Anticancer and Antibacterial Properties of Curcumin-Loaded Mannosylated Solid Lipid Nanoparticles for the Treatment of Lung Diseases.

Lung cancer and Mycobacterium avium complex infection are lung diseases associated with high incidence and mortality rates. Most conventional anticancer drugs and antibiotics have certain limitations, including high drug resistance rates and adverse effects. Herein, we aimed to synthesize mannose surface-modified solid lipid nanoparticles (SLNs) loaded with curcumin (Man-CUR SLN) for the effective treatment of lung disease. The synthesized Man-CUR SLNs were analyzed using various instrumental techniques for structural and physicochemical characterization. Loading curcumin into SLNs improved the encapsulation efficiency and drug release capacity, as demonstrated by high-performance liquid chromatography analysis. Furthermore, we characterized the anticancer effect of curcumin using the A549 lung cancer cell line. Cells treated with Man-CUR SLN exhibited an increased cellular uptake and cytotoxicity. Moreover, treatment with free CUR could more effectively reduce cancer migration than treatment with Man-CUR SLNs. Similarly, free curcumin elicited a stronger apoptosis-inducing effect than that of Man-CUR SLNs, as demonstrated by reverse transcription-quantitative PCR analysis. Finally, we examined the antibacterial effects of free curcumin and Man-CUR SLNs against Mycobacterium intracellulare (M.i.) and M.i.-infected macrophages, revealing that Man-CUR SLNs exerted the strongest antibacterial effect. Collectively, these findings indicate that mannose-receptor-targeted curcumin delivery using lipid nanoparticles could be effective in treating lung diseases. Accordingly, this drug delivery system can be used to target a variety of cancers and immune cells.

Seasonal vitamin D levels and lupus low disease activity state in systemic lupus erythematosus.

BACKGROUND: Seasonal variation and sunlight exposure can impact serum vitamin D levels, potentially influencing lupus symptoms. We investigated seasonal vitamin D levels and their correlation with clinical manifestations and disease activity in systemic lupus erythematosus (SLE). METHODS: Serum 25(OH) vitamin D3 (25(OH)D3) levels were categorised as deficient (25(OH)D3 < 10 ng/mL), insufficient (10-30 ng/mL) and sufficiency (>30 ng/mL) in participants analysed in winter (n = 407) and summer (n = 377). Logistic regression analysis was performed to assess the impact of vitamin D levels on achieving a lupus low disease activity state (LLDAS), stratified by season. RESULTS: The mean serum 25(OH)D3 levels differed significantly between the winter and summer measurement groups (22.4 vs. 24.2 ng/mL; p = .018). The prevalences of vitamin D deficiency, insufficiency and sufficiency in the winter group were 12.8%, 66.6% and 20.6%, respectively, compared with 4.5%, 67.9% and 27.6% in the summer group. Achieving LLDAS was highest in the vitamin D sufficiency group (winter: 56.6%, summer: 55%) and lowest in the vitamin D deficiency group (winter: 15.4%, summer: 13.6%), with significant differences (all p < .001). Multivariate analysis identified SLE disease activity index ≤4, normal anti-double-stranded DNA and vitamin D sufficiency as significant factors for achieving LLDAS in both seasons. CONCLUSIONS: Sufficient vitamin D levels are important for achieving LLDAS in patients with SLE during winter and summer. Therefore, physicians should pay attention to the adequacy of vitamin D levels and consider recommending vitamin D supplementation for patients with vitamin D insufficiency.

