Sesquiterpenes and α-pyrones from an endophytic fungus Xylaria curta YSJ-5.

Chemical investigation of the culture extract of an endophyte Xylaria curta YSJ-5 from Alpinia zerumbet (Pers.) Burtt. et Smith resulted in the isolation of eight previously undescribed compounds including five eremophilane sesquiterpenes xylarcurenes A-E, one norsesquiterpene xylarcurene F, and two α-pyrone derivatives xylarpyrones A-B together with eight known related derivatives. Their chemical structures were extensively established based on the 1D- and 2D-NMR spectroscopic analysis, modified Mosher's method, electronic circular dichroism calculations, single-crystal X-ray diffraction experiments, and the comparison with previous literature data. All these compounds were tested for in vitro cytotoxic, anti-inflammatory, α-glucosidase inhibitory, and antibacterial activities. As a result, 6-pentyl-4-methoxy-pyran-2-one was disclosed to display significant antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus with minimal inhibitory concentration value of 6.3 µg/mL.

A Novel Albumin-Related Nutrition Biomarker Predicts Breast Cancer Prognosis in Neoadjuvant Chemotherapy: A Two-Center Cohort Study.

BACKGROUND: Recently, there has been a growing focus on the prognostic significance of nutrition-related biomarkers. We attempted to explore the association between a novel albumin-related nutrition marker called "lymphocyte × albumin (LA)" and disease-free survival (DFS) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). METHODS: In total, 711 non-metastatic breast cancer patients who underwent NAC at two medical centers were retrospectively analyzed. We performed least absolute shrinkage and selection operator (LASSO) Cox regression analysis as well as multivariate Cox regression analyses to identify the variables associated with DFS and to establish a predictive nomogram. RESULTS: The nomogram incorporated four variables based on the multivariate analysis of DFS in the training cohort: LA, ypN stage, ypT stage, and hormone receptor status. In comparison with the traditional TNM staging system, the nomogram demonstrated superior discrimination, calibration ability, and clinical usefulness in both the training set and internal and external validation sets. Furthermore, patients stratified into different risk groups resulted in significant differences in DFS. CONCLUSIONS: LA is an independent prognostic biomarker, and LA-based prognostic nomogram offers a more precise assessment of DFS for breast cancer patients treated with NAC, potentially serving as a valuable tool for personalized prognostic predictions.

Pan-Immune-Inflammatory Value in Patients with Non-Small-Cell Lung Cancer Undergoing Neoadjuvant Immunochemotherapy.

Background: We aimed to investigate the predictive value of a systematic serum inflammation index, pan-immune-inflammatory value (PIV), in pathological complete response (pCR) of patients treated with neoadjuvant immunotherapy to further promote ideal patients' selection. Methods: The clinicopathological and baseline laboratory information of 128 NSCLC patients receiving neoadjuvant immunochemotherapy between October 2019 and April 2022 were retrospectively reviewed. We performed least absolute shrinkage and selection operator (LASSO) algorithm to screen candidate serum biomarkers for predicting pCR, which further entered the multivariate logistic regression model to determine final biomarkers. Accordingly, a diagnostic model for predicting individual pCR was established. Kaplan-Meier method was utilized to estimate curves of disease-free survival (DFS), and the Log rank test was analyzed to compare DFS differences between patients with and without pCR. Results: Patients with NSCLC heterogeneously responded to neoadjuvant immunotherapy, and those with pCR had a significant longer DFS than patients without pCR. Through LASSO and the multivariate logistic regression model, PIV was identified as a predictor for predicting pCR of patients. Subsequently, a diagnostic model integrating with PIV, differentiated degree and histological type was constructed to predict pCR, which presented a satisfactory predictive power (AUC, 0.736), significant agreement between actual and our nomogram-predicted pathological response. Conclusion: Baseline PIV was an independent predictor of pCR for NSCLC patients receiving neoadjuvant immunochemotherapy. A significantly longer DFS was achieved in patients with pCR rather than those without pCR; thus, the PIV-based diagnostic model might serve as a practical tool to identify ideal patients for neoadjuvant immunotherapeutic guidance.

