Identification of a Difluorinated Alkoxy Sulfonyl Chloride as a Novel Antitumor Agent for Hepatocellular Carcinoma through Activating Fumarate Hydratase Activity.

Fenofibrate is known as a lipid-lowering drug. Although previous studies have reported that fenofibrate exhibits potential antitumor activities, IC50 values of fenofibrate could be as high as 200 µM. Therefore, we investigated the antitumor activities of six synthesized fenofibrate derivatives. We discovered that one compound, SIOC-XJC-SF02, showed significant antiproliferative activity on human hepatocellular carcinoma (HCC) HCCLM3 cells and HepG2 cells (the IC50 values were 4.011 µM and 10.908 µM, respectively). We also found this compound could inhibit the migration of human HCC cells. Transmission electron microscope and flow cytometry assays demonstrated that this compound could induce apoptosis of human HCC cells. The potential binding sites of this compound acting on human HCC cells were identified by mass spectrometry-cellular thermal shift assay (MS-CETSA). Molecular docking, Western blot, and enzyme activity assay-validated binding sites in human HCC cells. The results showed that fumarate hydratase may be a potential binding site of this compound, exerting antitumor effects. A xenograft model in nude mice demonstrated the anti-liver cancer activity and the mechanism of action of this compound. These findings indicated that the antitumor effect of this compound may act via activating fumarate hydratase, and this compound may be a promising antitumor candidate for further investigation.

[Research Progress of SOA Formation from Anthropogenic VOCs Under Complex Pollution Condition].

Although the air quality in China has been greatly improved in recent years, the air pollution remains severe. The annual mean PM2.5 concentrations have not met the second grade of the National Ambient Air Quality Standards in China and are still much higher than the guideline value of the World Health Organization. Thus, the PM2.5 concentration needs to be further reduced. Secondary organic aerosol (SOA) is an important component of PM2.5 and has an important impact on air quality, global climate change, and human health. Therefore, understanding the formation mechanism of SOA is an important basis to control SOA and further reduce PM2.5. As an important precursor of SOA, volatile organic compounds (VOCs) can be oxidized by oxidants such as ·OH, NO3[KG-*2/3]·, Cl·, and O3 to generate low volatile organic compounds and further to form SOA through gas-particle partitioning, homogeneous nucleation, aqueous phase reaction, and heterogeneous reaction processes. The formation of SOA can be affected by many factors, such as the types and initial concentrations of VOCs, VOCs/NOx ratios, relative humidity (RH), temperature (T), seed aerosols, oxidants, aqueous phase process, and photochemical process. The observed SOA concentration is always underestimated by air quality models because a comprehensive understanding of the complexity of SOA chemical composition and formation mechanisms is still lacking, especially that under the highly complex air pollution conditions in China. Therefore, the formation mechanism and influencing factors of SOA under highly complex air pollution conditions have become an important concern in the field of atmospheric sciences. Recently, much laboratory work has focused on the formation of SOA under complex conditions. The research progress of SOA formation from different anthropogenic VOCs are reviewed here, and the methods used and the impact of different influencing factors on SOA formation are introduced. Finally, the key scientific issues that exist in the research of the SOA mechanism at present are put forward, and the future research direction is projected.

Research Status and Prospect of Living Wills / 中国医学伦理学

This paper analyzed the research status of living wills at home and abroad from three aspects: the status of living wills knowledge-attitude-practice, the influencing factors of the living wills development, and the effects of living wills. It also provided some suggestions for promoting the development of living wills in China. In foreign countries, a large number of quantitative and qualitative studies have been carried out in this regard, and the research contents were relatively in-depth. However, China initiated late in this field, and the research contents and methods were relatively simple. Living wills not only protect patients’ decision-making right, but also promote the rational distribution of medical resources, as well as ensure the fairness of health services. For China, with a large population and uneven distribution of health resources, living wills have broad implementation prospects.

Perioperative risk factors associated with unplanned neurological intensive care unit readmission following elective supratentorial brain tumor resection.

