A sugary solution: Harnessing polysaccharide-based materials for osteoporosis treatment.

Osteoporosis, a prevalent skeletal disorder characterized by diminished bone density, compromised microstructure, and heightened fracture susceptibility, poses a growing public health concern exacerbated by aging demographics. Polysaccharides-based materials, derived from a diverse range of sources, exhibit exceptional biocompatibility. They possess a structure similar to the extracellular matrix, which can enhance cell adhesion in vivo, and demonstrate superior biological activity compared to artificial materials. This study delved into an in-depth examination of the various biomaterials and polysaccharide families associated with the treatment of osteoporosis. This article elucidates the benefits and attributes of polysaccharide-based materials in contrast to current clinical treatment modalities, delineating how these materials address prevalent challenges in the clinical management of osteoporosis. An overview of the prospective applications of polysaccharide-based materials in the future is also provided, as well as outlines the challenges that should be addressed prior to the clinical implementation of such materials.

Analysis of the regulatory role of miR-34a-5p/PLCD3 in the progression of osteoarthritis.

Osteoarthritis is a heterogeneous disease with a complex etiology. However, there is no effective treatment strategy at present. The purpose of this study was to explore the miRNA‒mRNA regulatory network and molecular mechanism that regulate the progression of osteoarthritis. In this article, we downloaded datasets (GSE55457, GSE82107, GSE143514 and GSE55235) from Gene Expression Omnibus (GEO) to screen differentially expressed mRNAs in osteoarthritis. Then, through weighted gene coexpression network (WGCNA), functional enrichment, protein‒protein interaction (PPI) network, miRNA‒mRNA coexpression network, ROC curve, and immune infiltration analyses and qPCR, the mRNA PLCD3, which was highly expressed in osteoarthritis and had clinical predictive value, was screened. We found that PLCD3 directly targets miR-34a-5p through DIANA and dual-luciferase experiments. The expression levels of PLCD3 and miR-34a-5p were negatively correlated. In addition, CCK-8 and wound healing assays showed that the miR-34a-5p mimic inhibited hFLS-OA cell proliferation and promoted hFLS-OA cell migration. PLCD3 overexpression showed the opposite trend. Western blotting further found that overexpression of miR-34a-5p reduced the protein expression levels of p-PI3K and p-AKT, while overexpression of PLCD3 showed the opposite trend. In addition, combined with the effect of the PI3K/AKT pathway inhibitor BIO (IC50 = 5.95 µM), the results showed that overexpression of miR-34a-5p increased the inhibitory effects of BIO on p-PI3K and p-AKT protein expression, while overexpression of PLCD3 significantly reversed these inhibitory effects. Overall, the miR-34a-5p/PLCD3 axis may mediate the PI3K/AKT pathway in regulating cartilage homeostasis in synovial osteoarthritis. These data indicate that miR-34a-5p/PLCD3 may be a new prognostic factor in the pathology of synovial osteoarthritis.

A Germline-Targeting Chimpanzee SIV Envelope Glycoprotein Elicits a New Class of V2-Apex Directed Cross-Neutralizing Antibodies.

