Novel benzimidazolyl tetrahydroprotoberberines: Design, synthesis, antimicrobial evaluation and multi-targeting exploration.

A series of novel benzimidazolyl tetrahydroprotoberberines were conveniently designed and efficiently synthesized from berberine via direct cyclization of tetrahydroprotoberberine aldehyde and o-phenylene diamines under metal-free aerobic oxidation. All the new compounds were characterized by IR, 1H NMR, 13C NMR and HRMS spectra. The antimicrobial evaluation revealed that the 5-fluorobenzimidazolyl derivative 5b was the most active antibacterial and antifungal molecule with broad spectrum in comparison to Berberine, Chloromycin, Norfloxacin and Fluconazole. It triggered almost no resistance development against MRSA even after 15 passages. Further studies demonstrated that compound 5b could not only effectively interact with Topo IA by hydrogen bonds, but also intercalate into calf thymus DNA and cleave pBR322 DNA, which might be responsible for its powerful bioactivities.

The complete mitochondrial genome of Triplophysa erythraea (Huang et al. 2019) (Cypriniformes, Nemacheilidae).

In this study, the complete mitochondrial genome of Triplophysa erythraea was determined for the first time. Results showed the mitogenome was 16 565 bp, including 2 ribosomal RNA genes, 22 transfer RNA genes, 13 protein-coding genes and 2 non-coding regions. The overall base composition of its mitochondrial genome was 28.9% A, 25.2% T, 28.7% C and 17.2% G. Phylogenetic tree revealed that Triplophysa erythraea had the closest relationship with Triplophysa xiangxiensis, which was also found in Xiangxi Tujia and Miao Nationality Autonomous Prefecture, Hunan province. In general, this study provided valuable information for conservation genetics analyses of Triplophysa erythraea and further displayed the evolution of species within the genus Triplophysa.

Prognostic value of a nomogram model for postoperative liver metastasis of colon cancer.

BACKGROUND: Colon cancer is one of the most common malignant tumors of the digestive system. Liver metastasis after colon cancer surgery is the primary cause of death in patients with colon cancer. AIM: To construct a novel nomogram model including various factors to predict liver metastasis after colon cancer surgery. METHODS: We retrospectively analyzed 242 patients with colon cancer who were admitted and underwent radical resection for colon cancer in Zhejiang Provincial People's Hospital from December 2019 to December 2022. Patients were divided into liver metastasis and non-liver metastasis groups. Sex, age, and other general and clinicopathological data (preoperative blood routine and biochemical test indexes) were compared. The risk factors for liver metastasis were analyzed using single-factor and multifactorial logistic regression. A predictive model was then constructed and evaluated for efficacy. RESULTS: Systemic inflammatory index (SII), C-reactive protein/albumin ratio (CAR), red blood cell distribution width (RDW), alanine aminotransferase, preoperative carcinoembryonic antigen level, and lymphatic metastasis were different between groups (P < 0.05). SII, CAR, and RDW were risk factors for liver metastasis after colon cancer surgery (P < 0.05). The area under the curve was 0.93 for the column-line diagram prediction model constructed based on these risk factors to distinguish whether liver metastasis occurred postoperatively. The actual curve of the column-line diagram predicting the risk of postoperative liver metastasis was close to the ideal curve, with good agreement. The prediction model curves in the decision curve analysis showed higher net benefits for a larger threshold range than those in extreme cases, indicating that the model is safer. CONCLUSION: Liver metastases after colorectal cancer surgery could be well predicted by a nomogram based on the SII, CAR, and RDW.

Portal vein gas combined with pneumatosis intestinalis and emphysematous cystitis: A case report and literature review.

