An insight into the potentials of carbon dots for in vitro live-cell imaging: recent progress, challenges, and prospects.

Carbon dots (CDs) are a strong alternative to conventional fluorescent probes for cell imaging due to their brightness, photostability, tunable fluorescence emission, low toxicity, inexpensive preparation, and chemical diversity. Improving the targeting efficiency by modulation of the surface functional groups and understanding the mechanisms of targeted imaging are the most challenging issues in cell imaging by CDs. Firstly, we briefly discuss important features of fluorescent CDs for live-cell imaging application in this review. Then, the newest modulated CDs for targeted live-cell imaging of whole-cell, cell organelles, pH, ions, small molecules, and proteins are elaborately discussed, and their challenges in these fields are explained.

Evaluating the efficacy and safety of topical sirolimus 0.2% cream as adjuvant therapy with pulsed dye laser for the treatment of port wine stain: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Port Wine Stain (PWS) is a congenital capillary malformation. Although multiple treatments are required, the gold standard treatment for PWS is Pulsed Dye Laser (PDL). Given its anti-angiogenic effects, sirolimus can be considered as an adjuvant to PDL in PWS. AIM: To evaluate the efficacy and safety of topical sirolimus (Rapamycin) 0.2% cream as adjuvant therapy for PDL for PWS. METHODS: In this randomized double-blind placebo-controlled trial, 15 patients with PWS were enrolled. Each lesion was divided into upper and lower parts, and each part was assigned randomly to receive PDL (4 sessions, 2 months apart) plus sirolimus vs PDL and placebo. The response was evaluated using colorimetry, investigator global assessment (IGA), and patient global assessment (PGA) every two months for eight continuous months. RESULTS: According to the colorimetric analysis, medial and lateral sides of the treatment and placebo parts did not differ significantly (both P-value > .05). However, according to PGA and IGA, there was a significant difference in favor of sirolimus (P-values = .041 and .039, respectively). Itching and dryness (86.7%), contact dermatitis (20%) were the most common adverse effects in the sirolimus group, while none of them were observed in placebo. CONCLUSION: Although the improvement was significant subjectively, topical sirolimus 0.2% as an adjuvant to PDL does not appear to improve PWS erythema using calorimetric assessment.

Carbon dots with pH-responsive fluorescence: a review on synthesis and cell biological applications.

This review summarizes state of the art synthesis and applications of carbon dots (CDs) with pH-responsive fluorescence. Following an introduction, the first section covers methods for the preparation of pH-responsive CDs, with subsections on general methods for preparing CDs (by hydrothermal, solvothermal, electrochemical, microwave, laser ablation, pyrolysis or chemical oxidation polymerization methods), and on precursors for synthesis. This is followed by a section on the mechanisms of pH-responsivity (by creating new functional groups, change of energy levels, protonation and deprotonation, aggregation, or by introduction shells). Several Tables are presented that give an overview of the wealth of methods and materials. A final section covers applications of carbon dots (CDs) with pH-responsive fluorescence for sensing, drug delivery, and imaging. The conclusion summarizes the current status, addresses challenges, and gives an outlook on potential future trends. Graphical abstract The synthesis and biological applications of carbon dots(CDs) with pH-responsive fluorescence are summarized. Precursors and methods for preparation of pH-responsive CDs, mechanisms of pH-responsivity, and biological applications of CDs with pH-responsive fluorescence for sensing, drug delivery, and imaging are discussed.

On-chip analysis of carbon dots effect on yeast replicative lifespan.

Carbon dots (CDs) are promising nanomaterials for biosensing, bioimaging, and drug delivery due to their large surface area, excellent optical properties, and thermal and chemical stability. However, biosafety of CDs is still understudied, and there is not a generally accepted standard to evaluate the toxicity of CDs. We present a gradient network generator microfluidic device for dose-dependent testing of toxicity of CDs to a unicellular eukaryotic model organism, yeast Pichia pastoris. We fully characterized the microfluidic model and compare its performance with a conventional method. The gradient generator increased the contact area between the mixing species and enabled a high-throughput testing of CDs in a wide range of concentrations in cell chambers. Real time monitoring of yeast cell proliferation in the presence of CDs showed dose-dependent growth inhibition and various budding cell shape profiles. Comparing the result of microfluidic platform and conventional method revealed statistically significant differences in the proliferation rate of the cells between the two platforms. To understand the toxicity mechanism, we studied binding of CDs to P. pastoris and found increasing interactions of CDs with the cell surface at CDs larger concentrations. This study demonstrated the utility of the gradient generator microfluidic device as a convenient tool for toxicity assessment of nanomaterials at a cellular level.

