Roles of neuroligins in central nervous system development: focus on glial neuroligins and neuron neuroligins.

Neuroligins are postsynaptic cell adhesion molecules that are relevant to many neurodevelopmental disorders. They are differentially enriched at the postsynapse and interact with their presynaptic ligands, neurexins, whose differential binding to neuroligins has been shown to regulate synaptogenesis, transmission, and other synaptic properties. The proper functioning of functional networks in the brain depends on the proper connection between neuronal synapses. Impaired synaptogenesis or synaptic transmission results in synaptic dysfunction, and these synaptic pathologies are the basis for many neurodevelopmental disorders. Deletions or mutations in the neuroligins genes have been found in patients with both autism and schizophrenia. It is because of the important role of neuroligins in synaptic connectivity and synaptic dysfunction that studies on neuroligins in the past have mainly focused on their expression in neurons. As studies on the expression of genes specific to various cells of the central nervous system deepened, neuroligins were found to be expressed in non-neuronal cells as well. In the central nervous system, glial cells are the most representative non-neuronal cells, which can also express neuroligins in large amounts, especially astrocytes and oligodendrocytes, and they are involved in the regulation of synaptic function, as are neuronal neuroligins. This review examines the mechanisms of neuron neuroligins and non-neuronal neuroligins in the central nervous system and also discusses the important role of neuroligins in the development of the central nervous system and neurodevelopmental disorders from the perspective of neuronal neuroligins and glial neuroligins.

Overall Survival Advantage of Omentum Preservation Over Omentectomy for Advanced Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Since 1910, omentectomy has been an essential component of radical gastrectomy for advanced gastric cancer. However, researchers have recently questioned the benefit of omentectomy in radical gastrectomy. The aim of this meta-analysis was to compare omentectomy and omentum preservation in gastrectomy for advanced gastric cancer in terms of survival outcomes and short-term outcomes. METHODS: The PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched. Studies that compared omentum preservation with omentectomy were included. Overall survival (OS) and relapse-free survival (RFS) were analyzed as primary outcomes. RESULTS: Of 3509 records screened, one randomized clinical trial and five propensity-score matched retrospective studies with 1661 patients were selected. Omentum preservation was associated with improved OS (hazard ratio [HR] = 0.757, 95% confidence interval [CI] = 0.603-0.950, P = 0.016, I2 = 0%), but not with improved RFS (HR = 0.821, 95% CI = 0.668-1.009, P = 0.060, I2 = 9%) compared with omentectomy for advanced gastric cancer. Furthermore, less blood loss and shorter operation time were found in the omentum preservation group than in the omentectomy group. Additionally, the rate of peritoneal recurrence, the number of harvested lymph nodes, and the incidences of postoperative complications and ileus were comparable in the two groups. CONCLUSIONS: Basing on the current literature, gastrectomy with omentum preservation was associated with improved OS and short-term outcomes compared with omentectomy for advanced gastric cancer. Further randomized trials are required to confirm the survival benefit of omentum-preserving gastrectomy.

High ligation of the inferior mesenteric artery and anastomotic leakage in anterior resection for rectal cancer: a systematic review and meta-analysis of randomized controlled trial studies.

AIM: Surgeons have concerns whether high ligation (HL) of the inferior mesenteric artery (IMA) increases the incidence of anastomotic leakage (AL). This meta-analysis aimed to evaluate the influence of HL of the IMA on AL compared with low ligation (LL). METHODS: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov databases were searched. Randomized controlled trial studies that compared HL with LL of the IMA in anterior resection for rectal cancer and reported AL outcomes were eligible for inclusion. The odds ratios and mean differences were analysed by a random-effects model. Trial sequential analysis was performed to minimize the risk of random errors. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the quality of evidence for outcomes. RESULTS: Of the 531 records screened, five randomized controlled trials with 779 patients were selected for analysis. The pooled incidence of AL was 12.1% (95% Cl 7.77-18.26) in the HL group and 9.7% (95% Cl 5.79-15.82) in the LL group (OR 1.20, 95% CI 0.77-1.87, P = 0.42). In trial sequential analysis, the cumulative Z-score curve exceeded the futility boundary, although the required information size of 1060 had not been reached. The quality of evidence was judged to be high according to the GRADE approach. CONCLUSIONS: This meta-analysis shows that HL of the IMA does not increase the incidence of AL in anterior resection for rectal cancer.

