Drug-loaded dual targeting graphene oxide-based molecularly imprinted composite and recognition of carcino-embryonic antigen

Despite extensive research on functional graphene oxide for anticancer drug delivery, the sensitivity of traditional protein targeting ligands to the environment limits the practical applications of targeted drug delivery. A unique molecularly imprinted magnetic graphene oxide was used as a novel drug delivery system for the treatment of tumors. Molecularly imprinted polymers (MIPs) synthesized by molecular imprinting technology have the advantages of good stability against chemical and enzymatic attacks, high specificity for a target template, and resistance to harsh environments. In our work, the MIP was used for specificity to tumor cells with carcino-embryonic (CEA) tumor markers as the template, and dopamine as the functional monomer was grafted on boronic acid-functionalized magnetic graphene oxide. The structure of the nanoparticles was optimized and characterized in detail by vibrating sample magnetometry, X-ray diffraction analysis, UV-vis spectroscopy, and flow cytometry. The prepared polymer has magnetic properties, specific recognition to CEA, biocompatibility and pH sensitivity for drug delivery. Cell culture research was carried out on the tumor cells and normal cells. The composites exhibited dual targeting properties that not only magnetically target but also specifically increase the drug cytotoxicity to the tumor cells by selectively binding to CEA. On the basis of these results, this study developed a novel approach for targeting tumor cells for drug delivery without needing to modify the protein ligand.

In the research we designed a CEA-molecularly imprinted polymers using molecular imprinting technique with CEA tumor marker as template, boronic acid functionalized MGO as substrate for dual targeted delivery of drug to tumor cells.     

The broad-spectrum and ultra-sensitive detection of zeranol and its analogues by an enzyme-linked immunosorbent assay in cattle origin samples

Zeranol (α-zearalanol) has been used as a growth promoter in livestock since 1969 in some non-EU countries; the residues of zeranol and its five analogues in animal origin foods may endanger human health due to their strong estrogenic and anabolic activities. Therefore, it is urgent to establish simple, rapid, real-time, broad-spectrum and high-sensitivity detection methods for the residues of zeranol and its analogues. In this study, an ultrasensitive indirect-competition enzyme-linked immunosorbent assay (ic-ELISA) was established for the rapid multi-residue detection of zeranol and its five analogues in cattle origin samples, which was based on a broad-spectrum monoclonal antibody (mAb) that specifically bound to zeranol and its analogues with high sensitivity. The half maximal inhibitory concentration (IC₅₀) values for zeranol, β-zearalanol, zearalanone, α-zearalenol, β-zearalenol, and zearalenone were 0.103, 0.080, 0.161, 0.177, 0.254, and 0.194 ng mL⁻¹, respectively, the recovery rates of cattle origin samples spiked with zeranol ranged from 79.2–104.2%, and the coefficient of variation (CV) values were less than 11.4%. Excellent correlation (R² = 0.9845) was obtained between the results of HPLC-MS/MS and ic-ELISA. In conclusion, the developed ic-ELISA could be employed as an ultrasensitive and broad-spectrum detection method for monitoring trace ZEN residues in cattle origin foods.

This paper presents a broad-spectrum and ultra-sensitive ic-ELISA method for the rapid detection of zeranol and its analogues in cattle origin samples.     

