Curcumin alleviates orofacial allodynia and improves cognitive impairment via regulating hippocampal synaptic plasticity in a mouse model of trigeminal neuralgia.

OBJECTIVE: Cognitive impairment, one of the most prevalent complications of trigeminal neuralgia, is troubling for patients and clinicians due to limited therapeutic options. Curcumin shows antinociception and neuroprotection pharmacologically, suggesting that it may have therapeutic effect on this complication. This study aimed to investigate whether curcumin alleviates orofacial allodynia and improves cognitive impairment by regulating hippocampal CA1 region synaptic plasticity in trigeminal neuralgia. METHODS: A mouse model of trigeminal neuralgia was established by partially transecting the infraorbital nerve (pT-ION). Curcumin was administered by gavage twice daily for 14 days. Nociceptive thresholds were measured using the von Frey and acetone test, and the cognitive functions were evaluated using the Morris water maze test. Dendritic spines and synaptic ultrastructures in the hippocampal CA1 area were observed by Golgi staining and transmission electron microscopy. RESULTS: Curcumin intervention increased the mechanical and cold pain thresholds of models. It decreased the escape latency and distance to the platform and increased the number of platform crossings and dwell time in the target quadrant of models, and improved spatial learning and memory deficits. Furthermore, it partially restored the disorder of the density and proportion of dendritic spines and the abnormal density and structure of synapses in the hippocampal CA1 region of models. CONCLUSION: Curcumin alleviates abnormal orofacial pain and cognitive impairment in pT-ION mice by a mechanism that may be related to the synaptic plasticity of hippocampal CA1, suggesting that curcumin is a potential strategy for repairing cognitive dysfunction under long-term neuropathic pain conditions.

The role of T cells in acute ischemic stroke.

Acute ischemic stroke (AIS) is associated with high rates of disability and mortality, exerting a substantial impact on overall survival and health-related quality of life. Treatment of AIS remains challenging given that the underlying pathologic mechanisms remain unclear. However, recent research has demonstrated that the immune system plays a key role in the development of AIS. Numerous studies have reported infiltration of T cells into ischemic brain tissue. While some types of T cells can promote the development of inflammatory responses and aggravate ischemic damage in patients with AIS, other T cells appear to exert neuroprotective effects via immunosuppression and other mechanisms. In this review, we discuss the recent findings regarding the infiltration of T cells into ischemic brain tissue, and the mechanisms governing how T cells can facilitate tissue injury or neuroprotection in AIS. Factors influencing the function of T cells, such as intestinal microflora and sex differences, are also discussed. We also explore the recent research on the effect of non-coding RNA on T cells after stroke, as well as the potential for specifically targeting T cells in the treatment of stroke patients.

Heidihuangwan alleviates renal fibrosis in rats with 5/6 nephrectomy by inhibiting autophagy.

Renal fibrosis is a common pathway for the progression of various chronic kidney diseases (CKD), and the formation and deterioration will eventually lead to end-stage renal failure, which brings a heavy medical burden to the world. HeidihuangWan (HDHW) is a herbal formulation with stable and reliable clinical efficacy in the treatment of renal fibrosis. However, the mechanism of HDHW in treating renal fibrosis is not clear. In this study, we aimed to investigate the mechanism of HDHW to improve renal fibrosis. Wistar rats were randomly divided into the normal control group, 5/6 Nephrectomy group, astragaloside IV (AS-IV) group, HDHW group, and HDHW + IGF-1R inhibitor (JB1) group. Except for the normal control group, the rat renal fibrosis model was established by 5/6 nephrectomy and intervened with drugs for 8 weeks. Blood samples were collected to evaluate renal function. Hematoxylin-Eosin (HE), Periodic Acid-Schiff (PAS), Modified Masson's Trichrome (Masson) staining were used to evaluate the pathological renal injury, and immunohistochemistry and Western blotting were used to detect the protein expression of renal tissue. The results showed that HDHW was effective in improving renal function and reducing renal pathological damage. HDHW down-regulated the levels of fibrosis marker proteins, including α-smooth muscle actin (α-SMA), vimentin, and transforming growth factors-ß(TGF-ß), which in turn reduced renal fibrosis. Further studies showed that HDHW down-regulated the expression of autophagy-related proteins Beclin1 and LC3II, indicating that HDHW inhibited autophagy. In addition, we examined the activity of the class I phosphatidylinositol-3 kinase (PI3K)/serine-threonine kinase (Akt)/mTOR pathway, an important signaling pathway regulating autophagy, and the level of insulin-like growth factor 1 (IGF-1), an upstream activator of PI3K/Akt/mTOR. HDHW upregulated the expression of IGF-1 and activated the PI3K/Akt/mTOR pathway, which may be a vital pathway for its inhibition of autophagy. Application of insulin-like growth factor 1 receptor (IGF-1R) inhibitor further confirmed that the regulation of autophagy and renal fibrosis by HDHW was associated with IGF-1-mediated activation of the PI3K/Akt/mTOR pathway. In conclusion, our study showed that HDHW inhibited autophagy by upregulating IGF-1 expression, promoting the binding of IGF-1 to IGF-1R, and activating the PI3K/Akt/mTOR signaling pathway, thereby reducing renal fibrosis and protecting renal function. This study provides support for the application and further study of HDHW.

