Calcified chondroid mesenchymal neoplasm: report of a case involving the temporomandibular joint region and review of the literature.

The calcified chondroid mesenchymal neoplasm (CCMN) represents a recently recognized tumor type with only 50 well-documented cases in the English-language literature. Herein we report an additional case of CCMN presenting as a large mass in the temporomandibular joint region of a 41-year-old female. A review of previously reported cases and the current case of CCMN shows the following features: 1) average age 52 years (range 14-87 years) and an approximately even sex distribution; 2) most frequently involved sites: distal extremities (including foot, hand, wrist, forearm) (n=41) and temporomandibular joint/temporal/parotid region (n=9); 3) multilobular soft tissue tumor with chondroid to cartilaginous matrix, often grungy or lace-like calcifications, and variable cytologic atypia; 4) frequently detected FN1 rearrangement (n=15), including FN1 fusion with FGFR2 (n=7) or other receptor tyrosine kinases; 5) 2 reported local recurrences (after incomplete excision); 6) no reports of malignant biologic behavior.

Benefits of heat-killed Lactobacillus acidophilus on growth performance, nutrient digestibility, antioxidant status, immunity, and cecal microbiota of rabbits.

Introduction: Heat-killed probiotics, as a type of inactivated beneficial microorganisms, possess an extended shelf life and broader adaptability compared to their live counterparts. This study aimed to investigate the impact of heat-killed Lactobacillus acidophilus (L. acidophilus, LA) - a deactivated probiotic on the growth performance, digestibility, antioxidant status, immunity and cecal microbiota of rabbits. Methods: Two hundred weaned Hyla rabbits were randomly allocated into five equal groups (CON, L200, L400, L600, and L800). Over a 28-day period, the rabbits were fed basal diets supplemented with 0, 200, 400, 600, and 800 mg/kg of heat-killed LA, respectively. Results: Results revealed a significant reduction in the feed-to-gain ratio (F/G) in the L600 and L800 groups (p < 0.05). Additionally, the L800 group exhibited significantly higher apparent digestibility of crude fiber (CF) and crude protein (CP) (p < 0.05). Regarding digestive enzyme activities, enhanced trypsin and fibrinase activities were observed in the L600 and L800 groups (p < 0.05). Concerning the regulation of the body's antioxidant status, the L800 group demonstrated elevated levels of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) in both serum and ileal tissue (p < 0.05). In terms of immune capacity modulation, serum tumor necrosis factor-α (TNF-α) levels were significantly lower in the L600 and L800 groups (p < 0.05), while immunoglobulin A (IgA) and immunoglobulin M (IgM) levels were higher (p < 0.05). Additionally, the L800 group exhibited a substantial increase in secretory immunoglobulin A (SIgA) levels in the intestinal mucosa (p < 0.05). In comparison to the CON group, the L800 group exhibited a significant increase in the relative abundance of Phascolarctobacterium and Alistipes in the cecum (p < 0.05). Phascolarctobacterium demonstrated a positive correlation with SIgA (p < 0.05), IgM (p < 0.01), and Glutathione peroxidase (GSH-Px) (p < 0.05), while displaying a negative correlation with TNF-α levels (p < 0.05). Concurrently, Alistipes exhibited positive correlations with IgA (p < 0.05), IgM (p < 0.05), SIgA (p < 0.01), GSH-Px (p < 0.05), SOD (p < 0.05), and T-AOC (p < 0.01), and a negative correlation with TNF-α (p < 0.05). Discussion: In conclusion, the dietary incorporation of 600 mg/kg and 800 mg/kg of heat-killed LA positively influenced the growth performance, nutrient digestibility, antioxidant status, immune capacity and cecal microbiota of rabbits. This highlights the potential benefits of utilizing heat-killed probiotics in animal nutrition.

Cancer diagnosis using label-free SERS-based exosome analysis.

