Summary
Vermicomposting using black soldier fly (BSF) larvae (Hermetia illucens) has gradually become a promising biotechnology for waste management, but knowledge about the larvae gut microbiome is ...sparse. In this study, 16S rRNA sequencing, SourceTracker, and network analysis were leveraged to decipher the influence of larvae gut microbiome on food waste (FW) biodegradation. The microbial community structure of BSF vermicompost (BC) changed greatly after larvae inoculation, with a peak colonization traceable to gut bacteria of 66.0%. The relative abundance of 11 out of 21 metabolic function groups in BC were significantly higher than that in natural composting (NC), such as carbohydrate‐active enzymes. In addition, 36.5% of the functional genes in BC were significantly higher than those in NC. The changes of metabolic functions and functional genes were significantly correlated with the microbial succession. Moreover, the bacteria that proliferated in vermicompost, including Corynebacterium, Vagococcus, and Providencia, had strong metabolic abilities. Systematic and complex interactions between the BSF gut and BC bacteria occurred over time through invasion, altered the microbial community structure, and thus evolved into a new intermediate niche favourable for FW biodegradation. The study highlights BSF gut microbiome as an engine for FW bioconversion, which is conducive to bioproducts regeneration from wastes.
The microbial community of vermicompost changed greatly after addition of black soldier fly (BSF) larvae, and gradually became similar to that in the BSF gut. The metabolic functions of vermicompost were strengthened by the BSF larvae gut microbiome, leading to enhancing food waste biodegradation. Complex interactions occurred between the bacteria in the BSF larvae gut and the vermicompost through invasion.
Small interfering RNA (siRNA) enables efficient target gene silencing by employing a RNA interference (RNAi) mechanism, which can compromise gene expression and regulate gene activity by cleaving ...mRNA or repressing its translation. Twenty years after the discovery of RNAi in 1998, ONPATTRO™ (patisiran) (Alnylam Pharmaceuticals, Inc.), a lipid formulated siRNA modality, was approved for the first time by United States Food and Drug Administration and the European Commission in 2018. With this milestone achievement, siRNA therapeutics will soar in the coming years. Here, we review the discovery and the mechanisms of RNAi, briefly describe the delivery technologies of siRNA, and summarize recent clinical advances of siRNA therapeutics.
The tumor-related myeloid derived suppressor cells (MDSCs), important immunosuppressive cells in tumor microenvironment, play an important role in the cancer progression. This study is aimed to ...investigate the crosstalk between MDSCs and oral squamous cell carcinoma (OSCC) cells and their role in the malignant progression of OSCC.
Immunochemistry (IHC) was used to investigate the expression of CD33 in 200 OSCC, 36 premalignant. CD33+ MDSCs were sorted and enriched via magnetic-activated cell sorting (MACS) from OSCC patients or health donor, and their phenotypes were identified by flow cytometry. With a co-culture system of MDSCs and OSCC, the effects of MDSCs on OSCC proliferation, apoptosis, migration invasion, epithelial-mesenchymal transition (EMT), and vasculogenic mimicry formation (VM) formation were assessed, respectively. Besides, peripheral blood mononuclear cells (PBMCs) from health donor were cultured with OSCC supernatant, the level of MDSCs and expressions of Arginase (Arg-1) and inducible nitric oxide synthase (iNOS) were measured.
The number of MDSCs was increased in tumor tissues of OSCC patients, and was positively related to the T stage, pathological grade, lymph node metastasis and poor prognosis. Tumor-related MDSCs of the co-culture system promoted OSCC progression by contributing to cell proliferation, migration and invasion as well as inducing EMT and VM. In turn, OSCC cells had potential to induce MDSCs differentiation from PBMCs and increase the expression of Arg-1 and iNOS.
These indicated that the crosstalk between MDSCs and tumor cells facilitated the malignant progression of OSCC cells and the immune suppressive properties of MDSCs, which may provide new insights into tumor treatment on targeting tumor-associated immunosuppressive cells.
