In the article, the funding source was missed.
Financial Management ; Hand ; Pilot Projects ; Rehabilitation ; Therapeutic Uses

Psoriasis is a chronic, recurrent, heterogeneous, cutaneous inflammatory skin disease for which there is no cure. It affects approximately 7.5 million people in the United States. Currently, several biologic agents that target different molecules implicated in the pathogenic processes of psoriasis are being assessed in diverse clinical studies. However, relapse usually occurs within weeks or months, meaning there is currently no cure for psoriasis. Therefore, recent studies have discovered diverse new potential treatments for psoriasis: inhibitors of bacteria such as Staphylococcus aureus, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and neuropilin 1 (NRP1). A promising approach that has recently been described involves modifying antimicrobial peptides to develop new cutaneous anti-bacterial agents that target inflammatory skin disease induced by Staphylococcus. Increased expression of TRAIL and its death receptors DR4 and DR5 has been implicated in the pathogenesis of plaque psoriasis. In addition, TRAIL has the ability to inhibit angiogenesis by inducing endothelial cell death and by negative regulation of VEGF-induced angiogenesis via caspase-8-mediated enzymatic and non-enzymatic functions. Since NRP1 regulates angiogenesis induced by multiple signals, including VEGF, ECM and semaphorins, and also initiates proliferation of keratinocytes through NF-κB signaling pathway in involved psoriatic skin, targeting NRP1 pathways may offer numerous windows for intervention in psoriasis. In this review, we will focus on the current knowledge about the emerging role of synthetic antimicrobial peptides, TRAIL and NRP1 blocking peptides in the pathogenesis and treatment of psoriasis.
Anti-Bacterial Agents ; Bacteria ; Biological Factors ; Endothelial Cells ; Keratinocytes ; Necrosis ; Neuropilin-1 ; Peptides ; Psoriasis ; Receptors, Death Domain ; Recurrence ; Semaphorins ; Skin ; Skin Diseases ; Staphylococcus ; Staphylococcus aureus ; Therapeutic Uses ; TNF-Related Apoptosis-Inducing Ligand ; United States ; Vascular Endothelial Growth Factor A

Although efficacies and proportions of tympanoplasty performed via endoscopic ear surgery (EES) have gradually introduced, it remains unclear whether total EES is a good alternative to microscopic ear surgery (MES). Herein, we aimed to compare therapeutic effects of EES and MES in patients receiving tympanoplasty or myringoplasty. A search of MEDLINE, PubMed, and Embase databases was conducted to compare the efficacies of EES and MES. Two investigators independently reviewed all studies and extracted data with a standardized form. We assessed risk of bias and calculated pooled odds ratio (OR) estimates with a 95% confidence interval (CI). Thirteen studies (607 EES patients and 678 MES patients) met inclusion criteria for quantitative meta-analysis. In pooled analysis, those who undergo EES have 0.99 times the OR of graft success compared to those with MES (95% CI, 0.84 to 1.16; P=0.894). In qualitative analysis, comparable hearing improvement was observed between the two groups, despite inconsistent audiometric evaluation. The air-bone gaps (ABGs) improved 2.02 dB less in EES than in MES (mean difference of improvements of ABGs, 2.02; 95% CI, –3.84 to –0.20; P=0.029); however, substantial heterogeneity and publication bias limited the integrity of this analysis. Further, EES significantly decreased canalplasty rate, wound complications, and operation time, compared to MES. Moreover, patients receiving EES reported higher cosmetic satisfaction than patients receiving MES. EES can be a good alternative to MES in terms of comparable graft success rate and hearing outcomes in patients receiving tympanoplasty or myringoplasty. Moreover, EES was less invasive, resulting in higher cosmetic satisfaction, reduced morbidity, and shorter operation time. Our results may affect decision-making and outcome prediction in cases of EES; however, confirmation is needed to clarify potential bias.
Bias (Epidemiology) ; Ear ; Endoscopes ; Hearing ; Humans ; Myringoplasty ; Odds Ratio ; Population Characteristics ; Publication Bias ; Research Personnel ; Therapeutic Uses ; Transplants ; Tympanoplasty ; Wounds and Injuries

