Endoplasmic reticulum stress mediated by ROS participates in cadmium exposure-induced MC3T3-E1 cell apoptosis.

Cadmium (Cd), as one of the seventh most toxic heavy metal pollutants, widely persisted in the environment, leading to osteoblast dysfunction and ultimately Cd-related skeletal disease. However, the damaging effects of Cd on cellular functions and the potential pathogenic mechanisms are still unclear. In our study, Cd is believed to induce mitochondrial dysfunction and endoplasmic reticulum stress (ERS) in a dose-dependent manner, thereby leading to apoptosis, as evident by elevated Drp1, Fis1, GRP78, CHOP, ATF4, P-EIF2α, P-PERK, BAX, cleaved caspase 3 proteins expression and ROS levels, and decreased the levels of Mfn2, OPA1, Bcl2, and intracellular Collagen I, B-ALP, RUNX2, and BGP genes. Additionally, when the exogenous addition of NAC and 4-PBA was added, it was found that NAC and 4-PBA had a positive moderating effect on Cd-induced cell dysfunction. Mechanistically, Cd-induced oxidative stress and apoptosis by upregulating the PERK-EIF2α-ATF4-CHOP signaling pathway and inhibiting the Nrf2/NQO1 pathway. In conclusion, we found that Cd was involved in mitochondrial dysfunction, ERS, and apoptosis in MC3T3-E1 cells, While NAC and 4-PBA relieved ERS and attenuated cell apoptosis.

Daytime, evening, and overnight: the 24-h radiology cycle and impact on interpretative accuracy.

PURPOSE: To assess the influence of time of day when a study is interpreted on discrepancy rates for common and advanced studies performed in the acute community setting. METHODS: This retrospective study used the databank of a U.S. teleradiology company to retrieve studies between 2012 and 2016 with a preliminary report followed by a final report by the on-site client hospital. Neuroradiology, abdominal radiology, and musculoskeletal radiology studies were included. Teleradiologists were fellowship trained in one of these subspecialty areas. Daytime, evening, and overnight times were defined. Associations between major and minor discrepancies, time of day, and whether the study was common or advanced were tested with significance set at p = .05. RESULTS: A total of 5,883,980 studies were analyzed. There were 8444 major discrepancies (0.14%) and 17,208 minor discrepancies (0.29%). For common studies, daytime (0.13%) and evening (0.13%) had lower major discrepancy rates compared to overnight (0.14%) (daytime to overnight, RR = 0.57, 95%CI: 0.45, 0.72, p < 0.01 and evening to overnight, RR = 0.57, 95%CI: 0.49,0.67, p < 0.01). Minor discrepancy rates for common studies were decreased for evening (0.29%) compared to overnight (0.30%) (RR = 0.89, 95%CI: 0.80,0.99, p = 0.029). For advanced studies, daytime (.15%) had lower major discrepancy rates compared to evening (0.20%) and overnight (.23%) (daytime to evening, RR = 0.77, 95%CI: 0.61, 0.97, p = 0.028 and daytime to overnight, RR = 0.66, 95%CI: 0.50, 0.87, p ≤ 0.01). CONCLUSION: Significantly higher major discrepancy rates for studies interpreted overnight suggest the need for radiologists to exercise greater caution when interpreting studies overnight and may require practice management strategies to help optimize overnight work conditions. The lower major discrepancy rates on advanced studies interpreted during the daytime suggest the need for reserving advanced studies for interpretation during the day when possible.

Interpretations of Examinations Outside of Radiologists' Fellowship Training: Assessment of Discrepancy Rates Among 5.9 Million Examinations From a National Teleradiology Databank.

