3D-SeboSkin Model for Human ex vivo Studies of Hidradenitis Suppurativa/Acne Inversa

Dermatology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Xiaoxiao Hou ◽  
Amir M. Hossini ◽  
Georgios Nikolakis ◽  
Ottfried Balthasar ◽  
Andreas Kurtz ◽  
...  
Keyword(s):  
Differential Expression ◽  
Hidradenitis Suppurativa ◽  
Structural Integrity ◽  
Ex Vivo ◽  
Human Model ◽  
Acne Inversa ◽  
Inflammatory Skin Disease ◽  
Preclinical Research ◽  
Dermal Tissue ◽  
Uninvolved Skin

<b><i>Background:</i></b> Hidradenitis suppurativa/acne inversa (HS) is a chronic, recurrent inflammatory skin disease. Its pivotal pathogenetic event is believed to be the occlusion of the hair follicle generating a perifollicular lympho-histiocytic inflammation. However, knowledge of the exact HS pathogenesis requires further research. <b><i>Objective:</i></b> To develop a human HS model applicable in preclinical research which could help to understand the pathophysiology of HS and to determine the action of therapeutic candidates. <b><i>Methods:</i></b> The 3D-SeboSkin technology was applied to maintain explants of involved and uninvolved skin of HS patients ex vivo for 3 days. Detection of differential expression of previously detected HS biomarkers was performed by immunohistochemistry in a group of female patients (<i>n</i> = 9, mean age 37.2 ± 8.4 years). <b><i>Results:</i></b> The application of the 3D-SeboSkin model preserved the structural integrity of lesional and perilesional HS skin ex vivo, as previously described for healthy skin. Moreover, the HS 3D-SeboSkin setting maintained the differential expression and pattern of several HS biomarkers (S100A9, KRT16, SERPINB3) in epidermal and dermal tissue and the appendages. <b><i>Conclusion:</i></b> We have validated HS 3D-SeboSkin as a reproducible, human model, which is appropriate for preclinical lesional and perilesional HS skin studies ex vivo.

Pathogenese der Hidradenitis suppurativa/Acne inversa

Der Hautarzt ◽  
2021 ◽  
Author(s):  
G. Nikolakis ◽  
G. Kokolakis ◽  
K. Kaleta ◽  
K. Wolk ◽  
R. Hunger ◽  
...  
Keyword(s):  
Hidradenitis Suppurativa ◽  
Acne Inversa

scholarly journals Moderately Inducing Autophagy Reduces Tertiary Brain Injury after Perinatal Hypoxia-Ischemia

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 898
Author(s):  
Brian H. Kim ◽  
Maciej Jeziorek ◽  
Hur Dolunay Kanal ◽  
Viorica Raluca Contu ◽  
Radek Dobrowolski ◽  
...  
Keyword(s):  
Cell Death ◽  
Structural Integrity ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Brain Slices ◽  
Brain Structures ◽  
Improved Outcomes ◽  
Hypoxia Ischemia ◽  
Tgfβ Receptor ◽  
Progressive Neurodegeneration

Recent studies of cerebral hypoxia-ischemia (HI) have highlighted slowly progressive neurodegeneration whose mechanisms remain elusive, but if blocked, could considerably improve long-term neurological function. We previously established that the cytokine transforming growth factor (TGF)β1 is highly elevated following HI and that delivering an antagonist for TGFβ receptor activin-like kinase 5 (ALK5)—SB505124—three days after injury in a rat model of moderate pre-term HI significantly preserved the structural integrity of the thalamus and hippocampus as well as neurological functions associated with those brain structures. To elucidate the mechanism whereby ALK5 inhibition reduces cell death, we assessed levels of autophagy markers in neurons and found that SB505124 increased numbers of autophagosomes and levels of lipidated light chain 3 (LC3), a key protein known to mediate autophagy. However, those studies did not determine whether (1) SB was acting directly on the CNS and (2) whether directly inducing autophagy could decrease cell death and improve outcome. Here we show that administering an ALK5 antagonist three days after HI reduced actively apoptotic cells by ~90% when assessed one week after injury. Ex vivo studies using the lysosomal inhibitor chloroquine confirmed that SB505124 enhanced autophagy flux in the injured hemisphere, with a significant accumulation of the autophagic proteins LC3 and p62 in SB505124 + chloroquine treated brain slices. We independently activated autophagy using the stimulatory peptide Tat-Beclin1 to determine if enhanced autophagy is directly responsible for improved outcomes. Administering Tat-Beclin1 starting three days after injury preserved the structural integrity of the hippocampus and thalamus with improved sensorimotor function. These data support the conclusion that intervening at this phase of injury represents a window of opportunity where stimulating autophagy is beneficial.

