Development of Pigmentation-Regulating Agents by Drug Repositioning

Skin color is determined by the processes of melanin synthesis and distribution. Problems in various molecules or signaling pathways involved in melanin synthesis contribute to skin pigmentation defects. Several trials have been conducted on the production of pigmentation-regulating agents, and drug repositioning has emerged as a modern technique to identify new uses for existing drugs. Our research team has researched substances or drugs associated with pigmentation control and, as a result, nilotinib, sorafenib, and ICG-001 have been found to promote pigmentation, while 5-iodotubercidin inhibits pigmentation. Therefore, these substances or medications were suggested as potential therapeutics for pigmentation disorders by drug repositioning.

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Targeted Delivery of Natural Bioactives and Lipid-nanocargos against Signaling Pathways Involved in Skin Cancer

Current Medicinal Chemistry ◽

10.2174/0929867327666201104151752 ◽

2020 ◽

Vol 27 ◽

Author(s):

Mohammad Kashif Iqubal ◽

Aiswarya Chaudhuri ◽

Ashif Iqubal ◽

Sadaf Saleem ◽

Madan Mohan Gupta ◽

...

Keyword(s):

Skin Cancer ◽

Signaling Pathways ◽

Signaling Pathway ◽

Targeted Delivery ◽

Skin Pigmentation ◽

Wnt Signaling Pathway ◽

Human Beings ◽

Radiation Chemical ◽

Cell Leukemia Virus Type ◽

Human T Cell

: At present, skin cancer is a widespread malignancy in human beings. Among diverse population types, Caucasian populations are much more prone in comparison to darker skin populations due to the comparative lack of skin pigmentation. Skin cancer is divided into malignant and non-melanoma skin cancer, which is additionally categorized as basal and squamous cell carcinoma. The exposure to ultraviolet radiation, chemical carcinogen (polycyclic aromatic hydrocarbons, arsenic, tar, etc.), and viruses (herpes virus, human papillomavirus, and human T-cell leukemia virus type-1) are major contributing factors of skin cancer. There are distinct pathways available through which skin cancer develops, such as the JAKSTAT pathway, Akt pathway, MAPKs signaling pathway, Wnt signaling pathway, to name a few. Currently, several targeted treatments are available, such as monoclonal antibodies, which have dramatically changed the line of treatment of this disease but possess major therapeutic limitations. Thus, recently many phytochemicals have been evaluated either alone or in combination with the existing synthetic drugs to overcome their limitations and have found to play a promising role in the prevention and treatment. In this review, complete tracery of skin cancer, starting from the signaling pathways involved, newer developed drugs with their targets and limitations along with the emerging role of natural products alone or in combination as potent anticancer agents and their molecular mechanism involved has been discussed. Apart from this, various nanocargos have also been mentioned here, which can play a significant role in the management and treatment of different types of skin cancer.

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Evaluation of a resorufin-based fluorescent probe for tyrosinase detection in skin pigmentation disorders

Bio-Design and Manufacturing ◽

10.1007/s42242-021-00138-3 ◽

2021 ◽

Author(s):

Yibo Hu ◽

Hongliang Zeng ◽

Jiaxing Jiang ◽

Sheng Yang ◽

Jinhua Huang ◽

...

Keyword(s):

Fluorescent Probe ◽

Skin Pigmentation ◽

Pigmentation Disorders

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Paracrine Secreted Frizzled-Related Protein 4 Inhibits Melanocytes Differentiation in Hair Follicle

Stem Cells International ◽

10.1155/2017/2857478 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Haiying Guo ◽

Mingxing Lei ◽

Yuhong Li ◽

Yingxin Liu ◽

Yinhong Tang ◽

...

Keyword(s):

Wnt Signaling ◽

Hair Follicle ◽

Skin Pigmentation ◽

Related Protein ◽

Skin Cells ◽

Melanocyte Stem Cells ◽

Potential Therapeutic Application ◽

Pigmentation Disorders

Wnt signaling plays crucial role in regulating melanocyte stem cells/melanocyte differentiation in the hair follicle. However, how the Wnt signaling is balanced to be overactivated to control follicular melanocytes behavior remains unknown. Here, by using immunofluorescence staining, we showed that secreted frizzled-related protein 4 (sFRP4) is preferentially expressed in the skin epidermal cells rather than in melanocytes. By overexpression of sFRP4 in skin cells in vivo and in vitro, we found that sFRP4 attenuates activation of Wnt signaling, resulting in decrease of melanocytes differentiation in the regenerating hair follicle. Our findings unveiled a new regulator that involves modulating melanocytes differentiation through a paracrine mechanism in hair follicle, supplying a hope for potential therapeutic application to treat skin pigmentation disorders.