The Effect of Fenugreek in Type 2 Diabetes and Prediabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Fenugreek is a widely used herbal medicine as a complementary therapy for diabetes mellitus. Lots of clinical trials have proved its beneficial effect on glycemic control parameters and lipid profiles. Thus, we conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of fenugreek as a treatment for type 2 diabetes mellitus. We searched PubMed, Embase, Cochrane, China Knowledge Resource Integrated Database (CNKI), Korean studies Information Service System (KISS), Research Information Sharing Service (RISS), and ScienceON to select RCTs which used fenugreek targeting hyperglycemia with a control group. We used either a random effect model or a fixed model in a meta-analysis of Fasting blood glucose (FBG), 2 h plasma glucose during a 75 g oral glucose tolerance test (OGTT) (2-hPG), homeostatic model assessment for insulin resistance (HOMA-IR), glycosylated hemoglobin (HbA1c)/total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), body mass index (BMI). After screening, a total of 10 studies (706 participants) remained. Fenugreek significantly reduced FBG, 2-hPG, and HbA1c, but it did not significantly decrease HOMA-IR. Moreover, it significantly improved TC, TG, and HDL-C, while there were no significant differences in LDL-C and BMI. Hepatic or renal toxicity was not observed, and there were no severe adverse events associated with fenugreek despite mild gastrointestinal side effects in some studies. In conclusion, fenugreek improves overall glycemic control parameters and lipid profile safely.

Alleviation of imiquimod-induced psoriasis-like symptoms in Rorα-deficient mouse skin.

Retinoic acid receptor-related orphan receptor α (RORα) plays a vital role in various physiological processes, including metabolism, cancer, circadian rhythm, cerebellar development, and inflammation. Although RORα is expressed in the skin, its role in skin physiology remains poorly elucidated. Herein, Rorα was expressed in the basal and suprabasal layers of the epidermis; however, keratinocyte-specific Rorα deletion did not impact normal epidermal formation. Under pathophysiological conditions, Rorα-deficient mice exhibited alleviated psoriasis-like symptoms, including relatively intact epidermal stratification, reduced keratinocyte hyperproliferation, and low-level expression of inflammatory cytokines in keratinocytes. Unexpectedly, the splenic population of Th17 cells was significantly lower in keratinocytespecific RORα deficient mice than in the control. Additionally, Rorα-deficiency reduced imiquimod-induced activation of nuclear factor-κB and STAT3 in keratinocytes. Therefore, we expect that RORα inhibitors act on immune cells and keratinocytes to suppress the onset and progression of psoriasis.as an adjuvant for cancer immunotherapy. [BMB Reports 2023; 56(5): 296-301].

Clinical Outcomes of Operating an Acute Palliative Care Unit at a Comprehensive Cancer Center.

PURPOSE: Acute palliative care units (APCUs) are inpatient services in tertiary hospitals that provide intensive symptom management and assist in hospital discharge for transitions to hospice care. We aimed to analyze the clinical outcomes of operating an APCU at a comprehensive cancer center. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 1,440 consecutive patients admitted to the APCU and analyzed demographic and clinical information, discharge outcomes, symptom assessments using the Edmonton Symptom Assessment System, spiritual distress, and financial distress. RESULTS: The median age of patients was 67.0 (range, 23-97) years, and 41% were female. The most common primary cancer types were lung (21.9%), hepatopancreatobiliary (14.1%), and colorectal cancers (12.9%). The median length of stay was 8.0 days (range, 1-60 days), and 31.0% of patients died in the APCU. Death in the APCU showed a significant decrease over time, and overall inpatient death in oncology wards did not increase after APCU opening. In total, 44.7% of patients were discharged to government-certified hospice centers. The proportion of patients discharged to certified hospice centers increased from 32.2% in 2015 to 62.4% in 2018. Among 715 patients with a follow-up evaluation 1 week after admission, Edmonton Symptom Assessment System symptom scores, spiritual distress, and financial distress showed statistically significant improvements compared with the baseline symptom scores (P < .001). This improvement was limited to patients who did not die in the APCU. CONCLUSION: Patients with advanced cancer admitted to the APCU may experience significant improvements in distressing symptoms. The majority of patients requiring transition to hospice were successfully transferred to certified hospice centers. The percentage discharged alive improved over time.

Novel Plant Extract Ameliorates Metabolic Disorder through Activation of Brown Adipose Tissue in High-Fat Diet-Induced Obese Mice.

