Vazquezyildiz7790
in of OA joints. These findings may provide valuable basis for the treatment of OA.
Costal chondrocytes (CCs), as a promising donor cell source for cell-based therapy for cartilage repair, have strong tendency of hypertrophy and calcification, which limited CCs from further application in cartilage regenerative medicine. Erastin Ferroptosis activator Synovium-derived stromal cells (SDSCs), have shown their beneficial effect for chondrocytes to maintain phenotype. This study aims to investigate whether SDSCs could help CCs to maintain chondrogenic phenotype and suppress hypertrophic differentiation in cartilage repairs.
CCs were directly cocultured with SDSCs in pellet or indirectly cocultured using a conditioned medium in vitro for 3 weeks. Cartilage matrix formation and hypertrophic differentiation of CCs were analyzed by RT-PCR, biochemical assays, and histological staining. Cocultured pellets were implanted into the osteochondral defects made on the femoral groove of the rats. Then, macroscopic and histological evaluations were performed.
Pellets formed by CCs alone and CCs cocultured with SDSCs reveal equal carntial usage of SDSCs in CCs-based cartilage repair therapy to suppress newly formed cartilage calcification and improve clinical outcomes.
These results suggest that SDSCs may maintain the phenotype of CCs and prevent the hypertrophic differentiation of CCs in cartilage repair.The Translational Potential of this Article CCs is a promising donor cell source for cell-based therapy for cartilage repair. Based on our study, cocultured with SDSCs weakened the tendency of hypertrophy and calcification of CCs, which provide a potential usage of SDSCs in CCs-based cartilage repair therapy to suppress newly formed cartilage calcification and improve clinical outcomes.
To comprehensively analyze the global level and trends of prevalence, incidence and years lived with disability (YLDs) for low back pain (LBP) from 1990 to 2019 by age, sex and sociodemographic index (SDI).
Publicly available modelled data and methods were obtained from the Global Burden of Diseases (GBD) study 2019, and used to evaluate the global burden of LBP through a systematic analysis.
Globally, the age-standardized prevalence, incidence and YLDs rate of LBP were slightly decreased from 1990 to 2019, but the number of the prevalent cases, incident cases and YLDs had substantially increased, and LBP remains the leading cause of YLDs in 2019 worldwide. The number of prevalent cases was increased with age and peaked at the age of 45-54 years for both sexes, and the global prevalence rate was higher in females than in males and increased with age, peaking at the 80-84 age group in both sexes in 2019. link2 Overall, a positive association between the age-standardized YLD rate and SDI was observed over the pomparable information on global LBP burden, which is of clinical translational significance.
Our recent studies demonstrate that the focal adhesion protein Kindlin-2 exerts crucial functions in the mesenchymal stem cells, mature osteoblasts and osteocytes in control of early skeletal development and bone homeostasis in mice. However, whether Kindlin-2 plays a role in osteoprogenitors remains unclear.
Mice lacking Kindlin-2 expression in osterix (Osx)-expressing cells (i.e., osteoprogenitors) were generated. Micro-computerized tomography (μCT) analyses, histology, bone histomorphometry and immunohistochemistry were performed to determine the effects of Kindlin-2 deletion on skeletal development and bone mass accrual and homeostasis. Bone marrow stromal cells (BMSCs) from mutant mice (
) and control littermates were isolated and determined for their osteoblastic differentiation capacity.
Kindlin-2 was highly expressed in osteoprogenitors during endochondral ossification. Deleting Kindlin-2 expression in osteoprogenitors impaired both intramembranous and endochondral ossifications. Mutaoprogenitor cells controls chondrogenesis and bone mass. We may define a novel therapeutic target for treatment of skeletal diseases, such as chondrodysplasia and osteoporosis.
With the advances in biological technologies over the past 20 years, a number of new therapies to promote bone healing have been introduced. Particularly in the spinal surgery field, more unprecedented biological therapeutics become available to enhance spinal fusion success rate along with advanced instrumentation approaches. Yet surgeons may not have been well informed about their safety and efficacy profiles in order to improve clinical practices. Therefore there is a need to summarize the evidence and bring the latest progress to surgeons for better clinical services for patients.
We comprehensively reviewed the literatures in regard to the biological therapeutics for enhancement of spinal fusion published in the last two decades.
Autograft bone is still the gold standard for bone grafting in spinal fusion surgery due to its good osteoconductive, osteoinductive, and osteogenic abilities. Accumulating evidence suggests that adding rhBMPs in combination with autograft effectively promotes the fusion ridence, the safety and efficacy of present and emerging products are becoming more evident. These emerging therapeutics will shift the landscape of perioperative therapy for the enhancement of spinal fusion.
As the world's population continues to grow older, the number of spinal fusion cases grows substantially due to increased surgical needs for spinal degenerative disease (SDD). Critical advancements in biological therapeutics that promote spinal fusion have brought better clinical outcomes to patients lately. With the accumulation of higher-level evidence, the safety and efficacy of present and emerging products are becoming more evident. These emerging therapeutics will shift the landscape of perioperative therapy for the enhancement of spinal fusion.
Elevated tumor necrosis factor alpha (TNF-α) expression is correlated with the progression of intervertebral disc degeneration (IVDD). Progranulin binding to tumor necrosis factor receptor (TNFR) and its derivative Atsttrin are effective for treating inflammatory arthritis. We hypothesize that Atsttrin has a protective effect in IVDD through different roles of TNFR receptor type 1 (TNFR1) and TNFR receptor type 2 (TNFR2) in degenerated discs.
