[Effects of plumbagin on proliferation and apoptosis of human hepatocellular carcinoma cells based on CKB/p53 signaling pathway].

To investigate the effects of plumbagin on the proliferation and apoptosis of human hepatoma Huh-7 cells and its mechanism based on the creatine kinase B(CKB)/p53 signaling pathway. Huh-7 cells were treated with plumbagin from 1 to 12 µmol·L~(-1) for cell counting kit-8(CCK-8) assay, and 1, 3, and 6 µmol·L~(-1) were determined as low, medium, and high concentrations of plumbagin for subsequent experiments. CKB gene was knocked out in Huh-7 cells by clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated proteins(Cas)-9 gene editing technology. CKB overexpression lentivirus was transfected into Huh-7 cells to up-regulate the expression of CKB. Cell proliferation and apoptosis were detected by plate cloning assay and flow cytometry. The mRNA expression of CKB was detected by quantitative real-time PCR(qRT-PCR). CKB, p53, mouse double minute 2 homolog(MDM2), B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), and caspase-3 protein were detected by Western blot(WB). The results showed that plumbagin significantly inhibited the proliferation of Huh-7 cells and induced cell apoptosis. Compared with the control group, the apoptosis level was significantly increased in the plumbagin group, while the apoptosis level was significantly decreased in the plumbagin combined with the apoptosis inhibitor group. Plumbagin significantly down-regulated the protein expression levels of CKB, Bcl-2, and MDM2 and up-regulated the protein expression levels of p53, Bax, and caspase-3. Knockdown of the CKB gene decreased the proliferative ability of Huh-7 cells, increased the apoptotic rate, decreased the expression levels of Bcl-2 and MDM2 proteins, and increased the expression levels of p53, Bax, and caspase-3 proteins. After up-regulation of CKB expression, the proliferation ability of Huh-7 cells was enhanced, and the protein expression levels of Bcl-2 and MDM2 were elevated. The protein expression levels of p53, Bax, and caspase-3 were decreased. In addition, plumbagin reversed the effect of overexpression of CKB on the proliferation and apoptosis of Huh-7 cells. In conclusion, plumbagin significantly inhibited the proliferative ability of Huh-7 cells, and the mechanism may be related to the inhibition of CKB expression, activation of the p53 signaling pathway, and regulation of the expression of mitochondrial-associated apoptotic proteins, ultimately inducing cell apoptosis.

The impact of maternal smoking during pregnancy and the age of smoking initiation on incident dementia: A prospective cohort study.

INTRODUCTION: The impact of early-life tobacco exposure on dementia has remained unknown. METHODS: Using the UK Biobank, the associations of maternal smoking during pregnancy (MSDP) and age of smoking initiation (ASI) with the onset time of all-cause dementia were estimated with accelerated failure time models. The effects of MSDP and ASI on brain structure and their genetic correlation to Alzheimer's disease (AD) were analyzed. A Mendelian randomization (MR) analysis was conducted. RESULTS: The time ratios for smokers starting in childhood, adolescence, and adulthood (vs never smokers) were 0.87 (0.76 to 0.99), 0.92 (0.88 to 0.96), and 0.95 (0.89 to 1.01). MSDP and smoking in adolescence altered many brain regions, including the hippocampus. In genetic analysis, MSDP was genetically and causally linked to AD, and a younger ASI was genetically correlated to a higher AD risk. DISCUSSION: Early-life smoking accelerated dementia onset and was genetically correlated to AD. MSDP demonstrated genetic and causal linkage to AD risks. HIGHLIGHTS: Unlike the commonly used Cox proportional hazards model, this article uses a parametric survival analysis method - the accelerated failure model - to explore the relationship between exposure to onset time. It can be used as an alternative method when the proportional hazards assumption is not met. Genetic analyses including genetic correlation study and MR analysis and brain structure analyses were conducted to support our findings and explore the potential mechanisms. The study reveals the relationship between different smoking initiation periods and the onset time of dementia and shows that earlier smoking exposure has a more significant impact on dementia. It emphasizes the importance of preventing early smoking. In the future, more research focusing on the relationship between early exposure and dementia is called for to provide more detailed prevention measures for dementia that cover all age groups.

