Sex modifies the predictive value of computed tomography combined with serum potassium for primary aldosteronism subtype diagnosis.

Objective: We aimed to investigate the predictive value of the CT findings combined with serum potassium levels for primary aldosteronism (PA) subtype diagnosis, with a particular interest in sex differences. Methods: In this retrospective study, we eventually included 482 PA patients who underwent successful adrenal venous sampling (AVS) and had available data. We diagnosed the subjects as having either unilateral (n = 289) or bilateral PA (n = 193) based on AVS. We analyzed the concordance rate between AVS and adrenal CT combined with serum potassium and performed a logistic regression analysis to assess the prevalence of unilateral PA on AVS. Results: The total diagnostic concordance rate between CT findings and AVS was 51.5% (248/482). The prevalence of hypokalemia in men and women was 47.96% (129/269) and 40.85% (87/213), respectively. The occurrence of unilateral lesions on CT and hypokalemia was significantly associated with an increased prevalence of unilateral PA [odds ratio (OR) 1.537; 95% confidence interval (CI) 1.364-1.731; p < 0.001]. In male participants, G2 (bilateral lesion on CT and normokalemia), G3 (unilateral lesion on CT and normokalemia), G4 (bilateral normal on CT and hypokalemia), G5 (bilateral lesion on CT and hypokalemia), and G6 (unilateral lesion on CT and hypokalemia) were significantly increased for the prevalence of unilateral PA on AVS (G2: OR 4.620, 95% CI 1.408-15.153; G3: OR 6.275, 95% CI 2.490-15.814; G4: OR 3.793, 95% CI 1.191-12.082; G5: OR 16.476, 95% CI 4.531-59.905; G6: OR 20.101, 95% CI 7.481-54.009; all p < 0.05), compared with G1 (patients with bilateral normal on CT and normokalemia). However, among female participants, we found an increased likelihood for unilateral PA in patients with unilateral lesions on CT and hypokalemia alone (OR 10.266, 95% CI 3.602-29.259, p < 0.001), while no associations were found in other groups (all p > 0.05). Sex had a significant effect on modifying the relationship between unilateral PA and the combination of CT findings and serum potassium (p for interaction <0.001). Conclusion: In conclusion, our results indicated that CT findings combined with serum potassium levels have a great value for predicting the subtype of PA and are stronger in men.

Significance of computed tomography combined with postural stimulation test in predicting laterality of primary aldosteronism.

BACKGROUNDS: Adrenal venous sampling (AVS) represents the gold standard for classifying primary aldosteronism (PA). However, AVS is a technically demanding, expensive and invasive procedure. Computed tomography (CT) scans is recommended as the initial study of classification diagnosis by the current guidelines. In addition, postural stimulation test (PST) has been used to provide additional subtype diagnostic information. OBJECTIVE: This work aimed to evaluate the diagnostic utility of the adrenal CT combined with PST in the classification diagnosis of PA. METHODS: We analyzed PA patients who underwent AVS from November 2017 to February 2022 at a single center. Subtype classification of PA was determined by AVS. We analyzed the concordance rate between AVS outcomes, adrenal CT, and PST, and explored the value of adrenal CT combined with PST for predicting laterality of PA. RESULTS: Total 531 PA patients were included in the present study. The concordance rate between AVS and the adrenal CT was 51.0%(271/531). Receiver operating characteristic (ROC) curve of PST showed that the area under curve (AUC) was 0.604 [95% confidence interval (CI): 0.556, 0.652], the optimal cut-off value was 30%. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) of PST for diagnosis bilateral PA on AVS was 72.8, 46.2%, 0.48, 0.71, 1.35, and 0.59, respectively. The prevalence of unilateral PA on AVS in patients with unilateral lesion on CT and negative PST, unilateral lesion on CT and positive PST, bilateral normal or lesions on CT and negative PST, and bilateral normal or lesions on CT and positive PST was 82.4% (108/131), 59.9% (91/152), 50.7% (37/73), and 44.6% (78/175), respectively. The sensitivity, specificity, PPV, NPV, +LR, and -LR of adrenal CT combined with PST for the diagnosis of unilateral PA were 34.4, 89.4%, 0.82, 0.49, 3.25, and 0.73, respectively. CONCLUSIONS: The combination of CT findings and PST can improve the accuracy of predicting laterality of PA.