Evaluation of the Effects of Anti-PD-1 Therapy on Triple-Negative Breast Cancer in Mice by Diffusion Kurtosis Imaging and Dynamic Contrast-Enhanced Imaging.

BACKGROUND: The monitoring of immunotherapies is still based on changes in the tumor size in imaging, with a long evaluation period and low sensitivity. PURPOSE: To investigate the effectiveness of diffusion kurtosis imaging (DKI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the therapeutic efficacy of anti-programmed death-1 (PD-1) therapy in a mouse triple negative breast cancer (TNBC) model. STUDY TYPE: Prospective. ANIMAL MODEL: A total of 54 BALB/c mouse subcutaneous 4 T1 transplantation models of TNBC. FIELD STRENGTH/SEQUENCE: A 3.0-T; turbo spin echo (TSE) T2-weighted imaging, DKI with seven b values (0, 500, 1000, 1500, 2000, 2500, and 3000 sec/mm2 ) and T1-twist DCE acquisition series. ASSESSMENT: DKI and DCE-MRI parameters were evaluated by two radiologists independently. Regions of interest (ROIs) were drawn manually on the maximum cross-sectional area of the lesion; care was taken to avoid necrotic areas. The tumor cell density, the CD45 and CD31 levels were analyzed by two pathologists. STATISTICAL TESTS: The two-tailed unpaired t-test, Mann-Whitney U test, Fisher's exact test and Pearson correlation coefficient were performed. A P < 0.05 was considered statistically significant. RESULTS: The apparent diffusion coefficient (ADC), mean diffusivity (MD), Ktrans and Kep values were significantly different between the two groups at each time point after treatment. There were significant differences in the mean kurtosis (MK) and Ve values between the two groups at 5 and 10 days after treatment but no significant differences at 15 days (P = 0.317 and 0.183, respectively). The ADC and MD values were significantly correlated with tumor cell density (ADC, r = -0.833; MD, r = 0.890) and the CD45 level (ADC, r = 0.720; MD, r = 0.718). The Ktrans and Kep values were significantly correlated with the CD31 level (Ktrans , r = 0.820; Kep , r = 0.683). DATA CONCLUSION: DKI and DCE-MRI could reflect the changes in tumor microstructure and tumor tissue vasculature after anti-PD-1 therapy, respectively. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

Metabolomic Identification of Exosome-Derived Biomarkers for Schizophrenia: A Large Multicenter Study.

