The Effects of Online-Based Interventions for Chronic Low Back Pain Patients: A Clinical Trial

Objective@#Chronic low back pain (LBP) is a huge social burden, and optimal exercise therapies for chronic LBP patients are continuously being studied. To evaluate the effects of digital intervention on pain and disability in patients with chronic LBP, we performed a prospective cohort study. Method: From February 2020 to January 2021, 25 patients with chronic LBP were recruited. Digital intervention contains education contents and video demonstration for individually prescribed exercise. The exercise prescription was renewed every 4 weeks according to subjects’ condition and accomplishment of exercise. This intervention was performed for more than 30 weeks. The pain intensity was assessed using a numeric rating scale (NRS) while their degree of disability was assessed using the Roland-Morris Disability Questionnaire (RMDQ). The pain intensity and disability was evaluated at short term (8∼20 weeks) and long term (30 weeks). @*Results@#As a result, pain intensity (NRS) decreased significantly over the short term and long term (p<0.05). However, pain related disability (RMDQ score) did not change significantly over the follow-up period (p=0.554). @*Conclusion@#Our findings indicate that online-based digital intervention reduced the intensity of chronic LBP. Further research is needed to identify methods to cost-effectively and consistently manage chronic LBP.

A case report of successfully treated metachronous gastrointestinal stromal tumor and colon cancer / 고신대학교의과대학학술지

The diagnosis of gastrointestinal stromal tumor (GIST) has become relatively common in recent years, but little is known about its association with other malignancies. We present a rare case of successfully treated metachronous GIST and colon cancer with concurrent FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy and imatinib. A 63-year-old man presented with abdominal pain that had started 2 weeks ago, and endoscopic ultrasonography showed masses that were compatible with GIST on the duodenum. He underwent Whipple surgery. One year after the GIST diagnosis, two liver masses were found on abdominal computed tomography images taken for surveillance. A liver biopsy showed metastatic adenocarcinoma, not GIST. Colonoscopy was then performed to identify the primary site of the metastatic adenocarcinoma in the liver, and sigmoid colon cancer was found. He received 12 cycles of adjuvant FOLFOX concurrently with adjuvant imatinib. There were no serious adverse events of grade 3 or higher from either imatinib or chemotherapy. He has completed adjuvant imatinib and FOLFOX chemotherapy and there is no evidence of disease recurrence. When a synchronous or metachronous tumor is found in a GIST patient, the clinician should keep in mind the possibility of another primary tumor of different histopathology, as well as GIST recurrence.

A Study of Dry Mouth and Gastrointestinal Disorders in Patients Taking Antidepressant / 우울ㆍ조울병

Background@#The purpose of this study was to identify the characteristics of dry mouth and gastrointestinal (GI) disorders in antidepressant patients. @*Methods@#The study included 103 antidepressant-taking patients. Antidepressants were classified according to their mode of action. The GI disorders were investigated using the medical records of the patients. The Patient Health Questionnaire-15 and a questionnaire for assessing dry mouth symptoms were used in this study. @*Results@#The score for “overall discomfort due to dry mouth in daily life” (31.72±33.82), “dry mouth at night or in the morning” (47.86±35.87), and “dry mouth during the day” (39.83±31.67) were slightly higher than “discomfort in chewing or swallowing foods”. According to somatization severity, the mean values were 116.36±113.34 in the mild, 213.18±136.98 in the moderate, and 277.59±201.44 in the severe, the between-group difference was significant (F=10.294, p<0.001). According to the class of antidepressants, the mean score was 180.00±147.5 for vortioxetine, 194.25±169.33 for selective serotonin reuptake inhibitors (SSRIs), 223.61±156.70 for serotonin and norepinephrine reuptake inhibitors (SNRIs), 75.00±57.00 for norepinephrine dopamine reuptake inhibitors (NDRIs), 201.67±174.66 for Nassau, and 116.67±132.03 for agomelatine. A total of 67 (65.0%) patients had at least one GI disorder. @*Conclusion@#The study findings are expected to help increase medication compliance in antidepressant patients by better controlling the side effects experienced by the patients.

