Metabolic and Transcriptomic Profile Revealing the Differential Accumulating Mechanism in Different Parts of Dendrobium nobile.

Dendrobium nobile is an important orchid plant that has been used as a traditional herb for many years. For the further pharmaceutical development of this resource, a combined transcriptome and metabolome analysis was performed in different parts of D. nobile. First, saccharides, organic acids, amino acids and their derivatives, and alkaloids were the main substances identified in D. nobile. Amino acids and their derivatives and flavonoids accumulated strongly in flowers; saccharides and phenols accumulated strongly in flowers and fruits; alkaloids accumulated strongly in leaves and flowers; and a nucleotide and its derivatives and organic acids accumulated strongly in leaves, flowers, and fruits. Simultaneously, genes for lipid metabolism, terpenoid biosynthesis, and alkaloid biosynthesis were highly expressed in the flowers; genes for phenylpropanoids biosynthesis and flavonoid biosynthesis were highly expressed in the roots; and genes for other metabolisms were highly expressed in the leaves. Furthermore, different members of metabolic enzyme families like cytochrome P450 and 4-coumarate-coA ligase showed differential effects on tissue-specific metabolic accumulation. Members of transcription factor families like AP2-EREBP, bHLH, NAC, MADS, and MYB participated widely in differential accumulation. ATP-binding cassette transporters and some other transporters also showed positive effects on tissue-specific metabolic accumulation. These results systematically elucidated the molecular mechanism of differential accumulation in different parts of D. nobile and enriched the library of specialized metabolic products and promising candidate genes.

[Correlation analysis and breeding application of agronomic traits and quality indexes in Dendrobium nobile].

The present study aimed to explore the correlation between agronomic traits and quality indexes of Dendrobium nobile and its application value in agricultural breeding. The cultivated strains of D. nobile in Hejiang-Chishui producing areas were extensively collected,and the main agronomic traits and quality indexes were measured. The agronomic traits with significant correlation with quality indexes were screened out by the correlation analysis,and then the parental lines and self-bred F_1 generation plants were furtherverified. Among 96 lines of D. nobile,the content of soluble polysaccharides showed a significant negative correlation with dendrobine( P < 0. 01),and no significant correlation with agronomic traits in stems and leaves. The content of dendrobine exhibited a significant positive correlation with the stem width-thickness ratio( at the largest cross section; P < 0. 01),and no significant correlation with other agronomic traits. Regression analysis further verified the positive correlation between dendrobine content and stem width-thickness ratio( R2> 0. 9). Two lines,JC-10 and JC-35,with significant differences in stem width-thickness ratio were screened out( P <0. 05). The corresponding F1 generation plants by self-pollination both showed that the dendrobine content was higher with greater stem width-thickness ratio( P < 0. 01). The experimental results suggested that within a certain range,the dendrobine content was higher in D. nobile with flatter stem. Therefore,in the breeding of D. nobile,this specific trait could be used for screening plants with high content of quality indexes such as dendrobine.

Spliceosomal protein eftud2 mutation leads to p53-dependent apoptosis in zebrafish neural progenitors.

Haploinsufficiency of EFTUD2 (Elongation Factor Tu GTP Binding Domain Containing 2) is linked to human mandibulofacial dysostosis, Guion-Almeida type (MFDGA), but the underlying cellular and molecular mechanisms remain to be addressed. We report here the isolation, cloning and functional analysis of the mutated eftud2 (snu114) in a novel neuronal mutant fn10a in zebrafish. This mutant displayed abnormal brain development with evident neuronal apoptosis while the development of other organs appeared less affected. Positional cloning revealed a nonsense mutation such that the mutant eftud2 mRNA encoded a truncated Eftud2 protein and was subjected to nonsense-mediated decay. Disruption of eftud2 led to increased apoptosis and mitosis of neural progenitors while it had little effect on differentiated neurons. Further RNA-seq and functional analyses revealed a transcriptome-wide RNA splicing deficiency and a large amount of intron-retaining and exon-skipping transcripts, which resulted in inadequate nonsense-mediated RNA decay and activation of the p53 pathway in fn10a mutants. Therefore, our study has established that eftud2 functions in RNA splicing during neural development and provides a suitable zebrafish model for studying the molecular pathology of the neurological disease MFDGA.

