An immune regulatory CCT repeat containing oligodeoxynucleotide capable of causing hair loss in male mice

2016 ◽  
Vol 35 (11) ◽  
pp. 1161-1172
Author(s):  
Y Xu ◽  
J Liu ◽  
L Hua ◽  
Y Xiao ◽  
Y Tian ◽  
...  
Keyword(s):  
Hair Loss ◽  
Messenger Rna ◽  
Hair Follicles ◽  
Male Mice ◽  
Mouse Splenocytes ◽  
Genetic Traits ◽  
Ifn Γ ◽  
Group 2

An oligodeoxynucleotide with CCT repeats (CCT ODN) has been found in our previous study to selectively downregulate Toll-like receptor 7/9 (TLR7/9)-mediated immune responses both in vitro and in vivo. In this study, we unexpectedly found that CCT ODN induced severe patchy hair loss around the mouth in male F1 mice (female Balb/c × male C57BL/6) with lupus-like nephritis induced by injecting allogenic lymphocytes and also in male Balb/c mice, but not in female F1 mice and Balb/c mice and either gender of C57BL/6 mice. Increased infiltration of natural killer group 2, member D (NKG2D+) cells in hair loss skin and upregulated interferon-gamma (IFN-γ) messenger RNA expression in cultured splenocytes were observed in male Balb/c mice. The CCT ODN-conditioned supernatants of cultured mouse splenocytes caused catagen-like changes to hair follicles (HFs). We hypothesized that the CCT ODN could induce patchy hair loss in the male mice with certain genetic traits by mobilizing NKG2D+ cells to HFs and by inducing the production of IFN-γ from immune cells. Taken together these data indicated that a gender and genetic preference of immune-regulatory oligonucleotides is causing unexpected clinical situations such as hair loss.

scholarly journals The ETS1 transcription factor is required for the development and cytokine-induced expansion of ILC2

2016 ◽  
Vol 213 (5) ◽  
pp. 687-696 ◽  
Author(s):  
Erin C. Zook ◽  
Kevin Ramirez ◽  
Xiaohuan Guo ◽  
Grant van der Voort ◽  
Mikael Sigvardsson ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Messenger Rna ◽  
Critical Factor ◽  
Protective Role ◽  
Lymphoid Cells ◽  
Allergic Lung Inflammation ◽  
Factor Inhibitor ◽  
Group 2

Group 2 innate lymphoid cells (ILC2s) are a subset of ILCs that play a protective role in the response to helminth infection, but they also contribute to allergic lung inflammation. Here, we report that the deletion of the ETS1 transcription factor in lymphoid cells resulted in a loss of ILC2s in the bone marrow and lymph nodes and that ETS1 promotes the fitness of the common progenitor of all ILCs. ETS1-deficient ILC2 progenitors failed to up-regulate messenger RNA for the E protein transcription factor inhibitor ID2, a critical factor for ILCs, and these cells were unable to expand in cytokine-driven in vitro cultures. In vivo, ETS1 was required for the IL-33–induced accumulation of lung ILC2s and for the production of the T helper type 2 cytokines IL-5 and IL-13. IL-25 also failed to elicit an expansion of inflammatory ILC2s when these cells lacked ETS1. Our data reveal ETS1 as a critical regulator of ILC2 expansion and cytokine production and implicate ETS1 in the regulation of Id2 at the inception of ILC2 development.

scholarly journals Hair follicle-derived mesenchymal stem cells decrease alopecia areata mouse hair loss and reduce inflammation around the hair follicle

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Weiyue Deng ◽  
Yuying Zhang ◽  
Wei Wang ◽  
Aishi Song ◽  
Omar Mukama ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hair Follicle ◽  
Hair Loss ◽  
Alopecia Areata ◽  
In Vitro Model ◽  
Ifn Γ ◽  
Vitro Model

