Reassessing endothelial-to-mesenchymal transition in mouse bone marrow: insights from lineage tracing models.

Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) play crucial roles in supporting hematopoiesis and hematopoietic regeneration. However, whether ECs are a source of BMSCs remains unclear. Here, we evaluate the contribution of endothelial-to-mesenchymal transition to BMSC generation in postnatal mice. Single-cell RNA sequencing identifies ECs expressing BMSC markers Prrx1 and Lepr; however, this could not be validated using Prrx1-Cre and Lepr-Cre transgenic mice. Additionally, only a minority of BMSCs are marked by EC lineage tracing models using Cdh5-rtTA-tetO-Cre or Tek-CreERT2. Moreover, Cdh5+ BMSCs and Tek+ BMSCs show distinct spatial distributions and characteristic mesenchymal markers, suggestive of their origination from different progenitors rather than CDH5+ TEK+ ECs. Furthermore, myeloablation induced by 5-fluorouracil treatment does not increase Cdh5+ BMSCs. Our findings indicate that ECs hardly convert to BMSCs during homeostasis and myeloablation-induced hematopoietic regeneration, highlighting the importance of using appropriate genetic models and conducting careful data interpretation in studies concerning endothelial-to-mesenchymal transition.

Aged bone matrix-derived extracellular vesicles as a messenger for calcification paradox.

Adipocyte differentiation of bone marrow mesenchymal stem/stromal cells (BMSCs) instead of osteoblast formation contributes to age- and menopause-related marrow adiposity and osteoporosis. Vascular calcification often occurs with osteoporosis, a contradictory association called "calcification paradox". Here we show that extracellular vesicles derived from aged bone matrix (AB-EVs) during bone resorption favor BMSC adipogenesis rather than osteogenesis and augment calcification of vascular smooth muscle cells. Intravenous or intramedullary injection of AB-EVs promotes bone-fat imbalance and exacerbates Vitamin D3 (VD3)-induced vascular calcification in young or old mice. Alendronate (ALE), a bone resorption inhibitor, down-regulates AB-EVs release and attenuates aging- and ovariectomy-induced bone-fat imbalance. In the VD3-treated aged mice, ALE suppresses the ovariectomy-induced aggravation of vascular calcification. MiR-483-5p and miR-2861 are enriched in AB-EVs and essential for the AB-EVs-induced bone-fat imbalance and exacerbation of vascular calcification. Our study uncovers the role of AB-EVs as a messenger for calcification paradox by transferring miR-483-5p and miR-2861.

Clinical effects and gut microbiota changes of using probiotics, prebiotics or synbiotics in inflammatory bowel disease: a systematic review and meta-analysis.

PURPOSE: Probiotics have been reported to be beneficial for inflammatory bowel disease (IBD), but the types, number of strains, dosage, and intervention time of probiotics used remain controversial. Furthermore, the changes of gut microbiota in IBD's patients are also intriguing. Thus, this meta-analysis was to explore the clinical effects and gut microbiota changes of using probiotics, prebiotics and synbiotics in IBD. METHODS: The search was performed in PubMed, Web of Science and the Cochrane library from inception to April 2020. Qualified randomized controlled trials were included. IBD's remission rate, disease activity index and recurrence rate were extracted and analyzed. Changes in the gut microbiota of patients with IBD are comprehensively described. RESULTS: Thirty-eight articles were included. Probiotics, prebiotics and synbiotics can induce/maintain IBD's remission and reduce ulcerative colitis (UC) disease activity index (RR = 1.13, 95% CI 1.02, 1.26, P < 0.05; SMD = 1.00, 95% CI 0.27, 1.73, P < 0.05). In subgroup analyses of IBD remission rate and UC disease activity index, we obtained some statistically significant results in some subgroup (P < 0.05). To some extent, probiotic supplements can increase the number of beneficial bacteria (especially Bifidobacteria) in the intestinal tract of patients with IBD. CONCLUSIONS: Our results support the treatment of IBD (especially UC) with pro/pre/synbiotics, and synbiotics are more effective. Probiotic supplements that are based on Lactobacillus and Bifidobacterium or more than one strain are more likely to be beneficial for IBD remission. The dose of 1010-1012 CFU/day may be a reference range for using probiotics to relieve IBD.

