Inhibition of METTL3 alleviated LPS-induced alveolar epithelial cell apoptosis and acute lung injury via restoring neprilysin expression.

AIMS: To investigate the role and mechanisms of methyltransferase-like 3 (METTL3) in the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury (ALI). MAIN METHODS: LPS intratracheally instillation was applied in alveolar epithelial cell METTL3 conditional knockout (METTL3-CKO) mice and their wild-type littermates. In addition, METTL3 inhibitor STM2457 was used. LPS treatment on mouse lung epithelial 12 (MLE-12) cell was applied to establish an in vitro model of LPS-induced ALI. H&E staining, lung wet-to-dry ratio, and total broncho-alveolar lavage fluid (BALF) concentrations were used to evaluate lung injury. Overall, the m6A level was determined with the m6A RNA Methylation Quantification Kit and dot blot assay. Expression of METTL3 and neprilysin were measured with immunohistochemistry, immunofluorescence, immunofluorescence-fluorescence in situ hybridization, and western blot. Apoptosis was detected with TUNEL, western blot, and flow cytometry. The interaction of METTL3 and neprilysin was determined with RIP-qPCR and MeRIP. KEY FINDINGS: METTL3 expression and apoptosis were increased in alveolar epithelial cells of mice treated with LPS, and METTL3-CKO or METTL3 inhibitor STM2457 could alleviate apoptosis and LPS-induced ALI. In MLE-12 cells, LPS-Induced METTL3 expression and apoptosis. Knockdown of METTL3 alleviated, while overexpression of METTL3 exacerbated LPS-induced apoptosis. LPS treatment reduced neprilysin expression, the intervention of neprilysin expression negatively regulated apoptosis without affecting METTL3 expression, and mitigated the promoting effect of METTL3 on LPS-induced apoptosis. Additionally, METTL3 could bind to the mRNA of neprilysin, and reduce its expression. SIGNIFICANCE: Our findings revealed that inhibition of METTL3 could exert anti-apoptosis and ALI-protective effects via restoring neprilysin expression.

MiR-223-3p-loaded exosomes from bronchoalveolar lavage fluid promote alveolar macrophage autophagy and reduce acute lung injury by inhibiting the expression of STK39.

This study investigated the molecular mechanism by which bronchoalveolar lavage fluid exosomes (BALF-exo) alleviated acute lung injury (ALI). BALF-exo was isolated from mice. LPS was used to induce inflammation in rat alveolar macrophages (NR8383). NR8383 cell models were treated with BALF-exo or BALF-exo loaded with miR-223-3p mimics/inhibitors, or STK39 was overexpressed in NR8383 cells before LPS and BALF-exo treatment. These cells were subjected to apoptosis, autophagy, and inflammation assays. RNA immunoprecipitation and dual-luciferase reporter assay were conducted to verify the binding between miR-223-3p and STK39. LPS-induced ALI mouse models were treated with BALF-exo loaded with miR-223-3p mimics. miR-223-3p was lowly expressed in BALF-exo from LPS-treated mice. BALF-exo loaded with miR-223-3p mimics increased viability and autophagy and decreased apoptosis and inflammation in NR8383 cell models. Inhibition of miR-223-3p in BALF-exo or overexpression of STK39 in NR8383 cells repressed the therapeutic effect of BALF-exo in LPS-treated NR8383 cells. STK39 was a target gene of miR-223-3p. miR-223-3p shuttled by BALF-exo negatively regulated the expression of STK39 in NR8383 cells. BALF-exo loaded with miR-223-3p mimics also reduced lung injuries in ALI mice. In conclusion, miR-223-3p loaded in BALF-exo alleviates ALI by targeting STK39 in alveolar macrophages.

Downregulation of miR-223 promotes HMGB2 expression and induces oxidative stress to activate JNK and promote autophagy in an in vitro model of acute lung injury.

