Cel-CS1K: A Celastrol-Chitosan Conjugate for Treating Diet-Induced Obesity.

Celastrol (Cel), extracted from Tripterygium wilfordii Hook, is a potential antiobesity drug, except for its adverse reactions in clinic. In the present study, we synthesized a promising celastrol-chitosan conjugate (Cel-CS1K) and evaluated its antiobesity effect and biological safety in diet-induced obese mice. Cel-CS1K showed higher drug loading (over 10 wt %), good solubility (18-19 mg/mL) in water, slower peak time (Tmax = 4 h), and clearance (T1/2 = 8.97 h) in rats. Cel-CS1K effectively attenuated the cytotoxicity, celastrol-induced apoptosis, and fat accumulation of hepatocytes. Cel-CS1K reduced body weight and dietary amount same as the free Cel but with lower toxicity in blood, liver, and testis. Cel-CS1K improved the glucose homeostasis, HDL-C level, insulin sensitivity, and leptin sensitivity, while it significantly reduced the gene expression levels of LDL-C, TG, and TC in obese mice. Furthermore, the adipose-related gene expression levels provided evidence in support of a role for Cel-CS1K in losing weight by the multimode regulation. Overall, Cel-CS1K provides a translatable therapeutic strategy for the treatment of diet-induced obese humans.

Altered spontaneous brain activities in maintenance hemodialysis patients with cognitive impairment and the construction of cognitive function prediction models.

OBJECTIVE: The brain neuromechanism in maintenance hemodialysis patients (MHD) with cognitive impairment (CI) remains unclear. The study aimed to probe the relationship between spontaneous brain activity and CI by using resting-state functional magnetic resonance imaging (rs-fMRI) data. METHODS: Here, 55 MHD patients with CI and 28 healthy controls were recruited. For baseline data, qualitative data were compared between groups using the χ2 test; quantitative data were compared between groups using the independent samples t-test, ANOVA test, Mann-Whitney U-test, or Kruskal-Wallis test. Comparisons of ALFF/fALFF/ReHo values among the three groups were calculated by using the DPABI toolbox, and then analyzing the correlation with clinical variables. p < .05 was considered a statistically significant difference. Furthermore, back propagation neural network (BPNN) was utilized to predict cognitive function. RESULTS: Compared with the MHD-NCI group, the patients with MHD-CI had more severe anemia and higher urea nitrogen levels, lower mALFF values in the left postcentral gyrus, lower mfALFF values in the left inferior temporal gyrus, and greater mALFF values in the right caudate nucleus (p < .05). The above-altered indicators were correlated with MOCA scores. BPNN prediction models indicated that the diagnostic efficacy of the model which inputs were hemoglobin, urea nitrogen, and mALFF value in the left central posterior gyrus was optimal (R2 = 0.8054), validation cohort (R2 = 0.7328). CONCLUSION: The rs-fMRI can reveal the neurophysiological mechanism of cognitive impairment in MHD patients. In addition, it can serve as a neuroimaging marker for diagnosing and evaluating cognitive impairment in MHD patients.

Study on the taste-masking effect and mechanism of Acesulfame K on berberine hydrochloride.

OBJECTIVE: In our previous taste-masking study, we found that Acesulfame K (AK) had a better taste-masking effect than other high-efficiency sweeteners for several representative bitter natural drugs in aqueous decoction. Furthermore, we performed a preliminary taste-masking study of AK for representative bitter API Berberine Hydrochloride (BH) and found that it had a good taste-masking effect. We also found that flocculent precipitation was generated in the BH solution, but it was not clear whether it was related to the good taste-masking effect. This study was conducted to explore the taste-masking effect and mechanism of AK on BH. METHODS: The taste-masking effect of AK on BH was evaluated based on the Traditional Human Taste Panel Method and the electronic tongue evaluation method. DSC, XRD, and molecular simulation techniques were used to explore the mechanism of AK on BH, from the macro level and molecular level, respectively. RESULTS: When evaluating the taste-masking effect, we found that 0.1% AK had the best taste-masking effect on BH, while higher concentrations had a worse taste-masking effect. DSC and XRD revealed that the flocculent precipitation was a complex AK-BH. Finally, by simulating the binding of AK, BH, and TAS2R46 receptors, we found the unique taste-masking mechanism of AK. CONCLUSION: The sweet taste stimulus of AK can mask the bitter taste stimulus of BH, and AK can generate AK-BH with BH to reduce the contact between BH and bitter taste receptors. Additionally, it could block the expression of the TAS2R46 receptors.

