Diesel exhaust particle exposure exacerbates ciliary and epithelial barrier dysfunction in the multiciliated bronchial epithelium models.

Airway epithelium, the first defense barrier of the respiratory system, facilitates mucociliary clearance against inflammatory stimuli, such as pathogens and particulates inhaled into the airway and lung. Inhaled particulate matter 2.5 (PM2.5) can penetrate the alveolar region of the lung, and it can develop and exacerbate respiratory diseases. Although the pathophysiological effects of PM2.5 in the respiratory system are well known, its impact on mucociliary clearance of airway epithelium has yet to be clearly defined. In this study, we used two different 3D in vitro airway models, namely the EpiAirway-full-thickness (FT) model and a normal human bronchial epithelial cell (NHBE)-based air-liquid interface (ALI) system, to investigate the effect of diesel exhaust particles (DEPs) belonging to PM2.5 on mucociliary clearance. RNA-sequencing (RNA-Seq) analyses of EpiAirway-FT exposed to DEPs indicated that DEP-induced differentially expressed genes (DEGs) are related to ciliary and microtubule function and inflammatory-related pathways. The exposure to DEPs significantly decreased the number of ciliated cells and shortened ciliary length. It reduced the expression of cilium-related genes such as acetylated α-tubulin, ARL13B, DNAH5, and DNAL1 in the NHBEs cultured in the ALI system. Furthermore, DEPs significantly increased the expression of MUC5AC, whereas they decreased the expression of epithelial junction proteins, namely, ZO1, Occludin, and E-cadherin. Impairment of mucociliary clearance by DEPs significantly improved the release of epithelial-derived inflammatory and fibrotic mediators such as IL-1ß, IL-6, IL-8, GM-CSF, MMP-1, VEGF, and S100A9. Taken together, it can be speculated that DEPs can cause ciliary dysfunction, hyperplasia of goblet cells, and the disruption of the epithelial barrier, resulting in the hyperproduction of lung injury mediators. Our data strongly suggest that PM2.5 exposure is directly associated with ciliary and epithelial barrier dysfunction and may exacerbate lung injury.

Moderating AKT signaling with baicalein protects against weight loss by preventing muscle atrophy in a cachexia model caused by CT26 colon cancer.

Cancer cachexia is a type of energy-wasting syndrome characterized by fatigue, anorexia, muscle weakness, fat loss, and systemic inflammation. Baicalein, a flavonoid with bioactive properties, has demonstrated the ability to mitigate cardiac and skeletal muscle atrophy in different experimental settings. This effect is achieved through the inhibition of muscle proteolysis, suggesting its potential in preserving skeletal muscle homeostasis. In this study, we investigated the anti-cancer cachexia effects of baicalein in the regulation of muscle and fat wasting, both in vivo and in vitro. Baicalein attenuated body weight loss, including skeletal muscle and white adipose tissue (WAT), in CT26-induced cachectic mice. Moreover, baicalein increased muscle fiber thickness and suppressed the muscle-specific ubiquitin-protease system, including F-box only protein 32 and muscle RING-finger protein-1, by activating AKT phosphorylation both in vivo and in vitro. The use of LY294002, a particular inhibitor of AKT, eliminated the observed impact of baicalein on the improvement of muscle atrophy. In conclusion, baicalein inhibits muscle proteolysis and enhances AKT phosphorylation, indicating its potential role in cancer cachexia-associated muscle atrophy.

Impact of Remimazolam versus Sevoflurane Anesthesia on Cerebral Oxygenation and Intracranial Pressure during Gynecological Laparoscopy with Mild Hypercapnia.