HIV-1 and its SIV precursors share a broadly neutralizing antibody (bNAb) epitope in variable loop 2 (V2) at the envelope glycoprotein (Env) trimer apex. Here, we tested the immunogenicity of germ line-targeting versions of a chimpanzee SIV (SIVcpz) Env in human V2-apex bNAb heavy-chain precursor-expressing knock-in mice and as chimeric simian-chimpanzee immunodeficiency viruses (SCIVs) in rhesus macaques (RMs). Trimer immunization of knock-in mice induced V2-directed NAbs, indicating activation of V2-apex bNAb precursor-expressing mouse B cells. SCIV infection of RMs elicited high-titer viremia, potent autologous tier 2 neutralizing antibodies, and rapid sequence escape in the canonical V2-apex epitope. Six of seven animals also developed low-titer heterologous plasma breadth that mapped to the V2-apex. Antibody cloning from two of these animals identified multiple expanded lineages with long heavy chain third complementarity determining regions that cross-neutralized as many as 7 of 19 primary HIV-1 strains, but with low potency. Negative stain electron microscopy (NSEM) of members of the two most cross-reactive lineages confirmed V2 targeting but identified an angle of approach distinct from prototypical V2-apex bNAbs, with antibody binding either requiring or inducing an occluded-open trimer. Probing with conformation-sensitive, nonneutralizing antibodies revealed that SCIV-expressed, but not wild-type SIVcpz Envs, as well as a subset of primary HIV-1 Envs, preferentially adopted a more open trimeric state. These results reveal the existence of a cryptic V2 epitope that is exposed in occluded-open SIVcpz and HIV-1 Env trimers and elicits cross-neutralizing responses of limited breadth and potency. IMPORTANCE An effective HIV-1 vaccination strategy will need to stimulate rare precursor B cells of multiple bNAb lineages and affinity mature them along desired pathways. Here, we searched for V2-apex germ line-targeting Envs among a large set of diverse primate lentiviruses and identified minimally modified versions of one chimpanzee SIV Env that bound several human V2-apex bNAb precursors and stimulated one of these in a V2-apex bNAb precursor-expressing knock-in mouse. We also generated chimeric simian-chimpanzee immunodeficiency viruses and showed that they elicit low-titer V2-directed heterologous plasma breadth in six of seven infected rhesus macaques. Characterization of this antibody response identified a new class of weakly cross-reactive neutralizing antibodies that target the V2-apex, but only in occluded-open Env trimers. The existence of this cryptic epitope, which in some Env backgrounds is immunodominant, needs to be considered in immunogen design.

Retracted: Fangchinoline Promotes Autophagy and Inhibits Apoptosis in Osteoporotic Rats.

An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures.Reference:Wenjun Zhu, Wenge Ding, Xiaojun Shang, Ding Zhu, Xiaoyu Dai. Fangchinoline Promotes Autophagy and Inhibits Apoptosis in Osteoporotic Rats. Med Sci Monit, 2019; 25: 324-332. DOI: 10.12659/MSM.912624.

Serum calcium-phosphorus product for predicting the risk of osteoporotic vertebral compression fractures in elderly patients: a retrospective observational study.

BACKGROUND: This study retrospectively analyzed and evaluated the potential correlations of serum calcium, serum phosphorus, and calcium-phosphorus product (Ca-P product) with the incidence of osteoporotic vertebral compression fractures (OVCFs), with the aim of exploring whether the Ca-P product can be used as a serological indicator to predict the risk of OVCFs. METHODS: This study randomly enrolled 400 elderly patients in our hospital with OVCFs and 400 patients with hip and knee arthroplasty due to femoral head necrosis or osteoarthritis from August 2013 to April 2021. Age, sex, past medical history, and admission biochemical indicators, including albumin, blood urea nitrogen, serum creatinine, serum calcium and serum phosphorus, were collected for statistical analysis. RESULTS: Albumin, serum calcium, serum phosphorus, Ca-P product, corrected serum calcium and corrected Ca-P product were lower in the OVCF group than in the non-OVCF group (P < 0.05). Multivariate logistic regression analysis showed that low values of serum calcium, serum phosphorus, Ca-P product, corrected blood calcium, and corrected Ca-P product can all be risk factors for OVCF. The ROC curve showed that the Ca-P product and corrected Ca-P product were effective in predicting the risk of OVCFs. The predictive value of the Ca-P product was the best; the cutoff point was 29.88, the sensitivity was 0.72 and the specificity was 0.62. The cutoff point of the corrected Ca-P product was 30.50, the sensitivity was 0.74, and the specificity was 0.62. CONCLUSION: The Ca-P product and corrected Ca-P product can be used as serological indicators to predict the risk of OVCFs in elderly individuals. Early clinical interventions targeting this risk factor can further reduce the risk of OVCFs. Also, timely and regular testing of the serum calcium and phosphorus level is recommended and encouraged for this group of people.

Preoperative erythrocyte sedimentation rate in patients with rheumatoid arthritis predicts deep vein thrombosis following total knee arthroplasty.

