Light-Based Therapy: Novel Approach to Treat COVID-19.

The pandemic outbreak of Coronavirus disease 2019 (COVID-19) which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), is a new viral infection in all countries around the world. An increase in inflammatory cytokines, fever, dry cough, and pneumonia are the main symptoms of COVID-19. A shared of growing clinical evidence confirmed that cytokine storm correlates with COVID-19 severity which is also a crucial cause of death from COVID-19. The success of anti-inflammatory therapies in the recovery process of COVID-19 patients has been well established. Over the years, phototherapy (PhT) has been identified as a promising non-invasive treatment approach for inflammatory conditions. New evidence suggests that PhT as an anti-inflammatory therapy may be effective in treating acute respiratory distress syndrome (ARDS) and COVID-19. This review aims to a comprehensive overview of the direct and indirect effects of anti-inflammatory mechanisms of PhT in ARDS and COVID-19 patients.

The state of the art of biomedical applications of optogenetics.

BACKGROUND AND OBJECTIVE: Optogenetics has opened new insights into biomedical research with the ability to manipulate and control cellular activity using light in combination with genetically engineered photosensitive proteins. By stimulating with light, this method provides high spatiotemporal and high specificity resolution, which is in contrast to conventional pharmacological or electrical stimulation. Optogenetics was initially introduced to control neural activities but was gradually extended to other biomedical fields. STUDY DESIGN: In this paper, firstly, we summarize the current optogenetic tools stimulated by different light sources, including lasers, light-emitting diodes, and laser diodes. Second, we outline the variety of biomedical applications of optogenetics not only for neuronal circuits but also for various kinds of cells and tissues from cardiomyocytes to ganglion cells. Furthermore, we highlight the potential of this technique for treating neurological disorders, cardiac arrhythmia, visual impairment, hearing loss, and urinary bladder diseases as well as clarify the mechanisms underlying cancer progression and control of stem cell differentiation. CONCLUSION: We sought to summarize the various types of promising applications of optogenetics to treat a broad spectrum of disorders. It is conceivable to expect that optogenetics profits a growing number of patients suffering from a range of different diseases in the near future.

Systemic Photodynamic Therapy With Chlorine e6 as a Photosensitizer for the Treatment of Nodular BCC: A Case Report.

Introduction: Photodynamic therapy (PDT) is a demonstrated therapeutic method for basal cellcarcinoma (BCC), which is the most common human cancer. Here, we present a case report about systemic PDT with chlorine e6 as a photosensitizer (PS) for BCC treatment. Case Report: A 78-year-old man was diagnosed with a history of a 4-year nodular BCC in the nasal area. The patient was under control and treatment for hypertension and type 2 diabetes. Chlorine e6 was injected intravenously at a 0.08 mg/kg dosage in 500 cc normal saline within 20 minutes. Three hours after injection, laser irradiation was performed with a wavelength of 665 nm, a dosage of 150 J/cm2, and an irradiance value of 150 mW/cm2. His nodular BCC was completely cured without any side effects after one session of PDT with chlorine e6. Conclusion: Systemic PDT with chlorine e6 as a PS may be safe and effective in removing BCC lesions due to the data obtained in a two-month follow-up.

Ultrasound and Sonogenetics: A New Perspective for Controlling Cells with Sound.

An important challenge in neurobiology is to stimulate a single neuron, especially in deep areas of the brain. The optogenetics methods need a surgical operation to convey light sources to targeted cells. Nowadays, non-invasive tools such as sonogenetics with the ability to modulate and visualizing cellular and molecular processes have attracted much attention. The study of the biological functions of living organisms always requires tools for monitoring and imaging dynamically. Current sonogenetic approaches use ultrasound as a non-invasive tool to precisely control cellular function. In general, sonogenetics includes the development of mechano-sensitive proteins, approaches for introducing their genes to specific cells, targeted stimulation, and finally, reading the outcome. Hence, to prepare a short review of emerging technology sonogenetics, we summarized the introduction of sound waves, the mechano-sensitive proteins commonly used in sonogenetics, and potential therapeutic applications of sonogenetics for biological research and medicine. This short review would beneficiate in the translation of sonogenetics from present in-vitro and in-vivo investigations to clinical therapies.

Optogenetic Stimulation of Primary Cardiomyocytes Expressing ChR2.

