Carbohydrate digestion by α-glucosidase and subsequent glucose uptake at the brush border are critical for postprandial blood glucose control. Any specific inhibitors are useful as hyperglycemia ...modulating agents. In this study, it was postulated that an array of active components in mulberry leaf extract (MLE) may provide higher potency in inhibiting intestinal glucose absorption compared to the single component 1-deoxynojirimycin (DNJ), which is recognized as a promising inhibitor of intestinal glucose absorption. Both MLE and DNJ were active in inhibiting α-glucosidase. However, in Caco-2 cells, only MLE showed significant inhibition of 2-deoxyglucose uptake, whereas DNJ was ineffective. For glucose loading, co-administration of MLE resulted in potent inhibitions of glucose responses compared to those by DNJ in Sprague Dawley (SD) rats, but this was not found for maltose loading. These novel findings add evidence that the unabsorbed phytochemicals in MLE compete with glucose for intestinal glucose transporters, but DNJ itself does not. We also evaluated the timing of MLE consumption. By administering MLE for 30 min before glucose loading, the incremental area under the curve (IAUC) was significantly lowered in the rats, as compared to a simultaneously administered group. Similarly, cellular glucose uptake was significantly reduced in Caco-2 cells following pretreatment.
Summary
Objective
Although papillary thyroid microcarcinoma (PTMC) has a favourable long‐term prognosis, disease recurrence after initial treatment remains a problem and controversy exists regarding ...the role of radioactive iodine (RAI) ablation in PTMC. We performed this study to evaluate the effect of RAI ablation on disease recurrence in patients with PTMC.
Patients and Methods
Between 1994 and 2004, 2579 patients underwent thyroid surgery for thyroid cancer at Samsung Medical Center. Among these patients, 704 patients with PTMC presumed disease‐free after initial treatment were followed up for disease recurrence (median, 64 months; range, 1–185 months). Patients with PTMC with microscopic extrathyroidal extension, cervical lymph node metastases or multifocality were considered to be in the intermediate‐risk group for recurrence.
Results
Disease recurrence was found in six patients at a median of 29 months (range, 10–70 months) after initial treatment; all six patients with recurrent tumours had received RAI treatment after total thyroidectomy. Disease‐related mortality was not observed, even after recurrence. Based on a Cox regression model considering the standardized inverse probability of treatment weight (IPTW) within each propensity score stratum of patients with a similar likelihood of having received RAI ablation, the likelihood ratio for recurrence did not differ between the RAI ablation group and no RAI group (P = 0·17). When we performed a subgroup analysis considering only patients with PTMC at intermediate‐risk for recurrence, RAI ablation again did not have a significant effect on recurrence (P = 0·79).
Conclusions
Radioactive iodine ablation after total thyroidectomy in low‐ and intermediate‐risk patients with PTMC did not prevent recurrent tumours. Future randomized, controlled, multicenter prospective trials involving a larger sample of patients followed‐up for a longer duration are warranted to confirm our findings.
ObjectiveThe presence of central neck lymph node (LN) metastases (defined as pN1a according to Tumor Node Metastasis classification) in papillary thyroid cancer (PTC) is known as an independent risk ...factor for recurrence. Extent of LN metastasis and the completeness of removal of metastatic LN must have an impact on prognosis but they are not easy to measure. Moreover, the significance of the size of metastatic tumors in LNs has not been clarified. This study was to evaluate the impact of the extent of LN metastasis and size of metastatic tumors on the recurrence in pathological N1a PTC.DesignThis retrospective observational cohort study enrolled 292 PTC patients who underwent total thyroidectomy with central neck dissection from 1999 to 2005. LN ratio was defined as the number of metastatic LNs divided by the number of removed LNs, which was regarded as variable reflecting both extent of LN metastasis and completeness of resection, and LN size as the maximal diameter of tumor in metastatic LN.ResultsThe significant risk factors for recurrence in univariate analysis were large primary tumor size (defined as larger than 2 cm), high LN ratio (defined as higher than 0.4), and presence of macrometastasis (defined as larger than 0.2 cm). Age, sex, clinical node status, and microscopic perithyroidal extension had no effect on recurrence. In multivariate analysis, high LN ratio and presence of macrometastasis were independent risk factors for recurrence.ConclusionLN ratio and size of metastatic nodes had a significant prognostic value in pathological N1a PTC. We suggest that risk stratification of pathological N1a PTC according to the pattern of LN metastasis such as LN ratio and size would give valuable information to clinicians.
