Baicalein triggers ferroptosis in colorectal cancer cells via blocking the JAK2/STAT3/GPX4 axis.

Colorectal cancer (CRC) is a prevalent form of gastrointestinal malignancy with challenges in chemotherapy resistance and side effects. Effective and low toxic drugs for CRC treatment are urgently needed. Ferroptosis is a novel mode of cell death, which has garnered attention for its therapeutic potential against cancer. Baicalein (5, 6, 7-trihydroxyflavone) is the primary flavone extracted from the dried roots of Scutellaria baicalensis that exhibits anticancer effects against several malignancies including CRC. In this study, we investigated whether baicalein induced ferroptosis in CRC cells. We showed that baicalein (1-64 µM) dose-dependently inhibited the viability of human CRC lines HCT116 and DLD1. Co-treatment with the ferroptosis inhibitor liproxstatin-1 (1 µM) significantly mitigated baicalein-induced CRC cell death, whereas autophagy inhibitor chloroquine (25 µM), necroptosis inhibitor necrostatin-1 (10 µM), or pan-caspase inhibitor Z-VAD-FMK (10 µM) did not rescue baicalein-induced CRC cell death. RNA-seq analysis confirmed that the inhibitory effect of baicalein on CRC cells is associated with ferroptosis induction. We revealed that baicalein (7.5-30 µM) dose-dependently decreased the expression levels of GPX4, key regulator of ferroptosis, in HCT116 and DLD1 cells by blocking janus kinase 2 (JAK2)/STAT3 signaling pathway via direct interaction with JAK2, ultimately leading to ferroptosis in CRC cells. In a CRC xenograft mouse model, administration of baicalein (10, 20 mg/kg, i.g., every two days for two weeks) dose-dependently inhibited the tumor growth with significant ferroptosis induced by inhibiting the JAK2/STAT3/GPX4 axis in tumor tissue. This study demonstrates that ferroptosis contributes to baicalein-induced anti-CRC activity through blockade of the JAK2/STAT3/GPX4 signaling pathway, which provides evidence for the therapeutic application of baicalein against CRC.

Platelet-inhibitory phenolic constituents from the fruits of Daemonorops draco.

Eight previously undescribed phenolic compounds, dracoropins A - H (1-8), along with two known analogues (9 and 10) were isolated from the fruits of Daemonorops draco. Four pairs of isomers (1a/1b, 2a/2b, 3a/3b, and 4a/4b) were resolved by using chiral-phase HPLC separation. Their structures, including the absolute configurations of the resolved isomers, were elucidated by analysis of spectroscopic data (1D and 2D NMR, IR, and HRESIMS), single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 1, 2, and 3 bear a rare 2-phenylbenzo[d]-1,3-dioxepine skeleton. All the isolates were evaluated for their inhibitory activity against ATP release in thrombin-activated platelets. Compounds 2b, 3a, and 6 could significantly inhibit ATP release in thrombin-activated platelets.

Two new triterpenoids from the fruits of Aphanamixis polystachya.

Two new triucallane triterpenoids, polystanin F (1) and polystanin G (2), along with eight known compounds (3-10) were isolated from the fruits of Aphanamixis polystachya. Their structures were established on the basis of extensive spectroscopic analysis. Moreover, eight compounds were evaluated for their in vitro cytotoxicity against three cancer cell lines (liver cancer RT112, colon cancer HCT-116 and breast cancer M231) using the MTT method. Compound 7 showed significant cytotoxic activity against HCT-116 with IC50 1.27 µM.

Trimeric chalchonoids from the total phenolic extract of Chinese dragon's blood (the red resin of Dracaena cochinchinensis).

Four new chalchonoid trimers, named cochinchinenins N-Q (1-4), along with a pair of known enantiomers (5-6), were isolated from the total phenolic extract of Chinese dragon's blood (the red resin of Dracaena cochinchinensis). The planar structures of 1-4 were elucidated by extensive spectroscopic analysis including HRESIMS and 1D/2D NMR. The absolute configurations of new compounds were established by ECD data. Compound 1 exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells with IC50 value of 11.5 ± 1.7 µM.

Flower extract of Caragana sinica. ameliorates DSS-induced ulcerative colitis by affecting TLR4/NF-κB and TLR4/MAPK signaling pathway in a mouse model.

