Resistant dextrin protects against pathological bone loss in ovariectomized rats and inhibits RANKL-induced osteoclastogenesis.

BACKGROUND: Osteoporosis is a common disease in postmenopausal women characterized by systemic bone mass loss, microstructure fragility and increased incidence of fractures. Resistant dextrin (RD) is a soluble fiber with beneficial metabolic effects. However, the beneficial effect of RD in osteoporosis remains to be determined. METHODS: In this study, we investigated the effect of dietary RD supplement on osteoporosis in ovariectomized (OVX) rats. Both the control (sham) and OVX group rats were gavaged with RD (10 g/kg/d) or equal amount of saline for 12 weeks, and histological and biomechanical analyses were conducted to evaluate bone microstructure and strength. Furthermore, we also evaluated the effects of RD on osteoclastogenesis in bone marrow macrophages (BMMs) by detecting the expression of osteoclast-related genes using qRT-PCR and Western blot analysis. RESULTS: The results showed that in OVX rats the bone strength and microstructure characteristics were significantly improved with RD supplement for 12 weeks. Additionally, the mRNA and protein expression of osteoclast markers, such as CTSK, NF-κB and NFATC1, were significantly down-regulated in BMMs isolated from RD supplement group. RD also suppressed RANKL-induced osteoclastogenesis in BMMs. CONCLUSION: These findings suggest that RD ameliorates osteoporosis in OVX rats by inhibiting osteoclast differentiation. RD suppresses RANKL-induced osteoclastogenesis possibly through modulating Akt and NF-κB signaling pathways. These data indicate that a dietary supplement of RD might serve as an intervention strategy for menopausal osteoporosis.

Comparison of prognosis of patients with endometrial cancer after hysteroscopy versus dilatation and curettage: A multicenter retrospective study.

Introduction: Hysteroscopy is a useful procedure for diagnosing endometrial cancer. There is controversy regarding whether hysteroscopy affects the prognosis of endometrial cancer by prompting cancer cell into intraperitoneal dissemination. Our purpose was to confirm whether hysteroscopy could be a risk factor of the tumor stage, recurrence and survival rate of endometrial cancer. Methods: This multicenter retrospective study included all consecutive patients who had endometrial carcinoma diagnosed preoperatively with hysteroscopy and directed endometrial biopsy (HSC, group A) and dilatation and curettage (D&C, group B) between February 2014 and December 2018 at the Fujian Provincial, China. We compared the demographic feature, clinical characteristics and prognosis between the two groups. Results: A total of 429 patients were included in the study (Group A, n = 77; Group B, n = 352). There was no significant difference between their baseline characteristics [including age, BMI, histological type and International Federation of Gynecology and Obstetrics (FIGO) stage]. By comparing several pathological conditions that may affect prognosis, there were no significant differences between the two groups in the peritoneal cytology, depth of myometrial invasion, the positivity of lymph nodes, lymphovascular space invasion and paraaortic lymph node dissection. Finally, no significant difference was found between the two groups in overall survival (OS) (P = 0.189) or recurrence free survival (RFS) (P = 0.787). Conclusion: Under certain inflation pressure and distension medium, hysteroscopic examination and lesion biopsy ensure the safety and have no adverse effects on prognosis compared to conventional curettage.

Stable directional emission in active optical waveguides shielding external environmental influences.

The skillful confinement of light brought by the composite waveguide structure has shown great possibilities in the development of photonic devices. It has greatly expanded the application range of an on-chip system in dark-field imaging and confined the laser when containing an active medium. Here we experimentally proved a stable directional emission in an active waveguide composed of metal and photonic crystal, which is almost completely unaffected by the external environment and different from the common local light field that is seriously affected by the structure. When the refractive index of samples on the surface layer changes, it can ensure the constant emission intensity of the internal mode, while still retaining the external environmental sensitivity of the surface mode. It can also be used for imaging and sensing as a functional slide. This research of chip-based directional emission is very promising for various applications including quantitative detection of biological imaging, coupled emission intensity sensing, portable imaging equipment, and tunable micro lasers.

Chinese mothers' intention to vaccinate daughters against human papillomavirus (HPV), and their vaccine preferences: a study in Fujian Province.