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Characterization of Chicken Skin Yellowness and Exploration of Genes Involved in Skin Yellowness Deposition in Chicken

Frontiers in Physiology ◽

10.3389/fphys.2021.585089 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jingwen Wu ◽

Zetong Lin ◽

Genghua Chen ◽

Qingbin Luo ◽

Qinghua Nie ◽

...

Keyword(s):

Skin Color ◽

Skin Pigmentation ◽

Differentially Expressed ◽

Economic Trait ◽

Chicken Skin ◽

Before And After ◽

Skin Coloration ◽

Insight Into ◽

Selection Of

Skin color is an important economic trait in meat-type chickens. A uniform bright skin color can increase the sales value of chicken. Chickens with bright yellow skin are more popular in China, especially in the broiler market of South China. However, the skin color of chickens can vary because of differences in breeds, diet, health, and individual genetics. To obtain greater insight into the genetic factors associated with the process of skin pigmentation in chickens, we used a colorimeter and high-resolution skin photographs to measure and analyze the skin color of chickens. By analyzing 534 chickens of the same breed, age, and feed condition, we found that the yellowness values of the chickens varied within this population. A significant positive correlation was found between the cloacal skin yellowness values before and after slaughter, and the cloacal skin yellowness value of live chickens was positively correlated with the overall body skin yellowness value. Additionally, chicken skin yellowness exhibited low heritability, ranging from 0.07 to 0.27. Through RNA sequencing, 882 genes were found to be differentially expressed between the skin with the highest and lowest yellowness values. Some of these differentially expressed genes may play an important role in yellow pigment deposition in chicken skin, which included TLR2B, IYD, SMOC1, ALDH1A3, CYP11A1, FHL2, TECRL, ACACB, TYR, PMEL, and GPR143. In addition, we found that the expression and variations of the BCO2 gene, which is referred to as the yellow skin gene, cannot be used to estimate the skin yellowness value of chickens in this population. These data will help to further our understanding of chicken skin yellowness and might contribute to the selection of specific chicken strains with consistent skin coloration.

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Prediction of Eye, Hair and Skin Color in Admixed Populations of Latin America

10.1101/2020.12.09.415901 ◽

2020 ◽

Author(s):

Sagnik Palmal ◽

Kaustubh Adhikari ◽

Javier Mendoza-Revilla ◽

Macarena Fuentes-Guajardo ◽

Caio C. Silva de Cerqueira ◽

...

Keyword(s):

Native American ◽

Skin Color ◽

Prediction Accuracy ◽

Prediction Models ◽

Skin Pigmentation ◽

Genetic Ancestry ◽

Learning Approaches ◽

Latin Americans ◽

Eye Color ◽

The Impact

AbstractWe report an evaluation of prediction accuracy for eye, hair and skin pigmentation based on genomic and phenotypic data for over 6,500 admixed Latin Americans (the CANDELA dataset). We examined the impact on prediction accuracy of three main factors: (i) The methods of prediction, including classical statistical methods and machine learning approaches, (ii) The inclusion of non-genetic predictors, continental genetic ancestry and pigmentation SNPs in the prediction models, and (iii) Compared two sets of pigmentation SNPs: the commonly-used HIrisPlex-S set (developed in Europeans) and novel SNP sets we defined here based on genome-wide association results in the CANDELA sample. We find that Random Forest or regression are globally the best performing methods. Although continental genetic ancestry has substantial power for prediction of pigmentation in Latin Americans, the inclusion of pigmentation SNPs increases prediction accuracy considerably, particularly for skin color. For hair and eye color, HIrisPlex-S has a similar performance to the CANDELA-specific prediction SNP sets. However, for skin pigmentation the performance of HIrisPlex-S is markedly lower than the SNP set defined here, including predictions in an independent dataset of Native American data. These results reflect the relatively high variation in hair and eye color among Europeans for whom HIrisPlex-S was developed, whereas their variation in skin pigmentation is comparatively lower. Furthermore, we show that the dataset used in the training of prediction models strongly impacts on the portability of these models across Europeans and Native Americans.