OBJECTIVE: The aim of this study was to describe the clinical and procedural risk factors associated with the unplanned neurosurgical intensive care unit (NICU) readmission of patients after elective supratentorial brain tumor resection and serves as an exploratory analysis toward the development of a risk stratification tool that may be prospectively applied to this patient population. METHODS: This was a retrospective observational cohort study. The electronic medical records of patients admitted to an institutional NICU between September 2018 and November 2021 after elective supratentorial brain tumor resection were reviewed. Demographic and perioperative clinical factors were recorded. A prognostic model was derived from the data of 4892 patients recruited between September 2018 and May 2021 (development cohort). A nomogram was created to display these predictor variables and their corresponding points and risks of readmission. External validation was evaluated using a series of 1118 patients recruited between June 2021 and November 2021 (validation cohort). Finally, a decision curve analysis was performed to determine the clinical usefulness of the prognostic model. RESULTS: Of the 4892 patients in the development cohort, 220 (4.5%) had an unplanned NICU readmission. Older age, lesion type, Karnofsky Performance Status (KPS) < 70 at admission, longer duration of surgery, retention of endotracheal intubation on NICU entry, and longer NICU length of stay (LOS) after surgery were independently associated with an unplanned NICU readmission. A total of 1118 patients recruited between June 2021 and November 2021 were included for external validation, and the model's discrimination remained acceptable (C-statistic = 0.744, 95% CI 0.675-0.814). The decision curve analysis for the prognostic model in the development and validation cohorts showed that at a threshold probability between 0.05 and 0.8, the prognostic model showed a positive net benefit. CONCLUSIONS: A predictive model that included age, lesion type, KPS < 70 at admission, duration of surgery, retention of endotracheal intubation on NICU entry, and NICU LOS after surgery had an acceptable ability to identify elective supratentorial brain tumor resection patients at high risk for an unplanned NICU readmission. These risk factors and this prediction model may facilitate better resource allocation in the NICU and improve patient outcomes.

Perioperative Risk Factors Associated with Unplanned Neurological Intensive Care Unit Events Following Elective Infratentorial Brain Tumor Resection.

BACKGROUND: Our aim of this study was to identify risk factors and develop a prediction model for unplanned neurological intensive care unit (NICU) events after elective infratentorial brain tumor resection in order to propose an individualized admission to the NICU tailored to patient needs. METHODS: Patients admitted to our NICU between September 2018 and May 2021 after elective infratentorial brain tumor resection were reviewed. Prolonged NICU stays and unplanned NICU admissions were defined as unplanned NICU events. The prognostic model of unplanned NICU events was developed using a forward stepwise logistic regression analysis, and external validation was evaluated. The C-statistic was used to assess discrimination, and a smooth, nonparametric calibration line was used to assess calibration graphically in the model. RESULTS: Of the 1,710 patients in the development cohort, unplanned NICU events occurred in 162 (9.5%). Based on the lesion type, a Karnofsky Performance Status score <70 at admission, longer duration of surgery, bleeding in the operative area evident on postoperative computed tomography, higher fibrinogen and blood glucose levels at admission, and more intraoperative blood loss were independently associated with unplanned NICU events. The external validation test showed good discrimination (C-statistic = 0.811) and calibration (Hosmer-Lemeshow P = 0.141) for unplanned NICU events. CONCLUSIONS: Several patient and operative characteristics are associated with a greater likelihood of the occurrence of unplanned NICU events. In the future, we may be able to provide better help for the resource allocation of NICUs according to these risk factors and prediction models.

