Microenvironment-triggered cascade metal-polyphenolic nanozyme for ROS/NO synergistic hyperglycemic wound healing.

Wound infection of hyperglycemic patient often has extended healing period and increased probability due to the high glucose level. However, achieving precise and safe therapy of the hyperglycemic wound with specific wound microenvironment (WME) remains a major challenge. Herein, a WME-activated smart L-Arg/GOx@TA-Fe (LGTF) nanozymatic system composed of generally recognized as safe (GRAS) compound is engineered. The nanozymatic system combining metal-polyphenol nanozyme (tannic acid-Fe3+, TA-Fe) and natural enzyme (glucose oxidase, GOx) can consume the high-concentration glucose, generating reactive oxygen species (ROS) and nitric oxide (NO) in situ to synergistically disinfect hyperglycemia wound. In addition, glucose consumption and gluconic acid generation can lower glucose level to promote wound healing and reduce the pH of WME to enhance the catalytic activities of the LGTF nanozymatic system. Thereby, low-dose LGTF can perform remarkable synergistic disinfection and healing effect towards hyperglycemic wound. The superior biosafety, high catalytic antibacterial and beneficial WME regulating capacity demonstrate this benign GRAS nanozymatic system is a promising therapeutic agent for hyperglycemic wound.

Application Effects of Individualized Diet Nursing Combined with the Modified Glasgow-Blatchford Scoring System in Upper Gastrointestinal Bleeding.

Background: Upper gastrointestinal bleeding encompasses bleeding arising from esophageal, gastric, duodenal, or pancreaticobiliary lesions above the Treitz ligament. Research indicates a close association between improper diet and upper gastrointestinal bleeding. Objective: This study aims to investigate the application effects of individualized diet nursing combined with the modified Glasgow-Blatchford scoring system in patients with upper gastrointestinal bleeding. Design: A randomized controlled study was conducted. Setting: The study took place at the First Hospital of Hebei Medical University. Participants: From January 2021 to October 2022, 80 patients with upper gastrointestinal bleeding were selected at our hospital. Using a random number table, they were divided into a control group and an observation group, each comprising 40 cases. Interventions: The control group received routine nursing, while the observation group received individualized diet nursing based on the Glasgow-Blatchford score in addition to routine nursing. Primary Outcome Measures: (1) bleeding frequency, hemostasis time, and hospital stay; (2) re-bleeding rate; (3) Glasgow-Blatchford scores; (4) quality of life; and (5) nursing satisfaction. Results: In the observation group, bleeding frequency, hemostasis time, and hospital stay significantly reduced compared to the control (P < .05). Post-nursing, the observation group had a lower re-bleeding rate (χ2=11.25, P < .05). Before nursing, no statistical differences existed in Glasgow-Blatchford and quality of life scores between groups (P > .05). Post-nursing, both groups saw reduced Glasgow-Blatchford scores, more so in the observation group (P < .05). Quality of life scores increased in both, more notably in the observation group (P < .05). Overall nursing satisfaction was higher in the observation group (P < .05). Conclusions: Individualized diet nursing, based on the Glasgow-Blatchford score, improves cure rates and quality of life and warrants promotion.

The association of hypophysitis with immune checkpoint inhibitors use: Gaining insight through the FDA pharmacovigilance database.

The use of immune checkpoint inhibitor (ICI) marked a revolutionary change in cancer treatment and opened new avenues for cancer therapy, but ICI can also trigger immune-related adverse events (irAEs). Here, we investigated the publicly available US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to gain insight into the possible association between immune checkpoint inhibitors and hypophysitis. Data on adverse events (AEs) due to hypophysitisfor nivolumab, pembrolizumab, ipilimumab, and atezolizumab were collected from the US FDA Adverse Event Reporting System from the first quarter of 2004 to the second quarter of 2021, and the signals for hypophysitis associated with the four drugs were examined using the reporting odds ratio (ROR) method. The number of reported hypophysitis events ≥ 3 and the lower limit of the 95% confidence interval (CI) of the ROR > 1 were considered positive for hypophysitis signals. A total of 1252 AE reports of hypophysitis associated with nivolumab, pembrolizumab, ipilimumab, and atezolizumab were collected, including 419, 149, 643, and 41 cases, respectively. The RORs of hypophysitis were 289.58 (95% CI 258.49-324.40), 171.74 (95% CI 144.91-203.54), 2248.57 (95% CI 2025.31-2496.45), and 97.29 (95% CI 71.28-132.79), respectively. All four drugs were statistically correlated with the target AE, with the correlation being, in descending order, ipilimumab, nivolumab, pembrolizumab, and atezolizumab. Nivolumab, pembrolizumab, ipilimumab, and atezolizumab have all been associated with hypophysitis, which can negatively impact quality of life, and early recognition and management of immune checkpoint inhibitor-related hypophysitis is critical.

