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Sunscreens are topical preparations containing any number of ultraviolet filters (UVFs). The first part of the review will focus on the recent Food and Drug Administration (FDA) regulations of 2019 and general use of these agents. While sunscreen products are becoming more regulated in the United States, we still lag behind other countries in our options for UVFs. Sun protection to prevent skin cancer and aging changes should be a combination of sun avoidance, protective structures, and clothing as well as use of sunscreen products. Newer and safer products are needed to help supplement and replace older agents as well as improve their cosmetic acceptability. This will be a review of ingredients, local toxicities (i.e. contact dermatitis, photocontact dermatitis), special considerations for children, and cosmesis of sunscreen preparations. Part 2 will focus on the environmental, ecological and human toxicities that have been increasingly related to UVFs.

Highlights • Conditioned Fear Stress (CFS) reduced the locomotor activity of the animals. • CFS showed no influence on the progression of neoplasia. • No association between HNSCC staging and BAI scores were observed. • There is no relationship between CFS and oral squamous cell carcinoma., Cancer patients present a higher risk of experiencing anxiety disorders (AD). However, it is not clear if AD might be associated with cancer development. Thus, our study aimed to evaluate if AD might be related to head and neck squamous cell carcinoma (HNSCC) development. The combination of an applied animal basic study and a retrospective diagnostic case and control study in patients was performed. As a result, we obtained that stress reduced the locomotor activity of the animals in the group stress and stress + 4NqO (p < 0.0001). The stress showed no influence on the progression of neoplasia in mice. In the same way, the case group did not present differences in anxiety scores in comparison to control. Moreover, no association between HNSCC staging and anxiety scores was observed. In conclusion, our in vivo findings in humans and animals have shown that there is no relationship between AD and oral squamous cell carcinoma.

Graphical abstract, The 2019 novel coronavirus (2019-nCoV; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) has witnessed a rapid and global proliferation since its early identification in patients with severe pneumonia in Wuhan, China. As of 27th May 2020, 2019-nCoV cases have risen to >5 million, with confirmed deaths of 350,000. However, Coronavirus disease (COVID-19) diagnostic and treatment measures are yet to be fully unraveled, given the novelty of this particular coronavirus. Hence, no drug or vaccine has been adapted for treatment, and the accuracy of the current diagnostic tests is debatable. Therefore, existing antiviral agents used for severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) were repurposed for COVID-19, taking their biological features into consideration. This study provides a concise review of the current and emerging detection and supervision technologies for SARS-CoV-2, which is the viral etiology of COVID19, and their performance characteristics, with emphasis on the novel Nano-based diagnostic tests (protein corona sensor array and magnetic levitation) and treatment measures (treatment protocols based on nano-silver colloids) for COVID-19.

BackgroundDepressive and neurocognitive disorders are debilitating conditions that account for the leading causes of years lived with disability worldwide. Overcoming these disorders is an extremely important public health problem today. However, there are no biomarkers that are objective or easy-to-obtain in daily clinical practice, which leads to difficulties in assessing treatment response and developing new drugs. Due to advances in technology, it has become possible to quantify important features that clinicians perceive as reflective of disorder severity. Such features include facial expressions, phonic/speech information, body motion, daily activity, and sleep. The overall goal of this proposed study, the Project for Objective Measures Using Computational Psychiatry Technology (PROMPT), is to develop objective, noninvasive, and easy-to-use biomarkers for assessing the severity of depressive and neurocognitive disorders.MethodsThis is a multi-center prospective study. DSM-5 criteria for major depressive disorder, bipolar disorder, and major and minor neurocognitive disorders are inclusion criteria for the depressive and neurocognitive disorder samples. Healthy samples are confirmed to have no history of psychiatric disorders by Mini-International Neuropsychiatric Interview, and have no current cognitive decline based on the Mini Mental State Examination. Participants go through approximately 10-minute interviews with a psychiatrist/psychologist, where participants talk about non-specific topics such as everyday living, symptoms of disease, hobbies, etc. Interviews are recorded using RGB and infrared cameras, and an array microphone. As an option, participants are asked to wear wrist-band type devices during the observational period. The interviews take place ≤10 times within up to five years of follow-up. Various software is used to process the raw video, voice, infrared, and wearable device data. A machine learning approach is used to predict the presence of symptoms, severity, and the improvement/deterioration of symptoms.DiscussionThe PROMPT goal is to develop objective digital biomarkers for assessing the severity of depressive and neurocognitive disorders in the hopes of guiding decision-making in clinical settings as well as reducing the risk of clinical trial failure. Challenges may include the large variability of samples, which makes it difficult to extract the features that commonly reflect disorder severity.Trial RegistrationUMIN000021396, University Hospital Medical Information Network (UMIN)