BACKGROUND. In community settings, radiologists commonly function as multispecialty radiologists, interpreting examinations outside of their area of fellowship training. OBJECTIVE. The purpose of this article was to compare discrepancy rates for preliminary interpretations of acute community-setting examinations that are concordant versus discordant with interpreting radiologists' area of fellowship training. METHODS. This retrospective study used the databank of a U.S. teleradiology company that provides preliminary interpretations for client community hospitals. The analysis included 5,883,980 acute examinations performed from 2012 to 2016 that were preliminarily interpreted by 269 teleradiologists with a fellowship of neuroradiology, abdominal radiology, or musculoskeletal radiology. When providing final interpretations, client on-site radiologists voluntarily submitted quality assurance (QA) requests if preliminary and final interpretations were discrepant; the teleradiology company's QA committee categorized discrepancies as major (n = 8444) or minor (n = 17,208). Associations among examination type (common vs advanced), relationship between examination subspecialty and the teleradiologist's fellowship (concordant vs discordant), and major and minor discrepancies were assessed using three-way conditional analyses with generalized estimating equations. RESULTS. For examinations with a concordant subspecialty, the major discrepancy rate was lower for common than for advanced examinations (0.13% vs 0.26%; relative risk [RR], 0.50, 95% CI, 0.42-0.60; p < .001). For examinations with a discordant subspecialty, the major discrepancy rate was lower for common than advanced examinations (0.14% vs 0.18%; RR, 0.81; 95% CI, 0.72-0.90; p < .001). For common examinations, the major discrepancy rate was not different between examinations with concordant versus discordant subspecialty (0.13% vs 0.14%; RR, 0.90; 95% CI, 0.81-1.01; p = .07). For advanced examinations, the major discrepancy rate was higher for examinations with concordant versus discordant subspecialty (0.26% vs 0.18%; RR, 1.45; 95% CI, 1.18-1.79; p < .001). The minor discrepancy rate was higher among advanced examinations for those with concordant versus discordant subspecialty (0.34% vs 0.29%; RR, 1.17; 95% CI, 1.00-1.36; p = .04), but not different for other comparisons (p > .05). CONCLUSION. Major and minor discrepancy rates were not higher for acute community-setting examinations outside of interpreting radiologists' fellowship training. Discrepancy rates increased for advanced examinations. CLINICAL IMPACT. The findings support multispecialty radiologist practice in acute community settings. Efforts to match examination and interpreting radiologist sub-specialty may not reduce diagnostic discrepancies.

Epicardial adipose tissue volume is greater in men with severe psoriasis, implying an increased cardiovascular disease risk: A cross-sectional study.

BACKGROUND: Patients with psoriasis have elevated risk of coronary artery disease. OBJECTIVE: Do patients with severe psoriasis have larger epicardial adipose tissue volumes (EAT-V) that are associated with cardiovascular risk? METHODS: For this cross-sectional study, we recruited dermatology patients with severe psoriasis and control patients without psoriasis or rheumatologic disease themselves or in a first-degree relative. Participants aged 34 to 55 years without known coronary artery disease or diabetes mellitus underwent computed tomography (CT); EAT-V was obtained from noncontrast CT heart images. RESULTS: Twenty-five patients with psoriasis (14 men, 11 women) and 16 controls (5 men, 11 women) participated. Groups had no statistical difference in age, body mass index, various cardiovascular risk factors (except high-sensitivity C-reactive protein in men), CT-determined coronary artery calcium scores or plaque, or family history of premature cardiovascular disease. Mean EAT-V was greater in the psoriasis group compared to controls (P = .04). There was no statistically significant difference among women; however, male patients with psoriasis had significantly higher EAT-V than controls (P = .03), even when corrected for elevated high-sensitivity C-reactive protein (P = .05). LIMITATIONS: A single-center convenience sample may not be representative. CONCLUSION: Males with psoriasis without known coronary disease or diabetes had greater EAT-V than controls. EAT-V may be an early identifier of those at increased risk for cardiovascular events.

Prospects of circadian clock in joint cartilage development.

Altering the food intake, exercise, and sleep patterns have a great influence on the homeostasis of the biological clock. This leads to accelerated aging of the articular cartilage, susceptibility to arthropathy and other aspects. Deficiency or overexpression of certain circadian clock-related genes accelerates the cartilage deterioration and leads to phenotypic variation in different joints. The process of joint cartilage development includes the formation of joint site, interzone, joint cavitation, epiphyseal ossification center, and cartilage maturation. The mechanism by which, biological clock regulates the cell-cycle, growth, metabolism, and other biological processes of chondrocytes is poorly understood. Here, we summarized the interaction between biological clock proteins and developmental pathways in chondrogenesis and provided the evidence from other tissues that further predicts the molecular patterns of these protein-protein networks in activation, proliferation, and differentiation. The purpose of this review is to gain deeper understanding of the evolution of cartilage and its irreversibility seen in damage and aging.

Puerarin inhibits the development of osteoarthritis through antiinflammatory and antimatrix-degrading pathways in osteoarthritis-induced rat model.