[Effects of intranasal administration of tripterygium glycoside-bearing liposomes on behavioral cognitive impairment of mice induced by central nervous system inflammation].

Tripterygium glycosides liposome(TPGL) were prepared by thin film-dispersion method, which were optimized accor-ding to their morphological structures, average particle size and encapsulation rate. The measured particle size was(137.39±2.28) nm, and the encapsulation rate was 88.33%±1.82%. The mouse model of central nervous system inflammation was established by stereotaxic injection of lipopolysaccharide(LPS). TPGL and tripterygium glycosides(TPG) were administered intranasally for 21 days. The effects of intranasal administration of TPG and TPGL on behavioral cognitive impairment of mice due to LPS-induced central ner-vous system inflammation were estimated by animal behavioral tests, hematoxylin-eosin(HE) staining of hippocampus, real-time quantitative polymerase chain reaction(RT-qPCR) and immunofluorescence. Compared with TPG, TPGL caused less damage to the nasal mucosa, olfactory bulb, liver and kidney of mice administered intranasally. The behavioral performance of treated mice was significantly improved in water maze, Y maze and nesting experiment. Neuronal cell damage was reduced, and the expression levels of inflammation and apoptosis related genes [tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), BCL2-associated X(Bax), etc.] and glial activation markers [ionized calcium binding adaptor molecule 1(IBA1) and glial fibrillary acidic protein(GFAP)] were decreased. These results indicated that liposome technique combined with nasal delivery alleviated the toxic side effects of TPG, and also significantly ameliorated the cognitive impairment of mice induced by central nervous system inflammation.

The correlation of pericoronary adipose tissue with coronary artery disease and left ventricular function.

OBJECTIVE: We sought to investigate the correlation of pericoronary adipose tissue with coronary artery disease and left ventricular (LV) function. METHODS: Participants with clinically suspected coronary artery disease were enrolled. All participants underwent coronary computed tomography angiography (CCTA) and echocardiography followed by invasive coronary angiography (ICA) within 6 months. Pericoronary adipose tissue (PCAT) was extracted to analyze the correlation with the Gensini score and LV function parameters, including IVS, LVPW, LVEDD, LVESD, LVEDV, LVESV, FS, LVEF, LVM, and LVMI. The correlation between PCAT and the Gensini score was assessed using Spearman's correlation analysis, and that between the PCAT volume or FAI and LV function parameters was determined using partial correlation analysis. RESULTS: One hundred and fifty-nine participants (mean age, 64.55 ± 10.64 years; men, 65.4% [104/159]) were included in the final analysis. Risk factors for coronary artery disease, such as hypertension, diabetes, dyslipidemia, and a history of smoking or drinking, had no significant association with PCAT (P > 0.05), and there was also no correlation between PCAT and the Gensini score. However, the LAD-FAI was positively correlated with the IVS (r = 0.203, P = 0.013), LVPW (r = 0.218, P = 0.008), LVEDD (r = 0.317, P < 0.001), LVESD (r = 0.298, P < 0.001), LVEDV (r = 0.317, P < 0.001), LVESV (r = 0.301, P < 0.001), LVM (r = 0.371, P < 0.001), and LVMI (r = 0.304, P < 0.001). Also, the LCX-FAI was positively correlated with the LVEDD (r = 0.199, P = 0.015), LVESD (r = 0.190, P = 0.021), LVEDV (r = 0.203, P = 0.013), LVESV (r = 0.197, P = 0.016), LVM (r = 0.220, P = 0.007), and LVMI (r = 0.172, P = 0.036), and the RCA-FAI was positively correlated with the LVEDD (r = 0.258, P = 0.002), LVESD (r = 0.238, P = 0.004), LVEDV (r = 0.266, P = 0.001), LVESV (r = 0.249, P = 0.002), LVM (r = 0.237, P = 0.004), and LVMI (r = 0.218, P = 0.008), respectively. Finally, the total volume was positively correlated with FS (r = 0.167, P = 0.042). CONCLUSION: The FAI was positively correlated with the LV function but was not associated with the severity of coronary artery disease.

