Interferon-regulatory factor-1 boosts bevacizumab cardiotoxicity by the vascular endothelial growth factor A/14-3-3γ axis.

Aim: Myocardial injury is a significant cause of death. This study investigated the role and underlying mechanism of interferon-regulatory factor-1 (IRF1) in bevacizumab (BVZ)-induced cardiomyocyte injury.

Methods And Results: HL-1 cells and C57BL/6 mice receiving BVZ treatment were used to establish in vitro and in vivo models of myocardial injury.

Structures, Biosynthesis, and Bioactivity of Oligomycins from the Marine-Derived sp. FXY-T5.

Oligomycins are potent antifungal and antitumor agents. Mass spectrometry (MS)- and nuclear magnetic resonance (NMR)-based metabolomic fingerprinting analysis of marine-derived actinomycetes in our in-house library provided an oligomycin-producing strain, sp. FXY-T5.

CREB-binding protein and HIF-1α/β-catenin to upregulate miR-322 and alleviate myocardial ischemia-reperfusion injury.

Myocardial ischemia/reperfusion injury (MIRI) is a prevalent condition associated with numerous critical clinical conditions. miR-322 has been implicated in MIRI through poorly understood mechanisms. Our preliminary analysis indicated potential interaction of CREB-binding protein (CBP), a transcriptional coactivator and acetyltransferase, with HIF-1α/β-catenin, which might regulate miR-322 expression.

Interconvertible Pyridone Alkaloids from the Marine-Derived Fungus QDU1.

Eleven new pyridone alkaloids, penicipyridones A-K (-), and three new tetramic acids, tolypocladenols D-F (-), were isolated from rice media cultures of the marine-derived fungus QDU1. Their structures, including absolute configurations, were determined by comprehensive analyses of spectroscopic data, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction data. Interestingly, several of the penicipyridones undergo interconversions between hydroxy and methoxy groups at C-4 in acidic MeOH solution.

Cytochalasans with Inhibitory Activity against NPC1L1 from the Endophytic Fungus F5.

Mass spectrometry (MS)-based metabolic profiling of the endophytic fungus F5 guided the isolation of five novel cytochalasans, chamisides B-F (), and two known ones, chaetoconvosins C and D ( and ). Their structures including stereochemistry were unambiguously determined by MS, nuclear magnetic resonance, and single-crystal X-ray diffraction analyses. Compounds share a new 5/6/5/5/7-fused pentacyclic skeleton in cytochalasans and are appropriately proposed to be the key biosynthetic precursors of co-isolated cytochalasans with a 6/6/5/7/5, 6/6/5/5/7, or 6/6/5 ring system.

Metabolic profiling for the discovery of two rare fusidane-type heterodimers from the fungal endophyte Acremonium pilosum F47.

In our process of studying fusidane-type antibiotics, metabolomics-guided chemical investigation on the endophytic Acremonium pilosum F47 led to the isolation of two unique heterodimers, acremonidiols B and C (1 and 2) consisting of a fusidane-type triterpenoid motif and a steroid unit. Four biosynthetically related known natural products including fusidic acid (FA, 3), as well as ergosterol derivatives (4-6) were also obtained. Their structures were determined by the analyses of ESI-HRMS and NMR data.

Metabolic Profiling for the Discovery of Structurally Diverse Gibberellins and Their Precursors from the Endophytic Fungus sp. NJ-F5.

Gibberellins (GAs) are well-known tetracyclic diterpenoid phytohormones since the 1950s. In this work, eight skeletally diverse GAs (-) including four new compounds (-), and three known ent-kaurene diterpenoids (-), were isolated from the endophytic fungus sp. NJ-F5 by integrating mass spectrometry (MS)- and nuclear magnetic resonance (NMR)-based metabolic profiling.

Evaluation of the safety and efficacy of a novel Anatomical classification and dUal anchoRing theory to Optimize the tavR strategy for pure severe Aortic regurgitation (AURORA): a prospective cohort study.

Background: Success rate of transcatheter aortic valve replacement (TAVR) in aortic regurgitation (AR) patients is relatively low on account of the absence of calcified anchoring structures. Morphological classification and corresponding TAVR strategies for AR are lacking yet.

Methods: The AURORA study is a prospective, multicenter, single-arm cohort study to evaluate the safety and efficacy of transfemoral TAVR for severe AR in patients with high or prohibitive risk for surgery.

Naphtho-Gamma-Pyrones (NPs) with Obvious Cholesterol Absorption Inhibitory Activity from the Marine-Derived Fungus S-48.

Eight naphtho-gamma-pyrones (NPs) (-), together with four known biosynthetically related coumarin derivatives (-), were isolated from the potato dextrose agar media of a marine-derived fungus S-48. Among them, natural compounds and were tentatively subjected to benzohydrazide reaction to evaluate the importance of pyran rings in NPs. Their structures were elucidated by extensive 1D and 2D NMR spectroscopic data and MS spectra.

Structurally Various Sorbicillinoids From an Endophytic Fungus SS-g13.

Three new sorbicillinoids, including trimer trisorbicillinone E (), acremosorbicillinoids A and B ( and ), and a new alkaloid acremokaloid A (), and a new natural product 2,3-acetyl-β-methyltryptophan (), were isolated from an endophytic fungus SS-g13, which is found in plant root. In addition, eight known sorbicillinoids () were also obtained. The new compound structures were established using NMR, HRESIMS spectra, and reported spectroscopic data.

miR-322/miR-503 clusters regulate defective myoblast differentiation in myotonic dystrophy RNA-toxic by targeting Celf1.

