Dual targeting total saponins of Pulsatilla of natural polymer crosslinked gel beads with multiple therapeutic effects for ulcerative colitis treatment.

Oral colon targeted drug delivery system (OCTDDS) is desirable for the treatment of ulcerative colitis (UC). In this study, we designed a partially oxidized sodium alginate-chitosan crosslinked microsphere for UC treatment. Dissipative particle dynamics (DPD) was used to study the formation and enzyme response of gel beads from a molecular perspective. The formed gel beads have a narrow particle size distribution, a compact structure, low cytotoxicity and great colon targeting in vitro and in vivo. Animal experiments demonstrated that gel beads promoted colonic epithelial barrier integrity, decreased the level of pro-inflammatory factors, accelerated the recovery of intestinal microbial homeostasis in UC rats and restored the intestinal metabolic disorders. In conclusion, our gel bead is a promising approach for the treatment of UC and significant for the researches on the pathogenesis and treatment mechanism of UC.

Fluoxetine Ameliorates the Aggravation of UC Symptoms in C57BL/6 Mice Induced by CUMS.

OBJECTIVE: Patients with chronic ulcerative colitis (UC) often have mental symptoms such as depression and anxiety, and stress can lead to gastrointestinal diseases. However, the correlation between mental stress and UC is unclear. In this paper, chronic unpredictable mild stress (CUMS) was utilized to evaluate the involvement of mental factors in the pathogenesis of UC. METHODS: The CUMS model was used to evaluate the direct/indirect involvement of mental factors in the pathogenesis of UC. The behavior was evaluated by the open field, forced swimming, and tail suspension tests. Body weight, the disease activity index (DAI) score, colon length, and HE staining of colon tissue were used to evaluate the action of CUMS and fluoxetine. RESULTS: The results showed that weight loss and the DAI score increased in CUMS mice, but they had no meaningful effect on colon length and morphological structure of colon tissue. However, CUMS aggravated dextran sulfate sodium (DSS)-induced colon length shortening and colon morphological structure damage. Fluoxetine significantly improved the DAI score, shortened colon length, and damaged morphology and structure of the colons induced by CUMS combined with DSS in mice. Fluoxetine also decreased the level of IL-6 in the serum and the TNF-α and IFN-γ levels of colon tissue. Fluoxetine simultaneously improved behavioral abnormalities induced by CUMS combined with DSS in mice. CONCLUSION: CUMS aggravated the UC symptoms induced by DSS, and fluoxetine could improve the UC symptoms due to its improvement in the inflammatory level and behavioral abnormalities.

Stem cell competition driven by the Axin2-p53 axis controls brain size during murine development.

Cell competition acts as a quality-control mechanism that eliminates cells less fit than their neighbors to optimize organ development. Whether and how competitive interactions occur between neural progenitor cells (NPCs) in the developing brain remains unknown. Here, we show that endogenous cell competition occurs and intrinsically correlates with the Axin2 expression level during normal brain development. Induction of genetic mosaicism predisposes Axin2-deficient NPCs to behave as "losers" in mice and undergo apoptotic elimination, but homogeneous ablation of Axin2 does not promote cell death. Mechanistically, Axin2 suppresses the p53 signaling pathway at the post-transcriptional level to maintain cell fitness, and Axin2-deficient cell elimination requires p53-dependent signaling. Furthermore, mosaic Trp53 deletion confers a "winner" status to p53-deficient cells that outcompete their neighbors. Conditional loss of both Axin2 and Trp53 increases cortical area and thickness, suggesting that the Axin2-p53 axis may coordinate to survey cell fitness, regulate natural cell competition, and optimize brain size during neurodevelopment.

A reasonable identification of the early recurrence time based on microvascular invasion for hepatocellular carcinoma after R0 resection: A multicenter retrospective study.

