Gut microbiota modulation: a narrative review on a novel strategy for prevention and alleviation of ovarian aging.

The global rise in life expectancy corresponds with a delay in childbearing age among women. Ovaries, seen as the chronometers of female physiological aging, demonstrate features of sped up aging, evidenced by the steady decline in both the quality and quantity of ovarian follicles from birth. The multifaceted pathogenesis of ovarian aging has kindled intensive research interest from the biomedical and pharmaceutical sectors. Novel studies underscore the integral roles of gut microbiota in follicular development, lipid metabolism, and hormonal regulation, forging a nexus with ovarian aging. In this review, we outline the role of gut microbiota in ovarian function (follicular development, oocyte maturation, and ovulation), compile and present gut microbiota alterations associated with age-related ovarian aging. We also discuss potential strategies for alleviating ovarian aging from the perspective of gut microbiota, such as fecal microbiota transplantation and probiotics.

Sphingobium sp. SJ10-10 encodes a not-yet-reported chromate reductase and the classical Rieske dioxygenases to simultaneously degrade PAH and reduce chromate.

Both polycyclic aromatic hydrocarbons (PAHs) and heavy metals persist in the environment and are toxic to organisms. Their co-occurrence makes any of them difficult to remove during bioremediation and poses challenges to environmental management and public health. Microorganisms capable of effectively degrading PAHs and detoxifying heavy metals concurrently are required to improve the bioremediation process. In this study, we isolated a new strain, Sphingobium sp. SJ10-10, from an abandoned coking plant and demonstrated its capability to simultaneously degrade 92.6 % of 75 mg/L phenanthrene and reduce 90 % of 3.5 mg/L hexavalent chromium [Cr(VI)] within 1.5 days. Strain SJ10-10 encodes Rieske non-heme iron ring-hydroxylating oxygenases (RHOs) to initiate PAH degradation. Additionally, a not-yet-reported protein referred to as Sphingobium chromate reductase (SchR), with low sequence identity to known chromate reductases, was identified to reduce Cr(VI). SchR is distributed across different genera and can be classified into two classes: one from Sphingobium members and the other from non-Sphingobium species. The widespread presence of SchR in those RHO-containing Sphingobium members suggests that they are excellent candidates for bioremediation. In summary, our study demonstrates the simultaneous removal of PAHs and Cr(VI) by strain SJ10-10 and provides valuable insights into microbial strategies for managing complex pollutant mixtures.

A ghost epigastric pain.

A 16-year-old woman complained of intermittent epigastric pain for one year. The gastroscopy, colonoscopy and laboratory findings were normal. Physical examination was unremarkable other than upper abdominal tenderness. The symptom was not relieved in past medical treatment. The abdominal computed tomography (CT) scan revealed appendix wall swelling and suspected appendicitis. Endoscopic retrograde appendicitis therapy (ERAT) with eyeMax (Micro-tech, China) was proposed to perform after informed consent obtained. A colonoscopy with a transparent cap (Olympus, Japan) attached to the tip was inserted into the cecum, and advanced the level of appendicular orifice. Subsequently, the Gerlach's valve was pushed aside using the transparent cap. Finally, the eyeMax was placed in the appendicular orifice, slowly moved forward in appendicular lumen. The eyeMax showed a lot of appendicular stones, and irrigated repeatedly. The stones were expulsed smoothly. The patient was discharged two days later without recurrent epigastric pain on follow-up and to date.

Successful removal of a duodenal lesion in difficult location using "a sandwich method".

A 69-year-old woman was diagnosed with a duodenal adenoma near major duodenal papilla during cancer screening examination (Figure 1A). Therefore, endoscopic mucosal resection (EMR) was proposed to remove the duodenal lesion. Unfortunately, satisfactory visualization of the duodenal lesion was not obtained during gastroscopic operation. Unexpectedly, duodenoscopy provided optimal visualization of the duodenal lesion. Consequently, the "sandwich method" using duodenoscopy-gastroscopy-duodenoscopy was successfully performed to remove the challenging duodenal lesion. Firstly, the duodenoscopy was used to create a submucosal bleb through injecting saline containing 0.3 % indigo carmine. Subsequently, the gastroscopy with a transparent capwas used to remove the duodenal lesion with en bloc resection. Then, the duodenoscopy was reused to close the mucosal defect. Finally, pathologic examination showed a tubule-villous adenoma. The patient was recovered uneventfully, and discharged 2 days later.

