7-Methoxy-13-dehydroxypaxilline: New indole diterpenoid from an endophytic fungus Penicillium sp. Nb 19.

ABSTACTA chemical investigation of the endophyte Penicillium sp. Nb 19, isolated from leaves of the traditionally medical plant Baphicacanthus cusia (Nees) Bremek., yielded one new indole diterpenoid, 7-methoxy-13-dehydroxypaxilline (1) together with seven known metabolites (2-8). The obtained structure of compound 1 was elucidated by its spectroscopic data. In addition, the absolute configuration of compound 6 was confirmed by ECD for the first time. Compounds 1-6 were evaluated for antitumor activity against MCF-7, HepG2, and HCCC-9810 cell lines.

Analysis of retinal arteriolar and venular parameters in primary open angle glaucoma.

AIM: To measure the retinal vessels of primary open angle glaucoma (POAG) patients on spectral domain optical coherence tomography (SD-OCT) with a full-width at half-maximum (FWHM) algorithm to better explore their structural changes in the pathogenesis of POAG. METHODS: In this retrospective case-control study, the right eyes of 32 patients with POAG and 30 healthy individuals were routinely selected. Images of the supratemporal and infratemporal retinal vessels in the B zones were obtained by SD-OCT, and the edges of the vessels were identified by the FWHM method. The internal and external diameters, wall thickness (WT), wall cross-sectional area (WCSA) and wall-to-lumen ratio (WLR) of the blood vessels were studied. RESULTS: Compared with the healthy control group, the POAG group showed a significantly reduced retinal arteriolar outer diameter (RAOD), retinal arteriolar lumen diameter (RALD) and WSCA in the supratemporal (124.22±12.42 vs 138.32±10.73 µm, 96.09±11.09 vs 108.53±9.89 µm, and 4762.02±913.51 vs 5785.75±1148.28 µm2, respectively, all P<0.05) and infratemporal regions (125.01±15.55 vs 141.57±10.77 µm, 96.27±13.29 vs 110.83±10.99 µm, and 4925.56±1302.88 vs 6087.78±1061.55 µm2, all P<0.05). The arteriolar WT and WLR were not significantly different between the POAG and control groups, nor were the retinal venular outer diameter (RVOD), retinal venular lumen diameter (RVLD) or venular WT in the supratemporal or infratemporal region. There was a positive correlation between the arteriolar parameters and visual function. CONCLUSION: In POAG, narrowing of the supratemporal and infratemporal arterioles and a significant reduction in the WSCA is observed, while the arteriolar WT and WLR do not change. Among the venular parameters, the external diameter, internal diameter, WT, WLR, and WSCA of the venules are not affected.

Proliferation Inhibitory Activity of Quinones from Blaps rynchopetera Defense Secretion on Colorectal Tumor Cells.

OBJECTIVE: To explore the proliferation inhibitory effect of quinones from Blaps rynchopetera defense secretion on colorectal tumor cell lines. METHODS: Human colorectal cancer cell HT-29, human colorectal adenocarcinoma cell Caco-2 and normal human colon epithelial cell CCD841 were chosen for the evaluation of inhibitory activity of the main quinones of B. rynchopetera defense secretion, including methyl p-benzoquinone (MBQ), ethyl p-benzoquinone (EBQ), and methyl hydroquinone (MHQ), through methyl thiazolyl tetrazolium assay. The tumor-related factors, cell cycles, related gene expressions and protein levels were detected by enzyme-linked immunosorbent assy, flow cytometry, RT-polymerase chain reaction and Western blot, respectively. RESULTS: MBQ, EBQ, and MHQ could significantly inhibit the proliferation of Caco-2, with half maximal inhibitory concentration (IC50) values of 7.04 ± 0.88, 10.92 ± 0.32, 9.35 ± 0.83, HT-29, with IC50 values of 14.90 ± 2.71, 20.50 ± 6.37, 13.90 ± 1.30, and CCD841, with IC50 values of 11.40 ± 0.68, 7.02 ± 0.44 and 7.83 ± 0.05 µg/mL, respectively. Tested quinones can reduce the expression of tumor-related factors tumor necrosis factor α, interleukin (IL)-10, and IL-6 in HT-29 cells, selectively promote apoptosis, and regulate the cell cycle which can reduce the proportion of cells in the G1 phase and increase the proportion of the S phase. Meanwhile, tested quinones could up-regulate mRNA and protein expression of GSK-3ß and APC, while down-regulate that of ß-catenin, Frizzled1, c-Myc, and CyclinD1 in the Wnt/ß-catenin pathway of HT-29 cells. CONCLUSION: Quinones from B. rynchopetera defense secretion could inhibit the proliferation of colorectal tumor cells and reduce the expression of related factors, which would be functioned by regulating cell cycle, selectively promoting apoptosis, and affecting Wnt/ß-catenin pathway-related mRNA and protein expressions.

