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Article ; Online: The genetic aspects of hidradenitis suppurativa.

Balić, Anamaria / Marinović, Branka / Bukvić Mokos, Zrinka

2023 Volume 41, Issue 5, Page(s) 551–563

Abstract: Genetic aspects have a substantial role in hidradenitis suppurativa (HS) pathogenesis. A positive family history of HS occurs in about one-third of HS cases and is significantly higher in patients with early onset of the disease. Recent twin studies have ...

Abstract	Genetic aspects have a substantial role in hidradenitis suppurativa (HS) pathogenesis. A positive family history of HS occurs in about one-third of HS cases and is significantly higher in patients with early onset of the disease. Recent twin studies have shown a high heritability in HS, fortifying the importance of genetic factors in disease pathogenesis. Based on existing knowledge on the genomics of HS, the disease can be categorized as familial HS, sporadic, syndromic HS, and "HS plus" associated with other syndromes. In familial HS, autosomal dominant transmission is proposed, and monogenic inheritance is rare. This monogenic trait is related to mutations of γ-secretase component genes and Notch signaling or defects in inflammasome function. With newly discovered gene mutations, such as those related to innate and adaptive immunity, skin microbiome, inflammasome, epidermal homeostasis, and keratinization pathway, we can define HS as a polygenic, multifactorial, autoinflammatory disease. To fully elucidate the genetic aspects of HS, we need extensive, long-term global collaborations.
MeSH term(s)	Humans ; Hidradenitis Suppurativa/genetics ; Hidradenitis Suppurativa/complications ; Inflammasomes/genetics ; Signal Transduction/genetics ; Amyloid Precursor Protein Secretases/genetics
Chemical Substances	Inflammasomes ; Amyloid Precursor Protein Secretases (EC 3.4.-)
Language	English
Publishing date	2023-08-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	1064149-x
ISSN	1879-1131 ; 0738-081X
ISSN (online)	1879-1131
ISSN	0738-081X
DOI	10.1016/j.clindermatol.2023.08.022
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Article ; Online: Dermoscopy of Zosteriform and Swirling Pattern Type 1 Segmental Darier Disease.

Balić, Anamaria / Garces Rene, Joan / Radoš, Jaka

Acta dermatovenerologica Croatica : ADC

2023 Volume 30, Issue 3, Page(s) 191–193

Abstract: Dear Editor, Segmental Darier disease (DD) is a rare disease with around 40 described English literature cases. It is hypothesized that one of the causes of the disease is a post-zygotic somatic mutation for the calcium ATPase pump, only present in ... ...

Abstract	Dear Editor, Segmental Darier disease (DD) is a rare disease with around 40 described English literature cases. It is hypothesized that one of the causes of the disease is a post-zygotic somatic mutation for the calcium ATPase pump, only present in lesional skin. There are two types of segmental DD: type 1, where lesions follow Blaschko's lines unilaterally, and type 2, characterized by focal areas of increased severity in patients with generalized DD (1). Type 1 segmental DD is not easily diagnosed due to the lack of positive family history, the late onset of the disease in the third or fourth decade of life, and lack of DD-associated features. The differential diagnosis of type 1 segmental DD includes acquired papular dermatoses distributed in linear or zosteriform fashion, such as lichen planus, psoriasis, lichen striatus, or linear porokeratosis (2). We report two cases of segmental DD, of which the first case was a 43-year-old woman who presented with pruritic skin changes five years in duration and a history of seasonal aggravation. On examination, light brownish to reddish keratotic small papules were observed on the left abdomen and inframammary area, arranged in a swirling pattern (Figure 1, a). Dermoscopy showed polygonal or roundish yellowish/brown areas surrounded with whitish structureless areas (Figure 1, b). The histopathological correlations for dermoscopic brownish polygonal or round areas are hyperkeratosis, parakeratosis, and dyskeratotic keratinocytes, which were present in the biopsy specimen (Figure 1, c). The patient was prescribed 0.1% tretinoin gel, which led to marked improvement (Figure 1, d). The second case was a 62-year-old woman who presented with a flare of small red-brown papules, eroded papules, and some yellowish crusts arranged in a zosteriform pattern on the right side of the upper abdomen (Figure 2, a). Dermoscopy showed polygonal, roundish, yellowish areas surrounded with whitish and reddish structureless areas (Figure 2, b). Histopathology mainly revealed compact orthokeratosis and small foci of parakeratosis, marked granular layer with dyskeratotic keratinocytes, and foci of suprabasal acantholysis consistent with the diagnosis of DD (Figure 2, d, d). The patient was prescribed topical steroid cream and 0.1% adapalene cream, which also led to improvement. In both of our cases, a final diagnosis of type 1 segmental DD was established based on clinico-histopathologic correlation, since acantholytic dyskeratotic epidermal nevus could not have been ruled out only based on the histopathology report as it is clinically and histologically indistinguishable from segmental DD. However, the late age of onset and aggravation resulting from external factors such as heat, sunlight, and sweat supported the diagnosis of segmental DD. Although the final diagnosis of type 1 segmental DD is typically established based on clinico-histopathological correlation, we find dermoscopy particularly useful in aiding the diagnosis by eliminating differential diagnoses and being aware of their well-known dermoscopic patterns.
MeSH term(s)	Female ; Humans ; Adult ; Middle Aged ; Darier Disease/pathology ; Parakeratosis/pathology ; Dermoscopy ; Skin/pathology
Language	English
Publishing date	2023-02-22
Publishing country	Croatia
Document type	Case Reports ; Journal Article
ZDB-ID	1180727-1
ISSN	1847-6538 ; 1330-027X
ISSN (online)	1847-6538
ISSN	1330-027X
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Article ; Online: Isolation of Dental Stem Cell-Enriched Populations from Continuously Growing Mouse Incisors.

