A Novel Superparamagnetic-Responsive Hydrogel Facilitates Disc Regeneration by Orchestrating Cell Recruitment, Proliferation, and Differentiation within Hostile Inflammatory Niche.

In situ disc regeneration is a meticulously orchestrated process, which involves cell recruitment, proliferation and differentiation within a local inflammatory niche. Thus far, it remains a challenge to establish a multi-staged regulatory framework for coordinating these cellular events, therefore leading to unsatisfactory outcome. This study constructs a super paramagnetically-responsive cellular gel, incorporating superparamagnetic iron oxide nanoparticles (SPIONs) and aptamer-modified palladium-hydrogen nanozymes (PdH-Apt) into a double-network polyacrylamide/hyaluronic acid (PAAm/HA) hydrogel. The Aptamer DB67 within magnetic hydrogel (Mag-gel) showed a high affinity for disialoganglioside (GD2), a specific membrane ligand of nucleus pulposus stem cells (NPSCs), to precisely recruit them to the injury site. The Mag-gel exhibits remarkable sensitivity to a magnetic field (MF), which exerts tunable micro/nano-scale forces on recruited NPSCs and triggers cytoskeletal remodeling, consequently boosting cell expansion in the early stage. By altering the parameters of MF, the mechanical cues within the hydrogel facilitates differentiation of NPSCs into nucleus pulposus cells to restore disc structure in the later stage. Furthermore, the PdH nanozymes within the Mag-gel mitigate the harsh inflammatory microenvironment, favoring cell survival and disc regeneration. This study presents a remote and multi-staged strategy for chronologically regulating endogenous stem cell fate, supporting disc regeneration without invasive procedures.

Gut microbial alterations in arginine metabolism determine bone mechanical adaptation.

Although mechanical loading is essential for maintaining bone health and combating osteoporosis, its practical application is limited to a large extent by the high variability in bone mechanoresponsiveness. Here, we found that gut microbial depletion promoted a significant reduction in skeletal adaptation to mechanical loading. Among experimental mice, we observed differences between those with high and low responses to exercise with respect to the gut microbial composition, in which the differential abundance of Lachnospiraceae contributed to the differences in bone mechanoresponsiveness. Microbial production of L-citrulline and its conversion into L-arginine were identified as key regulators of bone mechanoadaptation, and administration of these metabolites enhanced bone mechanoresponsiveness in normal, aged, and ovariectomized mice. Mechanistically, L-arginine-mediated enhancement of bone mechanoadaptation was primarily attributable to the activation of a nitric-oxide-calcium positive feedback loop in osteocytes. This study identifies a promising anti-osteoporotic strategy for maximizing mechanical loading-induced skeletal benefits via the microbiota-metabolite axis.

Bibliometric analysis of breast cancer-related lymphedema research trends over the last 2 decades.

Objective: As breast cancer cases rise globally, post-mastectomy lymphedema garners increasing scholarly attention. This study aims to conduct a comprehensive bibliometric analysis of Breast Cancer-Related Lymphedema (BCRL) research from 2003 to 2022, identifying trends and providing global research insights for future studies. Method: The literature for this analysis was extracted from the Web of Science (WoS) Core Collection, encompassing 1199 publications, including 702 articles and 101 reviews, totaling 803. Using advanced bibliometric tools such as VOSviewer and CiteSpace, quantitative and visual analyses were performed to map collaboration networks, research clusters, and emerging trends. The search strategy included specific terms related to lymphedema, breast cancer, and BCRL, ensuring a comprehensive representation of the research landscape. Results: The bibliometric analysis revealed a steady increase in BCRL publications over the studied period, reaching a peak in 2018. The United States emerged as the leading contributor to BCRL literature, with China also demonstrating a significant presence. Collaboration networks were visualized, showcasing the interconnectedness of institutions and researchers globally. Key research hotspots identified include preventive strategies, complex decongestive therapy, and reconstructive interventions. Conclusion: In conclusion, this pioneering bibliometric analysis provides a comprehensive overview of BCRL research trends and collaborations globally. The findings contribute valuable insights into the evolution of the field, highlighting areas of focus and emerging research themes. This study serves as a foundational resource for researchers, clinicians, and policymakers, fostering evidence-based practices and interventions for BCRL in the future.

Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52.

A major impedance to neuronal regeneration after peripheral nerve injury (PNI) is the activation of various programmed cell death mechanisms in the dorsal root ganglion. Ferroptosis is a form of programmed cell death distinguished by imbalance in iron and thiol metabolism, leading to lethal lipid peroxidation. However, the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear. Ferroportin (Fpn), the only known mammalian nonheme iron export protein, plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis. Here, we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis. We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn, and stimulation of lipid peroxidation. Early administration of the potent arterial vasodilator, hydralazine (HYD), decreases the ubiquitination of Fpn after PNI by binding to UBA52, leading to suppression of neuronal cell death and significant acceleration of axon regeneration and motor function recovery. HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

A Novel Superparamagnetic Multifunctional Nerve Scaffold: A Remote Actuation Strategy to Boost In Situ Extracellular Vesicles Production for Enhanced Peripheral Nerve Repair.

Extracellular vesicles (EVs) have inherent advantages over cell-based therapies in regenerative medicine because of their cargos of abundant bioactive cues. Several strategies are proposed to tune EVs production in vitro. However, it remains a challenge for manipulation of EVs production in vivo, which poses significant difficulties for EVs-based therapies that aim to promote tissue regeneration, particularly for long-term treatment of diseases like peripheral neuropathy. Herein, a superparamagnetic nanocomposite scaffold capable of controlling EVs production on-demand is constructed by incorporating polyethyleneglycol/polyethyleneimine modified superparamagnetic nanoparticles into a polyacrylamide/hyaluronic acid double-network hydrogel (Mag-gel). The Mag-gel is highly sensitive to a rotating magnetic field (RMF), and can act as mechano-stimulative platform to exert micro/nanoscale forces on encapsulated Schwann cells (SCs), an essential glial cell in supporting nerve regeneration. By switching the ON/OFF state of the RMF, the Mag-gel can scale up local production of SCs-derived EVs (SCs-EVs) both in vitro and in vivo. Further transcriptome sequencing indicates an enrichment of transcripts favorable in axon growth, angiogenesis, and inflammatory regulation of SCs-EVs in the Mag-gel with RMF, which ultimately results in optimized nerve repair in vivo. Overall, this research provides a noninvasive and remotely time-scheduled method for fine-tuning EVs-based therapies to accelerate tissue regeneration, including that of peripheral nerves.

Quantitative Biofabrication Platform for Collagen-Based Peripheral Nerve Grafts with Structural and Chemical Guidance.

Owing to its crucial role in the human body, collagen has immense potential as a material for the biofabrication of tissues and organs. However, highly refined fabrication using collagen remains difficult, primarily because of its notably soft properties. A quantitative biofabrication platform to construct collagen-based peripheral nerve grafts, incorporating bionic structural and chemical guidance cues, is introduced. A viscoelastic model for collagen, which facilitates simulating material relaxation and fabricating collagen-based neural grafts, achieving a maximum channel density similar to that of the native nerve structure of longitudinal microchannel arrays, is established. For axonal regeneration over considerable distances, a gradient printing control model and quantitative method are developed to realize the high-precision gradient distribution of nerve growth factor required to obtain nerve grafts through one-step bioprinting. Experiments verify that the bioprinted graft effectively guides linear axonal growth in vitro and in vivo. This study should advance biofabrication methods for a variety of human tissue-engineering applications requiring tailored cues.

A Novel Magnetic Responsive miR-26a@SPIONs-OECs for Spinal Cord Injury: Triggering Neural Regeneration Program and Orienting Axon Guidance in Inhibitory Astrocytic Environment.

