Bioinformatics analysis of hub genes as osteoarthritis prognostic biomarkers.

Osteoarthritis (OA) is a progressive cartilage degradation disease, concomitant with synovitis, osteophyte formation, and subchondral bone sclerosis. Over 37% of the elderly population is affected by OA, and the number of cases is increasing as the global population ages. Therefore, the objective of this study was to identify and analyze the hub genes of OA combining with comprehensive bioinformatics analysis tools to provide theoretical basis in further OA effective therapies. Two sample sets of GSE46750 contained 12 pairs OA synovial membrane and normal samples harvested from patients as well as GSE98918 including 12 OA and non-OA patients were downloaded from the Gene Expression Omnibus database (GEO) database. Differentially expressed genes (DEGs) were identified using Gene Expression Omnibus 2R (GEO2R), followed by functional enrichment analysis, protein-protein interaction networks construction. The hub genes were identified and evaluated. An OA rat model was constructed, hematoxylin and eosin staining, safranin O/fast green staining, cytokines concentrations of serum were used to verify the model. The hub genes expression level in the knee OA samples were verified using RT-qPCR. The top 20 significantly up-regulated and down-regulated DEGs were screened out from the two datasets, respectively. The top 18 GO terms and 10 KEGG pathways were enriched. Eight hub genes were identified, namely MS4A6A, C1QB, C1QC, CD74, CSF1R, HLA-DPA1, HLA-DRA and ITGB2. Among them, the hub genes were all up-regulated in in vivo OA rat model, compared with healthy controls. The eight hub genes identified (MS4A6A, C1QB, C1QC, CD74, CSF1R, HLA-DPA1, HLA-DRA and ITGB2) were shown to be associated with OA. These genes can serve as disease markers to discriminate OA patients from healthy controls.

Slug Flow Coprecipitation Synthesis of Uniformly-Sized Oxalate Precursor Microparticles for Improved Reproducibility and Tap Density of Li(Ni0.8Co0.1Mn0.1)O2 Cathode Materials.

The microparticle quality and reproducibility of Li(Ni0.8Co0.1Mn0.1)O2 (NCM811) cathode materials are important for Li-ion battery performance but can be challenging to control directly from synthesis. Here, a scalable reproducible synthesis process is designed based on slug flow to rapidly generate uniform micron-size spherical-shape NCM oxalate precursor microparticles at 25-34 °C. The whole process takes only 10 min, from solution mixing to precursor microparticle generation, without needing aging that typically takes hours. These oxalate precursors are convertible to spherical-shape NCM811 oxide microparticles, through a preliminary design of low heating rates (e.g., 0.1 and 0.8 °C/min) for calcination and lithiation. The outcome oxide cathode particles also demonstrate improved tap density (e.g., 2.4 g mL-1 for NCM811) and good specific capacity (202 mAh g-1 at 0.1 C) in coin cells and reasonably good cycling performance with LiF coating.

Scalable Advanced Li(Ni0.8Co0.1Mn0.1)O2 Cathode Materials from a Slug Flow Continuous Process.

Li[Ni0.8Co0.1Mn0.1]O2 (LNCMO811) is the most studied cathode material for next-generation lithium-ion batteries with high energy density. However, available synthesis methods are time-consuming and complex, restricting their mass production. A scalable manufacturing process for producing NCM811 hydroxide precursors is vital for commercialization of the material. In this work, a three-phase slug flow reactor, which has been demonstrated for its ease of scale-up, better synthetic control, and excellent uniform mixing, was developed to control the initial stage of the coprecipitation of NCM811 hydroxide. Furthermore, an equilibrium model was established to predict the yield and composition of the final product. The homogeneous slurry from the slug flow system was obtained and then transferred into a ripening vessel for the necessary ripening process. Finally, the lithium-nickel-cobalt-manganese oxide was obtained through the calcination of the slug flow-derived precursor with lithium hydroxide, having a tap density of 1.3 g cm-3 with a well-layered structure. As-synthesized LNCMO811 shows a high specific capacity of 169.5 mAh g-1 at a current rate of 0.1C and a long cycling stability of 1000 cycling with good capacity retention. This demonstration provides a pathway toward scaling up the cathode synthesis process for large-scale battery applications.

Recrystallization of Adenosine for Localized Drug Delivery.

