Uncommon Epoxyquinols Pyrrolocytosporin A and Cytosporin E2 from the Fungus Eutypella sp. D-1.

Two uncommon epoxyquinols, pyrrolocytosporin A (1) and cytosporin E2 (2), along with the known cytosporin Y1 (3), were isolated from the solid defined medium of the Arctic-derived fungus Eutypella sp. D-1. Their structures were established through comprehensive analyses of spectroscopic and electronic circular dichroism data. Structurally, compound 1 represented the first nitrogen-containing epoxyquinol characterized by a pyrrole fused cytosporin framework, while compound 2 contained an uncommon cyclic carbonate functionality. The antibacterial, immunosuppressive, anti-inflammatory, and cytotoxic activities of all compounds were evaluated. Among the three metabolites, only compound 1 exhibited inhibitory effects on nitric oxide production induced by lipopolysaccharide with an IC50 value of 6.55 µM. Additionally, only compound 2 displayed inhibitory activity against ConA-induced T-cell proliferation with an IC50 value of 9.85 µM.

Eutypellaolides A-J, Sesquiterpene diversity expansion of the polar fungus Eutypella sp. D-1.

Eight new 12,8-eudesmanolide sesquiterpenes, eutypellaolides A-H (1-8), and two new eudesmane-type sesquiterpenes, eutypellaolides I-J (9-10), along with four known 12,8-eudesmanolide compounds 11-14, were isolated from the culture extract of the polar fungus Eutypella sp. D-1 by one strain many compounds (OSMAC) approach. The structures of these compounds were determined through comprehensive spectroscopic data and experimental and calculated ECD analysis. Antibacterial, immunosuppressive, and PTP1B inhibition activities of these compounds were evaluated. Compounds 1 and 11 exhibited strong inhibitory activities against Bacillus subtilis and Staphylococcus aureus, with each showing an MIC value of 2 µg/mL. Compound 9 displayed weak immunosuppressive activity against ConA-induced T-cell proliferation with an inhibitory rate of 61.7% at a concentration of 19.8 µM. Compounds 5, 11, and 14 exhibited weak PTP1B inhibition activities with IC50 values of 44.8, 43.2, and 49.5 µM, respectively.

Effects of electroacupuncture preconditioning on microglial cells and serum inflammatory factors in the early stage of ischemic stroke. / ç”µé’ˆé¢„å¤„ç†å¯¹ç¼ºè¡€æ€§ä¸­é£Žå°é¼ æ—©æœŸå°èƒ¶è´¨ç»†èƒžåŠè¡€æ¸ ç‚Žæ€§å› å­çš„å½±å“.

OBJECTIVES: To investigate the effects on the motor function, cortex blood flow perfusion, microglial cells, and the contents of serum inflammatory factors, i.e. interleukin-1ß (IL-1ß), transforming growth factor-ß (TGF-ß), and interleukin-10 (IL-10) after electroacupuncture (EA) preconditioning at "Baihui" (GV20) and "Dazhui" (GV14) in the mice with ischemic stroke, so as to explore the mechanism of EA preconditioning for improving motor function after ischemic stroke. METHODS: C57BL/6 mice were randomly divided into sham-operation group, model group, and EA preconditioning group (EA group), with 15 mice in each group. A photothrombotic method was used to induce the model of unilateral ischemic stroke and motor impairment. The mice in the EA group received EA preconditioning, 20 min each time, once daily for 7 consecutive days before modeling. The motor function of mice was evaluated by the grid-walking test and cylinder test before and after modeling. Laser speckle blood flow video monitoring system was employed to assess the cerebral blood flow perfusion in the primary motor cortex of mice. The contents of IL-1ß, TGF-ß, and IL-10 in the serum were measured by ELISA, and the expressions of microglial cell and M2 subtype cell marker in the primary motor cortex were detected using immunofluorescence staining. RESULTS: After modeling, compared with the sham-operation group, the grid error rate and the dragging rate of the affected limb were increased (P<0.01)；the utilization rate of the affected limb and percentage of the blood perfusion in the affected cortex to healthy side were decreased (P<0.01)；the contents of serum IL-1ß, TGF-ß, and IL-10 were increased (P<0.01, P<0.05)；and the microglia in the primary motor cortex on the affected side showed ameboid, the fluorescence intensity of ionized calcium-binding adapter molecule 1 (IBA1) and CD206 was increased (P<0.01) in the model group. In the EA group, when compared with the model group, the grid error rate and the dragging rate of affected limb were decreased (P<0.01)；the utilization rate of affected limb and the percentage of blood perfusion were increased (P<0.05)；the content of serum IL-1ß was decreased (P<0.01), while the contents of TGF-ß and IL-10 were increased (P<0.01)；and the microglia in the primary motor cortex on the affected side got more round and were distributed more densely, the fluorescence intensity of IBA1 and CD206 was increased (P<0.01). CONCLUSIONS: Electroacupuncture preconditioning at "GV20" and "GV14" can up-regulate the expression of microglial cells, especially the M2 subtype cell marker, and increase the contents of the anti-inflammatory factors and decrease that of the pro-inflammatory factors in the serum, thereby alleviate the inflammatory reaction.

