CBL0137 and NKG2A blockade: a novel immuno-oncology combination therapy for Myc-overexpressing triple-negative breast cancers.

The MYC proto-oncogene is upregulated in >60% of triple-negative breast cancers (TNBCs), it can directly promote tumor cell proliferation, and its overexpression negatively regulates anti-tumor immune responses. For all these reasons, MYC has long been considered as a compelling therapeutic target. However, pharmacological inhibition of MYC function has proven difficult due to a lack of a drug-binding pocket.

Effect of a topical traditional Chinese herbal medicine on skin microbiota in mouse model of atopic dermatitis.

This study aims to explore the impact of the herbal ointment Chushi Zhiyang Ruangao (CSZYRG) on the skin's microecological environment in a mouse model of atopic dermatitis (AD) and to understand the underlying mechanisms involved. The AD model was established in C57 mice using calpolitol (a hypocalcemic analog of vitamin D3; MC903). Medication-free matrix ointment, CSZYRG, and mometasone furoate cream (positive control group) were applied to the injured areas.

Momordin Ic ameliorates psoriasis skin damage in mice via the IL-23/IL-17 axis.

Psoriasis, a chronic and easily recurring inflammatory skin disease, causes a great economic burden to the patient's family because the etiology and mechanism are still unclear and the treatment cycle is long. In this study, the function and related mechanisms of Momordin Ic in psoriasis were investigated. The IMQ-induced mouse psoriasis model was constructed.

Dendrobium officinale polysaccharide promotes angiogenesis as well as follicle regeneration and hair growth through activation of the WNT signaling pathway.

Introduction: Hair loss is one of the common clinical conditions in modern society. Although it is not a serious disease that threatens human life, it brings great mental stress and psychological burden to patients. This study investigated the role of dendrobium officinale polysaccharide (DOP) in hair follicle regeneration and hair growth and its related mechanisms.

Dendrobium officinale Polysaccharide (DOP) inhibits cell hyperproliferation, inflammation and oxidative stress to improve keratinocyte psoriasis-like state.

Purpose: Psoriasis is a skin disease characterized by excessive proliferation, inflammation and oxidative stress in keratinocytes. The present study aimed to investigate the therapeutic effects of Dendrobium officinale polysaccharide (DOP) on keratinocyte psoriasis-like models.

Methods: The HaCaT keratinocyte inflammation models were induced by interleukin (IL)-22 or lipopolysaccharide (LPS), respectively, and oxidative stress damage within cells was elicited by HO and treated using DOP.

Skin-Grafting and Dendritic Cell "Boosted" Humanized Mouse Models Allow the Pre-Clinical Evaluation of Therapeutic Cancer Vaccines.

Vaccines have been hailed as one of the most remarkable medical advancements in human history, and their potential for treating cancer by generating or expanding anti-tumor T cells has garnered significant interest in recent years. However, the limited efficacy of therapeutic cancer vaccines in clinical trials can be partially attributed to the inadequacy of current preclinical mouse models in recapitulating the complexities of the human immune system. In this study, we developed two innovative humanized mouse models to assess the immunogenicity and therapeutic effectiveness of vaccines targeting human papillomavirus (HPV16) antigens and delivering tumor antigens to human CD141 dendritic cells (DCs).

Multiparametric flow cytometry to characterize vaccine-induced polyfunctional T cell responses and T cell/NK cell exhaustion and memory phenotypes in mouse immuno-oncology models.

Suitable methods to assess immunogenicity and therapeutic efficacy of cancer vaccines in preclinical cancer models are critical to overcome current limitations of cancer vaccines and enhance the clinical applicability of this promising immunotherapeutic strategy. In particular, availability of methods allowing the characterization of T cell responses to endogenous tumor antigens is required to assess vaccine potency and improve the antigen formulation. Moreover, multiparametric assays to deeply characterize tumor-induced and therapy-induced immune modulation are relevant to design mechanism-based combination immunotherapies.

Dendrobium officinale Polysaccharide (DOP) Promotes Hair Regrowth in Testosterone-Induced Bald Mice.

