Pyroptosis is a form of proinflammatory gasdermin-mediated programmed cell death. Abnormal mucosal inflammation in the intestine is a critical risk factor for colitis-associated colorectal cancer ...(CAC). However, it is unknown whether pyroptosis participates in the development of CAC.
To investigate the role of gasdermin E (GSDME)-mediated pyroptosis in the development of CAC, Gsdme
mice and their wild-type (WT) littermate controls were challenged with azoxymethane (AOM) and dextran sodium sulfate (DSS) to induce a CAC model. Neutralizing antibodies against high-mobility group box protein 1 (HMGB1) were used to determine the role of HMGB1 in CAC. To identify the role of ERK1/2 in HMGB1-induced colon cancer cell proliferation, we performed western blotting and CCK8 assays using the ERK1/2-specific inhibitor U0126 in CT26 colon cancer cells.
In the CAC model, Gsdme
mice exhibited reduced weight loss and colon shortening, attenuated rectal prolapse, and reduced tumor numbers and sizes compared to WT littermates. Furthermore, treatment with neutralizing anti-HMGB1 antibodies decreased the numbers and sizes of tumors, ERK1/2 activation and proliferating cell nuclear antigen (PCNA) expression in AOM/DSS-challenged WT mice. In addition, our in vitro experiments demonstrated that HMGB1 induced proliferation and PCNA expression in CT26 colon cancer cells through the ERK1/2 pathway.
GSDME-mediated pyroptosis promotes the development of CAC by releasing HMGB1, which induces tumor cell proliferation and PCNA expression through the ERK1/2 pathway. This finding reveals a previously unrecognized link between pyroptosis and CAC tumorigenesis and offers new insight into CAC pathogenesis.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Crohn's disease (CD) is a kind of refractory intestinal inflammatory diseases. Pyroptosis was recently identified as a gasdermin-mediated proinflammatory cell death. However, it is unclear whether ...gasdermin-mediated pyroptosis participates in the pathogenesis of CD. Here, we show that the pyroptosis-inducing fragment GSDME N-terminal is obviously detected in the inflamed colonic mucosa but not in the uninflamed mucosa of patients with CD, suggesting that GSDME-mediated pyroptosis may be correlated with intestinal mucosal inflammation in CD. To investigate the role of GSDME in colitis development, Gsdme
mice and wild-type (WT) littermate controls were treated with 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce colitis. We found that Gsdme
mice exhibit less-severe intestinal inflammation than WT controls do. Furthermore, our results indicate that GSDME-mediated epithelial-cell pyroptosis induces intestinal inflammation through the release of proinflammatory intracellular contents. In summary, we show that GSDME participates in the pathogenesis of CD through GSDME-mediated pyroptosis to release proinflammatory cytokines.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Formalin-fixed paraffin-embedded (FFPE) tissues constitute a vast and valuable patient material bank for clinical history and follow-up data. It is still challenging to achieve single cell/nucleus ...RNA (sc/snRNA) profile in FFPE tissues. Here, we develop a droplet-based snRNA sequencing technology (snRandom-seq) for FFPE tissues by capturing full-length total RNAs with random primers. snRandom-seq shows a minor doublet rate (0.3%), a much higher RNA coverage, and detects more non-coding RNAs and nascent RNAs, compared with state-of-art high-throughput scRNA-seq technologies. snRandom-seq detects a median of >3000 genes per nucleus and identifies 25 typical cell types. Moreover, we apply snRandom-seq on a clinical FFPE human liver cancer specimen and reveal an interesting subpopulation of nuclei with high proliferative activity. Our method provides a powerful snRNA-seq platform for clinical FFPE specimens and promises enormous applications in biomedical research.