Obesity is characterized by excessive body fat accumulation due to unbalanced energy intake and expenditure. Potential therapeutic targets for anti-obesity include the inhibition of white adipose tissue (WAT) hypertrophy and hyperplasia and the activation of brown adipose tissue (BAT). Not only the activation of BAT but also the browning of WAT have gained increasing attention in research fields as an alternative method in the prevention and treatment of obesity. Here, we investigated possible mechanisms underlying the anti-obesity effect of Phlomis umbrosa Turcz. root ethanol extract (PUE) in an obesogenic animal model. PUE treatment can reduce diet-induced obesity and modulate obesity-associated metabolic disorders, including insulin resistance, hepatic steatosis, and inflammation. In the liver, PUE improved hepatic steatosis by suppressing hepatic lipogenesis and lipid absorption while increasing biliary sterol excretion and hepatic fatty acid oxidation compared to the high-fat group. Moreover, PUE increased energy expenditure and regulated fecal lipid excretion, leading to reduced body weight gain. In particular, PUE remarkably activated the browning of subWAT via upregulation of the browning-related protein and gene expression and promoted BAT activation. In conclusion, these findings provide the potential therapeutic usefulness into the effects of PUE in the treatment of obesity and metabolic disorders. Furthermore, it suggests that PUE treatment can regulate energy metabolism via activating BAT and browning subWAT.

Thalamo-cortical network is associated with harmaline-induced tremor in rodent model.

Essential tremor (ET) is the most frequent form of pathologic tremor and one of the most common adult-onset neurologic impairments. However, underlying mechanisms by which structural alterations within the tremor circuit generate the pathological state and how rhythmic neuronal activities propagate and drive tremor remains unclear. Harmaline (HA)-induced tremor model has been most frequently utilized animal model for ET studies, however, there is still a dearth of knowledge over the degree to whether HA-induced tremor mimics the actual underlying pathophysiology of ET, particularly the involvement of thalamo-cortical region. In this study, we investigated the electrophysiological response of the motor circuit including the ventrolateral thalamus (vlTh) and the primary motor cortex (M1), and the modulatory effect of thalamic deep brain stimulation (DBS) using a rat HA-induced tremor model. We found that the theta and high-frequency oscillation (HFO) band power significantly increased after HA administration in both vlTh and M1, and the activity was modulated by the tremor suppression drug (propranolol) and the thalamic DBS. The theta band phase synchronization between the vlTh and M1 was significantly enhanced during the HA-induced tremor, and the transition of cross-frequency coupling in vlTh was found to be associated with the state of HA-induced tremor. Our findings support that the HA tremor could be useful as a valid preclinical model of ET in the context of thalamo-cortical neural network interaction.

Materials and device design for advanced phototherapy systems.

Phototherapy has recently emerged as a promising solution for cancer treatment due to its multifunctionality and minimal invasiveness. Notwithstanding the limited penetration depth of light through skin, the ability of photopharmaceutical device systems to deliver light to desired lesions is important. The device system deploys advanced biocompatible materials and fabrication technologies for electronics, and eventually enables more efficient phototherapy. In this review, we focus on diverse optical electronics to illuminate the lesion site with light. Then, moving on to the phototherapy, we highlight photo-thermal therapy with light absorbing materials, photo-activated chemotherapy with light sensitive materials, and photo-dynamic therapy using photosensitizers. Furthermore, we introduce a drug delivery system that can deliver these photopharmaceutical agents spatiotemporally to the tumor site. To this end, we provide a general overview of materials and devices for phototherapy and discuss critical issues and pending limitations of such phototherapy.

Prevalence and Factors of Osteoporosis and High Risk of Osteoporotic Fracture in Patients with Ankylosing Spondylitis: A Multicenter Comparative Study of Bone Mineral Density and the Fracture Risk Assessment Tool.