Transition Metal High-Entropy Nanozyme: Multi-Site Orbital Coupling Modulated High-Efficiency Peroxidase Mimics.

Strong substrate affinity and high catalytic efficiency are persistently pursued to generate high-performance nanozymes. Herein, with unique surface atomic configurations and distinct d-orbital coupling features of different metal components, a class of highly efficient MnFeCoNiCu transition metal high-entropy nanozymes (HEzymes) is prepared for the first time. Density functional theory calculations demonstrate that improved d-orbital coupling between different metals increases the electron density near the Fermi energy level (EF ) and shifts the position of the overall d-band center with respect to EF , thereby boosting the efficiency of site-to-site electron transfer while also enhancing the adsorption of oxygen intermediates during catalysis. As such, the proposed HEzymes exhibit superior substrate affinities and catalytic efficiencies comparable to that of natural horseradish peroxidase (HRP). Finally, HEzymes with superb peroxidase (POD)-like activity are used in biosensing and antibacterial applications. These results suggest that HEzymes have great potential as new-generation nanozymes.

Exposure Order to Photoaging and Humic Acids Significantly Modifies the Aggregation and Transformation of Nanoplastics in Aqueous Solutions.

The colloidal stability of nanoplastics in aqueous solutions is greatly regulated by photoaging and dissolved organic matter (DOM). However, how the exposure order to sunlight and DOM modifies the environmental behavior of nanoplastics is seldomly determined. Here, with two different exposure orders, we investigated the impact of molecular-weight (MW)-fractionated humic acids (HAs) derived from biochar and the Suwannee River, respectively, on the aggregation of poly(ethylene terephthalate) nanoplastics (PET-NPs) in mono- and divalent electrolyte solutions. For exposure pattern (i) (photoaging followed by HA coating), photoaged PET-NPs had more oxidized surfaces and exhibited 22-320% higher binding affinity to HAs (especially the higher MW fractions) than the pristine counterparts, which greatly improved the dispersion of PET-NPs. For exposure pattern (ii) (HA coating followed by photoaging), HA-PET assemblies were formed, the dispersion of which increased with increasing irradiation time and was significantly higher than that of the samples in the exposure pattern (i) at the end of the experiment. This high dispersion of photoaged HA-PET assemblies was ascribed to the extra oxidation of PET by reactive oxygen species generated in the PET-HA interfaces during photoaging. These findings highlight the "active nature" of HA-PET assemblies, which provide new insight into the reaction of HA with nanoplastics beyond adsorption in the natural environment.

Tannic acid-derived selective capture of bacteria from apple juice.

Given the enormous burden pathogens pose on human health, rapid capture and removal of bacteria for sterilization or further bacterial detection is essential. Herein, tannic acid-functionalized virus-like Fe3O4 (vFe3O4-TA) was established for bacterial enrichment. We investigated the ability of vFe3O4-TA to capture Gram-negative bacteria (E. coli, S. flex and S. typhi) and Gram-positive bacteria (S. aureus, MRSA and LM), respectively. Compared to the capture efficiency of <15 % for Gram-negative bacteria, vFe3O4-TA showed excellent selectivity and efficiency in isolating Gram-positive bacteria with >87 % removal efficiency. GFN-xTB semiempirical quantum chemical calculations revealed that the selective recognition originates from the high affinity between TA and peptidoglycan. Without impacting ingredients, the TA-mediated trapper also shows excellent ability to distinguish Gram-positive bacteria in juice samples. These results are expected to reveal the interaction of TA with bacteria, and inaugurate a potential natural safe tool for food safety control, medical treatment and environmental remediation.