Exosomes have been suggested as promising targets for the diagnosis and treatment of neurological diseases, including schizophrenia (SCZ), but the potential role of exosome-derived metabolites in these diseases was rarely studied. Using ultra-performance liquid chromatography-tandem mass spectrometry, we performed the first metabolomic study of serum-derived exosomes from patients with SCZ. Our sample comprised 385 patients and 332 healthy controls recruited from 3 clinical centers and 4 independent cohorts. We identified 25 perturbed metabolites in patients that can be used to classify samples from patients and control participants with 95.7% accuracy (95% CI: 92.6%-98.9%) in the training samples (78 patients and 66 controls). These metabolites also showed good to excellent performance in differentiating between patients and controls in the 3 test sets of participants, with accuracies 91.0% (95% CI: 85.7%-96.3%; 107 patients and 62 controls), 82.7% (95% CI: 77.6%-87.9%; 104 patients and 142 controls), and 99.0% (95% CI: 97.7%-100%; 96 patients and 62 controls), respectively. Bioinformatic analysis suggested that these metabolites were enriched in pathways implicated in SCZ, such as glycerophospholipid metabolism. Taken together, our findings support a role for exosomal metabolite dysregulation in the pathophysiology of SCZ and indicate a strong potential for exosome-derived metabolites to inform the diagnosis of SCZ.

De Winter syndrome and ST-segment elevation myocardial infarction can evolve into one another: Report of two cases.

BACKGROUND: The de Winter electrocardiography (ECG) pattern is a sign that implies proximal left anterior descending coronary artery occlusion in patients with chest pain. The previous view was that the de Winter ECG pattern is static. CASE SUMMARY: A 65-year-old man presented with sudden chest pain at rest associated with diaphoresis for 55 min. The first ECG showed only T-wave inversion in III and aVF leads. Another ECG was performed at the 100th minute, showing upsloping ST segments depressed with tall and symmetrical T waves in the precordial leads; the J point was raised by 0.1 mV at the aVR lead. The patient was referred to our catheterization laboratory. A third ECG showed ST segment elevation by 0.2 mV in the I and aVL leads. The patient underwent emergency coronary angiography, which revealed complete proximal left anterior descending coronary (LAD) occlusion. The second patient presented with a 1-h history of sudden-onset, severe, substernal crushing chest pain. The first ECG showed ST-segment elevation (0.1-1.7 mV) in I, aVL, and precordial leads. The patient was referred to the catheterization laboratory. On arrival, his symptoms alleviated, and ECG showed that the ST-segments had significantly fallen back. The third ECG showed a typical de Winter pattern. Coronary angiography revealed 99% stenosis of the middle LAD. CONCLUSION: The de Winter ECG pattern is transient and dynamic, and it reflects proximal or mid-LAD subtotal occlusion rather than total occlusion.

Downregulation of DPF3 promotes the proliferation and motility of breast cancer cells through activating JAK2/STAT3 signaling.

It is reported that the genetic variation of DPF3 is a risk factor of breast cancer through large-scale association research. However, the expression, function and mechanism in breast cancer is unknown. We applied qPCR and western blotting to detect the levels of DPF3 in breast cancer tissues. MTT and Anchorage-independent growth ability assay were used to evaluate the effect of DPF3 on cell proliferation. Wound healing and transwell invasion assay were performed to detect the role of DPF3 on cell motility ability. Herein, we found that the mRNA and protein levels of DPF3 are both significantly downregulated in breast cancer tissues. And downregulation of DPF3 can promote the proliferation and motility of breast cancer cells. Further investigation illustrated that downregulation of DPF3 can activate the JAK2/STAT3 signaling. In conclusion, we found that the downregulation of DPF3 plays an indispensable function in the progression of breast cancer, and may be served as a novel therapeutic target to therapy breast cancer.

Derivatization method for the quantification of lactic acid in cell culture media via gas chromatography and applications in the study of cell glycometabolism.

Lactic acid represents an important metabolite that reflects mitochondria function and may further serve as energy source for cancer cells. In light of this physiological and pathological significance, we developed a novel and sensitive gas chromatography method to detect lactic acid in cell culture media. Here, ethyl chloroformate was selected as derivative reagent and the derivatization process was further optimized in terms of number of reagents and reaction time as well as extraction reagents. Under optimal conditions, good linearity was achieved in the tested calibration range. The limit of detection (LOD) was determined to be 0.67 µmol/L, the recovery rates were 99.6%-106% and the precision rate RSD was <5.49%. Furthermore, this method has been applied to quantify the secretion of lactic acid in cells exposed to mono­2­ethylhexyl phthalate at different doses and in cancer cells over time. Taken in concert, our method proved to be both sensitive and reliable and may be applied for studies on mitochondrial function and cell glycolysis conditions.

