CYBERMED LIFE - ORGANIC  & NATURAL LIVING

Cybermedlife - Therapeutic Actions Light Therapy

An open-label pilot study of a home wearable light therapy device for postpartum depression.

Abstract Title: An open-label pilot study of a home wearable light therapy device for postpartum depression. Abstract Source: Arch Womens Ment Health. 2018 Mar 30. Epub 2018 Mar 30. PMID: 29603017 Abstract Author(s): Leslie M Swanson, Helen J Burgess, Jennifer Zollars, J Todd Arnedt Article Affiliation: Leslie M Swanson Abstract: We sought to establish the feasibility and preliminary effects of home-wearable light therapy for postpartum depression, and its effects on circadian measures. Eight women within 6 months postpartum were prescribed 60 min of daily morning light therapy for 5 weeks. The device was well tolerated. Significant improvements were observed in self-report and clinician-rated depression symptoms, with little change in objective circadian measures. Home-wearable light therapy is feasible for postpartum women and may be a promising treatment for postpartum depression. Clinicaltrials.gov Identifier: NCT02769858. Article Published Date : Mar 29, 2018

Optimal Laser Phototherapy Parameters for Pain Relief.

Abstract Title: Optimal Laser Phototherapy Parameters for Pain Relief. Abstract Source: Photomed Laser Surg. 2018 Mar 27. Epub 2018 Mar 27. PMID: 29583080 Abstract Author(s): Rohit J Kate, Sarah Rubatt, Chukuka S Enwemeka, Wendy E Huddleston Article Affiliation: Rohit J Kate Abstract: BACKGROUND AND OBJECTIVE: Studies on laser phototherapy for pain relief have used parameters that vary widely and have reported varying outcomes. The purpose of this study was to determine the optimal parameter ranges of laser phototherapy for pain relief by analyzing data aggregated from existing primary literature. MATERIALS AND METHODS: Original studies were gathered from available sources and were screened to meet the pre-established inclusion criteria. The included articles were then subjected to meta-analysis using Cohen's d statistic for determining treatment effect size. From these studies, ranges of the reported parameters that always resulted into large effect sizes were determined. These optimal ranges were evaluated for their accuracy using leave-one-article-out cross-validation procedure. RESULTS: A total of 96 articles met the inclusion criteria for meta-analysis and yielded 232 effect sizes. The average effect size was highly significant: d = +1.36 (confidence interval [95% CI] = 1.04-1.68). Among all the parameters, total energy was found to have the greatest effect on pain relief and had the most prominent optimal ranges of 120-162 and 15.36-20.16 J, which always resulted in large effect sizes. The cross-validation accuracy of the optimal ranges for total energy was 68.57% (95% CI = 53.19-83.97). Fewer and less-prominent optimal ranges were obtained for the energy density and duration parameters. None of the remaining parameters was found to be independently related to pain relief outcomes. CONCLUSIONS: The findings of meta-analysis indicate that laser phototherapy is highly effective for pain relief. Based on the analysis of parameters, total energy can be optimized to yield the largest effect on pain relief. Article Published Date : Mar 26, 2018

Precision Light for the Treatment of Psychiatric Disorders. 📎

Abstract Title: Precision Light for the Treatment of Psychiatric Disorders. Abstract Source: Neural Plast. 2018 ;2018:5868570. Epub 2018 Jan 11. PMID: 29593784 Abstract Author(s): Sevag Kaladchibachi, Fabian Fernandez Article Affiliation: Sevag Kaladchibachi Abstract: Circadian timekeeping can be reset by brief flashes of light using stimulation protocols thousands of times shorter than those previously assumed to be necessary for traditional phototherapy. These observations point to a future where flexible architectures of nanosecond-, microsecond-, and millisecond-scale light pulses are compiled to reprogram the brain's internal clock when it has been altered by psychiatric illness or advanced age. In the current review, we present a chronology of seminal experiments that established the synchronizing influence of light on the human circadian system and the efficacy of prolonged bright-light exposure for reducing symptoms associated with seasonal affective disorder. We conclude with a discussion of the different ways that precision flashes could be parlayed during sleep to effect neuroadaptive changes in brain function. This article is a contribution to a special issue oncurated by editors Shimon Amir, Karen Gamble, Oliver Stork, and Harry Pantazopoulos. Article Published Date : Dec 31, 2017

Photobiomodulation therapy promotes neurogenesis by improving post-stroke local microenvironment and stimulating neuroprogenitor cells.

Abstract Title: Photobiomodulation therapy promotes neurogenesis by improving post-stroke local microenvironment and stimulating neuroprogenitor cells. Abstract Source: Exp Neurol. 2017 Oct 19. Epub 2017 Oct 19. PMID: 29056360 Abstract Author(s): Luodan Yang, Donovan Tucker, Yan Dong, Chongyun Wu, Yujiao Lu, Yong Li, Juan Zhang, Timon Cheng-Yi Liu, Quanguang Zhang Article Affiliation: Luodan Yang Abstract: Recent work has indicated that photobiomodulation (PBM) may beneficially alter the pathological status of several neurological disorders, although the mechanism currently remains unclear. The current study was designed to investigate the beneficial effect of PBM on behavioral deficits and neurogenesis in a photothrombotic (PT) model of ischemic stroke in rats. From day 1 to day 7 after the establishment of PT model, 2-minute daily PBM (CW, 808nm, 350mW/cm(2), total 294J at scalp level) was applied on the infarct injury area (1.8mm anterior to the bregma and 2.5mm lateral from the midline). Rats received intraperitoneal injections of 5-bromodeoxyuridine (BrdU) twice daily (50mg/kg) from day 2 to 8 post-stoke, and samples were collected at day 14. We demonstrated that PBM significantly attenuated behavioral deficits and infarct volume induced by PT stroke. Further investigation displayed that PBM remarkably enhanced neurogenesis and synaptogenesis, as evidenced by immunostaining of BrdU, Ki67, DCX, MAP2, spinophilin, and synaptophysin. Mechanistic studies suggested beneficial effects of PBM were accompanied by robust suppression of reactive gliosis and the production of pro-inflammatory cytokines. On the contrary, the release of anti-inflammatory cytokines, cytochrome c oxidase activity and ATP production in peri-infarct regions were elevated following PBM treatment. Intriguingly, PBM could effectively switch an M1 microglial phenotype to an anti-inflammatory M2 phenotype. Our novel findings indicated that PBM is capable of promoting neurogenesis after ischemic stroke. The underlying mechanisms may rely on: 1) promotion of proliferation and differentiation of internal neuroprogenitor cells in the peri-infarct zone; 2) improvement of the neuronal microenvironment by altering inflammatory status and promoting mitochondrial function. These findings provide strong support for the promising therapeutic effect of PBM on neuronal repair following ischemic stroke. Article Published Date : Oct 18, 2017

Nonpharmacological Treatments for Post-Stroke Depression: An Integrative Review of the Literature.

Abstract Title: Nonpharmacological Treatments for Post-Stroke Depression: An Integrative Review of the Literature. Abstract Source: Res Gerontol Nurs. 2017 May 30:1-14. Epub 2017 May 30. PMID: 28556875 Abstract Author(s): Niloufar Niakosari Hadidi, Roberta L Huna Wagner, Ruth Lindquist Article Affiliation: Niloufar Niakosari Hadidi Abstract: Stroke is the fifth leading cause of death and the number one cause of long-term disability. Seventy-five percent of annual stroke victims are older than 65. Post-stroke depression (PSD) is a common consequence of stroke, with the estimated prevalence ranging from 25% to 79%. Although several studies have investigated the impact of pharmacological interventions on PSD, there is a significant gap in knowledge regarding the efficacy of nonpharmacological measures for treatment of PSD. The purpose of the current integrative literature review was to synthesize the state of knowledge on selected nonpharmacological treatments for PSD and present findings regarding the efficacy of investigated treatments. Twenty-one studies published from 1992-2016 were identified and synthesized. Results indicated that studies demonstrating improvement in depressive symptoms included ecosystem-focused therapy, life review therapy, problem solving therapy, meridian acupressure, repetitive transcranial magnetic stimulation, music therapy, exercise, light therapy, motivational interviewing, and robotic-assisted neurorehabilitation. [Res Gerontol Nurs. 2017; x(x):xx-xx.]. Article Published Date : May 29, 2017

A Systematic Review of Bright Light Therapy for Eating Disorders.

