Search

The purpose of this longitudinal follow-up study was to investigate the risk of ischemic stroke nationwide in patients with seropositive rheumatoid arthritis (RA) and controls who were matched in age and sex. Patient data were collected from the National Health Insurance Service (NHIS) Health Screening (HEALS) cohort. Using the International Classification of Diseases code M05 (seropositive RA), with a prescription of any disease-modifying anti-rheumatic drug (DMARD), RA was identified. A total of 2,765 patients and 13,825 control subjects were included in our study. The 12-year incidence of ischemic stroke in each group was calculated using the Kaplan–Meier method. The risk ratio of ischemic stroke was estimated using Cox proportional hazards regression. Sixty-four patients (2.31%) in the seropositive RA group and 512 (3.70%) in the control group experienced ischemic stroke (P < 0.001) during the follow-up period. The hazard ratio of ischemic stroke in the seropositive RA group was 1.32 (95% confidence interval (CI), 1.02–1.73) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in the seropositive RA group was 1.40 (95% CI, 1.07–1.82) after adjusting for demographics and comorbid medical disorders. According to the subgroup analysis, the hazard ratios of ischemic stroke risks in the female and hypertensive subgroups were 1.44 (95% CI, 1.05–1.97) and 1.66 (95% CI, 1.16–2.38), respectively. In the non-diabetes and non-dyslipidemia subgroups, the corresponding hazard ratios of ischemic stroke were 1.47 (95% CI, 1.11–1.95) and 1.43 (95% CI, 1.07–1.91). Seropositive RA patients have an increased risk of ischemic stroke. In female, hypertension, non-diabetes, and non-dyslipidemia RA subgroups, even without the traditional risk factors for stroke (except for hypertension), increased the risk, which could be potentially attributed to RA. [ABSTRACT FROM AUTHOR]

Abstract: Increased permeability of the brain–blood barrier (BBB) in the piriform cortex (PC) has been reported in various animal models of temporal lobe epilepsy. Since BBB disruption induced by epileptogenic insult has not fully clarified, we attempted to determine whether changes in BBB-related molecules are associated with vasogenic edema in the PC. One day after status epilepticus (SE), PC neurons and astrocytes showed a pyknotic nucleus and shrunken cytoplasm accompanied by vasogenic edema. At this time point, SMI-71 (an endothelial barrier antigen) immunoreactivity had decreased in the PC. Prior to vasogenic edema formation (12h after SE), dystrophin immunoreactivity disappeared within astrocytes, while the change in glial fibrillary acidic protein immunoreactivity was negligible. However, glucose transporter-1 (an endothelial cell marker) had increased at 12h after SE. These findings indicate that dysfunction of dystrophin induced by SE may result in endothelial and astroglial damage with BBB breakdown and increase vascular permeability, leading to vasogenic edema that is involved in pathogenesis of epileptogenesis. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this nationwide longitudinal cohort study is to determine the risk of congestive heart failure (CHF) associated with a seropositive rheumatoid arthritis (RA) population in Korea. Methods: In this study, National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data from 2002 to 2003 were used. The cohort was followed up with for 12 years until December of 2015. Seropositive RA was defined as a patient prescribed with a disease-modifying anti-rheumatic drug (DMARD) among patients with the International Classification of Diseases code M05 (seropositive RA). Patients who were diagnosed before 2004 were excluded. The seropositive RA group consisted of 2765 patients, and a total of 13,825 patients were in the control group. The Kaplan–Meier method was used to calculate the 12-year CHF incidence rate for each group. A Cox proportional hazards regression analysis was used to estimate the hazard ratio of CHF. Results: The hazard ratio of CHF in the seropositive RA group was 2.41 (95% confidence interval (CI): 1.40–4.14) after adjusting for age and sex. The adjusted hazard ratio of CHF in the seropositive RA group was 2.50 (95% CI: 1.45–4.30) after adjusting for age, sex, income, and comorbidities. In females aged ≥65 and aged <65, the incidence rates in the non-hypertension, non-diabetes mellitus, and non-dyslipidemia subgroups were significantly higher in the seropositive RA group than in the control group. Conclusions: This nationwide longitudinal cohort study shows an increased risk of CHF in patients with seropositive RA. [ABSTRACT FROM AUTHOR]

