Stem cell division and its critical role in mammary gland development and tumorigenesis: current progress and remaining challenges.

The origin of breast cancer (BC) has traditionally been a focus of medical research. It is widely acknowledged that BC originates from immortal mammary stem cells (MaSCs) and that these stem cells participate in two division modes: symmetric cell division (SCD) and asymmetric cell division (ACD). Although both of these modes are key to the process of breast development and their imbalance is closely associated with the onset of BC, the molecular mechanisms underlying these phenomena deserve in-depth exploration. In this review, we first outline the molecular mechanisms governing ACD/SCD and analyze the role of ACD/SCD in various stages of breast development. We describe that the changes in telomerase activity, the role of polar proteins, and the stimulation of ovarian hormones subsequently lead to two distinct consequences: breast development or carcinogenesis. Finally, gene mutations, abnormalities in polar proteins, modulation of signal-transduction pathways, and alterations in the microenvironment disrupt the balance of breast cancer stem cells (BCSCs) division modes and cause BC. Important regulatory factors such as mammalian Inscuteable (mInsc), Numb, Eya1, PKCα, PKCθ, p53, and IL-6 also play significant roles in regulating pathways of ACD/SCD and may constitute key targets for future research on stem cell division, breast development, and tumor therapy.

[Correlation between frailty and erectile dysfunction in elderly males].

OBJECTIVE: To investigate the correlation of frailty with ED in Chinese elderly men. METHODS: This community-based study was conducted with a sample of 258 Chinese men aged 60 to 83 years old in Fuyang City, Anhui Province. All the participants completed a standard questionnaire on demographics, lifestyle, underlying diseases and medical and sexual histories. They also scored on the Chinese version of Tilburg Frailty Indicator (TFI) and International Index of Erectile Function-5 (IIEF-5). RESULTS: The incidence rates of ED and frailty in the elderly men were 85.27% and 75.58%, respectively. The ED patients, compared with the non-ED males, had a significantly older age (ï¼»71.25 ± 5.83ï¼½ vs ï¼»66.92 ± 5.44ï¼½ yr, P < 0.01) and higher body mass index (ï¼»24.37 ± 3.31ï¼½ vs ï¼»23.35 ± 2.97ï¼½ kg/m 2, P < 0.05), incidence of diabetes mellitus (38.0% vs 19.2%, P < 0.05) and TFI scores (8.61 ± 4.29 vs 5.95 ± 4.36, P < 0.05), but lower education and frequency of irregular intercourse (less than once a week) (all P<0.05). Multivariate analysis indicated that diabetes (OR：3.292，95% CI：1.236－8.768), irregular intercourse (OR：2.425，95% CI：1.114－5.279), and scores of frailty (OR：4.502，95% CI：1.905－10.640) were regarded as independent risk factors for ED (all P < 0.05). CONCLUSION: There is a strong correlation between ED and frailty in elderly men. Sexual health care for elderly ED patients should be more focused on the multidimensional assessment and treatment of senile frailty.

A central amygdala input to the dorsal vagal complex controls gastric motility in mice under restraint stress.

Background/aims: Psychological and physiological stress can cause gastrointestinal motility disorders. Acupuncture has a benign regulatory effect on gastrointestinal motility. However, the mechanisms underlying these processes remain unclear. Methods: Herein, we established a gastric motility disorder (GMD) model in the context of restraint stress (RS) and irregular feeding. The activity of emotional center-central amygdala (CeA) GABAergic neurons and gastrointestinal center-dorsal vagal complex (DVC) neurons were recorded by electrophysiology. Virus tracing and patch clamp analysis of the anatomical and functional connection between the CeAGABA → dorsal vagal complex pathways were performed. Optogenetics inhibiting or activating CeAGABA neurons or the CeAGABA → dorsal vagal complex pathway were used to detect changes in gastric function. Results: We found that restraint stress induced delayed gastric emptying and decreased gastric motility and food intake. Simultaneously, restraint stress activated CeA GABAergic neurons, inhibiting dorsal vagal complex neurons, with electroacupuncture (EA) reversing this phenomenon. In addition, we identified an inhibitory pathway in which CeA GABAergic neurons project into the dorsal vagal complex. Furthermore, the use of optogenetic approaches inhibited CeAGABA neurons and the CeAGABA → dorsal vagal complex pathway in gastric motility disorder mice, which enhanced gastric movement and gastric emptying, whereas activation of the CeAGABA and CeAGABA → dorsal vagal complex pathway mimicked the symptoms of weakened gastric movement and delayed gastric emptying in naïve mice. Conclusion: Our findings indicate that the CeAGABA → dorsal vagal complex pathway may be involved in regulating gastric dysmotility under restraint stress conditions, and partially reveals the mechanism of electroacupuncture.

