Corrigendum: Peroxisome proliferator-activated receptor-α: A pivotal regulator of the gastrointestinal tract.

[This corrects the article DOI: 10.3389/fmolb.2022.864039.].

An Unexpected Alteration Colonic Mucus Appearance in the Constipation Model via an Intestinal Microenvironment.

Due to the lack of research between the inner layers in the structure of colonic mucous and the metabolism of fatty acid in the constipation model, we aim to determine the changes in the mucous phenotype of the colonic glycocalyx and the microbial community structure following treatment with Rhubarb extract in our research. The constipation and treatment models are generated using adult male C57BL/6N mice. We perform light microscopy and transmission electron microscopy (TEM) to detect a Muc2-rich inner mucus layer attached to mice colon under different conditions. In addition, 16S rDNA sequencing is performed to examine the intestinal flora. According to TEM images, we demonstrate that Rhubarb can promote mucin secretion and find direct evidence of dendritic structure-linked mucus structures with its assembly into a lamellar network in a pore size distribution in the isolated colon section. Moreover, the diversity of intestinal flora has noticeable changes in constipated mice. The present study characterizes a dendritic structure and persistent cross-links have significant changes accompanied by the alteration of intestinal flora in feces in models of constipation and pretreatment with Rhubarb extract.

Peroxisome Proliferator-Activated Receptor-α: A Pivotal Regulator of the Gastrointestinal Tract.

Peroxisome proliferator-activated receptor (PPAR)-α is a ligand-activated transcription factor distributed in various tissues and cells. It regulates lipid metabolism and plays vital roles in the pathology of the cardiovascular system. However, its roles in the gastrointestinal tract (GIT) are relatively less known. In this review, after summarizing the expression profile of PPAR-α in the GIT, we analyzed its functions in the GIT, including physiological control of the lipid metabolism and pathologic mediation in the progress of inflammation. The mechanism of this regulation could be achieved <i>via</i> interactions with gut microbes and further impact the maintenance of body circadian rhythms and the secretion of nitric oxide. These are also targets of PPAR-α and are well-described in this review. In addition, we also highlighted the potential use of PPAR-α in treating GIT diseases and the inadequacy of clinical trials in this field.

GLP-1 and Underlying Beneficial Actions in Alzheimer's Disease, Hypertension, and NASH.

GLP-1 is derived from intestinal L cells, which takes effect through binding to GLP-1R and is inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Since its discovery, GLP-1 has emerged as an incretin hormone for its facilitation in insulin release and reduction of insulin resistance (IR). However, GLP-1 possesses broader pharmacological effects including anti-inflammation, neuro-protection, regulating blood pressure (BP), and reducing lipotoxicity. These effects are interconnected to the physiological and pathological processes of Alzheimer's disease (AD), hypertension, and non-alcoholic steatohepatitis (NASH). Currently, the underlying mechanism of these effects is still not fully illustrated and a better understanding of them may help identify promising therapeutic targets of AD, hypertension, and NASH. Therefore, we focus on the biological characteristics of GLP-1, render an overview of the mechanism of GLP-1 effects in diseases, and investigate the potential of GLP-1 analogues for the treatment of related diseases in this review.

Functions of Dendritic Cells and Its Association with Intestinal Diseases.

Dendritic cells (DCs), including conventional DCs (cDCs) and plasmacytoid DCs (pDCs), serve as the sentinel cells of the immune system and are responsible for presenting antigen information. Moreover, the role of DCs derived from monocytes (moDCs) in the development of inflammation has been emphasized. Several studies have shown that the function of DCs can be influenced by gut microbes including gut bacteria and viruses. Abnormal changes/reactions in intestinal DCs are potentially associated with diseases such as inflammatory bowel disease (IBD) and intestinal tumors, allowing DCs to be a new target for the treatment of these diseases. In this review, we summarized the physiological functions of DCs in the intestinal micro-environment, their regulatory relationship with intestinal microorganisms and their regulatory mechanism in intestinal diseases.

Rhubarb extract relieves constipation by stimulating mucus production in the colon and altering the intestinal flora.

