Effect of liposomal bupivacaine for preoperative erector spinae plane block on postoperative pain following video-assisted thoracoscopic lung surgery: a protocol for a multicenter, randomized, double-blind, clinical trial.

Background: There is still a controversy about the superiority of liposomal bupivacaine (LB) over traditional local anesthetics in postoperative analgesia after thoracic surgery. This study aims to determine the effect of LB versus bupivacaine hydrochloride (HCl) for preoperative ultrasound-guided erector spinae plane block (ESPB) on postoperative acute and chronic pain in patients undergoing video-assisted thoracoscopic lung surgery. Methods: This multicenter, randomized, double-blind, controlled trial will include 272 adult patients scheduled for elective video-assisted thoracoscopic lung surgery. Patients will be randomly assigned, 1:1 and stratified by site, to the liposomal bupivacaine (LB) group or the bupivacaine (BUPI) HCl group. All patients will receive ultrasound-guided ESPB with either LB or bupivacaine HCl before surgery and patient-controlled intravenous analgesia (PCIA) as rescue analgesia after surgery. The numeric rating scale (NRS) score will be assessed after surgery. The primary outcome is the area under the curve of pain scores at rest for 0-72 h postoperatively. The secondary outcomes include the total amount of opioid rescue analgesics through 0-72 h postoperatively, time to the first press on the PCIA device as rescue analgesia, the area under the curve of pain scores on activity for 0-72 h postoperatively, NRS scores at rest and on activity at different time points during the 0-72 h postoperative period, Quality of Recovery 15 scores at 72 h after surgery, and NRS scores on activity on postsurgical day 14 and postsurgical 3 months. Adverse events after the surgery are followed up to the postsurgical day 7, including postoperative nausea and vomiting, fever, constipation, dizziness, headache, insomnia, itching, prolonged chest tube leakage, new-onset atrial fibrillation, severe ventricular arrhythmia, deep venous thrombosis, pulmonary embolism, pulmonary atelectasis, cardiac arrest, ileus, urinary retention, chylothorax, pneumothorax, and organ failure. Analyzes will be performed first according to the intention to treat principle and second with the per-protocol analysis. Discussion: We hypothesize that LB for preoperative ultrasound-guided ESPB would be more effective than bupivacaine HCl in reducing postoperative pain in video-assisted thoracoscopic lung surgery. Our results will contribute to the optimization of postoperative analgesia regimens for patients undergoing video-assisted thoracoscopic lung surgery.Clinical trial registration:http://www.chictr.org.cn, identifier ChiCTR2300074852.

Research progress in rodent models of endometriosis.

Endometriosis is a common and frequent disease in gynecology; its etiology and pathogenesis are partially understood and still not clear. The construction of suitable animal models is beneficial for basic research related to the disease. Currently, rodents have the advantages of low cost, fast reproduction, easy rearing, and a similar endometrial structure to humans. Depending on the purpose of the experiment, different molding methods have their advantages. In this paper, we describe the traditional methods of constructing endometriosis rodent models, compare their advantages and disadvantages, and introduce newly developed rodent models, such as cell line injection models, pain models, genetically engineered mouse models, fluorescent tracer models, iron overload models, chemical induction models, and methods of constructing rodent models of different subtypes of endometriosis. Fertility and treatment of endometriosis rodent models are also described. This study provides a reference for researchers in the selection of animal models for pathogenesis and drug treatment studies.

The roles of chromatin regulatory factors in endometriosis.