Background: Androgenetic alopecia can affect up to 70% of males and 40% of females; however, certain therapeutic medications offer partial and transitory improvement but with major side effects. Dendrobium officinale polysaccharide (DOP) has been reported to improve androgen-related hair loss in mice, but the molecular mechanism remains unclear.

Objectives: To explore the effects of DOP on androgenetic alopecia.

Biophysical properties of hydrogels for mimicking tumor extracellular matrix.

The extracellular matrix (ECM) is an essential component of the tumor microenvironment. It plays a critical role in regulating cell-cell and cell-matrix interactions. However, there is lack of systematic and comparative studies on different widely-used ECM mimicking hydrogels and their properties, making the selection of suitable hydrogels for mimicking different in vivo conditions quite random.

Targeting Replication Stress Using CHK1 Inhibitor Promotes Innate and NKT Cell Immune Responses and Tumour Regression.

Drugs selectively targeting replication stress have demonstrated significant preclinical activity, but this has not yet translated into an effective clinical treatment. Here we report that targeting increased replication stress with a combination of Checkpoint kinase 1 inhibitor (CHK1i) with a subclinical dose of hydroxyurea targets also promotes pro-inflammatory cytokine/chemokine expression that is independent of cGAS-STING pathway activation and immunogenic cell death in human and murine melanoma cells. In vivo, this drug combination induces tumour regression which is dependent on an adaptive immune response.

Saponin Momordin Ic Modulates HaCaT Cell Proliferation and Apoptosis via the Wnt/-Catenin Pathway.

Psoriasis is a chronic, recurrent, immunoinflammatory disease. For a long period, Traditional Chinese Medicine (TCM) is considered a reliable alternative therapy for patients with psoriasis. Fructus Kochiae (or ) and its principle saponin, Momordin Ic, have been reported to protect against inflammation.

Tumor-Microenvironment-on-a-Chip for Evaluating Nanoparticle-Loaded Macrophages for Drug Delivery.

Targeted drug delivery remains attractive but challenging for cancer therapy. Cell-mediated drug delivery has emerged as a promising strategy to improve targeted drug delivery to tumors due to the intrinsic ability of certain types of cells (., macrophage) to pass through physiological barriers and specifically home to tumors.

Enhancing chimeric antigen receptor T-cell immunotherapy against cancer using a nanoemulsion-based vaccine targeting cross-presenting dendritic cells.

Objectives: Adoptive transfer of chimeric antigen receptor (CAR)-modified T cells is a form of cancer immunotherapy that has achieved remarkable efficacy in patients with some haematological cancers. However, challenges remain in CAR T-cell treatment of solid tumours because of tumour-mediated immunosuppression.

Methods: We have demonstrated that CAR T-cell stimulation through T-cell receptors (TCRs) can generate durable responses against solid tumours in a variety of murine models.

miR-203 promotes HaCaT cell overproliferation through targeting LXR-α and PPAR-γ.

Psoriasis is an immune-mediated chronic inflammatory skin disease. Keratinocyte hyperproliferation has been regarded as a significant event in psoriasis pathogenesis. Considering the vital role of miRNA-mediated mRNA repression in psoriasis pathogenesis, in the present study, we attempted to investigate the mechanism of keratinocyte overproliferation from the point of miRNA-mRNA regulation.

miR124-3p/FGFR2 axis inhibits human keratinocyte proliferation and migration and improve the inflammatory microenvironment in psoriasis.

Keratinocyte hyperproliferation has been regarded as a central event in psoriasis pathogenesis. Investigating the mechanisms of keratinocyte hyperproliferation might provide novel strategies for psoriasis treatment. we demonstrated that fibroblast growth factor receptor 2 (FGFR2) expression was abnormally upregulated within psoriatic lesion tissues and HaCaT cells under rIL-22 stimulation.

Isoimperatorin (ISO) reduces melanin content in keratinocytes via miR-3619/CSTB and miR-3619/CSTD axes.

Melanin metabolism disorders may cause severe impacts on the psychological and social activities of patients. Different from the other two steps of melanin metabolism, namely synthesis and transport, little has been known about the mechanism of melanin degradation. Isoimperatorin (ISO) suppressed the activity of tyrosinase, an essential enzyme in melanin biosynthesis, hence, we investigated the effects and mechanism of ISO in melanin reduction.