Spinal cord injury (SCI) causes axonal damage and demyelination, neural cell death, and comprehensive tissue loss, resulting in devastating neurological dysfunction. Neural stem/progenitor cell (NSPCs) transplantation provides therapeutic benefits for neural repair in SCI, and glial cell line-derived neurotrophic factor (GDNF) has been uncovered to have capability of stimulating axonal regeneration and remyelination after SCI. In this study, to evaluate whether GDNF would augment therapeutic effects of NSPCs for SCI, GDNF-encoding or mock adenoviral vector-transduced human NSPCs (GDNF-or Mock-hNSPCs) were transplanted into the injured thoracic spinal cords of rats at 7 days after SCI. Grafted GDNF-hNSPCs showed robust engraftment, long-term survival, an extensive distribution, and increased differentiation into neurons and oligodendroglial cells. Compared with Mock-hNSPC- and vehicle-injected groups, transplantation of GDNF-hNSPCs significantly reduced lesion volume and glial scar formation, promoted neurite outgrowth, axonal regeneration and myelination, increased Schwann cell migration that contributed to the myelin repair, and improved locomotor recovery. In addition, tract tracing demonstrated that transplantation of GDNF-hNSPCs reduced significantly axonal dieback of the dorsal corticospinal tract (dCST), and increased the levels of dCST collaterals, propriospinal neurons (PSNs), and contacts between dCST collaterals and PSNs in the cervical enlargement over that of the controls. Finally grafted GDNF-hNSPCs substantially reversed the increased expression of voltage-gated sodium channels and neuropeptide Y, and elevated expression of GABA in the injured spinal cord, which are involved in the attenuation of neuropathic pain after SCI. These findings suggest that implantation of GDNF-hNSPCs enhances therapeutic efficiency of hNSPCs-based cell therapy for SCI.
Animals ; Axons ; Cell Death ; Cell Movement ; Cell- and Tissue-Based Therapy ; Cicatrix ; Demyelinating Diseases ; gamma-Aminobutyric Acid ; Glial Cell Line-Derived Neurotrophic Factor ; Humans ; Hyperalgesia ; Myelin Sheath ; Neuralgia ; Neurites ; Neuroglia ; Neurons ; Neuropeptide Y ; Paraplegia ; Pyramidal Tracts ; Rats ; Regeneration ; Spinal Cord Injuries ; Spinal Cord ; Therapeutic Uses ; Transplants ; Voltage-Gated Sodium Channels

BACKGROUND AND OBJECTIVES: Most studies in cardiac regeneration have explored bone marrow mesenchymal stem cells (BM-MSC) with variable therapeutic effects. Amniotic fluid MSC (AF-MSC) having extended self-renewal and multi-potent properties may be superior to bone marrow MSC (BM-MSC). However, a comparison of their cardiomyogenic potency has not been studied yet.METHODS: The 5-azacytidine (5-aza) treated AF-MSC and BM-MSC were evaluated for the expression of GATA-4, Nkx2.5 and ISL-1 transcripts and proteins by quantitative RT-PCR and Western blotting, respectively as well as for the expression of cardiomyogenic differentiation markers cardiac troponin-T (cTNT), beta myosin heavy chain (βMHC) and alpha sarcomeric actinin (ASA) by immunocytochemistry.RESULTS: The AF-MSC as compared to BM-MSC had significantly higher expression of GATA-4 (183.06±29.85 vs. 9.80±0.05; p<0.01), Nkx2.5 (8.3±1.4 vs. 1.82±0.32; p<0.05), and ISL-1 (39.59±4.05 vs. 4.36±0.39; p<0.01) genes as well as GATA-4 (2.01±0.5 vs. 0.6±0.1; p<0.05), NKx2.5 (1.9±0.14 vs. 0.8±0.2; p<0.01) and ISL-1 (1.7±0.3 vs. 0.9±0.1; p<0.05) proteins. The AF-MSC also had significantly elevated expression of cTNT (5.0×10⁴±0.6×10⁴ vs. 3.5 ×10⁴±0.8×10⁴; p<0.01), β-MHC (15.7×10⁴±0.9×10⁴ vs. 8.2×10⁴±0.6×10⁴; p<0.01) and ASA (18.6×10⁴±4.9×10⁴ vs. 13.1×10⁴±3.0×10⁴; p<0.05) than BM-MSC.CONCLUSIONS: Our data suggest that AF-MSC have greater cardiomyogenic potency than BM-MSC, and thus may be a better source of MSC for therapeutic applications in cardiac regenerative medicine.
Actinin ; Amniotic Fluid ; Antigens, Differentiation ; Azacitidine ; Blotting, Western ; Bone Marrow ; Female ; Humans ; Immunohistochemistry ; Mesenchymal Stromal Cells ; Regeneration ; Regenerative Medicine ; Therapeutic Uses ; Troponin T ; Ventricular Myosins