BACKGROUND: Early and late recurrence of hepatocellular carcinoma (HCC) have different clinical outcomes, especially for those accompanied by microvascular invasion (MVI), but the definition of early recurrence remains controversial. Therefore, a reasonable identification of the early recurrence time for HCC is urgently needed. METHODS: Resected recurrence patients were enrolled and divided into two cohorts, one for identification of the early recurrence time and another for verification of the accuracy of the point. Univariable and multivariable Cox regression analyses were adopted to identify the prognostic factors of recurrence HCC (rHCC) and Kaplan-Meier method was applied to analyze the overall survival (OS). The appropriate cutoff value was determined by the exhaustive method using different recurrence intervals from 1 to 24 months in turn. RESULTS: In total, 292 resected rHCC patients were analyzed to calculate the early recurrence interval, and another 421 resected rHCC patients with MVI were enrolled to verify the efficacy of adjuvant transarterial chemoembolization (TACE) in this recurrence interval. MVI was identified as an independent risk factor by multivariable analysis. The OS of rHCC patients without MVI is better than that of patients with MVI when the recurrence time was within 13 months, while not beyond 13 months. The verification cohort demonstrated that adjuvant TACE provided longer survival for rHCC with MVI when the recurrence time was within 13 months, while not beyond 13 months. CONCLUSION: For HCC patients with MVI who underwent R0 resection, 13 months may be a reasonable early recurrence time point, and within this interval, postoperative adjuvant TACE may result in longer survival compared with surgery alone.

LZTFL1 inhibits kidney tumor cell growth by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway.

LZTFL1 is a tumor suppressor located in chromosomal region 3p21.3 that is deleted frequently and early in various cancer types including the kidney cancer. However, its role in kidney tumorigenesis remains unknown. Here we hypothesized a tumor suppressive function of LZTFL1 in clear cell renal cell carcinoma (ccRCC) and its mechanism of action based on extensive bioinformatics analysis of patients' tumor data and validated it using both gain- and loss-functional studies in kidney tumor cell lines and patient-derive xenograft (PDX) model systems. Our studies indicated that LZTFL1 inhibits kidney tumor cell proliferation by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway and inducing cell cycle arrest at G1. Clinically, we found that LZTFL1 is frequently deleted in ccRCC. Downregulation of LZTFL1 is associated with a poor ccRCC outcome and may be used as prognostic maker. Furthermore, we show that overexpression of LZTFL1 in PDX via lentiviral delivery suppressed PDX growth, suggesting that re-expression of LZTFL1 may be a therapeutic strategy against ccRCC.

Trajectories of Efficacy and Cognitive Function During Electroconvulsive Therapy Course in Young Adults with Treatment-Resistant Depression.

Objective: Little is known about the effectiveness and cognitive side-effects of electroconvulsive therapy (ECT) in young adults with treatment-resistant depression (TRD). The primary aim of this prospective longitudinal observational trial was to examine the clinical features and cognitive outcomes of young adults with TRD undergoing ECT. Methods: Changes in depressive symptoms and objective and subjective cognitive function were assessed using repeated evaluation at baseline, after each ECT session, and at one-month follow-up using the Montgomery-Äsberg Depression Rating Scale (MADRS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Forward Digital Span Test (FDST), and part of the Columbia Subjective Side Effects Schedule. Results: Of 41 inpatients, 35 (85.4%) and 12 (29.3%) met the criteria for response and remission after ECT, respectively. The greatest clinical improvements occurred during the first 3-4 ECT sessions. While 34 patients reported subjective cognitive impairment increased with ECT, immediate and delayed memory (RBANS) significantly increased after ECT, consistent with FDST results. Objective cognition significantly improved during follow-up, but subjective cognition remained impaired. Conclusion: ECT is effective in young adults with TRD. Although subjective cognitive impairment increased during treatment, objective cognitive impairments were not observed.

Knockdown of lncRNA HOXD-AS2 Improves the Prognosis of Glioma Patients by Inhibiting the Proliferation and Migration of Glioma Cells.

Objective: Increasing studies reported that long noncoding RNAs are involved in regulating glioma progression. However, the specific roles and mechanisms of lncRNAs in glioma remain unclear. Here, we sought to explore the functions of HOXD-AS2 in glioma progression. Methods: Gene expressions of lncRNAs in 5 normal brain tissue specimens and 5 glioblastoma tissue specimens were detected by gene expression profile chip technology. Bioinformatic analysis was performed to see whether differential expression of lncRNAs played any significant role in glioma occurrence and progression. The relationship between HOXD-AS2 level and clinical prognosis of the patients was analyzed. HOXD-AS2 was specifically interfered with by siRNA technology to observe its effects on U251 cell growth, proliferation, apoptosis, and invasion. Results: The expression level of HOXD-AS2 gene in glioma was significantly higher than that in the normal brain tissue, which was related to the tumor grade. The level of HOXD-AS2 gene in patients with high-grade glioma was higher than that in patients with low-grade glioma. High expression of HOXD-AS2 gene was a risk factor for poor prognosis of glioma patients. Knocking down the expression of HOXD-AS2 in glioma cell line U251 arrested the cell cycle and reduced the cell proliferation. Furthermore, it could significantly reduce the migration ability of the cells but had no significant effect on the invasion. Conclusion: HOXD-AS2 is an oncogenic lncRNA associated with the poor prognosis of glioma. Knockdown of HOXD-AS2 may reduce the growth of glioma, which may provide a new avenue for treatment.