The characteristic and prognostic role of blood inflammatory markers in patients with Huntington's disease from China.

Objectives: This study aims to elucidate the role of peripheral inflammation in Huntington's disease (HD) by examining the correlation of peripheral inflammatory markers with clinical manifestations and disease prognosis. Methods: This investigation involved 92 HD patients and 92 matched healthy controls (HCs). We quantified various peripheral inflammatory markers and calculated their derived metrics including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). Clinical assessments spanning cognitive, motor, and disease severity were administered. Comparative analysis of inflammatory markers and clinical correlations between HD and controls was performed. Kaplan-Meier survival analysis and Cox regression model were used to assess the effect of inflammatory markers on survival. Results: The study revealed that HD patients had significantly reduced lymphocyte counts, and LMR. Conversely, NLR, PLR, and SII were elevated compared to HCs. Lymphocyte levels inversely correlated with the age of onset and monocyte levels inversely correlated with the UHDRS-total functional capacity (TFC) scores. After adjusting for age, sex, and CAG repeat length, lymphocyte count, NLR, PLR, and SII were significantly correlated with the progression rate of TFC scores. Elevated levels of white blood cells and monocytes were associated with an increased risk of disability and mortality in the HD cohort. Conclusion: Our findings indicate that HD patients display a distinct peripheral inflammatory profile with increased NLR, PLR, and SII levels compared to HCs. The peripheral inflammation appears to be linked with accelerated disease progression and decreased survival in HD.

DOVE: Doodled vessel enhancement for photoacoustic angiography super resolution.

Deep-learning-based super-resolution photoacoustic angiography (PAA) has emerged as a valuable tool for enhancing the resolution of blood vessel images and aiding in disease diagnosis. However, due to the scarcity of training samples, PAA super-resolution models do not generalize well, especially in the challenging in-vivo imaging of organs with deep tissue penetration. Furthermore, prolonged exposure to high laser intensity during the image acquisition process can lead to tissue damage and secondary infections. To address these challenges, we propose an approach doodled vessel enhancement (DOVE) that utilizes hand-drawn doodles to train a PAA super-resolution model. With a training dataset consisting of only 32 real PAA images, we construct a diffusion model that interprets hand-drawn doodles as low-resolution images. DOVE enables us to generate a large number of realistic PAA images, achieving a 49.375% fool rate, even among experts in photoacoustic imaging. Subsequently, we employ these generated images to train a self-similarity-based model for super-resolution. During cross-domain tests, our method, trained solely on generated images, achieves a structural similarity value of 0.8591, surpassing the scores of all other models trained with real high-resolution images. DOVE successfully overcomes the limitation of insufficient training samples and unlocks the clinic application potential of super-resolution-based biomedical imaging.

A Handheld Microwave Thermoacoustic Imaging System With an Impedance Matching Microwave-Sono Probe for Breast Tumor Screening.

Microwave-induced thermoacoustic imaging (MTAI) is a promising alternative for breast tumor detection due to its deep imaging depth, high resolution, and minimal biological hazards. However, due to the bulky size and complicated system configuration of conventional benchtop MTAI, it is limited to imaging various anatomical sites and its application in different clinical scenarios. In this study, a handheld MTAI system equipped with a compact impedance matching microwave-sono and an ergonomically designed probe was presented and evaluated. The probe integrates a flexible coaxial cable for microwave delivery, a miniaturized microwave antenna, a linear transducer array, and wedge-shaped polystyrene blocks for efficient acoustic coupling, achieving microwave illumination and ultrasonic detection coaxially, and enabling high signal-to-noise ratio (SNR). Phantom experiments demonstrated that the maximum imaging depth is 5 cm (SNR = 8 dB), and the lateral and axial resolutions are 1.5 mm and 0.9 mm, respectively. Finally, three healthy female volunteers of different ages were subjected to breast thermoacoustic tomography and ultrasound imaging. The results showed that the h-MTAI data are correlated with the data of ultrasound imaging, indicating the safety and effectiveness of the system. Thus, the proposed h-MTAI system might contribute to breast tumor screening.