Macrostines A and B: Tetracyclic fisicoccane from the fungus Periconia macrospinosa WTG-10.

Two previous unreported fusicoccane diterpenoids macrostines A and B, together with seven known compounds were isolated from an extract of the fungus Periconia macrospinosa WTG-10. Their structures were elucidated by detailed analysis of spectroscopic data, NMR calculations with DP4+, and their absolute configurations were further determined by quantum chemical calculations of ECD spectra or X-crystallography. Macrostines A and B showed no cytotoxicity, antimicrobial activity and inhibitory effect on nitric oxide production in LPS-activated RAW264.7 macrophages. Compound 9 showed moderate activity against Bacillus subtilis.

Polyketides with antimicrobial activities from Penicillium canescens DJJ-1.

Two undescribed polyketides canecines A-B, one unreported cyclopentenone canecine C, together with 12 known compounds were isolated from an extract of the fungus Penicillium canescens DJJ-1. Their structures were elucidated by detailed analysis of spectroscopic data, NMR calculations with dJ-DP4 or DP4+, and their absolute configurations were further determined by quantum chemical calculations of ECD spectra or X-crystallography. Canecine A was a grisan polyketide featuring a dimethyltetrahydro-4H-furo[2,3-b]pyran. Canecine A exhibited significant inhibitory activity against Candida albicans with an MIC value of 1 µg/mL and showed inhibitory effect on nitric oxide production in LPS-activated RAW264.7 macrophages. These results enrich the structural diversities of polyketides from endophytic fungi.

A new cycloheptane derivative from the fungus Penicillium crustosum JT-8.

A new highly oxygenated cycloheptane derivative crustane (1), along with fourteen known compounds (2-15) were isolated from Penicillium crustosum JT-8. The structure of compound 1 was determined by extensive spectroscopic data, DP4+ probability analyses and dimolybdenum CD method. Compound 1 exhibited moderate antibacterial activity against Staphylococcus aureus with MIC of 4.0 µg/mL.

A new cyclopentenone derivative from Trichoderma atroviride HH-01.

A new cyclopentenone derivative, atrovinol (1), together with ten known compounds (2-11) were isolated from Trichoderma atroviride HH-01, an endophytic fungus from Illigera rhodantha (Hernandiaceae). Their structures were identified by HRESIMS, 1 D/2D NMR, and electronic circular dichroism (ECD) spectra. Compound 1 exhibited moderate inhibitory activity against Staphylococcus aureus and Bacillus subtilis with MIC values of 8.0 µg/mL and 16.0 µg/mL, respectively.

A new sesquiterpenoid from the aconitum-derived fungus Aspergillus fumigatus M1.

A new bergamotane sesquiterpenoid, fumigatanol (1), along with nine known compounds (2-10) were isolated from the Aconitum-derived fungus Aspergillus fumigatus M1. Their structures were established on the basis of extensive spectroscopic analyses, ECD experiment and NMR computational method. Antibacterial and cytotoxic activities of compound 1 were evaluated and no obvious antibacterial and cytotoxic activities were observed at concentrations of 256 µg/mL and 40.00 µM, respectively.

Application of symptom-based mind mapping combined with PBL teaching method in emergency trauma standardized resident training in MDT model.

Explore the feasibility and effectiveness of accepting mind mapping combined with problem-based learning (PBL) teaching method in the standardized training of emergency surgery residents in the multi-disciplinary team (MDT) model of emergency trauma. Eighty-nine doctors under training who rotated in the Department of Emergency Surgery of the First Affiliated Hospital of Anhui Medical University from January 2021 to January 2022 were selected as the study subjects, and randomly divided into a group receiving mind mapping combined with PBL teaching and a group receiving traditional lecture-based learning teaching. Mini-clinical evaluation exercise (Mini-CEX), direct observation of procedural skills (DOPS), teaching adherence, and satisfaction assessments were completed at the time of discharge from the department. There were no significant differences between the observation and control group trainees in terms of gender, age, education, and entry grades. Both groups of doctors were better able to participate in their respective teaching modes and made significant progress. The participants in the observation group had significantly higher Mini-CEX, DOPS, and teaching satisfaction scores than the control group (P < .05). Under the MDT model of emergency trauma, the combination of mind mapping and PBL teaching can improve the comprehensive clinical ability of the trainees more than participating in the traditional lecture-based learning teaching, which is worth promoting and implementing in the clinical standardized training.