SnO2 quantum dots-functionalized Ti3C2 MXene nanosheets for electrochemical determination of dopamine in body fluids.

A novel SnO2 quantum dots (SnO2QDs)-functionalized Ti3C2 MXene nanocomposite was prepared via in situ synthesis method, resulting in well-regulated the nucleation and growth of SnO2QDs to evenly distribute onto MXene nanosheets. Ultra-small size SnO2QDs decorated on the surface of Ti3C2 MXene nanosheets can effectively prevent the restacking of MXene and remarkably increase the electroactive surface area of the electrode, which can further increase electrocatalytic activity toward dopamine. Then, an ultrasensitive electroanalytical method based on SnO2QDs-functionalized Ti3C2 MXene nanocomposite for dopamine monitoring was developed, and the effects of experimental condition were investigated systematically. Under optimized conditions, the prepared sensor presented a linear dependence for dopamine in the concentration range from 0.004 to 8.0 µM with the detection limit of 2.0 nM (S/N = 3). Moreover, it selectively perceived dopamine in presence of physiological interferents in urine and serum samples with excellent linearities (correlation coefficients higher than 0.9920). The relative recoveries were in the range 97.67-105.3% and 103.0-106.8%, while the limits of quantitation were 10.12 nM and 9.62 nM in urine and serum sample, respectively, demonstrating the method suitability for dopamine sensing and being envisioned as a promising candidate for neurotransmitter monitoring in biological diagnosis.

TP-CSO: A Triptolide Prodrug for Pancreatic Cancer Treatment.

Triptolide (TP) is a potential drug candidate for the treatment of cancer, but its use was hampered by its systemic toxicity and poor water solubility. Hence, a TP-CSO prodrug was synthesized by conjugating TP to chitosan oligosaccharide (CSO), and characterized by 1H NMR, FTIR, DSC and XRD analyses. The TP-CSO containing about 4 wt% of TP exhibited excellent water solubility (15 mg/mL) compared to TP (0.017 mg/mL). Compared with TP, the pharmacokinetics of the conjugate after oral administration showed a three-fold increase in the half-life in the blood circulation and a 3.2-fold increase in AUC (0-∞). The orally administered TP-CSO could more effectively inhibit tumor progression but with much lower systemic toxicity compared with TP, indicating significant potential for further clinical trials. In conclusion, CSO-based conjugate systems may be useful as a platform for the oral delivery of other sparingly soluble drugs.

Novel Ascorbic Acid Co-Crystal Formulations for Improved Stability.

A series of co-crystals of ascorbic acid were prepared with equimolar amounts of co-crystal formers (CCFs), including isonicotinic acid, nicotinic acid, 3,4-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid and m-hydroxybenzoic acid, by slow solvent evaporation and solvent-assisted grinding. The co-crystals were characterized by single-crystal X-ray diffraction spectroscopy, powder X-ray diffraction, IR spectroscopy, differential scanning calorimetry and thermogravimetric analysis. Molecular dynamics (MD) simulations further validated the interaction energy and the possible intermolecular hydrogen bonds among VC and CCFs. The co-crystals showed improved stability when exposed to different wavelengths of light, pH and temperatures compared to the free analogue, especially at higher pH (~9) and lower temperature (~4 °C).

[Mechanism of Puerariae Lobatae Radix against lung cancer by inhibiting histone demethylase LSD1].