BACKGROUND: We investigated the prevalence of and the factors associated with a high risk of osteoporotic fractures in Korean patients with ankylosing spondylitis (AS). METHODS: This was a multicenter, retrospective study including 219 AS patients from five university hospitals; the control group was selected by matching age and sex with those of the AS patients. The fracture risk was evaluated based on bone mineral density (BMD) measured by dual-energy X-ray absorptiometry and the fracture risk assessment tool (FRAX) with/without BMD. RESULTS: The mean age of the patients was 47.6 years, and 144 (65.8%) patients were men. According to the WHO criteria and FRAX with/without BMD, the candidates for pharmacological treatment were 44 (20.1%), 20 (13.2%), and 23 (15.1%) patients, respectively, significantly more than those in the healthy control group. Among them, the proportion of patients receiving osteoporosis treatment was 39.1-75%. In logistic regression analysis, menopause was an independent factor for the high risk of fracture according to the WHO criteria and FRAX with/without BMD. C-reactive protein level (odds ratio (OR) 3.8 and OR 6) and glucocorticoid use (OR 1.5 and OR 1.7) were associated with a high risk of osteoporotic fracture based on FRAX without BMD and osteoporosis diagnosed according to the WHO criteria. CONCLUSIONS: Our study suggests that both FRAX and WHO criteria may be complementary for treatment decisions to reduce osteoporotic fractures in patients with AS.

Differentiation of Microencapsulated Neonatal Porcine Pancreatic Cell Clusters in Vitro Improves Transplant Efficacy in Type 1 Diabetes Mellitus Mice.

BACKGROUND: Neonatal porcine pancreatic cell clusters (NPCCs) have been proposed as an alternative source of ß cells for islet transplantation because of their low cost and growth potential after transplantation. However, the delayed glucose lowering effect due to the immaturity of NPCCs and immunologic rejection remain as a barrier to NPCC's clinical application. Here, we demonstrate accelerated differentiation and immune-tolerant NPCCs by in vitro chemical treatment and microencapsulation. METHODS: NPCCs isolated from 3-day-old piglets were cultured in F-10 media and then microencapsulated with alginate on day 5. Differentiation of NPCCs is facilitated by media supplemented with activin receptor-like kinase 5 inhibitor II, triiodothyronine and exendin-4 for 2 weeks. Marginal number of microencapsulated NPCCs to cure diabetes with and without differentiation were transplanted into diabetic mice and observed for 8 weeks. RESULTS: The proportion of insulin-positive cells and insulin mRNA levels of NPCCs were significantly increased in vitro in the differentiated group compared with the undifferentiated group. Blood glucose levels decreased eventually after transplantation of microencapsulated NPCCs in diabetic mice and normalized after 7 weeks in the differentiated group. In addition, the differentiated group showed nearly normal glucose tolerance at 8 weeks after transplantation. In contrast, neither blood glucose levels nor glucose tolerance were improved in the undifferentiated group. Retrieved graft in the differentiated group showed greater insulin response to high glucose compared with the undifferentiated group. CONCLUSION: in vitro differentiation of microencapsulated immature NPCCs increased the proportion of insulin-positive cells and improved transplant efficacy in diabetic mice without immune rejection.

Factors affecting quality of life in patients with rheumatoid arthritis in South Korea: a cross-sectional study.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease that significantly reduces the quality of life (QOL) of affected patients. Many studies have emphasized the deterioration of QOL during the treatment of patients with RA, but factors that affect this phenomenon in Koreans with RA remain unclear. METHODS: In this cross-sectional study, 166 Korean patients with RA were enrolled, and their general characteristics, disease-related characteristics, fatigue, feelings of depression, self-efficacy, social support, and QOL were assessed. RESULTS: The overall mean score for RA-specific QOL was 5.8 out of 10. Fatigue, depression, self-efficacy, and social support were found to be significantly associated with the QOL of patients with RA. Notably, self-efficacy was found to be the most significant predictor of QOL. CONCLUSIONS: Compared to patients with RA in Western countries, Korean patients with RA, even those with better physical function, seem to have a lower QOL. Identification of the relevant physical, psychological, and social factors affecting QOL in Koreans with RA is beneficial for clinical practice. Incorporation of strategies to address these factors, such as cognitive behavioral therapy, should be considered for the holistic management of RA. Key Points • Korean patients with RA report lower levels of QOL. • Factors associated with the QOL of patients with RA were fatigue, depression, self-efficacy, and social support. • Self-efficacy was the strongest factor affecting QOL in this population; thus, it would be beneficial for clinical practitioners to incorporate cognitive-behavioral approaches into patient education to enhance self-management. • Our findings suggest that QOL and psychological factors should also be regularly evaluated for the holistic management of patients with RA.