Associations among vitamin D, tobacco smoke, and hypertension: A cross-sectional study of the NHANES 2001-2016.

The interrelationships among vitamin D, tobacco smoking, and hypertension are currently unknown. This study was conducted to determine the relationship between vitamin D levels and hypertension and the effect of tobacco smoke exposure levels on this relationship among US adults. We performed a cross-sectional analysis of adult participants from the 2001-2016 National Health and Nutrition Examination Survey (NHANES). Serum 25-hydroxyvitamin D concentration was used as a biomarker of vitamin D status, and tobacco smoke exposure levels were objectively evaluated by serum cotinine levels. Among 22,875 eligible adults who were not receiving antihypertensive medications, the prevalence of hypertension, vitamin D deficiency (<50 mmol/L), and cotinine ≥3 ng/mL was 13.9%, 34.9%, and 29.4%, respectively. Serum cotinine and vitamin D levels were independently associated with hypertension risk after controlling for confounders (P < 0.05). When stratified by the cotinine group (<0.05, 0.05-3 and ≥3 ng/mL), we found that the risk of hypertension associated with vitamin D deficiency was higher among subjects with cotinine levels ≥3 ng/mL compared with the other strata [OR (95% CI) 1.30 (1.09, 1.54) vs. 1.53 (1.19, 1.96) vs. 1.64 (1.30, 2.06); P for heterogeneity test <0.05]. Furthermore, serum cotinine levels were negatively correlated with vitamin D levels. These findings suggested that the increased risk of hypertension could be partly attributed to low vitamin D levels induced by tobacco smoke exposure, in addition to the effects of tobacco smoke exposure and vitamin D deficiency themselves.

A retrospective comparison of albumin versus mannitol priming fluid with relation to postoperative atrial fibrillation.

BACKGROUND AND AIM OF THE STUDY: Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery which can result in increased mortality and increased healthcare costs. During Hurricane Maria (2017), a nationwide shortage of mannitol occurred, and our institution switched to the utilization of albumin as a priming fluid solution. We observed decreased rates of POAF during that time and began alternating albumin and mannitol priming fluid solutions. We hypothesized this observation may be from altered perinexal conduction from albumin utilization. METHODS: A retrospective chart review of all patients from January 2020 through December 2020 who underwent cardiac surgery was performed, to determine if albumin was associated with reduced POAF rates. Two hundred and thirteen patients were identified and 4 were excluded. Two hundred and nine patients (110 albumin priming fluid and 99 mannitol priming fluid) were included in our final analysis. RESULTS: Analysis was performed for all patients with POAF and in patients with new-onset AF (without a history of prior AF) after surgery. POAF rates showed no statistically significant difference between cohorts. For all patients, POAF occurred in 43% of the albumin subgroup and 47% of the mannitol subgroup (p = .53) and for patients with new-onset AF, POAF occurred in 35% of the albumin subgroup versus 42% of the mannitol subgroup (p = .36). Logistic regression revealed that age, ejection fraction and cardiopulmonary bypass time was associated with POAF, in our cohort. CONCLUSIONS: The use of albumin compared to mannitol as priming fluid solutions was not associated with statistically significant reductions in POAF rate, in our population.

Early Cardiac Rehabilitation to Reduce Heart Failure Readmissions.

PURPOSE: This research was conducted to determine whether early participation in cardiac rehabilitation (CR) reduces readmissions following heart failure (HF) hospitalization. METHODS: A retrospective quasiexperimental comparison group design was used. Electronic medical records were abstracted for HF patients discharged between March 2013 and December 2017. The treatment group was defined as patients with HF who attended ≥1 CR session within 6 wk following discharge. The comparison group was defined as patients with HF without additional HF hospitalizations during the previous year, discharged to home/self-care, and did not attend CR within 6 wk. Readmission rates at 30 d and 6 wk were compared between groups using χ 2 analysis and logistic regression. RESULTS: Out of 8613 patients with HF, 205 (2.4%) attended ≥1 CR within 6 wk post-discharge. The treatment group had lower, but not statistically significant, readmission rates than the comparison group for 30-d readmissions for HF ( P = .13), and 6-wk readmission rates for HF ( P = .05). The treatment group had lower all-cause readmissions at 30 d (P < .01) and 6 wk ( P < .01) than the comparison group. Multivariable logistic regression revealed that early CR attendance was associated with reduced 30-d all-cause readmissions (adjusted OR = 0.4: 95% CI, 0.2-0.7) and 6-wk all-cause readmissions (adjusted OR = 0.5: 95% CI, 0.3-0.8). CONCLUSIONS: This study contributes to the existing evidence for allowing early unrestricted CR participation with the aim of improving the health of patients with HF and reducing rehospitalization rates.

