A Psychological Intervention Program for Patients with Cerebral Infarction.

INTRODUCTION: Cerebral infarction is one of the most common cerebrovascular diseases. The sequelae caused by cerebral infarction, including limb paralysis, crooked mouth corners, language barriers, etc., seriously affect the patient's physical and mental health and enthusiasm for rehabilitation training. Therefore, psychological intervention has important positive significance for the rehabilitation and nursing of patients with cerebral infarction. METHODS: This is a single-blind controlled study. 168 patients with cerebral infarction who met the inclusion criteria and visited our hospital from January 2018 to January 2020 were randomly divided into a control group (n = 84) and an intervention group (n = 84). The patients in the intervention group received an additional 3-month psychological treatment on the basis of the patients in the control group. The National Institutes of Health Stroke Scale (NIHSS), Activities of Daily Living (ADL) scale, Mini-Mental State Examination (MMSE), and Hamilton Depression Rating Scale (HAMD) were measured before and after the psychological intervention. RESULTS: The 3-month psychological intervention we designed significantly reduced the NIHSS and HAMD scores of patients with cerebral infarction compared with traditional rehabilitation care for cerebral infarction, implying that our psychological intervention courses can improve patients' cognitive function and suppress patients' depression. Consistently, our psychological intervention also significantly improved ADL and MMSE scores 3 months after the onset of cerebral infarction patients, implying that this psychological intervention helped patients recover their daily functions relative to conventional care. CONCLUSION: Psychological intervention can be used as an adjunct therapy in the treatment and nursing of patients with cerebral infarction.

Polymeric Microneedle Arrays with Glucose-Sensing Dynamic-Covalent Bonding for Insulin Delivery.

The ongoing rise in diabetes incidence necessitates improved therapeutic strategies to enable precise blood glucose control with convenient device form factors. Microneedle patches are one such device platform capable of achieving therapeutic delivery through the skin. In recent years, polymeric microneedle arrays have been reported using methods of in situ polymerization and covalent crosslinking in microneedle molds. In spite of promising results, in situ polymerization carries a risk of exposure to toxic unreacted precursors remaining in the device. Here, a polymeric microneedle patch is demonstrated that uses dynamic-covalent phenylboronic acid (PBA)-diol bonds in a dual role affording both network crosslinking and glucose sensing. By this approach, a pre-synthesized and purified polymer bearing pendant PBA motifs is combined with a multivalent diol crosslinker to prepare dynamic-covalent hydrogel networks. The ability of these dynamic hydrogels to shear-thin and self-heal enables their loading to a microneedle mold by centrifugation. Subsequent drying then yields a patch of uniformly shaped microneedles with the requisite mechanical properties to penetrate skin. Insulin release from these materials is accelerated in the presence of glucose. Moreover, short-term blood glucose control in a diabetic rat model following application of the device to the skin confirms insulin activity and bioavailability. Accordingly, dynamic-covalent crosslinking facilitates a route for fabricating microneedle arrays circumventing the toxicity concerns of in situ polymerization, offering a convenient device form factor for therapeutic insulin delivery.

Comparison of the clinical outcomes of percutaneous vertebroplasty vs. kyphoplasty for the treatment of osteoporotic Kümmell's disease:a prospective cohort study.