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New conceptual approaches toward dentin regeneration using the drug repositioning strategy with Wnt signaling pathways

International Journal of Oral Biology ◽

10.11620/ijob.2021.46.2.67 ◽

2021 ◽

Vol 46 (2) ◽

pp. 67-73

Author(s):

Eui-Seon Lee ◽

◽

Tae-Young Kim ◽

Yam Prasad Aryal ◽

Kihyun Kim ◽

...

Keyword(s):

Wnt Signaling ◽

Signaling Pathways ◽

Drug Repositioning ◽

Dentin Regeneration

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Differential Interactome Based Drug Repositioning Unraveled Abacavir, Exemestane, Nortriptyline Hydrochloride, and Tolcapone as Potential Therapeutics for Colorectal Cancers

Frontiers in Bioinformatics ◽

10.3389/fbinf.2021.710591 ◽

2021 ◽

Vol 1 ◽

Author(s):

Hande Beklen ◽

Sema Arslan ◽

Gizem Gulfidan ◽

Beste Turanli ◽

Pemra Ozbek ◽

...

Keyword(s):

Drug Repositioning ◽

Positive Control ◽

Drug Candidates ◽

Novel Biomarkers ◽

Critical Requirement ◽

Nortriptyline Hydrochloride ◽

In Silico Molecular Docking ◽

Prognostic Power ◽

Potential Therapeutics

There is a critical requirement for alternative strategies to provide the better treatment in colorectal cancer (CRC). Hence, our goal was to propose novel biomarkers as well as drug candidates for its treatment through differential interactome based drug repositioning. Differentially interacting proteins and their modules were identified, and their prognostic power were estimated through survival analyses. Drug repositioning was carried out for significant target proteins, and candidate drugs were analyzed via in silico molecular docking prior to in vitro cell viability assays in CRC cell lines. Six modules (mAPEX1, mCCT7, mHSD17B10, mMYC, mPSMB5, mRAN) were highlighted considering their prognostic performance. Drug repositioning resulted in eight drugs (abacavir, ribociclib, exemestane, voriconazole, nortriptyline hydrochloride, theophylline, bromocriptine mesylate, and tolcapone). Moreover, significant in vitro inhibition profiles were obtained in abacavir, nortriptyline hydrochloride, exemestane, tolcapone, and theophylline (positive control). Our findings may provide new and complementary strategies for the treatment of CRC.

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African Skin: Different Types, Needs and Diseases

International Journal of TROPICAL DISEASE & Health ◽

10.9734/ijtdh/2019/v36i330143 ◽

2019 ◽

pp. 1-13

Author(s):

Olumayowa Abimbola Oninla ◽

Samuel Olorunyomi Oninla ◽

Bolaji Ibiesa Otike-Odibi ◽

Mufutau Muphy Oripelaye ◽

Fatai Olatunde Olanrewaju ◽

...

Keyword(s):

Skin Color ◽

Skin Diseases ◽

Skin Pigmentation ◽

Geographical Location ◽

Skin Care ◽

Skin Type ◽

Protective Properties ◽

Tropical Regions ◽

The Right

Microscopic structures in the skin are basically the same in all races. Differences are found in histology and physiology of the skin resulting in different skin types, needs and prevailing skin diseases. Skin pigmentation (with the photo-protective properties), and the barrier function of the stratum corneum are the main differences between African and Caucasian skin. The geographic distribution of UV radiation (UVR) has a positive correlation with geographical location. The darker-skinned populations are closer to the equator where there are high amounts of UVR especially in the tropical regions of the world. African skin has the greatest variability in skin color. Africa has both white and dark skinned individuals with the darker-skinned populations being mostly around the equator. Leslie Baumann introduced four parameters that more accurately characterized skin types than previous classification of dry, oily, normal and combination skin. These are dry or oily – D/O; sensitive or resistant – S/R; pigmented or non-pigmented – P/N, and wrinkled or unwrinkled skin – W/T. Combinations of these further produced sixteen skin phenotypes. Dark skinned individuals often have the PT types while the light skinned mostly have the NW types. Skin needs basically depends on the type. Identifying the skin type is fundamental to providing the right skin care. According to Baumann, the fundamental elements of skin care are mild cleansing, hydrating (moisturization with humectants and emollients), replenishing (with lipids, ceramides and fatty acids) and skin protection (UV protection and increased humidity). Skin diseases are associated with skin type. Eczema is more typical in people with DS combinations while acne is associated with OS skin type (especially OSNT and OSPT). Prevalence of skin diseases varies within African communities from 35% to 87% with skin infections affecting 22-46% and eczemas 13-21% of patients in various studies.

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