Investigation the cytotoxicity and photo-induced toxicity of carbon dot on yeast cell.

Carbon dots (CDs) as a new fluorescent material with excellent water solubility, chemical inertness, and easy surface modification are a good candidate for bioimaging and biosensing due to their low toxicity and good biocompatibility. Although carbon is not an intrinsically toxic substance, carbon nanomaterials such as CDs may cause risks to human health and the potentially hazardous effects of CDs on various living systems must be completely determined. So far, cytotoxicity studies of CDs have focused on human cells and are mainly conducted on limited cell lines. In the present study, toxicity assessment of CDs was evaluated on yeast cells Pichia pastoris as a unicellular eukaryotic model. Results revealed dose-dependent toxicity of CDs on yeast cells and less relative cell growth in 25 mg/ml of CDs as compared to the control group. CDs binding curve confirmed the interaction between CDs and surface of yeast cells. SEM images showed that the CDs caused cell shrinkage and hole formation on the surface of yeast cells and also induced slightly cell deformation. It was demonstrated that CDs could generate the ROS dose-dependently. Finally, results showed the growth inhibition and ROS generation effects of CDs were enhanced at light exposure, as an important environmental factor. These findings could have important implications for applications of CDs.

Quality of life in mild and severe alopecia areata patients.

BACKGROUND: Alopecia areata is a relapsing hair disorder characterized by a sudden hairloss and has a considerable impact on patient's quality of life. The goal of this study was to determine quality of life among patients with mild and severe forms of alopecia areata and compare the two groups. METHODS: During one year, 176 patients (96 mild, 80 severe) were selected and asked to complete Dermatology Life Quality Index (DLQI) questionnaires. RESULTS: Our study revealed that the severe group was predominantly female and had higher amount of unemployment, more prolonged disease duration, unstable disease course and facial involvement. The mean DLQI scores in the severe and mild groups were 10.7 ± 7.5 and 5.4 ± 6.8, respectively which was significantly different and severe group had higher DLQI scores and more quality of life impairment. As well, there was a significant association between total DLQI scores and acute stress during last 6 months. CONCLUSIONS: Our study confirms that alopecia areata considerably impacts quality of life and this is more pronounced in patients with severe disease and those who had acute stress recently.

New Insight into the Concept of Carbonization Degree in Synthesis of Carbon Dots to Achieve Facile Smartphone Based Sensing Platform.

Direct pyrolysis of citric acid (CA) has been proved to be a facile bottom-up technique for making pristine carbon dots (CD) with homogenous size distribution. However, limited reports are available on systematic optimization of carbonization degree. In this investigation, pyrolysis temperatures between 160 °C and 220 °C were studied, based on CA thermal decomposition path, using various heating durations. The effect of the formation of more carbonized carbon particles (MCCPs), as the major byproduct of this method, on photoluminescence properties of CDs was also considered. The NaOH amount that neutralizes the solution and the effect of dilution on the emission intensity, were introduced as simple and accessible factors for monitoring carbonization degree, and an estimate of MCCP/CD ratio, respectively. The results show that the CDs fabricated at 160 °C, 50 minutes attain almost twice higher quantum yield (QY) of 29% than highest QY reported based on pyrolysis of CA. The so-prepared CDs can be employed as excellent candidates for turn-off sensing. As a proof of concept, detection limit of 50 nM for Hg2+ was achieved using a facile and inexpensive smartphone set-up that is able to quantify and compare fluorescent intensity in several samples simultaneously.