Balic, Anamaria

Methods in molecular biology (Clifton, N.J.)

2019 Volume 1922, Page(s) 29–37

Abstract: Continuous growth of the rodent incisor is enabled by epithelial and mesenchymal stem cells (ESCs and MSCs) which unceasingly replenish enamel and dentin, respectively, that wear by persistent animal gnawing. Lineage tracing studies have provided ... ...

Abstract	Continuous growth of the rodent incisor is enabled by epithelial and mesenchymal stem cells (ESCs and MSCs) which unceasingly replenish enamel and dentin, respectively, that wear by persistent animal gnawing. Lineage tracing studies have provided evidence that ESCs contribute to all epithelial lineages of the tooth in vivo. Meanwhile, in the mouse incisor, MSCs continuously contribute to odontoblast lineage and tooth growth. However, in vitro manipulation of ESCs has shown little progress, mainly due to lack of appropriate protocol to successfully isolate, culture, expand, and differentiate ESCs in vitro without using the co-culture system. In this chapter we describe the isolation of the Sox2-GFP+ cell population that is highly enriched in ESCs. Isolated cells can be used for various types of analyses, including in vitro culture, single cell-related analyses, etc. Furthermore, we describe ways to obtain populations enriched in the incisor MSCs using FACS sorting of antibody-labeled cells. Easily accessible FACS sorting enables easy and relatively fast isolation of the cells labeled by the fluorescent protein.
MeSH term(s)	Animals ; Cell Separation/methods ; Incisor/cytology ; Mesenchymal Stem Cells ; Mice ; SOXB1 Transcription Factors ; Stem Cells
Chemical Substances	SOXB1 Transcription Factors ; Sox2 protein, mouse
Language	English
Publishing date	2019-03-04
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-9012-2_4
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Article ; Online: Concise Review: Cellular and Molecular Mechanisms Regulation of Tooth Initiation.

Balic, Anamaria

Stem cells (Dayton, Ohio)

2018 Volume 37, Issue 1, Page(s) 26–32

Abstract: Development of teeth depends on the reciprocal interactions between the surface epithelium (ectoderm) and the underlying neural crest-derived mesenchyme. These interactions are facilitated by the conserved signaling pathways, which build a complex ... ...

Abstract	Development of teeth depends on the reciprocal interactions between the surface epithelium (ectoderm) and the underlying neural crest-derived mesenchyme. These interactions are facilitated by the conserved signaling pathways, which build a complex network of signals and transcription factors. Tooth development starts at specific and predetermined loci in the oral ectoderm and is described as a morphologically distinct thickening of oral ectoderm, named dental lamina. Cells within the dental lamina invaginate into the underlying mesenchyme, generating placodes that mark the onset of individual tooth development. In the following stages of development, the tooth epithelium buds and folds transitioning through various shapes, including bud, cap, and bell shapes, which also identify the specific stages of tooth development. Although much of the molecular regulation of tooth development has been unraveled, the regulation of the initial stages of tooth development, as well as the cellular mechanisms that govern tooth development remain largely unknown. This review provides a systematic overview of the current knowledge on the molecular and cellular mechanisms that guide initial stages of tooth development and outlines the challenges which temper the progress. Stem Cells 2019;37:26-32.
MeSH term(s)	Cell Biology ; Humans ; Odontogenesis/immunology ; Tooth/embryology
Language	English
Publishing date	2018-11-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1143556-2
ISSN	1549-4918 ; 1066-5099
ISSN (online)	1549-4918
ISSN	1066-5099
DOI	10.1002/stem.2917
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Article ; Online: Biology Explaining Tooth Repair and Regeneration: A Mini-Review.