BACKGROUND: Beta-carotene (BC) is a carotenoid which exerts anti-cancer effects in several types of cancer, including colorectal cancer. Epigenetic modifications of genes, such as histone deacetylation and DNA hypermethylation, have also been detected in various types of cancer. To understand the molecular mechanism underlying cancer preventive and therapeutic effects of BC, microRNAs (miRNAs), histone acetylation, and global DNA methylation in colon cancer stem cells (CSCs) were investigated.METHODS: HCT116 colon cancer cells positive for expression of CD44 and CD133 were sorted by flow cytometry and used in subsequent experiments. Cell proliferation was examined by the MTT assay and self-renewal capacity was analyzed by the sphere formation assay. The miRNA sequencing array was used to detect miRNAs regulated by BC. Histone acetylation levels were measured by the Western blot analysis. mRNA expression of DNA methyltransferases (DNMTs) was examined by qPCR and global DNA methylation levels were determined by enzyme-linked immunosorbent assay.RESULTS: Treatment of CD44⁺CD133⁺ colon CSCs with BC caused a reduction in both cell proliferation and sphere formation. Analysis of the miRNA sequencing array showed that BC regulated expression of miRNAs associated with histone acetylation. Histone H3 and H4 acetylation levels were elevated by BC treatment. In addition, BC treatment down-regulated DNMT3A mRNA expression and global DNA methylation in colon CSCs.CONCLUSIONS: These results suggest that BC regulates epigenetic modifications for its anti-cancer effects in colon CSCs.
Acetylation ; beta Carotene ; Blotting, Western ; Cell Proliferation ; Colon ; Colonic Neoplasms ; Colorectal Neoplasms ; DNA Methylation ; DNA ; Enzyme-Linked Immunosorbent Assay ; Epigenomics ; Flow Cytometry ; Histones ; Methyltransferases ; MicroRNAs ; RNA, Messenger ; Stem Cells ; Therapeutic Uses

The butanol extract of Asparagus cochinchinensis roots fermented with Weissella cibaria (BAW) effectively prevents inflammation and remodeling of airway in the ovalbumin (OVA)-induced asthma model. To characterize biomarkers that can predict the anti-asthmatic effects induced by BAW treatment, we measured the alteration of endogenous metabolites in the serum of OVA-induced asthma mice after administration of low concentration BAW (BAWLo, 250 mg/kg) and high concentration BAW (BAWHi, 500 mg/kg) using ¹H nuclear magnetic resonance (¹H-NMR) spectral data. The number of immune cells and serum concentration of IgE as well as thickness of the respiratory epithelium and infiltration of inflammatory cells in the airway significantly recovered in the OVA+BAW treated group as compared to the OVA+Vehicle treated group. In the metabolic profile analysis, the pattern recognition showed completely separate clustering of serum analysis parameters between the OVA+Vehicle and OVA+BAW treated groups. Of the total endogenous metabolites, 19 metabolites were upregulated or downregulated in the OVA+Vehicle treated group as compared to the Control treated group. However, only 4 amino acids (alanine, glycine, methionine and tryptophan) were significantly recovered after BAWLo and BAWHi treatment. This study provides the first results pertaining to metabolic changes in the asthma model mice treated with OVA+BAW. Additionally, these findings show that 4 metabolites can be used as one of biomarkers to predict the anti-asthmatic effects.
Amino Acids ; Animals ; Asthma ; Biomarkers ; Fermentation ; Glycine ; Immunoglobulin E ; Inflammation ; Magnetic Resonance Spectroscopy ; Metabolome ; Metabolomics ; Methionine ; Mice ; Ovalbumin ; Respiratory Mucosa ; Therapeutic Uses ; Weissella

