A multifaceted and inclusive methodology for the detection of sarcopenia in patients undergoing bariatric surgery: an in-depth analysis of current evidence.

Bariatric surgery is widely recognized as the most effective intervention for obesity and offers benefits beyond weight loss. However, not all patients achieve satisfactory weight loss, balanced changes in body composition, and resolution of comorbidities. Therefore, thorough pre- and postoperative evaluations are important to predict success and minimize adverse effects. More comprehensive assessments require broadening the focus beyond body weight and fat measurements to consider quantitative and qualitative evaluations of muscles. Introducing the concept of sarcopenia is useful for assessing the degradative and pathological changes in muscles associated with cardiometabolic function, physical performance, and other obesity-related comorbidities in patients undergoing bariatric surgery. However, there is currently no consensus or definition regarding the research and clinical use of sarcopenia in patients undergoing bariatric surgery. Therefore, this review aimed to define the concept of sarcopenia applicable to patients undergoing bariatric surgery, based on the consensus reached for sarcopenia in the general population. We also discuss the methods and significance of measuring muscle mass, quality, and strength, which are key variables requiring a comprehensive assessment.

The Effect of Pregabalin on Microglia Differentiation in Rat with Neuropathic pain: A Preliminary Study.

This study investigated the effects of pregabalin on microglial differentiation in rats with neuropathic pain (NP) induced by sciatic nerve ligation and transection. After confirming NP, the rats were randomly allocated to either a pregabalin or control group. The pregabalin group received intraperitoneal injections of 10 mg/kg pregabalin, while the control group received an equivalent volume of normal saline following surgery. On postoperative day 28, neuronal damage, microglial activity, and microglial differentiation were assessed. The pregabalin group exhibited significantly less neuronal damage compared to the control group, along with a significant decrease in activated microglial expression in both the brain and spinal cord. Pregabalin treatment also significantly altered the microglial phenotype expression, with a decrease in the M1 phenotype percentage and an increase in the M2 phenotype percentage in both the brain (M1 phenotype: 43.52 ± 12.16% and 18.00 ± 8.57% in the control and pregabalin groups, respectively; difference: 27.26 [15.18-42.10], p = 0.002; M2 phenotype: 16.88 ± 6.47% and 39.63 ± 5.82% in the control and pregabalin groups, respectively; difference 22.04 [17.17-32.70], p < 0.001) and the spinal cord ipsilateral to nerve injury (M1 phenotype: 44.35 ± 12.12% and 13.78 ± 5.39% in the control and pregabalin groups, respectively; difference 30.46 [21.73-44.45], p < 0.001; M2 phenotype: 7.64 ± 3.91% and 33.66 ± 7.95% in the control and pregabalin groups, respectively; difference 27.41 [21.21-36.30], p < 0.001). Overall, pregabalin treatment significantly decreased the microglial M1 phenotype while increasing the microglial M2 phenotype in NP rats.

Discovery and Prediction Study of the Dominant Pharmacological Action Organ of Aconitum carmichaeli Debeaux Using Multiple Bioinformatic Analyses.

Herbs, such as Aconitum carmichaeli Debeaux (ACD), have long been used as therapies, but it is difficult to identify which organs of the human body are affected by the various compounds. In this study, we predicted the organ where the drug predominantly acts using bioinformatics and verified it using transcriptomics. We constructed a computer-aided brain system network (BSN) and intestinal system network (ISN). We predicted the action points of ACD using network pharmacology (NP) analysis and predicted the dockable proteins acting in the BSN and ISN using statistical-based docking analysis. The predicted results were verified using ACD-induced transcriptome analysis. The predicted results showed that both the NP and docking analyses predominantly acted on the BSN and showed better hit rates in the hub nodes. In addition, we confirmed through verification experiments that the SW1783 cell line had more than 10 times more differentially expressed genes than the HT29 cell line and that the dominant acting organ is the brain, using network dimension spanning analysis. In conclusion, we found that ACD preferentially acts in the brain rather than in the intestine, and this multi-bioinformatics-based approach is expected to be used in future studies of drug efficacy and side effects.

The Preventive Effect of Urinary Trypsin Inhibitor on Postoperative Cognitive Dysfunction, on the Aspect of Behavior, Evaluated by Y-Maze Test, via Modulation of Microglial Activity.

