Renormalization of metabolic coupling treats age-related degenerative disorders: an oxidative RPE niche fuels the more glycolytic photoreceptors

Retinitis pigmentosa is characterized by a dysregulation within the metabolic coupling of the retina, particularly between the glycolytic photoreceptors and the oxidative retina pigment epithelium. This phenomenon of metabolic uncoupling is seen in both aging and retinal degenerative diseases, as well as across a variety of cell types in human biology. Given its crucial role in the health and maintenance of these cell types, the metabolic pathways involved present a suitable area for therapeutic intervention. Herein, this review covers the scope of this delicate metabolic interplay, its dysregulation, how it relates to the retina as well other cell types, and finally concludes with a summary of various strategies aimed at reinstating normal metabolic coupling within the retina, and future directions within the field.

Revisiting the Role of GSK3, A Modulator of Innate Immunity, in Idiopathic Inclusion Body Myositis

Idiopathic or sporadic inclusion body myositis (IBM) is the leading age-related (onset > 50 years of age) autoimmune muscular pathology, resulting in significant debilitation in affected individuals. Once viewed as primarily a degenerative disorder, it is now evident that much like several other neuro-muscular degenerative disorders, IBM has a major autoinflammatory component resulting in chronic inflammation-induced muscle destruction. Thus, IBM is now considered primarily an inflammatory pathology. To date, there is no effective treatment for sporadic inclusion body myositis, and little is understood about the pathology at the molecular level, which would offer the best hopes of at least slowing down the degenerative process. Among the previously examined potential molecular players in IBM is glycogen synthase kinase (GSK)-3, whose role in promoting TAU phosphorylation and inclusion bodies in Alzheimer’s disease is well known. This review looks to re-examine the role of GSK3 in IBM, not strictly as a promoter of TAU and Abeta inclusions, but as a novel player in the innate immune system, discussing some of the recent roles discovered for this well-studied kinase in inflammatory-mediated pathology.

Phenolic Compounds in Calafate Berries Encapsulated by Spray Drying: Neuroprotection Potential into the Ingredient

Calafate is a berry rich in anthocyanins that presents higher content of polyphenols than other fruits. Its compounds have been described previously, however, the potential thereof in preventing and treating degenerative disorders has not yet been studied. Due to its astringency, the consumption of this berry in its natural state is limited. To profit from the aforementioned properties and reduce palatability issues, calafate berry extracts were microencapsulated by spray drying, a rapid, cost-effective and scalable process, and were then compared with freeze drying as a control. The stability of its contents and its in-vitro potential, with respect to AChE activity and neuroprotection, were measured from the obtained microcapsules, resulting from temperature treatments and different encapsulant contents. The results indicated that the spray-dried powders were stable, despite high temperatures, and their encapsulation exhibited nearly 50% efficiency. The highest quantity of polyphenols and 3-O-glycosylated anthocyanins was obtained from encapsulation with 20% maltodextrin, at 120 °C. Temperature did not affect the microcapsules’ biological action, as demonstrated by their antioxidant activities. The prevention of Aβ peptide cytotoxicity in PC12 cells (20%) revealed that encapsulated calafate can confer neuroprotection. We conclude that spray-drying is an appropriate technique for scaling-up and producing new value-added calafate formulations with anti-neurodegenerative effects and vivid colors.

Assessment of a Novel Bioflavonoids and Phytonutrient Formulation in Enhancing Cellular Aerobic Glycolysis, Immunity, Sports Performance, and Mitigating Inflammation

Metabolic competence in conjunction with well-balanced nutritional support is extremely important for normal biochemical and physiological functions, as well as for enhanced athletic performance. Research-affirmed nutraceuticals enriched in structurally diverse phytonutrients including bioflavonoids may help to boost athletic, functional, and biophysiological competence. Occurrence of chronic degenerative disorders is associated with an increase in anaerobic events, namely, the inability to effectively use oxygen and water, and inability to use nutrients for cellular energy production and management, metabolic homeostasis, and waste removal. Earlier clinical studies in our laboratories using the WADA compliant bioflavonoid-enriched Prodosomed VMP35 Multinutrient Complex (“Prodovite®”) demonstrated that it boosted aerobic metabolic competence and provided protection against diverse chronic degenerative anaerobic disorders. We hypothesized that Prodosomed VMP35 may serve as a novel supplement to boost athletic performance. The objective of the study was to conduct selected focused pilot studies to demonstrate the efficacy of a WADA compliant Prodosomed VMP35 to improve athletic competence and performance in a variety of sports activities. The efficacy of VMP35 was assessed in different models of sports performance/athletic competence including power lifting, resistance training, cycling, and selected case studies. VMP35 supplementation restored aerobic metabolic events, minimized oxidative stress, and improved athletic performance, recovery, and immune competence. These pilot clinical studies demonstrate that iron-free VMP35 restores aerobic metabolism by restoring iron-dependent hemoglobin to red blood cells, bolstering neutrophils in the blood (immune support), and significantly improving performance output in a diverse range of athletic activities.