Addressing the challenge of promoting directional axonal regeneration in a hostile astrocytic scar, which often impedes recovery following spinal cord injury (SCI), remains a daunting task. Cell transplantation is a promising strategy to facilitate nerve restoration in SCI. In this research, a pro-regeneration system is developed, namely miR-26a@SPIONs-OECs, for olfactory ensheathing cells (OECs), a preferred choice for promoting nerve regeneration in SCI patients. These entities show high responsiveness to external magnetic fields (MF), leading to synergistic multimodal cues to enhance nerve regeneration. First, an MF stimulates miR-26a@SPIONs-OECs to release extracellular vesicles (EVs) rich in miR-26a. This encourages axon growth by inhibiting PTEN and GSK-3ß signaling pathways in neurons. Second, miR-26a@SPIONs-OECs exhibit a tendency to migrate and orientate along the direction of the MF, thereby potentially facilitating neuronal reconnection through directional neurite elongation. Third, miR-26a-enriched EVs from miR-26a@SPIONs-OECs can interact with host astrocytes, thereby diminishing inhibitory cues for neurite growth. In a rat model of SCI, the miR-26a@SPIONs-OECs system led to significantly improved morphological and motor function recovery. In summary, the miR-26a@SPIONS-OECs pro-regeneration system offers innovative insights into engineering exogenous cells with multiple additional cues, augmenting their efficacy for stimulating and guiding nerve regeneration within a hostile astrocytic scar in SCI.

Bibliometric Analysis of Research Trends on Manual Therapy for Low Back Pain Over Past 2 Decades.

Purpose: Low back pain (LBP) is a prevalent musculoskeletal disorder, and manual therapy (MT) is frequently employed as a non-pharmacological treatment for LBP. This study aims to explore the research hotspots and trends in MT for LBP. MT has gained widespread acceptance in clinical practice due to its proven safety and effectiveness. The study aims to analyze the developments in the field of MT for LBP over the past 23 years, including leading countries, institutions, authoritative authors, journals, keywords, and references. It endeavors to provide a comprehensive summary of the existing research foundation and to analyze the current cutting-edge research trends. Methods: Relevant articles between 2000 and 2023 were retrieved from the Web of Science Core Collection (WOSCC) database. We used the software VOSviewer and CiteSpace to perform the analysis and summarize current research hotspots and emerging trends. Results: Through screening, we included 1643 papers from 2000 to 2023. In general, the number of articles published each year showed an upward trend. The United States had the highest number of publications and citations. Canadian Memorial Chiropractic College was the most published research institution. The University of Pittsburgh in the United States had the most collaboration with other research institutions. Long, Cynthia R. was the active author. Journal of Manipulative and Physiological Therapeutics was the most prolific journal with 234 publications. Conclusion: This study provides an overview of the current status and trends of clinical studies on MT for LBP in the past 23 years using the visualization software, which may help researchers identify potential collaborators and collaborating institutions, hot topics, and new perspectives in research frontiers, while providing new clinical practice ideas for the treatment of LBP.

M2-like macrophages polarized by Foxp3- Treg-of-B cells ameliorate imiquimod-induced psoriasis.

Our group have demonstrated that splenic B cells contributed to the CD4+ CD25- naive T cells conversion into CD4+ CD25+ Foxp3- regulatory T cells without adding appended cytokines, named Treg-of-B cells which were potent suppressors of adaptive immunity. We like to investigate whether Treg-of-B cells could promote alternatively activated macrophage (M2 macrophages) polarization and alleviate inflammatory disease, psoriasis. In this study, we co-cultured the bone marrow-derived macrophages (BMDMs) with Treg-of-B cells under LPS/IFN-γ stimulation and analyzed the M2-associated gene and protein using qPCR, western blotting, and immunofluorescence staining. We also examined the therapeutic effect of Treg-of-B cell-induced M2 macrophage for skin inflammation using imiquimod (IMQ)-induced psoriatic mouse model. Our results showed that BMDMs co-cultured with Treg-of-B cells upregulated typical M2-associated molecules, including Arg-1, IL-10, Pdcd1lg2, MGL-1, IL-4, YM1/2 and CD206. In an inflammatory environment, TNF-α and IL-6 production by macrophages co-cultured with Treg-of-B cells was decreased significantly. The molecular mechanism revealed that Treg-of-B cells promoted M2 macrophage polarization via STAT6 activation in a cell contact-dependent manner. Moreover, the treatment with Treg-of-B cell-induced M2 macrophages attenuated the clinical manifestations of psoriasis, such as scaling, erythema and thickening in the IMQ-induced psoriatic mouse model. T cell activation in draining lymph nodes was decreased in the Treg-of-B cell-induced M2 macrophage group after IMQ application. In conclusion, our findings suggested that Foxp3- Treg-of-B cells could induce alternatively activated M2 macrophages through STAT6 activation, providing a cell-based therapeutic strategy for psoriasis.