BACKGROUND Remimazolam has the advantage of better hemodynamic stability compared with other anesthetics. We compared the effects of remimazolam and sevoflurane on cerebral oxygenation, intracranial pressure, and intraoperative hemodynamic parameters during mild hypercapnia in patients undergoing laparoscopy in the Trendelenburg position. MATERIAL AND METHODS Sixty-two patients (20-65 years old) scheduled for gynecological laparoscopy were randomly allocated to either the remimazolam (n=31) or sevoflurane (n=31) group. Respiratory and hemodynamic parameters and regional cerebral oxygen saturation (rSO2) were recorded. Intracranial pressure was measured using the optic nerve sheath diameter (ONSD). RESULTS The change over time in rSO2 did not differ between groups (P=0.056). The change in ONSD over time showed a significant intergroup difference (P=0.002). ONSD significantly changed over time (P=0.034) in the sevoflurane group but not in the remimazolam group (P=0.115). The changes in mean arterial pressure and heart rate over time showed significant intergroup differences (P=0.045 and 0.031, respectively). The length of stay and the use of rescue antiemetics and analgesics in the postanesthetic care unit were significantly lower in the remimazolam group than in the sevoflurane group (P=0.023, 0.038, and 0.018, respectively). CONCLUSIONS Remimazolam can provide a favorable hemodynamic profile and attenuate the increase in ONSD during gynecological laparoscopy compared with sevoflurane anesthesia during lung-protective ventilation with mild hypercapnia. Remimazolam can provide faster and better postoperative recovery than sevoflurane anesthesia.

Effects of Remimazolam Anesthesia with Two Induction Doses on Hemodynamics and Recovery Profile in Older Patients: Comparison with Propofol Anesthesia.

Remimazolam has advantages such as hemodynamic stability and rapid onset. We investigated the effects of induction doses on hemodynamics and recovery profiles for remimazolam compared to propofol in older patients. Sixty-nine patients aged >65 years were randomly assigned to either the propofol anesthesia group (P group) or the remimazolam anesthesia group with an induction dose of 6 mg/kg/h (R6 group) or 12 mg/kg/h (R12 group), followed by 1 mg/kg/h. P group was anesthetized with 4 µg/mL of propofol effect-site concentration (Ce) with target-control infusion, followed by 2.5-3 µg/mL of Ce. The primary outcome was the difference between the baseline mean arterial pressure (MAP) and the lowest MAP during anesthesia (ΔMAP). ΔMAP was comparable between the P, R6, and R12 groups (43.8 ± 13.8 mmHg, 39.2 ± 14.3 mmHg, and 39.2 ± 13.5 mmHg, p = 0.443). However, the frequencies of vasoactive drug use were 54.5%, 17.4%, and 30.4% (p = 0.029), and the median doses of ephedrine 3 (0-6) mg, 0 (0-0) mg, and 0 (0-0) mg (p = 0.034), which were significantly different. This study showed remimazolam anesthesia with an induction dose of 6 mg/kg/h, rather than 12 mg/kg/h, could reduce the requirement for vasoactive drugs compared to propofol anesthesia.

Exogenous 8-Hydroxydeoxyguanosine Attenuates PM2.5-Induced Inflammation in Human Bronchial Epithelial Cells by Decreasing NLRP3 Inflammasome Activation.

Particulate matter 2.5 (PM2.5) induces lung injury by increasing the generation of reactive oxygen species (ROS) and inflammation. ROS aggravates NLRP3 inflammasome activation, which activates caspase-1, IL-1ß, and IL-18 and induces pyroptosis; these factors propagate inflammation. In contrast, treatment with exogenous 8-hydroxydeoxyguanosine (8-OHdG) decreases RAC1 activity and eventually decreases dinucleotide phosphate oxidase (NOX) and ROS generation. To establish modalities that would mitigate PM2.5-induced lung injury, we evaluated whether 8-OHdG decreased PM2.5-induced ROS generation and NLRP3 inflammasome activation in BEAS-2B cells. CCK-8 and lactate dehydrogenase assays were used to determine the treatment concentration. Fluorescence intensity, Western blotting, enzyme-linked immunosorbent assay, and immunoblotting assays were also performed. Treatment with 80 µg/mL PM2.5 increased ROS generation, RAC1 activity, NOX1 expression, NLRP3 inflammasome (NLRP3, ASC, and caspase-1) activity, and IL-1ß and IL-18 levels in cells; treatment with 10 µg/mL 8-OHdG significantly attenuated these effects. Furthermore, similar results, such as reduced expression of NOX1, NLRP3, ASC, and caspase-1, were observed in PM2.5-treated BEAS-2B cells when treated with an RAC1 inhibitor. These results show that 8-OHdG mitigates ROS generation and NLRP3 inflammation by inhibiting RAC1 activity and NOX1 expression in respiratory cells exposed to PM2.5.