Phyllofenones F-M, Scalarane Sesterterpenes from the Marine Sponge Phyllospongia foliascens.

Eight new scalarane sesterterpenes, phyllofenones F-M (1-8), together with two known analogues, carteriofenones B and A (9-10), were isolated from the marine sponge Phyllospongia foliascens collected from the South China Sea. The structures of these compounds were determined based on extensive spectroscopic and quantum chemical calculation analysis. The antibacterial and cytotoxic activity of these compounds was evaluated. Among them, only compounds 4 and 6 displayed weak inhibitory activity against Staphylococcus aureus and Escherichia coli, with MIC values of 16 µg/mL and 8 µg/mL, respectively. Compounds 1-10 exhibited cytotoxic activity against the HeLa, HCT-116, H460, and SW1990 cancer cell lines, with IC50 values ranging from 3.4 to 19.8 µM.

Factors associated with low skeletal muscle index among patients with Crohn's disease.

OBJECTIVE: Disease-related skeletal muscle loss is highly prevalent among patients with Crohn's disease. Low skeletal muscle mass lead to disability and interventions to prevent skeletal mass loss as an effective strategy to prevent disability. The aim of this article was to identify the factor associated with skeletal muscle loss of Crohn's disease and seek for management target for the prevention of sarcopenia-related disability. METHODS: Patients with Crohn's disease were divided into low and normal skeletal muscle mass groups based on L3 skeletal muscle index using abdominal CT scans. The clinical and laboratory parameters and colonoscopy were compared between the two groups. Univariate and multivariate regression logistic models were built to identify the prognostic markers of Crohn's disease-associated muscle loss. RESULTS: A total of 191 Crohn's disease patients were enrolled in this study, of whom 116 (60.73%) were detected to have low L3 skeletal muscle index, including 71 (68.26%) males. The multivariate logistic regression analysis showed that age (OR: 1.031, 95%CI: 1.006-1.057), female gender (OR: 2.939, 95%CI: 1.386-6.233), disease duration (OR: 0.988, 95%CI: 0.980-0.996), endoscopic disease activity (simple endoscopic score for Crohn's disease) (OR: 0.923, 95%CI: 0.855-0.996), serum albumin (OR: 1.079, 95%CI: 1.009-1.154), and serum creatinine (OR: 1.037, 95%CI: 1.011-1.063) were associated with L3 skeletal muscle index among Crohn's disease patients. CONCLUSION: The gender, age, and duration of disease were uncontrollable factors associated with muscle loss of Crohn's disease. The treatment target of mucosal healing and improved nutritional status may be beneficial for maintaining muscle mass among Crohn's disease patients.

Cytosporin Derivatives from Arctic-Derived Fungus Eutypella sp. D-1 via the OSMAC Approach.