Autophagy and Aging: Roles in Skeletal Muscle, Eye, Brain and Hepatic Tissue.

Autophagy is an evolutionary conserved degradative process contributing to cytoplasm quality control, metabolic recycling and cell defense. Aging is a universal phenomenon characterized by the progressive accumulation of impaired molecular and reduced turnover of cellular components. Recent evidence suggests a unique role for autophagy in aging and age-related disease. Indeed, autophagic activity declines with age and enhanced autophagy may prevent the progression of many age-related diseases and prolong life span. All tissues experience changes during aging, while the role of autophagy in different tissues varies. This review summarizes the links between autophagy and aging in the whole organism and discusses the physiological and pathological roles of autophagy in the aging process in tissues such as skeletal muscle, eye, brain, and liver.

M1 macrophage-derived exosomes aggravate bone loss in postmenopausal osteoporosis via a microRNA-98/DUSP1/JNK axis.

Macrophages (Mφs) are master regulators of the immune response and may serve as therapeutic targets in aging societies. This study aimed to determine the function of M1Mφ-exosomes (Exos) in the development of osteoporosis (OP) and the involvement of microRNA (miR)-98 and dual specificity phosphatase 1 (DUSP1). A murine model of OP was established using ovariectomies (OVX). Bone loss was observed in OVX-treated mice, as manifested by reduced bone mineral density and decreased number of bone trabecula. The bone loss was further aggravated by treatment with M1Mφ-Exos. Exos also suppressed osteogenic differentiation of MC3T3-E1 cells. miRNA microarray analysis revealed that the miR-98 level was notably upregulated in cells after Exo treatment, and DUSP1 was confirmed as a target of miR-98. Meanwhile, downregulation of miR-98 or upregulation of DUSP1 restored the osteogenic differentiation ability of MC3T3-E1 cells. In addition, upregulation of DUSP1 reduced bone loss in murine bone tissues and suppressed JNK phosphorylation. In summary, M1Mφ-derived exosomal miR-98 exacerbates bone loss and OP by downregulating DUSP1 and activating the JNK signaling pathway. miR-98 may therefore serve as a therapeutic target in OP management.

High-security photoacoustic identity recognition by capturing hierarchical vascular structure of finger.

Currently, most biometric methods mainly use single features, making them easily forged and cracked. In this study, a novel triple-layers biometric recognition method, based on photoacoustic microscopy, is proposed to improve the security of biometric identity recognition. Using the photoacoustic (PA) dermoscope, three-dimensional absorption-structure information of the fingers was obtained. Then, by combining U-Net, Gabor filtering, wavelet analysis and morphological transform, a lightweight algorithm called photoacoustic depth feature recognition algorithm (PADFR) was developed to automatically realize stratification (the fingerprint, blood vessel fingerprint and venous vascular), extracting feature points and identity recognition. The experimental results show that PADFR can automatically recognize the PA hierarchical features with an average accuracy equal to 92.99%. The proposed method is expected to be widely used in biometric identification system due to its high security.

Opportunistic Screening Using Low-Dose CT and the Prevalence of Osteoporosis in China: A Nationwide, Multicenter Study.