A high-efficient and stable artificial superoxide dismutase based on functionalized melanin nanoparticles from cuttlefish ink for food preservation.

Natural superoxide dismutase (SOD), consisting of proteins and metal cofactors, is widely used in food preservation because of its good antioxidant activity. However, due to the poor stability of SOD enzyme, its activity was reduced in the process of moving into the film, resulting in limited application. Based on the structure of the active site of the natural enzyme, Cu2+ was used to functionalize the melanin nanoparticles (NMPs) in ink of cuttlefish, and an SOD-like nanozyme (Cu-NMPs) with high stability, high activity and strong free radical scavenging capacity was constructed. In order to apply the constructed simulated enzyme to food preservation, the simulated enzyme was embedded into carrageenan (Carr) films to prepare the composite film for food packaging. The results showed that when the concentration of Cu-NMPs was 10 µg/mL, the ·O2- rate could reach more than 80 %, the activity exceeded that of 60 U/mL natural SOD. In addition, the fresh-keeping test of cherry tomatoes showed that Carr/Cu-NMPs composite film extended the storage time of cherry tomatoes by more 3 days. Therefore, the present work showed that nanozymes with advanced catalytic capabilities can be constructed by metal ions and NMPs, thus successfully combined with food packaging for food preservation.

Preparation and Characterization of Phenolic Acid-Chitosan Derivatives as an Edible Coating for Enhanced Preservation of Saimaiti Apricots.

In this study, caffeic acid (CA) and chlorogenic acid (CGA) were incorporated onto chitosan (CS) using free radical grafting initiated by a hydrogen peroxide/ascorbic acid (H2O2/Vc) redox system. The structural properties of the CA (CA-g-CS) and CGA (CGA-g-CS) derivatives were characterized by UV-Vis absorption, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), nuclear magnetic resonance (NMR), and thermal stability analysis. Then, the antioxidant and antibacterial properties were evaluated, and the effect of CGA-g-CS on the postharvest quality of Saimaiti apricot was studied. It proved that phenolic acids were successfully grafted onto the CS. The grafting ratios of CA-g-CS and CGA-g-CS were 126.21 mg CAE/g and 148.94 mg CGAE/g. The antioxidation and antibacterial activities of CGA-g-CS were better than those of CA-g-CS. The MICs of CGA-g-CS against E. coli, S. aureus, and B. subtilis were 2, 1, and 2 mg/mL. The inhibitory zones of 20 mg/mL CGA-g-CS against the three bacteria were 19.16 ± 0.35, 16.33 ± 0.91, and 16.24 ± 0.05 mm. The inhibitory effects of 0.5% CGA-g-CS on the firmness, weight loss, SSC, TA, relative conductivity, and respiration rate of the apricot were superior. Our results suggest that CGA-g-CS can be potentially used as an edible coating material to preserve apricots.

Effect of root exudates on the release, surface property, colloidal stability, and phytotoxicity of dissolved black carbon.

In this study, the release of dissolved black carbon (DBC) from bulk-BC, its surface properties, colloidal stability, and oxidative stress to rice seedlings in the presence and absence of rice root exudates were compared. The bulk-BCs were prepared at 550 °C and derived from wood chips and pig manure, respectively. The release of DBC from bulk-BC was significantly enhanced (20.19-23.63%) by the introduction of root exudates, where low molecular weight organic acids played a dominating role in the dissociation of DBC from carbon skeleton. The surface properties of DBC were greatly modified by root exudates including decreases in the surface area (18.13%) and mineral contents (43.90-69.57%). The O-containing groups and graphitization were also enhanced by 11.46% and 18.65%, respectively. Meanwhile, the presence of root exudates not only reduced the colloidal stability of DBC but also lowered the intensity of free radicals (19.44-22.22%) in DBC. Consequently, the oxidative stress of DBC to rice seedlings was significantly (p < 0.05) alleviated, evidenced by reduced antioxidative enzyme activities (5.67-29.25%) and soluble protein content (15.75-46.79%) in rice plants. These results indicate that the interaction between DBC and root exudates could remarkably modify the surface properties and reactivity of DBC, which has profound implications for understanding the behavior and functions of DBC in the environment.