This experimental study was designed to evaluate the effect of ulinastatin, a urinary trypsin inhibitor, on postoperative cognitive dysfunction (POCD) in rats under general anesthesia with isoflurane, on the aspect of behavior, as evaluated using a Y-maze test and focusing on microglial activity. Ulinastatin (50,000 U/mL) and normal saline (1 mL) were randomly (1:1) administered intraperitoneally to the ulinastatin and control groups, respectively, before general anesthesia. Anesthesia with isoflurane 1.5 volume% was maintained for 2 h. The Y-maze test was used to evaluate cognitive function. Neuronal damage using caspase-1 expression, the degree of inflammation through cytokine detection, and microglial activation with differentiation of the phenotypic expression were evaluated. Twelve rats were enrolled in the study and evenly allocated into the two groups, with no dropouts from the study. The Y-maze test showed similar results in the two groups before general anesthesia (63 ± 12% in the control group vs. 64 ± 12% in the ulinastatin group, p = 0.81). However, a significant difference was observed between the two groups after general anesthesia (17 ± 24% in the control group vs. 60 ± 12% in the ulinastatin group, p = 0.006). The ulinastatin group showed significantly lower expression of caspase-1. Pro-inflammatory cytokine levels were significantly lower in the ulinastatin group than in the control group. The ulinastatin group had a significantly lower microglial activation (41.74 ± 10.56% in the control group vs. 4.77 ± 0.56% in the ulinastatin, p < 0.001), with a significantly lower activation of M1 phenotypes (52.19 ± 7.83% in the control group vs. 5.58 ± 0.76% in the ulinastatin group, p < 0.001). Administering ulinastatin before general anesthesia prevented neuronal damage and cognitive decline after general anesthesia, in terms of the aspect of behavior, as evaluated by the Y-maze test. The protective effect of ulinastatin was associated with the inhibition of microglial activation, especially the M1 phenotype.

Exogenous Lipoxin A4 attenuates IL4-induced Mucin Expression in Human Airway Epithelial Cells.

Introduction: The proinflammatory cytokine interleukin-4 (IL-4) induces mucus hypersecretion by human airway epithelial cells and the MAP kinase signalling pathway may be important in terms of IL-4-induced MUC5AC gene expression. Lipoxin A4 (LXA4) is an arachidonic acid-derived mediator that promotes inflammation by binding to the anti-inflammatory receptors (ALXs) or the formyl-peptide receptor like-1 (FPRL1) protein expressed by airway epithelial cells. Here, we explore the effects of LXA4 on IL-4-induced mucin gene expression in, and secretion from, human airway epithelial cells. Methods: We co-treated cells with IL-4 (20 ng/mL) and LXA4 (1 nM) and measured the expression levels of mRNAs encoding MUC5AC and 5B via real-time polymerase chain reaction; protein expression levels were determined by Western blotting and immunocytofluorescence. The ability of IL-4 and LXA4 to suppress protein expression was determined by Western blotting. Results: IL-4 increased MUC5AC and 5B gene and protein expression. LXA4 suppressed IL-4-induced MUC5AC and 5B gene and protein expression by interacting with the IL4 receptor and mitogen-activated protein kinase (MAPK) pathway, including both phospho-p38 MAPK and phospho-extracellular signal-regulated kinase (phospho-ERK). IL-4 and LXA4 increased and decreased, respectively, the number of cells that stained with anti-MUC5AC and 5B antibodies. Conclusions: LXA4 may regulate mucus hypersecretion induced by IL4 in human airway epithelial cells.