Distinct Prognostic Factors of Ground Glass Opacity and Pure-Solid Lesion in Pathological Stage I Invasive Lung Adenocarcinoma.

Background: Ground glass opacity (GGO) is associated with favorable survival in lung cancer. However, the relevant evidence of the difference in prognostic factors between GGO and pure-solid nodules for pathological stage I invasive adenocarcinoma (IAC) is limited. We aimed to identify the impact of GGO on survival and find prognostic factor for part-GGO and pure-solid patients. Methods: Between December 2007 and August 2018, patients with pathological stage I IAC were retrospectively reviewed and categorized into the pure-GGO, part-GGO, and pure-solid groups. Survival curves were analyzed by the Kaplan-Meier method and compared by log-rank tests. Least absolute shrinkage and selection operator and Cox regression models were used to obtained prognostic factors for disease-free survival (DFS) and overall survival (OS). Results: The number of patients with pure-GGO, part-GGO, and pure-solid was 134, 540, and 396, respectively. Part-GGO patients with consolidation-tumor-ratio (CTR) > 0.75 had similar outcome to those with pure-solid nodules. In part-GGO patients, CTR was negatively associated with OS (P = 0.007) and solid tumor size (STS) was negatively associated with DFS (P < 0.001). Visceral pleural invasion (VPI) was negatively associated with OS (P = 0.040) and DFS (P = 0.002). Sublobectomy was negatively associated with OS (P = 0.008) and DFS (P = 0.005), while extended N1 stations examination was associated with improved DFS (P = 0.005) in pure-solid patients. Conclusions: Though GGO component is a positively prognostic factors of patients with pathological stage I IAC, a small proportion of GGO components is not associated with favorable survival. VPI, STS and CTR are the significant predictors for part-GGO patients. Sublobectomy, especially wedge resection should be used cautiously in pure-solid patients.

Spontaneous remission of hepatic myelopathy in a patient with alcoholic cirrhosis: A case report.

BACKGROUND: Hepatic myelopathy (HM) is a rare neurological complication of advanced cirrhosis. Prognosis of patients with HM is generally poor without timely liver transplantation or interventional therapy. Self-resolving HM in patients with alcoholic cirrhosis has never been reported. CASE SUMMARY: A 53-year-old man with alcoholic cirrhosis and recurrent overt hepatic encephalopathy for 1 year was admitted for lower extremity weakness, slow movement, and stumbling gait. The patient was diagnosed with HM after excluding other causes of spastic paraparesis. The patient refused liver transplantation. However, the patient kept total abstinence and received a multidisciplinary treatment for complications of decompensated cirrhosis. The symptoms of HM resolved gradually after 2 years of treatment. All complications of alcoholic cirrhosis resolved after 4 years of follow-up. CONCLUSION: The case demonstrates that HM can resolve in patients without liver transplan-tation after total abstinence and systemic management of complications.

[Effects of electroacupuncture on sexual development and ovarian estrogen receptor ß expression in female adolescent obese rats].

