Natural curcumin (
1), demethoxycurcumin (
2) and bisdemethoxycurcumin (
3) isolated from
Curcuma longa (turmeric), and synthetic curcumin analogs (
A
1–7
,
B
1–7
,
C
1–6
and
D
1–7
) were evaluated ...in vitro for the α-glucosidase inhibitory activity via UV and circular dichroism (CD) spectroscopy. The results indicated that natural curcuminoid compound
3 showed a remarkable inhibitory effect with IC
50 of 23.0 μM, and the synthetic compounds
A
2
,
B
2
,
C
2
and
D
2
showed potent inhibitory effects with IC
50 of 2.8, 2.6, 1.6 and 8.2 μM, respectively. Kinetic study exhibited that the mechanism of α-glucosidase inhibition of both
3 and
C
2
was non-competitive. The structure activity relationship revealed that the
ortho dihydroxyl groups could form a more tight interaction with α-glucosidase to exert more potential inhibitory activities.
To investigate transmission patterns of diabetes and their relationships with clinical characteristics in Hong Kong Chinese patients with late-onset (age > or =35 years) type 2 diabetes.
This study ...involved 2,310 patients consecutively selected from a hospital clinic-based diabetes registry. These patients all reported the diabetes status of their parents as well as siblings.
Approximately 36% of the 2,310 patients reported at least 1 affected parent or sibling (25 and 21% reported at least 1 diabetic parent and sibling, respectively). These patients, irrespective of their sex, were more likely to have a diabetic mother than a diabetic father (17 vs. 13% of the male patients and 18 vs. 9% of the female patients, P<0.01). The male patients were more likely than the female patients to have a diabetic father (13 vs. 9%, P<0.01). The female patients with a diabetic mother were found to have higher levels of plasma total cholesterol compared with the female patients with a diabetic father in multiple comparisons with adjustment for significance (5.56+/-1.30 vs. 5.09+/-0.95 mmol/l, P<0.05). In 2-group comparisons, there was also evidence that the male patients with a diabetic father had higher BMI values than the male patients with a diabetic mother (25.9+/-3.5 vs. 25.0+/-3.5 kg/m2, P<0.05).
We found familial clustering of diabetes in the Hong Kong Chinese population as well as a significant maternal influence and a male sex-specific paternal effect. We suggest that both maternal and paternal factors may be implicated in the development of type 2 diabetes in the Chinese population.
The transcription factor C/EBPα is required for granulopoiesis and frequently disrupted in human acute myeloid leukemia (AML). Here, we show disruption of C/EBPα blocks the transition from the common ...myeloid to the granulocyte/monocyte progenitor but is not required beyond this stage for terminal granulocyte maturation. C/EBPα-deficient hematopoietic stem cells (HSCs) have increased expression of Bmi-1 and enhanced competitive repopulating activity. Bone marrow in adult C/EBPα-deficient mice was filled with myeloblasts, similar to human AML, supporting the notion that disruption of C/EBPα cooperates with other events in the development of leukemia. Therefore, C/EBPα is not only essential for granulocyte development but, in addition, is a regulator of hematopoietic stem cell activity.
Cancer is thought to arise from multiple genetic events that establish irreversible malignancy. A different mechanism might be present in certain leukaemias initiated by a chromosomal translocation. ...We have taken a new approach to determine if ablation of the genetic abnormality is sufficient for reversion by generating a conditional transgenic model of BCR-ABL1 (also known as BCR-ABL)-induced leukaemia. This oncogene is the result of a reciprocal translocation and is associated with different forms of leukaemia. The most common form, p210 BCR-ABL1, is found in more than 90% of patients with chronic myelogenous leukaemia (CML) and in up to 15% of adult patients with de novoacute lymphoblastic leukaemia (ALL). Efforts to establish a useful transgenic model have been hampered by embryonic lethality when the oncogene is expressed during embryogenesis, by reduced penetrance or by extremely long latency periods. One model uses the 'knock-in' approach to induce leukaemia by p190 BCR-ABL1(ref. 10). Given the limitations of models with p210, we used a different experimental approach. Lethal leukaemia developed within an acceptable time frame in all animals, and complete remission was achieved by suppression of BCR-ABL1expression, even after multiple rounds of induction and reversion. Our results demonstrate that BCR-ABL1is required for both induction and maintenance of leukaemia.
The low melting point of Zn and the high melting point of ZnO, as well as their hexagonal crystal structures, present great advantages for designing and fabricating various metal/semiconductor ...core/shell nanostructures. By controlling the kinetics in the Zn and ZnO system, the lower‐energy facets, and the oxidation rates of different surfaces, we can control the fabrication of Zn/ZnO core/shell single‐crystal, polycrystalline, and mesoporous nanodisks, as well as a variety of ZnO nanotubes. The oxidation of a Zn nano‐object leads to the formation of Zn/ZnO core/shell nanodisks. A lower oxidation temperature results in the formation of a single‐crystal‐like Zn/ZnO core/shell structure, while a higher oxidation temperature leads to the formation of textured and even polycrystalline nanostructures. A re‐sublimation process of Zn in the core leaves a ZnO shell structure. This is an approach for synthesizing metal/semiconductor core/shell or composite nanostructures. This article offers a detailed description of the kinetics controlling the procedures, the nanostructures obtained, their morphological and crystal structures, and their formation mechanisms.
