The hemostatic and anti-inflammatory effects of intravenous single-dose of tranexamic acid in double-segment posterior lumbar interbody fusion: a case control study.

This study aims to observe the hemostatic and anti-inflammatory effects of intravenous administration of tranexamic acid (TXA) in dual segment posterior lumbar interbody fusion (PLIF). The data of 53 patients with lumbar disease treated with double-segment PLIF were included in this study. The observation group was received a single-dose intravenous of TXA (1 g/100 mL) 15 min before skin incision after general anesthesia. The control group was not received TXA. The observation indicators included postoperative activated partial prothrombin time (APTT), thrombin time (PT), thrombin time (TT), fibrinogen (FIB), platelets (PLT), and postoperative deep vein thrombosis in the lower limbs, surgical time, intraoperative bleeding volume, postoperative drainage volume, transfusion rate, postoperative hospital stay, red blood cell (RBC), hemoglobin (HB), hematocrit (HCT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) on the 1st, 4th, 7th, and last tested day after surgery. All patients successfully completed the operation, and there was no deep vein thrombosis after operation. There was no statistically significant difference in postoperative APTT, PT, TT, FIB, PLT, surgical time, and postoperative hospital stay between the two groups (p > 0.05). The intraoperative bleeding volume, postoperative drainage volume, and transfusion rate in the observation group were lower than those in the control group, and the differences were statistically significant (p < 0.05). There was no statistically significant difference in RBC, HB, HCT, CRP, and ESR between the two groups on the 1st, 4th, 7th, and last tested day after surgery (p > 0.05). Intravenous administration of TXA in dual segment PLIF does not affect coagulation function and can reduce bleeding volume, postoperative drainage volume, and transfusion rate. Moreover, it does not affect the postoperative inflammatory response.

The effect of preoperative use of anticoagulants on the hemostatic effect of intravenous application of tranexamic acid in PLIF: a case control study.

Intravenous application of tranexamic acid (TXA) in posterior lumbar interbody fusion (PLIF) can effectively reduce blood loss without affecting coagulation function. However, it has not been reported whether preoperative use of anticoagulants may affect the efficacy of TXA in PLIF. The purpose of this study is to observe the effect of preoperative use of anticoagulants on coagulation indicators and blood loss after PLIF receiving intravenous unit dose TXA. A retrospective analysis was conducted on data from 53 patients with PLIF between 2020.11 and 2022.9, who received intravenous application of a unit dose of TXA (1 g/100 mL) 15 min before the skin incision after general anesthesia. Those who used anticoagulants within one week before surgery were recorded as the observation group, while those who did not use anticoagulants were recorded as the control group. The main observation indicators include surgical time, intraoperative blood loss, postoperative drainage volume, blood transfusion, and red blood cell (RBC), hemoglobin (HB), and hematocrit (HCT) measured on the 1st, 4th, 7th, and last-test postoperative days. Secondary observation indicators included postoperative incision healing, deep vein thrombosis of lower limbs, postoperative hospital stay, and activated partial thrombin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (FIB), and platelets (PLT) on the 1st and 4th days after surgery. The operation was successfully completed in both groups, the incision healed well after operation, and no lower limb deep vein thrombosis occurred. There was no significant difference in surgical time, intraoperative blood loss, postoperative drainage volume, and blood transfusion between the two groups (p > 0.05). There was no significant difference in the RBC, HB, and HCT measured on the 1st, 4th, 7th, and last-test postoperative days between the two groups (p > 0.05). There was no statistically significant difference in APTT, PT, TT, FIB and PLT between the two groups on the 1st and 4th postoperative days (p > 0.05). There was no significant difference in postoperative hospital stay between the two groups (p > 0.05). The use of anticoagulants within one week before surgery does not affect the hemostatic effect of intravenous unit dose TXA in PLIF.

Alleviation of Glucocorticoid-Induced Osteoporosis in Rats by Ethanolic Reynoutria multiflora (Thunb.) Moldenke Extract.

