Explore the vast range of titles available.

Gracilioether M (6) and 11,12-dihydrogracilioether M (7), two polyketides with a [2(5H)-furanylidene]ethanoate moiety, along with known plakortone G (9) and its new naturally occurring derivative 9,10-dihydroplakortone G (8), were isolated from the Caribbean marine sponge Plakortis halichondrioides. The structures and absolute configuration of 6, 7, and 8 were characterized by analysis of HRESIMS and NMR spectroscopic data, chemical derivatization, and side-by-side comparisons with published NMR data of related analogs. Compounds 6 and 7 and a mixture of 8 and 9 were evaluated for cytotoxicity against MCF-7 human breast cancer cells. In addition, the in vitro antiplasmodial activity against Plasmodium berghei of these compounds was scrutinized using a drug luminescence assay.

Mitogen-activated protein kinase (MAPK) signaling pathways control fundamental aspects of growth and development in fungi. In the soil-inhabiting ascomycete Fusarium oxysporum, which causes vascular wilt disease in more than a hundred crops, the MAPKs Fmk1 and Mpk1 regulate an array of developmental and virulence-related processes. The downstream components mediating these disparate functions are largely unknown. Here we find that the GATA-type transcription factor Pro1 integrates signals from both MAPK pathways to control a subset of functions, including quorum sensing, hyphal fusion and chemotropism. By contrast, Pro1 is dispensable for other downstream processes such as invasive hyphal growth and virulence, or response to cell wall stress. We further show that regulation of Pro1 activity by these upstream pathways occurs at least in part at the level of transcription. Besides the MAPK pathways, upstream regulators of Pro1 transcription also include the Velvet regulatory complex, the signaling protein Soft (Fso1) and the transcription factor Ste12 which was previously shown to act downstream of Fmk1. Collectively, our results reveal a role of Pro1 in integrating the outputs from different signaling pathways of F. oxysporum thereby mediating key developmental decisions in this important fungal pathogen.

The Lamiaceae family are utilized as ornamental, medicinal, and food supplements throughout the world. The current study focuses on a comparative analysis of the phenolic compositions and bioactivities (including antioxidant, anticholinergic, and antibacterial activities) of ethanolic extracts derived from the aerial parts of the two species (Lavandula stoechas L. and Thymus sipyleus Boiss). The presence of phenolic compounds and phytochemicals in the plant extracts was identified using the LC-MS/MS technique. The LC-MS/MS analysis revealed that vanillic acid (125,596.66 µg/L) was the most abundant phytochemical in L. stoechas. Kaempferol (8550.52 µg/L) was the most abundant substance in Thymus sipyleus. The assessment of the antioxidant efficacy of the species extracts was conducted using the DPPH (2.2-diphenyl-1-picryl-hydrazyl-hydrate), ABTS (2.2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)), Fe[sup.3+]–Fe[sup.2+] reducing, and CUPRAC (Cu[sup.2+]–Cu[sup.+] reducing) assays. The anticholinergic activity of the samples was determined using the acetylcholinesterase (AChE) inhibition assay. The results of antioxidant activity were higher in the T. sipyleus than in the L. stoechas ethanol extracts. The extracts of L. stoechas exhibited radical scavenging activity ranging from 15 to 18%, while T. sipyleus had activity effects ranging from 34% to 38%. The AChE inhibition potential for L. stoechas and T. sipyleus extracts as IC[sub.50] values were 0.221 ± 0.01 mg/mL and 0.067 ± 0.02 mg/mL, respectively. The antibacterial effects of the ethanolic extracts of these species against pathogenic bacteria isolates were determined using the MIC (minimal inhibitory concentration) method. These findings indicated that the extracts from L. stoechas and T. sipyleus possess the potential to be natural antioxidants in the realm of food preservation. Additionally, their antioxidant, anticholinergic, and antimicrobial properties suggest potential therapeutic utility in the management of certain diseases.

