Probiotics Composition Harbors Against Osteoarthritis and Inflammation through GABA in Mice

Background: Osteoarthritis (OA) is an age-related disease with multifactorial etiology and its prevalence growing globally. The role of Gut microbiota is inevitable concerning musculoskeletal disease and health. A method of controlling inflammation and cartilage destruction through changes in gut microbiota is proposed. Previously reported data lack the specific approach to microbial clusters and biomarkers in understanding the interactions between host and microbiome.Method: We adopted a novel approach to elaborate the positive influence of S. thermophilus and L. pentosus to treat Anterior cruciate ligament transection (ACLT) induced OA in vivo. For in vitro analysis Human Chondrocyte Cell Line (C28/I2) was used to analyze chondrogenic effect of microbes and GABA. Tukey’s multiple-comparisons test or Two-stage linear step-up procedure of Benjamini, Krieger, and Yekutieli test were used to statistically analyze the data.Results: The gut microbiota-joint axis promoted chondrogenesis and inhibited catabolism. Selected bacteria produced GABA as postbiotic. This study is the first to represent the chondrogenic and protective effects of γ-aminobutyric acid (GABA) on human chondrocytes and cartilage tissue in mice. Oral administration of it down-regulated cartilage degradation in OA-induced mice and decreased inflammation.Conclusion: We speculated the positive results from GABA and probiotics producing GABA against OA. GABA may have functional roles in chondrocyte maturation /differentiation. This data provides a foundation for further studies to elucidate the role of GABA producing microbes and GABA in the regulation of cartilaginous cell proliferation. These findings open future horizons to understand the gut-joint axis and for the treatment of OA. Thus probiotic / GABA therapy could act as a nutraceutical modulator for OA.

The relation between the gut microbiome and osteoarthritis: A systematic review of literature

Background Along with mechanical and genetic factors, emerging evidence suggests that the presence of low-grade inflammation has a role in the pathogenesis of osteoarthritis (OA) and seems to be related to the microbiome composition of the gut. Purpose To provide evidence whether there is clinical or preclinical evidence of gut-joint axis in the pathogenesis and symptoms of OA. Methods An extensive review of the current literature was performed using three different databases. Human, as well as animal studies, were included. The risk of bias was identified using ROBINS and SYRCLE tools, while the quality of evidence was assessed using GRADE and CAMADARES criteria. Results A total of nineteen articles were included. Multiple animal studies demonstrated that both obesity, and high-fat and high-sugar diets resulted in a gut dysbiosis status characterized by increased Firmicutes/Bacteroidetes (F/B) phyla ratio and increased permeability. These changes were associated with increased lipopolysaccharide serum levels, which consequently resulted in synovitis and OA severity. The administration of pre-and probiotics partially reversed this bacterial composition. In addition, in human studies, a decreased amount of gut Bacteroidetes, subsequent increased F/B ratio, have also been observed in OA patients. Conclusions Our review confirms preliminary yet sound evidence supporting a gut-joint axis in OA in primarily preclinical models, by showing an association between diet, gut dysbiosis and OA radiological severity and self-reported symptoms. Clinical studies are needed to confirm these findings, and to investigate whether interventions targeting the composition of the microbiome will have a beneficial clinical effect.

Enumeration and instantaneous mobility analysis of a class of 3-UPU parallel manipulators with equilateral triangular platforms

In this study, several joint axis orientations on equilateral platforms and the limbs of 3-UPU parallel manipulators (PMs) are examined. The generated joint layouts for the platforms were matched with each other to generate and enumerate manipulator architectures based on certain assumptions. The structures of thus obtained manipulators are examined and limb types were determined. These limb types were analyzed using screw theory. The instantaneous mobility of the manipulators and the motion characteristics of the moving platforms are tabulated. The finite mobility analysis of one of the manipulators is performed using a software package as an example. Among several different 3-UPU PM architectures, 118 novel 3-UPU PMs with non-parasitic 3-degrees-of-freedom are significantly important. The classified 3-UPU PMs with determined motion characteristics can be used by researchers as a design alternative for their specific design task.

An approach for mobility and force/motion transmissibility analysis of parallel mechanisms based on screw theory and CAD technology

By integrating screw theory with computer-aided design (CAD) technology, this paper presents an effective and automated methodology for mobility and force/motion transmissibility analysis of parallel mechanisms (PMs). In this approach, A kinematic diagram of a PM termed as the conceptual model, which consists of a solid assembly and several skeleton elements in the form of datum entities and non-geometric entities such as parameters, equations and semantic information, is built by using the 3D modeling capabilities of SolidWorks. For each limb of the PM, a rule-based reasoning (RBR) system is developed based upon the dual and reciprocal properties of screw systems, allowing its own twist/wrench subspaces to be determined automatically by using the joint axis features extracted from the conceptual model. These considerations lead to an automated procedure that can be used to generate the general Jacobian of PMs, allowing the mobility and force/motion transmissibility analysis to be carried out automatically, a work that had to be done manually in the past. Based on the proposed approach, a software package is developed and examples are given to verify its effectiveness.