LncRNA ZNF883-Mediated NLRP3 Inflammasome Activation and Epilepsy Development Involve USP47 Upregulation.

The goal of this study was to characterize the mechanisms of long noncoding RNA (lncRNA) ZNF883 regulating NOD-like receptor 3 (NLRP3) inflammasome activation in epilepsy (EP). Rat and cellular EP models were established using pilocarpine and magnesium-free extracellular fluid, respectively, to detect the differential expression of ZNF883, microRNA (miR)-138-5p, ubiquitin-specific peptidase 47 (USP47), and NLRP3. The pathology of the hippocampal neurons was examined by whole-cell patch clamping. The expression of ZNF883, miR-138-5p, and USP47 was modified in epileptic neurons, and the EP rats were injected with sh-ZNF883. Then, alterations in ZNF883, miR-138-5p, and USP47 levels were measured. The histopathology of the hippocampus was detected, along with the detection of IL-6, IL-1ß, TNF-α, and NLRP3. Neuronal apoptosis in the rat and cellular EP models was determined. The relationship among ZNF883, miR-138-5p, and USP47 as well as the regulation of NLRP3 ubiquitination by USP47 was determined. ZNF883, USP47, and NLRP3 were increasingly expressed and miR-138-5p was downregulated in epileptic neurons and rats, concurrent with aggravated inflammation and apoptosis. ZNF883 overexpression in epileptic neurons elevated USP47 expression. ZNF883 targeted miR-138-5p and miR-138-5p negatively regulated USP47. In epileptic neurons, inhibiting miR-138-5p or overexpressing USP47 partially reversed the ZNF883 silencing-induced inhibition on NLRP3 inflammasome activation, neuronal apoptosis, and epileptiform activity. ZNF883 silencing in EP rats decreased USP47 and NLRP3, increased miR-138-5p, and inhibited inflammation and apoptosis. USP47 reversed the ubiquitination of NLRP3. ZNF883 inhibits NLRP3 ubiquitination and promotes EP through upregulating USP47 by sponging miR-138-5p.

Genome-wide identification of BAM (ß-amylase) gene family in jujube (Ziziphus jujuba Mill.) and expression in response to abiotic stress.

BACKGROUND: Elevated temperature and drought stress have substantial impacts on fruit quality, especially in terms of sugar metabolism and content. ß-Amylase (BAM) plays a critical role in regulating jujube fruit sugar levels and abiotic stress response. Nevertheless, little is known about the regulatory functions of the BAM genes in jujube fruit. RESULTS: Nine jujube BAM genes were identified, clustered into four groups, and characterized to elucidate their structure, function, and distribution. Multiple sequence alignment and gene structure analysis showed that all ZjBAM genes contain Glu-186 and Glu-380 residues and are highly conserved. Phylogenetic and synteny analysis further indicated that the ZjBAM gene family is evolutionarily conserved and formed collinear pairs with the BAM genes of peach, apple, poplar, Arabidopsis thaliana, and cucumber. A single tandem gene pair was found within the ZjBAM gene family and is indicative of putative gene duplication events. We also explored the physicochemical properties, conserved motifs, and chromosomal and subcellular localization of ZjBAM genes as well as the interaction networks and 3D structures of ZjBAM proteins. A promoter cis-acting element analysis suggested that ZjBAM promoters comprise elements related to growth, development, phytohormones, and stress response. Furthermore, a metabolic pathways annotation analysis showed that ZjBAMs are significantly upregulated in the starch and sucrose metabolism, thereby controlling starch-maltose interconversion and hydrolyzing starch to maltose. Transcriptome and qRT-PCR analyses revealed that ZjBAMs respond positively to elevated temperature and drought stress. Specifically, ZjBAM1, ZjBAM2, ZjBAM5, and ZjBAM6 are significantly upregulated in response to severe drought. Bimolecular fluorescence complementation analysis demonstrated ZjBAM1-ZjAMY3, ZjBAM8-ZjDPE1, and ZjBAM7-ZjDPE1 protein interactions that were mainly present in the plasma membrane and nucleus. CONCLUSION: The jujube BAM gene family exhibits high evolutionary conservation. The various expression patterns of ZjBAM gene family members indicate that they play key roles in jujube growth, development, and abiotic stress response. Additionally, ZjBAMs interact with α-amylase and glucanotransferase. Collectively, the present study provides novel insights into the structure, evolution, and functions of the jujube BAM gene family, thus laying a foundation for further exploration of ZjBAM functional mechanisms in response to elevated temperature and drought stress, while opening up avenues for the development of economic forests in arid areas.