Analysis of Cross-Reactivity and Allergic Symptoms of 19 Allergens: Results from NHANES 2005-2006.

INTRODUCTION: We explored the cross-reactivity among 19 common allergen sources and evaluated the influence of serum IgE concentrations and the number of sensitized allergens on the incidence of allergic symptoms. METHODS: We conducted this cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 which is a program of studies designed to assess the health and nutritional status of adults and children in the USA. After excluding participants with missing data from the allergen IgE test, allergy questionnaire, and respiratory health questionnaire, a total of 7,224 participants aged 6 years and older were included, as children younger than 6 years old did not complete all 19 allergen-specific IgE tests. Spearman correlation analysis was used to analyze the cross-reactivity between allergen sources. An independent sample Kruskal-Wallis test was performed to investigate the relationship between the serum-specific IgE levels of 19 allergens and the incidence of allergic symptoms. RESULTS: The cross-reactivity between D. farinae and D. pteronyssinus was the strongest (ρ = 0.88), and cross-reactivity of cross-species was universal. With the increase in serum-specific IgE levels of D. farinae, D. pteronyssinus, oak, and birch, the incidence of sneezing increased (p < 0.05). With the increase in serum-specific IgE levels of cats, dogs, peanuts, Aspergillus, and Alternaria, the incidence of wheezing increased (p < 0.05). The incidence of rash was positively correlated with serum-specific IgE levels of D. farinae, D. pteronyssinus, shrimp, and peanut (p < 0.05). The incidence of wheezing continued to increase with an increase in sensitized allergens. When participants were sensitized to <10 allergens, the incidence of sneezing continued to increase as the number of sensitized allergens increased, whereas the incidence of rash did not have a clear association with the number of sensitized allergens. CONCLUSION: Species that are biologically close are more likely to have antigen cross-reactivity, while cross-reactivity among different species is common. Different allergens tend to cause different allergic symptoms. Different allergic sites in the body have inconsistent responses to the number of sensitized allergens.

Lycorine ameliorates isoproterenol-induced cardiac dysfunction mainly via inhibiting inflammation, fibrosis, oxidative stress and apoptosis.

Alleviating cardiac dysfunction improves the prognosis of heart failure patients. Lycorine is an alkaloid with several beneficial biological properties. Here, we used mice to evaluate the effect of lycorine on cardiac dysfunction elicited by isoproterenol. Mice were divided into four groups: control, lycorine, isoproterenol, and isoproterenol + lycorine. Mice in the combined group were treated daily with 10 mg/kg isoproterenol intraperitoneally for 2 weeks and 5 mg/kg lycorine was given simultaneously intraperitoneally for 4 weeks. Cardiac structure and function were assessed by echocardiography, hematoxylin and eosin staining, and Masson's trichrome staining. Isoproterenol-induced cardiac dysfunction and histopathological injury that was significantly improved by treatment with lycorine. Western blotting and the quantitative real-time polymerase chain reaction were used to explore the molecular mechanisms of these effects. Levels of the inflammatory cytokines, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α, were increased by treatment with isoproterenol; these increases were significantly reduced by lycorine, with involvement of the NF-κB signaling pathway. The fibrotic factors, collagen I and collagen III, were increased by isoproterenol and decreased by treatment with lycorine through inhibiting activation of the Smad signaling pathway. In addition, lycorine alleviated oxidative stress as evidenced by a reduction in total reactive oxygen species in the isoproterenol + lycorine group compared to the isoproterenol group. Lycorine exerted an anti-apoptotic effect as evidenced by upregulating Bcl-2 and downregulating Bax. Overall, our findings demonstrate that lycorine protects against cardiac dysfunction induced by isoproterenol by inhibiting inflammation, fibrosis, oxidative stress, and apoptosis.

Medial Rectus Anastomosis Under Endoscopic Endonasal Orbital Approach With Image-Guided Navigation: A New Way of Repairing a Ruptured Medial Rectus.