Biologic therapy for amyloid A amyloidosis secondary to rheumatoid arthritis treated with interleukin 6 therapy: Case report and review of literature.

INTRODUCTION: Secondary amyloidosis is a rare complication of rheumatoid arthritis (RA) that is histologically characterized by the deposition of amyloid fibrils in target organs, such as the kidneys and gastrointestinal tract. Controlling the inflammatory response is essential to prevent organ dysfunction in amyloid A (AA) amyloidosis secondary to RA, and no clear treatment strategy exists. PATIENT CONCERNS AND DIAGNOSIS: A 66-year-old woman with RA, who had been treated with disease-modifying anti-rheumatic drugs for 1 year, presented with recurrent abdominal pain and prolonged diarrhea. Endoscopy showed chronic inflammation, and colon tissue histology confirmed AA amyloidosis. INTERVENTIONS AND OUTCOMES: After tocilizumab therapy was begun, her diarrhea and abdominal pain subsided, and articular symptoms improved. Biologic drugs for RA have been used in patients with secondary AA amyloidosis, including tumor necrosis factor and Janus kinase inhibitors, interleukin 6 blockers, and a T cell modulator. Here, we systematically review existing case reports and compare the outcomes of RA-related AA amyloidosis after treatment with various drugs. CONCLUSION: The data indicate that biologic drugs like tocilizumab might be treatments of choice for AA amyloidosis secondary to RA.

Animal Venom for Medical Usage in Pharmacopuncture in Korean Medicine: Current Status and Clinical Implication.

Animal venoms, widespread throughout the world, are complex mixtures, the composition of which depends on the venom-producing species. The objective of this study was to contribute to the development of animal venom-based medicines by investigating the use of animal venom pharmacopuncture in Korean medicine (KM) institutions. We surveyed 256 public health centers from 1 through 31 October 2019 as guided by the Ministry of Health and Welfare (MoHW). A questionnaire developed by an expert group was distributed and collected for statistical analysis. The survey identified three types of animal venom-based pharmacopuncture: bee, snake, and toad venoms. The medications are based on a single animal venom ingredient and produced in 11 external herbal dispensaries (EHDs). Each animal venom is processed, refined, and freeze-dried in a cleanroom to produce a powder formulation that is later measured, diluted, filtered, filled, sealed, sterilized, and packaged as pharmacopuncture injections used in KM institutions. Bee venom therapy is effective in treating musculoskeletal pain, snake venom therapy is effective in controlling bleeding during surgery, and toad venom therapy is effective in cancer treatment. The study suggests that bee, snake, and toad venoms could be used in medical institutions and have the potential for drug development.

Development of Hazardous Materials Management Standard for Decoction Type of Personalized Herbal Medicine.

OBJECTIVES: This study was conducted to development of hazardous materials management standards for the decoction type of personalized herbal medicines (PHMs). METHODS: This study was conducted in two stages. We searched documents about criteria to use words such as 'Herb', 'Herbal medicine', and 'Botanical Drug' and summarized the results. We organized the committee consisted of seven experts, and held two meetings to reach an agreement on hazardous management standards of the decoction type of PHMs. RESULTS: The seven documents were presented in the literature review and six items related to hazardous management standards of decoction were identified. The second expert meeting brought that a total of six items, including heavy metal, pesticide residues, sulfur dioxide, benzopyrene, mycotoxin, and micro-organism limits, were selected for safety management of decoction type of PHMs. Also, the criteria and test methods for each standard were suggested for monitoring the decoction type of PHMs. CONCLUSION: The study suggested hazardous material management standards and criteria for the decoction types of PHMs. In the future, it would be necessary to conduct a pilot test to ensure the validity and credibility of the safety management standard and criteria. Furthermore, the government level safety management system should be introduced to verify the safety of decoction medicines.

Intervention Study on the Efficacy and Safety of Platycodon grandiflorus Ethanol Extract in Overweight or Moderately Obese Adults: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Trial.