We aimed to develop a biocompatible treatment to overcome the limitations of polymethyl methacrylate (PMMA) vertebroplasty for osteoporotic compression fracture patients. We synthesized an injectable hydrogel containing PMMA. Mesenchymal stem cell (MSC) spheroids were included in the injectable PMMA‐doped gel (= PMMA‐doped spheroid gel). In vitro, the osteogenic/anti‐inflammatory effects of the embedded spheroids were investigated by the quantitative real‐time polymerase chain reaction method. In vivo, we used ovariectomy (OVX)‐induced osteoporotic rats with injured femurs to investigate the pain‐relief effects. The OVX rats were divided into four groups according to the materials injected (non, PMMA, PMMA gel, and PMMA‐spheroid gel) into the lesion. The immunofluorescence (IF) intensity levels of painful markers in dorsal root ganglia (DRG) were measured. In vitro, a volumetric ratio of the gel of 8 (gel):2 (PMMA) was non‐cytotoxic for MSCs and promoted the expression of osteogenic/anti‐inflammatory markers. In vivo, the values of several bone parameters in the PMMA‐doped spheroid gel group showed remarkable increases compared to those in the PMMA group. In addition, the IF intensity levels of the painful markers were noticeably decreased in the PMMA‐spheroid gel group. We, therefore, suggest that this treatment can be useful for osteoporotic vertebral compression fracture patients. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the anti-inflammatory effect of tegoprazan (TEGO) in lipopolysaccharide (LPS)-stimulated bone-marrow-derived macrophages (BMMs). To this end, compared to methylprednisolone (MP; positive control), we evaluated whether TEGO effectively differentiates LPS-stimulated BMMs into M2-phenotype macrophages. Moreover, the expression of pro- and anti-inflammatory cytokines genes influenced by TEGO was measured using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. TEGO was found to reduce nitric oxide (NO) production in BMMs significantly. In addition, TEGO significantly decreased and increased the gene expression levels of pro-inflammatory and anti-inflammatory cytokines, respectively. In addition, we evaluated the phosphorylated values of the extracellular signal-regulatory kinase (ERK) and p38 in the mitogen-activated protein (MAP) kinase signaling pathway through Western blotting. TEGO significantly reduced the phosphorylated values of the ERK and p38. In other words, TEGO suppressed the various pro-inflammatory responses in LPS-induced BMMs. These results show that TEGO has the potential to be used as an anti-inflammatory agent. [ABSTRACT FROM AUTHOR]

The purpose of this nationwide longitudinal follow-up study is to investigate the relationship between Parkinson's disease (PD) and congestive heart failure (CHF) patients in Korea. Patient data were collected using the National Health Insurance Service (NHIS) Health Screening (HEALS) cohort. The International Classification of Diseases 10-CM code G-20 distinguished 6475 PD patients who were enrolled in the PD group. After removing 1039 patients who were not hospitalized or attended an outpatient clinic less than twice, the total number of participants was reduced to 5436 individuals. Then, 177 patients diagnosed before 1 January 2004 were removed for relevancy, leaving us with 5259 PD patients. After case–control matching was completed using 1:5 age- and gender-coordinated matching, 26,295 people were chosen as part of the control group. The Cox proportional hazards regression analysis and the Kaplan–Meier technique were used to assess the risk of CHF in patients with Parkinson's disease. After controlling for age and gender, the hazard ratio of CHF in the PD group was 5.607 (95% confidence interval (CI), 4.496–6.993). After that, the hazard ratio of CHF in the PD group was modified against for comorbid medical disorders, resulting in a value of 5.696 (95% CI, 4.566–7.107). In subgroup analysis, CHF incidence rates were significantly increased in the PD group compared to the control group (males and females; aged ≥ 65 and <65; the non-diabetes and diabetes, hypertension and non-hypertension, and dyslipidemia and non-dyslipidemia subgroups). This nationwide longitudinal study shows a higher incidence rate of CHF in PD patients. [ABSTRACT FROM AUTHOR]