PURPOSE: Endometriosis is an estrogen-dependent inflammatory disease and one of the most common gynecological diseases in women of reproductive age. The aim of the review was to explore the relationship between the chromatin regulatory factors and endometriosis. METHODS: By searching for literature on chromatin regulators and endometriosis in PuMed. Finally, 98 documents were selected. RESULTS: Chromatin regulators (CRs) are essential epigenetic regulatory factors that can regulate chromatin structure changes and are usually divided into three categories: DNA methylation compounds, histone modification compounds, and chromatin remodeling complexes. Noncoding RNAs are also chromatin regulators and can form heterochromatin by binding to protein complexes. Chromatin regulators cause abnormal gene expression by regulating chromatin structure, thereby affecting the occurrence and development of endometriosis. CONCLUSION: This review summarizes the participation of chromatin regulators in the mechanisms of endometriosis, and these changes in related chromatin regulators provide a comprehensive reference for diagnosis and treatment of endometriosis.

Combination of high-frequency electrocautery therapy and ALA-PDT in hyperkeratotic vulvar lichen sclerosus: Series of seven cases.

SIGNIFICANCE: ALA-PDT effectively treats Vulvar lichen sclerosus et atrophicus (VLSA), but it requires multiple repetitions for satisfactory results. To enhance efficacy, we employed a combination of high-frequency electrocautery therapy and ALA-PDT in treating seven VLSA patients. APPROACH: Lesions and leukoplakia in the seven women with VLSA were removed using a high-frequency generator. PDT was administered after wound healing, and it was repeated six times. Follow-up assessments were carried out at 1, 3, and 6 months to evaluate the severity of pruritus and investigate lesion repigmentation. RESULTS: Following the combined therapy, the disappearance of pruritus was observed in all patients, and normal color and thickness were restored to their skin. Two patients reported mild pruritus with a score of 2 one month after treatment, which persisted until the 6-month follow-up, while the remaining patients remained free from pruritus. No recurrence of skin lesions was observed in any of the patients. CONCLUSIONS: The combined therapy for the treatment of VLSA is found to be convenient, effective, and easily promotable.

Tanshinone Alleviates UVA-induced Melanogenesis in Melanocytes via the Nrf2-regulated Antioxidant Defense Signaling Pathway.

BACKGROUND: As a complex of natural plant compounds, tanshinone is renowned for its remarkable antioxidant properties. However, the potential impact of tanshinone on melanocyte pigmentation regulation has yet to be elucidated. This study aimed to explore the protective effects of tanshinone I (T-I) and dihydrotanshinone (DHT) on melanogenesis by modulating nuclear factor E2-related factor 2 (Nrf2) signaling and antioxidant defenses in human epidermal melanocyte (HEM) cells. METHODS: HEM cells and Nrf2 knockdown HEM cells were subjected to ultraviolet A (UVA) and treated with T-I and/or DHT. Then, the anti-melanogenic properties of T-I and DHT were examined by assessing tyrosinase activity, melanogenesis-related proteins, and melanin content in UVA-irradiated HEM cells. Furthermore, the antioxidant activities of T-I and DHT were evaluated by assessing oxidant formation and modulation of Nrf2-related antioxidant defenses, including reactive oxygen species (ROS), glutathione (GSH) content, and the activity and expression of antioxidant enzymes, such as catalase (CAT), heme oxygenase-1 (HO-1), and superoxide dismutase (SOD). RESULTS: Our findings revealed that T-I and DHT diminished melanogenesis in UVAirradiated HEM cells, activated Nrf2-antioxidant response element signaling, and enhanced antioxidant defenses in the irradiated cells. Furthermore, Nrf2 knockdown by shRNA abolished the anti-melanogenesis effects of T-I and DHT on HEM cells against oxidative damage. CONCLUSION: These results suggest that T-I and DHT inhibit UVA-induced melanogenesis in HEM cells, possibly through redox mechanisms involving Nrf2 signaling activation and increased antioxidant defenses. This indicates that T-I and DHT have potential as whitening agents in cosmetics and medical treatments for hyperpigmentation disorders.

The Effectiveness and Safety of Dupilumab for the Treatment of Recalcitrant Chronic Actinic Dermatitis: A Case Series.

