Asiatic acid prevents glucocorticoid-induced femoral head osteonecrosis via PI3K/AKT pathway.

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) represents a predominant etiology of non-traumatic osteonecrosis, imposing substantial pain, restricting hip mobility, and diminishing overall quality of life for affected individuals. Centella asiatica (L.) Urb. (CA), an herbal remedy deeply rooted in traditional oriental medicine, has exhibited noteworthy therapeutic efficacy in addressing inflammation and facilitating wound healing. Drawing from CA's historical applications, its anti-inflammatory, anti-apoptotic, and antioxidant attributes may hold promise for managing GIONFH. Asiatic acid (AA), a primary constituent of CA, has been substantiated as a key contributor to its anti-apoptotic, antioxidant, and anti-inflammatory capabilities, showcasing a close association with orthopedic conditions. For the investigation of whether AA could alleviate GIONFH through suppressing oxidative stress, apoptosis, and to delve into its potential cellular and molecular mechanisms, the connection between AA and disease was analyzed through network pharmacology. DEX-induced apoptosis in rat osteoblasts and GIONFH in rat models, got utilized for the verification in vitro/vivo, on underlying mechanism of AA in GIONFH. Network pharmacology analysis reveals a robust correlation between AA and GIONFH in multiple target genes. AA has demonstrated the inhibition of DEX-induced osteoblast apoptosis by modulating apoptotic factors like BAX, BCL-2, Cleaved-caspase3, and cleaved-caspase9. Furthermore, it effectively diminishes the ROS overexpression and regulates oxidative stress through mitochondrial pathway. Mechanistic insights suggest that AA's therapeutic effects involve phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) pathway activation. Additionally, AA has exhibited its potential to ameliorate GIONFH progression in rat models. Our findings revealed that AA mitigated DEX-induced osteoblast apoptosis and oxidative stress through triggering PI3K/AKT pathway. Also, AA can effectively thwart GIONFH occurrence and development in rats.

Taxifolin-mediated Nrf2 activation ameliorates oxidative stress and apoptosis for the treatment of glucocorticoid-induced osteonecrosis of the femoral head.

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is the main complication secondary to long-term or excessive use of glucocorticoids (GCs). Taxifolin (TAX) is a natural antioxidant with various pharmacological effects, such as antioxidative stress and antiapoptotic properties. The purpose of this study was to explore whether TAX could regulate oxidative stress and apoptosis in GIONFH by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. We conducted qRT-PCR, Western blotting, TUNEL assays, flow cytometry, and other experiments in vitro. Microcomputed tomography analysis, hematoxylin-eosin staining, and immunohistochemical staining were performed to determine the therapeutic effect of TAX in vivo. TAX mitigated the overexpression of ROS and NOX gene expression induced by DEX, effectively reducing oxidative stress. Additionally, TAX could alleviate DEX-induced osteoblast apoptosis, as evidenced by qRT-PCR, Western blotting, and other experimental techniques. Our in vivo studies further demonstrated that TAX mitigates the progression of GIONFH in rats by combating oxidative stress and apoptosis. Mechanistic exploration revealed that TAX thwarts the progression of GIONFH through the activation of the Nrf2 pathway. Overall, our research herein reports that TAX-mediated Nrf2 activation ameliorates oxidative stress and apoptosis for the treatment of GIONFH.

MiR-146b-5p enriched bioinspired exosomes derived from fucoidan-directed induction mesenchymal stem cells protect chondrocytes in osteoarthritis by targeting TRAF6.

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degradation and inflammation. In recent years, mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) have attracted widespread attention for their potential role in modulating OA pathology. However, the unpredictable therapeutic effects of exosomes have been a significant barrier to their extensive clinical application. In this study, we investigated whether fucoidan-pretreated MSC-derived exosomes (F-MSCs-Exo) could better protect chondrocytes in osteoarthritic joints and elucidate its underlying mechanisms. In order to evaluate the role of F-MSCs-Exo in osteoarthritis, both in vitro and in vivo studies were conducted. MiRNA sequencing was employed to analyze MSCs-Exo and F-MSCs-Exo, enabling the identification of differentially expressed genes and the exploration of the underlying mechanisms behind the protective effects of F-MSCs-Exo in osteoarthritis. Compared to MSCs-Exo, F-MSCs-Exo demonstrated superior effectiveness in inhibiting inflammatory responses and extracellular matrix degradation in rat chondrocytes. Moreover, F-MSCs-Exo exhibited enhanced activation of autophagy in chondrocytes. MiRNA sequencing of both MSCs-Exo and F-MSCs-Exo revealed that miR-146b-5p emerged as a promising candidate mediator for the chondroprotective function of F-MSCs-Exo, with TRAF6 identified as its downstream target. In conclusion, our research results demonstrate that miR-146b-5p encapsulated in F-MSCs-Exo effectively inhibits TRAF6 activation, thereby suppressing inflammatory responses and extracellular matrix degradation, while promoting chondrocyte autophagy for the protection of osteoarthritic cartilage cells. Consequently, the development of a therapeutic approach combining fucoidan with MSC-derived exosomes provides a promising strategy for the clinical treatment of osteoarthritis.