Secondary osteoporosis is frequently due to the use of high-dose glucocorticoids (GCs). The existing strategy for managing glucocorticoid-induced osteoporosis (GIOP) is considered insufficient and remains in a state of ongoing evolution. Therefore, it is crucial to develop more precise and effective agents for the treatment of GIOP. The constituents of Reynoutria multiflora (Thunb.) Moldenke, specifically Polygonum multiflorum (PM) Thunb, have previously shown promise in mitigating osteopenia. This study aimed to investigate the therapeutic effects of an ethanolic PM extract (PMR30) against GIOP in male rats. Prednisone (6 mg/kg/day, GC) was continuously administered to rats to induce GIOP, and they were subjected to treatment with or without ethanolic PMR30 for a duration of 120 days. Serum was collected for biochemical marker analysis. Bone histomorphometric, histological, and TUNEL analyses were performed on tibia samples. The protein expressions of LC3, Agt5, and Beclin 1 in the femur underwent examination through western blotting. Prolonged and excessive GC treatment significantly impeded bone formation, concomitant with reduced bone mass and body weight. It also suppressed OCN and OPG/RANKL in serum, and decreased Beclin 1 and LC3 in bone. Simultaneously, there was an elevation in bone resorption markers and apoptosis. Treatments with both high dose and low dose of PMR30 alleviated GIOP, stimulated bone formation, and upregulated OCN and OPG/RANKL, while suppressing TRACP-5b, CTX-I, and apoptosis. The impact of PMR30 possibly involves the enhancement of autophagy proteins (LC3, Agt5, and Beclin 1) and the inhibition of apoptosis within the bone. PMR30 holds promise as a prospective therapeutic agent for preventing and treating GIOP.

Dyclonine relieves the Parkinson's disease progression in rotenone-induced Drosophila model.

It has been estimated that there will be 930 million Parkinson's disease (PD) patients in 2030 in the whole world. However, no therapy has been effective for PD until now. Only levodopa is the available primary drug for the treatment of motor symptoms. Therefore, it is an urgent task to develop new drugs to inhibit the progression of PD and improve the quality of the patient's life. Dyclonine which was found to have antioxidant activity and would benefit patients with Friedreich's ataxia, is a commonly used local anesthetic. Here, we reported that dyclonine improved the motor ability and loss of dopaminergic neurons in the rotenone-induced Drosophila PD model for the first time. Furthermore, dyclonine upregulated the Nrf2/HO pathway, decreased the ROS and MDA levels, and inhibited the apoptosis of neurons in the brain of PD model flies. Hence, dyclonine might be an attractive FDA-approved drug for the exploration of effective PD therapy.

Effect of androgen on bone metabolism in hyperuricemic rats.

Introduction: This study aimed to investigate the effect of androgen on bone metabolism in hyperuricemic rats. Material and methods: Forty male Wistar rats were randomly divided into four groups: sham operation group, simple hyperuricemic group, hyperuricemic castration group, and simple castration group. A rat model of chronic hyperuricemia was established using potassium oxonate and ethambutol. Blood was sampled from the vena angularis at week 0, 4, 6, 8 and 12 after surgery to detect for uric acid, calcium, phosphorus and alkaline phosphatase, and investigate the effect of androgen on bone metabolism in hyperuricemic rats. Results: From the 4th week, compared with the sham operation group, the differences in uric acid levels between the simple hyperuricemic group and hyperuricemia castration group were statistically significant (p < 0.05), suggesting the successful establishment of the model of hyperuricemia. At the 6th week, uric acid levels decreased in the two hyperuricemic groups, and the difference from the sham operation group decreased (p = 0.05), showing that the modeling method had deteriorated. At the 8th week, the differences in uric acid levels between the two castration groups and sham operation group were statistically significant (p < 0.05). At the 12th week, the differences in serum levels of phosphorus between the simple hyperuricemic group and hyperuricemic castration group were statistically significant (p < 0.05). Conclusions: Androgen can induce bone metabolism changes in rats with hyperuricemia.

Improvement the Flame Retardancy and Thermal Conductivity of Epoxy Composites via Melamine Polyphosphate-Modified Carbon Nanotubes.

