Macrophage modulation with dipeptidyl peptidase-4 inhibitors:A new frontier for treating diabetic cardiomyopathy?

This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy(DCM)treatment by dipeptidyl peptidase-4(DPP-4)inhibitors.Zhang et al studied teneligliptin,a DPP-4 inhibitor used for diabetes management,and its potential cardioprotective effects in a diabetic mouse model.They suggested teneligliptin administration may reverse established markers of DCM,including cardiac hypertrophy and compromised function.It also inhibited the NLRP3 inflammasome and reduced inflammatory cytokine production in diabetic mice.Macrophages play crucial roles in DCM pathogenesis.Chronic hyperglycemia disturbs the balance between pro-inflammatory(M1)and antiinflammatory(M2)macrophages,favoring a pro-inflammatory state contributing to heart damage.Here,we highlight the potential of DPP-4 inhibitors to modulate macrophage function and promote an anti-inflammatory environment.These compounds may achieve this by elevating glucagon-like peptide-1 levels and potentially inhibiting the NLRP3 inflammasome.Further studies on teneligliptin in combination with other therapies targeting different aspects of DCM could be suggested for developing more effective treatment strategies to improve cardiovascular health in diabetic patients.

Aryl hydrocarbon receptor dynamics in esophageal squamous cell carcinoma:From immune modulation to therapeutic opportunities

Esophageal squamous cell carcinoma(ESCC)is a substantial global health burden.Immune escape mechanisms are important in ESCC progression,enabling cancer cells to escape the surveillance of the host immune system.One key player in this process is the Aryl Hydrocarbon Receptor(AhR),which influences multiple cellular processes,including proliferation,differentiation,metabolism,and immune regulation.Dysregulated AhR signaling participates in ESCC development by stimulating carcinogenesis,epithelial-mesenchymal transition,and immune escape.Targeting AhR signaling is a potential therapeutic approach for ESCC,with AhR ligands showing efficacy in preclinical studies.Additionally,modification of AhR ligands and combination therapies present new opportunities for therapeutic intervention.This review aims to address the knowledge gap related to the role of AhR signaling in ESCC pathogenesis and immune escape.

Antimicrobial chemical constituents from endophytic fungus Phoma sp.

Objective:To evaluate the antiniicrobial polenlial of different extracts of the endophytic fungus Phoma sp.and the tentative identification of their active constituents.Methods:The extract and compounds were screened for antimicrobial activity using the Agar Well Diffusion Method.Four compounds were purified using column chromatography and tlieir structures were assigned using～1H and～(13)C NMR spectra,DEPT,2D COSY,HMQC and HMBC experiments.Results:The ethyl acetate fraction of Phoma sp.showed good antifungal,antibacterial,and algicidal properties.One new dihydrofuran derivative,named phomafuranol(1),together with tliree known compounds,phomalacton(2),(3R)-5-hydroxymellein(3)and emodin(4)were isolated from the ethyl acetate fraction of Phoma sp.Preliminary studies indicated that phomalacton(2)displayed strong antibacterial,good antifungal and antialgal activities.Similarly(3R)-5-hydroxymellein(3)and emodin(4)showed good antifungal,antibacterial and algicidal properties.Conclusions:Antimicrobial activities of the ethyl acetate fraction of the endophytic fungus Phoma sp.and isolated compounds clearly demonstrate that Phoma sp.and its active compounds represent a great potential for the food,cosmetic and pharmaceutical industries.

Dimethylformamide Dimethyl Acetal (DMFDMA) in Heterocyclic Synthesis: Synthesis of Polysubstituted Pyridines, Pyrimidines, Pyridazine and Their Fused Derivatives

Reaction of N,N’-dimethylformamide dimethyl acetal (DMFDMA) with malononitrile dimer 8 (1:1) mole afforded 9 while, this reaction when carried out in (2:1) mole to give amidine 11 which can be used for the preparation of pyrimidine 13, amidine 14 and pyridine 19 when reacted with 4-nitroaniline, 4-methylaniline and alkoxide respectively. Malononitrile dimer reacted with diazonium chloride to give pyridazine 21, which can be reacted with DMFDMA, AcOH/HCl and cyanoacetamide to give pyridazine 22, 23 and pyrido[4,3-c] pyridazine 24 respectively. The latter reacted with DMFDMA to afford tricyclic compound 25.

