Acute Myeloid Leukemia with Myelodysplasia-Related Changes in a Patient with Crohn’s Disease Treated with Immunosuppressive Therapy

We report a case of acute myeloid leukemia with myelodysplasia-related changes in a patient with Crohn’s disease. The patient was diagnosed with Crohn’s disease at the age of 47 years and was treated with the tumor necrosis factor α inhibitors adalimumab and infliximab, and a short course of azathioprine. Four years later, the patient developed acute myeloid leukemia with myelodysplasia that involved mainly erythropoiesis. Crohn’s disease is associated with an increased risk of cancers including hematological malignancies. Cancer surveillance including hematology assessment is warranted to monitor the patients on immunosuppressive therapy

Trans-Anastomotic Drainage Tube Placement After Hand-Sewn Anastomosis in Patients Undergoing Intersphincteric Resection for Low Rectal Cancer: An Alternative Drainage Method

Anastomotic leakage (AL) is a common complication after intersphincteric resection (ISR). It significantly reduces quality of life and causes great distress to patients. Although traditional drainage (e.g., anal and pelvic catheters) may reduce the impact of AL to some extent, their role in reducing the incidence of AL remains controversial. In this study, we developed a novel drainage technique involving the placement of drainage tubes through the gap between sutures during handsewn anastomosis, to reduce the occurrence of anastomotic leakage. We retrospectively analyzed 34 consecutive patients who underwent intersphincteric resection requiring handsewn anastomosis between February 1, 2017, and January 1, 2021. Patients were classified into the trans-anastomotic drainage tube group (TADT, n = 14) and the non-TADT group (n = 20) based on whether trans-anastomotic tube placement was performed. The incidence of postoperative complications, such as AL, was compared between the two groups, and anal function of patients at 1-year post-ISR was evaluated. Six cases of AL occurred in the non-TADT group, while none occurred in the TADT group; this difference was statistically significant (p=0.031). The TADT group also had a shorter hospital stay (p=0.007). There were no other significant intergroup differences in operation time, blood loss, pain score, anastomotic stenosis, intestinal obstruction, or incidence of wound infection. In the 30 patients (88.2%) evaluated for anal function, there were no significant intergroup differences in stool frequency, urgency, daytime/nocturnal soiling, Wexner incontinence score, or Kirwan grading. Taken together, trans-anastomotic tube placement is a novel drainage method that may reduce AL after ISR requiring handsewn anastomosis and without adversely affecting anal function

Switching the ligand-exchange reactivities of chloro-bridged cyclopalladated azobenzenes for the colorimetric sensing of thiocyanate

A dinuclear cyclopalladated complex of methyl orange shows a sensitive chromogenic response towards thiocyanate over a series of other anions in aqueous solution at physiological pH.National Natural Science Foundation of China [20705029, 20835005]; Science & Technology Project of Fujian Province [2005J001]; Natural Science Foundation of Fujian Province of China [A0610028

miR-144-3p Promotes Adipogenesis Through Releasing C/EBPα From Klf3 and CtBP2

MicroRNAs (miRNAs), a class of small non-coding RNAs, have been proved as novel and potent regulators of adipogenesis. A previous study has found out that miR-144-3p was a biomarker of type 2 diabetes, but the role of miR-144-3p in regulating adipogenesis was still unclear. In the present study, the expression of miR-144-3p increased in obese mice and during the 3T3-L1 differentiation process. Overexpression of miR-144-3p suppressed the expression of cell cycle regulatory factors and inhibited pre-adipocytes proliferation. Besides, overexpression of miR-144-3p accelerated lipid accumulation in adipocytes and positively regulated adipogenesis, which was also accompanied by increasing the expression of genes related to fatty acid synthesis and decreasing the expression of genes involved in fatty acid oxidation. Furthermore, luciferase activity assays indicated that miR-144-3p directly targeted Klf3 and CtBP2. The process was also confirmed by the mRNA and protein expression of Klf3 and CtBP2, which were suppressed by miR-144-3p. Furthermore, miR-144-3p targeting Klf3/CtBP2 would induce C/EBPα activity by releasing corepressors (Klf3 and CtBP2) from its promoter region. Moreover, we also observed that miR-144-3p could promote adipogenesis in mice injected with miR-144-3p agomir through tail-vein injection. Taken together, these results support that miR-144-3p can facilitate adipogenesis both in vitro and in vivo, which implies that miR-144-3p could be a target for therapeutic intervention in obesity and metabolic syndrome in the future

