The therapeutic effects of mesenchymal stem cells (MSCs) in musculoskeletal diseases (MSDs) have been verified in many human and animal studies. Although some tissues contain MSCs, the number of cells harvested from those tissues and rate of proliferation in vitro are not enough for continuous transplantation. In order to produce and maintain stable MSCs, many attempts are made to induce differentiation from pluripotent stem cells (iPSCs) into MSCs. In particular, it is also known that the paracrine action of stem cell-secreted factors could promote the regeneration and differentiation of target cells in damaged tissue. MicroRNAs (miRNAs), one of the secreted factors, are small non-coding RNAs that regulate the translation of a gene. It is known that miRNAs help communication between stem cells and their surrounding niches through exosomes to regulate the proliferation and differentiation of stem cells. While studies have so far been underway targeting therapeutic miRNAs of MSDs, studies on specific miRNAs secreted from MSCs are still minimal. Hence, our ultimate goal is to obtain sufficient amounts of exosomes from iPSC-MSCs and develop them into therapeutic agents, furthermore to select specific miRNAs and provide safe cell-free clinical setting as a cell-free status with purpose of delivering them to target cells. This review article focuses on stem cell therapy on MSDs, specific microRNAs regulating MSDs and updates on novel approaches.

The therapeutic effects of mesenchymal stem cells (MSCs) in musculoskeletal diseases (MSDs) have been verified in many human and animal studies. Although some tissues contain MSCs, the number of cells harvested from those tissues and rate of proliferation in vitro are not enough for continuous transplantation. In order to produce and maintain stable MSCs, many attempts are made to induce differentiation from pluripotent stem cells (iPSCs) into MSCs. In particular, it is also known that the paracrine action of stem cell-secreted factors could promote the regeneration and differentiation of target cells in damaged tissue. MicroRNAs (miRNAs), one of the secreted factors, are small non-coding RNAs that regulate the translation of a gene. It is known that miRNAs help communication between stem cells and their surrounding niches through exosomes to regulate the proliferation and differentiation of stem cells. While studies have so far been underway targeting therapeutic miRNAs of MSDs, studies on specific miRNAs secreted from MSCs are still minimal. Hence, our ultimate goal is to obtain sufficient amounts of exosomes from iPSC-MSCs and develop them into therapeutic agents, furthermore to select specific miRNAs and provide safe cell-free clinical setting as a cell-free status with purpose of delivering them to target cells. This review article focuses on stem cell therapy on MSDs, specific microRNAs regulating MSDs and updates on novel approaches.

BACKGROUND: Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naïve newly-diagnosed type 2 diabetes mellitus. METHODS: A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was measured at week 24. RESULTS: The reduction in the levels of HbA1c was −1.62%±0.07% in the vogmet group and −1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of <6.5% (P=0.002) or <7% (P=0.039). Glycemic variability was also significantly improved with vogmet treatment, estimated by M-values (P=0.004). Gastrointestinal adverse events and hypoglycemia (%) were numerically lower in the vogmet-treated group. Moreover, a significant weight loss was observed with vogmet treatment compared with metformin (−1.63 kg vs. −0.86 kg, P=0.039). CONCLUSION: Vogmet is a safe antihyperglycemic agent that controls blood glucose level effectively, yields weight loss, and is superior to metformin in terms of various key glycemic parameters without increasing the risk of hypoglycemia.
Blood Glucose ; Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Hemoglobin A, Glycosylated ; Humans ; Hypoglycemia ; Metformin ; Weight Loss

PURPOSE: The purpose of this report is to organize the history of Korean Mothersafe, a professional teratology information center. Throughout its domestic and international activities, Mothersafe has firm role to write journals and books, to provide counseling, to run educational courses on maternal and fetal toxicology, and so on. This paper delineates the achievements in last ten years and discusses the vision of Mothersafe. METHODS: In order to formulate the accomplishments of Korean Mothersafe, the volume of counseling calls are carefully reviewed by their contents, counselees, and the consultation results, etc. Textbooks and journals based on the data from Mothersafe are evaluated. Other roles of the Mothersafe, such as hosting symposium and running public programs are also noted. RESULTS: Korean Mothersafe provided 76,555 counseling to 45,933 expectant women and 30,622 breast-feeding women. The database has total 52,130 enrollments from 2010 to 2019. A total of 33 papers are published regarding medication, alcohol, smoking, radiation, etc. A specialized book on maternal-fetal toxicology was published and teratology part of obstetrics textbook was updated. Education programs and symposiums were held and primary care programs for expectant parents are run by Mothersafe. CONCLUSION Korean Mothersafe has contributed to safe environments for numerous pregnant and breast-feeding women regarding medication, drinking, smoking, and other hazardous substances. The huge database provided evidence for researches, textbooks and seminars, etc. Korean Mothersafe is now facing a new challenge to go forward through social dynamics with many issues regarding prevention and continuance of pregnancy, abortion, and so on.

