In vitro and in vivo studies on exogenous polyamines and α-difluoromethylornithine to enhance bone formation and suppress osteoclast differentiation.

Exogenous polyamines, including putrescine (PUT), spermidine (SPD), and spermine (SPM), and the irreversible inhibitor of the rate-limiting enzyme ornithine decarboxylase (ODC) of polyamine biosynthesis, α-difluoromethylornithine (DFMO), are implicated as stimulants for bone formation. We demonstrate in this study the osteogenic potential of exogenous polyamines and DFMO in human osteoblasts (hOBs), murine monocyte cell line RAW 264.7, and an ovariectomized rat model. The effect of polyamines and DFMO on hOBs and RAW 264.7 cells was studied by analyzing gene expression, alkaline phosphatase (ALP) activity, tartrate-resistant acid phosphatase (TRAP) activity, and matrix mineralization. Ovariectomized rats were treated with polyamines and DFMO and analyzed by micro computed tomography (micro CT). The mRNA level of the early onset genes of osteogenic differentiation, Runt-related transcription factor 2 (Runx2) and ALP, was significantly elevated in hOBs under osteogenic conditions, while both ALP activity and matrix mineralization were enhanced by exogenous polyamines and DFMO. Under osteoclastogenic conditions, the gene expression of both receptor activator of nuclear factor-κB (RANK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) was reduced, and TRAP activity was suppressed by exogenous polyamines and DFMO in RAW 264.7 cells. In an osteoporotic animal model of ovariectomized rats, SPM and DFMO were found to improve bone volume in rat femurs, while trabecular thickness was increased in all treatment groups. Results from this study provide in vitro and in vivo evidence indicating that polyamines and DFMO act as stimulants for bone formation, and their osteogenic effect may be associated with the suppression of osteoclastogenesis.

Targeted HAI-2 deletion causes excessive proteolysis with prolonged active prostasin and depletion of HAI-1 monomer in intestinal but not epidermal epithelial cells.

Mutations of SPINT2, the gene encoding the integral membrane, Kunitz-type serine inhibitor HAI-2, primarily affect the intestine, while sparing many other HAI-2-expressing tissues, causing sodium loss in patients with syndromic congenital sodium diarrhea. The membrane-bound serine protease prostasin was previously identified as a HAI-2 target protease in intestinal tissues but not in the skin. In both tissues, the highly related inhibitor HAI-1 is, however, the default inhibitor for prostasin and the type 2 transmembrane serine protease matriptase. This cell-type selective functional linkage may contribute to the organ-selective damage associated with SPINT 2 mutations. To this end, the impact of HAI-2 deletion on matriptase and prostasin proteolysis was, here, compared using Caco-2 human colorectal adenocarcinoma cells and HaCaT human keratinocytes. Greatly enhanced prostasin proteolytic activity with a prolonged half-life and significant depletion of HAI-1 monomer were observed with HAI-2 loss in Caco-2 cells but not HaCaT cells. The constitutive, high level prostasin zymogen activation observed in Caco-2 cells, but not in HaCaT cells, also contributes to the excessive prostasin proteolytic activity caused by HAI-2 loss. HAI-2 deletion also caused increased matriptase zymogen activation, likely as an indirect result of increased prostasin proteolysis. This increase in activated matriptase, however, only had a negligible role in depletion of HAI-1 monomer. Our study suggests that the constitutive, high level of prostasin zymogen activation and the cell-type selective functional relationship between HAI-2 and prostasin renders Caco-2 cells more susceptible than HaCaT cells to the loss of HAI-2, causing a severe imbalance favoring prostasin proteolysis.

Novel Aptamer-Based Small-Molecule Drug Screening Assay to Identify Potential Sclerostin Inhibitors against Osteoporosis.