Migration inhibitory factor and cluster of differentiation 74-mediated dendritic cell apoptosis exacerbates acute acetaminophen-induced liver injury.

INTRODUCTION: We investigated the role of macrophage migration inhibitory factor (MIF) on dendritic cells (DC) during acetaminophen (APAP)-induced acute liver injury (ALI) in mice. METHODS: First, we randomly divided the mice into experimental (ALI model) and control groups, then intraperitoneally injected 600 mg/kg of APAP or phosphate-buffered saline, respectively. Then, we collected liver tissue and serum samples to evaluate liver inflammation using serum alanine aminotransferase level and hematoxylin and eosin (H&E) staining of liver tissues. Flow cytometry was used to identify changes in the quantity and percentage of DCs, as well as the expression of cluster of differentiation (CD) 74 and other apoptosis-related markers in the liver. Next, we randomly divided the mice into APAP-vehicles, APAP-bone marrow-derived dendritic cells (BMDCs), APAP-MIF, APAP-IgG (isotype immunoglobin G antibody) groups (four mice per group), after APAP injection, we injected control extracts, BMDCs, mouse recombinant MIF antibodies, or IgG antibodies into the tail vein. Lastly, the severity of the liver injury and the number of DCs were assessed. RESULTS: The APAP-induced ALI mice had increased hepatic MIF expression but significantly lower amounts of hepatic DCs and apoptotic DCs than healthy mice; CD74 expression on the HDCs also increased markedly. Supplementing APAP-induced ALI mice with BMDCs or MIF antibodies significantly increased the number of hepatic DCs compared with the control mice, alleviating liver damage. CONCLUSION: The MIF/CD74 signaling pathway may mediate hepatic DC apoptosis and promote liver damage.

A population of stem cells with strong regenerative potential discovered in deer antlers.

The annual regrowth of deer antlers provides a valuable model for studying organ regeneration in mammals. We describe a single-cell atlas of antler regrowth. The earliest-stage antler initiators were mesenchymal cells that express the paired related homeobox 1 gene (PRRX1+ mesenchymal cells). We also identified a population of "antler blastema progenitor cells" (ABPCs) that developed from the PRRX1+ mesenchymal cells and directed the antler regeneration process. Cross-species comparisons identified ABPCs in several mammalian blastema. In vivo and in vitro ABPCs displayed strong self-renewal ability and could generate osteochondral lineage cells. Last, we observed a spatially well-structured pattern of cellular and gene expression in antler growth center during the peak growth stage, revealing the cellular mechanisms involved in rapid antler elongation.

Core-shell oxygen-releasing fibers for annulus fibrosus repair in the intervertebral disc of rats.

The repair of annulus fibrosus (AF) defect after discectomy in the intervertebral disc (IVD) has presented a challenge over the past decade. Hostile microenvironments in the IVD, including, compression and hypoxia, are critical issues that require special attention. Till date, little information is available on potential strategies to cope with the hypoxia dilemma in AF defect sites. In this study, perfluorotributylamine (PFTBA) core-shell fibers were fabricated by coaxial electrospinning to construct oxygen-releasing scaffold for promoting endogenous repair in the AF after discectomy. We demonstrated that PFTBA fibers (10% chitosan, chitosan: PCL, 1:6) could release oxygen for up to 144 â€‹h. The oxygen released from PFTBA fibers was found to protect annulus fibrosus stem cells (AFSCs) from hypoxia-induced apoptosis. In addition, the PFTBA fibers were able to promote proliferation, migration and extracellular matrix (ECM) production in AFSCs under hypoxia, highlighting their therapeutic potential in AF defect repair. Subsequent in vivo studies demonstrated that oxygen-supplying fibers were capable of ameliorating disc degeneration after discectomy, which was evidenced by improved disc height and morphological integrity in rats with the oxygen-releasing scaffolds. Further transcriptome analysis indicated that differential expression genes (DEGs) were enriched in "oxygen transport" and "angiogenesis", which likely contributed to their beneficial effect on endogenous AF regeneration. In summary, the oxygen-releasing scaffold provides novel insights into the oxygen regulation by bioactive materials and raises the therapeutic possibility of oxygen supply strategies for defect repair in AF, as well as other aerobic tissues.