BACKGROUND: With the extensive development of endoscopic sinus surgery, iatrogenic medial rectus muscle injury should be treated with caution. Traditional methods to repair a ruptured medial rectus need an anterior orbitotomy approach, with more injury and difficulty in finding the posterior end of the ruptured medial rectus. OBJECTIVE: To explore a new method to repair a ruptured medial rectus. METHODS: Eight cases of iatrogenic medial rectus rupture after endoscopic sinus surgery were reviewed from July 2015 to January 2019. Assisted by image-guided navigation, the ruptured medial rectus was sutured under an endoscopic endonasal orbital approach. Two methods were designed to suture the ruptured medial rectus. Optic nerve and orbital decompression were performed in 5 cases with visual impairment. The extent of exotropia and diplopia were followed up for 5 to 33 months after surgery. RESULTS: With the help of image guidance, the posterior and anterior ends of the ruptured medial rectus of all patients were pinpointed, and operations using medial rectus anastomosis were successfully completed in 7 patients. The exotropia of these patients was corrected, and they have recovered. The vision of 2 patients recovered. There were no minor or major complications intraoperatively or postoperatively. CONCLUSION: Assisted by image-guided navigation, medial rectus anastomosis under an endoscopic endonasal orbital approach is a feasible method. The key to preventing orbital complications is strict professional training, including identification of the Onodi air cell and correct application of powered instrumentation.

Diagnostic Modality of Clostridioides difficile Infection Predicts Treatment Response and Outcomes in Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) patients are at increased risk of developing Clostridioides difficile infection (CDI). Common methods to diagnose CDI involve a combination of tests including the toxin A/B enzyme immunoassay (Toxin) and toxin gene polymerase chain reaction assay (PCR). Disease outcomes in Toxin+ versus Toxin-PCR+ IBD patients remain unclear. AIMS: This study aimed to examine the response to antibiotics and risk of IBD therapy escalation in Toxin+ versus Toxin-PCR+ patients. METHODS: IBD patients at an academic center with CDI diagnosis based on Toxin+ or Toxin-PCR+ from 2012 to 2017 were identified. Comparisons of response to antibiotics within 30 days and escalation of IBD therapy within 90 days of CDI diagnosis between these two groups were analyzed by Chi-square analysis. Multivariable regression analysis examined factors associated with antibiotic response. RESULTS: Among 92 patients included, 61% had Crohn's disease and 39% had ulcerative colitis. 70% tested Toxin-PCR+. 60% received vancomycin or fidaxomicin to treat CDI. 82% of Toxin+ patients responded to antibiotics compared to 25% of Toxin-PCR+ patients (p < 0.001). 21% of Toxin+ patients required IBD therapy escalation compared to 63% of Toxin-PCR+ patients (p < 0.001). When adjusted for the types of antibiotics used, IBD subtypes, and immunosuppression status, positivity to Toxin (OR 14.85, CI 4.62-47.72) was the most significant predictor of response to antibiotics. CONCLUSIONS: Toxin+ compared to Toxin-PCR+ IBD patients had a significantly higher rate of response to antibiotics and lower chances of requiring IBD therapy escalation. Future outcome studies involving CDI in IBD patients should be stratified by modality of diagnosis.

Patterns of Clinical Care Subsequent to Nonindicated Vitamin D Testing in Primary Care.

BACKGROUND: Exponential increases in nonindicated, low-value vitamin D testing have been reported over the past 15 years. Downstream effects of such testing have not been well quantified. METHODS: The purpose of this study was to describe patterns of vitamin D testing within primary care of a large regional health system and to explore downstream health service utilization subsequent to nonindicated testing. Instances of vitamin D testing in 2015 were obtained by an electronic health record-automated search. A subset of patients for whom vitamin D testing was classified as nonindicated was identified, and vitamin D-related service utilization was tracked for 24 months. RESULTS: Of the 77,836 adult primary care patient records identified in 2015, vitamin D tests were conducted on 8,042 (10.3%), with 24.3% of tests yielding abnormal results. In the nonindicated test subset (n = 574), substantial clinical variability was illustrated by 85 care pathways and 26 vitamin D prescriptions. Forty-five percent of abnormal vitamin D lab tests were not followed up with repeat vitamin D tests. Vitamin D-related services (laboratory tests, imaging, and prescriptions) occurred at an average rate of 1.6 services per patient during the 24 months following nonindicated vitamin D testing. Some of these services were also classified as nonindicated. CONCLUSIONS: Evidence of a health service cascade following nonindicated vitamin D testing exists. Opportunities for improved consistency and quality of care related to vitamin D were observed in our health system. These results may inform clinical pathways related the prevention, evaluation, and treatment of low vitamin D.