Effect of nutrition education by childcare teachers on food serving sizes / 한국영양학회지

Purpose@#Adequate nutrition is to be provided for normal growth and development during early childhood. Currently, childcare teachers provide lunch to most children in Korea. The purpose of this study was to investigate the portion size provided by teachers and examine the effect of education on food serving size. @*Methods@#The subjects were childcare teachers (n = 120) in charge of children aged 3–5 years at a daycare center in Hanam-si. The survey was conducted through questionnaires which included questions on the general characteristics of the teachers, their nutritional education status, and the source of nutrition information. In addition, the portion sizes of items on the menu currently provided to children were measured and the data were analyzed. To assess the effectiveness of education in determining serving size, the subjects were randomly equally divided into two groups. In the first group (n = 60) theoretical education on nutrition and serving sizes was given, whereas in the second (n = 60), practical education on these topics was provided. @*Results@#The difference between the actual portion size of rice and the serving size announced on the menu was observed to decrease along with the increase in the experience of the teacher, although the differences in the main dish and kimchi were higher. The gap between the serving size mentioned in the menu and the portion size distributed widened as the age of the teachers increased. Notably, the difference between the portion size and the serving size of food decreased after both practical and theoretical education. Furthermore, the effect of education on the serving size of the main dishes (p < 0.001), side dishes (p < 0.01), and kimchi (p < 0.01) was observed to be greater in the practical education group than in the theoretical education group. @*Conclusion@#Regular education should be provided to teachers on the serving sizes mentioned in the menu, as the quantity of food served depends on the experience and age of teachers. In the case of rice, theoretical education alone sufficed to ensure a proper serving size. However, hands-on training on the main and side dishes, and kimchi would be much more helpful.

Diagnosis of Lung Cancer in a Patient with Chronic Knee Pain Caused by Hypertrophic Osteoarthropathy

Patients with chronic knee pain are common, and symptoms are usually caused by degenerative disorders of the knee joint. Although hypertrophic osteoarthropathy (HOA) is a rare cause of knee pain in patients who visit the department of rehabilitation medicine, clinicians should consider this paraneoplastic syndrome. Herein, we report an uncommon case of hypertrophic pulmonary osteoarthropathy (HPO) in a patient with chronic knee pain who was finally diagnosed with lung cancer. A 49-year-old male was referred to the department of rehabilitation medicine from a local clinic for uncontrolled bilateral knee pain. The plain radiograph and magnetic resonance image (MRI) of the knee showed symmetric periosteal reaction and prepatellar bursitis. For additional evaluation, bone scan was done, and it revealed symmetric linear uptake along the diaphyseal and metaphyseal surfaces of both femurs and tibias, a typical feature of HPO. A plain chest radiograph was taken and showed a mass at the left hilar region. The patient was finally diagnosed with non-small cell lung cancer. After receiving chemotherapy for lung cancer, knee pain improved.

Extensive Leukoencephalopathy in Spastic Paraplegia Type 4: Possible Role of Cerebral Autosomal Arteriopathy With Subcortical Infarcts and Leukoencephelopathy

Despite recent advances in next-generation sequencing, the underlying etiology of adult-onset leukoencephalopathy has been difficult to elucidate. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a representative hereditary adult-onset leukoencephalopathy associated with vasculopathy. Leukoencephalopathy in spastic paraplegia type 4 (SPG4) is known to be rare, but it might be underestimated because most spastic paraplegia with leukoencephalopathy is rarely considered. We report a case of co-occurring SPG4 and CADASIL. A 61-year-old male presented with sudden visual impairment after a headache. He showed a spastic gait and had a family history with similar symptoms. An SPG4 gene mutation and a pathogenic variant in the NOTCH3 gene were found. This case shows that the diverse and complex clinical manifestations of patients with extensive leukoencephalopathy are related to more than one gene mutation. We also suggest the necessity for relevant genetic tests in the diagnosis of adult-onset leukoencephalopathy.

Isolated Intracranial Rosai–Dorfman Disease Mimicking Meningioma: A Case Report

Rosai–Dorfman Disease (RDD) is a rare lymphoproliferative disease, and the occurrence of isolated intracranial RDD is extremely rare. Most cases of intracranial RDDs present as dural masses showing homogenous enhancement on MRI, which makes it difficult to differentiate these masses from meningiomas before surgery unless massive cervical lymphadenopathy is observed. We herein report a rare case of isolated intracranial RDD in a 65-year-old male. Brain MRI revealed a well-defined enhancing mass-like lesion involving the right frontal convexity and subtle diffusion restriction. However, only a subtle blush was observed on the preoperative cerebral angiogram. Although instances of isolated intracranial RDD are rare, it should be considered as a potential differential diagnosis when a dural mass with hypovascularity is visualized on the cerebral angiogram.