Comparative Analysis of Olfactory and Gustatory Function of Patients With COVID-19 Olfactory Dysfunction and Non-COVID-19 Postinfectious Olfactory Dysfunction.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is known to have a high incidence of loss of smell and taste. However, studies in the early stages of the COVID-19 pandemic have evaluated these symptoms using subjective surveys and simple olfactory tests only. Hence, we compared the olfactory and gustatory characteristics of patient groups with COVID-19 olfactory dysfunction (C19OD) and non-COVID-19 postinfectious olfactory dysfunction (PIOD) using an objective olfactory test and evaluated the significance of olfactory training in both patient groups. METHODS: We retrospectively analyzed the medical records of 14 patients with a decreased sense of smell after having positive COVID-19 polymerase chain reaction results, and 56 patients with PIOD with no history of confirmed COVID-19. Participants were evaluated using the Korean version of the Sniffin' stick (KVSS) II, and chemical gustometry and olfactory training was assessed during their first visit. Olfactory training was then re-evaluated after an average of 8 (± 6) weeks. RESULTS: The average age of participants in the C19OD group was lower than in those in the non-COVID-19 PIOD group. The proportion of men in the C19OD group was higher than in the non-COVID-19 PIOD group. At baseline assessment, the C19OD group had better olfactory and gustatory functions. After olfactory training, the non-COVID-19 PIOD patient group showed a significant increase in all KVSS II Total, T, D, and I scores, but there was a non-significant increase in all scores in the C19OD group. CONCLUSION: The C19OD group had better olfactory and gustatory function than the non-COVID-19 PIOD group at the initial assessment. After olfactory training, there was an increase in olfactory function test scores in both groups. Olfactory training may be helpful in C19OD, as in non-COVID-19 PIOD.

The Effect of Ketamine on Endoplasmic Reticulum Stress in Rats with Neuropathic Pain.

This study aimed to investigate the effects of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, on endoplasmic reticulum (ER) stress in rats with neuropathic pain (NP). NP was induced in rats through ligation and transection of the sciatic nerve. After confirmation of NP, the animals were randomly divided into ketamine and control groups. The ketamine group was administered 50 mg/kg of ketamine at 15, 18, and 21 days after surgery. The expression of NMDA receptor subtype 2B (NR2B) and ER stress markers in the spinal cord (L5) was evaluated. The ipsilateral side of the surgery in the ketamine group was less sensitive to mechanical and cold stimulations. The expression of NR2B on the ipsilateral side was significantly lower in the ketamine group than in the control group (18.93 ± 1.40% vs. 31.08 ± 0.74%, p < 0.05). All markers for ER stress on the ipsilateral side of the surgery in both groups had higher expression than those on the contralateral side. The expression of activating transcription factor-6 (ATF-6) on the ipsilateral side was significantly lower in the ketamine group than in the control group (p < 0.05). Systemic administration of ketamine inhibited the expression of NMDA receptors and improved NP symptoms. Among the markers of ER stress, the therapeutic effect of ketamine is associated with the inhibition of ATF-6 expression.

Production of Plant-Derived Japanese Encephalitis Virus Multi-Epitope Peptide in Nicotiana benthamiana and Immunological Response in Mice.

The current production of the Japanese encephalitis virus (JEV) vaccine is based on animal cells, where various risk factors for human health should be resolved. This study used a transient expression system to express the chimeric protein composed of antigenic epitopes from the JEV envelope (E) protein in Nicotiana benthamiana. JEV multi-epitope peptide (MEP) sequences fused with FLAG-tag or 6× His-tag at the C- or N-terminus for the purification were introduced into plant expression vectors and used for transient expression. Among the constructs, vector pSK480, which expresses MEP fused with a FLAG-tag at the C-terminus, showed the highest level of expression and yield in purification. Optimization of transient expression procedures further improved the target protein yield. The purified MEP protein was applied to an ICR mouse and successfully induced an antibody against JEV, which demonstrates the potential of the plant-produced JEV MEP as an alternative vaccine candidate.

Effects of general anaesthesia with an inhalational anaesthetic agent on the expression of exosomes in rats.

Background: We hypothesized that the expression of exosomes under general anaesthesia with an inhalational anaesthetic agent would be changed. The study was designed to confirm the effect of general anesthesia with an inhalational anaesthetic agent on the expression of exosomes in rats. Methods: After intraperitoneal administration for the mixture of ketamine and xylazine, tracheal intubation was performed. Just before the connection to ventilator, Control group and Anaesthesia group, according to anaesthesia with isoflurane, were allocated. The expressions of exosomes were checked in bronchoalveolar lavage (BAL), the blood and the tissues from the lung and the brain. Cytokines in the blood were also assessed. Results: The expressions of cluster of differentiation (CD)63 and CD81 as markers for the exosomes in the blood was increased after anaesthesia with isoflurane (CD63, 0.078 ± 0.057 % in Control group vs. 0.180 ± 0.036 % in Anaesthesia group, p = 0.02; CD81, 0.028 ± 0.034 % in Control group vs. 0.245 ± 0.054 % in Anaesthesia group, p < 0.01). However, the increased expression of them were not checked in BAL, and the tissues from the lung and the brain. The cytokines in the blood did not show any significant difference before and after anaesthesia with isoflurane. Conclusion: General anaesthesia with an inhalational anaesthetic agent increased the expression of exosomes in the blood. However, the change was limited in the blood, not the alveoli and the brain.

