Two effective clinical prediction models to screen for obstructive sleep apnoea based on body mass index and other parameters.

BACKGROUND AND OBJECTIVE: The diagnosis of obstructive sleep apnea (OSA) relies on polysomnography which is time-consuming and expensive. We therefore aimed to develop two simple, non-invasive models to screen adults for OSA. METHODS: The effectiveness of using body mass index (BMI) and a new visual prediction model to screen for OSA was evaluated using a development set (1769 participants) and confirmed using an independent validation set (642 participants). RESULTS: Based on the development set, the best BMI cut-off value for diagnosing OSA was 26.45 kg/m2, with an area under the curve (AUC) of 0.7213 (95% confidence interval (CI), 0.6861-0.7566), a sensitivity of 57% and a specificity of 78%. Through forward conditional logistic regression analysis using a stepwise selection model developed from observed data, seven clinical variables were evaluated as independent predictors of OSA: age, BMI, sex, Epworth Sleepiness Scale score, witnessed apnoeas, dry mouth and arrhythmias. With this new model, the AUC was 0.7991 (95% CI, 0.7668-0.8314) for diagnosing OSA (sensitivity, 75%; specificity, 71%). The results were confirmed using the validation set. A nomogram for predicting OSA was generated based on this new model using statistical software. CONCLUSIONS: BMI can be used as an indicator to screen for OSA in the community. We created an internally validated, highly distinguishable, visual and parsimonious prediction model comprising BMI and other parameters that can be used to identify patients with OSA among outpatients. Use of this prediction model may help to improve clinical decision-making.

Discovery of vanadium complexes bearing tridentate schiff base ligands as novel LSD1 inhibitors.

Lysine specific demethylase (LSD1) plays a pivotal role in epigenetic modulation of gene expression. Abberrant expression of LSD1 was associated with the progress and oncogenesis of multiple human cancers. Herein, we report the preliminary anti-LSD1 evaluation of the synthetic vanadium (V) complexes. Among them, complex 2 showed a moderate inhibitory effect against LSD1 with IC50 value of 19.0 µM, as well as good selectivity over MAO-A/B. Complex 2 is the first vanadium based LSD1 inhibitor, which provides a novel scaffold for the development of LSD1 inhibitor.

[Design, synthesis, antibacterial and anti-cell proliferation activities of [1,2,4]triazino[3,4-h] [1,8]naphthyridine-8-one-7-carboxylic acid derivatives].

To discover novel fluoroquinolone lead compounds as possible anti-infective or/and antitumor chemotherapies, combination principle of pharmacophore-based drug design, a series of novel tricyclic fluoroquinolone title compounds, [1,2,4]triazino[3,4-h][1,8]naphthyridine-8-one-7-carboxylic acid derivatives ( 5a-5p), were designed and synthesized with a fused [1,2,4]-triazine ring unit. Their structures were characterized by spectral data and elemental analysis and the in vitro antibacterial and anti-cell proliferation activities were also evaluated. The results showed that the titled compounds exhibited more significant inhibitory activities against drug-resistant bacteria (Methicillin-resistant Staphylococcus aureus and multi drug-resistant Escherichia coli strains) and three tested cancer cell lines (human hepatoma SMMC-7721, murine leukemia L1210 and human murine leukemia HL60 cells). Interestingly, SAR showed that compounds with electron-donating groups attached to benzene ring had stronger antibacterial activity than antitumor activity, but electron-withdrawing compounds displayed more potential antitumor activity than antibacterial activity, especially antitumor activity of nitro compounds was comparable to comparison doxorubicin. Thus, novel triazine-fused tricyclic fluoroquinolones as potent anti-infective or/and antitumor lead compounds are valuable to pay attention and for further development.

[Synthesis and anti-proliferative activity of fluoroquinolone (rhodanine unsaturated ketone) amide derivatives].