Hyaluronan-modified superparamagnetic iron oxide nanoparticles for bimodal breast cancer imaging and photothermal therapy.

Theranostic nanoparticles with both imaging and therapeutic abilities are highly promising in successful diagnosis and treatment of the most devastating cancers. In this study, the dual-modal imaging and photothermal effect of hyaluronan (HA)-modified superparamagnetic iron oxide nanoparticles (HA-SPIONs), which was developed in a previous study, were investigated for CD44 HA receptor-overexpressing breast cancer in both in vitro and in vivo experiments. Heat is found to be rapidly generated by near-infrared laser range irradiation of HA-SPIONs. When incubated with CD44 HA receptor-overexpressing MDA-MB-231 cells in vitro, HA-SPIONs exhibited significant specific cellular uptake and specific accumulation confirmed by Prussian blue staining. The in vitro and in vivo results of magnetic resonance imaging and photothermal ablation demonstrated that HA-SPIONs exhibited significant negative contrast enhancement on T2-weighted magnetic resonance imaging and photothermal effect targeted CD44 HA receptor-overexpressing breast cancer. All these results indicated that HA-SPIONs have great potential for effective diagnosis and treatment of cancer.

Experimental and Theoretical Study on Terahertz Spectra for Regenerated Cellulose.

In this work, regenerated cellulose films were prepared with an iced dissolution method, while the physical morphologies and crystal types of the products were systematically characterized with scanning electron microscope (SEM), Fourier transform infrared(FTIR), while X-Ray Diffraction (XRD). The results demonstrate that the as-prepared continuous and uniform films are indeed cellulose Ⅱ, whose morphology and crystal type are significantly different from those of the degreased cotton. Moreover, Terahertz time domain system (THz-TDS) and FTIR were employed to measure the THz spectra of the regenerated cellulose films. Accordingly, the THz characteristic peaks for the regenerated cellulose films are experimentally identified for the first time. In addition, the increase of the THz transmittance with the decrease of the wavenumber is attributed to the existence of amorphous components in the regenerated cellulose films. Although the shapes of Far-IR spectra in the range of 100～700 cm-1 are similar, the absorption peaks of the regenerated cellulose films move to lower wavenumbers (blue shift) compared with those of the degreased cotton. Based on this, we developed a new approach to distinguish the allomorphism of cellulose Ⅱ and cellulose Iß by Far-IR. Particularly, geometry optimization and IR calculation for the crystal structure of cellulose Ⅱ have been successfully processed by Density Functional Theory (DFT) using periodic boundary condition via CASTEP package. The calculated absorption peak positions are in good agreement with those experimentally measured. Consequently, the THz characteristic peaks of the regenerated cellulose films have been systematically and successfully assigned. Theoretical calculations reveal that the peaks at 42 and 54 cm-1 are assigned to the lattice vibration modes coupled with translational mode and rotational mode, respectively. Moreover, the absorption peaks in the range of 68～238 cm-1 are related with the torsion vibration of ­CH2OH group and deformation vibration of C­H bond and O­H bond, while those in the range of 351～583 cm-1 are assigned to the skeletal vibration of C­O­C bond and pyranoid ring, and those at 611 and 670 cm-1 are originated from the out-of-plane bending vibration of O­H bond. Each absorption peak is involved in more than single vibration mode. The THz spectra presented in this work, together with the theoretical simulations, indicate that the THz responses of regenerated cellulose are closely associated with both its chemical constituents and molecular structure. These results will be helpful not only for better understanding the relations between the molecular structure of the regenerated cellulose and its THz spectrum, but also for providing valuable information for future studies on the physical mechanisms of THz responses of other partially-crystalline polymers and organic biological macromolecules.

[Preventive Effect of Different Compatibilities of Ramulus Cinnamomi and Radix Paeomlae alba in Guizhi Decoction on Cardiac Sympathetic Denervation Induced by 6-OHDA].