BACKGROUND: Excessive autophagic activity in alveolar epithelial cells is one of the main causes of acute lung injury (ALI), but the underlying molecular mechanism has not been fully elucidated. Previous studies have shown that microRNAs (miRs) are involved in regulating autophagy in several diseases. This study aimed to determine the role of miR-223 in excessive autophagic activity in alveolar epithelial cells and the underlying mechanism to identify a novel therapeutic targets for the development of new drugs to treat acute respiratory distress syndrome (ARDS). METHODS: A549 cells were treated with lipopolysaccharide (LPS) to establish an ALI in vitro model. The expression of miR-223 and its role of miR-223 in regulating oxidative stress and autophagy in the LPS-treated A549 cells, were examined using RT-PCR, flow cytometry and ELISA. A luciferase reporter assay was performed to verify the interaction between miR-223 and the high-mobility group box 2 (HMGB2) protein. RESULTS: The results showed that the LPS treatment downregulated miR-223 expression in alveolar epithelial cells. We further proved that miR-223 directly targeted the 3-untranslated region of the HMGB2 gene and the downregulation of miR-223 increased HMGB2 protein level, which activated the JNK signalling pathway and thus induced oxidative stress and autophagy in LPS-treated alveolar epithelial cells. Knockdown of HMGB2 protein deactivated the JNK signalling pathway and inhibited autophagy and oxidative stress in alveolar epithelial cells. CONCLUSIONS: The results of this study suggest that miR-223 regulates oxidative stress and autophagy in alveolar epithelial cells by targeting HMGB2 via the JNK signalling pathway.

Adiponectin regulates osteocytic MLO-Y4 cell apoptosis in a high-glucose environment through the AMPK/FoxO3a signaling pathway.

Clinical studies have shown that persistent hyperglycemia following oxidative stress is associated with the apoptosis of osteocytes in diabetics. Adiponectin (APN) can ameliorate oxidative stress, and its receptors have been identified in bone-forming cells. However, the relationship between APN and osteocyte apoptosis has not been fully elucidated. This study aimed to investigate whether APN could prevent osteocyte apoptosis and regulate reactive oxygen species (ROS) generation in a high-glucose environment. Hoechst staining and fluorescence microscopy were used to observe the apoptosis of osteocytic MLO-Y4 cells. Real-time quantitative polymerase chain reaction and Western blot analysis were used to detect the expression of Caspase 3, Caspase 8, and Bcl-2. ROS generation was investigated with an active oxygen kit and fluorescence microscopy. Furthermore, the expression of proteins in the AMPK/FoxO3A signaling pathway was also studied by Western blot analysis. In a high-glucose environment, APN promoted the proliferation of MLO-Y4 osteocytes and the expression of Bcl-2 but inhibited the expression of Caspase 3, Caspase 8, and ROS in a dose-dependent manner. APN promoted the activation of p-AMPK and p-AMPK/AMPK, which reached their highest levels at 10 min and returned to baseline at 30 min. The expression of p-FoxO3A/FoxO3A in both the cytoplasm and nucleus peaked at 15 min, and this expression was returned to baseline at 60 min. In summary, APN has an antiapoptotic effect and regulates ROS generation in MLO-Y4 osteocytes in a high-glucose environment. The AMPK/FoxO3A signaling pathway might be a key signaling pathway that participates in the effect of APN on regulating osteocyte apoptosis in diabetics.

Silencing of methyltransferase-like 3 inhibits oesophageal squamous cell carcinoma.

Methyltransferase-like 3 (METTL3) is a methyltransferase responsible for N6-methyladenosine mRNA modifications, which has been demonstrated to serve oncogenic roles in various types of cancer; however, the exact function of METTL3 in oesophageal squamous cell carcinoma (ESCC) has not been determined. The present study aimed to explore the regulatory role of METTL3 in ESCC. In the present study, reverse transcription-quantitative PCR and western blotting were used to examine mRNA and protein expression, CCK-8 assays and flow cytometry were used to determine cellular viability and apoptosis, and wound healing and Transwell assays were conducted to study cellular migration and invasion. The expression levels of METTL3 were significantly higher in ESCC tissues and cell lines compared with adjacent non-tumour tissues and the normal oesophageal epithelial cell line HET-1A, respectively. Increased METTL3 expression was associated with an advanced clinical stage of ESCC and poorer prognosis. Furthermore, the genetic knockdown of METTL3 using small interfering RNA significantly suppressed ESCC growth, invasion and migration in vitro, and induced cellular apoptosis, in addition to reducing the phosphorylation levels of PI3K and AKT. In conclusion, the present study demonstrated that the upregulation of METTL3 promoted ESCC progression, and that inhibition of METTL3 significantly suppressed the malignant phenotypes of ESCC cells, at least in part, by downregulating PI3K/AKT signalling activity. Thus, it is suggested that METTL3 may be a promising therapeutic target for ESCC.