OBJECTIVES: This study aimed to find out the protective effects and preliminary mechanisms of the flower extract of Caragana sinica (FEC) on dextran sulfate sodium salt (DSS)-induced colitis. MATERIALS AND METHODS: The ulcerative colitis models of mice induced by 3% DSS were established and treated with FEC. Body weight changes, disease activity index (DAI), colon histopathological score, anti-oxidant ability, and the level of inflammatory cytokines were determined. The expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) were assessed in colonic tissue by immunohistochemical staining. Western blot was used to analyze the expression of TLR4/ nuclear factor kappa-B (NF-κB) and TLR4/ mitogen-activated protein kinase (MAPK) signaling pathway-related proteins. RESULTS: FEC significantly prevented body weight loss and colonic shortening and reduced the disease activity index and histopathological score (P<0.05). Moreover, FEC treatment remarkably down-regulated the levels of myeloperoxidase (MPO), interleukin-1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) and up-regulated the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and interleukin 10 (IL-10) in the colon of DSS mice (P<0.05). Furthermore, the expression of TLR4/NF-κB and TLR4/MAPK pathway-related proteins was inhibited by FEC (P<0.05). CONCLUSION: Our findings demonstrated that FEC could serve as a potential therapeutic agent for treatment of ulcerative colitis.

Targeting the ILK/YAP axis by LFG-500 blocks epithelial-mesenchymal transition and metastasis.

Metastasis is the main cause of mortality in patients with cancer. Epithelial-mesenchymal transition (EMT), a crucial process in cancer metastasis, is an established target for antimetastatic drug development. LFG-500, a novel synthetic flavonoid, has been revealed as a potential antitumor agent owing to its various activities, including modulation of EMT in the inflammatory microenvironment. Here, using a transforming growth factor beta (TGF-ß)-induced EMT models, we found that LFG-500 inhibited EMT-associated migration and invasion in human breast cancer, MCF-7, and lung adenocarcinoma, A549, cell lines, consistent with the observed downregulation of YAP activity. Further studies demonstrated that LGF-500-induced suppression of YAP activation was mediated by integrin-linked kinase (ILK), suggesting that the ILK/YAP axis might be feasible target for anti-EMT and antimetastatic treatments, which was verified by a correlation analysis with clinical data and tumor specimens. Hence, our data support the use of LGF-500 as an antimetastatic drug in cancer therapy and provide evidence that the ILK/YAP axis is a feasible biomarker of cancer progression and a promising target for repression of EMT and metastasis in cancer therapy.

[Correlation of Serum Concentration of Nilotinib with Clinical Efficacy in Patients with Chronic Myeloid Leukemia].

OBJECTIVE: To investigate the correlation of the serum minimal concentrations (Cmins) of nilotinib(NIL) with the clinical efficacy and adverse events (AEs) in CML patients. METHODS: A total of 54 patients were divided into two groups according to the dosage of nilotinib. 44 cases received dose of 600-800 mg/d were classified as group A; while 10 cases received dose of 400 mg/d as group B. The Cmins of nilotinib were determmined by liquid chromatography-tandem mass spectrometry. RESULTS: Median Cmins of nilotinib in 54 patients was 1.71 (0.52-5.93) µg/ml. Cmins of nilotinib in group A and group B were 2.09± 1.21 µg/ml and 0.94± 0.27 µg/ml respectively, Cmins of group A was significantly higher than that of group B (P=0.001). In group A, 24 out of 44 cases obtained major molecular response (MMR) in 12 months, while 20 cases did not reach MMR in 12 months; the serum drug concentrations were 1.70± 0.75 µg/ml and 2.03± 0.82 µg/ml respectively, without statistically significant differences between these 2 subgroups(P=0.154). However, Cmins of nilotinib in patients with III-IV grade of adverse events were significantly higher than those in patients with 0-II grade of adverse events (3.09± 1.76 µg/ml vs 1.76± 0.68 µg/ml)(P=0.018). There was no statistic diffence in Cmins of nilotinib with MMR in 12 months of group A MMR 1.15± 0.27 µg/ml vs no MMR 0.83± 0.24 µg/ml(P=0.051). The MMR rate at 12 months in group A was 54.5%(24/44) and that in group B was 40%(4/10) (P=0.494). But the incidence of grade III-IV adverse events in group A was 29.5%(13/44), which was significantly higher than that of group B[0/10(0%)]. CONCLUSION: Cmins of nilotinib shows significant individual differences. The Cmins of nilotinib relate with the dosage and grade III-IV of adverse events. The lower dose of nilotinib may maintain a good therapeutic effect and significantly reduce the adverse events.

