Ketamine and its enantiomers for depression: a bibliometric analysis from 2000 to 2023.

Ketamine has demonstrated rapid and sustained antidepressant effects, marking its emergence as an innovative treatment of depression. Despite the growing number of preclinical and clinical studies exploring the antidepressant effects of ketamine and its enantiomers, a comprehensive bibliometric analysis in this field has yet to be conducted. This study employs bibliometric methods and visualization tools to examine the literature and identify key topics related to the antidepressant effects of ketamine and its enantiomers. We sourced publications on the antidepressant effects of ketamine and its enantiomers from the Web of Science Core Collection (WOSCC) database, covering the period from 2000 to 2023. Tools such as VOSviewer, CiteSpace and the R package "bibliometrix" were utilized for visual analysis. The study included 4,274 publications, with a notable increase in publications peaking in 2022. Co-occurrence analysis highlighted two primary research focal points: the efficacy and safety of ketamine and its enantiomers in treating depression, and the mechanisms behind their antidepressant effects. In conclusion, this analysis revealed a significant increase in research on the antidepressant effects of ketamine and its enantiomers over the past two decades, leading to the approval of esketamine nasal spray for treatment-resistant depression. The rapid antidepressant effects of ketamine have spurred further studies into its mechanisms of action and the search for new antidepressants with fewer side effects.

Efficacy and safety of esketamine for perioperative depression in patients undergoing elective surgery: A meta-analysis of randomized controlled trials.

BACKGROUND: Depression is a prevalent mood disorder during the perioperative period, with both preoperative concurrent depression and new-onset postoperative depression impacting postoperative recovery. Recent studies have indicated that the dissociative anesthetic esketamine may alleviate perioperative depressive symptoms. OBJECTIVE: This meta-analysis aimed to assess the efficacy and safety of esketamine in treating perioperative depression. METHODS: We selected randomized controlled trials comparing esketamine to placebo in terms of postoperative depressive symptoms. The primary outcome was postoperative depression scores, with secondary outcomes including the prevalence of postoperative depression, pain scores using the Visual Analogue Scale or Numeric Rating Scale, and incidences of adverse reactions such as nausea/vomiting, dizziness, dreams/nightmares, hallucinations. RESULTS: We enrolled a total of 17 studies involving 2462 patients. The esketamine group demonstrated a significant reduction in postoperative depression scores within one week after surgery (SMD -0.47, 95% CI (-0.66, -0.27), P < 0.001) and over the long term (SMD -0.44, 95% CI (-0.79, -0.09), P = 0.01). Furthermore, esketamine significantly decreased the prevalence of postoperative depression both within one week (RR 0.46, 95% CI (0.33, 0.63), P < 0.001) and over the long term (RR 0.50, 95% CI (0.36, 0.70), P < 0.001). Additionally, esketamine effectively relieved pain on the first postoperative day compared to control. However, it also increased the risks of dizziness and hallucinations for a short time. CONCLUSION: This meta-analysis suggests that the intraoperative or postoperative application of esketamine could be a potentially effective treatment for perioperative depression, although the increased risk of adverse reactions should be considered.

Perylene-Mediated Cytoskeletal Dysfunction Remodels Cancer-Associated Fibroblasts to Augment Antitumor Immunotherapy.

Targeted reprogramming of cancer-associated fibroblasts (CAFs) is one of the most essential cancer therapies. However, how to reprogram active CAFs toward deactivated state still remains immense challenge. To tackle this challenge, herein, one perylene N, N'-bis(2-((dimethylammonium)ethylene)-2-(methoxylethyl))-1, 6, 7, 12-tetrachloroperylene-3, 4, 9, 10-tetracarboxylic diimide (PDIC-OC) is prepared, which can trigger endogenous reactive oxygen species (ROS) burst to result in cytoskeletal dysfunction and cell apoptosis so that suppress transforming growth factor ß (TGF-ß) production. As a result, PDIC-OC can reprogram the activated CAFs and relieve immunosuppressive tumor microenvironment by efficient polarization of M2-typed macrophages into M1-typed ones, downregulation of alpha-smooth muscle actin (α-SMA), alleviation of hypoxic state to promote infiltration of cytotoxic T lymphocytes, and ultimately realizes outstanding antitumor performance on B16F10 tumor-xenografted and lung-metastatic mouse model even at low concentration of 1 mg kg-1 body weight. This work thus presents a novel strategy that cytoskeleton dysfunction and cell apoptosis cooperatively suppress the secretion of TGF-ß to reprogram CAFs and meanwhile clarifies intrinsic mechanism for perylene-triggered chemo-immunotherapy against hypoxic tumors.