In the present study, we investigated berberine-induced apoptosis and the signaling pathways underlying its activity in FaDu head and neck squamous cell carcinoma cells. Berberine did not affect the ...viability of primary human normal oral keratinocytes. In contrast, the cytotoxicity of berberine was significantly increased in FaDu cells stimulated with berberine for 24 h. Furthermore, berberine increased nuclear condensation and apoptosis rates in FaDu cells than those in untreated control cells. Berberine also induced the upregulation of apoptotic ligands, such as FasL and TNF-related apoptosis-inducing ligand, and triggered the activation of caspase-8, -7 and -3, and poly(ADP ribose) polymerase, characteristic of death receptor-dependent extrinsic apoptosis. Moreover, berberine activated the mitochondria-dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bax, Bad, Apaf-1, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL. In addition, berberine increased the expression of the tumor suppressor p53 in FaDu cells. The pan-caspase inhibitor Z-VAD-fmk suppressed the activation of caspase-3 and prevented cytotoxicity in FaDu cells treated with berberine. Interestingly, berberine suppressed cell migration through downregulation of vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and p38, components of the mitogen-activated protein kinase pathway that are associated with the expression of MMP and VEGF, was suppressed in FaDu cells treated with berberine for 24 h. Therefore, these data suggested that berberine exerted anticancer effects in FaDu cells through induction of apoptosis and suppression of migration. Berberine may have potential applications as a chemotherapeutic agent for the management of head and neck squamous carcinoma.
Background: Expression of platelet-derived growth factor (PDGF) and activation (by autophosphorylation) of its receptor (PDGF-R), a tyrosine kinase, are associated with the growth of metastatic ...prostate tumor cells in the bone parenchyma. The tyrosine kinase inhibitor STI571 blocks the PDGF signaling pathway by inhibiting PDGF-R autophosphorylation. We examined the effects of STI571, given alone or with paclitaxel (Taxol), on tumor growth in a mouse model of prostate cancer metastasis. Methods: Human prostate cancer PC-3MM2 cells were injected into the tibias of male nude mice. Three days later the mice (20 per group) were randomly assigned to 5 weeks of treatment with oral and injected water (control), daily oral STI571, weekly injected paclitaxel, or STI571 plus paclitaxel. Lesions in bone and the surrounding muscles were then harvested and analyzed by histology, western blotting (for PDGF-R phosphorylation), immunohistochemistry (for expression of proangiogenic molecules), and double immunofluorescence (to identify endothelial cells and apoptotic tumor cells). Growth of bone lesions was monitored by digital radiography. Bone lesions from control mice were used to establish short-term cell cultures for analysis of PDGF-R phosphorylation. All statistical tests were two-sided. Results: PC-3MM2 cells cultured from bone lesions and treated in vitro with STI571 had less phosphorylated PDGF-R than untreated cells. In control mice, bone lesions expressed high levels of PDGF and activated (i.e., phosphorylated) PDGF-R, whereas lesions in the adjacent musculature did not. Activated PDGF-R was present on the surface of endothelial cells within the bone lesions but not in endothelial cells of uninjected bone. Mice treated with STI571 or STI571 plus paclitaxel had a lower tumor incidence, smaller tumors, and less bone lysis and lymph node metastasis than mice treated with water or paclitaxel alone (P<.001 for all). Mice treated with STI571 or STI571 plus paclitaxel had less phosphorylated PDGF-R on tumor cells and tumor-associated endothelial cells, less tumor cell proliferation, statistically significantly more apoptotic tumor cells (all P<.001), and fewer tumor-associated endothelial cells (P<.001) than control mice. Conclusions: Endothelial cells appear to express phosphorylated PDGF-R when they are exposed to tumor cells that express PDGF. Using STI571 to inhibit PDGF-R phosphorylation may, especially in combination with paclitaxel, produce substantial therapeutic effects against prostate cancer bone metastasis.
To examine the function of SIRT1 in neuronal differentiation, we employed all-trans retinoic acid (ATRA)-induced differentiation of neuroblastoma cells. Nicotinamide inhibited neurite outgrowth and ...tyrosine hydroxylase (TH) expression. Inhibition of PARP or histone deacetylase did not inhibit TH expression, showing the effect to be SIRT1 specific. Expression of FOXO3a and its target proteins were increased during the differentiation and reduced by nicotinamide. FOXO3a deacetylation was increased by ATRA and blocked by nicotinamide. SIRT1 and FOXO3a siRNA inhibited ATRA-induced up-regulation of TH and differentiation. Taken together, these results indicate that SIRT1 is involved in ATRA-induced differentiation of neuroblastoma cells via FOXO3a.
The dynamics of the tail vehicle implementing acceleration-based connected cruise control (CCC) are given byḣ(t)=v1(t)-v(t),v̇(t)=αV(h(t-τ))-v(t-τ)+βḣ(t-τ)+∑k=1nγkv̇k(t-σk).
The dynamics of non-CCC ...vehicles are given byḣi(t)=vi+1(t)-vi(t),v̇i(t)=αV(hi(t-τ))-vi(t-τ)+βḣi(t-τ).
Three examples are shown in the figure below for a five-car platoon, such that γ1, γ2>0 in case A, γ1, γ3>0 in Case B, and γ1, γ4>0 in case C. Display omitted
•Acceleration-based connected cruise control (CCC) is implemented for heterogeneous platoons.•The ad-hoc nature of wireless vehicle-to-vehicle (V2V) communication is exploited.•The design is robust against variation of human parameters and is scalable for large systems.•Delays are used as design parameters in order to ensure string stability.•It is demonstrated that acceleration feedback shall be used in a selective manner.
