Bone-Targeting AAV-Mediated Gene Silencing in Osteoclasts for Osteoporosis Therapy

Improper activity of bone-resorbing osteoclasts results in low bone density and deterioration of bone structure, which increase the risk of fractures. Anti-resorptive therapies targeting osteoclasts have proven effective in preserving bone mass, but these therapeutic agents lead to defective new bone formation and numerous potential side effects. In this study, we demonstrate that recombinant adeno-associated virus, serotype 9 (rAAV9) can deliver to osteoclasts an artificial microRNA (amiR) that silences expression of key osteoclast regulators, RANK (receptor activator for nuclear factor κB) and cathepsin K (rAAV9.amiR-rank, rAAV9.amiR-ctsk), to prevent bone loss in osteoporosis. As rAAV9 is highly effective for the transduction of osteoclasts, systemic administration of rAAV9 carrying amiR-rank or amiR-ctsk results in a significant increase of bone mass in mice. Furthermore, the bone-targeting peptide motif (Asp)14 or (AspSerSer)6 was grafted onto the AAV9-VP2 capsid protein, resulting in significant reduction of transgene expression in non-bone peripheral organs. Finally, systemic delivery of bone-targeting rAAV9.amiR-ctsk counteracts bone loss and improves bone mechanical properties in mouse models of postmenopausal and senile osteoporosis. Collectively, inhibition of osteoclast-mediated bone resorption via bone-targeting rAAV9-mediated silencing of ctsk is a promising gene therapy that can preserve bone formation and mitigate osteoporosis, while limiting adverse off-target effects.ope

6 Months and 12 Months Persistence with Intravenous Injection of Ibandronate -Preliminary Study-

Objectives: This study was to evaluate persistence of quarterly intravenous injection of ibandronate and factors relative to persistence. Methods: In this retrospective study, 136 postmenopausal women with osteopenia or osteoporosis who received injections of ibandronate between August 2007 and October 2008 were evaluated for persistence to intravenous ibandronate, reasons for their choice of ibandronate, reasons for stopping medication, acute inflammatory reaction, and other medications after stopping ibandronate by chart review, questionnaire, and telephone interview. Results: Persistence at 6 months and 12 months was 88.1% and 82.8%, respectively. Patients chose ibandronate for reasons of convenience of a quarterly injection, GI trouble, and the inconvenience of oral bisphosphonates, and other medications. Reasons for stopping ibandronate included adverse effects, inconvenience of a direct visit to the hospital at quarterly intervals, cost, and so on. Acute inflammatory reactions were more noticeable in the non-persistent group than in the persistent group, and a previous history of oral bisphosphonate did not affect occurrence of acute inflammatory reactions. Conclusion: Intravenous ibandronate is a good alternative to oral osteoporosis medications due to the convenience for quarterly injection and no GI trouble, and may increase persistence of osteoporosis medicationope

Design and Implementation of a Mobile-based Sarcopenia Prediction and Monitoring System

This paper confirmed the technical reliability of mobile-based sarcopenia prediction and monitoring system. In implementing the developed system, we designed using only sensors built into a smartphone without a separate external device. The prediction system predicts the possibility of sarcopenia without visiting a hospital by performing the SARC-F survey, the 5-time chair stand test, and the rapid tapping test. The Monitoring system tracks and analyzes the average walking speed in daily life to quickly detect the risk of sarcopenia. Through this, it is possible to rapid detection of undiagnosed risk of undiagnosed sarcopenia and initiate appropriate medical treatment. Through prediction and monitoring system, the user may predict and manage sarcopenia, and the developed system can have a positive effect on reducing medical demand and reducing medical costs. In addition, collected data is useful for the patient-doctor communication. Furthermore, the collected data can be used for learning data of artificial intelligence, contributing to medical artificial intelligence and e-health industry.ope

Pectinase-treated Panax ginseng ameliorates hydrogen peroxide-induced oxidative stress in GC-2 sperm cells and modulates testicular gene expression in aged rats

