Summary
Is gout a risk factor for future osteoporosis? This large population-based study comprising two matched groups of individuals with and without gout demonstrates that patients with gout have a ...20% increase in the risk of developing osteoporosis in future through an 8-year follow-up.
Introduction
To examine if gout is associated with an increased risk of osteoporosis.
Methods
We conducted a nationwide population-based retrospective matched-cohort study. Two matched cohorts (
n
= 36,458 with gout and 71,602 without gout) assembled and recruited from the Longitudinal Health Insurance Dataset containing 1 million subjects. Exclusion criteria were missing data, age < 20 years, short follow-up period, and pre-existing osteoporosis. Both cohorts were followed up until incident osteoporosis, death, or the end of the study. Person-year data and incidence rates were evaluated. A multivariable Cox model was used to derive an adjusted hazard ratio (aHR) after controlling for socioeconomic proxy, geographical difference, glucocorticoid and allopurinol exposure, various prespecified medical conditions, and comorbidities.
Results
Men comprised 72.8% of the cohorts. With a follow-up of 183,729 and 359,900 person-years for the gout and non-gout cohorts, 517 and 811 incidents of osteoporosis occurred, respectively, after excluding osteoporosis incidents in the first 3 years of follow-up. The cumulative incidence of osteoporosis was statistically higher in the gout cohort than in the non-gout cohort, at 3.3 versus 2.1% (
P
= 0.0036, log-rank). Our Cox model showed a 1.2-fold increase in the incidence of osteoporosis in the gout cohort, with an aHR of 1.2 (95% confidence interval, 1.06–1.35).
Conclusions
This first population-based epidemiologic study supports the hypothesis that compared with individuals without gout; those with gout have a modest increase in the risk of developing osteoporosis in future.
Objective
We aimed at studying the role of the most deregulated miR‐99a, identifying its downstream targets, and exploring the clinical potential of miR‐99a and its target(s) in oral cancer.
Subjects ...and Methods
Following confirmation of miR‐99a deregulation in nine oral lines and 26 pairwise clinical specimens, miR‐99a‐manipulated oral cancer cells were subjected to cell proliferation, migration, invasion, and in vivo murine metastasis assays. We characterized putative miR‐99a target(s) using luciferase reporter assays and genetic manipulation. The inverse relation of miR‐99a and its target(s) was examined in clinical specimens using real‐time PCR and Western blot analysis.
Results
MiR‐99a down‐regulation was confirmed both in tested oral cancer cell lines and clinical specimens. Ectopic miR‐99a expression inhibited oral cancer cell migration and invasion. Anti‐miR‐99a, silencing miR‐99a functions, had the opposite effect. Myotubularin‐related protein 3 (MTMR3) with one evolutionarily conserved seed region in the 3′‐untranslated region was a novel miR‐99a target. Depleting MTMR3 expression significantly reduced cell proliferation, migration, or invasion. There was an inverse expression of miR‐99a and MTMR3 protein in oral cancer lines and clinical specimens.
Conclusion
miR‐99a repressed oral cancer cell migration and invasion partly through decreasing MTMR3 expression. MTMR3 may serve as a therapeutic target for oral cancer treatment.
Colorectal carcinoma (CRC) is characterized by unlimited proliferation and suppression of apoptosis, selective advantages for tumor survival, and chemoresistance. Lipopolysaccharide (LPS) signaling ...is involved in both epithelial homeostasis and tumorigenesis, but the relative roles had by LPS receptor subunits CD14 and Toll-like receptor 4 (TLR4) are poorly understood. Our study showed that normal human colonocytes were CD14(+)TLR4(-), whereas cancerous tissues were CD14(+)TLR4(+), by immunofluorescent staining. Using a chemical-induced CRC model, increased epithelial apoptosis and decreased tumor multiplicity and sizes were observed in TLR4-mutant mice compared with wild-type (WT) mice with CD14(+)TLR4(+) colonocytes. WT mice intracolonically administered a TLR4 antagonist displayed tumor reduction associated with enhanced apoptosis in cancerous tissues. Mucosa-associated LPS content was elevated in response to CRC induction. Epithelial apoptosis induced by LPS hypersensitivity in TLR4-mutant mice was prevented by intracolonic administration of neutralizing anti-CD14. Moreover, LPS-induced apoptosis was observed in primary colonic organoid cultures derived from TLR4 mutant but not WT murine crypts. Gene silencing of TLR4 increased cell apoptosis in WT organoids, whereas knockdown of CD14 ablated cell death in TLR4-mutant organoids. In vitro studies showed that LPS challenge caused apoptosis in Caco-2 cells (CD14(+)TLR4(-)) in a CD14-, phosphatidylcholine-specific phospholipase C-, sphingomyelinase-, and protein kinase C-ζ-dependent manner. Conversely, expression of functional but not mutant TLR4 (Asp299Gly, Thr399Ile, and Pro714His) rescued cells from LPS/CD14-induced apoptosis. In summary, CD14-mediated lipid signaling induced epithelial apoptosis, whereas TLR4 antagonistically promoted cell survival and cancer development. Our findings indicate that dysfunction in the CD14/TLR4 antagonism may contribute to normal epithelial transition to carcinogenesis, and provide novel strategies for intervention against colorectal cancer.