PURPOSE: To thoroughly evaluate preoperative risk factors for deep venous thrombosis (DVT) in patients with knee rheumatoid arthritis (RA) undergoing unilateral total knee arthroplasty (TKA). METHODS: Clinical data of 106 patients with knee RA who underwent unilateral TKA from August 2014 to October 2020 were collected. All patients received ultrasonic examination of the veins of both lower extremities on the third day after TKA and were divided into DVT and non-DVT groups. The associations between age, gender, body mass index (BMI), history of diabetes/hypertension, common serum lipid levels, indicators related to coagulation function, blood viscosity, erythrocyte sedimentation rate (ESR) and postoperative DVT were statistically compared and analyzed. RESULTS: ESR was significantly correlated with DVT risk after TKA (OR = 1.844, 95% CI = 1.022-2.981, P = 0.019). Receiver operating characteristic (ROC) curve analysis showed the optimal cut-off point of ESR for predicting DVT was 42 mm/h with a sensitivity of 95.5% and specificity of 66.7%. CONCLUSION: An increased preoperative ESR value is a risk factor for DVT in patients with knee RA following unilateral TKA. Pre-surgery control of ESR level and prevention of postoperative DVT in these patients are worthy of attention.

Exact Association Between Preoperative Blood Viscosity and Postoperative Deep Venous Thrombosis Risk in Knee Osteoarthritis Patients: A 10-Year Retrospective Study.

Several lines of evidence have suggested a sustainable relationship between blood viscosity (BV) and deep vein thrombosis (DVT). But there was a lack of data on the association of preoperative BV and postoperative acute DVT. For patients who accepted total knee arthroplasty (TKA) caused by primary knee osteoarthritis (KOA), this study tried to investigate whether preoperative BV relevant parameters might affect DVT risk following TKA. We reviewed a total of 750 consecutive KOA patients treated by unilateral TKA in our hospital from March 2010 to May 2020. All patients undergoing TKA were routinely examined by the color Doppler ultrasound on the third postoperative day and were assigned into DVT and non-DVT groups. Statistical comparisons of BV relevant parameters which mainly including whole BV (low, midst, and high shear rates), plasma viscosity, whole blood reductive viscosity (BRV; low, midst, and high shear rates) were made comprehensively. It could be found that low whole BRV (low shear rate) before TKA was significantly related to postoperative DVT risk in all patients, especially in female patients after stratifying by gender (p < .05). Our results implied that low whole BRV might be a remarkable risk factor of DVT in primary KOA patients after TKA. Timely and effective DVT prophylaxis for these patients is much required.

Evaluation of Deep Vein Thrombosis Risk Factors After Arthroscopic Posterior Cruciate Ligament Reconstruction: A Retrospective Observational Study.

We evaluated the risk factors of deep venous thrombosis (DVT) after knee arthroscopic posterior cruciate ligament (PCL) reconstruction in patients with only PCL injury. From August 2014 to December 2020, a total of 172 patients who had accepted knee arthroscopic PCL reconstruction underwent the color Doppler ultrasound of bilateral lower-extremities deep veins on 3 days postoperatively. Based on the inspection results, patients were divided into DVT group (18 males and 8 females, mean age 43.62 years) and non-DVT group (108 males and 38 females, mean age 33.96 years). The potential associations of DVT risk and age, gender, body mass index (BMI), diabetes, hypertension, smoking and other factors were analyzed. An old age (OR = 1.090; 95% CI = 1.025-1.158; P = 0.006), a high BMI (OR = 1.509; 95% CI = 1.181-1.929; P = 0.001) and an increased post-surgery D-dimer (OR = 5.034; 95% CI = 2.091-12,117; P ≤ 0.001) value were significantly associated with an elevated DVT risk after knee arthroscopic PCL reconstruction. Increased age, BMI, and postoperative D-dimer were risk factors of DVT following knee arthroscopic PCL reconstruction in patients with only PCL injury.

Achievement of narrow-band blue-emitting phosphors KScSr1-y Ca y Si2O7:Bi3+ by the migration of luminescence centers.