To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone (rhodanine α, ß-unsaturated ketone) amine derivatives (5a-5r) were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone (rhodanine α, ß-unsaturated ketone) amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues.

[Synthesis and antitumor activity of fluoroquinolon-3-yl-s-triazole sulfide ketones and their derivatives from ciprofloxacin].

To discover an efficient strategy for the conversion of the antibacterial activity of fluoroquinolones into the antitumor activity, the three series of C-3 s-triazole-based derivatives including sulfide ketones (6a-6g), thiosemicarbazones (7a-7g) and fused heterocyclic thiazolotriazoles (8a-8g) were synthesized from ciprofloxacin (1), respectively. The structures were characterized by elemental analysis and spectral data. The antitumor activity was tested against three tumor cell lines (Hep-3B, Capan-1 and HL60) using the MTT assay. The three types of compounds all exhibited stronger anti-proliferative activities than ciprofloxacin in the test. The order of their activities was in compounds 7>8>6, and the order of selectivity against cancer cell lines was Capan-1, Hep-3B and HL60. Meanwhile, the SAR revealed that some compounds with electron-drawing group substituted such as fluoro- and nitro-phenyl compounds (6f, 7f, 8f) and (6g, 7g, 8g) displayed more significant activity than the control compounds, especially the IC50 values of thiosemicarbazone compounds 7f and 7g against Capan-1 was comparable to doxorubicin. Thus, a five-membered triazole as the C-3 bioisostere modified with the functionalized side-chain of sulfide-ketone thiosemicarbazone warrants special attention and further investigation.

[Synthesis and anti-proliferative activity of fluoroquinolone C-3 fused heterocyclic α,ß-unsaturated ketones derived from ciprofloxacin].

To discover novel antitumor fluoroquinolone lead compounds from a rational modification for antibacterial fluoroquinolones, a fused heterocyclic ketone corresponding to thiazolo[2,3- b][1,2,4]triazolone used as a bioisosteric replacement of the C-3 carboxylic acid group of ciprofloxacin 1, and further modification by a Claisen condensation reaction with substituted benzaldehydes formed novel fluoroquinolone C-3 fuse heterocyclic α, ß-unsaturated ketones as the title compounds (6a-6r), separately. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS, and the in vitro anti-proliferative activity against human hepatoma Hep-3B cells, pancreatic Capan-1 cells and leukemia HL60 cells was evaluated by a MTT assay. The preliminary results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. In particular, compounds carrying an electron-withdrawing carboxyl (6k, 6m) or sulfonamide substituent (6q, 6r) attached to benzene ring were comparable to or better than constractive drug doxorubicin against Capan-1 cells. As such, it suggests that it is favorable for a fused heterocyclic α, ß-unsaturated ketone scaffold instead of the C-3 carboxylic acid group to improve the antitumor activity of fluoroquinolones.

[Synthesis, antitumor activity and SAR of C-3 oxadiazole sulfanylacetylhydrazone-substituted fluoroquinolone analogues].

To explore an efficient strategy for the conversion of antibacterial fluoroquinolones into antitumor fluoroquinolones, an azole heterocyclic ring of oxadiazole instead of the C-3 carboxylic acid group with a functionalized hydrazone group as a modified side-chain, fifteen novel 2-(fluoroquinolon-3-yl)-oxadiazole-5- sulfanylacetylhydrazone derivatives 7a-7o were designed and synthesized on the basis of the pharmacophore hybridization principle from pefloxacin, separately. The structures for fifteen title compounds were characterized by elemental analysis, 1H NMR and MS, and their in vitro antitumor activity against Hep-3B cell line was evaluated by a MTT assay. The results showed that the title compounds exhibited more significantly inhibitory activity than that of the parent pefloxacin, in which compounds with electron-withdrawing group attached on aryl ring had more potency than that of compounds with electron donating group, especially compounds with a carboxylic substituent were comparable to comparison doxorubicin. It suggests that it is favorable for an improvement of antitumor activity to remain a carboxylic acid unit at the aromatic ring.