Type A aortic dissection developed after type B dissection with the presentation of shoulder pain: A case report.

BACKGROUND: Aortic dissection (AD) is a life-threatening condition with a high mortality rate without immediate medical attention. Early diagnosis and appropriate treatment are critical in treating patients with AD. In the emergency department, patients with AD commonly present with classic symptoms of unanticipated severe chest or back pain. However, it is worth noting that atypical symptoms of AD are easily misdiagnosed. CASE SUMMARY: A 51-year-old woman was first diagnosed with scapulohumeral periarthritis due to left shoulder pain. After careful examination of her previous medical history and contrast-enhanced computed tomography angiography, the patient was diagnosed with a new type A AD after chronic type B dissection in the ascending aorta. The patient was successfully treated with surgical replacement of the dissected aortic arch and remains in good health. CONCLUSION: New retrograde type A AD after chronic type B dissection is relatively rare. It is worth noting that a physician who has a patient with suspected AD should be vigilant. Both patient medical history and imaging tests are crucial for a more precise diagnosis.

Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway.

BACKGROUND: Induction therapy for acute myeloid leukemia (AML) is an anthracycline-based chemotherapy regimen. However, many patients experience a relapse or exhibit refractory disease (R/R). There is an urgent need for more effective regimens to reverse anthracycline resistance in these patients. METHODS: In this paper, Twenty-seven R/R AML patients with anthracycline resistance consecutively received chidamide in combination with anthracycline-based regimen as salvage therapy at the Chinese PLA General Hospital. RESULTS: Of the 27 patients who had received one course of salvage therapy, 13 achieved a complete response and 1 achieved a partial response. We found that the HDAC3-AKT-P21-CDK2 signaling pathway was significantly upregulated in anthracycline-resistant AML cells compared to non-resistant cells. AML patients with higher levels of HDAC3 had lower event-free survival (EFS) and overall survival (OS) rates. Moreover, anthracycline-resistant AML cells are susceptible to chidamide, a histone deacetylase inhibitor which can inhibit cell proliferation, increase cell apoptosis and induce cell-cycle arrest in a time- and dose-dependent manner. Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway. CONCLUSION: Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application.

Association of whole grains intake and the risk of digestive tract cancer: a systematic review and meta-analysis.

BACKGROUND: Several epidemiological studies have investigated the association between whole grains intake and digestive tract cancer risk; however, the results are still controversial. The purpose of this meta-analysis was to assess the association. METHODS: Studies published before March 2020 were searched in database and other sources. The risk ratio (RR) with the 95% confidence interval (CI) were pooled using fix or random-effects models. RESULTS: This meta-analysis included 34 articles reporting 35 studies, 18 studies of colorectal cancer, 11 studies of gastric cancer and 6 studies of esophagus cancer, involving 2,663,278 participants and 28,921 cases. Comparing the highest-intake participants with the lowest-intake participants for whole grains, we found that the intake of whole grains were inversely related to colorectal cancer (RR = 0.89, 95% CI: 0.84-0.93, P < 0.001), gastric cancer (RR = 0.64, 95% CI: 0.53-0.79, P < 0.001), esophagus cancer (RR = 0.54, 95% CI: 0.44-0.67, P < 0.001), respectively. However, subgroup analysis of colorectal cancer found no significant association in the case-control studies and studies of sample size < 500, and subgroup analysis of gastric cancer found no significant association in the cohort studies and studies of American population. No study significantly affected the findings in the sensitivity analysis. No publication bias was found in the studies for colorectal cancer and esophagus cancer except in the studies for gastric cancer. CONCLUSION: This meta-analysis provides further evidence that whole grains intake was associated with a reduced risk of digestive tract cancer. Our result supports the dietary guidelines that increase whole grains intake to reduce the risk of digestive tract cancer.