Effect of High-Flow Nasal Oxygenation on Gastric Insufflation in Patients Undergoing Laryngeal Microsurgery under Tubeless General Anesthesia with Neuromuscular Blockade.

BACKGROUND: High-flow nasal oxygenation is an oxygen delivery method by which high concentrations of heated humidified oxygen are supplied via the nasal cavity. This study aimed to investigate the effect of high-flow nasal oxygenation on gastric volume change in adult patients undergoing laryngeal microsurgery under tubeless general anesthesia with neuromuscular blockade. METHODS: Patients aged 19-80 years with an American Society of Anesthesiologists physical status 1 or 2 who were scheduled to undergo laryngoscopic surgery under general anesthesia were recruited. Patients received high-flow nasal oxygenation therapy at 70 L/min during surgery under general anesthesia with neuromuscular blockade. The cross-sectional area of the gastric antrum was measured via ultrasound in the right lateral position before and after high-flow nasal oxygenation, and the gastric volume was calculated. The duration of apnea, i.e., the duration of administration of high-flow nasal oxygenation in the paralyzed state, was also recorded. RESULTS: Of the 45 patients enrolled, 44 completed the study. There were no significant differences in the antral cross-sectional area in the right lateral position, gastric volume, and gastric volume per kg between before and after high-flow nasal oxygenation application. The median duration of apnea was 15 (interquartile range, 14-22) min. CONCLUSION: High-flow nasal oxygenation at 70 L/min during apnea with the mouth open did not influence the gastric volume in patients undergoing laryngeal microsurgery under tubeless general anesthesia with neuromuscular blockade.

Comparisons of Mechanical Power and Respiratory Mechanics in Pressure-Controlled Ventilation and Volume-Controlled Ventilation during Laparoscopic Cholecystectomy in Elderly Patients.

We compared the effects of pressure-controlled volume-guaranteed ventilation (PCV) and volume-controlled ventilation (VCV) on respiratory mechanics and mechanical power (MP) in elderly patients undergoing laparoscopy. Fifty patients aged 65-80 years scheduled for laparoscopic cholecystectomy were randomly assigned to either the VCV group (n = 25) or the PCV group (n = 25). The ventilator had the same settings in both modes. The change in MP over time was insignificant between the groups (p = 0.911). MP significantly increased during pneumoperitoneum in both groups compared with anesthesia induction (IND). The increase in MP from IND to 30 min after pneumoperitoneum (PP30) was not different between the VCV and PCV groups. The change in driving pressure (DP) over time were significantly different between the groups during surgery, and the increase in DP from IND to PP30 was significantly higher in the VCV group than in the PCV group (both p = 0.001). Changes in MP during PCV and VCV were similar in elderly patients, and MP increased significantly during pneumoperitoneum in both groups. However, MP did not reach clinical significance (≥12 J/min). In contrast, the PCV group had a significantly lower increase in DP after pneumoperitoneum than the VCV group.

Panax ginseng C.A. meyer alleviates benign prostatic hyperplasia while preventing finasteride-induced side effects.