m6A-immune-related lncRNA prognostic signature for predicting immune landscape and prognosis of bladder cancer.

BACKGROUND: N6-methyladenosine (m6A) related long noncoding RNAs (lncRNAs) may have prognostic value in bladder cancer for their key role in tumorigenesis and innate immunity. METHODS: Bladder cancer transcriptome data and the corresponding clinical data were acquired from the Cancer Genome Atlas (TCGA) database. The m6A-immune-related lncRNAs were identified using univariate Cox regression analysis and Pearson correlation analysis. A risk model was established using least absolute shrinkage and selection operator (LASSO) Cox regression analyses, and analyzed using nomogram, time-dependent receiver operating characteristics (ROC) and Kaplan-Meier survival analysis. The differences in infiltration scores, clinical features, and sensitivity to Talazoparib of various immune cells between low- and high-risk groups were investigated. RESULTS: Totally 618 m6A-immune-related lncRNAs and 490 immune-related lncRNAs were identified from TCGA, and 47 lncRNAs of their intersection demonstrated prognostic values. A risk model with 11 lncRNAs was established by Lasso Cox regression, and can predict the prognosis of bladder cancer patients as demonstrated by time-dependent ROC and Kaplan-Meier analysis. Significant correlations were determined between risk score and tumor malignancy or immune cell infiltration. Meanwhile, significant differences were observed in tumor mutation burden and stemness-score between the low-risk group and high-risk group. Moreover, high-risk group patients were more responsive to Talazoparib. CONCLUSIONS: An m6A-immune-related lncRNA risk model was established in this study, which can be applied to predict prognosis, immune landscape and chemotherapeutic response in bladder cancer.

Comparisons of the Relationships Between Multiple Lipid Indices and Diabetic Kidney Disease in Patients With Type 2 Diabetes: A Cross-Sectional Study.

Background: Dyslipidemia is a well-recognized risk factor for diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). Growing evidences have shown that compared with the traditional lipid parameters, some lipid ratios may provide additional information of lipid metabolism. Thus, the present study aimed to investigate which lipid index was most related to DKD. Methods: This study was a cross-sectional study that enrolled patients with T2D from January 2021 to October 2021. Each participant was screened for DKD, and the diagnostic criterion for DKD is estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 or urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g for 3 months. Fasting blood was collected to determine lipid profiles by an automatic biochemical analyzer, and lipid ratios were calculated based on corresponding lipid parameters. Spearman's correlation analyses were conducted to assess the correlations between lipid indices and kidney injury indices, and binary logistic regression analyses were conducted to explore the relationship between lipid indices and the risk of DKD. Results: A total of 936 patients with T2D were enrolled in the study, 144 (15.38%) of whom had DKD. The LDL-C/Apo B ratios were positively correlated with eGFR (r = 0.146, p < 0.05) and inversely correlated to cystatin C and UACR (r = -0.237 and -0.120, both p < 0.001). Multiple logistic regression demonstrated that even after adjusting for other clinical covariates, the LDL-C/Apo B ratios were negatively related to DKD, and the odds ratio (95% confidence interval) was 0.481 (0.275-0.843). Furthermore, subgroup analyses revealed that compared with patients with normal lipid profiles and a high LDL-C/Apo B ratio, the odds ratio of DKD in patients with normal lipid metabolism and a low LDL-C/Apo B ratio was 2.205 (1.136-4.280) after adjusting for other clinical covariates. Conclusion: In patients with T2D, the LDL-c/Apo B ratio was most closely associated with DKD among various lipid indices, and a lower LDL-C/Apo B ratio was associated with increased risks of DKD among patients with T2D.