Investigations of specialised metabolites of endophyte Diaporthe destruens hosted in Illigera orbiculata C. Y. Wu.

A chemical investigation of the endophytic fungus Diaporthe destruens from the Hernandiaceae plant Illigera orbiculata C. Y. Wu collected from southern Yunnan Province, China, led to the isolation of six undescribed compounds, including two azaphilone analogs, which are a pair of epimers (13R-hydroxy-chermesinone A and 13S-hydroxy-chermesinone A); a pyrrole derivative (1-(4-(methoxymethyl)-1H-pyrrol-3-yl)ethan-1-one); an isoindolone derivative (4-hydroxy-6-methoxyisoindolin-1-one); a benzylbenzene derivative (destruensine A) and a conjectural fragment of polyketide ((2R,4R)-2-(methoxymethyl)pentane-1,4-diol) along with nine known compounds. Their structures were elucidated by spectroscopic methods and HRESIMS, and the absolute configurations were further confirmed by electronic circular dichroism (ECD) and chemical derivatization. The antimicrobial activities, anti-acetylcholinesterase activities, antiproliferation, and NO production inhibitory effects of compounds 1-15 were evaluated.

A new cytotoxic indole alkaloid from the fungus Penicillium polonicum TY12.

A new dimeric monoterpene indole alkaloid polonidine A (1), along with five known compounds, cyclopenol (2), verrucosidin (3), fructigenine A (4), 3-O-methylviridicatin (5) and aurantiomides C (6), were isolated from Penicillium polonicum TY12. Their structures were established on the basis of extensive spectroscopic analyses. Compound 1 exhibited moderate cytotoxic activities and moderate antibacterial activity against Bacillus subtilis with MIC of 4.0 µg/mL.

A new tremulane sesquiterpene from Irpex lacteus by solid-state fermentation.

A new tremulane sesquiterpene, lactedine (1), along with seven known tremulane sesquiterpenes (2-8) and one known triterpene (9) were isolated from the fungus Irpex lacteus. Their structures were established on the basis of extensive spectroscopic data and DP4+ probability analyses.

Bioactive cytochalasans from the fungus Arthrinium arundinis DJ-13.

The investigation of the metabolites from Arthrinium arundinis DJ-13 grown in solid medium revealed six undescribed cytochalasans, arundisins A-F and twelve known compounds. Their structures were initially investigated in detail by spectroscopic analyses and were further confirmed by X-crystallography and ECD experiments. In the in vitro bioassays, arundisins A and B showed cytotoxic activity against the MCF-7 breast cancer cell line with IC50 values of 18.82 ± 0.36 and 15.20 ± 0.42 µM, respectively. Arundisin F exhibited potent antibacterial activity against Escherichia coli with MIC of 8.00 µg/mL (kanamycin, 2.00 µg/mL), and arundisin D displayed gently antibacterial activity against Candida albicans with MIC of 32.00 µg/mL (Nystatin, 1.00 µg/mL).

Bioactive sesterterpenoids from the fungus Penicillium roqueforti YJ-14.

Seven previously undescribed sesterterpenes were characterized from Penicillium roqueforti YJ-14 by solid fermentation. Their structures were initially investigated in detail by spectroscopic analyses and HR-ESI-MS and were further confirmed by X-crystallography. In in vitro bioassays, compounds 1, 5 and 7 showed cytotoxic activity against the MCF-7 breast cancer cell line with IC50 values of 7.98 ±â€¯0.93, 6.42 ±â€¯0.41 and 7.32 ±â€¯0.18 µM, respectively. Compounds 5 and 7 displayed significant cytotoxicity against the A549 lung cancer cell line (IC50 values of 4.83 ±â€¯0.22 µM and 4.58 ±â€¯0.85 µM, respectively). In addition, compound 5 showed an obvious inhibitory effect on nitric oxide production in LPS-activated RAW264.7 macrophages with an IC50 value of 9.53 ±â€¯0.16 µM.

Four new phenanthrene derivatives from Bulbophyllum retusiusculum.

Three new dihydrophenanthrenes, retusiusine D (1), retusiusine E (2), retusiusine F (3), and a new phenanthrene retusiusine G (4), together with two known dihydrophenanthrenes 4,7-dihydroxy-2,3-methylenedioxy-9,10-dihydrophenanthrene (5) and epemeranthol-A (6) were isolated from the tubers of Bulbophyllum retusiusculum. Their structures were established on the basis of extensive spectroscopic analyses. Compounds 1 and 2 exhibited potent cytotoxic activities against SMMC-7721 and weak cytotoxic activities against HL-60. Compound 4 showed moderate cytotoxic activity against SMMC-7721 and MCF-7.

