Sensitivity, precision, and accuracy of fs-LIBS for heavy metal detection in flowing aqueous solutions.

This investigation employs femtosecond laser-induced breakdown spectroscopy (fs-LIBS) to measure the concentrations of chromium (Cr), lead (Pb), and copper (Cu) in flowing aqueous solutions. The fs pulsed laser excites the water, generating plasma in a dynamic setting that prevents liquid splashing-a notable advantage over static methods. The flowing water column maintains a stable liquid level, circumventing the laser focus irregularities due to liquid-level fluctuations. Calibration curves, based on a linear function, reveal limits of detection (LODs) as low as 0.0179 µg/mL for Cr, 0.1301 µg/mL for Pb, and 0.0120 µg/mL for Cu. The reliability of the experiment is confirmed by R2 values exceeding 0.99. These findings offer valuable insights for the analysis of trace heavy metals in flowing aqueous solutions using fs-LIBS, demonstrating the technique's potential for environmental monitoring.

EphA2-specific microvesicles derived from tumor cells facilitate the targeted delivery of chemotherapeutic drugs for osteosarcoma therapy.

Despite advances in surgery and chemotherapy, the survival of patients with osteosarcoma (OS) has not been fundamentally improved over the last two decades. Microvesicles (MVs) have a high cargo-loading capacity and are emerging as a promising drug delivery nanoplatform. The aim of this study was to develop MVs as specifically designed vehicles to enable OS-specific targeting and efficient treatment of OS. Herein, we designed and constructed a nanoplatform (YSA-SPION-MV/MTX) consisting of methotrexate (MTX)-loaded MVs coated with surface-carboxyl Fe3O4 superparamagnetic nanoparticles (SPIONs) conjugated with ephrin alpha 2 (EphA2)-targeted peptides (YSAYPDSVPMMS, YSA). YSA-SPION-MV/MTX showed an effective targeting effect on OS cells, which was depended on the binding of the YSA peptide to EphA2. In the orthotopic OS mouse model, YSA-SPION-MV/MTX effectively delivered drugs to tumor sites with specific targeting, resulting in superior anti-tumor activity compared to MTX or MV/MTX. And YSA-SPION-MV/MTX also reduced the side effects of high-dose MTX. Taken together, this strategy opens up a new avenue for OS therapy. And we expect this MV-based therapy to serve as a promising platform for the next generation of precision cancer nanomedicines.

Effects of Au6 and Au20 Adsorption Sites of Cyromazine-Au Complexes by Raman Spectroscopy and Density Functional Theory.

Cyromazine, when used as an insect growth regulator and low-toxicity insecticide, may degrade into melamine and pose a potential threat to the environment and soil health, which has thus attracted extensive research on eliminating such a harmful effect. In this paper, density functional theory (DFT)/LC-BLYP/6-311G(d,p) is used to optimize the geometric structure and analyze the vibration of cyromazine. The DFT/LC-BLYP/def2-SVP is used for the cyromazine-Au complex optimization and vibration analysis. The molecular electrostatic potential (MEP), frontier molecular orbitals (FMOs), vibration frequency, electrophilicity-based charge transfer (ECT) descriptor, binding energy (BE), polarizability, normal Raman spectroscopy (NRS), and surface-enhanced Raman spectroscopy (SERS) of cyromazine adsorbing on Au6 and Au20 are calculated. The study of the chemical enhancement mechanism of SERS of cyromazine at different adsorption sites of Au6 or Au20 confirms the existence of a charge transfer between cyclopromazine and Au6 and Au20, which can adsorb and form stable cyromazine-Au complexes. The results show that N2, H13, and N4 are the adsorption sites of Au6 and Au20. The Raman spectra of the cyromazine-Au complex can be selectively enhanced with a factor up to 9.07. Compared with those of cyromazine-Au6, the Raman spectra of cyromazine-Au20 are enhanced more significantly.

Injectable photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered exosomes for osteoarthritis therapy.