A chemical investigation of the Arctic-derived fungus Eutypella sp. D-1 based on the OSMAC (one strain many compounds) approach resulted in the isolation of five cytosporin polyketides (compounds 1-3 and 11-12) from rice medium and eight cytosporins (compounds 2 and 4-11) from solid defined medium. The structures of the seven new compounds, eutypelleudesmane A (1), cytosporin Y (2), cytosporin Z (3), cytosporin Y1 (4), cytosporin Y2 (5), cytosporin Y3 (6), and cytosporin E1 (7), were elucidated by analyzing their detailed spectroscopic data. Structurally, cytosporin Y1 (4) may be a key intermediate in the biosynthesis of the isolated cytosporins, rather than an end product. Compound 1 contained a unique skeleton formed by the ester linkage of two moieties, cytosporin F (12) and the eudesmane-type sesquiterpene dihydroalanto glycol. Additionally, the occurrence of cyclic carbonate moieties in compounds 6 and 7 was found to be rare in nature. The antibacterial, immunosuppressive, and cytotoxic activities of all compounds derived from Eutypella sp. D-1 were evaluated. Unfortunately, only compounds 3, 6, 8, and 10-11 displayed immunosuppressive activity, with inhibitory rates of 62.9%, 59.5%, 67.8%, 55.8%, and 68.7%, respectively, at a concentration of 5 µg/mL.

Phyllospongianes A-E, Dinorscalarane Sesterterpenes from the Marine Sponge Phyllospongia foliascens.

Phyllospongianes A-E (1-5), five new scalarane derivatives featuring an unprecedented 6/6/6/5 tetracyclic dinorscalarane scaffold, along with the known probable biogenetic precursor, 12-deacetylscalaradial (6), were isolated from the marine sponge Phyllospongia foliascens. The structures of the isolated compounds were determined by analysis of spectroscopic data and electronic circular dichroism experiments. Compounds 1-5 are the first 6/6/6/5 tetracyclic scalarane derivatives to be reported within the scalarane family. Compounds 1, 2, and 4 exhibited antibacterial activity against Vibrio vulnificus, Vibrio parahemolyticus, Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, and Pseudomonas aeruginosa with MIC values ranging from 1 to 8 µg/mL. Furthermore, compound 3 exhibited significant cytotoxic activity on MDA-MB-231, HepG2, C4-2-ENZ, MCF-7, H460, and HT-29 cancer cell lines with IC50 values in the range between 0.7 and 13.2 µM.

Quality by design driven development and evaluation of thermosensitive hydrogel loaded with IgY and LL37-SLNs to combat experimental periodontitis.

Egg yolk immunoglobulin (IgY) and LL37, potent antibacterial substances, can fight against periodontitis. This work aimed to develop a locally injectable hydrogel for potential co-delivery of special IgY and LL37-loaded solid lipid nanoparticles (LL37-SLNs) to synergistically inhibit the proliferation of oral pathogens, thus relieving periodontal inflammation and redness. The formulation of thermosensitive hydrogel loaded with IgY and LL37-SLNs was developed by adopting the Quality by Design approach. Then the formulations were optimized by two-factor three-level full factorial design by Design-Expert software. Finally, the optimized formulation was characterized and estimated in vitro and in vivo. In vitro release and antibacterial activity studies have revealed that the optimized formulation was homogeneous and can be released slowly, with sustainably antibacterial power. And the physical and chemical composition analysis and morphological observations further confirmed the sustained-release capability. On the other hand, in vivo studies proved that the optimized formulation significantly decreased gingival redness, bleeding, and plaque formation, avoided excessive resorption of alveolar bone, and reduced the levels of inflammatory factor in periodontitis rats. In conclusion, the optimized thermosensitive hydrogel loaded with IgY and LL37-SLNs may be a promising local sustained-release preparation for the effective treatment of periodontal diseases.

Bioactive Scalarane-Type Sesterterpenoids from Marine Sources.