Little is known regarding Chinese mothers' intention to vaccinate their daughters against human papillomavirus (HPV) since the HPV vaccine was approved for use in China in 2016. The aim was to explore maternal HPV vaccination acceptance, preference for 2-, 4- or 9-valent HPV vaccine and acceptance of domestically manufactured HPV vaccines. Study participants were mothers of primary school children in Southeastern region of Fujian. An online cross-sectional survey was undertaken between June and August 2019. Among the total of 3,586 completed responses (response rate 28.5%), the intention to vaccinate daughter against HPV was high (83.3%). Higher maternal education and perceived benefit and barriers were associated with greater intention to vaccinate. Among mothers who did not intend to vaccinate their daughters, the three most common reasons were daughter being too young to receive HPV vaccination (40.6%), fear of side effects (31.9%) and vaccine price is too high (16.0%). The largest proportion (41.4%) preferred their daughter to be vaccinated with the 9-valent HPV vaccine (9vHPV). Greater preference for 9vHPVwas strongly associated with higher maternal education level and annual household income. The majority of mothers expressed a preference for imported HPV vaccine (56.3%). Our result indicates that lower intentions to vaccinate daughters against HPV among less educated and lower-income mothers may lead to significant social inequalities in HPV vaccine uptake in the country.

Berberine improves intralipid-induced insulin resistance in murine.

Insulin resistance (IR) is a major metabolic risk factor even before the onset of hyperglycemia. Recently, berberine (BBR) is found to improve hyperglycemia and IR. In this study, we investigated whether BBR could improve IR independent of hyperglycemia. Acute insulin-resistant state was induced in rats by systemic infusion of intralipid (6.6%). BBR was administered via different delivery routes before or after the beginning of a 2-h euglycemic-hyperinsulinemic clamp. At the end of experiment, rats were sacrificed, gastrocnemius muscle was collected for detecting mitochondrial swelling, phosphorylation of Akt and AMPK, as well as the mitochondrial permeability regulator cyclophilin D (CypD) protein expression. We showed that BBR administration markedly ameliorated intralipid-induced IR without affecting blood glucose, which was accompanied by alleviated mitochondrial swelling in skeletal muscle. We used human skeletal muscle cells (HSMCs), AML12 hepatocytes, human umbilical vein endothelial cells, and CypD knockout mice to investigate metabolic and molecular alternations. In either HSMCs or AML12 hepatocytes, BBR (5 µM) abolished palmitate acid (PA)-induced increase of CypD protein levels. In CypD-deficient mice, intralipid-induced IR was greatly attenuated and the beneficial effect of BBR was diminished. Furthermore, we demonstrated that the inhibitory effect of BBR on intralipid-induced IR was mainly mediated by skeletal muscle, but not by intestine, liver, or microvasculature; BBR administration suppressed intralipid-induced upregulation of CypD expression in skeletal muscle. These results suggest that BBR alleviates intralipid-induced IR, which is related to the inhibition of CypD protein expression in skeletal muscle.

Association Between Forearm Bone Mineral Density and Metabolic Obesity in a Northern Chinese Population.

Context: The link between obesity and bone health is controversial. Most studies classify obesity based on body mass index. However, differences in metabolic status may affect bone health. Purpose: To explore the potential relationship of metabolic obesity with forearm bone mineral density (BMD) in a northern Chinese population. Methods: This is a retrospective study involving a total of 2122 subjects divided into four groups: a metabolically healthy normal-weight (MHNW) group, a metabolically healthy obesity (MHO) group, a metabolically unhealthy, but normal-weight (MUNW) group, and a metabolically unhealthy obesity (MUO) group. Analysis of covariance was performed to compare forearm BMD among the groups. The covariates included age, weight, and height, along with menopause status in women. Partial correlation analysis and multiple linear regression models were used to explore the associations of forearm BMD with clinical parameters. Results: Young middle-aged men with MHO had significantly higher forearm BMD than those in the MUO group. In addition, forearm BMD of young middle-aged women was higher in the MHNW group than in the MUNW group. Partial correlation analysis and multiple linear regression analysis suggested that homeostasis model assessment of insulin resistance (HOMA-IR) was negatively correlated with forearm BMD in young middle-aged male subjects with MUO, and waist circumference (WC) and low-density lipoprotein cholesterol (LDL-C) showed a significant negative relationship with forearm BMD in young middle-aged female MUNW subjects. Conclusions: Men in the MUO group and women in the MUNW group were more likely to have lower forearm BMD if they were of young middle age. Metabolic obesity could be a better method for defining obesity when exploring the relationship between obesity and bone health in Chinese individuals. WC, LDL-C, and insulin resistance might be negative predictors of bone health.