Osteoarthritis (OA) is a common degenerative joint disease urgently needing effective treatments. Bone marrow mesenchymal stromal cell-derived exosomes (Exo) are considered good drug carriers whereas they have limitations such as fast clearance and low retention. This study aimed to overcome the limitations of Exo in drug delivery using multiple strategies. Novel photocrosslinking spherical gelatin methacryloyl hydrogel (GelMA)-encapsulated cartilage affinity WYRGRL (W) peptide-modified engineered Exo were developed for OA treatment and the performance of the engineered Exo (W-Exo@GelMA) loaded with a small inhibitor LRRK2-IN-1 (W-Exo-L@GelMA) was investigated in vitro and in vivo. The W-Exo-L@GelMA showed an effective targeting effect on chondrocytes and a pronounced action on suppressing catabolism and promoting anabolism in vitro. Moreover, W-Exo-L@GelMA remarkably inhibited OA-related inflammation and immune gene expression, rescuing the IL-1ß-induced transcriptomic responses. With enhanced retention in the joint, W-Exo-L@GelMA demonstrated superior anti-OA activity and cartilage repair ability in the OA murine model. The therapeutic effect was validated in the cultured human OA cartilage. In conclusion, photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered Exo exhibit notable potential in OA therapy. Engineering Exo by a series of strategies enhanced the targeting ability and retention and cartilage-targeting and Exo-mediated drug delivery may offer a novel strategy for OA treatment.Clinical trial registration: Not applciable.

Exploring the Femtosecond Filamentation Threshold in Liquid Media Using a Mach-Zehnder Interferometer.

We experimentally studied the supercontinuum induced by femtosecond filamentation in different liquid media. Using a Mach-Zehnder interferometer, we determined the relative filamentation thresholds (Pth) of these media. Research has shown that the value of the filamentation threshold is greater than that of Pcr (critical power for self-focusing), which can mainly be attributed to the strong dispersion effect. Changing the focal length of the focusing lens affects filamentation dynamics, thereby affecting the measured results regarding the filamentation threshold. With shorter focal lengths, the linear focusing (i.e., geometrical focusing) regime dominates, and the measured values of Pth for different liquid media are almost the same; as the focal length becomes larger, self-focusing starts to play a role, making the values of Pth for different media different from each other. This study presents an efficient method for investigating the femtosecond filamentation phenomenon in liquid media, helpful to provide further insights into the physical mechanism of supercontinuum generation via femtosecond filamentation in liquid media.

Inhibition of GAB2 expression has a protective effect on osteoarthritis:An in vitro and in vivo study.

Osteoarthritis is a chronic age-related degenerative disease associated with varying degrees of pain and joint mobility disorders. Grb2-associated-Binding protein-2 (GAB2) is an intermediate molecule that plays a role downstream in a variety of signaling pathways, such as inflammatory signaling pathways. The role of GAB2 in the pathogenesis of OA has not been fully studied. In this study, we found that GAB2 expression was elevated in chondrocytes after constructing in vivo and in vitro models of OA. Inhibition of GAB2 by siRNA decreased the expression of MMP3, MMP13, iNOS, COX2, p62, and increased the expression of COL2, SOX9, ATG7, Beclin-1 and LC3II/LC3I. Furthermore, inhibition of GAB2 expression inhibited interleukin-1ß (IL-1ß) -induced mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling. In vivo studies, we found that reduced GAB2 expression effectively delayed cartilage destruction in a mouse model of OA induced by destabilisation of the medial meniscus (DMM). In conclusion, our study demonstrates that GAB2 is a potential therapeutic target for OA.

Propagation distance-resolved characteristics of copper plasma emission induced by axicon-focused femtosecond laser filamentation in air.