PD-L1- and calcitriol-dependent liposomal antigen-specific regulation of systemic inflammatory autoimmune disease.

Autoimmune diseases resulting from MHC class II-restricted autoantigen-specific T cell immunity include the systemic inflammatory autoimmune conditions rheumatoid arthritis and vasculitis. While currently treated with broad-acting immunosuppressive drugs, a preferable strategy is to regulate antigen-specific effector T cells (Teffs) to restore tolerance by exploiting DC antigen presentation. We targeted draining lymph node (dLN) phagocytic DCs using liposomes encapsulating 1α,25-dihydroxyvitamin D3 (calcitriol) and antigenic peptide to elucidate mechanisms of tolerance used by DCs and responding T cells under resting and immunized conditions.

NKT Cell-Driven Enhancement of Antitumor Immunity Induced by Clec9a-Targeted Tailorable Nanoemulsion.

Invariant natural killer T (iNKT) cells are a subset of lymphocytes with immune regulatory activity. Their ability to bridge the innate and adaptive immune systems has been studied using the glycolipid ligand α-galactosylceramide (αGC). To better harness the immune adjuvant properties of iNKT cells to enhance priming of antigen-specific CD8 T cells, we encapsulated both αGC and antigen in a Clec9a-targeted nanoemulsion (TNE) to deliver these molecules to cross-presenting CD8 dendritic cells (DC).

Tumor-Vasculature-on-a-Chip for Investigating Nanoparticle Extravasation and Tumor Accumulation.

Nanoparticle tumor accumulation relies on a key mechanism, the enhanced permeability and retention (EPR) effect, but it remains challenging to decipher the exact impact of the EPR effect. Animal models in combination with imaging modalities are useful, but it is impossible to delineate the roles of multiple biological barriers involved in nanoparticle tumor accumulation. Here we report a microfluidic tumor-vasculature-on-a-chip (TVOC) mimicking two key biological barriers, namely, tumor leaky vasculature and 3D tumor tissue with dense extracellular matrix (ECM), to study nanoparticle extravasation through leaky vasculature and the following accumulation in tumor tissues.

Self-adjuvanting nanoemulsion targeting dendritic cell receptor Clec9A enables antigen-specific immunotherapy.

Non-antigen-specific stimulatory cancer immunotherapies are commonly complicated by off-target effects. Antigen-specific immunotherapy, combining viral tumor antigen or personalized neoepitopes with immune targeting, offers a solution. However, the lack of flexible systems targeting tumor antigens to cross-presenting dendritic cells (DCs) limits clinical development.

Immunomodulatory liposomes targeting liver macrophages arrest progression of nonalcoholic steatohepatitis.

Objective: Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic macrophage inflammation, steatosis and fibrosis. Liposomes injected intravenously passively target hepatic myeloid cells and have potential to deliver immunomodulatory compounds and treat disease. We investigated targeting, delivery, immunomodulation and efficacy of liposomes in mice with diet-induced NASH.

MicroRNA-124 alleviates chronic skin inflammation in atopic eczema via suppressing innate immune responses in keratinocytes.

Chronic skin inflammation in atopic eczema is associated with elevated expression of proinflammatory genes and activation of innate immune responses in keratinocytes. MicroRNAs (miRNAs) are short, single-stranded RNA molecules that silence genes via the degradation of target mRNAs or inhibition of translation. Recent studies have demonstrated that miR-124 is associated with regulation of inflammation factors in several diseases.

MiR-330 inhibits IL-22-induced keratinocyte proliferation through targeting CTNNB1.

Psoriasis is a common chronic inflammatory skin disease which is characterized by hyperproliferation and aberrant differentiation of keratinocytes; however the exact pathogenesis is largely unknown. Interleukin-22 (IL-22) has demonstrated its vital role in T cell-mediated immune response by interacting with keratinocytes in the pathogenesis of psoriasis. The microRNAs (miRNAs) are a class of small non-coding RNA molecules that play important roles in cellular processes by regulating gene expression at the post-transcriptional level.