Erythropoietin suppresses osteoblast apoptosis and ameliorates steroid-induced necrosis of the femoral head in rats by inhibition of STAT1-caspase 3 signaling pathway.

BACKGROUND: Steroid-induced avascular necrosis of the femoral head (SANFH) is characterized by osteoblast apoptosis, leading to a loss of bone structure and impaired hip joint function. It has been demonstrated that erythropoietin (EPO) performs a number of biological roles. OBJECTIVE: We examined the effects of EPO on SANFH and its regulation of the STAT1-caspase 3 signaling pathway. METHOD: In vitro, osteoblasts were treated with dexamethasone (Dex) or EPO. We identified the cytotoxicity of EPO by CCK-8, the protein expression of P-STAT1, cleaved-caspase9, cleaved-caspase3, Bcl-2, BAX, and cytochrome c by Western blotting, and evaluated the apoptosis of osteoblasts by flow cytometry. In vivo, we analyzed the protective effect of EPO against SANFH by hematoxylin and eosin (H&E), Immunohistochemical staining, and Micro-computed tomography (CT). RESULTS: In vitro, EPO had no apparent toxic effect on osteoblasts. In Dex-stimulated cells, EPO therapy lowered the protein expression of BAX, cytochrome c, p-STAT1, cleaved-caspase9, and cleaved-caspase3 while increasing the expression of Bcl-2. EPO can alleviate the apoptosis induced by Dex. In vivo, EPO can lower the percentage of empty bone lacunae in SANFH rats. CONCLUSION: The present study shows that EPO conferred beneficial effects in rats with SANFH by inhibiting STAT1-caspase 3 signaling, suggesting that EPO may be developed as a treatment for SANFH.

Difference of high-salinity-induced inhibition of ammonia-oxidising bacteria and nitrite-oxidising bacteria and its applications.

The difficulty in achieving stable partial nitritation (PN) is a challenge that limits the application of mainstream anaerobic ammonium oxidation (anammox). This study proposes high-salinity treatment as a novel strategy for inactivating nitrite-oxidising bacteria (NOB). The study indicated that NOB are more sensitive to high salinity than ammonia-oxidising bacteria (AOB). The inhibitory effect on the nitrifier gradually increased with increasing salinity from 0 to 100 g NaCl/L. After 24 h and 35 g NaCl/L inhibition, the AOB and NOB activities were 36.65% and 7.15% of their original activities, respectively. After one high-salinity treatment, nitrite accumulation rate (NAR) was above 33% during nitrification. Moreover, the sludge characteristics remained almost unchanged after suppression. A novel process for achieving mainstream PN was proposed and evaluated based on the results. An energy consumption analysis showed that mainstream PN/anammox based on the ex situ high-salinity treatment can achieve higher energy self-sufficiency compared with activated sludge.

Extracts of Oldenlandia diffusa protects chondrocytes via inhibiting apoptosis and associated inflammatory response in osteoarthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Osteoarthritis (OA) is a type of joint disorder that is marked by the gradual breakdown of cartilage and persistent inflammation of the synovial membrane, and is a leading cause of disability among elderly people worldwide. Oldenlandia diffusa (OD) is a member of the Rubiaceae family, and various researches have revealed that it possesses antioxidant, anti-inflammatory, and anti-tumor properties. Extracts of Oldenlandia diffusa is commonly used in traditional oriental medicine to treat various illnesses, including inflammation and cancer. AIM OF THE STUDY: This study is aimed at investigating the anti-inflammatory and anti-apoptosis effects of OD and its potential mechanisms on IL-1ß-induced mouse chondrocytes, as well as its characteristics in a mouse osteoarthritis model. MATERIALS AND METHODS: In this study, the key targets and potential pathways of OD were determined through network pharmacology analysis and molecular docking. The potential mechanism of OD in osteoarthritis was verified by in vitro and in vivo studies. RESULTS: The results of network pharmacology showed that Bax, Bcl2, CASP3, and JUN are key candidate targets of OD for the treatment of osteoarthritis. There is a strong correlation between apoptosis and both OA and OD. Additionally, molecular docking results show that ß-sitosterol in OD can strongly bind with CASP3 and PTGS2. In vitro experiments showed that OD pretreatment inhibited the expression of pro-inflammatory factors induced by IL-1ß, such as COX2, iNOS, IL-6, TNF-α, and PGE2. Furthermore, OD reversed IL-1ß-mediated degradation of collagen II and aggrecan within the extracellular matrix (ECM). The protective effect of OD can be attributed to its inhibition of the MAPK pathway and inhibition of chondrocyte apoptosis. Additionally, it was found that OD can alleviate cartilage degradation in a mouse model of knee osteoarthritis. CONCLUSION: Our study showed that ß-sitosterol, one of the active components of OD, could alleviate the inflammation and cartilage degeneration of OA by inhibiting chondrocyte apoptosis and MAPK pathway.