Interaction between a common variant in FADS1 and erythrocyte polyunsaturated fatty acids on lipid profile in Chinese Hans.

Little is known about the associations of FADS1 genetic variants with circulating levels of PUFA and lipids in Asian populations who have a different dietary pattern and dyslipidemia prevalence compared with Western populations. In a population-based sample of 3,210 unrelated Han Chinese living in Beijing and Shanghai, we examined a FADS1 genetic variant, rs174550, in relation to blood PUFA and lipid levels. C-allele of rs174550 was significantly associated with levels of erythrocyte PUFAs in upstream and downstream pathways of delta-5 desaturase (D5D) (P ≤ 0.003). Moreover, rs174550 C-allele was associated with a lower HDL cholesterol level (P = 0.02) in total population and a higher triglyceride level (P = 0.0002) in Beijing residents. Interestingly, erythrocyte levels of 18:2n-6 and 18:3n-3 modified the effect of rs174550 on HDL cholesterol level: stronger associations between rs174550 C-allele and lower HDL cholesterol levels were exhibited when erythrocyte 18:2n-6 or 18:3n-3 level was low (P for interaction = 0.02 and 0.03, respectively). These data suggested that FADS1 genetic variant was associated with circulating PUFA and lipid levels and that its effect on HDL cholesterol might depend on PUFA status in the Han Chinese population.

Protective Effect of Sevoflurane Preconditioning on Cardiomyocytes Against Hypoxia/Reoxygenation Injury by Modulating Iron Homeostasis and Ferroptosis.

To investigate the mechanism whereby sevoflurane (Sev) protects cardiomyocytes from hypoxia/reoxygenation (H/R) injury. The rat cardiomyocyte line H9C2 was exposed to hypoxia (1% oxygen) for 24 h, followed by reoxygenation for 2 h to construct a model of H/R injury. H9C2 was exposed to 2.4% Sev for 45 min before creating a hypoxic environment to observe the effect of Sev. MTT was taken to assess the viability of each group of cells, flow cytometry to detect cell apoptosis, and qRT-PCR or western blot to detect the expression of iron metabolism-related proteins and apoptosis-related proteins in the cells. And the kit determined the levels of total Fe and Fe2+ as well as factors related to oxidative stress in the cells. Administration of Sev significantly increased the cell viability of the H/R group while decreasing the expression of apoptosis-related proteins (Bax, cleaved caspase-3). Ferroportin 1 and mitochondrial ferritin, which are associated with iron metabolism, were considerably up-regulated by Sev, while iron regulatory protein 1, divalent metal transporter 1, and transferrin receptor 1 were significantly down-regulated in H/R cells. Additionally, Sev substantially reduced the levels of total Fe and Fe2+, reactive oxygen species, malondialdehyde, and 4-hydroxynonenal in H/R cells. In conclusion, Sev relieves H/R-induced cardiomyocyte injury by regulating iron homeostasis and ferroptosis.

Associations between common variants in GC and DHCR7/NADSYN1 and vitamin D concentration in Chinese Hans.