Stable photoelectrochemical solar fuel production requires protective coatings to achieve effective charge separation, transport, and injection at the semiconductor–liquid interfaces, implying that ...the coating should energetically align its intermediate band (IB) with both the photoabsorber's band edge and co‐catalyst's potentials. Yet approaches to adjust coating IB positions to accommodate various semiconductor light absorbers for constructing efficient and stable photoelectrodes have not been developed. Herein, three types of transition metal (M = Mn2+, Mn3+, and Cr3+ ions) alloyed TiO2 coatings are discovered using atomic layer deposition (ALD). The IB energetics of these coatings are characterized by X‐ray photoelectron spectroscopy and are found to be tunable inside the TiO2 bandgap, through varying ALD growth conditions. By applying these coatings to n‐type GaP and integrating with IrOx co‐catalysts, the water‐oxidation J–E performance is comparable to an uncoated corroding GaP photoanode. It reaches the bulk recombination limit of the GaP and achieves ≈28% absorbed photon to current efficiency under 475‐nm light excitation (6.48 mW cm−2) and 100‐h stable water oxidation. The outstanding performance and stability are attributed to the efficient charge separation and hole transport, as allowed by the energy alignment of the coating IB and the GaP valence band edge.
Transition metal alloyed atomic layer deposition coatings have tunable intermediate bands that enable energetic alignment with model photoabsorbers, such as GaP, and achieve efficient charge separation and 100‐h stable water oxidation in neutral pH phosphate buffer.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Advances in single-cell and spatially resolved omics technologies have revolutionized research in biology and medicine. These technologies allow for the detailed study of individual cells, providing ...insights into tissue heterogeneity and cell interactions. Single-cell RNA sequencing (scRNA-seq) has seen significant advancements, enabling the establishment of the Human Cell Atlas and the analysis of hundreds of thousands of cells. Metabolomics and proteomics at the single-cell level are also emerging fields, although they come with challenges due to the complexity of the metabolome and the inability to directly amplify proteins. Spatially resolved transcriptomics (SRT) aims to preserve spatial information during gene expression profiling, and various methods, such as in situ hybridization and sequencing-based approaches, have been developed. The integration of single-cell and spatially resolved data allows for a comprehensive understanding of tissue organization and dynamics. However, current technologies have limitations, and further improvements and computational tools are needed to fully exploit their potential. With continued investment and innovation, single-cell and spatially resolved omics have the potential to transform research and clinical practice, leading to improved human health and wellbeing.
Full text
Available for:
FFLJ, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, ODKLJ, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Bacteria colonize almost all parts of the human body and can differ significantly. However, the population level transcriptomics measurements can only describe the average bacteria ...population behaviors, ignoring the heterogeneity among bacteria. Here, we report a droplet-based high-throughput single-microbe RNA-seq assay (smRandom-seq), using random primers for in situ cDNA generation, droplets for single-microbe barcoding, and CRISPR-based rRNA depletion for mRNA enrichment. smRandom-seq showed a high species specificity (99%), a minor doublet rate (1.6%), a reduced rRNA percentage (32%), and a sensitive gene detection (a median of ~1000 genes per single
E. coli
). Furthermore, smRandom-seq successfully captured transcriptome changes of thousands of individual
E. coli
and discovered a few antibiotic resistant subpopulations displaying distinct gene expression patterns of SOS response and metabolic pathways in
E. coli
population upon antibiotic stress. smRandom-seq provides a high-throughput single-microbe transcriptome profiling tool that will facilitate future discoveries in microbial resistance, persistence, microbe-host interaction, and microbiome research.
Bipolar disorder, as a major mental illness, has a high lifetime suicide attempt rate in patients, and suicidal behavior is most likely to occur during depressive episodes. Therefore, in-depth study ...of its mechanism is essential for prevention, early detection and intervention of suicide. With the development of magnetic resonance imaging (MRI) technology, it has been found that there are abnormalities in the brain structure and function in suicidal patients with bipolar disorder. This article reviews the studies on suicide in bipolar disorder patients by MRI from four aspects: structure, function, structure-function, and central metabolism and cerebral blood flow perfusion, and summarizes the suicide-related changes. This review focuses on distinguishing the brain MRI changes under different mood states and diverse definitions of suicide, aiming to provide reference for further exploration of the pathophysiological mechanism of suicide in bipolar disorder.