Novel Insights into the Impact of Nano-Biochar on Composition and Structural Transformation of Mineral/Nano-Biochar Heteroaggregates in the Presence of Root Exudates.

Multiple lines of existing evidence indicate that natural organic matter (NOM) could protect poorly crystalline Fe(III) (oxyhydr)oxides from Fe(II)-catalyzed mineral transformation. Conversely, we find that nano-sized biochar (nano-BC), a pyrogenic form of NOM, promotes the phase transformation of ferrihydrite (Fh) in nano-BC/Fh heteroaggregates in the presence of aqueous Fe(II) and rice root exudates. The nano-BC/Fh heteroaggregates are composed of a core-shell like structure where the inner-layered nano-BC is more compacted and plays the dominant role in accelerating the phase transformation of Fh relative to that in the outer sphere. The extent of phase transformation is more regulated by the reversible redox reactions between quinone and hydroquinone in nano-BC than the electron transfer via its condensed aromatic structures. Furthermore, the reductive organic acids in root exudates contribute to the mineral transformation of nano-BC/Fh associations by donating electrons to Fe(III) through nano-BC. Our results suggest that heteroaggregates between nano-BC and Fe minerals are subjected to partial dissociation during their co-transport, and the stably attached nano-BC is favorable to the phase transformation of poorly crystalline Fe minerals (e.g., Fh), which might have profound implications on biogeochemical cycles of carbon and Fe in the prevailing redox environments.

Comparison of Modified Above-Knee and Conventional Surgery with the Stripping of the Great Saphenous Vein of Varicose Veins of the Lower Extremities: A Retrospective Study.

OBJECTIVE: To compare the clinical effects of modified above-knee and conventional surgery with the stripping of the great saphenous vein of varicose veins of the lower extremities. METHODS: Clinical data of patients with a varicose vein of the lower extremity from May 2016 to May 2018 were collected. A retrospective study was conducted on the patients receiving modified above-knee and conventional surgery with the great saphenous vein stripping. The baseline characteristics and long-term follow-up data were compared between the groups. RESULTS: There were no significant differences in baseline characteristics between the two groups (P > 0.05). The surgeries were successfully performed by the same group of surgeons under local anesthesia and neuraxial anesthesia. The hospital stay, operation time, intraoperative blood loss, total length, and number of incisions in the above-knee group were comparable to those in the conventional surgery group (P > 0.05). The incidence of saphenous nerve injury and subcutaneous hematoma in the above-knee group was lower than that in the conventional surgery group (P < 0.05). There were no significant differences in recurrent varicose vein incidences (P > 0.05). After surgery, the venous clinical severity score (VCSS) and chronic venous insufficiency questionnaire (CIVIQ-14) scores of both groups were higher than those before operation (P < 0.05). There was no significant difference in VCSS score or CIVIQ-14 scores between the two groups postoperation (P > 0.05). At 24 months after surgery, the above-knee group (71.8%) and conventional surgery group (73.2%) resulted in changes of at least two CEAP-C clinical classes lower than baseline, respectively. CONCLUSION: The modified above-knee technique can ensure clinical outcomes, reduce intraoperative blood loss and complication incidences, and shorten the operative time. This gives evidence that the modified above-knee technique is worthy of clinical application.

Potential toxicity of nanoplastics to fish and aquatic invertebrates: Current understanding, mechanistic interpretation, and meta-analysis.