Hilar interneuron vulnerability distinguishes aged rats with memory impairment

Hippocampal interneuron populations are reportedly vulnerable to normal aging. The relationship between interneuron network integrity and age‐related memory impairment, however, has not been tested directly. That question was addressed in the present study using a well‐characterized model in which outbred, aged, male Long‐Evans rats exhibit a spectrum of individual differences in hippocampal‐dependent memory. Selected interneuron populations in the hippocampus were visualized for stereological quantification with a panel of immunocytochemical markers, including glutamic acid decarboxylase‐67 (GAD67), somatostatin, and neuropeptide Y. The overall pattern of results was that, although the numbers of GAD67‐ and somatostatin‐positive interneurons declined with age across multiple fields of the hippocampus, alterations specifically related to the cognitive outcome of aging were observed exclusively in the hilus of the dentate gyrus. Because the total number of NeuN‐immunoreactive hilar neurons was unaffected, the decline observed with other markers likely reflects a loss of target protein rather than neuron death. In support of that interpretation, treatment with the atypical antiepileptic levetiracetam at a low dose shown previously to improve behavioral performance fully restored hilar SOM expression in aged, memory‐impaired rats. Age‐related decreases in GAD67‐ and somatostatin‐immunoreactive neuron number beyond the hilus were regionally selective and spared the CA1 field of the hippocampus entirely. Together these findings confirm the vulnerability of hippocampal interneurons to normal aging and highlight that the integrity of a specific subpopulation in the hilus is coupled with age‐related memory impairment. J. Comp. Neurol. 521:3508‐3523, 2013. © 2013 Wiley Periodicals, Inc.     

Association between anatomical variations of the posterior communicating artery and the presence of aneurysms

Objectives: Posterior communicating artery aneurysms (PcoAA) account for 30–35% of intracranial aneurysms. The anatomical factors involved in the formation of PCoAA are poorly known. The study aimed to investigate the anatomical variations in the posterior communicating artery (PcoAs) and the presence of PCoAA.

Methods: All 154 patients hospitalized from January 2008 to December 2013 at the department of neurology of our hospital were included in this study; 76 were confirmed with PCoAA upon cerebral angiography and 78 were confirmed without cranial artery aneurysm (controls). According to the blood supply pattern, variations of the PCoAA were classified as Type P0, P-I, or P-II. The angles of C7 and C6 of the internal carotid artery on each side were analyzed.

Results: Compared with controls, patients with PCoAA had a higher frequency of abnormal posterior communicating artery (Types P-I and P-II) (p < 0.001). The angles of C7 and C6 on the contralateral side in the PCoAA group were significantly greater than on the affected side, and significantly lesser than in controls (p < 0.001). There was no difference in the angle between the culprit artery and the contralateral one.

Discussion: Abnormal PCoAs (Types P-I and P-II) might be more vulnerable to PCoAA development, and Type P-II was the most vulnerable. There was a correlation between the angles of C7 and C6 part of the internal carotid artery and the presence of symptomatic PCoAA, with smaller angles being associated with increased frequency of symptomatic PCoAA.     

Bladder and bowel dysfunction following small-volume epidural blood patch for spontaneous intracranial hypotension

Epidural blood patch (EBP) is an effective procedure for the treatment of spontaneous intracranial hypotension (SIH). Neurological compromise following EBP, although rare, is recognized as a serious potential complication. We describe a 33-year-old female patient in whom long-term bladder and bowel dysfunction developed following a small volume (10 mL) EBP to treat SIH. We also discuss the possible pathophysiological mechanisms related to this complication in the postprocedure setting.     

Carvacrol Attenuates Diabetes-Associated Cognitive Deficits in Rats

Carvacrol (CAR), a naturally occurring phenolic monoterpene, has been demonstrated to possess various biological actions. The present study was designed to investigate the neuroprotective effect of CAR on diabetes-associated cognitive deficit (DACD) in a rat model of diabetes and exploring its potential molecular mechanism. Diabetic rats were treated with CAR by the doses of 25, 50, and 100 mg/kg for 7 weeks. Morris water maze was used for behavioral evaluation of memory. Cytoplasmic and nuclear fractions of cerebral cortex and hippocampus were prepared for the quantification of oxidative stress (MDA, SOD, and GSH), NF-κB p65 unit, TNF-α, IL-1β, and caspase-3. After 7 weeks of streptozotocin injection, the rats produced remarkable increase in escape latency, coupled with increased oxidative stress (increased MDA level and decreased SOD as well as reduced GSH), NF-κB p65 unit, TNF-α, IL-1β, and caspase-3 in different regions of diabetic rat brain. Interestingly, coadministration of CAR significantly and dose-dependently prevented behavioral, biochemical, and molecular changes associated with diabetes. In summary, our findings provide the first evidence that CAR can remarkably attenuate DACD and suggest the involvement of oxidative stress, inflammation, and apoptotic cascades in the development of cognitive impairment caused by diabetes. The pharmacological effect of CAR suggests that it may be used as a promising agent for the treatment of conventional antihyperglycemic regiments as well as DACD.     