[Near-infrared quantum cutting downconversion luminescence of Yb3+ ion cooperative energy transferred from YVO4 matrix donor].

The present manuscript researches the near infrared quantum cutting luminescence phenomena of Yb3+ ion in YVO4 crystal matrix The luminescence spectra, excitation spectra and fluorescence lifetimes were measured. It was found that the excitation of YVO4 crystal matrix energy band by 322.0 nm light can result in the effective secondary cooperative energy transfer of Yba+ ion from the YVO4 crystal matrix It results in the intense 985.5 nm 2F(5/2)-->2F(7/2) near infrared quantum cutting luminescence of Yb3+ ion. Meanwhile, the 430.O nm luminescence intensity of YVO4 crystal matrix decreases greatly. From the experimental measurements, it was found that the lifetime of 430.0 nm fluorescence of (A) Yb(1.5) : YVO4 crystal is tauA = 3.785 s and that of (B) YVO4 crystal is tauB=22.72 s. It was found also that the theoretical efficiency up limit of quantum cutting of (A) Yb(1.5) : YVO4 crystal is about eta1.5%=183-3%.

[Clinical study of the characteristics of lymph node metastasis in thoracic esophageal cancer].

OBJECTIVE: To explore the characteristics of lymph node metastasis in thoracic esophageal cancer in order to provide evidence for the extent of lymph node dissection and the operation access. METHODS: A retrospective study was performed on the specimens of 72 patients who underwent radical operation of right transthoracic approach and the features of lymph node metastasis were explored. RESULTS: Lymph node metastases were found in 48 of 72 patients (66.7%). In 1495 lymph nodes dissected, metastases was identified in 181 lymph nodes (12.1%). The rate of lymph node metastasis in the right and left recurrent laryngeal nerve was 30.6% and 12.5% respectively. Lymph node metastasis was associated with tumor size and tumor invasion depth (both P<0.05), while tumor location and differentiation of tumor cells were not significant (both P>0.05). CONCLUSIONS: The lymph node metastasis in thoracic esophageal carcinoma can be easily found in the right recurrent laryngeal nerve. The best surgical approach of thoracic esophageal carcinoma is the right transthoracic approach.

A modified sagittal spine postural classification and its relationship to deformities and spinal mobility in a chinese osteoporotic population.

BACKGROUND: Abnormal posture and spinal mobility have been demonstrated to cause functional impairment in the quality of life, especially in the postmenopausal osteoporotic population. Most of the literature studies focus on either thoracic kyphosis or lumbar lordosis, but not on the change of the entire spinal alignment. Very few articles reported the spinal alignment of Chinese people. The purpose of this study was threefold: to classify the spinal curvature based on the classification system defined by Satoh consisting of the entire spine alignment; to identify the change of trunk mobility; and to relate spinal curvature to balance disorder in a Chinese population. METHODOLOGY/PRINCIPAL FINDINGS: 450 osteoporotic volunteers were recruited for this study. Spinal range of motion and global curvature were evaluated noninvasively using the Spinal-Mouse® system and sagittal postural deformities were characterized. RESULTS: We found a new spine postural alignment consisting of an increased thoracic kyphosis and decreased lumbar lordosis which we classified as our modified round back. We did not find any of Satoh's type 5 classification in our population. Type 2 sagittal alignment was the most common spinal deformity (38.44%). In standing, thoracic kyphosis angles in types 2 (58.34°) and 3 (58.03°) were the largest and lumbar lordosis angles in types 4 (13.95°) and 5 (-8.61°) were the smallest. The range of flexion (ROF) and range of flexion-extension (ROFE) of types 2 and 3 were usually greater than types 4 and 5, with type 1 being the largest. CONCLUSIONS/SIGNIFICANCE: The present study classified and compared for the first time the mobility, curvature and balance in a Chinese population based on the entire spine alignment and found types 4 and 5 to present the worst balance and mobility. This study included a new spine postural alignment classification that should be considered in future population studies.

[Assessment of land use environmental impacts in urban built-up area: a case study in main built-up area of Nanchang City].