Paraflavitalea pollutisoli sp. nov., Pollutibacter soli gen. nov. sp. nov., Polluticoccus soli gen. nov. sp. nov., and Terrimonas pollutisoli sp. nov., four new members of the family Chitinophagaceae from polluted soil.

A taxonomic investigation was conducted on four bacterial strains isolated from soil contaminated with polycyclic aromatic hydrocarbons and heavy metals. Phylogenetic analysis revealed that these strains belonged to the family Chitinophagaceae. Examination of the 16S rRNA genes indicated that their sequence identities were below 97.6 % compared to any known and validly nominated bacterial species. The genomes of the four strains ranged from 4.12 to 8.76 Mb, with overall G + C molar contents varying from 41.28 % to 50.39 %. Predominant cellular fatty acids included iso-C15:0, iso-C15:1 G, and iso-C17:0 3-OH. The average nucleotide identity ranged from 66.90 % to 74.63 %, and digital DNA-DNA hybridization was 12.5-12.8 %. Based on the genomic and phenotypic features of the new strains, four novel species and two new genera were proposed within the family Chitinophagaceae. The ecological distributions were investigated by data-mining of NCBI databases, and results showed that additional strains or species of the newly proposed taxa were widely distributed in various environments, including polluted soil and waters. Functional analysis demonstrated that strains H1-2-19XT, JS81T, and JY13-12T exhibited resistance to arsenite (III) and chromate (VI). The proposed names for the four novel species are Paraflavitalea pollutisoli (type strain H1-2-19XT = JCM 36460T = CGMCC 1.61321T), Terrimonas pollutisoli (type strain H1YJ31T = JCM 36215T = CGMCC 1.61343T), Pollutibacter soli (type strain JS81T = JCM 36462T = CGMCC 1.61338T), and Polluticoccus soli (type strain JY13-12T = JCM 36463T = CGMCC 1.61341T).

The ligand binding domain of a type IV pilus chemoreceptor PilJ has a different fold from that of another PilJ-type receptor McpN.

Bacterial chemoreceptors sense the extracellular signals and regulate bacterial motilities, biofilm formation, etc. The periplasmic ligand binding domains of chemoreceptors occur as different structural folds and recognize a diversity of chemical molecules. In Pseudomonas aeruginosa (PAO1), two bacterial chemoreceptors, McpN (PA2788) and PilJ (PA0411), are proposed to both contain a PilJ-like ligand-binding domain (LBD) (Pfam motif PF13675) and involved in nitrate chemotaxis and type IV pilus-mediated motility, respectively. The LBDs of McpN and PilJ consist of 135 and 263 residues, respectively, and share very low sequence identity, suggesting they might occur as different structures. Here, we found that PilJ-LBD folded into an HBM module, the same as the sensor domains of McpS-LBD and TorS-LBD, but it differed from that of McpN-LBD. We also observed a trimer in SEC and AUC and proposed a trimeric model based on the crystal structure. Based on the sequence, we classified the Pfam containing McpN-LBD and PilJ-LBD into three classes: sPilJ (single PilJ) represented by McpN-LBD with only one PilJ domain, dPilJ (dual PilJ) that contained dual PilJ domains, and hPilJ (hybrid PilJ) that comprises of a PilJ domain and another non-PilJ domain. Our work indicates a significant structural difference between the ligand binding domains of PilJ and McpN and will help our further study on both kinds of chemoreceptors.

TC2N inhibits distant metastasis and stemness of breast cancer via blocking fatty acid synthesis.

BACKGROUND: Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. METHODS: Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. RESULTS: Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. CONCLUSIONS: Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.

A case of achalasia associated with early esophageal cancer.

A 65-year-old man was admitted to our hospital complaining of reflux for more than 20 years. After endoscopy and barium-swallow examination, he was diagnosed with achalasia as well as a squamous cell carcinoma. Therefore, peroral endoscopic myotomy (POEM) combined with endoscopic submucosal dissection (ESD) was performed simultaneously. During the procedure, a mucosal erosion with a clear boundary was shown in the middle segment of the esophagus. ESD was first performed and the lesion was removed en-bloc. Subsequent POEM therapy was performed after marking the left esophageal wall 10cm above the cardia. After submucosal injection, the submucosal plane was created through a length 2cm longitudinal incision, then the muscle was cut a length of 10 cm into the esophagus and 2 cm below the cardia, and finally the incision was closed by clips. Pathological examination revealed high-grade intraepithelial neoplasia of squamous epithelium (carcinoma in situ) with a negative margin. The patient was recovered without complication four days after the procedure. The endoscopy showed perfect healing of the esophageal lesions during two-months follow-up , and the reflux symptom was resolved.