BACKGROUND: Portal venous gas (PVG) is a rare clinical condition usually indicative of severe disorders, including necrotizing enterocolitis, bowel ischemia, or bowel wall rupture/infarction. Pneumatosis intestinalis (PI) is a rare illness characterized by an infiltration of gas into the intestinal wall. Emphysematous cystitis (EC) is relatively rare and characterized by intramural and/or intraluminal bladder gas best depicted by cross-sectional imaging. Our study reports a rare case coexistence of PVG presenting with PI and EC. CASE SUMMARY: An 86-year-old woman was admitted to the emergency room due to the progressive aggravation of pain because of abdominal fullness and distention, complicated with vomiting and stopping defecation for 4 d. The abdominal computed tomography (CT) plain scan indicated intestinal obstruction with ischemia changes, gas in the portal vein, left renal artery, superior mesenteric artery, superior mesenteric vein, some branch vessels, and bladder pneumatosis with air-fluid levels. Emergency surgery was conducted on the patient. Ischemic necrosis was found in the small intestine approximately 110 cm below the Treitz ligament and in the ileocecal junction and ascending colon canals. This included excision of the necrotic small intestine and right colon, fistulation of the proximal small intestine, and distal closure of the transverse colon. Subsequently, the patient displayed postoperative short bowel syndrome but had a good recovery. She received intravenous fluid infusion and enteral nutrition maintenance every other day after discharge from the community hospital. CONCLUSION: Emergency surgery should be performed when CT shows signs of PVG with PI and EC along with a clinical situation strongly suggestive of bowel ischemia.

Synthesis, biological evaluation and cellular localization study of fluorescent derivatives of Jiyuan Oridonin A.

Jiyuan Oridonin A (JOA) is a naturally occurring ent-kaurane diterpenoid that exhibits significant potential in the field of anti-tumor drug development. However, its detailed anti-cancer mechanism of action has not been fully understood. In order to investigate its anticancer mode of action, two series of novel fluorescent derivatives of JOA conjugated with naphthalimide dyes were synthesized, and their antitumor activity against five selected cancer cell lines (MGC-803, SW1990, PC-3, TE-1 and HGC-27) was evaluated. Compared with JOA, the anti-tumor activity of the vast majority of compounds were improved. Among them, B12 exhibited promising anti-proliferative activity against HGC-27 cells with IC50 value of 0.39 ± 0.09 µM. Fluorescence imaging studies demonstrated that probe B12 could enter HGC-27 cells in a dose-dependent and time-dependent manner and was mainly accumulated in mitochondria. Preliminary biological mechanism studies indicated that B12 was able to inhibit cell cloning and migration. Further studies suggested that B12-induced apoptosis was related to the mitochondrial pathway. Overall, our results provide new approaches to explore the molecular mechanism of the natural product JOA, which would contribute to its further development as an antitumor agent.

[Surgery of ventilation tube insertion in the middle ear and the external auditory canal for chronic secretory otitis media in children].

OBJECTIVE: To study the therapeutic effect of ventilation tube insertion in the middle ear and the external auditory canal on chronic secretory otitis media in children. METHODS: A retrospective study on 30 patients (40 ears) with chronic secretory otitis media and who underwent the operation of middle ear exploration and ventilation tube insertion in the middle ear and the external auditory canal was performed. Poor tympanic membrane, even with adhesion, was seen in 23 ears. Ten patients had evidence of bilateral secretory otitis media. From this group one ear was first injected with drugs (dexamethasone, mucosolvin, etc) and then tube insertion into the auditory tube was performed; the other ear only received drug injections into the auditory tube. The remaining 20 patients who had evidence of unilateral secretory otitis media only received drug injections into the auditory tube. RESULTS: The tubes inserting into the auditory tube all dropped out 5-8 days after operation. None of the ventilation tubes into the middle ear dropped out and the patients' tympanum recovered after the ventilation tubes were removed (6-8 months after operation). The total cure rate was 87.5% (35/40) and the improvement rate was 12.5% (5/40). The operation of inserting tubes into the auditorytube did not improve the therapeutic effects. In the 0.5-2 years postoperative follow-up, middle ear effusions recurred in one ear, and three ears were transferred from type C to type A. CONCLUSIONS: The surgery of ventilation tube insertion in the middle ear and the external auditory canal for chronic secretory otitis media can prevent the tympanic membrane from damage and dropping out of the ventilation tube and reduce recurrence in children. It is a preferred selection for the patients with poor tympanic membrane or adhesive tympanic membrane. It is no use to insert the tube into the auditory tube for the improvement of therapeutic effects.

Novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents: Design, synthesis and biological evaluation.

A series of novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents were designed, synthesized and characterized by IR, NMR and HRMS spectra. The biological evaluation in vitro revealed that some of the target compounds exerted good antibacterial and antifungal activity in comparison with the reference drugs. Noticeably, compound 7d could effectively inhibit the growth of A. flavus, E. coli DH52 and MRSA with MIC values of 1, 1 and 8 µg/mL, respectively. Further studies revealed that pyrimidine derivative 7d could exhibit bactericidal mode of action against both Gram positive (S. aureus and MRSA) and Gram negative (P. aeruginosa) bacteria. The active molecule 7d showed low cell toxicity and did not obviously trigger the development of resistance in bacteria even after 16 passages. Furthermore, compound 7d was able to beneficially regulate reactive oxygen species (ROS) generation for an excellent safety profile. Molecular docking study revealed that compound 7d could bind with DNA gyrase by the formation of hydrogen bonds. The preliminary exploration for antimicrobial mechanism disclosed that compound 7d could effectively intercalate into calf thymus DNA to form a steady supramolecular complex, which might further block DNA replication to exert the powerful bioactivities. The binding investigation of compound 7d with human serum albumins (HSA) revealed that this molecule could be effectively transported by HSA.

Design, synthesis and biological evaluation of novel Schiff base-bridged tetrahydroprotoberberine triazoles as a new type of potential antimicrobial agents.

A series of novel Schiff base-bridged tetrahydroprotoberberine (THPB) triazoles were designed, synthesized and characterized for the first time. Antimicrobial assay showed that some of the prepared compounds exerted stronger antibacterial and antifungal activities than the reference drugs. Especially, THPB triazole 7a gave low MIC values of 0.5, 1 and 2 µg mL-1 against B. yeast, M. luteus and MRSA, respectively. Further experiments indicated that the highly active molecule 7a was able to rapidly kill the MRSA strain and did not trigger the development of bacterial resistance even after 14 passages. The preliminary exploration for the antimicrobial mechanism revealed that compound 7a could effectively intercalate into calf thymus DNA to form a 7a-DNA supramolecular complex, and its Zn2+ complex had the ability to directly cleave pUC19 DNA, which suggested that compound 7a might be a potentially dual-targeting antibacterial molecule. It was also found that compound 7a could be efficiently stored and carried by human serum albumin (HSA), and the hydrophobic interactions and hydrogen bonds played important roles in the transportation of HSA to the active molecule 7a.

Novel Naphthalimide Aminothiazoles as Potential Multitargeting Antimicrobial Agents.

A series of novel naphthalimide aminothiazoles were developed for the first time and evaluated for their antimicrobial activity. Some prepared compounds possessed good inhibitory activity against the tested bacteria and fungi. Noticeably, the piperazine derivative 4d displayed superior antibacterial activity against MRSA and Escherichia coli with MIC values of 4 and 8 µg/mL, respectively, to reference drugs. The most active compound 4d showed low toxicity against mammalian cells with no obvious triggering of the development of bacterial resistance, and it also possessed rapid bactericidal efficacy and efficient membrane permeability. Preliminarily investigations revealed that compound 4d could not only bind with gyrase-DNA complex through hydrogen bonds but could effectively intercalate into MRSA DNA to form 4d-DNA supramolecular complex, which might be responsible for the powerful bioactivity. Further transportation behavior evaluation indicated that molecule 4d could be effectively stored and carried by human serum albumin, and the hydrophobic interactions and hydrogen bonds played important roles in the binding process.