We aimed to investigate whether mitochondrial dysfunction in extracellular cerebrospinal fluid (CSF), which is associated with autophagy and mitophagy, might be involved in neurological outcomes in adult patients with hemorrhagic moyamoya disease (MMD) whose pathogenesis related to poor outcomes is not well-known. CSF samples were collected from 43 adult MMD patients and analyzed according to outcomes at 3 months. Fluorescence-activated cell sorter analysis (FACS) and the JC-1 red/green ratio were used to assess mitochondrial cells and intact mitochondrial membrane potential (MMP). We performed quantitative real-time polymerase chain reaction and Western blotting analyses of autophagy and mitophagy-related markers, including HIF1α, ATG5, pBECN1, BECN1, BAX, BNIP3L, DAPK1, and PINK1. Finally, FACS analysis with specific fluorescence-conjugated antibodies was performed to evaluate the potential cellular origin of CSF mitochondrial cells. Twenty-seven females (62.8%) with a mean age of 47.4 ± 9.7 years were included in the study. Among 43 patients with hemorrhagic MMD, 23 (53.5%) had poor outcomes. The difference in MMP was evident between the two groups (2.4 ± 0.2 in patients with poor outcome vs. 3.5 ± 0.4 in patients with good outcome; p = 0.02). A significantly higher expression (2–ΔCt) of HIF1α, ATG5, DAPK1 followed by BAX and BNIP3L mRNA and protein was also observed in poor-outcome patients compared to those with good outcomes. Higher percentage of vWF-positive mitochondria, suggesting endothelial cell origins, was observed in patients with good outcome compared with those with poor outcome (25.0 ± 1.4% in patients with good outcome vs. 17.5 ± 1.5% in those with poor outcome; p < 0.01). We observed the association between increased mitochondrial dysfunction concomitant with autophagy and mitophagy in CSF cells and neurological outcomes in adult patients with hemorrhagic MMD. Further prospective multicenter studies are needed to determine whether it has a diagnostic value for risk prediction. [ABSTRACT FROM AUTHOR]

In this study, we aimed to investigate the recovery after traumatic spinal cord injury (SCI) by inducing cellular differentiation of transplanted neural stem cells (NSCs) into neurons. We dissociated NSCs from the spinal cords of Fisher 344 rat embryos. An injectable gel crosslinked with glycol chitosan and oxidized hyaluronate was used as a vehicle for NSC transplantation. The gel graft containing the NSC and positively charged gold nanoparticles (pGNP) was implanted into spinal cord lesions in Sprague–Dawley rats (NSC‐pGNP gel group). Cellular differentiation of grafted NSCs into neurons (stained with β‐tubulin III [also called Tuj1]) was significantly increased in the NSC‐pGNP gel group (***p < 0.001) compared to those of two control groups (NSC and NSC gel groups) in the SCI conditions. The NSC‐pGNP gel group showed the lowest differentiation into astrocytes (stained with glial fibrillary acidic protein). Regeneration of damaged axons (stained with biotinylated dextran amines) within the lesion was two‐fold higher in the NSC‐pGNP gel group than that in the NSC gel group. The highest locomotor scores were also found in the NSC‐pGNP gel group. These outcomes suggest that neuron‐inducing pGNP gel graft embedding embryonic spinal cord‐derived NSCs can be a useful type of stem cell therapy after SCI. [ABSTRACT FROM AUTHOR]

Objectives: In this study, we study the transplantation of tauroursodeoxycholic acid (TUDCA)‐induced M2‐phenotype (M2) macrophages and their ability to promote anti‐neuroinflammatory effects and functional recovery in a spinal cord injury (SCI) model. Methods: To this end, compared to the granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), we evaluated whether TUDCA effectively differentiates bone marrow–derived macrophages (BMDMs) into M2 macrophages. Results: The M2 expression markers in the TUDCA‐treated BMDM group were increased more than those in the GM‐CSF‐treated BMDM group. After the SCI and transplantation steps, pro‐inflammatory cytokine levels and the mitogen‐activated protein kinase (MAPK) pathway were significantly decreased in the TUDCA‐induced M2 group more than they were in the GM‐CSF‐induced M1 group and in the TUDCA group. Moreover, the TUDCA‐induced M2 group showed significantly enhanced tissue volumes and improved motor functions compared to the GM‐CSF‐induced M1 group and the TUDCA group. In addition, biotinylated dextran amine (BDA)–labelled corticospinal tract (CST) axons and neuronal nuclei marker (NeuN) levels were increased in the TUDCA‐induced M2 group more than those in the GM‐CSF‐induced M1 group and the TUDCA group. Conclusions: This study demonstrates that the transplantation of TUDCA‐induced M2 macrophages promotes an anti‐neuroinflammatory effect and motor function recovery in SCI. Therefore, we suggest that the transplantation of TUDCA‐induced M2 macrophages represents a possible alternative cell therapy for SCI. [ABSTRACT FROM AUTHOR]