H-type blood vessels participate in alveolar bone remodeling during murine tooth extraction healing.

OBJECTIVES: We aimed to investigate whether skeletal-specific H-type blood vessels exist in alveolar bone and how they function in alveolar bone remodeling. MATERIALS AND METHODS: H-type vessels with high expression of CD31 and Endomucin (CD31hi Emcnhi ) were immunostained in alveolar bone. Abundance and age-related changes in CD31hi Emcnhi endothelial cells (H-ECs) were detected by flow cytometry. Osteoprogenitors association with H-type vessels and bone mass were detected in tooth extraction model of alveolar bone remodeling by immunohistofluorescence and micro-CT, respectively. Transcription and expression of H-EC feature genes during in vitro Notch inhibition were measured by RT-qPCR and immunocytofluorescence. RESULTS: We verified that H-type vessels existed in alveolar bone, the abundance of which was highest at infancy age, then decreased but maintained a constant level during aging. In tooth extraction model, H-ECs significantly increased with concomitant perivascular accumulation of Runx2+ osteoprogenitors and gradually augmentation of bone mass. Notch inhibition of in vitro cultured H-ECs resulted in decreased expression levels of Emcn and hes1, but not Pecam1 or Kdr genes, with decreased expression levels of H-EC numbers, accordingly. CONCLUSIONS: The present study suggests that H-type vessels promote osteogenesis during alveolar bone remodeling. Notch signaling pathway regulates expression of Emcn and possibly determines fate and functions of alveolar H-ECs.

Dynamic Correlation Analysis Method of Air Pollutants in Spatio-Temporal Analysis.

Pollutant analysis and pollution source tracing are critical issues in air quality management, in which correlation analysis is important for pollutant relation modeling. A dynamic correlation analysis method was proposed to meet the real-time requirement in atmospheric management. Firstly, the spatio-temporal analysis framework was designed, in which the process of data monitoring, correlation calculation, and result presentation were defined. Secondly, the core correlation calculation method was improved with an adaptive data truncation and grey relational analysis. Thirdly, based on the general framework and correlation calculation, the whole algorithm was proposed for various analysis tasks in time and space, providing the data basis for ranking and decision on pollutant effects. Finally, experiments were conducted with the practical data monitored in an industrial park of Hebei Province, China. The different pollutants in multiple monitoring stations were analyzed crosswise. The dynamic features of the results were obtained to present the variational correlation degrees from the proposed and contrast methods. The results proved that the proposed dynamic correlation analysis could quickly acquire atmospheric pollution information. Moreover, it can help to deduce the influence relation of pollutants in multiple locations.

Spatio-Temporal Prediction for the Monitoring-Blind Area of Industrial Atmosphere Based on the Fusion Network.

The monitoring-blind area exists in the industrial park because of private interest and limited administrative power. As the atmospheric quality in the blind area impacts the environment management seriously, the prediction and inference of the blind area is explored in this paper. Firstly, the fusion network framework was designed for the solution of "Circumjacent Monitoring-Blind Area Inference". In the fusion network, the nonlinear autoregressive network was set up for the time series prediction of circumjacent points, and the full connection layer was built for the nonlinear relation fitting of multiple points. Secondly, the physical structure and learning method was studied for the sub-elements in the fusion network. Thirdly, the spatio-temporal prediction algorithm was proposed based on the network for the blind area monitoring problem. Finally, the experiment was conducted with the practical monitoring data in an industrial park in Hebei Province, China. The results show that the solution is feasible for the blind area analysis in the view of spatial and temporal dimensions.