Abstract Background Alopecia areata (AA) is a common autoimmune hair loss disease with increasing incidence. Corticosteroids are the most widely used for hair loss treatment; however, long-term usage of hormonal drugs is associated with various side effects. Mesenchymal stem cells (MSCs) therapy has been studied extensively to curb autoimmune diseases without affecting immunity against diseases. Methods Hair follicle-derived MSCs (HF-MSCs) were harvested from the waste material of hair transplants, isolated and expanded. The therapeutic effect of HF-MSCs for AA treatment was investigated in vitro AA-like hair follicle organ model and in vivo C3H/HeJ AA mice model. Results AA-like hair follicle organ in vitro model was successfully established by pre-treatment of mouse vibrissa follicles by interferon-γ (IFN-γ). The AA-like symptoms were relieved when IFN-γ induced AA in vitro model was co-cultured with HF-MSC for 2 days. In addition, when skin grafted C3H/HeJ AA mice models were injected with 106 HF-MSCs once a week for 3 weeks, the transcription profiling and immunofluorescence analysis depicted that HF-MSCs treatment significantly decreased mouse hair loss and reduced inflammation around HF both in vitro and in vivo. Conclusions This study provides a new therapeutic approach for alopecia areata based on HF-MSCs toward its future clinical application.

scholarly journals Topical Minoxidil-Loaded Nanotechnology Strategies for Alopecia

Cosmetics ◽  
2020 ◽  
Vol 7 (2) ◽  
pp. 21 ◽  
Author(s):  
Ana Cláudia Santos ◽  
Miguel Pereira-Silva ◽  
Catarina Guerra ◽  
Diana Costa ◽  
Diana Peixoto ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Hair Loss ◽  
Skin Permeation ◽  
Therapeutic Strategies ◽  
Hair Follicles ◽  
Related Condition ◽  
Age Related ◽  
Topical Minoxidil

Androgenetic alopecia (AGA) is a multifactorial and age-related condition characterized by substantial hair loss affecting both men and women. Conventional treatments include the use of topical minoxidil (MNX) formulations to stimulate hair growth and restore hair condition. However, those treatments are associated with limited performance and a lack of tolerability and compliance due to the emergence of adverse effects. Considering that the development of nanotechnology-based formulations as hair loss therapeutic strategies has been clearly growing, topical MNX delivery by means of these innovative formulations is known to enhance MNX skin permeation and depot formation into hair follicles, allowing for MNX-controlled release, increased MNX skin bioavailability and enhanced therapeutic efficacy with minimal adverse effects. This review highlights the potential of nanotechnology-based MNX delivery formulations for improved hair loss therapeutics, including a thorough assessment of their in vitro and in vivo performances, as well as regulatory and nanosafety considerations.

Clinical, Trichoscopic And Immunohistochemical Evaluation of Autologous Adipose Derived Adult Stem Cell Injection in the Treatment of Female Pattern Hair Loss

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Hoda Ahmed Moneib ◽  
Ghada Fathy Mohamed ◽  
Naglaa Samir Ahmed ◽  
Mahy El-Bassiouny El-Sayed Abou-Noor
Keyword(s):  
Hair Follicle ◽  
Hair Loss ◽  
Adult Stem Cells ◽  
Adult Stem Cell ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Dermal Papilla Cells ◽  
Female Pattern Hair Loss

Abstract Background Cellular and cell-derived components of adipose-derived tissue for the purposes of dermatologic and aesthetic rejuvenation applications have become increasingly studied and integrated into clinical practice. The hair follicle goes through phases of growth, regression, and quiescence, and it is suspected that adipocytes secrete factors to promote activation of hair follicles dermal papilla cells, increasing migration, and proliferation in vitro; as well as increasing conversion of hair follicles from the telogen to anagen phase in vivo. Objectives Evaluation of efficacy and safety of adipose-derived adult stem cells (ADSCs) injection in hair follicle regeneration in female pattern hair loss (FPHL). Methods 33 patients were included and divided into 3 groups according to Sinclair’s classification according to severity. ADSCs were extracted from lipoaspirate and injected into the frontoparietal scalp. Patients were assessed clinically, trichoscopically and immunohistochemically. Results At week 24, there was improvement of hair thickness and count, both in frontal and occipital areas. Histopathological and immunohistochemical assessment at week 12 showed decrease of perifollicular inflammation and decrease of DKK-1 immunostaining. Conclusion The use of ADSCs in treatment of FPHL in subjects included in this study showed improvement of perifollicular inflammation, in addition to density and thickness of hair.