Opportunistic screening for osteoporosis can be performed using low-dose computed tomography (LDCT) imaging obtained for other clinical indications. In this study we explored the CT-derived bone mineral density (BMD) and prevalence of osteoporosis from thoracic LDCT in a large population cohort of Chinese men and women. A total of 69,095 adults (40,733 men and 28,362 women) received a thoracic LDCT scan for the purpose of lung cancer screening between 2018 and 2019, and data were obtained for analysis from the China Biobank Project, a prospective nationwide multicenter population study. Lumbar spine (L1 -L2 ) trabecular volumetric bone mineral density (vBMD) was derived from these scans using quantitative computed tomography (QCT) software and the American College of Radiology QCT diagnostic criteria for osteoporosis were applied. Geographic regional differences in the prevalence of osteoporosis were assessed and the age-standardized, population prevalence of osteoporosis in Chinese men and women was estimated from the 2010 China census. The prevalence of osteoporosis by QCT for the Chinese population aged >50 years was 29.0% for women and 13.5% for men, equating to 49.0 million and 22.8 million, respectively. In women, this rate is comparable to estimates from dual-energy X-ray absorptiometry (DXA), but in men, the prevalence is double. Prevalence varied geographically across China, with higher rates in the southwest and lower rates in the northeast. Trabecular vBMD decreased with age in both men and women. Women had higher peak trabecular vBMD (185.4 mg/cm3 ) than men (176.6 mg/cm3 ) at age 30 to 34 years, but older women had lower trabecular vBMD (62.4 mg/cm3 ) than men (92.1 mg/cm3 ) at age 80 years. We show that LDCT-based opportunistic screening could identify large numbers of patients with low lumbar vBMD, and that future cohort studies are now required to evaluate the clinical utility of such screening in terms of fracture prevention and supporting national health economic analyses. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..

Circular RNA 0086996 regulates growth and migration of osteosarcoma cells via miR-125b-5p.

Circular RNAs (CircRNAs) have been found to be critical in tumorigenesis; however, the role of CircRNAs in osteosarcoma is to be further studied. In this study, we preliminarily identified the up-expressed CircRNAs and its downstream microRNA in osteosarcoma and investigated its potential regulation mechanism. Hsa_circ_0086996 (Circ_0086996) was found to upregulated in tumor tissue compared to adjacent tissue. Circ_0086996 was significantly overexpressed in osteosarcoma tissue, as well as in osteosarcoma cell lines of SAOS2 and MG-63. Circ_0086996 knockdown significantly suppressed cell proliferation, migration, and invasion. Circ_0086996 knockdown also induced cell cycle arrest in G0/G1 phaseand promoted cell apoptosis in SAOS2 and MG-63 cells. Bioinformatics analysis revealed that miR-125b-5p might be of complementary binding region with Circ_0086996, which was confirmed by dual-luciferase reporter assay. Moreover, Circ_0086996 could reverse the effect of miR-125b-5p, as knockdown of Circ_0086996 or application of miR-125b-5p both can inhibit cell proliferation, migration, invasion and promote cell apoptosis and cell cycle arrest. Our study discovers that Circ_0086996 acts as miR-125b-5p sponge to mediate the tumorigenicity, which could act as a potential biomarker for the osteosarcoma and provides a novel insight for the mechanism in osteosarcoma.

Spatial weight matrix in dimensionality reduction reconstruction for micro-electromechanical system-based photoacoustic microscopy.

A micro-electromechanical system (MEMS) scanning mirror accelerates the raster scanning of optical-resolution photoacoustic microscopy (OR-PAM). However, the nonlinear tilt angular-voltage characteristic of a MEMS mirror introduces distortion into the maximum back-projection image. Moreover, the size of the airy disk, ultrasonic sensor properties, and thermal effects decrease the resolution. Thus, in this study, we proposed a spatial weight matrix (SWM) with a dimensionality reduction for image reconstruction. The three-layer SWM contains the invariable information of the system, which includes a spatial dependent distortion correction and 3D deconvolution. We employed an ordinal-valued Markov random field and the Harris Stephen algorithm, as well as a modified delay-and-sum method during a time reversal. The results from the experiments and a quantitative analysis demonstrate that images can be effectively reconstructed using an SWM; this is also true for severely distorted images. The index of the mutual information between the reference images and registered images was 70.33 times higher than the initial index, on average. Moreover, the peak signal-to-noise ratio was increased by 17.08% after 3D deconvolution. This accomplishment offers a practical approach to image reconstruction and a promising method to achieve a real-time distortion correction for MEMS-based OR-PAM.

Electrothermal-MEMS-induced nonlinear distortion correction in photoacoustic laparoscopy.