Background: Although dupilumab is an effective treatment approach for chronic actinic dermatitis (CAD) in some cases, its effectiveness and safety in CAD have not been sufficiently assessed. Purpose: Evaluation of the effectiveness and safety of dupilumab in patients with recalcitrant CAD was performed. Methods: We retrospectively reviewed the medical records of CAD patients treated with dupilumab. Data regarding demographics were collected, and disease severity scores were assessed using the following: Clinical Severity Score of CAD (CSS-CAD), Atopic Dermatitis Control Tool (ADCT), Dermatology Life Quality Index (DLQI), and Numeric Rating Scale (NRS)-itch scores. Results: After 12 weeks of treatment, there was a significant decrease in disease severity scores of 16 CAD patients. Only one patient achieved a good response and most of the patients (62.5%, 10/16) had no significant symptom improvement after 4 weeks of treatment. However, after 12 weeks of treatment, 43.75% (7/16) of the patients reached excellent response (>75% improvement of CSS-CAD), 31.25% (5/16) good response (50%-75% improvement of CSS-CAD), 6.25% (1/16) partial response (25%-50% improvement of CSS-CAD), and only 18.75% (3/16) no response (<25% improvement of CSS-CAD). One patient complained of injection site reaction at the first injection. Conclusion: This study supports dupilumab as an effective and safe treatment option for patients with recalcitrant CAD. Patients may require at least 4 weeks of treatment before the partial response is noted.

Associations between microbial presence in follicular fluid with IVF outcomes: a systematic review and meta-analysis.

PURPOSE: The aim of the study was to synthesize disparate studies to investigate potential impact of microbial presence in FF of infertile women on IVF outcomes. METHODS: Following preliminary searches to find medical subject heading (MeSH) terms plus free terms, a systematic search was performed in the PubMed, Cochrane Library, Embase, Web of Science, and Clinicaltrials.gov databases from January 10, 2022, to July 5, 2023. Data collected for each study were analyzed using RevMan 5.4 software available on the Cochrane website. RESULTS: After correcting for contamination from the vagina, the FFs of 289 women were detected positively by microbial culture and identification, ELISA, and IPA. The pregnancy rate of the FF-positive group was significantly lower than the FF-negative group (19.7% vs. 32.2%) and (OR: 0.57, 95% CI: 0.28-1.14, P=0.11; I2=56%) while the fertilization rate was almost equal (60.0% vs. 62.0%) and (OR: 1.03, 95% CI: 0.88-1.20, P=0.72; I2=0%). Evidence quality was very low. CONCLUSIONS: The different species of microorganisms in FF of infertile women may have different effects on IVF outcomes. The Lactobacillus spp. may have a positive effect, while other microorganisms may have the opposite effect.

Integrated analysis reveals SMARCD1 is a potential biomarker and therapeutic target in skin cutaneous melanoma.

OBJECTIVE: SMARCD1 is a part of the SWI/SNF chromatin remodeling complex family, which consists of transcription factors that are implicated in various types of cancer. Examining SMARCD1 expression in human cancers can provide valuable insights into the development and progression of skin cutaneous melanoma (SKCM). METHODS: Our study comprehensively examined the association between SMARCD1 expression and numerous factors, including prognosis, tumor microenvironment (TME), immune infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI) in SKCM. Then we utilized immunohistochemical staining to measure the SMARCD1 expression in both SKCM tissues and normal skin tissues. Furthermore, we conducted in vitro experimentation to evaluate the effects of SMARCD1 knockdown on SKCM cells. RESULTS: We found that aberrant expression of SMARCD1 across 16 cancers was strongly correlated with overall survival (OS) and progression-free survival (PFS). In addition, our research revealed that SMARCD1 expression is associated with multiple factors in different types of cancer, including immune infiltration, TME, immune-related genes, MSI, TMB, and sensitivity to anti-cancer drugs. SMARCD1 is likely involved in various SKCM signaling pathways and biological processes. Additionally, our research revealed that an SMARCD1-based risk factor model accurately predicted OS in SKCM patients. Furthermore, the downregulation of SMARCD1 expression demonstrated a significant inhibition of SKCM cell proliferation and migration, as well as an increase in apoptosis and cell cycle arrest. CONCLUSION: We conclude that SMARCD1 is a promising diagnostic, prognostic, and therapeutic biomarker for SKCM, and its expression has significant clinical implications for the development of novel treatment strategies.