Introduction: Non-clinical cardiovascular drug safety assessment is the main step in the progress of new pharmaceutical products. Cardiac drug safety testing focuses on a delayed rectifier potassium channel block and QT interval prolongation, whereas optogenetics is a powerful technology for modulating the electrophysiological properties of excitable cells. Methods: For this purpose, the blue light-gated ion channel, channelrhodopsin-2 (ChR2), has been introduced into isolated primary neonatal cardiomyocytes via a lentiviral vector. After being subjected to optical stimulation, transmembrane potential and intracellular calcium were assessed. Results: Here, we generated cardiomyocytes expressing ChR2 (light-sensitive protein), that upon optical stimulation, the cardiomyocytes depolarized result from alterations of membrane voltage and intracellular calcium. Conclusion: This cell model was easily adapted to a cell culture system in a laboratory, making this method very attractive for therapeutic research on cardiac optogenetics.

A Parallel Randomized Clinical Trial for Comparison of Two Methods of Maggot Therapy, Free-Range Larvae and Larval-bag, in Diabetic Ulcer (Wagner 2).

In the present study, the efficiency of two formulations of maggot therapy: free-range larvae on the wounds and larvae in a special bag (larval-bag), was compared for healing diabetic ulcers with Wagner 2 diabetic ulcer. This study was conducted as a parallel randomized clinical trial. Out of 281 patients with Wagner grade 2 diabetic ulcers referred to the wound clinic, 54 patients who met the inclusion criteria were randomly assigned to intervention groups. The disinfected larvae of Lucilia sericata were put on the wounds with 2 methods, free-range larvae and larval-bag. Follow up was done at every 48 h interval until the full appearance of granulated tissues. The main measures were wound bed preparation, removing of necrotic tissues, appearing of granulated tissues, and removing of bacterial infections in the wounds. Statistical analysis based on the Kaplan-Meier curve and the Wilcoxon (Breslow) test showed a significant reduction in wound healing time by using free-range larvae in comparison with larval-bag (P = .03). The median time to debridement was 4 days in the free-range larval group (95% confidence interval: 3-9 days) while it was 9 days in the larval-bag group (95% confidence interval: 5-16 days). Debridement rate (proportion of removed necrotic tissue surfaces) at any time in the free-ranged larvae group was 1.78 times that of the bagged larvae group (95% confidence interval 1.01-3.15, P = .036). There was no significant difference between free-range larval use and larval-bag in the acceptability of maggot therapy by patients (P = .48). It can be concluded that both of two formulations of the larval therapy (free-range larvae and larval-bag) could be recommended for cleaning out and bed preparation of diabetic ulcers. However, using free-range larvae is hardly recommended on the wounds which are eligible to use.

Effect of Low-Level Laser Therapy and Sinensetin (Combination therapy) on Tumor Cells (Hela) and Normal Cells (CHO).

Introduction: Cervical and ovarian cancers are well-known causes of death among women in developing countries. There are various technologies to treat cancer cells, but the polyphenolic compound is a natural one and has an anti-cancer effect. Sinensetin is one of them and is found in Orthosiphon stamineus and citrus fruits. Since combination therapy is more effective than drug treatment alone, in this study, we investigated combination therapy using sinensetin and low-level laser therapy (LLLT) to enhance treatment. Methods: The cancer cells purchased from Pasteur Institute, Iran, were cultured. The cells were treated with various concentrations of sinensetin (0.1-1-10-50,150 µg/mL for 24 hours), wavelengths of laser therapy (660 nm) and power density (3 J/cm2) for different times)30, 60, and 90 seconds) separately. Furthermore, sensitivity of cells to sinensetin, LLLT and combined therapy was determined by clonogenic assays. To measure DNA damage and repair at individual cell level used comet assay. To examine the intracellular generation of reactive oxygen species used 2',7'-dichlorodihydrofluorescein (DCFH) as an intracellular probe. To analyze data we used SPSS software and comparison between groups was used (ANOVA) and t test statistical analyses were performed using SPSS 17 software. Data are presented as means - standard error of mean. The level of statistical significance was set at a two-tailed P value of 0.05. All tests were performed in triplicate. Results: Our results demonstrated that the doubling time for CHO is more than Hella cells, with 20.7 and 27.7 h for each cell respectively. The pretreatments (first LLLT, then sinensetin) can decrease the viability of both cell lines more than the first treatment (sinensetin + LLLT). In the clonogenic assay, the pretreatment of cells with LLLT and Sinensetin significantly reduced the surviving fraction of both cell lines. MTT results showed that pretreatment with LLLT and Sinensetin can increase cell death compared to Sinensetin and LLLT alone. Production of ROS within the cell was enhanced with LLLT + sinensetin. Conclusion: Our result indicated that combined therapy with LLLT and Sinensetin can treat CHO and Hela cells better than the other groups. Combination treatment with sinensetin-LLLT and the other treatment means, sinensetin and LLLT alone, did not change the cell viability significantly.