OBJECTIVE: To observe the effect of electroacupuncture on sexual development and ovarian estrogen receptor ß(ER-ß) expression in female adolescent obese rats induced by high-fat diet, so as to explore its underlying mechanisms of improving adolescent obesity. METHODS: Female SD rats (age of 21 days) were randomly divided into control, model and acupuncture groups, with 6 rats in each group. The obese model was established by feeding high-fat diet for 6 weeks. Rats of the acupuncture group received electroacupuncture(2 Hz, 0.5-1.2 mA)stimulation at bilateral "Sanyinjiao"(SP6), "Fenglong"(ST40) and "Zusanli"(ST36) for 30 min, once a day for 14 days. The body mass and abdominal circumference of rats were measured before and after treatment. The contents of serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were detected by ELISA. The number of corpus luteum and follicle were observed by HE staining. The expression levels of ER-ß mRNA and protein in ovary were detected by fluorescence quantitative PCR and Western blot, respectively. RESULTS: Compared with the control group, the body mass and abdominal circumference, the contents of serum FSH and E2, and the expression levels of ER-ß mRNA and protein in ovary were significantly increased (P<0.05)in the model group, while the number of mature follicles and corpus luteum increased significantly. Compared with the model group, the body mass and abdominal circumference, the contents of serum FSH and E2, and the expression levels of ER-ß mRNA and protein in ovary were significantly decreased (P<0.05) in the acupuncture group, while the number of mature follicles and corpus luteum decreased significantly. CONCLUSION: Electroacupuncture can effectively improve the levels of sex hormone and the development of ovary, down-regulate the expression levels of ER-ß mRNA and protein in ovary, so as to regulate the process of sexual development of female adolescent obese rats induced by high-fat diet.

Integrative Analysis of Bioinformatics and Machine Learning Algorithms Identifies a Novel Diagnostic Model Based on Costimulatory Molecule for Predicting Immune Microenvironment Status in Lung Adenocarcinoma.

Costimulatory molecules are an indispensable signal for activating immune cells. However, the features of many costimulatory molecule genes (CMGs) in lung adenocarcinoma (LUAD) are poorly understood. This study systematically explored expression patterns of CMGs in the tumor immune microenvironment (TIME) status of patients with LUAD. Their expression profiles were downloaded from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Two robust TIME subtypes ("hot" and "cold") were classified by K-means clustering and estimation of stromal and immune cells in malignant tumor tissues using expression data. The "hot" subtype presented higher infiltration in activated immune cells and enrichments in the immune cell receptor signaling pathway and adaptive immune response. Three CMGs (CD80, LTB, and TNFSF8) were screened as final diagnostic markers by means of Least Absolute Shrinkage Selection Operator and Support Vector Machine-Recursive Feature Elimination algorithms. Accordingly, the diagnostic nomogram for predicting individualized TIME status showed satisfactory diagnostic accuracy in The Cancer Genome Atlas training cohort as well as GSE31210 and GSE180347 validation cohorts. Immunohistochemistry staining of 16 specimens revealed an apparently positive correlation between the expression of CMG biomarkers and pathologic response to immunotherapy. Thus, this diagnostic nomogram provided individualized predictions in TIME status of LUAD patients with good predictive accuracy, which could serve as a potential tool for identifying ideal candidates for immunotherapy.

Novel Signatures Based on the Lymphocyte-to-C-Reactive Protein Ratio Predict the Prognosis of Patients with Early Breast Cancer: A Retrospective Study.

Background: The value of the lymphocyte-to-C-reactive protein (CRP) ratio (LCR) in early breast cancer (BC) is unclear. We explored the correlation between the LCR and survival of patients with early BC and established effective LCR-based prognostic signatures for predicting prognosis. Methods: In this retrospective study, we randomized 623 patients with early-stage BC diagnosed in December 2010 to October 2012 at the Sun Yat-sen University Cancer Center to training and verification datasets. The median follow-up of all patients was 109 months. The survival differences were calculated by Kaplan-Meier method using the Log rank test. For overall survival (OS) and disease-free survival (DFS), the independent factors in the training dataset were identified using univariate and multivariate Cox analyses, in which two-tailed P-values < 0.05 were considered statistically significant. Based on this, we respectively constructed novel signatures for survival prediction and validated the efficiency of signatures through the concordance index (C-index), calibration and receiver operating characteristic (ROC) curves in both datasets. Results: The LCR, lymphatic vessel invasion (LVI), progesterone receptor (PR) status, and Ki67 index were independent prognostic factors of OS. And the LCR and LVI are associated to DFS too. High LCR was associated with better OS and DFS. We constructed the prediction signatures based on those independent prognostic factors and calculated the risk scores. Patients in the training dataset with higher risk scores had significantly worse prognosis (P < 0.001). The signature had excellent discrimination capacity, with an OS C-index of 0.785 [95% confidence interval (CI): 0.713-0.857] and 0.750 (95% CI: 0.669-0.832) in the training and verification datasets, respectively. The time-ROC curves also suggest accurate prediction by the signature. Conclusion: The LCR was a significant prognostic predictor of OS and DFS in early BC. The LCR-based prognostic signatures could be a useful tool for individualized therapeutic guidance.