In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies., Graphical abstract The latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells were highlighted. It also provides the necessary information about siRNA development and its mechanism of action.Image 1

Objective: Coronavirus disease 2019 (COVID-19) has emerged as a pandemic, affecting nearly 180 million people worldwide as of June 22nd, 2021. In previous studies, the association between the mean Vitamin D (Vit D) concentration of each country and COVID-19 infection and mortality rate in European countries was examined. The aim of this study was to critically evaluate the relationship between Vit D mild and severe deficiency prevalence in each country and COVID-19 infection, recovery, and mortality using updated data and a different methodological approach. Research Methods & Procedures: Information on Vit D concentration/deficiency for each country was retrieved through literature search. As of June 22nd, 2021, COVID-19 infections and mortalities per one million population as well as total recoveries were obtained. The association between Vit D deficiency and COVID-19 infection, recovery, and mortality were explored using correlation coefficients and scatterplots. Results: Non-significant correlations were observed between the number of COVID-19 infections (r=0.363; p=0.116), and recoveries (r=0.388, p=0.091) with the prevalence of mild Vit D deficiency (

Ultraviolet (UV) radiation from indoor tanning equipment is a known cause of skin cancer; however, little is known about how the availability of indoor tanning salons has been impacted by indoor tanning legislation, including Ontario's Skin Cancer Prevention Act: Tanning Beds (SCPA). Tanning salon listings were obtained from the 2001 to 2017 editions of InfoCanada's Ontario Business to Business Sales and Marketing directories. Using descriptive statistics and regression analysis, we assessed the number of tanning salons before and after: 1) the 2006 International Agency for Research on Cancer (IARC) report on indoor tanning and skin cancer; 2) the 2009 World Health Organization (WHO) reclassification of artificial UV radiation as carcinogenic; and 3) the passing and enactment of Ontario's SCPA in 2013 and 2014, respectively. There were fewer tanning salon listings in the years after vs. before the IARC report, the WHO reclassification, and the passing and enactment of the SCPA. The number of tanning salons in Ontario, Canada has been declining since 2006, which may reflect a decline in indoor tanning bed use. Key public health policy instruments, including legislation and public education, appear to be associated with this trend, suggesting they may contribute to deterring indoor tanning., Highlights • Number of tanning salons in Ontario, Canada decreased from 2006 to 2017. • Number of tanning salons declined after passing and enactment of indoor tanning legislation. • Number of tanning salons declined after international report and decision on carcinogenic nature of tanning devices. • Legislation, expert exhortation, and public education may contribute to declines in tanning salon availability.

Graphical Abstract Unlabelled image Combination of Budesonide and Colchicine Dry powder inhaler Liposomes proved to be effective for Idiopathic Pulmonary fibrosis., Dry powder inhaler Liposomes were prepared to investigate the effectiveness of pulmonary delivery of Colchicine and Budesonide for Idiopathic Pulmonary fibrosis. Budesonide (BUD) and Colchicine (COL) liposomes were prepared by thin layer film hydration method (TFH) using 1,2-Dipalmitoyl-sn-glycero-3- phosphoglycerol sodium (DPPG), Hydrogenated Soyaphosphotidylcholine (HSPC), Soyaphosphatidylcholine (SPC), cholesterol (CHOL) and drug in different weight ratios. The optimum lipid composition for BUD (74.22 ± 0.97%) was DPPG: HSPC: CHOL (4:5:1) and for COL (50.94 ± 2.04%) was DPPG: SPC: CHOL (3:6:1). These compositions retained drug for a longer period of time so selected for further study. Liposomes were found to be spherical in shape with mean size below 100 nm. Liposomes lyophilized using Mannitol as carrier and cryoprotectant showed high entrapment efficiency (97.89 - 98.6%). The powder was dispersed through an Andersen cascade impactor to evaluate the performance of the aerosolized powder. It was found that prepared liposomal dry powder inhaler (DPIs) sustained the drug release up to 24 hours. Optimized Budesonide DPI Formulation B2 (86.53 ± 1.9%), Colchicine DPI Formulation C2 (90.54 ± 2.3 %) and BUD and COL DPI Combination M2 (89.91 ± 1.8%, 91.23 ± 1.9%). Histopathological results, measurements of lung hydroxyproline content, Myeloperoxidase activity indicated that liposomal dry powder inhaler administration attenuates lung fibrosis induced by bleomycin. Long term stability studies indicated that lyophilised BUD and COL liposomes were stable for 6 months at (25 °C ± 2 °C, 60% ± 5% RH) and refrigerated conditions (2 - 8 °C). These results supported that combination of budesonide and colchicine liposomal dry powder inhaler pulmonary drug delivery for treatment of idiopathic Pulmonary Fibrosis exhibits prolonged drug retention at targeted site and reduces the systemic exposure.