Network Analysis of Common Genes and Transcriptional Factors between Celiac Disease and Inflammatory Bowel Diseases.

BACKGROUND Understanding the associations among different disorders remarkably improves their diagnosis and treatments. Celiac disease is the most complicated and prevalent form of immune-mediated diseases. On the other hand, inflammatory bowel diseases lead to inflammation of the intestine with an unknown cause. Although inflammatory bowel diseases have been often thought of as an autoimmune disorder, they can be triggered by whatever that can lead to the inflammation in the whole bowel. Henceforth, both aforementioned diseases are related to autoimmune attacks and cause a sort of inflammatory event, which exploring trade-off among them supposedly will lead to discovering important genes and, in turn, to the possible common therapeutic protocols. In the current study, we aimed to determine the correlation between the common genes in celiac disease and inflammatory bowel diseases. METHODS 314 and 851 genes correlated with celiac disease and inflammatory bowel diseases respectively extracted from DisGeNET were subjected to an in-silico data analysis framework to mine prognosticates genes and the associated pathways. RESULTS 149 shared genes between these diseases regulated by highlighted transcription factors NFKB1, IRF1, STAT1, HSF1, GATA3 were characterized as discriminating molecules, which by further screening were enriched in pathways mostly involved in apoptosis, T cell activation, and cytokine, chemokine, and interleukin signaling. CONCLUSION We observed that the identified common genes were associated with a wide range of pathogenic mechanisms underlying these diseases.

Modulation of cardiac optogenetics by vitamin A.

Cardiac optogenetics is an emergent research area and refers to the delivery of light-activated proteins to excitable heart tissue and the subsequent use of light for controlling the electrical function with high spatial and temporal resolution. Channelrhodopsin-2 (ChR2) is a light-sensitive ion channel with the chromophore, all trans retinal, derived from vitamin A (all-trans-retinol; retinol). In this study, we explored whether exogenous vitamin A can be a limiting factor in the light responsiveness of cardiomyocytes-expressing ChR2. We showed that in cardiomyocytes virally transduced with ChR2 (H134R)-enhanced yellow fluorescent protein, vitamin A supplements lower than 10 µM significantly increased ChR2 expression. Adding 1 µM vitamin A changed light-induced transmembrane potential difference significantly, whereas 5 µM dramatically induced membrane depolarization and triggered intracellular calcium elevation. We concluded that vitamin A supplementation can modulate the efficiency of ChR2 and provide a complementary strategy for improving the performance of optogenetic tools.

Efficacy of Maggot Therapy on Staphylococcus aureus and Pseudomonas aeruginosa in Diabetic Foot Ulcers: A Randomized Controlled Trial.

PURPOSE: This study was conducted to evaluate the antimicrobial effects of medicinal maggots of Lucilia sericata on Staphylococcus aureus and Pseudomonas aeruginosa on diabetic foot ulcers (DFUs). DESIGN: Randomized controlled trial. SUBJECTS AND SETTING: The sample comprised 50 adult patients from the clinic of the Academic Center for Education, Culture and Research of Tehran University of Medical Sciences, Iran. All participants who had at least 1 DFU present for at least 12 weeks, an arterial brachial index value of more than 0.6, and a hemoglobin A1c value of less than 8% were included in this study. METHODS: Subjects were randomly selected for the maggot-treated (treatment) or conventional treatment (control) group. Conventional treatments such as antibiotic therapy, debridement, and offloading were done for both groups, but maggot therapy (MT) was added to the protocol of the treatment group. Bacterial burden was monitored and compared for both groups using cultures collected using swab technique. Wound secretions were measured and compared in both groups. RESULTS: The number of infected cases with S aureus in the treatment group was significantly reduced after 48 hours in comparison with the control group (P = .047). The number of infected cases with P aeruginosa was significantly reduced after 96 hours (P = .002). We also found that wound secretions in the treatment group were significantly higher than in the control group (P < .00). CONCLUSIONS: Our findings indicate that MT is a safe and efficacious treatment of DFUs.

A Comparative Study of 660 nm Low-Level Laser and Light Emitted Diode in Proliferative Effects of Fibroblast Cells.