By controlling the kinetics in the Zn/ZnO system, the lower energy facets, and the oxidation rates of different surfaces, Zn/ZnO core/shell single‐crystal, polycrystalline, and mesoporous nanodisks, as well as a variety of nanotubes of ZnO can be fabricated (see Figure). The kinetics controlling the procedures and the formation mechanisms of the nanostructures are reported.
Pancreatic cancer, associated with poor prognosis and low survival rate, has been the fourth leading cause of cancer-related death in the US. Although gemcitabine (Gem) is the first-line ...chemotherapeutic drug in the management of pancreatic cancer, the median survival extension is only 1.5 months, indicating unsatisfactory clinical results. Therefore, exploring agents that can enhance the anti-cancer activity of Gem would be an attractive strategy.
Our previous studies have demonstrated that eriocalyxin b (EriB), an ent‑kaurane diterpenoid isolated from Isodon eriocalyx (Dunn.) Hara, possesses anti-pancreatic cancer effects, thus acting as a potential therapeutic agent. In this study, we further investigated whether EriB or the ethanol extract of I. eriocalyx (Isodon) could potentiate the cytotoxic activity of Gem in human pancreatic adenocarcinoma cells. In addition, the mechanism associated with their effects was also studied.
The anti-proliferation effect was assessed by MTT assay and Ki-67 immunostaining. The combination effect (addition, synergism and antagonism) of various agents was calculated by the Calcusyn software (Biosoft), utilizing the T.C. Chou Method. Apoptosis was detected using Annexin V and PI double staining followed by quantitative flow cytometry. Protein expression regulated by various treatments was analyzed by western blotting.
The combination index revealed that Gem and EriB (or Isodon extract) had synergistic anti-proliferative effect. Both cellular apoptotic and anti-proliferative effects of Gem were significantly increased after combination with EriB (or Isodon extract). The underlying mechanisms involved in the combination effects were elucidated, which include: (1) increased activation of the caspase cascade; (2) reduction of PDK1 and AKT phosphorylation; (3) induction of JNK phosphorylation by Isodon and Gem combination.
Gem and EriB (or Isodon extract) taken together in combination regulated PDK1/AKT1/caspase and JNK signaling and promoted apoptosis synergistically, which may contribute to the much increased anti-proliferative activity compared to either agent alone.
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Outstanding problems in magnetospheric substorms include what causes substorm onsets and whether substorms have some specific periodicity. This paper provides observations and interpretations that ...relate to these problems. We study a specific type of geosynchronous particle injections during magnetic storms and the possible relationship between the solar wind and injections. Three storm events are analyzed: the March–April 2001, October 2000, and September 1998 storms. During the main phase or initial recovery phase of the storms, recurrent particle injections with a period of 2–3 hours were observed by geosynchronous satellites. The particle fluxes exhibited a well‐defined “sawtooth” profile with gradual decreases (flux dropouts) followed by rapid increases (injections). The sawtooth injections coincided well with AE increases and are interpreted as the signature of periodic substorms. In one case, sawtooth substorm injections were correlated with continuous solar wind pressure oscillations. In two other cases, sawtooth substorm injections occurred after a solar wind pressure impulse arrived at the magnetosphere. The observations show that substorms during storm times can be indeed periodic with a period of 2–3 hours and that solar wind variations may trigger the periodic substorms. We suggest that magnetospheric substorms have an intrinsic cycle time of 2–3 hours. If solar wind pressure oscillations with periods comparable to the substorm cycle time are imposed on the magnetosphere, some magnetospheric resonant state may be excited, and periodic substorms can be triggered. Otherwise, if the solar wind oscillates too fast, not enough energy is accumulated in the magnetotail for substorms to occur; if the period of solar wind pressure oscillations is too long, magnetospheric energy may be released through other processes including internally triggered substorms.
Abstract Background The boundary of nephroureterctomy has been revisited and lymph node dissection has been recommended recently. We investigated the role of synchronous ipsilateral adrenalectomy in ...treating patients with upper tract urothelial carcinoma. Methods 110 patients with clinically localized upper tract urothelial carcinoma treated by nephroureterectomy and bladder cuff resection were retrospectively evaluated. 70 patients underwent nephroureterectomy without concomitant ipsilateral adrenalectomy, whereas nephroureterectomy and ipsilateral adrenalectomy was performed in other 40 patients. Cancer specific, metastasis and local recurrence free survival during a follow-up of median 46 months were analyzed. Results No patient had adrenal metastasis among the 40 adrenalectomized patients. A total of 4 patients developed local recurrences; including 1 of the 70 adrenalectomy-sparing and 3 of the 40 adrenalectomized patients ( p = 0.102, chi-square test). Five patients with adrenalectomy and four without adrenalectomy had distant metastases ( p = 0.212, chi-square test). The five-year local recurrence free survival ( p = 0.09, log-rank test), metastasis-free survival ( p = 0.292, log-rank test), and cancer-specific survival ( p = 0.117, log-rank test) did not have significant difference between both groups. Conclusions This is the only study in recent 2 decades to evaluate the necessity of synchronous adrenalectomy in treating localized upper tract urothelial carcinoma. Adrenal-sparing nephroureterectomy seems justified for clinically localized upper tract urothelial carcinoma.
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