Abstract Title: A Systematic Review of Bright Light Therapy for Eating Disorders. Abstract Source: Prim Care Companion CNS Disord. 2016 Oct 27 ;18(5). Epub 2016 Aug 27. PMID: 27835724 Abstract Author(s): Marshall T Beauchamp, Jennifer D Lundgren Article Affiliation: Marshall T Beauchamp Abstract: Objective: Bright light therapy is a noninvasive biological intervention for disorders with nonnormative circadian features. Eating disorders, particularly those with binge-eating and night-eating features, have documented nonnormative circadian eating and mood patterns, suggesting that bright light therapy may be an efficacious stand-alone or adjunctive intervention. The purpose of this systematic literature review, using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, was (1) to evaluate the state of the empirical treatment outcome literature on bright light therapy for eating disorders and (2) to explore the timing of eating behavior, mood, and sleep-related symptom change so as to understand potential mechanisms of bright light therapy action in the context of eating disorder treatment. Data Sources: A comprehensive literature search using PsycInfo and PubMed/MEDLINE was conducted in April 2016 with no date restrictions to identify studies published using bright light therapy as a treatment for eating disorders. Keywords included combinations of terms describing disordered eating (eating disorder, anorexia nervosa, bulimia nervosa, binge eating, binge, eating behavior, eating, and night eating) and the use of bright light therapy (bright light therapy, light therapy, phototherapy). After excluding duplicates, 34 articles were reviewed for inclusion. Study Selection and Data Extraction: 14 published studies of bright light therapy for eating disorders met inclusion criteria (included participants with an eating disorder/disordered-eating behaviors; presented as a case study, case series, open-label clinical trial, or randomized/nonrandomized controlled trial; written in English; and published and available by the time of manuscript review). Results: Results suggest that bright light therapy is potentially effective at improving both disordered-eating behavior and mood acutely, although the timing of symptom response and the duration of treatment effects remain unknown. Conclusions: Future research should systematically control for placebo response, assess symptom change frequently and across a broad range of systems, and evaluate the longer-term efficacy of bright light therapy for eating disorders. Article Published Date : Oct 26, 2016

Bright Light Therapy as Augmentation of Pharmacotherapy for Treatment of Depression: A Systematic Review and Meta-Analysis.

Abstract Title: Bright Light Therapy as Augmentation of Pharmacotherapy for Treatment of Depression: A Systematic Review and Meta-Analysis. Abstract Source: Prim Care Companion CNS Disord. 2016 Oct 20 ;18(5). Epub 2016 Aug 20. PMID: 27835725 Abstract Author(s): Thomas M Penders, Cornel N Stanciu, Alexander M Schoemann, Philip T Ninan, Richard Bloch, Sy A Saeed Article Affiliation: Thomas M Penders Abstract: Background: Bright light therapy has demonstrated efficacy and is an accepted treatment for seasonal depression. It has been suggested that bright light therapy may have efficacy in nonseasonal depressions. Also, there is evidence that bright light therapy may improve responsiveness to antidepressant pharmacotherapy. Data Sources: We searched PubMed/MEDLINE, PsycINFO, PsycARTICLES, CINAHL, EMBASE, Scopus, and Academic OneFile for English-language literature published between January 1998 and April 2016, using the keywords bright light therapy AND major depression, bright light therapy AND depress*, bright light therapy AND bipolar depression, bright light therapy AND affective disorders, circadian rhythm AND major depression, circadian rhythm AND depress*, and circadian rhythm AND affective disorder. Study Selection and Data Extraction: Studies that reported randomized trials comparing antidepressant pharmacotherapy with bright light therapy≥ 5,000 lux for ≥ 30 minutes to antidepressant pharmacotherapy without bright light therapy for the treatment of nonseasonal depression were included. Studies of seasonal depression were excluded. Following review of the initial 112 returns, 2 of the authors independently judged each trial, applying the inclusionary and exclusionary criteria. Ten studies were selected as meeting these criteria. Subjects in these studies were pooled using standard techniques of meta-analysis. Results: Ten studies involving 458 patients showed improvement using bright light therapy augmentation versus antidepressant pharmacotherapy alone. The effect size was similar to that of other accepted augmentation strategies, roughly 0.5. Conclusions: Analysis of pooled data from randomized trials provides evidence for the efficacy of use of bright light therapy≥ 5,000 lux for periods ≥ 30 minutes when used as augmentation to standard antidepressant pharmacotherapy in the treatment of major depressive disorder and bipolar depression without a seasonal pattern. Article Published Date : Oct 19, 2016

Effects of melatonin and bright light treatment in childhood chronic sleep onset insomnia with late melatonin onset: A randomised controlled study.

Abstract Title: Effects of melatonin and bright light treatment in childhood chronic sleep onset insomnia with late melatonin onset: A randomised controlled study. Abstract Source: Sleep. 2016 Oct 10. Epub 2016 Aug 10. PMID: 27748241 Abstract Author(s): Annette van Maanen, Anne Marie Meijer, Marcel G Smits, Kristiaan B van der Heijden, Frans J Oort Article Affiliation: Annette van Maanen Abstract: STUDY OBJECTIVES: Chronic sleep onset insomnia with late melatonin onset is prevalent in childhood, and has negative daytime consequences. Melatonin treatment is known to be effective in treating these sleep problems. Bright light therapy might be an alternative treatment, with potential advantages over melatonin treatment. In this study, we compare the effects of melatonin and bright light treatment with a placebo condition in children with chronic sleep onset insomnia and late melatonin onset. METHODS: 84 children (mean age 10.0 years, 61% boys) first entered a baseline week, after which they received melatonin (N=26), light (N=30), or placebo pills (N=28) for three to four weeks. Sleep was measured daily with sleep diaries and actigraphy. Before and after treatment children completed a questionnaire on chronic sleep reduction, and Dim Light Melatonin Onset (DLMO) was measured. Results were analysed with linear mixed model analyses. RESULTS: Melatonin treatment and light therapy decreased sleep latency (sleep diary) and advanced sleep onset (sleep diary and actigraphy), although for sleep onset the effects of melatonin were stronger. In addition, melatonin treatment advanced DLMO and had positive effects on sleep latency and sleep efficiency (actigraphy data), and sleep time (sleep diary and actigraphy data). However, wake after sleep onset (actigraphy) increased with melatonin treatment. No effects on chronic sleep reduction were found. CONCLUSIONS: We found positive effects of both melatonin and light treatment on various sleep outcomes, but more and stronger effects were found for melatonin treatment. NEDERLANDS TRIAL REGISTER (NTR): NTR4045 (http://www.trialregister.nl). Article Published Date : Oct 09, 2016

A sham-controlled randomized trial of adjunctive light therapy for non-seasonal depression.

Abstract Title: A sham-controlled randomized trial of adjunctive light therapy for non-seasonal depression. Abstract Source: J Affect Disord. 2016 Oct ;203:1-8. Epub 2016 Aug 26. PMID: 27267951 Abstract Author(s): Magdalena Chojnacka, Anna Z Antosik-Wójcińska, Monika Dominiak, Dorota Bzinkowska, Agnieszka Borzym, Marlena Sokół-Szawłowska, Gabriela Bodzak-Opolska, Dorota Antoniak, Łukasz Święcicki Article Affiliation: Magdalena Chojnacka Abstract: BACKGROUND: The aim of the study was to examine the efficacy and safety of morning bright light therapy (BLT) in the treatment of patients with a current major depressive episode (MDE) in bipolar and unipolar disorder without a seasonal pattern. It was a randomized, sham-controlled trial. METHODS: Adults, ages 18-70 years were randomized to treatment either with BLT or a sham negative ion generator (as a placebo control). The subjects were required to be on a stable and therapeutic dose of psychotropic medication for at least 4 weeks prior to enrollment and their treatment had to be insufficiently effective. Their clinical state was monitored at the baseline and at the end of treatment. The Hamilton Depression Rating Scale-21 items (HDRS-21), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI-II), Clinical Global Impression-Severity (CGI-S) and Patient Global Impression (PGI) were used. The results were analyzed with an intention-to-treat (ITT) analysis. RESULTS: Ninety-five patients were enrolled (50 diagnosed with bipolar disorder and 45 with unipolar depression). Fifty-two patients were randomized to treatment with BLT and forty-three were in the placebo group (ITT population). Eighty-three subjects completed the study. There were 12 dropouts (5 in the light group and 7 in the placebo group). After 14 days of treatment, a significant improvement was found in all groups (p<0.001). The subjects treated with BLT did not significantly differ in terms of improvement in HDRS-21 scores at the endpoint when compared to patients treated with placebo (p=0.2). However, further analysis demonstrated significantly higher response (50% v. 27.9%, p=0.02) and remission rates (28.8% v. 11.6%, p=0.04) among patients treated with morning BLT when compared to placebo group. It should be noted that in the population of drug-resistant patients, BLT was more efficacious than placebo. There were no statistically significant differences between unipolar and bipolar disorders (p=0.4). CONCLUSION: Although overall improvement in HDRS-21 scores were not superior in the BLT group, both response and remission rates were significantly higher among patients treated with BLT relative to those receiving the sham intervention. BLT was also more efficacious than placebo in the population of patients with drug-resistant depression. Further studies to define the subpopulation of patients with non-seasonal depression who may benefit the most from BLT are needed. Article Published Date : Sep 30, 2016

Photo Inactivation of Streptococcus mutans Biofilm by Violet-Blue light.

