Accumulation of ß-aminoisobutyric acid mediates hyperalgesia in ovariectomized mice through Mas-related G protein-coupled receptor D signaling.

Hyperalgesia is typified by reduced pain thresholds and heightened responses to painful stimuli, with a notable prevalence in menopausal women, but the underlying mechanisms are far from understood. ß-Aminoisobutyric acid (BAIBA), a product of valine and thymine catabolism, has been reported to be a novel ligand of the Mas-related G protein coupled receptor D (MrgprD), which mediates pain and hyperalgesia. Here, we established a hyperalgesia model in 8-week-old female mice through ovariectomy (OVX). A significant increase in BAIBA plasma level was observed and was associated with decline of mechanical withdrawal threshold, thermal and cold withdrawal latency in mice after 6 weeks of OVX surgery. Increased expression of MrgprD in dorsal root ganglion (DRG) was shown in OVX mice compared to Sham mice. Interestingly, chronic loading with BAIBA not only exacerbated hyperalgesia in OVX mice, but also induced hyperalgesia in gonadally intact female mice. BAIBA supplementation also upregulated the MrgprD expression in DRG of both OVX and intact female mice, and enhanced the excitability of DRG neurons in vitro. Knockout of MrgprD markedly suppressed the effects of BAIBA on hyperalgesia and excitability of DRG neurons. Collectively, our data suggest the involvement of BAIBA in the development of hyperalgesia via MrgprD-dependent pathway, and illuminate the mechanisms underlying hyperalgesia in menopausal women.

Age-related decline in melatonin contributes to enhanced osteoclastogenesis via disruption of redox homeostasis.

BACKGROUND: Increased oxidative stress contributes to enhanced osteoclastogenesis and age-related bone loss. Melatonin (MT) is an endogenous antioxidant and declines with aging. However, it was unclear whether the decline of MT was involved in the enhanced osteoclastogenesis during the aging process. METHODS: The plasma level of MT, oxidative stress status, bone mass, the number of bone marrow-derived monocytes (BMMs) and its osteoclastogenesis were analyzed in young (3-month old) and old (18-month old) mice (n = 6 per group). In vitro, BMMs isolated from aged mice were treated with or without MT, followed by detecting the change of osteoclastogenesis and intracellular reactive oxygen species (ROS) level. Furthermore, old mice were treated with MT for 2 months to investigate the therapeutic effect. RESULTS: The plasma level of MT was markedly lower in aged mice compared with young mice. Age-related decline in MT was accompanied by enhanced oxidative stress, osteoclastogenic potential and bone loss. MT intervention significantly suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, decreased intracellular ROS and enhanced antioxidant capacity of BMMs from aged mice. MT supplementation significantly attenuated oxidative stress, osteoclastogenesis, bone loss and deterioration of bone microstructure in aged mice. CONCLUSIONS: These results suggest that age-related decline of MT enhanced osteoclastogenesis via disruption of redox homeostasis. MT may serve as a key regulator in osteoclastogenesis and bone homeostasis, thereby highlighting its potential as a preventive agent for age-related bone loss.

Tanshinone IIA attenuates osteoarthritis via inhibiting aberrant angiogenesis in subchondral bone.

Excessive angiogenesis in subchondral bone is a pathological feature of osteoarthritis (OA). Tanshinone IIA (TIIA), an active compound found in Salvia miltiorrhiza, demonstrates significant anti-angiogenic properties. However, the effect of TIIA on abnormal subchondral angiogenesis in OA is still unclear. This study aims to investigate the mechanism of TIIA in modulating subchondral bone angiogenesis during OA and assess its therapeutic potential in OA. Our findings demonstrate that TIIA attenuated articular cartilage degeneration, normalized subchondral bone remodeling, and effectively suppressed aberrant angiogenesis within subchondral bone in monosodium iodoacetate (MIA)-induced OA mice. Additionally, the angiogenesis capacity of primary CD31hiEmcnhi endothelial cells was observed to be significantly reduced after treatment with TIIA in vitro. Mechanically, TIIA diminished the proportion of hypertrophic chondrocytes, ultimately leading to a substantial reduction in the secretion of vascular endothelial growth factor A (VEGFA). The supernatant of hypertrophic chondrocytes promoted the tube formation of CD31hiEMCNhi endothelial cells, whereas TIIA inhibited this process. Furthermore, TIIA effectively suppressed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) along with its downstream MAPK pathway in CD31hiEmcnhi endothelial cells. In conclusion, our data indicated that TIIA could effectively inhibit the abnormal angiogenesis in subchondral bone during the progression of OA by suppressing the VEGFA/VEFGR2/MAPK pathway. These findings significantly contribute to our understanding of the abnormal angiogenesis in OA and offer a promising therapeutic target for OA treatment.