Inter-Critically Reheated CGHAZ of Ultra-High-Strength Martensitic Steel with Different Cooling Rates.

The mechanical properties of steel's inter-critically reheated coarse-grained heat-affected zone (ICR CGHAZ) directly affects the service life of machinery equipment. The hardness and toughness of ICR CGHAZ can be optimized simultaneously through tailoring microstructure where cooling rate plays a key role. In this work, the samples with different cooling rates was prepared using thermal simulation. The granite bainite (GB), bainite ferrite (BF) and MA were formed at a 1 °C/s (CR1) cooling rate, while BF and MA were formed at 10 °C/s (CR2) and 30 °C/s (CR3) cooling rates. With the increase of cooling rate, the effective grain size decreased and the number of hard phases increased, resulting in monotonic increase of hardness (260HV3, 298HV3 and 323HV3). CR1 had sparsely distributed coarse slender MA and CR3 possessed tail-head connected MA along PAGBs, which was detrimental to toughness. Therefore, CR2 possessed the best toughness(25J). The microstructural evolution mechanism of ICR CGHAZ with different cooling rates is investigated, corresponding hardening and toughening mechanisms are discussed.

Spiradiclisliboensis (Rubiaceae), a new species from limestone mountain areas in Guizhou, China.

Spiradiclisliboensis L. Wu & W. J. Liu, a new species in tribe Ophiorrhizeae of Rubiaceae from limestone mountain areas of Guizhou, south-western China, is described and illustrated. It is similar to S.guangdongensis and S.jingxiensis, but differs from the latter two by the following traits: stipule triangular, inflorescence sessile or with peduncle up to 0.5 mm long, pedicel 0.8-2.2 mm long, corolla white, salverform, corolla tube 1.6-2.2 cm long, corolla tube of long-styled morph inside with a villous ring and stigmas positioned at the throat of the corolla tube. The conservation status is assessed as "Vulnerable" (VU) according to the IUCN Red List Categories and Criteria.

Epigenetic modifications in esophageal cancer: An evolving biomarker.

Esophageal cancer is a widespread cancer of the digestive system that has two main subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA). In the diverse range of cancer therapy schemes, the side effects of conventional treatments remain an urgent challenge to be addressed. Therefore, the pursuit of novel drugs with multiple targets, good efficacy, low side effects, and low cost has become a hot research topic in anticancer therapy. Based on this, epigenetics offers an attractive target for the treatment of esophageal cancer, where major mechanisms such as DNA methylation, histone modifications, non-coding RNA regulation, chromatin remodelling and nucleosome localization offer new opportunities for the prevention and treatment of esophageal cancer. Recently, research on epigenetics has remained at a high level of enthusiasm, focusing mainly on translating the basic research into the clinical setting and transforming epigenetic alterations into targets for cancer screening and detection in the clinic. With the increasing emergence of tumour epigenetic markers and antitumor epigenetic drugs, there are also more possibilities for anti-esophageal cancer treatment. This paper focuses on esophageal cancer and epigenetic modifications, with the aim of unravelling the close link between them to facilitate precise and personalized treatment of esophageal cancer.