BACKGROUND: Percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) are widely used in the treatment of Kümmell's disease. The purpose of this article is to investigate the clinical efficacy of PVP and PKP for Kümmell's disease. METHODS: The clinical data that 56 cases of Kümmell's disease treated with either PVP (28 cases) or PKP (28 cases) from December 2015 to December 2017 were prospectively analyzed. Gender, age, course of disease, injury segment, bone mineral density (BMD), visual analogue scale (VAS), Oswestry disability index (ODI), imaging measurement indexes before surgery between the two groups showed no significant difference (all P > 0.05). The bone cement leakage rate, bone cement injection amount, operation time, VAS, ODI, the rate of vertebral compression, correction rate of kyphosis and refracture rate of adjacent vertebra in 2 years were compared between the two groups to calculate clinical efficacy. RESULTS: The two groups were followed up for 24-48 months. There was no significant difference in the follow-up time, amount of bone cement injected, incidence of bone cement leakage and refracture rate of adjacent vertebrae between the two groups (all P > 0.05). The operation time, intraoperative blood loss and fluoroscopy times of the PVP group were significantly lower than those of the PKP group (all P = 0.000). VAS score and ODI of the two groups were significantly lower at 1 day, 1 year and 2 years after surgery than before surgery (all P < 0.05), but there was not statistically significant difference between the two groups at each time point after surgery (all P > 0.05). The rate of vertebral compression and kyphosis correction in the two groups were significantly corrected (P < 0.05, respectively) and decreased significantly with time (all P < 0.05), But there was not significant difference between the two groups at any time point (all P > 0.05). CONCLUSION: Both PVP and PKP can achieve similar effects in the treatment of Kümmell's disease. Because the cost, operation time, blood loss, radiation exposure and surgical procedure of PVP are less than those of PKP, PVP has more clinical priority value.

A self-cleaning, mechanically robust membrane for minimizing the foreign body reaction: towards extending the lifetime of sub-Q glucose biosensors.

Long-term, subcutaneously implanted continuous glucose biosensors have the potential to improve diabetes management and reduce associated complications. However, the innate foreign body reaction (FBR) both alters the local glucose concentrations in the surrounding tissues and compromises glucose diffusion to the biosensor due to the recruitment of high-metabolizing inflammatory cells and the formation of a dense, collagenous fibrous capsule. Minimizing the FBR has mainly focused on "passively antifouling" materials that reduce initial cellular attachment, including poly(ethylene glycol) (PEG). Instead, the membrane reported herein utilizes an "actively antifouling" or "self-cleaning" mechanism to inhibit cellular attachment through continuous, cyclic deswelling/reswelling in response to normal temperature fluctuations of the subcutaneous tissue. This thermoresponsive double network (DN) membrane is based on N-isopropylacrylamide (NIPAAm) and 2-acrylamido-2-methylpropane sulfonic acid (AMPS) (75:25 and 100:0 NIPAAm:AMPS in the 1st and 2nd networks, respectively; "DN-25%"). The extent of the FBR reaction of a subcutaneously implanted DN-25% cylindrical membrane was evaluated in rodents in parallel with a PEG-diacrylate (PEG-DA) hydrogel as an established benchmark biocompatible control. Notably, the DN-25% implants were more than 25× stronger and tougher than the PEG-DA implants while maintaining a modulus near that of subcutaneous tissue. From examining the FBR at 7, 30 and 90 days after implantation, the thermoresponsive DN-25% implants demonstrated a rapid healing response and a minimal fibrous capsule (~20-25 µm), similar to the PEG-DA implants. Thus, the dynamic self-cleaning mechanism of the DN-25% membranes represents a new approach to limit the FBR while achieving the durability necessary for long-term implantable glucose biosensors.

Ratiometric Fluorescent Polymeric Thermometer for Thermogenesis Investigation in Living Cells.

Intracellular temperature has a fundamental effect on cellular events. Herein, a novel fluorescent polymer ratiometric nanothermometer has been developed based on transferrin protein-stabilized gold nanoclusters as the targeting and fluorescent ratiometric unit and the thermosensitve polymer as the temperature sensing unit. The resultant nanothermometer could feature a high and spontaneous uptake into the HeLa cells and the ratiometric temperature sensing over the physiological temperature range. Moreover, the precise temperature sensing for intracellular heat generation in HeLa cells following calcium ions stress has been achieved. This practical intracellular thermometry could eliminate the interference of the intracellular surrounding environment in cancer cells without a microinjection procedure, which is user-friendly. The prepared new nanothermometer can provide tools for unveiling the intrinsic relationship between the intracellular temperature and ion channel function.

Preparation and characterization of a novel injectable strontium-containing calcium phosphate cement with collagen.