Competition of Carrier Kinetics Contributes to Amplified Spontaneous Emission in Quasi-2D/3D (PBA)2MAn-1PbnBr3n+1 Thin Films under Strip Light Mode.

Quasi-2D halide perovskites have potential in lasing due to their amplified spontaneous emission (ASE) properties. The ASE of (PBA)2MAn-1PbnBr3n+1 thin films has been confirmed by photoluminescence (PL) testing using stripe light excitation (SLE). The ASE threshold decreases with decreasing environmental temperature (TE) or increasing number of inorganic layers (n). Using the transient absorption technique, the Auger recombination and the cooling process of the high-activity carrier are accelerated with the decrease of n or TE. A new ASE mechanism is proposed where high-activity carriers directly emit photons under photon perturbation from adjacent sites, leading to the accumulation and amplification of emitted photons only in the SLE region for ASE to occur. In addition, the reduction of n promotes light scattering between nano-thin layers, which supports a rapid increase in the ASE signal after the ASE threshold is crossed.

The association of preoperative high-sensitivity cardiac troponin i and long-term outcomes in colorectal cancer patients received tumor resection surgery.

BACKGROUND: This study aimed to evaluate the association between preoperative hs-cTnI and long-term mortality and major adverse cardiovascular events (MACE) in colorectal cancer patients. METHODS: This single-center retrospective cohort study included 1105 consecutive colorectal cancer patients who received tumor resection surgery between January 2018 and June 2020. Inclusion criteria were an age ≥ 18 years and had been tested for hs-cTnI on admission within 7 days prior to tumor resection surgery. Exclusion criteria were emergent surgery, failure to received tumor resection surgery, hospital death, there was clinical evidence of unstable coronary artery disease or pulmonary embolism occurred before operation according to medical record. The primary endpoint was all-cause death. Secondary endpoint was major adverse cardiovascular events (MACE). RESULTS: A total of 1105 patients were enrolled: 1032 with normal hs-cTnI and 73 with elevated hs-cTnI. The mean follow-up was 24.4 ± 10.8 months, 176 patients died and 39 patients met MACE. In the elevated troponin group, 50%, 32.1% and 17.9% died from cancer, cardiovascular and other causes, while those in the normal troponin group were 75.7%, 2% and 22.3%, there was statistical difference between 2 groups (P < 0.001). Patients with elevated preoperative hs-cTnI had significantly higher mortality (P < 0.001) and more MACE (P < 0.001) compared with those with normal hs-cTnI. A propensity-matching analysis were performed, resulting in 151 patients with normal hs-cTnI and 60 patients with elevated hs-cTnI. The matched population had the similar results for all-cause death (P = 0.009) and MACE (P = 0.001). The results were consistent after further excluding 147 patients who had received chemoradiotherapy prior to surgery in subgroup analysis. The results of multivariate Cox regression analysis shown that hs-cTnI was one of the best predictors for all-cause death (hazard ratio [HR] 2.278; 95% confidence interval [CI] 1.19-4.361) and MACE (HR, 3.523; 95%CI, 1.477-8.403) in total populations, similar results were found in subgroup analysis. CONCLUSIONS: Colorectal cancer patients without myocardial ischemia manifestation but with elevated hs-cTnI prior to tumor resection surgery were at increased risk for long-term all-cause death and MACE, irrespective of whether they have received chemoradiotherapy prior to surgery.

Perylene-Based Reactive Oxygen Species Supergenerator for Immunogenic Photochemotherapy against Hypoxic Tumors.

Reactive oxygen species (ROS) can act as cytotoxic radicals to directly kill tumor cells and concurrently trigger immunogenic cell death (ICD) to efficiently achieve tumor therapy. Thus motivated, we herein present one perylene monoamide-based ROS supergenerator (PMIC-NC) that not only induces hypoxia-enhanced Type-I ROS burst aided by proton transients but also triggers Type-I/II ROS production by electron or energy transfer under near-infrared (NIR) light irradiation and also elicits a strong ICD effect. More interesting, the mitochondria- and lung-specific distribution of PMIC-NC also boosts the tumor therapeutic efficiency. As a result, PMIC-NC was employed for NIR-triggered photodynamic therapy, hypoxia-enhanced chemotherapy and also displayed robust immunogenicity for systemic tumor eradication. This work thus contributes one proof-of-concept demonstration of perylene as an integrated therapeutic platform for efficient immunogenic photochemotherapy against hypoxic tumors.