Separation anxiety (SA) is a serious behavioral problem in dogs. In this study, salivary cortisol was studied to determine if the owner's odor or voice could reduce SA in dogs. Twenty-eight dogs with SA were divided into three groups: group 1 (control), group 2 (with owner's clothes during the separation period; SP) and group 3 (a recording of the owner's voice was played during SP). The dog's saliva was collected after the owner and their dog were in the experimental room for 5 min (PRE). The dog was then separated from the owner for 20 min and saliva collected four times at intervals of 5 min (SP1-4). Finally, the owner was allowed back into the room to calm the dog for 5 min, after which saliva was collected (POST). Evaluation of salivary cortisol concentrations by ELISA revealed that the ratios of SP1 concentration to PRE or POST concentrations were significantly higher in group 1 than in group 2 or 3. Additionally, the concentrations of SP1-PRE and SP1-POST among groups differed significantly. These findings indicate that the owner's odor or voice may be helpful to managing stress in dogs with SA.
Acoustic Stimulation* ; Animals ; Anxiety, Separation* ; Clothing ; Dogs* ; Enzyme-Linked Immunosorbent Assay ; Hydrocortisone* ; Odors ; Physiology ; Problem Behavior ; Saliva ; Voice

PURPOSE: We propose an equation that predicts graft function after kidney transplantation by using donated kidney volume and recipient body surface area (BSA). MATERIALS AND METHODS: Included were 261 cases of living kidney transplantation between 2007 and 2009. Preoperative computed tomography scans were performed and the donated kidney volume was measured by use of a three-dimensional reconstruction program (Ripidia). The estimated glomerular filtration rate (eGFR) was calculated by using the modification of diet in renal disease formula. Donated kidney volume, preoperative renal function, and demographic factors of both donors and recipients were evaluated as predictors. RESULTS: The mean ages of the donors and recipients were 40.8 and 41.6 years, respectively. The mean donated kidney volume and donated kidney volume/recipient BSA ratio were 153.4 mL and 96.9 mL/m2, respectively. Mean preoperative and postoperative 12-month eGFR of recipients were 7.1 and 59.7 mL/min, respectively, and the mean preoperative eGFR of donors was 92.2 mL/min. Donated kidney volume/recipient BSA ratio, donor age, and recipient gender were the significant predictors of eGFR level (p<0.001) and eGFR<45 mL/min at postoperative 12 months (p=0.005, p<0.001, and p=0.006). From the multiple linear regression equation and predicted probability from logistic regression, we could calculate the equation for the ratio of living donor kidney volume to recipient BSA on graft function. CONCLUSIONS: Graft kidney volume/recipient BSA ratio, donor age, and recipient gender were predictors of graft function 12 months after kidney transplantation. Although we are concerned only with the preoperative, this equation model could help physicians to counsel patients concerning their postoperative prognosis and to avoid insufficient volume donations.
Body Surface Area* ; Delayed Graft Function ; Demography ; Diet ; Glomerular Filtration Rate ; Humans ; Kidney Transplantation ; Kidney* ; Linear Models ; Living Donors* ; Logistic Models ; Organ Size ; Prognosis ; Tissue Donors ; Transplantation ; Transplants*

BACKGROUND/AIMS: Reactivation of hepatitis B virus (HBV) has been reported in HBV surface antigen (HBsAg)-positive patients undergoing chemotherapy, as well as HBsAg-negative patients with antibodies against HBV core antigen (HBcAg) and/or HBsAg (HBsAb). Chemotherapy-including rituximab-has recently been identified as a predictive factor for HBV reactivation in HBsAg-negative patients with malignant lymphoma. The aim of our study was to identify the factors predictive of HBV reactivation after chemotherapy in patients with malignant lymphoma. METHODS: We conducted a retrospective analysis of medical records from patients diagnosed with malignant lymphoma at Gachon University Gil Medical Center in City, County from January 2005 to December 2010. We subsequently determined HBsAg, HBsAb and anti-HBc status in the 196 patients treated with chemotherapy. RESULTS: The mean age of the patients was 57.3 +/- 14.5 years; 56.3% were male. A total of 172 of 196 (88%) patients in the study population were HBsAg (+) prior to chemotherapy. Three patients (3/11, 27.3%) in the HBsAg (+) group had confirmed HBV reactivation after chemotherapy. In addition, 26 of 196 (13%) patients in the study population tested HBcAg (+) positive prior to chemotherapy. One patient (1/15, 6.7%) in the HBsAg (-)/HBcAb (+) group had confirmed HBV reactivation. In the four patients with HBV reactivation, infection was resolved after treatment with 0.5 mg entecavir or 100 mg lamivudine. CONCLUSIONS: Reactivation of HBV after systemic chemotherapy can occur in HBsAg (-) patients. We recommend that malignant lymphoma patients undergoing chemotherapy be screened for HBV infection status, including HBcAg, and followed closely to prevent HBV reactivation.
Antibodies ; Antigens, Surface ; Drug Therapy* ; Hepatitis B Core Antigens ; Hepatitis B Surface Antigens ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis* ; Humans ; Lamivudine ; Lymphoma* ; Male ; Medical Records ; Retrospective Studies

