Topical minoxidil and dietary supplement for the treatment of chemotherapy-induced alopecia in childhood: a retrospective cohort study.

Chemotherapy-induced alopecia (CIA) is a common and debilitating condition in children, with limited research on its characteristics and treatment. Therefore, this study aims to describe the characteristics of pediatric patients with CIA and the treatment outcomes of topical minoxidil and L-cystine, medicinal yeast, and pantothenic acid complex-based dietary supplements (CYP). This retrospective cohort study analyzed data from patients who underwent high-dose conditioning chemotherapy followed by hematopoietic stem cell transplantation and were treated with either topical minoxidil or CYP for CIA between January 2011 and January 2022. Among the 70 patients evaluated, 61 (87.1%) experienced clinical improvement. Patients in the groups with superior treatment outcomes received a greater cumulative amount of minoxidil and underwent treatment for a more extended duration (P < 0.05) than those in the other groups. All 70 (100%) patients received topical minoxidil, and 42 (60%) were administered CYP. Hair thickness was significantly higher in the combination therapy group than in the minoxidil monotherapy group (21.4% vs. 9.3%, P = 0.02). However, only 3 (4.3%) patients reported mild and self-limiting adverse events. In conclusion, our study shows that minoxidil and CYP administration represent viable treatment options for pediatric CIA.

Hair loss after drug reaction with eosinophilia and systemic symptoms (DRESS): A multicentric retrospective case series.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous drug adverse reaction characterized by various cutaneous and systemic manifestations. However, reports on the various patterns of alopecia after DRESS are lacking. Thus, we aimed to describe cases of alopecia after DRESS and review the literature. This multicentric retrospective study reviewed the records of 182 patients diagnosed with DRESS from 2009 to 2021; of these, 10 who had alopecia after DRESS were included. Patients were diagnosed with permanent alopecia (n = 4), telogen effluvium (n = 5), and alopecia areata (n = 1), and were treated with topical minoxidil or alfatradiol (6; 60%), topical corticosteroids (3; 30%), dietary supplements (6; 60%), systemic corticosteroids (1; 10%), and intralesional corticosteroid injection (2; 20%). Although patients with permanent alopecia did not show hair regrowth after 6 months, those with telogen effluvium and alopecia areata experienced marked clinical improvement within 6 months. Various types of alopecia can persist over an extended period, even after the resolution of an acute episode of DRESS.

Lucidumol A, Purified Directly from Ganoderma lucidum, Exhibits Anticancer Effect and Cellular Inflammatory Response in Colorectal Cancer.

Colorectal cancer (CRC) is a deadly disease regardless of sex, and a few therapeutic approaches have been fully developed at advanced stages, even if some strategies have durable clinical benefits, such as immunotherapy and chemotherapy. Ganoderma lucidum has been recognized as an organism that suppresses tumors and inflammation; however, the molecular mechanisms induced by a triterpenoid in Ganoderma lucidum, Lucidumol A, have not yet been fully explored in CRC and inflammatory responses. To this end, we extracted Lucidumol A from Ganoderma lucidum and analyzed its anticancer effect and anti-inflammatory potential in CRC cell lines and RAW264.7 macrophage-derived cell lines, respectively. A series of in vitro experiments including cell survival, wound healing, and migration assays were performed to determine the role of Lucidumol A in the CRC cell line. We also analyzed inflammatory responses using qRT-PCR, Western Blot, and ELISA in RAW 264.7 macrophaged-derived cell lines exposed to various concentrations of Lucidumol A. Lucidumol A efficiently suppressed the metastatic potential of CRC at very low concentrations. Furthermore, significant anti-inflammatory activities were observed in Lucidumol A-treated RAW264.7 cells through modulation of inflammation-associated marker genes and cytokines. In conclusion, Lucidumol A plays an important role in Ganoderma lucidum-dependent tumor suppression and anti-inflammation, suggesting different strategies to treat CRC patients, and other diseases evoked by proinflammatory cytokines, despite the need to explore further its mechanism of action.

