Therapeutic effects of phlorotannins in the treatment of neurodegenerative disorders

Phlorotannins are natural polyphenolic compounds produced by brown marine algae and are currently found in nutritional supplements. Although they are known to cross the blood–brain barrier, their neuropharmacological actions remain unclear. Here we review the potential therapeutic benefits of phlorotannins in the treatment of neurodegenerative diseases. In mouse models of Alzheimer’s disease, ethanol intoxication and fear stress, the phlorotannin monomer phloroglucinol and the compounds eckol, dieckol and phlorofucofuroeckol A have been shown to improve cognitive function. In a mouse model of Parkinson’s disease, phloroglucinol treatment led to improved motor performance. Additional neurological benefits associated with phlorotannin intake have been demonstrated in stroke, sleep disorders, and pain response. These effects may stem from the inhibition of disease-inducing plaque synthesis and aggregation, suppression of microglial activation, modulation of pro-inflammatory signaling, reduction of glutamate-induced excitotoxicity, and scavenging of reactive oxygen species. Clinical trials of phlorotannins have not reported significant adverse effects, suggesting these compounds to be promising bioactive agents in the treatment of neurological diseases. We therefore propose a putative biophysical mechanism of phlorotannin action in addition to future directions for phlorotannin research

Myeloid cells protect corneal nerves against sterile injury through negative-feedback regulation of TLR2–IL-6 axis

Background Mounting evidence suggests that the immune system plays detrimental or protective roles in nerve injury and repair. Main body Herein we report that both CD11bhiLy6Ghi and CD11bhiLy6ChiLy6Glo myeloid cells are required to protect corneal nerves against sterile corneal injury. Selective depletion of CD11bhiLy6Ghi or CD11bhiLy6ChiLy6Glo cells resulted in aggravation of corneal nerve loss, which correlated with IL-6 upregulation. IL-6 neutralization preserved corneal nerves while reducing myeloid cell recruitment. IL-6 replenishment exacerbated corneal nerve damage while recruiting more myeloid cells. In mice lacking Toll-like receptor 2 (TLR2), the levels of IL-6 and myeloid cells were decreased and corneal nerve loss attenuated, as compared to wild-type and TLR4 knockout mice. Corneal stromal fibroblasts expressed TLR2 and produced IL-6 in response to TLR2 stimulation. Conclusion Collectively, our data suggest that CD11bhiLy6Ghi and CD11bhiLy6ChiLy6Glo myeloid cells confer corneal nerve protection under sterile injury by creating a negative-feedback loop to suppress the upstream TLR2–IL-6 axis that drives corneal nerve loss

Arthroscopic transosseous anchorless rotator cuff repair reduces bone defects related to peri-implant cyst formation: a comparison with conventional suture anchors using propensity score matching

Background The transosseous anchorless repair (ToR) technique was recently introduced to avoid suture anchor-related problems. While favorable outcomes of the ToR technique have been reported, no previous studies on peri-implant cyst formation with the ToR technique exist. Therefore, this study compared the clinical outcomes and prevalence of peri-implant cyst formation between the ToR technique and the conventional transosseous equivalent technique using suture anchors (SA). Methods Cases with arthroscopic rotator cuff repair (ARCR) between 2016 and 2018 treated with the double-row suture bridge technique were retrospectively reviewed. Patients were divided into ToR and SA groups. To compare clinical outcomes, 19 ToR and 57 SA cases without intraoperative implant failure were selected using propensity score matching (PSM). While intraoperative implant failure rate was analyzed before PSM, retear rate, peri-implant cyst formation rate, and functional outcomes were compared after PSM. Results The intraoperative implant failure rate (ToR, 8% vs. SA, 15.3%) and retear rate (ToR, 5.3% vs. SA, 19.3%) did not differ between the two groups (all P>0.05). However, peri-implant cysts were not observed in the ToR group, while they were observed in 16.7% of the SA group (P=0.008). Postoperative functional outcomes were not significantly different between the two groups (all P>0.05). Conclusions The ToR technique produced comparable clinical outcomes to conventional techniques. Considering the prospect of potential additional surgeries, the absence of peri-implant cyst formation might be an advantage of ToR. Furthermore, ToR might reduce the medical costs related to suture anchors and, thereby, could be a useful option for ARCR. Level of evidenceIII

Microporation is a valuable transfection method for efficient gene delivery into human umbilical cord blood-derived mesenchymal stem cells