The Landscape of Non-Coding RNA in an Adult Pig Model of Intrauterine Growth Restriction

Background/Aims: Intrauterine growth restriction (IUGR) is a risk factor for adult metabolic syndrome, but how this disease is regulated by lncRNAs and circRNAs remains elusive. Methods: Here, we employed adult IUGR and normal pigs as models to evaluate the expression of various global lncRNAs and circRNAs in pig livers using RNA-seq. Results: In total, we obtained 1,162 million raw reads of approximately 104.54 Gb high quality data. After a strict five-step filtering process, 3,368 lncRNAs were identified, including 300 differentially expressed lncRNAs (p < 0.05) in the IUGR group relative to the control group. The cis-regulatory analysis identified target genes that were enriched in specific GO terms and pathways (p < 0.05), including amino acid metabolism, oxidoreductase activity, PPAR signaling pathway, and insulin signaling pathway. These are closely related to the observed phenotypes of increased gluconeogenesis and impaired mitochondrial oxidative phosphorylation in adulthood of the IUGR group. Additionally, we also identified 403 circRNAs, of which 44 were differentially expressed (p < 0.05). Interestingly, our results identified ATF4-miR214-circRNA7964 and TCF7-miR22-3p-circRNA16347 as two competing endogenous networks, which were closely associated with the observed increase in hepatic gluconeogenesis in the IUGR group. Conclusion: Together, this study reveals a multitude of candidate lncRNAs and circRNAs involved in the development of IUGR pigs, which could facilitate further researches on the molecular mechanisms of metabolic syndrome

Transcriptome Analyses Reveal Adult Metabolic Syndrome With Intrauterine Growth Restriction in Pig Models

Epidemiological data have indicated that intrauterine growth retardation (IUGR) is a risk factor for the adult metabolic syndrome in pigs. However, the causative genetic mechanism leading to the phenotype in adulthood has not been well characterized. In the present study, both normal and IUGR adult pigs were used as models to survey the differences in global gene expression in livers through transcriptome sequencing. The transcriptome libraries generated 104.54 gb of data. In normal and IUGR pigs, 16,948 and 17,078 genes were expressed, respectively. A total of 1,322 differentially expressed genes (DEGs) were identified. Enrichment analysis of the DEGs revealed that the top overrepresented gene ontology (GO) terms and pathways were related to oxidoreductase activity, ATPase activity, amino catabolic process, glucose metabolism, and insulin signaling pathway. The increased gluconeogenesis (GNG) and decreased glycogen synthesis in the liver contributed to the glucose intolerance observed in IUGR. The reduced expression of insulin signaling genes (such as PI3K and AKT) indicated an elevated risk of diabetes in adulthood. Together, these findings provide a comprehensive understanding of the molecular mechanisms of adult IUGR pigs and valuable information for future studies of therapeutic intervention in IUGR metabolic syndrome

Bee‑safe peptidomimetic acaricides achieved by comparative genomics

The devastating Varroa mite (Varroa destructor Anderson and Trueman) is an obligatory ectoparasite of the honey bee, contributing to significant colony losses in North America and throughout the world. The limited number of conventional acaricides to reduce Varroa mites and prevent disease in honey bee colonies is challenged with wide-spread resistance and low target-site selectivity. Here, we propose a biorational approach using comparative genomics for the development of honey beesafe and selective acaricides targeting the Varroa mite-specific neuropeptidergic system regulated by proctolin, which is lacking in the honey bee. Proctolin is a highly conserved pentapeptide RYLPT (Arg-Tyr-Leu-Pro-Thr) known to act through a G protein-coupled receptor to elicit myotropic activity in arthropod species. A total of 33 different peptidomimetic and peptide variants were tested on the Varroa mite proctolin receptor. Ligand docking model and mutagenesis studies revealed the importance of the core aromatic residue Tyr2 in the proctolin ligand. Peptidomimetics were observed to have significant oral toxicity leading to the paralysis and death of Varroa mites, while there were no negative effects observed for honey bees. We have demonstrated that a taxon-specific physiological target identified by advanced genomics information offers an opportunity to develop Varroa miteselective acaricides, hence, expedited translational processes