A novel aptamer-based competitive drug screening platform for osteoporosis was devised in which fluorescence-labeled, sclerostin-specific aptamers compete with compounds from selected chemical libraries for the binding of immobilized recombinant human sclerostin to achieve high-throughput screening for potential small-molecule sclerostin inhibitors and to facilitate drug repurposing and drug discovery. Of the 96 selected inhibitors and FDA-approved drugs, six were shown to result in a significant decrease in the fluorescence intensity of the aptamer, suggesting a higher affinity toward sclerostin compared with that of the aptamer. The targets of these potential sclerostin inhibitors were correlated to lipid or bone metabolism, and several of the compounds have already been shown to be potential osteogenic activators, indicating that the aptamer-based competitive drug screening assay offered a potentially reliable strategy for the discovery of target-specific new drugs. The six potential sclerostin inhibitors suppressed the level of both intracellular and/or extracellular sclerostin in mouse osteocyte IDG-SW3 and increased alkaline phosphatase activity in IDG-SW3 cells, human bone marrow-derived mesenchymal stem cells and human fetal osteoblasts hFOB1.19. Potential small-molecule drug candidates obtained in this study are expected to provide new therapeutics for osteoporosis as well as insights into the structure-activity relationship of sclerostin inhibitors for rational drug design.

An Intermediate Concentration of Calcium with Antioxidant Supplement in Culture Medium Enhances Proliferation and Decreases the Aging of Bone Marrow Mesenchymal Stem Cells.

Human bone marrow stem cells (HBMSCs) are isolated from the bone marrow. Stem cells can self-renew and differentiate into various types of cells. They are able to regenerate kinds of tissue that are potentially used for tissue engineering. To maintain and expand these cells under culture conditions is difficult-they are easily triggered for differentiation or death. In this study, we describe a new culture formula to culture isolated HBMSCs. This new formula was modified from NCDB 153, a medium with low calcium, supplied with 5% FBS, extra growth factor added to it, and supplemented with N-acetyl-L-cysteine and L-ascorbic acid-2-phosphate to maintain the cells in a steady stage. The cells retain these characteristics as primarily isolated HBMSCs. Moreover, our new formula keeps HBMSCs with high proliferation rate and multiple linage differentiation ability, such as osteoblastogenesis, chondrogenesis, and adipogenesis. It also retains HBMSCs with stable chromosome, DNA, telomere length, and telomerase activity, even after long-term culture. Senescence can be minimized under this new formulation and carcinogenesis of stem cells can also be prevented. These modifications greatly enhance the survival rate, growth rate, and basal characteristics of isolated HBMSCs, which will be very helpful in stem cell research.

(-)-Epigallocatechin-3-Gallate (EGCG) Enhances Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells.

Osteoporosis is the second most-prevalent epidemiologic disease in the aging population worldwide. Cross-sectional and retrospective evidence indicates that tea consumption can mitigate bone loss and reduce risk of osteoporotic fractures. Tea polyphenols enhance osteoblastogenesis and suppress osteoclastogenesis in vitro. Previously, we showed that (-)-epigallocatechin-3-gallate (EGCG), one of the green tea polyphenols, increased osteogenic differentiation of murine bone marrow mesenchymal stem cells (BMSCs) by increasing the mRNA expression of osteogenesis-related genes, alkaline phosphatase activity and, eventually, mineralization. We also found that EGCG could mitigate bone loss and improve bone microarchitecture in ovariectomy-induced osteopenic rats, as well as enhancing bone defect healing partially via bone morphogenetic protein 2 (BMP2). The present study investigated the effects of EGCG in human BMSCs. We found that EGCG, at concentrations of both 1 and 10 µmol/L, can increase mRNA expression of BMP2, Runx2, alkaline phosphatase (ALP), osteonectin and osteocalcin 48 h after treatment. EGCG increased ALP activity both 7 and 14 days after treatment. Furthermore, EGCG can also enhance mineralization two weeks after treatment. EGCG without antioxidants also can enhance mineralization. In conclusion, EGCG can increase mRNA expression of BMP2 and subsequent osteogenic-related genes including Runx2, ALP, osteonectin and osteocalcin. EGCG further increased ALP activity and mineralization. Loss of antioxidant activity can still enhance mineralization of human BMSCs (hBMSCs).