Nanoplastics (NPs) are widely detected in aquatic ecosystems and attracting considerable attention. Although ecotoxicological impacts of NPs on aquatic biota are increasingly identified, the extent and magnitude of these detrimental effects on fish and aquatic invertebrates still lack systematic quantification and mechanistic interpretation. Here, the toxicity, influencing factors, and related mechanisms of NPs to fish and aquatic invertebrates are critically reviewed and summarized based on a total of 634 biological endpoints through a meta-analysis, where five vital response categories including growth, consumption, reproduction, survival, and behavior were emphasized to elucidate the negative impacts of NPs to fish and aquatic invertebrates from physiological to molecular levels. Our results revealed that NPs significantly decreased the survival, behavior, and reproduction of fish and/or aquatic invertebrates by 56.1%, 24.2%, and 36.0%, respectively. NPs exposure increased the oxidative stress and oxidative damage by 72.0% and 9.6%, respectively; while significantly decreased antioxidant prevention system and neurotransmission by 24.4% and 15.9%, respectively. Also, the effects of particle size, functional group, and concentration range of NPs on the physiological and biochemical reactions in the living organisms were discussed. This information is helpful to more accurately understanding the underlying toxic mechanisms of NPs to aquatic biota and guiding future studies.

Dextran-stabilized Fe-Mn bimetallic oxidase-like nanozyme for total antioxidant capacity assay of fruit and vegetable food.

The total antioxidant capacity (TAC) has become increasingly vital for evaluating antioxidant food quality in the field of healthcare. Herein, a convenient and sensitive method for TAC assay was proposed based on the absorbance difference of reaction systems between various antioxidants existed in food and Dex-FeMnzyme/oxTMB. Under the optimum condition, the limit of detection (LOD) of the colorimetric sensor was 1.17 µM with the linear concentration range from 1 µM to 30 µM. The analysis results demonstrated the excellent feasibility of practical application in fruit and vegetable food, which offered a new avenue for the establishment of colorimetric biosensors.

Photochemical Transformation and Catalytic Activity of Dissolved Black Nitrogen Released from Environmental Black Carbon.

Biomass combustion results in the formation and wide distribution of black carbon (BC) in soils, wherein the dissolved fractions are among the most active components. Although the presence of dissolved black nitrogen (DBN) in BC has been identified, its environmental behavior and implication are not understood. This study investigated the photochemical transformation and catalytic activity of DBN under simulated solar irradiation. DBN is more easily transformed than dissolved BC due to its photoactive heteroaromatic N structure, and the half-life of DBN produced at 500 °C (8.6 h) is two times shorter than that of the dissolved BC counterpart (23 h). Meanwhile, solar irradiation is favorable for the homoaggregation of DBN. During irradiation, DBN generates not only reactive oxygen species (e.g., 1O2, O2-, and •OH) but also reactive nitrogen species (mainly •ON), which account for its higher photocatalytic degradation of bisphenol A than dissolved BC. These findings shed new light on the impact of heteroatoms on the phototransformation and activity of BC as well as cycling of N in terrestrial systems.

2-Deoxy-D-Glucose Exhibits Anti-seizure Effects by Mediating the Netrin-G1-KATP Signaling Pathway in Epilepsy.

Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. The glycolytic inhibitor 2-deoxy-D-glucose (2-DG) has been reported to exert antiepileptic effects by upregulating KATP subunits (kir6.1 and kir6.2). We evaluated whether 2-DG exhibits anti-seizure effect by mediating the netrin-G1-KATP signaling pathway in epilepsy. In a mouse epilepsy model induced by lithium chloride-pilocarpine, 2-DG intervention increased the mRNA and protein expression levels of kir6.1 and kir6.2, and these increases were significantly reversed after knocking down netrin-G1 expression. Similarly, in cultured neurons with a magnesium-free medium, we found that the frequency of spontaneous postsynaptic potentials (SP) was increased, and in the meanwhile, expression levels of kir6.1 and kir6.2 were increased after pretreatment with 2DG. These effects were remarkably reversed after knocking down netrin-G1. Thus, our findings show that 2DG exhibits anti-seizure effects through the netrin-G1-KATP signaling pathway.