PURPOSE: To develop a novel injectable strontium-containing calcium phosphate cement with collagen. METHODS: A novel calcium phosphate bone cement (CPC) was prepared with the addition of strontium element, collagenl, and modified starch; the injectability, solidification time, microstructure, phase composition, compressive strength, anti-collapsibility and histological properties of material were evaluated. RESULTS: The results showed that the material could be injected with an excellent performance; the modified starch significantly improved the anti-washout property of cement; with the liquid to solid ratio of 0.3, the largest compressive strength of cement was obtained (48.0 MPa ± 2.3 MPa); histological examination of repair tissue showed that the bone was repaired after 16 weeks; the degradation of cement was consistent with the new bone growth. CONCLUSION: A novel injectable collagen-strontium-containing CPC with excellent compressive strength and suitable setting time was prepared, with addition of modified starch. The CPC showed a good anti-washout property and the degradation time of the cement met with the new bone growing. This material is supposed to be used in orthopedic and maxillofacial surgery for bone defects.

[Anti-tumor effects of DDP-PLLA-CNTs on human cholangiocarcinoma cell line in vitro].

OBJECTIVE: To explore the antitumor effects of DDP-PLLA-CNTs on human cholangiocarcinoma cell line. METHODS: DDP-PLLA-CNTs were prepared with the method of ultrasound emulsification. The morphology of DDP-PLLA-CNTs was determined by scanning electron microscope (SEM). And its drug loading and drug release curve in vitro was detected by UV-Vis-NIR spectrophotometer. CCK8 was used to test the cytotoxic effects of DDP-PLLA-CNTs at different concentrations on QBC939 cell proliferation.Flow cytometry was employed to measure the changes of apoptotic rate. RESULTS: With excellent controlled-release characteristic of in vitro drug release, DDP-PLLA-CNTs inhibited the proliferation and significantly increased the apoptotic rate of QBC939 cell line. CONCLUSION: DDP-PLLA-CNTs have drug sustained-release characteristics and can significantly inhibit the proliferation of QBC939 cell line.

[Short-term and long-term effects of all-ceramic onlay on restoration of premolars and its influence on dental function].

PURPOSE: To investigate the short-term and long-term effects of all-ceramic onlay on restoration of premolars and its influence on dental function. METHODS: Ninety-five premolars receiving root canal treatment in People's Hospital of Peking University from January 2017 to January 2018 were enrolled, and randomly divided into two groups based on different repairing methods. Patients in the control group (n=47) received full crown restoration, while patients in the experimental group(n=48) received all-ceramic onlay restoration. The success, survival and failure rates of the teeth were compared. The United States Public Health Service(USPHS) and occlusal function of the prosthesis were compared 6, 12 and 36 months after treatment. The data were processed using SPSS 19.0 software package. RESULTS: The success and survival rate of the experimental group were higher than those of the control group, but without significant difference (P＞0.05). The morphology, marginal integrity, marginal coloration, surface texture, secondary caries, gingival health and proximal contacts showed no significant difference between the two groups 12 months after treatment(P＞0.05). Thirty-six months after treatment, the marginal integrity, marginal coloration and surface texture showed no significant difference between the two groups (P＞0.05), while the morphology, secondary caries, gingival health and proximal contacts were significantly better in the experimental group than in the control group (P＜0.05). The occlusal function between the affected side and contralateral side of both groups showed no significant difference 6, 12 and 36 months after treatment(P＞0.05). CONCLUSIONS: All-ceramic onlay restoration of premolars has high success and survival rate, and good short-term and long-term restoration effect, which is beneficial to improve the occlusal function of the affected teeth.

Silicone-containing thermoresponsive membranes to form an optical glucose biosensor.