Efficacy of low-fluence 1064 nm Q-switched Nd: YAG laser for the treatment of melasma: A meta-analysis and systematic review.

BACKGROUND: Melasma is considered as a type of acquired facial pigmentary disorder that is challenging to treat. Low-fluence 1064 nm Q-switched Nd: YAG laser (LQSNY) has clinical benefits against melasma; however, there are some disputes. OBJECTIVE: To explore these contentious views, we conducted a meta-analysis and systematic review to evaluate the efficacy and safety of LQSNY monotherapy and combined therapy for the treatment of melasma. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for relevant articles from inception to July 2021. The resulting data were analyzed using the Review Manager 5.3 software. RESULTS: Twelve eligible studies comprising 358 patients were included. No significant differences in melasma area and severity index (MASI) were observed between the LQSNY and drug groups (mean difference (MD):-0.26, 95% confidence interval (CI):-1.16-0.64, p = 0.57). We found that combination therapy with LQSNY and drugs had a greater MASI improvement compared with LQSNY therapy alone (MD: 1.78, 95% CI 0.93-2.63, p < 0.0001); nevertheless, no statistically significant results were found in melanin index (MI) and self-assessment. The melasma improvement was similar when using LQSNY alone and LQSNY combined with other lasers in terms of RMASI (MD 0.05, 95% CI:-0.61, 0.70, p = 0.56). Compared with intense pulsed light (IPL) alone, LQSNY with IPL provided an added benefit for melasma severity (MD:3.23, 95% CI:0.65-5.81, p = 0.01). CONCLUSION: Low-fluence 1064 nm Q-switched Nd: YAG laser can be applied as an alternative treatment for drug intolerance. Combination therapy with LQSNY and drugs or other lasers may have pleasantly surprising efficacy, but numerous studies are still needed to verify this.

Efficacy of NB-UVB as Add-on Therapy to Antihistamine in the Treatment of Chronic Urticaria: A Systematic Review and Meta-analysis.

INTRODUCTION: Narrow-band ultraviolet B (NB-UVB) phototherapy has been used for the treatment of chronic urticaria (CU), but the clinical efficacy of this treatment modality requires further evidence. A systematic review and meta-analysis of randomized clinical trials were conducted to evaluate the efficacy and safety of NB-UVB as add-on therapy in the treatment of CU. METHODS: A literature search was conducted in the Cochrane, Embase, PubMed, Web of Science, CNKI, CBM, VIP and WanFang databases up to October 2020. A total of nine studies involving 713 participants met the inclusion criteria. RESULTS: Two trials showed a significant difference in the Urticaria Activity Score between therapy with NB-UVB + antihistamines and that with antihistamines alone (mean difference 8.23, 95% confidence interval [CI] 5.78-10.68, p < 0.00001). Six trials (563 participants) showed a significant benefit of NB-UVB as add-on therapy to antihistamines in the total effective rate (risk ratio [RR] 1.56, 95% CI 1.39-1.75, p < 0.00001). In terms of adverse events, no statistically significant differences were found for NB-UVB + antihistamines versus antihistamines alone (RR 1.10, 95% CI 0.67-1.79, p = 0.71). Combination therapy of NB-UVB + antihistamines yielded a significantly lower risk of recurrence (RR 0.25, 95% CI 0.14-0.44, p < 0.00001). CONCLUSION: Our meta-analysis suggests that combination therapy of NB-UVB + antihistamines is significantly more effective in treating CU than antihistamines alone.

Lycopene protects neuroblastoma cells against oxidative damage via depression of ER stress.