Exosomes, carrying distinctive biomolecules reflective of their parent cell's status and origin, show promise as liquid biopsy biomarkers for cancer diagnosis. However, their clinical translation remains challenging due to their relatively low concentration in body fluids. Surface-Enhanced Raman spectroscopy (SERS) has recently gained significant attention as a label-free and sensitive technique for exosome analysis. This review explores label-free SERS for exosome detection, covering exosome isolation and characterization methods, advancements in SERS substrates, and fingerprint analysis techniques using machine learning. Furthermore, we emphasize the challenges and offer insights into the future prospects of SERS-based exosome analysis to enhance cancer diagnosis.

Butyrate alleviates alcoholic liver disease-associated inflammation through macrophage regulation and polarization via the HDAC1/miR-155 axis.

BACKGROUND: We recently found that butyrate could ameliorate inflammation of alcoholic liver disease (ALD) in mice. However, the exact mechanism remains incompletely comprehended. Here, we examined the role of butyrate on ALD-associated inflammation through macrophage (Mψ) regulation and polarization using in vivo and in vitro experiments. METHODS: For in vivo experiments, C57BL/6J mice were fed modified Lieber-DeCarli liquid diets supplemented with or without ethanol and sodium butyrate (NaB). After 6 weeks of treatment, mice were euthanized and associated indicators were analyzed. For in vitro experiments, lipopolysaccharide (LPS)-induced inflammatory murine RAW264.7 cells were treated with NaB or miR-155 inhibitor/mimic to verify the anti-inflammatory effect and underlying mechanism. RESULTS: The administration of NaB alleviated pathological damage and associated inflammation, including LPS, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß levels in ALD mice. NaB intervention restored the imbalance of macrophage polarization by inhibiting inducible nitric oxide synthase (iNOS) and elevating arginase-1 (Arg-1). Moreover, NaB reduced histone deacetylase-1 (HDAC1), nuclear factor kappa-B (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and miR-155 expression in ALD mice, but also increased peroxisome proliferator-activated receptor-γ (PPAR-γ). Thus, MiR-155 was identified as a strong regulator of ALD. To further penetrate the role of miR-155, LPS-stimulated RAW264.7 cells co-cultured with NaB were treated with the specific inhibitor or mimic. Intriguingly, miR-155 was capable of negatively regulated inflammation with NaB intervention by targeting SOCS1, SHIP1, and IRAK-M genes. CONCLUSION: Butyrate suppresses the inflammation in mice with ALD by regulating macrophage polarization via the HDAC1/miR-155 axis, which may potentially contribute to the novel therapeutic treatment for the disease.

Assessment for 11q and other chromosomal aberrations in large B-cell/high-grade B cell lymphomas of germinal center phenotype lacking BCL2 expression.

The WHO classifications of hematolymphoid malignancies have recognized several distinct entities within the large B cell lymphomas, including the more recently described high-grade B cell lymphoma with 11q aberration (HGBCL-11q). We utilized genomic array to assess for chromosome 11q abnormalities in a broad set of aggressive B cell lymphomas from 27 patients with a focus on younger adults. The findings suggest more frequent alterations of 11q in diffuse large B cell lymphoma (DLBCL)/HGBCL-GC BCL2-, in comparison to cases of Burkitt lymphoma (BL) or DLBCL-GC BCL2+, and confirm a low genomic complexity score of BL. Variability identified in patterns of 11q alterations suggests genomic array studies may afford value over FISH testing as we continue to understand HGBCL-11q as a distinct entity, and interrogate cases of DLBCL/HGBCL-GC BCL2-.

Delay-dependent Lurie-Postnikov type Lyapunov-Krasovskii functionals for stability analysis of discrete-time delayed neural networks.