Recent studies have identified common variants in or near GC, CYP2R1 and NADSYN1/DHCR7 to be associated with 25-hydroxyvitamin D [25(OH)D] levels in European populations. We aimed to examine whether these variants also influence 25(OH)D levels in Chinese. Seven common variants were successfully genotyped and tested for associations with plasma 25(OH)D levels in a population-based cohort of 3,210 Chinese Hans from Beijing and Shanghai. Six common variants at GC (rs4588, rs7041, rs2282679 and rs1155563) and NADSYN1/DHCR7 (rs3829251 and rs1790349) loci were all significantly associated with lower plasma 25(OH)D levels (-0.036 ≤ ß ≤ -0.076 per risk-allele, P ≤ 5.7 × 10(-5)), while CYP2R1-rs2060793 showed a trend toward association with 25(OH)D levels in the Shanghai subpopulation (P = 0.08), but not in the Beijing subpopulation (P = 0.82). Haplotype-based association analyses of the four GC variants showed that only the haplotype that contained all risk-alleles (TACC) was significantly associated with lower plasma 25(OH)D levels (ß = -0.085, P = 2.3 × 10(-9)), while the haplotype containing the risk-alleles of rs4588 and rs2282679 (TATC) was marginally associated with lower 25(OH)D levels (ß = -0.054, P = 0.0562) when compared with GCTA haplotype carrying the four protective alleles. Most notably, conditional analyses showed that only GC-rs4588 and GC-rs2282679 (r (2) = 0.97) remained significantly associated with 25(OH)D concentrations (P ≤ 1.9 × 10(-5)) after adjusting for the other two SNPs in GC. In conclusion, GC and NADSYN1/DHCR7 loci individually and collectively contribute to variation in plasma vitamin D levels in Chinese Hans.

Association between circular stapler size and anastomotic leakage after laparoscopic low anterior resection for rectal cancer.

Background: Anastomotic leakage (AL) is one of the most severe and frequent complications occurring after laparoscopic low anterior resection (LAR) for rectal cancer. This study aimed to examine the association between circular stapler size and AL after laparoscopic LAR. Methods: This retrospective single-institution study involved 181 patients with rectal cancer who underwent laparoscopic LAR performed by a single surgical team between July 2016 and June 2021. The characteristics of the patients were analyzed. Risk factors for AL were identified via univariate and multivariate analyses. Additionally, a further propensity score matching (PSM) analysis was performed to reduce the selection bias. Results: Among the 181 patients who underwent laparoscopic LAR for rectal cancer, 17 (9.4%) developed clinical AL. In the univariate and multivariate analyses, male sex, incomplete intestinal obstruction, and the usage of a 32-mm stapler during the surgery were independent risk factors for the occurrence of AL. Furthermore, the PSM analysis confirmed that the incidence of AL with a 32-mm stapler was higher than that with a 29-mm stapler after laparoscopic low anterior resection. However, there was no difference in the incidence of anastomotic bleeding and stenosis. Conclusion: Choosing a smaller-diameter circular stapler may reduce the incidence of AL after laparoscopic LARfor rectal cancer without increasing the incidence of anastomotic stenosis.

Comparison of Survival Among Adults With Rectal Cancer Who Have Undergone Laparoscopic vs Open Surgery: A Meta-analysis.

Importance: Two large randomized clinical trials (RCTs) found that laparoscopic surgery failed to yield noninferior pathologic outcomes compared with open surgery for patients with rectal cancer. The results raised concerns regarding the effectiveness of the laparoscopic approach for patients with rectal cancer. Objective: To compare the long-term oncologic outcomes of laparoscopic and open surgery for patients with rectal cancer. Data Sources: PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were searched from database inception to August 13, 2021. Studies published in English were retrieved. Study Selection: The meta-analysis included RCTs that compared laparoscopic surgery with open surgery for patients with rectal cancer and reported the outcome of disease-free survival (DFS) or overall survival (OS). The following exclusion criteria were used: (1) non-RCTs, (2) studies without long-term survival outcomes of interest, and (3) studies that did not report Kaplan-Meier survival curves. Data Extraction and Synthesis: This meta-analysis was performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline for individual participant data development groups. Individual participant data on DFS and OS were extracted from the published Kaplan-Meier survival curves. One-stage and 2-stage meta-analyses were performed. Main Outcomes and Measures: Meta-analyses were conducted for DFS and OS. Hazard ratios (HRs) were used as effective measures. Results: Of 8471 records screened, 10 articles with 12 RCTs and 3709 participants were selected. The reconstructed survival curves for the combined population showed that the 5-year estimated DFS rates were 72.2% (95% CI, 69.4%-74.8%) for the laparoscopic group and 70.1% (95% CI, 67.0%-73.0%) for the open surgery group, and the 5-year estimated OS rates were 76.2% (95% CI, 73.8%-78.5%) for the laparoscopic group and 72.7% (95% CI, 69.8%-75.3%) for open surgery group. In 1-stage meta-analyses, DFS had a nonsignificant HR of 0.92 (95% CI, 0.80-1.06; P = .26), which suggested that DFS in the laparoscopic and open surgery groups was comparable; however, OS was significantly better in the laparoscopic group (HR, 0.85; 95% CI, 0.74-0.97; P = .02). The results were confirmed by 2-stage meta-analyses and were validated by sensitivity analysis with large RCTs. Conclusions and Relevance: A similar DFS but significantly better OS were found for patients who have undergone laparoscopic surgery compared with open surgery for rectal cancer. These findings address concerns regarding the effectiveness of laparoscopic surgery and support the routine use of laparoscopic surgery for patients with rectal cancer.