Linalyl acetate as a potential preventive agent against muscle wasting in rheumatoid arthritis rats chronically exposed to nicotine.

Cigarette smoking has detrimental effects on rheumatoid arthritis (RA), characterized by muscle wasting. Linalyl acetate (LA), the main component of Lavandula angustifolia Mill (lavender) oil, has anti-inflammatory properties. We investigated the detrimental effects of chronic nicotine exposure in rats with RA, as well as the abilities of lavender oil and LA to prevent muscle wasting. Rats with RA induced by type II collagen were exposed to nicotine for 22 days from day 1. Lavender oil or LA was administered twice a week during the experiment. Compared with control, collagen-induced arthritis (CIA) and chronic nicotine exposure plus CIA (NicoCIA) showed increases in hind paw thickness and serum interleukin (IL)-6 and decreases in body weight and serum insulin-like growth factor (IGF)-1 levels. Moreover, weight and fiber cross-sectional area of the gastrocnemius muscle were much lower, and mitochondrial membrane potential of the gastrocnemius muscle was higher, in the NicoCIA than in the CIA. These alterations in the NicoCIA were prevented by lavender oil and LA. Importantly, LA showed greater activity than lavender oil in preventing IGF-1 reduction in the NicoCIA. These findings suggest that lavender oil and LA may have preventive benefit in RA by counteracting muscle wasting associated with chronic nicotine exposure.

The Preventive Effect of the Phenotype of Tumour-Associated Macrophages, Regulated by CD39, on Colon Cancer in Mice.

BACKGROUND: This study was designed to investigate the effect of cluster differentiation (CD)39 and CD73 inhibitors on the expresion of tumour-associated macrophages (TAMs), M1- versus M2-tumour phenotypes in mice with colon cancer. METHODS: An in vivo study of co-culture with colon cancer cells and immune cells from the bone marrow (BM) of mice was performed. After the confirmation of the effect of polyoxotungstate (POM-1) as an inhibitor of CD39 on TAMs, the mice were randomly divided into a control group without POM-1 and a study group with POM-1, respectively, after subcutaneous injection of CT26 cells. On day 14 after the injection, the mice were sacrificed, and TAMs were evaluated using fluorescence-activated cell sorting. RESULTS: In the in vivo study, the co-culture with POM-1 significantly increased the apoptosis of CT26 cells. The cell population from the co-culture with POM-1 showed significant increases in the expression of CD11b+ for myeloid cells, lymphocyte antigen 6 complex, locus C (Ly6C+) for monocytes, M1-tumour phenotypes from TAMs, and F4/80+ for macrophages. In the in vivo study, tumour growth in the study group with POM-1 was significantly limited, compared with the control group without POM-1. The expressions of Ly6C+ and major histocompatibility complex class II+ for M1-tumour phenotypes from TAMs on F4/80+ from the tumour tissue in the study group had significantly higher values compared with the control group. CONCLUSION: The inhibition of CD39 with POM-1 prevented the growth of colon cancer in mice, and it was associated with the increased expression of M1-tumour phenotypes from TAMs in the cancer tissue.

Methylation of the CDX2 promoter in Helicobacter pylori-infected gastric mucosa increases with age and its rapid demethylation in gastric tumors is associated with upregulated gene expression.

Pathological changes in the epigenetic landscape of chromatin are hallmarks of cancer. The caudal-type homeobox gene CDX2 is not expressed in normal gastric epithelia but rather in adult intestinal epithelia, and it is overexpressed in intestinal metaplasia (IM). However, it remains unclear how CDX2 transcription is suppressed in normal gastric epithelial cells and overexpressed in IM. Here, we demonstrate that methylation of the CDX2 promoter increases with age in Helicobacter pylori-positive, noncancerous gastric tissue, whereas the promoter is demethylated in paired gastric tumors in which CDX2 is upregulated. Moreover, we also found that the CDX2 promoter is demethylated in IM as well as gastric tumor. Immunohistochemistry revealed that CDX2 is present in foci of parts of the gastric mucosae but highly expressed in IM as well as in gastric tumors, suggesting that the elevated level of CDX2 in IM and gastric tumors may be attributable to promoter demethylation. Our data suggest that CDX2 repression may be associated with promoter methylation in noncancerous H. pylori-positive mucosa but its upregulation might be attributable to increased promoter activity mediated by chromatin remodeling during gastric carcinogenesis.