Puerarin is an isoflavone isolated from the medicinal plant Pueraria lobata. The purpose of this study was to study the antiinflammatory and antimatrix-degrading effects of puerarin in a rat osteoarthritis (OA) model and its protective effects on joints. The rat OA model was established by anterior cruciate ligament transection (ACLT) surgery. Rats (n = 40) were divided into nontreated OA, OA + celecoxib (2.86 mg/kg), OA + puerarin (50 and 100 mg/kg), and control groups. Two weeks after surgical induction, puerarin was administered by gavage daily for 8 weeks. After 8 weeks, macroscopic observation and histopathological images showed that cartilage damage was reduced after puerarin and celecoxib treatment, the intensity of Safranin O staining was high, and the OARSI scores were significantly reduced compared to the OA group. Puerarin reduced the expression of MMP-3, MMP-13, ADAMTS-5, and COX-2 in the cartilage tissue of ACLT rats, inhibited the production of IL-1ß, IL-6, and TNF-α inflammatory factors, increased Type II collagen content, and altered the expression of serum OA cartilage degradation/bone turnover biomarkers (CTX-I, CTX-II, COMP, and PIINP). Based on these findings, we speculate that puerarin supplement to attain recovery from OA damage.

Digital Breast Tomosynthesis Slab Thickness: Impact on Reader Performance and Interpretation Time.

Background Digital breast tomosynthesis (DBT) helps reduce recall rates and improve cancer detection compared with two-dimensional (2D) mammography but has a longer interpretation time. Purpose To evaluate the effect of DBT slab thickness and overlap on reader performance and interpretation time in the absence of 1-mm slices. Materials and Methods In this retrospective HIPAA-compliant multireader study of DBT examinations performed between August 2013 and July 2017, four fellowship-trained breast imaging radiologists blinded to final histologic findings interpreted DBT examinations by using a standard protocol (10-mm slabs with 5-mm overlap, 1-mm slices, synthetic 2D mammogram) and an experimental protocol (6-mm slabs with 3-mm overlap, synthetic 2D mammogram) with a crossover design. Among the 122 DBT examinations, 74 mammographic findings had final histologic findings, including 31 masses (26 malignant), 20 groups of calcifications (12 malignant), 18 architectural distortions (15 malignant), and five asymmetries (two malignant). Durations of reader interpretations were recorded. Comparisons were made by using receiver operating characteristic curves for diagnostic performance and paired t tests for continuous variables. Results Among 122 women, mean age was 58.6 years ± 10.1 (standard deviation). For detection of malignancy, areas under the receiver operating characteristic curves were similar between protocols (range, 0.83-0.94 vs 0.84-0.92; P ≥ .63). Mean DBT interpretation time was shorter with the experimental protocol for three of four readers (reader 1, 5.6 minutes ± 1.7 vs 4.7 minutes ± 1.4 [P < .001]; reader 2, 2.8 minutes ± 1.1 vs 2.3 minutes ± 1.0 [P = .001]; reader 3, 3.6 minutes ± 1.4 vs 3.3 minutes ± 1.3 [P = .17]; reader 4, 4.3 minutes ± 1.0 vs 3.8 minutes ± 1.1 [P ≤ .001]), with 72% reduction in both mean number of images and mean file size (P < .001 for both). Conclusion A digital breast tomosynthesis reconstruction protocol that uses 6-mm slabs with 3-mm overlap, without 1-mm slices, had similar diagnostic performance compared with the standard protocol and led to a reduced interpretation time for three of four readers. © RSNA, 2020 See also the editorial by Chang in this issue.

Optimizing Electronic Release of Imaging Results through an Online Patient Portal.