Clinical effect of minimally invasive duodenum preserving pancreatic head resection for benign and pre-malignant lesions of pancreatic head / 中华外科杂志

Objective: To examine the clinical effect of minimally invasive duodenum preserving pancreatic head resection(DPPHR) for benign and pre-malignant lesions of pancreatic head. Methods: The clinical data of patients with diagnosis of benign or pre-malignant pancreatic head tumor were retrospectively collected and analyzed,all of them underwent laparoscopic or robotic DPPHR between October 2015 and September 2021 at Division of Gastrointestinal and Pancreatic surgery,Zhejiang Provincial People's Hospital. Thirty-three patients were enrolled with 10 males and 23 females. The age(M(IQR)) was 54(32) years old(range: 11 to 77 years old) and the body mass index was 21.9(2.9)kg/m2(range: 18.1 to 30.1 kg/m2). The presenting symptoms included abdominal pain(n=12), Whipple triad(n=2), and asymptomatic(n=19). There were 7 patients with hypertension and 1 patient with diabetes mellitus. There were 19 patients who were diagnosed as American Society of Anesthesiologists class Ⅰ and 14 patients who were diagnosed as class Ⅱ. The student t test,U test, χ2 test or Fisher exact test was used to compare continuous data or categorized data,respectively. All the perioperative data and metabolic morbidity were analyzed and experiences on minimally invasive DPPHR were concluded. Results: Fourteen patients underwent laparoscopic DPPHR,while the rest of 19 patients received robotic DPPHR. Indocyanine green fluorescence imaging was used in 19 patients to guide operation. Five patients were performed pancreatico-gastrostomy and the rest 28 patients underwent pancreaticojejunostomy. Pathological outcomes confirmed 9 solid pseudo-papillary neoplasms, 9 intraductal papillary mucinous neoplasms, 7 serous cystic neoplasms, 6 pancreatic neuroendocrine tumors, 1 mucous cystic neoplasm, 1 chronic pancreatitis. The operative time was (309.4±50.3) minutes(range:180 to 420 minutes),and the blood loss was (97.9±48.3)ml(range:20 to 200 ml). Eighteen patients suffered from postoperative complications,including 3 patients experienced severe complications(Clavien-Dindo Grade ≥Ⅲ). Pancreatic fistula occurred in 16 patients,including 8 patients with biochemical leak,7 patients with grade B pancreatic fistula and 1 patient with grade C pancreatic fistula. No one suffered from the duodenal necrosis and none perioperative death was occurred. The length of hospital stay was 14(7) days (range:6 to 87 days). The follow-up was 22.6(24.5)months(range:2 to 74 months). None suffered from recurrence or metastasis. During the follow-up,all the patients were free of refractory cholangitis. Moreover,in the term of endocrine dysfunction,no postoperative new onset of diabetes mellitus were observed in the long-term follow-up. However,in the view of exocrine insufficiency,pancreatic exocrine insufficiency and non-alcoholic fatty liver disease (NAFLD) was complicated in 2 and 1 patient,respectively,with the supplement of pancreatic enzyme,steatorrhea and weight loss relieved,but NAFLD was awaited to be seen. Conclusions: Minimally invasive DPPHR is feasible and safe for benign or pre-malignant lesions of pancreatic head. Moreover,it is oncological equivalent to pancreaticoduodenectomy with preservation of metabolic function without refractory cholangitis.

Identification of VWF as a Novel Biomarker in Lung Adenocarcinoma by Comprehensive Analysis.