Postchemotherapy gross residual tumor in non-high-risk neuroblastoma: Clinical significance and the role of adjuvant therapy.

BACKGROUND: Although survival rate among patients with non-high-risk neuroblastoma is excellent, a gross residual tumor (GRT) is often present at the end of treatment. However, reliable data do not exist on the relevance of a GRT for the risk of progression and the role of adjuvant therapy for patients with GRT. METHODS: A retrospective review of 131 patients with non-high-risk neuroblastoma who underwent chemotherapy was performed. GRT was defined as >1 cm3 residual soft tissue density on end-of-chemotherapy scans. Progression-free survival (PFS) and overall survival (OS) rates were compared between patients with GRT and those without GRT. A proportional hazards model was also used to assess the effects of GRT and adjuvant therapies, including radiation and isotretinoin therapy on outcomes. RESULTS: GRT was found in 52 (40%) patients in the study cohort. Correlation was not found between GRT and outcomes (PFS; p = .954, OS; p = .222). In multivariable analysis, GRT remained a nonsignificant predictor of outcome after adjusting for confounders. Local radiation and isotretinoin therapy did not affect outcome for patients with GRT. However, within GRT subgroups, the degree of volume reduction, as well as absolute residual volume in the primary tumor after induction treatment, were significantly associated with outcomes. CONCLUSION: GRT in non-high-risk neuroblastoma may not indicate active disease that requires additional treatment. However, risk of progression is increased in patients with GRT whose response to treatment was less prominent, thus adjuvant therapy should be reserved only for those patients.

A Complex of Cirsium japonicum var. maackii (Maxim.) Matisum. and Thymus vulgaris L. Improves Menopausal Symptoms and Supports Healthy Aging in Women.

We evaluated the efficacy and safety of MS-10® for the treatment of menopausal symptoms. A double-blind randomized placebo-controlled clinical trial was performed in 71 premenopausal women for 4 and 12 weeks. A total of 12 individual menopausal symptom scores were assessed using the Kupperman index. MS-10 treatment effectively improved the symptoms by ∼48%. In addition, the quality of life of the women improved by 36% from four perspectives: vasomotor, psychosocial, physical, and sexual symptoms as evaluated using the menopause-specific quality of life (MenQoL) questionnaire. Our results show that MS-10 improves insulin-like growth factor-1 (IGF-1) and estrogen utilization through receptor activation, which are thought to have causative therapeutic effects on menopause and aging inhibition in women. Improvement of Enthotheline-1 (ET-1) in the blood after MS-10 intake led to an improvement in menopausal vascular symptoms. Improvements in bone formation and absorption markers such as osteocalcin, bone-specific alkaline phosphatase (BSALP), C-telopeptides of type I collagen (CTx), deoxypyridinoline (deoxyPYD), and N-telopeptides of type I collagen (NTx) in blood or urine indicate that MS-10 fundamentally improves bone health in women. By confirming the improvement of the psychological well-being index based on the improvement of stress hormone cortisol, MS-10 can solve causative psychological and physical stress-related symptoms. Moreover, various safety tests, such as those for female hormones, were confirmed. Therefore, it can be confirmed that MS-10 is a natural pharmaconutraceutical that causatively and safely improves health of women and aids in antiaging processes.

YES-10 Improves Stress, Tension, and Fatigue by Reducing Cortisol and IL-6 Levels.