Hsa-let-7f-1-3p targeting the circadian gene Bmal1 mediates intervertebral disc degeneration by regulating autophagy.

The intervertebral disc has an intrinsic circadian rhythm, elimination of which leads to stress in nucleus pulposus cells (NPCs), contributing to intervertebral disc degeneration (IDD). Disruption or deletion of Bmal1 (a core transcription factor) results in complete loss of circadian rhythms, make mice susceptibility to IDD. However, the underlying mechanism by which Bmal1 mediates IDD is remains enigmatic, and whether there are other upstream factors regulating Bmal1 in NPCs. In our study, we first found that the decrease of Bmal1 was significantly correlated with the grades of IDD. With gain- and loss-of-function, Bmal1 shown a protective effect on NPC viability and functions. Transcriptomic and proteomic landscape reveals the functional contributions of Bmal1, and phosphoproteomic analysis links to autophagy. Bioinformatics analysis identified that a novel miRNA hsa-let-7f-1-3p was directly target Bmal1 3'UTR and negatively correlated with NPC function. Finally, our animal model confirmed the protective role of Bmal1 in rat IDD and this effect could be attenuated by hsa-let-7f-1-3p. The hsa-let-7f-1-3p/Bmal1/autophagy axis provides a potential therapeutic strategy for the clinical treatment of IDD.

Discovery of novel immunotherapeutic drug candidates for sciatic nerve injury using bioinformatic analysis and experimental verification.

Inflammation following nerve injury and surgery often causes peripheral nerve adhesion (PNA) to the surrounding tissue. Numerous investigations independently examined the prevention or inhibition of PNA, however, an intervention targeting macrophages has not been fully elucidated. Basement membrane (BM) genes are known to modulate central nervous system (CNS) inflammation, however, their activities in the peripheral nervous system (PNS) remains undiscovered. In this report, we carried out weighted correlation network analysis (WCNA) to screen for principal sciatic nerve injury (SNI) module genes. Once an association between the module and BM genes was established, the protein-protein interaction (PPI) and immune infiltration analyses were employed to screen for relevant BM-related immune genes (Itgam, SDC1, Egflam, and CD44) in SNI. Subsequently, using the Drug SIGnatures (DSigDB) database and molecular docking, we demonstrated that Trichostatin A (TSA) interacted with key immune genes. TSA is known to enhance M2 macrophage expression and attenuate fibrosis. Nevertheless, the significance of the epigenetic modulation of macrophage phenotypes in dorsal root ganglion (DRG) is undetermined after SNI. In this article, we examined the TSA role in fibrogenesis and macrophage plasticity associated with DRG. We revealed that TSA enhanced M2 macrophage aggregation, inhibited fibroblast activation, and improved sciatic nerve regeneration (SNR) and sensory functional recovery (FR) after SNI. In addition, TSA suppressed M1 macrophages and enhanced M2 macrophage invasion within the DRG tissue. Furthermore, TSA dramatically reduced IL-1ß and TNFα levels, while upregulating IL-10 level. In summary, this research revealed for the first time that TSA alleviates fibrosis in DRG by promoting an M1 to M2 macrophage transition, which, in turn, accelerates SNR.

Sequential oxygen supply system promotes peripheral nerve regeneration by enhancing Schwann cells survival and angiogenesis.