Adenosine (ADO) is an endogenous metabolite with immense potential to be repurposed as an immunomodulatory therapeutic, as preclinical studies have demonstrated in models of epilepsy, acute respiratory distress syndrome, and traumatic brain injury, among others. The currently licensed products Adenocard and Adenoscan are formulated at 3 mg/mL of ADO for rapid bolus intravenous injection, but the systemic administration of the saline formulations for anti-inflammatory purposes is limited by the nucleoside's profound hemodynamic effects. Moreover, concentrations that can be attained in the airway or the brain through direct instillation or injection are limited by the volumes that can be accommodated in the anatomical space (<5 mL in humans) and the rapid elimination by enzymatic and transport mechanisms in the interstitium (half-life <5 s). As such, highly concentrated formulations of ADO are needed to attain pharmacologically relevant concentrations at sites of tissue injury. Herein, we report a previously uncharacterized crystalline form of ADO (rcADO) in which 6.7 mg/mL of the nucleoside is suspended in water. Importantly, the crystallinity is not diminished in a protein-rich environment, as evidenced by resuspending the crystals in albumin (15% w/v). To the best of our knowledge, this is the first report of crystalline ADO generated using a facile and organic solvent-free method aimed at localized drug delivery. The crystalline suspension may be suitable for developing ADO into injectable formulations for attaining high concentrations of the endogenous nucleoside in inflammatory locales.

Asprin-loaded strontium-containing α-calcium sulphate hemihydrate/nano-hydroxyapatite composite promotes regeneration of critical bone defects.

Our laboratory originally synthesized strontium(Sr)-containing α-calcium sulphate hemihydrate/nano-hydroxyapatite composite (Sr-α-CSH/n-HA) and demonstrated its ability to repair critical bone defects. This study attempted to incorporate aspirin into it to produce a better bone graft material for critical bone defects. After 5% Sr-α-CSH was prepared by coprecipitation and hydrothermal methods, it was mixed with aspirin solution of different concentrations (50 µg/ml, 200 µg/ml, 800 µg/ml and 3200 µg/ml) at a fixed liquid-solid ratio (0.54 v/w) to obtain aspirin-loaded Sr-α-CSH/n-HA composite. In vitro experiments were performed on the composite extracts. The tibial defects (3 mm*5 mm) in SD rat model were filled with the composite for 4 weeks and 12 weeks to evaluate its osteogenic capacity in vivo. Our results showed its capability of proliferation, migration and osteogenesis of BMSCs in vitro got improved. In vivo treatment with 800 µg/ml aspirin-loaded Sr-α-CSH/n-HA composite led to significantly more new bone formation in the defects compared with Sr-α-CSH/n-HA composite and significantly promoted the expression of osteogenic-related genes and inhibited osteoclast activity. In general, our research suggests that aspirin-loaded Sr-α-CSH/n-HA composite may have a greater capacity of repairing tibial defects in SD rats than simple Sr-α-CSH/n-HA composite.

Opportunities and challenges of real-time release testing in biopharmaceutical manufacturing.

Real-time release testing (RTRT) is defined as "the ability to evaluate and ensure the quality of in-process and/or final drug product based on process data, which typically includes a valid combination of measured material attributes and process controls" (ICH Q8[R2]). This article discusses sensors (process analytical technology, PAT) and control strategies that enable RTRT for the spectrum of critical quality attributes (CQAs) in biopharmaceutical manufacturing. Case studies from the small-molecule and biologic pharmaceutical industry are described to demonstrate how RTRT can be facilitated by integrated manufacturing and multivariable control strategies to ensure the quality of products. RTRT can enable increased assurance of product safety, efficacy, and quality-with improved productivity including faster release and potentially decreased costs-all of which improve the value to patients. To implement a complete RTRT solution, biologic drug manufacturers need to consider the special attributes of their industry, particularly sterility and the measurement of viral and microbial contamination. Continued advances in on-line and in-line sensor technologies are key for the biopharmaceutical manufacturing industry to achieve the potential of RTRT. Related article: http://onlinelibrary.wiley.com/doi/10.1002/bit.26378/full.

Turning Ineffective Transplatin into a Highly Potent Anticancer Drug via a Prodrug Strategy for Drug Delivery and Inhibiting Cisplatin Drug Resistance.