Cyclophosphamide promotes breast cancer cell migration through CXCR4 and matrix metalloproteinases.

Cyclophosphamide is indicated for the treatment of cancerous diseases such as breast cancer and cervical cancer. Recent studies have shown that cyclophosphamide may induce cancer metastasis, but the cause of this unexpected adverse effect is not fully understood. In this study, we investigate the effect of cyclophosphamide on cancer cell migration and its correlation to chemokine (C-X-C motif) receptor 4 (CXCR4), a biomarker for cancer metastasis. Two human cancer cell lines with significant difference in endogenous CXCR4 expression, the breast cancer cell line, MDA-MB-231, and the melanoma cell line, MDA-MB-435S, were treated with various concentrations of cyclophosphamide, followed by the assessment of CXCR4 expression and cell migration. We found that the migration ability of MDA-MB-231 cells was enhanced with increasing concentrations of cyclophosphamide, which induced the cell-surface expression of CXCR4, but had no effect on the overall amount of CXCR4. In MDA-MB-435S cells, in which CXCR4 was barely detectable, cyclophosphamide was unable to activate cell-surface CXCR4, and did not promote cell migration. Studies on the mRNA expression profile of matrix metalloproteinases (MMPs) in MDA-MB-231 cells further indicate that MMP9 and MMP13 may be involved in the action of cyclophosphamide. The protein expression of both MMP9 and MMP13 was increased in the presence of cyclophosphamide. Results from this study provide the molecular basis for the possible pathway of cyclophosphamide to induce cancer metastasis.

The effect of catalase on migration and invasion of lung cancer cells by regulating the activities of cathepsin S, L, and K.

Abundant clinical evidences indicate that up-regulation of several cathepsins in many human cancers is correlated with malignant progression and poor patient prognosis. In addition, a decrease in catalase activity or accumulation of hydrogen peroxide correlates with cancer metastasis. Recent studies indicate that cathepsin activation and expression can be modulated via H2O2 treatment. However, the actual relationship between catalase and cathepsins is not yet fully understood. In the present study, we found that catalase expression (or activity) was higher, while intracellular and extracellular Cat S, Cat L, and Cat K activities were lower in the non-invasive CL1-0 cells compared to the highly invasive CL1-5 cells. After CL1-0 cells were transfected with catalase-shRNA, the corresponding ROS (H2O2) level and Cat S, Cat L, or Cat K expression (or activity) was up-regulated, accompanied by an increase in cell migration and invasion. On the other hand, ROS (H2O2) level, cathepsin S, L, and K activities, cell migration and invasion were decreased in catalase-overexpressed CL1-5 cells. It is suggested that catalase may regulate cathepsin activity by controlling the production of ROS (H2O2), leading to variation in migration and invasion ability of lung cancer cells.

Effects of novel human cathepsin S inhibitors on cell migration in human cancer cells.

Elevated cathepsin S (Cat S) level is correlated with higher migration ability in tumor cells. This study investigates the inhibitory effect of novel synthetic α-ketoamide compounds on cathepsin activity and cancer cell migration. The effect of several α-ketoamide compounds on the activity of recombinant cathepsins (Cat S, Cat L and Cat K) was examined. Two highly metastatic cancer cell lines were incubated with three Cat S-specific compounds (6n, 6 w and 6r) to analyze their effect on cellular Cat S activity and cell migration. At a 100 nM concentration, compounds 6n, 6r and 6 w effectively inhibited Cat S activity. Cat S activity and cell migration were significantly reduced in CL1-3 cells after treatment with either 6n or 6 w at 5 µM. Similar results were also obtained when A2058 cells were treated with 6n. These results highlight the therapeutic potential of α-ketoamide compounds, especially 6n and 6 w, to prevent or delay cancer metastasis.

PPARγ silencing enhances osteogenic differentiation of human adipose-derived mesenchymal stem cells.