Glucose biosensors that could be subcutaneously injected and interrogated without a physically connected electrode and transmitter affixed to skin would represent a major advancement in reducing the user burden of continuous glucose monitors (CGMs). Towards this goal, an optical glucose biosensor was formed by strategically tailoring a thermoresponsive double network (DN) membrane to house a phosphorescence lifetime-based glucose sensing assay. This membrane was selected based on its potential to exhibit reduced biofouling via 'self-cleaning' due to cyclical deswelling/reswelling in vivo. The membrane was strategically tailored to incorporate oxygen-sensitive metalloporphyrin phosphor, Pd meso-tetra(sulfophenyl)-tetrabenzoporphyrin ([PdPh4(SO3Na)4TBP]3) (HULK) and glucose oxidase (GOx). Specifically, electrostatic interactions and colvalent bonds were used to stabilize HULK and GOx within the membrane, respectively. Enhancing the oxygen permeability of the membrane was necessary to achieve sensitivity of HULK/GOx to physiological glucose levels. Thus, silicone microparticles were incorporated at two concentrations. Key properties of SiHy-0.25 and SiHy-0.5 microparticle-containing compositions were compared to a control having no microparticles (SiHy-0). The discrete nature of the silicone microparticles maintained the desired thermosensitivity profile and did not impact water content. While the modulus decreased with silicone microparticle content, membranes were more mechanically robust versus a conventional hydrogel. SiHy-0.25, owing to apparent phase separation, displayed greater glucose diffusion and oxygen permeability versus SiHy-0.5. Furthermore, SiHy-0.25 biosensors exhibited the greatest glucose sensitivity range of 100 to 300 mg dL-1versus only 100 to 150 mg dL-1 for both SiHy-0 and SiHy-0.5 biosensors.

[Comparison of the stress distribution of microtitanium and bioresorbable plates in fixation of mandibulotomy].

PURPOSE: The aim of this study was to compare the stress distribution of microtitanium plate and bioresorbable plates in fixation of mandibulotomy. METHODS: Three dimensional models of different internal fixation systems in mandibular resection were established, and three dimensional finite element analysis was carried out to compare the displacement changes of fracture segments and stress distribution of titanium plates under the same stress conditions. RESULTS: The maximum stress value of titanium plate was 49.8 MPa, and that of absorbable plate was 4.42 MPa. The maximum stress value of titanium plate was far greater than that of absorbable plate. However, all the stresses were less than their yield limits. It can be seen from the relative displacement comparison that when the mini-titanium plate was fixed on the mandible, the maximum displacement value was 0.1 mm; when absorbable plate was used for fixation, the maximum displacement value was 0.2 mm, and the relative displacement of both plates was small. CONCLUSIONS: These results suggest that the stiffness and internal strength of bioabsorbable fixation system are sufficient to support bone healing at the mandible site.

Characterization and Absorption Kinetics of a Novel Multifunctional Nanoliposome Stabilized by Sea Cucumber Saponins Instead of Cholesterol.

Cholesterol was usually used to stabilize liposome, although there have been controversies on the relationship between dietary cholesterol and health. The present study aimed to prepare a novel multifunctional nanoliposomes stabilized by sea cucumber-derived saponins using ultrasound-assisted film dispersion method. A novel uniform liposome with a mass ratio of egg yolk lecithin/sea cucumber saponins at 75:25 was successfully prepared to encapsulate saponin, and the particle size was 164.8 ± 1.70 nm with a PDI value of 0.214 ± 0.022 and zeta potential of -15.97 ± 1.23 mV. The digestion and absorption results in vivo showed that the dietary saponins in liposome form could delay the peak time of saponins and prolong their residence time in the serum. Moreover, saponins were more easily converted into their corresponding metabolites after administration with saponins in the liposome form. The novel liposome as an efficient carrier with multiple functions had great potential in the development of functional food and biomedical applications.

Biodegradable 131 Iodine-Labeled Microspheres: Potential Transarterial Radioembolization Biomaterial for Primary Hepatocellular Carcinoma Treatment.