Trimethoxy-benzaldehyde levofloxacin hydrazone inducing the growth arrest and apoptosis of human hepatocarcinoma cells.

BACKGROUND: In order to search for new structural modification strategies on fluoroquinolones, we have designed and synthesized a series of fluoroquinolone derivatives by linking various hydrazine compounds to the C-3 carboxyl group of levofloxacin and assessed their anticancer activities. Several novel levofloxacin derivatives displayed potent cytotoxicity against the tested cancer cell lines in vitro. In the present study, we investigated the effect of 1-Cyclopropyl-6-fluoro-4-oxo-7- piperazin-1, 4-dihydro- quinoline- 3-carboxylic acid benzo [1,3] dioxol-5- ylmethylene- hydrazide (QNT11) on the apoptosis of human hepatocarcinoma cells in vitro. METHODS: The inhibition effects of QNT11 on cell proliferation were examined by MTT assay. Cell apoptosis was determined by TUNEL and DNA agarose gel electrophoresis method. The topoisomerase ΙΙ activity was measured by agarose gel electrophoresis using Plasmid pBR322 DNA as the substrate. Cell cycle progression was analyzed using flow cytometry in conjunction with ethanol fixation and propidium iodide staining. Mitochondrial membrane potential (△ψm) was measured by high content screening image system. The caspase-9, caspase-8, caspase-3, Bcl-2, Bax, CDK1, Cyclin B1and cytochrome c protein expressions were detected by Western blot analysis. RESULTS: QNT11 showed selective cytotoxicity against Hep3B, SMMC-7721, MCF-7 and HCT-8 cell lines with IC50 values of 2.21 µM, 2.38 µM, 3.17 µM and 2.79 µM, respectively. In contrast, QNT11 had weak cytotoxicity against mouse bone marrow mesenchymal stem cells (BMSCs) with IC50 value of 7.46 µM. Treatment of Hep3B cells with different concentrations of QNT11 increased the percentage of the apoptosis cells significantly, and agarose gel electrophoresis revealed the ladder DNA bands typical of apoptotic cells, with a decrease in the mitochondrial membrane potential. Compared to the control group, QNT11 could influence the DNA topoisomerase IIactivity and inhibit the religation of DNA strands, thus keeping the DNA in fragments. There was a significant increase of cytochrome c in the cytosol after 24 h of treatment with QNT11 and a decrease in the mitochondrial compartment. Observed changes in cell cycle distribution by QNT11 treated might be caused by insufficient preparation for G2/M transition. In addition, QNT11 increased the protein expression of Bax, caspase-9, caspase-8, caspase-3, as well as the cleaved activated forms of caspase-9, caspase-8 and caspase-3 significantly, whereas the expression of Bcl-2 decreased. CONCLUSIONS: Our results showed that QNT11 as a fluoroquinolone derivative exerted potent and selectively anticancer activity through the mechanism of eukaryotic topoisomerase II poisoning. The growth inhibition was in large part mediated via apoptosis-associated mitochondrial dysfunction and regulation of Bcl-2 signaling pathways.

Essential role of autophagy in fucoxanthin-induced cytotoxicity to human epithelial cervical cancer HeLa cells.