Dermoscopic Changes of Melanocytic Nevi after Psoralen-Ultraviolet A and Narrow-Band Ultraviolet B Phototherapy.

BACKGROUND: Phototherapy may alter the morphologic features of melanocytic nevi. Dermoscopy is a non-invasive method for evaluation of skin lesions, specifically melanocytic nevi. AIMS AND OBJECTIVES: This study was designed to evaluate the effects of narrowband ultraviolet B (NB-UVB) and psoralen-ultraviolet A (PUVA) therapy on the dermoscopic features of nevi. METHODS: A total of 74 melanocytic nevi were randomly selected from 20 patients. Out of those, 54 nevi received NB-UVB, while 20 received PUVA. 50% of the nevi in each group were exposed to radiation, while the remaining nevi were covered with an opaque tape. All nevi were demoscopically evaluated before and after 30 or 60 sessions of phototherapy. RESULTS: Overall demoscopic changes were observed in 34/37 (91.8%) of the uncovered nevi compared to 16/37 (43.2%) of the covered nevi (P value 0.0001). The most common changes were new dot/globule formation (62.1%), darkening (32.4%), nevus enlargement (27%), and patchy pigmentation (18.8%). Compared to NB-UVB, dermoscopic changes were more frequent in both covered and uncovered nevi of the PUVA group. (P values 0.041 and 0.0172, respectively). New dot/globule formation was observed more frequently in the covered and uncovered nevi of PUVA group. CONCLUSION: PUVA and NB-UVB induce dermoscopic changes in the majority of the irradiated nevi. However, PUVA is associated with higher frequency of dermoscopic changes in both covered and uncovered nevi.

Treatment of erosive oral lichen planus with methotrexate.

BACKGROUND AND OBJECTIVES: Erosive oral lichen planus (EOLP) is a chronic inflammatory disease of the oral mucosa causing significant pain and impairment of the quality of life. No immediate and definitive cure is available, especially in its chronic and most recalcitrant forms. The objective of this study was to evaluate the efficacy of methotrexate treatment in EOLP. PATIENTS AND METHODS: A prospective open trial of oral methotrexate 15 mg QWK in 18 patients with EOLP (clinically and histopathologically confirmed) unresponsive to at least one previous topical or systemic medication. DURATION: Twelve weeks followed by twelve weeks of follow-up. RESULTS: Partial response or better was achieved in 15 (83.3%) patients. A statistically significant reduction in Thongprasom scale score was observed (mean value 5 at baseline, 3.08 ± 1.11 at week 12, 2.94 ± 0.97 at week 24, P value < 0.001). A statistically significant reduction was noted in the pain visual analogue scale (mean value 6.55 ± 2.33 at baseline, 2.46 ± 2.18 at week 12, 2.29 ± 1.93 at week 24, P value < 0.001). Adverse events occurred in four (22.2%) patients, requiring discontinuation of treatment in one patient. CONCLUSION: Methotrexate is a valuable therapeutic option in longstanding recalcitrant EOLP, particularly with respect to the improvement of subjective symptoms. Randomized controlled trials are required.

Evaluation of prolactin levels in patients with newly diagnosed pemphigus vulgaris and its correlation with pemphigus disease area index.