This paper addresses the influence of time-varying delay and nonlinear activation functions with sector restrictions on the stability of discrete-time neural networks. Compared to previous works that mainly focuses on the influence of delay information, this paper devotes to activation nonlinear functions information to help compensate the analysis technique based on Lyapunov-Krasovskii functional (LKF). A class of delay-dependent Lurie-Postnikov type integral terms involving sector constraints of nonlinear activation function is proposed to complement the LKF construction. The less conservative criteria for the stability analysis of discrete-time delayed networks is given by using improved LKF. Numerical examples show that conservatism can be reduced by the delay-dependent integral terms involving nonlinear activation functions.

Microvascular reperfusion of fibrinolysis followed by percutaneous coronary intervention versus primary percutaneous coronary intervention for ST-segment-elevation acute myocardial infarction.

Background: Primary percutaneous coronary intervention (PPCI) has been widely recognized as the preferred treatment for ST-segment-elevation myocardial infarction (STEMI). However, substantial numbers of STEMI patients cannot receive timely PPCI. Early fibrinolysis followed by routine percutaneous coronary intervention (FPCI) has been proposed as an effective and safe alternative for eligible patients. To date, few studies have compared FPCI with PPCI in terms of microvascular reperfusion. This study aimed to evaluate the microvascular function of FPCI and PPCI. Methods: STEMI patients at the Peking University First Hospital and Miyun Hospital were enrolled in this retrospective study between January 2015 to December 2020. Microvascular function documented by the coronary angiography-derived index of microvascular resistance (caIMR) was measured at the final angiogram after revascularization. The primary end point was the caIMR of the culprit vessels. The secondary end points were in-hospital and follow-up major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal recurrent myocardial infarction, target-vessel revascularization (TVR), and non-fatal stroke/transient ischemic attacks (TIA). Details of the adverse clinical events were obtained from telephone interviews and electronic medical record systems until January 2022. Results: In total, 496 STEMI patients were enrolled in this cross-sectional retrospective study. Of these patients, 81 underwent FPCI, and 415 underwent PPCI. At the baseline, the PPCI patients had a higher-risk profile than the FPCI patients. The time from symptom onset to reperfusion therapy was significantly shorter in the FPCI group than the PPCI group (median 3.0 vs. 4.5 hours; P<0.001). The caIMR was significantly lower in the FPCI group than the PPCI group (median 20.34 vs. 40.33; P<0.001). The median follow-up duration was 4.1 years. During the follow-up period, the rate of MACE was lower in the FPCI group than the PPCI group [7 (10.1%) vs. 82 (20.8%), P=0.048]. After propensity score matching to adjust for the imbalances at the baseline, the caIMR remained significant and the clinical outcomes did not differ significantly between the two groups. Conclusions: In eligible STEMI patients, clinically successful FPCI may be associated with better microvascular reperfusion and comparable clinical outcomes as compared with PPCI.

Sodium Selenite Ameliorates Silver Nanoparticles Induced Vascular Endothelial Cytotoxic Injury by Antioxidative Properties and Suppressing Inflammation Through Activating the Nrf2 Signaling Pathway.