The extract of Clematis mandshurica Rupr. (CMR) inhibits the production of proinflammatory mediators from lipopolysaccharide-stimulated peritoneal macrophages and concanavalin A-stimulated splenocytes. Erigeron annuus Pers. (EAP) extract suppresses the production of reactive oxygen species (ROS) from preadipocytes. Furthermore, the mixture of the leaf extracts of CMR and EAP, YES-10®, protected against nerve injuries induced by ischemia/reperfusion, suggesting a ROS-scavenging action. These observations show the anti-inflammatory action of YES-10. Inflammatory cytokines can cause alterations in mental function, including depression, by influencing the neurotransmitter system. Thus, it was hypothesized that YES-10 could improve mental health, such as depression, anxiety, and sense of well-being. Seventy-two subjects were recruited and randomly divided into YES-10 or placebo groups (n = 36 per group). Each group was daily administered two capsules orally, containing 200 mg of YES-10 or placebo, for 4 weeks in a double-blinded manner and tested for levels of depression, anxiety, well-being, and mental fitness using the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Psychosocial Well-being Index (PWI), and Mental Fitness Scale (MFS). In addition, the levels of cortisol (a stress hormone), interleukin-6 (IL-6) (an inflammatory cytokine), and 8-hydroxydeoxyguanosine (8-OHdG; a marker of oxidative stress) in the serum were measured. The BDI, BAI, PWI, and MFS scores decreased significantly, and the serum levels of cortisol, IL-6, and 8-OHdG were lowered significantly (P < .05), suggesting that YES-10 has the ability to improve mental health by relieving stress and by decreasing inflammation and oxidative stress.

Pinus thunbergii bark extract rich in flavonoids promotes hair growth in dorsal skin by regulating inflammatory cytokines and increasing growth factors in mice.

Korean maritime pine bark (Pinus thunbergii) has been used as an alternative medicine due to its beneficial properties, including anti­inflammatory effects. To date, the anti­inflammatory and hair growth­promoting effects of Pinus densiflora bark extract have remained elusive. Therefore, in the present study, Pinus thunbergii bark was extracted with pure water (100˚C) and the extract was examined to determine its polyphenol and flavonoid content. C57BL/6 mice were used to assess the effects of the extract to promote hair growth. The extract (1, 2 and 4%) was topically applied onto shaved dorsal skin and hair growth was observed for 17 days. A significant increase in hair growth was observed with 2 and 4% extract. Based on this finding, the optimal dose of the extract for effective hair growth promotion was determined to be 2%. The mechanisms of hair growth promotion were investigated via immunohistochemical analysis of changes in inflammatory cytokines and growth factors in the hair follicles following treatment with 2% extract. The treatment reduced the levels of TNF­α and IL­1ß, which are pro­inflammatory cytokines, while it enhanced the levels of IL­4 and IL­13, which are anti­inflammatory cytokines, in the hair follicles. In addition, elevated insulin­like growth factor I and vascular epidermal growth factor were detected in hair follicles following treatment. Based on these findings, it was suggested that the extract of Pinus thunbergii bark may be utilized for hair loss prevention and/or hair growth promotion.

P=O Functionalized Black Phosphorus/1T-WS2 Nanocomposite High Efficiency Hybrid Photocatalyst for Air/Water Pollutant Degradation.

Research on layered two-dimensional (2D) materials is at the forefront of material science. Because 2D materialshave variousplate shapes, there is a great deal of research on the layer-by-layer-type junction structure. In this study, we designed a composite catalyst with a dimension lower than two dimensions and with catalysts that canbe combined so that the band structures can be designed to suit various applications and cover for each other's disadvantages. Among transition metal dichalcogenides, 1T-WS2 can be a promising catalytic material because of its unique electrical properties. Black phosphorus with properly controlled surface oxidation can act as a redox functional group. We synthesized black phosphorus that was properly surface oxidized by oxygen plasma treatment and made a catalyst for water quality improvement through composite with 1T-WS2. This photocatalytic activity was highly efficient such that the reaction rate constant k was 10.31 × 10-2 min-1. In addition, a high-concentration methylene blue solution (20 ppm) was rapidly decomposed after more than 10 cycles and showed photo stability. Designing and fabricating bandgap energy-matching nanocomposite photocatalysts could provide a fundamental direction in solving the future's clean energy problem.

Clinical implication of residual MIBG-positive disease in the follow-up of high-risk neuroblastoma treated with tandem high-dose chemotherapy and autologous stem cell transplantation.