In this study, the effectiveness of bioremediating 1,2-dichloroethane (DCA)-contaminated groundwater under different oxidation–reduction processes was evaluated. Microcosms were constructed using ...indigenous bacteria and activated sludge as the inocula and cane molasses and a slow polycolloid-releasing substrate (SPRS) as the primary substrates. Complete DCA removal was obtained within 30 days under aerobic and reductive dechlorinating conditions. In anaerobic microcosms with sludge and substrate addition, chloroethane, vinyl chloride, and ethene were produced. The microbial communities and DCA-degrading bacteria in microcosms were characterized by 16S rRNA-based denatured-gradient-gel electrophoresis profiling and nucleotide sequence analyses. Real-time polymerase chain reaction was applied to evaluate the variations in Dehalococcoides spp. and Desulfitobacterium spp. Increase in Desulfitobacterium spp. indicates that the growth of Desulfitobacterium might be induced by DCA. Results indicate that DCA could be used as the primary substrate under aerobic conditions. The increased ethene concentrations imply that dihaloelimination was the dominate mechanism for DCA biodegradation.
•DCA can be used as the primary substrate and degraded by the indigenous microbial consortia.•Reductive dechlorination of DCA can be enhanced by the supplement of substrates and sludge.•Dihaloelimination is the dominant mechanism for DCA dechlorination and ethene is the end product.•SPRS can serve as the primary substrate and creates anaerobic conditions for DCA dechlorination.•Reductive dechlorination is a feasible option for DCA-contaminated groundwater remediation.
DCA can serve as the primary substrate and degraded by indigenous bacteria aerobically. Dihaloelimination is the dominant mechanism and ethene is the end product via dechlorination.
This paper presented a multi-axis synchronous motion-sensing platform with virtual reality (VR) to enhance the depth of immersion. Multidisciplinary technologies have been integrated in this system, ...such as interactive technology, spatial position, tactile stimulation, and scenario sensing, to build a complete system of multi-axis VR sensing mechanism. This platform was consisted of servo motors with precision planetary gear reducer, drivers, and three crank linkages under 3 degrees of freedom (DoF) for working on a larger range of motion and able to support higher loading with lower folding height. A servo motor with reducer was connected to each linkage to control and drive the platform directly. The kinematic analysis of motion types on a heave, roll, and pitch was applied to validate the motion of this platform. The target speeds of step response experiments were 1000 rpm, 800 rpm, and 600 rpm, respectively. The rising time was upgraded by 15–18% in the experiment of the position loop. The results show that Cascade design can improve the response of this system. In addition, Visual Studio C# and EtherCAT communication transmission with the motion control card were utilized to establish the motion control system and human machine interface (HMI) to check the system status immediately. Finally, the platform was combined with VR image content that we designed. The motion-sensing platform could receive fast dynamic response. The simulation and control feedback of the synchronous bi-directional control can be realized the immersion of the virtual image and real world motion interactively. This system could highly enhance the immersion experience.
Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized clinically by the proliferation of one or more hematopoietic lineage(s). The ...classical Philadelphia-chromosome (Ph)-negative MPNs include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The Asian Myeloid Working Group (AMWG) comprises representatives from fifteen Asian centers experienced in the management of MPN. This consensus from the AMWG aims to review the current evidence in the risk stratification and treatment of Ph-negative MPN, to identify management gaps for future improvement, and to offer pragmatic approaches for treatment commensurate with different levels of resources, drug availabilities and reimbursement policies in its constituent regions. The management of MPN should be patient-specific and based on accurate diagnostic and prognostic tools. In patients with PV, ET and early/prefibrotic PMF, symptoms and risk stratification will guide the need for early cytoreduction. In younger patients requiring cytoreduction and in those experiencing resistance or intolerance to hydroxyurea, recombinant interferon-α preparations (pegylated interferon-α 2A or ropeginterferon-α 2b) should be considered. In myelofibrosis, continuous risk assessment and symptom burden assessment are essential in guiding treatment selection. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in MF should always be based on accurate risk stratification for disease-risk and post-HSCT outcome. Management of classical Ph-negative MPN entails accurate diagnosis, cytogenetic and molecular evaluation, risk stratification, and treatment strategies that are outcome-oriented (curative, disease modification, improvement of quality-of-life).
A novel series of 6,7,2',3',4'-substituted-1,2,3,4-tetrahydro-2-phenyl- 4-quinolones were synthesized and evaluated for interactions with tubulin and for cytotoxic activity against a panel of human ...tumor cell lines, including ileocecal carcinoma (HCT-8), breast cancer (MCF-7), lung carcinoma (A-549), epidermoid carcinoma of the nasopharynx (KB), renal cancer (CAKI-1), and melanoma cancer (SKMEL-2). Most compounds (18, 20, 22-27) showed potent cytotoxic and antitubulin effects. The most active compounds (23, 26, 27) demonstrated strong cytotoxic effects with ED50 values in the nanomolar or subnanomolar range in almost all tumor cell lines. Three active racemates (20, 22, 25) were separated into the enantiomers, and generally, the optically pure (-)-isomers (20a, 22a, 25a) exhibited greater biological activity than the racemates or (+)-isomers. Cytotoxicity and antitubulin activity were closely correlated, with the most active compounds (23, 26, 27) having effects comparable to those of colchicine, podophyllotoxin, and combretastatin A-4.
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