It is well known that Bessel beams have non-diffractive characteristics, which can be generated by Gaussian beams focused by an ideal axicon. In general, the length of filament generated by Bessel beams is longer than that by Gaussian beams and the electron density in the filament generated by Bessel beams is more uniform. This paper experimentally studied the propagation distance-resolved characteristics of copper plasma emission induced by axicon-focused femtosecond laser filamentation in the air. The evolution of the spectral intensity, plasma temperature, and electron density with the filament propagation path was obtained. The experiment results showed that when the base angle of the axicon was 5.0°, the spectral intensity along with the filament propagation path was more stable than that the base angle of the axicon was 0.5°. The changes in the plasma temperature and electron density along the filament propagation path were consistent with the change in the spectral intensity. This work provides a demonstration for the applications of filament-induced breakdown spectroscopy (FIBS), such as long-distance detection.

Improvement of LIBS signal stability for NaCl solution using femtosecond laser-induced water film.

This paper studies the analysis of Na element concentration in NaCl aqueous solution using laser-induced breakdown spectroscopy (LIBS). The NaCl solution is transformed to a thin water film. The water film can provide a stable liquid surface, and overcome the disadvantage that laser focusing position cannot be fixed due to liquid level fluctuation (when nanosecond laser is used as the excitation light source, there is serious liquid splash phenomenon, which affects the signal stability). And, femtosecond pulse laser is used to excite the water film to produce the plasma, avoiding liquid splashing. The measured emission lines are Na (I) at 589.0 nm and 589.6 nm. The calibration curves of sodium are plotted by measuring different concentrations of NaCl solution. The linear correlation coefficients of Na (I) lines at 589.0 nm and 589.6 nm are 0.9928 and 0.9914, respectively. In addition, the relative standard deviation is also calculated; its range is from 1.5% to 4.5%. The results indicate that the combination of femtosecond laser and water film can significantly improve the signal stability for liquid analysis in LIBS.

Ultrafast dynamics on fluorescence quenching of rhodamine 6G by graphene oxide.

Fluorescence quenching of rhodamine 6G by graphene oxide (GO) was investigated using steady-state fluorescence spectroscopy and ultrafast time-resolved absorption spectroscopy. The steady-state fluorescence spectra showed that rhodamine 6G fluorescence was effectively quenched by titrating the GO to the rhodamine 6G solutions. For lower GO concentrations, transient dynamic curves followed two-exponential decay parameters. For higher GO concentrations, the dynamic curves could not be fitted well, and three-exponential decay parameters were appropriate. The results indicated that there was a new transition process (electron transfer) in the exited rhodamine 6G and GO solution.

Spectral resolved study of filamentation effect on the nonlinear absorption in carbon disulfide.

A Z-scan system using spectrometers as detectors is established to investigate nonlinear absorption and white light continuum separately, in which absorption coefficient that is coincident with previous work was obtained. After Z-scan experiments, spot photographs were captured to further study the spatial properties of filaments in CS2, and we obtained similar space between dual filaments with previous work. Using the experimental setup, we find that plasma generation is the main effect impacting the nonlinear absorption and refraction process, and this impact can be eliminated in the case of CS2. Therefore, effect of filamentation can be neglected for CS2. Though it is easy to generate filaments in CS2 at relatively low intensity, fitting the Z-scan curve with three-photon model at 800 nm for CS2 is reasonable. In addition, the thickness of sample can affect extracted absorption coefficient of CS2 by affecting the length of filamentation.

Downregulated microRNA-340-5p promotes proliferation and inhibits apoptosis of chondrocytes in osteoarthritis mice through inhibiting the extracellular signal-regulated kinase signaling pathway by negatively targeting the FMOD gene.