Transarterial radioembolization with radionuclide-labeled microspheres is successfully used in hepatocellular carcinoma (HCC) treatment, but the non-biodegradability and rapid settlement of the microsphere material are associated with unsatisfied distribution and unable for multiple administrations. In this study, a novel biodegradable chitosan-collagen composite microsphere (CCM) with ideal settlement rate is prepared. The Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) results indicate CCMs have desirable shapes with diameters around 10 µm, and considerable biodegradability within 12 weeks. These CCMs are successfully radiolabeled with 131 I and processed efficiency of 70.4 MBq mg-1 of microspheres as well as favorable stability in vitro. Then, 131 I-CCMs are injected into rats with orthotopic HCC via the hepatic artery which effectively improves the median overall survival from 19 to 44 days (p < 0.05). Single photon emission computed tomography (SPECT/CT) imaging and immunohistochemical analysis indicate well-localized biodistribution and consistent stability of 131 I-CCMs in the liver over 28 days. Magnetic resonance imaging (MRI) and gross specimens monitoring confirm the inhibited tumor growth after 131 I-CCMs treatment. In conclusion, these biodegradable 131 I-CCMs exhibit optimal radiolabeling efficiency, stability, and favorably radioembolization effect for orthotopic HCC in a rodent model, suggesting potential for interventional cancer therapy.

Stimuli-responsive multifunctional metal-organic framework nanoparticles for enhanced chemo-photothermal therapy.

Construction of stimuli-responsive multifunctional nanoparticles is critical for nanotherapeutic delivery. Though metal-organic frameworks (MOFs) have been emerged as promising delivery vehicles, the therapeutic efficacy of MOFs in cancer treatment is limited by the lack of a general approach for the preparation of stimuli-responsive multifunctional MOFs. We show that the combination of a versatile coating material polydopamine with MOFs enables facile integration of different functional therapeutics, obtaining stimuli-responsive multifunctional MOFs with extensive photothermal efficiency and outstanding capability to abrogate tumors by chemo-photothermal therapy. Exemplary MOFs including ZIF-8, UiO-66, and MIL-101 were utilized to prepare stimuli-responsive multifunctional MOFs to illustrate the generality of the strategy. This approach enables targeted drug delivery and stimuli-responsive release of multi-therapeutics and allows combination therapy with excellent in vitro and in vivo antitumor activity. Taking into account the diversity of MOFs and different functional molecules, this work provides flexible access to programmable MOF nanoparticles for specific biological applications.

Improved accuracy of hemimandibular reconstructions involving the condyle by utilizing hydroformed reconstruction plates rather than hand-bent stock plates.

BACKGROUND: Computer-aided design/computer-aided manufacturing (CAD/CAM) surgical templates allow precise mandibular reconstructive surgery. However, their clinical accuracy is limited by manual plate bending. Digitally hydroformed plates maintain a digital workstream in virtual planning. METHODS: Twelve patients with Brown's class IIc mandibular defects were randomized into two groups: group I (experimental), the reconstruction plate was digitally hydroformed, and group II (control), surgeries were performed CAD/CAM guided with the reconstruction plate manually prebent. The linear and angular deviations of reconstruction outcomes were compared to surgical simulation in both groups. RESULTS: The mean linear and angular deviations of middle and posterior segments were 2.14 ± 0.79 mm, 3.71 ± 0.95 mm, 8.73° ± 1.91°, and 9.06° ± 0.96° in group I and 4.31 ± 0.78 mm, 6.74 ± 1.40 mm, 16.35° ± 0.72°, and 31.48° ± 3.38° in group II, respectively. Measurements in group I were significantly lower than group II (P < .005). CONCLUSION: Digital hydroforming for plate prebent is a reliable method that helps improving the clinical accuracy of CAD/CAM-guided mandibular reconstruction surgery.

Preparation of liposome encapsulating angiotensin-I-converting enzyme inhibitory peptides from sunflower protein hydrolysates.