Penctrimertone, a bioactive citrinin dimer from the endophytic fungus Penicillium sp. T2-11.

Penctrimertone (1), a novel citrinin dimer bearing a 6/6/6/6 tetracyclic ring scaffold, along with two known compounds xerucitrinic acid A (2) and citrinin (3) were isolated from the endophytic fungus Penicillium sp. T2-11. Their structures were unequivocally established by a comprehensive interpretation of the spectroscopic data, with the stereochemistry for 1 was defined by a combination of TDDFT-ECD calculations and the DP4+ probability analysis based on NMR chemical shift calculations. Bioassays revealed that compound 1 exhibited noticeable antimicrobial activities and moderate cytotoxicity. A plausible biosynthetic pathway of 1 was also proposed.

Dose distribution of brachytherapy for locally advanced (stage IIB) cervical cancer.

PURPOSE: The aim of the study was to compare the dose distributions of combined intracavitary and interstitial (IC/IS) brachytherapy with 3-catheter IC brachytherapy in treating locally advanced (stage IIB) cervical cancer. METHODS AND MATERIALS: In total, 46 patients were included, each with stage IIB cervical cancer, local lesion sizes ≥5 cm, and tumors that had not regressed after 45 Gy/25 F external intensity-modulated radiotherapy. To identify the dosimetric advantage of delivering a local boost to high-risk (HR)-cervix in IC/IS, patients were divided into two groups: IC/IS and IC/IS + HR-cervix. The differences in dosimetric parameters were compared between the two groups. Comparisons were then made between the parameters of the four planning methods: IC (Point A), IC (three dimensional [3D]), IC/IS, and IC/IS + HR-cervix. RESULTS: In patients with IC/IS implants, the relative uterine tandem dwell time was significantly extended in the IC/IS + HR-cervix group, and the V150 and V200 volumes of HR-cervix were increased (all p < 0.001), whereas the D90 and D100 values of the IC/IS + HR-cervix group were lower than those in the IC/IS group. In pairwise comparisons, HR-cervix V150 and V200 values were lowest in the IC/IS group, followed by the IC (3D), IC/IS + HR-cervix, and IC (Point A) groups. All differences were statistically significant (p < 0.05), with the exception of IC/IS vs. IC (3D). CONCLUSIONS: When treating locally advanced cervical cancer (stage IIB, local residual volume ≥5 cm after external radiotherapy), the IC/IS + HR-cervix optimization method can meet the HR clinical target volume D90 dose requirement, normal tissue dose limits, and can escalate doses to local areas of the cervix.

A new menthane-type monoterpenoid from fermented Illigera aromatica with Clonostachys rogersoniana 828H2.

A new menthane-type monoterpenoid, illigerate E (1), as well as two known ones, (1R*,3R*,4S*,6R*)-6,8-dihydroxymenthol (2) and cis-4-hydroxy-5-(1-hydroxy-1-methylethyl)-2-methyl-2-cyclohexene-1-one (3), were isolated from fermented Illigera aromatica with Clonostachys rogersoniana 828H2. Their structures were identified by HRESIMS and 1D/2D NMR spectra. Their inhibitory effects of NO production in RAW 264.7 macrophages were estimated.

Three new diterpenoid alkaloids isolated from Aconitum brevicalcaratum.

In the present study, three new aconitine-type diterpenoid alkaloids brochyponines A-C (1-3) were isolated from the roots of Aconitum brevicalcaratum. Their structures were established on the basis of extensive spectroscopic analyses (IR, HR-ESI-MS, and 1D and 2D NMR). The NMR data of salt form for compound 1 in CDCl3 were also measured.

New phenylpropanoids from Bulbophyllum retusiusculum.

Two new phenylpropanoids, retusiusines A (1) and B (2), and a pair of new phenylpropyl enantiomers, (±)-retusiusine C (3a and 3b), together with eight known compounds, dihydroconiferyl dihydro-p-coumarate (4), methyl 3-(4-hydroxyphenyl) propionate (5), 3-(4-hydroxyphenyl)-propanoic acid (6), dihydroferulic acid (7), methyl 3-(4-methoxyphenyl) propionate (8), 3-(3,4-dimethoxyphenyl)-2-propenal (9), trans-p-coumaric acid (10) and dihydroconiferyl alcohol (11), were isolated from the tubers of Bulbophyllum retusiusculum. The absolute configurations of the new compounds were determined by calculating their electronic circular dichroism (ECD), spectra and specific optical rotations and comparing the calculated values with the experimental data. Compound 2 exhibited potent antifungal activity against Candida albicans (16 µg/mL). Compound 3 showed moderate antibacterial activity against Bacillus subtilis (64 µg/mL).