Histone lysine-specific demethylase 1(LSD1) has become a promising molecular target for lung cancer therapy. Upon the screening platform for LSD1 activity, some Chinese herbal extracts were screened for LSD1 activity inhibition, and the underlying mechanism was preliminarily investigated at both molecular and cellular levels. The results of LSD1 inhibition showed that Puerariae Lobatae Radix extract can effectively reduce LSD1 expression to elevate the expression of H3 K4 me2 and H3 K9 me2 substrates in H1975 and H1299 cells. Furthermore, Puerariae Lobatae Radix was evaluated for its anti-lung cancer activity. It had a potent inhibitory ability against the proliferation and colony formation of both H1975 and H1299 cells. Flow cytometry and DAPI staining assays indicated that Puerariae Lobatae Radix can induce the apoptosis of lung cancer cells. In addition, it can significantly suppress the migration and reverse the epithelial-mesenchymal transition(EMT) process of lung cancer cells by activating E-cadherin and suppressing the expression of N-cadherin, slug and vimentin. To sum up, Puerariae Lobatae Radix displayed a robust inhibitory activity against lung cancer, and the mechanism may be related to the down-regulation of LSD1 expression to induce the cell apoptosis and suppress the cell migration and EMT process. These findings will provide new insights into the action of Puerariae Lobatae Radix as an anti-lung cancer agent and offer new ideas for the study on the anti-cancer action of Chinese medicine based on the epigenetic modification.

Preparation of Progesterone Co-Crystals Based on Crystal Engineering Strategies.

Three co-formers of 2-chloro-4-nitroaniline (CNA), 2,5-dihydroxybenzoic acid (DHB), and 4,4'-biphenol (DOD) were selected to prepare the co-crystal of progesterone (PROG) based on crystal engineering strategies. These co-crystals were successfully obtained via slow evaporation from different solutions and were characterized by single-crystal X-ray diffraction spectroscopy, powder X-ray diffraction, IR spectroscopy, and differential scanning calorimetry. Different binding networks were observed in the co-crystal structures of PROG. The PROG-CNA co-crystal had the fastest rates and highest concentrations of PROG in PBS solution compared with PROG or other co-crystals in the dissolution experiments. This might be attributable to more stable and abundant interactions between the PROG and CNA molecules. Our investigations provide positive support for the selection of suitable co-formers using crystal engineering strategies.

Effects of Portulaca Oleracea Extract on Acute Alcoholic Liver Injury of Rats.

The present study was envisaged to investigate the chemical constituents and the intervention effects of Portulaca oleracea extract (POE) on acute alcoholic liver injury of rats. The chemical composition of POE was detected by high performance liquid chromatography (HPLC). Sixty male Wistar rats were divided into 6 groups: Normal control (NC) group, acute alcoholic liver injury model group (ALI), low, medium and high dose of POE (25, 50, 100 mg/kg) groups and bifendate (BF, 3.75 mg/kg) group. Each group was given by intragastrical administration for 7 days. Alcoholic liver injury was induced in the experimental model by administering 50% ethanol at 8 mL/kg and repeated administration after 6 h, for a period of 7 days. The results showed that pretreatment with POE significantly reduced the ethanol-elevated serum level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and triglyceride (TG). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in liver were enhanced followed by administration of POE, while the content of nitric oxide (NO) and malondialdehyde (MDA) was found to decrease. Hepatic content of tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was also reduced by POE treatment. These results indicated that POE could increase the antioxidant capacity and relieve the inflammatory injury of the liver cells induced by ethanol. Meanwhile, in our study, POE reduced the expression of miR-122, acetyl coenzyme A carboxylase (ACC) 1 mRNA and protein and increased the expression of lipoprotein lipase (LPL) mRNA and protein in liver, which indicated that POE could improve the lipid metabolism disorder induced by ethanol. Our findings suggested that POE had protective effects on acute alcoholic liver injury of rats.

Discrete stacking of aromatic oligoamide macrocycles.