IVDD models were established in TNFR1
, TNFR2
mice and their control littermates. Nucleus Pulpous (NP) samples from human patients and IVDD murine models were evaluated by X-ray, micro-MRI, μCT, histological staining and immunofluorescence staining. NP cells isolated from wild-type (WT), TNFR1
and TNFR2
mice were treated with TNF-α or Atsttrin and then assayed by Western blotting, qRT-PCR, and ELISA.
TNFR1 and TNFR2 expression was significantly elevated in the disc tissues of both human patients and IVDD murine models. TNFR1 knockout contributed to reduced dthe potential use of Atsttrin as a therapeutic agent against IVDD in mice.
Diabetes mellitus could cause numerous complications and health problems including abnormality of endochondral bone formation during embryogenesis. However, the underlying mechanisms still remain obscure.
Streptozotoci (STZ) was injected to induce pregestational diabetes mellitus (PGDM) mouse model. The femurs of E18.5 mouse embryos from control and PGDM groups were harvested. Morphological staining was implemented to determine the abnormality of the bone development. The expressions of the key genes participating in osteogenesis (e.g., Sox9, Runx2, and Osterix), the NF-κB signaling molecules (e.g., P50, P65, IκBα), and the corresponding regulatory factors (e.g., Bmp2, phospho-p38) were evaluated by immunofluorescence, quantitative PCR and western blot. Finally, in vitro chondrocyte differentiation model was employed to verify the role of NF-κB on the expressions of chondro-osteogenic markers.
Alcian blue/alizarin red double staining and H&E staining demonstrated the restriction of skeletal developm effects of dysfunctional trans-differentiation of hypertrophic chondrocytes in the embryonic growth plate induced by maternal diabetic mellitus.
Our data revealed that NF-κB signaling was involved in mediation effects of dysfunctional trans-differentiation of hypertrophic chondrocytes in the embryonic growth plate induced by maternal diabetic mellitus.Biosynthesis of itaconic acid occurs through decarboxylation of the TCA cycle intermediate cis-aconitate. Engineering of efficient itaconate producers often requires elimination of the highly active isocitrate dehydrogenase to conserve cis-aconitate, leading to 2-ketoglutarate auxotrophy in the producing strains. Supplementation of glutamate or complex protein hydrolysate then becomes necessary, often in large quantities, to support the high cell density desired during itaconate fermentation and adds to the production cost. Here, we present an alternative approach to overcome the glutamate auxotrophy in itaconate producers by synthetically introducing the Weimberg pathway from Burkholderia xenovorans for 2-ketoglutarate biosynthesis. Because of its independence from natural carbohydrate assimilation pathways in Escherichia coli, the Weimberg pathway is able to provide 2-ketoglutarate using xylose without compromising the carbon flux toward itaconate. With xylose concentration carefully tuned to minimize excess 2-ketoglutarate flux in the stationary phase, the final strain accumulated 20 g/L of itaconate in minimal medium from 18 g/L of xylose and 45 g/L of glycerol. Necessity of the recombinant Weimberg pathway for growth also allowed us to maintain multi-copy plasmids carrying in operon the itaconate-producing genes without addition of antibiotics. Use of the Weimberg pathway for growth restoration is applicable to other production systems with disrupted 2-ketoglutarate synthesis.In SF6 insulated high-voltage gas power systems, H2O is the most problematic impurity which not only decreases insulation performance but also creates an acidic atmosphere that promotes corrosion. Corrosion damages electrical equipment and leads to leaks, which pose serious safety hazards to people and the environment. A QEPAS-based sensor system for the sub-ppm level H2O detection in SF6 buffer gas was developed by use of a near-infrared commercial DFB diode laser. Since the specific physical constants of SF6 are strongly different from that of N2 or air, the resonant frequency and Q-factor of the bare quartz tuning fork (QTF) had changed to 32,763 Hz and 4173, respectively. The optimal vertical detection position was 1.2 mm far from the QTF opening. After the experimental optimization of acoustic micro-resonator (AmR) parameters, gas pressures, and modulation depths, a detection limit of 0.49 ppm was achieved for an averaging time of 1 s, which provided a powerful prevention tool for the safety monitoring in power systems.We report an unknown taxon of bot fly (Diptera Oestridae Oestrinae) in red river hogs (Potamochoerus porcus Linnaeus, 1758) in Cross River State, Nigeria. From direct observation and interviews with local hunters, we document that, remarkably, the parasite typically occurs within the intracranial supra-meningeal space - i.e., between the inner wall of the skull and the brain - but without causing visible inflammation or clinical signs. The parasite is most similar (up to 87.9%) to Rhinoestrus usbekistanicus based on cytochrome oxidase subunit 1 DNA sequencing but is sufficiently divergent phylogenetically to represent a new or previously un-sequenced taxon. Morphologically, the parasite shares some, but not all, features with R. link3 nivarleti. Local cultural belief systems attribute aspects of red river hog behavior (e.g. intelligence, elusiveness) to the parasite, suggesting a prolonged presence in the red river hog population. The parasite's unusual anatomic location may be aberrant, or it may be a protective adaptation to life in red river hogs, which forage vigorously with their snouts.