Scalarane-type sesterterpenoids have received considerable attention in the scientific literature due to their diverse carbon skeletons and various biological activities and pharmacological properties. Among all these derivatives are commonly isolated from marine sponges and are occasionally derived from shell-less mollusks, such as nudibranchs. This review comprehensively discusses the marine-derived natural sources that give rise to these scalarane-type sesterterpenoids, providing the names, their chemical structures, biological properties, with emphasis on anticancer activity and literature references related to these metabolites. A critical summary of the 221 compounds generated from January 2010 up to December 2021 for their potential as anticancer agents is presented.

Palitantin derivatives from the Antarctic fungus Geomyces sp. 3-1.

Two new polyketides, palitantins B and C (1 and 2), along with one known related compound (+)-palitantin (3) were obtained from the culture of the Antarctic fungus Geomyces sp. 3-1. The structures of the new compounds were elucidated by detailed analysis of HRESIMS, NMR, CD, and ECD data. Compound 3 showed potent PTP1B inhibitory activity with an IC50 value of 7.9 µM (ursolic acid as positive control, IC50 = 8.3 µM).

Acupuncture-Related Therapies for Parkinson's Disease: A Meta-Analysis and Qualitative Review.

Objective: This systematic review and meta-analysis aimed to assess the effects of the combination of acupuncture-related therapies with conventional medication compared with conventional medication in patients with Parkinson's disease (PD). Methods: A literature search within eight databases [including Medline, Embase, the Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP, and Wanfang Database] was performed covering a time frame from their inception to August 2020. Randomized controlled trials (RCTs) comparing acupuncture-related therapies combined with conventional medication vs. conventional medication in patients with PD were eligible. Two authors independently assessed the risk of bias. Assessments were performed with the total and subscales scores of the Unified Parkinson's Disease Rating Scale (UPDRS), 39-item Parkinson's Disease Questionnaire (PDQ-39), the dosage of Madopar, Mini-Mental State Examination (MMSE), and 17-item Hamilton Depression Scale (HAMD). Data were analyzed by adopting the Cochrane Collaboration's RevMan 5.4 (Review Man, Copenhagen, Denmark); and mean effect sizes and 95% confidence intervals were estimated. Tests for heterogeneity were used to assess differences in treatment effects across different types of acupuncture used. Results: Sixty-six trials met the inclusion criteria, of which 61 trials provided data for the meta-analysis. We defined high-quality articles as those with a low risk of bias in four or more domains; and only 10 (15.15%) articles were of high quality. Compared with the controls, acupuncture-related therapies with conventional medication achieved a benefit in the primary outcomes of UPDRS (motor subscore: -3.90, -4.33 to -3.49, P < 0.01; total score: -7.37 points, -8.91 to -5.82, P < 0.001; activities of daily living subscore: -3.96, -4.96 to -2.95, P < 0.01). For the subgroup difference test among the effects of different acupuncture methods, significant differences existed in outcomes with the UPDRS-III, UPDRS-I, UPDRS-IV, and PDQ-39 scores and Madopar dosage, while non-significant differences existed with the UPDRS-total, UPDRS-II, HAMD, and MMSE scores. Conclusions: Acupuncture-related therapies combined with conventional medication may benefit individuals with PD. Our review findings should be considered with caution because of the methodological weaknesses in the included trials. Future, large randomized trials of acupuncture-related therapies for PD with high methodological quality are warranted. Systematic Review Registration: Identifier CRD42021228110.

Mind-Body Exercises for Non-motor Symptoms of Patients With Parkinson's Disease: A Systematic Review and Meta-Analysis.