PURPOSE: Osteoarthritis (OA) is a degenerative joint disease that leads to the destruction of joint function. The aim of this study is to investigate the effects of microRNA-340-5p (miR-340-5p) and its target gene, FMOD, on the proliferation and apoptosis of chondrocytes in mice with OA through the extracellular signal-regulated kinase (ERK) signaling pathway. MATERIALS: Twenty healthy C57BL/6J mice aged 15 months with a weight of 50 ± 2 g were selected. Ten mice were treated using a unilateral knee anterior cruciate ligament transection as well as a medial meniscectomy to establish the OA model. Besides, another 10 mice were used as the control group. METHODS: A reverse transcription quantitative polymerase chain reaction and Western blot analysis methods were used to examine the expressions of related genes in cells of each group. A 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide assay and flow cytometry were also conducted to evaluate the cell function after transfection had been completed. RESULTS: The expressions of fibromodulin (FMOD), type II collagen (Col II), B-cell lymphoma-2 (Bcl-2), sex-determining region of Y chromosome (SRY)-related high-mobility group-box gene 9 (Sox9), and proliferating cell nuclear antigen (PCNA) were decreased, whereas the expressions of miR-340-5p, runt-related transcription factor-2 (Runx2), Bcl-2-associated X protein (Bax), and ERK1/2 were elevated in the OA mice. Downregulation of miR-340-5p and upregulation of FMOD decreased the expressions of Runx2, Bax, and ERK1/2, and cell apoptosis of chondrocytes, and increased the expressions of FMOD, Col II, Bcl-2, Sox9, and PCNA, and cell proliferation. CONCLUSION: This study suggests that downregulation of miR-340-5p plays a role in promoting cell proliferation and suppressing cell apoptosis of chondrocytes in OA mice through inhibition of the ERK signaling pathway via the FMOD gene.

(2R,3R)Dihydromyricetin inhibits osteoclastogenesis and bone loss through scavenging LPS-induced oxidative stress and NF-κB and MAPKs pathways activating.

Osteolysis is a serious complication of several chronic inflammatory diseases and is closely associated with a local chronic inflammatory reaction with a variety of causes. However, similarities exist in the mechanisms of their pathological processes. Inflammatory factors and oxidative stress-induced nuclear factor κB (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways play a center role in bone erosion. Dihydromyricetin (DMY) is a natural compound with anti-inflammatory and antioxidative effect, which are commonly used in chronic pharyngitis and alcohol use disorders. In the current study, we identified that DMY attenuated lipopolysaccharide (LPS)-induced oxidative stress through inhibiting the production of reactive oxygen species (ROS) and nitric oxide (NO), downregulated COX-2 and iNOS, and promoted the activity of the antioxidative system by activating superoxide dismutase (SOD) and Nrf2/HO-1 pathway. To further investigate the underlying mechanism, we found that DMY inhibits osteoclast (OC) differentiation and bone resorption activity through blocking the RANKL-induced activation of the NF-κB and MAPKs signaling pathways and then downregulated c-Fos and NFATc1, which is essential for OC differentiation. Furthermore, DMY inhibited LPS-induced osteolysis in vivo. Collectively, these results indicate that DMY might be a promising prophylactic antiosteoclastic/resorptive agent in preventing or treating bone lysis diseases.

Association between polymorphisms in vitamin D receptor gene and adolescent idiopathic scoliosis: a meta-analysis.

PURPOSE: This meta-analysis was performed to clarify whether the two single nucleotide polymorphisms (ApaI and BsmI) in vitamin D receptor (VDR) gene conferred susceptibility to adolescent idiopathic scoliosis (AIS). METHODS: A comprehensive literature search in five online databases (PubMed, EMBASE, ISI Web of Science, CNKI, and Wanfang) was performed to identify studies that analyzed the association between VDR gene polymorphisms and risk of AIS. Observational studies met the predetermined inclusion criteria were selected for meta-analysis. The most appropriate genetic model was identified using a genetic model-free approach. Meta-analysis was performed using RevMan 5.3 software. RESULTS: Five eligible studies were included in this meta-analysis, which involved a total of 717 cases and 554 controls. A statistically significant association was observed between BsmI polymorphism and AIS (OR 1.90, 95% CI 1.32, 2.62). In subgroup analysis by ethnicity, the association between BsmI polymorphism and AIS was significant in Asians (OR 2.06, 95% CI 1.56, 2.73) but not in Caucasians (OR 0.70, 95% CI 0.23, 2.19). However, the ApaI polymorphism was not associated with AIS. Moreover, no evidence of association between BMD and the two VDR gene polymorphisms was detected. CONCLUSIONS: Meta-analysis of existing data suggested that BsmI was associated with increased risk of AIS in Asian populations. Nevertheless, further studies with rigorous design and more ethnic groups are encouraged to validate our findings. These slides can be retrieved under Electronic Supplementary Material.

