Bioactive peptide relieves glucocorticoid-induced osteoporosis by giant macrocyclic encapsulation.

Bioactive peptides play a crucial role in the field of regenerative medicine and tissue engineering. However, their application in vivo and clinic is hindered by their poor stability, short half-life, and low retention rate. Herein, we propose a novel strategy for encapsulating bioactive peptides using giant macrocycles. Platelet-derived growth factor (PDGF) bioactive mimicking peptide Nap-FFGVRKKP (P) was selected as the representative of a bioactive peptide. Quaterphen[4]arene (4) exhibited extensive host-guest complexation with P, and the binding constant was (1.16 ± 0.10) × 107 M-1. In vitro cell experiments confirmed that P + 4 could promote the proliferation of BMSCs by 2.27 times. Even with the addition of the inhibitor dexamethasone (Dex), P + 4 was still able to save 76.94% of the cells in the control group. Compared to the Dex group, the bone mass of the mice with osteoporosis in the P + 4 group was significantly increased. The mean trabecular thickness (Tb.Th) increased by 17.03%, and the trabecular bone volume fraction (BV/TV) values increased by 40.55%. This supramolecular bioactive peptide delivery strategy provides a general approach for delivering bioactive peptides and opens up new opportunities for the development of peptide-based drugs.

Therapeutic Efficacy of Nasal Corticosteroids in COVID-19-Related Olfactory Dysfunction: A Comprehensive Systematic Review and Meta-analysis.

OBJECTIVE: Olfactory disturbance is one of the main symptoms of coronavirus disease-2019 (COVID-19). Various olfactory disorders caused by viral infections are treated with nasal corticosteroids. This study aimed to evaluate the safety and efficacy of nasal corticosteroids in the treatment of olfactory disorders caused by the severe acute respiratory syndrome coronavirus 2. DATA SOURCES: We searched the Web of Science, Embase, PubMed, and Cochrane Library databases for clinical trials of nasal corticosteroids for treating COVID-19 olfactory dysfunction. REVIEW METHODS: We assessed the effect of nasal corticosteroids on olfactory function in COVID-19-affected individuals using a Meta-analysis of published studies, considering the number of patients who fully recovered from olfactory dysfunction, olfactory scores following treatment, and olfactory recovery time. RESULTS: Seven studies involving 930 patients were analyzed. The Meta-analysis results revealed that the olfactory score of the experimental group was 1.40 points higher than that of the control group (standardized mean difference [MD]: 1.40, 95% confidence interval [95% CI]: 0.34-2.47, P < .00001). However, the differences in the outcomes of cure rate (risk ratio: 1.18, 95% CI: 0.89-1.69, P = .21) and recovery time (MD: -1.78, 95% CI: -7.36 to 3.81, P = .53) were not statistically significant. Only 1 study reported adverse effects of nasal steroid treatment, namely tension, anger, and stomach irritation. CONCLUSION: Although nasal steroid therapy does not result in significant adverse effects, it proves ineffective in the treatment of COVID-19 olfactory dysfunction.

Decoding unusual MR findings: Spinal cord edema in atypical cervical spondylotic myelopathy-A case report and literature review.

We report a case of a young man with a slow progression of cervical spondylotic myelopathy (CSM). Cervical magnetic resonance imaging (MRI) revealed a mild cervical discbulging at C5-C6 and an area of atypically enlarged intramedullary high signal intensity extending from C4-C7 (T2-weighted) with contrast enhancement at C5-C6 (T1-weighted). Neurological and radiological diagnoses tend to favor demyelinating diseases, which interfere with the diagnosis of CSM. Patients were followed up and examined by MRI at 3 months, 1 year, and 2 years after surgery. The patient's symptoms improved immediately postoperatively. The functional result according to the modified Japanese Orthopedic Association (JOA) score improved from 10 to 13 within 3 months. He continued to improve neurologically over the first postoperative year. Two years postoperatively, a T2-weighted MRI showed that the edema signal had disappeared completely, and a fat-saturated T2-weighted MRI showed only slight abnormal signal. The numbness and weakness of the extremities had improved, and his JOA score was 16. Spinal cord edema is occasionally seen with CSM. In the case presented, the contrast enhancement was localized at the site of the greatest narrowing of the spinal canal and compression of the spinal cord. This coincidence was the best indicator of a mechanical cause of the spinal cord changes. This feature should increase physician's confidence in distinguishing CSM from intramedullary tumors and myelitis. Surgical decompression may be beneficial in improving neurologic outcomes.

Identification and characterization of extrachromosomal circular DNA in age-related osteoporosis.