OBJECTIVE: To observe the preventive effect of different compatibilities of Ramulus Cinnamomi (RC) and Radix Paeomiae alba (RPA) in Guizhi Decoction (GZD) on neurotransmitters and their rate-limiting enzymes, and neurotrophic factors of cardiac sympathetic denervation model rats induced by 6-hydroxydopamine (6-OHDA). METHODS: Totally 54 male Wistar rats were randomly divided into 6 groups, i.e., the blank control group, the model group, the methycobal group, the 2:1 (RC/RPA) Guishao group, the 1:2 Guishao group, and the 1:1 Guishao group, 9 in each group. Sympathetic denervation was induced by intraperitoneal injection of 6-OHDA for three successive days. Rats in the methycobal group and GZD groups were administered with corresponding decoction by gastrogavage 1 week before modeling (methycobal at the daily dose 0.15 mg/kg; GZD at the daily dose of 4.0, 5.5, 5.5 g crude drugs/kg for GZD 1:1, 1:2, and 2:1 groups). All medication lasted for 10 successive days. Levels of norepinephrine (NE), tyrosine hydroxylase (TH), choline acetyl-transferase (ChAT), nerve growth factor (NGF), growth associated protein43 (GAP-43) and ciliary neurotrophic factor (CNTF) in myocar- dial homogenates of right atrium and ventricular septum were detected by ELISA. RESULTS: Compared with the blank control group, levels of NE, TH, TH/ChAT ratio, and GAP-43 in myocardial homogenates of right atrium and ventricular septum decreased in the model group, and level of NGF increased (P < 0.01, P < 0.05). Compared with the model group, levels of NE and GAP-43 increased in the right atrium and interventricular septum; NGF level of the ventricular septum decreased in the methycobal group and each GZD groups. TH and TH/ChAT ratio in the right atrium increased in the 2:1 Guishao group and the 1:2 Guishao group (P < 0.01, P < 0.05); NGF levels in the right atrium and interventricular septum decreased only in the 1:1 Guishao group (P < 0.01, P< 0.05). Compared with the methycobal group, levels of NE, TH, and GAP-43 in the right atrium and interventricular septum increased, and NGF levels in the right atrium and interventricular septum decreased in the 1:1 Guishao group (P < 0.05). Compared with the methycobal group, levels of NE and GAP-43 in interventricular septum increased in the 2:1 Guishao group (P < 0.05). CONCLUSION: GZD (with the proportion between RC and RPA 2:1 and 1:1) could improve contents of neurotransmitters and their rate-limiting enzymes, as well as neurotrophic factors in cardiac sympathetic denervation model rats induced by 6-OHDA, alleviate cardiac sympathetic denervation induced by 6-OHDA, and maintain the balance of sympathetic-vagal nerve system.

[Effects of Different Compatibilities of Ramulus Cinnamomi and Peony in Guizhi Decoction on Diabetic Cardiac Autonomic Neuropathy].