Background The hypoxia-inducible factor-1[alpha] (HIF-1[alpha])/Bcl-2/adenovirus E1B 19-kDa interacting protein (BNIP3) pathway, a key regulator of mitophagy, has demonstrated protective effects in renal and cardiac ischemia/reperfusion (I/R) injury. However, its specific role and mechanism in cerebral I/R injury (CIRI) are not fully understood. Methods An oxygen-glucose deprivation/reoxygenation (OGD/R) model in SH-SY5Y neuroblastoma cells and a transient middle cerebral artery occlusion (MCAO) model in rats were established to simulate CIRI. HIF-1[alpha] overexpression plasmids was then introduced into the two models. Mitophagic activity was assessed through immunoblotting of BNIP3, microtubule-associated protein 1 light chain 3B (LC3B), and p62 protein, quantification of LC3B-mitochondria colocalization, and transmission electron microscopic analysis of mitochondrial ultrastructure and autophagosomes. NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome activation was evaluated by measuring levels of NLRP3, cleaved caspase-1, interleukin (IL)-1β, and IL-18. The cell-type specificity of the HIF-1[alpha]/BNIP3/mitophagy pathway was evaluated by comparative analysis in SH-SY5Y neuronal cells and BV-2 microglia. Mechanistic dependency was tested NLRP3 agonist nigericin using the autophagy inhibitor 3-methyladenine (3-MA) and the specific NLRP3 inflammasome agonist nigericin in rescue experiments. In addition, cerebral infarction and neurological deficits were assessed in rats. Results HIF-1[alpha] transcriptionally upregulated BNIP3 in SH-SY5Y cells. HIF-1[alpha] overexpression increased BNIP3 and LC3B II levels, reduced p62 level, increased autophagosome accumulation, and enhanced mitophagy in SH-SY5Y cells. This enhanced mitophagy suppressed OGD/R-induced apoptosis and NLRP3 inflammasome activation, while these effects were abolished by 3-MA or nigericin. Comparative analysis revealed the HIF-1[alpha]/BNIP3/mitophagy pathway to be a predominant and potent mechanism in SH-SY5Y cells, rather than BV-2 microglia. In addition, HIF-1[alpha] overexpression enhanced mitophagy and attenuated NLRP3 inflammasome activation in brain tissues, thereby alleviating cerebral infarction and neurological deficits in MCAO rats. Conclusions Activation of the HIF-1[alpha]/BNIP3 pathway drives protective mitophagy to suppress the NLRP3 inflammasome in neuronal cells, thereby conferring neuroprotection against CIRI. This study provides mechanistic insights into the protective role of HIF-1[alpha]/BNIP3-mediated mitophagy against CIRI, highlighting its potential as a therapeutic target for ischemic injury. Keywords: Cerebral I/R injury, Mitophagy, HIF-1[alpha], BNIP3, NLRP3 inflammasome

Background The antibiotic rifaximin is used to treat non-constipated irritable bowel syndrome (IBS). Methane production is associated with constipation and its severity in constipation-predominant IBS (C-IBS). A previous retrospective study suggested that rifaximin and neomycin was superior to neomycin alone in improving symptoms in methane-positive subjects. Aims To determine the effectiveness of neomycin alone or with rifaximin in improving symptoms in methane-positive C-IBS subjects. Methods A double-blind, randomized, placebo-controlled trial was performed from 2010 to 2013 at three tertiary care centers. Subjects aged 18–65 with C-IBS (Rome II criteria) and breath methane (>3 ppm) meeting the inclusion and exclusion criteria were recruited. Subjects completed a baseline symptom questionnaire rating the severity of abdominal and bowel symptoms on a visual analog scale and were randomized to receive neomycin and placebo or neomycin and rifaximin for 14 days. Symptom severity was assessed by weekly questionnaire for 2 weeks of therapy and 4 additional weeks of follow-up. Results Thirty-one subjects (16 neomycin and placebo, 15 neomycin and rifaximin) were included in the intention-to-treat analysis. Constipation severity was significantly lower in the neomycin and rifaximin group (28.6 ± 30.8) compared to neomycin alone (61.2 ± 24.1) ( P  = 0.0042), with greater improvement in constipation ( P  = 0.007), straining ( P  = 0.017) and bloating ( P  = 0.020), but not abdominal pain. In the neomycin and rifaximin group, subjects with methane <3 ppm after treatment reported significantly lower constipation severity (30.5 ± 21.8) than subjects with persistent methane (67.2 ± 32.1) ( P  = 0.020). Conclusions Rifaximin plus neomycin is superior to neomycin alone in improving multiple C-IBS symptoms. This effect is predicted by a reduction in breath methane.

Trichosporon asahii is an opportunistic pathogen that can cause severe or even fatal infections in patients with low immune function. sPLA2 plays different roles in different fungi and is also related to fungal drug resistance. However, the mechanism underlying its drug resistance to azoles has not yet been reported in T. asahii. Therefore, we investigated the drug resistance of T. asahii PLA2 (TaPLA2) by constructing overexpressing mutant strains (TaPLA2[sup.OE]). TaPLA2[sup.OE] was generated by homologous recombination of the recombinant vector pEGFP-N1-TaPLA2, induced by the CMV promoter, with Agrobacterium tumefaciens. The structure of the protein was found to be typical of sPLA2, and it belongs to the phospholipase A2_3 superfamily. TaPLA2[sup.OE] enhanced antifungal drug resistance by upregulating the expression of effector genes and increasing the number of arthrospores to promote biofilm formation. TaPLA2[sup.OE] was highly sensitive to sodium dodecyl sulfate and Congo red, indicating impaired cell wall integrity due to downregulation of chitin synthesis or degradation genes, which can indirectly affect fungal resistance. In conclusion, TaPLA2 overexpression enhanced the resistance to azoles of T. asahii by enhancing drug efflux and biofilm formation and upregulating HOG-MAPK pathway genes; therefore, it has promising research prospects.