In recent years, efforts have been made to develop narrow-band emission phosphors with excellent performance. Herein, a series of KScSr1-y Ca y Si2O7:0.07Bi3+ narrow-band phosphors were synthesized by a co-substitution method, and the crystal structure, the occupancy of activated ions and luminescence properties were studied in detail. The substitution of Ca2+ for Sr2+ ions resulted in the migration of the activated Bi3+ from the K site to Sr site, accompanied by the regulation of the emission peak from 410 nm to 455 nm, the peak emission half width from 52 nm to 40 nm, and the color purity from the original 78% to 88%. In addition, a warm white LED with low CCT = 3401 K, CRI = 95.5, and CIE color coordinates of (0.3447, 0.3682) has been obtained through the combination of KSS0.6C0.4S:0.07Bi3+ with a commercial green and red phosphor on a UV (370 nm) chip. The results not only provided a strategy based on the manipulation of chemical composition and crystal structure to tune spectral distribution, but also broadens the choice of activators of narrow-band blue-emitting phosphors.

Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth.

Neutralizing antibodies elicited by HIV-1 coevolve with viral envelope proteins (Env) in distinctive patterns, in some cases acquiring substantial breadth. We report that primary HIV-1 envelope proteins-when expressed by simian-human immunodeficiency viruses in rhesus macaques-elicited patterns of Env-antibody coevolution very similar to those in humans, including conserved immunogenetic, structural, and chemical solutions to epitope recognition and precise Env-amino acid substitutions, insertions, and deletions leading to virus persistence. The structure of one rhesus antibody, capable of neutralizing 49% of a 208-strain panel, revealed a V2 apex mode of recognition like that of human broadly neutralizing antibodies (bNAbs) PGT145 and PCT64-35S. Another rhesus antibody bound the CD4 binding site by CD4 mimicry, mirroring human bNAbs 8ANC131, CH235, and VRC01. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design.

The correlation between the Th17/Treg cell balance and bone health.

With the ageing of the world population, osteoporosis has become a problem affecting quality of life. According to the traditional view, the causes of osteoporosis mainly include endocrine disorders, metabolic disorders and mechanical factors. However, in recent years, the immune system and immune factors have been shown to play important roles in the occurrence and development of osteoporosis. Among these components, regulatory T (Treg) cells and T helper 17 (Th17) cells are crucial for maintaining bone homeostasis, especially osteoclast differentiation. Treg cells and Th17 cells originate from the same precursor cells, and their differentiation requires involvement of the TGF-ß regulated signalling pathway. Treg cells and Th17 cells have opposite functions. Treg cells inhibit the differentiation of osteoclasts in vivo and in vitro, while Th17 cells promote the differentiation of osteoclasts. Therefore, understanding the balance between Treg cells and Th17 cells is anticipated to provide a new idea for the development of novel treatments for osteoporosis.

Gut Microbiome and Osteoporosis.

Gut microbiome refers to the microbes that live in human digestive tract and are symbiotic with the human body. They participate in the regulation of various physiological and pathological processes of the human body and are associated with various diseases. The pathological process of osteoporosis is affected by gut microbes. The molecular mechanisms of osteoporosis mainly include: 1) Intestinal barrier and nutrient absorption (involving SCFAs). 2) Immunoregulation (Th-17 and T-reg cells balance). 3) Regulation of intestinal-brain axis (involving 5-HT). Gut microbes can increase bone mass and improve osteoporosis by inhibiting osteoclast proliferation and differentiation, inducing apoptosis, reducing bone resorption, or promoting osteoblast proliferation and maturation. However, the therapeutic effect of gut microbes on osteoporosis remains to be further proven. At present, some of the findings on the impact of gut microbes on osteoporosis has been applied in clinical, including early diagnosis and intervention of osteoporosis and adjuvant therapy. In this article, we reviewed the molecular mechanisms underlying the regulatory effect of gut microbes on osteoporosis and the clinical practice of using gut microbes to improve bone health.

Mobility of metal(loid)s in Pb/Zn tailings under different revegetation strategies.