Silver nanoparticles (AgNP) are the dominant nanomaterials in commercial products and the medical field, but the widespread occurrence of AgNP has become a global threat to human health. Growing studies indicate that AgNP exposure can induce vascular endothelial toxicity by excessive oxidative stress and inflammation, which is closely related to cardiovascular disease (CVD), but the potential intrinsic mechanism remains poorly elucidated. Thus, it has been crucial to control the toxicological effects of AgNP in order to improve their safety and increase the outcome of their applications.Multiple researches have demonstrated that sodium selenite (Se) possesses the capability to counteract the toxicity of AgNP, but the functional role of Se in AgNP-induced CVD is largely unexplored. The aim of this study was to explore the potential protective effect of Se on AgNP-induced vascular endothelial lesion and elucidate the underlying mechanisms. An in vivo model of toxicity in animals was established by the instillation of 200 µL of AgNP into the trachea of rats both with (0.2 mg/kg/day) and without Se treated. In vitro experiments, human umbilical vein endothelial cells (HUVECs) were incubated with AgNP (0.3 µg/mL ) and Se for a duration of 24 h. Utilizing transmission electron microscopy, we observed that the internalization of AgNP-induced endothelial cells was desquamated from the internal elastic lamina, the endoplasmic reticulum was dilated, and the medullary vesicle formed. Se treatment reduced the levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), inhibited the release of pro-inflammatory cytokines (specifically tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6), improved endothelial cell permeability, integrity, and dysfunction, and prevented damage to the aortic endothelium caused by AgNP. Importantly, we found that Se showed the capacity against AgNP with biological functions in guiding the intracellular reactive oxygen species (ROS) scavenging and meanwhile exhibiting anti-inflammation effects. Se supplementation decreased the intracellular ROS release and suppressed NOD-like receptor protein 3 (NLRP3) and nuclear factor kappa-B (NF-κB) mediated inflammation within AgNP-intoxicated rats and HUVECs. The anti-oxidant stress and anti-inflammatory effects of Se were at least partly dependent on nuclear factor erythroid 2-related factor 2 (Nrf2). Overall, our results indicated that the protectiveness of Se against AgNP-induced vascular endothelial toxicity injury was at least attributed to the inhibition of oxidative ROS and pro-inflammatory NF-κB/NLRP3 inflammasome by activating the Nrf2 and antioxidant enzyme (HO-1) signal pathway.

Lactobacillus-driven feed fermentation regulates microbiota metabolism and reduces odor emission from the feces of pigs.

IMPORTANCE: Our present study showed that dietary supplementation with feed fermented by Lactobacillus could promote the growth performance of pigs, regulate the microbiota, and inhibit the growth of harmful bacteria. It could prevent the accumulation of toxic substances and reduce odor emission from pig feces, thereby reducing environmental pollution. In addition, one key triumph of the present study was the isolation of Weissella cibaria ZWC030, and the strain could inhibit the production of skatole in vitro in our present results.

Within-Host Resistance and Virulence Evolution of a Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae ST11 Under Antibiotic Pressure.

Background: Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) has recently aroused an extremely severe health challenge and public concern. However, the underlying mechanisms of fitness costs that accompany antibiotic resistance acquisition remain largely unexplored. Here, we report a hv-CRKP-associated fatal infection and reveal a reduction in virulence due to the acquisition of aminoglycoside resistance. Methods: The bacterial identification, antimicrobial susceptibility, hypermucoviscosity, virulence factors, MLST and serotypes were profiled.The clonal homology and plasmid acquisition among hv-CRKP strains were detected by XbaI and S1-PFGE. The virulence potential of the strains was evaluated using Galleria mellonella larvae infection model, serum resistance assay, capsular polysaccharide quantification, and biofilm formation assay. Genomic variations were identified using whole-genome sequencing (WGS). Results: Four K. pneumoniae carbapenemase (KPC)-producing CRKP strains were consecutively isolated from an 86-year-old patient with severe pneumonia. Whole-genome sequencing (WGS) showed that all four hv-CRKP strains belonged to the ST11-KL64 clone. PFGE analysis revealed that the four ST11-KL64 hv-CRKP strains could be grouped into the same PFGE type. Under the pressure of antibiotics, the antimicrobial resistance of the strains increased and the virulence potential decreased. Further sequencing, using the Nanopore platform, was performed on three representative isolates (WYKP586, WYKP589, and WYKP594). Genomic analysis showed that the plasmids of these three strains underwent a large number of breaks and recombination events under antibiotic pressure. We found that as aminoglycoside resistance emerged via acquisition of the rmtB gene, the hypermucoviscosity and virulence of the strains decreased because of internal mutations in the rmpA and rmpA2 genes. Conclusion: This study shows that ST11-KL64 hv-CRKP can further evolve to acquire aminoglycoside resistance accompanied by decreased virulence to adapt to antibiotic pressure in the host.

Strategies and Progress of Raman Technologies for Cellular Uptake Analysis of the Drug Delivery Systems.