PURPOSE: Vascular disorders and viral infections are considered the main causes of sudden hearing loss (SHL), although its pathogenesis remain unclear. Treatments include carbogen inhalation and lipo-prostaglandin E1 (lipo-PGE1), both of which have circulation-enhancing effects. We investigated the effectiveness of carbogen inhalation and lipo-PGE1 in SHL. MATERIALS AND METHODS: This retrospective review included 202 patients with idiopathic SHL who visited our clinic within 14 days of symptom onset between January 2006 and June 2010. All patients received oral prednisolone for 10 days. Of the 202 patients, 44 received no additional treatment, 106 received additional carbogen inhalation, and 52 received additional lipo-PGE1. Hearing improvement was measured using Siegel's criteria. RESULTS: Overall recovery rates were 67.9% in the carbogen group, 53.8% in the lipo-PGE1 group, and 52.3% in the steroid-only control group (p=0.097). Limited to type 1 and type 2 categories of Sigels's criteria, the carbogen group had a significantly higher recovery rate (53.8%) than the lipo-PGE1 group (26.9%) and the steroid-only control group (38.6%) (p=0.005). CONCLUSION: Carbogen inhalation added to steroid was a more effective treatment than lipo-PGE1 added to steroid or steroid alone in patients with SHL.
Alprostadil ; Hearing ; Hearing Loss, Sudden* ; Humans ; Inhalation* ; Prednisolone ; Retrospective Studies ; Therapeutic Uses*

PURPOSE: Hyperhomocysteinemia is known as a risk factor for atherosclerosis. Preclinical arteriosclerosis is noted and premature atherosclerosis is known to be accelerated in Kawasaki disease (KD) patients. Genetic polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene result in elevated plasma homocysteine concentrations and are known to be associated with the development of coronary artery disease. Our hypothesis is that single nucleotide polymorphisms (SNPs) of the MTHFR gene are related to the development of KD and coronary artery lesions (CALs). METHODS: For this study, we selected 3 candidate single nucleotide polymorphisms (SNPs) (rs2274976, rs1801131, and rs1801133) of MTHFR. These SNPs are located on chromosome 1p36.3. We included 101 KD patients and 306 healthy adults as controls in this study. CALs were seen in 38 patients. Genotypes of the selected SNPs were determined by direct sequencing and analyzed with SNPAlyze. RESULTS: The genetic distribution and allelic frequency of the 3 MTHFR SNPs (rs2274976, rs1801131, and rs1801133) were not significantly different in patients with KD compared to the control group (P=0.71, 0.17, and 0.96, respectively). There was no difference in the genetic distribution of the MTHFR SNPs between the normal control group and the CAL group (P=0.43, 0.39, 0.52 respectively). CONCLUSION: The genetic distribution of the MTHFR SNPs (rs2274976, rs1801131, and rs1801133) was not different in the KD group compared to the control group. In addition, the genetic distribution of these SNPs was not different in the CAL group compared to the control group in the Korean population.
Adult ; Arteriosclerosis ; Atherosclerosis ; Coronary Artery Disease ; Coronary Vessels ; Genotype ; Homocysteine ; Humans ; Hyperhomocysteinemia ; Methylenetetrahydrofolate Reductase (NADPH2) ; Mucocutaneous Lymph Node Syndrome ; Oxidoreductases ; Plasma ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Risk Factors ; Tetrahydrofolates

OBJECTIVE: To verify the feasibility of initial parameters of ultrasonography or electromyography for the prediction of effect after steroid injection therapy in a carpal tunnel syndrome (CTS) patient. METHOD: We recruited individuals with clinical and electrodiagnostic evidence of CTS. Results from the Boston self-assessment questionnaire, median motor and sensory nerve conduction studies, and median nerve ultrasonography were evaluated at baseline, 1 month, and 6 months after injection. Evaluation of median nerve ultrasonography parameters included measurements taken at the maximal swelling point (MS), 2 cm proximal from MS (2MS), and 12 cm proximal from MS (12MS), and its ratio (MS/12MS, 2MS/12MS) was calculated. The correlation between improvement of the symptom score after treatment and baseline parameters was estimated. RESULTS: Fourteen individuals (14 women, mean age 53.8 years) with 22 affected wrists were enrolled. After steroid injection therapy, clinical and electromyographic parameters showed significant improvements at 1 month or 6 months after injection, and ultrasonographic parameters showed significant changes in maximal area and area ratio (MS/12MS) of the median nerve. Symptom score improvement showed a positive correlation in the initial 2MS and ratio of 2MS/12MS after 6 months (p<0.05). CONCLUSION: Most of the improvements occurred during the first month after injection and lasted up to 6 months. The initial median nerve swelling and its ratio may be a useful predictor of response after steroid injection.
Boston ; Carpal Tunnel Syndrome ; Electromyography ; Female ; Humans ; Median Nerve ; Neural Conduction ; Self-Assessment ; Wrist ; Surveys and Questionnaires