Perylene-Mediated Electron Leakage in Respiratory Chain to Trigger Endogenous ROS Burst for Hypoxic Cancer Chemo-Immunotherapy.

Perylene derivatives can be stimulated by the hypoxic tumor microenvironment to generate radical anion that is proposed to arouse electron exchange with oxidizing substance, and in turn, realize reactive oxygen species (ROS) burst. Here, three perylene therapeutic agents, PDI-NI, PDIB-NI, and PDIC-NI, are developed and it is found that the minimum lowest unoccupied molecular orbital (LUMO) energy level makes PDIC-NI most easily accept electrons from the oxidative respiratory chain to form lots of anions, and the resultant maximum ROS generation, establishing an unambiguous mechanism for the formation of perylene radical anions in the cell, presents solid evidence for LUMO energy level determining endogenous ROS burst. Stirringly, PDIC-NI-induced ROS generation arouses enhanced mitochondrial oxidative stress and concurrently activates immunogenic cell death (ICD), which not only efficiently kills lung tumor cells but also reprograms immunosuppressive tumor microenvironment, including the cytokine secretion, dendritic cell maturation, as well as cytotoxic T lymphocytes activation, to inhibit the growth of xenografted and metastasis tumor, presenting a proof-of-concept demonstration of perylene that acts as an integrated therapeutic agent to well realize hypoxia-activated chemotherapy with ICD-induced immunotherapy on lung cancer.

Status of TWEAK DNA methylation and mRNA expression in systemic lupus erythematosus.

OBJECTIVE: Draw upon research into the serum concentration, mRNA expression, and DNA methylation of TNF-like weak inducer of apoptosis (TWEAK) in the peripheral blood of systemic lupus erythematosus patients and healthy controls in an attempt to investigate the epigenetics associated with TWEAK in the pathogenesis of systemic lupus erythematosus (SLE). METHODS: A total of 178 SLE patients (SLE group) and 131 sex-age matched healthy controls (HC group) were recruited. Enzyme-linked immunosorbent assays (ELISA) was used to detect serum protein concentration of TWEAK. TWEAK mRNA expression was analyzed by Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Methylation levels of the promotor of TWEAK were measured using quantitative DNA methylation analysis on the MassARRAY spectrometry. RESULTS: Serum TWEAK concentrations were not statistically significant in SLE patients and HCs. Nevertheless, serum TWEAK concentrations were significantly lower in patients with renal involvement when compared to those without it. Serum TWEAK concentrations were reduced in clinically active patients (SLEDAI ≥ 10) compared with clinically stable patients (SLEDAI < 10). It was also significantly associated with SLEDAI. Compared with the HC group, the TWEAK mRNA expression in the SLE group was significantly lower. The global DNA methylation levels of TWEAK in the SLE group were observed to be significantly higher than the HC group. SLE patients with renal involvement, and the clinically active patients had higher TWEAK global methylation as well as exhibited variation in certain CpG island methylation. Furthermore, TWEAK methylation negatively correlated with TWEAK mRNA expression. CONCLUSION: This study suggests that TWEAK DNA methylation is a valuable as a focus for epigenetic studies because of it potentially influencing TWEAK gene expression in SLE patients. Aberrant DNA methylation of TWEAK may be involved in the initiation and development of SLE.

Activity enhancement of a photo-generated carrier in CsPbBr3 nanocrystals improved by Cd element.

Doping Cd element into perovskite materials is an effective strategy to improve the photoelectric property. However, the further discussion for carrier dynamic behavior in perovskites affected by Cd element remains not sufficient. In this research letter, based on steady and transient spectroscopy, it is found that adding Cd element into CsPbBr3 nanocrystals can enhance the activity of photo-generated carriers and accompany with the optimization of crystal structure. The former improves the carrier heating effect, which makes carrier keep high temperature for a long time and accelerate the bimolecular and the Auger recombination simultaneously. The latter can restrict the monomolecular recombination through passivating the defect states. Finally, they together improve the photoluminescence characteristics of the Cd doped CsPbBr3 nanocrystals and make them exhibit a huge potential in the fields of optoelectronics or photo-catalysis.