BACKGROUND: Prolactin is a hormone; in addition to it known roles, it has immunomodulatory effects on lymphocytes maturation and immunoglobulins production. Hyperprolactinemia has been demonstrated in various autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, type I diabetes mellitus, and Graves' disease. In view of the prolactin immunomodulatory roles, studying prolactin levels in pemphigus as an autoimmune blistering disease may introduce new ways of understanding disease etiology and developing treatment strategies. OBJECTIVE: Our purpose was to determine the prolactin levels in patients with newly diagnosed pemphigus vulgaris and study its correlation with pemphigus disease area index. LIMITATION: Our study was limited by the lack of a control group. METHODS: In this cross-sectional study, prolactin and anti-desmoglein 1 and 3 autoantibodies levels were measured in 50 patients with newly diagnosed pemphigus vulgaris in Razi Dermatology Hospital. Pemphigus severity and extent was estimated using the Pemphigus Disease Area Index. RESULTS: Of the 50 patients, 18 were male and 32 were female with a mean age of 41.56 ± 13.66 years. Mean prolactin (PRL) level was 15.60 ± 11.72 ng/ml (10.68 in males and 18.37 in females). Mean anti-desmoglein 1 and 3 autoantibodies were 135.8 ± 119.8 and 245.8 ± 157.4 U/ml, respectively. Eleven out of 50 patients had a higher than normal prolactin range. No relation was found between prolactin level and disease activity (p = .982). Also, correlation studies show no relation between prolactin and anti-desmoglein 1 and 3 autoantibodies levels (respectively, p = .771 and .738). In comparing the extent of the disease between the two groups with normal and high prolactin, paired t-test showed no significance (p = .204). CONCLUSION: In our study, 22% of patients had hyperprolactinemia, which was greater among females. The highest PRL level was detected in mucocutaneous group. Although serum PRL levels were higher in patients with a greater Pemphigus Disease Area Index, it did not reach statistical significance.

The efficacy of methotrexate plus pioglitazone vs. methotrexate alone in the management of patients with plaque-type psoriasis: a single-blinded randomized controlled trial.

Recently, thiazolidinediones have shown to be efficacious with a favorable safety profile when used in the treatment of chronic plaque-type psoriasis. The aim of this study was to evaluate and compare the efficacy and safety of a combination of methotrexate plus pioglitazone and methotrexate alone in plaque-type psoriasis. A total of 44 adult patients with plaque-type psoriasis were included in the study. Patients were randomized to treatment with methotrexate alone (group A) or methotrexate plus pioglitazone (group B) for 16 weeks. The primary efficacy outcome measure was psoriasis area and severity index (PASI) score change between the study groups at week 16 relative to baseline. The secondary efficacy outcome measure was dermatology life quality index (DLQI) score change between the two groups at week 16 relative to baseline. The PASI 75 score was also measured. After 16 weeks of therapy, the percentage of reduction in the mean PASI score was 70.3% in group B and 60.2% in group A. PASI 75 was achieved in 14 patients (63.6%) in group B compared with two patients (9.1%) in group A within 16 weeks, which was significant (P < 0.001). At 16 weeks from the baseline, a 63.6% decrease in the mean DLQI score of group B was seen, while the decrease for group A was 56.9%. Pioglitazone enhances the therapeutic effect of methotrexate in plaque-type psoriasis, as demonstrated by a reduction in the mean PASI scores. In terms of DLQI, there was no extra benefit by the addition of pioglitazone to methotrexate therapy.

Genital warts in 250 Iranian patients and their high- risk sexual behaviors.

BACKGROUND AND OBJECTIVE: Genital wart is the most common sexually transmitted disease worldwide. Sexual risk factors and sexual behavior pattern may be different in various countries. In this study, we tried to evaluate demographic information and some sexual behaviors and risk factors in Iranian patients with genital warts. METHODS: In this cross-sectional study, 250 patients with anogenital warts were evaluated. They had been referred to the Sexually Transmitted Diseases Clinic of Razi Hospital. Demographic information and sexual risk factors and pattern of sexual behaviors were recorded in the questionnaires. RESULTS: One hundred twenty-five men and 125 women with genital warts were evaluated. The most common age group was 20- 30 years old; 24.8% were single; 29.6% had academic education; 35 (14%) of the patients had started sexual activity before 15 years of age; 92% reported unsafe sex;  seven (2.8%) of them were HIV infected; two cases (0.8%) were homosexual; and seven cases (2.8%) were bisexual. Genital herpes simplex type 2 was the most common coincident sexually transmitted disease (6.4%). CONCLUSION: Genital wart in men may be as common as women, married and singles, and mostly involves younger people. Sexual high-risk behaviors and unsafe sex make them at risk for HIV infection. Sexual health education should be considered in high-risk groups.

Bullous pemphigoid in Iranian patients: a descriptive study on 122 cases.