Outcome and Prognostic Factors of High-Risk Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND Allogeneic transplantation remains one of the best therapies for high-risk acute myeloid leukemia (HR-AML). MATERIAL AND METHODS This study retrospectively analyzed 126 patients with HR-AML after allogeneic hematopoietic stem cell transplantation (allo-HCST). RESULTS The disease-free survival (DFS) rates of 1 year and 3 years were 58.83% (95%CI: 50.75-68.20%) and 53.09% (95%CI: 44.59-63.22%) respectively. The cumulative relapse rates of 1 year and 3 years were 21.1% (95%CI: 14.4-28.8%) and 25.9% (95%CI: 18.1-34.5%) respectively. The cumulative incidences of III to IV acute graft-versus-host disease (aGVHD) for 100 days was 8.70% (95%CI: 4.6-14.5%). The cumulative rate of extensive chronic graft-versus-host disease (cGVHD) for 1-year was 4.1% (95%CI: 1.5-8.7%). The cumulative transplantation related mortality rate of 1 year and 3 years were 20.1% (95%CI: 13.6-27.6%) and 21.0% (95%CI: 14.3-28.6%) respectively. Univariate analysis revealed that lower overall survival was correlated with age, bacterial or fungal infection, disease status at transplantation, III-IV aGVHD, post-transplantation lymphoproliferative disorders (PTLD), white blood cell engraftment, and extramedullary involvement (P<0.05). The results of multivariate analysis were that the aforementioned factors were also related to lower overall survival except for PTLD (P<0.05). The results of univariate and multivariate analysis were that extramedullary involvement, III-IV aGVHD, and status pre-transplantation influenced DFS (P<0.05). The risk factors for relapse were status pre-transplantation and extramedullary involvement by univariate and multivariate analysis (P<0.05). CONCLUSIONS HR-AML has inferior prognosis. Our study indicated the necessity of achieving remission status prior to hematopoietic stem cell transplantation, and administration of preventive treatments on high-risk patients after hematopoietic stem cell transplantation. In addition, adequate prevention and treatment of complications are needed.

[Discussion on safety evaluation and risk control measures of Epimedii Folium].

Epimedii Folium,a commonly used traditional Chinese medicine,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism. However,in recent years,the number of reports on adverse reactions of Epimedii Folium and its Chinese patent medicines such as Xianling Gubao Capsules and Zhuanggu Guanjie Pills has been gradually increased,and the toxicity of Epimedii Folium has attracted more and more attention. In this article,the ancient and modern literature on Epimedii Folium was traced through a comprehensive and systematic literature analysis method. According to the 2015 edition of the Chinese Pharmacopoeia,Epimedii Folium refers to the dried leaves of Epimedii Folium brevicomu,E. sugittutum,E. pubescens or E. koreuuum. The Chinese Pharmacopoeia also includes E. wushanense of Wushan Epimedium,which is the same plant variety as Epimedium. The study showed that there were differences in the geographical distribution,composition and toxicity among five species of Epimedium. This paper also explained the toxicity mechanism as well as efficacy enhancing and toxicity reducing effects of Epimedii Folium,and reported its related adverse reaction cases. Through a retrospective comparative study on the toxicity of the modern Chinese patent medicines Xianling Gubao Capsules and Zhuanggu Guanjie Pills containing Epimedii Folium,it was believed that Epimedii Folium had cardiovascular system toxicity,neurotoxicity,hepatotoxicity,long-term toxicity,acute toxicity,genotoxicity and special toxicity; its safe medication factors included patient syndrome,doctor factors,drug factors,processing and compatibility factors. Meanwhile,strategies were proposed to improve patient safety medication awareness,standardize Epimedii Folium varieties and quality supervision,and the toxicity of Epimedii Folium was studied,hoping to draw attention from scholars to the safety of Epimedii Folium,improve the safe use of Epimedii Folium,and prevent adverse reactions.

Outcome of Rituximab-Based Treatment for Post-Transplant Lymphoproliferative Disorder After Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience.