Nanoparticle (NP)-based drug delivery systems have the potential to significantly enhance the pharmacological and therapeutic properties of drugs. These systems enhance the bioavailability and biocompatibility of pharmaceutical agents via enabling targeted delivery to specific tissues or organs. However, the efficacy and safety of these systems are largely dependent on the cellular uptake and intracellular transport of NPs. Thus, it is crucial to monitor the intracellular behavior of NPs within a single cell. Yet, it is challenging due to the complexity and size of the cell. Recently, the development of the Raman instrumentation offers a versatile tool to allow noninvasive cellular measurements. The primary objective of this review is to highlight the most recent advancements in Raman techniques (spontaneous Raman scattering, bioorthogonal Raman scattering, coherence Raman scattering, and surface-enhanced Raman scattering) when it comes to assessing the internalization of NP-based drug delivery systems and their subsequent movement within cells.

Phosphatidic acid binding to Patched contributes to the inhibition of Smoothened and Hedgehog signaling in Drosophila wing development.

Hedgehog (Hh) signaling controls growth and patterning during embryonic development and homeostasis in adult tissues. Hh binding to the receptor Patched (Ptc) elicits intracellular signaling by relieving Ptc-mediated inhibition of the transmembrane protein Smoothened (Smo). We uncovered a role for the lipid phosphatidic acid (PA) in the regulation of the Hh pathway in Drosophila melanogaster. Deleting the Ptc C-terminal tail or mutating the predicted PA-binding sites within it prevented Ptc from inhibiting Smo in wing discs and in cultured cells. The C-terminal tail of Ptc directly interacted with PA in vitro, an association that was reduced by Hh, and increased the amount of PA at the plasma membrane in cultured cells. Smo also interacted with PA in vitro through a binding pocket located in the transmembrane region, and mutating residues in this pocket reduced Smo activity in vivo and in cells. By genetically manipulating PA amounts in vivo or treating cultured cells with PA, we demonstrated that PA promoted Smo activation. Our findings suggest that Ptc may sequester PA in the absence of Hh and release it in the presence of Hh, thereby increasing the amount of PA that is locally available to promote Smo activation.

Clinical Validation of FusionPlex RNA Sequencing and Its Utility in the Diagnosis and Classification of Hematologic Neoplasms.

Recurrent gene rearrangements result in gene fusions that encode chimeric proteins, driving the pathogenesis of many hematologic neoplasms. The fifth edition World Health Organization classification and International Consensus Classification 2022 include an expanding list of entities defined by such gene rearrangements. Therefore, sensitive and rapid methods are needed to identify a broad range of gene fusions for precise diagnosis and prognostication. In this study, we validated the FusionPlex Pan-Heme panel analysis using anchored multiplex PCR/targeted RNA next-generation sequencing for routine clinical testing. Furthermore, we assessed its utility in detecting gene fusions in myeloid and lymphoid neoplasms. The validation cohort of 61 cases demonstrated good concordance between the FusionPlex Pan-Heme panel and other methods, including chromosome analysis, fluorescence in situ hybridization, RT-PCR, and Sanger sequencing, with an analytic sensitivity and specificity of 95% and 100%, respectively. In an independent cohort of 28 patients indicated for FusionPlex testing, gene fusions were detected in 21 patients. The FusionPlex Pan-Heme panel analysis reliably detected fusion partners and patient-specific fusion sequences, allowing accurate classification of hematologic neoplasms and the discovery of new fusion partners, contributing to a better understanding of the pathogenesis of the diseases.

Disruption of the Keap1-mTORC2 axis by cancer-derived Keap1/mLST8 mutations leads to oncogenic mTORC2-AKT activation.