Comparison of the Quality of Various Polychromatic and Monochromatic Dual-Energy CT Images with or without a Metal Artifact Reduction Algorithm to Evaluate Total Knee Arthroplasty

Objective@#To compare the quality of various polychromatic and monochromatic images with or without using an iterative metal artifact reduction algorithm (iMAR) obtained from a dual-energy computed tomography (CT) to evaluate total knee arthroplasty. @*Materials and Methods@#We included 58 patients (28 male and 30 female; mean age [range], 71.4 [61–83] years) who underwent 74 knee examinations after total knee arthroplasty using dual-energy CT. CT image sets consisted of polychromatic image sets that linearly blended 80 kVp and tin-filtered 140 kVp using weighting factors of 0.4, 0, and -0.3, and monochromatic images at 130, 150, 170, and 190 keV. These image sets were obtained with and without applying iMAR, creating a total of 14 image sets. Two readers qualitatively ranked the image quality (1 [lowest quality] through 14 [highest quality]). Volumes of high- and low-density artifacts and contrast-to-noise ratios (CNRs) between the bone and fat tissue were quantitatively measured in a subset of 25 knees unaffected by metal artifacts. @*Results@#iMAR-applied, polychromatic images using weighting factors of -0.3 and 0.0 (P-0.3i and P0.0i, respectively) showed the highest image-quality rank scores (median of 14 for both by one reader and 13 and 14, respectively, by the other reader;p < 0.001). All iMAR-applied image series showed higher rank scores than the iMAR-unapplied ones. The smallest volumes of low-density artifacts were found in P-0.3i, P0.0i, and iMAR-applied monochromatic images at 130 keV. The smallest volumes of high-density artifacts were noted in P-0.3i. The CNRs were best in polychromatic images using a weighting factor of 0.4 with or without iMAR application, followed by polychromatic images using a weighting factor of 0.0 with or without iMAR application. @*Conclusion@#Polychromatic images combined with iMAR application, P-0.3i and P0.0i, provided better image qualities and substantial metal artifact reduction compared with other image sets.

CT Follow-Up of Postoperative Bronchopleural Fistula:Risk Factors for Progression to Chronic Complicated Infection

Purpose@#We evaluated the risk factors for progression to chronic complicated bronchopleural fistula (BPF) after pulmonary resection using follow-up CT. @*Materials and Methods@#We retrospectively reviewed 45 cases with BPF that had undergone pulmonary resection during 2010-2018. We compared the clinical and radiological characteristics of those with complicated BPF (n = 24) and those without complicated (sterilized) BPF (n = 21). The clinical and radiological risk factors for progression to chronic complicated BPF were examined by logistic regression analysis. @*Results@#The thickness of the pleural cavity wall (p = 0.022), the size of the pleural cavity (p = 0.029), and the size increase of BPF on follow-up (p = 0.012) were significantly different between the two groups. The risk factors for progression to chronic complicated BPF were age > 70 years (odds ratio, 6.43; 95% confidence interval, 1.2–33.7), the thickness of the cavity wall > 5 mm (odds ratio, 52.5; 95% confidence interval, 5.1–545.4), and an increase in the size of the pleural cavity on follow-up CT (odds ratio, 12.5; 95% confidence interval, 2.1–73.5), only in the univariate analysis. @*Conclusion@#The risk factors for progression to chronic complicated BPF can be evaluated using follow-up CT.