Panax ginseng C.A. Meyer, a widely used traditional medicine in East Asia, shows many beneficial effects on immune function, male erectile dysfunction, cancer, excessive oxidants, and aging issues. However, its effect on benign prostatic hyperplasia (BPH) and its potential in the treatment of side effects related to finasteride (Fi), an FDA-approved drug for BPH, are less known. This study aimed to verify the therapeutic effects of a water extract of P. ginseng (PGWE) on BPH in testosterone propionate (TP)-induced BPH rats and TP-treated RWPE-1 human epithelial cells, and the inhibitory potential on the Fi-induced side effects is also explored. In the TP-induced BPH rat model, PGWE alleviated the pathological markers of BPH such as weight and epithelial thickness of the prostate, and the serum level of dihydrotestosterone. PGWE downregulated androgen-related BPH factors such as 5α-reductase 2 and androgen receptor. PGWE also showed prostatic cell apoptosis accompanied by increased expression of Bax and decreased expression of Bcl-xL and cleaved-caspase 3, respectively, in addition to increasing mitochondrial dynamics in both in vivo and in vitro BPH models. Notably, reduced sperm count, one of the serious side effects of Fi, in the epididymis of BPH rats was recovered with PGWE treatment, suggesting less toxicity to sperm development by PGWE. PGWE also protected against Fi-induced sperm loss when PGWE was administered in combination with Fi without compromising the therapeutic effects of Fi on BPH. Based on these findings, we propose that PGWE could be an alternative therapeutic agent for BPH.

Effective concentration of remifentanil for successful i-gel insertion during remimazolam induction.

BACKGROUND: Remifentanil can be used as adjuvants during remimazolam induction without neuromuscular blockade. We evaluated the 95% effective concentration (EC) of remifentanil effect-site concentration (Ce) for the successful insertion of an i-gel using the biased-coin up-and-down method in adult patients during remimazolam induction. METHODS: Forty 19-65 year-old patients scheduled to undergo surgery using i-gel were enrolled. Anesthesia was induced using remimazolam infusion (12 mg/kg/h). Simultaneously, remifentanil was infused at a predetermined Ce. After 5 min of anesthesia induction, the i-gel was inserted. The 95% EC (EC95) of remifentanil in each patient was determined using a biased-coin up-and-down method based on a successful insertion in a preceding patient. The step size of remifentanil Ce was 0.4 ng/ml. If the insertion failed, remifentanil Ce was increased in the next patient. Following successful insertions, the corresponding concentration decreased in subsequent patients with a probability of 1/19 or was maintained with a probability of 18/19. The time from remimazolam infusion initiation to a bispectral index (BIS) < 60 (time to BIS60) and hemodynamic variables were measured and recorded. RESULTS: The EC95 (95% CI) of Ce was 2.07 (1.94, 2.87) ng/ml. The overall time to BIS60 was 154.0 ± 39.9 s. No patient experienced significant hypotension or bradycardia during remimazolam induction. CONCLUSIONS: The EC95 of remifentanil Ce was 2.07 (1.94, 2.87) ng/ml for successful i-gel insertion during remimazolam induction at 12 mg/kg/h without hemodynamic instability in adult patients. Future studies should measure remifentanil Ce in elderly patients or using remimazolam at various infusion doses.

Effect of Low or High Pressure Alveolar Recruitment Maneuver on Postoperative Pain and Quality of Recovery in Patients with Obesity Undergoing Laparoscopic Sleeve Gastrectomy.

Background: This study aimed to evaluate whether a low- or high-pressure alveolar recruitment maneuver (ARM) might reduce postoperative pain and improve the quality of recovery after laparoscopic bariatric surgery. Methods: 90 patients with a body mass index > 30 kg/m2 scheduled for laparoscopic sleeve gastrectomy were randomly assigned to control (n = 30), low ARM (n = 30), or high ARM groups (n = 30). For the low and high ARM groups, ARM was repeated five times to hold the peak airway pressure at 30 cmH2O and 60 cmH2O for 5 s, respectively, before removal of the trocar. Conventional methods to reduce post-laparoscopic pain, such as intraperitoneal saline irrigation, hemovac drainage, and gentle abdominal compression were performed in all patients, regardless of the assigned group. Results: Shoulder and surgical site pain scores 24 h postoperatively and rescue meperidine requirement were similar between the groups (p = 0.141, 0.101, and 0.82, respectively). The quality of recovery 40 (QoR40) score 24 h postoperatively was similar between the groups (p = 0.755). Postoperative pulmonary complications were similar between the groups (p = 0.124). Conclusion: Application of a low- or high-pressure ARM in addition to conventional methods to remove remnant peritoneal CO2 gas did not reduce postoperative shoulder or surgical site pain or improve the quality of recovery after laparoscopic sleeve gastrectomy.