The mechanistic target of the rapamycin (mTOR) pathway, which participates in the regulation of cellular growth and metabolism, is aberrantly regulated in various cancer types. The mTOR complex 2 (mTORC2), which consists of the core components mTOR, Rictor, mSin1, and mLST8, primarily responds to growth signals. However, the coordination between mTORC2 assembly and activity remains poorly understood. Keap1, a major sensor of oxidative stress in cells, functions as a substrate adaptor for Cullin 3-RING E3 ubiquitin ligase (CRL3) to promote proteasomal degradation of NF-E2-related factor 2 (NRF2), which is a transcription factor that protects cells against oxidative and electrophilic stress. In the present study, we demonstrate that Keap1 binds to mLST8 via a conserved ETGE motif. The CRL3Keap1 ubiquitin ligase complex promotes non-degradative ubiquitination of mLST8, thus reducing mTORC2 complex integrity and mTORC2-AKT activation. However, this effect can be prevented by oxidative/electrophilic stresses and growth factor signaling-induced reactive oxygen species (ROS) burst. Cancer-derived Keap1 or mLST8 mutations disrupt the Keap1-mLST8 interaction and allow mLST8 to evade Keap1-mediated ubiquitination, thereby enhancing mTORC2-AKT activation and promoting cell malignancy and remodeling cell metabolism. Our findings provide new insights into the molecular mechanisms of Keap1/mLST8 mutation-driven tumorigenesis by promoting mTORC2-AKT activation, which is independent of the canonical NRF2 pathway.

Comparison of Structural Features of CRISPR-Cas Systems in Thermophilic Bacteria.

The clustered regularly interspaced short palindromic repeat (CRISPR) is an adaptive immune system that defends most archaea and many bacteria from foreign DNA, such as phages, viruses, and plasmids. The link between the CRISPR-Cas system and the optimum growth temperature of thermophilic bacteria remains unclear. To investigate the relationship between the structural characteristics, diversity, and distribution properties of the CRISPR-Cas system and the optimum growth temperature in thermophilic bacteria, genomes of 61 species of thermophilic bacteria with complete genome sequences were downloaded from GenBank in this study. We used CRISPRFinder to extensively study CRISPR structures and CRISPR-associated genes (cas) from thermophilic bacteria. We statistically analyzed the association between the CRISPR-Cas system and the optimum growth temperature of thermophilic bacteria. The results revealed that 59 strains of 61 thermophilic bacteria had at least one CRISPR locus, accounting for 96.72% of the total. Additionally, a total of 362 CRISPR loci, 209 entirely distinct repetitive sequences, 131 cas genes, and 7744 spacer sequences were discovered. The average number of CRISPR loci and the average minimum free energy (MFE) of the RNA secondary structure of repeat sequences were positively correlated with temperature whereas the average length of CRISPR loci and the average number of spacers were negatively correlated. The temperature did not affect the average number of CRISPR loci, the average length of repeats, or the guanine-cytosine (GC) content of repeats. The average number of CRISPR loci, the average length of the repeats, and the GC content of the repeats did not reflect temperature dependence. This study may provide a new basis for the study of the thermophilic bacterial adaptation mechanisms of thermophilic bacteria.

Investigation of factors affecting sodium alginate fouling mechanisms in a microfiltration process under non-constant-flux and non-constant-pressure conditions.

Variations in transmembrane pressure and permeate flux are closely related to membrane fouling. In this study, a laboratory-scale submerged microfiltration system was used to investigate the influence of sodium alginate (SA) concentration and peristaltic pump rotation speed on the fouling under the conditions of (1) the same driving force and non-aerated-PAC, (2) different driving forces and non-aerated-PAC, and (3) different driving forces and aerated-PAC. The results showed that the normalized transmembrane pressure (TMP') increased linearly with decreasing normalized permeate flux (J') during the early microfiltration stage regardless of the operating conditions, indicating that the SA microfiltration process controlled by the peristaltic pump was non-constant-flux and non-constant-pressure. The latter filtration stage was considered constant-pressure filtration when 200-1,200 mg/L of SA was filtrated at the same rotation speed. During filtration of 800 mg/L of SA under the non-aerated-PAC condition, the later filtration stage was considered constant-pressure filtration when the peristaltic pump rotated at slower speeds of 15 and 30 rpm. This approached constant-flux filtration when the peristaltic pump rotated at faster speeds of 60 and 90 rpm, and PAC-aeration scouring was an effective measure for mitigating membrane fouling by SA.