Extrachromosomal circular DNA (eccDNA) was once thought to mainly exist in tumour cells, although it was later shown to be ubiquitous in healthy tissues as well. However, the characteristics and properties of eccDNA in healthy tissue or non-cancer tissue are not well understood. This study first analyses the properties, possible formation mechanisms and potential functions of eccDNA in osteoporotic or normal bone tissue. We used circle-seq to demonstrate the expression spectrum of the eccDNA in the bone tissue. A bioinformatics analysis was performed for the differentially expressed eccDNA, and it enriched the Hippo signalling pathway, PI3K-Akt signalling pathway, Ras signal-ling pathway and other signalling pathways that are closely related to osteoporosis (OP). Then, we used real-time polymerase chain reaction and Sanger sequencing to assess human bone marrow mesenchymal stem cells and obtained the base sequence of the eccDNA cyclization site. Overall, eccDNAs in bone tissue are common and may play a significant role in pathways connected to age-related osteoporosis progression.

Comparison of the Effects of Metformin and Thiazolidinediones on Bone Metabolism: A Systematic Review and Meta-Analysis.

OBJECTIVES: Studies have shown that people with diabetes have a high risk of osteoporosis and fractures. The effect of diabetic medications on bone disease cannot be ignored. This meta-analysis aimed to compare the effects of two types of glucose-lowering drugs, metformin and thiazolidinediones (TZD), on bone mineral density and bone metabolism in patients with diabetes mellitus. METHODS: This systematic review and meta-analysis were prospectively registered on PROSPERO, and the registration number is CRD42022320884. Embase, PubMed, and Cochrane Library databases were searched to identify clinical trials comparing the effects of metformin and thiazolidinediones on bone metabolism in patients with diabetes. The literature was screened by inclusion and exclusion criteria. Two assessors independently assessed the quality of the identified studies and extracted relevant data. RESULTS: Seven studies involving 1656 patients were finally included. Our results showed that the metformin group had a 2.77% (SMD = 2.77, 95%CI [2.11, 3.43]; p < 0.00001) higher bone mineral density (BMD) than the thiazolidinedione group until 52 weeks; however, between 52 and 76 weeks, the metformin group had a 0.83% (SMD = -0.83, 95%CI: [-3.56, -0.45]; p = 0.01) lower BMD. The C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (PINP) were decreased by 18.46% (MD = -18.46, 95%CI: [-27.98, -8.94], p = 0.0001) and 9.94% (MD = -9.94, 95%CI: [-16.92, -2.96], p = 0.005) in the metformin group compared with the TZD group.

Corrigendum: Efficacy of umbilical cord mesenchymal stromal cells for COVID-19: a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fimmu.2022.923286.].

Exosomes derived from human umbilical cord mesenchymal stem cells promote osteogenesis through the AKT signaling pathway in postmenopausal osteoporosis.

Postmenopausal osteoporosis (PMO) is a relatively common disease characterized by low bone mass and microstructural changes of trabecular bone. The reduced bone strength is caused a variety of complications, including fragility fracture and sarcopenia. We used CCK-8 and EdU assays to evaluate cell proliferation rates. The osteogenesis effect was detected using ALP staining, alizarin red staining, and q-PCR. In vivo, the effects of exosomes derived from HUC-MSCs were evaluated using HE staining, IHC staining and Masson staining. In addition, we explored the mechanism of exosomes and found that the AKT signaling pathway played an important role in osteogenesis and cell proliferation. This paper mainly explored the function of exosomes derived from human umbilical cord mesenchymal stem cells (HUC-MSCs) and provided a new strategy for the treatment of postmenopausal osteoporosis. In conclusion, exogenous administration of exosomes can contribute to the treatment postmenopausal osteoporosis to a certain extent.

Efficacy of umbilical cord mesenchymal stromal cells for COVID-19: A systematic review and meta-analysis.

Objectives: A major challenge for COVID-19 therapy is dysregulated immune response associated with the disease. Umbilical cord mesenchymal stromal cells (UC-MSCs) may be a promising candidate for COVID-19 treatment owing to their immunomodulatory and anti-inflammatory functions. Therefore, this study aimed to evaluate the effectiveness of UC-MSCs inpatients with COVID-19. Method: Medline, Embase, PubMed, Cochrane Library, and Web of Science databases were searched to collect clinical trials concerning UC-MSCs for the treatment of COVID-19. After literature screening, quality assessment, and data extraction, a systematic review and meta-analysis of the included study were performed. Results: This systematic review and meta-analysis were prospectively registered on PROSPERO, and the registration number is CRD42022304061. After screening, 10 studies involving 293 patients with COVID-19 were eventually included. Our meta-analysis results showed that UC-MSCs can reduce mortality (relative risk [RR] =0.60, 95% confidence interval [CI]: [0.38, 0.95], P=0.03) in COVID-19 patients. No significant correlation was observed between adverse events and UC-MSC treatment (RR=0.85, 95% CI: [0.65, 1.10], P=0.22; RR=1.00, 95%CI: [0.64, 1.58], P=1.00). In addition, treatment with UC-MSCs was found to suppress inflammation and improve pulmonary symptoms. Conclusions: UC-MSCs hold promise as a safe and effective treatment for COVID-19. Systematic Review Registartion: PROSPERO, identifier CRD42022304061.