Surface chemical modification of carbon nanotubes can enhance the compatibility with polymers and improve flame retardancy performances. In this work, the double bond active sites were constructed on the surface of carbon nanotubes modified by the γ-methacryloyloxypropyl trimethoxysilane (KH570). Glycidyl methacrylate (GMA) was further grafted onto the surface of carbon nanotubes via free radical polymerization. Finally, the flame retardant melamine polyphosphate (MPP) was bonded to the surface of carbon nanotubes by the ring-opening reaction. This modification process was proved to be achieved by infrared spectroscopy and thermogravimetric test. The carbon nanotubes modified by flame retardant were added into the epoxy matrix and cured to prepare flame retardant and thermal conductive composites. The flame retardancy of composites were studied by cone calorimetry, UL94 vertical combustion test and limiting oxygen index. The thermal conductivity of composites was characterized by laser thermal conductivity instrument. The results showed that when the addition amount of flame retardant MPP-modified carbon nanotubes in composites was 10 wt%, the flame retardant level of UL94 reached to V2, the limiting oxygen index increased from 25.1 of pure epoxy resin to 28.3, the PHRR of pure epoxy resin was reduced from 800 kW/m2 to 645 kW/m2 of composites and thermal conductivity of composites was enhanced from 0.21 W/m·K-1 of pure epoxy resin to 0.42 W/m·K-1 of the composites.

[Mechanism of Tibetan medicine Pterocephalus hookeri extract in treatment of rheumatoid arthritis based on serum metabonomics].

Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF/MS) was used to investigate the effect of Pterocephalus hookeri on serum metabolism of adjuvant arthritis(AA) model rats induced by complete Freund's adjuvant. After the AA model was properly induced, the serum of rats was collected 30 days after treatment. UPLC-Q-TOF-MS chromatograms were collected and analyzed by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The results revealed that compared with the control group, the model group showed increased content of 12 biomarkers in the serum(P<0.05) and reduced content of the other nine biomarkers(P<0.05). P. hookeri extract could recover the above-mentioned 19 biomarkers to a certain range. Pathway enrichment showed that these markers mainly involved eight metabolic pathways, including valine, leucine, and isoleucine degradation, arachidonic acid metabolism, arginine and proline metabolism, glycerol phospholipid metabolism, primary bile acid biosynthesis, bile acid biosynthesis, tryptophan metabolism, and unsaturated fatty acid biosynthesis. The findings of this study demonstrate that P. hookeri extract can regulate metabolic disorders and promote the regression of metabolic phenotype to the normal level to exert the therapeutic effect on AA rats. This study is expected to provide a certain scientific basis for the biological research on the treatment of rheumatoid arthritis by P. hookeri.

Chlorogenic acid, a natural product as potential inhibitor of COVID-19: virtual screening experiment based on network pharmacology and molecular docking.

Chlorogenic acid (CGA) is a potential inhibitor of Coronavirus Disease 2019 (COVID-19). ACE2 and its co-expressed proteins are SARS-CoV-2 receptors, which have been linked to SARS-CoV-2 infection and considered as the key target of SARS-CoV-2 in entering target cells. Here, network pharmacology was used to investigate the mechanism by which CGA affected COVID-19. A total of 70 potential targets related to the treatment of COVID-19 were obtained, among which NFE2L2, PPARG, ESR1, ACE, IL6, and HMOX1 might be the main potential targets. Finally, CGA and potential target proteins were scored by molecular docking, and the prediction results of network pharmacology were preliminarily verified. Moreover, CGA had potential anti-SARS-CoV-2 activity via integrating three common receptors in clinical practice compared with clinical trial drugs registered for the treatment of COVID-19, as shown by molecular docking. The mechanism of CGA against COVID-19 was initially investigated using network pharmacology, followed by molecular docking.

Acetylene hydrochlorination over tin nitrogen based catalysts: effect of nitrogen carbon-dots as nitrogen precursor.

The catalysts comprising the main active compounds of Sn-Nx were synthesized using trichlorophenylstannane ((C6H5)Cl3Sn), nitrogen carbon-dots (NCDs), and activated carbon (AC) as starting materials, and the activity and stability of catalysts was evaluated in the acetylene hydrochlorination. According to the results on the physical and chemical properties of catalysts (TEM, XRD, BET, XPS and TG), it is concluded that NCDs@AC can increase (C6H5)Cl3Sn dispersity, retard the coke deposition of (C6H5)Cl3Sn/AC and lessen the loss of (C6H5)Cl3Sn, thereby further promoting the stability of (C6H5)Cl3Sn/AC. Based on the characterization results of C2H2-TPD and HCl adsorption experiments, we proposed that the existence of Sn-Nx can effectively strengthen the reactants adsorption of catalysts. By combing the FT-IR, C2H2-TPD and Rideal-Eley mechanism, the catalytic mechanism, in which C2H2 is firstly adsorbed on (C6H5)Cl3Sn to form (C6H5)Cl3Sn-C2H2 and then reacted with HCl to produce vinyl chloride, is proposed.