Purpose To determine an optimal embargo period preceding release of radiologic test results to an online patient portal. Materials and Methods This prospective discrete choice conjoint survey with modified orthogonal design was administered to patients by trained interviewers at four outpatient sites and two institutions from December 2016 to February 2018. Three preferences for receiving imaging results associated with a possible or known cancer diagnosis were evaluated: delay in receipt of results (1, 3, or 14 days), method of receipt (online portal, physician's office, or phone), and condition of receipt (before, at the same time as, or after health care provider). Preferences (hereafter, referred to as utilities) were derived from parameter estimates (ß) of multinomial regression stratified according to study participant and choice set. Results Among 464 screened participants, the response and completion rates were 90.5% (420 of 464) and 99.5% (418 of 420), respectively. Participants preferred faster receipt of results (P < .001) from their physician (P < .001) over the telephone (P < .001). Each day of delay decreased preference by 13 percentage points. Participants preferred immediate receipt of results through an online portal (utility, -.57) if made to wait more than 6 days to get results in the office and more than 11 days to get results by telephone. Compared with receiving results in their physician's office on day 7 (utility, -.60), participants preferred immediate release through the online portal without physician involvement if followed by a telephone call within 6 days (utility, -0.49) or an office visit within 2 days (utility, -.53). Older participants preferred physician-directed communication (P < .001). Conclusion The optimal embargo period preceding release of results through an online portal depends on the timing of traditional telephone- and office-based styles of communication. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Arenson et al in this issue.

Breast care problems on call: training residents to manage effectively.

PURPOSE: Our aim was to assess and address the challenges radiology residents face when managing breast imaging emergencies on call and to determine if targeted educational interventions improved resident confidence and knowledge. METHODS: We created surveys to determine resident comfort level with and knowledge of appropriate management of breast imaging emergencies. We also created structured educational interventions to improve resident confidence and knowledge. The effectiveness of these interventions was assessed with pre- and post-intervention surveys given to the 43 residents at our institution. RESULTS: Thirty-six of the 43 residents at our institution completed both surveys. The results showed that 33 of 36 residents (91.7%) felt an increase in their comfort level after utilizing one or both of the interventions. There was also significant improvement in resident knowledge; the average resident score on the knowledge questions improved from 40 to 68% (p < 0.0001). CONCLUSION: Managing breast imaging emergencies on call can be challenging and stressful for residents. Educational interventions such as our targeted teaching tools can significantly improve resident confidence and knowledge. Presenting dedicated teaching materials directed at a previously identified knowledge deficit and source of stress significantly improved resident knowledge base and confidence in managing breast imaging emergencies on call.

Ginkgolide C inhibits ROS-mediated activation of NLRP3 inflammasome in chondrocytes to ameliorate osteoarthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba, as the most widely available medicinal plant worldwide, has been frequently utilized for treat cardiovascular, cerebrovascular, diabetic and other diseases. Due to its distinct pharmacological effects, it has been broadly applications in pharmaceuticals, health products, dietary supplements, and so on. Ginkgolide C (GC), a prominent extract of Ginkgo biloba, possesses potential in anti-inflammatory and anti-oxidant efficacy. AIMS OF THE STUDY: To determine whether GC mitigated the progressive degeneration of articular cartilage in a Monosodium Iodoacetate (MIA)-induced osteoarthritis (OA) rat model by inhibiting the activation of the NLRP3 inflammasome, and the specific underlying mechanisms. MATERIALS AND METHODS: In vivo, an OA rat model was established by intra-articular injection of MIA. The protective effect of GC (10 mg/kg) on articular cartilage was evaluated. Application of ATDC5 cells to elucidate the mechanism of the protective effect of GC on articular cartilage. Specifically, the expression levels of molecules associated with cartilage ECM degrading enzymes, OS, ERS, and NLRP3 inflammasome activation were analyzed. RESULTS: In vivo, GC ameliorated MIA-induced OA rat joint pain, and exhibited remarkable anti-inflammatory and anti- ECM degradation effects via inhibition of the activation of NLRP3 inflammasome, the release of inflammatory factors, and the expression of matrix-degrading enzymes in cartilage. Mechanically, GC inhibited the activation of NLRP3 inflammasome by restraining ROS-mediated p-IRE1α and activating Nrf2/NQO1 signal path, thereby alleviating OA. The ROS scavenger NAC was as effective as GC in reducing ROS production and inhibiting the activation of NLRP3 inflammasome. CONCLUSIONS: GC have exerted chondroprotective effects by inhibiting the activation of NLRP3 inflammasome.

Neoadjuvant chemotherapy for high-grade serous ovarian cancer: radiologic-pathologic correlation of response assessment and predictors of progression.