BACKGROUND Post-transplant lymphoproliferative disorder (PTLD) is a rare complication following solid organ transplantation and allogeneic hematopoietic stem cell transplantation (Allo-HSCT), which gives rise to high mortality rates. MATERIAL AND METHODS This was a single-center retrospective analysis based on 27 patients who were diagnosed with PTLD following Allo-HSCT between January 1, 2007 and June 2018 at the Chinese PLA General Hospital. The purpose of this analysis was to investigate responses and prognostic factors of rituximab-based treatment. RESULTS Twenty-seven patients were treated with rituximab. Among them, 20 of 27 patients (74.07%) had a complete response, 2 of 27 patients (7.41%) had a partial response, 5 of 27 patients (18.52%) had no response, and 22 of 27 patients (81.48%) cleared Epstein-Barr virus (EBV) copies. There were no obvious side effects. The 1-year overall survival (OS) estimate was 46.8% (95% CI, 23.1-65.5%). Univariate analysis revealed that lower OS was correlated with Eastern Cooperative Oncology Group (ECOG) score standard (3-4), Epstein-Barr virus (EBV) viral load (≥106 copies/mL), bacteria or fungal infection, and EBV reactivation were positive after treatment with 1 or 2 doses of rituximab (P<0.05). Multivariate analysis showed that each of the following were independently associated with lower OS (P<0.05): female, ECOG score standard (3-4), and EBV reactivation were positive after treatment with 1 or 2 doses of rituximab. CONCLUSIONS Our results demonstrated that rituximab-based treatment was a safe and effective strategy for patients who were diagnosed with PTLD following Allo-HSCT. The identified prognostic factors may help to detect which PTLD patients are at a higher risk of mortality.

Tetramethylpyrazine Facilitates Functional Recovery after Spinal Cord Injury by Inhibiting MMP2, MMP9, and Vascular Endothelial Cell Apoptosis.

BACKGROUND: Spinal cord injury (SCI) is a major public health issue that leads to neurological dysfunctions and morbidities in patients. Tetramethylpyrazine (TMP) plays a neuroprotective role in SCI; however, the underlying mechanism has not been fully elucidated. OBJECTIVE: In the present study, we aimed to investigate the mechanisms and therapeutic effects of TMP on SCI. METHODS: A contusion SCI model was established that used a modified Allen's method. In the TMP group, TMP (200 mg/kg) was injected daily for 5 days post-injury, while in the Negative Control (NC) group, an equal volume of normal saline was injected. Hindlimb motor function was evaluated using the Basso, Beattie, Bresnahan (BBB) scale. The effects of TMP on protein levels of the matrix metalloproteinases 2 (MMP2) and 9 (MMP9), Bax and cleaved caspase-3 were determined by western blotting. Apoptotic changes in vascular endothelial cells were evaluated using immunofluorescence and TUNEL staining. Alterations in 3D vessel morphology after treatment with TMP were assessed by synchrotron radiation micro-CT (SRµCT). RESULTS: TMP treatment significantly improved recovery in hindlimb motor function and attenuated vascular endothelial cell apoptosis in rats with SCI. Additionally, TMP treatment markedly decreased the protein levels of MMP2 and MMP9, pro-apoptotic bax and cleaved caspase-3 while promoting angiogenesis, as evidenced by vessel visualization using SRµCT. CONCLUSION: These results indicate that TMP attenuated SCI-induced neurological impairments by the down-regulation of the expression of MMP2 and MMP9 proteins, the inhibition of vascular endothelial cell apoptosis, and the promotion of angiogenesis.

Investigation on etiology of hepatic venous obstruction Budd-Chiari syndrome.