OBJECTIVE: To observe the preventive effect different compatibilities of Ramulus Cinnamomi (RC) and peony in Guizhi Decoction (GD) on diabetic cardiac autonomic neuropathy (DCAN). METHODS: Totally 60 male rats were randomly divided into 5 groups, i.e., the blank control DM group, the model group, the methycobal group, the 1:1 (RC/peony) Guishao group, the 2:1 Guishao group, and the 1:2 Guishao group, 10 in each group. Rats were pretreated with corresponding drugs for 1 week, and then induced diabetes by intraperitoneal injection of STZ. Drugs were administrated by gastrogavage for 4 more weeks after STZ-injection. Enzyme-linked immunosorbent assay (ELISA) was employed to detect levels of tyrosine hydroxylase (TH), choline acetyltransferase (CHAT), nerve growth factor. (NGF), and ciliary neurotrophic factor (CNTF) in myocardial homogenates. RESULTS: After 4-week modeling, body weight (BW) was obviously lower, but blood glucose (BG) was higher in STZ rats than in rats of the blank control DM group. There was no statistical difference in BW or BG among the 5 groups (P >0.05). Compared with the blank control group, TH, TH/CHAT, and NGF in left ventricle and ventricular septum increased, CHAT and CNTF increased in the model group (P < 0.05, P < 0.01). Compared with the model group, TH and TH/CHAT in left ventricle decreased (P < 0.05, P < 0.01), CNTF in left ventricle increased (P < 0.05), CHAT in left ventricle and ventricular septum increased (P < 0.05, P < 0.01) in the methycobal group. TH and TH/CHAT in left ventricle and ventricular septum decreased, CNTF in left ventricle and ventricular septum increased (P < 0.05, P < 0.01), CHAT in left ventricle and ventricular septum increased (P < 0.01), NGF in ventricular septum decreased (P < 0.01) in the 1:1 Guishao group. TH/CHAT in left ventricle decreased (P < 0.01), CHAT and CNTF in left ventricle and ventricular septum increased (P < 0.05, P < 0.01) in the 1:2 Guishao group. Compared with the methycobal group, CHAT in left ventricle decreased, TH and TH/CHAT in left ventricle increased in the 2:1 Guishao group (P < 0.05, P < 0.01). TH and TH/CHAT in ventricular septum decreased (P < 0.05), CHAT and CNTF in left ventricle and ventricular septum increased (P < 0.05, P < 0.01) in the 1:1 Guishao group. Compared with the 1:2 Guishao group and the 2:1 Guishao group, CHAT in left ventricle increased, TH/CHAT in left ventricle decreased, TH and TH/CHAT in ventricular septum decreased, CHAT in ventricular septum increased, CNTF in left ventricle and ventricular septum also increased in the 1:1 Guishao group (all P < 0.01). CONCLUSIONS: STZ model rats had autonomic neural injury, manifested as lowered vagal nerve activity and hyperactive sympathetic nerves. GD could effectively suppress hyperactive cardiac sympathetic nerves and protect the vagus. Besides, GD (1:1) showed the optimal effect in regulating the balance of cardiac autonomic nerves and could be used in early prevention of DCAN.

[Study on Characteristics of Terahertz Spectra of Organic Functional Groups].

Fourier transform infrared (FTIR) was exploited to measure terahertz (THz) spectra in the wave number range of 30-300 cm(-1) for saturated straight chain organic molecules at room temperature. The results reveal that different organic functional groups exhibit different THz spectral characteristics. The absorption peaks of vibration modes of organic crystal lattice locate in high frequency range of THz, while those of vibration modes of intermolecular hydrogen (H) bonds appear in low frequency range of THz. Moreover, a typical absorption peak of intermolecular H bonds caused by saturated straight-chain monohydric alcohol hydroxyl functional groups locates at 57 cm(-1), while a characteristic absorption peak of intermolecular hydrogen bonds caused by triacontanoic acid carboxyl functional groups appears at 74 cm(-1). The intermolecular H bonds not only result in that the THz absorbing abilities of triacontanol and triacontanoic acid are significantly stronger than that of triacontane, but also cause regular red-shift and blue-shift of the THz absorption peaks of triacontanoic acid, as compared with those of triacontanol. In addition, density functional theory (DFT) B3LYP/6-311G(d,p) basis set was employed to simulate the THz spectra of saturated straight-chain alkane, alkanol and acid, respectively. The simulation results indicate that for the organic molecules with stronger intermolecular H bonds, lower consistent degree of the THz spectrum simulated from monomer molecule with the THz spectrum experimentally measured will occur. Moreover, the simulation results of dimer structures agree well with the measured spectra as compared to those simulated from monomer molecule structures. The results presented in this work are of great significance not only to the study of the THz spectral characteristics of other organic functional groups, but also to the clarification of the vibration modes of organic molecules. Particularly, our results are also helpful for clarifying the THz response theory of organics, and for exploiting the applications of organic materials in THz devices.

Increased interhemispheric functional connectivity in college students with non-clinical depressive symptoms in resting state.

The underlying neural basis of non-clinical depressive symptoms (nCDSs) remains unclear. Interhemispheric functional connectivity has been suggested as one of the most robust characteristics of brain's intrinsic functional architecture. Here, we investigated the functional connectivity between homotopic points in the brain using the voxel-mirrored homotopic connectivity (VMHC) approach. We performed VMHC analysis on resting-state functional magnetic resonance imaging (rs-fMRI) data from 17 individuals with nCDSs and 20 healthy controls (HCs) who were enrolled from a sample of 1105 college students. We found increased VMHCs in the bilateral posterior cerebellum and fusiform gyrus in nCDSs subjects compared with HCs. Furthermore, receiver operating characteristic (ROC) curves indicated that VMHC values in the posterior cerebellum lobes could use to differente nCDSs from HCs [area under the curve (AUC), 0.756; p<0.01]. We suggest increased VMHCs indicate a possible compensatory mechanism involved in the pathophysiology of nCDSs. VMHC values of the posterior cerebellum lobes might serve as a reliable biomarker for identifying nCDSs.