Innate DNA sensing via the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) mechanism surveys microbial invasion and cellular damage and thus participates in various human ...infectious diseases, autoimmune diseases and cancers. However, how DNA sensing rapidly and adaptively shapes cellular physiology is incompletely known. Here we identify the STING-PKR-like endoplasmic reticulum kinase (PERK)-eIF2α pathway, a previously unknown cGAS-STING mechanism, enabling an innate immunity control of cap-dependent messenger RNA translation. Upon cGAMP binding, STING at the ER binds and directly activates the ER-located kinase PERK via their intracellular domains, which precedes TBK1-IRF3 activation and is irrelevant to the unfolded protein response. The activated PERK phosphorylates eIF2α, forming an inflammatory- and survival-preferred translation program. Notably, this STING-PERK-eIF2α pathway is evolutionarily primitive and physiologically critical to cellular senescence and organ fibrosis. Pharmacologically or genetically targeting this non-canonical cGAS-STING pathway attenuated lung and kidney fibrosis. Collectively, the findings identify an alternative innate immune pathway and its critical role in organ fibrosis, report an innate immunity-directed translation program and suggest the therapeutic potential for targeting the STING-PERK pathway in treating fibrotic diseases.
Background
CKLF-like MARVEL transmembrane domain-containing 6
(
CMTM6
) is a critical regulator of tumor immunology among various cancers. However, the role and underlying molecular mechanism of
...CMTM6
in oral squamous cell carcinoma (OSCC) progression remains unclear.
Methods
The expression of
CMTM6
,
PD-L1
and
CD163
in OSCC tissues were detected by immunohistochemistry on tissue microarray. The effect of
CMTM6
knockdown on OSCC cells and macrophage polarization were analyzed by CCK-8 assay, apoptotic assay, would-healing assay, transwell assay and qPCR. OSCC cell derived exosomes were obtained by ultracentrifugation and the mechanistic studies were conducted by qPCR and Western Blot. 4-Nitroquinoline N-oxide (4NQO) induced OSCC mice were used for verifying the effect of
CMTM6
downregulation on M2 macrophage infiltration and tumor growth.
Results
In OSCC samples, higher
CMTM6
expression has been obviously associated with higher pathological stage of OSCC patients,
CD163
+ macrophages infiltration and
PD-L1
expression.
CMTM6
knockdown of OSCC cells inhibited proliferative, migrative and invasive abilities of OSCC cells, as well as inhibited M2 macrophage polarization in vitro with downregulating
PD-L1
expression. Importantly, exosomes from OSCC cells shuttled
CMTM6
to macrophages and promoted M2-like macrophage polarization through activating ERK1/2 signaling. In addition, in 4NQO-induced OSCC mice,
CMTM6
level was positively associated with
CD163
,
CD206
and
PD-L1
as well as M2-like macrophage infiltration.
Conclusion
OSCC cell-secreted exosomal
CMTM6
induces M2-like macrophages polarization to promote malignant progression via ERK1/2 signaling pathway, revealing a novel crosstalk between cancer cells and immune cells in OSCC microenvironment.
Graphene quantum dots (GQDs) as novel nanomaterials, have received significant interest in the field of biomedical applications. It is worth noting that a large amount of research is devoted to ...GQDs-based nanocomposites for cancer treatment, especially for photodynamic therapy (PDT), in that they can act not only as more favorable photosensitizers (PSs) but also nanoplatforms for delivering PSs. In this review, the biological behavior and physicochemical properties of GQDs for PDT are described in detail, and the application of GQDs-based nanocomposites in improved PDT and PDT-based combination therapies is analyzed, which may provide a new strategy for designing efficient PDT systems for cancer treatment.
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•The synthesis methods of GQDs have important effects on their physicochemical properties.•GQDs exhibit excellent biocompatibility and optical properties.•GQDs have great potential in photodynamic therapy.•PDT-based combination therapies show good synergistic effects.•Precisely tailoring properties of GQDs plays a key role in their application.