Comparing No-Show Rates of Neurology Outpatients with and without Parkinson's Disease: A Real-World Assessment of the Parkinsonian Personality Profile.

BACKGROUND: Parkinson's disease (PD) has been hypothesized to be associated with certain personality traits, including conscientiousness and punctuality. However, research aimed at quantifying these traits is largely derived from questionnaire-based personality inventories rather than real-world observations. OBJECTIVE: To explore the presence of a parkinsonian personality profile by assessing the no-show rate of patients with PD versus other neurological disorders. METHODS: We extracted data from our electronic health record for all neurology appointments over a 78-month interval. Additionally, we obtained primary care appointment data for the same patients over the same timeframe. For each appointment we collected appointment date/time, check-in time, provider, age, sex, insurance type, days between appointment date and scheduling, diagnosis code, and no-show status. RESULTS: 19,433 unique patients (400 with PD) accounting for a total of 252,347 outpatient appointments were included in our analysis. The overall no-show rate for PD patients was 3% versus 7.4% for patients with other neurologic disorders (OND). No show rates for PD patients were lower than those with OND for both neurology appointments (2.7% versus 13.6%) and for primary care visits (3.1% versus 5.9%). CONCLUSIONS: Patients with PD have lower no-show rates than patients with OND. Additionally, the no-show rate for patients with PD did not differ between their neurology and primary care appointments, confirming that patient's personality rather than provider traits account for this difference, and supporting the presence of a parkinsonian personality.

Role of IFT88 in icariin­regulated maintenance of the chondrocyte phenotype.

Maintenance of the chondrocyte phenotype is crucial for cartilage repair during tissue engineering. Intraflagellar transport protein 88 (IFT88) is an essential component of primary cilia, shuttling signals along the axoneme. The hypothesis of the present study was that IFT88 could exert an important role in icariin­regulated maintenance of the chondrocyte phenotype. To this end, the effects of icariin on proliferation and differentiation of the chondrogenic cell line, ATDC5, were explored. Icariin­treated ATDC5 cells and primary chondrocytes expressed IFT88. Icariin has been demonstrated to aid in the maintenance of the articular cartilage phenotype in a rat model of post­traumatic osteoarthritis (PTOA). Icariin promoted chondrocyte proliferation and expression of the chondrogenesis marker genes, COL II and SOX9, increased ciliary assembly, and upregulated IFT88 expression in a concentration­ and time­dependent manner. Icariin­treated PTOA rats secreted more cartilage matrix compared with the controls. Knockdown of IFT88 expression with siRNA reduced extracellular signal­regulated kinase (ERK) phosphorylation, and icariin upregulated IFT88 expression by promoting ERK phosphorylation. Thus, IFT88 serves a major role in icariin­mediated maintenance of the chondrocyte phenotype, promoting ciliogenesis and IFT88 expression by increasing ERK phosphorylation. Icariin may therefore be useful for maintenance of the cartilage phenotype during tissue engineering.

Knowledge Gaps in the Management of Postoperative Crohn's Disease: A US National Survey.

BACKGROUND: Postoperative recurrence (POR) of Crohn's disease (CD) is common. Guidelines on POR management have recently been issued, but clinical practice may vary. AIMS: To examine the current clinical practice of POR management in the USA METHODS: A web-based survey was sent to all members of the American Gastroenterological Association and the American College of Gastroenterology. The survey consisted of multiple-choice questions with clinical scenarios to assess how participants manage POR. RESULTS: A total of 189 responses were received from practices in 34 states. 44% of participants were from academic settings. The median number of CD patients seen each month was 20-30 patients per participant. The majority of participants considered smoking, prior intestinal surgery, penetrating disease, perianal fistula, early disease onset, and long extent of disease as high-risk factors for POR. To diagnose and grade endoscopic recurrence, 57% of participants used an endoscopic scoring system; 86% defined clinical recurrence using a combination of symptoms and endoscopic findings; and 79% of participants routinely performed colonoscopy after surgery. In high-risk patients, 65% offered medical prophylaxis-most often biologics and/or immunomodulators-immediately after surgery, while 34% offered medical prophylaxis regardless of the patient's risk of POR. 64% of participants never stopped medical prophylaxis once initiated. CONCLUSIONS: Most gastroenterologists routinely perform colonoscopy to guide POR management. The majority of these providers continue medical prophylaxis indefinitely regardless of subsequent endoscopic findings. Further research is needed to determine the risks and benefits of continuing versus deescalating therapy in patients with potentially surgically induced remission.