The effect of spacers in dual drug-polymer conjugates toward combination therapeutic efficacy.

Recently, a great effort has been made to perfect the therapeutic effect of solid tumor, from single-agent therapy to combined therapy and many other polymer-drug conjugations with dual or more anticancer agents due to their promising synergistic effect and higher drug level accumulation towards tumor tissues. Different polymer-drug spacers present diverse therapeutic efficacy, therefore, finding an appropriate spacer is desirable. In this study, dual drugs that are doxorubicin (DOX) and mitomycin C (MMC) were conjugated onto a polymer carrier (xyloglucan) via various peptide or amide bonds, and a series of polymers drug conjugates were synthesized with different spacers and their effect on tumor treatment efficacy was studied both in vitro and in vivo. The result shows that the synergistic effect is better when using different linker to conjugate different drugs rather than using the same spacer to conjugate different drugs on the carrier. Particularly, the finding of this works suggested that, using peptide bond for MMC and amide bond for DOX to conjugate dual drugs onto single XG carrier could improve therapeutic effect and synergy effect. Therefore, in polymer-pharmaceutical formulations, the use of different spacers to optimize the design of existing drugs to enhance therapeutic effects is a promising strategy.

Glucocorticoid-induced dose-related and site-specific bone remodelling, microstructure, and mechanical changes in cancellous and cortical bones.

The study investigated the effects of long-term glucocorticoid (GC) administration on bone remodelling, microstructure, and biomechanical strength in cortical and cancellous (trabecular) bones. Thirty-one female Sprague-Dawley rats were randomly divided into three dexamethasone (Dex) dosage groups, 1.0, 2.5, and 5.0 mg/kg twice a week for 8 weeks, and one control group treated with saline. At the end of the experiment, the tibia of one side and the fourth lumbar vertebrae were processed into sections for a histomorphometric analysis, while the femur of the same side and the fifth vertebrae were isolated for a biomechanical test. A dose-dependent decline in bone formation was observed in both trabecular and cortical (periosteal and endosteal) bones. In contrast, bone resorption was inhibited only in cancellous bone in the two higher dose groups and not dose-related. The ratio of Node/Termini increased, while marrow star volume (MSV) decreased in all Dex groups in metaphyseal trabecular bones, both of which were dose-dependent. Subendosteal cortex porosity increased in parallel with non-uniform trabecular distribution, but cortical thickness remained unchanged. Interestingly, there were no significant changes in microstructure or mechanical strength in lumbar trabecular bone. The cortical elastic load was dose-independently reduced in all three Dex groups when compared with the control group. In summary, bone remodelling was dose-dependently inhibited in cancellous bones but enhanced in intracortical bones. The non-uniform distribution of trabecular bone and increased porosity in the inner edge of cortical bone were both in parallel with GC dosage, and the porosity increase was more likely to occur, leading to reduced cortical mechanical strength.

Predicting and Exploring the Mechanisms of Erzhi Pill in Prevention and Treatment of Osteoporosis Based on Network Pharmacology and Zebrafish Experiments.

BACKGROUND: Erzhi Pill (EZP), a traditional Chinese medicine (TCM) prescription, has been widely applied to improve bone metabolism and treat osteoporosis (OP) in China. However, its effective constituents and mechanisms remain unclear. METHODS: By combining network pharmacology and zebrafish experiments, an integrative method was employed to address this problem. Firstly, the disease targets of OP were collected from two public gene databases. Secondly, the active compounds and drug targets of EZP were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). Thirdly, a drug-target-disease interaction network was constructed, and the key active components were identified by analyzing the topological characteristics of the network. Finally, these predicted results were tested by zebrafish experiments and compared with those from the literature. Specifically, quercetin as an important representative active component of EZP was applied to wild type and transgenic zebrafish larvae to assess its effects on skull mineralization and osteoplastic differentiation. RESULTS: Our study identified 72 active compounds, 220 targets and 166 signaling pathways probably involved in the prevention and treatment of OP by EZP, wherein quercetin, apigenin, daidzein, luteolin, ursolic acid and kaempferol could be the key compounds, while PI3K-Akt signaling pathway, TNF signaling pathway and IL-17 signaling pathway could be the key signaling pathways. The experiments indicated that quercetin attenuated both the decrease of skull mineralization and the inhibition of skull osteoplastic differentiation in zebrafish larvae trigged by dexamethasone. CONCLUSION: Our study not only investigated potentially effective constituents and mechanisms of EZP in the prevention and treatment of OP, but also provided a reference for the in-depth research, development and application of TCM.