Genome-wide researches and applications on Dendrobium.

MAIN CONCLUSION: This review summarizes current knowledge of chromosome characterization, genetic mapping, genomic sequencing, quality formation, floral transition, propagation, and identification in Dendrobium. The widely distributed Dendrobium has been studied for a long history, due to its important economic values in both medicine and ornamental. In recent years, some species of Dendrobium and other orchids had been reported on genomic sequences, using the next-generation sequencing technology. And the chloroplast genomes of many Dendrobium species were also revealed. The chromosomes of most Dendrobium species belong to mini-chromosomes, and showed 2n = 38. Only a few of genetic studies were reported in Dendrobium. After revealing of genomic sequences, the techniques of transcriptomics, proteomics and metabolomics could be employed on Dendrobium easily. Some other molecular biological techniques, such as gene cloning, gene editing, genetic transformation and molecular marker developing, had also been applied on the basic research of Dendrobium, successively. As medicinal plants, insights into the biosynthesis of some medicinal components were the most important. As ornamental plants, regulation of flower related characteristics was the most important. More, knowledge of growth and development, environmental interaction, evolutionary analysis, breeding of new cultivars, propagation, and identification of species and herbs were also required for commercial usage. All of these studies were improved using genomic sequences and related technologies. To answer some key scientific issues in Dendrobium, quality formation, flowering, self-incompatibility and seed germination would be the focus of future research. And genome related technologies and studies would be helpful.

Modified Tumescent Solution for Creating Working Space During Endoscopic Thyroidectomy.

OBJECTIVE: To study the feasibility of gas-liquid mixing tumescent solution for creating a working space (WS) in endoscopic thyroidectomy (ET). MATERIALS AND METHODS: A prospective study was performed on 186 patients with thyroid tumor who had undergone ET via chest and breast approach. Patients were randomly divided into 2 groups to receive traditional tumescent solution as group A and modified tumescent solution (gas-liquid mixing tumescent solution) as group B. This study compares the following surgical outcome parameters between the 2 groups, including changes of blood pressure, heart rate, and oxygen saturation before and after creating a WS, time for creating a WS, operative time, hemorrhage volume for creating a WS, overall hemorrhage volume, overall postoperative drainage volume, postoperative pain score, postoperative hospitalization, number of retrieved lymph nodes, total serum calcium, serum parathyroid hormone, and cases of transient and permanent recurrent laryngeal nerve palsy. RESULTS: No postoperative bleeding, permanent recurrent laryngeal nerve palsy, incision and surgical site infection, air embolism, flap injury occurred in both groups. The mean time for creating a WS and the whole operation in group B was significantly shorter than that in group A ( P < .05). There were no statistically significant differences in both groups in terms of other observation index ( P > .05). CONCLUSION: The clinical application of gas-liquid mixing tumescent solution can effectively reduce the time for creating a WS and whole operative time, and worthy of being widely used in ET as a safe and effective technique.

Optimizing robotic thyroid surgery: lessons learned from an retrospective analysis of 104 cases.

Background: Robotic assistance in thyroidectomy is a developing field that promises enhanced surgical precision and improved patient outcomes. This study investigates the impact of the da Vinci Surgical System on operative efficiency, learning curve, and postoperative outcomes in thyroid surgery. Methods: We conducted a retrospective cohort study of 104 patients who underwent robotic thyroidectomy between March 2018 and January 2022. We evaluated the learning curve using the Cumulative Sum (CUSUM) analysis and analyzed operative times, complication rates, and postoperative recovery metrics. Results: The cohort had a mean age of 36 years, predominantly female (68.3%). The average body mass index (BMI) was within the normal range. A significant reduction in operative times was observed as the series progressed, with no permanent hypoparathyroidism or recurrent laryngeal nerve injuries reported. The learning curve plateaued after the 37th case. Postoperative recovery was consistent, with no significant difference in hospital stay duration. Complications were minimal, with a noted decrease in transient vocal cord palsy as experience with the robotic system increased. Conclusion: Robotic thyroidectomy using the da Vinci system has demonstrated a significant improvement in operative efficiency without compromising safety. The learning curve is steep but manageable, and once overcome, it leads to improved surgical outcomes and high patient satisfaction. Further research with larger datasets and longer follow-up is necessary to establish the long-term benefits of robotic thyroidectomy.