BACKGROUND: The implication of residual metaiodobenzylguanidine (MIBG)-positive disease in the era of tandem high-dose chemotherapy (HDCT) with autologous stem cell transplantation (auto-SCT) has not yet been established in neuroblastoma. Moreover, most published studies have not evaluated the long-term prognosis of patients with residual MIBG-positive disease following treatment completion. Therefore, we investigated the prognostic significance of residual MIBG-positive disease at each treatment phase and after treatment completion. METHODS: We assessed MIBG scans labeled with either iodine-123 (123 I) or 131 I from 150 patients with MIBG-avid and high-risk neuroblastoma enrolled in the NB-2004, -2009, and -2014 trials at postinduction, posttandem HDCT/auto-SCT, and completion of treatment. RESULTS: The residual MIBG-positive disease at postinduction and posttandem HDCT/auto-SCT evaluation was highly correlated with the risk of progression. However, at treatment completion, there was no significant difference in survival and risk of progression between patients with residual MIBG-positive disease and MIBG-negative patients. Patients with persistent MIBG-positive disease at the end of treatment were more likely to have indolent tumor characteristics, such as favorable histology at diagnosis, lower incidence of MYCN amplification, and slow response to chemotherapy. CONCLUSION: Residual MIBG-positive disease during treatment predicted unfavorable outcomes for patients with high-risk neuroblastoma, even under tandem HDCT/auto-SCT. However, persistent MIBG uptake at the completion of all treatments may not always indicate an active disease.

Factors associated with the comprehensive needs of caregivers of childhood cancer survivors in Korea.

PURPOSE: Caregivers of childhood cancer survivors (CCS) have diverse needs, which should be addressed to provide comprehensive cancer care. We aimed to evaluate the unmet needs of caregivers of CCS. METHODS: The subjects were 700 caregivers recruited at three major hospitals in South Korea. We collected study data using self-administered questionnaires and a thorough review of medical records. We assessed the unmet needs of caregivers using the comprehensive needs assessment tool for cancer caregivers and evaluated factors associated with the highest tertile range of unmet needs by multiple logistic regression analysis. RESULTS: The greatest unmet needs of caregivers had to do with healthcare staff, followed by information. Compared with father-caregivers, mother-caregivers had greater unmet needs related to health and psychological problems, family/social support, and religious/spiritual support, with odds ratios (95% confidence interval) of 3.79 (2.52-5.69), 3.17 (2.09-4.81), and 1.69 (1.14-2.50), respectively. Compared with caregivers of the youngest CCS (< 6 years), caregivers of CCS aged 12-18 years and caregivers of the oldest CCS (≥ 19 years) respectively showed 2.62 (1.24-5.52) and 3.18 (1.34-7.55) times greater unmet needs for information. Caregivers of CCS who received haematopoietic stem-cell transplantation had a 2.01-fold (1.14-3.57) greater need for practical support. CONCLUSION: Caregivers of CCS had substantial unmet needs required for comprehensive care for CCS. Several individual characteristics of caregivers and their children were significantly associated with greater unmet needs of the caregivers. IMPLICATIONS FOR CANCER SURVIVORS: Personalized support based on the characteristics of both CCS and their caregivers is required to provide comprehensive care for CCS.

Coronary CT Angiography CAD-RADS versus Coronary Artery Calcium Score in Patients with Acute Chest Pain.

Background The Coronary Artery Disease Reporting and Data System (CAD-RADS) was established in 2016 to standardize the reporting of coronary artery disease at coronary CT angiography (CCTA). Purpose To assess the prognostic value of CAD-RADS at CCTA for major adverse cardiovascular events (MACEs) in patients presenting to the emergency department with chest pain. Materials and Methods This multicenter retrospective observational cohort study was conducted at four qualifying university teaching hospitals. Patients presenting to the emergency department with acute chest pain underwent CCTA between January 2010 and December 2017. Multivariable Cox regression analysis was used to evaluate risk factors for MACEs, including clinical factors, coronary artery calcium score (CACS), and CAD-RADS categories. The prognostic value compared with clinical risk factors and CACS was also assessed. Results A total of 1492 patients were evaluated (mean age, 58 years ± 14 years [standard deviation]; 759 men). During a median follow-up period of 31.5 months, 103 of the 1492 patients (7%) experienced MACEs. Multivariable Cox regression analysis showed that a moderate to severe CACS was associated with MACEs after adjusting for clinical risk factors (hazard ratio [HR] range, 2.3-4.4; P value range, <.001 to <.01). CAD-RADS categories from 3 to 4 or 5 (HR range, 3.2-8.5; P < .001) and high-risk plaques (HR = 3.6, P < .001) were also associated with MACEs. The C statistics revealed that the CAD-RADS score improved risk stratification more than that using clinical risk factors alone or combined with CACS (C-index, 0.85 vs 0.63 [P < .001] and 0.76 [P < .01], respectively). Conclusion The Coronary Artery Disease Reporting and Data System classification had an incremental prognostic value compared with the coronary artery calcium score in the prediction of major adverse cardiovascular events in patients presenting to the emergency department with acute chest pain. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Vliegenthart in this issue.