Peroxisome proliferator-activated receptor gamma (PPARγ) is the master regulator of adipogenesis, and has been indicated as a potential therapeutic target to promote osteoblast differentiation. However, recent studies suggest that suppression of PPARγ inhibits adipogenesis, but does not promote osteogenic differentiation in human bone marrow-derived mesenchymal stem cells (hBMSCs). It was reasoned that the osteogenic effect of PPARγ suppression may be masked by the strong osteogenesis-inducing condition commonly used, resulting in a high degree of matrix mineralization in both control and experimental groups. This study investigates the role of PPARγ in the lineage commitment of human adipose-derived mesenchymal stem cells (hADSCs) by interfering with the function of PPARγ mRNA through small interfering RNAs (siRNAs) specific for PPARγ2. By applying an osteogenic induction condition less potent than that used conventionally, we found that PPARγ silencing led to retardation of adipogenesis and stimulated a higher level of matrix mineralization. The mRNA level of PPARγ decreased to 47% of control 2 days after treatment with 50 nmol/l PPARγ2 siRNA, while its protein expression was 60% of mock control. In the meantime, osteogenic marker genes, including bone morphogenic protein 2 (BMP2), runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin (OC), were up-regulated under PPARγ silencing. Our results suggest that transient suppression of PPARγ promotes the onset of osteogenesis, and may be considered a new strategy to stimulate bone formation in bone tissue engineering using hADSCs.

Exogenous polyamines promote osteogenic differentiation by reciprocally regulating osteogenic and adipogenic gene expression.

Polyamines are naturally occurring organic polycations that are ubiquitous in all organisms, and are essential for cell proliferation and differentiation. Although polyamines are involved in various cellular processes, their roles in stem cell differentiation are relatively unexplored. In this study, we found that exogenous polyamines, putrescine, spermidine, and spermine, promoted osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) without inducing cell death or apoptosis. Alkaline phosphatase (ALP) activity and the mRNA level of osteogenic genes, including Runx2, ALP, osteopontin, and osteocalcin, were up-regulated by exogenous polyamines. When hBMSCs were cultured at high cell density favoring adipocyte formation, exogenous polyamines resulted in down-regulation of adipogenic genes such as PPARγ, aP2, and adipsin. Extracellular matrix mineralization, a marker for osteoblast maturation, was enhanced in the presence of exogenous polyamines, while lipid accumulation, an indication of adipogenic differentiation, was attenuated. Exogenous polyamines increased the mRNA expression of polyamine-modulated factor 1 (PMF-1) and its downstream effector, spermidine/spermine N(1)-acetyltransferase (SSAT), while that of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, was suppressed. These results lead to possible connections between polyamine metabolism and osteogenic differentiation pathways. To summarize, this study provides evidence for the involvement of polyamines in osteogenic differentiation of hBMSCs, and is the first to demonstrate that osteogenic and adipogenic differentiation are reciprocally regulated by exogenous polyamines.

Label-free optical and electrical immunoassays based on lyotropic chromonic liquid crystals: Implications of real-time detection and kinetic analysis.

Conventional liquid crystal (LC)-based biosensors utilize predominantly thermotropic LCs as the signal-transducing media, which are less environmentally sustainable compared with lyotropic counterparts. In this study, the nematic phase of the anionic azo dye sunset yellow (SSY), a type of lyotropic chromonic liquid crystals (LCLCs), was employed in the optical and electrical biosensing of bovine serum albumin (BSA) and the cancer biomarker CA125. The optical response observed under a polarizing optical microscope was quantified by image analysis, taking advantage of the specific absorption of SSY. The electrical response derived from the dielectric spectra of SSY provided a new alternative for quantitative bioassay based on nematic LCLCs. The limit of detection (LOD) of the optical and electrical protein assay was ∼10-11- and ∼10-10-g/ml BSA, respectively, whereas that of the optical and electrical immunoassay was 5.97 × 10-11 and 6.02 × 10-12 g/ml for CA125, respectively. Moreover, real-time monitoring and kinetic analysis, which are hardly achievable for the hydrophobic thermotropic LCs, were demonstrated by dispersing CA125 in nematic SSY and subsequently recording the optical response over time during the specific binding between CA125 and the immobilized anti-CA125 antibody. Results from this study further the potential of nematic LCLCs in biosensing, especially in dielectric and real-time detection.