FOXO3/TRIM22 axis abated the antitumor effect of gemcitabine in non-small cell lung cancer via autophagy induction.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for more than 80% of the total lung cancer and gemcitabine (GEM)-based chemotherapy is the first-line therapeutic approach for NSCLC treatment. Owing to acquired chemo-resistance, the prognosis of NSCLC patients receiving GEM treatment is still poor. METHODS: Dysregulation of mRNAs in GEM-resistant (GR) NSCLC cells comparing to parental cells were profiled by analyzing GSEA6914 datasets from GEO database. Additionally, qRT-PCR were performed on clinically collected patient serum samples and transplanted tumor tissues and GEM-resistant (GR)/sensitive (GS) cell lines. In order to explore the functional role of tripartite motif protein 22 (TRIM22), gain and loss-of-function cell models were constructed in A549 and A549/GR respectively. MTT and Annexin V-FITC/propidium iodide (PI) staining assay were carried out to access the response to GEM of A549 and A549/GR cells. Observation of RFP-LC3 puncta and western blot detection of autophagy markers were used to evaluate autophagy. Bi-luciferase reporter assay was used to confirm the transcriptional regulatory relationship. Rescue experiments were carried out to confirm the FOXO3/TRIM22 regulatory axis in GEM susceptibility. RESULTS: TRIM22 was significantly upregulated in GR patient serum samples, transplanted tumor tissues and NSCLC cells which was negatively transcriptional regulated by FOXO3. TRIM22 overexpression attenuated the sensitivity of A549 to GEM and its depletion promoted the sensitivity of A549/GR to GEM. Additionally, TRIM22 promoted GEM-induced pro-survival autophagy to protected NSCLC cells from apoptosis. CONCLUSIONS: TRIM22 was significantly upregulated in GR lung adenocarcinoma cell line A549 which is negatively transcriptional regulated by FOXO3. Due to the enhancement of pro-survival autophagy induced by TRIM22, the A549 cells became less sensitive to GEM. This study may provide a basis for screening target of liquid biopsy for predicting GEM sensitivity in NSCLC.

Chemical Sympathectomy Impairs Peri-implant Osseointegration in Mice: Role of the Sympathetic Nervous System in Osseointegration.

PURPOSE: The possibility that the sympathetic nervous system (SNS) controls bone remodeling has been raised; however, the actual function of the SNS in osseointegration is still unknown. This study aimed to investigate the effect of chemical sympathectomy on peri-implant osseointegration in adult mice. MATERIALS AND METHODS: Forty C57BL/6J mice (8-week-old) were divided into two groups: a sympathectomy group and a control group, which were administered 6-hydroxydopamine and saline, respectively, by intraperitoneal injection for 5 days. Then, the mice were exposed to implant surgery. Analyses of serum chemistry, microcomputed tomography, biomechanical test, and bone histomorphometry were employed at 2 and 4 weeks. RESULTS: Compared with the control, the chemical sympathectomy group had a higher serum level of C-terminal collagen I cross-links but lower serum osteocalcin. After 4 weeks, peri-implant trabecular microstructure, including trabecular volume, trabecular thickness, the percentage of osseointegration, and bone-to-implant contact, was lower; however, the trabecular separation was higher in the sympathectomy group mice in comparison with the control group. In addition, the strength of bone-titanium integration measured by the biomechanical resistance test was lower. Furthermore, histomorphologic evidence revealed that the osteoclast counts were higher in the sympathectomy group, while the mineral apposition rate and the bone formation rate per bone surface were significantly lower. CONCLUSION: Within the limitations of this experimental study, the data showed that chemical sympathectomy has a negative effect in peri-implant osseointegration, suggesting that the SNS may need to be taken into consideration in terms of peri-implant bone healing.

Selective ß2-adrenoreceptor signaling regulates osteoclastogenesis via modulating RANKL production and neuropeptides expression in osteocytic MLO-Y4 cells.