Use of Acupuncture for the Treatment of Sports-Related Injuries in Athletes: A Systematic Review of Case Reports.

Acupuncture is one of the representative complementary and alternative medicine treatments used for various types of pain. This systematic review summarized and analyzed clinical case reports/series utilizing acupuncture for treating sports injuries in athletes, thereby providing the basis for further research to establish clinical evidence on acupuncture treatment in sports medicine. A comprehensive literature search was conducted in Embase including MEDLINE up to 21 August 2019 without language and publication date restrictions. Due to the heterogeneity of each study, explanatory and descriptive analyses were performed. As a result, in each case report/series, it was confirmed that acupuncture was applied for treating various types of sports injuries experienced by athletes. Acupuncture can help relieve short-term pain and recover from dysfunction and has been used as a useful, noninvasive, and conservative modality for managing sports injuries such as lateral meniscus rupture, femoral acetabular impingement, ganglion cysts, and sports hernia. In addition, acupuncture has been suggested as a treatment worth trying for diseases such as yips and delayed onset muscle soreness. The included cases showed some potential of acupuncture in the treatment of various types of sports injuries, beyond pain control in musculoskeletal disorders. However, considering that this review was based on case reports/series, a limited understanding of the clinical value of acupuncture in athletes is required. In the future, more specific research questions and hypotheses should be addressed to generate evidence based on experimental research.

Topical Application of Aronia melanocarpa Extract Rich in Chlorogenic Acid and Rutin Reduces UVB-Induced Skin Damage via Attenuating Collagen Disruption in Mice.

Aronia melanocarpa, a black chokeberry, contains high levels of phenolic acids and polyphenolic flavonoids and displays antioxidative and anti-inflammatory effects. Through high-performance liquid chromatography for extracts from Aronia melanocarpa, we discovered that the extract contained chlorogenic acid and rutin as major ingredients. In this study, we examined the protective effects of the extract against ultraviolet B- (UVB)-induced photodamage in the dorsal skin of institute of cancer research (ICR) mice. Their dorsal skin was exposed to UVB, thereafter; the extract was topically applied once a day for seven days. Photoprotective properties of the extract in the dorsal skin were investigated by clinical skin severity score for skin injury, hematoxylin and eosin staining for histopathology, Masson's trichrome staining for collagens. In addition, we examined change in collagen type I and III, and matrix metalloproteinase (MMP)-1 and MMP-3 by immunohistochemistry. In the UVB-exposed mice treated with the extract, UVB-induced epidermal damage was significantly ameliorated, showing that epidermal thickness was moderated. In these mice, immunoreactivities of collagen type I and III were significantly increased, whereas immunoreactivities of MMP-1 and 3 were significantly decreased compared with those in the UVB-exposed mice. These results indicate that treatment with Aronia melanocarpa extract attenuates UV-induced photodamage by attenuating UVB-induced collagen disruption: these findings might be a result of the chlorogenic acid and rutin contained in the extract. Based on the current results, we suggest that Aronia melanocarpa can be a useful material for developing photoprotective adjuvant.

Tanycytic TSPO inhibition induces lipophagy to regulate lipid metabolism and improve energy balance.