[CaMKIIα-positive excitatory hippocampal neurons mediate "Zusanli" (ST36) electroacupuncture induced increase of gastric function in mice].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Zusanli"(ST36)on gastric function (food consumption and gastric emptying rate) and excitability of hippocampal glutamatergic neurons in mice, so as to explore its mechanism underlying enhancing gastrointestinal function. METHODS: The present study includes 2 parts. 1) C57BL/6 mice were randomly divided into normal and EA groups (n=12 in each group). EA (2 Hz/15 Hz, 1-3 mA) was applied to bilateral ST36 for 20 min, once daily for 7 days. In each group, 6 mice were used to measure the food consumption and gastric emptying rate, and the other 6 mice used to detect the hippocampal glutamate secretion content by using in vivo microdialysis and high performance liquid chromatography. 2) Thirty CaMKIIα-Cre mice received microinjection of a recombinant adeno-associated viral vector containing inhibitory designer receptor exclusively activated by a designer drug (DREADD, AAV-DIO-hM4Di-eYFP) into the hippocampus. Twenty-one days later, 3 mice were selected to observe the expression of eYFP-labeled hM4Di by immunohistochemistry, and 15 mice employed to observe the electrical activities of hM4Di-eYFP positive neurons exposed in chemogenetic activating drug Clozapine N-oxide (CNO) perfusion conditions (n=3) and without CNO in the recording chamber (n=6 in the control and EA groups) by using whole cell patch clamp. The rest 12 CaMKII-Cre mice were equally randomized into AAV-DIO-hM4Di-eYFP+CNO group and AAV-DIO-hM4Di-eYFP+CNO+EA group, and CNO was given by intraperitoneal injection for observing the effect of EA on gastric function. RESULTS: 1) In C57BL/6 mice, compared with the normal group, the food consumption, gastric emptying rate, and the glutamate content in the hippocampus were obviously increased in the EA group (P<0.01). 2) In CaMKIIα-Cre mice, the hM4Di-eYFP positive neurons distributing in the hippocampus showed an obvious increase of firing rates in the EA group relevant to the control group (P<0.01), and a hyperdepolarization potential after application of CNO. No significant changes were found between the AAV-DIO-hM4Di-eYFP+CNO and AAV-DIO-hM4Di-eYFP+CNO+EA groups in the food consumption and gastric emptying rate (P>0.05), suggesting an elimination of EA effect after acute DREADD-mediated activation of the CaMKIIα-positive hippocampal excitatory neurons. CONCLUSION: EA at ST36 can promote food intake and gastric emptying in normal mice but not in CaMKIIα-Cre mice with activated hippocampal hM4Di receptors，suggesting a contribution of the CaMKIIα-positive hippocampal excitatory neurons (glutamatergic neurons in particular) to the enhanced gastrointestinal function of EA at ST36.

Acupuncture at Gastric Back-Shu and Front-Mu Acupoints Enhances Gastric Motility via the Inhibition of the Glutamatergic System in the Hippocampus.

Acupuncture strongly alleviates gastrointestinal symptoms and especially promotes gastrointestinal motility. However, the mechanism underlying these processes is poorly understood. This study was designed to examine the effect of electroacupuncture (EA) at gastric back-shu (BL21) and front-mu (RN12) acupoints on gastric motility in functional dyspepsia (FD) rats and to investigate the mechanisms of its effects on the glutamatergic system in the hippocampus. We found that EA at RN12 or BL21 enhanced gastric motility in FD rats, whereas EA at the combination of RN12 and BL21 showed an additional effect. Microdialysis combined with HPLC showed that EA reduced the glutamate content in the hippocampus, and the NMDAR-NO-cGMP signalling pathway was downregulated, as determined by Western blot assays, in FD rats. In addition, we found that decreased gastric motility was significantly restored by the hippocampal infusion of an NMDAR, nNOS, or sGC antagonist. Interestingly, EA had no further effects on gastric motility in the presence of these antagonists in FD rats. Taken together, these results suggest that the hippocampal glutamatergic system is involved in the regulation of gastric motility by EA at RN12 and BL21.

Stilbenoids from aerial parts of Dendrobium plicatile.

Chemical investigation of Dendrobium plicatile Lindl resulted in the isolation and identification of one new bibenzyl, 2-chloro-3, 4'-dihydroxy-3',5-dimethoxybibenzyl (1), as well as 15 known stilbenoids. The structures of this new compound was elucidated by extensive spectroscopic analysis, including HRESIMS, 1H and 13C NMR, DEPT, HMBC, COSY, HMQC, NOESY. Compounds 2, 3 and 5 were obtained from this genus for the first time, compounds 8, 10, 13 and 14 were obtained from this plant for the first time. In addition, the new compound exhibited potent cytotoxic activities against the human breast cancer (MDA-MB231) cell line, the hepatocellular carcinoma (HepG2) cell line and the human lung carcinoma (A549) cell line, with IC50 3.41, 3.02, 2.80 µM, respectively.

NSE from diffuse large B-cell lymphoma cells regulates macrophage polarization.