Liposomal angiotensin-I-converting enzyme inhibitory (ACEI) peptides were prepared from sunflower protein hydrolysates by the thin­film ultrasonic method. Response surface methodology (RSM), in combination with fractional factorial designs and central composite design methods were utilized to optimize entrapment efficiency and balance the drug release. We found that the ratio of phospholipids to cholesterol, ultrasound time and the ratio of phospholipids to ACEI peptides were significant factors affecting entrapment efficiency (P<0.001). Optimal preparation conditions of liposomal­ACEI peptides were the ratio of soybean phospholipids to cholesterol (w/w) of 4.1:1, PEG­2000 dosage (%) of 4, NaCl concentration in PBS (mM) of 50, hydration temperature of 45˚C, ultrasound time of 8.05 min and the ratio of soybean phospholipids to ACEI peptides of 15:1 (w/w). The experimental entrapment efficiency of liposomal­ACEI peptides was (91.25±0.182%). Moreover, the balanced release rate of liposome encapsulated ACEI in phosphate buffer was 77.83% after 12 h.

Sea cucumber saponin liposomes ameliorate obesity-induced inflammation and insulin resistance in high-fat-diet-fed mice.

Obesity has become a worldwide concern in recent years, which may cause many diseases. Much attention has been paid to food components that are considered to be beneficial in preventing chronic metabolic diseases. The present study was conducted to investigate the effects of sea cucumber saponin liposomes on certain metabolic markers associated with obesity. C57/BL6 mice fed with high-fat diet were treated with different forms of sea cucumber saponins for eight weeks. The results showed that liposomes exhibited better effects on anti-obesity and anti-hyperlipidemia activities than the common form of sea cucumber saponins. Sea cucumber saponin liposomes could also effectively alleviate adipose tissue inflammation by reducing pro-inflammatory cytokine releases and macrophage infiltration. Moreover, sea cucumber saponin liposomes improved insulin resistance by altering the uptake and utilization of glucose. Taken together, our results indicated that the intake of sea cucumber saponin liposomes might be able to ameliorate obesity-induced inflammation and insulin resistance.

[Influence of culture mode on bacterial cellulose production and its structure and property].

Acetobacter xylinum NUST4.2 has been applied in the studies to examine the production, structure and thermal property of bacterial cellulose (BC) produced in stationary culture and in the stirred tank reactor. These differences are as follows: BC yield reached 7.5 g/L in stationary culture for 6 days and its productivity was 0.052 g/L/h. BC production reached 3.13 g/L in the stirred tank reactor for 72h and its productivity was 0.043 g/L/h. SEM showed that there was almost no difference between network structure built of entangled cellulose ribbons produced in static culture and in the reactor. But the cellulose ribbons produced in static culture were a much more entangled and denser network with curved and overlapping cellulose ribbons in comparison with that one produced in the stirred tank reactor. Also the thickness of the cellulose ribbons seems to differ between the two BC samples, with the one from static culture distinguished by the slightly thinner ribbons. FT-IR revealed that there was no effect of stirring on the chemical structure of BC, but intermolecular hydrogen bond of cellulose was weakened. Furthermore, BC synthesized in static culture displayed I(alpha)-rich cellulose. XRD results indicated that no remarkable change in the cellulose crystallographic form of the BC samples. Nevertheless, BC produced in static culture was characterized by a higher crystallinity, higher I(alpha) content and higher crystalline size than cellulose that was produced in the reactor. All of these results revealed that stirring in the reactor interfere strongly in the process of nascent microfibrils crystallization, favoring the formation of smaller size microfibrils and increased I(beta), the more stable allomorph. Compared with cotton cellulose, the changes of thermal decomposition behavior in the BC samples were that BC produced in static culture displayed better thermal stability, but BC produced in the stirred reactor displayed better flame retarding.

The role of nitrous oxide in stroke.