Clinically ineffective transplatin is highly potent against cancer cells when transformed into a transplatin(IV) prodrug nanoparticle. Herein, a hydrophobic transplatin(IV) was synthesized by H2O2-oxidization of transplatin and attachment of two hydrophobic aliphatic chains. Transplatin(IV) was subsequently encapsulated by a biodegradable amphiphilic copolymer, MPEG-PLA, forming a well-defined spherical micelles (M(TransPt)). Transplatin(IV) was protected efficiently and could be released under a simulated cancerous intracellular condition. Compared to the cisplatin and transplatin, M(TransPt) showed the highest Pt uptake and a clathrin-dependent endocytosis pathway. Most importantly, M(TransPt) displayed a nanomolar IC50 on A2780 cells and a great potency on cisplatin resistant A2780DDP cell line. Overall, this nanoplatform for delivering trans-geometry platinum(IV) drug exhibits excellent characteristics for enhancing efficacy and overcoming cisplatin drug resistance, and holds a strong promise for clinical use in the near future.

Nanoparticle-mediated delivery of multinuclear platinum(IV) prodrugs with enhanced drug uptake and the activity of overcoming drug resistance.

Here, a nanoparticle-mediated delivery of multinuclear platinum(IV) prodrugs [biodegradable polymer-di-cisPt(IV)] for overcoming cisplatin drug resistance is reported. From the MTT assays, lower IC50 values of polymer-di-cisPt(IV) on A2780DDP cells than A2780 were observed with the lowest resistance factor of 0.7. Inductively coupled plasma mass spectroscopy results showed that more drugs were delivered into cancer cells and greater number of Pt-DNA adducts were formed with the use of the polymer-di-cisPt(IV) conjugate nanoparticles. By a mechanistic study with endocytosis inhibitors to treat A2780 cells, we proved that polymer-di-cisPt(IV) conjugate nanoparticles were internalized by the cancer cells through endocytosis rather than through passive diffusion or copper transporter 1-mediated active transportation. This well illustrates the way how the polymer-di-cisPt(IV) micelles overcome cisplatin resistance.

Association between child and adolescent obesity and parental weight status: a cross-sectional study from rural North China.

OBJECTIVE: To investigate the relationship between child and adolescent obesity, and parental weight status. METHODS: Height and weight were measured in Chinese children and adolescents aged 6-17 years old. Information was collected concerning parental weight and height, and possible covariates, using a questionnaire. The body mass index (BMI) of each study participant and their parents was calculated. On the basis of the BMI, parents were categorized as normal, overweight or obese, and children and adolescents were categorized as normal or obese. RESULTS: Of the 5,041 participants included in the study, 6.82% were obese. Child or adolescent obesity was significantly associated with parental obesity. When both parents were obese, there was a 3.62-fold increased risk of obesity compared with those whose parents were of normal weight. Obesity in fathers was associated with a heightened risk of obesity in female children, whereas obesity in mothers was associated with a heightened risk of obesity in male children. CONCLUSIONS: Parental obesity was a predictor of obesity in children and adolescents. It is therefore of key importance to prevent obesity in children who have one or more obese parents.

A correlate analysis of UV absorption spectra of compound danshen tablets from different manufactures / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the value of UV absorption spectrum for identification and quality control of compound Danshen tablets and pills.</p><p><b>METHOD</b>UV absorption spectra of compound Danshen tablets and pills, and other drugs were scanned using ultraviolet spectrophotometer (water as the solvent). Pearson's correlation coefficients (Pearson's R) were displayed in the correlations table obtained from SPSS correlate, and deltaR defined as the absolute value of the difference between Pearson's R and its mirror image in the table were used for measuring the spectral similarity between two drugs from different manufacturers.</p><p><b>RESULT</b>Regarding compound Danshen tablets and pills, the spectral similarity between different batch drugs from same manufacturer was very high with Pearson's R = 0.995-0.9999, and the similarity between two manufactures was high with Pearson's R = 0.92-0.997 and deltaR < 0.02. Compared with the spectra of compound Danshen tablets and pills, the spectral similarity of the other drugs was low with Pearson's R = 0.25-0.98 and deltaR > 0.02.</p><p><b>CONCLUSION</b>The results showed that UV absorption spectrum could be suitable for identification and quality control of compound Danshen tablets and pills.</p>