Lycopene is a pigment derived from tomatoes and other red fruits, and has potent antioxidant and antitumor effects. However, its potential role in alleviating oxidative damage in neuronal cells is not well defined. In this study, we investigated the effects of lycopene on H2 O2 -induced damage in neuroblastoma cells, as well as the underlying mechanisms. Exposure to H2 O2 markedly decreased the viability of SH-SY5Y cells and increased LDH release, both of which were reversed by lycopene pretreatment. Lycopene also ameliorated H2 O2 -induced damage and reduced the expression of apoptotic markers, such as Bcl-2, Bax, and cleaved caspase 3. In addition, the H2 O2 -induced oxidative markers, including MDA, 8-OHdG, and protein carbonyls, were also downregulated by lycopene. Exogenous H2 O2 activated the GRP78/PERK/eIF2α signaling pathway, which was inhibited by pretreatment with lycopene. Finally, lycopene significantly ameliorated ER stress-induced activation and nuclear translocation of CHOP. Overexpression of CHOP markedly reversed the antiapoptotic effects of lycopene, indicating that it is essential for the latter's protective effects. Taken together, lycopene protects neuroblastoma cells from oxidative stress and ER stress-induced damage by inhibiting the PERK-CHOP signaling pathway, which is a potential therapeutic target in neurodegenerative diseases. PRACTICAL APPLICATION: Lycopene demonstrated antioxidative damage properties in protecting the neural system in vitro. The present study provides a novel preventive strategy against neurodegenerative diseases. Increased consumption of lycopene-based products and lycopene-rich fruits and vegetables may result in a lower risk for neurodegenerative diseases.

Lycopene alleviates oxidative stress via the PI3K/Akt/Nrf2pathway in a cell model of Alzheimer's disease.

BACKGROUND & AIMS: Oxidative stress (OS) plays an important role in neurodegenerative diseases such as Alzheimer's disease (AD). Lycopene is a pigment with potent antioxidant and anti-tumor effects. However, its potential role in central nervous system is not well-defined. The aim of this study was to investigate the effect of lycopene on the cell model of AD and determine its underlying mechanisms. METHODS: M146L cell is a double-transfected (human APP gene and presenlin-1 gene) Chinese hamster ovary (CHO) cell line that overexpresses ß -amyloid (Aß) and is an ideal cell model for AD. We treated cells with lycopene, and observed the effect of lycopene on M146L cells. RESULTS: Oxidative stress and apoptosis in M146L cells were significantly higher than those in CHO cells, suggesting that Aß induced OS and apoptosis. Lycopene alleviated OS and apoptosis, activated the PI3K/Akt/Nrf2 signaling pathway, upregulated antioxidant and antiapoptotic proteins and downregulated proapoptotic proteins. Additionally, lycopene inhibited ß -secretase (BACE) activity in M146L cells. These results suggest that lycopene inhibits BACE activity and protects M146L cells from oxidative stress and apoptosis by activating the PI3K/Akt/Nrf2 pathway. CONCLUSION: Lycopene possibly prevents Aß-induced damage by activating the PI3K/Akt/Nrf2 signaling pathway and reducing the expression of BACE in M146L cells.

Cyclovirobuxine D inhibits cell proliferation and migration and induces apoptosis in human glioblastoma multiforme and low­grade glioma.