The ß2-adrenergic receptor (ß2-AR) signaling on bone cells is the major contributor in the effect of the sympathetic nervous system on bone turnover. However, it remains unclear whether receptor activator of nuclear factor κ-Β ligand (RANKL) modulation and neuropeptides expression in osteocytes are responsible for the mechanism. This study used ß2-AR stimulation to investigate cell cycle and proliferation, the gene and protein expression of RANKL, and osteoprotegerin (OPG), as well as neuropeptides regulation in osteocytic MLO-Y4 cells. Clenbuterol (CLE; a ß2-AR agonist) slightly promoted the growth of MLO-Y4 cells in a concentration-dependent effect but had no effect on the proliferation index. And the concentration of 10-8 M showed a significant increase in the S-phase fraction on day 3 in comparison with the control. Additionally, CLE-promoted osteoclast formation and bone resorption in osteocytic MLO-Y4 cell-RAW264.7 cell cocultures. RANKL expression level and the ratio of RANKL to OPG in MLO-Y4 cells were enhanced in CLE treatment but were rescued by blocking ß2-AR signaling. However, neuropeptide Y and α-calcitonin gene-related peptide, two neurogenic markers, were inhibited in CLE treatment of MLO-Y4 cells, which was reversed by a ß2-AR blocker. The results indicate that osteocytic ß2-AR plays an important role in the regulation of RANKL/OPG and neuropeptides expression, and ß2-AR signaling in osteocytes can be used as a new valuable target for osteoclast-related pathologic disease.

Determination of Sulfonamides in Chicken Muscle by Pulsed Direct Current Electrospray Ionization Tandem Mass Spectrometry.

A simple and rapid approach for the simultaneous detection of trace amounts of six sulfonamides in chicken muscle was developed using pulsed direct current electrospray ionization tandem mass spectrometry (pulsed-dc ESI-MS/MS). The pretreatment of chicken muscle samples consisted of two steps: acetonitrile extraction and n-hexane delipidation. Sulfonamides do not need to be derivatized or chromatographed prior to pulsed-dc ESI-MS/MS. The factors affecting the performance of pulsed-dc ESI-MS/MS were studied. Under optimum conditions, the quantitative performance of pulsed-dc ESI-MS/MS was validated according to European Union Decision 2002/657/EC, and the sensitivity of pulsed-dc ESI-MS/MS was 3 times higher than that of ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The limits of detection obtained by pulsed-dc ESI-MS/MS were in the range of 0.07-0.11 µg/kg. The proposed method was simple, rapid, and sensitive, and was successfully used for quantitation and rapid screening of sulfonamides in real chicken muscle samples.

Beta-adrenergic signaling affect osteoclastogenesis via osteocytic MLO-Y4 cells' RANKL production.

The sympathetic nervous system play a pivotal role in bone remodeling through ß-adrenoceptor (ß-AR). However, it is not well documented whether the ß-adrenoceptor pathway has the potential to influence osteocytes. In this study, cell viability, the expression of ß-AR subtypes, enzymes of catecholamine synthesis or degradation, bone-related gene and protein in osteocytic MLO-Y4 cells were investigated by ß-adrenergic stimulation. Isoproterenol (ISO) promoted RANKL to OPG expression in osteocytes, as well as osteoclasts formation in osteocytes-RAW264.7 cell co-cultures but not RAW264.7 cell monoculture. The ISO-stimulated effect was enhanced in ß1-AR antagonist pretreatment, but was rescued by blocking ß2-AR. The results indicate that ß1-and ß2-AR play reciprocal roles on MLO-Y4 cells in the regulation of osteoclastogenesis, and osteocyte ß-adrenergic signaling might be a new valuable therapy for bone disease.

A case of autologous pericardium patch in treatment of aortoesophageal fistula.

Aortoesophageal fistula (AEF) is a rare but fatal complication caused by foreign body ingestion. Aortic replacement and endovascular stent graft are the common repair surgeries. The materials to repair an aortic defect in AEF are typically homograft or allograft, but the use of an autologous pericardium patch is rarely reported. Here we reported a patient with AEF and severe mediastinal infection induced by chicken bone ingestion. In this case, the autologous pericardium patch was used as the repair material.

Definitive Treatment for Aortoesophageal Fistula by Endovascular Stent Graft.

Aortoesophageal fistula (AEF) is a rare and dangerous complication of foreign body ingestion. Endovascular angioplasty has now become a useful option to control fatal hemorrhage, but it still remains controversial to whether endovascular stenting could be used as a definitive procedure or as a temporary measure before definitive surgical treatment. We have successfully treated two AEF cases using thoracic endovascular aortic repair (TEVAR) as definitive treatment to close aortic defect. The separate 2-year and 6-month follow-ups show that patients are in good condition.