Intraoperative AI-assisted early prediction of parathyroid and ischemia alert in endoscopic thyroid surgery.

BACKGROUND: The preservation of parathyroid glands is crucial in endoscopic thyroid surgery to prevent hypocalcemia and related complications. However, current methods for identifying and protecting these glands have limitations. We propose a novel technique that has the potential to improve the safety and efficacy of endoscopic thyroid surgery. PURPOSE: Our study aims to develop a deep learning model called PTAIR 2.0 (Parathyroid gland Artificial Intelligence Recognition) to enhance parathyroid gland recognition during endoscopic thyroidectomy. We compare its performance against traditional surgeon-based identification methods. MATERIALS AND METHODS: Parathyroid tissues were annotated in 32 428 images extracted from 838 endoscopic thyroidectomy videos, forming the internal training cohort. An external validation cohort comprised 54 full-length videos. Six candidate algorithms were evaluated to select the optimal one. We assessed the model's performance in terms of initial recognition time, identification duration, and recognition rate and compared it with the performance of surgeons. RESULTS: Utilizing the YOLOX algorithm, we developed PTAIR 2.0, which demonstrated superior performance with an AP50 score of 92.1%. The YOLOX algorithm achieved a frame rate of 25.14 Hz, meeting real-time requirements. In the internal training cohort, PTAIR 2.0 achieved AP50 values of 94.1%, 98.9%, and 92.1% for parathyroid gland early prediction, identification, and ischemia alert, respectively. Additionally, in the external validation cohort, PTAIR outperformed both junior and senior surgeons in identifying and tracking parathyroid glands (p < 0.001). CONCLUSION: The AI-driven PTAIR 2.0 model significantly outperforms both senior and junior surgeons in parathyroid gland identification and ischemia alert during endoscopic thyroid surgery, offering potential for enhanced surgical precision and patient outcomes.

An early history of human breast cancer: West meets East.

Cancer has been increasingly recognized as a global issue. This is especially true in countries like China, where cancer incidence has increased likely because of changes in environment and lifestyle. However, cancer is not a modern disease; early cases have been recorded in ancient medical books in the West and in China. Here, we provide a brief history of cancer, focusing on cancer of the breast, and review the etymology of ai, the Chinese character for cancer. Notable findings from both Western and Chinese traditional medicine are presented to give an overview of the most important, early contributors to our evolving understanding of human breast cancer. We also discuss the earliest historical documents to record patients with breast cancer.

Efficacy of anlotinib combined with radioiodine to treat scalp metastasis of papillary thyroid cancer: A case report and review of literature.

BACKGROUND: Papillary thyroid cancer (PTC) is one of the well-differentiated thyroid tumors. Cutaneous metastasis from differentiated thyroid cancers occurs in < 1% of primary thyroid carcinomas but produces the worst survival prognosis. The multi-targeting tyrosine kinase inhibitor anlotinib has been approved to treat refractory advanced non-small-cell lung cancer as well as advanced soft-tissue and clear cell sarcomas in China. CASE SUMMARY: In a patient with scalp metastasis caused by PTC, thyroid and skull metastasis tumor sizes were significantly reduced after a trial of neoadjuvant anlotinib therapy for 3 cycles. Anlotinib maintenance medication after thyroidectomy further reduced the metastatic skull tumor size thereby preventing the requirement for craniotomy. CONCLUSION: The outcome of the present trial confirmed the potential of anlotinib therapy to treat scalp metastasis induced by PTC and point the way for the treatment of similar diseases in the future.

Arctigenin alleviates ER stress via activating AMPK.