Budd-Chiari syndrome (BCS) is an uncommon clinical condition with a complex etiology. Pathogenesis of BCS is still poorly understood. We included hepatic veno-occlusive lesion tissues of 20 patients (patients group) with hepatic venous obstruction BCS and compared with 20 similar tissues with other etiologies (control group). Morphological changes in hepatic veno-occlusive lesion tissues and the positive expression of proliferating cell nuclear antigen (PCNA), C-myc, and P-53 were observed by the pathological examination (H&E staining) and immunohistochemistry assay. Our results showed that PCNA and C-myc positive cell densities were significantly higher in patient group than control group. P-53 positive cell density showed increasing trends in patients than control group. Moreover, we observed irregular hyperplasia in intimal tissue, fibrous connective tissue, and smooth muscle cell, accompanied by tissue degeneration (hyaloid degeneration and fibrinoid degeneration) and a large quantity of inflammatory cell infiltration. In conclusion, an overexpression of PCNA, C-myc, and a weak positive expression of P53 might launch the extremely irregular hepatic venous intimal hyperplasia, which is probably one of the etiologies of hepatic venous obstruction BCS.

[Meta-analysis on elemene injection combined with cisplatin chemotherapeutics in treatment of non-small cell lung cancer].

To research databases of Cochrane library, Web of Science, PubMed, FMJS, CBM, VIP, CNKI and Wanfang Data Konwledge Service Platform by computers as at July 5, 2012, which was supplemented with other search results. The findings were included into randomized controlled trials (RCTs) of elemene injection combined with cisplatin chemotherapeuties in treating small cell lung cancer (NSCLC). Data was separately collected by two researchers for literature quality evaluation, and a Meta analysis was made with RevMan 5. 2 software, in order to assess the efficacy and safety of elemene injection combined with cisplatin chemotherapeutics in treating NSCLC. Totally 11 RCTs or 844 cases were included. Meta analysis results suggested that compared with cisplatin chemotherapy alone, the combination of elemene injection and cisplatin chemotherapeutics showed a higher clinical benefit rate ( OR = 2. 03, 95% CI:1.43-2. 88, P <0. 000 1) and a better quality of life (OR = 3.23, 95% CI:2. 20-4. 74, P <0. 000 01). Besides,the combination could also reduce leucopenia (OR =0. 50, 95% CI:0. 33-0. 76, P <0. 001) , and thrombocytopenia (OR =0. 38, 95% CI:0. 16-0. 85, P <0. 02), increase CD4 (MD = 3.32, 95% C1:2. 94-3.70, P <0. 000 01), and CD4/CD8 (MD = 0. 36, 95% CI:0. 28-0. 44, P < 0. 000 01) , and relieve gastrointestinal reactions such as nausea and vomiting (OR = 0. 37, 95% CI: 0. 19-0. 71, P = 0. 003). The analysis indicates that elemene can enhance the chemotherapeutic effect on NSCLC, improve the quality of life, and reduce adverse effect of platinum-contained chemotherapeutics, thereby being worth promoting in clinic.

Establishing a disc degeneration model using computed tomography-guided percutaneous puncture technique in the rabbit.

BACKGROUND: Various animal models have been developed to investigate the complex mechanisms leading to intervertebral disc disorders and to evaluate the different therapeutic options. The needle puncture technique is commonly used to induce intervertebral degeneration in animal models. The present study aimed to establish a rabbit model of intervertebral disc degeneration using a simple, minimally invasive procedure. METHODS AND MATERIALS: The animal model was created in the rabbit using computed tomography-guided percutaneous puncture technology. An 18-gauge needle was used to induce a disc injury with a 5-mm puncture depth. Radiographic, histologic, and biochemical analyses and magnetic resonance imaging were performed to assess the consequent disc degeneration. RESULTS: Significant disc space narrowing was observed as early as 4 wk, and osteophytes were formed at 12 wk after puncture. The magnetic resonance imaging assessment demonstrated a progressive loss of T2-weighted signal intensity at the stabbed discs throughout the 12-wk period. The histologic analysis showed a progressive loss of the normal architecture from 4 wk to the end point. The biochemical assays suggested that the expression of proteoglycan decreased progressively with increasing time. CONCLUSIONS: A simple, but minimally invasive, intervertebral disc degeneration model was established successfully using computed tomography-guided percutaneous puncture technology in the rabbit. The puncture procedure can be performed with minimal damage and handling of the other structures, ensuring a uniform reproducible disc degeneration model.