Bullous pemphigoid is an immunobullous disease with high mortality and morbidity. Different aspects and characteristics in the patients vary in different areas in the world. Our objective was to study clinical and demographic characteristics of bullous pemphigoid in Iranian patients. In a retrospective descriptive study, we reviewed 122 patients with bullous pemphigoid within 1987-2007. Demographic characteristics, clinical manifestations, treatment, relapses and outcome were evaluated. The mean age of 122 patients was 65 ± 18.11 years including 35.2% male and 64.8% female. The most common manifestations were cutaneous bullae (97.5%). 27% had oral lesions. 30.3% had eosinophillia. 90 patients(73.8%) received oral prednisolone, 29 patients (23.8%) topical steroid, 2 patients tetracycline and 1 patient dapsone. 89 patients were followed after admission. Out of them 44 patients experienced first relapse and 22 patients second relapse. 41 cases (46%) were completely controlled. 11 cases (12%) were not controlled. Clinical and general characteristics of bullous pemphigoid patients differ in various regions in the world.

Evaluation of the effect of disease duration in generalized vitiligo on its clinical response to narrowband ultraviolet B phototherapy.

BACKGROUND/PURPOSE: Narrowband ultraviolet B (NB-UVB) has been accepted as an effective therapy for generalized vitiligo. On the other hand, different factors seem to contribute to a good response. The purpose of this study is to evaluate the influence of disease duration on its clinical response to NB-UVB phototherapy. METHODS: In this open and uncontrolled study, vitiligo was considered 'recent' when the duration of disease was less than or equal to 4 years and 'long standing' when it was greater than 4 years. The patients received NB-UVB thrice weekly with an initial dose of 200 mJ/cm(2) and 10% increments at each subsequent treatment. After categorizing the clinical response to four groups (mild, moderate, good, and excellent), duration of disease and clinical response to NB-UVB were correlated statistically using the t-test. RESULTS: There were 63 patients: 34 women and 29 men, aged 6-60 years. The mean of disease duration was 10.13 ± 9.1 years. Vitiligo was 'recent' in 26 and 'long standing' in 37 patients. The mean of overall response was 51.94 ± 18.48%. Higher grades of response were more prevalent in patients with recent vitiligo than those with long-standing disease, and there was also statistically significant difference in overall response between these two groups of disease duration (P = 0.023). CONCLUSION: The early treatment of generalized vitiligo may enhance the chance of successful repigmentation.

Comparison of risk factors of single Basal cell carcinoma with multiple Basal cell carcinomas.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignant skin tumor. Although mortality attributable to BCC is not high, the disease is responsible for considerable morbidity. There is evidence that the number of patients who develop more than one BCC is increasing. AIMS: The aim of this study was to elucidate possible risk factors for developing Multiple BCC. PATIENTS AND METHODS: Patients with histologically proven BCC (n = 218) were divided into two groups (single BCC and Multiple BCC) according to the number of their tumors and their profile were reviewed. Probable risk factors were compared between these two groups. RESULTS: Among 33 evaluated risk factors, mountainous area of birth, past history of BCC, history of radiotherapy (in childhood due to tinea capitis), abnormal underlying skin at the site of tumor, and pigmented pathologic type showed significant differences between the two groups. CONCLUSIONS: The high rate of additional occurrences of skin cancers among patients with previously diagnosed BCC emphasizes the need of continued follow-up of these individuals. Those with higher risk require closest screening.

Pemphigus and pregnancy: a 23-year experience.

BACKGROUND: Studies on the interaction of pemphigus and pregnancy are limited to case reports and small case series. Pregnancy is not rare in Iranian pemphigus patients due to lower age at onset of the disease. AIM: We sought to investigate the outcome of pregnancy and the course of pemphigus in pemphigus patients in a retrospective study. METHODS: The files of 779 pemphigus women younger than 50 presenting to our center from 1984 till 2006 were examined for any mention of pregnancy. Data related to outcome of pregnancy and the course of the disease were collected. RESULTS: Sixty-six patients with a history of pregnancy were identified. Forty-eight known pemphigus patients experienced one or more pregnancies during their disease (total pregnancy number: 52). The course of pemphigus was as follows in this group: 28 cases (54%) of exacerbation, 15 cases (31%) with no alteration, and 9 cases (17%) showing improvement. The rate of abortion was 9.6% (5 cases). In 18 cases, the disease had started during pregnancy, 2 of them (11%) ended in an abortion. Overall, postpartum flare was seen in 33 cases (47.1%). CONCLUSION: Pemphigus may be exacerbated during or after pregnancy, but often to a mild degree. Although the rate of stillbirth was not as high as previously reported, the rate of abortion was considerable. Pregnancy may have an uneventful course, especially in patients in clinical remission; nevertheless, careful monitoring of the high risk mother and fetus is mandatory.