Stevioside targets the NF-κB and MAPK pathways for inhibiting inflammation and apoptosis of chondrocytes and ameliorates osteoarthritis in vivo.

Osteoarthritis (OA) is a joint disease that is characterized by articular cartilage degeneration and destruction. Stevioside (SVS) is a diterpenoid glycoside extracted from Stevia rebaudiana Bertoni with some specific effects against inflammatory and apoptotic, whereas it is still unclear what function SVS has in osteoarthritis. This study focuses on the anti-inflammatory and anti-apoptosis functions of SVS on chondrocytes induced by interleukin (IL)-1beta, and the role of SVS in an osteoarthritis model for mice. We can detect the production of inflammatory factors such as nitric oxide (NO) and prostaglandin E2 (PGE2) using real-time quantitative polymerase chain reaction (RT-qPCR), the Griess reaction, and enzyme linked immunosorbent assay (ELISA). On the basis of Western blot, we have observed the protein expressions of cartilage matrix metabolism, inflammatory factors, and apoptosis of chondrocytes. Simultaneously, the pharmacological effects of SVS in mice were evaluated by hematoxylin and eosin (HE), toluidine blue, Safranin O, and immunohistochemical staining. The results show that SVS slows extracellular matrix degradation and chondrocyte apoptosis. In addition, SVS mediates its cellular effect by inhibiting the activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. Meanwhile, molecular docking studies revealed that SVS has excellent binding capabilities to p65, extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). The study suggests that SVS can be developed as a potential osteoarthritis treatment.

Plantamajoside suppresses the activation of NF-κB and MAPK and ameliorates the development of osteoarthritis.

Osteoarthritis (OA) is a common degenerative bone and joint disorder characterized by progressive cartilage degeneration and secondary synovial inflammation. It is a common chronic joint disorder that affects people of all ages (especially the old). Plantamajoside is a phenylpropanoside derived from plantain. It has a variety of biological properties, including antioxidant, anti-malignant cell proliferation, and anti-inflammatory properties. In this study, the latent mechanism of plantamajoside was explored by slowing the in-vivo and in-vitro progression of osteoarthritis. The results revealed that plantamajoside pre-conditioning inhibited IL-1ß induced pro-inflammatory factors like COX-2, iNOS, IL-6, and TNF-α. Moreover, plantamajoside also reversed the IL-1 ß mediated type II collagen and aggrecan degradation within the extracellular matrix (ECM). The protective effects of plantamajoside have been attributed to the inhibition of both MAPK and NF-κB pathways. Furthermore, our in-vivo research found that plantamajoside could slow the progression of OA in mice. Finally, all findings point to plantamajoside as a potential anti-OA therapeutic candidate.

A challenge for healthcare system resilience after an earthquake: The crowdedness of a first-aid hospital by non-urgent patients.

