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.
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.
A photothermal bacterium (PTB) is reported for tumor‐targeted photothermal therapy (PTT) by using facultative anaerobic bacterium Shewanella oneidensis MR‐1 (S. oneidensis MR‐1) to biomineralize ...palladium nanoparticles (Pd NPs) on its surface without affecting bacterial activity. It is found that PTB possesses superior photothermal property in near infrared (NIR) regions, as well as preferential tumor‐targeting capacity. Zeolitic imidazole frameworks‐90 (ZIF‐90) encapsulating photosensitizer methylene blue (MB) are hybridized on the surface of living PTB to further enhance PTT efficacy. MB‐encapsulated ZIF‐90 (ZIF‐90/MB) can selectively release MB at mitochondria and cause mitochondrial dysfunction by producing singlet oxygen (1O2) under light illumination. Mitochondrial dysfunction further contributes to adenosine triphosphate (ATP) synthesis inhibition and heat shock proteins (HSPs) down‐regulated expression. The PTB‐based therapeutic platform of PTB@ZIF‐90/MB demonstrated here will find great potential to overcome the challenges of tumor targeting and tumor heat tolerance in PTT.
A bacteria‐based photothermal therapeutic platform comprising PTB@ZIF‐90/MB is developed, which reveals great potential to augment photothermal therapy efficacy by tackling the challenges of tumor targeting and heat resistance.
Synthetic biology based on bacteria has been displayed in antitumor therapy and shown good performance. In this study, an engineered bacterium Escherichia coli MG1655 is designed with NDH‐2 enzyme ...(respiratory chain enzyme II) overexpression (Ec‐pE), which can colonize in tumor regions and increase localized H2O2 generation. Following from this, magnetic Fe3O4 nanoparticles are covalently linked to bacteria to act as a catalyst for a Fenton‐like reaction, which converts H2O2 to toxic hydroxyl radicals (•OH) for tumor therapy. In this constructed bioreactor, the Fenton‐like reaction occurs with sustainably synthesized H2O2 produced by engineered bacteria, and severe tumor apoptosis is induced via the produced toxic •OH. These results show that this bioreactor can achieve effective tumor colonization, and realize a self‐supplied therapeutic Fenton‐like reaction without additional H2O2 provision.
A Fenton‐like bioreactor based on bacteria is reported for tumor therapy without exogenous H2O2 provision. It is found that this bioreactor can achieve effective tumor colonization, and realize a self‐supplied therapeutic Fenton‐like reaction without additional H2O2 provision.
Synthetic biology based on bacteria has been displayed in antitumor therapy and shown good performance. In this study, an engineered bacterium Escherichia coli MG1655 is designed with NDH-2 enzyme ...(respiratory chain enzyme II) overexpression (Ec-pE), which can colonize in tumor regions and increase localized H
O
generation. Following from this, magnetic Fe
O
nanoparticles are covalently linked to bacteria to act as a catalyst for a Fenton-like reaction, which converts H
O
to toxic hydroxyl radicals (•OH) for tumor therapy. In this constructed bioreactor, the Fenton-like reaction occurs with sustainably synthesized H
O
produced by engineered bacteria, and severe tumor apoptosis is induced via the produced toxic •OH. These results show that this bioreactor can achieve effective tumor colonization, and realize a self-supplied therapeutic Fenton-like reaction without additional H
O
provision.
By leveraging the ability of Shewanella oneidensis MR‐1 (S. oneidensis MR‐1) to anaerobically catabolize lactate through the transfer of electrons to metal minerals for respiration, a lactate‐fueled ...biohybrid (Bac@MnO2) was constructed by modifying manganese dioxide (MnO2) nanoflowers on the S. oneidensis MR‐1 surface. The biohybrid Bac@MnO2 uses decorated MnO2 nanoflowers as electron receptor and the tumor metabolite lactate as electron donor to make a complete bacterial respiration pathway at the tumor sites, which results in the continuous catabolism of intercellular lactate. Additionally, decorated MnO2 nanoflowers can also catalyze the conversion of endogenous hydrogen peroxide (H2O2) into generate oxygen (O2), which could prevent lactate production by downregulating hypoxia‐inducible factor‐1α (HIF‐1α) expression. As lactate plays a critical role in tumor development, the biohybrid Bac@MnO2 could significantly inhibit tumor progression by coupling bacteria respiration with tumor metabolism.
MnO2 nanoflowers were modified on the cell surface of electrochemically active bacteria, S. oneidensis MR‐1. The biohybrids, which couple bacterial respiration with tumor metabolism, can catabolize intercellular lactate and prevent intracellular lactate production in the tumor, thereby inducing significant tumor inhibition.
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.