Suppression of microRNA-141 suppressed p53 to protect against neural apoptosis in epilepsy by SIRT1 expression.

We investigated that microRNA (miRNA)-141 protects against epilepsy-induced apoptosis and its reaction mechanism. The serum expression of miRNA-141 in epilepsy model mice and control volunteer was measured by quantitative reverse-transcription polymerase chain reaction. We found that miRNA-141 serum expression was upregulated in patients with epilepsy. Overexpression of miRNA-141 induced nerve cell apoptosis, suppressed proliferation, promoted caspase-3/9, Bax and p53 protein expression, and reduced silent information regulator 1 (SIRT1) protein expression in vitro model. In addition, the downexpression miRNA-141 using si-miRNA-141 reduced nerve cell apoptosis and increased proliferation, suppressed caspase-3/9, Bax and p53 protein expression, induced SIRT1 protein expression. SIRT1 inhibitor (nicotinamide) decreased SIRT1, reduced the effects of miRNA-141 on nerve cell apoptosis in vitro model of epilepsy through SIRT1/p53. SIRT1 agonist also reduced the effects of miRNA-141 overexpression on nerve cell apoptosis in vitro model of epilepsy through SIRT1/p53. Our preliminary findings indicate that anti-miRNA-141 protects against epilepsy-induced apoptosis via SIRT1/p53 expression.

Comparative Epidemiological Investigation of Alzheimer's Disease and Colorectal Cancer: The Possible Role of Gastrointestinal Conditions in the Pathogenesis of AD.

Alzheimer's disease (AD) is a neurodegenerative disorder that affects approximately 35 million people worldwide, and diet has been reported to influence the prevalence/incidence of AD. Colorectal cancer is among the most common cancers in Western populations, and the correlation between constipation and the occurrence of colorectal cancer has been identified in a number of studies, which show that a Westernized diet is a mutual risk factor. Constipation is a growing health problem, particularly in middle-aged and older adults. As the most common gastrointestinal disorder in adults, constipation affects 2-20% of the world population, and it is associated with several diseases, such as diabetes, Parkinson's disease, and others. Comparing the epidemiological data on colorectal cancer and AD, we find that colorectal cancer and AD have similar epidemiologic feature, which is both disease correlate with high prevalence of constipation. Therefore, we hypothesized that constipation may influence Alzheimer's disease in a similar way that it contributes to colorectal cancer. This review aimed to systemically elucidate the evidence that constipation contributes to Alzheimer's disease progression.

Novel thymopentin release systems prepared from bioresorbable PLA-PEG-PLA hydrogels.

Copolymers were synthesized by ring opening polymerization of l- or d-lactide in the presence of dihydroxyl PEG with molar mass of 6000, 12,000 and 20,000, using zinc lactate as catalyst. Bioresorbable hydrogels were obtained by mixing PLLA-PEG-PLLA and PDLA-PEG-PDLA aqueous solutions due to stereocomplexation between PLLA and PDLA chains. Rheological measurements show that the hydrogels present typical viscoelastic behaviors, although degradation could occur during the gelation process. Thymopentin was taken as a model drug to evaluate the potential of PLA-PEG-PLA hydrogels as carrier of hydrophilic drugs. Various parameters such as copolymer concentration, drug load, copolymer composition and the difference between sol and gel were considered. The release profiles are characterized by an initial burst followed by slower release. Higher copolymer concentration leads to slower release rate and less burst effect due to more compact structure which disfavors drug diffusion. Similarly, higher molar mass of the copolymers disfavors the release of TP5, and hydrogels composed of both PLLA/PEG and PDLA/PEG present slower release rates than single copolymer solutions. In contrast, drug load exhibits little influence on the release profiles due to the high water solubility of TP5. In all cases, nearly 80% of TP5 is released. In vivo studies proved the potential of TP5 containing hydrogels, especially those with a concentration of 25%. Both the CD4(+)/CD8(+) ratio and the morphology of thymus indicate the immunization efficacy of the TP5 release systems based on PLA/PEG hydrogels.