Hypothalamic glial cells named tanycytes, which line the 3rd ventricle (3V), are components of the hypothalamic network that regulates a diverse array of metabolic functions for energy homeostasis. Herein, we report that TSPO (translocator protein), an outer mitochondrial protein, is highly enriched in tanycytes and regulates homeostatic responses to nutrient excess as a potential target for an effective intervention in obesity. Administration of a TSPO ligand, PK11195, into the 3V, and tanycyte-specific deletion of Tspo reduced food intake and elevated energy expenditure, leading to negative energy balance in a high-fat diet challenge. Ablation of tanycytic Tspo elicited AMPK-dependent lipophagy, breaking down lipid droplets into free fatty acids, thereby elevating ATP in a lipid stimulus. Our findings suggest that tanycytic TSPO affects systemic energy balance through macroautophagy/autophagy-regulated lipid metabolism, and highlight the physiological significance of TSPO in hypothalamic lipid sensing and bioenergetics in response to overnutrition. ABBREVIATIONS: 3V: 3rd ventricle; ACAC: acetyl-Coenzyme A carboxylase; AGRP: agouti related neuropeptide; AIF1/IBA1: allograft inflammatory factor 1; AMPK: AMP-activated protein kinase; ARC: arcuate nucleus; Atg: autophagy related; Bafilo: bafilomycin A1; CAMKK2: calcium/calmodulin-dependent protein kinase kinase 2, beta; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CNS: central nervous system; COX4I1: cytochrome c oxidase subunit 4I1; FFA: free fatty acid; GFAP: glial fibrillary acidic protein; HFD: high-fat diet; ICV: intracerebroventricular; LAMP2: lysosomal-associated membrane protein 2; LD: lipid droplet; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MBH: mediobasal hypothalamus; ME: median eminence; MEF: mouse embryonic fibroblast; NCD: normal chow diet; NEFM/NFM: neurofilament medium; NPY: neuropeptide Y; OL: oleic acid; POMC: pro-opiomelanocortin-alpha; PRKN/Parkin: parkin RBR E3 ubiquitin protein ligase; Rax: retina and anterior neural fold homeobox; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; RER: respiratory exchange ratio; siRNA: small interfering RNA; SQSTM1: sequestosome 1; TG: triglyceride; TSPO: translocator protein; ULK1: unc-51 like kinase 1; VCO2: carbon dioxide production; VMH: ventromedial hypothalamus; VO2: oxygen consumption.

Hook-wire localization versus lipiodol localization for patients with pulmonary lesions having ground-glass opacity.

OBJECTIVES: Accurate and safe preoperative localization is useful for video-assisted thoracic surgery of small pulmonary lesions with ground-glass opacity (GGO). However, the optimal localization method is unclear. The aim of this study was to compare the usefulness and safety of the lipiodol and hook-wire localization techniques for video-assisted thoracic surgery of GGO lesions. METHODS: This prospective, non-randomized comparative study was conducted between April 2014 and December 2016 at 8 qualifying university teaching hospitals. Two-hundred-fifty patients with pulmonary lesions having GGO were included. Patients were assigned in a 1:1 ratio to either the lipiodol (n = 125, 4 hospitals) or hook-wire group (n = 125, 4 hospitals) for preoperative localization procedures. Participants underwent preoperative localization via the lipiodol or hook-wire technique followed by thoracoscopic surgery. The primary endpoint was the procedure success rate. RESULTS: The procedure success rates (hook-wire vs lipiodol group) were 94.40% versus 99.16% (P = .08). Localization-related complications occurred in 53.60% versus 48.33% of patients (P = .49). Hemorrhage rates were significantly greater in the hook-wire group than in the lipiodol group (21.6% vs 5.83%, P < .001). The lipiodol procedure time was significantly longer than that of the hook-wire technique (20.69 ± 9.34 vs 17.15 ± 7.91 minutes, P = .001). The initially positive surgical resection margin was significantly greater in the hook-wire group than in the lipiodol group (10.89% vs 2.38%, P = .02). CONCLUSIONS: There was no significant difference in success rate between the hook-wire and lipiodol methods. However, the hemorrhage rate was significantly greater in the hook-wire group, whereas the hook-wire group showed greater initially positive surgical resection margins.