Abstract Title: Photo Inactivation of Streptococcus mutans Biofilm by Violet-Blue light. Abstract Source: Curr Microbiol. 2016 Sep ;73(3):426-33. Epub 2016 Aug 8. PMID: 27278805 Abstract Author(s): Grace F Gomez, Ruijie Huang, Meoghan MacPherson, Andrea G Ferreira Zandona, Richard L Gregory Article Affiliation: Grace F Gomez Abstract: Among various preventive approaches, non-invasive phototherapy/photodynamic therapy is one of the methods used to control oral biofilm. Studies indicate that light at specific wavelengths has a potent antibacterial effect. The objective of this study was to determine the effectiveness of violet-blue light at 380-440 nm to inhibit biofilm formation of Streptococcus mutans or kill S. mutans. S. mutans UA159 biofilm cells were grown for 12-16 h in 96-well flat-bottom microtiter plates using tryptic soy broth (TSB) or TSB with 1 % sucrose (TSBS). Biofilm was irradiated with violet-blue light for 5 min. After exposure, plates were re-incubated at 37 °C for either 2 or 6 h to allow the bacteria to recover. A crystal violet biofilm assay was used to determine relative densities of the biofilm cells grown in TSB, but not in TSBS, exposed to violet-blue light. The results indicated a statistically significant (P < 0.05) decrease compared to the non-treated groups after the 2 or 6 h recovery period. Growth rates of planktonic and biofilm cells indicated a significant reduction in the growth rate of the violet-blue light-treated groups grown in TSB and TSBS. Biofilm viability assays confirmed a statisticallysignificant difference between violet-blue light-treated and non-treated groups in TSB and TSBS. Visible violet-blue light of the electromagnetic spectrum has the ability to inhibit S. mutans growth and reduce the formation of S. mutans biofilm. This in vitro study demonstrated that violet-blue light has the capacity to inhibit S. mutans biofilm formation. Potential clinical applications of light therapy in the future remain bright in preventing the development and progression of dental caries. Article Published Date : Aug 31, 2016

Combination therapy of orally administered glycyrrhizin and UVB improved active-stage generalized vitiligo. 📎

Abstract Title: Combination therapy of orally administered glycyrrhizin and UVB improved active-stage generalized vitiligo. Abstract Source: Braz J Med Biol Res. 2016 Jul 25 ;49(8). PMID: 27464024 Abstract Author(s): K H Mou, D Han, W L Liu, P Li Article Affiliation: K H Mou Abstract: Glycyrrhizin has been used clinically for several years due to its beneficial effect on immunoglobulin E (IgE)-induced allergic diseases, alopecia areata and psoriasis. In this study, glycyrrhizin, ultraviolet B light (UVB) or a combination of both were used to treat active-stage generalized vitiligo. One hundred and forty-four patients between the ages of 3 and 48 years were divided into three groups: group A received oral compound glycyrrhizin (OCG); group B received UVB applications twice weekly, and group C received OCG+UVB. Follow-ups were performed at 2, 4, and 6 months after the treatment was initiated. The Vitiligo Area Scoring Index (VASI) and the Vitiligo Disease Activity (VIDA) instrument were used to assess the affected body surface, at each follow-up. Results showed that 77.1, 75.0 and 87.5% in groups A, B and C, respectively, presented repigmentation of lesions. Responsiveness to therapy seemed to be associated with lesion location and patient compliance. Adverse events were limited and transient. This study showed that, although the three treatment protocols had positive results, OCG and UVB combination therapy was the most effective and led to improvement in disease stage from active to stable. Article Published Date : Jul 24, 2016

PURLs: Light therapy for nonseasonal major depressive disorder? 📎

Abstract Title: PURLs: Light therapy for nonseasonal major depressive disorder? Abstract Source: J Fam Pract. 2016 Jul ;65(7):486-8. PMID: 27565102 Abstract Author(s): Kehinde Eniola, Angela Bacigalupo, Anne Mounsey Article Affiliation: Kehinde Eniola Abstract: While bright light therapy already has a place in the treatment of seasonal affective disorder, a recent trial spotlights its utility beyond the winter months. Article Published Date : Jun 30, 2016

Efficacy of Bright Light Treatment, Fluoxetine, and the Combination in Patients With Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial. 📎

Abstract Title: Efficacy of Bright Light Treatment, Fluoxetine, and the Combination in Patients With Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial. Abstract Source: JAMA Psychiatry. 2016 Jan ;73(1):56-63. PMID: 26580307 Abstract Author(s): Raymond W Lam, Anthony J Levitt, Robert D Levitan, Erin E Michalak, Amy H Cheung, Rachel Morehouse, Rajamannar Ramasubbu, Lakshmi N Yatham, Edwin M Tam Article Affiliation: Raymond W Lam Abstract: IMPORTANCE: Bright light therapy is an evidence-based treatment for seasonal depression, but there is limited evidence for its efficacy in nonseasonal major depressive disorder (MDD). OBJECTIVE: To determine the efficacy of light treatment, in monotherapy and in combination with fluoxetine hydrochloride, compared with a sham-placebo condition in adults with nonseasonal MDD. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo- and sham-controlled, 8-week trial in adults (aged 19-60 years) with MDD of at least moderate severity in outpatient psychiatry clinics in academic medical centers. Data were collected from October 7, 2009, to March 11, 2014. Analysis was based on modified intent to treat (randomized patients with≥1 follow-up rating). INTERVENTIONS: Patients were randomly assigned to (1) light monotherapy (active 10,000-lux fluorescent white light box for 30 min/d in the early morning plus placebo pill); (2) antidepressant monotherapy (inactive negative ion generator for 30 min/d plus fluoxetine hydrochloride, 20 mg/d); (3) combination light and antidepressant; or (4) placebo (inactive negative ion generator plus placebo pill). MAIN OUTCOMES AND MEASURES: Change score on the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to the 8-week end point. Secondary outcomes included response (≥50% reduction in MADRS score) and remission (MADRS score ≤10 at end point). RESULTS: A total of 122 patients were randomized (light monotherapy, 32; fluoxetine monotherapy, 31; combination therapy, 29; placebo, 30). The mean (SD) changes in MADRS score for the light, fluoxetine, combination, and placebo groups were 13.4 (7.5), 8.8 (9.9), 16.9 (9.2), and 6.5 (9.6), respectively. The combination (effect size [d] = 1.11; 95% CI, 0.54 to 1.64) and light monotherapy (d = 0.80; 95% CI, 0.28 to 1.31) were significantly superior to placebo in the MADRS change score, but fluoxetine monotherapy (d = 0.24; 95% CI, -0.27 to 0.74) was not superior to placebo. For the respective placebo, fluoxetine, light,and combination groups at the end point, response was achieved by 10 (33.3%), 9 (29.0%), 16 (50.0%), and 22 (75.9%) and remission was achieved by 9 (30.0%), 6 (19.4%), 14 (43.8%), and 17 (58.6%). Combination therapy was superior to placebo in MADRS response (β = 1.70; df = 1; P = .005)and remission (β = 1.33; df = 1; P = .02), with numbers needed to treat of 2.4 (95% CI, 1.6 to 5.8) and 3.5 (95% CI, 2.0 to 29.9), respectively. All treatments were generally well tolerated, with few significant differences in treatment-emergent adverse events. CONCLUSIONS AND RELEVANCE: Bright light treatment, both as monotherapy and in combination with fluoxetine, was efficacious and well tolerated in the treatment of adults with nonseasonal MDD. The combination treatment had the most consistent effects. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00958204. Article Published Date : Dec 31, 2015