Platycodon grandiflorus root extract (PGE) has shown various properties, such as anti-hyperlipidemia, anti-diabetic, and anti-obesity, but mostly in animal studies. Therefore, we conducted a preliminary study on the anti-obesity effect of PGE in 108 Korean adults (aged 20-60 years, 30 kg/m2 ≥ body mass index ≥ 23 kg/m2). The participants were randomly assigned to four groups and were administered the placebo, PGE571 (571 mg as PGE), PGE1142 (1142 mg as PGE), and PGE2855 (2855 mg as PGE), independently, for 12 weeks. Body composition, nutrient intake, computed tomography scan, and plasma adipokines, as well as hepatic/renal function markers, were assessed. The PGE571 group revealed a significant decrease in body fat mass and body fat percentage when compared with the placebo group. Moreover, the total abdominal and subcutaneous fat areas were significantly decreased following PGE (PGE2855 group) supplementation. These results provide useful information on the anti-obesity effect of PGE for overweight and obese adult humans.

Comparing Verum and Sham Acupuncture in Fibromyalgia Syndrome: A Systematic Review and Meta-Analysis.

OBJECTIVES: Acupuncture is often used for relieving symptoms of fibromyalgia syndrome (FMS). Our aim is to ascertain whether verum acupuncture is more effective than sham acupuncture in FMS. METHODS: We collected RCTs to investigate the effects of verum acupuncture and sham acupuncture on pain, sleep quality, fatigue, and general status in FMS patients. The databases used for data retrieval were PubMed, Central Cochrane, EMBASE, PsycINFO, CNKI, VIP, OASIS, KoreaMed, and RISS. Selection/exclusion from the retrieved records was performed according to prespecified criteria, and the final selected records were assessed according to the Cochrane risk of bias tool. The results of the included trials were synthesized on the basis of outcomes, and subgroup analysis depended on the type of add-on sham acupuncture that was performed. RESULTS: Ten RCTs (690 participants) were eligible, and eight RCTs were eventually included in the meta-analysis. The synthesis showed a sizable effect of verum acupuncture compared with sham acupuncture on pain relief (standardized mean difference (SMD) -0.49, Z = 3.26, P=0.001; I 2 = 59%), improving sleep quality (SMD -0.46, Z = 3.24, P=0.001; I 2 = 0%), and reforming general status (SMD -0.69, Z = 6.27, P < 0.00001; I 2 = 4%). However, efficacy on fatigue was insignificant (SMD -0.10, Z = 0.51, P=0.61; I 2 = 46%). When compared with a combination of simulation and improper location of needling, the effect of verum acupuncture for pain relief was the most obvious. CONCLUSIONS: Verum acupuncture is more effective than sham acupuncture for pain relief, improving sleep quality, and reforming general status in FMS posttreatment. However, evidence that it reduces fatigue was not found.

Current Status of Management on Pharmacopuncture in Korea through Introduction of an Accreditation System.

OBJECTIVES: Pharmacopuncture is a new form of acupuncture treatment that injects herbal medicine into acupuncture points. This paper introduces the management status of pharmacopuncture through accreditation, and examines the effect of accreditation on pharmacopuncture management. METHODS: The Accreditation System of External Herbal Dispensaries (EHDs) of traditional Korean medicine clinics announced by the Ministry of Health and Welfare in September 2018 were investigated. RESULTS: The Accreditation System of EHDs assesses and certifies herbal medicine and pharmacopuncture preparations. Regular components for the 'pharmacopuncture' certification consist of nine standards, 30 categories, and 165 items. The nine standards include: herbal dispensary facilities, clean room management, management and organization operation, employee management, document management, continuous quality control, herbal medicine management, management of preparation, and pavement management. CONCLUSION: Through EHD accreditation and certification system, traditional Korean medicine clinics and EHDs can now manage pharmacopuncture medicine quality and promise safe pharmacopuncture treatment for the people.

Establishment of Normative Self-Rated Health Status Data and Association between Ideal Life Expectancy and Social Wellness of General Population in Korea.