Based on the relevant studies of land use environmental impacts and the characteristics of urban land use, a conceptual model on the assessment of land use environmental impacts in urban built-up area was established. This model grouped the land use environmental impacts in built-up area into four basic processes, i. e., detailization, abstractization, matching, and evaluation. A case study was conducted in the main built-up area of Nanchang City, with noise, smell, dust, and hazard as the impact factors. In the test area, noise had a widespread impact, its impacting area accounting for 59% of the total, smell and dust impacts centralized in the east and south parts, while hazard impact was centralized in the southeast part, an industrial area. This assessment model of four basic processes was practical, and could provide basis for the decision-making of urban land use management and planning.

Microsensor in vivo monitoring of oxidative burst in oilseed rape (Brassica napus L.) leaves infected by Sclerotinia sclerotiorum.

Oxidative burst is the rapid and transient production of large amounts of reactive oxygen species, including superoxide anion, hydrogen peroxide (H(2)O(2)), and hydroxyl radical. A rapid and simple technique was employed for in vivo detection of oxidative burst in oilseed rape (Brassica napus L.) leaves, using a modified electrode. Platinum (Pt) micro-particles were dispersed on a Pt electrode, coated with a poly (o-phenylenediamine) film. This exhibited high sensitivity, selectivity and stability in H(2)O(2) detection. Amperometry was used to obtain satisfactory linear relationships between reductive current intensities and H(2)O(2) concentrations at -0.1 V potential in different electrolytes. This electrode was used in vivo to detect oxidative burst in oilseed rape following fungal infection. Oxidative bursts induced by infection of the fungal pathogen Sclerotinia sclerotiorum (Lib.) de Bary exhibited notably different mechanisms between a susceptible and a resistant glucose oxidase-transgenic genotype.

Electrocatalysis of emodin at multi-wall nanotubes.

In this article, the electrochemical behavior of emodin at multi-wall carbon nanotube modified glassy carbon electrodes (MWNTs/GCE) was studied. The result showed that MWNTs/GCE had high electrocatalytic activity for emodin. And the electrocatalytic redox process was a two-charge-two-proton process. Diffusion coefficient (D(R)) of 8.403 x 10(-5) cm(2) s(-1) of emodin was obtained. Further experiments demonstrated that the oxidative peaks increased linearly with emodin concentrations in the range of 1.0 x 10(-6) to 1.0 x 10(-4) M with a limit of detection of 3.0 x 10(-7) M. This electrochemical method was accurate and reliable, therefore, it might provide a novel way for emodin detection.

Electrochemical behavior of levodopa at multi-wall carbon nanotubes-quantum dots modified glassy carbon electrodes.

A multi-wall carbon nanotubes (MWNTs)-quantum dots (QDs) composite-modified glassy carbon electrode (GCE) was prepared. The complex was characterized by transmission electron microscopy (TEM). The electrochemical behavior of levodopa at MWNTs and QDs-modified GCEs (MWNTs-QDs/GCE) was studied by cyclic voltammetry (CV) and chronocoulometry (CC). It was found that its electrochemical behavior was a two-charge-two-proton process. The modified electrode had high electrocatalytic activity for levodopa with a standard heterogeneous rate constant of 0.595 cm s(-1), which was greatly increased compared with the values for bare GCE and individual MWNTs modified GCE. The better electrocatalytic activity for levodopa at MWNTs-QDs/GCE may due to a synergistic effect between MWNTs and QDs. This result provides a novel way to promote research on biomicromolecules at nano-dimensions.

In vivo measurements of changes in pH triggered by oxalic acid in leaf tissue of transgenic oilseed rape.

Oxalic acid (OA), a non-host-specific toxin secreted by Sclerotinia sclerotiorum during pathogenesis, has been demonstrated to be a major phytotoxic and pathogenic factor. Oxalate oxidase (OXO) is an enzyme associated with the detoxification of OA, and hence the introduction of an OXO gene into oilseed rape (Brassica napus L.) to break down OA may be an alternative way of increasing the resistance of the plant to Sclerotinia sclerotiorum. In order to investigate the activation of OXO in transgenic oilseed rape, a convenient and accessible method was used to monitor changes in pH in response to stress induced by OA. The pH sensor, a platinum microcylinder electrode modified using polyaniline film, exhibited a linear response within the pH range from 3 to 7, with a Nernst response slope of 70 mV/pH at room temperature. The linear correlation coefficient was 0.9979. Changes induced by OA in the pH values of leaf tissue of different oilseed rape species from Brassica napus L. were monitored in real time in vivo using this electrode. The results clearly showed that the transgenic oilseed rape was more resistant to OA than non-transgenic oilseed rape.