Trends of inflammatory markers and cytokines after one month of phototherapy in patients with rheumatoid arthritis. 📎

Abstract Title: Trends of inflammatory markers and cytokines after one month of phototherapy in patients with rheumatoid arthritis. Abstract Source: Acta Med Acad. 2015 Nov ;44(2):102-8. PMID: 26702905 Abstract Author(s): José Meneses Calderón, Irma González Sánchez, Guillermo Aburto Huacuz, Arely Sarai Alonso Barreto, María Del Carmen Colín Ferreyra, Hugo Mendieta Zerón Article Affiliation: José Meneses Calderón Abstract: OBJECTIVE: to evaluate changes in the expression of tumor necrosis factor-α in patients with rheumatoid arthritis submitted to phototherapy. MATERIALS AND METHODS: This was an open label study, enrolling ten patients. The phototherapy scheme within a range of 425 to 650 nm, 11.33 Joules/cm2, 30 cm above the chest was as follows: a) 45-min daily sessions from Monday to Friday for 2 to 3 months; b) three, 45- min weekly sessions for 1 to 2 months; c) twice weekly 45-min sessions for 1 to 2 months, and d) one weekly session for 1 to 2 months until completion. Erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor were measured in peripheral blood and tumor necrosis factor-α, interleukin-1β, and interleukin-10 in leukocytes by quantitative real-time Reverse transcriptase-Polymerase chain reaction. In all the patients the next indexes: Karnofsky scale, Rheumatoid Arthritis-specific quality of life instrument, Steinbrocker Functional Capacity Rating and the Visual Analog Scale were evaluated. RESULTS: Erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor declined notoriously after the indicated sessions. In gene expression, there was a tendency in tumor necrosis factor-α to decrease after 1 month, from 24.5±11.4 to 18±9.2 relative units, without reaching a significant statistical difference. The four tested indexes showed improvement. CONCLUSION: Phototherapy appears to be a plausible complementary option to reduce the inflammatory component in rheumatoid arthritis. Article Published Date : Oct 31, 2015

Low-level laser therapy (LLLT) associated with aerobic plus resistance training to improve inflammatory biomarkers in obese adults.

Abstract Title: Low-level laser therapy (LLLT) associated with aerobic plus resistance training to improve inflammatory biomarkers in obese adults. Abstract Source: Lasers Med Sci. 2015 May 10. Epub 2015 May 10. PMID: 25958170 Abstract Author(s): Raquel Munhoz da Silveira Campos, Ana Raimunda Dâmaso, Deborah Cristina Landi Masquio, Antonio Eduardo Aquino, Marcela Sene-Fiorese, Fernanda Oliveira Duarte, Lian Tock, Nivaldo Antonio Parizotto, Vanderlei Salvador Bagnato Article Affiliation: Raquel Munhoz da Silveira Campos Abstract: Recently, investigations suggest the benefits of low-level laser (light) therapy (LLLT) in noninvasive treatment of cellulite, improvement of body countering, and control of lipid profile. However, the underlying key mechanism for such potential effects associated to aerobic plus resistance training to reduce body fat and inflammatory process, related to obesity in women still unclear. The purpose of the present investigation was to evaluate the effects of combined therapy of LLLT and aerobic plus resistance training in inflammatory profile and body composition of obese women. For this study, it involved 40 obese women with age of 20-40 years. Inclusion criteria were primary obesity and body mass index (BMI) greater than 30 kg/m(2) and less than 40 kg/m(2). The voluntaries were allocated in two different groups: phototherapy group and SHAM group. The interventions consisted on physical exercise training and application of phototherapy (808 nm), immediately after the physical exercise, with special designed device. Proinflammatory/anti-inflammatory adipokines were measured. It was showed that LLLT associated to physical exercise is more effective than physical exercise alone to increase adiponectin concentration, an anti-inflammatory adipokine. Also, it showed reduced values of neck circumference (cm), insulin concentration (μU/ml), and interleukin-6 (pg/ml) in LLLT group. In conclusion, phototherapy can be an important tool in the obesity, mostly considering its potential effects associated to exercise training inattenuating inflammation in women, being these results applicable in the clinical practices to control related risk associated to obesity. Article Published Date : May 09, 2015
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Repetitive verbal behaviors are not always harmful signs: Compensatory plasticity within the language network in aphasia.

Related Articles Repetitive verbal behaviors are not always harmful signs: Compensatory plasticity within the language network in aphasia. Brain Lang. 2019 Jan 18;190:16-30 Authors: Torres-Prioris MJ, López-Barroso D, Roé-Vellvé N, Paredes-Pacheco J, Dávila G, Berthier ML Abstract Repetitive verbal behaviors such as conduite d'approche (CdA) and mitigated echolalia (ME) are well-known phenomena since early descriptions of aphasia. Nevertheless, there is no substantial fresh knowledge on their clinical features, neural correlates and treatment interventions. In the present study we take advantage of three index cases of chronic fluent aphasia showing CdA, ME or both symptoms to dissect their clinical and neural signatures. Using multimodal neuroimaging (structural magnetic resonance imaging and [18]-fluorodeoxyglucose positron emission tomography during resting state), we found that despite of the heterogeneous lesions in terms of etiology (stroke, traumatic brain injury), volume and location, CdA was present when the lesion affected in greater extent the left dorsal language pathway, while ME resulted from preferential damage to the left ventral stream. The coexistence of CdA and ME was associated with involvement of areas overlapping with the structural lesions and metabolic derangements described in the subjects who showed one of these symptoms (CdA or ME). These findings suggest that CdA and ME represent the clinical expression of plastic changes that occur within the spared language network and its interconnected areas in order to compensate for the linguistic functions that previously relied on the activity of the damaged pathway. We discuss the results in the light of this idea and consider alternative undamaged neural networks that may support CdA and ME. PMID: 30665003 [PubMed - as supplied by publisher]

High-dose melphalan and autologous peripheral blood stem cell transplantation in patients with AL amyloidosis and cardiac defibrillators.

Related Articles High-dose melphalan and autologous peripheral blood stem cell transplantation in patients with AL amyloidosis and cardiac defibrillators. Bone Marrow Transplant. 2019 Jan 21;: Authors: Phull P, Sanchorawala V, Brauneis D, Sloan JM, Siddiqi OK, Quillen K, Sarosiek S Abstract Cardiac deposition of misfolded light chains is the leading cause of morbidity and mortality in patients with immunoglobulin (AL) amyloidosis. Cardiac defibrillators can be used in the management of patients with advanced cardiac amyloidosis, but data concerning the use of these devices in patients undergoing treatment with high-dose melphalan followed by autologous peripheral blood stem cell transplantation (HDM/SCT) is limited. Herein we describe a single-institution experience of HDM/SCT in 15 patients with cardiac defibrillators. During the peri-transplant period, five of these patients (33%) had detectable cardiac arrhythmias and two patients (13%) had implantable cardiac defibrillator (ICD) discharges. Thirteen of the 14 evaluable patients (93%) achieved at least a partial hematologic response. Transplant-related mortality was 6.7% and median overall survival was 40.8 months, with multiple patients achieving an overall survival of >10 years. These data highlight the feasibility of HDM/SCT in patients with an ICD due to advanced cardiac AL amyloidosis, but highlight the need for additional research to appropriately determine which patients will benefit from this aggressive therapy. PMID: 30664726 [PubMed - as supplied by publisher]

Primary small bowel lymphoma presenting as invagination.

Related Articles Primary small bowel lymphoma presenting as invagination. Turk J Surg. 2018 Dec 01;34(4):331-333 Authors: İflazoğlu N, Mengeloğlu A, Korkmaz NŞ, Karaalioğlu B, Yülüklü M Abstract One of the causes of invagination in adults is primary small bowel lymphoma. Primary small bowel lymphomas are rare, present themselves with complications due to diagnostic difficulties, and are diagnosed only after surgical intervention. In case of invagination, one of the complications of these tumors, namely primary small bowel lymphoma, should also be considered as a cause in the diagnosis. In this paper, the diagnosis and therapy of a rare case of primary polypoid-type small intestinal lymphoma demonstrating findings of obstruction due to invagination have been presented and discussed in the light of the literature. PMID: 30664435 [PubMed]

Sodium houttuyfonate inhibits LPS‑induced mastitis in mice via the NF‑κB signalling pathway.