ONECUT2 upregulation is associated with CpG hypomethylation at promoter-proximal DNA in gastric cancer and triggers ACSL5.

Many studies have focused on global hypomethylation or hypermethylation of tumor suppressor genes, but less is known about the impact of promoter hypomethylation of oncogenes. We previously showed that promoter methylation may gradually increase or decrease during the transition from gastric mucosa (GM) to intestinal metaplasia (IM) to gastric cancer (GC). In our study, we focused on regional CpG hypomethylation of the promoter-proximal DNA of the transcription factor ONECUT2 (OC2) in IM and GC cells. We validated the hypomethylation of promoter-proximal DNA of OC2 in 160 primary GCs, in which methylation level correlated negatively with OC2 mRNA level. IM and GC cells stained positively for OC2, whereas GM cells did not. Stable transfection of OC2 in GC cells promoted colony formation, cell migration, invasion and proliferation. Moreover, OC2 knockdown with a short hairpin RNA suppressed tumorigenesis in nude mice. In addition, chromatin immunoprecipitation coupled with DNA sequencing and RNA-seq analyses revealed that OC2 triggered ACSL5, which is strongly expressed in IM of the stomach but not in GM, indicating that OC2 and ACSL5 are early-stage biomarkers for GC. We also observed a high correlation between the levels of OC2 and ACSL5 mRNAs in the GENT database These results suggest that epigenetic alteration of OC2 upregulates its expression, which then activates ACSL5; thus, OC2 is induced in IM by epigenetic alteration and triggers ACSL5 expression, and thus OC2 and ACSL5 may cooperatively promote intestinal differentiation and GC progression.

The effect of repetitive exposure to intravenous anesthetic agents on the immunity in mice.

Introduction: This study was designed to assess the effect of repetitive exposure to intravenous anesthetic agents on the immunity in mice. Materials and Methods: The mice were divided into six groups: three intravenous anesthetic agents groups (dexmedetomidine, midazolam and propofol groups), and three corresponding control groups (CD, CM, and CP groups). The intravenous injections were administered once per day for 5 days. The immunity of mice was checked after the last intravenous injection. Histopathology and immunochemistry of liver and kidneys were evaluated. Cytokine levels in the blood was also checked. vs. evaluated with cytokine levels in the blood. Results: Cluster of differentiation (CD)4+ T cells were significantly less expressed in dexmedetomidine and propofol groups, compared with the corresponding control groups [34.08 ± 5.63% in the dexmedetomidine group vs. 59.74 ± 8.64% in the CD group, p < 0.05; 25.28 ± 7.28% in the propofol group vs. 61.12 ± 2.70% in the Cp group, p < 0.05]. Apoptosis of CD4+ T cells was increased significantly in dexmedetomidine and propofol groups, compared with the corresponding control groups. Histopathological findings of liver and kidneys did not show any specific differences of any of three intravenous anesthetic agents groups with their corresponding control groups, although immunohistochemical examination indicated significantly lower expression of Toll-like receptor-4 from liver and kidneys in dexmedetomidine and propofol groups. The cytokine levels were not different between the groups. Conclusion: Repetitive exposure to dexmedetomidine and propofol reduced the expression of CD4+ T cells but did not induce any significant liver or kidney injuries.

Impact of general anaesthesia on endoplasmic reticulum stress: propofol vs. isoflurane.

