Redesigning Berberines and Sanguinarines to Target Soluble Epoxide Hydrolase for Enhanced Anti-Inflammatory Efficacy.

Amino-berberine has remained underexplored due to limited biological evaluation and total synthesis approaches. In inflammation therapy, soluble Epoxide Hydrolase (sEH) is a promising target, yet natural scaffolds remain underutilized. Our study advances the field by redesigning natural compounds─berberine and sanguinarine─with strategic urea modifications and hydrogenated frameworks, creating novel sEH inhibitors with enhanced efficacy.

Design and structure-activity relationships of ether-linked alkylides: Hybrids of 3-O-descladinosyl macrolides and quinolone motifs.

Ketolides (3-keto) such as TE-802 and acylides (3-O-acyl) like TEA0929 are ineffective against constitutively resistant pathogens harboring erythromycin ribosomal methylation (erm) genes. Following our previous work on alkylides (3-O-alkyl), we explored the structure-activity relationships of hybrids combining (R/S) 3-descladinosyl erythromycin with 6/7-quinolone motifs, featuring extended ether-linked spacers, with a focus on their efficacy against pathogens bearing constitutive erm gene resistance. Optimized compounds 17a and 31f not only reinstated efficacy against inducibly resistant pathogens but also demonstrated significantly augmented activities against constitutively resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes, which are typically refractory to existing C-3 modified macrolides.

Synthetic macrolides overcoming MLSK-resistant pathogens.

Conventional macrolide-lincosamide-streptogramin B-ketolide (MLSK) antibiotics are unable to counter the growing challenge of antibiotic resistance that is conferred by the constitutive methylation of rRNA base A2058 or its G2058 mutation, while the presence of unmodified A2058 is crucial for high selectivity of traditional MLSK in targeting pathogens over human cells. The absence of effective modes of action reinforces the prevailing belief that constitutively antibiotic-resistant Staphylococcus aureus remains impervious to existing macrolides including telithromycin. Here, we report the design and synthesis of a novel series of macrolides, featuring the strategic fusion of ketolide and quinolone moieties.

Design, synthesis and structure-activity relationships of novel non-ketolides: 9-Oxime clarithromycin featured with seven-to thirteen-atom-length diamine linkers at 3-OH.

We report here on the structure-activity relationships of hybrids combining 3-descladinosyl clarithromycin with quinolones linked by extended diamine connectors. Several hybrids, exemplified by 23Bc, 23Be, 23Bf, 26Be, and 30Bc, not only restored potency against inducibly resistant pathogens but also exhibited significantly enhanced activities against constitutively resistant strains of Staphylococcus pneumoniae and Staphylococcus pyogenes, which express high-level resistance independent of clarithromycin or erythromycin induction. Additionally, the novel hybrids showed susceptibility against Gram-negative Haemophilus influenzae.

Establishment and validation of symptomatic patients colorectal screening score for predicting colorectal neoplasia risk.

Objectives: Currently, most colorectal neoplasia (CRN) screening strategies target asymptomatic individuals. However, studies on patients with non-specific gastrointestinal symptoms (NSGS) are limited. We aimed to develop a CRN risk score specifically for patients with NSGS.

miR‑31 promotes tumorigenesis in ulcerative colitis‑associated neoplasia via downregulation of SATB2.

Ulcerative colitis (UC) features chronic, non-infectious inflammation of the colon. The risk of ulcerative colitis‑associated neoplasia (UCAN) increases in direct association with the duration of this disease. Whether miRNAs exert a regulatory effect on the pathogenesis of UCAN has remained to be elucidated.

Reevaluation of a rightward shift in colorectal cancer: A single-center retrospective study in Tianjin.

Objectives: Some Western reports have shown a proximal shift in colorectal cancer (CRC), but there are few studies in China. This study aimed to provide more information for the management and screening of CRC by investigating trends in the anatomic distribution of CRC among the Chinese population in recent years.

Methods: A retrospective study was conducted on patients with CRC admitted to the Digestive Endoscopy Center of Tianjin Medical University General Hospital between January 2000 and December 2017.

Hemostatic effect of topical hemocoagulase spray in digestive endoscopy.