CircME1 promotes aerobic glycolysis and sunitinib resistance of clear cell renal cell carcinoma through cis-regulation of ME1.

Circular RNAs (circRNAs) play critical roles in clear cell renal cell carcinoma (ccRCC). However, their involvement in sunitinib resistance remains largely unknown. Herein, we identified a novel circRNA, named circME1, which contributes to sunitinib resistance development in ccRCC. CircME1 also promoted proliferation, migration, and invasion of ccRCC cells. Further mechanism analysis showed that circME1 interacted with U1 snRNP at the promoter of its parental gene ME1, thereby upregulating the expression of ME1, enhancing aerobic glycolysis of ccRCC, and promoting its malignant phenotype. Furthermore, ME1 specific inhibitor could effectively repress the oncogenic functions of circME1. Taken together, our study demonstrates that the circME1/ME1 pathway is involved in ccRCC progression and sunitinib resistance development, which may be exploited for anticancer therapy.

Single-Cell RNA Sequencing Unravels Upregulation of Immune Cell Crosstalk in Relapsed Pediatric Ependymoma.

Ependymoma (EPN) is a malignant glial tumor occurring throughout central nervous system, which commonly presents in children. Although recent studies have characterized EPN samples at both the bulk and single-cell level, intratumoral heterogeneity across subclones remains a confounding factor that impedes understanding of EPN biology. In this study, we generated a high-resolution single-cell dataset of pediatric ependymoma with a particular focus on the comparison of subclone differences within tumors and showed upregulation of cilium-associated genes in more highly differentiated subclone populations. As a proxy to traditional pseudotime analysis, we applied a novel trajectory scoring method to reveal cellular compositions associated with poor survival outcomes across primary and relapsed patients. Furthermore, we identified putative cell-cell communication features between relapsed and primary samples and showed upregulation of pathways associated with immune cell crosstalk. Our results revealed both inter- and intratumoral heterogeneity in EPN and provided a framework for studying transcriptomic signatures of individual subclones at single-cell resolution.

[Investigation of Virulence Variation of Enterovirus 71 Strains during Thermal Adaptive Evolution].

Objective: To study the virulence variation of enterovirus 71 (EV71) during thermal adaptive evolution, providing references for the prevention and control of the EV71-related hand, foot and mouth disease. Methods: Parental strains and thermal-adapted strains originating from EV71 sibling strains (lineage #100 and #101) were used for plaque assay validation, CCK-8 cytotoxicity experiment, and host proteomics studies after Vero cell infection. Plaque morphology and cell inhibition rate of the viral strains were obtained. Mass spectrometry was used to examine and analyze the functions of proteins that were differential expressed in the host cells. Results: Plaque morphology variation was found only in the heat-adapted strain of lineage #101. Increase in cell inhibition rate was observed in all the thermal-adapted strains, but the amount of increase varied in different strains. According to the results of clustering analysis and principal component analysis, after infection of Vero cells, the host cell protein profile of the heat-adapted strains was similar to that of the parental strains and the host cell protein profile of cold-adapted strains was similar to that of cell-adapted strains. It showed that 500 kinds of proteins presented inter-group difference in their expression, with 239 kinds being up-regulated proteins and 261 being down-regulated. The function of the up-regulated proteins were related to post-translational protein modification, while the functions of the down-regulated proteins were related to SRP-dependent cotranslational protein translocation/targeting to membrane and retrograde protein transport. Conclusion: Virulence variations of enterovirus 71 may accompany thermal adaptive evolution, but its mechanism of action still awaits further investigation.