BACKGROUND: Constipation, mainly characterized by the difficulty in defecation, is a clinical symptom caused by a variety of factors. It can be manifested as normal or slow colonic transport abnormalities, which can occur alone or concurrently with defecation disorders. As there is not uniform definition and assessment standard, no clear plan could be used for the treatment of constipation. Although rhubarb, a traditional Chinese medicine, plays a therapeutic role in diseases involving constipation symptoms, the detailed mechanism of it in treating constipation remains unclear. METHODS: A model of constipation-induced by diphenoxylate was prepared. Immunofluorescent staining was used to detect the expression of mucin 2 (MUC2), calnexin and chymase in colon. Western blotting was used to detect changes of tryptase and calnexin in the colon. And real-time polymerase chain reaction (PCR) was utilized to detect the changes of immunoglobulin-binding protein (Bip), X-box binding protein 1 (Xbp1) and C/EBP homologous protein (CHOP) of colonic goblet cells in mRNA levels. ELISA and biochemical kits were utilized to detect the changes of MUC2, Trefoil factor 3 (TFF3), acetylcholine, histamine and C-C motif chemokine ligand 5 (CCL5) in the colon. And the changes of colonic mucosa and intestinal flora of constipation model mice caused by rhubarb extract (RE) were analyzed to identify the mechanism of RE on the treatment of constipation. RESULTS: RE promotes the secretion of colonic mucus by recruiting mast cells and enhancing the content of histamine and Ach in the mice colon. In the process, RE causes up-regulation of Bip and CHOP mRNA expression and down-regulation of Xbp1 and Xbp1s mRNA expression that induces ER stress of colonic epithelium associated with changes in the intestinal flora diversity and short-chain fatty acids content. CONCLUSION: RE could relieve constipation by promoting the secretion of colonic mucus via mast cells activation and improving the intestinal microenvironment.

lncRNA KLF3-AS1 Suppresses Cell Migration and Invasion in ESCC by Impairing miR-185-5p-Targeted KLF3 Inhibition.

Esophageal squamous cell carcinoma (ESCC) is a common cancer occurring in males and females worldwide. Accumulating evidence continues to highlight the crucial roles of long non-coding RNAs (lncRNAs) in the process of tumorigenesis. However, the regulatory mechanism of lncRNAs in ESCC remains unclear. The aim of this study is to elucidate the role of lncRNA Krüppel-like factor 3 antisense RNA 1 (KLF3-AS1) in ESCC by regulating miR-185-5p and KLF3. Initially, ESCC cell spheres with stem cell-like properties were prepared by suspension culture, and subsequently characterized by assessing colony formation ability and stem cell markers. LncRNA KLF3-AS1 was found to be poorly expressed in ESCC and could upregulate the expression of KLF3 by binding to miR-185-5p. lncRNA KLF3-AS1 upregulation was observed to inhibit miR-185-5p, thereby contributing to decreased expression of SOX2 and Oct4 (octamer-binding transcription factor 4). Furthermore, enhancement of lncRNA KLF3-AS1 resulted in reduced colony formation ability, cell invasion and migration, and tumor volume in vivo while promoting cell apoptosis in ESCC through downregulation of miR-185-5p. Collectively, this study indicated that lncRNA KLF3-AS1 inhibited ESCC cell invasion and migration by impairing miR-185-5p-mediated inhibition of KLF3, highlighting a promising novel potential target for ESCC treatment.

Atomically Precise Gold-Levonorgestrel Nanocluster as a Radiosensitizer for Enhanced Cancer Therapy.

Gold nanoclusters have become promising radiosensitizers due to their ultrasmall size and robust ability to adsorb, scatter, and re-emit radiation. However, most of the previously reported gold nanocluster radiosensitizers do not have a precise atomic structure, causing difficulties in understanding the structure-activity relationship. In this study, a structurally defined gold-levonorgestrel nanocluster consisting of Au8(C21H27O2)8 (Au8NC) with bright luminescence (58.7% quantum yield) and satisfactory biocompatibility was demonstrated as a nanoradiosensitizer. When the Au8NCs were irradiated with X-rays, they produced reactive oxygen species (ROS), resulting in irreversible cell apoptosis. As indicated by in vivo tumor formation experiments, tumorigenicity was significantly suppressed after one radiotherapy treatment with the Au8NCs. In addition, compared with tumors treated with X-rays (4 Gy) alone, tumors treated with the nanosensitizer exhibited an inhibition rate of 74.2%. This study contributes to the development of atomically precise gold nanoclusters as efficient radiosensitizers.

Two N,N'-bis-(pyridin-4-yl)pyridine-2,6-dicarboxamide coordination compounds.

The molecular structures of tetra-aqua-[N,N'-bis-(pyridin-4-yl)pyridine-2,6-dicar-boxamide]-sulfatomanganese(II) dihydrate, [Mn(SO4)(C17H13N5O2)(H2O)4]·2H2O or [Mn(H2L1)(SO4)(H2O)4]·2H2O, (I), and tetra-aqua-bis[N,N'-bis-(pyridin-4-yl)pyridine-2,6-dicar-boxamide]cadmium(II) sulfate tetra-hydrate, [Cd(C17H13N5O2)2(H2O)4]SO4·4H2O or [Cd(H2O)4(H2L1)2]·SO4·4H2O, (II), both contain a central metal atom in a distorted octa-hedral geometry coordinated equatorially by four oxygen atoms from water mol-ecules. In (I), the axial positions are occupied by a nitro-gen atom from H2L1 and an oxygen atom from the sulfate anion, whereas in (II), the axial positions contain two nitro-gen atoms from two different H2L1 ligands and the sulfate anion acts as the charge-balancing ion. π-π stacking between pyridine rings and a network of hydrogen bonds involving the water molecules and the sulfate anions play a crucial role in the mol-ecular self-assembly of the two structures.