Rapid measurement of free cyanide in liquor by ion chromatography with pulsed amperometric detection.

This study investigated the measurement of free cyanide in liquor by ion chromatography coupled with pulsed amperometric detection (IC-PAD). Eluent concentration, interferent evaluation and method performance were discussed. Results show that free cyanide in liquor can be rapidly determined by the optimised IC-PAD method. A sample requires only 1:100 dilution and simple filtration before being subjected to IC-PAD. The linear range is 1-5000 µg/L with an R value of 0.9998. The detection limit is 1 µg/L for a 25 µL injection loop. The overall relative standard deviation (RSD) of the method is less than 5%, and the recovery range is from 98.1% to 105.0%. This study has been proven significant and may have potential applications in liquors analysis.

A sensitive and selective chemosensor for ascorbic acid based on a fluorescent nitroxide switch.

Ascorbic acid (AsA), also known as vitamin C, is a vital small-molecule antioxidant with multiple functions in vivo. It's the major natural antioxidant found in plants and is also an essential component of human nutrition. AsA plays a key role in many diseases-related biological metabolism. Therefore, sensitive and selective detection of AsA is greatly important in pharmaceutical, clinical and food industry. Here a sensitive and selective sensor for ascorbic acid detection based on the recovered fluorescence of NAPS-NO (N-propyl-triethoxysilane-4-(4-ylamino-1-oxy-2,2,6,6-tetramethylpiperdine)- naphthalimide) probe is described. The fluorescence of the naphthalimide moiety of NAPS-NO is inhibited by the nitroxide group, which is covalently linked to the fluorophore. Then, ascorbic acid reacts rapidly with the nitroxide moiety of NAPS-NO to form hydroxylamine, and the fluorescence properties of the naphthalimide moiety are recovered and the ESR signal decayed. Over a wide range from 80 nM to 50 µM, a good linear relationship between the fluorescence intensity and the concentration of ascorbic acid was found and the detection limit was estimated to be as low as 20 nM. To confirm the practical usefulness of the fluorophore-nitroxide probe, we demonstrated the use of NAPS-NO for the measurement of AsA in human blood serum and also successfully determined the concentration of AsA in HEK 293 cell lysate. Results from confocal laser scanning microscopy experiments demonstrated that this chemosensor is cell permeable and can be used as a fluorescent probe for monitoring ascorbic acid in living cells.

[Experimental study on novel hybrid artificial trachea transplantation].

We developed and designed a new type of artificial trachea. The basic structure of the artificial trachea was polytetrafluoroethylene vascular prosthesis linked with titanium rings on both sides. Dualmesh was sutured on titanium rings. This experimentation follows the replacement of trachea in dogs with a combined artificial trachea to investigate the feasibility of this type of prosthesis. Sixteen dogs were implanted with the combined artificial trachea after resection of 5 cm of cervical trachea. The 5 cm-long trachea of dogs on the necks were resected and the reconstruction of the defect of the trachea was performed with trachea prosthesis. According to the method of trachea reconstruction, the models were divided into 2 groups, artificial trachea implantation group (the control group, n = 8) and group of artificial trachea implantation with growth factor (the experimental group, n = 8). Then computer tomography scan (CT), bronchoscope and pathologic examination were conducted periodically to observe the healing state of the hybrid artificial trachea. None of the dogs died during operation of cervical segmental trachea construction. But four dogs in the control group died of apnea in succession because artificial trachea was displaced and the lumen was obstructed, while 2 dogs died in the experimental group. In the first month there was granulation around anastomosis with slight stenosis. The rest of dogs were well alive until they were sacrificed 14 months later. The mean survival time of the experimental group was longer than that of the control group. The rate of infection, anastomotic dehiscence, severe stenosis and accidental death in the experimental group were lower than the control group (P < 0.05). Artificial trachea was encapsulated by fibrous tissue and no mucous membrane was seen in the lumen of the artificial trachea. The artificial trachea can be used to reconstruction of the defect of the trachea with long-term survival of the animals. The unique design of artificial trachea reduces stenosis around anastomosis effectively but infections and split or displacement of the artificial trachea are still major problems affecting long-term survival of the animals. Application of growth factors to a certain extent promotes tissue healing by changing the local environment.

[Trachea repair and reconstruction with new composite artificial trachea transplantation].