A Melanin-like Nanoenzyme for Acute Lung Injury Therapy via Suppressing Oxidative and Endoplasmic Reticulum Stress Response.

Nanoenzyme-mediated catalytic activity is emerging as a novel strategy for reactive oxygen species (ROS) scavenging in acute lung injury (ALI) treatment. However, one of the main hurdles for these metal-containing nanoenzymes is their potential toxicity and single therapeutic mechanism. Herein, we uncovered a melanin-like nanoparticles derived from the self-polymerization of 1,8-dihydroxynaphthalene (PDH nanoparticles), showing a significant anti-inflammation therapeutic effect on ALI mice. The prepared PDH nanoparticles rich in phenol groups could not only act as radical scavengers to alleviate oxidative stress but could also chelate calcium overload to suppress the endoplasmic reticulum stress response. As revealed by the therapeutic effect in vivo, PDH nanoparticles significantly prohibited neutrophil infiltration and the secretion of proinflammatory cytokines (TNF-α and IL-6), thus improving the inflammatory cascade in the ALI model. Above all, our work provides an effective anti-inflammatory nanoplatform by using the inherent capability of melanin-like nanoenzymes, proposing the potential application prospects of these melanin-like nanoparticles for acute inflammation-induced injury treatment.

Biomimetic Melanosomes Promote Orientation-Selective Delivery and Melanocyte Pigmentation in the H2O2-Induced Vitiligo Mouse Model.

Extremely limited drug retention and depigmentation represent the greatest barriers against vitiligo treatment advancement. Here, inspired by biological melanosomes, the primary melanin transporter, we developed biomimetic melanosomes to combat reactive oxygen species (ROS)-mediated melanocyte damage and depigmentation. Briefly, methylprednisolone (MPS) and melanin-mimicking polydopamine (PDA) were encapsulated inside lysine-proline-valine (KPV)-modified deformable liposomes (KPV-Lipos). Owing to their phospholipid bilayer flexibility and the specific affinity for melanocortin 1 receptor (MC1R), KPV-Lipos exhibited 1.43-fold greater skin deposition than traditional liposomes. The binding of KPV and its receptor also contributed to activating the cAMP-tyrosinase (TYR) signaling pathway, improving the endogenous melanin content. In addition, PDA mimicked melanosomes as it effectively increased the exogenous melanin content and scavenged ROS. Meanwhile, MPS inhibited inflammatory cytokine secretion, limiting the depigmented area. Ultimately, the biomimetic melanosomes affected the skin color of mice with H2O2-induced vitiligo. These melanosomes show potential as a universal platform for the self-supply of melanin by self-driven melanin synthesis with exogenous supplementation. Furthermore, this study offers ideas for the production of artificial packed melanosome substitutes for melanocyte-related diseases.

Endogenous Enzyme-responsive Nanoplatforms for Anti-tumor Therapy.

The emergency of responsive drug delivery systems has contributed to reduced cytotoxicity, improved permeability in tissues and extended circulation time of the active drug. In particular, enzyme-responsive nanoplatforms have attracted a lot of attention due to the specificity and efficiency of an enzyme-catalyzed reaction. In this review, enzyme-based mono responsive drug delivery systems designed in the past 5 years have been summarized. These drug delivery systems were introduced by different tumor-related enzymes such as matrix metalloproteinase, esterase, hyaluronidase, caspase and cathepsin. Moreover, the enzyme-sensitive nanoplatforms activated by dual-stimuli have been also described. Although great progress had been made in the past years, the translation into clinical practice is still difficult. Thus, three obstacles (enzyme heterogeneity, reaction environment, animal model) were also discussed. In short, enzyme-activated drug delivery systems offer great potential in treating cancers.

Correlation of lower 2 h C-peptide and elevated evening cortisol with high levels of depression in type 2 diabetes mellitus.