[Warming acupuncture combined with "three steps and seven methods" of tuina for chronic nonspecific low back pain of yang deficiency and cold-dampness blockage: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy and possible mechanism of warming acupuncture combined with "three steps and seven methods" of tuina and simple "three steps and seven methods" of tuina in treatment of chronic nonspecific low back pain (NLBP) of yang deficiency and cold-dampness blockage. METHODS: A total of 138 patients were randomized into an observation group (69 cases, 5 cases dropped off) and a control group (69 cases, 7 cases dropped off). In the control group, "three steps and seven methods" of tuina was applied. On the basis of the treatment in the control group, warming acupuncture was applied at Shenshu (BL 23), Yaoyangguan (GV 3), Mingmen (GV 4), Weizhong (BL 40) and ashi points. The treatment was given once a day, 6 times a week for 3 weeks in both groups. Before and after treatment, the short form of McGill pain questionnaire (SF-MPQ) score, Oswestry disability index (ODI) score, finger-to-floor distance (FFD), Schober test distance, fear-avoidance beliefs questionnaire (FABQ) score and yang deficiency and cold-dampness blockage score were observed, the serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6 and thromboxane B2 (TXB2) were detected in both groups. The recurrence rate was evaluated in follow-up of 6 months after treatment. RESULTS: After treatment, the scores of PRI, PPI, VAS, ODI, FABQ and FFD, yang deficiency and cold-dampness blockage scores were decreased compared before treatment in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.01); the Schober test distances were increased compared before treatment in both groups (P<0.01), and that in the observation group was larger than the control group (P<0.01). After treatment, the serum levels of TNF-α, IL-1ß, IL-6 and TXB2 were decreased compared before treatment in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.01). In follow-up, the recurrence rate was 12.8% (6/47) in the observation group, which was lower than 34.3% (12/35) in the control group (P<0.05). CONCLUSION: Warming acupuncture combined with "three steps and seven methods" of tuina can effectively alleviate pain in patients with chronic NLBP of yang deficiency and cold-dampness blockage, improve activity and dysfunction of waist, the clinical efficacy is superior to simple "three steps and seven methods" of tuina, its mechanism may be relate to the inhibition of inflammatory reaction.

Prognostic Comparison Between Liver Resection and Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma Patients With Bile Duct Tumor Thrombus: A Propensity-Score Matching Analysis.

Background: Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rare. The aim of this study is to evaluate the long-term prognosis of liver resection (LR) versus transcatheter arterial chemoembolization (TACE) in these patients. Methods: Data from HCC patients with BDTT who underwent liver resection and TACE were analyzed respectively. Propensity score matching (PSM) analysis was performed in these patients. Results: A total of 145 HCC patients with BDTT were divided into two groups: the LR group (n = 105) and the TACE group (n = 40). The median OS in the LR group was 8.0 months longer than that in the TACE group before PSM (21.0 vs. 13.0 months, P <0.001) and 9.0 months longer after PSM (20.0 vs. 11.0 months, P <0.001). The median DFS in the LR group was 3.5 months longer than that in the TACE group before PSM (7.0 vs. 3.5 months, P = 0.007) and 5 months longer after PSM (7.0 vs. 2.0 months, P = 0.007). Conclusion: If surgery is technically feasible, liver resection provides better prognosis for HCC patients with BDTT compared with TACE.

Single-cell transcriptomic profiling of the hypothalamic median eminence during aging.

Aging is a slow and progressive natural process that compromises the normal functions of cells, tissues, organs, and systems. The aging of the hypothalamic median eminence (ME), a structural gate linking neural and endocrine systems, may impair hormone release, energy homeostasis, and central sensing of circulating molecules, leading to systemic and reproductive aging. However, the molecular and cellular features of ME aging remain largely unknown. Here, we describe the transcriptional landscape of young and middle-aged mouse ME at single-cell resolution, revealing the common and cell type-specific transcriptional changes with age. The transcriptional changes in cell-intrinsic programs, cell-cell crosstalk, and cell-extrinsic factors highlight five molecular features of ME aging and also implicate several potentially druggable targets at cellular, signaling, and molecular levels. Importantly, our results suggest that vascular and leptomeningeal cells may lead the asynchronized aging process among diverse cell types and drive local inflammation and cellular senescence via a unique secretome. Together, our study uncovers how intrinsic and extrinsic features of each cell type in the hypothalamic ME are changed by the aging process, which will facilitate our understanding of brain aging and provide clues for efficient anti-aging intervention at the middle-aged stage.

[Intervention effects of miR-125b-5p on cognitive dysfunction induced by traumatic brain injury in rats and its mechanisms].