Pterocephanoside A, a new iridoid from a traditional Tibetan medicine, Pterocephalus hookeri.

This work obtained and identified pterocephanoside A (1), one new iridoid glucoside derivative with rare structure of three iridoid glycosides linked to cyclopenta[c]pyran-3(1H)-one, and 10 known iridoids (2-11) from Pterocephalus hookeri through silica gel column chromatography and semi-preparative HPLC. The structure of the new compound was confirmed by 1D and 2D NMR and HRMS data analysis. Compounds 1 and 2 were isolated from this plant for the first time. The iridoids mostly possessed seco-iridoid subtype and iridoid subtype skeletons from P. hookeri. Compounds 1, 3, 4, and 6-11 showed weak anti-inflammatory activity.

Traditional uses, phytochemistry, pharmacology, and toxicology of Pterocephalus hookeri (C. B. Clarke) Höeck: a review.

Pterocephalus hookeri (C. B. Clarke) Höeck is a member of the Dipsacaceae family and has been used in traditional Tibetan medicine for thousands of years. P. hookeri clears heat, detoxifies, stops dysentery, eliminates distemper, dispels wind, and relieves stagnation and is mainly prescribed for heat syndrome, dysentery, arthritis, and plague. Approximately 93 chemical compounds have been isolated and identified from P. hookeri, including iridoid glycosides, lignan and triterpenoids. Meanwhile, modern pharmacological studies have shown that P. hookeri has anti-inflammatory, anti-rheumatoid arthritis, analgesic, anticancer, and neuroprotection activities. However, studies on the in vivo pharmacokinetics and mechanism of action, discovery of quality markers, and qualitative and quantitative analysis are still insufficient. Hence, this paper provides a comprehensive review of the ethnic medicine, phytochemistry, pharmacology, and toxicology of P. hookeri to increase the understanding of the medicinal value of P. hookeri.

A Novel Missense Mutation of the CSF1R Gene Causes Incurable CSF1R-Related Leukoencephalopathy: Case Report and Review of Literature.

CSF1R-related leukoencephalopathy, mainly caused by the mutation of the colony stimulating factor 1 receptor (CSF1R) gene on chromosome 5, is an underestimated neurological disease typically presenting as early-onset cognitive decline and personality changes. Currently, there is no specific treatment for CSF1R-related leukoencephalopathy. Most clinicians failed to recognize this disease during an early disease stage, leading to a high rate of misdiagnosis. Although rare, an increasing amount of CSF1R-related leukoencephalopathy cases have been reported recently. In this study, we first report a 35-year-old woman with CSF1R-related leukoencephalopathy carrying a novel missense mutation c.2463G >C (p.W821C) of CSF1R. An extensive literature research was performed in order to better understand the broader genetic and clinical characteristics of CSF1R-related leukoencephalopathy. A total of 147 patients with CSF1R-related leukoencephalopathy confirmed either by the genetic test or brain biopsy were identified. Among them, 49 patients were sporadic, and the rest of individuals had a family history originating from 46 different families. Our study indicated that the average age of CSF1R-related leukoencephalopathy onset was 41.4 years. Typical clinical symptoms of CSF1R-related leukoencephalopathy include cognitive decline, movement disorders, behavior changes and mental disorders. Genetic studies have reported 93 missense mutations, 13 splicing mutations, 6 deletion/insertion mutations, 1 code shift mutation and 1 nonsense mutation of the CSF1R gene in patients with CSF1R-related leukoencephalopathy. Early genetic detection and brain biopsy would be helpful for a confirmed diagnosis, and more translational studies are needed to combat this devastating disease.

Cycloastragenol prevents age-related bone loss: Evidence in d-galactose-treated and aged rats.