Effect of Erector Spinae Plane Block on Postoperative Pain after Laparoscopic Colorectal Surgery: A Randomized Controlled Study.

The erector spinae plane (ESP) block can be used to reduce pain and opioid requirements after abdominal surgery. We evaluated the effect of the ESP block on postoperative pain score, analgesic use, and quality of recovery (QoR) score in patients undergoing laparoscopy. Fifty-nine patients undergoing elective laparoscopic colorectal surgery were randomly assigned to control (n = 30) or ESPB (n = 29) groups after anesthesia induction. In the ESPB group, an ultrasound-guided ESP block was performed immediately after induction using 20 mL of 0.5% ropivacaine bilaterally. The primary outcome was the postoperative pain score, which was evaluated using the 11-point numeric rating scale (NRS) (0 = no pain, 10 = worst imaginable pain), in the recovery room. NRS "at rest" and "on cough" and total dose of fentanyl rescue (in the recovery room) as well as NRS "at rest" and the cumulative administered fentanyl dose of patient-controlled analgesia (24 h post-surgery) were significantly lower in the ESPB group than in the control group. The postoperative QoR score did not differ between the groups. Bilateral ESP block after induction reduced pain scores and opioid requirements for 24 h postoperatively but did not improve the QoR in patients undergoing laparoscopic colorectal surgery.

Therapeutic role of Glycyrrhiza Uralensis fisher on benign prostatic hyperplasia through 5 alpha reductase regulation and apoptosis.

BACKGROUND: Benign prostatic hyperplasia (BPH) is an age-related disease in adult men. There are two pharmacological treatments for BPH. However, these synthetic materials have various risks, many studies are being conducted to develop new drugs from natural sources. PURPOSE: In this study, we proposed a beneficial effect of Glycyrrhiza uralensis Fischer on the development and progression of BPH, focusing on the androgen receptor (AR) and 5α-reductase 2 (5AR2) signaling axis. METHODS: To explain the therapeutic efficacy of a water extract of G. uralensis (GUWE) for BPH, we used testosterone propionate (TP)-induced BPH rat models and TP-treated RWPE-1 human prostate epithelial cells. RESULTS: In the TP-induced BPH rat models, GUWE reduced the enlarged prostate weight, prostate index, prostate epithelial thickness, and serum DHT levels. In addition, the protein levels of AR and 5AR2 in prostate tissues were significantly decreased by GUWE treatment. Furthermore, GUWE induced apoptosis signaling through an increase of Bcl-2 associated X protein (Bax), caspase 3, and Poly (ADP-ribose) polymerase (PARP) and a decrease of B-cell lymphoma-extra-large (Bcl-xL) in prostate tissues of TP-induced BPH rats. These findings were also confirmed in TP-treated RWPE-1 cells. Fi treatment markedly decreased the sperm count in the epididymis of BPH rats, but GUWE treatment did not affect the sperm count, suggesting less toxicity. CONCLUSION: These findings suggested that GUWE reduces the development of BPH by inhibiting AR-5AR2 and activating the apoptosis signaling pathway. Furthermore, unlike finasteride, GUWE did not affect sperm count. Therefore, we suggest that GUWE has a potential as a safer alternative option for BPH treatment.

Ellagic acid improves benign prostate hyperplasia by regulating androgen signaling and STAT3.