Gliomas are the most common neoplasm of the human central nervous system. Glioblastoma multiforme (GBM) is one of the most serious types of gliomas. Although considerable progress has been made in the development of cancer therapeutic agents, several antineoplastic drugs fail to penetrate the blood­brain barrier (BBB), resulting in a low survival rate of glioma patients. Recent studies have revealed that the traditional Chinese medicine Buxus microphylla contains the main active component Cyclovirobuxine D (CVB­D), which can cross the BBB with a novel delivery system. However, it remains unclear whether CVB­D exerts anticancer effects against GBM and low­grade glioma (LGG). The aim of the present study was to explore the feasibility of CVB­D as a new effective agent in the treatment of GBM and LGG. The ability of CVB­D to inhibit GBM and LGG cell proliferation was detected by CCK8 assay. Flow cytometry was used to detect cell cycle progression and apoptosis induction by Annexin V­FITC/PI assay. The expression levels of the apoptosis­associated proteins, namely cleaved caspase­3 and Bax/Bcl­2, were detected by western blot analysis. The mitochondrial membrane potential (ΔΨm) was detected by Rh123 dyed fluorescence micrograph. Hoechst staining was used to observe the morphological characteristics of the apoptotic cells. The scratch test was used to evaluate the migration of GBM and LGG cells. The results indicated that CVB­D reduced cell viability of T98G and Hs683 cells. Flow cytometry demonstrated that CVB­D­treated cells were arrested at the S phase of their cell cycle. The expression levels of the apoptosis­associated proteins were increased in CVB­D­treated cells. Rh123 and Hoechst staining indicated morphological changes and mitochondrial membrane potential changes of the cells undergoing apoptosis. The data confirmed that CVB­D inhibited cell proliferation by arresting the cell cycle of GBM and LLG cells and that it promoted the induction of cell apoptosis by altering the mitochondrial membrane potential. The findings of the present study indicate the potential value of CVB­D in the treatment of glioma.

Plasma amyloid beta level changes in aged mice with cognitive dysfunction following sevoflurane exposure.

INTRODUCTION: Previous studies have stated that cognitive impairment induced by anesthetics was associated with amyloid beta (Aß). However, few researchers have investigated the transport of Aß inside and outside of the brain. AIM: We attempted to probe the effects of sevoflurane on cognitive functions, the plasma Aß, and transporters of Aß in aged mice. The receptor for advanced glycation end-products (RAGE) is an Aß influx protein, and Low-density lipoprotein receptor-related protein-1 (LRP-1) is an Aß efflux protein. METHODS: Aged mice were divided into the control group and the sevoflurane group. The mice were exposed to 100% oxygen or 2.5% sevoflurane for 2 h. The abilities of spatial learning and memory in mice were tested using the Morris water maze. Aß concentrations of plasma were measured with enzyme-linked immunosorbent assay kits. The RAGE and LRP-1 gene levels in the brain were assessed with quantitative polymerase chain reaction, and the protein levels were determined by western blot analysis. The locations of RAGE in the brain were confirmed via immunofluorescence. RESULTS: In the sevoflurane group mice, the escape latency was increased on the 5th day of training, and the time spent in the target quadrant was decreased on the 7th day after anesthesia. Sevoflurane reduced the concentration of plasma Aß1-40. In addition, sevoflurane increased both gene and protein levels of RAGE in the brain, and increased RAGE proteins co-localized with the hippocampal vascular endothelial cells. CONCLUSION: RAGE over-expression in the hippocampal vascular endothelial cells possibly resulted in the excessive transport of the plasma Aß1-40 into the brain after treatment with sevoflurane, which was associated with sevoflurane-induced cognitive dysfunction in aged mice.

Studies on APP metabolism related to age-associated mitochondrial dysfunction in APP/PS1 transgenic mice.

The aging brain with mitochondrial dysfunction and a reduced adenosine 5'-triphosphate (ATP) has been implicated in the onset and progression of ß-Amyloid (Aß)-induced neuronal toxicity in AD. To unravel the function of ATP and the underlying mechanisms on AD development, APP/PS1 double transgenic mice and wild-type (WT) C57 mice at 6 and 10 months of age were studied. We demonstrated a decreased ATP release in the hippocampus and platelet of APP/PS1 mice, comparing to C57 mice at a relatively early age. Levels of Aß were raised in both hippocampus and platelet of APP/PS1 mice, accompanied by a decrease of α-secretase activity and an increase of ß-secretase activity. Moreover, our results presented an age-dependent rise in mitochondrial vulnerability to oxidation in APP/PS1 mice. In addition, we found decreased pSer473-Akt levels, increased GSK3ß activity by inhibiting phosphorylation at Ser9 in aged APP/PS1 mice and these dysfunctions probably due to down-regulation of Bcl-2 and up-regulation of cleaved caspase-3. Therefore, we demonstrate that PI3K/Akt/GSK3ß signaling pathway could be involved in Aß-associated mitochondrial dysfunction of APP/PS1 mice and APP abnormal metabolism in platelet might provide potential biomarkers for early diagnosis of AD.

