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The gut microbiota regulates the biological processes of organisms acting like ‘another’ genome, affecting the health and disease of the host. MicroRNAs, as important physiological regulators, have been found to be involved in health and disease. Recently, the gut microbiota has been reported to affect host health by regulating host miRNAs. For example, Fusobacterium nucleatum could aggravate chemoresistance of colorectal cancer by decreasing the expression of miR-18a* and miR-4802. What’s more, miRNAs can shape the gut microbiota composition, ultimately affecting the host's physiology and disease. miR-515-5p and miR-1226-5p could promote the growth of Fusobacterium nucleatum ( Fn ) and Escherichia coli ( E.coli ), which have been reported to drive colorectal cancer. Here, we will review current findings of the interactions between the gut microbiota and microRNAs and discuss how the gut microbiota–microRNA interactions affect host pathophysiology including intestinal, neurological, cardiovascular, and immune health and diseases.

Hepatocyte growth factor (HGF) is a peptide-containing multifunctional cytokine that acts on various epithelial cells to regulate cell growth, movement and morphogenesis, and tissue regeneration of injured organs. HGF is sequestered by heparin-like protein in its inactive form and is widespread in the extracellular matrix of most tissues. When the liver loses its average mass, volume, or physiological and biochemical functions due to various reasons, HGF binds to its specific receptor c-Met (cellular mesenchymal-epithelial transition) and transmits the signals into the cells, and triggers the intrinsic kinase activity of c-Met. The downstream cascades of HGF/c-Met include JAK/STAT3, PI3K/Akt/NF-κB, and Ras/Raf pathways, affecting cell proliferation, growth, and survival. HGF has important clinical significance for liver fibrosis, hepatocyte regeneration after inflammation, and liver regeneration after transplantation. And the development of HGF as a biological drug for regenerative therapy of diseases, that is, using recombinant human HGF protein to treat disorders in clinical trials, is underway. This review summarizes the recent findings of the HGF/c-Met signaling functions in liver regeneration.

Aging is associated with age-related diseases and an increase susceptibility of cancer. Dissecting the molecular mechanisms that underlie aging and longevity would contribute to implications for preventing and treating the age-dependent diseases or cancers. Multiple signaling pathways such as the insulin/IGF-1 signaling pathway, TOR signaling, AMPK pathway, JNK pathway and germline signaling have been found to be involved in aging and longevity. And DAF-16/FOXO, as a key transcription factor, could integrate different signals from these pathways to modulate aging, and longevity via shuttling from cytoplasm to nucleus. Hence, understanding how DAF-16/FOXO functions will be pivotal to illustrate the processes of aging and longevity. Here, we summarized how DAF-16/FOXO receives signals from these pathways to affect aging and longevity. We also briefly discussed the transcriptional regulation and posttranslational modifications of DAF-16/FOXO, its co-factors as well as its potential downstream targets participating in lifespan according to the published data in and in mammals, and in most cases, we may focus on the studies in which has been considered to be a very good animal model for longevity research.

Esophageal squamous cell carcinoma (ESCC) is a highly prevalent tumor and is associated with ethnicity, genetics, and dietary intake. Non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) have been reported as functional regulatory molecules involved in the development of many human cancers, including ESCC. Recently, several ncRNAs have been detected as oncogenes or tumor suppressors in ESCC progression. These ncRNAs influence the expression of specific genes or their associated signaling pathways. Moreover, interactions of ncRNAs are evident in ESCC, as miRNAs regulate the expression of lncRNAs, and further, lncRNAs and circRNAs function as miRNA sponges to compete with the endogenous RNAs. Here, we discuss and summarize the findings of recent investigations into the role of ncRNAs (miRNAs, lncRNAs, and circRNAs) in the development and progression of ESCC and how their interactions regulate ESCC development.

Superelasticity associated with the martensitic transformation has found a broad range of engineering applications 1 , 2 . However, the intrinsic hysteresis 3 and temperature sensitivity 4 of the first-order phase transformation significantly hinder the usage of smart metallic components in many critical areas. Here, we report a large superelasticity up to 15.2% strain in [001]-oriented NiCoFeGa single crystals, exhibiting non-hysteretic mechanical responses, a small temperature dependence and high-energy-storage capability and cyclic stability over a wide temperature and composition range. In situ synchrotron X-ray diffraction measurements show that the superelasticity is correlated with a stress-induced continuous variation of lattice parameter accompanied by structural fluctuation. Neutron diffraction and electron microscopy observations reveal an unprecedented microstructure consisting of atomic-level entanglement of ordered and disordered crystal structures, which can be manipulated to tune the superelasticity. The discovery of the large elasticity related to the entangled structure paves the way for exploiting elastic strain engineering and development of related functional materials. NiCoFeGa single crystals exhibit large non-hysteretic superelasticity over broad temperature and composition ranges. It is attributed to the continuous phase transition with applied stress, which is related to the fluctuation of entangled ordered and disordered crystal structures.