Alzheimer's disease (AD) is a neurodegenerative process characterized by the accumulation of extracellular deposits of amyloid β-peptide (Aβ), which induces neuronal death. Monomeric Aβ is not toxic but tends to aggregate into β-sheets that are neurotoxic. Therefore to prevent or delay AD onset and progression one of the main therapeutic approaches would be to impair Aβ assembly into oligomers and fibrils and to promote disaggregation of the preformed aggregate. Albumin is the most abundant protein in the cerebrospinal fluid and it was reported to bind Aβ impeding its aggregation. In a previous work we identified a 35-residue sequence of clusterin, a well-known protein that binds Aβ, that is highly similar to the C-terminus (CTerm) of albumin. In this work, the docking experiments show that the average binding free energy of the CTerm-Aβ1–42 simulations was significantly lower than that of the clusterin-Aβ1–42 binding, highlighting the possibility that the CTerm retains albumin's binding properties. To validate this observation, we performed in vitro structural analysis of soluble and aggregated 1 μM Aβ1–42 incubated with 5 μM CTerm, equimolar to the albumin concentration in the CSF. Reversed-phase chromatography and electron microscopy analysis demonstrated a reduction of Aβ1–42 aggregates when the CTerm was present. Furthermore, we treated a human neuroblastoma cell line with soluble and aggregated Aβ1–42 incubated with CTerm obtaining a significant protection against Aβ-induced neurotoxicity. These in silico and in vitro data suggest that the albumin CTerm is able to impair Aβ aggregation and to promote disassemble of Aβ aggregates protecting neurons., Graphical Abstract Unlabelled Image, Highlights • Albumin binds amyloid with higher affinity than clusterin. • The albumin C-terminus retains the amyloid binding ability of the whole albumin. • The albumin C-terminus impairs amyloid assembly. • The albumin C-terminus favors the disassemble of amyloid aggregates. • The albumin C-terminus protects neurons against aggregated amyloid.

Ozone (O3) exposure has been reported to contribute to various cutaneous inflammatory conditions, such as eczema, psoriasis, rush etc. via a redox-inflammatory pathway. O3 is too reactive to penetrate cutaneous tissue; it interacts with lipids present in the outermost layer of skin, resulting in formation of oxidized molecules and hydrogen peroxide (H2O2). Interestingly, several inflammatory skin pathologies demonstrate altered levels of antimicrobial peptides (AMPs). These small, cationic peptides are found in various cells, including keratinocytes, eccrine gland cells, and seboctyes. Classically, AMPs function as antimicrobial agents. Recent studies indicate that AMPs also play roles in inflammation, angiogenesis, and wound healing. Since altered levels of AMPs have been detected in pollution-associated skin pathologies, we hypothesized that exposure to O3 could affect the levels of AMPs in the skin. We examined levels of AMPs using qRT-PCR, Western blotting, and immunofluorescence in vitro (human keratinocytes), ex vivo (human skin explants), and in vivo (human volunteer subjects exposed to O3) and observed increased levels of all the measured AMPs upon O3 exposure. In addition, in vitro studies have confirmed the redox regulation of AMPs in keratinocytes. This novel finding suggests that targeting AMPs could be a possible defensive strategy to combat pollution-associated skin conditions., Graphical abstract Image 1, Highlights • AMPs (hBDs1-3, CAMP) increase in O3 exposed human skin by a redox mechanism. • Transcriptional upregulation of AMPs in response to O3 exposure is due to an altered redox status. • Pollution increase AMPs could be the connection between pollution exposure and the development/exacerbation of inflammatory skin conditions.