Glycosaminoglycan-targeted iron oxide nanoparticles for magnetic resonance imaging of liver carcinoma.

To develop an efficient probe for targeted magnetic resonance (MR) imaging of liver carcinoma, the surface modification of superparamagnetic iron oxide nanoparticles (SPIONs) was carried out by conjugating a naturally-occurring glycosaminoglycan with specific biological recognition to human hepatocellular liver carcinoma (HepG2) cells. These modified SPIOs have good water dispersibility, superparamagnetic property, cytocompatibility and high magnetic relaxivity for MR imaging. When incubated with HepG2 cells, they demonstrated significant cellular uptake and specific accumulation, as confirmed by Prussian blue staining and confocal microscopy. The in vitro MR imaging of HepG2 cells and in vivo MR imaging of HepG2 tumors confirmed their effectiveness for targeted MR imaging of liver carcinoma.

Inferior vena cava leiomyosarcoma confirmed by catheter suction biopsy during digital subtraction angiography.

Leiomyosarcoma of vascular origin is a rare disease and most cases arise in the inferior vena cava. Inferior vena cava leiomyosarcoma (IVCLMS) usually presents in females in their sixth decade of life. The clinical symptoms are often non-specific and the diagnosis is often delayed. Current imaging techniques can accurately differentiate inferior vena cava neoplasms from other non-neoplastic lesions. However, definitive diagnosis of IVCLMS needs histologic evidence. We report a case of IVCLMS in a 61-year old Chinese woman. This is the first IVCLMS case confirmed by catheter suction biopsy during digital subtraction angiography.

[Characterization and simulation of far-infrared spectroscopy for saturated monohydric alcohols].

Fourier transform infrared-attenuated total reflection (FTIR-ATR) was employed to measure the far-infrared (FIR) spectra in wavenumbers of 30-300 cm(-1) for six kinds of saturated monohydric alcohols, namely: methanol, ethanol, propanol, isopropanol, butanol and isobutanol. Further analysis of the FIR spectra for these monohydric alcohols with similar chemical structures reveals that absorption peaks are observed obviously for these alcohols in the 30-150 cm(-1) band, whereas not obvious peaks are measured in the 150-300 cm(-1) band. Moreover, it was found that the monohydric alcohols with higher hydroxy concentration possess lower average FIR transmission. In addition, the average FIR transmissions of linear chain monohydric alcohols are higher than those of the branched chain ones. Furthermore, the density functional theory (DFT) B3LYP/6-311G(d,p) basis set was employed to simulate the structures optimization and to calculate the responding frequencies of the methanol monomer and polymer. Simulation result indicates that no absorption peaks are found in the 30-150 cm(-1) band for the methanol monomer molecule, whereas there are obvious absorption peaks for the methanol polymers in the same band. In addition, the simulated absorption peak positions for the methanol polymers are in agreement with those experimentally measured. Both results indicate that the absorption of the methanol in Terahertz (THz) is attributed to the collective vibrations of different kinds of polymer, and that the polymer for methanol is mainly trimmer. This paper not only provides a new way to investigate the responding frequencies of organic molecule in THz band, but also is helpful for the FTIR-ATR study of other organic molecules.

In vivo assessment of the vascular disrupting effect of M410 by DCE-MRI biomarker in a rabbit model of liver tumor.