Background/aims: Diffuse large B-cell lymphoma (DLBCL) is a highly common type of malignant and heterogeneous non-Hodgkin's lymphoma. Tumor-associated macrophages, specially the M2-type, promote tumor progression and drug resistance. The clinical outcome of patients with high neuron-specific enolase (NSE) expression is worse than that with low NSE expression. The tumor-promoting mechanism of NSE, however, remains unclear. This study explored the role of NSE in macrophage polarization associated with the immune microenvironment of DLBCL. Results: Our results showed that NSE protein expression was higher in lymphoma cell lines than in the B lymphocytes. Functional studies demonstrated that upregulation of NSE in lymphoma cells could promote M2 polarization and migration ability of macrophage, thereby consequently promoting the progression of lymphoma in vitro and in vivo. Further mechanism studies revealed that lymphoma-derived exosomes could mediate NSE into macrophages, NSE enhanced nuclear p50 translocation with subsequent defective classical nuclear factor-κB activity in macrophages. Conclusions: These results indicate that NSE may be a potential target for lymphoma therapy and a prognosis marker for lymphoma.

Elevated BNP caused by recombinant human interleukin-11 treatment in patients with chemotherapy-induced thrombocytopenia.

Thrombocytopenia is a condition characterized by abnormally low levels of thrombocytes and often induced by chemotherapy. Recombinant human interleukin-11 (rhIL-11) is a cytokine that can stimulate thrombopoiesis and is commonly used to treat thrombocytopenia. We observed the side effects of rhIL-11 in 24 leukemia patients with chemotherapy-induced thrombocytopenia. To determine the cardiovascular effects of rhIL-11, we detected changes in the patients' serum brain natriuretic peptide (BNP), blood pressure fluctuations, weight change, and whether edema or heart failure occurred in leukemia patients after chemotherapy. The results showed that BNP was significantly elevated after using rhIL-11 (P < 0. 05) but regressed after 2-4 days. Furthermore, nine patients had edema and experienced weight gain, and four experienced acute left heart failure. In addition, the average blood pressure was 119/75 mmHg (range 139/86 mmHg to 99/64 mmHg) before rhIL-11 administration and 127/79 mmHg (range 146/89 mmHg to 108/69 mmHg) after rhIL-11 use. In conclusion, although rhIL-11 is useful for treating chemotherapy-induced thrombocytopenia, it is important to monitor the patients' clinical status and re-examine BNP levels frequently during the use of rhIL-11. Furthermore, senile patients should be given special attention. However, the appropriate timing to begin and discontinue rhIL-11 treatment needs further investigation.

Spiradicliskarstana (Rubiaceae), a new species from Yunnan, China.

Spiradicliskarstana, a new species of Spiradiclis (Rubiaceae) collected from Yunnan, China, is described for the first time. It is morphologically close to S.jingxiensis, but differs from the latter mainly by its inflorescences with 5-9 flowers, its 1.5-2.4 mm long peduncles, its stipules shorter than 1 mm and the 5-12 pairs of secondary veins. The conservation status is assessed as "Vulnerable" (VU) according to the IUCN Red List Categories and Criteria.

Two new stilbenoids from aerial parts of Flickingeria fimbriata.

Two new stilbenoids, named 2,3 -dimethoxyl-7-hydroxyl-1,4-phenanthrenedione (1) and 2-methoxyl-3-methyl-7-hydroxyl-9,10-dihydro-1,4-phenanthrenedione (2), together with two known stilbenoids including densiflorol B (3) and ephemeranthoquinone (4), were isolated from aerial parts of Flickingeria fimbriata (Bl.) Hawkes. The structures of two new compounds were elucidated by extensive spectroscopic analysis, including HRESIMS, 1H and 13C NMR, DEPT, HMBC, COSY, HMQC, NOESY. All the compounds were obtained from this genus for the first time. In addition, they all exhibited moderate cytotoxic activities against HepG2 cell lines.

Asparagine synthetase expression is associated with the sensitivity to asparaginase in extranodal natural killer/T-cell lymphoma in vivo and in vitro.

BACKGROUND: Although asparagine synthetase (AsnS) is associated with drug resistance in leukemia, its function in extranodal natural killer (NK)/T-cell lymphoma (ENKTL) remains unclear. METHODS: The present study investigated the relationship between baseline AsnS mRNA levels and response to asparaginase in ENKTL cell lines. It also determined whether upregulating or downregulating the AsnS mRNA level induces or reverses asparaginase-resistant phenotype. RESULTS: Interestingly, considerable differences were observed in the sensitivity to asparaginase of the five ENKTL cell lines. The AsnS expression levels were positively correlated with the IC50 values. In addition, the asparaginase resistance was induced or reversed by upregulating or downregulating the AsnS mRNA level in vivo and in vitro. Functional analyses indicated that AsnS did not affect the proliferation and apoptosis of ENKTL cells in the absence of asparaginase. CONCLUSION: Together, the data stress the importance of AsnS in the sensitivity to asparaginase in ENKTL and suggest a different therapeutic strategy for patients with a different level of AsnS expression.