Balic, Anamaria

Gerontology

2018 Volume 64, Issue 4, Page(s) 382–388

Abstract: The tooth is an intricate composition of precisely patterned, mineralized matrices and soft tissues. Mineralized tissues include enamel (produced by the epithelial cells called ameloblasts), dentin and cementum (produced by mesenchymal cells called ... ...

Abstract	The tooth is an intricate composition of precisely patterned, mineralized matrices and soft tissues. Mineralized tissues include enamel (produced by the epithelial cells called ameloblasts), dentin and cementum (produced by mesenchymal cells called odontoblasts and cementoblasts, respectively), and soft tissues, which include the dental pulp and the periodontal ligament along with the invading nerves and blood vessels. It was perceived for a very long time that teeth primarily serve an esthetical function. In recent years, however, the role of healthy teeth, as well as the impact of oral health on general well-being, became more evident. Tooth loss, caused by tooth decay, congenital malformations (tooth agenesis), trauma, periodontal diseases, or age-related changes, is usually replaced by artificial materials which lack many of the important biological characteristics of the natural tooth. Human teeth have very low to almost absent regeneration potential, due to early loss of cell populations with regenerative capacity, namely stem cells. Significant effort has been made in recent decades to identify and characterize tooth stem cells, and to unravel the developmental programs which these cells follow in order to generate a tooth.
MeSH term(s)	Aging/pathology ; Aging/physiology ; Animals ; Epithelial-Mesenchymal Transition/physiology ; Humans ; Models, Biological ; Odontogenesis/physiology ; Regeneration/physiology ; Stem Cell Niche/physiology ; Tooth/cytology ; Tooth/growth & development ; Tooth/physiology
Language	English
Publishing date	2018-03-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	193798-4
ISSN	1423-0003 ; 0304-324X
ISSN (online)	1423-0003
ISSN	0304-324X
DOI	10.1159/000486592
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Article ; Online: Use of Trowell-Type Organ Culture to Study Regulation of Dental Stem Cells.

Juuri, Emma / Balic, Anamaria

Journal of visualized experiments : JoVE

2021 , Issue 173

Abstract: Organ development, function, and regeneration depend on stem cells, which reside within discrete anatomical spaces called stem cell niches. The continuously growing mouse incisor provides an excellent model to study tissue-specific stem cells. The ... ...

Abstract	Organ development, function, and regeneration depend on stem cells, which reside within discrete anatomical spaces called stem cell niches. The continuously growing mouse incisor provides an excellent model to study tissue-specific stem cells. The epithelial tissue-specific stem cells of the incisor are located at the proximal end of the tooth in a niche called the cervical loop. They provide a continuous influx of cells to counterbalance the constant abrasion of the self-sharpening tip of the tooth. Presented here is a detailed protocol for the isolation and culture of the proximal end of the mouse incisor that houses stem cells and their niche. This is a modified Trowell-type organ culture protocol that enables in vitro culture of tissue pieces (explants), as well as the thick tissue slices at the liquid/air interface on a filter supported by a metal grid. The organ culture protocol described here enables tissue manipulations not feasible in vivo, and when combined with the use of a fluorescent reporter(s), it provides a platform for the identification and tracking of discrete cell populations in live tissues over time, including stem cells. Various regulatory molecules and pharmacological compounds can be tested in this system for their effect on stem cells and their niches. This ultimately provides a valuable tool to study stem cell regulation and maintenance.
MeSH term(s)	Animals ; Incisor ; Mice ; Organ Culture Techniques ; Stem Cell Niche ; Stem Cells
Language	English
Publishing date	2021-07-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/62462
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Article: Do We Utilize Our Knowledge of the Skin Protective Effects of Carotenoids Enough?

Balić, Anamaria / Mokos, Mislav

Antioxidants (Basel, Switzerland)

2019 Volume 8, Issue 8

Abstract: Due to their potential health-promoting effects, carotenoids have drawn both scientific and public attention in recent years. The primary source of carotenoids in the human skin is diet, mainly fruits, vegetables, and marine product, but they may ... ...