Optical and flexoelectric biosensing based on a hybrid-aligned liquid crystal of anomalously small bend elastic constant.

Liquid crystal (LC)-based biosensors rely on the response of the LC molecules to perturbation generated by analytes at the interface, leading to the susceptible change in molecular alignment or orientation. The sensitivity of these biosensors is primarily dependent on the LC's material properties and surface anchoring strength. By incorporation of an unconventional mesogenic compound (CB7CB) coupled with the hybrid-alignment cell configuration, this work presents a binary nematic LC for label-free biosensing, manifesting a novel sensing technology that takes advantage of CB7CB-induced flexoelectricity in the transducer. Herein, we prepared LC mixtures by blending a typical rod-like nematic LC (E7) with the bent-core mesogen CB7CB in various weight ratios and studied the effect of the CB7CB content on E7/CB7CB-based biosensing performance in vertically aligned and hybrid-aligned nematic (HAN) cells. Owing to the anomalously small bend elastic constant K33 in CB7CB, the mixture designated CB45 with the highest CB7CB weight percentage (45 wt% in this study) was best applicable to biosensing in HAN cells. When observed under a polarizing optical microscope, CB45 in the HAN geometry showed the capability of detection of as low as 10-10 g/mL for the protein standard bovine serum albumin (BSA). Moreover, the quantitation of the assay was fulfilled by both dielectric and light transmission measurements of the hybrid-aligned cholesteric CB45/R5011. The limit of detection of 7 × 10-10 g/mL was achieved by spectrometric analysis. To the best of our knowledge, this work is the first to demonstrate flexoelectric biosensing on the basis of flexoelectric polarization associated with giant flexoelectricity in CB7CB partially constituting the LC transducer.

Antioxidant, Anti-Inflammatory and Antiproliferative Effects of Osmanthus fragrans (Thunb.) Lour. Flower Extracts.

Osmanthus fragrans (Thunb.) Lour. flowers (OF-F) have been traditionally consumed as a functional food and utilized as folk medicine. This study evaluated the antioxidant, anti-inflammatory and cytotoxic effects of OF-F extracts on prostate cancer cells (DU-145) and determined possible protein-ligand interactions of its compounds in silico. The crude OF-F extracts-water (W) and ethanol (E) were tested for phytochemical screening, antioxidant, anti-inflammatory, and anti-cancer. Network and molecular docking analyses of chemical markers were executed to establish their application for anticancer drug development. OF-F-E possessed higher total polyphenols (233.360 ± 3.613 g/kg) and tannin (93.350 ± 1.003 g/kg) contents than OF-F-W. In addition, OF-F-E extract demonstrated effective DPPH scavenging activity (IC50 = 0.173 ± 0.004 kg/L) and contained a high FRAP value (830.620 ± 6.843 g Trolox/kg). In cell culture experiments, OF-F-E significantly reduced NO levels and inhibited cell proliferation of RAW-264.7 and DU-145 cell lines, respectively. Network analysis revealed O. fragrans (Thunb.) Lour. metabolites could affect thirteen molecular functions and thirteen biological processes in four cellular components. These metabolites inhibited key proteins of DU-145 prostate cancer using molecular docking with rutin owning the highest binding affinity with PIKR31 and AR. Hence, this study offered a new rationale for O. fragrans (Thunb.) Lour. metabolites as a medicinal herb for anticancer drug development.

Proliferation and differentiation potential of human adipose-derived mesenchymal stem cells isolated from elderly patients with osteoporotic fractures.