GPBAR1/TGR5 is a novel plasma membrane-bound G protein-coupled bile acid (BA) receptor. BAs are known to induce the expression of inflammatory cytokines in the liver with unknown mechanism. Here we show that without other external stimuli, TGR5 activation alone induced the expression of interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α) in murine macrophage cell line RAW264.7 or murine Kupffer cells. The TGR5-mediated increase of pro-inflammatory cytokine expression was suppressed by JNK inhibition. Moreover, the induced pro-inflammatory cytokine expression in mouse liver by 1% cholic acid (CA) diet was blunted in JNK-/- mice. TGR5 activation by its ligands enhanced the phosphorylation levels, DNA-binding and trans-activities of c-Jun and ATF2 transcription factors. Finally, the induced pro-inflammatory cytokine expression in Kupffer cells by TGR5 activation correlated with the suppression of Cholesterol 7α-hydroxylase (Cyp7a1) expression in murine hepatocytes. These results suggest that TGR5 mediates the BA-induced pro-inflammatory cytokine production in murine Kupffer cells through JNK-dependent pathway. This novel role of TGR5 may correlate to the suppression of Cyp7a1 expression in hepatocytes and contribute to the delicate BA feedback regulation.

Background The gut microbiome is the totality of microorganisms, bacteria, viruses, protozoa, and fungi within the gastrointestinal tract. The gut microbiome plays key roles in various physiological and pathological processes through regulating varieties of metabolic factors such as short-chain fatty acids, bile acids and amino acids. Nuclear receptors, as metabolic mediators, act as a series of intermediates between the microbiome and the host and help the microbiome regulate diverse processes in the host. Recently, nuclear receptors such as farnesoid X receptor, peroxisome proliferator-activated receptors, aryl hydrocarbon receptor and vitamin D receptor have been identified as key regulators of the microbiome-host crosstalk. These nuclear receptors regulate metabolic processes, immune activity, autophagy, non-alcoholic and alcoholic fatty liver disease, inflammatory bowel disease, cancer, obesity, and type-2 diabetes. Conclusion In this review, we have summarized the functions of the nuclear receptors in the gut microbiome-host axis in different physiological and pathological conditions, indicating that the nuclear receptors may be the good targets for treatment of different diseases through the crosstalk with the gut microbiome.

Apelin, an endogenous neuropeptide, has been identified as the cognate ligand for the G-protein-coupled receptor APJ. Apelin, APJ messenger RNA, and protein are widely expressed in the central nervous system and peripheral tissues of humans and animals. The apelin/APJ system has been implicated in diverse physiological and pathological processes. The present article reviews the progress of the latest research investigating the apelin/APJ system in pain, depression, anxiety, memory, epilepsy, neuroprotection, stroke, and brain injury and protection, and highlights its promising potential as a therapeutic target for treatment of psychosis and neuropathy.

Spexin (SPX), also called neuropeptide Q (NPQ), is a novel endogenous neuropeptide. Spexin gene and protein are widely expressed in central nervous system and peripheral tissues in humans, rodents, goldfish, etc. A few of physiological and pathological roles of spexin are gradually emerged recently. This article summarized the roles of spexin in feeding behavior, gastrointestinal motility, obesity, diabetes, energy metabolism, endocrine, mental diseases, and cardiovascular function. Given the broad roles of spexin, this neuropeptide has attracted much interest from investigators and will be as a promising future target for novel therapeutic research and drug design.

The overactivation of canonical Wnt/β‐catenin pathway and the maintenance of cancer stem cells (CSCs) are essential for the onset and malignant progression of most human cancers. However, their regulatory mechanism in colorectal cancer (CRC) has not yet been well demonstrated. Low‐density lipoprotein receptor‐related protein 5 (LRP5) has been identified as an indispensable co‐receptor with frizzled family members for the canonical Wnt/β‐catenin signal transduction. Herein, we show that activation of LRP5 gene promotes CSCs‐like phenotypes, including tumorigenicity and drug resistance in CRC cells, through activating the canonical Wnt/β‐catenin and IL‐6/STAT3 signalling pathways. Clinically, the expression of LRP5 is upregulated in human CRC tissues and closely associated with clinical stages of patients with CRC. Further analysis showed silencing of endogenous LRP5 gene is sufficient to suppress the CSCs‐like phenotypes of CRC through inhibiting these two pathways. In conclusion, our findings not only reveal a regulatory cross‐talk between canonical Wnt/β‐catenin signalling pathway, IL‐6/STAT3 signalling pathway and CD133‐related stemness that promote the malignant behaviour of CRC, but also provide a valuable target for the diagnosis and treatment of CRC.