Emerging evidence has shown that dynamic crosstalk among cells in the tumor microenvironment modulates the progression and chemotherapeutic responses of cancer. Extracellular vesicles comprise a ...crucial form of intracellular communication through horizontal transfer of bioactive molecules, including long non–coding RNA (lncRNA), to neighboring cells. Three main types of extracellular vesicles are exosomes, microvesicles and apoptotic bodies, exhibiting a wide range of sizes and different biogenesis. Over the last decade, dysregulation of extracellular vesicle lncRNA has been revealed to remodel the tumor microenvironment and induce aggressive phenotypes of tumor cells, thereby facilitating tumor growth and development. This review will focus on extracellular vesicle lncRNA‐mediated crosstalk between tumor cells and recipient cells, including tumor cells as well as stromal cells in the tumor microenvironment, and overview the mechanisms by which lncRNA are selectively sorted into extracellular vesicles, which may pave the way for their clinical application in cancer diagnosis and treatment.
Emerging evidence has shown that dynamic crosstalk among cells in the tumor microenvironment modulates the progression and chemotherapeutic responses of cancer. Recently, dysregulation of extracellular vesicle lncRNA has been revealed to remodel the tumor microenvironment and induce an aggressive phenotype of cancer cells, thereby facilitating tumor growth and development. This review focuses on extracellular vesicle lncRNA‐mediated crosstalk in the tumor microenvironment and the mechanisms by which lncRNA are selectively sorted into extracellular vesicles, which may pave the way for its clinical application in cancer diagnosis and treatment.
Noncoding RNAs (ncRNAs) have been demonstrated to closely associate with gene regulation and encompass the well-known microRNAs (miRNAs), as well as the most recently acknowledged long noncoding RNAs ...(lncRNAs). Current evidence indicates that lncRNAs can interact with miRNAs and these interactions play crucial roles in cancer metastasis, through regulating critical events especially the epithelial-mesenchymal transition (EMT). This review summarizes the types of lncRNA-miRNA crosstalk identified to-date and discusses their influence on the epithelial-mesenchymal plasticity and clinical metastatic implication.
The activation of CXCL12/CXCR4 axis participated in the progression of multiple cancers, but potential effect in terms of perineural invasion (PNI) in SACC remained ambiguous. In this study, we ...identified that CXCL12 substantially expressed in nerve cells. CXCR4 strikingly expressed in tumour cells, and CXCR4 expression was closely associated with the level of EMT‐associated proteins and Schwann cell hallmarks at nerve invasion frontier in SACC. Activation of CXCL12/CXCR4 axis could promote PNI and up‐regulate relative genes of EMT and Schwann cell hallmarks both in vitro and in vivo, which could be inhibited by Twist silence. After overexpressing S100A4, the impaired PNI ability of SACC cells induced by Twist knockdown was significantly reversed, and pseudo foot was visualized frequently. Collectively, the results indicated that CXCL12/CXCR4 might promote PNI by provoking the tumour cell to differentiate towards Schwann‐like cell through Twist/S100A4 axis in SACC.
The Hippo pathway regulates cell proliferation, apoptosis, and stem cell self-renewal, and its inactivation in animal models causes organ enlargement followed by tumorigenesis. Hippo pathway ...deregulation occurs in many human cancers, but the underlying mechanisms are not fully understood. Here, we report tyrosine phosphorylation of the Hippo pathway tumor suppressor LATS1 as a mechanism underlying its regulation by cell adhesion. A tyrosine kinase library screen identified Src as the kinase to directly phosphorylate LATS1 on multiple residues, causing attenuated Mob kinase activator binding and structural alteration of the substrate-binding pocket in the kinase domain. Cell matrix adhesion activated the Hippo pathway effector transcription coactivator YAP partially through Src-mediated phosphorylation and inhibition of LATS1. Aberrant Src activation abolished the tumor suppressor activity of LATS1 and induced tumorigenesis in a YAP-dependent manner. Protein levels of Src in human breast cancer tissues correlated with accumulation of active YAP dephosphorylated on the LATS1 target site. These findings reveal tyrosine phosphorylation of LATS1 by Src as a novel mechanism of Hippo pathway regulation by cell adhesion and suggest Src activation as an underlying reason for YAP deregulation in tumorigenesis.
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