Related Articles Sodium houttuyfonate inhibits LPS‑induced mastitis in mice via the NF‑κB signalling pathway. Mol Med Rep. 2019 Jan 10;: Authors: Liu P, Yang C, Lin S, Zhao G, Zhang T, Guo S, Jiang K, Wu H, Qiu C, Guo M, Deng G Abstract Sodium houttuyfonate (SH) has been indicated to play an important anti‑inflammatory role. Previous studies have confirmed that SH can inhibit the NF‑κB pathway in lipopolysaccharide (LPS)‑induced mastitis in bovine mammary epithelial cells. However, the effects of SH on LPS‑induced mastitis in animals should be verified to further evaluate its actual value. In the present study, the anti‑inflammatory effects of SH were investigated in mouse models and a mouse mammary epithelial cell line. Hematoxylin and eosin staining (H&E) showed that SH therapy significantly alleviated the pathological changes in mammary glands. Myeloperoxidase (MPO) activity analysis demonstrated that SH substantially decreased MPO activity in vivo. RT‑qPCR results showed that SH reduced the expression of interleukin (IL)‑1, IL‑6 and tumor necrosis factor α both in vivo and in vitro. In addition, western blot results indicated that SH suppressed the phosphorylation of nuclear factor kappa‑light‑chain‑enhancer of activated B‑cells (NF‑κB) p65 protein and reduced the degradation of inhibitor of kappa light polypeptide gene enhancer in B‑cells alpha protein in vivo and in vitro. These results demonstrated that SH ameliorates LPS‑induced mastitis by inhibiting the NF‑κB pathway. PMID: 30664199 [PubMed - as supplied by publisher]

Profiling of apoptosis- and autophagy-associated molecules in human lung cancer A549 cells in response to cisplatin treatment using stable isotope labeling with amino acids in cell culture.

Related Articles Profiling of apoptosis- and autophagy-associated molecules in human lung cancer A549 cells in response to cisplatin treatment using stable isotope labeling with amino acids in cell culture. Int J Oncol. 2019 Jan 18;: Authors: Wang Z, Liu G, Jiang J Abstract Cis‑diammine‑dichloro‑platinum II‑based adjuvant chemotherapy provides an alternative therapy to improve the survival of patients with lung tumors, especially those with non‑small cell lung cancer (NSCLC). However, drug resistance is a large clinical problem and its underlying mechanism remains unclear. In the present study, NSCLC A549 cells were treated with a low concentration of cisplatin in order to observe and determine the development of chemoresistance, via growth curves, colony forming assays and apoptosis assays. Then the induction of autophagy was examined in the cisplatin‑treated A549 cells with a fluorescence reporter. Profiled proteins in the cisplatin‑treated A549 cells were also assessed using the stable isotope labeling by amino acids in cell culture (SILAC) method, and then the differentially expressed molecules were verified. The results demonstrated that A549 cells became less sensitive to cisplatin [resistant A549 cells (A549R)] following 20 passages in the medium containing a low concentration of cisplatin, with less apoptotic cells post‑cisplatin treatment. A549R cells grew more efficiently in the cisplatin medium, with more colony formation and more cells migrating across the baseline. In addition, NSCLC results demonstrated that more autophagy‑related proteins (ATGs) were expressed in the A549R cells. Furthermore, the western blotting results confirmed this upregulation of ATGs in A549R cells. In addition, two repeated SILAC screening experiments recognized 15 proteins [glucose‑regulated protein, 78 kDa (GRP78), heat shock protein 71, pre‑mRNA processing factor 19, polypyrimidine tract binding protein 1, translationally controlled tumor protein, Cathepsin D, Cytochrome c, thioredoxin domain containing 5, MutS homolog (MSH) 6, Annexin A2 (ANXA2), BRCA2 and Cyclin dependent kinase inhibitor 1A interacting protein, MSH2, protein phosphatase 2A 55 kDa regulatory subunit Bα, Rho glyceraldehyde‑3‑phosphate‑dissociation inhibitor 1 and ANXA4] that were upregulated by >1.5‑fold in heavy (H)‑ and light (L)‑labeled A549R cells. In addition, 16 and 14 proteins were downregulated by >1.5‑fold in the H‑ and L‑labeled A549R cells, respectively. The majority of the downregulated proteins were associated with apoptosis. In conclusion, the present study isolated a cisplatin‑resistant human lung cancer A549 cell clone, with reduced apoptosis and high levels of autophagy, in response to cisplatin treatment. In cisplatin‑resistant A549R cells, SILAC proteomics recognized the high expression of GRP78 and other proteins that are associated with anti‑apoptosis and/or autophagy promotion. PMID: 30664195 [PubMed - as supplied by publisher]

Synergistic anticancer effect of acteoside and temozolomide-based glioblastoma chemotherapy.

Related Articles Synergistic anticancer effect of acteoside and temozolomide-based glioblastoma chemotherapy. Int J Mol Med. 2019 Jan 11;: Authors: Hwang TW, Kim DH, Kim DB, Jang TW, Kim GH, Moon M, Yoon KA, Choi DE, Park JH, Kim JJ Abstract Temozolomide (TMZ) is an alkylating agent commonly used as a first‑line treatment for high‑grade glioblastoma. However, TMZ has short half‑life and frequently induces tumor resistance, which can limit its therapeutic efficiency. In the present study, it was hypothesized that combined treatment with TMZ and acteoside has synergistic effects in glioblastoma therapy. Using cell viability and wound‑healing assays, it was determined that this treatment regimen reduced cell viability and migration to a greater extent than either TMZ or acteoside alone. Following previous reports that TMZ affected autophagy in glioma cells, the present study examined the effects of TMZ + acteoside combination treatment on apoptosis and autophagy. The TMZ + acteoside combination treatment increased the cleavage of caspase‑3 and levels of B‑cell lymphoma 2 (Bcl‑2)‑associated X protein and phosphorylated p53, and decreased the level of Bcl‑2. The combination treatment increased microtubule‑associated protein 1 light chain 3 and apoptosis‑related gene expression. It was also determined that TMZ + acteoside induced apoptosis and autophagy through the mitogen‑activated protein kinase signaling pathway. These findings suggest that acteoside has beneficial effects on TMZ‑based glioblastoma therapy. PMID: 30664150 [PubMed - as supplied by publisher]

IGENDA protocol: gender differences in awareness, knowledge and perception of cardiovascular risk: an Italian multicenter study.

Related Articles IGENDA protocol: gender differences in awareness, knowledge and perception of cardiovascular risk: an Italian multicenter study. J Cardiovasc Med (Hagerstown). 2019 Jan 16;: Authors: Maffei S, Cugusi L, Meloni A, Deidda M, Colasante E, Marchioli R, Surico N, Mercuro G, Working Group of Gender Cardiovascular Disease of the Italian Society of Cardiology (SIC), Italian Society of Obstetrics, Gynecology (SIGO) Abstract AIMS: Recent reports evidenced gender differences in the knowledge, perception and awareness of cardiovascular risk factors (CVRFs) and cardiovascular diseases (CVDs). Despite the number of high-quality trials that attempted to establish the efficacy of different preventive interventions on CVDs, in the Italian scenario the differences by gender in awareness, knowledge and perception of CVD have not been addressed yet. So, the aims of this cross-sectional, observational and multicenter study will be to evaluate the gender differences in the awareness and perception of CVD risk, to assess the knowledge of CVD symptoms and preventive behaviors/barriers in men and women participating in this study, and to provide a national primary care approach for gender-oriented cardiovascular prevention strategies and therapy. METHODS: A self-administered questionnaire will be completed by 5000 consecutive Italian women and men aged 18-70 years. Moreover, a health questionnaire will be completed by the physicians. RESULTS: The present study will be the largest to be conducted in Italy, and probably in the European countries, to comprehensively demonstrate the current level of the knowledge, awareness and perception of CVRFs and CVD in both men and women. CONCLUSION: The present project could shed new light on the knowledge, awareness and perception of CVRFs and CVDs. If substantial differences will be detected by gender, the findings of this study may contribute to ultimately provide a new gender-oriented primary care approach inside the Italian healthcare system related to cardiovascular prevention and therapy strategies. PMID: 30664071 [PubMed - as supplied by publisher]

Photothermal Controlled Generation of Alkyl Radical from Organic Nanoparticles for Tumor Treatment.