AIM: To investigate the effects and the molecular mechanisms of fucoxanthin, a major carotenoid found in edible seaweed, on HeLa cells. METHODS: The cytotoxicity of fucoxanthin was evaluated using MTT assay. Cell cycle and apoptosis were evaluated using flow cytometric analysis. Autophagy was detected with acridine orange staining and transient transfection of the GFP-LC3 plasmid into the cells. Protein expression was detected with Western blotting. RESULTS: Treatment of HeLa cells with fucoxanthin (10-80 µmol/L) for 48 h caused dose-dependent cytotoxicity with an IC50 value of 55.1±7.6 µmol/L. Fucoxanthin (10, 20, and 40 µmol/L) dose-dependently induced G0/G1 arrest, but did not change the apoptosis of HeLa cells. The same concentrations of fucoxanthin dose-dependently increased the protein expression of LC3 II (the autophagosome marker) and Beclin 1 (the initiation factor for autophagosome formation) in HeLa cells. Moreover, fucoxanthin dose-dependently decreased the levels of phosphorylated Akt and its downstream proteins p53, p70S6K, and mTOR, and increases the expression of PTEN in HeLa cells. Pretreatment of HeLa cells with 3-methyladenine (5 mmol/L) blocked the cytotoxic effect of fucoxanthin as well as fucoxanthin-induced autophagy. CONCLUSION: Fucoxanthin exerts autophagy-dependent cytotoxic effect in HeLa cells via inhibition of Akt/mTOR signaling pathway.

[Synergistic antitumor effects of tanshinone II A in combination with cisplatin via apoptosis in the prostate cancer cells].

Treatment with the combination of Chinese herbs and cytotoxic chemotherapies showed a higher survival rate in clinical trials. In this report, the results demonstrated that the tanshinone II A, a key component of Salvia miltiorrhiza bunge, when it is combined with the cytotoxic drug cisplatin showed synergistic antitumor effects on human prostate cancer PC3 cells and LNCaP cells in vitro. Antiproliferative effects were detected with MTT assay. Cell cycle distribution and apoptosis were detected by flow cytometer. Protein expression was detected by Western blotting. The intracellular concentration of cisplatin was detected by high performance liquid chromatography. The results demonstrated that tanshinone II A significantly enhanced the antiproliferative effects of cisplatin on human prostate cancer PC3 cells and LNCaP cells with the increase of the intracellular concentration of cisplatin. These effects were correlated with cell cycle arrested at S phase and cell apoptosis. The apoptosis might be achieved through death receptor pathway and mitochondrial pathway. Furthermore, the Bcl-2 family members were also involved in this apoptotic process. Collectively, these results indicated that the combination of tanshinone II A and cisplatin had a better treatment effect in vitro not only on androgen-dependent LNCaP cells but also on androgen-independent PC3 cells.

[Molecular mechanism of ophiopogonin B induced cellular autophagy of human cervical cancer HeLa cells].

This study is to investigate the antitumor activity of ophiopogonin B (OP-B). MTT assay, flow cytometric analysis, acridine orange staining, Lyso-Tracker Red staining and HeLa-GFP-LC3 transfect cells assay were used to detect the proliferation activity, apoptosis and autophagy of HeLa cells. The results showed that OP-B exerted potent antiproliferative activity on HeLa cells, the cell growth inhibition effect of OP-B was not due to apoptosis and OP-B could induce autophagy of HeLa cells. OP-B also induced the protein expression up-regulation of Beclin-1 and promoted LC3 I transformation LC3 II, which were representative proteins of autophagy. Furthermore, 3-MA, an inhibitor of autophagy, not only inhibited OP-B-mediated autophagy but also almost completely reversed the antiproliferative effect of OP-B, suggesting that the growth inhibition effect of OP-B was autophagy dependent. Western blotting demonstrated that OP-B inhibited the phosphorylation of Akt and its' downstream vital protein, such as mTOR and p70S6K. In addition, OP-B also induced the protein expression up-regulation of PTEN, which is a negative regulation protein for Akt/mTOR signaling pathway. However, OP-B did not affect the protein expression of total Akt. Collectively, the antitumor effects of OP-B were autophagy-dependent via repression Akt/mTOR signaling pathway. Therefore, OP-B is a prospective inhibitor of Akt/mTOR and may be used as an alternative compound to treat cervical carcinoma.

Case Report: A rare case of non-small cell lung cancer with STRN-ALK fusion in a patient in very poor condition treated with first-line ensartinib.

