Causal relationship between circulating inflammatory factors and osteoporosis: a bidirectional Mendelian randomization study.

OBJECTIVE: Osteoporosis (OP), a persistent metabolic bone disorder linked with inflammation, has an undetermined cause. In our research, we employed bidirectional Mendelian randomization (MR) to investigate the interplay between OP and inflammation agents. MATERIALS AND METHODS: We performed two-way pooled-level MR analyses to characterize the causal relationship between 41 circulating inflammatory modulators and OP. Genetic variation data for the 41 regulatory factors associated with inflammation were obtained from genome-wide association studies (GWASs) of human cytokines. Bone mineral density (BMD) was utilized as a phenotype for OP in our approach. The BMD dataset, sourced from the GEFOS consortium, a large GWAS meta-analysis study and UK Biobank, was classified based on varied sections [whole body (TB), lumbar spine (LS), femoral neck (FN), forearm (FA), and heel] and age brackets (0-15 years, 15-30 years, 30-45 years, 45-60 years, and above 60 years). Primary MR analyses were executed using the inverse variance weighting (IVW) method, and sensitivity analyses were performed using the MR-Egger, weighted median, simple model, and weighted model. Cochran's Q test was utilized to evaluate the existence of heterogeneity. We used MR-Egger regression and MR multiplicity of residuals and outliers (MR-PRESSO) to assess pleiotropy. RESULTS: After false discovery rate (FDR) correction, elevated levels of circulating interleukin-8 (IL-8) [ß = 0.072 (0.031-0.114), p < 0.01], macrophage inflammatory protein-1b (MIP-1ß) [ß = 0.008 (0.003-0.013), p < 0.01; ß = 0.026 (0.009-0.042), p < 0.01], and cutaneous T-cell attracting chemokine (CTACK) [ß = 0.037 (0.017-0.056), p < 0.01] was associated with a reduced risk of OP. Reduced levels of hepatocyte growth factor (HGF), IL-1ra, IL-10, macrophage colony-stimulating factor (MCSF), and MIP-1α were associated with a reduced risk of OP [ß = -0.030 (-0.047 - -0.013), p < 0.01; ß = -0.025 (-0.041 - -0.010), p < 0.01; ß = -0.018 (-0.029 - -0.007), p < 0.01; ß = -0.060 (-0.097 - -0.024), p < 0.01; ß = -0.118 (-0.190 - -0.047), p < 0.01]. We observed a significant causal correlation between FN-BMD and MCP-3 (FDR < 0.05). The occurrence of OP may also lead to elevated levels of MCP3 [ß = -0.466 (-0.714 - -0.217), p < 0.01]. The reliability of the results was confirmed by sensitivity analyses. CONCLUSIONS: This study demonstrated the pathogenic role of circulating inflammatory modulators in OP using bidirectional MR analysis. This further deepens the understanding of OP pathogenesis and provides new ideas for therapeutic intervention in OP.

The regulation of oxytocin receptor gene expression during adipogenesis.

Although it has been reported that oxytocin stimulates lipolysis in adipocytes, changes in the expression of oxytocin receptor (OTR) mRNA in adipogenesis are still unknown. The present study aimed to investigate the expression of OTR mRNA during adipocyte differentiation and fat accumulation in adipocytes. OTR mRNA was highly expressed in adipocytes prepared from mouse adipose tissues compared to stromal-vascular cells. OTR mRNA expression was increased during the adipocyte differentiation of 3T3-L1 cells. OTR expression levels were higher in subcutaneous and epididymal adipose tissues of 14-week-old male mice compared to 7-week-old male mice. Levels of OTR mRNA expression were higher in adipose tissues at four different sites of mice fed a high-fat diet than in those of mice fed a normal diet. The OTR expression level was also increased by refeeding for 4 h after fasting for 16 h. Oxytocin significantly induced lipolysis in 3T3-L1 adipocytes. In conclusion, a new regulatory mechanism is demonstrated for oxytocin to control the differentiation and fat accumulation in adipocytes via activation of OTR as a part of the hypothalamic-pituitary-adipose axis.

Self-aligned growth of single-walled carbon nanotubes using optical near-field effects.

Self-aligned growth of ultra-short single-walled carbon nanotubes (SWNTs) was realized by utilizing optical near-field effects in a laser-assisted chemical vapor deposition (LCVD) process. By introducing the optical near-field effects, bridge structures containing single suspended SWNT channels were successfully fabricated through the LCVD process at a relatively low substrate temperature. Raman spectroscopy and I-V analyses have been carried out to characterize the SWNT-bridge structures. Numerical simulations using a high-frequency structure simulator revealed that significant enhancement of local heating occurs at metallic electrode tips under laser irradiation; it is about one order of magnitude higher than that in the rest of the electrodes. This technique suggests a novel approach to in situ low-temperature fabrication of SWNT-based devices in a precisely controlled manner, based on the nanoscale heating enhancement induced by the optical near-field effects.

Tip-enhanced near-field Raman spectroscopy with a scanning tunneling microscope and side-illumination optics.

Conventional Raman spectroscopy (RS) suffers from low spatial resolution and low detection sensitivity due to the optical diffraction limit and small interaction cross sections. It has been reported that a highly localized and significantly enhanced electromagnetic field could be generated in the proximity of a metallic tip illuminated by a laser beam. In this study, a tip-enhanced RS system was developed to both improve the resolution and enhance the detection sensitivity using the tip-enhanced near-field effects. This instrument, by combining RS with a scanning tunneling microscope and side-illumination optics, demonstrated significant enhancement on both optical sensitivity and spatial resolution using either silver (Ag)-coated tungsten (W) tips or gold (Au) tips. The sensitivity improvement was verified by observing the enhancement effects on silicon (Si) substrates. Lateral resolution was verified to be below 100 nm by mapping Ag nanostructures. By deploying the depolarization technique, an apparent enhancement of 175% on Si substrates was achieved. Furthermore, the developed instrument features fast and reliable optical alignment, versatile sample adaptability, and effective suppression of far-field signals.

A relapsed case of imported tertian malaria after a standard course of hydroxychloroquine and primaquine therapy.

Resistance of Plasmodium species to antimalarial agents has become increasingly challenging to the management and prevention of malaria. We experienced an imported case of tertian malaria due to Plasmodium vivax relapsed after a seemingly successful treatment with conventional course of hydroxychloroquine and primaquine. A 35-year-old man developed fever three days after return from India and mainland China. After his illness was diagnosed as tertian malaria, he was managed with hydroxychloroquine and then primaquine (primaquine base 15 mg/day for 14 days). Thereafter peripheral blood smears showed no malarial parasites, and there was no relapse of symptom until the 55th post-treatment day, however, six months after the above treatment tertian malaria relapsed. He was managed with the same medications again and malaria did not relapse for 10 months.