An Aging-Related Gene Signature-Based Model for Risk Stratification and Prognosis Prediction in Lung Squamous Carcinoma.

Aging is an inevitable process characterized by a decline in many physiological activities, and has been known as a significant risk factor for many kinds of malignancies, but there are few studies about aging-related genes (ARGs) in lung squamous carcinoma (LUSC). We designed this study to explore the prognostic value of ARGs and establish an ARG-based prognosis signature for LUSC patients. RNA-sequencing and corresponding clinicopathological data of patients with LUSC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The ARG risk signature was developed on the basis of results of LASSO and multivariate Cox analysis in the TCGA training dataset (n = 492). Furthermore, the GSE73403 dataset (n = 69) validated the prognostic performance of this ARG signature. Immunohistochemistry (IHC) staining was used to verify the expression of the ARGs in the signature. A five ARG-based signature, including A2M, CHEK2, ELN, FOS, and PLAU, was constructed in the TCGA dataset, and stratified patients into low- and high-risk groups with significantly different overall survival (OS) rates. The ARG risk score remained to be considered as an independent indicator of OS in the multivariate Cox regression model for LUSC patients. Then, a prognostic nomogram incorporating the ARG risk score with T-, N-, and M-classification was established. It achieved a good discriminative ability with a C-index of 0.628 (95% confidence interval [CI]: 0.586-0.671) in the TCGA cohort and 0.648 (95% CI: 0.535-0.762) in the GSE73403 dataset. Calibration curves displayed excellent agreement between the actual observations and the nomogram-predicted survival. The IHC staining discovered that these five ARGs were overexpression in LUSC tissues. Besides, the immune infiltration analysis in the TCGA cohort represented a distinctly differentiated infiltration of anti-tumor immune cells between the low- and high-risk groups. We identified a novel ARG-related prognostic signature, which may serve as a potential biomarker for individualized survival predictions and personalized therapeutic recommendation of anti-tumor immunity for patients with LUSC.

Aspersteroids A-C, Three Rearranged Ergostane-type Steroids from Aspergillus ustus NRRL 275.

Aspersteroid A (1), a highly rearranged 1(10 → 6)-abeo-18,22-cyclosterol, together with two new 18,22-cyclosterols (2 and 3), was isolated from the culture extract of Aspergillus ustus NRRL 275. Their structures were determined by spectroscopic analysis, X-ray diffraction, modified Mosher's method, and Rh2(OCOCF3)4-induced electronic circular dichroism experiments. Compound 1 represents a new carbon skeleton with an uncommon 6/6/6/5/5 ring system, which is presumably biosynthesized from A-ring scission, double 1,2-shifts, and C-18/C-22 cyclization. Compound 1 exhibited potent immunosuppressive and antimicrobial activities.

[11]-Chaetoglobosins from Pseudeurotium bakeri Induce G2/M Cell Cycle Arrest and Apoptosis in Human Cancer Cells.

Twelve new [11]-chaetoglobosins, chaetopseudeurins A-L (1-12), were identified from the fermentation of the endophytic fungus Pseudeurotium bakeri P1-1-1. Their structures with absolute configurations were elucidated by detailed interpretation of NMR spectroscopy, mass spectrometry, and single-crystal X-ray diffraction. Compounds 2 and 5-7 exhibited significant cytotoxicities against seven human cancer cell lines, with IC50 values ranging from 4.7 ± 1.0 to 12.2 ± 0.7 µM, and induced G2/M cell cycle arrest and apoptosis in MCF-7 and A427 cells dose dependently. Western blot analysis showed that compound 2 induced apoptosis of MCF-7 cells via the Bcl-2/caspase-3/PARP pathway.