BACKGROUND: A number of studies have explored the association between depression and ghrelin, leptin, and cortisol; further, postprandial C-peptide levels have a therapeutic effect on type 2 diabetes mellitus (T2DM). However, the relationship between C-peptide and depression in patients with diabetes, remains unclear. The aim of this study was to explore the association between depression and ghrelin, leptin, cortisol, and C-peptide in patients with diabetes. METHODS: We enrolled 50 adults without T2DM, 77 non-depressed adults with T2DM (free of Axis-I psychiatric disorders as assessed using the Mental Illness Needs Index (MINI), Patient Health Questionnaire (PHQ-9 score ≤ 4)) and 59 patients with T2DM and depression (PHQ-9 ≥ 7 and positive by the Structured Clinical Interview for DSM-5). The age range of the participants was 45-59 years of age. We compared the above three groups and explored the association between ghrelin, leptin, cortisol, C-peptide, and depression in patients with diabetes. A post-hoc power-analysis was finished. RESULTS: Compared with the non-depression T2DM group, the depression T2DM group had significantly higher blood glucose fluctuations. Further, compared with the non-depression T2DM and non-diabetic groups, the depression T2DM group had significantly lower levels of post-meal 2-h C-peptide and elevated evening cortisol (p < 0.01). Regression analysis revealed a significant negative correlation between depression severity and 2-h postprandial C-peptide in patients with diabetes (p < 0.01) and a significant positive correlation with midnight cortisol levels (p < 0.01). A post hoc power analysis showed that we had an adequate sample size and met the minimum requirement to attain 80% power. A post hoc power calculation also demonstrated that this study basically achieved power of 80% at 5% alpha level. CONCLUSIONS: Our findings indicate a correlation of low fasting levels of 2-h C-peptide as well as higher midnight cortisol levels with higher depression severity in middle-aged patients with T2DM.

Recent Progress and Future Directions: The Nano-Drug Delivery System for the Treatment of Vitiligo.

Vitiligo is a depigmentation disease that seriously affects the physical health, mental health and quality of life of a patient. Therapeutic aim at control immunoreaction by relieving oxidative stress. Unfortunately, the cuticle barrier function and lack of specific accumulation lead to unsatisfactory therapeutic outcomes and side effects. The introduction and innovation of nanotechnology offers inspiration and clues for the development of new strategies to treat vitiligo. However, not many studies have been done to interrogate how nanotechnology can be used for vitiligo treatment. In this review, we summarize and analyze recent studies involving nano-drug delivery systems for the treatment of vitiligo, with a special emphasis on liposomes, niosomes, nanohydrogel and nanoparticles. These studies made significant progress by either increasing drug loading efficiency or enhancing penetration. Based on these studies, there are three proposed principles for topical nano-drug delivery systems treatment of vitiligo including the promotion of transdermal penetration, enhancement of drug retention and facilitation of melanin regeneration. The presentation of these ideas may provide inspirations for the future development of topical drug delivery systems that will conquer vitiligo.

Renal Sympathetic Denervation Improves Outcomes in a Canine Myocardial Infarction Model.

BACKGROUND Myocardial infarction (MI) is the main cause of heart failure (HF), and sympathetic nerve activity is associated with prognosis chronic heart failure. Renal sympathetic denervation (RDN) is noted for its powerful effect on the inhibition of sympathetic nerve activity. This study investigated the effect of RDN on heart failure in dogs after myocardial infarction. MATERIAL AND METHODS The experimental animals were randomized into 2 groups: the MI group (n=12) and the sham operation group (n=6). In the MI group we established an MI model by permanently ligating the left anterior descending branch. After 4 weeks, the MI dogs were randomly divided into 2 groups: the MI+RDN group (MI+renal sympathetic denervation, n=6) and the simple MI group (n=6). Animals in the MI+RDN group underwent both surgical and chemical renal denervation. RESULTS Compared with sham operation group, left ventricular fraction shortening (LVFS) and left ventricular ejection fraction (LVEF) were significantly reduced in the simple MI group, while the reduction was partly reversed in the MI+RDN group. RDN reduced sympathetic nerve activity and release of B-type natriuretic peptide (BNP) and Angiotensin II (AngII) in the MI+ RDN group but not in the simple MI group. CONCLUSIONS Canine renal sympathetic denervation prevents myocardial malignant remodeling by lowering the activity of the systemic sympathetic nerve and inhibiting renin-angiotensin-aldosterone system (RASS) activation, providing a new target and method for the treatment of heart failure.