PURPOSE: Neoadjuvant chemotherapy is often administered for high-grade serous ovarian carcinoma (HGSC) prior to cytoreductive surgery. We evaluated treatment response by CT (simplified peritoneal carcinomatosis index [S-PCI]), pathology (chemotherapy response score [CRS]), laboratory markers (serum CA-125), and surgical outcomes, to identify predictors of disease-free survival. METHODS: For this retrospective, HIPAA-compliant, IRB-approved study, we identified 396 women with HGSC receiving neoadjuvant chemotherapy between 2010 and 2019. Two hundred and ninety-nine patients were excluded (surgery not performed; imaging/pathology unavailable). Pre- and post-treatment abdominopelvic CTs were assigned CT S-PCI scores 0-24 (higher score indicating more tumor). Specimens were assigned CRS of 1-3 (minimal to complete response). Clinical data were obtained via chart review. Univariate, multivariate, and survival analyses were performed. RESULTS: Ninety-seven women were studied, with mean age of 65 years ± 10. Interreader agreement was good to excellent for CT S-PCI scores (ICC 0.64-0.77). Despite a significant decrease in CT S-PCI scores after treatment (p < 0.001), mean decrease in CT S-PCI did not differ significantly among CRS categories (p = 0.20) or between patients who were optimally versus suboptimally debulked (p = 0.29). In a survival analysis, lower CRS (more viable tumor) was associated with shorter time to progression (p < 0.001). A joint Cox proportional-hazard models showed that only residual pathologic disease (CRS 1/2) (HR 4.19; p < 0.001) and change in CA-125 (HR 1.79; p = 0.01) predicted progression. CONCLUSION: HGSC response to neoadjuvant therapy by CT S-PCI did not predict pathologic CRS score, optimal debulking, or progression, revealing discordance between imaging, pathologic, biochemical, and surgical assessments of tumor response.

Combined detection of serum CTX-II and C2C in a rat model of ACLT-induced osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative bone and joint disease that often occurs in aging animals. Currently, there are still no biomarkers that can effectively diagnose OA in the early stage. To identify possible biomarkers, here we examined changes in the expression of C-telopeptide fragments of type II collagen (CTX-II) and collagenase generated carboxy-terminal neoepitope of type II collagen (C2C) in serum at different time points in an anterior cruciate ligament transection (ACLT)-induced rat OA model. The serum levels of CTX-II and C2C, and the OARSI score in the ACLT group were increased from week two until the end of the experiment. The AUC of the combined biomarkers was higher than that of CTX-II or C2C alone. Moreover, serum levels of CTX-II and C2C were positively correlated with the OARSI score. The results suggest that the combined detection of serum CTX-II and C2C concentrations may have potential for assessing and diagnosing OA at early stages.

Is There Gender Bias in Radiology Job Postings?

BACKGROUND: Words can convey subtle cultural stereotypes and perpetuate subconscious gender biases. Wording in job advertisements that appeals to 1 gender and deters others may unintentionally skew the applicant pool and affect the early phase of the recruitment process. "Masculine" tone can lead to decreased interest among women applicants while 'feminine' wording may not affect a man's decision to apply for the job. In this study, we evaluated the presence and extent of subtle gender bias in job advertisements for radiology faculty positions. METHODS: All job postings for faculty radiologists were retrieved from the American College of Radiology Career Center website in July 2020. The complete job advertisement was analyzed using Gender Decoder, a publicly available web-based application, to determine number and percentage of female or male coded words and the overall tone of the ad. The job posts were also stratified by subspecialty, leadership positions and academic versus private practice environments. RESULTS: Of the 623 job postings reviewed, a little over half (52.0%) of job postings were feminine coded, 26.6% had a masculine tone and 21.3% had a neutral tone. Of the leadership (division director) positions, 50.0% (4/8) had a masculine tone, 37.5% had a feminine tone, and 12.5% had a neutral tone. Among various specialties, pediatric radiology had the lowest percentage of job posts with a masculine tone (10.5%) while nuclear medicine had the highest percentage (41.7%). The most commonly used feminine words were: "support," "responsible," "commitment" and the most common masculine words were: "competitive," "leader," "active." CONCLUSIONS: Most of the imaging job advertisements were feminine coded, with masculine tone in overall 26.6% posts and neutral tone in about a fifth. Leadership posts had a higher percentage of masculine tone. Awareness of these biases is important to enable diversity in recruitment and to ensure a diverse applicant pool.

Oleanolic acid, a small-molecule natural product, inhibits ECM degeneration in osteoarthritis by regulating the Hippo/YAP and Wnt/ß-catenin pathways.