Natural borneol is a novel chemosensitizer that enhances temozolomide-induced anticancer efficiency against human glioma by triggering mitochondrial dysfunction and reactive oxide species-mediated oxidative damage.

BACKGROUND: Temozolomide (TMZ)-based chemotherapy represents an effective way for treating human glioma. However, its clinical application is limited because of its side effects and resistance to standard chemotherapy. Hence, the search for novel chemosensitizers to augment their anticancer efficiency has attracted much attention. Natural borneol (NB) has been identified as a potential chemosensitizer in treating human cancers. However, the synergistic effect and mechanism of NB and TMZ in human glioma have not been investigated yet. MATERIALS AND METHODS: U251 human glioma cells were cultured, and the cytotoxicity and apoptosis of NB and/or TMZ were examined by MTT assay, flow cytometric analysis and Western blot. Nude mice tumor model was also employed to evaluate the in vivo anticancer effect and mechanism. RESULTS: The results showed that the combined treatment of NB and TMZ more effectively inhibited human glioma growth via triggering mitochondria-mediated apoptosis in vitro, accompanied by the caspase activation. Combined treatment of NB and TMZ also caused mitochondrial dysfunction through disturbing Bcl-2 family expression. Further investigation revealed that NB enhanced TMZ-induced DNA damage through inducing reactive oxide species (ROS) overproduction. Moreover, glioma tumor xenograft growth in vivo was more effectively inhibited by the combined treatment with NB and TMZ through triggering apoptosis and anti-angiogenesis. CONCLUSION: Taken together, our findings validated that the strategy of using NB and TMZ could be a highly efficient way to achieve anticancer synergism.

ENO2 Promotes Cell Proliferation, Glycolysis, and Glucocorticoid-Resistance in Acute Lymphoblastic Leukemia.

BACKGROUND/AIMS: The metabolic features of cancer cells have long been acknowledged to be altered and to provide new therapeutic opportunities. The expression of glycolytic enzyme enolase 2 (ENO2) was found to be closely associated with the clinical features of acute lymphoblastic leukemia (ALL) patients, but its functions remain unclear in ALL. METHODS: We evaluated the association between ENO2 mRNA expression in bone marrow mononuclear cells (BM-MNCs) and the efficacy of chemotherapy, and further explored the function of ENO2 in ALL. The molecular mechanisms of ENO2 expression and its effects on cell growth, glycolysis and glucocorticoid resistance were explored by Cell Counting Kit-8, glucose-consumption assay, Quantitative RT-PCR, Western blotting and in vivo tumorigenesis in NOD/SCID mice. RESULTS: The results showed that ENO2 mRNA expression in BM-MNCs was significantly decreased when patients completed induction chemotherapy and reached complete remission (CR). ENO2 mRNA expression was increased when patients suffered relapse. Functional studies demonstrated that ENO2 promoted cell growth, glycolysis, and glucocorticoid resistance, all of which were effectively inhibited when ENO2 was silenced with shRNAs. Further studies revealed that ENO2 up-regulated various glycolysis-related genes and enhanced Akt activity with subsequent glycogen synthase kinase3ß (GSK-3ß) phosphorylation, inducing cell proliferation and glycolysis. The combination of silencing ENO2 and 2-deoxyglucose (2-DG) synergistically inhibited leukemia cell survival. CONCLUSIONS: These results indicate that ENO2 may be a biological marker for monitoring chemotherapeutic efficacy and relapse in ALL. ENO2 may provide a potential therapeutic strategy for ALL.

Design and synthesis of 4-(2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazol-7-yl)-N-(5-(piperazin-1-ylmethyl)pyridine-2-yl)pyrimidin-2-amine as a highly potent and selective cyclin-dependent kinases 4 and 6 inhibitors and the discovery of structure-activity relationships.

