Hippuric acid alleviates dextran sulfate sodium-induced colitis via suppressing inflammatory activity and modulating gut microbiota.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease associated with metabolic disorder and gut dysbiosis. Decreased abundance of hippuric acid (HA) was found in patients with IBD. HA, metabolized directly from benzoic acid in the intestine and indirectly from polyphenols, serves as a marker of polyphenol catabolism. While polyphenols and benzoic acid have been shown to alleviate intestinal inflammation, the role of HA in this context remains unknown. Herein, we investigated the effects and mechanism of HA on DSS-induced colitis mice. The results revealed that HA alleviated clinical activity and intestinal barrier damage, decreased pro-inflammatory cytokine production. Metagenomic sequencing suggested that HA treatment restored the gut microbiota, including an increase in beneficial gut bacteria such as Adlercreutzia, Eubacterium, Schaedlerella and Bifidobacterium_pseudolongum. Furthermore, we identified 113 candidate genes associated with IBD that are potentially under HA regulation through network pharmacological analyses. 10 hub genes including ALB, IL-6, HSP90AA1, and others were identified using PPI analysis and validated using molecular docking and mRNA expression analysis. Additionally, KEGG analysis suggested that the renin-angiotensin system (RAS), NF-κB signaling and Rap1 signaling pathways were important pathways in the response of HA to colitis. Thus, HA may provide novel biotherapy options for IBD.

Visualizing the global trends of peptides in wound healing through an in-depth bibliometric analysis.

Wound healing is a complicated and multistage biological process for the repair of damaged/injured tissues, which requires intelligent designs to provide comprehensive and convenient treatment. Peptide-based wound dressings have received extensive attention for further development and application due to their excellent biocompatibility and multifunctionality. However, the current lack of intuitive analysis of the development trend and research hotspots of peptides applied in wound healing, as well as detailed elaboration of possible research hotspots, restricted obtaining a comprehensive understanding and development in this field. The present study analysed publications from the Web of Science (WOS) Core Collection database and visualized the hotspots and current trends of peptide research in wound healing. Data between January 1st, 2003, and December 31st, 2022, were collected and subjected to a bibliometric analysis. The countries, institutions, co-authorship, co-citation reference, and co-occurrence of keywords in this subject were examined using VOSviewer and CiteSpace. We provided an intuitive, timely, and logical overview of the development prospects and challenges of peptide application in wound healing and some solutions to the major obstacles, which will help researchers gain insights into the investigation of this promising field.

FSCN1 promotes proliferation, invasion and glycolysis via the IRF4/AKT signaling pathway in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a disease with increasing incidence worldwide that leads to deformity and death. In OSCC, fascin actin-bundling protein 1 (FSCN1) is an oncogene involved in the tumorigenesis process. However, the functions and potential mechanisms of FSCN1 in the OSCC tumorigenesis process have not been reported thus far. METHODS: We used qRT‒PCR to detect the expression of FSCN1 in 40 paired OSCC tumor tissues (tumor) and neighboring noncancerous tissues. The role of FSCN1 was also assessed in vitro through colony formation, CCK-8, and transwell assays. Moreover, glucose consumption was detected. Western blotting was used to confirm the interaction of FSCN1, IRF4 and AKT. RESULTS: FSCN1 was remarkably overexpressed in OSCC tissues and cell lines compared to corresponding controls. In addition, colony formation, CCK-8, and transwell assays revealed a notable reduction in OSCC growth and invasion when FSCN1 was silenced. FSCN1 silencing remarkably suppressed OSCC glycolysis. Mechanistic studies showed that FSCN1 achieves its function partially by activating interferon regulatory factor 4 (IRF4) and the AKT pathway in OSCC. CONCLUSION: In conclusion, our study investigated the functions and mechanisms of the FSCN1/IRF4/AKT pathway in OSCC progression. In OSCC, FSCN1 is likely to be a biomarker and therapeutic target.

A pediatric case of primary amoebic meningoencephalitis due to Naegleria fowleri diagnosed by next-generation sequencing of cerebrospinal fluid and blood samples.

BACKGROUND: Primary amoebic meningoencephalitis (PAM) is a rare, acute and fatal disease of the central nervous system caused by infection with Naegleria fowleri (Heggie, in Travel Med Infect Dis 8:201-6, 2010). Presently, the majority of reported cases in the literature have been diagnosed through pathogen detection pathogens in the cerebrospinal fluid (CSF). This report highlights the first case of pediatric PAM diagnosed with amoeba infiltration within CSF and bloodstream of an 8-year-old male child, validated through meta-genomic next-generation sequencing (mNGS). CASE PRESENTATION: An 8-year-old male child was admitted to hospital following 24 h of fever, headache and vomiting and rapidly entered into a coma. CSF examination was consistent with typical bacterial meningitis. However, since targeted treatment for this condition proved to be futile, the patient rapidly progressed to brain death. Finally, the patient was referred to our hospital where he was confirmed with brain death. CSF and blood samples were consequently analyzed through mNGS. N. fowleri was detected in both samples, although the sequence copy number in the blood was lower than for CSF. The pathogen diagnosis was further verified by PCR and Sanger sequencing. CONCLUSIONS: This is the first reported case of pediatric PAM found in mainland China. The results indicate that N. fowleri may spread outside the central nervous system through a damaged blood-brain barrier.