Benefits of Early Ambulation in Elderly Patients Undergoing Lumbar Decompression and Fusion Surgery: A Prospective Cohort Study.

OBJECTIVE: To evaluate the effects of early ambulation on elderly patients' postoperative physical functional outcomes, complications, 90-day readmission rate, and the length of postoperative hospital stay. METHODS: This is a prospective cohort study conducted between June 2019 and December 2019. The study enrolled 86 elderly patients (39 males) with newly diagnosed lumbar degenerative disease undergoing single-segment decompression and fusion surgerywere enrolled. Of all 86 patients, 39 voluntarily joined the early ambulation group, and 47 joined the regular ambulation group. The early ambulation group included patients ambulated within 4 h postoperatively, whereas the regular ambulation group included patients who were ambulatory at a minimum of 24 h after surgery. Participants' baseline characteristics, surgical information, ambulation ability, degree of pain, functional scores, postoperative complications, 90-day readmission rate, and length of postoperative hospital stay were recorded. RESULTS: Participants' baseline demographic characteristics were balanced between the early ambulation group and the regular ambulation group. The operative time and blood loss were similar between groups. The time before the first-time ambulation was 4 ± 0.5 h in the early ambulation group and 28 ± 4.5 h in the regular ambulation group. Ambulating distance was significantly longer in the early ambulation group compared with the regular ambulation group on the 1st (63 ± 45 vs 23 ± 60 m), the 2nd (224 ± 100 vs 101 ± 130 m), and the 3rd (280 ± 102.5 vs 190 ± 170 m) ambulation days based on generalized estimating equation analyses. Generalized estimating equation analyses also demonstrated that the ambulating time was longer in the early ambulation group compared with the regular ambulation group on the 1st (10 ± 5 vs 10 ± 5 min), the 2nd (19 ± 7 vs 15 ± 5 min), and the 3rd (22 ± 16.5 vs 27 ± 12 min) ambulation days. Patients in the regular ambulation group experienced a higher degree of pain than the early ambulation group patients, with an odds ratio of 1.627 (P = 0.002). Short-term functional independence was superior in the early ambulation group, with a lower Roland-Morris disability questionnaire score (P = 0.008) and Oswestry disability index (P < 0.001). The incidences of postoperative urinary retention (early ambulation group: 7.7%, regular ambulation group: 25.5%, P = 0.030) and ileus (early ambulation group: 0%, regular ambulation group: 12.8%, P = 0.030) were significantly higher in the regular ambulation group. The prevalence of at least one complication rate was significantly lower in the early ambulation group than in the regular ambulation group (early ambulation group, 23.1%; regular ambulation group, 46.8%, P = 0.022). The duration of indwelling of the drainage catheter was shorter in the early ambulation group (early ambulation group, 68 ± 24 h; regular ambulation group, 78 ± 20 h, P = 0.001), and the length of the postoperative hospital stay was also shorter in the early ambulation group (early ambulation group, 4 ± 0 days; regular ambulation group: 5 ± 2 days, P < 0.001). However, there was no statistical difference in the 90-day readmission rate between groups. CONCLUSION: Early ambulation improved patients' postoperative functional status, decreased the incidence of complications, and shortened postoperative hospital stay in elderly patients undergoing lumbar decompression and fusion surgery.

Hypothemycin-Type Resorcylic Acid Lactones with Immunosuppressive Activities from a Podospora sp.

Twelve new hypothemycin-type resorcylic acid lactones, three 10-membered (1-3) and nine 14-membered (4-12), together with seven known analogues (13-19), were obtained from the solid rice-based culture of Podospora sp. G214. Their structures were elucidated utilizing spectroscopic analysis, and the absolute configurations were determined by modified Mosher's method, Mo2(OAc)4-induced electronic circular dichroism experiments, and single-crystal X-ray diffraction. Compounds 1, 5, 10, and 12-19 exhibited potent immunosuppressive activities against concanavalin A-induced T cell proliferation with IC50 values ranging from 6.0 to 25.1 µM and lipopolysaccharide-induced B cell proliferation with IC50 values ranging from 6.2 to 29.1 µM. Further studies revealed that 1 induced apoptosis in activated T cells through the JNK-mediated mitochondrial pathway.