Cyclin-dependent kinases 4/6 play an important role in regulation of cell cycle, and overexpress in a variety of cancers. Up to now, new CDK inhibitors still need to be developed due to its poor selectivity. Herein we report a novel series of 4-(2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazole-7-yl)-N-(5-(piperazin-1-ylmethyl)pyridine-2-yl)pyrimidin-2-amine anologues as potent CDK 4/6 inhibitors based on LY2835219 (Abemaciclib). Compound 10d, which exhibits approximate potency on CDK4/6 (IC50 = 7.4/0.9 nM), has both good pharmacokinetic characters and high selectivity on CDK1 compared with LY2835219. Overall, compound 10d could be a promising candidate and a good starting point as anticancer drugs.

A new pair of enantiomeric lignans from the fruits of Morinda citrifolia and their absolute configuration.

A new pair of sesamin-type lignan enantiomers (±)-morifolia A (1a/1b) together with eight known analogues (2-9) were isolated from the fruits of Morinda citrifolia. Their structures were established by spectroscopic data and the absolute configurations of 1a/1b were determined by ECD calculation. All compounds were examined for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages, and compounds 1a, 1b, 2-4 and 7-9 exhibited pronounced inhibition with IC50 values in the range of 1.97-8.01 (µM, being more active than the positive control, quercetin (IC50 = 15.32 (M).

High level of soluble interleukin-2 receptor in serum predicts treatment resistance and poor progression-free survival in multiple myeloma.

The IL-2/IL-2 receptor (IL-2R) system plays a central role in maintaining normal T cell immunity, and its disturbance is associated with several hematologic disorders. Studies have found in several types of lymphoma that abnormal amounts of soluble IL-2R (sIL-2R) may result in imbalance of the IL-2/IL-2R system and hence of the T cell immunoregulation. Whether the level of sIL-2R in blood could predict treatment outcomes or not needs to be investigated in multiple myeloma (MM) patients. The level of sIL-2R in serum was measured using enzyme-linked immunosorbent assay (ELISA) in 81 patients with newly diagnosed MM. Twenty-six patients (32.1%) were treated with bortezomib-based regimens and 55patients (67.9%) received old drugs-based regimens. The mean concentration of sIL-2R for myeloma patients was 8.51 ng/ml, significantly higher than that of healthy controls (0.56 ng/ml, p < 0.0001). The best cutoff value for sIL-2R in predicting high risk for disease progression is 6.049 ng/ml with an area under curve (AUC) of 0.665 (p = 0.013). Thirty-six patients (44.4%) were classified as higher sIL-2R level group (> 6.049 ng/ml), and 45 patients (55.6%) as lower group (≤ 6.049 ng/ml). The overall response rate (ORR) was 60.0% in lower sIL-2R level group, and 41.7% in higher level group (p = 0.156). The median progression-free survival (PFS) and overall survival (OS) was 12 months (range, 2.0-65 months) and 20 months (range, 2.0-118 months), respectively. In a multivariate survival analysis, including Eastern Cooperative Oncology Group performance status score, treatment response, and sIL-2R level, it was found that all these three parameters were significantly independent prognostic factors for PFS (p = 0.032, 0.016, and 0.043, respectively), but none factors maintained their value in predicting OS. Subgroup analysis revealed that high level of sIL-2R is correlated with significantly inferior PFS in patients treated with bortezomib-based regimens (p = 0.004). Serum sIL-2R level is an independent prognostic factor for PFS, indicating novel drugs targeting the imbalance of IL-2/IL-2R system may be a promising strategy in MM.

Phenolic compounds from the stems of Flickingeria fimbriata.

Chemical investigation of Flickingeria fimbriata (Bl.) Hawkes (Orchidaceae) resulted in the isolation and identification of one new dihydrophenanthrene, 1,2,5,6,7-pentamethoxy-9,10-dihydrophenanthrene (1), together with seven known dihydrophenanthrenes, erianthridin (2), coelonin (3), 4-methoxy-9,10-dihydrophenanthrene-1,2,7-triol (4), lusianthridin (5), ephemeranthol A (6), flavanthridin (7) and hircinol (8), four known phenanthrenes, epheranthol B (9), nudol (10), denthyrsinin (11) and confusarin (12), and one known bibenzyl, batatasin III (13). The structure of the new compound was elucidated by spectroscopic analysis (HRMS, 1D and 2D NMR). All the compounds were isolated from F. fimbriata for the first time except for compounds 5 and 12, and compounds 1, 3, 4, 8, 10, 11 and 13 were obtained from this genus for the first time. Compounds 1-4 showed moderate cytotoxic activity against HepG2 cells.