Clinical and endoscopic characteristics and management of 220 cases with serrated polyps.

BACKGROUND: Serrated polyps are considered the precursor lesions of colorectal cancer through the serrated pathway. In the present study, we aimed to evaluate and discuss the clinical and endoscopic characteristics and management of serrated polyps. METHODS: The data of 220 cases with serrated polyps between September 2018 and November 2021 in Shenzhen People's Hospital were retrospectively analyzed. RESULTS: Of all these cases, 32 were hyperplastic polyps, 36 were traditional serrated adenomas, 126 were sessile serrated lesions, 25 were SSLs with dysplasia, and one was an unclassified serrated adenoma. Although most patients were males aged ≥50 years and most serrated polyps were located in the distal colon and rectum with a size of 6-10 mm and the shape of type 0-Is, there was no significant difference (P > 0.05). Serrated polyps of ≤5 mm in size and type 0-IIa were mostly removed by cold biopsy forceps. Cold snare polypectomy was primarily used for those of 6-10 mm in size. Endoscopic mucosal resection was used for those of 6-20 mm, and endoscopic submucosal dissection was used for those of ≥20 mm (P < 0.05). All complications occurred in SSL patients with or without dysplasia (P < 0.05). CONCLUSIONS: Clinical and endoscopic characteristics were beneficial for distinguishing and diagnosing serrated polyps. In addition, management options were crucial to prevent recurrence and progression. However, the detection rate of serrated polyps was relatively low. Therefore, prospective multicenter studies with large samples are necessary to better assess colorectal serrated polyps.

An unpredictable gastrointestinal bleed.

A 65-year-old male complained of persistent melena for 6 days, and displayed anemia symptoms without hematemesis, vomiting, and abdominal distention. He was diagnosed as ruptured aneurysm of aortic sinus Valsalva, and had received coronary artery occlusion 1 month ago. After the operation, he was continually prescribed clopidogrel 75 mg once daily. The laboratory examination showed blood hemoglobin concentration was 60 g/L without other conspicuous abnormality. Unfortunately, neither esophagogastroduodenoscopy (EGD) nor colonoscopy found no obvious bleeding lesions. And abdominal computed tomography angiography (CTA) and enhanced computed tomography (CT) showed no obvious abnormal findings. Moreover, capsule endoscopy revealed small intestinal with mucosal erosion (Figure 1A). After discontinued clopidogrel, blood transfusion, and support therapy, his symptoms was resolved with negative fecal occult blood, continued clopidogrel 75 mg once daily, and uneventfully discharged 1 week later.

"Clip coupled with an elastic ring" internal traction for endoscopic submucosal dissection of a rectal neuroendocrine tumor: a junior endoscopist experience.

A 64-year-old female was found a rectal neuroendocrine tumor (NET) for cancer screening examination. Endoscopic ultrasonography (EUS) revealed a hypoechoic lesion (8.3*6.6 mm) originating from the submucosa layer. "Clip coupled with elastic ring" internal traction for endoscopic submucosal dissection (ESD) was used to remove the NET according to the procedure removal of a duodenal tumor1. The procedures are following: 1. Marking around the lesion with a margin of approximately 5 mm. 2. Submucosal injection and circumference incision around the lesion. 3. Applied clip coupled with elastic ring internal traction. 4. Submucosal injection. 5.Precise dissection was performed with the NET being en bloc resection. 5. Closed the mucosal defect. Finally, the Histopathology confirmed a neuroendocrine tumor.

An unpredictable gastrointestinal bleed

A 65-year-old male complained of persistent melena for 6 days, and displayed anemia symptoms without hematemesis, vomiting, and abdominal distention. He was diagnosed as ruptured aneurysm of aortic sinus Valsalva, and had received coronary artery occlusion 1 month ago. After the operation, he was continually prescribed clopidogrel 75 mg once daily. The laboratory examination showed blood hemoglobin concentration was 60 g/L without other conspicuous abnormality. Unfortunately, neither esophagogastroduodenoscopy (EGD) nor colonoscopy found no obvious bleeding lesions. And abdominal computed tomography angiography (CTA) and enhanced computed tomography (CT) showed no obvious abnormal findings. Moreover, capsule endoscopy revealed small intestinal with mucosal erosion (Figure 1A). After discontinued clopidogrel, blood transfusion, and support therapy, his symptoms was resolved with negative fecal occult blood, continued clopidogrel 75 mg once daily, and uneventfully discharged 1 week later. (AU)

