Evaluation of Respiratory Muscle Activation Using Respiratory Motor Control Assessment (RMCA) in Individuals with Chronic Spinal Cord Injury

During breathing, activation of respiratory muscles is coordinated by integrated input from the brain, brainstem, and spinal cord. When this coordination is disrupted by spinal cord injury (SCI), control of respiratory muscles innervated below the injury level is compromised^1,2 leading to respiratory muscle dysfunction and pulmonary complications. These conditions are among the leading causes of death in patients with SCI³. Standard pulmonary function tests that assess respiratory motor function include spirometrical and maximum airway pressure outcomes: Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV₁), Maximal Inspiratory Pressure (PI_max) and Maximal Expiratory Pressure (PE_max)^4,5. These values provide indirect measurements of respiratory muscle performance⁶. In clinical practice and research, a surface electromyography (sEMG) recorded from respiratory muscles can be used to assess respiratory motor function and help to diagnose neuromuscular pathology. However, variability in the sEMG amplitude inhibits efforts to develop objective and direct measures of respiratory motor function⁶. Based on a multi-muscle sEMG approach to characterize motor control of limb muscles⁷, known as the voluntary response index (VRI)⁸, we developed an analytical tool to characterize respiratory motor control directly from sEMG data recorded from multiple respiratory muscles during the voluntary respiratory tasks. We have termed this the Respiratory Motor Control Assessment (RMCA)⁹. This vector analysis method quantifies the amount and distribution of activity across muscles and presents it in the form of an index that relates the degree to which sEMG output within a test-subject resembles that from a group of healthy (non-injured) controls. The resulting index value has been shown to have high face validity, sensitivity and specificity^9-11. We showed previously⁹ that the RMCA outcomes significantly correlate with levels of SCI and pulmonary function measures. We are presenting here the method to quantitatively compare post-spinal cord injury respiratory multi-muscle activation patterns to those of healthy individuals.     

The effects of resveratrol on cyclooxygenase-1 and cyclooxygenase-2 mRNA and protein levels in diabetic rat kidneys

Cyclooxygenase (COX), which have the isoforms of COX-1 and COX-2, is the key enzyme of prostaglandins biosynthesis. Especially, COX-2 is induced in inflammatory disease such as Diabetes Mellitus (DM). Resveratrol (RSV), a natural antioxidant, has a beneficial role in prevention of inflammatory disease. We investigated the changes of COX-1 and COX-2 mRNA expression and protein level in diabetic rat kidney after RSV treatment. Three months-old, 44 Wistar albino male rats, which were divided into six groups such as control group, sodium citrate buffer (sham control) group, diabetic group (DM), Dimethyl Sulfoxide induced control group, RSV treated sham control group (RSV) and RSV treated diabetic group (DM + RSV) were used for the study. Experimental diabetes was induced by intraperitoneal injection of 55 mg/kg Streptozotocin. After the induction of chronic diabetes 10 mg/kg per day RSV was administered intraperitoneally for 4 weeks. In this study. RSV has no significant effect on COX-1 mRNA expression in diabetic rat kidney (P > 0.05). Immunohistochemical study showed that COX-1 expression was slightly inhibited in RSV group and was not significantly supressed in DM + RSV group. When comparing control and treated groups, there were no significant differences in COX-2 mRNA or protein levels (P > 0.05). In conclusion, our results indicate that resveratrol do not significantly affect COX gene and protein expression. Therefore, different therapy strategies such as combination with other antidiabetic drugs may tried in STZ induced animal model for reducing diabetic symptoms and altering COX-1 and COX-2 mRNA or protein levels.     