Aim: To evaluate the hemostatic effect of topical hemocoagulase spray in digestive endoscopy.

Methods: Eighty-nine patients who developed oozing bleeding during endoscopic treatment from September 2014 to October 2014 at Center for Digestive Endoscopy, Tianjin Medical University General Hospital were randomly divided into either a study group (n = 39) or a control group (n = 50). The study group was given topical hemocoagulase spray intraoperatively, while the control group was given traditional 8% norepinephrine spray.

IL-37b gene transfer enhances the therapeutic efficacy of mesenchumal stromal cells in DSS-induced colitis mice.

Aim: To investigate whether the transfer of the IL-37b gene, a newly identified inhibitor of both innate and adaptive immunity, could improve the therapeutic efficacy of mesenchumal stromal cells (MSCs) in inflammatory bowel disease (IBD).

Methods: The expression of IL-37 in biopsied specimens of the patients with active ulcerative colitis (UC) was detected using RT-PCR and immunohistochemistry. Mice were treated with 3% dextran sulfate sodium (DSS) for 8 days to induce colitis.

[DNA methylation of microRNA-34b/c and microRNA-124a in gastric cancer].

Objective: To explore the effects of DNA methylation of microRNA (miRNA) gene on their expressions in patients with gastric carcinoma.

Methods: A total of 80 subjects were divided into gastric carcinoma group (n = 40) and control group (n = 40). The DNA methylation status of miRNA-34b/c and miRNA-124a gene promoters was detected by DNA methylation specific polymerase chain reaction (MSP) in gastric carcinoma tissues and normal mucosal tissues.

[Correlation of E-cadherin hypermethylation to tumorigenesis and development of gastric cancer].

Background & Objective: CpG island hypermethylation in promoter region of E-cadherin (E-cad) gene plays an important role in tumorigenesis of many tumors. This study was to explore the correlation of E-cadherin hypermethylation to tumorigenesis and development of gastric cancer.

Methods: Methylation-specific polymerase chain reaction (MSP) was used to detect the methylation of E-cad gene in 41 specimens of gastric cancer, 40 specimens of premalignant gastric lesions and 38 specimens of normal gastric tissues.

[A study of interleukin-10 gene polymorphism in irritable bowel syndrome].

Objective: To investigate whether three diallelic polymorphisms at the position -1082, -819 and -592 in the promoter region of the IL-10 gene were associated with diarrhea-predominant irritable bowel syndrome (D-IBS).

Methods: The IL-10 gene -1082, -819 and -592 position polymorphisms were genotyped by amplification refractory mutation systems-polymerase chain reaction (ARMS-PCR) methods in 43 patients with D-IBS and 41 healthy subjects (HS).

Results: Compared with HS, D-IBS patients had a greater frequency of T/T genotype at IL-10 gene promoter -819 position (67.

[Differential expression of motility-related protein-1/CD9 gene in gastric cancers and premalignant lesions].

Objective: To clone and identify gastric cancer-related genes and explore the possible pathogenic mechanism of gastric cancer.

Methods: The differentially expressed cDNA bands were isolated by fluorescent mRNA differential display in gastric cancer specimens, matched normal gastric mucosa and premalignant lesions. The motility-related protein-1 (MRP-1/CD9) gene was one of the down-regulated genes.

[Serotonin transporter gene polymorphism in irritable bowel syndrome].

Objective: To investigate the association of serotonin transporter (SERT) gene polymorphism with irritable bowel syndrome (IBS).

Methods: The VNTRs and 5-HTTLPR polymorphism of SERT gene was assessed with polymerase chain reaction in 81 patients with IBS and 48 healthy subjects(HS).

Results: Compared with HS, IBS patients have a greater frequency of STin2.

[Study of genes related to gastric cancer and its premalignant lesions with fluorescent differential display].

Background & Objective: It is generally recognized that development of gastric cancer arises gradually from premalignant lesions (chronic atrophic gastritis, intestinal metaplasia and dysplasia). Differential display of mRNA is a valuable tool for the identification of differentially expressed genes in human carcinogenesis and development. The search for differentially expressed genes in gastric cancer and its premalignant lesions may help to define molecular alterations in the gastric mucosa tissue that may precede the development of gastric cancer.