Mechanistic and physiological approaches of fecal microbiota transplantation in the management of NAFLD

Inflammation Research - Non-alcoholic fatty liver disease (NAFLD) is a multifaceted disease allied with various metabolic disorders, obesity and dysbiosis. Gut microbiota plays an influential role...     

A Comparative Study on Morphochemical Properties and Osteogenic Cell Differentiation within Bone Graft and Coral Graft Culture Systems

The objective of this study was to compare the morphological and chemical composition of bone graft (BG) and coral graft (CG) as well as their osteogenic differentiation potential using rabbit mesenchymal stem cells (rMSCs) in vitro. SEM analysis of BG and CG revealed that the pores in these grafts were interconnected, and their micro-CT confirmed pore sizes in the range of 107-315 µm and 103-514 µm with a total porosity of 92% and 94%, respectively. EDS analysis indicated that the level of calcium in CG was relatively higher than that in BG. FTIR of BG and CG confirmed the presence of functional groups corresponding to carbonyl, aromatic, alkyl, and alkane groups. XRD results revealed that the phase content of the inorganic layer comprised highly crystalline form of calcium carbonate and carbon. Atomic force microscopy analysis showed CG had better surface roughness compared to BG. In addition, significantly higher levels of osteogenic differentiation markers, namely, alkaline phosphatase (ALP), Osteocalcin (OC) levels, and Osteonectin and Runx2, Integrin gene expression were detected in the CG cultures, when compared with those in the BG cultures. In conclusion, our results demonstrate that the osteogenic differentiation of rMSCs is relatively superior in coral graft than in bone graft culture system.     

Muscle Fibers are Injured at the Time of Acute and Chronic Rotator Cuff Repair

BackgroundRotator cuff tears are a common source of shoulder pain and disability. Even after surgical repair, some patients continue to have reduced function and progression of fatty degeneration. Because patients with chronic cuff tears often experience muscle shortening, it is possible that repairing the tendon to its anatomic footprint induces a stretch-induced muscle injury that could contribute to failures of the repair and perhaps ongoing pain.Questions/purposesWe hypothesized that, compared with acutely torn and repaired muscles, the stretch that is required to repair a chronically torn cuff would result in more muscle fiber damage. Specifically, we asked: (1) Is there muscle fiber damage that occurs from repair of an acutely torn rotator cuff and does it vary by location in the muscle; and (2) is the damage greater in the case of repair of a chronic injury?MethodsWe used an open surgical approach to create a full-thickness rotator cuff tear in rats, and measured changes in muscle mass, length, and the number of fibers containing the membrane impermeable Evans Blue Dye after acute (1 day) or chronic (28 days) cuff tear or repair in rats. Differences between groups were tested using a one-way ANOVA followed by Tukey’s post hoc sorting.ResultsChronic tears resulted in 24% to 35% decreases in mass and a 20% decrease in length. The repair of acutely and chronically torn muscles resulted in damage to 90% of fibers in the distal portion of the muscle. In the proximal portion, no differences between the acutely torn and repaired groups and controls were observed, whereas repairing the chronically torn group resulted in injury to almost 70% of fibers.ConclusionsIn a rat model, marked injury to muscle fibers is induced when the tendons of torn rotator cuffs are repaired to their anatomic footprint.

Clinical Relevance

In this animal model, we found that repair of chronically torn cuff muscles results in extensive injury throughout the muscle. Based on these findings, we posit that inducing a widespread injury at the time of surgical repair of chronically torn rotator cuff muscles may contribute to the problems of failed repairs or continued progression of fatty degeneration that is observed in some patients that undergo rotator cuff repair. Therapeutic interventions to protect muscle fiber membranes potentially could enhance outcomes for patients undergoing rotator cuff repair. To evaluate this, future studies that evaluate the use of membrane sealing compounds or drugs that upregulate endogenous membrane-sealing proteins are warranted.     

The Effect of Granulocyte-colony Stimulating Factor on Rotator Cuff Healing After Injury and Repair

Background

The failure rate of tendon-bone healing after repair of rotator cuff tears remains high. A variety of biologic- and cell-based therapies aimed at improving rotator cuff healing have been investigated, and stem cell-based techniques have become increasingly more common. However, most studies have focused on the implantation of exogenous cells, which introduces higher risk and cost. We aimed to improve rotator cuff healing by inducing endogenous stem cell mobilization with systemic administration of granulocyte-colony stimulating factor (G-CSF).