Objective: This study aimed to systematically evaluate the effects of mind-body exercise on global cognitive function, depression, sleep disorders, fatigue level, and quality of life (QOL) in a Parkinson's disease (PD) population. Methods: Total six English and Chinese databases were searched for articles published up to May 2021. Randomized controlled trials (RCTs) evaluating mind-body excises on non-motor symptoms of PD were included. The Cochrane risk of bias tool was used to assess the methodological quality, and we defined high-quality studies as having a low risk of bias in four or more domains. Global cognitive function was considered the primary outcome and was assessed using the Montreal Cognitive Assessment (MoCA). The secondary outcomes included QOL, fatigue, depression, and sleep quality, which were measured using the Parkinson's Disease Questionnaire (PDQ-39), 16-item Parkinson's Disease Fatigue Scale (PFS-16), Beck Depression Inventory (BDI), and revised Parkinson's Disease Sleep Scale (PDSS-2), respectively. Subgroup analyses were conducted for global cognitive function and QOL to assess the optimal treatment measure across the various mind-body exercises. Results: Fourteen RCTs with 404 patients were finally included in the meta-analysis. Eight (57.14%) studies were of high quality. The pooled results showed that mind-body exercises generally had a significant advantage over the control intervention in improving global cognitive function (MD = 1.68; P = 0.0008). The dose subgroup analysis revealed that the low dose (60-120 min per week) and moderate dose (120-200 min per week) significantly increased MoCA scores compared with the control group (MD = 2.11, P = 0.01; MD = 1.27, P = 0.02, respectively). The duration subgroup analysis indicated a significant difference in the effect of the duration (6-10 and >15 weeks) on increasing MoCA scores compared with the control group (MD = 3.74, P < 0.00001; MD = 1.45, P = 0.01, respectively). Conclusion: Mind-body exercise may improve global cognitive function, sleep quality, and QOL in the PD population. In addition, low to moderate doses and appropriate durations significantly improved global cognitive function. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [CRD42021275522].

Eutypellacytosporins A-D, Meroterpenoids from the Arctic Fungus Eutypella sp. D-1.

The Arctic fungus Eutypella sp. D-1, previously found to produce a variety of cytotoxic cyclopropyl-fused and cyclobutyl-fused pimarane diterpenoids when grown in the defined medium, was induced to produce unusual metabolites by growing on solid rice medium. A chemical investigation on the rice medium extract led to the isolation of four new meroterpenoids, eutypellacytosporins A-D (1-4), along with the known biogenetically related compound cytosporin D (5). The structures of the new compounds were elucidated by their detailed spectroscopic analysis and modified Mosher's method. Compounds 1-4 may be formed by the 12,32-ester linkage of two moieties, cytosporin D (5) and decipienolide A or B. All isolated compounds, except 5, showed weak cytotoxicity against DU145, SW1990, Huh7, and PANC-1 cell lines with IC50 values ranging from 4.9 to 17.1 µM.

Cytotoxic Microcolin Lipopeptides from the Marine Cyanobacterium Moorea producens.

Nine new linear lipopeptides, microcolins E-M (1-9), together with four known related compounds, microcolins A-D (10-13), were isolated from the marine cyanobacterium Moorea producens using bioassay-guided and LC-MS/MS molecular networking approaches. Catalytic hydrogenation of microcolins A-D (10-13) yielded two known compounds, 3,4-dihydromicrocolins A and B (14, 15), and two new derivatives, 3,4-dihydromicrocolins C and D (16, 17), respectively. The structures of these new compounds were determined by a combination of spectroscopic and advanced Marfey's analysis. Structurally unusual amino acid units, 4-methyl-2-(methylamino)pent-3-enoic (Mpe) acid and 2-amino-4-methylhexanoic acid (N-Me-homoisoleucine), in compounds 1-3 and 8, respectively, are rare residues in naturally occurring peptides. These metabolites showed significant cytotoxic activity against H-460 human lung cancer cells with IC50 values ranging from 6 nM to 5.0 µM. The variations in structure and attendant biological activities provided fresh insights concerning structure-activity relationships for the microcolin class of lipopeptides.

Peroxiredoxin V Inhibits Emodin-induced Gastric Cancer Cell Apoptosis via the ROS/Bcl2 Pathway.