Abstract	Due to their potential health-promoting effects, carotenoids have drawn both scientific and public attention in recent years. The primary source of carotenoids in the human skin is diet, mainly fruits, vegetables, and marine product, but they may originate from supplementation and topical application, too. In the skin, they accumulate mostly in the epidermis and act as a protective barrier to various environmental influences. Namely, the skin is exposed to numerous environmental factors, including ultraviolet radiation (UVR), air pollution, and smoking, that cause oxidative stress within the skin with consequent premature (extrinsic) aging. UVR, as the most prominent environmental factor, may cause additional detrimental skin effects, such as sunburn, DNA damage, and skin cancer. Therefore, photoprotection is the first line intervention in the prevention of premature aging and skin cancer. Numerous studies have demonstrated that carotenoids, particularly β-carotene, lycopene, lutein, and astaxanthin, have photoprotective effects, not only through direct light-absorbing properties, but also through their antioxidant effects (scavenging reactive oxygen species), as well as by regulation of UV light-induced gene expression, modulation of stress-dependent signaling, and/or suppression of cellular and tissue responses like inflammation. Interventional studies in humans with carotenoid-rich diet have shown its photoprotective effects on the skin (mostly by decreasing the sensitivity to UVR-induced erythema) and its beneficial effects in prevention and improvement of skin aging (improved skin elasticity and hydration, skin texture, wrinkles, and age spots). Furthermore, carotenoids may be helpful in the prevention and treatment of some photodermatoses, including erythropoietic protoporphyria (EPP), porphyria cutanea tarda (PCT) and polymorphous light eruption (PMLE). Although UVR is recognized as the main etiopathogenetic factor in the development of non-melanoma skin cancer (NMSC) and melanoma, and the photoprotective effects of carotenoids are certain, available studies still could not undoubtedly confirm the protective role of carotenoids in skin photocarcinogenesis.
Language	English
Publishing date	2019-07-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox8080259
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Article: Biology Explaining Tooth Repair and Regeneration: A Mini-Review

Balic, Anamaria

Gerontology

2018 Volume 64, Issue 4, Page(s) 382–388

Institution	Institute of Biotechnology, University of Helsinki, Helsinki, Finland
Abstract	The tooth is an intricate composition of precisely patterned, mineralized matrices and soft tissues. Mineralized tissues include enamel (produced by the epithelial cells called ameloblasts), dentin and cementum (produced by mesenchymal cells called odontoblasts and cementoblasts, respectively), and soft tissues, which include the dental pulp and the periodontal ligament along with the invading nerves and blood vessels. It was perceived for a very long time that teeth primarily serve an esthetical function. In recent years, however, the role of healthy teeth, as well as the impact of oral health on general well-being, became more evident. Tooth loss, caused by tooth decay, congenital malformations (tooth agenesis), trauma, periodontal diseases, or age-related changes, is usually replaced by artificial materials which lack many of the important biological characteristics of the natural tooth. Human teeth have very low to almost absent regeneration potential, due to early loss of cell populations with regenerative capacity, namely stem cells. Significant effort has been made in recent decades to identify and characterize tooth stem cells, and to unravel the developmental programs which these cells follow in order to generate a tooth.
Keywords	Tooth development ; Aging ; Tooth stem cells ; Tooth regeneration ; Tooth repair
Language	English
Publishing date	2018-03-13
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Regenerative and Technological Section / Mini-Review
ZDB-ID	193798-4
ISSN	1423-0003 ; 0304-324X
ISSN (online)	1423-0003
ISSN	0304-324X
DOI	10.1159/000486592
Database	Karger publisher's database

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Article: Do We Utilize Our Knowledge of the Skin Protective Effects of Carotenoids Enough?