Simulation for damaged parts recognition of sports injury biological images / Simulação para reconhecimento de partes danificadas em imagens biológicas de lesões esportivas de alta intensidade / Simulación para el reconocimiento de partes dañadas en imágenes biológicas de lesiones deportivas

ABSTRACT Introduction To reduce or avoid injuries during high-intensity sports and help treat the injured part, the method of recognizing biological images of the damaged part is a crucial point of current research. Objective To reduce the damage caused by high-intensity sports and improve the efficiency of injury treatment, this article explores the method of identifying damaged parts in biological imaging of high-intensity sports injuries. Methods A method is proposed to recognize damaged parts of biological images of high-intensity sports injuries based on an improved regional growth algorithm. Results A rough segmented image developed in black and white is obtained with the main body as the objective and background. Based on approximate segmentation, the region growth algorithm is used to accurately recognize the damaged region by improving the selection of the hotspots and the growth rules. Conclusion The recognition accuracy is high, and the recognition time is shorter. The algorithm proposed in this work can improve the precision of recognizing the damaged parts of the biological image of the sports injury and shorten the recognition time. It has the feasibility to determine the damaged parts of sports injuries. Level of evidence II; Therapeutic studies: investigation of treatment results.

RESUMO Introdução Para reduzir ou evitar lesões durante esportes de alta intensidade e auxiliar no tratamento da parte lesada, o método de reconhecimento de imagens biológicas da parte lesada é um ponto crucial das pesquisas atuais. Objetivo Para reduzir os danos causados por esportes de alta intensidade e melhorar a eficiência do tratamento de lesões, este artigo explora o método de identificação de partes danificadas em imagens biológicas de lesões esportivas de alta intensidade. Métodos é proposto um método para reconhecer partes danificadas de imagens biológicas de lesões esportivas de alta intensidade com base em um algoritmo de crescimento regional aprimorado. Resultados Uma imagem áspera segmentada desenvolvida em preto e branco é obtida com o corpo principal como objetivo e fundo. Com base na segmentação aproximada, o algoritmo de crescimento da região é usado para reconhecer com precisão a região danificada, melhorando a seleção de pontos quentes e regras de crescimento. Conclusão a precisão do reconhecimento é alta e o tempo de reconhecimento é menor. O algoritmo proposto neste trabalho pode melhorar a precisão do reconhecimento das partes danificadas da imagem biológica da lesão esportiva e encurtar o tempo de reconhecimento. Tem a viabilidade de determinar as partes danificadas de lesões esportivas. Nível de evidência II; Estudos terapêuticos: investigação dos resultados do tratamento.

RESUMEN Introducción Para reducir o evitar lesiones durante los deportes de alta intensidad y ayudar a tratar la parte lesionada, el método de reconocimiento de imágenes biológicas de la parte dañada es un punto crucial de la investigación actual. Objetivo Para reducir el daño causado por los deportes de alta intensidad y mejorar la eficiencia del tratamiento de lesiones, este artículo explora el método de identificación de partes dañadas en imágenes biológicas de lesiones deportivas de alta intensidad. Métodos Se propone un método para reconocer partes dañadas de imágenes biológicas de lesiones deportivas de alta intensidad basado en un algoritmo de crecimiento regional mejorado. Resultados Se obtiene una imagen segmentada rugosa revelada en blanco y negro con el cuerpo principal como objetivo y fondo. Basado en la segmentación aproximada, el algoritmo de crecimiento de la región se utiliza para reconocer con precisión la región dañada mejorando la selección de los puntos calientes y las reglas de crecimiento. Conclusión la precisión del reconocimiento es alta y el tiempo de reconocimiento es más corto. El algoritmo propuesto en este trabajo puede mejorar la precisión del reconocimiento de las partes dañadas de la imagen biológica de la lesión deportiva y acortar el tiempo de reconocimiento. Tiene la viabilidad de determinar las partes dañadas de las lesiones deportivas. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.

Tensile strain promotes osteogenic differentiation of bone marrow mesenchymal stem cells through upregulating lncRNA-MEG3.