After a violent earthquake, the supply of medical services may fall short of the rising demand, leading to overcrowding in hospitals, and, consequently, a collapse in the healthcare system. This paper takes the emergency care system in Taiwan as the research context, where first-aid hospitals are ranked to three levels, advanced, intermediate, and general, and, currently, emphasizes on a general emergency responsibility hospital. Having limited capacity and capability, a general emergency responsibility hospital treats minor and moderate injuries, from which the majority of earthquake-induced casualties suffer. The purpose of this study is to analyze the impact of this group of earthquake-induced non-urgent patients on the performance of a hospital. A patient flow model was built to represent patients' paths throughout emergency care. Based on the model, discrete event simulation was applied to simulate patients' trajectories and states of a hospital under four seismic scenarios, where patient visits are 1.4, 1.6, 1.9, and 2.3 times the normal number. A healthcare performance index, Crowdedness Index (CI), is proposed to measure crowdedness on a daily basis, which is defined as the ratio of the average waiting time for treatment to the recommended maximal waiting time. Results of simulations rendered the establishment of empirical equations, describing the relation between the maximum CIs and the patient growth ratios. In the most severe case in this study, the maximum CI exceeds 92 and it takes 10 days to recover from the quality drop. This highlights the problem a general emergency responsibility hospital may encounter if no emergency response measure is implemented. Findings are provided pertaining to the predication of a recovery curve and the alarming level of patient increase, which are supportive information for preparedness planning as well as response measure formulation to improve resilience.

CoMn2O4 Catalyst Prepared Using the Sol-Gel Method for the Activation of Peroxymonosulfate and Degradation of UV Filter 2-Phenylbenzimidazole-5-sulfonic Acid (PBSA).

In this study, a bimetallic oxide catalyst of cobalt-manganese (CoMn2O4) was synthesized using the sol-gel method, and it was then characterized using a variety of techniques such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) spectroscopy, X-ray photoelectron spectroscopy (XPS), and nitrogen adsorption-desorption isotherms. The obtained novel catalyst, i.e., CoMn2O4, was then used as an activator of peroxymonosulfate (PMS) for the catalytic degradation of a commonly-used UV filter, 2-phenylbenzimidazole-5-sulfonic acid (PBSA) in water. The effects of various factors (e.g., catalyst dosage, PMS concentration, reaction temperature, and pH) in the process were also evaluated. Chemical scavengers and electron paramagnetic resonance (EPR) tests showed that the •OH and SO4•- were the main reactive oxygen species. Furthermore, this study showed that CoMn2O4 is a promising catalyst for activating PMS to degrade the UV filters.

Two types of oscillation in unequally compartmentalized granular gases.

Granular oscillation in an unequally two-compartmentalized system is investigated experimentally, yielding two time periods: τ(LS) represents the time period for particles moving from the large to the small compartment, and τ(SL) is the time needed for movement in a reverse direction. We construct the phase diagram for the unequal system, discovering that there exist two different granular oscillation states. In the GOI state, τ(LS)>τ(SL) is observed, and (τ(LS)-τ(SL)) increases as the difference between the two compartment widths is enlarged. In contrast, τ(LS)<τ(SL) is found in the GOII state, where the total number of particles is considerably lower than that in the GOI state. A flux model, accompanied by a proposed generalized granular temperature, is adopted to quantitatively calculate the observed time periods for both granular oscillation states. We find that the proposed temperature in each compartment is crucial in discriminating τ(LS) from τ(SL), and this is supported by the molecular dynamics analysis of mean kinetic energy of particles in a single compartment.

Intruder-induced change in condensation temperature of granular gases.

The process from a gaseous state to a clustering state for a compartmentalized monodisperse granular gas is accompanied by a drop in the granular temperature to a condensation point. We show experimentally that adding an intruder generally results in a decrease in the condensation point, and a heavier intruder makes this decrease more pronounced. However, once the Brazil nut effect (the intruder on the top of clustering grains) occurs, the condensation point will rise. Through the balance of particle fluxes and the hydrodynamic balance of driving forces, we analytically calculated the condensation point for the monodisperse gases and the intruder-fluid mixtures. The analytical results match the experimental data.

Fractal dimension analysis of periapical reactive bone in response to root canal treatment.

OBJECTIVE: Mathematical morphology and box counting were used to extract trabecular pattern and to evaluate changes of reactive bone following root canal treatment. STUDY DESIGN: Periapical radiographs were digitized and processed with mathematical morphology operations known as skeletonization. The trabecular patterns resulting from this skeletonization process were further analyzed with fractal dimension (FD) analysis using the box-counting method. Two groups of regions of interest (ROI) were selected from 19 subjects for the analysis. RESULTS: Seventeen patients in one group and 13 patients in the other showed decreased FD in the reactive bone region after clinically successful root canal treatment (RCT). Significant changes in FD were noted 6 months after RCT (P < .05). Kappa analysis indicated significant reproducibility between the 2 groups of ROIs. CONCLUSIONS: Mathematical morphology combined with box counting showed decrease of FD in reactive bone regions after clinically successful endodontic treatment.

Outcomes from out-of-hospital cardiac arrest in Metropolitan Taipei: does an advanced life support service make a difference?