Over the past few decades, osteoarthritis (OA) has been a major health problem worldwide. It is urgent to develop new, effective, and safe drugs to treat OA. There are many pentacyclic triterpenoids in nature that are safe and have health benefits. Oleanolic acid (OLA), one of the pentacyclic triterpenoids, is a potential novel compound for treating OA; however, its mechanism of action is still unclear. In this study, the mechanism of resistance to extracellular matrix (ECM) degradation of OLA and its protective role in the amelioration of OA were investigated by in vivo and in vitro experiments. We found that OLA promoted interleukin-1ß (IL-1ß)-induced production of type II collagen (collagen II) in rat chondrocytes, decreased the expression of matrix metalloproteinase (MMP)-3 and MMP-13, and inhibited inflammatory cytokine (IL-1ß and TNF-α) and cartilage marker (CTX-II and COMP) levels, thereby hindering the pathological process of cartilage. Mechanistically, OLA inhibited the Wnt/ß-catenin pathway, activated the Hippo/YAP pathway, and hampered the ECM degradation process by inhibiting the nuclear translocation of ß-catenin and YAP. When we knocked down ß-catenin, OLA lost its stimulatory effect on the Hippo pathway. These findings confirm that OLA plays an anti-ECM degradation role by regulating the Wnt/ß-catenin and Hippo/YAP pathways. Overall, this study provides a theoretical basis for developing highly effective and low-toxic natural products for the prevention and treatment of OA.

Effects of Mitral Valve Prolapse on Quantification of Mitral Regurgitation and Ejection Fraction Using Cardiac MRI.

Purpose: To determine the impact of prolapsed volume on regurgitant volume (RegV), regurgitant fraction (RF), and left ventricular ejection fraction (LVEF) in patients with mitral valve prolapse (MVP) using cardiac MRI. Materials and Methods: Patients with MVP and mitral regurgitation who underwent cardiac MRI from 2005 to 2020 were identified retrospectively from the electronic record. RegV is the difference between left ventricular stroke volume (LVSV) and aortic flow. Left ventricular end-systolic volume (LVESV) and LVSV were obtained from volumetric cine images, with prolapsed volume inclusion (LVESVp, LVSVp) and exclusion (LVESVa, LVSVa) providing two estimates of RegV (RegVp, RegVa), RF (RFp, RFa), and LVEF (LVEFa, LVEFp). Interobserver agreement for LVESVp was assessed using intraclass correlation coefficient (ICC). RegV was also calculated independently using measurements from mitral inflow and aortic net flow phase-contrast imaging as the reference standard (RegVg). Results: The study included 19 patients (mean age, 28 years ± 16 [SD]; 10 male patients). Interobserver agreement for LVESVp was high (ICC, 0.98; 95% CI: 0.96, 0.99). Prolapsed volume inclusion resulted in higher LVESV (LVESVp: 95.4 mL ± 34.7 vs LVESVa: 82.4 mL ± 33.8; P < .001), lower LVSV (LVSVp: 100.5 mL ± 33.8 vs LVSVa: 113.5 mL ± 35.9; P < .001), and lower LVEF (LVEFp: 51.7% ± 5.7 vs LVEFa: 58.6% ± 6.3; P < .001). RegV was larger in magnitude when prolapsed volume was excluded (RegVa: 39.4 mL ± 21.0 vs RegVg: 25.8 mL ± 22.8; P = .02), with no evidence of a difference when including prolapsed volume (RegVp: 26.4 mL ± 16.4 vs RegVg: 25.8 mL ± 22.8; P > .99). Conclusion: Measurements that included prolapsed volume most closely reflected mitral regurgitation severity, but inclusion of this volume resulted in a lower LVEF.Keywords: Cardiac, MRI© RSNA, 2023See also commentary by Lee and Markl in this issue.

Bayesian Inferences on Neural Activity in EEG-Based Brain-Computer Interface.