Lung adenocarcinoma (LUAD) is one of the most malignant tumors with high morbidity and mortality worldwide due to the lack of reliable methods for early diagnosis and effective treatment. It's imperative to study the mechanism of its development and explore new biomarkers for early detection of LUAD. In this study, the Gene Expression Omnibus (GEO) dataset GSE43458 and The Cancer Genome Atlas (TCGA) were used to explore the differential co-expressed genes between LUAD and normal samples. Three hundred sixity-six co-expressed genes were identified by differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) method. Those genes were mainly enriched in ameboidal-type cell migration (biological process), collagen-containing extracellular matrix (cell component), and extracellular matrix structure constituent (molecular function). The protein-protein network (PPI) was constructed and 10 hub genes were identified, including IL6, VWF, CDH5, PECAM1, EDN1, BDNF, CAV1, SPP1, TEK, and SELE. The expression level of hub genes was validated in the GEPIA database, compared with normal tissues, VWF is lowly expressed and SPP1 is upregulated in LUAD tissues. The survival analysis showed increased expression of SPP1 indicated unfavorable prognosis whereas high expression of VWF suggested favorable prognosis in LUAD (p < 0.05). Based on the immune infiltration analysis, the relationship between SPP1 and VWF expression and macrophage, neutrophil, and dendritic cell infiltration was weak in LUAD. Quantitative real-time PCR (qRT-PCR) and western blotting were used to validate the expression of VWF and SPP1 in normal human bronchial epithelial (HBE) cell and three LUAD cell lines, H1299, H1975, and A549. Immunohistochemistry (IHC) was further performed to detect the expression of VWF in 10 cases LUAD samples and matched normal tissues. In summary, the data suggest that VWF is a potential novel biomarker for prognosis of LUAD.

lncRNA RP11-624L4.1 Is Associated with Unfavorable Prognosis and Promotes Proliferation via the CDK4/6-Cyclin D1-Rb-E2F1 Pathway in NPC.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in southern China and southeast Asia. Emerging evidence revealed that long noncoding RNAs (lncRNAs) might play important roles in the development and progression of many cancers, including NPC. The functions and mechanisms of the vast majority of lncRNAs involved in NPC remain unknown. In this study, a novel lncRNA RP11-624L4.1 was identified in NPC tissues using next-generation sequencing. In situ hybridization (ISH) was used to analyze the correlation between RP11-624L4.1 expression and the clinicopathological features or prognosis in NPC patients. RNA-Protein Interaction Prediction (RPISeq) predictions and RNA-binding protein immunoprecipitation (RIP) assays were used to identify RP11-624L4.1's interactions with cyclin-dependent kinase 4 (CDK4). As a result, we found that RP11-624L4.1 is hyper-expressed in NPC tissues, which was associated with unfavorable prognosis and clinicopathological features in NPC. By knocking down and overexpressing RP11-624L4.1, we also found that it promotes the proliferation ability of NPC in vitro and in vivo through the CDK4/6-Cyclin D1-Rb-E2F1 pathway. Overexpression of CDK4 in knocking down RP11-624L4.1 cells can partially rescue NPC promotion, indicating its role in the RP11-624L4.1-CDK4/6-Cyclin D1-Rb-E2F1 pathway. Taken together, RP11-624L4.1 is required for NPC unfavorable prognosis and proliferation through the CDK4/6-Cyclin D1-Rb-E2F1 pathway, which may be a novel therapeutic target and prognostic in patients with NPC.

Identification of a 3,3-difluorinated tetrahydropyridinol compound as a novel antitumor agent for hepatocellular carcinoma acting via cell cycle arrest through disturbing CDK7-mediated phosphorylation of Cdc2.

Tetrahydropyridinol derivatives were recently reported to exhibit good biological activities, and the incorporation of fluorine into organic molecules may have profound effects on their physical and biological properties. Therefore, we investigated the anticancer activities of six fluorinated tetrahydropyridinol derivatives that we synthesized previously. We found that only one compound, 3,3-difluoro-2,2-dimethyl-1,6-diphenyl-5-tosyl-1,2,3,6-tetrahydropyridin-4-ol, showed significant antiproliferative activity on human hepatocellular carcinoma HepG2 and HMCCLM3 cells (the IC50 values were 21.25 and 29.07 µM, respectively). We also found that this compound mediated cell cycle arrest in the G0/G1 phase at 30-40 µM. Western blot analysis demonstrated that the cell cycle arrest induced by this compound in HepG2 and HMCCLM3 cells was associated with a significant decrease in Cdc2 and cyclin B1, which led to the accumulation of the phosphorylated-Tyr15 (inactive) form of Cdc2 and low expression of M phase-promoting factor (cyclin B1/Cdc2). Moreover, cells treated with this compound exhibited decreased expression of cyclin-dependent kinase (CDK)-activating kinase (CDK7/cyclin H). This compound also induced cell apoptosis via activation of caspase-3. A xenograft model in nude mice demonstrated anti-liver cancer activity and the mechanism of action of this compound. These findings indicated that the anticancer effect of this compound was partially due to G0/G1 cell cycle arrest via inhibition of CDK7-mediated expression of Cdc2, and this compound may be a promising anticancer candidate for further investigation.