Extravillous trophoblast (EVT) cell invasion is a tightly regulated process that requires for a normal pregnancy. The epithelial-mesenchymal transition (EMT) has been implicated in EVT cell invasion. ...Growth differentiation factor-8 (GDF-8), a member of the transforming growth factor-beta (TGF-β) superfamily, is expressed in the human placenta and promotes EVT cell invasion by upregulating the expression of matrix metalloproteinase 2 (MMP2). However, the underlying molecular mechanism of GDF-8-induced MMP2 expression remains undetermined. Therefore, the present study aims to examine the role of Snail and Slug, the EMT-related transcriptional regulators, in GDF-8-stimulated MMP2 expression and cell invasion in HTR-8/SVneo human EVT cell line and primary cultures of human EVT cells.
HTR-8/SVneo and primary cultures of human EVT cells were used to examine the effect of GDF-8 on MMP2 expression and explore the underlying mechanism. For gene silencing and overexpression, the HTR-8/SVneo cell line was used to make the experiments more technically feasible. The cell invasiveness was measured by Matrigel-coated transwell invasion assay.
GDF-8 stimulated MMP2 expression in both HTR-8/SVneo and primary EVT cells. The stimulatory effect of GDF-8 on MMP2 expression was blocked by the inhibitor of TGF-β type-I receptors, SB431542. Treatment with GDF-8 upregulated Snail and Slug expression in both HTR-8/SVneo and primary EVT cells. The stimulatory effects of GDF-8 on Snail and Slug expression were blocked by pretreatment of SB431542 and siRNA-mediated knockdown of SMAD4. Interestingly, using the siRNA knockdown approach, our results showed that Snail but not Slug was required for the GDF-8-induced MMP2 expression and cell invasion in HTR-8/SVneo cells. The reduction of MMP2 expression in the placentas with preeclampsia (PE) was also observed.
These findings discover the physiological function of GDF-8 in the human placenta and provide important insights into the regulation of MMP2 expression in human EVT cells. Video Abstract.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Epigallocatechin‐3‐gallate (EGCG) is the most abundant and biologically active catechins extracted from green tea. The health benefits of EGCG have been extendedly studied. Ovarian steroidogenesis ...plays a pivotal role in maintaining normal reproductive function. Granulosa cells in the ovary are essential for steroid hormone production. To date, the effect of EGCG on steroidogenesis in human granulosa cells remains unclear. In the present study, we examine the physiological concentrations of EGCG on steroidogenesis in a steroidogenic human granulosa‐like tumor cell line, KGN. Our results demonstrate that treatment with EGCG upregulates steroidogenic acute regulatory protein (StAR) expression and increases progesterone (P4) production. EGCG does not affect the expression levels of other steroidogenesis‐related enzymes, such as P450 side‐chain cleavage enzyme, 3β‐hydroxysteroid dehydrogenase, and aromatase. In addition, we identify the expression of 67‐kDa laminin receptor (67LR) in KGN cells. Moreover, EGCG‐induced StAR expression and P4 production require the 67LR‐mediated activation of the PKA‐CREB signaling pathway. These results provide a better understanding of the function of EGCG on ovarian steroidogenesis, which may lead to the development of alternative therapeutic approaches for reproductive disorders.
This study demonstrates the stimulatory effect of the epigallocatechin‐3‐gallate (EGCG) on StAR expression and progesterone production in human granulosa cells. These effects are mediated by 67LR and require the 67LR‐mediated activation of the PKA‐CREB signaling pathway.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A novel aptamer-based fluorescent-sensing platform with a triple-helix molecular switch (THMS) was proposed as a switch for detecting the arsenic(III) ion. The triple helix structure was prepared by ...binding a signal transduction probe and arsenic aptamer. Additionally, the signal transduction probe labeled with fluorophore (FAM) and quencher (BHQ1) was employed as a signal indicator. The proposed aptasensor is rapid, simple and sensitive, with a limit of detection of 69.95 nM. The decrease in peak fluorescence intensity shows a linear dependence, with the concentration of As(III) in the range of 0.1 µM to 2.5 µM. The whole detection process takes 30 min. Moreover, the THMS-based aptasensor was also successfully used to detect As(III) in a real sample of Huangpu River water with good recoveries. The aptamer-based THMS also presents distinct advantages in stability and selectivity. The proposed strategy developed herein can be extensively applied in the field of food inspection.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