Micro-electro-mechanical systems (MEMS) scanner has significant advantages of miniature size, fast response and high stability, which is particularly applicable to photoacoustic laparoscopy (PAL). However, tilt angle-voltage curve of electrothermal MEMS shows a nonlinear character, which leads to inevitable nonlinear distortion in photoacoustic imaging. To overcome this problem, a nonlinear distortion correction was developed for the high-resolution forward-scanning electrothermal-MEMS-based PAL. The adaptive resampling method (ARM) was introduced to adaptively calibrate the projection of non-uniform scanning region to match the uniform scanning region. The correction performed low time complexity and high portability owing to the adaptive capacity of distortion decomposition in the reconstruction of physical models. Compared with the sample structure, phantom experiments demonstrated that the distortion was calibrated in all directions and the corrected image provided up to 96.82% high structural similarity in local subset. Furthermore, ARM was applied to imaging the abdominal cavity of rat and the vascular morphology was corrected in real-time display within a delay less than 2 seconds. All these results demonstrated that the nonlinear distortion correction possessed timely and effective correction in PAL, which suggested that it had the potential to employ to any other electrothermal-MEMS-based photoacoustic imaging systems for accurate and quantitative functional imaging.

Long-term delivery of alendronate through an injectable tetra-PEG hydrogel to promote osteoporosis therapy.

Pharmacotherapy for hypercalcemia, which is mainly caused by osteoporosis, is an effective method to regulate the in vivo calcium equilibrium. From this perspective, the development of a minimally invasive gelling system for the prolonged local delivery of bisphosphonates has practical significance in the clinical therapy of bone osteoporosis. Here, a biocompatible and injectable hydrogel based on a uniform tetra-PEG network carrying a PEG-modified alendronate (ALN) prodrug for the localized elution and long-term sustained release of anti-osteoporotic small molecule drugs is reported. The obtained ALN-based tetra-PEG hydrogels exhibit rapid gel formation and excellent injectability, thereby allowing for the easy injection and consequent adaptation of hydrogels into the bone defects with irregular shapes, which promotes the ALN-based tetra-PEG hydrogels with depot formulation capacity for governing the on-demand release of ALN drugs and local reinforcement of bone osteoporosis at the implantation sites of animals. The findings imply that these injectable hydrogels mediate the optimized release of therapeutic cargoes and effectively promote in situ bone regeneration via minimally invasive procedures, which is effective for clinical osteoporosis therapy.

Puerarin inhibits the osteoclastogenesis by inhibiting RANKL-dependent and -independent autophagic responses.

BACKGROUND: Puerarin exerts therapeutic effect on osteoporosis due to its inhibitory effect on the formation of osteoclasts. Puerarin is also widely established as an autophagy inhibitor. The study aimed to investigate the significance of autophagy in Puerarin-treated osteoclast formation. METHODS: Osteoclast precursors (OCPs) derived from bone marrow-derived macrophages (BMMs) were treated with Puerarin along with RANKL or without RANKL, and then the autophagic parameters of OCPs (including autophagic proteins, LC3 transformation, autophagosome or LC3-puncta) were observed through Western Blotting, Transmission Electron Microscopy and Immunofluorescence assays. Next, after using overexpression vectors of autophagic genes (Atg7, Atg5 and BECN1) to alter autophagy activity, OCP proliferation was measured by Ethynyl deoxyuridine (EdU) assays and Cell Counting Kit-8 (CCK-8) kit, and osteoclast differentiation was assessed by Tartrate-resistant acid phosphatase (TRAP) staining. RESULTS: The results showed that Puerarin could directly inhibit the autophagy and proliferation of OCPs. Importantly, overexpression of autophagic genes Atg5, Atg7 and BECN1 reversed Puerarin-inhibited OCP autophagy and proliferation. What's more, RANKL could promote the autography of OCPs, which was recovered by Puerarin treatment. Interestingly, different from single-Puerarin treatment, we found that in the presence of RANKL, only BECN1 overexpression significantly reversed Puerarin-inhibited osteoclast differentiation and OCP autophagy. CONCLUSION: In conclusion, Puerarin could inhibit the OCP autophagy in the presence or absence of RANKL, which blocked the OCP proliferation and osteoclast differentiation respectively. Moreover, BECN1 plays an essential role in Puerarin-inhibited osteoclastogenesis. Our study provides potential clue to further complete the intrinsic mechanism of Puerarin in treating osteoporosis.