BACKGROUND: With the aging of the population, osteoporosis is becoming more and more common. This progressive bone disease increases the risk of fractures and pain and causes serious harm to people's health and quality of life. Several studies, including our previous studies, confirmed that tensile strain can promote bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation in vitro. In this study, we further explored the mechanism by which tensile strain regulates BMSC differentiation. METHODS: A device designed by our group was used to apply tensile strain to BMSCs to study the effects of tensile strain on their differentiation. LncRNA-MEG3 overexpression and silencing models of BMSCs were constructed by lentivirus transfection to study the involvement of lncRNA-MEG3. We assessed osteogenic differentiation of BMSCs by alkaline phosphatase (ALP) staining and the expression of Runx2 mRNA and BMP2 mRNA, while adipogenic differentiation was evaluated by oil red staining and the expression of PPARγ mRNA and C/EBPα mRNA. RESULTS: We demonstrated that proper tensile strain can promote osteogenic differentiation of BMSCs while inhibiting differentiation into adipocytes, and simultaneously promote the expression of lncRNA-MEG3. The overexpression of lncRNA-MEG3 further promotes osteogenic differentiation of stressed BMSCs and inhibits expression of miR-140-5p; the knockdown of lncRNA-MEG3 induces the opposite effects. CONCLUSION: Appropriate mechanical stimulation can inhibit the expression of miR-140-5p by promoting lncRNA-MEG3 expression, thereby promoting the osteogenic differentiation of BMSCs. Our results provide a theoretical basis for physical exercise to improve the prevention and treatment of osteoporosis.

Next­generation sequencing of miRNAs and lncRNAs from rat femur and tibia under mechanical stress.

Exercise intervention has become one of the most effective methods to prevent and treat osteoporosis, which is a common age­related disease and seriously affects the health and quality of life of the elderly. However, the molecular mechanism remains to be elucidated. The present study demonstrated the exercise­induced promotion of osteogenic differentiation and inhibition of adipogenic differentiation in femur and tibia by establishing an animal exercise model using a treadmill exercise system. MicroRNA (miRNA/miR) and long non­coding (lnc)RNA sequencing analyses identified 16 upregulated and two downregulated miRNAs in the exercise group, as well as 44 upregulated lncRNAs and 39 downregulated lncRNAs in the exercise group. There was increased expression of miR­9942 and miR­7704 in both the femur and tibia and an upregulation of miR­30d, miR­5100 and miR­1260 in the femur of animals from the exercise group. In addition, four of the five most downregulated lncRNAs, including lncRNA MSTRG.2625, lncRNA MSTRG.1557, lncRNA MSTRG.691 and lncRNA MSTRG.7497, were demonstrated to be suppressed in both the femur and tibia after treadmill exercise. The results of the present study provided a valuable resource for further exploring the molecular mechanisms underlying the regulation of osteoporosis by exercise.

Emergency amputation necessitated within 24 hours by a human bite: a case report.

We herein review and analyze the diagnosis, treatment, and outcome of a severe infection caused by a human bite. A 68-year-old man was bitten on the forearm by a 3-year-old child. Rapid progression of infection, severe local and systemic poisoning, and diverse clinical manifestations were observed at presentation. Based on the medical history, physical signs, imaging examinations (X-ray films, color Doppler ultrasound, and computed tomography), laboratory examinations, and multidisciplinary consultation, the patient was diagnosed with gas gangrene or gas gangrene-like changes. Twenty-four hours after the injury, an emergency amputation was performed (open amputation with wound closure after 1 week). After the operation, the patient was sent to the intensive care unit for isolation and further anti-infection and anti-shock treatments. His condition gradually improved after treatment and he was discharged without further complications. Bacteriological and pathological examinations indicated Aeromonas hydrophila infection leading to extensive necrotizing fasciitis of the limb and severe systemic poisoning. In addition, pre-existing myelodysplastic syndrome progressing to acute myeloid leukemia was identified as a possible predisposing factor. Human bites can cause serious infections requiring timely treatment, particularly in patients with predisposing comorbidities.

Performance evaluation of silica microspheres functionalized by different amine-ligands for hydrophilic interaction chromatography.

In this work, for the first time five amine-ligands including mono-amine, di-amine, tri-amine, secondary and tertiary amine, were functionalized on mesoporous micro-silicas and developed as stationary phases for hydrophilic interaction liquid chromatography (HILIC). The investigations about the retention mechanisms, effects of different chromatographic conditions and stability were systematically conducted. Three kinds of polar and hydrophilic compounds (saccharides, sulfonamides, nucleosides and nucleobases) were selected as probe molecules to evaluate their separation performances. Among the five stationary phases, only aminopropyl-bonded silica has already gained wide developments and applications. Whereas, there are no related researches about the other four to be utilized as separation media. By a series of chromatographic evaluations, the results revealed the other four mesoporous micro-silica materials functionalized with di-amine, tri-amine, secondary and tertiary amine, had great potential to be explored as novel stationary phases of HILIC. Particularly, the two stationary phases functionalized with di-amine and tri-amine exhibited outstanding separation and retention abilities. This work offered some insights on the understanding of retention in HILIC mode and provided us possibility to explore other amine-based HILIC stationary phases.