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is of major medical and public health significance. It also serves as a good indicator in assessing the performance of local emergency medical services system (EMS). There have been arguments for and against the benefits of advanced life support (ALS) over basic life support with defibrillator (BLS-D) for treating OHCA. AIMS OF THE STUDY: The study was conducted to characterise the outcomes of cardiac arrest victims in an Asian metropolitan city; to evaluate the impacts of ALS versus BLS-D services; and to explore the possible patient and arrest factors that may be associated with the observed differences in the outcomes between the two pre-hospital care models. MATERIALS AND METHODS: Taipei is an Asian metropolitan city with an area of 272 km(2) and a population of 2.65 million. The fire-based BLS-D EMS system was in the process of phasing in ALS capability. While there were 40 BLS-D teams in the 12 city districts, two ALS teams were set up in the central part of the city. In this prospective study, all adult non-traumatic OHCA from September 2003 to August 2004 were included. Patient, arrest, care, and outcome variables for OHCA victims were collected from prehospital run sheets, automatic defibrillators, and emergency department and hospital records. RESULTS: Among 1423 OHCA included in the analysis, 1037 (73%) received BLS-D service, and 386 (27%) received ALS services. The initial shockable rhythms and early bystander CPR were strongly associated with better survival for victims of cardiac arrests. Compared to BLS-D, ALS patients had similar age, sex, witness status, the rate of bystander CPR, and response timeliness but more patients in asystole (84% versus 72%, p=0.005). Patients treated by ALS were more likely to result in significantly higher rates of return of spontaneous circulation (29% versus 21%; OR=1.51 (95% CI 1.15-2.00); p=0.002) and survival to emergency department/intensive care unit admission (23% versus 15%; OR=1.66 (95% CI 1.22-2.24); p=0.001), but there was no difference in the rate of survival to hospital discharge (7% versus 5%; OR=1.39 (95% CI 0.84-2.23); p=0.17). The outcome difference from ALS services was more pronounced among patients in asystole and without bystander CPR. CONCLUSIONS: In this metropolitan EMS in Asia, the implementation of ALS services improved the intermediate, but not the final outcomes. Communities with larger populations and lower incidence of initial shockable rhythms than the OPALS study should also prioritise their resources in setting up and optimising systems of basic life support and early defibrillations. Further studies are warranted to configure the optimal care model for combating cardiac arrest.

Digital imaging analysis with mathematical morphology and fractal dimension for evaluation of periapical lesions following endodontic treatment.

OBJECTIVE: To see if a method for digitizing trabecular pattern of bone could be used to quantitatively evaluate changes in bone pattern following endodontic treatment of teeth with periapical osteolytic lesions. STUDY DESIGN: Periapical radiographs were digitized and further processed with mathematical morphology operations known as skeletonization. The trabecular patterns resulting from this skeletonization process were further analyzed with fractal dimension analysis using box-counting. RESULTS: The periapical area in digitized radiographic images showed fractal behavior. Twenty-five of 27 patients showed increase of the fractal dimension after root canal treatment. Significant changes of the box-counting could be noted 3 months after root canal treatment (P < .05). CONCLUSIONS: Mathematical morphology operation and box-counting might be helpful in early detection of changes of periapical trabecular pattern after root canal treatment.

A pilot study applying digital radiography for estimating ratio of supported single-root surface area.

BACKGROUND: The prognosis of a tooth with periodontitis is affected by the amount of supporting bone. A key factor in retaining a tooth is the ratio of supported root surface. Currently, root surfaces cannot be accurately measured using conventional dental radiographs, which only measure the length of bone support on proximal surfaces. METHODS: Eight extracted, single-rooted teeth were 3-dimensionally digitized using a contact technique for true surface area measurements. Root length, projection area, and pixel values were then measured on digital radiographs. The accuracy of the ratio estimation of supported surface area from linear, area, and pixel values was calculated and compared. RESULTS: The mean error from linear estimation was 7.9%; the mean error from area estimation was 1.0%; and the mean error from pixel value estimation was 1.3%. One-way analysis of variance (ANOVA) showed significant differences in all estimations while Scheffé's analysis further revealed significant differences only in the linear estimation. CONCLUSIONS: A three-dimensional digitizing device could be used as a non-destructive method of measuring root surface area. The ratio of supported single-root surface area could be estimated with high accuracy from the projected area data acquired on the digital dental radiographs. The thickness data as reflected from the pixel values in the digital images did not improve the estimation accuracy. Estimations using only length data yielded significantly less accuracy. Digital dental x-ray images provide the potential for estimating the ratio of supported root surface efficiently.