scholarly journals Quality of Life in Hidradenitis Suppurativa: An Update

2021 ◽  
Vol 18 (11) ◽  
pp. 6131
Author(s):  
Pavel V. Chernyshov ◽  
Andrew Y. Finlay ◽  
Lucia Tomas-Aragones ◽  
Francoise Poot ◽  
Francesca Sampogna ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Hidradenitis Suppurativa ◽  
Acne Inversa ◽  
Health Related Quality ◽  
Number Of Patients ◽  
Related Quality ◽  
Health Related ◽  
Positive Effect ◽  
Specific Health

Knowledge on hidradenitis suppurativa/acne inversa (HS) is rapidly increasing. HS has a profound impact on patients and their family life. Several factors, such as comorbidities, unemployment and HS severity, make this impact even more severe. The most widely used instrument to measure this impact is the dermatology-specific DLQI. We also identified six HS-specific health-related quality of life (HRQoL) instruments. Of them, HIDRAdisk, HSIA, HiSQOL and HSQoL-24 are better validated but there is still lack of experience of its use. Several treatment methods showed positive effect on patients’ HRQoL. Surgery remains a method with a substantial positive effect on HRQoL. Several studies confirming a positive effect of adalimumab on the HRQoL of patients with HS were published during the last three years. Data on the influence of several other biologics on HRQoL of HS patients are controversial or based on studies with a small number of patients.

scholarly journals New Endeavors of (Micro)Tissue Engineering: Cells Tissues Organs on-Chip and Communication Thereof

2021 ◽  
pp. 1-15
Author(s):  
Haysam M.M.A.M. Ahmed ◽  
Liliana S. Moreira Teixeira
Keyword(s):  
Tissue Engineering ◽  
Food Additives ◽  
Market Potential ◽  
Model Systems ◽  
Human Model ◽  
Human Stem Cells ◽  
Animal Testing ◽  
Preclinical Research ◽  
On Chip

The development of new therapies is tremendously hampered by the insufficient availability of human model systems suitable for preclinical research on disease target identification, drug efficacy, and toxicity. Thus, drug failures in clinical trials are too common and too costly. Animal models or standard 2D in vitro tissue cultures, regardless of whether they are human based, are regularly not representative of specific human responses. Approaching near human tissues and organs test systems is the key goal of organs-on-chips (OoC) technology. This technology is currently showing its potential to reduce both drug development costs and time-to-market, while critically lessening animal testing. OoC are based on human (stem) cells, potentially derived from healthy or disease-affected patients, thereby amenable to personalized therapy development. It is noteworthy that the OoC market potential goes beyond pharma, with the possibility to test cosmetics, food additives, or environmental contaminants. This (micro)tissue engineering-based technology is highly multidisciplinary, combining fields such as (developmental) biology, (bio)materials, microfluidics, sensors, and imaging. The enormous potential of OoC is currently facing an exciting new challenge: emulating cross-communication between tissues and organs, to simulate more complex systemic responses, such as in cancer, or restricted to confined environments, as occurs in osteoarthritis. This review describes key examples of multiorgan/tissue-on-chip approaches, or linked organs/tissues-on-chip, focusing on challenges and promising new avenues of this advanced model system. Additionally, major emphasis is given to the translation of established tissue engineering approaches, bottom up and top down, towards the development of more complex, robust, and representative (multi)organ/tissue-on-chip approaches.

Hidradenitis suppurativa/Acne inversa

Der Hautarzt ◽  
2015 ◽  
Vol 66 (6) ◽  
pp. 413-422 ◽  
Author(s):  
J. Kirschke ◽  
S. Hessam ◽  
F.G. Bechara
Keyword(s):  
Hidradenitis Suppurativa ◽  
Acne Inversa
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