Balić, Anamaria / Mokos, Mislav

Antioxidants. 2019 July 31, v. 8, no. 8

2019

Abstract	Due to their potential health-promoting effects, carotenoids have drawn both scientific and public attention in recent years. The primary source of carotenoids in the human skin is diet, mainly fruits, vegetables, and marine product, but they may originate from supplementation and topical application, too. In the skin, they accumulate mostly in the epidermis and act as a protective barrier to various environmental influences. Namely, the skin is exposed to numerous environmental factors, including ultraviolet radiation (UVR), air pollution, and smoking, that cause oxidative stress within the skin with consequent premature (extrinsic) aging. UVR, as the most prominent environmental factor, may cause additional detrimental skin effects, such as sunburn, DNA damage, and skin cancer. Therefore, photoprotection is the first line intervention in the prevention of premature aging and skin cancer. Numerous studies have demonstrated that carotenoids, particularly β-carotene, lycopene, lutein, and astaxanthin, have photoprotective effects, not only through direct light-absorbing properties, but also through their antioxidant effects (scavenging reactive oxygen species), as well as by regulation of UV light-induced gene expression, modulation of stress-dependent signaling, and/or suppression of cellular and tissue responses like inflammation. Interventional studies in humans with carotenoid-rich diet have shown its photoprotective effects on the skin (mostly by decreasing the sensitivity to UVR-induced erythema) and its beneficial effects in prevention and improvement of skin aging (improved skin elasticity and hydration, skin texture, wrinkles, and age spots). Furthermore, carotenoids may be helpful in the prevention and treatment of some photodermatoses, including erythropoietic protoporphyria (EPP), porphyria cutanea tarda (PCT) and polymorphous light eruption (PMLE). Although UVR is recognized as the main etiopathogenetic factor in the development of non-melanoma skin cancer (NMSC) and melanoma, and the photoprotective effects of carotenoids are certain, available studies still could not undoubtedly confirm the protective role of carotenoids in skin photocarcinogenesis.
Keywords	DNA damage ; air pollution ; antioxidant activity ; astaxanthin ; beta-carotene ; diet ; environmental factors ; erythema ; fruits ; gene expression ; humans ; inflammation ; lutein ; lycopene ; melanoma ; oxidative stress ; porphyria ; protective effect ; radiation resistance ; reactive oxygen species ; skin (animal) ; skin neoplasms ; texture ; topical application ; ultraviolet radiation ; vegetables
Language	English
Dates of publication	2019-0731
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox8080259
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Pyogenic Granuloma of the Proximal Part of a Nail Unit in a Child.

Jurakić Tončić, Ružica / Balić, Anamaria / Ćurković, Danijela / Husar, Karmela

Acta dermatovenerologica Croatica : ADC

2021 Volume 291, Issue 1, Page(s) 62–63

Abstract: Dear Editor, We present a case of proximal pyogenic granuloma in 4-year-old child. The patient presented to our Department due to a fast-growing lesion on the proximal part of the nail unit. The lesion had appeared over several weeks, and it was ... ...

Abstract	Dear Editor, We present a case of proximal pyogenic granuloma in 4-year-old child. The patient presented to our Department due to a fast-growing lesion on the proximal part of the nail unit. The lesion had appeared over several weeks, and it was extremely painful for the child. On the day of the 1st visit, the lesion was not bleeding but was very painful during examination and photo-documentation. Clinically, it presented as an exogenous tumoral lesion of the proximal 1/3 of the nail, partially exulcerated with one part exhibiting coagulated hemorrhage and with uneven coloration (Figure 1). The lesion was not sharply demarcated. Dermoscopically, the majority of the lesion presented an unspecific dermoscopic structure, orange background color, and matched the criteria for a vascular lesion: few unspecific vessels and hemorrhage. The "sticky fiber" sign was also present (Figure 2). Since the lesion was fast-growing and due to the unspecific dermoscopic appearance, the child was referred to a pediatric surgeon and a complete excisional biopsy of the lesion was performed. The dermoscopy of pyogenic granuloma has been already described (1). The histology report confirmed pyogenic granuloma. Pyogenic granulomas of the nail unit are not a common finding, but our case confirms that even this location can be site of this type of benign lesion. It more commonly found in the periungual region and can be expected due to adverse effects of different kinds of systemic therapies. However, due to differential diagnosis that includes different types of tumors occurring at the nail unit, most importantly amelanotic melanoma and SCC, it is suggested to excise or take a biopsy of this type of lesion to be able to exclude aggressive tumor types, which are very rare but not impossible the in pediatric population (2). In cases of unquestionable diagnosis, several local treatments are available. Since the lesion presented a destructive nature in our case, we decided to perform excisional biopsy followed by histology, which in our case was both a diagnostic and therapeutic procedure.
MeSH term(s)	Child ; Child, Preschool ; Dermoscopy ; Diagnosis, Differential ; Granuloma, Pyogenic/diagnosis ; Granuloma, Pyogenic/surgery ; Humans ; Melanoma/diagnosis ; Skin Neoplasms/diagnosis ; Skin Neoplasms/surgery
Language	English
Publishing date	2021-09-02
Publishing country	Croatia
Document type	Case Reports ; Journal Article
ZDB-ID	1180727-1
ISSN	1847-6538 ; 1330-027X
ISSN (online)	1847-6538
ISSN	1330-027X
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