The Prevalence of Osteoporosis in China, a Nationwide, Multicenter DXA Survey.

A number of studies investigated the distribution of BMD values and the prevalence of osteoporosis in China, but their findings varied. Until now, a BMD reference database based on uniform measurements in a large-scale Chinese population has been lacking. A total of 75,321 Chinese adults aged 20 years and older were recruited from seven centers between 2008 and 2018. BMD values at the lumbar spine (L1 -L4 ), femoral neck, and total femur were measured by GE Lunar dual-energy X-ray absorptiometry systems. BMD values measured in each center were cross-calibrated by regression equations that were generated by scanning the same European spine phantom 10 times at every center. Cubic and multivariate linear regression were performed to assess associations between BMD values and demographic variables. Sex-specific prevalence of osteoporosis was age-standardized based on the year 2010 national census data for the Chinese population. The sex-specific BMD values at each site were negatively associated with age, positively associated with body mass index levels, and lower in the participants from southwest China than in those from other geographic regions after multivariate adjustment. Furthermore, BMD values at the femoral neck and total femur decreased with the year of BMD measurement. The peak BMD values at the lumbar spine, femoral neck, and total femur were 1.088 g/cm2 , 0.966 g/cm2 , and 0.973 g/cm2 , respectively, for men, and 1.114 g/cm2 , 0.843 g/cm2 , and 0.884 g/cm2 , respectively, for women. The age-standardized prevalence of osteoporosis at the spine or hip was 6.46% and 29.13% for men and women aged 50 years and older, respectively. Currently a total of 10.9 million men and 49.3 million women in China are estimated to have osteoporosis. In our national examination of BMD, we found that BMD values differed by demographic characteristics. We estimated the age-standardize prevalence of osteoporosis in China to be 6.46% and 29.13% respectively, for men and women aged 50 years and older.

The protocol for the Prospective Urban Rural Epidemiology China Action on Spine and Hip status study.

The Prospective Urban Rural Epidemiology (PURE) China Action on Spine and Hip status (CASH) study focused on the prevalence of osteoporosis and spinal fracture in China. The aim of the PURE CASH study is to determine the prevalence of osteoporosis and spinal fracture, and explore the potential relationship between spinal fracture and bone mineral density (BMD). This study is a prospective large-scale population study with a community-based sampling and recruitment strategy. The aim is to determine the prevalence of osteoporosis and vertebral fracture in this population, to evaluate the association between vertebral fractures and BMD values, and to assess the prediction power of BMD for incident fractures. Participants in the PURE CASH study are all from the PURE study in China, recruited from 12 centers in 7 Chinese provinces. The inclusion criteria are that participants should be aged more than 40 years and able to give informed consent. Exclusion criteria are pregnant women, individuals with metal implants in the lumbar spine, use of medications or the existence of any disease or condition known to have a major influence on BMD, and inability to give informed consent. A total of 3,457 participants undergo a quantitative computed tomography (QCT) scan of the upper abdomen. The scanning parameters are as follows: 120 kVp at all centers, mAs between 75 and 200, FOV 40 cm×40 cm. The BMD values of L1 to L3 are measured, and the average BMD calculated. The American College of Radiology QCT criteria for the diagnosis of osteoporosis is applied to determine the presence of osteoporosis. The scout view images of T4-L4 vertebrae are reviewed by two experienced radiologists for semi-quantification of vertebral fractures according to Genant's method.

Curcumin may serve an anticancer role in human osteosarcoma cell line U-2 OS by targeting ITPR1.