Combined anterior-posterior approach with enlarged sciatic foramen to remove sciatic notch dumbbell-shaped tumors.

BACKGROUND AND OBJECTIVES: To explore a new method for resecting huge sciatic notch dumbbell-shaped tumors. METHODS: Preoperative thin-slide scanning magnetic resonance images (MRI) and computerized tomography angiography (CTA) scans were conducted. The images were processed to reconstruct a 3-dimensional (3D) model. The relationship between the tumor and surrounding anatomical structures was accurately identified. By combining an anterior-posterior approach, about 1.0 × 5.0 cm2 c-shaped bone around the greater sciatic foramen was removed using piezosurgery osteotomy to enlarge the sciatic notch, after which retroperitoneal dumbbell-shaped tumors in the four patients were excised. RESULTS: Tumors in four patients were completely removed. Two patients obtain a total en bloc tumor resection; one patient was clinically determined to be a benign nerve-sheath tumor which was removed within the sciatic nerve sheath, and one patient had an extremely asymmetric tumor shape. The tumor unexpectedly split at the dumbbell isthmus across the greater sciatic foramen during blunt dissection, while both sections were completely removed. CONCLUSIONS: The combined anterior-posterior approach with an enlarged sciatic notch is an effective method to remove sciatic notch dumbbell-shaped tumors. Compared to the reported study, it is a new method probably helpful for selected patients.

miR-139 is up-regulated in osteoarthritis and inhibits chondrocyte proliferation and migration possibly via suppressing EIF4G2 and IGF1R.

Osteoarthritis (OA) is one of the most progressive articular cartilage erosions. microRNAs (miRNAs) play pivotal roles in OA modulation, but the role of miR-139 in OA remains elusive. This study aims to reveal the effects and possible mechanism of miR-139 in OA and chondrocytes. The levels of miR-139 and its possible targets eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) and insulin-like growth factor 1 receptor (IGF1R) were detected by qRT-PCR in the articular cartilages of 20 OA patients and 20 non-OA patients. Human chondrocyte CHON-001 cells were transfected with miR-139 mimic or inhibitor, as well as the siRNAs of EIF4G2 and IGF1R. Cell viability by MTT assay, proliferation by colony formation assay and migration by Transwell assay were performed. Results showed that miR-139 was up-regulated, while EIF4G2 and IGF1R mRNAs down-regulated in OA cartilages (P < 0.001), and negative correlations existed between the level of miR-139 and EIF4G2 or IGF1R. Overexpression of miR-139 in CHON-001 cells suppressed both mRNA and protein levels of EIF4G2 and IGF1R, and inhibited cell viability, colony formation number and cell migration, while miR-139 inhibitor induced the opposite effects. Knockdown of EIF4G2 or IGF1R in CHON-001 cells reversed the effects of miR-139 inhibitor on cell viability, colony formation and cell migration. These results indicate that miR-139 is capable of inhibiting chondrocyte proliferation and migration, thus being a possible therapeutic target for OA. The mechanism of miR-139 in chondrocytes may be related to its regulation on EIF4G2 and IGF1R.

Epoxyeicosanoids suppress osteoclastogenesis and prevent ovariectomy-induced bone loss.