“Clip coupled with an elastic ring” internal traction for endoscopic submucosal dissection of a rectal neuroendocrine tumor: a junior endoscopist experience

A 64-year-old female was found a rectal neuroendocrine tumor (NET) for cancer screening examination. Endoscopic ultrasonography (EUS) revealed a hypoechoic lesion (8.3*6.6 mm) originating from the submucosa layer. “Clip coupled with elastic ring” internal traction for endoscopic submucosal dissection (ESD) was used to remove the NET according to the procedure removal of a duodenal tumor1. The procedures are following: 1. Marking around the lesion with a margin of approximately 5 mm. 2. Submucosal injection and circumference incision around the lesion. 3. Applied clip coupled with elastic ring internal traction. 4. Submucosal injection. 5.Precise dissection was performed with the NET being en bloc resection. 5. Closed the mucosal defect. Finally, the Histopathology confirmed a neuroendocrine tumor. (AU)

Agromyces chromiiresistens sp. nov., Novosphingobium album sp. nov., Sphingobium arseniciresistens sp. nov., Sphingomonas pollutisoli sp. nov., and Salinibacterium metalliresistens sp. nov.: five new members of Microbacteriaceae and Sphingomonadaceae from polluted soil.

There are many unidentified microbes in polluted soil needing to be explored and nominated to benefit the study of microbial ecology. In this study, a taxonomic research was carried out on five bacterial strains which were isolated and cultivated from polycyclic aromatic hydrocarbons, and heavy metals polluted soil of an abandoned coking plant. Phylogenetical analysis showed that they belonged to the phyla Proteobacteria and Actinobacteria, and their 16S rRNA gene sequence identities were lower than 98.5% to any known and validly nominated bacterial species, suggesting that they were potentially representing new species. Using polyphasic taxonomic approaches, the five strains were classified as new species of the families Microbacteriaceae and Sphingomonadaceae. Genome sizes of the five strains ranged from 3.07 to 6.60 Mb, with overall DNA G+C contents of 63.57-71.22 mol%. The five strains had average nucleotide identity of 72.38-87.38% and digital DNA-DNA hybridization of 14.0-34.2% comparing with their closely related type strains, which were all below the thresholds for species delineation, supporting these five strains as novel species. Based on the phylogenetic, phylogenomic, and phenotypic characterizations, the five novel species are proposed as Agromyces chromiiresistens (type strain H3Y2-19aT = CGMCC 1.61332T), Salinibacterium metalliresistens (type strain H3M29-4T = CGMCC 1.61335T), Novosphingobium album (type strain H3SJ31-1T = CGMCC 1.61329T), Sphingomonas pollutisoli (type strain H39-1-10T = CGMCC 1.61325T), and Sphingobium arseniciresistens (type strain H39-3-25T = CGMCC 1.61326T). Comparative genome analysis revealed that the species of the family Sphingomonadaceae represented by H39-1-10T, H39-3-25T, and H3SJ31-1T possessed more functional protein-coding genes for the degradation of aromatic pollutants than the species of the family Microbacteriaceae represented by H3Y2-19aT and H3M29-4T. Furthermore, their capacities of resisting heavy metals and metabolizing aromatic compounds were investigated. The results indicated that strains H3Y2-19aT and H39-3-25T were robustly resistant to chromate (VI) and/or arsenite (III). Strains H39-1-10T and H39-3-25T grew on aromatic compounds, including naphthalene, as carbon sources even in the presence of chromate (VI) and arsenite (III). These features reflected their adaptation to the polluted soil environment.

Attractant and repellent induce opposing changes in the four-helix bundle ligand-binding domain of a bacterial chemoreceptor.

Motile bacteria navigate toward favorable conditions and away from unfavorable environments using chemotaxis. Mechanisms of sensing attractants are well understood; however, molecular aspects of how bacteria sense repellents have not been established. Here, we identified malate as a repellent recognized by the MCP2201 chemoreceptor in a bacterium Comamonas testosteroni and showed that it binds to the same site as an attractant citrate. Binding determinants for a repellent and an attractant had only minor differences, and a single amino acid substitution in the binding site inverted the response to malate from a repellent to an attractant. We found that malate and citrate affect the oligomerization state of the ligand-binding domain in opposing way. We also observed opposing effects of repellent and attractant binding on the orientation of an alpha helix connecting the sensory domain to the transmembrane helix. We propose a model to illustrate how positive and negative signals might be generated.