Aspirin ameliorates atherosclerotic immuno-inflammation through regulating the Treg/Th17 axis and CD39-CD73 adenosine signaling via remodeling the gut microbiota in ApoE-/- mice.

The gut microbiome has been implicated in the development of cardiovascular disease (CVD) and atherosclerosis (AS), a chronic inflammatory condition. Aspirin may improve the immuno-inflammatory status in AS by regulating microbiota dysbiosis. However, the potential role of aspirin in modulating gut microbiota and microbial-derived metabolites remains less explored. In this study, we investigated the effect of aspirin treatment on AS progression by modulating gut microbiota and microbial-derived metabolites in apolipoprotein E-deficient (ApoE-/-) mice. We analyzed the fecal bacterial microbiome and targeted metabolites, including short-chain fatty acids (SCFAs) and bile acids (BAs). The immuno-inflammatory status of AS was evaluated by analyzing regulatory T cells (Tregs), Th17 cells, and the CD39-CD73 adenosine signaling pathway involved in purinergic signaling. Our results indicated that aspirin altered gut microbiota, leading to an increase in the phylum Bacteroidetes and a decrease in the Firmicutes to Bacteriodetes (F/B) ratio. Aspirin treatment also increased levels of targeted SCFA metabolites, such as propionic acid, valeric acid, isovaleric acid, and isobutyric acid. Furthermore, aspirin impacted BAs by reducing the level of harmful deoxycholic acid (DCA) and increasing the levels of beneficial isoalloLCA and isoLCA. These changes were accompanied by a rebalancing of the ratio of Tregs to Th17 cells and an increase in the expression of ectonucleotidases CD39 and CD73, thereby ameliorating inflammation. These findings suggest that aspirin has an athero-protective effect with an improved immuno-inflammatory profile, partially attributed to its manipulation of the gut microbiota.

CTHRC1, a novel gene with multiple functions in physiology, disease and solid tumors (Review).

Collagen triple helix repeat containing 1 (CTHRC1) is a gene discovered in 2005; it is highly conserved, and no homologous proteins have been disclosed thus far. A number of studies have shown that CTHRC1 is present in normal tissues and organs, and it has vital functions in physiological processes, including participating in the regulation of metabolism, arterial remodeling, bone formation and myelination of the peripheral nervous system. It has been reported that abnormal expression of CTHRC1 is involved in the carcinogenesis of various human organs, such as the breast, colon, pancreas, lung, stomach and liver. Therefore, the present review aims to collate all known findings and results on the regulation of CTHRC1 expression and related signaling pathways. To conclude, this review also provides a hypothesis of the functional mechanism of this gene.

HUNK inhibits epithelial-mesenchymal transition of CRC via direct phosphorylation of GEF-H1 and activating RhoA/LIMK-1/CFL-1.

Epithelial-mesenchymal transition (EMT) is associated with the invasive and metastatic phenotypes in colorectal cancer (CRC). However, the mechanisms underlying EMT in CRC are not completely understood. In this study, we find that HUNK inhibits EMT and metastasis of CRC cells via its substrate GEF-H1 in a kinase-dependent manner. Mechanistically, HUNK directly phosphorylates GEF-H1 at serine 645 (S645) site, which activates RhoA and consequently leads to a cascade of phosphorylation of LIMK-1/CFL-1, thereby stabilizing F-actin and inhibiting EMT. Clinically, the levels of both HUNK expression and phosphorylation S645 of GEH-H1 are not only downregulated in CRC tissues with metastasis compared with that without metastasis, but also positively correlated among these tissues. Our findings highlight the importance of HUNK kinase direct phosphorylation of GEF-H1 in regulation of EMT and metastasis of CRC.