Metal tailings are potential sources of strong environmental pollution. In situ remediation involves the installation of a plant cover to stabilize materials and pollutants. Whether metal(loid)s are effectively immobilized in remediated tailing ponds submitted to heavy rainfall remains uncertain. In this study, tailing materials were collected from bare tailings (control), grass-planted (G) and grass-shrub planted (GS) areas on a former Pb/Zn mine site. Batch column experiments were performed with three rainfall intensities of 0.36, 0.48, and 0.50 mL min-1 for 18 d in the lab. The pH, Eh, Cd, Pb, Zn and As concentration in leachate were recorded. Selected leached tailing materials were finally characterized. Results showed that leachates from control were strongly acidic (pH 3.11-4.65), and that Cd, Pb, Zn and As were quickly released at high rate (e.g., 945 mg L-1 Zn). During the experiment up to 4% Cd present in the material was released and almost 1% Zn. With material collected from the G area, leachates were even more acidic (2.16-2.84) with a rainfall intensity of 0.50 mL min-1 and exhibited a high redox potential (588-639 mV). However, concentrations of metals in leachates were much lower than that in the control, except for Zn (e.g., 433 mg L-1), and they tended to decrease with time. Cumulative leaching rate was still relatively high (e.g., 0.68% Cd; 0.75% Zn) during the first eight days (stage I). However, with the GS treatment, leachate pH gradually raised from acid to alkaline values (3.9-8.2) during stage I, then remained high until the end of the experiment (stage II). Also, amounts of elements released during the 18 d were low in general. The releasing ratios of Cd (R2 > 0.95), Pb (R2 > 0.95), As (R2 > 0.87), and Zn (R2 > 0.90) fitted well with a two-constant model. In conclusion, under subtropical climate with heavy rainfall, phytostabilization is effective but immobilization of metals is higher with a combination of grass and shrub than with only grass to reduce leaching of As and Zn.

Genetic estrogen receptor alpha gene PvuII polymorphism in susceptibility to knee osteoarthritis in a Chinese Han population: A southern Jiangsu study.

BACKGROUND: Knee osteoarthritis (KOA) is the most prevalent type of arthritis and genetic factors play an important role in KOA pathogenesis. Some studies have reported the association of estrogen receptor alpha (ESRα) gene polymorphism and KOA susceptibility in different populations. This study was designed to verify whether ESRα gene polymorphism (rs2234693) was associated with primary KOA in a Chinese Han population living in the south of Jiangsu. METHODS: A case-control association study on single nucleotide polymorphism (SNP) rs2234693 was performed, and a total of 1953 subjects (1033 OA cases and 920 controls) were genotyped. Allele and genotype frequencies were compared between KOA cases and control participants. RESULTS: SNP rs2234693 was significantly associated with KOA in the dominant genetic model (TT + TC vs. CC) in all the subjects (odds ratio (OR) = 1.30; 95% confidence interval (CI) = 1.02-1.66; P = .03), and T allele frequency was also higher compared with allele C (OR = 1.38; 95% CI = 1.06-1.80; P = .02). After stratification by gender, there was no evident difference between the two groups in female and male subjects (P > .05). With a stratification for KOA severity, the combined genotype (TT + TC) (OR = 1.47; 95% CI = 1.12-1.94; P < .01) and T allele (OR = 1.61; 95% CI = 1.19-2.19; P < .01) were evidently associated with mild KOA, but not with severe KOA. CONCLUSIONS: ESRα gene is of considerable importance in the pathogenesis of early-stage KOA in a Chinese Han population living in southern Jiangsu.

Advances in the understanding of the role of type-H vessels in the pathogenesis of osteoporosis.

BACKGROUND: Angiogenesis in the bone and its role in bone metabolic plays a fundamental role in the pathology of osteoporosis. Type-H vessels have been reported to exhibit distinct morphological, molecular, and functional properties. This review is aimed to illustrate the relationship between type-H vessels in the bone and bone metabolism. METHODS: This manuscript reviews the articles on in vitro and in vivo experiments concerning the topic of type-H vessels and osteoporosis, and other researches in the area published by the author within the time frame from 2014 to 2019. RESULTS: Current literatures have demonstrated that age-related loss of type-H vessels plays a critical role in the pathogenesis of osteoporosis. Impaired bone mass can be reserved by enhancing the formation of type-H vessels. Activation of the Notch and Hif-1α signaling pathway in bone tissue and exogenous PDGF-BB treatment increase the number of type-H vessels, along with the restoration of bone mass. The effects of osteoblasts and low-intensity pulsed ultrasound (LIPUS) on type-H vessels remain to be further studied. CONCLUSIONS: These studies support unique functions for type-H vessels in the bone that may enable new therapeutic approaches to osteoporosis.