Endoscopic submucosal dissection coupled with "modified clip coupled with elastic ring" traction removing rectal neuroendocrine tumor.

A 50-year-old female complained of discomfort of lower abdomen, and a colonoscopy revealed a rectal neuroendocrine tumor (NET). Endoscopic ultrasonography (EUS) showed a hypoechoic lesion (8.5*7.6 mm) originating from the submucosa layer. Endoscopic submucosal dissection (ESD) coupled with "modified clip coupled with elastic ring" traction was performed to remove the NET. Following procedures previously described, we made a subtle change.

Therapeutic potential of gene therapy for gastrointestinal diseases: Advancements and future perspectives.

Advancements in understanding the pathogenesis mechanisms underlying gastrointestinal diseases, encompassing inflammatory bowel disease, gastrointestinal cancer, and gastroesophageal reflux disease, have led to the identification of numerous novel therapeutic targets. These discoveries have opened up exciting possibilities for developing gene therapy strategies to treat gastrointestinal diseases. These strategies include gene replacement, gene enhancement, gene overexpression, gene function blocking, and transgenic somatic cell transplantation. In this review, we introduce the important gene therapy targets and targeted delivery systems within the field of gastroenterology. Furthermore, we provide a comprehensive overview of recent progress in gene therapy related to gastrointestinal disorders and shed light on the application of innovative gene-editing technologies in treating these conditions. These developments are fueling a revolution in the management of gastrointestinal diseases. Ultimately, we discuss the current challenges (particularly regarding safety, oral efficacy, and cost) and explore potential future directions for implementing gene therapy in the clinical settings for gastrointestinal diseases.

A submucosal lesion of the rectum: an unexpected MALT.

A 57-year-old female was found a 12 mm × 10 mm submucosal lesion in the rectum with a smooth mucosa and telangiectasia The lesion was considered as a neuroendocrine tumor, and removed by endoscopic submucosal dissection (ESD) It was finally diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma with negative margin by pathological examination and histopathological test. MALT lymphoma in the rectum is rare and difficult to diagnose without histopathological test. In this case, the characteristic of this case is telangiectasia on the surface of lesion. Therefore, our findings suggested small lesion in rectum but big in impact.

Edible exosome-like nanoparticles from portulaca oleracea L mitigate DSS-induced colitis via facilitating double-positive CD4+CD8+T cells expansion.

Plant-derived exosome-like nanoparticles (PDENs) have been paid great attention in the treatment of ulcerative colitis (UC). As a proof of concept, we isolated and identified Portulaca oleracea L-derived exosome-like nanoparticles (PELNs) from edible Portulaca oleracea L, which exhibited desirable nano-size (~ 160 nm) and a negative zeta potential value (-31.4 mV). Oral administration of PELNs effectively suppressed the expressions of pro-inflammatory cytokines (TNF-α, IL-6, IL-12, and IL-1ß) and myeloperoxidase (MPO), increased levels of the anti-inflammatory cytokine (IL-10), and alleviated acute colitis in dextran sulfate sodium (DSS)-induced C57 mice and IL-10-/- mice. Notably, PELNs exhibited excellent stability and safety within the gastrointestinal tract and displayed specific targeting to inflamed sites in the colons of mice. Mechanistically, oral administration of PELNs played a crucial role in maintaining the diversity and balance of gut microbiota. Furthermore, PELNs treatment enhanced Lactobacillus reuteri growth and elevated indole derivative levels, which might activate the aryl-hydrocarbon receptor (AhR) in conventional CD4+ T cells. This activation downregulated Zbtb7b expression, leading to the reprogramming of conventional CD4+ T cells into double-positive CD4+CD8+T cells (DP CD4+CD8+ T cells). In conclusion, our findings highlighted the potential of orally administered PELNs as a novel, natural, and colon-targeted agent, offering a promising therapeutic approach for managing UC. Schematic illustration of therapeutic effects of oral Portulaca oleracea L -derived natural exosome-like nanoparticles (PELNs) on UC. PELNs treatment enhanced Lactobacillus reuteri growth and elevated indole derivative levels, which activate the aryl-hydrocarbon receptor (AhR) in conventional CD4+ T cells leading to downregulate the expression of Zbtb7b, reprogram of conventional CD4+ T cells into double-positive CD4+CD8+T cells (DP CD4+CD8+ T cells), and decrease the levels of pro-inflammatory cytokines.