Questions/purposes

We asked: (1) Does G-CSF administration increase local cellularity after acute rotator cuff repair? (2) Is there histologic evidence that G-CSF improved organization at the healing enthesis? (3) Does G-CSF administration improve biomechanical properties of the healing supraspinatus tendon-bone complex? (4) Are there micro-MRI-based observations indicating G-CSF-augmented tendon-bone healing?

Methods

After creation of full-thickness supraspinatus tendon defects with immediate repair, 52 rats were randomized to control or G-CSF-treated groups. G-CSF was administered for 5 days after repair and rats were euthanized at 12 or 19 postoperative days. Shoulders were subjected to micro-MR imaging, stress relaxation, and load-to-failure as well as blinded histologic and histomorphometric analyses.

Results

G-CSF-treated animals had significantly higher cellularity composite scores at 12 and 19 days compared with both control (12 days: 7.40 ± 1.14 [confidence interval {CI}, 5.98–8.81] versus 4.50 ± 0.57 [CI, 3.58–5.41], p = 0.038; 19 days: 8.00 ± 1.00 [CI, 6.75–9.24] versus 5.40 ± 0.89 [CI, 4.28–6.51], p = 0.023) and normal animals (12 days: p = 0.029; 19 days: p = 0.019). There was no significant difference between G-CSF-treated animals or control animals in ultimate stress (MPa) and strain, modulus (MPa), or yield stress (MPa) and strain at either 12 days (p = 1.000, p = 0.104, p = 1.000, p = 0.909, and p = 0.483, respectively) or 19 days (p = 0.999, p = 0.964, p = 1.000, p = 0.988, and p = 0.904, respectively). There was no difference in MRI score between G-CSF and control animals at either 12 days (2.7 ± 1.8 [CI, 1.08–4.24] versus 2.3 ± 1.8 [CI, 0.49–4.17], p = 0.623) or 19 days (2.5 ± 1.4 [CI, 1.05–3.94] versus 2.3 ± 1.5 [CI, 0.75–3.91], p = 0.737). G-CSF-treated animals exhibited significantly lower relative bone volume compared with normal animals in the entire humeral head (24.89 ± 3.80 [CI, 20.17–29.60) versus 32.50 ± 2.38 [CI, 29.99–35.01], p = 0.009) and at the supraspinatus insertion (25.67 ± 5.33 [CI, 19.04–32.29] versus 33.36 ± 1.69 [CI, 31.58–35.14], p = 0.027) at 12 days. Further analysis did not reveal any additional significant relationships with respect to regional bone volume or trabecular thickness between groups and time points (p > 0.05).

Clinical Relevance

Postoperative stem cell mobilization agents may be an effective way to enhance rotator cuff repair. Future studies regarding the kinetics of mobilization, the homing capacity of mobilized cells to injured tissues, and the ability of homing cells to participate in regenerative pathways are necessary.     

Establishing and managing a periodontal biobank for research: the sharing of experience

Periodontal bio‐repositories, which allow banking of clinically validated human data and biological samples, provide an opportunity to derive biomarkers for periodontal diagnosis, prognosis and therapeutic activities which are expected to improve patient management. This article presents the establishing of the Malaysian Periodontal Database and Biobank System (MPDBS) which was initiated in 2011 with the aim to facilitate periodontal research. Partnerships were established with collaborating centres. Policies on specimen access, authorship and acknowledgement policies were agreed upon by all participating centres before the initiation of the periodontal biobank. Ethical approval for the collection of samples and data were obtained from institutional ethics review boards. A broad‐based approach for informed consent was used, which covered areas related to quality of life impacts, genetics and molecular aspects of periodontal disease. Sample collection and processing was performed using a standardized protocol. Biobanking resources such as equipment and freezers were shared with the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). In the development of the MPDBS, challenges that were previously faced by the MOCDTBS were considered. Future challenges in terms of ethical and legal issues will be faced when international collaborations necessitate the transportation of specimens across borders.     

Infection--an underappreciated cause of bone pain in multiple myeloma

Bone pain, especially back pain, is a common presenting feature of myeloma patients. We report three multiple myeloma patients with exacerbations of back pain and referred shoulder pain resulting from vertebral infections. Two patients were treated with surgery, and one patient had computerized tomography-guided percutaneous needle aspiration for diagnostic purposes. All three patients received a prolonged course of antibiotics. Vertebral infection resolved with this treatment in all three patients without any recurrence. Previous dexamethasone therapy, together with an episode of bacteraemia, appears to be a predisposing factor for vertebral infection. Magnetic resonance imaging enabled the diagnosis in all three patients.