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer’s disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.
Alzheimer Disease ; Blood-Brain Barrier ; Brain ; Brain Neoplasms ; Essential Tremor ; High-Intensity Focused Ultrasound Ablation ; Immune System ; Magnetic Resonance Imaging ; Microbubbles ; Models, Animal ; Neurodegenerative Diseases ; Neurogenesis ; Parkinson Disease ; Plaque, Amyloid ; Sonication ; Therapeutic Uses ; Transducers ; Ultrasonography ; United States Food and Drug Administration

The purpose of this study was to investigate the feasibility and therapeutic effects of a novel concept hand rehabilitation device based on magnetics for subacute stroke patients with hand motor impairment. We developed an end effector type device that can induce various movements of the fingers in accordance with a magnetic field direction using electromagnets and permanent magnets. Subacute stroke patients with hand motor impairments were recruited and divided into two rehabilitation groups. Conventional rehabilitation therapies were also conducted equally in both groups. Active-assisted training of the affected hand was additionally administered for 30 minutes per day for 4 weeks using the developed equipment in the intervention group. Hand motor function and the activities of daily living were evaluated before and after the intervention. The Manual Function Test score significantly increased in the intervention group after 4 weeks of treatment (p = 0.039), and there was a significant difference in the degree of improvement between the two groups (p = 0.016). The scores of the motor Fugl-Meyer Assessment of the upper limb, the Wolf Motor Function Test score and time, and the motor Functional Independence Measure also improved in both groups (all p < 0.05). In addition, the patients in the intervention group showed greater improvements in these outcome measures than those in the control group did (all p < 0.05). An adjuvant rehabilitation therapy using a magnetic based device can be helpful to improve the hand motor function and activities of daily life in subacute stroke patients.
Activities of Daily Living ; Fingers ; Hand ; Humans ; Magnetic Fields ; Magnets ; Outcome Assessment (Health Care) ; Pilot Projects ; Rehabilitation ; Robotics ; Stroke ; Therapeutic Uses ; Upper Extremity ; Wolves

PURPOSE: The house dust mite (HDM) is one of the most important sources of indoor allergens and a significant cause of allergic rhinitis and allergic asthma. Our previous studies demonstrated that Vibrio vulnificus flagellin B (FlaB) plus allergen as a co-treatment mixture improved lung function and inhibited eosinophilic airway inflammation through the Toll-like receptor 5 signaling pathway in an ovalbumin (OVA)- or HDM-induced mouse asthma model. In the present study, we fused the major mite allergen Derp2 to FlaB and compared the therapeutic effects of the Derp2-FlaB fusion protein with those of a mixture of Derp2 and FlaB in a Derp2-induced mouse asthma model. METHODS: BALB/c mice sensitized with Derp2 + HDM were treated with Derp2, a Derp2 plus FlaB (Derp2 + FlaB) mixture, or the Derp2-FlaB fusion protein 3 times at 1-week intervals. Seven days after the final treatment, the mice were challenged intranasally with Derp2, and airway responses and Derp2-specific immune responses were evaluated. RESULTS: The Derp2-FlaB fusion protein was significantly more efficacious in reducing airway hyperresponsiveness, lung eosinophil infiltration, and Derp2-specific IgE than the Derp2 + FlaB mixture. CONCLUSIONS: The Derp2-FlaB fusion protein showed a strong anti-asthma immunomodulatory capacity, leading to the prevention of airway inflammatory responses in a murine disease model through the inhibition of Th2 responses. These findings suggest that the Derp2-FlaB fusion protein would be a promising vaccine candidate for HDM-mediated allergic asthma therapy.
Allergens ; Animals ; Asthma ; Eosinophils ; Flagellin ; Immunoglobulin E ; Inflammation ; Lung ; Mice ; Mites ; Ovalbumin ; Pyroglyphidae ; Rhinitis, Allergic ; Therapeutic Uses ; Toll-Like Receptor 5 ; Vibrio vulnificus