Retinal pigment epithelium (RPE) cell damage is implicated in the pathogenesis of age‐related macular degeneration (AMD). An increase of interferon‐γ (IFN‐γ) levels was observed in patients with AMD, ...but whether inflammatory factors are causally related to AMD progression is unclear. Here, we demonstrate a direct causal relationship between IFN‐γ and RPE cell death. IFN‐γ induced human retinal pigment epithelial cell (ARPE‐19) death accompanied by increases in Fe2+, reactive oxygen species, lipid peroxidation, and glutathione (GSH) depletion, which are main characteristics of ferroptosis. Mechanistically, IFN‐γ upregulates the level of intracellular Fe2+ through inhibiting Fe2+ efflux protein SLC40A1 and induces GSH depletion by blocking cystine/glutamate antiporter, System xc‐. At the same time, treatment with IFN‐γ decreases the level of glutathione peroxidase 4 (GPx4), rendering the cells more sensitive to ferroptosis. JAK1/2 and STAT1 inhibitors could reverse the reduction of SLC7A11, GPx4 and GSH expression induced by IFN‐γ, indicating IFN‐γ induces ARPE‐19 cell ferroptosis via activation of the JAK1‐2/STAT1/SLC7A11 signaling pathway. The above results were largely confirmed in IFN‐γ‐treated mice in vivo. Finally, we used sodium iodate (NaIO3)‐induced retinal degeneration to further explore the role of ferroptosis in AMD in vivo. Consistent with the role of IFN‐γ, treatment with NaIO3 decreased SLC7A11, GPx4 and SLC40A1 expressions. NaIO3‐induced RPE damage was accompanied by increased iron, lipid peroxidation products (4‐hydroxynonenal, malondialdehyde), and GSH depletion, and ferroptosis inhibitors could reverse the above phenomenon. Taken together, our findings suggest that inhibiting ferroptosis or reducing IFN‐γ may serve as a promising target for AMD.
IFN‐γ downregulates the expression of SLC7A11 via JAK1‐2/STAT1 signaling pathway, which results in decreases in cysteine transport and, subsequently, decreased GSH synthesis. Simultaneously, IFN‐γ increases intracellular Fe2+ levels through the inhibition of SLC40A1. GSH depletion and Fe2+ accumulation cause retinal pigment epithelial cells ferroptosis and accelerate the progression of AMD.
Kidney injury initiates metabolic reprogramming in tubule cells that contributes to the development of chronic kidney disease (CKD). Exercise has been associated with beneficial effects in patients ...with CKD. Here we show that the induction of a myokine, irisin, improves kidney energy metabolism and prevents kidney damage. In response to kidney injury, mice with muscle-specific PGC-1α overexpression (mPGC-1α) exhibit reduced kidney damage and fibrosis. Metabolomics analysis reveals increased ATP production and improved energy metabolism in injured kidneys from mPGC-1α mice. We identify irisin as a serum factor that mediates these metabolic effects during progressive kidney injury by inhibiting TGF-β type 1 receptor. Irisin depletion from serum blunts the induction of oxygen consumption rate observed in tubule cells treated with mPGC-1α serum. In mice, recombinant irisin administration attenuates kidney damage and fibrosis and improves kidney functions. We suggest that myokine-mediated muscle-kidney crosstalk can suppress metabolic reprograming and fibrogenesis during kidney disease.
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•The composite probiotics increased SCFA-producing bacteria and decreased Escherichia coli.•The composite probiotics promoted GLP-1 secretion by upregulation of GPR43/41, GCG and ...PC1/3 activity.•The composite probiotics inhibited apoptosis via regulating PI3K/AKT signaling pathways.
Previous studies have found that probiotic fermented camel milk has anti-diabetic effect by inducing (glucagon-like peptide-1) GLP-1 secretion. Probiotics are valuable in prevention and treatment of diabetes. As a result, our team islolated 14 probiotics from fermented camel milk. These probiotics have beneficial characteristics, but the possible anti-diabetic mechanisms remains unclear. The present study aimed to explore the possoble anti-diabetic mechanisms of 14 probiotics.
C57BL/Ks mice were normal group. The db/db mice were randomized into five groups: model group, metformin group, liraglutide group, low-dose and high-dose probiotic group. Biochemical parameters were determined by the respective assay kits. The levels of the short-chain fatty acids (SCFAs) and microbiota were respectively determined by gas chromatography and qRT-PCR. HE staining and immunofluorescence were used for histomorphological observation. Quantitative PCR and western-blot were determined the gene and protein expression of Bax, Bcl-2, Caspase-3 and PI3K/AKT.
Probiotics significantly improved blood glucose and blood lipid parameters, as well as the morphological changes of pancreas, liver and kidney. Probiotics improved the gut barrier function through increasing the levels of SCFA-producing bacteria and SCFAs as well as the expression of claudin-1 and mucin-2, and decreasing Escherichia coli and LPS level. In additon, probiotics enhanced insulin secretion through glucose-triggered GLP-1 secretion by upregulating G protein-coupled receptor 43/41 (GPR43/41), proglucagon and proconvertase 1/3 activity. Forthermore, probiotics protected pancreas against apoptosis, which may be dependent on the upregulation of PI3K/AKT pathway.
The anti-diabetic effect of 14 probiotics in db/db mice seem to be related to an increase of SCFA-producing bacteria, the improvement of intestinal barrier function and the upregulation of GLP-1 production, and indicate these probiotics might be a good candidate to prevent and treat diabetes.
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