Comparison of the Quality of Various Polychromatic and Monochromatic Dual-Energy CT Images with or without a Metal Artifact Reduction Algorithm to Evaluate Total Knee Arthroplasty

Objective@#To compare the quality of various polychromatic and monochromatic images with or without using an iterative metal artifact reduction algorithm (iMAR) obtained from a dual-energy computed tomography (CT) to evaluate total knee arthroplasty. @*Materials and Methods@#We included 58 patients (28 male and 30 female; mean age [range], 71.4 [61–83] years) who underwent 74 knee examinations after total knee arthroplasty using dual-energy CT. CT image sets consisted of polychromatic image sets that linearly blended 80 kVp and tin-filtered 140 kVp using weighting factors of 0.4, 0, and -0.3, and monochromatic images at 130, 150, 170, and 190 keV. These image sets were obtained with and without applying iMAR, creating a total of 14 image sets. Two readers qualitatively ranked the image quality (1 [lowest quality] through 14 [highest quality]). Volumes of high- and low-density artifacts and contrast-to-noise ratios (CNRs) between the bone and fat tissue were quantitatively measured in a subset of 25 knees unaffected by metal artifacts. @*Results@#iMAR-applied, polychromatic images using weighting factors of -0.3 and 0.0 (P-0.3i and P0.0i, respectively) showed the highest image-quality rank scores (median of 14 for both by one reader and 13 and 14, respectively, by the other reader;p < 0.001). All iMAR-applied image series showed higher rank scores than the iMAR-unapplied ones. The smallest volumes of low-density artifacts were found in P-0.3i, P0.0i, and iMAR-applied monochromatic images at 130 keV. The smallest volumes of high-density artifacts were noted in P-0.3i. The CNRs were best in polychromatic images using a weighting factor of 0.4 with or without iMAR application, followed by polychromatic images using a weighting factor of 0.0 with or without iMAR application. @*Conclusion@#Polychromatic images combined with iMAR application, P-0.3i and P0.0i, provided better image qualities and substantial metal artifact reduction compared with other image sets.

Anti-senescence and anti-wrinkle activities of 3-bromo-4,5-dihydroxybenzaldehyde from Polysiphonia morrowii Harvey in human dermal fibroblasts

Objective:To investigate the anti-senescence effect of 3-bromo-4,5-dihydroxybenzaldehyde (BDB) from Polysiphonia morrowii Harvey in human dermal fibroblasts (HDF). Methods:HDF were subjected to treatment of BDB and then treated with hydrogen peroxide (H2O2) to induce premature senescence. Senescence-associated β-galactosidase (SA-β-gal) activity in HDF was determined using the SA-β-gal staining method. Intracellular reactive oxygen species (ROS) production was measured using the 2',7'-dichlorodihydrofluorescein diacetate assay. Western blotting assay was performed to assess the level of antioxidant enzyme glutathione peroxidase 1 (GPX1). In addition, intracellular collagen and collagenase contents were analyzed using the respective ELISA kits. Elastase activity in HDF supernatants was measured from p-nitroaniline release and normalized using total protein content. Results:Treatment of HDF with H2O2 increased the activity of SA-β-gal, but BDB pre-treatment resulted in the reduction of SA-β-gal activity. Moreover, BDB significantly reduced H2O2-induced intracellular ROS production. BDB also markedly increased the level of GPX1, which was inhibited by 400 μM of H2O2. Furthermore, in in vitro study, BDB significantly increased intracellular collagen content and decreased matrix metalloproteinase-1 and elastase activities in HDF. Conclusions:Our results demonstrate that BDB shows anti-senescence and anti-wrinkle activities in vitro.

Combination therapy with cilostazol, aripiprazole, and donepezil protects neuronal cells from β-amyloid neurotoxicity through synergistically enhanced SIRT1 expression

Alzheimer’s disease (AD) is a multi-faceted neurodegenerative disease. Thus, current therapeutic strategies require multitarget-drug combinations to treat or prevent the disease. At the present time, single drugs have proven to be inadequate in terms of addressing the multifactorial pathology of AD, and multitarget-directed drug design has not been successful. Based on these points of views, it is judged that combinatorial drug therapies that target several pathogenic factors may offer more attractive therapeutic options. Thus, we explored that the combination therapy with lower doses of cilostazol and aripiprazole with add-on donepezil (CAD) might have potential in the pathogenesis of AD. In the present study, we found the superior efficacies of donepezil add-on with combinatorial mixture of cilostazol plus aripiprazole in modulation of expression of AD-relevant genes: Aβ accumulation, GSK-3β, P300, acetylated tau, phosphorylated-tau levels, and activation of α-secretase/ADAM 10 through SIRT1 activation in the N2a Swe cells expressing human APP Swedish mutation (N2a Swe cells). We also assessed that CAD synergistically raised acetylcholine release and choline acetyltransferase (CHAT) expression that were declined by increased β-amyloid level in the activated N2a Swe cells. Consequently, CAD treatment synergistically increased neurite elongation and improved cell viability through activations of PI3K, BDNF, β-catenin and a7-nicotinic cholinergic receptors in neuronal cells in the presence of Aβ1-42. This work endorses the possibility for efficient treatment of AD by supporting the synergistic therapeutic potential of donepezil add-on therapy in combination with lower doses of cilostazol and aripiprazole.