A novel variant of GALC in a familial case of Krabbe disease:Insights from structural bioinformatics and molecular dynamics simulation

Krabbe disease or globoid cell leukodystrophy(GLD;MIM#245200)is a rare and fatal lysosomal storage disease with an autosomal recessive mode of inheritance that results from the deficiency of galactocerebrosidase(GALC;E.C.3.2.1.46),a lysosomal enzyme encoded by the GALC gene.1 GALC breaks down galactosylceramide,a cerebroside located mainly in the myelin sheath.Defects in GALC cause the accumulation of a cytotoxic metabolite,galactosylsphingosine or psychosine,which can be toxic to oligodendrocytes and Schwann cells.2 The failure to digest galactosylceramide triggers the formation of multi-nucleated globoid cells,causing severe demyelination,axonopathy,and neuronal death.3 The reported frequency of Krabbe disease is 1 in 100,000 live births with symptoms including irritability,loss of motor ability,spasticity,ataxia,visual dysfunction,seizures,andcognitive impairment.

Endophytes from medicinal plants and their potential for producing indole acetic acid, improving seed germination and mitigating oxidative stress

Medicinal plants have been used by marginal communities to treat various ailments. However, the potential of endophytes within these bio-prospective medicinal plants remains unknown. The present study elucidates the endophytic diversity of medicinal plants（Caralluma acutangula, Rhazya stricta, and Moringa peregrina） and the endophyte role in seed growth and oxidative stress. Various organs of medicinal plants yielded ten endophytes, which were identified as Phoma sp.（6 isolates）, Alternaria sp.（2）, Bipolaris sp.（1）, and Cladosporium sp.（1） based on 18 S rD NA sequencing and phylogenetic analysis. The culture filtrates（CFs; 25%, 50%, and 100% concentrations） from these endophytes were tested against the growth of normal and dwarf mutant rice lines. Endophytic CF exhibited dose-dependent growth stimulation and suppression effects. CF（100%） of Phoma sp. significantly increased rice seed germination and growth compared to controls and other endophytes. This growth-promoting effect was due to the presence of indole acetic acid in endophytic CF. The gas chromatography/mass spectrometry（GC/MS） analysis showed the highest indole acetic acid content（（54.31±0.21） μmol/L） in Bipolaris sp. In addition, the isolate of Bipolaris sp. exhibited significantly higher radical scavenging and anti-lipid peroxidation activity than the other isolates. Bipolaris sp. and Phoma sp. also exhibited significantly higher flavonoid and phenolic contents. The medicinal plants exhibited the presence of bio-prospective endophytic strains, which could be used for the improvement of crop growth and the mitigation of oxidative stresses.

Antituberculosis and cytotoxic activities of triorganotin(Ⅳ) complexes

Five triorganotin（IV） （1-5） complexes of cinnamic acid, （Z）-2-acetamido-3-phenylacrylic acid, 3-methylbut-2-enoic acid, and 2,2-diphenylacetic acid have been synthesized and characterized by IH-13C-119Sn NMR, UV, and IR. The spectroscopic investigation demonstrated that the carboxylate group acts as a monodentate ligand in triorganotin（IV） compounds. Five triorganotin（IV） complexes were screened against the log phase culture of Mycobacterium tuberculosis H37Rv by colorimetric method using XTT dye as growth indicator. The MICs were found to he 0.08 and 1.25μg/mL.

Seimatoric acid and colletonoic acid:Two new compounds from the endophytic fungi,Seimatosporium sp.and Colletotrichum sp.

A new metabolite,named seimatoric acid（1）,representing a new oxobutanoic acid derivative has been isolated from Seimatosporium sp., in addition to four known compounds viz.,2-hydroxymethyl-4β,5α,6β-trihydroxycyclohex-2-enone（2）,（-）-phyllostine（3）,（＋）-epiepoxydon（4） and（＋）-epoxydon monoacetate（5）.Similarly one new benzoic acid derivative,named colletonoic acid（6） was isolated from the ethyl acetate fraction of Colletotrichum sp.The structures of the new compounds were elucidated by detailed ^1 H NMR,^13C NMR,COSY,HMQC.HMBC spectroscopic analysis,and HR-E1-MS.Seimatoric acid（1）was also isolated from another taxonomical unidentified fungal strain 4295 in ourgroup.The structures of the known compounds were elucidated by their spectral data comparison to literature data.Preliminary studies showed that colletonoic acid（6） showed good antibacterial,antifungal,and antialgal activities.