Local hypoxia in cellular grafts remains a challenge during the repair of peripheral nerve injury. Oxygen carriers (perfluorotributylamine, PFTBA) have been shown to provide oxygen to Schwann cells (SCs) for a short period. However, the limited oxygen supply from oxygen-carrying materials hinders the ability of such systems to counteract hypoxia over an extended period and limits their therapeutic potential. In this study, PFTBA/VEGF core-shell fibers were fabricated through coaxial electrospinning to construct an oxygen supply system that can sequentially provide oxygen, first via the oxygen carrier and subsequently by promoting angiogenesis via VEGF. Then, the oxygen release and proangiogenic effects of the PFTBA/VEGF core-shell fibers were examined in vitro. Furthermore, sequential oxygen supply conduits prepared using the fibers and filled with SCs were used to bridge 15-mm-long sciatic nerve defects in rats. The PFTBA-VEGF system was confirmed to protect SCs from hypoxia and promote angiogenesis in vitro. Subsequent in vivo studies showed that after the oxygen carried by PFTBA was exhausted, the VEGF could induce neovascularization, and the nascent blood vessels acted as sequential oxygen suppliers for SCs during nerve regeneration. In addition, rats transplanted with the sequential oxygen supply system showed significant morphological and functional improvements in axonal regeneration, the sciatic function index, and the muscle wet weight ratio. The final functional outcomes were similar after treatment with the sequential oxygen supply conduits and autografts. Western blots revealed that the VEGF in the system could upregulate p-AMPK, contributing to axon regeneration after sciatic nerve injury. The sequential oxygen supply system offers essential insights into the oxygen regulation of biomaterials and highlights the potential of oxygen supply strategies as therapeutic approaches for repairing defects in peripheral nerves and other aerobic tissues.

High-specificity protection against radiation-induced bone loss by a pulsed electromagnetic field.

Radiotherapy increases tumor cure and survival rates; however, radiotherapy-induced bone damage remains a common issue for which effective countermeasures are lacking, especially considering tumor recurrence risks. We report a high-specificity protection technique based on noninvasive electromagnetic field (EMF). A unique pulsed-burst EMF (PEMF) at 15 Hz and 2 mT induces notable Ca2+ oscillations with robust Ca2+ spikes in osteoblasts in contrast to other waveforms. This waveform parameter substantially inhibits radiotherapy-induced bone loss by specifically modulating osteoblasts without affecting other bone cell types or tumor cells. Mechanistically, primary cilia are identified as major PEMF sensors in osteoblasts, and the differentiated ciliary expression dominates distinct PEMF sensitivity between osteoblasts and tumor cells. PEMF-induced unique Ca2+ oscillations depend on interactions between ciliary polycystins-1/2 and endoplasmic reticulum, which activates the Ras/MAPK/AP-1 axis and subsequent DNA repair Ku70 transcription. Our study introduces a previously unidentified method against radiation-induced bone damage in a noninvasive, cost-effective, and highly specific manner.

Circadian Rhythm Modulates the Therapeutic Activity of Pulsed Electromagnetic Fields on Intervertebral Disc Degeneration in Rats.

Circadian rhythm (CR) imparts significant benefits in treating multiple diseases, such as heart diseases and arthritis. But the CR effect on intervertebral disc degeneration (IVDD) therapy remains unclear. Recent studies revealed that pulsed electromagnetic fields (PEMF) are capable of alleviating IVDD. In this study, we evaluated the CR-mediated regulation of PEMF therapeutic effect on IVDD induced by rat tail disc needle puncture. Our results demonstrated that the daytime PEMF stimulation (DPEMF) is more effective than the nighttime PEMF (NPEMF) in delaying IVDD. Moreover, the rats treated with DPEMF maintained better disc stability and histology after 8 weeks, relative to NPEMF. CR and PEMF cotherapies were also examined in cellular models, whereby serum shock was used to induce different levels of clock gene expression in the nucleus pulposus (NP), thus imitating CR in vitro. PEMF at ZT8 (higher level of clock gene expression) correlated with a higher extracellular matrix (ECM) component expression, compared to ZT20 (lower level of clock gene expression). Taken together, these data suggest a strong role of CR in regulating the beneficial effect of PEMF on IVDD. Our findings provide a potential clinical significance of CR in optimizing PEMF positive effects on IVDD.

Pulsed Electromagnetic Field Alleviates Intervertebral Disc Degeneration by Activating Sirt1-Autophagy Signaling Network.