Novel Transmitted/Founder Simian-Human Immunodeficiency Viruses for Human Immunodeficiency Virus Latency and Cure Research.

A robust simian-human immunodeficiency virus (SHIV)-macaque model of latency is critical to investigate eradicative and suppressive strategies that target HIV-1 Env. To this end, we previously reported a novel strategy for constructing SHIVs that bear primary or transmitted/founder (TF) Envs with modifications at Env residue 375 that enable efficient replication in Indian rhesus macaques (RM). Such TF SHIVs, however, have not been examined for their suitability for HIV-1 latency and cure research. Here, we evaluate two promising TF SHIVs, SHIV.D.191859 and SHIV.C.CH848, which encode TF subtype D and C HIV-1 Envs, respectively, for their viral kinetics and persistence during suppressive combination antiretroviral therapy (cART) and treatment interruption in RM. Our results suggest that the viral kinetics of these SHIVs in RM during acute, early, and chronic infection, and upon cART initiation, maintenance and discontinuation, mirror those of HIV-1 infection. We demonstrate consistent early peak and set point viremia, rapid declines in viremia to undetectable plasma titers following cART initiation, infection of long-lived cellular subsets and establishment of viral latency, and viral rebound with return to pretreatment set point viremia following treatment interruption. The viral dynamics and reservoir biology of SHIV.D.191859, and to a lesser extent SHIV.C.CH848, during chronic infection, cART administration, and upon treatment interruption suggest that these TF SHIVs are promising reagents for a SHIV model of HIV-1 latency and cure.IMPORTANCE Simian-human immunodeficiency viruses (SHIVs) have been successfully used for over 2 decades to study virus-host interactions, transmission, and pathogenesis in rhesus macaques. The majority of Env trimers of most previously studied SHIVs, however, do not recapitulate key properties of transmitted/founder (TF) or primary HIV-1 isolates, such as CCR5 tropism, tier 2 neutralization resistance, and native trimer conformation. Here, we test two recently generated TF SHIVs, SHIV.D.191859 and SHIV.C.CH848, which were designed to address these issues as components of a nonhuman primate model of HIV-1 latency. We conclude that the TF SHIV-macaque model reflects several hallmarks of HIV and SIV infection and latency. Results suggest that this model has broad applications for evaluating eradicative and suppressive strategies against the HIV reservoir, including Env-specific interventions, therapeutic vaccines, and engineered T cells.

Associations of Serum Lipids and Deep Venous Thrombosis Risk After Total Knee Arthroplasty in Patients With Primary Knee Osteoarthritis.

Deep venous thrombosis (DVT) of the lower extremities is a common complication after total knee arthroplasty (TKA). This study aimed to investigate the potential associations between serum lipids and the risk of DVT after TKA in patients with primary knee osteoarthritis (OA). A total of 431 patients who received TKA caused by primary knee OA were randomly enrolled. According to the results of the color Doppler ultrasound of bilateral lower extremities deep veins on the third day postoperatively, patients were divided into DVT and non-DVT groups. Comparisons of preoperative serum levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1, and apolipoprotein B were then performed by the Student's t test, χ2 test, and multivariate logistic regression analysis. For females, DVT patients had a higher serum LDL-C level at baseline (P = .043) compared with non-DVT patients. A higher LDL-C value was significantly associated with an elevated DVT risk following TKA in female patients (P = .037). In female patients with primary knee OA, preoperative serum LDL-C level may have an association with DVT risk after TKA. The relatively small male sample size may limit the accuracy of the findings.

LncRNA MSC-AS1 promotes osteogenic differentiation and alleviates osteoporosis through sponging microRNA-140-5p to upregulate BMP2.