Relationship of loneliness and subjective chewing discomfort in the elderly / 대한구강보건학회지

Objectives@#Loneliness was associated with not only social status but also general health. Psychological conditions in older people have negative effects on general health and oral health. The purpose of the study was to investigate the relationship between loneliness and subjective chewing discomfort in the elderly. @*Methods@#This cross-sectional study analyzed the Korean Social Life, Health, and Aging Project (KSHAP) for the questionnaire, UCLA loneliness scale data of 1,511 older adults living in a rural community. Logistic regression was conducted to identify the relevance of subjective chewing discomfort in the elderly according to the level of loneliness. @*Results@#According to the final model that after adjustment for other risk factors (age, gender, level of education, smoking, drinking, etc.), in the elderly who rarely feel loneliness group compared to the elderly who never feel loneliness was Odds ratio (OR) 1.256 (95% Confidence Interval [CI]: 0.99-1.60) and sometimes+often feel loneliness was OR 2.110 (95% CI: 1.39-3.21). @*Conclusions@#Loneliness is associated with subjective chewing discomfort in the elderly. Older people feeling loneliness are likely to have more subjective chewing discomfort.

Microsurgical treatment for the recurrent cerebral aneurysm initially treated using coil embolization

Objective@#Microsurgical treatment could be a good alternative for the treatment of recurrent cerebral aneurysm after coil embolization. The purpose of this study was to present our experience of microsurgical treatment for recurrent cerebral aneurysm previously treated using coil embolization. @*Methods@#From June 2012 to May 2019, 34 patients consecutively received microsurgical treatment for a recurrent cerebral aneurysm previously treated using coil embolization after it ruptured. @*Results@#Of the 34 patients with aneurysm, 33 had the aneurysm located in the anterior circulation. The most common location was the anterior communicating artery (13 cases). Immediate radiologic outcome at coil embolization was completed (n=6), residual neck (n=26), and residual sac (n=2). The reason for microsurgical treatment included rebleeding (n=12), persistent residual sac (n=1), and recurrence on follow-up study (n=21). Rebleeding occurred within 10 days after coil embolization in 10 cases, and the other 2 were due to regrowth. In the 20 recurred and saccular aneurysms, coil compaction was present in 11 aneurysms and regrowth in 9 aneurysms. Simple neck clipping (n=29) and clipping with coil mass extraction (n=3) was possible in the saccular aneurysms. The blood blister like aneurysm (n=2) were treated using bypass and endovascular internal carotid artery trapping. In the follow-up study group after microsurgical treatment there were no severe complications due to the treatment. Age, cause of retreatment, and modified Rankin Scale before microsurgery were associated with good outcome (p<0.001). @*Conclusions@#Microsurgical treatment may be a viable and effective option for treating recurrent aneurysms previously treated by endovascular techniques.

Assessment of the Location of the Peroneus Longus Tendon in the Cuboid Groove Using 3D Isotropic Fast Spin-Echo MRI