A brain-computer interface (BCI) is a system that translates brain activity into commands to operate technology. A common design for an electroencephalogram (EEG) BCI relies on the classification of the P300 event-related potential (ERP), which is a response elicited by the rare occurrence of target stimuli among common non-target stimuli. Few existing ERP classifiers directly explore the underlying mechanism of the neural activity. To this end, we perform a novel Bayesian analysis of the probability distribution of multi-channel real EEG signals under the P300 ERP-BCI design. We aim to identify relevant spatial temporal differences of the neural activity, which provides statistical evidence of P300 ERP responses and helps design individually efficient and accurate BCIs. As one key finding of our single participant analysis, there is a 90% posterior probability that the target ERPs of the channels around visual cortex reach their negative peaks around 200 milliseconds post-stimulus. Our analysis identifies five important channels (PO7, PO8, Oz, P4, Cz) for the BCI speller leading to a 100% prediction accuracy. From the analyses of nine other participants, we consistently select the identified five channels, and the selection frequencies are robust to small variations of bandpass filters and kernel hyper-parameters.

CF101 alleviates OA progression and inhibits the inflammatory process via the AMP/ATP/AMPK/mTOR axis.

CF101 (IB-MECA) is an adenosine A3 receptor agonist that has anti-inflammatory and pain-relieving properties. Adenosine A3 receptor activation can delay the process of Osteoarthritis(OA) and prevent the occurrence of OA. However, the mechanism of CF101 on OA is still unknown. This study aimed to investigate the effect of CF101 on rats induced by anterior cruciate ligament-transection (ACLT) and rat chondrocytes induced by IL-1ß. ACLT-induced OA rats were administered CF101, and autophagy levels were measured to determine whether CF101 had an autophagy-mediated protective effect on articular cartilage. Furthermore, the mechanism by which CF101 protected articular cartilage in IL-1ß-induced chondrocytes mimicking OA was investigated. In rats treated with ACLT, CF101 was able to delay the progression of OA, as well as reduce inflammation and type II collagen degradation factors. In addition, in vitro experiments revealed that CF101 reduced type II collagen degradation factors in OA chondrocytes. In rats treated with ACLT and OA chondrocytes, CF101 enhanced autophagy and increased the ratio of AMP/ATP and AMPK protein levels while decreasing mTOR expression. Treatment of OA chondrocytes with 3-MA prior to treatment with CF101 resulted in inhibition of autophagy factor levels, as well as increased levels of inflammatory factors and type II collagen degradation compared to the CF101 group. These findings demonstrated that CF101 could protect articular cartilage against OA by enhancing the ratio of ATP/AMP and altering the AMPK/mTOR pathway to enhance autophagy and reduce inflammation. In addition, inhibition of autophagy resulted in a reduced CF101 effect.

Melatonin Prevents Chondrocyte Matrix Degradation in Rats with Experimentally Induced Osteoarthritis by Inhibiting Nuclear Factor-κB via SIRT1.

Osteoarthritis (OA) is a common degenerative joint disease characterized by an imbalance of cartilage extracellular matrix (ECM) breakdown and anabolism. Melatonin (MT) is one of the hormones secreted by the pineal gland of the brain and has anti-inflammatory, antioxidant, and anti-aging functions. To explore the role of MT in rats, we established an OA model in rats by anterior cruciate ligament transection (ACLT). Safranin O-fast green staining showed that intraperitoneal injection of MT (30 mg/kg) could alleviate the degeneration of articular cartilage in ACLT rats. Immunohistochemical (IHC) analysis found that MT could up-regulate the expression levels of collagen type II and Aggrecan and inhibit the expression levels of matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-13 (MMP-13), and ADAM metallopeptidase with thrombospondin type 1 motif 4 (ADAMTS-4) in ACLT rats. To elucidate the mechanism of MT in protecting the ECM in inflammatory factor-induced rat chondrocytes, we conducted in vitro experiments by co-culturing MT with a culture medium. Western blot (WB) showed that MT could promote the expression levels of transforming growth factor-beta 1 (TGF-ß1)/SMAD family member 2 (Smad2) and sirtuin 2-related enzyme 1 (SIRT1) and inhibit the expression of levels of phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibi-tor (p-p65) and phosphorylated IκB kinase-α (p-IκBα). In addition, WB and real-time PCR (qRT-PCR) results showed that MT could inhibit the expression levels of MMP-3, MMP-13, ADAMTS-4, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in chondrocytes induced by interleukin-1ß (IL-1ß), and up-regulate the expression of chondroprotective protein type II collagen. We found that in vivo, MT treatment protected articular cartilage in the rat ACLT model. In IL-1ß-induced rat chondrocytes, MT could reduce chondrocyte matrix degradation by up-regulating nuclear factor-kB (NF-κB) signaling pathway-dependent expression of SIRT1 and protecting chondrocyte by activating the TGF-ß1/Smad2 pathway.