Multi-arterial phase MRI of hepatic vessels using gadoxetic acid: intraindividual comparison of CTA / 中华放射学杂志

Objective@#To investigate the value of multi-arterial phase differential sub-sampling with cartesian ordering (DISCO) technique in the evaluation of hepatic vascular anatomy with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA).@*Methods@#Forty-eight patients with suspected hepatic malignancy were prospectively enrolled and underwent both of Gd-EOB-DTPA enhanced DISCO MRI and CTA within two weeks. The hepatic arterial anatomy of two examination methods were evaluated by four-point scoring method. The arterial scores between DISCO and CTA images were compared by Wilcoxon test. The difference among multiple arterial scores of DISCO and CTA were compared by Kruskal-Wallis H test respectively.@*Results@#There was no difference of arterial scores in celiac artery, common hepatic artery, proper hepatic artery, left hepatic artery, right hepatic artery, first branch of right hepatic artery, splenic artery, left gastric artery and gastroduodenal artery between DISCO and CTA (P>0.05), but the arterial score of first branch of left hepatic artery [2 (2,2)] was lower than that of CTA [2 (2,3)] (Z=-3.138,P=0.002). In the multiple comparison among different arteries, there were differences between PHA and LAH (P<0.05), B-LHA and B-RHA (P<0.05) in DISCO, but no difference was found in CTA (P>0.05).@*Conclusion@#The DISCO sequence with Gd-EOB-DTPA enhancement MRI can supply comparable image quality to CTA in hepatic artery and its main branches display, which has no ionizing radiation and can also provide more diagnostic information for clinic.

Multi?arterial phase MRI of hepatic vessels using gadoxetic acid: intraindividual comparison of CTA / 中华放射学杂志

Objective To investigate the value of multi?arterial phase differential sub?sampling with cartesian ordering (DISCO) technique in the evaluation of hepatic vascular anatomy with gadolinium?ethoxybenzyl?diethylenetriamine pentaacetic acid (Gd?EOB?DTPA). Methods Forty?eight patients with suspected hepatic malignancy were prospectively enrolled and underwent both of Gd?EOB?DTPA enhanced DISCO MRI and CTA within two weeks. The hepatic arterial anatomy of two examination methods were evaluated by four?point scoring method. The arterial scores between DISCO and CTA images were compared by Wilcoxon test. The difference among multiple arterial scores of DISCO and CTA were compared by Kruskal?Wallis H test respectively. Results There was no difference of arterial scores in celiac artery, common hepatic artery, proper hepatic artery, left hepatic artery, right hepatic artery, first branch of right hepatic artery, splenic artery, left gastric artery and gastroduodenal artery between DISCO and CTA (P>0.05), but the arterial score of first branch of left hepatic artery [2 (2,2)] was lower than that of CTA [2 (2,3)] (Z=-3.138,P=0.002). In the multiple comparison among different arteries, there were differences between PHA and LAH (P<0.05), B?LHA and B?RHA (P<0.05) in DISCO, but no difference was found in CTA (P>0.05). Conclusion The DISCO sequence with Gd?EOB?DTPA enhancement MRI can supply comparable image quality to CTA in hepatic artery and its main branches display, which has no ionizing radiation and can also provide more diagnostic information for clinic.