OBJECTIVE: To construct a new composite artificial trachea and to investigate the feasibility of trachea repair and reconstruction with the new composite artificial trachea transplantation in dogs. METHODS: The basic skeleton of the new composite artificial trachea was polytetrafluoroethylene vascular prosthesis linked with titanium rings at both ends. Dualmesh was sutured on titanium rings. Sixteen dogs, weighing (14.9 +/- 2.0) kg, female or male, were selected. The 5 cm cervical trachea was resected to prepare the cervical trachea defect model. The trachea repair and reconstruction was performed with the new composite artificial trachea. Then fiberoptic bronchoscope examination, CT scan and three-dimensinal reconstruction were conducted at immediate, 1 month, and 6 months after operation. Gross observation and histological examination were conducted at 14 months to evaluate the repair and reconstruction efficacy. RESULTS: No dog died during operation of trachea reconstruction. One dog died of dyspnea at 37, 41, 55, 66, 140, and 274 days respectively because of anastomotic dehiscence and artificial trachea displacement; the other 10 dogs survived until 14 months. The fiberoptic bronchoscope examination, CT scan and three-dimensinal reconstruction showed that artificial tracheas were all in good location without twisting at immediate after operation; mild stenosis occurred and anastomoses had slight granulation in 6 dogs at 1 month; severe stenosis developed and anastomosis had more granulation in 1 dog and the other dogs were well alive without anastomotic stenosis at 6 months. At 14 months, gross observation revealed that outer surface of the artificial trachea were encapsulated by fibrous connective tissue in all of 10 dogs. Histological examination showed inflammatory infiltration and hyperplasia of fibrous tissue and no epithelium growth on the inner wall of the artificial trachea. CONCLUSION: The new composite artificial trachea can be used to repair and reconstruct defect of the trachea for a short-term. Anastomotic infection and dehiscence are major complications and problems affecting long survival.

Small compound 6-O-angeloylplenolin induces mitotic arrest and exhibits therapeutic potentials in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is a disease of cell cycle dysregulation while cell cycle modulation can be a target for MM therapy. In this study we investigated the effects and mechanisms of action of a sesquiterpene lactone 6-O-angeloylplenolin (6-OAP) on MM cells. METHODOLOGY/PRINCIPAL FINDINGS: MM cells were exposed to 6-OAP and cell cycle distribution were analyzed. The role for cyclin B1 to play in 6-OAP-caused mitotic arrest was tested by specific siRNA analyses in U266 cells. MM.1S cells co-incubated with interleukin-6 (IL-6), insulin-like growth factor-I (IGF-I), or bone marrow stromal cells (BMSCs) were treated with 6-OAP. The effects of 6-OAP plus other drugs on MM.1S cells were evaluated. The in vivo therapeutic efficacy and pharmacokinetic features of 6-OAP were tested in nude mice bearing U266 cells and Sprague-Dawley rats, respectively. We found that 6-OAP suppressed the proliferation of dexamethasone-sensitive and dexamethasone-resistant cell lines and primary CD138+ MM cells. 6-OAP caused mitotic arrest, accompanied by activation of spindle assembly checkpoint and blockage of ubiquitiniation and subsequent proteasomal degradation of cyclin B1. Combined use of 6-OAP and bortezomib induced potentiated cytotoxicity with inactivation of ERK1/2 and activation of JNK1/2 and Casp-8/-3. 6-OAP overcame the protective effects of IL-6 and IGF-I on MM cells through inhibition of Jak2/Stat3 and Akt, respectively. 6-OAP inhibited BMSCs-facilitated MM cell expansion and TNF-α-induced NF-κB signal. Moreover, 6-OAP exhibited potent anti-MM activity in nude mice and favorable pharmacokinetics in rats. CONCLUSIONS/SIGNIFICANCE: These results indicate that 6-OAP is a new cell cycle inhibitor which shows therapeutic potentials for MM.

[A new furanolabdane diterpene glycoside from Phlomis younghusbandii Mukerjee].

In order to find the compound basis of Phlomis younghusbandii Mukerjee that related to pharmacodynamic action, various chromatographic techniques were used to separate and purify the constituents of this plant, and physicochemical and spectral data were used to identify the structures of obtained compounds. A new furanolabdane diterpene glycoside, named as phlomisoside F, was isolated and identified, which was 15,16-epoxy-8(9),13(16), 14-labdatrien-7-ketone-19-oic acid-beta-D-glucopyranosyl ester.