Unlike the precise structural control typical of closed assemblies, curbing the stacking of disc- and ring-shaped molecules is quite challenging. Here we report the discrete stacking of rigid aromatic oligoamide macrocycles 1. With increasing concentration, the aggregation of 1 quickly plateaus, forming a discrete oligomer, as suggested by 1D (1)H, 2D nuclear Overhauser effect, and diffusion-ordered NMR spectroscopy. Quantum-chemical calculations indicate that the tetramer of 1 is the most stable among oligomeric stacks. X-ray crystallography revealed a tetrameric stack containing identical molecules adopting two different conformations. With a defined length and an inner pore capable of accommodating distinctly different guests, the tetramers of 1 densely pack into 2D layers. Besides being a rare system of conformation-regulated supramolecular oligomerization, the discrete stacks of 1, along with their higher-order assemblies, may offer new nanotechnological applications.

Improving the Solubility and Bioavailability of Progesterone Cocrystals with Selected Carboxylic Acids.

Progesterone (PROG) is a natural steroid hormone with low solubility and high permeability that belongs to biopharmaceutics classification system class II. In this study, novel pharmaceutical cocrystals of PROG were successfully prepared by solvent evaporation or a liquid-assisted grinding process aimed at enhancing its solubility and bioavailability. The cocrystal formers selected based on crystal engineering principles were carboxylic acids, namely, 4-formylbenzeneboronic acid (BBA), isophthalic acid (IPA), and 3-nitrophthalic acid (NPA). The cocrystal structures were characterized using multiple techniques. Single-crystal X-ray diffraction results showed that the carbonyl group, acting as a hydrogen bond acceptor, was pivotal in the cocrystal network formation, with C-H···O interactions further stabilizing the crystals. The cocrystals exhibited improved solubility and dissolution profiles in vitro, with no significant changes in hygroscopicity. The parallel artificial membrane permeability assay (PAMPA) models indicated that the cocrystals retained PROG's high permeability. Pharmacokinetic studies in Sprague-Dawley rats revealed that all cocrystals increased PROG exposure, with AUC(0~∞) values for PROG-BBA, PROG-IPA, and PROG-NPA being 742.59, 1201.72 and 442.67 h·ng·mL-1, respectively. These values are substantially higher compared to free PROG, which had an AUC(0~∞) of 301.48 h·ng·mL-1. Notably, PROG-IPA provided the highest AUC improvement, indicating a significant enhancement in bioavailability. Collectively, the study concludes that the cocrystal approach is a valuable strategy for optimizing the physicochemical properties and oral bioavailability of PROG, with potential implications for the development of other poor water-soluble drugs.

Morphological variation in Schizothorax oconnori, Schizothorax waltoni (Teleostei: Cyprinidae: Schizothoracinae), and their natural hybrids from the middle Yarlung Zangbo River, Tibet.

The morphological variation in Schizothorax oconnori, Schizothorax waltoni, and their natural hybrids was examined using conventional and image-based analysis approaches. In total, 38 specimens of S. oconnori, 35 of S. waltoni, and 37 natural hybrids were collected from the Shigatse to the Lhasa section of the Yarlung Zangbo River during June and July 2021. A total of 21 morphometric, 4 meristic, and 27 truss variables were employed for the classification of S. oconnori, S. waltoni, and natural hybrids. Principal component analysis (PCA) and factor analysis (FA), as well as discriminant function analysis (DFA) and cluster analysis (CA), were conducted to identify differences based on traditional and truss measurements. Four principal components explained 75.92% of the variation among the morphometric characters, while five principal components accounted for 79.69% of the variation among the truss distances. FA results showed that factor 1 was associated with head shape, and factor 2 was associated with fins based on morphometric characters. Among the truss characters, factor 1 was related to head shape, and factor 2 was related to chest shape. In DFA, morphometric measurements achieved higher accuracy (100%) compared to truss distances (94.55%). The head morphology of hybrids exhibited intermediate traits between S. oconnori and S. waltoni. Both morphometry-based and truss-based clustering indicated that the morphology of natural hybrids leaned toward S. oconnori. In conclusion, the combination of morphometric and truss analysis is beneficial for classifying S. oconnori, S. waltoni, and their natural hybrids. The presence of natural hybrids could be considered an evolutionary response to the differentiation of nutritional and spatial niches in the middle Yarlung Zangbo River.