Flood Control: How Milk-Derived Extracellular Vesicles Can Help to Improve the Intestinal Barrier Function and Break the Gut–Joint Axis in Rheumatoid Arthritis

Many studies provided compelling evidence that extracellular vesicles (EVs) are involved in the regulation of the immune response, acting as both enhancers and dampeners of the immune system, depending on the source and type of vesicle. Research, including ours, has shown anti-inflammatory effects of milk-derived EVs, using human breast milk as well as bovine colostrum and store-bought pasteurized cow milk, in in vitro systems as well as therapeutically in animal models. Although it is not completely elucidated which proteins and miRNAs within the milk-derived EVs contribute to these immunosuppressive capacities, one proposed mechanism of action of the EVs is via the modulation of the crosstalk between the (intestinal) microbiome and their host health. There is increasing awareness that the gut plays an important role in many inflammatory diseases. Enhanced intestinal leakiness, dysbiosis of the gut microbiome, and bowel inflammation are not only associated with intestinal diseases like colitis and Crohn’s disease, but also characteristic for systemic inflammatory diseases such as lupus, multiple sclerosis, and rheumatoid arthritis (RA). Strategies to target the gut, and especially its microbiome, are under investigation and hold a promise as a therapeutic intervention for these diseases. The use of milk-derived EVs, either as stand-alone drug or as a drug carrier, is often suggested in recent years. Several research groups have studied the tolerance and safety of using milk-derived EVs in animal models. Due to its composition, milk-derived EVs are highly biocompatible and have limited immunogenicity even cross species. Furthermore, it has been demonstrated that milk-derived EVs, when taken up in the gastro-intestinal tract, stay intact after absorption, indicating excellent stability. These characteristics make milk-derived EVs very suitable as drug carriers, but also by themselves, these EVs already have a substantial immunoregulatory function, and even without loading, these vesicles can act as therapeutics. In this review, we will address the immunomodulating capacity of milk-derived EVs and discuss their potential as therapy for RA patients.Review criteriaThe search terms “extracellular vesicles”, “exosomes”, “microvesicles”, “rheumatoid arthritis”, “gut-joint axis”, “milk”, and “experimental arthritis” were used. English-language full text papers (published between 1980 and 2021) were identified from PubMed and Google Scholar databases. The reference list for each paper was further searched to identify additional relevant articles.

Establishing a New Patient-Specific Implantation Technique for Total Ankle Replacement: An In Vitro Study

Background Revision rates after total ankle replacements (TARs) are higher compared with other total joint replacements. The present study aimed to establish a new patient-specific implantation (PSI) technique for TAR. Material and methods A total of 10 complete Caucasian cadaver legs had whole leg computed tomography scans. The individual geometrical ankle joint axis was determined, and based on this axis, the position of the prosthesis was planned. We assessed prosthesis placement, guiding block position, and preoperative and postoperative ankle rotational axes. Results The guiding block position interobserver reliability was 0.37 mm 0.45 (mean ± SD) for the tibial guiding block. The value for the first talar guiding block was 1.72 ± 1.3 mm and for the second talar guiding block, 0.61 ± 0.39 mm. The tibial slope as well as the frontal angles of the anatomical tibial axis compared to the tibial and talar articular surfaces showed no statistically relevant differences with numbers available. The deviation of the assessed preoperative joint axis to the postoperative joint axis was 14.6° ± 7.8. Conclusion The present study describes the results of an establishing process of a new PSI technique for TAR. The reliability of guiding block positioning and, thereby, prosthesis placement is sufficient. Level of Evidence: Biomechanical study

Design and kinematics of a novel double-ring truss deployable antenna mechanism

This paper aims to present the topological structure design and kinematic analysis of a novel double-ring truss deployable satellite antenna mechanism. First, a new topological scheme and a new rectangular prism deployable linkage unit are proposed for constructing the kind of antenna mechanisms. Second, the degree-of-freedom (DOF) of the deployable unit and the antenna mechanism are analyzed based on structure decomposition and screw theory. Third, the kinematic model of the double-ring truss deployable antenna mechanism is established based on its structural characteristics. Finally, a typical numerical example is used to illustrate the effectiveness of the designed mechanism and the established kinematic model. The new double-ring truss deployable antenna mechanism consists of the units with the better structural symmetry, and has simpler joint axis layouts, comparing with the same type of most existing mechanisms.