Association of TGF-ß1 and IL-10 Gene Polymorphisms with Osteoporosis in a Study of Taiwanese Osteoporotic Patients.

Osteoporosis is a rising health threat in the increasingly aging world population. It is a common skeletal disease strongly linked to genetic predisposition. We aim to identify the effects of the anti-inflammatory TGF-ß1- and IL-10-specific single-nucleotide polymorphism (SNP) combination on the risk for osteoporosis. We investigated and analyzed the relationships between three TGF-ß1 SNPs (-509C/T, +869 T/C and +29T/C), one IL-10 SNP (+1927A/C) and the level of bone mineral density (BMD), as well as the risk of osteoporosis in Taiwanese osteoporotic patients. A total of 217 subjects were recruited, including 88 osteoporotic patients and 129 healthy controls, for SNPs, BMD and clinical characteristics statistical analyses. Females with TGF-ß1 SNP (-509 C/C) and IL-10 SNP (+1927 C/C) genotypes showed a great benefit for femoral neck T-scores. However, the combination of TGF-ß1 SNP (-509 T/T) and IL-10 SNP (+1927 A/A) genotypes in all subjects showed a significant decrease in total hip BMD T-scores. The TGF-ß1 SNP (-509 C/T) genotype in all subjects and TGF-ß1 SNP (-509 T/T) and IL-10 SNP (+1927 A/C) genotypes in males showed positive effects on body height. The combination of the many SNPs in the anti-inflammatory TGF-ß1 and IL-10 genes may be cooperatively involved in the development of osteoporosis. Our data suggested that the specific SNP combination of TGF-ß1 (-509) and IL-10 (+1927) may act as a predictive factor for postmenopausal osteoporosis in Taiwanese women.

Kefir Peptides Prevent Estrogen Deficiency-Induced Bone Loss and Modulate the Structure of the Gut Microbiota in Ovariectomized Mice.

Osteoporosis is a major skeletal disease associated with estrogen deficiency in postmenopausal women. Kefir-fermented peptides (KPs) are bioactive peptides with health-promoting benefits that are produced from the degradation of dairy milk proteins by the probiotic microflora in kefir grains. This study aimed to evaluate the effects of KPs on osteoporosis prevention and the modulation of the composition of the gut microbiota in ovariectomized (OVX) mice. OVX mice receiving an 8-week oral gavage of 100 mg of KPs and 100 mg of KPs + 10 mg Ca exhibited lower trabecular separation (Tb. Sp), and higher bone mineral density (BMD), trabecular number (Tb. N) and bone volume (BV/TV), than OVX groups receiving Ca alone and untreated mice, and these effects were also reflected in bones with better mechanical properties of strength and fracture toughness. The gut microbiota of the cecal contents was examined by 16S rDNA amplicon sequencing. α-Diversity analysis indicated that the gut microbiota of OVX mice was enriched more than that of sham mice, but the diversity was not changed significantly. Treatment with KPs caused increased microbiota richness and diversity in OVX mice compared with those in sham mice. The microbiota composition changed markedly in OVX mice compared with that in sham mice. Following the oral administration of KPs for 8 weeks, the abundances of Alloprevotella, Anaerostipes, Parasutterella, Romboutsia, Ruminococcus_1 and Streptococcus genera were restored to levels close to those in the sham group. However, the correlation of these bacterial populations with bone metabolism needs further investigation. Taken together, KPs prevent menopausal osteoporosis and mildly modulate the structure of the gut microbiota in OVX mice.

Naringenin Attenuated Prostate Cancer Invasion via Reversal of Epithelial-to-Mesenchymal Transition and Inhibited uPA Activity.

BACKGROUND: Prostate cancer is highly prevalent with a high mortality among males worldwide. Naringenin has been demonstrated to exhibit multiple cellular functions. In this study, we examined the effects of naringenin on prostate cancer. MATERIALS AND METHODS: Transwell and zymography assays were used to detect cell migration and urokinase plasminogen activator (uPA) activity, respectively. Alternation of protein expression was measured by western blot analysis. RESULTS: Transwell assay and zymography revealed that naringenin suppressed the migration and invasion of PC-3 cells and uPA activity in proportion to the concentration of naringenin. Western blot analysis indicated that naringenin up-regulated E-cadherin expression, but down-regulated the expression of vimentin, SNAIL family zinc finger 1 (SNAI1), SNAIL family zinc finger 2 (SNAI2), and TWIST family bHLH transcription factor 1 (TWIST1). CONCLUSION: Naringenin inhibited the migration and invasion of PC-3 cells by reversing expression of proteins involved in epithelial-to-mesenchymal transition and down-regulation of uPA activity. Thus, naringenin may be a promising anti-metastasis agent for prostate cancer.