Oleanolic acid derivative self-assembled aggregates based on heparin and chitosan for breast cancer therapy.

Oleanolic acid is an active ingredient from natural products with anti-breast cancer activity. However, the poor solubility in water and low bioavailability have limited its effectiveness in clinic. To improve the anticancer activity of oleanolic acid, we synthesized a novel oleanolic quaternary ammonium (QDT), which, driven by electrostatic interactions, was introduced into heparin and coated with chitosan to obtain a QDT/heparin/chitosan nanoaggregate (QDT/HEP/CS NAs). QDT/HEP/CS NAs showed the negative zeta potential (-35.01 ± 4.38 mV), suitable mean particle size (150.45 ± 0.68 nm) with strip shape, and high drug loading (36 %). The coated chitosan had strong anti-leakage characteristics toward QDT under physiological conditions. More importantly, upon sustained release in tumor cells, QDT could significantly decrease the mitochondrial membrane potential and induce apoptosis of breast cancer cells. Further in vivo antitumor study on 4 T1 tumor-bearing mice confirmed the enhanced anticancer efficacy of QDT/HEP/CS NAs via upregulation of caspase-3, caspase-9 and cytochrome C, which was attributed to the high accumulation in tumor via the enhanced permeability and retention effect. Moreover, QDT/HEP/CS NAs significantly enhanced the biosafety and biocompatibility of QDT in vitro and in vivo. Collectively, the development of QDT/HEP/CS NAs with high antitumor activity, favorable biodistribution and good biocompatibility provided a safe, facile and promising strategy to improve the anti-cancer effect of traditional Chinese medicine ingredients.

Platforms of graphene/MXene heterostructure for electrochemical monitoring of rutin in drug and Tartary buckwheat tea.

The use of two-dimensional heterostructure composite as electrode modification material has become a new strategy to improve the electrocatalytic activity and electroactive sites of electrochemical sensor. Herein, a soluble heterostructure, namely rGO-PSS@MXene, was designed and synthesized by integrating poly (sodium p-styrenesulfonate)-functionalized reduced graphene oxide into MXene nanosheets via ultrasonic method. The interactive heterostructure can effectively alleviate the self-stacking of MXene and rGO, endowing them with superior electron transfer capacity and large specific surface area, thereby producing prominent synergistic electrocatalytic effect towards rutin. In addition, the excellent enrichment effect of rGO-PSS@MXene for rutin also plays an important role through the electrostatic and π-π stacking interactions. The electrochemical characteristics of rutin on the sensor were examined in detail and a sensitive sensing method was proposed. Under optimized conditions, the method showed satisfactory linear relationship for rutin in the concentration range of 0.005-10.0 µM, with limit of detection of 1.8 nM (S/N = 3). The quantitative validation results in herbal medicine and commercial Tartary buckwheat tea were highly consistent with the labeled quantity and the results of HPLC determination, respectively, suggesting the sensor possessed excellent selectivity and accuracy. This proposed strategy for rutin determination is expected to expand the application of MXene heterostructure in electrochemical sensors, and is envisioned as a promising candidate for quality monitoring of drugs and foods.

Clinical evolution of antisynthetase syndrome-associated interstitial lung disease after COVID-19 in a man with Klinefelter syndrome: A case report.

BACKGROUND: This study presents a case of rapidly developing respiratory failure due to antisynthetase syndrome (AS) following coronavirus disease 2019 (COVID-19) in a 33-year-old man diagnosed with Klinefelter syndrome (KS). CASE SUMMARY: A 33-year-old man with a diagnosis of KS was admitted to the Department of Pulmonary and Critical Care Medicine of a tertiary hospital in China for fever and shortness of breath 2 wk after the onset of COVID-19. Computed tomography of both lungs revealed diffuse multiple patchy heightened shadows in both lungs, accompanied by signs of partial bronchial inflation. Metagenomic next-generation sequencing of the bronchoalveolar lavage fluid suggested absence of pathogen. A biopsy specimen revealed organizing pneumonia with alveolar septal thickening. Additionally, extensive auto-antibody tests showed strong positivity for anti-SSA, anti-SSB, anti-Jo-1, and anti-Ro-52. Following multidisciplinary discussions, the patient received a final diagnosis of AS, leading to rapidly progressing respiratory failure. CONCLUSION: This study underscores the clinical progression of AS-associated interstitial lung disease subsequent to viral infections such as COVID-19 in patients diagnosed with KS.