Background: This study investigated the effects of propofol and isoflurane on endoplasmic reticulum (ER) stress in an animal model under general anaesthesia. Methods: Rats were randomly divided into Propofol and Isoflurane groups. Anaesthesia was maintained with propofol for Propofol group or isoflurane for Isoflurane group during 3 h. ER stress from lymphocytes in blood and tissues was evaluated between two groups after euthanasia. Reactive oxygen species (ROS) from lymphocytes in blood and tissues, and cytokines in blood were also checked. An immunohistochemical assay for ER stress marker from tissues was performed. Results: After anaesthesia, the levels of CCAAT-enhancer-binding protein homologous proteins (CHOP) in blood and liver were significantly higher in Isoflurane group, compared to Propofol group [blood, 31,499 ± 4,934 (30,733, 26,441-38,807) mean fluorescence intensity (MFI) in Isoflurane group vs. 20,595 ± 1,838 (20,780, 18,866-22,232) MFI in Propofol group, p = 0.002; liver, 28,342 ± 5,535 (29,421, 23,388-32,756) MFI in Isoflurane group vs. 20,004 ± 2,155 (19,244, 18,197-22,191) MFI in Propofol group, p = 0.020]. ROS in blood was significantly higher in Isoflurane group, compared to Propofol group. However, cytokines in blood and immunohistochemical assays in tissues were similar between groups. Conclusion: Significant higher of ER stress from blood and liver were observed in rats under anaesthesia with isoflurane, compared to those that received propofol. ROS from blood also showed significant higher under anaesthesia with isoflurane. However, these findings were not associated with any changes in cytokines in blood or immunohistochemical assay in tissues.

Phosphate supplementation for hypophosphatemia during continuous renal replacement therapy in adults.

BACKGROUND: Hypophosphatemia is common during continuous renal replacement therapy (CRRT) in critically ill patients and can cause generalized muscle weakness, prolonged respiratory failure, and myocardial dysfunction. This study aimed to investigate the efficacy and safety of adding phosphate to the dialysate and replacement solutions to treat hypophosphatemia occurring in intensive CRRT in critically ill patients. METHODS: We retrospectively analyzed 73 patients treated with intensive CRRT (effluent flow ≥35 ml/kg/hr) in the intensive care unit. The control group (group 1, n = 22) received no phosphate supplementation. The treatment groups received dialysate and replacement solution phosphate supplementation at 2.0 mmol/L (group 2, n = 26) or 3.0 mmol/L (group 3, n = 25). RESULTS: The CRRT-induced hypophosphatemia incidence was 59.0%. Correction of hypophosphatemia with phosphate supplementation changed the mean serum phosphorus levels to 1.24 ± 0.37 and 1.44 ± 0.31 mmol/L in groups 2 and 3, respectively (p = .02). The time required for correction was 1.65 ± 0.80 and 1.39 ± 1.43 days for groups 2 and 3, respectively and was significantly longer in group 2 (p = .02). After supplementation, hypophosphatemia, and hyperphosphatemia both occurred in 7% of group 2. Group 3 developed no hypophosphatemia, but 20% developed hyperphosphatemia. The serum phosphate levels in hyperphosphatemia cases returned to normal within 2.0 days (group 2) and 1.0 day (group 3) after stopping phosphate supplementation. CONCLUSION: Phosphate supplementation effectively corrected CRRT-induced hypophosphatemia in critically ill patients with an acute kidney injury. The use of 2 mmol/L phosphate is appropriate in patients with CRRT-induced hypophosphatemia, but a different concentration could be required to prevent hypophosphatemia at the start of CRRT.

Effect of Equipotent Doses of Propofol versus Sevoflurane Anesthesia on Regulatory T Cells after Breast Cancer Surgery.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Clusters of differentiation 39 and 73, enzymes expressed on the surface of regulatory T cells, promote cancer recurrence and metastasis by suppressing immune cells. The authors hypothesized that propofol is less immunosuppressive than volatile anesthetics. The objective of this randomized trial was to compare the changes in cluster of differentiation 39 and 73 expression on regulatory T cells between propofol- and sevoflurane-based anesthesia during breast cancer surgery. METHODS: A total of 201 patients having breast cancer surgery were randomly assigned and analyzed (n = 99 for propofol, n = 102 for sevoflurane). Blood samples were obtained immediately before anesthesia induction and 1 and 24 h postoperatively. The frequency of cluster of differentiation 39 and 73 expression on circulating regulatory T cells (primary outcome) and the frequency of circulating type 1 and type 17 helper T cells, natural killer cells, and cytotoxic T cells were investigated. Serum cytokines and the neutrophil-to-lymphocyte ratio were also evaluated. RESULTS: Changes in cluster of differentiation 39 and 73 expression on regulatory T cells over time did not differ with propofol and sevoflurane groups (difference [95% confidence interval]: 0.01 [-2.04 to 2.06], P = 0.995 for cluster of differentiation 39; -0.93 [-3.12 to 1.26], P = 0.403 for cluster of differentiation 73). There were no intergroup differences in type 1, type 17 helper T cells, natural killer cells, cytotoxic T cells, cytokines, or the neutrophil-to-lymphocyte ratio. CONCLUSIONS: Changes in immune cells were similar with propofol and sevoflurane during breast cancer surgery. The effect of anesthetics on the perioperative immune activity may be minimal during cancer surgery.

