Discovery of a Chimeric Polyketide Family as Cancer Immunogenic Chemotherapeutic Leads.

Discovery of cancer immunogenic chemotherapeutics represents an emerging, highly promising direction for cancer treatment that uses a chemical drug to achieve the efficacy of both chemotherapy and immunotherapy. Herein, we report a high-throughput screening platform and the subsequent discovery of a new class of cancer immunogenic chemotherapeutic leads. Our platform integrates informatics-based activity metabolomics for the rapid identification of microbial natural products with both novel structures and potent activities.

Discovery of A Chimeric Polyketide Family as Cancer Immunogenic Chemotherapeutic Leads.

Discovery of cancer immunogenic chemotherapeutics represents an emerging, highly promising direction for cancer treatment that uses a chemical drug to achieve the efficacy of both chemotherapy and immunotherapy. Herein we report a high-throughput screening platform and the subsequent discovery of a new class of cancer immunogenic chemotherapeutic leads. Our platform integrates informatics-based activity metabolomics for rapid identification of microbial natural products with both novel structures and potent activities.

Biosynthetic enzyme analysis identifies a protective role for TLR4-acting gut microbial sulfonolipids in inflammatory bowel disease.

The trillions of microorganisms inhabiting the human gut are intricately linked to human health. While specific microbes have been associated with diseases, microbial abundance alone cannot reveal the molecular mechanisms involved. One such important mechanism is the biosynthesis of functional metabolites.

Host-derived Interleukin 1α induces an immunosuppressive tumor microenvironment via regulating monocyte-to-macrophage differentiation.

Tumor-associated macrophages exhibit high heterogeneity and contribute to the establishment of an immunosuppressive tumor microenvironment (TME). Although numerous studies have demonstrated that extracellular factors promote macrophage proliferation and polarization, the regulatory mechanisms governing the differentiation process to generate phenotypically, and functionally diverse macrophage subpopulations remain largely unexplored. In this study, we examined the influence of interleukin 1α (IL-1α) on the development of an immunosuppressive TME using orthotopic transplantation murine models of breast cancer.

microRNA-Based Cancer Diagnosis and Therapy.

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression post-transcriptionally by impeding mRNA translation or stability [...

Microsphere-Enabled Modular Formation of Miniaturized In Vitro Breast Cancer Models.

In search of effective therapeutics for breast cancers, establishing physiologically relevant in vitro models is of great benefit to facilitate the clinical translation. Despite extensive progresses, it remains to develop the tumor models maximally recapturing the key pathophysiological attributes of their native counterparts. Therefore, the current study aimed to develop a microsphere-enabled modular approach toward the formation of in vitro breast tumor models with the capability of incorporating various selected cells while retaining spatial organization.

Type 17 mucosal-associated invariant T cells contribute to neutrophilic inflammation in patients with nasal polyps.

Background: Immune regulation in chronic rhinosinusitis with nasal polyps (CRSwNP) with a neutrophilic endotype remains unclear. Mucosal-associated invariant T (MAIT) cells are tissue-resident innate T lymphocytes that respond quickly to pathogens and promote chronic mucosal inflammation.

Objective: We aimed to investigate the roles of MAIT cells in neutrophilic CRSwNP.

Polymer/copper nanocomplex-induced lysosomal cell death promotes tumor lymphocyte infiltration and synergizes anti-PD-L1 immunotherapy for triple-negative breast cancer.

Our previous research discovered that combining the PDA-PEG polymer with copper ions can selectively kill cancer cells. However, the precise mechanism by which this combination functions was not fully understood. This study revealed that the PDA-PEG polymer and copper ions form complementary PDA-PEG/copper (Poly/Cu) nanocomplexes by facilitating copper ion uptake and lysosomal escape.

Biosynthetic Enzyme-guided Disease Correlation Connects Gut Microbial Metabolites Sulfonolipids to Inflammatory Bowel Disease Involving TLR4 Signaling.

The trillions of microorganisms inhabiting the human gut are intricately linked to human health. At the species abundance level, correlational studies have connected specific bacterial taxa to various diseases. While the abundances of these bacteria in the gut serve as good indicators for disease progression, understanding the functional metabolites they produce is critical to decipher how these microbes influence human health.

Trim-Away in adult animals through Nano-ERASER and its application in cancer therapy.

Trim-Away is a versatile intracellular protein degradation pathway that has been extensively explored . However, the application of Trim-Away is limited at oocyte and zygote stages due to the lack of an practical approach for intracellular antibody delivery. To broaden the application of Trim-Away, especially for clinical use, we developed a nanogel-based Nano-ERASER system.

Cancer resistance to immunotherapy: What is the role of cancer stem cells?

Immunotherapy is an emerging form of cancer therapy that is associated with promising outcomes. However, most cancer patients either do not respond to immunotherapy or develop resistance to treatment. The resistance to immunotherapy is poorly understood compared to chemotherapy and radiotherapy.

miR-489 Confines Uncontrolled Estrogen Signaling through a Negative Feedback Mechanism and Regulates Tamoxifen Resistance in Breast Cancer.

Approximately 75% of diagnosed breast cancer tumors are estrogen-receptor-positive tumors and are associated with a better prognosis due to response to hormonal therapies. However, around 40% of patients relapse after hormonal therapies. Genomic analysis of gene expression profiles in primary breast cancers and tamoxifen-resistant cell lines suggested the potential role of miR-489 in the regulation of estrogen signaling and development of tamoxifen resistance.