Incision pressing, a simple and effective intervention to reduce colorectal surgical site infection: A propensity score-matched study.

Background: Colorectal surgery is associated with a high risk of surgical site infection (SSI). In March 2017, we developed an intervention, called "PRESS", with the aim of reducing colorectal superficial SSI. This study assessed the effect of the new intervention in reducing the rates of superficial SSI in colorectal surgery. Methods: This study was a retrospective review of 312 PRESS+ patients compared to 171 historical control PRESS- patients who were 18 years of age or older and underwent elective colorectal surgery with clean-contaminated wounds from January 2015 to June 2020. In the PRESS+ groups, we pressed the incision downward hard with clean gauze after the interrupted suturing of the skin. Propensity score matching with 15 variables was performed in a 1:1 ratio to reduce selection bias. Univariate analysis and multivariate analysis were performed to identify risk factors associated with SSI. Results: The characteristics of the PRESS+ (n = 160) and PRESS- (n = 160) groups were well balanced after propensity score matching. The PRESS+ group had a lower superficial SSI rate (1.9% vs. 6.9%, P = 0.029) and a lower overall SSI rate (2.5% vs. 10.0%, P = 0.006) than the PRESS- group. Furthermore, multivariate analysis showed that the incisional press was an effective protective factor for superficial SSI (adjusted odds ratio = 0.215, 95% confidence interval = 0.057-0.818, P = 0.024). In addition, female sex (P = 0.048) and blood transfusion (P = 0.011) were demonstrated to be independent risk factors for superficial SSI. Conclusion: The incisional press after suturing is a simple, costless, and effective intervention in reducing superficial incisional SSI.

Non-steroidal anti-inflammatory drugs and clinical outcomes in patients with COVID-19.

The use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with coronavirus disease 2019 (COVID-19) has raised great concerns. The effect of NSAIDs on the clinical status of COVID-19 remains in question. Therefore, we performed a post-hoc analysis from the ORCHID trial. Patients with COVID-19 from the ORCHID trial were categorized into two groups according to NSAID use. The 28-day mortality, hospitalized discharge, and safety outcomes with NSAIDs for patients with COVID-19 were analyzed. A total of 476 hospitalized patients with COVID-19 were included; 412 patients (86.5%) did not receive NSAIDs, while 64 patients (13.5%) took NSAIDs as regular home medication. Patients who took NSAIDs did not have a significant increase in the risk of 28-day mortality (fully adjusted: hazard ratio [HR]: 1.12, 95% CI: 0.52-2.42) in the Cox multivariate analysis. Moreover, NSAIDs did not decrease hospital discharge through 28 days (fully adjusted: HR: 1.02, 95% CI: 0.75-1.37). The results of a meta-analysis including 14 studies involving 48,788 patients with COVID-19 showed that the use of NSAIDs had a survival benefit (summary risk ratio [RR]: 0.70, 95% CI: 0.54-0.91) and decreased the risk of severe COVID-19 (summary: RR: 0.79, 95% CI: 0.71-0.88). In conclusion, the use of NSAIDs is not associated with worse clinical outcomes, including 28-day mortality or hospital discharge in American adult hospitalized patients with COVID-19. Based on current evidence, the use of NSAIDs is safe and should not be cautioned against during the COVID-19 pandemic. Ongoing trials should further assess in-hospital treatment with NSAIDs for patients with COVID-19.