[Display omitted] • The synthesized aligned poly(lactic-co-glycolic acid) nanofibrous mat containing gold nanoparticles provides hydrophilic characteristics. • The nanofibrous mat conjugated with gold nanoparticles decreased the inflammatory responses. • The planted nanofibrous mat noticeably increased the cell survival and neuronal differentiation of transplanted neural stem cells. Transplanted cells rarely survive because of the inflammatory cytokines after spinal cord injury. To increase the survival, we synthesized a hydrophilic and aligned nanofibrous mat. We electrospun thiolate (SH)/aligned (A) poly(lactic-co-glycolic acid) (PLGA) nanofibrous mats. The PLGA-SH (A) nanofibrous mats were conjugated with gold nanoparticles (GNPs) to increase the hydrophilicity. The contact angle is decreased from 105.3° ± 5.2 (for randomly directional PLGA mats) to 28.1° ± 2.8 (for PLGA-GNP (A) mats). Green fluorescent protein (GFP)-expressing neural progenitor cells (NPCs) were dissociated from the embryonic spinal cords of Fisher 344 rats. We embedded the embryonic spinal-cord-derived NPCs in glycol chitosan (gC)-oxidized hyaluronate (oHA) hydrogels (=NPC graft). The NPC graft was transplanted into spinal-cord-injured Sprague-Dawley rats. Afterwards, the aligned PLGA-GNP nanofibrous mat was positioned onto the NPC-grafted region (=Injury + NPC graft + PLGA-GNP (A) nanofibrous mat (INP) group). We also added Injury (=I) and Injury + NPC graft (=IN) groups as control groups. The survival outcomes of transplanted NPCs were noticeably increased in the INP group compared to those in the IN group. We suggest a separate implanting therapy of NPCs and a hydrophilic PLGA-GNP (A) nanofibrous mat for spinal cord injuries. [ABSTRACT FROM AUTHOR]

[Display omitted] • PLGA-SH nanofibers were conjugated with SH-β-CD containing DEX and RVC. • PLGA-CD-DEX-RVC nanofibers were transplanted into the sciatic nerve in CCI rats. • PLGA-CD-DEX-RVC nanofibers can restrict drugs flow to motor nerves. • PLGA-CD-DEX-RVC nanofibers can relieve pain for extended periods. • PLGA-CD-DEX-RVC nanofibers can serve as a useful treatment for neuropathic pain. To treat neuropathic pain, dexamethasone (DEX, an anti-inflammatory agent) and ropivacaine (RVC, a local anesthetic) are injected into the epidural space of the patient's spine in clinics. This combinatorial drug treatment is short-acting and subjected to uncontrolled drug flow to the motor nerve. To overcome these limitations, we developed thiolate poly(lactic-co-glycolic acid) (PLGA-SH) nanofibers conjugated with mono-(6-mercapto-6-deoxy)-β-cyclodextrin (SH-β-CD) containing DEX and RVC. The anti-inflammatory effect in the PGLA-CD-DEX-RVC nanofibers was assessed using bone marrow-derived macrophages (BMMs) in vitro. We injured the sciatic nerve in Sprague Dawley (SD) rats to create a Chronic constriction injury (CCI) model for an in vivo assessment. Neuropathic pain was evaluated by testing the cold allodynia response, and by Immunofluorescence (IF) staining of transient receptor potential vanilloid 1 (TRPV1, a nociceptor marker) and ionized calcium-binding adaptor molecule 1 (iba1, a microglia marker). In this study, the synthesized PLGA-CD-DEX-RVC nanofibers sustainably released RVC and DEX for more than 48 h. The PLGA-CD-DEX-RVC nanofibers suppressed polarized M1 macrophages and increased polarized M2 macrophages. The allodynia cold sensitivity was consistently relieved in the PLGA-CD-DEX-RVC group for 14 days. Moreover, the expressions of the TRPV1 and iba1 were remarkably reduced in the PLGA-CD-DEX-RVC group on day 14. PLGA-CD-DEX-RVC nanofibers can restrict drugs flow to motor nerves and of relieving pain for extended periods. We suggest that PLGA-CD-DEX-RVC nanofibers can serve as a useful treatment for neuropathic pain in clinics. [ABSTRACT FROM AUTHOR]