Relationship between the residual in Tianhui medical slips and in / 中国针灸

Except the complete literature of , Tianhui medical slips unearthed in Chengdu also include a part of literature document on meridian, which was seriously damaged. Both of them were found in the same box together with . The title of the document chapter was not found in the residual medical slips. By investigated the textual content, it was discovered that such medical slips were different from the Mawangdui silk books, i.e. and , of Zhangjiashan bamboo slips of Han Dynasty, as well as in Tianhui medical slips. But, the sentences in description are similar to the sentences of in (), therefore, this residual slips was named as () by the collator. In the paper, by the comparison of this residual slip chapter with the unearthed literature document on meridian as well as in , the origin and evolution of meridian theory of traditional Chinese medicine in the Qin and Han dynasties were explained. By taking it as an example, the construction process of classical theory of traditional Chinese medicine was explored.

[Diurnal Variation of SOA Formation Potential from Ambient Air at an Urban Site in Beijing].

Secondary organic aerosol (SOA) is an important component of atmospheric fine particles (PM2.5). The study of the diurnal variation of SOA formation potential is important for understanding the evolution of SOA and its contribution to fine particle pollution. The oxidation flow reactor (OFR) was used to study the SOA formation potential of ambient air in summer at an urban site in Beijing. The high concentration of OH radicals in the reactor can oxidize the volatile organic compounds (VOCs) and lead to SOA formation. The hour average SOA formation potential varied between 3.9-9.4 µg·m-3 in a day and had a higher value at night than in the daytime. The lowest value of SOA formation potential was about 3.9 µg·m-3 observed at 16:00 in the afternoon. This variation of SOA formation potential is consistent with the typical VOCs, such as toluene, and inversely related to the concentration of ozone. In addition to the impact of change in the height of the boundary layer, experimental data showed that the reduction of VOCs in photo-oxidation in the daytime was an important reason for the decrease of SOA formation potential in daytime. Compared to similar studies in developed countries, the SOA formation potential was higher in Beijing due to the higher concentrations of VOCs and might make an important contribution to the fine particle pollution in Beijing.

Analysis of Differential Expressions of Long Non-coding RNAs in Nasopharyngeal Carcinoma Using Next-generation Deep Sequencing.

Background: Little knowledge about long non-coding RNAs(lncRNAs) in nasopharyngeal carcinoma (NPC) has been acquired. Methods: Next-generation sequencing was applied in 7 cases of NPC tissues and 7 cases of normal tissues in nasopharynx. PLEX, CNCI and CPAT soft-wares were used to predict novel lncRNAs. Real-time Quantitative PCR (qPCR) further validated the data in 20 cases of NPC tissues and 14 cases of normal tissues. Then the cis-regulators and trans-regulators and potential biological functions together with pathways were predicted by Bioinformatics. Results: Totally, 4248 novel lncRNAs were found to be expressed in our samples. And 2192 lncRNAs and 23342 mRNAs were considered to be differentially expressed in NPC. Among the results, 306 lncRNAs and 4599 mRNAs were significantly up-regulated, whereas 204 lncRNAs and 2059 mRNAs were significantly down-regulated, respectively. Moreover, 62 lncRNAs trans-regulated genes were involved in Epstein-Barr virus (EBV) infection pathway in our study. Jun proto-oncogene (JUN), which was related to a cis-regulator lncRNA RP4-794H19.1, was enriched in cancers and involved in Tumor Necrosis Factor (TNF) signaling pathway, might play a key role in NPC. Conclusion: These findings broadened the lncRNAs landscape of NPC tissues and shed light on the roles of these lncRNAs, which might be conducive to the comprehensive management of NPC.

Ginnalin A from Kujin tea (Acer tataricum subsp. ginnala) exhibits a colorectal cancer chemoprevention effect via activation of the Nrf2/HO-1 signaling pathway.