Aging has less effect on adipose-derived mesenchymal stem cells (ADSCs) than on bone marrow-derived mesenchymal stem cells (BMSCs), but whether the fact holds true in stem cells from elderly patients with osteoporotic fractures is unknown. In this study, ADSCs and BMSCs of the same donor were harvested and divided into two age groups. Group A consisted of 14 young patients (36.4 ± 11.8 years old), and group B consisted of eight elderly patients (71.4 ± 3.6 years old) with osteoporotic fractures. We found that the doubling time of ADSCs from both age groups was maintained below 70 hrs, while that of BMSCs increased significantly with the number of passage. When ADSCs and BMSCs from the same patient were compared, there was a significant increase in the doubling time of BMSCs in each individual from passages 3 to 6. On osteogenic induction, the level of matrix mineralization of ADSCs from group B was comparable to that of ADSCs from group A, whereas BMSCs from group B produced least amount of mineral deposits and had a lower expression level of osteogenic genes. The p21 gene expression and senescence-associated ß-galactosidase activity were lower in ADSCs compared to BMSCs, which may be partly responsible for the greater proliferation and differentiation potential of ADSCs. It is concluded that the proliferation and osteogenic differentiation of ADSCs were less affected by age and multiple passage than BMSCs, suggesting that ADSCs may become a potentially effective therapeutic option for cell-based therapy, especially in elderly patients with osteoporosis.

A Label-Free and Affordable Solution to Point-of-Care Testing Devices.

Clinical diagnosis and disease monitoring often require the detection of small-molecule analytes and disease-related proteins in body fluids [...].

Quantitative Biosensing Based on a Liquid Crystal Marginally Aligned by the PVA/DMOAP Composite for Optical Signal Amplification.

The working principle for a liquid crystal (LC)-based biosensor relies on the disturbance in the orderly aligned LC molecules induced by analytes at the LC-aqueous or LC-solid interface to produce optical signals that can be typically observed under a polarizing optical microscope (POM). Our previous studies demonstrate that such optical response can be enhanced by imposing a weak electric field on LCs so that they are readily tilted from the homeotropic alignment in response to lower concentrations of analytes at the LC-glass interface. In this study, an alternative approach toward signal amplification is proposed by taking advantage of the marginally tilted alignment configuration without applying an electric field. The surface of glass substrates was modified with a binary aligning agent of poly(vinyl alcohol) (PVA) and dimethyloctadecyl[3-(trimethoxysilyl)propyl] ammonium chloride (DMOAP), in which the amount of PVA was fine-tuned so that the interfacing LC molecules were slightly tilted but remained virtually homeotropically aligned to yield no light leakage under the POM in the absence of an analyte. Two nematic LCs, E7 and 5CB, were each sandwiched between two parallel glass substrates coated with the PVA/DMOAP composite for the detection of bovine serum albumin (BSA), a model protein, and cortisol, a small-molecule steroid hormone. Through image analysis of the optical appearance of E7 observed under the POM, a limit of detection (LOD) of 2.5 × 10-8 µg/mL for BSA and that of 3 × 10-6 µg/mL for cortisol were deduced. Both values are significantly lower than that obtained with only DMOAP as the alignment layers, which correspond to signal amplification of more than six orders of magnitude. The new approach for signal amplification reported in this work enables analytes of a wide range of molecular weights to be detected with high sensitivity.

A liquid-crystal aptasensing platform for label-free detection of a single circulating tumor cell.

Circulating tumor cells (CTCs), which are shed from a primary site into the bloodstream and lead to distal metastases, are pivotal as a prognostic marker for evaluating the treatment response of cancer patients. One of the major challenges of detecting CTCs is their scarcity in blood. We report herein a label-free liquid crystal (LC) cytosensor by adopting an aptamer against epithelial cell adhesion molecule (EpCAM) to capture EpCAM-positive cancer cells. The optical and dielectric signals transduced from the interaction between LC and different numbers of captured breast cancer cells were investigated. A limit of detection (LOD) of 5 CTCs was resulted from the optical biosensing approach relying on texture observation and image analysis of the optical signal in polarizing micrographs. The LOD was further lowered to a single CTC in the dielectric approach by studying the real- and imaginary-part dielectric constants of LC at 1 kHz and 30 Hz as well as the relaxation frequency. The LC-based EpCAM-specific dielectric cytosensor was successfully applied to single-cell CTC detection in cancer cell-spiked human serum and whole blood. This platform demonstrates the potential of LC-based biosensing technologies in cellular-level detection and quantitation, which is crucial to the early diagnosis of cancer metastasis and progression.