Combination therapy using Cel-CSO/Taxol NPs for reversing drug resistance in breast cancer through inhibiting PI3K/AKT/NF-κB/HIF-1α pathway.

The resistance of malignant tumors to multiple drugs is a significant obstacle in cancer treatment and prognosis. Accordingly, we synthesized a celastrol (Cel) prodrug (Cel-CSO) by conjugating chitosan oligosaccharides (CSO) to Cel for reversing Taxol resistance in chemotherapy, followed by self-assembly with Taxol into a novel nanoplatform of Cel-CSO/Taxol nanoparticles (termed NPs). NPs showed a suitable size (about 153 nm), excellent stability and prolonged release of Cel and Taxol in a manner that depended on both pH and time. NPs effectively inhibited the overexpression of multidrug resistance-related protein P-gp, hypoxia inducible factor-1α (HIF-1α), and triggered the MCF-7/Taxol cell apoptosis through inhibiting the PI3K/AKT/NF-κB/HIF-1α pathway. In tumor-bearing mice, NPs exhibited significant curative effects in inducing apoptosis of MCF-7/Taxol tumors which showed a low expression level of P-gp, microtubule-related proteins TUBB3 and Tau. The results indicated that NPs may be a promising strategy to overcome drug resistance caused by P-gp, which improve the antitumor effects in drug-resistant breast cancer.

Evaluation of risk factors for venous thromboembolism in Chinese women with epithelial ovarian cancer.

OBJECTIVE: Venous thromboembolism (VTE) is a life-threatening complication that often occurs in ovarian tumors. However, the risk factors for VTE are still undetermined. METHODS: We retrospectively analyzed VTE occurrence and its potential risk factors in 254 Chinese patients with ovarian tumor at Fudan University Cancer Hospital from July 2007 to June 2011. RESULTS: The VTE incidence was 7.1% (13/183) in epithelial ovarian cancer (EOC), and no VTE was found in ovarian borderline or benign tumor. D-dimer levels were significantly higher in EOC than in ovarian benign and borderline tumors. Furthermore, D-dimer levels increased with the advancement of EOC stages. Correlation analysis suggested that D-dimer levels were well correlated with platelet counting (PLT), prothrombin time (PT), white blood cell counting (WBC), cancer antigen (CA) 125, and CA153. Univariate logistic regression analysis found that D-dimer levels greater than 788 µg/L, PLT levels greater than 261 × 10(9)/L, PT greater than 11.7 seconds, CA125 greater than 760 U/mL, and ascites greater than 1500 mL are risk factors for VTE in EOC. Moreover, multivariate analysis grouped primary EOC, low differentiated grade, D-dimer greater than 788 µg/L, PT greater than 11.7 seconds, and CA125 greater than 760 U/mL as prediction factors for VTE. CONCLUSIONS: In addition to D-dimer and ascites, high levels of PLT, PT, and CA125, which are highly correlated with D-dimer, are independent risk factors for VTE.

Preliminary studies of a novel cyclopentadienyl tricarbonyl technetium-99m fatty acid derivative for myocardical imaging.

This study reports the synthesis and evaluation studies of 6'-cyclopentadienyl tricarbonyl technetium-99m 6'-oxo-11-(hexanamide)undecanoic acid (1). 1 was prepared with 26.5 ± 4.3% of radiochemical yield and more than 98% of radiochemical purity. Tissue distribution in mice showed that high radioactivity accumulated in the heart with moderate clearance. However, unfortunately, similar to those of other technetium-labeled fatty acid analogs, the biodistribution studies of 1 in mice showed poor heart-to-blood ratios, which suggested that 1 cannot be used as myocardial imaging agent, and it may provide a theoretical basis or a lab experience for corresponding fatty acid tracers studies.