Purpose@#To investigate normal location of the peroneus longus tendon (PL) in the cuboid groove by evaluating it between ankles with no significant abnormality (asymptomatic group) and those with retromalleolar PL dislocation (dislocation group) using three-dimensional isotropic fast spin-echo (3D-FSE) magnetic resonance imaging (MRI) of the ankle. @*Materials and Methods@#Thirty-six and 32 3D-FSE ankle MRI were assigned to the asymptomatic group and the dislocation group, respectively. Using multiplanar reformatted 3D-FSE, qualitative PL location (i.e., outside, overlying, and inside in relation to the cuboid groove), quantitative PL location (i.e., distance between the proximal margins of PL and cuboid groove), and cuboid groove size were measured in lateral, middle, and medial levels of the cuboid groove. @*Results@#In the asymptomatic group, 64%, 42%, and 11%, respectively, had the outside or overlying-located PL in lateral, middle, and medial levels of the cuboid groove and the quantitative location gradually decreased from lateral to medial level.Qualitative and quantitative PL locations were not significantly different between the asymptomatic group and dislocation group. Cuboid groove size showed significant negative correlation with quantitative PL location in both groups. @*Conclusion@#Outside- or overlying-located PL in lateral and middle levels of the cuboid groove would be a normal finding, regardless of PL status at the retromalleolar level.

Factors Influencing Self-Rated Oral Health in Elderly People Residing in the Community: Results from the Korea Community Health Survey, 2016

ObjectivesThe aim of this study was to examine the factors influencing perceived oral health in elderly individuals residing in the community.MethodsThis study used raw data from the Korea community health survey, 2016. Of the 64,223 participants that were elderly (aged ≥ 65 years), 61,280 (95.4%) were included for analysis. Self-rated oral health was the dependent variable and 6 independent variables including age, gender, type of area of residence (metropolitan or provincial), educational level, income, and living status with spouse were assessed. Oral function was studied based on mastication, pronunciation, and use of dentures, and oral health behavior included brushing teeth after breakfast, after lunch, after dinner, and before sleep). The EQ-5D questionnaire measured health-related quality of life (mobility, self-care, usual activities, pain/discomfort and anxiety/depression).ResultsAmong the general characteristics, age, gender, educational level, income, and living status with spouse were the factors that affected self-rated oral health. Mastication, pronunciation, use of dentures, and brushing after lunch, dinner, and before sleep were the factors that influenced self-rated oral function. All domains of the EQ-5D (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression) were factors that affected self-rated oral health.ConclusionThe results of the current investigation suggest that the development of management and education strategies for oral health promotion in the elderly, should focus on improving oral function and oral health behavior, taking into account the socio-economic and demographic characteristics that have been shown to be associated with poor self-rated oral function.

Embolization of Inferior Pancreaticoduodenal Artery Aneurysm with Celiac Stenosis or Occlusion: A Report of Three Cases and a Review of Literature

True pancreaticoduodenal artery aneurysms are relatively rare, approximately 50% of which are associated with stenosis or occlusion of the celiac axis. It is imperative to treat the condition immediately after diagnosis, considering that its rupture has a mortality rate of approximately 50%. The current most commonly used method to treat pancreaticoduodenal artery aneurysms is transcatheter arterial embolization. Here, we report three cases of embolization of inferior pancreaticoduodenal artery aneurysm with celiac stenosis or occlusion along with a literature review.

Antioxidant and anti-melanogenic activities of ultrasonic extract from Stichopus japonicus

Objective: To investigate the antioxidant and anti-melanogenesis activities of an ultrasonic extract of red sea cucumber, Stichopus japonicus, collected from Jeju Island. Methods: Antioxidant activity experiments were assessed by an electron spin resonance system and a cellular model of immortalized human keratinocytes (HaCaT) to determine its radical scavenging activity and protective effects against 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced oxidative stress. Anti-melanogenic activity of the ultrasonic extract of red sea cucumber was also examined using the melanoma cell model B16F10 and mushroom tyrosinase. Following the induction by α-melanocyte-stimulating hormone, the effects of the ultrasonic extract of red sea cucumber on intracellular tyrosinase activity, melanin content and the melanogenic protein expression of microphthalmia-associated transcription factor, tyrosinase, and tyrosinase-related proteins (TRP-1, and TRP-2) were examined. Results: The ultrasonic extract of red sea cucumber significantly scavenged 2,2-diphenyl-1-picrylhydrazyl and alkyl radicals [IC50:(0.924±0.035) and (0.327±0.006) mg/mL, respectively], as well as showed a protective effect against oxidative stress and attenuated generation of intracellular reactive oxygen species on AAPH-induced HaCaT cells, with no cytotoxicity (12.5-400 μg/mL). The ultrasonic extract of red sea cucumber also exhibited a tyrosinase inhibitory effect [IC50: (2.750±0.006) mg/mL]. On α-melanocyte-stimulating hormone-stimulated B16F10 melanoma cells, the ultrasonic extract of red sea cucumber (25-200 μg/mL) significantly inhibited not only melanin synthesis and tyrosinase activity, but also protein expressions of microphthalmia-associated transcriptional factor, tyrosinase, TRP-1, and TRP-2. Conclusions: The ultrasonic extract of red sea cucumber shows antioxidant and anti-melanogenic potential and may be a natural candidate for anti-aging as well as a whitening agent in the cosmeceuticals industry.