The present study aimed to prospectively monitor the vascular disrupting effect of M410 by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rabbits with VX2 liver tumors. Twenty-eight rabbits bearing VX2 tumors in the left lobe of the liver were established and randomly divided into treatment and control groups, intravenously injected with 25 mg/kg M410 or sterile saline, respectively. Conventional and DCE-MRI data were acquired on a 3.0-T MR unit at pretreatment, 4 h, 1, 4, 7 and 14 days post-treatment. Histopathological examinations [hematoxylin and eosin (H&E) and CD34 immunohistochemisty staining] were performed at each time point. The dynamic changes in tumor volume, kinetic DCE-MRI parameter [volume transfer constant (Ktrans)] and histological data were evaluated. Tumors grew slower in the M410 group 4-14 days following treatment, compared with rapidly growing tumors in the control group (P<0.05). At 4 h, 1 and 4 days, Ktrans significantly decreased in the M410 group compared with that in the control group (P<0.05). However, Ktrans values were similar in the two groups for the other time points studied. The changes in DCE-MRI parameters were consistent with the results obtained from H&E and CD34 staining of the tumor tissues. DCE-MRI parameter Ktrans may be used as a non-invasive imaging biomarker to monitor the dynamic histological changes in tumors following treatment with the vascular targeting agent M410.

Serum fibroblast growth factor 21 levels are correlated with the severity of diabetic retinopathy.

The aim of the study was to assess serum fibroblast growth factor 21 (FGF21) concentrations in Chinese type 2 diabetic patients with and without retinopathy and to assess the association between FGF21 and the severity of retinopathy. 117 diabetic patients were compared with 68 healthy controls. Fasting blood glucose, serum total cholesterol, serum triglycerides, serum insulin, and serum FGF21 levels were estimated. FGF21 concentrations in the patients were significantly higher than those in control. In the patient group there was a significant positive correlation between FGF21, insulin level, and homeostasis model assessment index. Serum FGF21 concentrations in patients with proliferative diabetic retinopathy or nonproliferative diabetic retinopathy were significantly higher than those in patients without diabetic retinopathy. When the presence of diabetes was defined as the final variable in the conditional logistic regression model with the FGF21 concentration as the continuous variable, FGF21 was significantly involved in the model. This study shows that the increase in serum concentration of FGF21 was associated with the severity of diabetic retinopathy and suggests that FGF21 may play a role in the pathogenesis of diabetic retinopathy and its degree.

Exosome-derived microRNA-29c induces apoptosis of BIU-87 cells by down regulating BCL-2 and MCL-1.

BACKGROUND: Aberrant expression of the microRNA-29 family is associated with tumorigenesis and cancer progression. As transport carriers, tumor-derived exosomes are released into the extracellular space and regulate multiple functions of target cells. Thus, we assessed the possibility that exosomes could transport microRNA- 29c as a carrier and correlations between microRNA-29c and apoptosis of bladder cancer cells. MATERIALS AND METHODS: A total of 28 cancer and adjacent tissues were examined by immunohistochemistry to detect BCL-2 and MCL-1 expression. Disease was Ta-T1 in 12 patients, T2-T4 in 16, grade 1 in 8, 2 in 8 and 3 in 12. The expression of microRNA-29c in cancer tissues was detected by quantitative reverse transcriptase PCR (QRT- PCR). An adenovirus containing microRNA-29c was used to infect the BIU-87 human bladder cancer cell line. MicroRNA-29c in exosomes was measured by QRT-PCR. After BIU-87 cells were induced by exosomes-derived microRNA-29c, QRT-PCR was used to detect the level of microRNA-29c. Apoptosis was examined by flow cytometry and BCL-2 and MCL-1 mRNA expressions were assessed by reverse transcription-polymerase chain reaction. Western blotting was used to determine the protein expression of BCL-2 and MCL-1. RESULTS: The expressions of BCL-2 and MCL-1 protein were remarkably increased in bladder carcinoma (p<0.05), but was found mainly in the basal and suprabasal layers in adjacent tissues. The expression of microRNA-29c in cancer tissues was negatively correlated with the BCL-2 and MCL-1. The expression level of microRNA-29c in exosomes and BIU-87 cells from the experiment group was higher than that in control groups (p<0.05). Exosome-derived microRNA-29c induced apoptosis (p<0.01). Although only BCL-2 was reduced at the mRNA level, both BCL-2 and MCL-1 were reduced at the protein level. CONCLUSIONS: Human bladder cancer cells infected by microRNA- 29c adenovirus can transport microRNA-29c via exosomes. Moreover, exosome-derived microRNA29c induces apoptosis in bladder cancer cells by down-regulating BCL-2 and MCL-1.