Case report: Two cases of Poirier-Bienvenu neurodevelopmental syndrome and review of literature.

The Poirier-Bienvenu neurodevelopmental syndrome (POBINDS) is a rare disease caused by mutations in the CSNK2B gene, which is characterized by intellectual disability and early-onset epilepsy. Mosaicism has not been previously reported in CSNK2B gene. POBINDS is autosomal dominant and almost all reported cases were de novo variants. Here, we report two patients were diagnosed with POBINDS. Using Whole Exome Sequencing (WES), we detected two novel CSNK2B variants in the two unrelated individuals: c.634_635del (p.Lys212AspfsTer33) and c.142C > T (p.Gln48Ter) respectively. Both of them showed mild developmental delay with early-onset and clustered seizures. The patient with c.634_635del(p.Lys212AspfsTer33) variant was mutant mosaicism, and the proportion of alleles in peripheral blood DNA was 28%. Further, the literature of patients with a de novo mutation of the CSNK2B gene was reviewed, particularly seizure semiology and genotype-phenotype correlations.

Recent advances in ocular graft-versus-host disease.

Ocular graft-versus-host-disease (GVHD) remains a significant clinical complication after allogeneic hematopoietic stem cell transplantation. Impaired visual function, pain, and other symptoms severely affect affected individuals' quality of life. However, the diagnosis of and therapy for ocular GVHD involve a multidisciplinary approach and remain challenging for both hematologists and ophthalmologists, as there are no unified international criteria. Through an exploration of the complex pathogenesis of ocular GVHD, this review comprehensively summarizes the pathogenic mechanism, related tear biomarkers, and clinical characteristics of this disease. Novel therapies based on the mechanisms are also discussed to provide insights into the ocular GVHD treatment.

Generalist in allogeneic hematopoietic stem cell transplantation for MDS or AML: Epigenetic therapy.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment for patients with myeloid malignancies such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, relapse and graft-versus-host disease (GvHD) still affect the survival of patients who receive allo-HSCT, and more appropriate therapeutic strategies should be applied at all stages of transplantation to prevent these adverse events. The use of epigenetics agents, such as hypomethylating agents (HMAs), has been explored to decrease the risk of relapse by epigenetic modulation, which is especially effective among AML patients with poor mutations in epigenetic regulators. Furthermore, epigenetic agents have also been regarded as prophylactic methods for GvHD management without abrogating graft versus leukemia (GvL) effects. Therefore, the combination of epigenetic therapy and HSCT may optimize the transplantation process and prevent treatment failure. Existing studies have investigated the feasibility and effectiveness of using HMAs in the pretransplant, transplant and posttransplant stages among MDS and AML patients. This review examines the application of HMAs as a bridge treatment to reduce the tumor burden and the determine appropriate dose during allo-HSCT. Within this review, we also examine the efficacy and safety of HMAs alone or HMA-based strategies in posttransplant settings for MDS and AML. Finally, we provide an overview of other epigenetic candidates, which have been discussed in the nontransplant setting.

Protective Role of Amiodarone on Reperfusion Arrhythmia in Patients of Acute Myocardial Infarction with Percutaneous Coronary Intervention Treatment.

With the development and popularity of percutaneous coronary intervention (PCI), ischemia-reperfusion injury (IRI) has attracted more and more clinical attention. Reperfusion arrhythmia (RA), one of the common manifestations during and after PCI, can affect the postoperative cardiac function of patients with acute myocardial infarction (AMI). Therefore, effective intervention on RA has important clinical significance. This study observed the effect of amiodarone on reperfusion arrhythmia (RA) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) and explored its possible mechanism. The results showed that amiodarone had good clinical efficacy in the prevention of RA in patients with AMI after PCI, and it could reduce the levels of serum IL-6, hs-CRP, CK-MB, and cTnI in patients and reduce the damage caused by reperfusion, thereby reducing the occurrence of RA.

Identification and Validation of a Dysregulated miRNA-Associated mRNA Network in Temporal Lobe Epilepsy.