Related Articles Photothermal Controlled Generation of Alkyl Radical from Organic Nanoparticles for Tumor Treatment. ACS Appl Mater Interfaces. 2019 Jan 21;: Authors: Xia R, Zheng X, Hu X, Liu S, Xie Z Abstract The therapeutic properties of light are well known for photodynamic or photothermal therapy, which could cause irreversible photodamage to tumor tissues. Although photodynamic therapy (PDT) has been proved in the clinic, the efficacy is not satisfactory because of complicated tumor microenvironments. For example, the hypoxia in solid tumor has a negative effect on the generation of singlet oxygen. In order to address the hypoxia issues in PDT, leveraging alkyl radical is an available option due to the oxygen-independent feature. In this work, a new kind of organic nanoparticles (TPP-NN NPs) from porphyrin and radical initiator is developed. Under near infrared light irradiation, TPP-NN NPs will splitting and release alkyl radical, which could induce the obvious cytotoxicity whether in normal or hypoxia environment. The photothermal controlled generation of alkyl radical could significantly inhibit the growth of cervical cancer, and show the ignorable systemic toxicity. This activatable radical therapy opens up new possibilities for application of PDT in hypoxia condition. PMID: 30663874 [PubMed - as supplied by publisher]

Quantifying Leukocyte Egress via Lymphatic Vessels from Murine Skin and Tumors.

Related Articles Quantifying Leukocyte Egress via Lymphatic Vessels from Murine Skin and Tumors. J Vis Exp. 2019 Jan 07;(143): Authors: Steele MM, Churchill MJ, Breazeale AP, Lane RS, Nelson NA, Lund AW Abstract Leukocyte egress from peripheral tissues to draining lymph nodes is not only critical for immune surveillance and initiation but also contributes to the resolution of peripheral tissue responses. While a variety of methods are used to quantify leukocyte egress from non-lymphoid, peripheral tissues, the cellular and molecular mechanisms that govern context-dependent egress remain poorly understood. Here, we describe the use of in situ photoconversion for quantitative analysis of leukocyte egress from murine skin and tumors. Photoconversion allows for the direct labeling of leukocytes resident within cutaneous tissue. Though skin exposure to violet light induces local inflammatory responses characterized by leukocyte infiltrates and vascular leakiness, in a head-to-head comparison with transdermal application of fluorescent tracers, photoconversion specifically labeled migratory dendritic cell populations and simultaneously enabled the quantification of myeloid and lymphoid egress from cutaneous microenvironments and tumors. The mechanisms of leukocyte egress remain a missing component in our understanding of intratumoral leukocyte complexity, and thus the application of the tools described herein will provide unique insight into the dynamics of tumor immune microenvironments both at steady state and in response to therapy. PMID: 30663703 [PubMed - in process]

Efficacy of lenalidomide as salvage therapy for patients with AL amyloidosis.

Related Articles Efficacy of lenalidomide as salvage therapy for patients with AL amyloidosis. Amyloid. 2019 Jan 20;:1-8 Authors: Kastritis E, Gavriatopoulou M, Roussou M, Bagratuni T, Migkou M, Fotiou D, Ziogas DC, Kanellias N, Eleutherakis-Papaiakovou E, Dialoupi I, Ntanasis-Stathopoulos I, Spyropoulou-Vlachou M, Psimenou E, Gakiopoulou H, Marinaki S, Papadopoulou E, Ntalianis A, Terpos E, Dimopoulos MA Abstract We retrospectively evaluated 55 consecutive patients who received at least one dose of lenalidomide for relapsed/refractory AL amyloidosis. Their median age was 63 years; 72% had heart and 75% kidney involvement and 13% were on dialysis; while 20%, 46% and 34% had Mayo stage -1, -2 and -3 disease, respectively. Median time from start of primary therapy to lenalidomide was 15 months (range 2-100) and median number of prior therapies was 1 (range 1-4); 73% of the patients had prior bortezomib and 42% were bortezomib-refractory. On intent to treat, haematologic response rate was 51% (5.5% CRs, 20% VGPRs) and was 56% versus 40% for patients with and without prior bortezomib and 47% versus 62.5% for bortezomib refractory versus non-refractory patients (p = .351). Organ response was achieved by 16% of evaluable patients (22% renal, 7% liver and 3% cardiac); however, 10 (21%) patients progressed to dialysis. Median survival post lenalidomide was 25 months. Bortezomib-refractory patients had worse outcome (median survival of 10.5 versus 25 months for bortezomib-sensitive patients versus not reached for bortezomib-naive patients, p = .011). Median lenalidomide dose was 10 mg and no patient received the 25 mg dose; however, in 60% a dose reduction was required. Median duration of lenalidomide therapy was 7.2 months and 46% discontinued lenalidomide before completion of planned therapy, mainly due to toxicity (26%) or disease progression/no response (13%). We conclude that although lenalidomide is a major salvage option for patients with relapsed/refractory AL amyloidosis, its toxicity in patients with AL amyloidosis is significant and doses should be adjusted for optimal tolerability. PMID: 30663408 [PubMed - as supplied by publisher]

Development of Lactobacillus kimchicus DCY51T-mediated gold nanoparticles for delivery of ginsenoside compound K: in vitro photothermal effects and apoptosis detection in cancer cells.

Related Articles Development of Lactobacillus kimchicus DCY51T-mediated gold nanoparticles for delivery of ginsenoside compound K: in vitro photothermal effects and apoptosis detection in cancer cells. Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):30-44 Authors: Kim YJ, Perumalsamy H, Markus J, Balusamy SR, Wang C, Ho Kang S, Lee S, Park SY, Kim S, Castro-Aceituno V, Kim SH, Yang DC Abstract We report a non-covalent loading of ginsenoside compound K (CK) onto our previously reported gold nanoparticles (DCY51T-AuCKNps) through one-pot biosynthesis using a probiotic Lactobacillus kimchicus DCY51T isolated from Korean kimchi. The ginsenoside-loaded gold nanoparticles were characterized by various analytical and spectroscopic techniques such as field emission transmission electron microscopy (FE-TEM), energy-dispersive X-ray (EDX) spectroscopy, elemental mapping, X-ray powder diffraction (XRD), selected area electron diffraction (SAED), Fourier-transform infrared (FTIR) spectroscopy and dynamic light scattering (DLS). Furthermore, drug loading was also determined by liquid chromatography-mass spectrometry (LC-MS). In addition, DCY51T-AuNps and DCY51T-AuCKNps were resistant to aggregation caused by pH variation or a high ionic strength environment. Cell-based study confirmed that DCY51T-AuCKNps exhibited slightly higher cytotoxicity compared to ginsenoside CK treatment in A549 cells (human lung adenocarcinoma cell line) and HT29 (human colorectal adenocarcinoma cell line). Upon laser treatment, DCY51T-AuCKNps showed enhanced cell apoptosis in A549, HT29 and AGS cells (human stomach gastric adenocarcinoma cell line) compared with only DCY51T-AuCKNps treated cells. In conclusion, this preliminary study identified that DCY51T-AuCKNps act as a potent photothermal therapy agents with synergistic chemotherapeutic effects for the treatment of cancer. PMID: 30663395 [PubMed - in process]

Enhancement of photodynamic cancer therapy by physical and chemical factors.

Related Articles Enhancement of photodynamic cancer therapy by physical and chemical factors. Angew Chem Int Ed Engl. 2019 Jan 20;: Authors: Yang M, Yang T, Mao C Abstract The viable use of photodynamic therapy (PDT) in cancer therapy has never been fully realized due to its undesirable effects on healthy tissues. Here we summarize some physicochemical factors that can make PDT a more viable and effective option in order to provide future oncological patients with better-quality treatment options. These physicochemical factors include light sources, photosensitizer (PS) carriers, microwave, electric fields, magnetic fields, and ultrasound. This review is meant to provide current information pertaining to PDT use, including a discussion of in vitro and in vivo studies. Emphasis is placed on the physicochemical factors and their potential benefits in overcoming the difficulty in transitioning PDT into the medical field. Multiple advanced techniques, such as employing X-rays as a light source, using nanoparticle-loaded stem cells and bacteriophage bionanowires as a PS carrier, as well as integration with immunotherapy, are among the future directions. PMID: 30663185 [PubMed - as supplied by publisher]

Exosomes from human umbilical cord mesenchymal stem cells enhance fracture healing through HIF-1α-mediated promotion of angiogenesis in a rat model of stabilized fracture.