The impact of Zataria multiflora Boiss extract on in vitro and in vivo Th1/Th2 cytokine (IFN-γ/IL4) balance

2013 ◽  
Vol 150 (3) ◽  
pp. 1024-1031 ◽  
Author(s):  
Mohammad Hossein Boskabady ◽  
Sakine Shahmohammadi Mehrjardi ◽  
Abadorrahim Rezaee ◽  
Houshang Rafatpanah ◽  
Sediqeh Jalali
Keyword(s):  
Zataria Multiflora ◽  
Th2 Cytokine ◽  
Ifn Γ ◽  
The Impact

scholarly journals Sarcoma IL-12 overexpression facilitates NK cell immunomodulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mary Jo Rademacher ◽  
Anahi Cruz ◽  
Mary Faber ◽  
Robyn A. A. Oldham ◽  
Dandan Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Lines ◽  
Nk Cell ◽  
Autologous Tumor ◽  
Murine Models ◽  
Lentiviral Transduction ◽  
Ifn Γ ◽  
Human Sarcoma

AbstractInterleukin-12 (IL-12) is an inflammatory cytokine that has demonstrated efficacy for cancer immunotherapy, but systemic administration has detrimental toxicities. Lentiviral transduction eliciting IL-12-producing human sarcoma for autologous reintroduction provides localized delivery for both innate and adaptive immune response augmentation. Sarcoma cell lines and primary human sarcoma samples were transduced with recombinant lentivirus engineering expression of human IL-12 (hu-IL-12). IL-12 expressing sarcomas were assessed in vitro and in vivo following implantation into humanized NSG and transgenic human IL-15 expressing (NSG.Tg(Hu-IL-15)) murine models. Lentiviral transduction (LV/hu-IL-12) of human osteosarcoma, Ewing sarcoma and rhabdomyosarcoma cell lines, as well as low-passage primary human sarcomas, engendered high-level expression of hu-IL-12. Hu-IL-12 demonstrated functional viability, eliciting specific NK cell-mediated interferon-γ (IFN-γ) release and cytotoxic growth restriction of spheroids in vitro. In orthotopic xenograft murine models, the LV/hu-IL-12 transduced human sarcoma produced detectable IL-12 and elicited an IFN-γ inflammatory immune response specific to mature human NK reconstitution in the NSG.Tg(Hu-IL-15) model while restricting tumor growth. We conclude that LV/hu-IL-12 transduction of sarcoma elicits a specific immune reaction and the humanized NSG.Tg(Hu-IL-15) xenograft, with mature human NK cells, can define in vivo anti-tumor effects and systemic toxicities. IL-12 immunomodulation through autologous tumor transduction and reintroduction merits exploration for sarcoma treatment.

scholarly journals Using the Microwell-mesh to culture microtissues in vitro and as a carrier to implant microtissues in vivo into mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Melissa E. Monterosso ◽  
Kathryn Futrega ◽  
William B. Lott ◽  
Ian Vela ◽  
Elizabeth D. Williams ◽  
...  
Keyword(s):  
Hair Follicles ◽  
Live Animal ◽  
Nsg Mice ◽  
Animal Imaging ◽  
Organ Specific ◽  
Bioluminescence Signal ◽  
Serial Transplantation ◽  
Live Animal Imaging

AbstractProstate cancer (PCa) patient-derived xenografts (PDXs) are commonly propagated by serial transplantation of “pieces” of tumour in mice, but the cellular composition of pieces is not standardised. Herein, we optimised a microwell platform, the Microwell-mesh, to aggregate precise numbers of cells into arrays of microtissues, and then implanted the Microwell-mesh into NOD-scid IL2γ−/− (NSG) mice to study microtissue growth. First, mesh pore size was optimised using microtissues assembled from bone marrow-derived stromal cells, with mesh opening dimensions of 100×100 μm achieving superior microtissue vascularisation relative to mesh with 36×36 μm mesh openings. The optimised Microwell-mesh was used to assemble and implant PCa cell microtissue arrays (hereafter microtissues formed from cancer cells are referred to as microtumours) into mice. PCa cells were enriched from three different PDX lines, LuCaP35, LuCaP141, and BM18. 3D microtumours showed greater in vitro viability than 2D cultures, but neither proliferated. Microtumours were successfully established in mice 81% (57 of 70), 67% (4 of 6), 76% (19 of 25) for LuCaP35, LuCaP141, and BM18 PCa cells, respectively. Microtumour growth was tracked using live animal imaging for size or bioluminescence signal. If augmented with further imaging advances and cell bar coding, this microtumour model could enable greater resolution of PCa PDX drug response, and lead to the more efficient use of animals. The concept of microtissue assembly in the Microwell-mesh, and implantation in vivo may also have utility in implantation of islets, hair follicles or other organ-specific cells that self-assemble into 3D structures, providing an important bridge between in vitro assembly of mini-organs and in vivo implantation.