Vaspin antagonizes high fat-induced bone loss in rats and promotes osteoblastic differentiation in primary rat osteoblasts through Smad-Runx2 signaling pathway.

BACKGROUND: Visceral adipose tissue-derived serine protease inhibitor (vaspin), an adipose-derived hormone, exhibits various biological functions. Recently, studies showed that vaspin is closely related to bone metabolism. However, how vaspin influences bone formation and its underlying mechanisms in high fat-induced obese rats and rat primary osteoblasts (OBs) are not fully understood. In this study, the effects of vaspin on bone mechanical parameters and microarchitecture were evaluated. METHODS: A total of 40 male Sprague-Dawley (SD) rats at 5-week old were fed with high fat diet (HFD) and normal diet (ND) for 12 weeks followed by treatment of vaspin for 10 weeks. Micro CT and three-point bending tests were conducted to evaluate bone microstructure and biomechanics. The alkaline phosphatase (ALP) activity, expression of Runt-related transcription factor 2 (Runx2), Osterix (Osx), Collegen alpha1 (Colla1) procollagen I N-terminal peptide (PINP), C-telopeptide of type I collagen (CTX), Smad2/3 and p-Smad2/3 was detected by different methods. RESULTS: Our data indicated that, compared with ND rats, HFD rats exhibited high body weight, decreased bone strength and deteriorative bone quality. In contrast, vaspin reduced the body weight, improved the whole body metabolic status, enhanced bone strength, trabecular bone mass, and expression of Runx2, Osx, PINP, and decreased the expression level of plasma CTX. In vitro studies showed that vaspin promoted osteogenic differentiation and ALP activity in rat primary OBs in a dose dependent manner. Vaspin also upregulated mRNA expression of osteogenesis-related genes Runx2, Osx and Colla1 and protein expression of Runx2, Smad2/3 and p-Smad2/3. CONCLUSIONS: Our results indicated that vaspin protects against HFD-induced bone loss, and promotes osteogenic differentiation by activating the Smad2/3-Runx2 signaling pathway.

Flaxseed oil ameliorated high-fat-diet-induced bone loss in rats by promoting osteoblastic function in rat primary osteoblasts.

BACKGROUND: α-Linolenic acid (ALA) is a plant-derived omega-3 unsaturated fatty acid that is rich in flaxseed oil (FO). The effect of FO on bone health is controversial. This study aims to evaluate the effect of FO on bone damage induced by a high-fat diet (HFD) and to explore the possible mechanism. METHODS: Male Sprague-Dawley rats were fed a normal control diet (NC, 10% fat), FO diet (NY, 10% fat), HFD (60% fat), or HFD containing 10% FO (HY, 60% fat) for 22 weeks. Micro CT and three-point bending tests were conducted to evaluate bone microstructure and biomechanics. Serum was collected for the detection of ALP, P1NP, and CTX-1. Rat primary osteoblasts (OBs) were treated with different concentrations of ALA with or without palmitic acid (PA) treatment. The ALP activity, osteogenic-related gene and protein expression were measured. RESULTS: Rats in the HFD group displayed decreased biomechanical properties, such as maximum load, maximum fracture load, ultimate tensile strength, stiffness, energy absorption, and elastic modulus, compared with the NC group ( p  < 0.05). However, HY attenuated the HFD-induced decreases in bone biomechanical properties, including maximum load, maximum fracture load, and ultimate tensile strength (p < 0.05). Trabecular bone markers such as trabecular volume bone mineral density (Tb. vBMD), trabecular bone volume/total volume (Tb. BV/TV), trabecular number (Tb. N), trabecular thickness (Tb. Th) were decreased, trabecular separation (Tb. Sp) and the structure model index (SMI) were increased in the HFD group compared with the NC group, and all parameters were remarkably improved in the HY group compared to the HFD group (p < 0.05). However, cortical bone markers such as cortical volume bone mineral density (Ct. vBMD), cortical bone volume/total volume (Ct. BV/TV) and cortical bone thickness (Ct. Th) were not significantly different among all groups. Moreover, the serum bone formation markers ALP and P1NP were higher and the bone resorption marker CTX-1 was lower in the HY group compared with levels in the HFD group. Compared with the NC group, the NY group had no difference in the above indicators. In rat primary OBs, PA treatment significantly decreased ALP activity and osteogenic gene and protein (ß-catenin, RUNX2, and osterix) expression, and ALA dose-dependently restored the inhibition induced by PA. CONCLUSIONS: FO might be a potential therapeutic agent for HFD-induced bone loss, most likely by promoting osteogenesis.