Introduction: In recent years, low-power lasers have been widely used in medicine. With the introduction of affordable light emitted diode (LED), clinical application of LED light has become more and more popular. However, some researchers believe that due to lack of coherence of the LED light, it can be different in terms of biological effects, in comparison with laser. In this study, the biological effects of low-level laser (LLL) to those of LED light are compared and discussed. Methods: Human skin fibroblast cell line Hu02 was irradiated with LLL and LED light with a wavelength of 660 nm, power output of 35 mW and in continuous mode and the control group was not irradiated. The biological effects were compared through analysis of cell proliferation, production of reactive oxygen species (ROS) within the cell and rate of cell division. Results: Our findings showed that production of ROS within the cell was linearly increased both in the LED and laser light irradiated cells. However, laser light is more incremental in comparison to LED light. The MTT results showed that laser light at low energy density (less than 5 J/cm2) increased the rate of cell proliferation after 24 hours. Although, the rate of cell division was increased in energy density of 1 J/cm2 compared to the control group, this increase was not statistically significant. Discussion: The findings indicated that the coherence properties of laser light provided more energy for the cells, and in a constant energy density, laser light created more oxidative stresses in comparison with LED light.

Assessing the Efficacy of Second-Line Antiretroviral Treatment for HIV Patients Failing First-Line Antiretroviral Therapy in Iran: A Cohort Study.

There are limited documents about HIV patients switched to second-line antiretroviral therapy (ART) in resource-limited countries. We aimed to assess the efficacy of second-line ART for HIV patients following first-line ART failure. This was a cohort study of HIV/AIDS patients with first-line ART treatment failure switched to second-line ART between January 2004 and March 2014, who followed for at least 12 months after switching. Fifty of studied patients (85%) were treated with regimens containing lopinavir/ritonavir (Kaletra) and nine of them (15%) treated with other regimes. Seven patients were experienced opportunistic infections in accordance with stage III and IV WHO classification. In this way, 11.8% of patients had aclinicalfailure, and 37 of them (62%) had immunological responses. Weight gain was evident in these patients, and there was a significant correlation between theincrease in CD4 and weight gain (P=0.007). Only 13 patients achieved HIV viral load testing that 6 of them had avirological response after 12 months on second-line ART. No significant associations were found between virological or immunological response and gender, age, and lopinavir/ritonavir regimens (P>0.05).With counselling and supporting in those failing first-line ART, inessential switching to more costly second-line ART can be prevented in the majority of patients. However, patients' need to second-line ART drugs has increased, for which national ART programmes and regular follow-up should be organized. The high cost of these drugs and limited access to viral load testing are main barriers to proper management of patients switched to second-line ART regimens.

HIV, HCV, HBV, HSV, and syphilis prevalence among female sex workers in Tehran, Iran, by using respondent-driven sampling.

To find out the prevalence of HIV, HCV, HBV, HSV, and syphilis infections among female sex workers (FSWs) in Tehran, a cross-sectional study by using respondent-driven sampling (RDS) method was conducted. From December 2012 to April 2013 FSWs in Tehran were recruited. Inclusion criteria consisted of trading sex during the 12 months prior to this study and selling sex for at least 6 months in participants' lifetime. Among 161 consenting participants, 5% were infected with HIV. Moreover, 8.1% of FSWs were HCV positive, 37.9% were of HSV type1/type2, 1.2% of participants were infected with HBV, and none of the participants were infected with syphilis. HIV-positive participants were significantly more likely to be co-infected with HSV type1/type2, be younger, have more sexual partners and especially more clients during seven days prior to this study and report more history of having at least one of sexually transmitted infections symptoms in 12 months prior the study. In the multiple logistic regression analysis, being infected with HSV and also being under 25 years of age were found to be independently associated with HIV infection. Compared with the prevalence of HIV among general population of Tehran, relatively high prevalence of HIV and other viral infections among FSWs should be considered. All in all, it is critical to commence effective counter-measures for this high-risk group if the aim is to prevent spreading of these viruses to general population.

Determination of the accuracy and optimal cut-off point for ELISA test in diagnosis of human brucellosis in Iran.

In endemic area the most challenging problem for brucellosis is to find a reliable diagnostic method. In this case-control study, we investigated the accuracy of ELISA test for diagnosis of human brucellosis and determined the optimal cut-off value for ELISA results in Iran. The laboratory diagnosis of brucellosis was performed by blood isolation of Brucella organism with a BACTEC 9240 system and/or detection of Brucella antibodies by standard agglutination test (titer ≥ 1:160). Serum level of ELISA IgG and ELISA IgM from 56 confirmed cases of brucellosis and 126 controls were compared with each other by Box plot graph and Receiver Operating Characteristic (ROC) curve. Box plot graphs showed the high degree of dispersion for IgG and IgM data in patients compared with all controls. We observed partially overlapping for IgM data (not for IgG) between cases and controls in graphs. The area under ROC curve for distinguishing between cases and controls was larger for IgG compared to IgM. Based on results of this study, ELISA IgG test was more reliable than ELISA IgM test in diagnosis of human brucellosis in Iran. Using a cut-off of 10 IU/ml and 50 IU/ml had most sensitivity (92.9%) and most specificity (100%) for ELISA IgG test, respectively.