<p>Abstract</p> <p>Background</p> <p>Mesenchymal stem cells (MSCs) are an attractive source of adult stem cells for therapeutic application in clinical study. Genetic modification of MSCs with beneficial genes makes them more effective for therapeutic use. However, it is difficult to transduce genes into MSCs by common transfection methods, especially nonviral methods. In this study, we applied microporation technology as a novel electroporation technique to introduce enhanced green fluorescent protein (EGFP) and brain-derived neurotropfic factor (BDNF) plasmid DNA into human umbilical cord blood-derived MSCs (hUCB-MSCs) with significant efficiency, and investigated the stem cell potentiality of engineered MSCs through their phenotypes, proliferative capacity, ability to differentiate into multiple lineages, and migration ability towards malignant glioma cells.</p> <p>Results</p> <p>Using microporation with EGFP as a reporter gene, hUCB-MSCs were transfected with higher efficiency (83%) and only minimal cell damage than when conventional liposome-based reagent (<20%) or established electroporation methods were used (30-40%). More importantly, microporation did not affect the immunophenotype of hUCB-MSCs, their proliferation activity, ability to differentiate into mesodermal and ectodermal lineages, or migration ability towards cancer cells. In addition, the BDNF gene could be successfully transfected into hUCB-MSCs, and BDNF expression remained fairly constant for the first 2 weeks <it>in vitro </it>and <it>in vivo</it>. Moreover, microporation of BDNF gene into hUCB-MSCs promoted their <it>in vitro </it>differentiation into neural cells.</p> <p>Conclusion</p> <p>Taken together, the present data demonstrates the value of microporation as an efficient means of transfection of MSCs without changing their multiple properties. Gene delivery by microporation may enhance the feasibility of transgenic stem cell therapy.</p

Early detection of cardiac involvement in Miyoshi myopathy: 2D strain echocardiography and late gadolinium enhancement cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Miyoshi myopathy (MM) is an autosomal recessive distal myopathy characterized by early adult onset. Cardiomyopathy is a major clinical manifestation in other muscular dystrophies and an important prognostic factor. Although dysferlin is highly expressed in cardiac muscle, the effect of dysferlin deficiency in cardiac muscle has not been studied. We hypothesized that early myocardial dysfunction could be detected by 2D strain echocardiography and late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR).</p> <p>Method</p> <p>Five consecutive MM patients (3 male) in whom we detected the DYSF gene mutation and age-matched healthy control subjects were included. None of the patients had history of cardiac disease or signs and symptoms of overt heart failure. Patients were studied using 2D strain echocardiography and CMR, with 2D strain being obtained using the Automated Function Imaging technique.</p> <p>Results</p> <p>All patients had preserved left ventricular systolic function. However, segmental Peak Systolic Longitudinal Strain (PSLS) was decreased in 3 patients. Global PSLS was significantly lower in patients with MM than in control subjects (p = 0.005). Basal anterior septum, basal inferior septum, mid anterior, and mid inferior septum PSLS were significantly lower in patients with MM than in control subjects (P < 0.0001, < 0.0001, 0.038 and 0.003, respectively). Four patients showed fibrosis by LGE. The reduced PSLS lesion detected by 2D strain tended to be in the same area as that which showed fibrosis by LGE.</p> <p>Conclusions</p> <p>Patients with MM showed subclinical involvement of the heart. 2D strain and LGE are sensitive methods for detecting myocardial dysfunction prior to the development of cardiovascular symptoms. The prognostic significance of these findings warrants further longitudinal follow-up.</p

Endotracheal intubation in rabbits using a video laryngoscope with a modified blade

Rabbits are being increasingly used as companion animals, and in research; thus, the need for proper veterinary care for rabbits has increased. Surgical access is more challenging in rabbits under inhalation anesthesia compared to other animals, such as dogs and cats. Rabbits have a very narrow and deep oral cavity, large incisors, and a large tongue. Moreover, their temporomandibular joint has limited mobility, making it more difficult to approach the larynx. Various methods have been proposed to overcome this difficulty. The video laryngoscope was introduced in 1999 and is useful when airway intubation is unsuccessful using a conventional laryngoscope. We postulated that a video laryngoscope with a modified size 1 Macintosh blade (McGrath MAC Video Laryngoscope, Medtronic, USA) would facilitate the intubation of New Zealand White rabbits. Sixteen specific-pathogen-free male New Zealand White rabbits weighing 3.45–4.70 kg were studied. All rabbits were intubated using the video laryngoscope. Typically, a 3.0 mm endotracheal tube was used for rabbits weighing  4 kg. During surgery, anesthesia was well maintained, and there were no major abnormalities in the animals’ conditions. No rabbit developed breathing difficulties or anorexia after recovering from anesthesia. We established an intubation method using a video laryngoscope with a modified blade and stylet in the supine (ventrodorsal) position and successfully applied it in 16 rabbits. It is useful for training novices and for treating rabbits in veterinary hospitals with few staff members and animal research facilities where there are insufficient human resources