BACKGROUND/AIM: Peroxiredoxin (Prx) protein family is aberrantly expressed in various cancers including gastric cancer. Among the six family members, Prx V has been known as an antioxidant enzyme which scavenges intracellular reactive oxygen species (ROS) and modulates cellular apoptosis. This study aimed at investigating the role of Prx V in apoptosis of gastric cancer cells. MATERIALS AND METHODS: Stably constructed Prx V knockdown, over-expression and mock AGS cells (a human gastric adenocarcinoma cell line) were used to study the effect of Prx V on emodin-induced apoptosis by western blotting, cell viability, apoptosis and ROS detection assays. RESULTS: Overexpression of Prx V significantly decreased emodin-induced cellular apoptosis and ROS levels compared to Mock and Prx V knockdown AGS cells. Also, overexpression of Prx V down-regulated the expression of pro-apoptotic proteins, Bad and cleaved PARP, and increased the expression of anti-apoptotic protein, Bcl2. CONCLUSION: Prx V suppresses AGS cell apoptosis via scavenging intracellular ROS and modulating apoptosis-related markers.

Libertellenones O-S and Eutypellenones A and B, Pimarane Diterpene Derivatives from the Arctic Fungus Eutypella sp. D-1.

Seven new pimarane-type diterpene derivatives, libertellenones O-S (1-5) and eutypellenones A and B (6 and 7), together with two known compounds (8 and 9), were isolated from the culture of Eutypella sp. D-1 obtained from high-latitude soil of the Arctic. Their structures were elucidated from spectroscopic data, as well as experimental and calculated electronic circular dichroism (ECD) analysis. Structurally, compounds 1-5 possess a cyclopropyl-fused pimarane diterpene moiety, whereas compounds 6 and 7 share an unusual cyclobutyl-fused pimarane diterpene skeleton. Compounds 1-9 exhibited cytotoxicities against HeLa, MCF-7, HCT-116, PANC-1, and SW1990 cells, with IC50 values in the range of 0.3 to 29.4 µM. Compounds 6 and 7 could dose-dependently inhibit the activity of NF-κB and exhibited significantly inhibitory effects on nitric oxide production induced by lipopolysaccharide.

Biotransformation of total coumarins of Radix Glehniae by Lecanicillium attenuatum W-1-9.

The biotransformation of total coumarins of Radix Glehniae by Lecanicillium attenuatum W-1-9 yielded three new products, lecaniside A (1), lecaniside B (2), and lecaniside C (3). The chemical structures of these metabolites were elucidated based on extensive spectral data, including 2D NMR and HRMS. The hydrogenation, dealkylation, glycosylation, and O-methylation reactions of these metabolites were observed in the present study. In the in vitro assays, compound 1 displayed a little PTP1B inhibitory activity.

Furanone derivative and sesquiterpene from Antarctic marine-derived fungus Penicillium sp. S-1-18.

A new furanone derivative, butanolide A (1), and a new sesquiterpene, guignarderemophilane F (2), together with six known compounds, were isolated from the fungus Penicillium sp. S-1-18 derived from Antarctic marine. The new structures were determined by spectroscopic studies such as 1D- and 2D-NMR and MS analyses. The absolute configuration of 1 was determined by the modified Mosher's method, while the absolute configuration of 2 was determined by calculated ECD spectroscopy. The isolated secondary metabolites were evaluated for their protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. Compound 1 showed moderate inhibitory activity against PTP1B with IC50 value of 27.4 µM.

De novo endo-functionalized organic cages as cooperative multi-hydrogen-bond-donating catalysts.

Two endo-functionalized organic cages as oxyanion hole mimics were achieved via dynamic covalent chemistry, which exhibit good size selectivity, catalytic activity and broad substrate scopes for Friedel-Crafts reactions. The modular character of the synthesis provides an easy way to modify the size, shape and inner function of the molecular cavity.

A new sesquiterpene lactone from fungus Eutypella sp. D-1.

We isolated and identified a new sesquiterpene lactone which we named eut-Guaiane sesquiterpene (1), along with four cytochalasins from the fungus Eutypella sp. derived from the soil of high latitude of Arctic. The new structure was determined by spectroscopic studies such as 1D and 2D NMR and MS analyses, while the known compounds were identified by comparison of the NMR data with those in literatures. New compound 1 exhibited strong antibacterial activity against Escherichia coli, Bacillus subtilis and Staphylococcus aureus. Besides, it showed a little cytotoxicity against SGC7901 cell line.