BACKGROUND AND AIMS: Aging-induced bone loss is a multifactorial, age-related, and progressive phenomenon among the general population and may further progress to osteoporosis and increase the risk of fractures. Cycloastragenol (CAG), currently the only compound reported that activates human telomerase, is thought to be able to alleviate or delay the symptoms of aging and chronic diseases. Previous research has suggested that CAG may have the potential to alleviate age-related bone loss. However, to date, no research has specifically focused on this aspect. In this study, we aimed to investigate whether CAG could prevent senile osteoporosis, and further reveal its underlying mechanism. METHODS: CAG treatment was administrated into two bone loss rat models (D-galactose administration and aging) for 20 weeks and 33 weeks, respectively. Serum biomarkers analyses, bone biomechanical tests, micro-computed tomography assessment, and bone histomorphometry analyses were performed on the bone samples collected at the endpoint, to determine whether CAG could prevent or alleviate age-related bone loss. Proteomic analysis was performed to reveal the changes in protein profiles of the bones, and western blot was used to further verify the identity of the key proteins. The viability, osteoblastic differentiation, and mineralization of MC3T3-E1 cells were also evaluated after CAG treatment in vitro. RESULTS: The results suggest that CAG treatment improves bone formation, reduces osteoclast number, alleviates the degradation of bone microstructure, and enhances bone biomechanical properties in both d-galactose- and aging-induced bone loss models. CAG treatment promotes viability, osteoblastic differentiation, and mineralization in MC3T3-E1 cells. Proteomic and western blot analyses revealed that CAG treatment increases osteoactivin (OA) expression to alleviate bone loss. CONCLUSION: The results revealed that CAG alleviates age-related bone loss and improves bone microstructure and biomechanical properties. This may due to CAG-induced increase in OA expression. In addition, the results support preclinical investigations of CAG as a potential therapeutic medicine for the treatment of senile osteoporosis.

Prediction of the mechanisms of Xiaoai Jiedu Recipe in the treatment of breast cancer: A comprehensive approach study with experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) holds a great promise for preventing complex chronic diseases through a holistic way. Certain Chinese medicine formulae from TCM are effective for treating and preventing cancer in clinical practice. Xiaoai Jiedu Recipe (XJR) is a Chinese medicine formula that has been used to treat breast cancer (BC). However, its active ingredients and therapeutic mechanisms on tumor are unclear. Therefore, further investigation is necessary. AIM OF THE STUDY: This study aims to elucidate the active compounds of XJR and its molecular mechanisms for the treatment of BC. MATERIALS AND METHODS: A comprehensive approach was used to clarify the pharmacodynamic basis of XJR and its pharmacological mechanism, including the acquisition of differentially expressed genes of BC, screening of active ingredients and their targets, construction of complex internetwork between drugs and diseases, and analysis of the key subnetwork. Finally, these results were validated by in vitro experiments and comparison with literature reviews. RESULTS: By using bioinformatics, 5211 differentially expressed genes of BC were identified, more than half of them had been reported in previous studies. By using network analysis, 113 potential bioactive compounds in the ten component herbs of XJR and 157 BC-related targets were identified, which were significantly enriched in 85 pathways and 1321 GO terms. The in vitro studies showed that quercetin and ursolic acid, the active components of XJR, could effectively inhibit the proliferation of breast cancer cells, and the combination of the two components could significantly decrease the mitochondrial membrane potential and suppress the activation of PI3K-Akt signaling pathway, thus inducing apoptosis of cancer cells. CONCLUSIONS: XJR played an important role in anti-BC through multi-component, multi-target and multi-pathway mechanisms, in which quercetin and ursolic acid may be the key active components. The anticancer effect of multi-component application was better than that of a single component. This study not only deepened our understanding of the role of TCM in the prevention and treatment of diseases, but also provided a reference for the in-depth research, development and application of the ancient medicine.

The development of bone microstructure, metabolism and biomechanics in lumbar vertebra under short-term glucocorticoid exposure.

Abstracts Objective: This study investigated the characteristics of bone microstructure, metabolism, and biomechanics in rat's lumbar vertebra undergoing short-term glucocorticoid administration. Methods: Forty 4-month-old female Sprague-Dawley rats were treated with either vehicle (Cont) or prednisone acetate (Pre) at 3.5 mg/kg/day, respectively for periods of 7 days and 21 days. The lumbar vertebras were processed for MicroCT scan, histomorphometry analysis, mechanical compression test, in addition to Dual-Energy X-ray absorptiometry scan, respectively. Results: The connective density (Conn. D) along with trabecular connection nodes decreased while trabecular termini increased in Pre at day 21 when compared to Cont at day 21 as well as Pre at day 0. The mineralizing surface (MS/BS), mineral apposition rate (MAR), bone formation rate (BFR), osteoblast surfaces (Ob.S/BS) were lower in Pre at day 21 than that in Cont at day 21, Pre at day 0 and Pre at day 7. Only the bending stiffness of compression test decreased in Pre group at day 21 compared to age-matched control. Conclusion: The results suggested that excess prednisone significantly inhibited bone formation and slightly depressed bone resorption in the lumbar vertebra of intact rats for the duration of 21 days. Accordingly, the trabecular spatial microstructure made an adjustment yet failed to maintain the anti-compression mechanical property.