Several cases of STRN-ALK fusion have been reported, and some anaplastic lymphoma kinase (ALK) inhibitors have been shown to be effective for treatment. Nevertheless, no cases of COVID-19 leading to heart failure and respiratory failure have been reported in people older than 70 years treated with ALK inhibitors. The present case report describes a 70-year-old patient with usual chronic obstructive pulmonary disease, diabetes, depression, and carotid plaque disease. Next-generation sequencing of tissue obtained by puncture biopsy revealed a STRN-ALK mutation accompanied by a TP53 mutation. The patient was treated with ensartinib and developed COVID-19 leading to heart failure and respiratory failure; nevertheless, he had a good clinical outcome and exhibited high treatment tolerability.

The necroptosis signature and molecular mechanism of lung squamous cell carcinoma.

BACKGROUND: Given the poor prognosis of lung squamous cell carcinoma (LUSC), the aim of this study was to screen for new prognostic biomarkers. METHODS: The TGCA_LUSC dataset was used as the training set, and GSE73403 was used as the validation set. The genes involved in necroptosis-related pathways were acquired from the KEGG database, and the differential genes between the LUSC and normal samples were identified using the GSEA. A necroptosis signature was constructed by survival analysis, and its correlation with patient prognosis and clinical features was evaluated. The molecular characteristics and drug response associated with the necroptosis signature were also identified. The drug candidates were then validated at the cellular level. RESULTS: The TCGA_LUSC dataset included 51 normal samples and 502 LUSC samples. The GSE73403 dataset included 69 samples. 159 genes involved in necroptosis pathways were acquired from the KEGG database, of which most showed significant differences between two groups in terms of genomic, transcriptional and methylation alterations. In particular, CHMP4C, IL1B, JAK1, PYGB and TNFRSF10B were significantly associated with the survival (p < 0.05) and were used to construct the necroptosis signature, which showed significant correlation with patient prognosis and clinical features in univariate and multivariate analyses (p < 0.05). Furthermore, CHMP4C, IL1B, JAK1 and PYGB were identified as potential targets of trametinib, selumetinib, SCH772984, PD 325901 and dasatinib. Finally, knockdown of these genes in LUSC cells increased chemosensitivity to those drugs. CONCLUSION: We identified a necroptosis signature in LUSC that can predict prognosis and identify patients who can benefit from targeted therapies.

Piperonal ciprofloxacin hydrazone induces growth arrest and apoptosis of human hepatocarcinoma SMMC-7721 cells.

AIM: To investigate the cytotoxic effects of piperonal ciprofloxacin hydrazone (QNT4), a novel antibacterial fluoroquinolone derivative, against human hepatocarcinoma SMMC-7721 cells. METHODS: Human hepatocarcinoma cells (SMMC-7721), human breast adenocarcinoma cells (MCF-7) and human colon adenocarcinoma cells (HCT-8) were tested. The effects of QNT4 on cell proliferation were examined using MTT assay. Cell apoptosis was determined using Hoechst 33258 fluorescence staining, TUNEL assay and agarose gel electrophoresis. The topoisomerase II activity was measured using agarose gel electrophoresis with the DNA plasmid pBR322 as the substrate. Mitochondrial membrane potential (Δψm) was measured using a high content screening imaging system. Protein expression of caspase-9, caspase-8, caspase-3, p53, Bcl-2, Bax, and cytochrome c was detected with Western blot analysis. RESULTS: Treatment with QNT4 (0.625-10 µmol/L) potently inhibited the proliferation of the cancer cells in time- and dose-dependent manners (the IC(50) value at 24 h in SMMC-7721 cells, MCF-7 cells and HCT-8 cells was 2.956±0.024, 3.710±0.027, and 3.694±0.030 µmol/L, respectively). Treatment of SMMC-7721 cells with QNT4 (0.2146, 2.964, and 4.600 µmol/L) for 24 h dose-dependently increased the percentage of apoptotic cells, elicited characteristic DNA "ladder" bands, and decreased the mitochondrial membrane potential. QNT4 dose-dependently increased topoisomerase II-mediated DNA breaks while inhibiting DNA relegation, thus keeping the DNA in fragments. Treatment of SMMC-7721 cells with QNT4 significantly increased cytochrome c in the cytosol, and decreased cytochrome c in the mitochondrial compartment. QNT4 (3-7.39 µmol/L) significantly increased the protein expression of p53, Bax, caspase-9, caspase-3, and the cleaved activated forms of caspase-9 and caspase-3 in SMMC-7721 cells. In contrast, the expression of Bcl-2 was decreased, while caspase-8 had no significant change. CONCLUSION: QNT4 induced the apoptosis of SMMC-7721 cells via inhibiting topoisomerase II activity and modulating mitochondrial-dependent pathways.