Induction of Winter Flounder Antifreeze Protein Messenger RNA at 4 C in vivo and in vitro

1986 ◽  
Vol 59 (6) ◽  
pp. 679-695 ◽  
Author(s):  
Jeffrey L. Price ◽  
Brian B. Gourlie ◽  
Yuan Lin ◽  
Ru Chih C. Huang
Keyword(s):  
Messenger Rna ◽  
Antifreeze Protein ◽  
Winter Flounder

scholarly journals Stimulation of Interleukin-10 Production by Acidic β-Lactoglobulin-Derived Peptides Hydrolyzed with Lactobacillus paracasei NCC2461 Peptidases

2004 ◽  
Vol 11 (2) ◽  
pp. 266-271 ◽  
Author(s):  
Guénolée Prioult ◽  
Sophie Pecquet ◽  
Ismail Fliss
Keyword(s):  
Oral Tolerance ◽  
Immunosuppressive Agents ◽  
Interleukin 10 ◽  
Lactobacillus Paracasei ◽  
In Vitro Hydrolysis ◽  
Ifn Γ ◽  
Immunomodulatory Peptides ◽  
Β Lactoglobulin

ABSTRACT We have previously demonstrated that Lactobacillus paracasei NCC2461 may help to prevent cow's milk allergy in mice by inducing oral tolerance to β-lactoglobulin (BLG). To investigate the mechanisms involved in this beneficial effect, we examined the possibility that L. paracasei induces tolerance by hydrolyzing BLG-derived peptides and liberating peptides that stimulate interleukin-10 (IL-10) production. L. paracasei peptidases have been shown to hydrolyze tryptic-chymotryptic peptides from BLG, releasing numerous small peptides with immunomodulating properties. We have now shown that acidic tryptic-chymotryptic peptides stimulate splenocyte proliferation and gamma interferon (IFN-γ) production in vitro. Hydrolysis of these peptides with L. paracasei peptidases repressed the lymphocyte stimulation, up-regulated IL-10 production, and down-regulated IFN-γ and IL-4 secretion. L. paracasei NCC2461 may therefore induce oral tolerance to BLG in vivo by degrading acidic peptides and releasing immunomodulatory peptides stimulating regulatory T cells, which function as major immunosuppressive agents by secreting IL-10.

The Role of microRNAs in Osteoporosis Diagnostics

2021 ◽  
Vol 30 (03) ◽  
pp. 222-229
Author(s):  
Matthias Hackl ◽  
Elisabeth Semmelrock ◽  
Johannes Grillari
Keyword(s):  
Bone Mass ◽  
Bone Metabolism ◽  
Messenger Rna ◽  
Biological Fluids ◽  
Clinical Diagnostics ◽  
Bone Architecture ◽  
Estrogen Metabolism ◽  
Age Related

AbstractMicroRNAs (miRNAs) are short (18–24 nucleotides) non-coding RNA sequences that regulate gene expression via binding of messenger RNA. It is estimated that miRNAs co-regulate the expression of more than 70% of all human genes, many of which fulfil important roles in bone metabolism and muscle function. In-vitro and in-vivo experiments have shown that the targeted loss of miRNAs in distinct bone cell types (osteoblasts and osteoclasts) results in altered bone mass and bone architecture. These results emphasize the biological relevance of miRNAs for bone health.MiRNAs are not only considered as novel bone biomarkers because of their biological importance to bone metabolism, but also on the basis of other favorable properties: 1) Secretion of miRNAs from cells enables “minimally invasive” detection in biological fluids such as serum. 2) High stability of miRNAs in serum enables the retrospective analysis of frozen blood specimens. 3) Quantification of miRNAs in the serum is based on the RT-PCR - a robust method that is considered as the gold standard for the analysis of nucleic acids in clinical diagnostics.With regard to osteoporosis, it has been shown that many of the known risk factors are characterized by distinct miRNA profiles in the affected tissues: i) age-related loss of bone mass, ii) sarcopenia, iii) changes in estrogen metabolism and related changes Loss of bone mass, and iv) diabetes. Therefore, numerous studies in recent years have dealt with the characterization of miRNAs in the serum of osteoporosis patients and healthy controls, and were able to identify recurring miRNA patterns that are characteristic of osteoporosis. These novel biomarkers have great potential for the diagnosis and prognosis of osteoporosis and its clinical outcomes.The aim of this article is to give a summary of the current state of knowledge on the research and application of miRNA biomarkers in osteoporosis.

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