Rhein ameliorates fatty liver disease through negative energy balance, hepatic lipogenic regulation, and immunomodulation in diet-induced obese mice.

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and inflammatory disorders. In this study, we tested the effect of rhein, a lipophilic anthraquinone derived from a traditional Chinese herbal medicine Rheum palmatum L., on NAFLD-associated hepatic steatosis, insulin resistance, and the T helper (Th)1/Th2 cytokine imbalance in high-fat diet-induced obese (DIO) mice. We found that oral administration of rhein for 40 days significantly increased energy expenditure, reduced body weight, particularly body fat content, improved insulin resistance, and lowered circulating cholesterol levels in DIO mice without affecting food intake. Rhein treatment also reduced liver triglyceride levels, reversed hepatic steatosis, and normalized alanine aminotransferase (ALT) levels in these mice. Gene analysis and Western blot showed that rhein markedly suppressed the expression of the lipogenic enzyme sterol regulatory element-binding protein-1c (SREBP-1c) and its target genes in the liver. Luciferase reporter assay revealed that rhein suppressed the transcriptional activity of SREBP-1c through its upstream regulator, liver X receptor (LXR). This suggests that rhein exerts its effects by targeting LXR, which is also supported by its inability to reduce body weight in LXR knockout mice. Moreover, multiplex ELISA displayed a downregulated Th1 response after rhein treatment. Rhein shifted the Th1/Th2 responses by inhibiting T-box expressed in T-cells (T-bet) expression and enhancing GATA-binding protein-3 (GATA-3) expression through increased signal transducer and activator of transcription 6 (STAT6) phosphorylation. These data indicate that rhein ameliorated NAFLD and associated disorders through LXR-mediated negative energy balance, metabolic regulatory pathways, and immunomodulatory activities involved in hepatic steatosis. The combined effects of rhein to target hepatic metabolic and immune pathways may be beneficial for complex metabolic diseases such as NAFLD.

SHANK2-FGFR1: A Novel FGFR1 Rearrangement in a Patient with Intestinal Adenocarcinoma.

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The role of the PI3K/AKT signalling pathway in bFGF/PDGF composite hydrogel promoting the repair of spinal cord injuries.

OBJECTIVE: This study aimed to explore the role of the PI3K/AKT signaling pathway in bFGF/PDGF composite hydrogel promoting the repair of spinal cord injuries. METHODS: In this study, the spinal cord injury rat model was established using Allen's punch method. Healthy male Sprague Dawley rats of the clean grade were randomly divided into four groups (n=18, each): sham operation group (group S), bFGF/PDGF composite hydrogel group (group A), bFGF/PDGF composite hydrogel + LY294002 (PI3K/AKT signaling pathway inhibitor) group (group B) and bFGF/PDGF composite hydrogel + IGF-1 (PI3K/AKT signaling pathway agonist) group (group C). After the operation, the motor function of the posterior limbs, the apoptosis of the spinal cord cells and the expression of PI3K, Akt and phosphorylated Akt (p-Akt) in the spinal cord tissues of the rats in each group were detected. RESULTS: BBB joint score were significantly higher (P<0.05). CONCLUSION: BFGF/PDGF composite hydrogel can significantly promote the repair of spinal cord injuries and the mechanism is closely correlated to the activation of the PI3K/AKT signaling pathway. KEY WORDS: BFGF, Cell apoptosis, PDGF, PI3K/Akt signaling pathway, Spinal cord injury.

Downregulation of the long noncoding RNA SNHG1 inhibits tumor cell migration and invasion by sponging miR-195 through targeting Cdc42 in oesophageal cancer.