In this paper, acceleration-based connected cruise control (CCC) is proposed to increase roadway traffic mobility. CCC is designed to be able to use acceleration signals received from multiple vehicles ahead through wireless vehicle-to-vehicle (V2V) communication. We consider various connectivity structures in heterogeneous platoons comprised of human-driven and CCC vehicles. We show that inserting a few CCC vehicles with appropriately designed gains and delays into the flow, one can stabilize otherwise string unstable vehicle platoons. Exploiting the flexibility of ad-hoc connectivity, CCC can be applied in a large variety of traffic scenarios. Moreover, using acceleration feedback in a selective manner, CCC provides robust performance and remains scalable for large systems of connected vehicles. Our conclusions are verified by simulations at the nonlinear level.
As a common type of structural defect, grain boundaries (GBs) play an important role in tailoring the physical and chemical properties of bulk crystals and their two-dimensional (2D) counterparts ...such as graphene and molybdenum disulfide (MoS
). In this study, we explore the atomic structures and dynamics of three kinds of high-symmetry GBs (α, β and γ) in monolayer MoS
. Atomic-resolution transmission electron microscopy (TEM) is used to characterize their formation and evolutionary dynamics, and atomistic simulation based analysis explains the size distribution of α-type GBs observed under TEM and the inter-GB interaction, revealing the stabilization mechanism of GBs by pre-existing sulfur vacancies. The results elucidate the correlation between the observed GB dynamics and the migration of sulfur atoms across GBs via a vacancy-mediated mechanism, offering a new perspective for GB engineering in monolayer MoS
, which may be generalized to other transition metal dichalcogenides.
BACKGROUNDBiliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC) are often confused with other intrahepatic cystic diseases.
AIMSThe aims of this study were to investigate predictive factors ...of biliary cystic tumor (BCT) and clinical characteristic of BCAC.
METHODSWe retrospectively reviewed preoperative diagnoses, overall characteristics and postoperative outcome of 20 BCTs and 19 cystadenoma-mimicking simple cysts that were pathologically confirmed.
RESULTSComparing with atypical simple cysts, symptoms, left-lobe cyst, thick wall, septation, mural nodule, bile duct dilatation and an increase of serum alkaline phosphatase were associated with BCTs. However, on multivariate analysis, mural nodule, left-lobe cyst, and an increase of serum alkaline phosphatase were significantly frequent in BCTs with odds ratios of 75.5, 13.8, and 33.0, respectively. Among the 20 BCTs, seven BCACs were diagnosed. The characteristics of BCACs were mural nodule (P<0.01), intrahepatic cyst debris (P<0.01), and bile duct dilation (P=0.04). Cystic fluid analysis provided no significant differences between BCT and simple cyst. After fine needle aspiration cytology of BCTs, all except one BCAC with atypical cell showed nonspecific findings. After complete surgical excision (97.4% of patients), only one patient with BCAC had recurrence during 29 months of follow-up period.
CONCLUSIONIn hepatic cysts with mural nodule, left-lobe cyst or increment of serum alkaline phosphatase seem to be indicative of BCTs in the diagnosis of suspicious hepatic cyst. Intracystic debris, bile duct dilation, and mural nodule may be suggestive clinical features of malignancy in BCTs.
ObjectiveA new risk stratification system was proposed to estimate the risk of recurrence in patients with differentiated thyroid carcinoma (DTC) using the response to initial therapy. Here, we ...describe the modified dynamic risk stratification system, which takes into consideration the status of serum anti-Tg antibody (TgAb), and validate this system for assessing the risk of recurrence in patients with DTC.Patients and methodsPatients who underwent total thyroidectomy with radioiodine remnant ablation due to DTC between 2000 and 2005 were included. We classified patients into four groups based on the response to the initial therapy (‘excellent’, ‘acceptable’, ‘biochemical incomplete’, and ‘structural incomplete’ response).ResultsThe median follow-up period of 715 patients with DTC was 8 years. The response to initial therapy was an important risk predictor for recurrent/persistent DTC. The relative risks (95% CI) of recurrence were 16.5 (6.3–43.0) in the ‘acceptable response’ group, 41.3 (15.4–110.8) in the ‘biochemical incomplete response’ group, and 281.2 (112.9–700.5) in the ‘structural incomplete response’ group compared with the ‘excellent response’ group (P<0.001, P<0.001, and P<0.001 respectively). The disease-free survival rate of the ‘excellent response’ group to initial therapy was 98.3% whereas that of the ‘structural incomplete response’ group was only 6.8%.ConclusionsOur study validates the usefulness of the modified dynamic risk stratification system including the status of serum TgAb for predicting recurrent/persistent disease in patients with DTC. Personalized risk assessment using the response to initial therapy could be useful for the follow-up and management of patients with DTC.
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