Benign prostate hyperplasia (BPH) is an age-related disease in men characterized by the growth of prostate cells and hyperproliferation of prostate tissue. This condition is closely related to chronic inflammation. In this study, we highlight the therapeutic efficacy of ellagic acid (EA) for BPH by focusing on the AR signaling axis and STAT3. To investigate the effect of EA on BPH, we used EA, a phytochemical abundant in fruits and vegetables, to treat testosterone propionate (TP)-induced BPH rats and RWPE-1 human prostate epithelial cells. The EA treatment reduced prostate weight, prostate epithelial thickness, and serum DHT levels in the TP-induced BPH rat model. In addition, EA improved testicular injury by increasing antioxidant enzymes in testis of the BPH rats. EA reduced the protein levels of AR, 5AR2, and PSA. It also induced apoptosis by regulating Bax, Bcl_xL, cytochrome c, caspase 9, and caspase 3 with increasing mitochondrial dynamics. Furthermore, EA reduced the expression of IL-6, TNF-α, and NF-κB, as well as phosphorylation of STAT3 and IκBα. These findings were also confirmed in TP-treated RWPE-1 cells. Overall, our data provide evidence of the role of EA in improving BPH through inhibition of AR and the STAT3 pathway.

Anmyungambi Decoction Ameliorates Obesity through Activation of Non-Shivering Thermogenesis in Brown and White Adipose Tissues.

Obesity is a burden to global health. Non-shivering thermogenesis of brown adipose tissue (BAT) and white adipose tissue (WAT) is a novel strategy for obesity treatment. Anmyungambi (AMGB) decoction is a multi-herb decoction with clinical anti-obesity effects. Here, we show the effects of AMGB decoction using high-fat diet (HFD)-fed C57BL6/J mice. All four versions of AMGB decoction (100 mg/kg/day, oral gavage for 28 days) suppressed body weight gain and obesity-related blood parameters in the HFD-fed obese mice. They also inhibited adipogenesis and induced lipolysis in inguinal WAT (iWAT). Especially, the AMGB-4 with 2:1:3:3 composition was the most effective; thus, further studies were performed with the AMGB-4 decoction. The AMGB-4 decoction displayed a dose-dependent body weight gain suppression. Serum triglyceride, total cholesterol, and blood glucose decreased as well. In epididymal WAT, iWAT, and BAT, the AMGB-4 decoction increased lipolysis markers. Additionally, the AMGB-4 decoction-fed mice showed an increased non-shivering thermogenic program in BAT and iWAT. Excessive reactive oxygen species (ROS) and suppressed antioxidative factors induced by the HFD feeding were also altered to normal levels by the AMGB-4 decoction treatment. Overall, our study supports the clinical use of AMGB decoction for obesity treatment by studying its mechanisms. AMGB decoction alleviates obesity through the activation of the lipolysis-thermogenesis program and the elimination of pathological ROS in thermogenic adipose tissues.

Effects of Anesthetic Techniques on the Risk of Postoperative Complications Following Lower Extremity Amputation in Diabetes Patients with Coagulation Abnormalities: A Retrospective Cohort Study Using Propensity Score Analysis.

Diabetic foot amputation is associated with high morbidity and mortality rates. To prevent cardiovascular complications along with vasculopathy in the course of diabetes mellitus, a high number of patients receive anticoagulant therapy. However, anticoagulants are contraindicated in neuraxial anesthesia limiting available anesthetic modalities. Therefore, in this retrospective study, we aimed to compare between general anesthesia and peripheral nerve block (PNB) with respect to postoperative complications following lower extremity amputation (LEA) in patients with coagulation abnormalities. In total, 320 adult patients who underwent LEA for diabetic foot were divided into two groups according to the anesthetic type (general anesthesia vs. PNB). The inverse probability of treatment weighting was performed to balance the baseline patient characteristics and surgical risk between the two groups. The adjusted analysis showed that compared with the general anesthesia group, the PNB group had lower risks of pneumonia (odds ratio: 0.091, 95% confidence interval [CI]: 0.010-0.850, p = 0.0355), acute kidney injury (odds ratio: 0.078, 95% CI: 0.007-0.871, p = 0.0382), and total major complications (odds ratio: 0.603, 95% CI: 0.400-0.910, p = 0.0161). Additionally, general anesthesia was associated with a higher amount of intraoperative crystalloid administration and a requirement for more frequent vasopressors. In conclusion, PNB appears to be protective against complications following LEA in diabetes patients with coagulopathy.