Overexpression of SET and MYND Domain-Containing Protein 2 (SMYD2) Is Associated with Tumor Progression and Poor Prognosis in Patients with Papillary Thyroid Carcinoma.

BACKGROUND SET and MYND domain-containing protein 2 (SMYD2), which is identified as a protein-lysine methyltransferase, plays a crucial role in the progression of some tumors such as bladder carcinoma. However, the clinical significance of SMYD2 in patients with papillary thyroid carcinoma (PTC) has not been elucidated. In the present study, we aimed to investigate the expression and role of SMYD2 in human PTC. MATERIAL AND METHODS Clinicopathological analysis was performed in 107 patients with PTC. Expression of SMYD2 was determined by immunohistochemistry staining, quantitative RT-PCR, or Western blotting in PTC tissues, adjacent normal tissues, and PTC cells (K1 and B-CPAP). The prognostic value of SMYD2 in PTC patients was assessed by univariate and multivariate analysis. Clinical outcomes were evaluated by Kaplan-Meier log-rank tests. Cell proliferation was examined in PTC cells following overexpression or knockdown of SMYD2. RESULTS SMYD2 was highly expressed in PTC tissues compared to adjacent thyroid tissues. Additionally, high expression of SMYD2 was significantly related to tumor size, lymph node metastasis, and TNM stage. Moreover, SMYD2 was identified as an independent prognosis factor by multivariate analysis. Using 2 PTC cell lines, K1 and B-CPAP, we demonstrated that high expression of SMYD2 can promote tumor cell proliferation. CONCLUSIONS SMYD2 expression was upregulated in PTC tissues and significantly related to the poorer prognosis of PTC patients. Our studies suggested the potential role of SMYD2 as a new therapeutic target and prognostic biomarker in human PTC.

Increased plasma osteoprotegerin concentrations in Type 1 diabetes with albuminuria.

OBJECTIVE: The aim of the present study was to determine the plasma osteoprotegerin (OPG) levels in Type 1 diabetic patients with albuminuria. METHODS: A total of 80 Type 1 diabetic subjects and 30 control subjects were enrolled. Diabetic subjects were divided into normoalbuminuric group, microalbuminuric group and macroalbuminuric group according to urinary albumin excretion rate (UAER) and serum creatinine measurements. Plasma osteoprotegerin level was measured by enzyme-linked immunoassay. RESULTS: The serum OPG levels were significantly elevated in patients with microalbuminuria (3.62 ± 0.70 ng/l) and macroalbuminuria (4.45 ± 0.76 ng/l) as compared with patients with normoalbuminuria (2.77 ± 0.78 ng/l) and control subjects (2.29 ± 0.37 ng/l). And the plasma osteoprotegerin level in macroalbuminuric group was also higher than that in microalbuminuria group. The plasma osteoprotegerin level had a positive correlation with the fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), glycohemoglobin A1c (HbA1C), highly sensitive C-reactive protein (hsCRP)and UAER. Multivariate regression analysis revealed that the plasma osteoprotegerin level was an independent factor associated with albuminuria in Type 1 diabetes. CONCLUSIONS: The plasma values of osteoprotegerin were elevated in Type 1 diabetic patients with nephropathy and gradually increased with the severity, so there is a association between plasma osteoprotegerin levels and the presence and severity of diabetic nephropathy. This finding supports the growing concept that osteoprotegerin may act as an important regulatory molecule in the angiopathy, and particularly, that it may be involved in the development of nephropathy in Type 1 diabetes.