Type 2 and Type 17 Invariant Natural Killer T Cells Contribute to Local Eosinophilic and Neutrophilic Inflammation and Their Function Is Regulated by Mucosal Microenvironment in Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by heterogeneous inflammatory endotypes of unknown etiology. Invariant natural killer T (iNKT) cells are multifunctional innate T cells that exhibit Th1-, Th2-, and Th17-like characteristics. We investigated functional relationships between iNKT cells and inflammatory subtypes of CRSwNP.

Identification and Biosynthesis of Pro-Inflammatory Sulfonolipids from an Opportunistic Pathogen .

Sulfonolipids (SoLs) are a unique class of sphingolipids featuring a sulfonate group compared to other sphingolipids. However, the biological functions and biosynthesis of SoLs in human microbiota have been poorly understood. Here, we report the discovery and isolation of SoLs from a human opportunistic pathogen DSM16776.

Correlational networking guides the discovery of unclustered lanthipeptide protease-encoding genes.

Bacterial natural product biosynthetic genes, canonically clustered, have been increasingly found to rely on hidden enzymes encoded elsewhere in the genome for completion of biosynthesis. The study and application of lanthipeptides are frequently hindered by unclustered protease genes required for final maturation. Here, we establish a global correlation network bridging the gap between lanthipeptide precursors and hidden proteases.

The diverse roles of YAP in the regulation of human nasal epithelial remodeling.

Yes-associated protein (YAP) is essential in maintaining tissue size. Aberrant epithelial remodeling is a key pathological alteration in both inflammation and benign tumors in nasal mucosa. We sought to investigate the expression and localization patterns of YAP in remodeled nasal epithelium of basal cell hyperplasia, goblet cell metaplasia and squamous metaplasia.

Immunogenic Cell Death: A Step Ahead of Autophagy in Cancer Therapy.

Immunogenic cell death (ICD) plays a major role in providing long lasting protective antitumor immunity by the chronic exposure of damage associated molecular patterns (DAMPs) in the tumor microenvironment (TME). DAMPs are essential for attracting immunogenic cells to the TME, maturation of DCs, and proper presentation of tumor antigens to the T cells so they can kill more cancer cells. Thus for the proper release of DAMPs, a controlled mechanism of cell death is necessary.

Local IL-17 positive T cells are functionally associated with neutrophil infiltration and their development is regulated by mucosal microenvironment in nasal polyps.

Objective And Design: IL-17 plays essential roles in neutrophilic inflammation in the lower respiratory tract, however, the characteristics of local IL-17 T cells in nasal inflammatory mucosa are not fully understood. We investigated the roles of IL-17 T cells in regulating neutrophil infiltration and the effect of the mucosal microenvironment in modulating IL-17 T cell differentiation in CRSwNP tissues.

Subjects: 47 polyp tissues from chronic rhinosinusitis with nasal polyps (CRSwNP) patients without corticosteroid therapy and 26 tissues from healthy mucosa were obtained.

Presence of Tertiary Lymphoid Organ in Nasal Inverted Papilloma Is Correlated with Eosinophil Infiltration and Local Immunoglobulin Production.

Introduction: Nasal inverted papilloma (NIP) is a benign tumour with multiple inflammatory cell infiltration. Tertiary lymphoid organs (TLOs) support local antibody production and play important roles in airway inflammation. However, the evidence of TLOs and local immunoglobulins in NIP has not been reported yet.

Emodin reduces Breast Cancer Lung Metastasis by suppressing Macrophage-induced Breast Cancer Cell Epithelial-mesenchymal transition and Cancer Stem Cell formation.

Our previous studies demonstrated that the natural compound emodin blocks the tumor-promoting feedforward interactions between cancer cells and macrophages, and thus ameliorates the immunosuppressive state of the tumor microenvironment. Since tumor-associated macrophages (TAMs) also affect epithelial mesenchymal-transition (EMT) and cancer stem cell (CSC) formation, here we aimed to test if emodin as a neoadjuvant therapy halts breast cancer metastasis by attenuating TAM-induced EMT and CSC formation of breast cancer cells. Bioinformatical analysis was performed to examine the correlation between macrophage abundance and EMT/CSC markers in human breast tumors.

Publisher Correction: Early-onset colorectal cancer: initial clues and current views.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Overexpression of microRNA-155 enhances the efficacy of dendritic cell vaccine against breast cancer.

MicroRNA 155 (miR-155) plays important roles in the regulation of the development and functions of a variety of immune cells. We previously revealed a vital role of miR-155 in regulating the function of dendritic cells (DCs) in breast cancer. miR-155 deficiency in DCs impaired their maturation, migration, cytokine production, and ability to activate T cells.

Early-onset colorectal cancer: initial clues and current views.

Over the past several decades, the incidence of early-onset colorectal cancer (EOCRC; in patients <50 years old) has increased at an alarming rate. Although robust and scientifically rigorous epidemiological studies have sifted out environmental elements linked to EOCRC, our knowledge of the causes and mechanisms of this disease is far from complete. Here, we highlight potential risk factors and putative mechanisms that drive EOCRC and suggest likely areas for fruitful research.