A Novel Inflammatory-Related Gene Signature Based Model for Risk Stratification and Prognosis Prediction in Lung Adenocarcinoma.

Inflammation is an important hallmark of cancer and plays a role in both neogenesis and tumor development. Despite this, inflammatory-related genes (IRGs) remain to be poorly studied in lung adenocarcinoma (LUAD). We aim to explore the prognostic value of IRGs for LUAD and construct an IRG-based prognosis signature. The transcriptomic profiles and clinicopathological information of patients with LUAD were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Least absolute shrinkage and selection operator (LASSO) analysis and multivariate Cox regression were applied in the TCGA set to generate an IRG risk signature. LUAD cases with from the GSE31210 and GSE30219 datasets were used to validate the predictive ability of the signature. Analysis of the TCGA cohort revealed a five-IRG risk signature consisting of EREG, GPC3, IL7R, LAMP3, and NMUR1. This signature was used to divide patients into two risk groups with different survival rates. Multivariate Cox regression analysis verified that the risk score from the five-IRG signature negatively correlated with patient outcome. A nomogram was developed using the IRG risk signature and stage, with C-index values of 0.687 (95% CI: 0.644-0.730) in the TCGA training cohort, 0.678 (95% CI: 0.586-0.771) in GSE30219 cohort, and 0.656 (95% CI: 0.571-0.740) in GSE30219 cohort. Calibration curves were consistent between the actual and the predicted overall survival. The immune infiltration analysis in the TCGA training cohort and two GEO validation cohorts showed a distinctly differentiated immune cell infiltration landscape between the two risk groups. The IRG risk signature for LUAD can be used to predict patient prognosis and guide individual treatment. This risk signature is also a potential biomarker of immunotherapy.

Pchaeglobolactone A, Spiropchaeglobosin A, and Pchaeglobosals A and B: Four Rearranged Cytochalasans from Chaetomium globosum P2-2-2.

Four novel rearranged cytochalasans (1-4) were isolated from an endophytic fungus Chaetomium globosum P2-2-2. Pchaeglobolactone A (1) possessed an unprecedented 13-aza-21-oxa-tetracyclo-[10.6.1.217,19.015,19]henicosane core. Spiropchaeglobosin A (2) was the first example of cytochalasans featuring a novel spiro[5.10]hexadecane unit. Pchaeglobosals A (3) and B (4) featured a unique 5/5/13 fused tricyclic ring system. Compounds 1-4 were tested for their antiproliferative, apoptosis, cell cycle arrest, and TRAIL-resistance-overcoming activities on cancer cell lines.

Total Knee Arthroplasty in Patients with Prior Femoral and Tibial Fractures: Outcomes and Risk Factors for Surgical Site Complications and Reoperations.