Magnetic thermally sensitive interpenetrating polymer network (IPN) nanogels: IPN-pNIPAm@Fe2O3-SiO2

In this paper, iron oxide-silica@poly(acrylamide-co-N,N-diethylacrylamide)/poly(N,N-diethylacrylamide) interpenetrating polymer network (IPN-pNIPAm@Fe₂O₃-SiO₂) nanogels, possessing both magnetic and thermo-sensitive properties were successfully prepared. The preparation approach involved two steps, consisting of nanoparticle self-assembly and in situ polymerization with monomers. The structural combination of interpenetrating polymer networks (IPNs) with the Fe₂O₃-SiO₂ nanoparticles led to a synergistic property enhancement of both IPNs and nanoparticles, which could increase the mechanical strength of hydrogels and decrease the aggregation of nanoparticles. The synergistic effect was induced by the compatibility of these two individual components. Furthermore, the swelling and shrinking behaviors of the IPN-pNIPAm@Fe₂O₃-SiO₂ nanogels revealed the reversible thermo-responsive properties of IPN nanogels. This fabrication approach for IPN-pNIPAm@Fe₂O₃-SiO₂ nanogels can provide a facile route for manufacturing smart nanocomposites with stability in aqueous solution and reversible swelling/deswelling stimuli-responsive properties to achieve multifunctional tasks in clinical therapy.

In this paper, iron oxide-silica@poly(acrylamide-co-N,N-diethylacrylamide)/poly(N,N-diethylacrylamide) interpenetrating polymer network (IPN-pNIPAm@Fe₂O₃-SiO₂) nanogels, possessing both magnetic and thermo-sensitive properties were successfully prepared.     

Oral Administration of Polaprezinc Attenuates Fluorouracil‐induced Intestinal Mucositis in a Mouse Model

5‐Fluorouracil (5‐FU) has broadly been applied to treat colorectal cancer as one of the most effective chemotherapeutic agents. However, it frequently causes intestinal mucosal injury and related side effects, such as abdominal pain and diarrhoea, which limit the use of 5‐FU in a clinic setting. Polaprezinc has gradually become known as a mucosal protective agent for the management of gastric ulcer. This study aimed to investigate the prophylactic efficacy of Polaprezinc administered orally against intestinal mucositis induced by 5‐FU in mice on the condition that the antitumour effect could not be compromised. We induced intestinal mucositis in SPF‐grade ICR mice with 5‐FU, and evaluated intestinal damage in the absence or presence of Polaprezinc. We examined the score of diarrhoea and the loss of weight after the 5‐FU treatment and assessed the integrity of villus and the proliferation of small intestine crypt cells by haematoxylin and eosin staining and PCNA immunohistochemical detection. The antitumour effect of 5‐FU on colorectal cancer was assessed with or without Polaprezinc in a xenograft model. The result showed that Polaprezinc significantly reduced the elevated diarrhoea score and the body‐weight loss caused by 5‐FU abolished histological abnormality and crypt cell hypoproliferation in a dose‐dependent manner, without affecting 5‐FU efficacy on colon xenograft tumour in mice. We conclude that Polaprezinc could inhibit 5‐FU‐induced diarrhoea and alleviate the weight loss during 5‐FU chemotherapy, as a possible candidate for treatment and prevention of intestinal mucositis, through protecting intestinal mucosa and improving the quality of life after chemotherapy.     

FLAIR vascular hyperintensity predicts early neurological deterioration in patients with acute ischemic stroke receiving endovascular thrombectomy

Neurological Sciences - Fluid-attenuated inversion recovery vascular hyperintensity (FVH) is frequently observed in patients with acute ischemic stroke (AIS). FVH is associated with functional...