Isobaric tags for relative and absolute quantitation-based quantitative proteomics analysis provides novel insights into the mechanism of cross-incompatibility between tree peony and herbaceous peony.

Interspecific hybridisation is the main method for improvement and breeding of tree peony (Paeonia ostii T.Hong & J.X.Zhang), but cross-incompatibility as the major factor restricting the rapid development of interspecific hybridisation. To better understand the molecular mechanisms involved in cross-incompatibility between tree peony (Paeonia ostii cv. Fengdanbai) and herbaceous peony (Paeonia lactiflora Pall. cv. Fenyunu), a quantitative proteomic analysis using isobaric tags for relative and absolute quantitation (iTRAQ) technology was performed on the stigma 24h after pollination. Of the 2900 proteins whose levels were quantitated, 685 proteins were differentially expressed in the stigma after hybrid pollination, in contrast to self-pollination. Functional annotation analysis showed that dysregulated proteins involved in RNA degradation, the Ca signalling pathway, the phosphatidylinositol signalling system and the mitogen-activated protein kinase (MAPK) signalling pathway may have made contributions to cross-incompatibility. The downregulated expression of enolase, DnaK (Heat Shock Proteins, HSP70), GroEL (Heat Shock Proteins, HSP60), calmodulin and glyoxalase I, and the upregulated expression of adenine nucleotide translocator indicated that the energy synthesis required by pollen tube growth, the signal pathway and the metabolic pathway related to the growth polarity of the pollen tube were blocked after hybrid pollination. Eight genes were selected to confirm their expression by quantitative real-time PCR. Compared with the STRING database, a protein-protein interaction network of the chosen proteins was constructed. These results provide fundamental and important information for research into the molecular mechanisms of cross-incompatibility in peony and should facilitate interspecific hybridisation in agricultural practice.

Renal Denervation Reduced Ventricular Arrhythmia After Myocardial Infarction by Inhibiting Sympathetic Activity and Remodeling.

Background Ventricular arrhythmia after myocardial infarction is the most important risk factor for sudden cardiac death, which poses a serious threat to human health. As the correlation between autonomic nervous systemic dysfunction and heart rhythm abnormality has been gradually revealed, remedies targeting autonomic nervous system dysfunction, especially the sympathetic nerve, have emerged. Among them, renal denervation is noted for its powerful effect on the inhibition of sympathetic nerve activity. We aim to investigate whether renal denervation can reduce ventricular arrhythmia after myocardial infarction and thus decrease the risk of sudden cardiac death. In addition, we explore the potential mechanism with respect to nerve activity and remodeling. Methods and Results Twenty-four beagles were randomized into the control (n=4), renal denervation (n=10), and sham (n=10) groups. Permanent left anterior descending artery ligation was performed to establish myocardial infarction in the latter 2 groups. Animals in the renal denervation group underwent both surgical and chemical renal denervation. Compared with dogs in the sham group, dogs in the renal denervation group demonstrated attenuated effective refractory period shortening and inhomogeneity, flattened restitution curve, increased ventricular threshold, and decreased ventricular arrhythmia. Heart rate variability assessment, catecholamine measurement, and nerve discharge recordings all indicated that renal denervation could reduce whole-body and local tissue sympathetic tone. Tissue analysis revealed a significant decrease in neural remodeling in both the heart and stellate ganglion. Conclusions Surgical and chemical renal denervation decreased whole-body and local tissue sympathetic activity and reversed neural remodeling in the heart and stellate ganglion. Consequently, renal denervation led to beneficial remodeling of the electrophysiological characteristics in the infarction border zone, translating to a decrease in ventricular arrhythmia after myocardial infarction.

Clinical Effects of "Selective Drug" Regulating Vagus Nerve Signal Pathway in Vagally-Mediated Atrial Fibrillation.