Abstract: Astrocytic tumor is one of the most common primary tumors of the adult brain. Although there are several biochemical markers for the categorization of astrocytic tumor, few markers are used for histopathological diagnosis. Therefore, we evaluated glial fibrillary acidic protein (GFAP)-δ, a product of alternative splicing variants of GFAP-α, as a diagnostic marker. GFAP-δ immunoreactive (GFAP-δ+) astrocyte was rarely detected in tissue samples from autopsy controls. In tissue samples from patients with low-grade astrocytic tumor (grades I and II), GFAP-δ+ cells appeared stellate, polygonal or round shape. In tissue samples from patients with high-grade astrocytic tumor (grades III and IV), GFAP-δ+ cells showed round or spindle shape. GFAP-δ immunoreactivities in grades III and IV astrocytic tumor cells were increased by 1.4- and 1.7-fold in comparison to grade I astrocytic tumor cells. GFAP-δ immunoreactivity was also observed in cell bodies along the margins of astrocytic tumor showing normal histological findings, even though astroglia had normal morphology (showing strong GFAP and glutamine synthase immunoreactivities and a stellate shape with well-developed processes). Furthermore, the malignancy of astrocytic tumor was directly correlated with the degree of GFAP-δ immunoreactivity. These findings suggest that GFAP-δ may be a useful diagnostic marker for the evaluation of functional cataplasia or proliferation of astrocytic tumor. [Copyright &y& Elsevier]

Neuroinflammation forms a glial scar following a spinal cord injury (SCI). The injured axon cannot regenerate across the scar, suggesting permanent paraplegia. Molecular chirality can show an entirely different bio-function by means of chiral-specific interaction. In this study, we report that d-chiral glutathione (D-GSH) suppresses the inflammatory response after SCI and leads to axon regeneration of the injured spinal cord to a greater extent than l-chiral glutathione (L-GSH). After SCI, axon regrowth in D-GSH-treated rats was significantly increased compared with that in L-GSH-treated rats (*** p < 0.001). Secondary damage and motor function were significantly improved in D-GSH-treated rats compared with those outcomes in L-GSH-treated rats (** p < 0.01). Moreover, D-GSH significantly decreased pro-inflammatory cytokines and glial fibrillary acidic protein (GFAP) via inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway compared with L-GSH (*** p < 0.001). In primary cultured macrophages, we found that D-GSH undergoes more intracellular interaction with activated macrophages than L-GSH (*** p < 0.001). These findings reveal a potential new regenerative function of chiral GSH in SCI and suggest that chiral GSH has therapeutic potential as a treatment of other diseases. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (GNPs) have been widely studied to inhibit differentiation into osteoclasts. However, reports of the inhibitory effects of silver nanoparticles (SNPs) during the process of differentiation into osteoclasts are rare. We compared the inhibitory effect of GNPs and SNPs during the process of differentiation into osteoclasts. Bone marrow-derived cells were differentiated into osteoclasts by the receptor activator of the nuclear factor-kappa-Β ligand (RANKL). The inhibitory effect of GNPs or SNPs during the process of differentiation into osteoclasts was investigated using tartrate-resistant acid phosphatase (TRAP) and actin ring staining. The formation of TRAP positive (+) multinuclear cells (MNCs) with the actin ring structure was most inhibited in the SNP group. In addition, the expression of specific genes related to the differentiation into osteoclasts, such as c-Fos, the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), TRAP, and Cathepsin K (CTSK) were also inhibited in the SNP groups. As a result, the levels related to differentiation into osteoclasts were consistently lower in the SNP groups than in the GNP groups. Our study suggests that SNPs can be a useful material for inhibiting differentiation into osteoclasts and they can be applied to treatments for osteoporosis patients. [ABSTRACT FROM AUTHOR]