Anti-Osteoporotic Effects of Combined Extract of Lycii Radicis Cortex and Achyranthes japonica in Osteoblast and Osteoclast Cells and Ovariectomized Mice.

Osteoporosis is characterized by low bone density and quality with high risk of bone fracture. Here, we investigated anti-osteoporotic effects of natural plants (Lycii Radicis Cortex (LRC) and Achyranthes japonica (AJ)) in osteoblast and osteoclast cells in vitro and ovariectomized mice in vivo. Combined LRC and AJ enhanced osteoblast differentiation and mineralized bone-forming osteoblasts by the up-regulation of bone metabolic markers (Alpl, Runx2 and Bglap) in the osteoblastic cell line MC3T3-E1. However, LRC and AJ inhibited osteoclast differentiation of monocytes isolated from mouse bone marrow. In vivo experiments showed that treatment of LRC+AJ extract prevented OVX-induced trabecular bone loss and osteoclastogenesis in an osteoporotic animal model. These results suggest that LRC+AJ extract may be a good therapeutic agent for the treatment and prevention of osteoporotic bone loss.

Anti-Osteoporotic Effects of Kukoamine B Isolated from Lycii Radicis Cortex Extract on Osteoblast and Osteoclast Cells and Ovariectomized Osteoporosis Model Mice.

Osteoporosis is an abnormal bone remodeling condition characterized by decreased bone density, which leads to high risks of fracture. Previous study has demonstrated that Lycii Radicis Cortex (LRC) extract inhibits bone loss in ovariectomized (OVX) mice by enhancing osteoblast differentiation. A bioactive compound, kukoamine B (KB), was identified from fractionation of an LRC extract as a candidate component responsible for an anti-osteoporotic effect. This study investigated the anti-osteoporotic effects of KB using in vitro and in vivo osteoporosis models. KB treatment significantly increased the osteoblastic differentiation and mineralized nodule formation of osteoblastic MC3T3-E1 cells, while it significantly decreased the osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. The effects of KB on osteoblastic and osteoclastic differentiations under more physiological conditions were also examined. In the co-culture of MC3T3-E1 cells and monocytes, KB promoted osteoblast differentiation but did not affect osteoclast differentiation. In vivo experiments revealed that KB significantly inhibited OVX-induced bone mineral density loss and restored the impaired bone structural properties in osteoporosis model mice. These results suggest that KB may be a potential therapeutic candidate for the treatment of osteoporosis.

The effects of resistance training on bone mineral density and bone quality in type 2 diabetic rats.

Resistance training (RT) has been known to be effective in maintaining and improving bone strength, which is based on bone mineral density (BMD) and bone quality. However, it is not clear whether RT is effective in improving bone strength in patients with type-2 diabetes mellitus (T2DM), who have a high risk of fracture. Therefore, we tested the effects of a 6-week RT regimen using percutaneous electrical stimulation in T2DM model rats, male Otsuka Long-Evans Tokushima Fatty (OLETF), and its control, Long-Evans Tokushima Otsuka (LETO). After 6 weeks of RT, tibial BMD in RT legs was significantly higher than that in control (CON) legs in both groups. In diaphyseal cortical bone, bone area/tissue area, and cortical thickness was significantly increased in RT legs compared with CON legs in both groups. Cortical porosity was highly observed in OLETF compared with LETO, but RT improved cortical porosity in both groups. Interestingly, trabecular number, trabecular thickness and trabecular space as well as BMD and bone volume/tissue volume in proximal tibial metaphyseal trabecular bone were significantly improved in RT legs compared with CON legs in both groups. In contrast, connectivity density and structural model index were not affected by RT. These results indicate that the 6-week RT regimen effectively increased BMD and improved bone quality in T2DM model rats as well as control rats. Therefore, RT may have the potential to improve bone strength and reduce fracture risk, even in patients with T2DM.

Perinatal Brain Docosahexaenoic Acid Concentration Has a Lasting Impact on Cognition in Mice.