OBJECTIVE: To investigate the effects and molecular mechanisms of miR-125b-5p on cognitive dysfunction caused by traumatic brain injury (TBI). METHODS: The rats were randomly divided into control group, TBI group (model group), NC Agomir group (false negative group) and miR-125b-5p agomir group (high expression group), with 5 rats in each group. The false negative group and the high expression group were injected with NC agomir and miR-125b-5p agomir, respectively. The brain injury model was established by modified Feeney method except control group. Animal behavioral experiments were utilized for evaluation of the motor coordination, learning and memory and the degree of nerve damage in rats; and enzyme-linked immunosorbent assays (ELISA) and Western blot (WB) were used for determination of the expression levels of inflammatory factors and nerve-related factors in the hippocampus of rats in each group respectively. Finally, combined with bioinformatics, downstream target genes of miR-125b-5p were predicted and verified by reverse transcription polymerase chain reaction (RT-PCR) and WB. RESULTS: Compared with control group, mir-125b-5p expression level, motor coordination ability, learning and memory ability, brain-derived neurotrophic factor(BDNF) and nerve growth factor(NGF) expression levels of rats in model group and false negative group were decreased significantly, the MNSS score, the expressions of interleukins (IL-1ß, IL 6), tumor necrosis factor-α(TNF-α) and glial fibrillary acid protein(GFAF) were increased significantly (P＜0.01);However, compared with model group and false negative group, the above situation of rats in high expression group was opposite (P＜0.01). Bioassay showed that MMP-15 was the downstream target gene of miR-125b-5p. Compared with the control group, the expression of MMP-15 in model group and false negative group was increased significantly (P＜0.01);Compared with model group and false negative group, the expression of MMP-15 in high expression group was decreased significantly (P＜0.01) . CONCLUSION: miR-125b-5p can improve cognitive dysfunction induced by TBI in rats, which may be related to regulating the expression level of MMP-15, thereby inhibiting the neuroinflammatory response after TBI and promoting neuronal regeneration.

Association of type 2 diabetes mellitus with incidences of microvascular invasion and survival outcomes in hepatitis B virus-related hepatocellular carcinoma after liver resection: A multicenter study.

BACKGROUND: Microvascular invasion (MVI) adversely affects long-term survival in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study aimed to examine the association between preoperative type 2 diabetes mellitus (T2DM) with incidences of MVI and prognosis in HBV-related HCC after liver resection (LR). MATERIAL AND METHODS: Data of HBV-related HCC patients who underwent LR as an initial therapy from four hospitals in China were retrospectively collected. Clinicopathological factors associated with the incidence of MVI were identified using univariate and multivariate logistic regression analysis. The recurrence-free survival (RFS) and overall survival (OS) curves between different cohorts of patients were generated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Of 1473 patients who were included, 219 (14.9%) patients had T2DM. Preoperative T2DM, HBV DNA load, antiviral treatment, AFP level, varices, and tumor encapsulation were identified to be independent predictors of the incidence of MVI. Patients with HBV-related HCC and T2DM had a higher incidence of MVI (65.8%) than those without T2DM (55.4%) (P = 0.004). The RFS and OS were significantly worse in patients with T2DM than those without T2DM (median RFS: 11.1 vs 16.7 months; OS: 26.4 vs 42.6 months, both P < 0.001). Equivalent results were obtained in HCC patients with MVI who had or did not have T2DM (median RFS: 10.0 vs 15.9 months; OS: 24.5 vs 37.9 months, both P < 0.001). CONCLUSIONS: Preoperative T2DM was an independent risk factor of incidence of MVI. Patients with HBV-related HCC and T2DM had worse prognosis than those without T2DM after LR.

Diterpenoids from Euphorbia helioscopia and their enhancement of NK cell-mediated killing of NSCLC cells.

Fourteen previously undescribed diterpenoids, including an unusual diterpenoid (1) with a 9,10-seco-jatrophane skeleton, ten jatrophane-type diterpenoids (2-11), two lathyrane-type diterpenoids (12, 13), and an abietane-type diterpenoid (14), together with thirty-six known ones (15-50), were isolated from the whole plants of Euphorbia helioscopia L. The structures of the new isolates were characterized by spectroscopic methods, single-crystal X-ray diffraction analysis, and computational prediction of ECD and chemical shifts. Thirty-nine abundant diterpenoids were evaluated for their enhancement of NK cell-mediated killing of NSCLC cells. As a result, compounds 24, 33, and 41 were found to significantly enhance the killing activity of NK cells towards H1299-luci cells and A549-luci cells at the concentration of 2.5 µM.