BACKGROUND The cardiac autonomic nervous system plays a crucial role in genesis and development of atrial fibrillation (AF) through the G protein signal transduction pathway. Therefore, intervening in the G protein signal transduction pathway may be a new "selective drug" method to regulate autonomic nerve activity to prevent vagally-mediated AF. MATERIAL AND METHODS Seventeen adult beagles were randomized into 3 groups: shame-operation control group (group A, n=5), empty vector gene control group (group B, n=6), and Gαi2ctp gene experimental group (group C, n=6). Group A was injected with normal saline into the anterior atrial wall, and group B and group C animals were injected with recombinant adenovirus with empty vector or Gαi2ctp vector in the same region. AF was induced by the method of rapid atrial pacing in groups B and C. To determine the clinical effect of vagal modulation, the effective refractory periods (ERP) and field action potential duration (FAPD) were evaluated by electrophysiological study. The expression levels of tyrosine hydroxylase (TH) and choline acetyl transferase (CHAT) in different parts were determined with immunohistochemistry. RESULTS After successful Gai2ctp gene transfer, in group B, the ERP and FAPD significantly decreased (P<0.05), and TH and CHAT expression observably increased (P<0.05), while those differences were absent between groups A and C (P>0.05). CONCLUSIONS Recombinant adenovirus-mediated overexpression of Gαi2ctp in canine myocardial cells can interfere with the activity of the vagus nerve, reverse the development and progression of electrical remodeling, and reduce the incidence of AF.

The association of short-term memory and cognitive impairment with ghrelin, leptin, and cortisol levels in non-diabetic and diabetic elderly individuals.

AIMS: This study assessed short-term memory and biochemical indicators with the levels of ghrelin, leptin, and cortisol between cognitive impairment and normal older adults with or without diabetes. METHODS: We enrolled 286 older adults (aged 65-85 years) with or without diabetes from the local community. Short-term memory was assessed using pictures of common objects; cognitive functioning was assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The physiological indexes assessed were plasma levels of fasting ghrelin and leptin, ghrelin level at 2_h after breakfast, 24-h urinary cortisol value, body mass index, and plasma cortisol levels at 8:00 a.m., 4:00 p.m., and 12:00 p.m. RESULTS: In both non-diabetic and diabetic subjects, short-term memory was significantly lower in the impaired cognition group (5.99 ± 2.90 in non-diabetic subjects and 4.71 ± 2.14 in diabetic subjects) than in the normal cognition group (8.14 ± 2.23 in non-diabetic subjects and 7.82 ± 3.37 in diabetic subjects). Baseline ghrelin level was significantly lower in the impaired cognition group (9.07 ± 1.13 ng/mL in non-diabetic subjects and 7.76 ± 1.34 ng/mL in diabetic subjects) than in the normal cognition group (10.94 ± 1.53 ng/mL in non-diabetic subjects and 9.93 ± 1.76 ng/mL in diabetic subjects); plasma cortisol levels at 8:00 a.m., 4:00 p.m., and 12:00 p.m. were significantly higher in the impaired cognition group than in the normal cognition group, while no significant difference was observed in plasma levels of fasting leptin between different groups. CONCLUSIONS: Fasting plasma ghrelin and cortisol levels may be markers of cognitive decline and memory loss. It is possible that adjusting their levels may have a therapeutic effect, and this should be investigated in future studies.

Over-expression of GmSN1 enhances virus resistance in Arabidopsis and soybean.

KEY MESSAGE: GmSN1 enhances virus resistance in plants most likely by affecting the expression of signal transduction and immune response genes. Soybean mosaic virus (SMV) infection causes severe symptom and leads to massive yield loss in soybean (Glycine max). By comparative analyzing gene expression in the SMV-resistant soybean cultivar Rsmv1 and the susceptible cultivar Ssmv1 at a transcriptome level, we found that a subgroup of Gibberellic Acid Stimulated Transcript (GAST) genes were down-regulated in SMV inoculated Ssmv1 plants, but not Rsmv1 plants. Sequence alignment and phylogenetic analysis indicated that one of the GAST genes, GmSN1, was closely related to Snakin-1, a well-characterized potato microbial disease resistance gene. When over-expressed in Arabidopsis and soybean, respectively, under the control of the 35S promoter, GmSN1 enhanced turnip mosaic virus resistance in the transgenic Arabidopsis plants, and SMV resistance in the transgenic soybean plants, respectively. Transcriptome analysis results showed that the up-regulated genes in the 35S:GmSN1 transgenic Arabidopsis plants were largely enriched in functional terms including "signal transduction" and "immune response". Real-time PCR assay indicated that the expression of GmAKT2, a potassium channel gene known to enhance SMV resistance when over-expressed in soybean, was elevated in the 35S:GmSN1 transgenic soybean plants. Taken together, our results suggest that GmSN1 enhances virus resistance in plants most likely by affecting the expression of signal transduction and immune response genes.