TLR Signaling and DNA Repair: Are They Associated?

Toll-like receptor (TLR) signaling is a well-characterized, innate immune cellular defense mechanism used to detect and respond to pathogen-associated molecular patterns (PAMPs). TLR signaling is highly conserved and has evolved to have both extracellular and endosomal receptors that recognize PAMPs from a wide range of microbial pathogens. Recent literature has emerged to show that activation of TLRs not only leads to the upregulation of cellular defense mechanisms, but also results in upregulation of DNA repair genes and increased functional DNA repair. Endosomal TLR agonists result in increased survival and repair after both ionizing and UV radiation, suggesting that the repair pathways for single- and double-strand breaks are affected. This review brings together these and other experimental findings to examine how DNA repair pathways may be linked to TLR signaling. Also discussed are the varied outcomes and related physiological implications that increased DNA repair after injury might have

A dog lover\u27s dilemma: Airborne allergic contact dermatitis to tylosin.

Airborne allergic contact dermatitis (AACD) can be caused by airborne chemicals settling on exposed body parts. Repeated exposure to an allergen can induce AACD in the areas of exposed skin (typically, the face, hands, and forearms). Case Report: A 67-year-old White woman presented in October 2019 with a 4-month history of severe pruritic facial and hand dermatitis, which began in June or July 2019

Allergens and Irritants Transcriptionally Upregulate CD80 Gene Expression in Human Keratinocytes

The human CD80 costimulatory molecule is an important signal between professional antigen-presenting cells and T helper cells. The immunobiology of CD80 expression by keratinocytes, especially during allergic and irritant contact dermatitis, however, is less well understood. CD80 cell surface expression and gene transcription by keratinocytes was increased when keratinocytes were exposed to certain allergens (chemicals that induce inflammation via hapten-specific T cells) and irritants (chemicals that are toxic to epidermal cells). Therefore, the human CD80 promoter was cloned and luciferase reporter constructs containing various promoter fragments were engineered. Promoter mapping of these CD80 constructs in transiently transfected keratinocytes showed that a construct containing the proximal 231 bp immediately upstream of the transcription start site of the CD80 promoter was most active in keratinocytes and was inducible to a level ranging from 2- to 10-fold higher in keratinocytes treated with certain allergens and irritants, compared with untreated keratinocytes. This pattern of promoter fragment activity in keratinocytes is identical to that found in professional antigen-presenting cells. This is the first demonstration that the CD80 promoter is active in keratinocytes and that this activity is further increased in keratinocytes treated with certain allergens and irritants. These data suggest that allergens and irritants may, in part, break peripheral tolerance by their direct effects on keratinocyte costimulatory molecule expression, thereby facilitating interactions with epidermotropic T helper cells via the CD80–CD28 or CTLA-4 pathways

New insights into HIV-1-primary skin disorders

Since the first reports of AIDS, skin involvement has become a burdensome stigma for seropositive patients and a challenging task for dermatologist and infectious disease specialists due to the severe and recalcitrant nature of the conditions. Dermatologic manifestations in AIDS patients act as markers of disease progression, a fact that enhances the importance of understanding their pathogenesis

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

A 2-step synthesis of Combretastatin A-4 and derivatives as potent tubulin assembly inhibitors

A series of combretastatin derivatives were designed and synthesised by a two-step stereoselective synthesis by use of Wittig olefination followed by Suzuki cross-coupling. Interestingly, all new compounds (2a-2i) showed potent cell-based antiproliferative activities in nanomolar concentrations. Among the compounds, 2a, 2b and 2e were the most active across three cancer cell lines. In addition, these compounds inhibited the polymerisation of tubulin in vitro more efficiently than CA-4. They caused cell cycle arrest in G2/M phase further confirming their ability to inhibit tubulin polymerisation

Immunologic Studies of Progesterone-Induced Neutrophilic Urticaria

A 33-year-old woman presented with recurring pruritic, erythematous papules around the mouth and on the hands, of 1.5 years' duration. These flares typically began several days before her menstrual cycle and persisted for approximately 1 week. Physical examination revealed urticarial plaques on the neck. Due to the nature of the eruption, which corresponded with her menstrual cycle, a diagnosis of autoimmune progesterone urticaria was considered and workup pursued