In vivo monitoring of superoxide anion from Alzheimer's rat brains with functionalized ionic liquid polymer decorated microsensor.

The superoxide anion (O2•-) is an important reactive oxygen species (ROS) in the brain system, which has been associated with the development of many neurological diseases, including Alzheimer's disease (AD). Herein, we introduced a carbon fiber microelectrode (CFME) based in vivo technique for specific and sensitive monitoring of the O2•- radical in the living brains of both normal and AD model rats. Compared with other reported superoxide dismutase (SOD) electrochemical biosensors, the microsensor presented in our work was featured in the coating of a functionalized ionic liquid polymer (PIL) onto PB nanoparticles (PBNPs) and carbon nanotubes (CNT). It was demonstrated that the cationic and carboxyl-rich PILs provided abundant interaction sites with SOD to prevent enzyme leakage from sensor, which was beneficial for the enhancement of sensitivity. Additionally, CCK-8 assay and autoxidation of pyrogallol tests showed that MCF-7 cells maintained a high viability after incubated with PIL and most of the SOD bioactivity was retained in the presence of PIL, which implied the PIL itself possessed an excellent biocompatibility. These properties allow the sensor to track the fluctuation of O2•- levels in vivo between normal and AD rats. This is the first report on application of functionalized PIL to reveal the O2•- related pathological process of AD.

Abnormal platelet amyloid-ß precursor protein metabolism in SAMP8 mice: Evidence for peripheral marker in Alzheimer's disease.

Senescence-accelerated mouse strains have proved to be an accelerated-aging model, which mimics numerous features with Alzheimer's disease (AD). Three, six, and nine-month senescence-accelerated resistant 1 and senescence-accelerated prone 8 (SAMP8) mice were used in the current study, to unravel potential mechanisms for dementia and explore new diagnostic approaches for AD. The amyloid-ß (Aß40) and Aß42 levels were elevated in hippocampi and platelets from SAMP8, along with a reduced α-secretase expression and an enhanced ß-secretase expression extent with age, compared to control mice. Furthermore, hippocampal Aß40 and Aß42 of SAMP8 were positively correlated with platelet of these mice with aging progression. In addition, ß-γ-secretase-modulated proteolytic proceeding of amyloid precursor protein in platelet might work through the PI3K/Akt/GSK3ß pathway. These results indicate that platelet could be a potential early marker in the periphery to study the age-correlative aggregation of the amyloid-ß peptide in patients with AD, while still requiring the considerable study.

Bioinformatics analyses of significant genes, related pathways and candidate prognostic biomarkers in glioblastoma.