Epoxyeicosatrienoic acids (EETs) are products of arachidonic acid metabolism catalyzed by cytochrome P450 epoxygenases. These small molecules are autocrine and paracrine lipid mediators with important roles in inflammation, cardiovascular function, and angiogenesis. Recent evidence has highlighted EETs as potent promoters of organ regeneration and malignant metastasis. We speculated that EETs might impact osteoclastogenesis and bone loss. Using both in vitro and in vivo studies, we observed that EETs significantly attenuated bone loss and inhibited osteoclast formation and activity, which were associated with a decreased receptor activator of NF-κB ligand (RANKL):osteoprotegerin ratio and serum levels of TNF-α and IL-1ß. At the molecular level, EETs abrogated RANKL-induced activation of NF-κB, activator protein-1 (AP-1), and MAPKs, including ERK and JNK, but not p38, during osteoclast formation. EETs also prevented the production of reactive oxygen species (ROS) following RANKL stimulation. As a result, EETs suppressed osteoclast-specific gene expression, including tartrate resistant acid phosphatase (TRAP), cathepsin K (CK), matrix metalloproteinase (MMP)-9, and receptor activator of NF-κB (RANK). In conclusion, our findings demonstrate that EETs inhibit osteoclastogenesis through modulation of multiple pathways both upstream and downstream of RANKL signaling. The administration or stabilized endogenous levels of EETs could represent a novel therapeutic strategy for osteoclast-related disorders, such as rheumatoid arthritis and postmenopausal osteoporosis.

Ultrafast carrier dynamics of carbon nanodots in different pH environments.

Ultrafast carrier relaxation dynamics in fluorescent carbon nanodots is investigated by femtosecond transient absorption spectra at different pH environments so as to understand the mechanism of fluorescence for the first time. Utilizing multi-wavelength global analysis to fit the measured signal via a sequential model, four different relaxation channels are found, which are attributed to electron-electron scattering and surface state trapping, optical phonon scattering, acoustic phonon scattering and electron-hole recombination respectively. The results reveal that the surface states are mainly composed of different oxygen-containing functional groups (epoxy, carbonyl and carboxyl) and carbon atoms on the edge of the carbon backbone and can effectively trap a large number of photo-excited electrons. The deprotonation of carboxyl groups at high pH will change the distribution of π electron cloud density between the carbon backbone and surface states and consequently, compared with the excited electrons in the acidic and neutral environments, those in the alkaline environment can be more easily trapped by the surface within 1 ps, thereby giving rise to stronger fluorescence emission.

CXCL12/CXCR4 Axis Regulates Aggrecanase Activation and Cartilage Degradation in a Post-Traumatic Osteoarthritis Rat Model.

We evaluated the role of the CXCL12/CXCR4 (C-X-C motif chemokine ligand 12/C-X-C chemokine receptor type 4) axis in aggrecanase-mediated cartilage degradation, and explored the underlying mechanism in a post-traumatic osteoarthritis rat model. Expression of CXCL12/CXCR4 and ADAMTS-5 was analyzed in the knees of osteoarthritic and non-arthritic rats using Western blot, ELISA, immunohistochemistry and immunofluorescence. Rodent studies were performed using Sprague-Dawley rats, with animals divided into three groups: Destabilization of the medial meniscus/AMD3100-treated (DMM/AMD3100-treated), DMM/PBS-treated, and sham controls. Rats were sacrificed after eight weeks, and samples were collected for histology and immunohistochemistry analyses. IL-1-pretreated primary chondrocytes were cultured with untreated control, CXCL12a, siNC + CXCL12a, or siRNA CXCR4 + CXCL12a, and analyzed for expression of relevant markers and cellular pathways. Higher levels of CXCL12 were detected in the knee fluid of osteoarthritic subjects, with strong staining for CXCR4 in chondrocytes and CXCL12 in synoviocytes together with enhanced expression of ADAMTS-5. DMM/AMD3100-treated rats showed a significantly reduced immunological response, with minimal evidence of pathology in both histological and immunohistochemical analyses. Treatment with CXCL12a increased the expression of ACAN, RUNX-2, and ADAMTS-4/5 in IL-1-pretreated primary chondrocytes, together with a decrease in the expression of SOX-9. Molecular analyses revealed strong induction of NF-κB activation, along with phosphorylation of MAPKs, and activation of canonical Wnt/ß-catenin signaling. In conclusion, inhibition of SDF-1α/CXCR4 signaling axis was able to inhibit aggrecanase expression and lessen cartilage degeneration in post-traumatic osteoarthritis rats.