OBJECTIVE: To investigate the outcomes of total knee arthroplasty (TKA) in patients with a prior femoral or tibial fracture, and identify the risk factors for surgical site complications and reoperations. METHODS: Seventy-one TKAs performed in 71 patients with a prior tibial or femoral fracture between January 2005 and December 2016 were reviewed retrospectively. Forty males (40 knees) and 31 females (31 knees) were included. The mean age at the time of TKA was 59.2 (range, 29-83) years. Outcomes were assessed using the Knee Society score before surgery and at the final follow-up visit. The patients' satisfaction rates were evaluated. Complications and reoperations were recorded by clinical and radiographic assessment. Logistic regression analysis was used to identify the risk factors for surgical site complications and reoperations. RESULTS: The median follow-up period was 4.7 (range, 3.2-7.1) years. The median knee range of motion increased from 90° preoperatively to 110° at the latest follow-up. The Knee Society knee score and function score improved from 35 (30, 40) and 40 (30, 50) to 90 (82, 93) and 90 (65, 100), respectively. The degree of overall satisfaction after TKA surgery was very satisfied in 41 patients, satisfied in 20 patients, neutral in four patients, dissatisfied in four patients, and very dissatisfied in two patients. The overall satisfaction (very satisfied and satisfied) rate was 85.9% (61 knees). Twelve knees (16.9%) had 19 surgical site complications. Six knees (8.3%) underwent reoperations, including one revision due to periprosthetic joint infection, one debridement and implant retention for superficial infection, two debridements for delayed wound healing, one open reduction and internal fixation for supracondylar fracture, and one re-fixation and bone grafting for hardware failure after a combined femoral shaft osteotomy and TKA. Preoperative patella baja was diagnosed in 12 knees, and was identified as a risk factor for surgical site complications and reoperations. CONCLUSIONS: TKA for post-fracture osteoarthritis significantly relieved pain and improved function, but the incidence of surgical site complications and reoperations was high. Preoperative patella baja was a risk factor for surgical site complications and reoperations.

P311 Promotes Lung Fibrosis via Stimulation of Transforming Growth Factor-ß1, -ß2, and -ß3 Translation.

Interstitial lung fibrosis, a frequently idiopathic and fatal disease, has been linked to the increased expression of profibrotic transforming growth factor (TGF)-ßs. P311 is an RNA-binding protein that stimulates TGF-ß1, -ß2, and -ß3 translation in several cell types through its interaction with the eukaryotic translation initiation factor 3b. We report that P311 is switched on in the lungs of patients with idiopathic pulmonary fibrosis (IPF) and in the mouse model of bleomycin (BLM)-induced pulmonary fibrosis. To assess the in vivo role of P311 in lung fibrosis, BLM was instilled into the lungs of P311-knockout mice, in which fibrotic changes were significantly decreased in tandem with a reduction in TGF-ß1, -ß2, and -ß3 concentration/activity compared with BLM-treated wild-type mice. Complementing these findings, forced P311 expression increased TGF-ß concentration/activity in mouse and human lung fibroblasts, thereby leading to an activated phenotype with increased collagen production, as seen in IPF. Consistent with a specific effect of P311 on TGF-ß translation, TGF-ß1-, -ß2-, and -ß3-neutralizing antibodies downregulated P311-induced collagen production by lung fibroblasts. Furthermore, treatment of BLM-exposed P311 knockouts with recombinant TGF-ß1, -ß2, and -ß3 induced pulmonary fibrosis to a degree similar to that found in BLM-treated wild-type mice. These studies demonstrate the essential function of P311 in TGF-ß-mediated lung fibrosis. Targeting P311 could prove efficacious in ameliorating the severity of IPF while circumventing the development of autoimmune complications and toxicities associated with the use of global TGF-ß inhibitors.

Antioxidant and Tyrosinase Inhibitory Activities of Seed Oils from Torreya grandis Fort. ex Lindl.

Torreya grandis Fort. ex Lindl. is a plant belonging to the Taxaceae family and Torreya grandis cv. Merrillii is the only grafted and thoroughbred species belonging to this species. In this study, we extracted five different seed oils, including T. grandis seed oil (TGSO), T. grandis "Xiangyafei" seed oil (XYSO), T. grandis "Zhimafei" seed oil (ZMSO), T. grandis "Majus"seed oil (TGMSO), and T. grandis "cunguangfei" seed oil (CGSO) using physical pressure. The resulting extracts were analyzed to determine their fatty acid composition, antioxidant activity, and inhibitory activity towards tyrosinase. The results of the antioxidant activity assays revealed that XYSO and ZMSO exhibited much greater DPPH radical scavenging activity and ferric reducing power than TGSO. Notably, all five of the seed oils showed dose-dependent inhibitory activity towards tyrosinase. XYSO and TGSO gave the highest activities of all of the seed oils tested in the current study against monophenolase and diphenolase, with IC50 values of 227.0 and 817.5µg/mL, respectively. The results of this study show that wild TGSOs exhibit strong antioxidant and tyrosinase inhibition activities. These results therefore suggest that wild TGSOs could be used as a potential source of natural antioxidant agents and tyrosinase inhibitors.