AIM: To investigate the protective effects of arctigenin (ATG), a phenylpropanoid dibenzylbutyrolactone lignan from Arctium lappa L (Compositae), against ER stress in vitro and the underlying mechanisms. METHODS: A cell-based screening assay for ER stress regulators was established. Cell viability was measured using MTT assay. PCR and Western blotting were used to analyze gene and protein expression. Silencing of the CaMKKß, LKB1, and AMPKα1 genes was achieved by RNA interference (RNAi). An ATP bioluminescent assay kit was employed to measure the intracellular ATP levels. RESULTS: ATG (2.5, 5 and 10 µmol/L) inhibited cell death and unfolded protein response (UPR) in a concentration-dependent manner in cells treated with the ER stress inducer brefeldin A (100 nmol/L). ATG (1, 5 and 10 µmol/L) significantly attenuated protein synthesis in cells through inhibiting mTOR-p70S6K signaling and eEF2 activity, which were partially reversed by silencing AMPKα1 with RNAi. ATG (1-50 µmol/L) reduced intracellular ATP level and activated AMPK through inhibiting complex I-mediated respiration. Pretreatment of cells with the AMPK inhibitor compound C (25 µmol/L) rescued the inhibitory effects of ATG on ER stress. Furthermore, ATG (2.5 and 5 µmol/L) efficiently activated AMPK and reduced the ER stress and cell death induced by palmitate (2 mmol/L) in INS-1 ß cells. CONCLUSION: ATG is an effective ER stress alleviator, which protects cells against ER stress through activating AMPK, thus attenuating protein translation and reducing ER load.

ATP bioluminescence rapid detection of total viable count in soy sauce.

The adenosine triphosphate (ATP) bioluminescence rapid determination method may be useful for enumerating the total viable count (TVC) in soy sauce, as it has been previously used in food and beverages for sanitation with good precision. However, many factors interfere with the correlation between total aerobic plate counts and ATP bioluminescence. This study investigated these interfering factors, including ingredients of soy sauce and bacteria at different physiological stages. Using the ATP bioluminescence method, TVC was obtained within 4 h, compared to 48 h required for the conventional aerobic plate count (APC) method. Our results also indicated a high correlation coefficient (r = 0.90) between total aerobic plate counts and ATP bioluminescence after filtration and resuscitation with special medium. The limit of quantification of the novel detection method is 100 CFU/mL; there is a good linear correlation between the bioluminescence intensity and TVC in soy sauce in the range 1 × 10(2) -3 × 10(4) CFU/mL and even wider. The method employed a luminescence recorder (Tristar LB-941) and 96-well plates and could analyse 50-100 samples simultaneously at low cost. In this study, we evaluated and eliminated the interfering factors and made the ATP bioluminescence rapid method available for enumerating TVC in soy sauce.

Expression of BCRP/ABCG2 Protein in Invasive Breast Cancer and Response to Neoadjuvant Chemotherapy.

BACKGROUND: Breast cancer resistance protein (BCRP), or ATP-binding cassette subfamily G member 2 (ABCG2), is an ATP-binding cassette (ABC) transporter that mediates energy-dependent transport of substrate drugs out of the cell. Its overexpression may contribute to intrinsic drug resistance in vitro. However, the current literature has not yet clarified the clinical significance of BCRP/ABCG2 in invasive breast carcinoma. OBJECTIVES: The purpose of this study was to validate the expression of BCRP/ABCG2 in invasive breast carcinoma and its role in response to neoadjuvant chemotherapy. METHODS: In this study, a pretherapeutic core biopsy was performed in 222 patients. BCRP/ABCG2 expression in carcinoma tissue was measured by immunohistochemistry. BCRP/ABCG2 expression correlations with clinicopathological features, molecular subtypes, and therapy response after neoadjuvant chemotherapy were investigated. RESULTS: The results showed that BCRP/ABCG2 was expressed in different molecular subtypes. The proportions of patients with high BCRP/ABCG2 expression were similar in luminal A and luminal B tumors (luminal B, 80%; luminal A, 78%), compared with other molecular subtypes (triple-negative, 63%; HER2+, 58%, p = 0.05). BCRP/ABCG2 expression and the number of lymphatic metastases (p = 0.001) and tumor size (p = 0.011) demonstrated a statistically significant correlation. Low BCRP/ABCG2 expression was associated with an increased pathological complete response (pCR) rate of 38%, higher than the 19% in tumors with high BCRP/ABCG2 expression (p = 0.002). In multivariable analysis, BCRP/ABCG2 and hormone receptor (HR) expression were identified as independent risk factors of pCR (p = 0.003 and p = 0.013, respectively). CONCLUSIONS: BCRP/ABCG2 is highly expressed in HR-positive breast cancer. High BCRP/ABCG2 expression is associated with lymphatic metastasis, tumor size, and poor pCR. BCRP/ABCG2 may be a novel potential biomarker that can predict clinical progression and therapy response after neoadjuvant chemotherapy.