The rates of pseudarthrosis remain high despite recent advances in bone graft substitutes for spinal fusion surgery. The aim of this single center, non-randomized, open-label clinical trial was to determine the feasibility of combined use of stromal vascular fraction (SVF) and β-tricalcium phosphate (β-TCP) for patients who require posterior lumbar interbody fusion (PLIF) and pedicle screw fixation. Two polyetheretherketone (PEEK) cages were inserted into the intervertebral space following complete removal of the intervertebral disc. The PEEK cage (SVF group) on the right side of the patient was filled with β-TCP in combination with SVF, and the cage on the left side (control group) was filled with β-TCP alone. Fusion rate and cage subsidence were assessed by lumbar spine X-ray and CT at 6 and 12 months postoperatively. At the 6-month follow-up, 54.5% of the SVF group (right-sided cages) and 18.2% of the control group (left-sided cages) had radiologic evidence of bone fusion (p = 0.151). The 12-month fusion rate of the right-sided cages was 100%, while that of the left-sided cages was 91.6% (p = 0.755). Cage subsidence was not observed. Perioperative combined use of SVF with β-TCP is feasible and safe in patients who require spinal fusion surgery, and it has the potential to increase the early bone fusion rate following spinal fusion surgery. [ABSTRACT FROM AUTHOR]

Abstract: Background: Recently, calcium phosphate (CaP) cement, instead of polymethylmethacrylate, has been injected into the compressed vertebral body. Calcium phosphate may have the potential for ectopic or heterotopic ossification and, thus, injected CaP cement can induce unwanted heterotopic ossifications in the human body. Case Description: The authors describe 2 cases of heterotopic ossifications after vertebroplasty using CaP in osteoporotic vertebral compression fractures. We performed percutaneous vertebroplasty using CaP cement in a 69-year-old woman with L2 compression fracture and an 80-year-old man with L1 compression fracture. Follow-up radiologic studies for both cases showed that heterotopic ossifications had developed around the CaP-augmented vertebral bodies and that the cemented vertebral bodies had recollapsed. Also, subsequent vertebral compression fractures had occurred. Conclusions: We suggest that heterotopic ossification may be complications of vertebroplasty with CaP. Therefore, we strongly recommended that the patients who undergo a vertebroplasty with CaP need strict observation. [Copyright &y& Elsevier]

Tauroursodeoxycholic acid (TUDCA) is a US FDA-approved hydrophilic bile acid for the treatment of chronic cholestatic liver disease. In the present study, we investigate the effects of TUDCA on the proliferation and differentiation of osteoblasts and its therapeutic effect on a mice model of osteoporosis. Following treatment with different concentrations of TUDCA, cell viability, differentiation, and mineralization were measured. Three-month-old female C57BL/6 mice were randomly divided into three groups (n = 8 mice per group): (i) normal mice as the control group, (ii) ovariectomy (OVX) group (receiving phosphate-buffered saline (PBS) treatment every other day for 4 weeks), and (iii) OVX group with TUDCA (receiving TUDCA treatment every other day for 4 weeks starting 6 weeks after OVX). At 11 weeks post-surgery, serum levels of procollagen type I N-terminal propeptides (PINP) and type I collagen crosslinked C-telopeptides (CTX) were measured, and all mice were sacrificed to examine the distal femur by micro-computed tomography (CT) scans and histology. TUDCA (100 nM, 1 µM) significantly increased the proliferation and viability of osteoblasts and osteoblast differentiation and mineralization when used in vitro. Furthermore, TUDCA neutralized the detrimental effects of methylprednisolone (methylprednisolone-induced osteoblast apoptosis). In the TUDCA treatment group the PINP level was higher and the CTX level was lower, but these levels were not significantly different compared to the PBS treatment group. Micro-CT and histology showed that the TUDCA treatment group preserved more trabecular structures in the distal femur compared to the PBS treatment group. In addition, the TUDCA treatment group increased the percentage bone volume with respect to the total bone volume, bone mineral density, and mice distal femur trabeculae compared with the PBS treatment group. Taken together, our findings suggest that TUDCA may provide a favorable effect on bones and could be used for the prevention and treatment of osteoporosis. [ABSTRACT FROM AUTHOR]