Ginnalin A (also known as acertannin) is one of the most important phenolic compounds of several beverage Acer plants. In this study, it is reported for the first time that ginnalin A is an activator of the Nrf2 signaling pathway in human colon cancer cells. Ginnalin A, isolated from the leaves of Acer tataricum subsp. ginnala, exhibited promising preventive activity against colon cancer cells (HCT116, SW480 and SW620) with IC50 values of 24.8 µM, 22.0 µM and 39.7 µM, respectively. In addition, it significantly reduced the colony formation of these cells. Flow cytometry analysis indicated that ginnalin A suppressed cancer proliferation via the induction of cell cycle arrest at the S-phase. Real time PCR analysis demonstrated that ginnalin A can upregulate the mRNA expression levels of Nrf2-related antioxidant genes Nrf2, HO-1 and NQO1. Western blotting analysis revealed that ginnalin A promoted the Nrf2 nuclear translocation and upregulated the proteins Nrf2, HO-1 and NQO1. Moreover, the upregulation of p62 and the inhibition of Keap1 were also found by Western blotting analysis. Therefore, the activation of the Nrf2 signaling pathway was probably induced through the upregulation of p62 and the inhibition of Keap1.

Chemopreventive effects of Ku-jin tea against AOM-induced precancerous colorectal lesions in rats and metabolomic analysis.

Ku-jin tea (KJT) is a health beverage prepared from the leaves of the plant Acer tataricum subsp. ginnala that has been consumed in some regions of China for thousands of years. KJT contains high levels of anti-inflammatory and antioxidative compounds such as ginnalins, but little is known about the chemopreventive effect of KJT on colon cancer. In this study, we investigated the preventive effects of KJT on colon carcinogenesis using the azoxymethane (AOM)-induced precancerous colorectal lesion model in rats. The results showed that the number of aberrant crypts, aberrant crypt foci (ACF) and crypts/focus in rats of the KJT + AOM group were significantly decreased compared with rats of the AOM group (p < 0.01). Further exploration of the prevention mechanism of KJT by UPLC-QTOF/MS-based urinary metabolomics showed that 5 metabolic pathways were modulated, including purine metabolism and amino acid metabolism, in the group with KJT. In addition, the levels of the immunomodulatory cytokines IL-1α and IL-10 were significantly decreased, and the levels of IL-2 in the serum of AOM rats increased after KJT treatment. Our present data suggest that KJT can inhibit AOM-induced colonic ACF formation and might be a useful chemopreventive agent against colorectal carcinogenesis.

Flotilin-1 promotes the tumorigenicity and progression of malignant phenotype in human lung adenocarcinoma.

Lung adenocarcinoma (LUAD) accounts for the most common histological subtype of lung cancer which remains the leading cause of cancer death worldwide. The discovery of more sensitive and specific novel target biomarkers for predicting the development and progression of LUAD is imperative. Flotillin-1 (Flot-1) has been reported to have important roles in the progression of several tumor types but not been reported in the progression of LUAD. Here, we demonstrated that the expression of flotillin-1 was upregulated in 5 LUAD cells. Moreover, multiple approaches were used to explore the tumorigenicity of flotillin-1 in LUAD cell lines. The expression levels of flotillin-1 were analyzed by immunoblotting after overexpression and siRNA-based knockdown. Cell proliferation, scratch wound healing, transwell migration and matrigel invasion and xenograft tumor growth assays were used to determine the role of flotillin-1 in LUAD progression. Downregulation of flotillin-1 reversed, whereas upregulation of flotillin-1 enhanced, the malignant phenotype of LUAD cells in vitro. Consistently, cells with flotillin-1 knockdown formed smaller tumors in nude mice than cells transfected with the empty vector. Furthermore, the control group demonstrated significantly more tumorigenic effects compared to the flotillin-1-silenced group in the xenograft model of LUAD. In all, there draws a conclusion that flotillin-1 is a tumorigenic protein that plays an important role in promoting the proliferation and tumorigenicity of LUAD, suggesting that flotillin-1 may represent a novel the therapeutic target to LUAD.

Transcriptome-Guided Mining of Genes Involved in Crocin Biosynthesis.