Background: Premature infants are deprived of prenatal accumulation of brain docosahexaenoic acid [DHA (22:6n-3)], an omega-3 fatty acid [ω-3 FA (n-3 FA)] important for proper development of cognitive function. The resulting brain DHA deficit can be reversed by ω-3 FA supplementation.Objective: The objective was to test whether there is a critical period for providing ω-3 FA to correct cognitive deficits caused by developmental ω-3 FA deprivation in mice.Methods: Twelve timed-pregnant mice [embryonic day 14 (E14), C57/BL6NCr] were fed an ω-3 FA-deficient diet containing 0.04% α-linolenic acid [ALA (18:3n-3)], and their offspring were fed the same deficient diet (Def group) or changed to an ω-3 FA-adequate diet containing 3.1% ALA at 3 wk, 2 mo, or 4 mo of age. In parallel, 3 E14 pregnant mice were fed the adequate diet and their offspring were fed the same diet (Adeq group) throughout the experiment. Brain FA composition, learning and memory, and hippocampal synaptic protein expression were evaluated at 6 mo by gas chromatography, the Morris water maze test, and western blot analysis, respectively.Results: Maternal dietary ω-3 FA deprivation decreased DHA by >50% in the brain of their offspring at 3 wk of age. The Def group showed significantly worse learning and memory at 6 mo than those groups fed the adequate diet. These pups also had decreased hippocampal expression of postsynaptic density protein 95 (43% of Adeq group), Homer protein homolog 1 (21% of Adeq group), and synaptosome-associated protein of 25 kDa (64% of Adeq group). Changing mice to the adequate diet at 3 wk, 2 mo, or 4 mo of age restored brain DHA to the age-matched adequate concentration. However, deficits in hippocampal synaptic protein expression and spatial learning and memory were normalized only when the diet was changed at 3 wk.Conclusion: Developmental deprivation of brain DHA by dietary ω-3 FA depletion in mice may have a lasting impact on cognitive function if not corrected at an early age.

Incorporation of high-dose 131I-metaiodobenzylguanidine treatment into tandem high-dose chemotherapy and autologous stem cell transplantation for high-risk neuroblastoma: results of the SMC NB-2009 study.

BACKGROUND: In our previous SMC NB-2004 study of patients with high-risk neuroblastomas, which incorporated total-body irradiation (TBI) with second high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), the survival rate was encouraging; however, short- and long-term toxicities were significant. In the present SMC NB-2009 study, only TBI was replaced with 131I-meta-iodobenzylguanidine (MIBG) treatment in order to reduce toxicities. METHODS: From January 2009 to December 2013, 54 consecutive patients were assigned to receive tandem HDCT/auto-SCT after nine cycles of induction chemotherapy. The CEC (carboplatin + etoposide + cyclophosphamide) regimen and the TM (thiotepa + melphalan) regimen with (for metastatic MIBG avid tumors) or without (for localized or MIBG non-avid tumors) 131I-MIBG treatment (18 or 12 mCi/kg) were used for tandem HDCT/auto-SCT. Local radiotherapy, differentiation therapy with 13-cis-retinoic acid, and immunotherapy with interleukin-2 were administered after tandem HDCT/auto-SCT. RESULTS: Fifty-two patients underwent the first HDCT/auto-SCT and 47 patients completed tandem HDCT/auto-SCT. There was no significant immediate toxicity during the 131I-MIBG infusion. Acute toxicities during the tandem HDCT/auto-SCT were less severe in the NB-2009 study than in the NB-2004 study. Late effects such as growth hormone deficiency, cataracts, and glomerulopathy evaluated at 3 years after the second HDCT/auto-SCT were also less significant in the NB-2009 study than in NB-2004 study. There was no difference in the 5-year event-free survival (EFS) between the two studies (67.5 ± 6.7% versus 58.3 ± 6.9%, P = 0.340). CONCLUSIONS: Incorporation of high-dose 131I-MIBG treatment into tandem HDCT/auto-SCT could reduce short- and long-term toxicities associated with TBI, without jeopardizing the survival rate. TRIAL REGISTRATION: ClinicalTrials.gov NCT03061656.