Risedronate inhibits bone marrow mesenchymal stem cell adipogenesis and switches RANKL/OPG ratio to impair osteoclast differentiation.

BACKGROUND: Osteoporosis is accompanied by an increase in bone marrow adipose tissue. Bone marrow adipogenesis has emerged as a therapeutic target for prevention of bone loss. Amino-bisphosphonates have been widely used for treatment of osteoporosis, but the mechanism through which amino-bisphosphonates inhibit osteoporosis remains unclear. The purpose of this study is to investigate the effects of bisphosphonates on bone marrow adipogenesis and the pro-osteoclastic factors produced by adipocytes in bone marrow microenvironment. MATERIALS AND METHODS: Human mesenchymal stem cells were obtained and purified from six volunteer donors. Each sample of cells was treated by increasing concentrations of risedronate with or without adipogenic induction for 14 d, and then droplets of the differentiated adipocytes were analyzed. The level of receptor activator of nuclear factor-κB ligand and osteoprotegerin, as well as pro-osteoclastic inflammatory factors interleukin-1, interleukin-6, and tumor necrosis factor α produced by adipocytes were evaluated by Western blot and ELISA assay. Moreover, the effect of risedronate on the activity of mammalian target of rapamycin complex 1, a key Ser/Thr kinase for initiation of adipocyte differentiation, was investigated. RESULTS: Risedronate not only dose-dependently inhibited the bone marrow adipogenesis from human mesenchymal stem cells but also suppressed receptor activator of nuclear factor-κB ligand, not osteoprotegerin, expression in differentiated adipocytes, as well as pro-osteoclastic inflammatory factors. Furthermore, the activity of mammalian target of rapamycin complex 1 was suppressed by risedronate. CONCLUSION: Our findings that risedronate influences the crosstalk between bone marrow adipocyte-osteoclast represent a novel mechanism for the anti-osteoporotic effects of risedronate.

Effects of anisodamine on the expressions of vascular endothelial growth factor and intercellular adhesion molecule 1 in experimental infusion phlebitis.

BACKGROUND: Infusion phlebitis is the most common side effect of clinical intravenous drug therapy and several clinical studies have demonstrated that anisodamine can effectively prevent the occurrence of infusion phlebitis. This study was designed to investigate effects of anisodamine on the expressions of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) in a rabbit model of infusion phlebitis and to analyze the mechanisms of anisodamine effect on the prevention and treatment of experimental infusion phlebitis. METHODS: Twenty-four specific pathogen-free male Japanese white rabbits were randomly assigned to the control group, the model group, the magnesium sulfate group and the anisodamine group. The rabbit model of infusion phlebitis, induced by intravenous administration, was established and expressions of VEGF and ICAM-1 were determined and contrasted with the control group treated with normal saline. We evaluated expression by histopathology, immunohistochemistry, reverse transcription-polymerase chain reaction, and Western blotting assay. RESULTS: Pathohistological changes of the model group were observed, such as loss of venous endothelial cells, inflammatory cell infiltration, edema and thrombus. The magnesium sulfate group and the anisodamine group showed significant protective effects on vascular congestion, inflammatory cell infiltration, proliferation, swelling of endothelium and perivascular hemorrhage. The model group showed the highest expressions of VEGF and ICAM-1 of the four groups (P < 0.01). On the contrary, anisodamine alleviated the inflammatory damage by significantly reducing the expressions of VEGF and ICAM-1 compared with the model group (P < 0.01). There was no significant difference in the expressions of VEGF and ICAM-1 between the magnesium sulfate group and the anisodamine group (P > 0.05). CONCLUSION: Anisodamine alleviates inflammatory damage by significantly reducing the expressions of VEGF and ICAM-1, and shows significant protective effects in an animal model of infusion phlebitis.