Meclizine Prevents Ovariectomy-Induced Bone Loss and Inhibits Osteoclastogenesis Partially by Upregulating PXR.

Pregnane X receptor (PXR) which belongs to the nuclear hormone receptor superfamily plays vital roles in several biological functions, especially in the inflammatory procedure. Besides that, PXR is revealed by recent studies to have essential effects on bone tissue. As an agonist of PXR, meclizine is a piperazine-derived histamine H1 antagonist, and has been frequently used for prevention and treatment of vomiting and nausea. Because osteoclastogenesis is characterized by the activation of inflammation-related signaling pathways, we speculated that meclizine may affect formation and function of osteoclast. In the present study, we explored the effect of meclizine on RANKL-induced osteoclastogenesis both in vivo and in vitro. In primary bone marrow-derived macrophages (BMMs), meclizine reduced osteoclast formation and bone resorption in a dose-dependent manner, while knockdown of PXR with siRNA partially abrogated the osteoclastogenesis inhibition of meclizine. On the one hand, at the molecular level, meclizine attenuated RANKL-induced activation of c-Fos, NFATc1, nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPKs), including ERK and p38, but not JNK. Meanwhile, meclizine reduced the expression of osteoclast-specific genes, including TRAP, MMP9, Cathepsin K and NFATc1. On the other hand, meclizine decreased OVX-induced bone loss by repressing osteoclast activity. In conclusion, our results indicated that meclizine inhibits osteoclastogenesis via regulation of several RANKL signaling pathways and PXR was involved in the processes. Therefore, meclizine may be considered as a novel therapeutic candidate for osteoclast-related diseases.

CD146+ skeletal stem cells from growth plate exhibit specific chondrogenic differentiation capacity in vitro.

Skeletal stem cells (SSCs) are a population of progenitor cells which give rise to postnatal skeletal tissues including bone, cartilage and bone marrow stroma, however not to adipose, haematopoietic or muscle tissue. Growth plate chondrocytes exhibit the ability of continuous proliferation and differentiation, which contributes to the continuous physiological growth. The growth plate has been hypothesized to contain SSCs which exhibit a desirable differentiation capacity to generate bone and cartilage. Due to the heterogeneity of the growth plate chondrocytes, SSCs in the growth plate are not well studied. The present study used cluster of differentiation (CD)146 and CD105 as markers to isolate purified SSCs. CD105+ SSCs and CD146+ SSCs were isolated using a magnetic activated cell sorting method. To quantitatively investigate the proliferation and differentiation ability, the colony-forming efficiency (CFE) and multi­lineage differentiation capacity of CD105+ SSCs and CD146+ SSCs were compared with unsorted cells and adipose-derived stem cells (ASCs). It was revealed that CD105+ and CD146+ subpopulations represented subsets of SSCs which generated chondrocytes and osteocytes, however not adipocytes. Compared with CD105+ subpopulations and ASCs, the CD146+ subpopulation exhibited a greater CFE and continuous high chondrogenic differentiation capacity in vitro. Therefore, the present study suggested that the CD146+ subpopulation represented a chondrolineage­restricted subpopulation of SSCs and may therefore act as a valuable cell source for cartilage regeneration.

Iguratimod prevents ovariectomy­induced bone loss and suppresses osteoclastogenesis via inhibition of peroxisome proliferator­activated receptor­Î³.