Human skin is composed of the cell-rich epidermis, the extracellular matrix (ECM) rich dermis, and the hypodermis. Within the dermis, a dense network of ECM proteins provides structural support to the skin and regulates a wide variety of signaling pathways which govern cell proliferation and other critical processes. Both intrinsic aging, which occurs steadily over time, and extrinsic aging (photoaging), which occurs as a result of external insults such as solar radiation, cause alterations to the dermal ECM. In this study, we utilized both quantitative and global proteomics, alongside single harmonic generation (SHG) and two-photon autofluorescence (TPAF) imaging, to assess changes in dermal composition during intrinsic and extrinsic aging. We find that both intrinsic and extrinsic aging result in significant decreases in ECM-supporting proteoglycans and structural ECM integrity, evidenced by decreasing collagen abundance and increasing fibril fragmentation. Intrinsic aging also produces changes distinct from those produced by photoaging, including reductions in elastic fiber and crosslinking enzyme abundance. In contrast, photoaging is primarily defined by increases in elastic fiber-associated protein and pro-inflammatory proteases. Changes associated with photoaging are evident even in young (mid 20s) sun-exposed forearm skin, indicating that proteomic evidence of photoaging is present decades prior to clinical signs of photoaging. GO term enrichment revealed that both intrinsic aging and photoaging share common features of chronic inflammation. The proteomic data has been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PXD015982., Highlights • Intrinsic aging and photoaging both decrease ECM-supporting proteoglycans and structural ECM. • Intrinsic aging produces reductions in elastic fiber and crosslinking enzyme abundance. • Photoaging results in increases in pro-inflammatory proteases and elastic fiber abundance. • Intrinsic aging and photoaging share common features associated with chronic inflammation. • Proteomic changes associated with photoaging are evident decades prior to clinical aging signs.

Sunscreen is a popular form of sun protection and when applied sufficiently (2 mg/cm2) has been shown to block the harmful molecular effects of ultraviolet radiation (UV). This field study tested the effectiveness of UV detection stickers to improve sunscreen use. During a rugby league two-day sporting event (28–29 February 2020) in Queensland, Australia interested players 14–18 years old were provided with access to free sunscreen on DAY-1 and during the subsequent day (DAY-2) were provided with a free UV detection sticker and access to sunscreen. On DAY-2, one UV detection sticker was handed out to 550 attendees. The sunscreen bottles were weighted periodically by research staff throughout both event days. Primary outcomes were sunscreen usage. Overall, 868 g of sunscreen was used across both DAY-1 and DAY-2, with 19% (167 g) of sunscreen used on DAY-1 and 81% (701 g) of sunscreen used on DAY-2. This resulted in a >3-fold improvement in sunscreen use on DAY-2 when the UV detection stickers were provided. We found UV detection stickers may improve use of sunscreen in adolescents during sporting events in high UV environments.

Field cancerization in organ transplant recipients (OTRs) is a frequent occurrence, setting the stage for multiple squamous cell carcinomas (SCCs). Immunosuppression directly promotes keratinocyte cancer formation and reduces tumor immunity. Photo damage is amplified in OTRs via several mechanisms including potentiation of the tumor-promoting effects of calcineurin inhibitors and anti-infective medications such as voriconazole. The challenge with field cancerization in OTRs is to stay ahead of repetitive epithelial tumor formation. We present a strategy to treat field cancerization using ingenol mebutate and discuss other nonregistered modalities and treatment options.

Introduction In addition to their important role in fighting infection, natural killer cells are cytotoxic to cancer cells. Studies demonstrated that some KIR genes were responsible for the reduction of the risk of Hodgkin's lymphoma (HL) while others were associated with an increased risk of HL. Aim The aim of this study is to assess KIR genotypic distribution in Lebanese patients with Hodgkin's lymphoma. Methods KIR genotype was analyzed in 41 HL patients and 120 healthy Lebanese individuals using the KIR Genotyping SSP kit. Results No significant association between HL and any KIR gene was found. Among HL patients, the AA, AB, and BB genotype frequencies were, respectively, 41.46%, 43.9% and 14.63% with an A:B ratio of 1.73:1. As for the controls, the AA, AB, and BB genotype frequencies were, respectively, 39.17%, 50%, and 10.83% with an A:B ratio of 1.79:1. Conclusion In this first study from the Mediterranean region, KIR genotype does not seem to be associated with Hodgkin's lymphoma. Further clinical and translational research is needed to rule out the protective or predisposing role of KIR genes in this important clinical entity., Highlights • KIR genotyping has been implicated in a variety of clinical and immunological disorders. • This is the second international but first Mediterranean paper describing KIR genes prevalence in Hodgkin’'s lymphoma. • Results were compared to a control sample and confirmed the negative association between KIR genes and Hodgkin’s lymphoma