Part IV: Design, synthesis and antitumor activity of fluoroquinolone C-3 heterocycles: bis-oxadiazole methylsulfide derivatives derived from ciprofloxacin.

To explore an efficient strategy for further development of anticancer fluoroquinolone candidates derived from ciprofloxacin, a heterocyclic ring as the bioisosteric replacement of C3 carboxyl group led to a key intermediate, oxadiazole thiol (5), which was further modified to the bis-oxadiazole methylsulfides (7a-7h) and the corresponding dimethylpiperazinium iodides (8a-8h), respectively. Structures were characterized by elemental analysis and spectra data, and their anticancer activities in vitro against CHO, HL60 and L1210 cancer cells were also evaluated by MTT assay. The preliminary results show that piperazinium compounds (8) possess more potent activity than that of corresponding free bases (7).

[Part IV. Synthesis and antitumor evaluation of s-triazolothiadiazines and pyrazolo s-triazoles derived from ciproxacin].

An efficient modified route based on the targeting mechanism of antibacterial fluoroquinolones for the shift from the antibacterial activity to the antitumor one was further developed. Using a fused heterocyclic ring, s-triazolothiadiazine as a carboxyl bioisostere of ciprofloxacin, the title compounds, 1-cyclopropyl-6-fluoro-7-piperazin-1-yl-3-(6-substituted-phenyl-7H-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazin-3-yl)-quinolin-4(1H)-ones (5a-5e) and their corresponding N-acetyl products (6a-6e), were designed and synthesized, separately. Meaningfully, a ring-contraction of fused six-membered thiadiazine occurred by a sulfur extrusion reaction gave new tri-acetylated fused heterocycles related to pyrazolo[5, 1-c][1, 2, 4] triazoles (7a-7e). The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated for the synthesized fifteen heterocycles compared to parent ciprofloxacin by methylthiazole trazolium (MTT) assay. Interestingly, the results displayed that fifteen fused heterocyclic compounds showed more significant growth inhibitory activity (IC50 < 25.0 micromo x L(-1)) than that of parent ciprofloxacin (IC50 > 150.0 micromol x L(-1)), and the active order decreased from 7a-7e to 5a-5e to 6a-6e, respective.

[Effects of plant growth regulator mepiquat chloride on content of active compounds in Scutellaria baicalensis].

OBJECTIVE: To study the effect of plant growth regulator mepiquat chloride (DPC) on the growing development of plant and the content of active compounds in Scutellaria baicalensis. METHOD: After spraying DPC during the seedling period, the length of taproot, fresh weight of root, diameter of taproot and the length of stem were measured. The contents of baicalin, baicalein and wogonin were determined by HPLC, respectively. Total flavonoids and scavenging DPPH were determined with ultraviolet spectrophotometry. RESULT: After spraying DPC, fresh weight of S. baicalensis root was significant increased, and root diameter was also increased. The contents of baicalin and total flavonoids were significantly increased and baicalein and wogonin were decreased remarkably. Compared with controls, scavenging activity of ethanol extracts on DPPH free radical was no significant changed after spraying DPC. CONCLUSION: Plant growth regulator DPC could regulate the growth on the ground and underground effectively, and could enhance the content of flavonoids compounds of S. baicalensis.