Assessment of sorghum genetic resources of Ethiopia for anthracnose (Colletotrichum sublineolum Henn.) resistance and agronomic traits

Sorghum anthracnose caused by Colletotrichum sublineolum Henn. is one of the key diseases limiting sorghum production and productivity. Development of anthracnose‐resistant sorghum genotypes possessing yield‐promoting agronomic traits is an important breeding goal in sorghum improvement programs. The objective of this study was to determine the responses of diverse sorghum genetic resources for anthracnose resistance and agronomic traits to identify desirable lines for breeding. A total of 366 sorghum collections and three standard checks were field evaluated during the 2016 and 2017 cropping seasons. Lines were artificially inoculated with a virulent pure isolate of the pathogen. Anthracnose disease severity was assessed to calculate the area under disease progress curve (AUDPC). Agronomic traits such as panicle length (PL), panicle width (PW), head weight (HW) and thousand grain weight (TGW) were measured. Lines showed highly significant differences (p < .001) for anthracnose severity, AUDPC and agronomic traits. Among the collections 32 lines developed levels of disease severity between 15% and 30% in both seasons. The following sorghum landraces were selected: 71708, 210903, 74222, 73955, 74685, 74670, 74656, 74183, 234112, 69412, 226057, 214852, 71420, 71484, 200126, 71557, 75120, 71547, 220014, 228179, 16212, 16173, 16133, 69088, 238388, 16168 and 71570. These landraces had a relatively low anthracnose severity possessing farmer‐preferred agronomic traits. The selected genotypes are useful genetic resources to develop anthracnose‐resistant sorghum cultivars.     

Mesenchymal stem cells as carrier of the therapeutic agent in the gene therapy of blood disorders

Nonhematopoietic stem cells as a delivery platform of therapeutic useful genes have attracted widespread attention in recent years, owing to gained a long lifespan, easy separation, high proliferation, and high transfection capacity. Mesenchymal stem/stromal cells (MSCs) are the choice of the cells for gene and cell therapy due to high self-renewal capacity, high migration rate to the site of the tumor, and with immune suppressive and anti-inflammatory properties. Hence, it has a high potential of safety genetic modification of MSCs for antitumor gene expression and has paved the way for the clinical application of these cells to target the therapy of cancers and other diseases. The aim of gene therapy is targeted treatment of cancers and diseases through recovery, change, or enhancement cell performance to the sustained secretion of useful therapeutic proteins and induction expression of the functional gene in intended tissue. Recent developments in the vectors designing leading to the increase and durability of expression and improvement of the safety of the vectors that overcome a lot of problems, such as durability of expression and the host immune response. Nowadays, gene therapy approach is used by MSCs as a delivery vehicle in the preclinical and the clinical trials for the secretion of erythropoietin, recombinant antibodies, coagulation factors, cytokines, as well as angiogenic inhibitors in many blood disorders like anemia, hemophilia, and malignancies. In this study, we critically discuss the status of gene therapy by MSCs as a delivery vehicle for the treatment of blood disorders. Finally, the results of clinical trial studies are assessed, highlighting promising advantages of this emerging technology in the clinical setting.     

Manufacturing biological medicines on demand: Safety and efficacy of granulocyte colony-stimulating factor in a mouse model of total body irradiation

Protein therapeutics, also known as biologics, are currently manufactured at centralized facilities according to rigorous protocols. The manufacturing process takes months and the delivery of the biological products needs a cold chain. This makes it less responsive to rapid changes in demand. Here, we report on technology application for on-demand biologics manufacturing (Bio-MOD) that can produce safe and effective biologics from cell-free systems at the point of care without the current challenges of long-term storage and cold-chain delivery. The objective of the current study is to establish proof-of-concept safety and efficacy of Bio-MOD-manufactured granulocyte colony-stimulating factor (G-CSF) in a mouse model of total body irradiation at a dose estimated to induce 30% lethality within the first 30 days postexposure. To illustrate on-demand Bio-MOD production feasibility, histidine-tagged G-CSF was manufactured daily under good manufacturing practice-like conditions prior to administration over a 16-day period. Bio-MOD-manufactured G-CSF improved 30-day survival when compared with saline alone (p = .073). In addition to accelerating recovery from neutropenia, the platelet and hemoglobin nadirs were significantly higher in G-CSF-treated animals compared with saline-treated animals (p < .05). The results of this study demonstrate the feasibility of consistently manufacturing safe and effective on-demand biologics suitable for real-time release.