Despite the poor prognosis of oesophageal cancer (EC), the molecular mechanisms of EC are still unclear. In recent years, role of lncRNA in cancer development attracted much attention. The present study aimed to investigate the effects of the long noncoding RNA SNHG1 on the migration and invasion of EC cells and the possible mechanisms involved. The effects of SNHG1 on cell proliferation, migration, and invasion were determined and its relationship with miR-195/Cdc42 axis was investigated. It was found SNHG1 and Cdc42 were significantly upregulated, and miR-195 was significantly downregulated in both EC tissues and cell lines. In addition, the inhibition of either SNHG1 or Cdc42 resulted in suppression of cell proliferation, migration, and invasion, while inhibition of miR-195 led to opposite results and reversed the effects of si-SNHG1. We also observed that higher SNHG1 predicted poorer prognosis of EC patients. In summary, inhibition of SNHG1 can suppress the cell migration and invasion of EC cells by sponging miR-195 through targeting Cdc42. This study might provide deeper insights into the SNHG1/miR-195/Cdc42 axis in EC.

Association between R1 resection and oncological outcome in resectable gastrointestinal stromal tumors without tumor rupture: A systematic review and meta-analysis.

BACKGROUND: The influence of positive microscopic margin (R1) resection on the prognosis of gastrointestinal stromal tumors (GISTs) is controversial. Tumor rupture is significantly associated with the occurrence of R1 resection and may be a confounder of R1 resection in GISTs. The present meta-analysis evaluated the real influence of R1 resection on the prognosis of GISTs by excluding the confounding effect of tumor rupture. METHODS: The PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases were searched. Studies that compared R1 with negative microscopic margin (R0) resection in GIST patients and reported the time-to-event data of recurrence-free survival (RFS) or disease-free survival (DFS) were eligible for inclusion. The quality of the observational studies was assessed using the Newcastle-Ottawa scale. RESULTS: Of the 4896 records screened, 23 retrospective studies with 6248 participants were selected. In the overall analysis, R1 resection resulted in a significantly shorter RFS/DFS than R0 resection for GISTs (HR = 1.80, 95% CI = 1.54-2.10, P < 0.001, I2 = 14%). However, the inferior RFS/DFS vanished when tumor rupture cases were excluded (HR = 1.34, 95% CI = 0.98-1.83, P = 0.07, I2 = 33%). Sensitivity analysis by high-quality studies brought about a more robust HR of 1.15 (95% CI = 0.88-1.50, P = 0.29), with low heterogeneity (I2 = 0%). The qualities of evidence for the outcomes were high. CONCLUSIONS: This meta-analysis shows that R1 resection did not influence the survival outcome of GISTs. Reresection may not be necessary when positive microscopic margins exist. This analysis could provide high-quality evidence for the development of guidelines.

Association between intraoperative application of microfibrillar collagen hemostat and anastomotic leakage after anterior resection for rectal cancer: A retrospective case-control study.

BACKGROUND: The purpose of the study was to evaluate the association between microfibrillar collagen hemostat and anastomotic leakage after anterior resection. METHOD: Between March 2015 and December 2019, a total of 203 consecutive rectal cancer patients who underwent elective anterior resection were included. Patient parameters were analyzed. The relevant risk factors were identified by univariate and multivariate analysis. Propensity score matching was performed to reduce the selection bias. RESULTS: In total, 26 (12.8%) of the 203 study patients developed clinical anastomotic leakage. The length of hospital stay was significantly prolonged by anastomotic leakage. In univariate analysis and multivariate analysis, male sex, low tumor location, and intraoperative application of microfibrillar collagen hemostat significantly increased the risk of anastomotic leakage. Furthermore, analysis after propensity score matching confirmed the independent role of microfibrillar collagen hemostat in anastomotic leakage. In addition, the median time of anastomotic leakage occurrence from the initial operation in patients with microfibrillar collagen hemostat was 9.00 days, which was significantly later than that in patients without microfibrillar collagen hemostat. CONCLUSION: In addition to male sex and low tumor location, intraoperative application of microfibrillar collagen hemostat was demonstrated to be a significant risk factor for anastomotic leakage. This finding suggested that surgeons should be fully aware of this potential risk in anterior resection. Because of the limitation of retrospective study, however, randomized controlled trials are needed to confirm this association in the future.