Related Articles Exosomes from human umbilical cord mesenchymal stem cells enhance fracture healing through HIF-1α-mediated promotion of angiogenesis in a rat model of stabilized fracture. Cell Prolif. 2019 Jan 20;:e12570 Authors: Zhang Y, Hao Z, Wang P, Xia Y, Wu J, Xia D, Fang S, Xu S Abstract OBJECTIVES: Exosomes, as important players in intercellular communication due to their ability to transfer certain molecules to target cells, are believed to take similar effects in promoting bone regeneration with their derived stem cells. Studies have suggested that umbilical cord mesenchymal stem cells (uMSCs) could promote angiogenesis. This study investigated whether exosomes derived from uMSCs (uMSC-Exos) could enhance fracture healing as primary factors by promoting angiogenesis. MATERIALS AND METHODS: uMSCs were obtained to isolate uMSC-Exos by ultrafiltration, with exosomes from human embryonic kidney 293 cells (HEK293) and phosphate-buffered saline (PBS) being used as control groups. NanoSight, laser light scattering spectrometer, transmission electron microscopy and Western blotting were used to identify exosomes. Next, uMSC-Exos combined with hydrogel were transplanted into the fracture site in a rat model of femoral fracture. Bone healing processes were monitored and evaluated by radiographic methods on days 7, 14, 21 and 31 after surgery; angiogenesis of the fracture sites was assessed by radiographic and histological strategies on post-operative day 14. In vitro, the expression levels of osteogenesis- or angiogenesis-related genes after being cultured with uMSC-Exos were identified by qRT-PCR. The internalization ability of exosomes was determined using the PKH67 assay. Cell cycle analysis, EdU incorporation and immunofluorescence staining, scratch wound assay and tube formation analysis were also used to determine the altered abilities of human umbilical vein endothelial cells (HUVECs) administered with uMSC-Exos in proliferation, migration and angiogenesis. Finally, to further explore the underlying molecular mechanisms, specific RNA inhibitors or siRNAs were used, and the subsequent effects were observed. RESULTS: uMSC-Exos had a diameter of approximately 100 nm, were spherical, meanwhile expressing CD9, CD63 and CD81. Transplantation of uMSC-Exos markedly enhanced angiogenesis and bone healing processes in a rat model of femoral fracture. In vitro, other than enhancing osteogenic differentiation, uMSC-Exos increased the expression of vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α (HIF-1α). uMSC-Exos were taken up by HUVECs and enhanced their proliferation, migration and tube formation. Finally, by using specific RNA inhibitors or siRNAs, it has been confirmed that HIF-1α played an important role in the uMSC-Exos-induced VEGF expression, pro-angiogenesis and enhanced fracture repair, which may be one of the underlying mechanisms. CONCLUSIONS: These results revealed a novel role of exosomes in uMSC-mediated therapy and suggested that implanted uMSC-Exos may represent a crucial clinical strategy to accelerate fracture healing via the promotion of angiogenesis. HIF-1α played an important role in this process. PMID: 30663158 [PubMed - as supplied by publisher]

Intelligent Photosensitive Mesenchymal Stem Cells and Cell-Derived Microvesicles for Photothermal Therapy of Prostate Cancer.

Related Articles Intelligent Photosensitive Mesenchymal Stem Cells and Cell-Derived Microvesicles for Photothermal Therapy of Prostate Cancer. Nanotheranostics. 2019;3(1):41-53 Authors: Huang L, Xu C, Xu P, Qin Y, Chen M, Feng Q, Pan J, Cheng Q, Liang F, Wen X, Wang Y, Shi Y, Cheng Y Abstract Targeted delivery of nanomedicines into the tumor site and improving the intratumoral distribution remain challenging in cancer treatment. Here, we report an effective transportation system utilizing both of mesenchymal stem cells (MSCs) and their secreted microvesicles containing assembled gold nanostars (GNS) for targeted photothermal therapy of prostate cancer. The stem cells act as a cell carrier to actively load and assemble GNS into the lysosomes. Accumulation of GNS in the lysosomes facilitates the close interaction of nanoparticles, which could result in a 20 nm red-shift of surface plasmon resonance of GNS with a broad absorption in the near infrared region. Moreover, the MSCs can behave like an engineering factory to pack and release the GNS clusters into microvesicles. The secretion of GNS can be stimulated via light irradiation, providing an external trigger-assisted approach to encapsulate nanoparticles into cell derived microvesicles. In vivo studies demonstrate that GNS-loaded MSCs have an extensive intratumoral distribution, as monitored via photoacoustic imaging, and efficient antitumor effect under light exposure in a prostate-cancer subcutaneous model by intratumoral and intravenous injection. Our work presents a light-responsive transportation approach for GNS in combination of MSCs and their extracellular microvesicles and holds the promise as an effective strategy for targeted cancer therapy including prostate cancer. PMID: 30662822 [PubMed - in process]

Near-infrared light-regulated cancer theranostic nanoplatform based on aggregation-induced emission luminogen encapsulated upconversion nanoparticles.

Related Articles Near-infrared light-regulated cancer theranostic nanoplatform based on aggregation-induced emission luminogen encapsulated upconversion nanoparticles. Theranostics. 2019;9(1):246-264 Authors: Jin G, He R, Liu Q, Lin M, Dong Y, Li K, Tang BZ, Liu B, Xu F Abstract Photodynamic therapy (PDT) has been widely applied in the clinic for the treatment of various types of cancer due to its precise controllability, minimally invasive approach and high spatiotemporal accuracy as compared with conventional chemotherapy. However, the porphyrin-based photosensitizers (PSs) used in clinics generally suffer from aggregation-caused reductions in the generation of reactive oxygen species (ROS) and limited tissue penetration because of visible light activation, which greatly hampers their applications for the treatment of deep-seated tumors. Methods: We present a facile strategy for constructing a NIR-regulated cancer theranostic nanoplatform by encapsulating upconversion nanoparticles (UCNPs) and a luminogen (2-(2,6-bis((E)-4-(phenyl(40-(1,2,2-triphenylvinyl)-[1,10-biphenyl]-4-yl)amino)styryl)-4H-pyran-4-ylidene)malononitrile, TTD) with aggregation-induced emission (AIEgen) characteristics using an amphiphilic polymer, and further conjugating cyclic arginine-glycine-aspartic acid (cRGD) peptide to yield [email protected] NPs. We then evaluated the bioimaging and anti-tumor capability of the [email protected] NPs under NIR light illumination in an in vitro three-dimensional (3D) cancer spheroid and in a murine tumor model, respectively. Results: With a close match between the UCNP emission and absorption of the AIEgen, the synthesized NPs could efficiently generate ROS, even under excitation through thick tissues. The NIR-regulated [email protected] NPs that were developed could selectively light up the targeted cancer cells and significantly inhibit tumor growth during the NIR-regulated PDT treatment as compared with the cells under white light excitation. Conclusion: In summary, the synthesized [email protected] NPs showed great potential in NIR light-regulated photodynamic therapy of deep-seated tumors. Our study will inspire further exploration of novel theranostic nanoplatforms that combine UCNPs and various AIEgen PSs for the advancement of deep-seated tumor treatments with potential clinical translations. PMID: 30662565 [PubMed - in process]

Self-Luminescing Theranostic Nanoreactors with Intraparticle Relayed Energy Transfer for Tumor Microenvironment Activated Imaging and Photodynamic Therapy.