The Fascinating Effects of Baicalein on Cancer: A Review.

Cancer is one of the leading causes of death worldwide and a major global health problem. In recent decades, the rates of both mortality and morbidity of cancer have rapidly increased for a variety of reasons. Despite treatment options, there are serious side effects associated with chemotherapy drugs and multiple forms of drug resistance that significantly reduce their effects. There is an accumulating amount of evidence on the pharmacological activities of baicalein (e.g., anti-inflammatory, antioxidant, antiviral, and antitumor effects). Furthermore, there has been great progress in elucidating the target mechanisms and signaling pathways of baicalein's anti-cancer potential. The anti-tumor functions of baicalein are mainly due to its capacities to inhibit complexes of cyclins to regulate the cell cycle, to scavenge oxidative radicals, to attenuate mitogen activated protein kinase (MAPK), protein kinase B (Akt) or mammalian target of rapamycin (mTOR) activities, to induce apoptosis by activating caspase-9/-3 and to inhibit tumorinvasion and metastasis by reducing the expression of matrix metalloproteinase-2/-9 (MMP-2/-9). In this review, we focused on the relevant biological mechanisms of baicalein involved in inhibiting various cancers, such as bladder cancer, breast cancer, and ovarian cancer. Moreover, we also summarized the specific mechanisms by which baicalein inhibited the growth of various tumors in vivo. Taken together, baicalein may be developed as a potential, novel anticancer drug to treat tumors.

Inhibition of SDF-1α/CXCR4 Signalling in Subchondral Bone Attenuates Post-Traumatic Osteoarthritis.

Previous studies showed that SDF-1α is a catabolic factor that can infiltrate cartilage, decrease proteoglycan content, and increase MMP-13 activity. Inhibiting the SDF-1α/CXCR4 signalling pathway can attenuate the pathogenesis of osteoarthritis (OA). Recent studies have also shown that SDF-1α enhances chondrocyte proliferation and maturation. These results appear to be contradictory. In the current study, we used a destabilisation OA animal model to investigate the effects of SDF-1α/CXCR4 signalling in the tibial subchondral bone and the OA pathological process. Post-traumatic osteoarthritis (PTOA) mice models were prepared by transecting the anterior cruciate ligament (ACLT), or a sham surgery was performed, in a total of 30 mice. Mice were treated with phosphate buffer saline (PBS) or AMD3100 (an inhibitor of CXCR4) and sacrificed at 30 days post ACLT or sham surgery. Tibial subchondral bone status was quantified by micro-computed tomography (µCT). Knee-joint histology was analysed to examine the articular cartilage and joint degeneration. The levels of SDF-1α and collagen type I c-telopeptidefragments (CTX-I) were quantified by ELISA. Bone marrow mononuclear cells (BMMCs) were used to clarify the effects of SDF-1α on osteoclast formation and activity in vivo. µCT analysis revealed significant loss of trabecular bone from tibial subchondral bone post-ACLT, which was effectively prevented by AMD3100. AMD3100 could partially prevent bone loss and articular cartilage degeneration. Serum biomarkers revealed an increase in SDF-1α and bone resorption, which were also reduced by AMD3100. SDF-1α can promote osteoclast formation and the expression oftartrate resistant acid phosphatase (TRAP), cathepsin K (CK), and matrix metalloproteinase (MMP)-9 in osteoclasts by activating the MAPK pathway, including ERK and p38, but not JNK. In conclusion, inhibition of SDF-1α/CXCR4signalling was able to prevent trabecular bone loss and attenuated cartilage degeneration in PTOA mice.