Bone Transport for Treatment of Traumatic Composite Tibial Bone and Soft Tissue Defects: Any Specific Needs besides the Ilizarov Technique?

OBJECTIVE: To evaluate the surgical efficacy of bone transport (Ilizarov technique) plus "shortening-lengthening," "flap surgery," and "open bone transport" as individualized treatments for traumatic composite tibial bone and soft tissue defects. METHODS: We retrospectively analyzed sixty-eight cases (mean age: 35.69 years, (range, 16-65)) treated from July 2014 to June 2017, including 29 middle, 18 distal, and 21 proximal tibial bone defects (4-18 cm, mean: 7.97 cm) with soft tissue defects (2.5 cm × 4.0 cm to 30.0 cm × 35.0 cm after debridement). We adopted the bone transport external fixator to fix the fracture after debriding the defect parts. In the meantime, we adopted the "shortening-lengthening technique," "flap surgery," and "open bone transport" as individualized treatment based on the location, range, and severity of the composite tibial bone and soft tissue defects. Postoperative follow-up was carried out. Surgical efficacy was assessed based on (1) wound healing; (2) bone defect healing rate; (3) external fixation time and index; (4) incidence/recurrence of deep infection; (5) postoperative complications; and (6) Association for the Study and Application of the Methods of Ilizarov (ASAMI) score. RESULTS: The mean duration from injury to reconstruction was 22 days (4-80 d), and the mean postoperative follow-up period was 30.8 months (18-54 m). After the repair and reconstruction, 2 open bone transport patients required infected bone removal first before continuing the bone transport treatment. No deep infection (osteomyelitis) occurred or recurred in the remaining patients, and no secondary debridement was required. Some patients had complications after surgery. All the postoperative complications, including flap venous crisis, nail channel reaction, bone nonunion, mechanical axis deviation, and refracture, were improved or alleviated. External fixation time was 12.5 ± 3.41 months, and the index was 1.63 ± 0.44. According to the ASAMI score, 76.47% of the outcomes were good/excellent. CONCLUSION: The Ilizarov technique yields satisfactory efficacy for composite tibial bone and soft tissue defects when combined with "shortening-lengthening technique," "flap surgery," and "open bone transport" with appropriate individualized treatment strategies.

Negative effects of high mechanical tensile strain stimulation on chondrocyte injury in vitro.

The mechanism underlying the development of osteoarthritis induced by high tensile strain is unclear. In this study, the effects of different degrees of mechanical tensile strain stimulation on Sprague-Dawley rat chondrocytes were explored. Rat chondrocytes were subjected to mechanical tensile strain at different intensities and frequencies (control group, low tensile strain group, intermediate tensile strain group, and high tensile strain group) using a self-made in vitro tensile strain device. After applying mechanical tensile strain, chondrocytes were collected to detect the expression of collagen II, Aggrecan, matrix metalloproteinase 13 (MMP13), ADAMTS5, and uncoupling protein 2 (UCP2) by real-time quantitative PCR and western blotting as well as reactive oxygen species (ROS) by fluorescence probes. Mechanical tensile strain at different frequencies and intensities had different effects on the biological functions of chondrocytes. Compared with the control group, the expression levels of Col II and Aggrecan in the low and intermediate tensile strain groups increased significantly, while the expression of MMP13 and ADAMTS5 decreased. There were no significant differences between the low and intermediate tensile strain groups. Col II and Aggrecan levels were significantly lower in the high tensile strain group than in the control group, while MMP13 and ADAMTS5 levels were higher. There were no significant differences in ROS production between the low and intermediate tensile strain groups and the control group, but the high tensile strain group exhibited significantly increased ROS production. The expression of UCP2 was significantly lower in the high tensile strain group than in all other groups. These results showed that stimulation with different levels of mechanical tensile strain has different effects on chondrocytes. Repeated high tensile strain promoted the anabolic function of chondrocytes, increased ROS production, and decreased UCP2. These results provide a potential mechanism by which osteoarthritis is induced by high mechanical tensile strain.