The present study aimed to determine the mechanisms of action of curcumin in osteosarcoma. Human osteosarcoma U-2 OS cells was purchased from the Cell Bank of the Chinese Academy of Sciences. RNA sequencing analysis was performed for 2 curcumin-treated samples and 2 control samples using Illumina deep sequencing technology. The differentially expressed genes were identified using Cufflink software. Enrichment and protein-protein interaction network analyses were performed separately using cluster Profiler package and Cytoscape software to identify key genes. Then, the mRNA levels of key genes were detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in U-2 OS cells. Finally, cell apoptosis, proliferation, migration and invasion arrays were performed. In total, 201 DEGs were identified in the curcumin-treated group. EEF1A1 (degree=88), ATF7IP, HIF1A, SMAD7, CLTC, MCM10, ITPR1, ADAM15, WWP2 and ATP5C1, which were enriched in 'biological process', exhibited higher degrees than other genes in the PPI network. RT-qPCR demonstrated that treatment with curcumin was able to significantly increase the levels of CLTC and ITPR1 mRNA in curcumin-treated cells compared with control. In addition, targeting ITPR1 with curcumin significantly promoted apoptosis and suppressed proliferation, migration and invasion. Targeting ITPR1 via curcumin may serve an anticancer role by mediating apoptosis, proliferation, migration and invasion in U-2 OS cells.

Basic fibroblast growth factor increases IFT88 expression in chondrocytes.

Intraflagellar transport protein 88 (IFT88) is protein crucial for the assembly and maintenance of primary cilia in chondrocytes. Primary cilia regulate mechanical and chemical signals in chondrocytes; however, the effects of cytokines on IFT88 expression and cilia formation and maintenance remain to be elucidated. Therefore, the role of basic fibroblast growth factor (bFGF) on IFT88 expression were examined in theATDC5 murine chondrocytic line, in order to investigate the signaling pathways involved in this process. bFGF treatment upregulated IFT88 expression in a dose­ and time­dependent manner in ATDC5 cells. The effects of bFGF on IFT88 protein expression were suppressed in the presence of the extracellular signal­regulated protein kinase (ERK) inhibitor PD0325901 and the FGF receptor inhibitor BGJ398. In addition, treatment with IFT88­trageting small interfering (si)RNA downregulated the protein expression of IFT88 and ERK, thus suggesting that the ERK signaling pathway may be involved in the regulation of IFT88 expression in ATDC5 cells. bFGF treatment increased the number of ciliated ATDC5 cells and primary cultured chondrocytes. Downregulation of IFT88 expression by PD0325901, BGJ398, or IFT88­targeting siRNA was revealed to reduce the number of ciliated cells. bFGF also upregulated the mRNA and protein expression of IFT88 in primary cultured chondrocytes. In conclusion, the findings of the present study suggested that bFGF may enhance the expression of IFT88, and promote primary cilia development, through the mitogen­activated protein kinase/ERK­mediated pathway in chondrocytes.

Dopamine-assisted fixation of drug-loaded polymeric multilayers to osteoarticular implants for tuberculosis therapy.

Currently, the major issues in the treatment of osteoarticular tuberculosis (TB) after implant placement are low drug concentration at the infected focus and drug resistance resulting from the long-term chemotherapy. The application of drug-loaded polymeric multilayers on implantable devices offers a promising solution to the problems. Herein, a poly(ethylene glycol)-based hydrogel film embedded with isoniazid (INH)-loaded alginate microparticles was fixed to Ti implants via adhesive polydopamine, subsequently capped by poly(lactic-co-glycolic acid) membranes for the sustained and localized delivery of the anti-TB drug. The antibacterial efficacy of the released INH was confirmed by a 4.5 ± 0.8 cm inhibition zone formed in the fourth week after inoculation of Mycobacterium tuberculosis. The INH-loaded Ti implants showed no toxicity to the osteoblast cell and provided a consistent drug release for nearly one week in vitro. The release profile in vivo showed a high local concentration and low systemic exposure. The local INH concentration could be kept higher than its minimum inhibitory concentration over a period of 8 weeks, which proves that it is a promising strategy to improve the severe osteoarticular TB treatment.