Related Articles Self-Luminescing Theranostic Nanoreactors with Intraparticle Relayed Energy Transfer for Tumor Microenvironment Activated Imaging and Photodynamic Therapy. Theranostics. 2019;9(1):20-33 Authors: Wu M, Wu L, Li J, Zhang D, Lan S, Zhang X, Lin X, Liu G, Liu X, Liu J Abstract The low tissue penetration depth of external excitation light severely hinders the sensitivity of fluorescence imaging (FL) and the efficacy of photodynamic therapy (PDT) in vivo; thus, rational theranostic platforms that overcome the light penetration depth limit are urgently needed. To overcome this crucial problem, we designed a self-luminescing nanosystem (denoted POCL) with near-infrared (NIR) light emission and singlet oxygen (1O2) generation abilities utilizing an intraparticle relayed resonance energy transfer strategy. Methods: Bis[3,4,6-trichloro-2-(pentyloxycarbonyl) phenyl] oxalate (CPPO) as a chemical energy source with high reactivity toward H2O2, poly[(9,9'-dioctyl-2,7-divinylene-fluorenylene)-alt-2-methoxy- 5-(2-ethyl-hexyloxy)-1,4-phenylene] (PFPV) as a highly efficient chemiluminescence converter, and tetraphenylporphyrin (TPP) as a photosensitizer with NIR emission and 1O2 generation abilities were coencapsulated by self-assembly with poly(ethyleneglycol)-co-poly(caprolactone) (PEG-PCL) and folate-PEG-cholesterol to form the POCL nanoreactor, with folate as the targeting group. A series of in vitro and in vivo analyses, including physical and chemical characterizations, tumor targeting ability, tumor microenvironment activated imaging and photodynamic therapy, as well as biosafety, were systematically investigated to characterize the POCL. Results: The POCL displayed excellent NIR luminescence and 1O2 generation abilities in response to H2O2. Therefore, it could serve as a specific H2O2 probe to identify tumors through chemiluminescence imaging and as a chemiluminescence-driven PDT agent for inducing tumor cell apoptosis to inhibit tumor growth due to the abnormal overproduction of H2O2 in the tumor microenvironment. Moreover, the folate ligand on the POCL surface can further improve the accumulation at the tumor site via a receptor-mediated mechanism, thus enhancing tumor imaging and the therapeutic effects both in vitro and in vivo but without any observable systemic toxicity. Conclusion: The nanosystem reported here might serve as a targeted, smart, precise, and noninvasive strategy triggered by the tumor microenvironment rather than by an outside light source for cancer NIR imaging and PDT treatment without limitations on penetration depth. PMID: 30662551 [PubMed - in process]

A formulated red ginseng extract inhibits autophagic flux and sensitizes to doxorubicin-induced cell death.

Related Articles A formulated red ginseng extract inhibits autophagic flux and sensitizes to doxorubicin-induced cell death. J Ginseng Res. 2019 Jan;43(1):86-94 Authors: Park HH, Choi SW, Lee GJ, Kim YD, Noh HJ, Oh SJ, Yoo I, Ha YJ, Koo GB, Hong SS, Kwon SW, Kim YS Abstract Background: Ginseng is believed to have antitumor activity. Autophagy is largely a prosurvival cellular process that is activated in response to cellular stressors, including cytotoxic chemotherapy; therefore, agents that inhibit autophagy can be used as chemosensitizers in cancer treatment. We examined the ability of Korean Red Ginseng extract (RGE) to prevent autophagic flux and to make hepatocellular carcinoma (HCC) cells become more sensitive to doxorubicin. Methods: The cytotoxic effects of total RGE or its saponin fraction (RGS) on HCC cells were examined by the lactate dehydrogenase assay in a dose- or time-dependent manner. The effect of RGE or RGS on autophagy was measured by analyzing microtubule-associated protein 1A/1B-light chain (LC)3-II expression and LC3 puncta formation in HCC cells. Late-stage autophagy suppression was tested using tandem-labeled green fluorescent protein (GFP)-monomeric red fluorescent protein (mRFP)-LC3. Results: RGE markedly increased the amount of LC3-II, but green and red puncta in tandem-labeled GFP-mRFP-LC3 remained colocalized over time, indicating that RGE inhibited autophagy at a late stage. Suppression of autophagy through knockdown of key ATG genes increased doxorubicin-induced cell death, suggesting that autophagy induced by doxorubicin has a protective function in HCC. Finally, RGE and RGS markedly sensitized HCC cells, (but not normal liver cells), to doxorubicin-induced cell death. Conclusion: Our data suggest that inhibition of late-stage autophagic flux by RGE is important for its potentiation of doxorubicin-induced cancer cell death. Therapy combining RGE with doxorubicin could serve as an effective strategy in the treatment of HCC. PMID: 30662297 [PubMed]

Predictors and Moderators of Cognitive and Behavioral Therapy Outcomes for OCD: A Patient-Level Mega-Analysis of Eight Sites.

Related Articles Predictors and Moderators of Cognitive and Behavioral Therapy Outcomes for OCD: A Patient-Level Mega-Analysis of Eight Sites. Behav Ther. 2019 Jan;50(1):165-176 Authors: Steketee G, Siev J, Yovel I, Lit K, Wilhelm S Abstract Cognitive (CT) and behavioral treatments (BT) for OCD are efficacious separately and in combination. Tailoring treatment to patient-level predictors and moderators of outcome has the potential to improve outcomes. The present study combined data from eight treatment clinics to examine the benefits of BT (n = 125), CT (n = 108), and CBT (n = 126), and study predictors across all treatments and moderators of outcome by treatment type. All three methods led to large benefits for OCD and depression symptoms. Residual gain scores for OCD symptoms were marginally smaller for BT compared to treatments containing CT. For depression, significantly more gains were evident for CBT than BT, and CT did not differ from either. Significantly fewer BT participants (36%) achieved clinically significant improvement compared to CT (56%), and this was marginally evident for CBT (48%). For all treatments combined, no predictors were identified in residual gain analyses, but clinically improved patients had lower baseline depression and stronger beliefs about responsibility/threat and importance/control of thoughts. Moderator analyses indicated that higher baseline scores on depression adversely affected outcomes for BT but not CT or CBT, and lower OCD severity and more education were associated with positive outcomes for CT only. A trend was evident for higher responsibility/threat beliefs to moderate clinical improvement outcomes for those receiving cognitive (CT and CBT), but not behavioral (BT) treatment. Medication status and comorbidity did not predict or moderate outcomes. Findings are discussed in light of models underlying behavioral and cognitive treatments for OCD. PMID: 30661557 [PubMed - in process]

Gold nanostructures absorption capacities of various energy forms for thermal therapy applications.

Related Articles Gold nanostructures absorption capacities of various energy forms for thermal therapy applications. J Therm Biol. 2019 Jan;79:81-84 Authors: Amini SM Abstract This mini-review has investigated the recent progress regarding gold nanostructures capacities of energy absorption for thermal therapy applications. Unselective thermal therapy of malignant and normal tissues could lead to irreversible damage to healthy tissues without effective treatment on target malignant tissues. In recent years, there has been a considerable progress in the field of cancer thermal therapy for treating target malignant tissues using nanostructures. Due to the remarkable physical properties of the gold nanoparticle, it has been considered as an exceptional element for thermal therapy techniques. Different types of gold nanoparticles have been used as energy absorbent for thermal therapy applications under several types of energy exposures. Electromagnetic, ultrasound, electric and magnetic field are examples for these energy sources. Well-known plasmonic photothermal therapy which applies electromagnetic radiation is under clinical investigation for the treatment of various medical conditions. However, there are many other techniques in this regard which should be explored. PMID: 30612690 [PubMed - indexed for MEDLINE]

The heat is on: A device that reduces cold stress-induced tachycardia in laboratory mice.

Related Articles The heat is on: A device that reduces cold stress-induced tachycardia in laboratory mice. J Therm Biol. 2019 Jan;79:149-154 Authors: Chan CE, Hare MT, Martin GW, Gordon CJ, Swoap SJ Abstract Mouse vivaria are typically maintained at an ambient temperature (Ta) of 20-26 °C which is comfortable for human researchers. However, as this Ta is well below the mouse thermoneutral zone (TNZ) of 30-32 °C, typical vivarium temperatures result in cold stress for mice. Recently, a cage has been developed that provides variable cage floor heating, allowing mice to behaviorally regulate body temperature through thermotaxis. A hand warmer provides supplemental heat, elevating cage floor surface temperature for 13 + hours up to 30 °C. This provides a heated surface for the entirety of the light phase. Here, we test the ability of these local heat sources to remove physiological signs of cold stress in mice housed at room temperature by analyzing heart rate (HR), activity, and body temperature in three experimental conditions: 23 °C, 23 °C + heated surface, or 30 °C. The location of C57Bl/6 J mice within the cage was recorded using an infrared camera. In the presence of supplemental heat at a Ta of 23 °C, mice resided atop of the area of the heated surface 85 ± 3% of the 12-h light phase, as compared to 7 ± 2% in the absence of supplemental heat. Further, addition of supplemental heat lowered light phase HR and activity to that seen at a Ta of 30 °C. These results indicate that provision of a local heat source is successful in reducing cold-induced tachycardia in mice housed at typical vivarium temperatures without increasing the ambient temperature of the entire laboratory and subjecting researchers to heat stress. PMID: 30612675 [PubMed - indexed for MEDLINE]
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