Xeroderma pigmentosum (XP) is an autosomal recessive genodermatosis caused by a germline loss of function in DNA repair enzymes.1, 2 This defect impairs physiologic DNA repair after ultraviolet (UV) radiation–induced damage, which can lead to photosensitivity in about half of all patients,3, 4 pigmentation abnormalities, and an increased risk of nonmelanoma skin cancers as well as melanoma.5 XP patients classically exhibit a 10,000-fold increase in the frequency of skin cancers arising in sun-exposed skin, eyes, and other mucosal areas (eg, lips and tongue), which appear at an early age.5 Prognosis and mortality of XP patients are mostly tightly related to the risk of metastasis of cutaneous squamous cell carcinomas and melanomas but also depend on the extent of the underlying DNA repair deficiency. The life expectancy of XP patients is reduced by 30 years.2, 6 Seven genetically distinct complementation groups of XP (designated XP-A through XP-G depending on the gene mutated) with germline loss of function mutations to enzymes are involved in nucleotide excision repair (NER).6 The degree of photosensitivity, risk of skin cancer, and risk of neurologic abnormality vary from complementation group to group.3 XP complementation group G (XP-G, OMIM 278780) represents one of the rarest subtypes of XP with mutations identified in the Excision Repair Cross-complementing Rodent Repair Deficiency Complementation Group 5 gene (ERCC5), which encodes an enzyme involved in the incision step during the removal of UV-damaged DNA. XP-G is one of the most clinically lethal subtypes of XP, wherein patients also exhibit clinical features of Cockayne syndrome (CS) or XP with neurologic symptoms. To date, there have been less than 20 XP-G cases reported in the literature.7, 8 Approximately 30 noncutaneous malignancies have also been associated with this lethal XP subtype.9 Herein, we report a Chinese proband patient who had XP group G diagnosed, resulting from 2 compound heterozygous germline mutations in ERCC5—a nonsense mutation from the father and a missense mutation from the mother. To the best of our knowledge, this patient is the first reported XP-G case identified in the Chinese population.

The incidence of skin cancer is rare in African Americans; however, there are several reports of patients with depigmented or hypopigmented lesions on sun-exposed areas, such as the scalp, who are at increased risk for squamous cell carcinoma (SCC). Decrease in melanin, immunosuppressive therapy, frequent ultraviolet exposure, human papillomavirus infection, chronic scarring, and inflammatory processes are factors associated with the development of SCC in black patients.1 We present a rare case of a 55-year-old African-American woman who had SCC within a discoid lupus erythematosus (DLE) lesion.

Photodynamic therapy (PDT) against cancer has gained attention due to the successful outcome in some cancers, particularly those on the skin. However, there have been limitations to PDT applications in deep cancers and, occasionally, PDT treatment resulted in tumor recurrence. A better understanding of the underlying molecular mechanisms of PDT-induced cytotoxicity and cytoprotection should facilitate the development of better approaches to inhibit the cytoprotective effects and also augment PDT-mediated cytotoxicity. PDT treatment results in the induction of iNOS/NO in both the tumor and the microenvironment. The role of NO in cytotoxicity and cytoprotection was examined. The findings revealed that NO mediates its effects by interfering with a dysregulated pro-survival/anti-apoptotic NF-κB/Snail/YY1/RKIP loop which is often expressed in cancer cells. The cytoprotective effect of PDT-induced NO was the result of low levels of NO that activates the pro-survival/anti-apoptotic NF-κB, Snail, and YY1 and inhibits the anti-survival/pro-apoptotic and metastasis suppressor RKIP. In contrast, PDT-induced high levels of NO result in the inhibition of NF-kB, Snail, and YY1 and the induction of RKIP, all of which result in significant anti-tumor cytotoxicity. The direct role of PDT-induced NO effects was corroborated by the use of the NO inhibitor, l-NAME, which reversed the PDT-mediated cytotoxic and cytoprotective effects. In addition, the combination of the NO donor, DETANONOate, and PDT potentiated the PDT-mediated cytotoxic effects. These findings revealed a new mechanism of PDT-induced NO effects and suggested the potential therapeutic application of the combination of NO donors/iNOS inducers and PDT in the treatment of various cancers. In addition, the study suggested that the combination of PDT with subtoxic cytotoxic drugs will result in significant synergy since NO has been shown to be a significant chemo-immunosensitizing agent to apoptosis., Graphical abstract, Highlights • PDT-mediated cytotoxic and cytoprotective effects depend also by the induction of NO from tumor. • The PDT-induced NO modulates the dysregulated NF-kB/Snail/RKIP loop. • The direct role of NO induction by PDT was corroborated by the use of the NO inhibitor, l-NAME. • The combination of an NO donor and PDT resulted in a increased cytotoxic effect, in vitro and in vivo. • Novel potential therapeutic applications are proposed for the use of PDT combined with NO donors.