SPAG5 contributes to the progression of gastric cancer by upregulation of Survivin depend on activating the wnt/ß-catenin pathway.

The sperm-associated antigen 5 (SPAG5) plays a key role in controlling cellular processes, including cell cycle progression and proliferation. However, the role of SPAG5 in gastric cancer (GC) remains unclear. Herein, our study showed that upregulation of SPAG5 was detected frequently in GC tissues, and was associated with significantly worse survival in patients with GC. Multivariate analyses revealed that high SPAG5 expression was an independent predictive marker for the poor prognosis of GC patients. Further, SPAG5 knockdown notably inhibited the proliferation abilities of GC in vivo and in vitro. Moreover, our results indicate that SPAG5 promotes cell progression by increasing Survivin expression, which has been reported to control the progression of GC. Moreover, our data demonstrate that Survivin is crucial for SPAG5-mediated GC cell progression in vitro and in vivo. Mechanistically, we demonstrated that SPAG5 promotes the progression of GC via enhancing the Wnt/ß-catenin/Survivin axis. Collectively, our data suggest that SPAG5 plays a crucial oncogenic role in GC tumorigenesis, and we provide a novel evidence that SPAG5 may be serve as a prognostic and therapeutic target for GC patients.

Metformin Regulates Cardiac Ferroptosis to Reduce Metabolic Syndrome-Induced Cardiac Dysfunction.

High-fat diet-induced metabolic syndrome (MetS) is closely associated with cardiac dysfunction. Recent research studies have indicated a potential association between MetS and ferroptosis. Furthermore, metformin can alleviate MetS-induced cardiac ferroptosis. Metformin is a classic biguanide anti-diabetic drug that has protective effects on cardiovascular diseases, which extend beyond its indirect glycemic control. This study aimed to assess whether MetS mediates cardiac ferroptosis, thereby causing oxidative stress and mitochondrial dysfunction. The results revealed that metformin can mitigate cardiac reactive oxygen species and mitochondrial damage, thereby preserving cardiac function. Mechanistic analysis revealed that metformin upregulates the expression of cardiac Nrf2. Moreover, Nrf2 downregulation compromises the cardio-protective effects of metformin. In summary, this study indicated that MetS promotes cardiac ferroptosis, and metformin plays a preventive and therapeutic role, partially through modulation of Nrf2 expression.

Aspertaichamide a, a novel cytotoxic prenylated indole alkaloid possessing a bicyclo[2.2.2]diazaoctane framework from a marine algal-derived endophytic fungus aspergillus taichungensis 299.

Filamentous fungi belonging to the genus Aspergillus are prodigious producers of alkaloids, particularly prenylated indole alkaloids, that often exhibit structurally diversified skeletons and potent biological activities. In this study, five prenylated indole alkaloids possessing a bicyclo[2.2.2]diazaoctane core ring system, including a novel derivative, namely aspertaichamide A (1), as well as four known compounds, (+)-stephacidin A (2), sclerotiamide (3), (-)-versicolamide B (4), and (+)-versicolamide B (5), were isolated and identified from A. taichungensis 299, an endophytic fungus obtained from the marine red alga Gelidium amansii. The chemical structures of the compounds were elucidated by comprehensive NMR and HRESIMS spectroscopic analyses. In addition to the previously reported prenylated indole alkaloids, aspertaichamide A (1) was characterized as having an unusual ring structure with the fusion of a 3-pyrrolidone dimethylbenzopyran to the bicyclo[2.2.2]diazaoctane moiety, which was rare in these kinds of compounds. The absolute configuration of 1 was determined by TDDFT-ECD calculations. In vitro cytotoxic assays revealed that the novel compound 1 possessed selective cytotoxic activity against five human tumor cell lines (A549, HeLa, HepG2, HCT-116, and AGS), with IC50 values of 1.7-48.5 µM. Most importantly, compound 1 decreased the viability of AGS cells in a concentration-dependent manner with an IC50 value of 1.7 µM. Further studies indicated that 1 may induce AGS cells programmed cell death via the apoptotic pathway.

Halometabolites isolated from the marine-derived fungi with potent pharmacological activities.

Halometabolites, usually produced in marine environment, are an important group of natural halogenated compounds with rich biological functionality and drugability and thus play a crucial role in pharmaceutical and/or agricultural applications. In the exploration of novel halometabolites from marine microorganisms, the growing number of halogenated compounds makes it necessary to fully present these metabolites with diverse structures and considerable bioactivities. This review particularly focuses on the chemodiversity and bioactivities of halometabolites from marine-derived fungi. As a result, a total of 145 naturally halogenated compounds, including 118 chlorinated, 23 brominated, and four iodinated compounds, were isolated from 17 genera of marine-derived fungi. Interestingly, many of halometabolites, especially for the brominated and iodinated compounds, are generated by the substitution of bromide and iodide ions for the chloride ion in cultivation process. In addition, these compounds possess diverse structural types, which are classified into polyketides (62.7%), phenols (16.6%), alkaloids (14.5%), and terpenoids (6.2%). Their cytotoxic, antibacterial, and anti-inflammatory activities indicate the high potential of these halogenated compounds as lead compounds for drug discovery.

Antimicrobial and cytotoxic phenolic bisabolane sesquiterpenoids from the fungus Aspergillus flavipes 297.

Phenolic bisabolane-type sesquiterpenoids (PBS) represent a rare class of natural products with diverse biological activities. In this study, chemical investigations of the fungus Aspergillus flavipes 297 resulted in the isolation and identification of seven PBS, including a pair of new enantiomers (+)-1a and (-)-1b, a new derivative 2, and five previously reported ones 3-7. The chemical structures of the isolated PBS were determined by extensive NMR and HRESIMS spectroscopic analysis. The absolute configurations of the separated enantiomers (+)-1a and (-)-1b were solved by comparison of the experimental ECD spectra with those of the TDDFT-ECD calculated spectra. The new compounds 1 and 2 represent rare cases of PBS bearing a methylsulfinyl group, which was distinct from the commonly-observed PBS structurally. All the isolated compounds 1-7 were evaluated their antimicrobial and cytotoxic activities. As a result, the tested compounds showed selective antimicrobial activity against several pathogenic bacteria and fungi with the MIC (minimum inhibiting concentrations) values ranging from 2 to 64 µg/mL. Moreover, enantiomers (+)-1a and (-)-1b, together with compound 2, exhibited promising cytotoxicity against MKN-45 and HepG2 cell lines, respectively, indicating that the methylsulfinyl substituent enhanced cytotoxicity to a certain degree.