Myotonic dystrophy (DM) is a genetic disorder featured by muscular dystrophy. It is caused by CUG expansion in the myotonic dystrophy protein kinase gene that leads to aberrant signaling and impaired myocyte differentiation. Many studies have shown that microRNAs are involved in the differentiation process of myoblasts.

Fusidic acid derivatives from the endophytic fungus F47.

Fusidic acid, a representative member of fungal fusidane triterpenoids, has been clinically used as an antibiotic. In the present study, fusidic acid (), and its known analogs 16-desacetylfusidic acid () and 3,20-dihydroxy-protosta-16,24-dien-29-oic acid (), together with one new derivative acremonidiol A (), were isolated from the endophytic fungus, F47. Their structures were determined by MS and NMR.

miR-140-5p mediates bevacizumab-induced cytotoxicity to cardiomyocytes by targeting the /14-3-3γ signal pathway.

Bevacizumab (BVZ) is the first recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGFA) approved by the FDA for the treatment of different kinds of cancers, especially colorectal cancer. Although the anti-tumor effects have been verified, the side effects of BVZ are also noteworthy, among which, cardiotoxicity may be the most serious side effect of BVZ. However, the exact mechanisms of cardiotoxicity induced by BVZ have been little explored.

Pleosporalins H and I, two new heptaketides from the endophytic fungus sp. F46 by using OSMAC strategy.

Two new heptaketides, pleosporalins H and I ( and ), as well as seven biosynthetically related known polyketides (-) were isolated from the endophytic fungus, sp. F46 by employing the one strain-many compounds (OSMAC) approach. The planar, relative and absolute structures of these compounds were identified by extensive spectroscopic analysis including HRMS, NMR, optical rotations and ECD calculations.

Dimeric 1,4-benzoquinone Derivatives with Cytotoxic Activities from the Marine-Derived Fungus sp. L129.

Two new dimeric 1,4-benzoquinone derivatives, peniquinone A () and peniquinone B (), a new dibenzofuran penizofuran A (), and a new pyrazinoquinazoline derivative quinadoline D (4), together with 13 known compounds (-), were isolated from a marine-derived fungus sp. L129. Their structures, including absolute configurations, were elucidated by extensive spectroscopic data and electronic circular dichroism calculations.

Chamiside A, a Cytochalasan with a Tricyclic Core Skeleton from the Endophytic Fungus Chaetomium nigricolor F5.

Chamiside A (1), a novel cytochalasan with a new 6/6/5-fused tricyclic core skeleton, was isolated from an endophytic fungus, Chaetomium nigricolor F5, harbored in the medicinal plant Mahonia fortunei. Its structure was unambiguously determined by extensive spectroscopic analyses, measurement of single-crystal X-ray diffraction, and electronic circular dichroism calculation. A biosynthetic pathway for the unique ring system in 1 was proposed.

Induced production of steroids by co-cultivation of two endophytes from Mahonia fortunei.

A new ergosterol derivative, 23R-hydroxy-(20Z,24R)-ergosta-4,6,8(14),20(22)-tetraen-3-one (1), and a biosynthetically related known compound, (22E,24R)-ergosta-4,6,8(14),22-tetraen-3-one (2), were isolated from the co-culture between endophytic fungus Pleosporales sp. F46 and endophytic bacterium Bacillus wiedmannii Com1 both inhibiting in the medicinal plant Mahonia fortunei. The structure of the new compound 1 was determined by extensive spectroscopic analysis using HRMS and NMR, together with the modified Mosher's ester method.

Acrepyrone A, a new -pyrone derivative from an endophytic fungus, SS-g13.

A new -pyrone derivative, acrepyrone A (), and three known sorbicillinoids, trichodimerol (), dihydrotrichodimerol () and tetrahydrotrichodimerol () were isolated from an endophytic fungus, SS-g13, harboured in the roots of the Chinese medicinal plant Their structures were determined by analysing MS, NMR, and ECD data. Compound was evaluated for its cytotoxic effect, antibacterial activity and quorum sensing inhibitory potential.

Inhibition of Smurf2 translation by miR-322/503 protects from ischemia-reperfusion injury by modulating EZH2/Akt/GSK3β signaling.

Myocardial ischemia-reperfusion (I/R) is a common and lethal disease that threatens people's life worldwide. The underlying mechanisms are under intensive study and yet remain unclear. Here, we explored the function of miR-322/503 in myocardial I/R injury.

Fupyrones A and B, two new -pyrones from an endophytic fungus, sp. F20.

Two new -pyrones, fupyrones A and B ( and ) and a biosynthetically related known -pyrone, 4-methyl-5,6-dihydro-2-pyran-2-one (), were isolated from an endophytic fungus, sp. F20, harbored in the stems of the Chinese medicinal plant . Their structures were determined on the basis of spectroscopic data including MS and NMR.

miRNA-133a attenuates lipid accumulation via TR4-CD36 pathway in macrophages.

lipid metabolism is the major causes of atherosclerosis. There is increasing evidence that miR-133a plays an important role in atherosclerosis. However, the regulatory mechanism of miR-133a in macrophages is still unclear.