Antioxidant and anti-melanogenic activities of ultrasonic extract from Stichopus japonicus

To investigate the antioxidant and anti-melanogenesis activities of an ultrasonic extract of red sea cucumber, Stichopus japonicus, collected from Jeju Island. Methods: Antioxidant activity experiments were assessed by an electron spin resonance system and a cellular model of immortalized human keratinocytes (HaCaT) to determine its radical scavenging activity and protective effects against 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced oxidative stress. Antimelanogenic activity of the ultrasonic extract of red sea cucumber was also examined using the melanoma cell model B16F10 and mushroom tyrosinase. Following the induction by ?-melanocytestimulating hormone, the effects of the ultrasonic extract of red sea cucumber on intracellular tyrosinase activity, melanin content and the melanogenic protein expression of microphthalmia-associated transcription factor, tyrosinase, and tyrosinase-related proteins (TRP-1, and TRP-2) were examined. Results: The ultrasonic extract of red sea cucumber significantly scavenged 2,2-diphenyl-1-picrylhydrazyl and alkyl radicals [IC50: (0.9240.035) and (0.3270.006) mg/mL, respectively], as well as showed a protective effect against oxidative stress and attenuated generation of intracellular reactive oxygen species on AAPHinduced HaCaT cells, with no cytotoxicity (12.5-400 ug/mL). The ultrasonic extract of red sea cucumber also exhibited a tyrosinase inhibitory effect [IC50: (2.7500.006) mg/mL]. On ?-melanocytestimulating hormone-stimulated B16F10 melanoma cells, the ultrasonic extract of red sea cucumber (25-200 ug/mL) significantly inhibited not only melanin synthesis and tyrosinase activity, but also protein expressions of microphthalmia-associated transcriptional factor, tyrosinase, TRP-1, and TRP-2. Conclusions: The ultrasonic extract of red sea cucumber shows antioxidant and anti-melanogenic potential and may be a natural candidate for anti-aging as well as a whitening agent in the cosmeceuticals industry.

Combination therapy with cilostazol, aripiprazole, and donepezil protects neuronal cells from β-amyloid neurotoxicity through synergistically enhanced SIRT1 expression

Alzheimer’s disease (AD) is a multi-faceted neurodegenerative disease. Thus, current therapeutic strategies require multitarget-drug combinations to treat or prevent the disease. At the present time, single drugs have proven to be inadequate in terms of addressing the multifactorial pathology of AD, and multitarget-directed drug design has not been successful. Based on these points of views, it is judged that combinatorial drug therapies that target several pathogenic factors may offer more attractive therapeutic options. Thus, we explored that the combination therapy with lower doses of cilostazol and aripiprazole with add-on donepezil (CAD) might have potential in the pathogenesis of AD. In the present study, we found the superior efficacies of donepezil add-on with combinatorial mixture of cilostazol plus aripiprazole in modulation of expression of AD-relevant genes: Aβ accumulation, GSK-3β, P300, acetylated tau, phosphorylated-tau levels, and activation of α-secretase/ADAM 10 through SIRT1 activation in the N2a Swe cells expressing human APP Swedish mutation (N2a Swe cells). We also assessed that CAD synergistically raised acetylcholine release and choline acetyltransferase (CHAT) expression that were declined by increased β-amyloid level in the activated N2a Swe cells. Consequently, CAD treatment synergistically increased neurite elongation and improved cell viability through activations of PI3K, BDNF, β-catenin and a7-nicotinic cholinergic receptors in neuronal cells in the presence of Aβ1-42. This work endorses the possibility for efficient treatment of AD by supporting the synergistic therapeutic potential of donepezil add-on therapy in combination with lower doses of cilostazol and aripiprazole.