Development of Artificial Intelligence for Parathyroid Recognition During Endoscopic Thyroid Surgery.

OBJECTIVE: We aimed to establish an artificial intelligence (AI) model to identify parathyroid glands during endoscopic approaches and compare it with senior and junior surgeons' visual estimation. METHODS: A total of 1,700 images of parathyroid glands from 166 endoscopic thyroidectomy videos were labeled. Data from 20 additional full-length videos were used as an independent external cohort. The YOLO V3, Faster R-CNN, and Cascade algorithms were used for deep learning, and the optimal algorithm was selected for independent external cohort analysis. Finally, the identification rate, initial recognition time, and tracking periods of PTAIR (Artificial Intelligence model for Parathyroid gland Recognition), junior surgeons, and senior surgeons were compared. RESULTS: The Faster R-CNN algorithm showed the best balance after optimizing the hyperparameters of each algorithm and was updated as PTAIR. The precision, recall rate, and F1 score of the PTAIR were 88.7%, 92.3%, and 90.5%, respectively. In the independent external cohort, the parathyroid identification rates of PTAIR, senior surgeons, and junior surgeons were 96.9%, 87.5%, and 71.9%, respectively. In addition, PTAIR recognized parathyroid glands 3.83 s ahead of the senior surgeons (p = 0.008), with a tracking period 62.82 s longer than the senior surgeons (p = 0.006). CONCLUSIONS: PTAIR can achieve earlier identification and full-time tracing under a particular training strategy. The identification rate of PTAIR is higher than that of junior surgeons and similar to that of senior surgeons. Such systems may have utility in improving surgical outcomes and also in accelerating the education of junior surgeons. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:2516-2523, 2022.

Prognostic Value of LRG1 in Breast Cancer: A Retrospective Study.

BACKGROUND: High expression of leucine-rich alpha-2-glycoprotein 1 (LRG1) is closely related to angiogenesis, which may play an important role in promoting invasion and metastasis. However, the current literature has yet to clarify the clinical significance of LRG1 in breast cancer. OBJECTIVES: The purpose of this work was to validate the correlation between LRG1 expression and prognosis in early breast cancer. METHODS: We utilized an LRG1 detection agent in 330 cases of early breast cancer. The correlation of LRG1 expression with clinicopathological features, patient recurrence, and survival was investigated. RESULTS: Compared with adjacent tissue samples, an elevated expression of LRG1 was observed in breast cancer samples. Moreover, LRG1 expression is associated with the number of lymphatic metastases and TNM pathological stage (p = 0.000, p = 0.000, respectively). For disease-free survival (DFS), the Kaplan-Meier curve indicated a poorer prognosis for the group with high LRG1 levels compared with the low LRG1 group (p = 0.000). A similar result was found for overall survival (OS; p = 0.000). The multivariate Cox regression indicated that LRG1 was still associated with DFS (HR 2.090, 95% CI 1.205-3.625, p = 0.009) and OS (HR 2.112, 95% CI 1.167-3.822, p = 0.013). The histological grade, TNM pathological stage, and molecular subtype were identified as independent risk factors affecting OS. CONCLUSION: In the malignant progression of breast cancer, high LRG1 levels are associated with lymphatic metastasis, histological grade, poor DFS, and poor OS. This study validates the use of LRG1 as a potential prognosis biomarker for early breast cancer.

Pre-clinical pharmacological profile of QF-036, a potent HIV-1 maturation inhibitor.