Salvianolic acid B stimulates osteogenesis in dexamethasone-treated zebrafish larvae.

AIM: Our previous studies show that salvianolic acid B (Sal B) promotes osteoblast differentiation and matrix mineralization. In this study, we evaluated the protective effects of Sal B on the osteogenesis in dexamethasone (Dex)-treated larval zebrafish, and elucidated the underlying mechanisms. METHODS: At 3 d post fertilization, wild-type AB zebrafish larvae or bone transgenic tg (sp7:egfp) zebrafish larvae were exposed to Sal B, Dex, or a mixture of Dex+Sal B for 6 d. Bone mineralization in AB strain larval zebrafish was assessed with alizarin red staining, and osteoblast differentiation in tg (sp7:egfp) larval zebrafish was examined with fluorescence scanning. The expression of osteoblast-specific genes in the larvae was detected using qRT-PCR assay. The levels of oxidative stress markers (ROS and MDA) in the larvae were also measured. RESULTS: Exposure to Dex (5-20 µmol/L) dose-dependently decreased the bone mineralization area and integral optical density (IOD) in wild-type AB zebrafish larvae and the osteoblast fluorescence area and IOD in tg (sp7:egfp) zebrafish larvae. Exposure to Dex (10 µmol/L) significantly reduced the expression of osteoblast-specific genes, including runx2a, osteocalcin (OC), alkaline phosphatase (ALP) and osterix (sp7), and increased the accumulation of ROS and MDA in the larvae. Co-exposure to Sal B (0.2-2 µmol/L) dose-dependently increased the bone mineralization area and IOD in AB zebafish larvae and osteoblast fluorescence in tg (sp7:egfp) zebrafish larvae. Co-exposure to Sal B (2 µmol/L) significantly attenuated deleterious alterations in bony tissue and oxidative stress in both Dex-treated AB zebafish larvae and tg (sp7:egfp) zebrafish larvae. CONCLUSION: Sal B stimulates bone formation and rescues GC-caused inhibition on osteogenesis in larval zebrafish by counteracting oxidative stress and increasing the expression of osteoblast-specific genes. Thus, Sal B may have protective effects on bone loss trigged by GC.

Tanshinol Rescues the Impaired Bone Formation Elicited by Glucocorticoid Involved in KLF15 Pathway.

Decreased bone formation is responsible for the pathogenesis of glucocorticoid- (GC-) induced osteoporosis (GIO), while the mechanism remains to be elucidated. The aim was to investigate how natural antioxidant tanshinol attenuates oxidative stress and rescues impaired bone formation elicited by GC in Sprague-Dawley rats and in C2C12 cells and/or MC3T3-E1 cells. The results showed that tanshinol prevented bone loss and decreased biomechanical characteristics and suppressed reduction of biomarkers related to osteogenesis in GIO rats. Further study revealed that tanshinol reversed decrease of transcription activity of Osterix-luc and rescued impairment of osteoblastic differentiation and bone formation involved in induction of KLF15 mRNA. Meanwhile, tanshinol diminished inhibition of protein expression of ß-catenin and Tcf4 and transcription activity of Tcf4-luc induced by GC, especially under conditions of KLF siRNA in vitro. Additionally, tanshinol attenuated increase of reactive oxygen species (ROS) generation, phosphorylation of p66(Shc) expression, TUNEL-positive cells, and caspase-3 activity elicited by KLF15 under conditions of GC. Taken together, the present findings suggest that tanshinol attenuated the decrease of bone formation and bone mass and bone quality elicited by GC involved in KLF15/Wnt signaling transduction and counteracted GC-evoked oxidative stress and subsequent cell apoptosis involved in KLF15/p66(Shc) pathway cascade.