Parasubindoles A-G, Seven Eremophilanyl Indoles from the Whole Plant of Parasenecio albus.

Parasubindoles A-G (1-7), seven eremophilanyl indoles with an unprecedented 12 H-cyclopentane[ b]naphthalenespiro-1,3'-indole skeleton, were isolated from the whole plant of Parasenecio albus. Their structures with absolute configurations were elucidated by spectroscopic methods, single-crystal X-ray diffraction, and ECD analyses. Plausible biosynthetic pathways of 1-7 were postulated.

Antitumor Effects and Mechanism of n-butanol Fraction from Aril of Torreya grandis in H22 Mice.

BACKGROUND: To determine the antitumor effects and its mechanism of n-butanol fraction from aril of Torreya grandis (BFAT) on H22 mice models of liver cancer. MATERIALS AND METHODS: Sixty ICR male mice were used to establish H22 mice models of liver cancer and then randomly divided into six groups, the normal control group, the model control group, the positive group (cyclophosphamide [CTX]), the BFAT-treated group (high, 4 g/kg, medium, 2 g/kg, and low, 1 g/kg). The animals were sacrificed 15 days after oral administration, and tumors were taken out for the tumor weights and antitumor rates, while thymus and spleen were taken for thymus index and spleen index. Blood in eyeball was collected for the determination of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (Alb), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase enzyme (GSH-Px), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), transforming growth factor-ß1 (TGF-ß1), and IL-10 in serum. Sections of tumor tissue were prepared, and morphological changes in tumor tissue cells were observed using hematoxylin and eosin staining technique. RESULTS: Compared with the model control group, the tumor inhibition rate of the high-dose administered group is 60.15%, which is quite closed to the effect of CTX. Moreover, the tumor weight is decreased, the indexes of spleen, thymus were increased significantly. Furthermore, the administration of BFAT significantly enhanced the activities of TNF-α, IL-2, SOD, and GSH-Px and reduced the levels of AST, ALT, MDA, Alb, TGF-ß1, and IL-10 (P < 0.01). CONCLUSIONS: The results demonstrated that n-butanol fraction from aril of T. grandis showed out antitumor activity without obviously liver damage through potentiating immunologic function and antioxidant activity of tumor-bearing mice and which may become one potential as anticancer drug alternatives or supplements. SUMMARY: High and medium groups could significant elevate the thymus and spleen indexes and the interleukin-2 and tumor necrosis factor-α level in serum of H22 micen-butanol fraction from aril of Torreya grandis (BFAT) could ameliorate the levels of aspartate aminotransferase, alanine aminotransferase and albumin to almost normal, and increase the concentrations of superoxide dismutase and glutathione peroxidase enzyme, decrease the malondialdehyde level in serum of mice significantlyBFAT may indirectly play the role of antitumor activity through improving immunologic functionBFAT had potent antitumor properties without obviously liver damage. Abbreviations used: DDP: Cisplatin; CTX: Cyclophosphamide; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; Alb: Albumin; MDA: Malondialdehyde; SOD: Superoxide dismutase; GSH-Px: Glutathione peroxide enzyme; TNF-α: Tumor necrosis factor-α; IL-2: Interleukin-2; TGF-ß1: Transforming growth factor-ß1; IL-10: Interleukin-10; HE: Hematoxylin and eosin; PBS: Phosphate-buffered saline; PFAT: Petroleum ether fraction from aril of Torreya grandis; EFAT: Ethyl acetate fraction from aril of Torreya grandis; BFAT: N-butanol fraction from aril of Torreya grandis.