Background: To investigate the effect of pectinase-treated Panax ginseng (GINST) in cellular and male subfertility animal models. Methods: Hydrogen peroxide (H2O2)-induced mouse spermatocyte GC-2spd cells were used as an in vitro model. Cell viability was measured using MTT assay. For the in vivo study, GINST (200 mg/kg) mixed with a regular pellet diet was administered orally for 4 mo, and the changes in the mRNA and protein expression level of antioxidative and spermatogenic genes in young and aged control rats were compared using real-time reverse transcription polymerase chain reaction and western blotting. Results: GINST treatment (50 μg/mL, 100 μg/mL, and 200 μg/mL) significantly (p < 0.05) inhibited the H2O2-induced (200 μM) cytotoxicity in GC-2spd cells. Furthermore, GINST (50 μg/mL and 100 μg/mL) significantly (p < 0.05) ameliorated the H2O2-induced decrease in the expression level of antioxidant enzymes (peroxiredoxin 3 and 4, glutathione S-transferase m5, and glutathione peroxidase 4), spermatogenesis-related protein such as inhibin-α, and specific sex hormone receptors (androgen receptor, luteinizing hormone receptor, and follicle-stimulating hormone receptor) in GC-2spd cells. Similarly, the altered expression level of the above mentioned genes and of spermatogenesis-related nectin-2 and cAMP response element-binding protein in aged rat testes was ameliorated with GINST (200 mg/kg) treatment. Taken together, GINST attenuated H2O2-induced oxidative stress in GC-2 cells and modulated the expression of antioxidant-related genes and of spermatogenic-related proteins and sex hormone receptors in aged rats. Conclusion: GINST may be a potential natural agent for the protection against or treatment of oxidative stress-induced male subfertility and aging-induced male subfertility.ope

Two cases of catamenial pneumothorax

Endometriosis is usually found in pelvic cavity such as in ovary. But, endometriosis has been described in other organs, although rare, such as intestine, kidney, lung, liver, gall bladder, and pancreas. Catamenial pneumothorax is defined as a recurrent pneumothorax within 72 hours of onset of menstruation and it is a rare cause of spontaneous pneumothorax. We, hereby, report two cases of successfully treated catamenial pneumothorax by gonadotrophin releasing hormone agonist with progestin or oral pill after surgical treatment.ope

Retrospective Multicenter Study on Clinical Aspects in Premature Ovarian Failure

Objectives: Premature ovarian failure (POF) is a syndrome defined as the cessation of ovarian function before the age of 40 years that is characterized by amenorrhoea associated with elevated gonadotropin levels. The aim of this study was to compare clinical manifestation of primary amenorrhea and secondary amenorrhea group. Methods: This study was designed as a retrospective multicenter study of 262 women with premature ovarian failure. Sixty eight women with primary amenorrhea and 194 women with secondary amenorrhea were evaluated and hormonal level, lipid profile, bone mineral density, and pregnancy rates were compared. Results: The estradiol level was markedly lower in primary amenorrhea than secondary amenorrhea. The pregnancy rate of 43.3% before the diagnosis in secondary amenorrhea was markedly higher than the rate of 0% in primary amenorrhea. The pregnancy rates after treatment was 5.9% in primary amenorrhea, but 1.0% after diagnosis and 2.8% after treatment in secondary amenorrhea. The pregnancy rate after hormonal treatment was 3.7% in total, 8.3% in primary amenorrhea, and 2.8% in secondary amenorrhea. In nine cases of pregnancy, seven cases were after estrogen-progestin (EP), one case was after clomiphene citrate and one case was after EP/human menopausal gonodotropin (hMG). And In nine cases of pregnancy, six cases resulted from oocyte donation. The prevalence of osteopenia/osteoporosis was markedly higher in primary amenorrhea than in secondary amenorrhea. Conclusion: Premature ovarian failure has negative influences on the physical and psychological health of young patients. Effective management should include earlier diagnosis and intensive medical intervention to relieve symptoms of estrogen deficiency and to treat long-term disease such as osteoporosis and in assisted pregnancy by oocyte donation.ope

Serum Thyroid Stimulating Hormone Levels Are Associated with the Presence of Coronary Atherosclerosis in Healthy Postmenopausal Women

Objectives : Menopause is a natural aging process causing estrogen deficiency, accelerating atherogenic processes including dyslipidemia. Prevalence of thyroid dysfunction is also high in postmenopausal women, and it is known to elevate the risk of cardiovascular disease (CVD). Therefore, we are to study on the associations in between serum thyroid stimulating hormone (TSH) and prevalence of CVD in postmenopausal women who have normal thyroid function. Methods : We performed a retrospective review of 247 Korean postmenopausal women who visited the health promotion center from January, 2007 to December, 2009. Postmenopausal women with normal serum TSH were included in the study. Coronary atherosclerosis was assessed by 64-row multidetector computed tomography. Results : In multiple linear regression analysis, serum TSH was associated with serum triglyceride (TG) (β = 0.146, P = 0.023). In multiple logistic regression analysis, increasing age and serum TSH were associated with an increased risk of coronary atherosclerosis in euthyroid postmenopausal women (odds ratio [OR] = 1.107 [1.024-1.197], P = 0.011 and OR = 1.303 [1.024-1.658], P = 0.031, respectively). Conclusions : It revealed that significant predictor of serum TSH was serum TG, and increasing age and TSH were found to have associations with an increased risk of coronary atherosclerosis in euthyroid postmenopausal women. Screening and assessing risks for CVD in healthy postmenopausal women would be helpful before atherosclerosis develops.ope