Iguratimod is known for its anti­inflammatory activities and therapeutic effects in patients with rheumatoid arthritis. It has previously been demonstrated that iguratimod attenuates bone destruction and osteoclast formation in the Walker 256 rat mammary gland carcinoma cell­induced bone cancer pain model. Therefore, it was hypothesized that iguratimod may additionally exhibit therapeutic effects on benign osteoclast­associated diseases including postmenopausal osteoporosis. In the present study, ovariectomized mice were used to investigate the effects of iguratimod in vivo. Bone marrow mononuclear cells were cultured to detect the effects of iguratimod on receptor activator of nuclear factor­κB ligand (RANKL)­induced osteoclastogenesis in vitro and the molecular mechanisms involved. It was demonstrated that iguratimod may prevent ovariectomy­induced bone loss by suppressing osteoclast activity in vivo. Consistently, iguratimod may inhibit RANKL­induced osteoclastogenesis and bone resorption in primary bone marrow mononuclear cells. At the molecular level, peroxisome proliferator­activated receptor­Î³ (PPAR­Î³)/c­Fos pathway, which is essential in RANKL­induced osteoclast differentiation, was suppressed by iguratimod. Subsequently, iguratimod decreased the expression of nuclear factor of activated T cells c1 and downstream osteoclast marker genes. The results of the present study demonstrated that iguratimod may inhibit ovariectomy­induced bone loss and osteoclastogenesis by modulating RANKL signaling. Therefore, iguratimod may act as a novel therapeutic to prevent postmenopausal osteoporosis.

Anti-rheumatic drug iguratimod protects against cancer-induced bone pain and bone destruction in a rat model.

The bone is one of the most common sites of metastasis in patients with cancer. Current treatments for bone metastases include bisphosphonates, denosumab, non-steroidal anti-inflammatory drugs and analgesics, but each of them has certain limitations. Cytokines and mediators released from various cells in the bone microenvironment may drive a vicious cycle of osteolytic bone metastases. Iguratimod (T-614), a novel disease-modifying anti-rheumatic drug, has demonstrated therapeutic effects by suppressing the production of inflammatory cytokines in rats and patients with rheumatoid arthritis. Therefore, the current study evaluated the hypothesis that iguratimod may protect against cancer-induced bone pain and bone metastasis in a rat model. For this purpose, rats inoculated with Walker 256 cells were treated with iguratimod from days 11-17 post-surgery. Mechanical paw withdrawal thresholds and expression levels of phosphorylated extracellular signal-related kinase (pERK) and c-Fos in the spinal cord were investigated to detect changes in bone pain. Bone destruction levels were detected using X-rays, hematoxylin and eosin and tartrate-resistant acid phosphatase staining. The results revealed that mechanical paw withdrawal thresholds and the expression levels of pERK and c-Fos declined in a dose-dependent manner in rats treated with iguratimod, and bone destruction severity was also reduced. These findings may provide important new insights into the treatment of bone metastasis symptoms.

Icariin promotes proliferation and osteogenic differentiation of rat adipose-derived stem cells by activating the RhoA-TAZ signaling pathway.

Icariin, the main active flavonoid glucoside isolated from Herba epimedii, has been demonstrated to be a potential alternative therapy to prevent postmenopausal osteoporosis. Icariin has also been shown to regulate the proliferation and osteogenic differentiation of rat bone marrow stromal cells (rBMSCs). However, the detailed molecular mechanism of icariin has remained largely unknown. Besides, no investigation has focused on the relevance of icariin in the regulation of rat adipose-derived stem cells (rASCs) proliferation and osteogenic differentiation. In the present study, we detected that icariin promotes proliferation and osteogenic differentiation of rASCs in a concentration range from 10-8M to 10-6M, with 10-7M to be the optimal concentration. We found that 10-7M icariin significantly increased active RhoA protein expression and ROCK substrate molecule p-MYPT1 expression in rASCs. C3 (the RhoA inhibitor) treatment abrogated the increased proliferation and osteogenic differentiation of rASCs induced by icariin. Interestingly, we also found that C3 abrogated the activation of TAZ induced by icariin. Depletion of TAZ by siRNA transfection significantly blocked icariin promoted proliferation and osteogenic differentiation of rASCs. However, icariin induced active RhoA protein expression was not affected by TAZ specific siRNA transfection, suggesting that RhoA lies upstream of TAZ. Taken together, our data indicate that icariin promotes proliferation and osteogenic differentiation of rASCs by activating the RhoA-TAZ signaling pathway.

Corrigendum: Meclizine Prevents Ovariectomy-Induced Bone Loss and Inhibits Osteoclastogenesis Partially by Upregulating PXR.

[This corrects the article on p. 693 in vol. 8, PMID: 29046637.].