QF-036 is an HIV-1 maturation inhibitor in pre-clinical development, and its antiviral activity against a laboratory HIV-1 strain and two drug-resistant strains was determined in the C8166 line. QF-036 was also subjected to absorption, distribution and metabolism (ADM) assessment in vitro, and pharmacokinetic profiles were evaluated in rats and monkeys. The 50% effective concentrations (EC50 ) of QF-036 against the three strains were 20.36 nM, 0.39 µM and 2.11 nM, respectively, demonstrating better antiviral potential than the first-generation antiviral maturation inhibitor bevirimat. QF-036 demonstrated moderate cell permeability, high plasma protein binding ability and good metabolic stability in vitro. After oral QF-036 administration to rats and monkeys, both species exhibited moderate bioavailability, and the plasma drug exposure increased in an approximately dose-proportional manner. When administered orally (30 mg/kg) to monkeys, the QF-036 plasma concentration (Cmax ) peaked at 3671 ng/mL (4.82 µM), 12 to 2410 times higher than the EC50 of laboratory or resistant HIV-1 strains. Moreover, the plasma concentration of QF-036 at 12 hours after administration was 263 ng/mL (0.35 µM), which approximately matched the highest EC50 value of the three test strains. The favourable viral inhibitory activity and pharmacokinetic properties provide critical support for QF-036 as a promising anti-HIV therapeutic candidate.

Identification and Validation of QTLs for Macronutrient Contents in Brown and Milled Rice Using Two Backcross Populations between Oryza sativa and O. rufipogon.

Mineral malnutrition as a prevalent public health issue can be alleviated by increasing the intake of dietary minerals from major staple crops, such as rice. Identification of the gene responsible for mineral contents in rice would help breed cultivars enriched with minerals through marker-assisted selection. Two segregating populations of backcross inbred lines (BIL) were employed to map quantitative trait loci (QTLs) for macronutrient contents in brown and milled rice, BC1F5, and BC2F4:5 derived from an interspecific cross of Xieqingzao B (Oryza sativa) and Dongxiang wild rice (O. rufipogon). Phenotyping the populations was conducted in multiple locations and years, and up to 169 DNA markers were used for the genotyping. A total of 17 QTLs for P, K, Na, Ca, and Mg contents in brown and milled rice distributed on eight regions were identified in the BC1F5 population, which is explained to range from 5.98% to 56.80% of phenotypic variances. Two regions controlling qCa1.1 and qCa4.1 were validated, and seven new QTLs for Ca and Mg contents were identified in the BC2F4:5 population. 18 of 24 QTLs were clustered across seven chromosomal regions, indicating that different mineral accumulation might be involved in common regulatory pathways. Of 24 QTLs identified in two populations, 16 having favorable alleles were derived from O. rufipogon and 10 were novel. These results will not only help understand the molecular mechanism of macronutrient accumulation in rice but also provide candidate QTLs for further gene cloning and grain nutrient improvement through QTL pyramiding.

[Thickness measurement of ultrathin SiO2 layer on Si by using XPS standard curve].

A new method of standard curve analysis associated with X-ray photoelectron spectroscopy (XPS) is presented for measuring the thickness of ultrathin SiO2 layer on Si substrate. In this method, XPS spectra of series SiO2/Si standard samples with different known thicknesses of silicon oxides are firstly recorded, and then the ratios of Si2p peak heights corresponding to SiO2 and Si, viz. R = H(SiO2/H(Si), are calculated. The known thicknesses of silicon oxides are plotted against the peak height ratios and an XPS standard curve is derived. Under the same experimental conditions, the samples with unknown thicknesses are measured by using XPS technique and then their thicknesses can be obtained from the XPS standard curve. The SiO2 /Si standard samples were provided by authoritative lab with the advanced analytical equipments and rich experiences, and the oxide thicknesses were measured by multiple techniques. The present results show that the standard curve, plotted in terms of accuracy of the oxide thickness from the standard samples, can be used for the thickness measurement for ultrathin SiO2 on Si, and this method is valuable in practice owing to the swiftness, convenience and accuracy.