The Role of Mitochondrial Metabolism, AMPK-SIRT Mediated Pathway, LncRNA and MicroRNA in Osteoarthritis.

Osteoarthritis (OA) is the most common joint disease characterized by degeneration of articular cartilage and causes severe joint pain, physical disability, and impaired quality of life. Recently, it was found that mitochondria not only act as a powerhouse of cells that provide energy for cellular metabolism, but are also involved in crucial pathways responsible for maintaining chondrocyte physiology. Therefore, a growing amount of evidence emphasizes that impairment of mitochondrial function is associated with OA pathogenesis; however, the exact mechanism is not well known. Moreover, the AMP-activated protein kinase (AMPK)-Sirtuin (SIRT) signaling pathway, long non-coding RNA (lncRNA), and microRNA (miRNA) are important for regulating the physiological and pathological processes of chondrocytes, indicating that these may be targets for OA treatment. In this review, we first focus on the importance of mitochondria metabolic dysregulation related to OA. Then, we show recent evidence on the AMPK-SIRT mediated pathway associated with OA pathogenesis and potential treatment options. Finally, we discuss current research into the effects of lncRNA and miRNA on OA progression or inhibition.

The Role of Autophagy in Osteoarthritic Cartilage.

Osteoarthritis (OA) is one of the most common diseases leading to physical disability, with age being the main risk factor, and degeneration of articular cartilage is the main focus for the pathogenesis of OA. Autophagy is a crucial intracellular homeostasis system recycling flawed macromolecules and cellular organelles to sustain the metabolism of cells. Growing evidences have revealed that autophagy is chondroprotective by regulating apoptosis and repairing the function of damaged chondrocytes. Then, OA is related to autophagy depending on different stages and models. In this review, we discuss the character of autophagy in OA and the process of the autophagy pathway, which can be modulated by some drugs, key molecules and non-coding RNAs (microRNAs, long non-coding RNAs and circular RNAs). More in-depth investigations of autophagy are needed to find therapeutic targets or diagnostic biomarkers through in vitro and in vivo situations, making autophagy a more effective way for OA treatment in the future. The aim of this review is to introduce the concept of autophagy and make readers realize its impact on OA. The database we searched in is PubMed and we used the keywords listed below to find appropriate article resources.

Label-Free Detection and Spectrometrically Quantitative Analysis of the Cancer Biomarker CA125 Based on Lyotropic Chromonic Liquid Crystal.

Compared with thermotropic liquid crystals (LCs), the biosensing potential of lyotropic chromonic liquid crystals (LCLCs), which are more biocompatible because of their hydrophilic nature, has scarcely been investigated. In this study, the nematic phase, a mesophase shared by both thermotropic LCs and LCLCs, of disodium cromoglycate (DSCG) was employed as the sensing mesogen in the LCLC-based biosensor. The biosensing platform was constructed so that the LCLC was homogeneously aligned by the planar anchoring strength of polyimide, but was disrupted in the presence of proteins such as bovine serum albumin (BSA) or the cancer biomarker CA125 captured by the anti-CA125 antibody, with the level of disturbance (and the optical signal thus produced) predominated by the amount of the analyte. The concentration- and wavelength-dependent optical response was analyzed by transmission spectrometry in the visible light spectrum with parallel or crossed polarizers. The concentration of CA125 can be quantified with spectrometrically derived parameters in a linear calibration curve. The limit of detection for both BSA and CA125 of the LCLC-based biosensor was superior or comparable to that of thermotropic LC-based biosensing techniques. Our results provide, to the best of our knowledge, the first evidence that LCLCs can be applied in spectrometrically quantitative biosensing.