Glioblastoma (GBM) is the most common type of malignant tumor of the central nervous system. The prognosis of patients with GBM is very poor, with a survival time of ~15 months. GBM is highly heterogeneous and highly aggressive. Surgical removal of intracranial tumors does provide a good advantage for patients as there is a high rate of recurrence. The understanding of this type of cancer needs to be strengthened, and the aim of the present study was to identify gene signatures present in GBM and uncover their potential mechanisms. The gene expression profiles of GSE15824 and GSE51062 were downloaded from the Gene Expression Omnibus database. Normalization of the data from primary GBM samples and normal samples in the two databases was conducted using R software. Then, joint analysis of the data was performed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the protein­protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed using Cytoscape software. Identification of prognostic biomarkers was conducted using UALCAN. In total, 9,341 DEGs were identified in the GBM samples, including 9,175 upregulated genes and 166 downregulated genes. The top 1,000 upregulated DEGs and all of the downregulated DEGs were selected for GO, KEGG and prognostic biomarker analyses. The GO results showed that the upregulated DEGs were significantly enriched in biological processes (BP), including immune response, cell division and cell proliferation, and the downregulated DEGs were also significantly enriched in BP, including cell growth, intracellular signal transduction and signal transduction by protein phosphorylation. KEGG pathway analysis showed that the upregulated DEGs were enriched in circadian entrainment, cytokine­cytokine receptor interaction and maturity onset diabetes of the young, while the downregulated DEGs were enriched in the TGF­ß signaling pathway, MAPK signaling pathway and pathways in cancer. All of the downregulated genes and the top 1,000 upregulated genes were selected to establish the PPI network, and the sub­networks revealed that these genes were involved in significant pathways, including olfactory transduction, neuroactive ligand­receptor interaction and viral carcinogenesis. In total, seven genes were identified as good prognostic biomarkers. In conclusion, the identified DEGs and hub genes contribute to the understanding of the molecular mechanisms underlying the development of GBM and they may be used as diagnostic and prognostic biomarkers and molecular targets for the treatment of patients with GBM in the future.

Highly efficient electrochemical sensing platform for sensitive detection DNA methylation, and methyltransferase activity based on Ag NPs decorated carbon nanocubes.

In this paper, we reported a sensitive and selective electrochemical method for quantify DNA methylation, analyzing DNA MTase activity and screening of MTase inhibitor based on silver nanoparticles (Ag NPs) decorated carbon nanocubes (CNCs) as signal tag. The Ag NPs/CNCs was prepared by in situ growth of nanosilver on carboxylated CNCs and used as a tracing tag to label antibody. The sensor was prepared by immobilizing the double DNA helix structure on the surface of gold electrode. When DNA MTase was introduced, the probe was methylated. Successively, anti-5-methylcytosine antibody labeled Ag NPs/CNCs was specifically conjugated on the CpG methylation site. The electrochemical stripping signal of the Ag NPs was used to monitor the activity of MTase. The electrochemical signal has a linear relationship with M.SssI activities ranging from 0.05 to 120U/mL with a detection limit of 0.03U/mL. In addition, we also demonstrated the method could be used for rapid evaluation and screening of the inhibitors of MTase. The newly designed strategy avoid the requirement of deoxygenation for electrochemical assay, and thus provide a promising potential in clinical application.

Functionalized poly (ionic liquid) as the support to construct a ratiometric electrochemical biosensor for the selective determination of copper ions in AD rats.

An efficient ratiometric electrochemical biosensor for Cu2+ determination was constructed using dual hydroxyl-functionalized poly (ionic liquid) (DHF-PIL) as the catalyst support. The DHF-PIL exhibited typical macroporous structure, which provided a high surface area of 39.31m2/g for the sufficient loading of biomolecules. The specific recognition of Cu2+ was accomplished by employing neurokinin B (NKB) for the first time, which could bind to Cu2+ to form a [CuII(NKB)2] complex with high specificity. Meanwhile, a common redox mediator, 2, 2'-Azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS) was modified into DHF-PIL by electrostatic interactions to act as an inner reference molecule, which provided a built-in correction for environmental effects and improving the detection accuracy. With this strategy, the developed electrochemical biosensor was capable of determining Cu2+ with a linear range between 0.9 and 36.1µM and low detection limit (LOD) and quantification limit (LOQ) of 0.24 and 0.6µM, respectively. The sensor also displayed a satisfactory selectivity against a series of interferences in the brain, including metal ions, amino acids and other endogenous compounds. Accordingly, the present biosensor was successfully applied to evaluate Cu2+ levels in normal and AD rats.