Werner syndrome in an Iranian family.

A 49-year-old man was first seen in our department for the evaluation of scleroderma-like skin changes and a nonhealing ulcer on his leg from years before referral. His medical history was of long duration. His growth was stunted at the age of 12. At 21 years of age, the patient noted graying of the scalp hair, most prominent on his temples, and the process was progressively completed by the age of 23. At the same age, atrophy and thinning of the skin and loss of subcutaneous fat resulted in a tense, shining, and adherent appearance of his skin, most obvious on his face and extremities. Soon after, he developed a high-pitched, hoarse voice. He had undergone bilateral cataract surgery at the age of 30. Around the age of 46, he developed a unilateral nonhealing chronic leg ulcer (Figure 1). He had separated from his wife because of infertility. He was the first offspring of his second-degree healthy relative parents. The other 3 siblings had similar signs and symptoms. Our patient gave the history of premature graying of the hair of his younger brother at the age of 18 and his 2 younger sisters at the age of 12 and 16. His brother had recently received diagnoses of bilateral cataract and diabetes mellitus. All of the siblings had ceased growth from early adolescence. On physical examination, our patient's weight was 48 kg and his height was 150 cm. He had normal intelligence. He was speaking with a high-pitched and childish voice. He had a bird-like appearance with a beak-shaped nose. Mottled and diffuse pigmentation and poikiloderma appearance was conspicuous on his neck (Figure 2). The entire skin was smooth, shiny, and scleroderma-like, and a marked decrease in the subcutaneous fat was noted over the extremities. A deep cutaneous ulcer was evident on his slimmed leg. Digital ulcers were not found, and radial and dorsalis pedis pulses were palpable. Clinodactyly of the toes were conspicuous. His nails were dystrophic and he had used dentures from the age of 20. On examination of the external genitalia, his testes were smaller than normal. In the biopsy taken from the leg ulcer, there were no signs of malignancy. There were no signs ofosteomyelitis on x-ray. Biopsy of the normal skin revealed atrophic epidermis and thick dermis with hyalinization of the collagen fibers and absence of pilosebaceous structures (Figure 3). The patient's scalp hair was thin and sparse and there were few axillary and pubic hairs. His fasting plasma glucose level was normal.

Pemphigus vulgaris and herpesviruses: is there any relationship?

BACKGROUND: Pemphigus is an autoimmune disorder, which results from interaction of exogenous and endogenous factors. One of these environmental factors is viral infections particularly, herpesviruses. We aimed to detect the presence of HSV 1 and 2 (herpes simplex virus) and HHV8 (human herpesvirus 8) in our patients who were suffering from pemphigus vulgaris. METHODS: In this cross-sectional study, 38 patients (19 male and 19 female patients) with pemphigus vulgaris were entered, 32 skins and six peripheral blood cells samples were obtained from the study population. Thereafter, the presence of HHV8 and HSV DNA were evaluated by using polymerase chain reaction (PCR). RESULTS: The mean age of patients was 45.05 ± 17.24 years (range: 16-81 years). Twelve patients mentioned history of herpes labial in the past (31.57%). Results of PCR test for detection of HSV and HHV8 DNA in all 32 skin samples and five peripheral blood samples and one case with skin and blood samples were reported negative. CONCLUSION: Inability to detect HHV8 and HSV DNA in this study suggests that herpesviruses may be only occasional factors for development or exacerbation of pemphigus vulgaris.