Perceptions of postmenopausal symptoms and treatment options among middle-aged Korean women

PURPOSE: To investigate the perceptions of postmenopausal symptoms and treatment options among middle-aged Korean women. MATERIALS AND METHODS: This cross-sectional study included 2330 Korean women. The women were administered a structured questionnaire to collect sociodemographic data and information regarding menopause and its treatment. RESULTS: More than half (65%) of the participants perceived menopause as a disease, and 66.8% knew hormone therapy (HT) is available for menopausal symptom treatment. However, only 19.7% of participants visited clinics for HT. The most common reasons for having negative views about HT were its adverse reactions (47.3%) and concerns about developing cancer (41.1%). For symptom management, 36.5% of the participants tried lifestyle modification instead of HT. CONCLUSION: The majority of Korean women regarded menopause as a disease. They were aware of HT for menopausal symptom treatment, but the use of HT was relatively low. Education about the safety and positive effects of HT and the importance of professional healthcare should be provided.ope

Effects of sarcopenia and sarcopenic obesity on joint pain and degenerative osteoarthritis in postmenopausal women

This study aimed to identify the prevalence of sarcopenia, obesity, and sarcopenic obesity and examine their association with radiographic knee osteoarthritis (OA) and knee pain in Korean postmenopausal women. This cross-sectional study utilized the data from Korean National Health and Nutrition Examination Surveys 2009-2011. The participants were categorized into 4 groups based on body composition: either sarcopenic (appendicular skeletal muscle < 23%) or not, either obese (body mass index ≥ 25.0 kg/m2) or not. The prevalence of radiographic knee OA and knee pain was calculated. The effect of hormone replacement therapy (HRT) was also evaluated. The prevalence of radiographic knee OA, knee pain, and both were all highest in the sarcopenic obese group and lowest in the control group (61.49% vs. 41.54%, 39.11% vs. 27.55%, 32.04% vs. 17.82%, all p < 0.001). Without sarcopenia, obese women showed significantly higher ratio of radiographic knee OA only (57.64% vs. 41.54%, p < 0.001). With sarcopenia, the coexistence of obesity presented higher ratio of radiographic knee OA, knee pain, and both compared to sarcopenia without obesity (61.49% vs. 41.82%, 39.11% vs. 27.61%, 32.04% vs. 17.60%, all p < 0.001). The use of HRT for more than 1 year was not associated with radiographic knee OA, knee pain, or both (p = 0.147, 0.689 and 0.649, respectively). Obesity with sarcopenia had greater effect on knee OA compared to obesity without sarcopenia. Moreover, HRT use for more than 1 year was not associated with the prevalence of knee OA. Therefore, more efforts should focus on reducing body fat and increasing muscle in postmenopausal women with knee OA.ope

Changes in the Expression of TBP-2 in Response to Histone Deacetylase Inhibitor Treatment in Human Endometrial Cells

Histone deacetylase inhibitors (HDACi) induce apoptosis preferentially in cancer cells by caspase pathway activation and reactive oxygen species (ROS) accumulation. Suberoylanilide hydroxamic acid (SAHA), a HDACi, increases apoptosis via altering intracellular oxidative stress through thioredoxin (TRX) and TRX binding protein-2 (TBP-2). Because ROS accumulation, as well as the redox status determined by TBP-2 and TRX, are suggested as possible mechanisms for endometriosis, we queried whether SAHA induces apoptosis of human endometrial cells via the TRX-TBP-2 system in endometriosis. Eutopic endometrium from participants without endometriosis, and ectopic endometrium from patients with endometriosis, was obtained surgically. Human endometrial stromal cells (HESCs) and Ishikawa cells were treated with SAHA and cell proliferation was assessed using the CCK-8 assay. Real-time PCR and Western blotting were used to quantify TRX and TBP-2 mRNA and protein expression. After inducing oxidative stress, SAHA was applied. Short-interfering TRX (SiTRX) transfection was performed to see the changes after TRX inhibition. The mRNA and protein expression of TBP-2 was increased with SAHA concentrations in HESCs significantly. The mRNA TBP-2 expression was decreased after oxidative stress, upregulated by adding 2.5 μM of SAHA. The TRX/TBP-2 ratio decreased, apoptosis increased significantly, and SiTRX transfection decreased with SAHA. In conclusion, SAHA induces apoptosis by modulating the TRX/TBP-2 system, suggesting its potential as a therapeutic agent for endometriosis.ope