Quality of Life among Persons with HIV/AIDS in Iran: Internal Reliability and Validity of an International Instrument and Associated Factors.

The purpose of this cross-sectional study on 191 HIV/AIDS patient was to prepare the first Persian translation of complete WHOQOL-HIV instrument, evaluate its reliability and validity, and apply it to determine quality of life and its associated factors in Tehran, Iran. Student's t-test was used to compare quality of life between groups. Mean Cronbach's α of facets in all six domains of instrument were more than 0.6 indicating good reliability. Item/total corrected correlations coefficients had a lower limit of more than 0.5 in all facets except for association between energy and fatigue facet and physical domain. Compared to younger participants, patients older than 35 years had significantly lower scores in overall quality of life (P = 0.003), social relationships (P = 0.021), and spirituality/religion/personal beliefs (P = 0.024). Unemployed patients had significantly lower scores in overall quality of life (P = 0.01), level of independence (P = 0.004), and environment (P = 0.001) compared to employed participants. This study demonstrated that the standard, complete WHOQOL-HIV 120 instrument translated into Farsi and evaluated among Iranian participants provides a reliable and valid basis for future research on quality of life for HIV and other patients in Iran.

Frequency of HIV Infection among Sailors in South of Iran by Rapid HIV Test.

Information on the prevalence and risk factors for HIV infection among sailors is scarce. The aim of this seroprevalence study was to evaluate the frequency of HIV infection among sailors in south of Iran using rapid HIV test. The study included 400 consecutive participants in Lengeh, Shahid Rajaie, and Shahid Bahonar ports in south of Iran in May 2010. We observed only one case (0.25%) of HIV infection in this sample of sailors. While prevalence appears low at present, we recommend periodic HIV serosurveillance with detailed behavioral measures for this population in the future.

Simulation of heat distribution and thermal damage patterns of diode hair-removal lasers: an applicable method for optimizing treatment parameters.

OBJECTIVE: We simulated the heat distribution and thermal damage patterns of diode hair-removal lasers for different spot sizes, pulse durations, and fluences as a guide for optimization. BACKGROUND: Recently, the concept of thermal damage time as a reference for pulse duration has become a subject of debate. METHODS: Laser-Induced-Temperature-Calculation-In-Tissue (LITCIT) was used for the simulations. Skin was modeled as two homogenous layers of epidermis/dermis and two coaxial cylinders as the hair shaft/ follicle. Opto-thermal coefficients of the components and the radiant parameters of the laser (diode, 810 nm) were defined. RESULTS: At constant fluences and pulse durations, the damage occurred deeper when larger spot sizes were used. At constant pulse duration, high fluences caused significant damage to the hair follicle and epidermis. By using longer pulse durations (≤ 400 ms) at constant fluences, there was more effective damage to the hair follicle while sparing the adjacent epidermis and dermis. Because of the time-dependent temperature profiles, an increased pulse duration creates a moderate, gradual rise in the target's temperature. Pulse durations > 400 ms are accompanied by unwanted dermis damage. CONCLUSIONS: Our results show that using very long pulse durations near the tissue damage time (≤ 400 ms) creates better efficacy in treating unwanted hairs while avoiding unwanted damage.

Treatment of oral lichen planus with photodynamic therapy mediated methylene blue: A case report

No disponible

Oral lichen planus (OLP) is a common chronic disease of uncertain origin. Many patients with OLP are refractory to all available therapies. The photodynamic therapy (PDT) was used as a possible alternative method in the treatment of lichen planus. Two patients with five oral lichen planus lesions were treated using topical PDT mediated by methylene blue (MB-PDT). The patients were followed up on sessions 3, 7, 15 days and 1 to 9 months after PDT. Clinical improvement was achieved in four lesions. Two lesions showed complete remission, and another two lesions had about 50% clinically improvement 3-9 months after a single session of PDT. No response detected in one lesion. MB-PDT blue seems to be an effective alternative treatment for control of OLP. In our opinion, this preliminary result warrant further studies in order to show the efficacy of MB-PDT in control of OLP for a longer period of time