PURPOSE: The purpose of this study was to establish normative data for holistic health parameters in the general Korean population and to investigate the factor associated with ideal life expectancy (ILE) among these holistic health parameters and sociodemographic variables. METHODS: This study used a questionnaire to obtain self-reported physical, mental, social, spiritual, and general health status and then evaluated their association with ILE. A total of 1,241 individuals responded to the questionnaire, from which we established a multidimensional health status reference data set representing the Korean population. To explain factors associated with ILE, we stratified results by age and gender and performed multiple logistic regression of sociodemographic variables and multidimensional health status. RESULTS: Women reported poor health status more frequently for all five health categories. The average ILE was 87.46 years versus 84.42 years of life expectancy in the general Korean population. Single marital status, higher income, and better social health were significantly associated with higher ILE. CONCLUSION: ILE could be a good indicator reflecting social wellness in a certain society. Comprehensive social health promotion programs can improve individuals' attitudes toward life expectancy, especially for vulnerable groups.

Specific PERK inhibitors enhanced glucose-stimulated insulin secretion in a mouse model of type 2 diabetes.

BACKGROUND: We have reported that partial PERK attenuation using PERK inhibitors (PI) enhanced glucose-stimulated insulin secretion (GSIS) from pancreatic islets and mice through induction of ER chaperone BIP. Therefore, we investigated if PI would have the same effects in a diabetic condition as well. METHODS: GSK2606414 was treated to mouse islets under 20-mM glucose and 0.5-mM palmitate to examine GSIS. To generate a mouse model of type 2 diabetes mellitus (DM), male C57BL/6J mice were fed with high-fat diet and injected with streptozotocin. Several doses (6-16 mg/kg/day) of GSK2656157 and glimepiride were administrated to the mice for 8 weeks, and metabolic phenotypes were evaluated such as body weight, blood glucose levels, insulin secretion and sensitivity, and then changes in the pancreas were measured. RESULTS: High-glucose and palmitate treatment significantly increased PERK phosphorylation in the isolated islets. Suppression of GSIS and glucose-stimulated Ca2+ transit was also observed. PI at 40 nM which decreased PERK phosphorylation by 40% significantly recovered the GSIS and cytosolic calcium. In the mice where significant weight gain and prominent hyperglycemia were induced, PI at 10 mg/kg/day significantly enhanced GSIS and reduced blood glucose levels compared to the vehicle. The effects were similar to those by 10 mg/kg/day of glimepiride. Administration of PI did not induce changes in beta cell mass or pancreatic insulin contents, however, high dose PI decreased pancreatic weight. CONCLUSION: PI at low dose significantly enhanced GSIS in vitro and in vivo under metabolic stress and improved hyperglycemia in the mice mimicking type 2 DM, suggesting a potential as a new therapeutic approach for type 2 DM.

Acupuncture for Infantile Colic: A Systematic Review of Randomised Controlled Trials.

INTRODUCTION: Infantile colic is a common condition causing considerable deterioration in the quality of life of both infants and their parents. Minimal acupuncture, a gentle needling technique without strong muscle stimulation, has primarily been used to treat this condition, but the clinical evidence of its efficacy and safety is yet to be established. The objective of this review was to assess clinical evidence of the safety and efficacy of acupuncture for infantile colic. METHODS: To identify studies for inclusion, PubMed, Cochrane Library, Google Scholar, China Knowledge Resource Integrated Database, Wanfang, and Oriental Medicine Advanced Searching Integrated System were searched until January 2017. Only randomised controlled trials of infantile colic in patients aged 0 to 25 weeks, who were treated with acupuncture, were included. To assess the quality, the risk of bias was determined for each study by two authors. The intention was to perform a meta-analysis, but this was not possible in this study due to considerable clinical heterogeneity among the included studies. RESULTS: Of the 601 studies identified, only four randomized controlled trials were included in this review. All included studies were conducted in northern European countries. Most studies showed a low risk of bias in most domains. Minimal acupuncture on LI4 or ST36 without strong stimulation was used in all studies. From the narrative analysis, acupuncture appears to be effective in alleviating the symptoms of colic, including crying and feeding and stooling problems, and may have only minor adverse effects. However, clinical evidence could not be confirmed owing to considerable clinical heterogeneity and the small sample sizes of the included studies. CONCLUSION: There is currently no conclusive evidence on the safety and efficacy of acupuncture for infantile colic. Rigorous full-scale randomized controlled trials will be necessary in future.