OBJECTIVES: This study is aimed at exploring the relationships between miRNAs and mRNAs and to characterize their biological functions in temporal lobe epilepsy (TLE). METHODS: Novel clinical significant miRNAs and target genes and their potential underlying mechanisms have been discovered and explored by mining miRNAs and mRNA expression data of TLE patients using various bioinformatics methods. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate the bioinformatic analysis results. RESULTS: A total of 6 dysregulated miRNAs and 442 differentially expressed genes (DEGs) related to TLE were obtained from GEO database (GSE114701 and GSE127871 datasets). A protein-protein interaction (PPI) network containing the 442 DEGs was established. mRNA response elements from the 6 dysregulated miRNAs were predicted using the miRDB and TargetScan bioinformatic tools. By merging the identified targets of the dysregulated miRNAs and the 247 downregulated DEGs, a miRNA-mRNA network was constructed revealing the interaction of miR-484 with eight mRNAs (ABLIM2, CEP170B, CTD-3193O13.9, EFNA5, GAP43, PRKCB, FXYD7, and NCAN). A weighted correlation network analysis (WGCNA) based on the eight genes was established and demonstrated that these mRNAs, except FXYD7 and NCAN, were hub genes in the network. Gene Oncology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the six hub genes were mainly involved in cellular-related biological functions and the neurotransmitter synapse pathway. The differences in expression levels of the miR-484 and the three hub genes (CTD-3193O13.9, EFNA5, and PRKCB) observed experimentally in TLE patients compared to those of healthy controls were consistent with the WGCNA prediction. CONCLUSION: Our study suggests that understanding the miRNA-mRNA interactions will provide insights into the epilepsy pathogenesis. In addition, our results indicate that miR-484 may be a promising novel biomarker for TLE.

Effect of breast-conserving surgery combined with sentinel lymph node biopsy and axillary preservation on the recurrence, metastasis, complications and cosmetic results of early breast cancer patients.

BACKGROUND: As one of the main malignant tumors, breast cancer remains a worldwide public health issue. Here, we aimed to analyze the effects of breast-conserving surgery (BCS) combined with sentinel lymph node biopsy (SLNB) and axillary preservation on the recurrence, metastasis, complications, and cosmetic results of early breast cancer patients (BCPs). METHODS: The clinical data of 143 BCPs admitted to our hospital from January 2017 to January 2019 were collected retrospectively, and all patients were female. Patients (76 cases) undergoing BCS combined with SLNB and axillary preservation treatment were set as the combined group, and 67 cases undergoing traditional modified radical surgery were set as the control group. After the perioperative conditions of patients in the two groups were compared, the patients were followed up for 14 months to record information on the quality of life, recurrence, metastasis, complications, and cosmetic results. RESULTS: The operation time, intraoperative blood loss, and extubation time of the combined group were significantly less than the control group (P<0.05); the quality of life of patients in both groups improved after treatment, but the quality of life of patients in the combined group was significantly higher than that of the control group (P<0.05); both groups of patients were followed up for 14 months after treatment, and there were no deaths. The rates of local recurrence and distant metastasis were 2.98% and 5.97% in the control group and 5.26% and 6.57% in the combined group, respectively, showing no significant difference between the two groups (P>0.05); the incidence of postoperative complications was 14.92% in the control group, which was significantly higher than the incidence of 3.94% of the combined group (P<0.05); the proportion of postoperative cosmetic results with an excellent and good rating was 59.7% in the control group, which was significantly lower than the 93.42% reported in the combined group (P<0.05). CONCLUSIONS: BCS combined with SLNB and axillary preservation provided good clinical and cosmetic results and can improve the quality of life of patients and reduce the rate of recurrence and metastasis.

Construction and in vivo evaluation of a thermosensitive hydrogel system loading with Pseudomonas aeruginosa DNA vaccine / 中国药科大学学报

@#A thermosensitive hydrogel system consisting of PLGA-PEG-PLGA hydrogel and Pseudomonas aeruginosa DNA vaccine was constructed and the immune efficacy of the system was evaluated. The PLGA-PEG-PLGA thermosensitive hydrogel containing Pseudomonas aeruginosa DNA vaccine was prepared by a simple physical mixing method. The gelation temperature, cytotoxicity, and release curve in vitro were tested.The degradability of hydrogel in vivo was evaluated. The mice were divided into control group (PBS), hydrogel group (Hydrogel), in vivo-jetPEI/plasmid DNA group (in vivo-jetPEI/pDNA), and hydrogel + in vivo-jetPEI/plasmid group (Gel+in vivo-jetPEI/pDNA). Mice were immunized three times with a ten-day interval. Two weeks after the last immunization, the mice were sacrificed. The proliferation of splenic lymphocytes, serum specific IgG antibodies and IFN-γ in supernatant of splenic lymphocytes were detected. The gelation temperature of PLGA-PEG-PLGA hydrogel was (32 ± 0.5) ℃. There was no obvious toxicity to cells in vitro, and about 80% of plasmid DNA was released after 7 days in vitro. PLGA-PEG-PLGA hydrogel was biodegradable, and degraded almost completely after 15 days in vivo. The spleen lymphocytes proliferated; the levels of specific IgG antibodies and IFN-γ of in vivo-jetPEI/pDNA and Gel+in vivo-jetPEI/pDNA groups increased. The hydrogel could enhance the immune response induced by DNA vaccine.Results suggest that the thermosensitive hydrogel system consisting of PLGA-PEG-PLGA hydrogel and Pseudomonas aeruginosa DNA vaccine is a promising new strategy for the development of PA vaccine.