Receptor for activated C kinase 1 in rats with ischemia-reperfusion injury: intravenous versus inhalation anaesthetic agents.

Background: The study examined the difference in the expression of the receptor for activated C kinase 1 (RACK1) between anaesthesia with propofol and isoflurane in rats with myocardial ischemia-reperfusion injury (IRI). Methods: Male Sprague-Dawley rats were studied. Anaesthesia was induced with xylazine 20 µg/g by intraperitoneal injection and maintained with propofol or isoflurane. Myocardial IRI was induced by ligating the left anterior descending artery for 1 hour. Reactive oxygen species (ROS), cardiomyocyte apoptosis, the expression of RACK1 and toll-like receptor 4 (TLR4), and the heart injury score were compared between the two groups. Results: Cardiomyocyte apoptosis with ROS was significantly lower in the propofol group than in the isoflurane group. The propofol group had significantly higher RACK1 expression and lower TLR4 expression, compared with the isoflurane group (RACK1, 1970.50 ± 120.50 vs. 1350.20 ± 250.30, p<0.05; TLR4, 980.50 ± 110.75 vs. 1275.50 ± 75.35, p<0.05). However, the heart injury scores in the two groups did not differ significantly (3.56 ± 0.29 vs. 4.33 ± 0.23 in the propofol and isoflurane groups, respectively, p=0.33). Conclusion: There were significant differences in inflammation and apoptosis, including the expression of RACK1 and TLR4, after myocardial IRI between the propofol and isoflurane groups. However, both groups had similar heart injury scores.

The Telomerase-Derived Anticancer Peptide Vaccine GV1001 as an Extracellular Heat Shock Protein-Mediated Cell-Penetrating Peptide.

Cell-penetrating peptides (CPPs), which can facilitate the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular delivery of macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes. The eHSP-GV1001 interaction may have biological effects in addition to its cytosolic delivery function. GV1001 was originally designed as a major histocompatibility complex (MHC) class II-binding cancer epitope, but its CPP properties may contribute to its strong anti-cancer immune response relative to other telomerase peptide-based vaccines. Cell signaling via eHSP-GV1001 binding may lead to unexpected biological effects, such as direct anticancer or antiviral effects. In this review, we focus on the CPP effects of GV1001 bound to eHSP90 and eHSP70.

The serum protein fetuin-B is involved in the development of acute myocardial infarction.

The rupture of an atherosclerotic plaque is one of the main causes of coronary artery thrombotic occlusion, leading to myocardial infarction. However, the exact mechanism and causal risk factors for plaque rupture remain unclear. To identify a potential molecule that can influence atherosclerotic plaque rupture, we investigated protein expression in serum from patients with acute myocardial infarction (AMI) and stable angina (SA), using proteomic analysis. The expression of six proteins, including fibrinogen, fetuin-B, keratin 9, proapolipoprotein and fibrinogen, were altered in serum from patients with AMI compared with serum from those with SA. Of these, fetuin-B, proapolipoprotein, fibrinogen γ-B-chain precursors and fibrinogen expression were greater in serum from patients with AMI than from patients with SA. Increased fetuin-B expression in serum from AMI patients was also confirmed by Western blot analysis. Treatment with recombinant human fetuin-B increased the migration in monocytes and macrophages in a concentration-dependent manner. Fetuin-B also affected vascular plaque-stabilizing factors, including lipid deposition and cytokine production in macrophages, the activation of matrix metalloproteinase (MMP)-2 in monocytes, and the activation of apoptosis and MMP-2 in vascular smooth muscle cells. Moreover, in vivo administration of fetuin-B decreased the collagen accumulation and smooth muscle cell content and showed an increased number of macrophages in the vascular plaque. From these results, we suggest that fetuin-B may act as a modulator in the development of AMI. This study may provide a therapeutic advantage for patients at high risk of AMI.