This study aims to explore the role of lncRNA MSC-AS1/microRNA-140-5p/BMP2 regulatory loop in promoting osteogenic differentiation of BMSCs. BMSCs were isolated from bone marrow of mice. Expression levels of MSC-AS1, microRNA-140-5p and BMP2 during osteogenic differentiation were detected by qRT-PCR. Meanwhile, regulatory effect of MSC-AS1 on osteogenic differentiation was detected through ALP staining and alizarin red staining. The binding sites between microRNA-140-5p and MSC-AS1 as well as between microRNA-140-5p and BMP2 were predicted by TargetScan, which were further confirmed by dual-luciferase reporter gene assay. In addition, protein levels of MSC-AS1/microRNA-140-5p/BMP2 were detected by Western blot. Finally, rescue experiments were conducted to clarify the regulatory effects of MSC-AS1/microRNA-140-5p/BMP2 axis on osteogenic differentiation. MSC-AS1 and BMP2 were found to be remarkably up-regulated during osteogenic differentiation, while microRNA-140-5p was conversely down-regulated. Meanwhile, knockdown of MSC-AS down-regulated expression levels of osteogenesis-associated genes and weakened the mineralization capacity of BMSCs. MicroRNA-140-5p was verified to bind to the 3'UTR of MSC-AS1 and BMP2 genes. Knockdown of MSC-AS1 in BMSCs could reduce the expression of microRNA-140-5p, while knockdown of microRNA-140-5p also down-regulated BMP2 level. In addition, co-silence of MSC-AS1 and microRNA-140-5p reversed the inhibitory effect of MSC-AS1 knockdown on osteogenic differentiation and protein levels of p-Smad1/5/8, RUNX2 and Osterix. MSC-AS1 might promote the osteogenic differentiation of BMSCs through sponging microRNA-140-5p to up-regulate BMP2, thus alleviating the progression of osteoporosis.

Angiogenesis Changes in Ovariectomized Rats with Osteoporosis Treated with Estrogen Replacement Therapy.

To investigate whether angiogenesis changes in early menopausal osteoporosis treated with estrogen replacement therapy, 120 rats were randomly divided into five groups: sham operation group (SHAM), ovariectomy group (OVX), and ovariectomy plus three different estrogen doses replacement therapy groups (OVX + E2). We detected the bone microarchitecture and measured the expression levels of estrogen receptor beta (ERß), vascular endothelial growth factor (VEGF), osteoprotegerin (OPG), and receptor activator of NF-κB ligand (RANKL). CD31 immunofluorescence and silica gel perfusion imaging were used to analyze the vascular distribution. We confirmed that the femur BMD of ovariectomized rats was significantly lower than SHAM group and OVX+E2 groups. After estrogen therapy, the local microvascular formation increased after estrogen treatment in a dose dependent manner. ERß was downregulated and VEGF was upregulated, positively correlated with estrogen dosage. We successfully constructed an osteoporosis model of ovariectomized rats with estrogen replacement therapy. We also found angiogenesis changed in early menopausal osteoporosis treated with estrogen replacement therapy. We indicated that estrogen replacement therapy increased angiogenesis through VEGF upregulation. However, we observed that, at the highest doses of estrogen studied, increased angiogenesis was associated with a decrease in BMD, the underlying mechanisms of which remain unclear.

Characterization of serotypes and virulence genes of Haemophilus parasuis isolates from Central Vietnam.

Haemophilus parasuis is a commensal Gram-negative bacterial pathogen in the upper respiratory tract of pigs, which causes Glässer's disease. More than 15 serotypes of H. parasuis have been identified with apparent differences in virulence. In this research, we surveyed the prevalence and distribution of serotypes and known virulence genes of the H. parasuis isolates collected from sick and healthy pigs in Quang Binh and Thua Thien Hue provinces in Central Vietnam. By using bacterial isolation and polymerase chain reaction (PCR), 56 out of 814 (6.9%) samples were positive for H. parasuis. The most prevalent serotypes were serotype 5 (15/56, 26.8%), followed by serotype 2 (13/56, 23.2%) and serotype 4 (10/56, 17.9%). The vta1 was the most frequently detected virulence gene which was present in 62.5% of the strains, followed by vta3 (42.9%), vta2 (39.3%), HPM-1371 (35.7%), capD (30.4%), HPM-1372 (12.5%), lsgB and HPM-1373 (both shared 8.9%). Strong correlations between some serotypes and known virulence genes were observed, in which virulence genes HPM-1371, HPM-1372, vta3, vta2 and capD were mainly clustered in serotypes 5/12, and vta2 clustered in serotype 2. This study presents the first baseline information on the epidemiological characteristics of H. parasuis isolates from Central Vietnam.