Gardenia jasminoides is used in traditional Chinese medicine and has drawn attention as a rich source of crocin, a compound with reported activity against various cancers, depression and cardiovascular disease. However, genetic information on the crocin biosynthetic pathway of G. jasminoides is scarce. In this study, we performed a transcriptome analysis of the leaves, green fruits, and red fruits of G. jasminoides to identify and predict the genes that encode key enzymes responsible for crocin production, compared with Crocus sativus. Twenty-seven putative pathway genes were specifically expressed in the fruits, consistent with the distribution of crocin in G. jasminoides. Twenty-four of these genes were reported for the first time, and a novel CCD4a gene was predicted that encodes carotenoid cleavage dioxygenase leading to crocin synthesis, in contrast to CCD2 of C. sativus. In addition, 6 other candidate genes (ALDH12, ALDH14, UGT94U1, UGT86D1, UGT71H4, and UGT85K18) were predicted to be involved in crocin biosynthesis following phylogenetic analysis and different gene expression profiles. Identifying the genes that encode key enzymes should help elucidate the crocin biosynthesis pathway.

Traditional uses, phytochemistry, and pharmacology of the genus Acer (maple): A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Acer (Aceraceae), commonly known as maple, comprises approximately 129 species that primarily grow in the northern hemisphere, especially in the temperate regions of East Asia, eastern North America, and Europe. These plants have been traditionally used to treat a wide range of diseases in East Asia and North America. Moreover, clinical studies have shown that medicinal plants belonging to Acer are highly effective in the treatment of rheumatism, bruises, hepatic disorders, eye disease, and pain, and in detoxification. This review provides a systematic and constructive overview of the traditional uses, chemical constituents, and pharmacological activities of plants of the genus Acer. MATERIAL AND METHODS: This review is based on a literature study of scientific journals and books from libraries and electronic sources such as SciFinder, ScienceDirect, Springer, PubMed, CNKI, Google Scholar, Baidu Scholar, and Web of Science. The literature in this review related to chemical constituents and pharmacological activities dates from 1922 to the end of October 2015. Furthermore, ethnopharmacological information on this genus was obtained from libraries and herbaria in China and USA. RESULTS: In traditional medicine, 40 species, 11 subspecies, and one varieta of the genus Acer are known to exhibit a broad spectrum of biological activities. To date, 331 compounds have been identified from 34 species of the genus Acer, including flavonoids, tannins, phenylpropanoids, diarylheptanoids, terpenoids, benzoic acid derivatives, and several other types of compounds, such as phenylethanoid glycosides and alkaloids. Preliminary pharmacological studies have shown that the extracts and compounds isolated from this genus exhibit a broad spectrum of biological activities such as antioxidant, antitumor, anti-inflammatory, antidiabetic, hepatoprotective, and antiobesity activities, as well as promoting osteoblast differentiation. To date, reports on the toxicity of Acer species to humans are very limited, and the major safety concern of these plants is in the veterinary field. CONCLUSIONS: Based on our systematic review, Acer species can be used to treat rheumatism, hepatic disorders, eye disease, pain, etc. effectively. Some indications from ethnomedicine have been validated by pharmacological activities, such as the anti-inflammatory and hepatoprotective activities of the species. The available literature showed that most of the activities of these species can be attributed to flavonoids and tannins. To ensure the safety and efficacy in clinical practice in the future, studies identifying active molecules and clarifying their pharmacological mechanisms as well as toxicity are needed.

Talaromyces rubrifaciens, a new species discovered from heating, ventilation and air conditioning systems in China.

A new Talaromyces species, T. rubrifaciens, was isolated from supply air outlets of heating, ventilation and air conditioning (HVAC) systems in three kinds of public building in Beijing and Nanjing, China. Morphologically it exhibits many characters of section Trachyspermi but is distinguished from other species of this section by restricted growth and broad and strictly biverticillate conidiophores. Phylogenetic analyses based on the internal transcribed spacer rDNA (ITS), ß-tubulin (BenA), calmodulin (CaM) and RNA polymerase second largest subunit (RPB2) genes reveal that T. rubrifaciens is a distinct species in section Trachyspermi.