immune development. We had previously reported a lower abundance of R. gnavus in infants with atopic dermatitis (AD) compared with that in healthy subjects. However, the underlying mechanisms remain unclear. In this study, we investigated the effect of orally administered R. gnavus on antibiotic treatment‐induced gut dysbiosis (and the underlying mechanism) in a mouse model of AD.
Methods
Four‐week‐old female BALB/C mice were administered antibiotic cocktails for 2 weeks. R. gnavus was orally administered throughout the study duration. At 6 weeks of age, AD was induced by epidermal sensitization with ovalbumin. AD phenotypes and systemic and gut immune responses were investigated.
Results
Orally administered R. gnavus significantly reduced AD‐associated parameters (i.e., transepidermal water loss, clinical score, total serum immunoglobulin (Ig) E level, OVA‐specific IgE level, and skin inflammation). R. gnavus treatment also resulted in significant downregulation of T helper 2–related cytokine mRNA and upregulation of interleukin (IL)‐10 and Foxp3 in the skin. The population of CD4+FOXP3+ T cells in mesenteric‐ and skin‐draining lymph nodes and butyrate levels in the cecum increased in R. gnavus‐administered AD mice.
Conclusions
Immune modulation by orally administered R. gnavus may alleviate AD symptoms through the enhancement of regulatory T‐cell counts and short‐chain fatty acids production in AD mice.
Metabolomic pathways in food allergy Lee, So‐Yeon; Park, Yoon Mee; Yoo, Hyun Ju ...
Pediatric allergy and immunology,
20/May , Letnik:
35, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Food allergy (FA) is a widespread issue, affecting as many as 10% of the population. Over the past two to three decades, the prevalence of FA has been on the rise, particularly in industrialized and ...westernized countries. FA is a complex, multifactorial disease mediated by type 2 immune responses and involving environmental and genetic factors. However, the precise mechanisms remain inadequately understood. Metabolomics has the potential to identify disease endotypes, which could beneficially promote personalized prevention and treatment. A metabolome approach would facilitate the identification of surrogate metabolite markers reflecting the disease activity and prognosis. Here, we present a literature overview of recent metabolomic studies conducted on children with FA.
Atopic dermatitis (AD) is a common skin disease in childhood whose diagnosis requires expertise in dermatology. Recent studies have indicated that host genes-microbial interactions in the gut ...contribute to human diseases including AD. We sought to develop an accurate and automated pipeline for AD diagnosis based on transcriptome and microbiota data. Using these data of 161 subjects including AD patients and healthy controls, we trained a machine learning classifier to predict the risk of AD. We found that the classifier could accurately differentiate subjects with AD and healthy individuals based on the omics data with an average F1-score of 0.84. With this classifier, we also identified a set of 35 genes and 50 microbiota features that are predictive for AD. Among the selected features, we discovered at least three genes and three microorganisms directly or indirectly associated with AD. Although further replications in other cohorts are needed, our findings suggest that these genes and microbiota features may provide novel biological insights and may be developed into useful biomarkers of AD prediction.
Background:
Lateral epicondylitis is a chronic tendinopathy of humeral origin of the common extensor tendon. Most patients show improvement after nonoperative treatment. However, 4% to 11% of ...patients require surgical treatment. Although corticosteroid injection is one of the most commonly applied nonoperative treatment methods, to the authors’ knowledge, no study has reported the effect of the number of preoperative corticosteroid injections on the final postoperative outcome. Thus, the objective of this study was to determine the effect of the number of preoperative corticosteroid injections on postoperative clinical outcomes.
Hypothesis:
The number of corticosteroid injections before surgical treatment does not affect postoperative clinical outcomes.
Study Design:
Case series; Level of evidence, 4.
Methods:
As a retrospective review, from January 2007 to December 2019, a total of 99 patients who had undergone surgical treatment of lateral epicondylitis with a modified Nirschl technique were enrolled. The number of preoperative corticosteroid injections was investigated by medical record review. Outcome measurements included visual analog pain scale; Disabilities of the Arm, Shoulder and Hand (DASH) score; Mayo Elbow Performance Score; and the Nirschl and Pettrone grade. Grip power and wrist extension power were measured using a digital dynamometer.
Results:
A total of 99 patients were included in this study. The mean total number of injections of patients was 4.37 ± 2.46 times (range, 1-15 times). Total duration of nonoperative treatment before surgery was 25.4 ± 20.5 months (range, 4-124.8 months). The mean postoperative follow-up period was 42.8 ± 28.0 months (range, 12-110 months). For all injection numbers, clinical scores showed significant improvement in visual analog pain scale, DASH score, Mayo elbow score, grip power, and wrist extension power after surgery. Regression analysis showed that the degree of improvement according to the injection number was not statistically significant. The Nirschl and Pettrone grade was excellent in 82 (82.8%) patients, good in 14 (14.1%) patients, fair in 2 (2%) patient, and failure in 1 (1%) patient.
Conclusion:
The number of preoperative corticosteroid injections does not appear to affect postoperative clinical outcomes of patients with lateral epicondylitis who undergo surgery with a modified Nirschl technique.
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