Single- and repeated-dose toxicity studies on the novel HIV maturation inhibitor QF-036 in Sprague-Dawley rats.

QF-036 is a novel human immunodeficiency virus (HIV) maturation inhibitor that is a lupine triterpenoid derivative. The objective of this study was to evaluate the safety of QF-036. A single oral toxicity and a 4-week repeated oral toxicity were investigated in Sprague-Dawley (SD) rats. The single oral toxicity study of QF-036 in SD rats showed that no mortality or visible pathological changes were noted at doses of 100, 300, and 1000 mg/kg. QF-036 exhibited a non-linear toxicokinetic profile over the dose range of 100-1000 mg/kg in the single dose study, and a saturation trend appeared at doses of 100 and 300 mg/kg. In the 4-week oral toxicity and toxicokinetic study, SD rats were given 0, 50, 100, and 200 mg/kg QF-036 once daily for 4 weeks, followed by a 4-week recovery period. No mortality or significant effects on food consumption, body weight, or behavior were observed. In addition, there were no test article-related changes in hematology, clinical biochemistry and histopathology. The no observed adverse effect level (NOAEL) was 200 mg/kg. The toxicokinetic study demonstrated a dose-dependent increase in the systemic exposure to QF-036 after 4 weeks of oral administration. There were no marked sex differences or drug accumulation observed for repeated doses of QF-036.

Determination of catechin in lotus rhizomes by high-performance liquid chromatography.

A novel method was developed to analyze lotus rhizome polyphenolic catechin using high-performance liquid chromatography (HPLC). The retain time of catechin was 14.72 min under the optimized condition. Mass spectrometry was further employed to qualify and quantify the purity of the catechin peak. Good linearity (R=0.9997) was obtained within the range of 50-1,000 ng. The coefficient of variance was determined as 5.2%, with a recovery rate of 97%. The detection and quantification limitations of catechin were 23 ng and 50 ng, respectively. The catechin level was 0.0025% in the lotus rhizome, and 0.011% in the knot of the lotus rhizome (Nelumbo nucifera cv. 'damao jie'). The optimized conditions of HPLC for catechin detection in the lotus rhizome matrix were as follows: the SuperlcosIL™ LC-18 analytical column (150 mm×4.6 mm, 5 µm), methanol-water-acetic acid (10:90:1, volume ratio) as the mobile phase, an UV detector at 280 nm, a flow rate of 0.8 ml/min, column temperature at 30°C, and an injection volume of 10 µl.

17-Acetoxyjolkinolide B irreversibly inhibits IkappaB kinase and induces apoptosis of tumor cells.

Nuclear factor-kappaB (NF-kappaB) is critically important for tumor cell survival, growth, angiogenesis, and metastasis. One of the key events in the NF-kappaB signaling is the activation of inhibitor of NF-kappaB kinase (IKK) in response to stimuli of various cytokines. We have identified 17-acetoxyjolkinolide B (17-AJB) from a traditional Chinese medicinal herb Euphorbia fischeriana Steud as a novel small-molecule inhibitor of IKK. 17-AJB effectively inhibited tumor necrosis factor-alpha-induced NF-kappaB activation and induced apoptosis of tumor cells. 17-AJB had no effect on binding of tumor necrosis factor-alpha to its receptor or on binding of NF-kappaB to DNA. It inhibited NF-kappaB nuclear translocation. Detailed analysis revealed that the direct target of 17-AJB was IKK. 17-AJB kept IKK in its phosphorylated form irreversibly. This irreversible modification of IKK inactivated its kinase activity, leading to its failure to activate NF-kappaB. The effect of 17-AJB on IKK was specific. It had no effect on other kinases such as p38, p44/42, and JNK. In addition, 17-AJB induced apoptosis in tumor cells. The effects of 17-AJB on apoptosis correlated with inhibition of expression of the NF-kappaB-regulated genes. Taken together, our data suggest that 17-AJB is a novel type NF-kappaB pathway inhibitor. Its unique interaction mechanism with IKK may render it a strong apoptosis inducer of tumor cells and a novel type anticancer drug candidate.