Ginkgolide C slows the progression of osteoarthritis by activating Nrf2/HO-1 and blocking the NF-κB pathway.

Osteoarthritis (OA) is driven by chronic low-grade inflammation and subsequent cartilage degradation. OA is the most prevalent degenerative joint disease worldwide, and its treatment remains a challenge. The aim of this study was to explore the potential effects and mechanism underlying the anti-OA properties of ginkgolide C (GC). Protective effects of GC on hydrogen peroxide (H2O2)-treated rat chondrocytes were evaluated using ELISA, qPCR, western blot analysis, flow cytometry, ROS detection and immunofluorescence in vitro. Ameliorating effects of GC on cartilage degeneration in rats were evaluated through behavioral assays, microcomputed tomography, histopathological analysis, western blot analysis and ELISA in vivo. In vitro, GC treatment inhibited the release of pro-apoptotic factors induced by H2O2 and promoted the release of the anti-apoptotic proteins. In addition, GC decreased the expression of matrix metalloproteinase (MMP3 and MMP13), thrombospondin motifs 4 (ADAMTS4), and inflammatory mediators inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and SOX9 thereby inhibiting extracellular matrix (ECM) degradation. Mechanistically, GC exerts its anti-apoptotic and anti-inflammatory effects by upregulating the oxidative stress signaling Nrf2/HO-1 pathway and preventing p65 from binding to DNA. Similarly, In a rat model with post-traumatic OA (PTOA) induced by anterior cruciate ligament transection (ACLT), GC inhibited joint pain, cartilage destruction, and abnormal bone remodeling of subchondral bone. GC inhibited H2O2-induced chondrocyte apoptosis through Nrf2/HO-1 and NF-κB axis, exerted anti-inflammatory effects, and inhibited cartilage degeneration in rat OA. Our findings advanced the concept that GC may contribute to cartilage metabolism through anti-inflammatory and anti-apoptotic effects, and the identified GC is a potential therapeutic agent for the treatment of OA.

Oral administration of live combined Bacillus subtilis and Enterococcus faecium alleviates colonic oxidative stress and inflammation in osteoarthritic rats by improving fecal microbiome metabolism and enhancing the colonic barrier.

Osteoarthritis (OA) causes intestinal damage. The protective effect of probiotics on the intestine is indeed effective; however, the mechanism of protection against intestinal damage in OA is not clear. In this study, we used meniscal/ligamentous injury (MLI) to mimic OA in rats and explored the colonic protective effects of Bacillus subtilis and Enterococcus faecium on OA. Our study showed that treatment with B. subtilis and E. faecium attenuated colonic injury and reduced inflammatory and oxidative stress factors in the serum of osteoarthritic rats. α- and ß diversity of the fecal flora were not different among groups; no significant differences were observed in the abundances of taxa at the phylum and genus levels. We observed the presence of the depression-related genera Alistipes and Paraprevotella. Analysis of fecal untargeted metabolism revealed that histamine level was significantly reduced in the colon of OA rats, affecting intestinal function. Compared to that in the control group, the enriched metabolic pathways in the OA group were primarily for energy metabolisms, such as pantothenate and CoA biosynthesis, and beta-alanine metabolism. The treatment group had enriched linoleic acid metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis, which were different from those in the control group. The differences in the metabolic pathways between the treatment and OA groups were more evident, primarily in symptom-related metabolic pathways such as Huntington's disease, spinocerebellar ataxia, energy-related central carbon metabolism in cancer, pantothenate and CoA biosynthesis metabolic pathways, as well as some neurotransmission and amino acid transport, and uptake- and synthesis-related metabolic pathways. On further investigation, we found that B. subtilis and E. faecium treatment enhanced the colonic barrier of OA rats, with elevated expressions of tight junction proteins occludin and Zonula occludens 1 and MUC2 mRNA. Intestinal permeability was reduced, and serum LPS levels were downregulated in the treatment group. B. subtilis and E. faecium also regulated the oxidative stress pathway Keap1/Nrf2, promoted the expression of the downstream protective proteins HO-1 and Gpx4, and reduced intestinal apoptosis. Hence, B. subtilis and E. faecium alleviate colonic oxidative stress and inflammation in OA rats by improving fecal metabolism and enhancing the colonic barrier.