Intervertebral disc (IVD) degeneration is regarded as a major contributor to low back pain (LBP), causing serious economic burden on individuals and society. Unfortunately, there are limited effective treatment for IVD degeneration. Pulsed electromagnetic field (PEMF) is an economical and effective physical therapy method, with reduced side-effects. It offers certain protection to a number of degenerative diseases. Therefore, understanding the underlying mechanism of PEMF on IVD is important for improving the PEMF therapeutic efficiency. In this study, PEMF up-regulated extracellular matrix (ECM) related genes in degenerated nucleus pulposus (NP) cells. It also increased SIRT1 expression and promoted autophagy in degenerated NP cells. In contrast, the autophagy suppressor 3-methyladenine (3-MA) reversed the beneficial effect of PEMF on ECM production. Similarly, the SIRT1 enzyme activity suppressor EX 527 also inhibited the effect of PEMF on autophagy and ECM production in NP cells, thereby suggesting that PEMF regulated ECM related genes expression through SIRT1-autophagy signaling pathway. Lastly, PEMF significantly reduced IVD degeneration in a rat model of IVD degeneration in vivo. In summary, our study uncovers a critical role of SIRT1-dependent autophagy signaling pathway in ECM protection and thus in the establishment of therapeutic effect of PEMF on IVD degeneration.

Nanoscale Modification of Titanium Implants Improves Behaviors of Bone Mesenchymal Stem Cells and Osteogenesis In Vivo.

The surficial micro/nanotopography and physiochemical properties of titanium implants are essential for osteogenesis. However, these surface characters' influence on stem cell behaviors and osteogenesis is still not fully understood. In this study, titanium implants with different surface roughness, nanostructure, and wettability were fabricated by further nanoscale modification of sandblasted and acid-etched titanium (SLA: sandblasted and acid-etched) by H2O2 treatment (hSLAs: H2O2 treated SLA). The rat bone mesenchymal stem cells (rBMSCs: rat bone mesenchymal stem cells) are cultured on SLA and hSLA surfaces, and the cell behaviors of attachment, spreading, proliferation, and osteogenic differentiation are further analyzed. Measurements of surface characteristics show hSLA surface is equipped with nanoscale pores on microcavities and appeared to be hydrophilic. In vitro cell studies demonstrated that the hSLA titanium significantly enhances cell response to attachment, spreading, and proliferation. The hSLAs with proper degree of H2O2 etching (h1SLA: treating SLA with H2O2 for 1 hour) harvest the best improvement of differentiation of rBMSCs. Finally, the osteogenesis in beagle dogs was tested, and the h1SLA implants perform much better bone formation than SLA implants. These results indicate that the nanoscale modification of SLA titanium surface endowing nanostructures, roughness, and wettability could significantly improve the behaviors of bone mesenchymal stem cells and osteogenesis on the scaffold surface. These nanoscale modified SLA titanium scaffolds, fabricated in our study with enhanced cell affinity and osteogenesis, had great potential for implant dentistry.

Quality of life in atopic dermatitis in Asian countries: a systematic review.

Atopic dermatitis (AD) is a common chronic inflammatory skin condition which impacts psychological wellbeing and social relationships. There have been studies of AD's impact on quality of life (QoL) in Western countries, but these findings cannot be directly extrapolated to Asian populations with genetic, environmental and cultural differences. Therefore, we aimed to systematically review the literature pertaining to QoL impairment in AD in East and Southeast Asia to characterize the impact of AD on patients and their families, and to identify the factors affecting the degree of QoL impairment. A search of English language papers was conducted on MEDLINE, EMBASE, PSYCInfo, Global Health and Web of Science. Observational studies measuring QoL using single or multi-item instruments in people with self-reported or physician diagnosed atopic dermatitis were included. 27 studies from 29 articles were included and synthesized. There is data documenting QoL impairment in AD sufferers and their families, across a wide range of Asian countries, healthcare settings and ages. Aspects of QoL impacted to a greater extent included symptoms of itch, feelings of embarrassment, and sleep disturbance. Severity of disease affects the degree of impairment of QoL, but there is no apparent link between QoL impairment and patient demographic factors, or other medical factors such as age at diagnosis or duration of illness. Our findings also highlighted the need for clinicians to actively explore the impact of patient's symptoms, especially in an Asian context where healthcare communications are traditionally doctor-centric.