Determination of glycemic monitoring marker 1,5-anhydroglucitol in plasma by liquid chromatography-electrospray tandem mass spectrometry.

Previous studies have shown that plasma 1,5-anhydroglucitol (1,5-AG) is markedly reduced among diabetic patients and therefore serves as a sensitive marker for short-term glycemic control. The current study describes the development of the liquid chromatography negative ion electrospray tandem mass spectrometry (LC-MS/MS) method to measure 1,5-AG in human plasma. The samples were pre-treated with protein precipitation and an isotope-labeled internal standard was used. Chromatographic separation was achieved on amide column (150 mm x 2.0mm i.d., 5 microm) followed by detection with multiple reaction monitoring mode. Linearity, accuracy, precision, recovery, matrix effect, and stability were evaluated during method validation over the range of 1-50 microg/mL. The validated method has been clinically applied among 159 type 2 diabetic patients and 290 control subjects. A marked reduction in 1,5-AG levels among the diabetic patients and significant between-gender difference in nondiabetic subjects were observed.

Effects of essential amino acids on lipid metabolism in mice and humans.

Eight amino acids are considered essential for human nutrition, and three of them, including leucine, isoleucine and valine, are called as branched-chain amino acids (BCAAs). We recently discovered that dietary deficiency of any BCAA for 7 days rapidly reduces the abdominal fat mass in mice. The goal of this study was to investigate (1) whether dietary deficiency of the other five essential amino acids (EAAs), including phenylalanine, threonine, tryptophan, methionine and lysine, would produce similar effects and (2) whether an association between serum AAs and obesity was observed in humans in Chinese Han population. Similar to BCAAs deprivation, dietary deficiency of any of these five EAAs for 7 days significantly reduced abdominal fat mass, which is likely caused by increased energy expenditure. Expression of genes and proteins related to lipolysis, however, were differentially regulated by different EAAs. These results suggest a crucial role of EAAs deprivation on lipid metabolism in mice. Our human studies revealed that levels of four EAAs (leucine, isoleucine, valine and phenylalanine) were elevated in obese humans compared with those in lean controls in Chinese Han population. Based on the results obtained from mice, we speculate that these four EAAs might play important roles in human obesity.

Honokiol ameliorates endothelial dysfunction through suppression of PTX3 expression, a key mediator of IKK/IκB/NF-κB, in atherosclerotic cell model.

Pentraxin 3 (PTX3) was identified as a marker of the inflammatory response and overexpressed in various tissues and cells related to cardiovascular disease. Honokiol, an active component isolated from the Chinese medicinal herb Magnolia officinalis, was shown to have a variety of pharmacological activities. In the present study, we aimed to investigate the effects of honokiol on palmitic acid (PA)-induced dysfunction of human umbilical vein endothelial cells (HUVECs) and to elucidate potential regulatory mechanisms in this atherosclerotic cell model. Our results showed that PA significantly accelerated the expression of PTX3 in HUVECs through the IκB kinase (IKK)/IκB/nuclear factor-κB (NF-κB) pathway, reduced cell viability, induced cell apoptosis and triggered the inflammatory response. Knockdown of PTX3 supported cell growth and prevented apoptosis by blocking PA-inducted nitric oxide (NO) overproduction. Honokiol significantly suppressed the overexpression of PTX3 in PA-inducted HUVECs by inhibiting IκB phosphorylation and the expression of two NF-κB subunits (p50 and p65) in the IKK/IκB/NF-κB signaling pathway. Furthermore, honokiol reduced endothelial cell injury and apoptosis by regulating the expression of inducible NO synthase and endothelial NO synthase, as well as the generation of NO. Honokiol showed an anti-inflammatory effect in PA-inducted HUVECs by significantly inhibiting the generation of interleukin-6 (IL-6), IL-8 and monocyte chemoattractant protein-1. In summary, honokiol repaired endothelial dysfunction by suppressing PTX3 overexpression in an atherosclerotic cell model. PTX3 may be a potential therapeutic target for atherosclerosis.