Stroke that is caused by poor blood flow into the brain results in cell death, including ischemia stroke due to lack of blood into brain tissue, and hemorrhage due to bleeding. Both of them will give rise to the dysfunction of brain. In general, the signs and symptoms of stroke are the inability of feeling or moving on one side of body, sometimes loss of vision to one side. Above symptoms will appear soon after the stroke has happened. If the symptoms and signs happen in 1 or 2 hours, we often call them as transient ischemic attack. Moreover, hemorrhagic stroke often leads to severe headache. It is known that neuronal death can happen after stroke, and it depends upon the activation of N-methyl-D-aspartate (NMDA) excitatory glutamate receptor which is the goal for a lot of neuroprotective agents. Nitrous oxide was discovered by Joseph Priestley in 1772, and then he and his friends, including the poet Coleridge and Robert Sauce, experimented with the gas. They found this gas could make patients loss the sense of pain and still maintain consciousness after inhalation. Shortly the gas was used as an anesthetic, especially in the field of dentists. Now, accroding to theme of Helene N. David and other scientists, both of nitrous oxide at 75 vol% and xenon at 50 vol% could reduce ischemic neuronal death in the cortex by 70% and decrease NMDA-induced Ca2+ influx by 30%. Therefore, more clinical and experimental studies are important to illuminate the mechanisms of how nitrous oxide protects brain tissue and to explore the best protocol of this gas in stroke treatment.

Folic acid-conjugated fluorescent polymer for up-regulation folate receptor expression study via targeted imaging of tumor cells.

Thoroughly investigation of folate receptor (FR) expression related to targeting drug delivery in tumor cells has been intensively pursued in recent years. Herein, a simple and versatile strategy for determination of FR expression based on targeted imaging of tumor cells with fluorescent nano-conjugates was developed. The fluorescent nano-conjugates were composed of poly 2-vinyl-4,4-dimethyl azlactone (PVDMA) as the linker, folic acid as the targeting unit and amino-Rhodamine B as the fluorescent ligand. Owing to possessing dimethyl azlactone groups in polymer framework, PVDMA could easily reacted with amines or alcohols, and form water soluble materials. Fluorescent imaging studies indicated that the prepared nano-conjugates could specifically target tumor cells and monitor the over expressing of FR. Moreover, the FR expression up-regulation in HeLa cells through medicines regulation has been further explored. This new protocol opens an effective way through synthesis and design of novel fluorescent nano-conjugates for FR expression investigation in tumor cells via targeted imaging, showing great potential in drug delivery mechanism study and cancer therapy.

High-Dose Fluoride Impairs the Properties of Human Embryonic Stem Cells via JNK Signaling.

Fluoride is a ubiquitous natural substance that is often used in dental products to prevent dental caries. The biphasic actions of fluoride imply that excessive systemic exposure to fluoride can cause harmful effects on embryonic development in both animal models and humans. However, insufficient information is available on the effects of fluoride on human embryonic stem cells (hESCs), which is a novel in vitro humanized model for analyzing the embryotoxicities of chemical compounds. Therefore, we investigated the effects of sodium fluoride (NaF) on the proliferation, differentiation and viability of H9 hESCs. For the first time, we showed that 1 mM NaF did not significantly affect the proliferation of hESCs but did disturb the gene expression patterns of hESCs during embryoid body (EB) differentiation. Higher doses of NaF (2 mM and above) markedly decreased the viability and proliferation of hESCs. The mode and underlying mechanism of high-dose NaF-induced cell death were further investigated by assessing the sub-cellular morphology, mitochondrial membrane potential (MMP), caspase activities, cellular reactive oxygen species (ROS) levels and activation of mitogen-activated protein kinases (MAPKs). High-dose NaF caused the death of hESCs via apoptosis in a caspase-mediated but ROS-independent pathway, coupled with an increase in the phospho-c-Jun N-terminal kinase (p-JNK) levels. Pretreatment with a p-JNK-specific inhibitor (SP600125) could effectively protect hESCs from NaF-induced cell death in a concentration- and time-dependent manner. These findings suggest that NaF might interfere with early human embryogenesis by disturbing the specification of the three germ layers as well as osteogenic lineage commitment and that high-dose NaF could cause apoptosis through a JNK-dependent pathway in hESCs.