Mesenchymal Stem/Stromal Cells and Fibroblasts: Their Roles in Tissue Injury and Regeneration, and Age-Related Degeneration

Mesenchymal stem/stromal cells (MSCs) and fibroblasts are present in normal tissues to support tissue homeostasis. Both share common pathways and have a number of common features, such as a spindle-shaped morphology, connective tissue localization, and multipotency. In inflammation, a nonspecific response to injury, fibroblasts and MSC are the main players.Two mechanisms of their mode of action have been defined: immunomodulation and regeneration. Following tissue injury, MSCs are activated, and they multiply and differentiate, to mitigate the damage. With aging and, in particular, in degenerative disorders of the musculoskeletal system (i.e., joint and bone disorders), the regenerative capacity of MSCs appears to be lost or diverted into the production of other nonfunctional cell types, such as adipocytes and fibroblasts. Fibroblasts are stromal cells that provide the majority of the structural framework of almost all types of tissues; i.e., the stroma. As such, fibroblasts also have significant roles in tissue development, maintenance, and repair. In their immunosuppressive role, MSCs and fibroblasts contribute to the normal resolution of inflammation that is a prerequisite for successful tissue repair. In this chapter, we review the common and opposing properties of different tissue-derived MSCs and fibroblasts under physiological and pathophysiological conditions. We consider injury and age-related degeneration of various tissues, and also some immunological disorders. Specifically, we address the distinct and common features of both cell types in health and disease, with a focus on human synovial joints. Finally, we also discuss the possible approaches to boost the complementary roles of MSCs and fibroblasts, to promote successful tissue regeneration.

P.219 The effect of peri-operative adverse events on long-term patient reported outcomes after lumbar spine surgery

Background: Peri-operative adverse events (AE) lead to patient disappointment and greater costs. There is a paucity of data on how AEs affect long-term outcomes. The purpose of this study is to examine peri-operative AEs and their impact on outcome after lumbar spine surgery. Methods: 3556 consecutive patients undergoing surgery for lumbar degenerative disorders enrolled in the Canadian Spine Outcomes and Research Network were analyzed. AEs were defined using the validated Spine AdVerse Events Severity system. Outcomes at 3,12, and 24 months post-operatively included the Owestry Disability Index (ODI), SF-12 Physical (PCS) and Mental (MCS) scales, visual analog scale (VAS) leg and back, Euroqol-5D (EQ5D), and satisfaction. Results: Adverse events occurred in 767 (21.6%) patients, 85 (2.4%) suffered major AEs. Patients with major AEs had worse OD (physical disability) scores and did not reach minimum clinically important differences at 2 years (no AE 25.7±19.2, major: 36.4±19.1, p<0.001). Major AEs were associated with worse ODI (physical disability) scores on multivariable linear regression (p=0.011). Conclusions: Major AEs after lumbar spine surgery lead to worse functional outcomes and lower satisfaction. This highlights the need to implement strategies aimed at reducing adverse events.

Effectiveness of Extracorporeal Shock Wave Therapy Reduces Leg Cramps in Patients of Lumbar Degenerative Disorders: A Retrospective Study

Background. The extracorporeal shock wave therapy (ESWT) has been fully utilized in orthopedics, but there are few studies in the treatment of lower limb spasm and pain caused by lumbar degenerative disorders (LDD). This study assesses the influence of ESWT in patients with LDD. Methods. From October 2017 to June 2019, 126 patients with LDD were enrolled. All patients received shock wave therapy, once every two days for four weeks in total. Each treatment consisted of 2,000 shocks with a frequency of 8-10 shocks per second. To analyze the therapeutic progress, the following tests were performed (before and after therapy; 1- and 3-month follow-up) to assess pain and functional efficiency: (1) Visual Analog Scale (VAS), (2) the frequency and duration of muscle cramps, and (3) Fugl-Meyer (LL). Results. Mean BMI of the participants was 26.1 ± 3.0 kg/m2. There was no statistically significant difference in terms of age or BMI between the groups ( p > 0.05 ). Although all scoring parameters improved in both groups, the improvement in the ESWT group was more pronounced in pain ( p < 0.001 and p < 0.001 , respectively). A review of the LMA scores of our patients demonstrated moderate functional limitations before treatment and increased functional status after treatment in all patients, while overall functional status was fully improved in patients of the ESWT group ( p < 0.001 ). Conclusion. The ESWT is particularly effective effect for patients with LDD. The use of ESWT has a significant long-term influence on the reduction of pain, leg cramps, and the improvement of the general functional state in relation to the conventional motor improvement program.