[Effect of different developmental stage on plant growth and active compounds in Scutellaria baicalensis].

OBJECTIVE: To study the developmental phase on the growth and active compounds in Scutellaria baicalensis. METHOD: Seeds of wild plants were collected from Laiwu and sowed in Fangshan (Beijing) and Laiwu (Shandong). Samples of aerial and underground parts were collected in five growth periods of sprouts, seedlings, flowering, seed drop and withered periods respectively. The length of taproot, fresh weight of root, diameter of taproot and the length of stem were determined. The content of active compounds and total flavonoids were determined by HPLC and ultraviolet spectrophotometry respectively. The transcripted level of PAL1, PAL2, PAL3, C4H, 4CL, CHS, GUS and UBGAT were analyzed with RT-PCR. RESULT: The results showed that the aerial part of S. baicalensis grew quickly before flowering stage, and the underground part grew mostly between the periods of flowering and withered. In the whole growing developmental periods, the content of total flavonoids was not changed significantly, the content of baicalin was increased gradually and the content of baicalein was decreased gradually. Expression level of PAL and 4CL was the highest in withered period, CHS was increased between flowering and seed drop and decreased in withered period. CONCLUSION: Seedlings and withered periods may be the key phase affecting the growth and active compounds in S. baicalensis.

SKA1/2/3 is a biomarker of poor prognosis in human hepatocellular carcinoma.

Background: Spindle and kinetochore-associated complex subunits 1-3 (SKA1-3) stabilize the kinetochore-attached spindle microtubules in metaphase. Due to the dysregulation in multiple cancers, SKA1-3 is considered a predictor for the prognosis of the patients. However, the potential clinical applications of SKA1-3, particularly in hepatocellular carcinoma (HCC) prognosis and progression, have completely unknown yet. Methods: For the analysis of SKA1-3 expression and applications in clinics in HCC patients, several databases, such as STRING, UALCAN, GEO, and TCGA, were searched. In addition, the underlying mechanisms of SKA for the regulation of HCC occurrence, development, and progression were also explored. Results: Compared to the normal controls, HCC patients showed dramatically elevated SKA1-3 expression at the mRNA level, and the values of the area under the curve (AUC) were 0.982, 0.887, and 0.973, respectively. Increased SKA1-3 expression levels were associated with the clinical stage, age, body mass index, tumor grade, tissue subtype, and Tp53 mutation status in HCC patients. The analyses of Kyoto Encyclopedia of Genes and Genome (KEGG) and Gene ontology (GO) demonstrated that SKA1-3 are enriched mainly in the Fanconi anemia, homologous recombination, spliceosome, DNA replication, and cell cycle signaling pathways. The hub genes, such as CDK1, CCNB1, CCNA2, TOP2A, BUB1, AURKB, CCNB2, BUB1B, NCAPG, and KIF11, were identified in protein-protein interactions (PPIs). The expression levels of hub genes were increased in HCC patients and predictive of a poor prognosis. Finally, the expression levels of SKA1-3 were determined using the GEO database. Conclusions: SKA1-3 are potential prognostic biomarkers of and targets for HCC. In addition, SKA1-3 may affect HCC prognosis via the Fanconi anemia pathway, homologous recombination, spliceosome, DNA replication, and cell cycle signaling pathway.

Part II: Design, synthesis and antitumor action of C3/C3 bisfluoroquinolones linked-cross 2, 5-[1, 3, 4]oxadiazole.

To develop a new small molecular probe for discovering an antitumor lead compound from the replacement of carboxylic group of two molecular antibacterial fluoroquinolones with a heterocyclic ring, a series of the C3/C3 bis-fluoroquinolones tethered with an 1, 3, 4-oxadiazole ring were synthesized as their respective HCl salts, and their structures were characterized by elemental analysis and spectral data. The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated via the respective IC50 values by methylthiazole trazolium (MTT) assay.