Comparison of the Effects of Normocapnia and Mild Hypercapnia on the Optic Nerve Sheath Diameter and Regional Cerebral Oxygen Saturation in Patients Undergoing Gynecological Laparoscopy with Total Intravenous Anesthesia.

Cerebral hemodynamics may be altered by hypercapnia during a lung-protective ventilation (LPV), CO2 pneumoperitoneum, and Trendelenburg position during general anesthesia. The purpose of this study was to compare the effects of normocapnia and mild hypercapnia on the optic nerve sheath diameter (ONSD), regional cerebral oxygen saturation (rSO2), and intraoperative respiratory mechanics in patients undergoing gynecological laparoscopy under total intravenous anesthesia (TIVA). Sixty patients (aged between 19 and 65 years) scheduled for laparoscopic gynecological surgery in the Trendelenburg position. Patients under propofol/remifentanil total intravenous anesthesia were randomly assigned to either the normocapnia group (target PaCO2 = 35 mmHg, n = 30) or the hypercapnia group (target PaCO2 = 50 mmHg, n = 30). The ONSD, rSO2, and respiratory and hemodynamic parameters were measured at 5 min after anesthetic induction (Tind) in the supine position, and at 10 min and 40 min after pneumoperitoneum (Tpp10 and Tpp40, respectively) in the Trendelenburg position. There was no significant intergroup difference in change over time in the ONSD (p = 0.318). The ONSD increased significantly at Tpp40 when compared to Tind in both normocapnia and hypercapnia groups (p = 0.02 and 0.002, respectively). There was a significant intergroup difference in changes over time in the rSO2 (p < 0.001). The rSO2 decreased significantly in the normocapnia group (p = 0.01), whereas it increased significantly in the hypercapnia group at Tpp40 compared with Tind (p = 0.002). Alveolar dead space was significantly higher in the normocapnia group than in the hypercapnia group at Tpp40 (p = 0.001). In conclusion, mild hypercapnia during the LPV might not aggravate the increase in the ONSD during CO2 pneumoperitoneum in the Trendelenburg position and could improve rSO2 compared to normocapnia in patients undergoing gynecological laparoscopy with TIVA.

Fruit of Gardenia jasminoides Induces Mitochondrial Activation and Non-Shivering Thermogenesis through Regulation of PPARγ.

The extract of the Gardenia jasminoides fruit (GJFE) can been consumed as an herbal tea or used as a yellow dye. Recently, studies report that GFJE exerts inhibitory effects on lipid accumulation and adipogenesis in white adipocytes. We evaluated the thermogenic actions of GJFE by focusing on mitochondrial activation and studying the underlying mechanisms. To investigate the role of GJFE on thermogenesis in mice, we used an acute cold exposure model. After 2 weeks of feeding, the cold tolerance of GJFE-fed mice was notably increased compared to PBS-fed mice. This was due to an increase in thermogenic proteins in the inguinal white adipose tissue of the cold-exposed mice. Moreover, GJFE significantly increased thermogenic factors such as peroxisome proliferator-activated receptor gamma (PPARγ), uncoupling protein 1 (UCP1), and PPARγ coactivator 1 alpha (PGC1α) in vitro as well. Factors related to mitochondrial abundance and functions were also induced by GJFE in white and beige adipocytes. However, the treatment of PPARγ inhibitor abolished the GJFE-induced changes, indicating that activation of PPARγ is critical for the thermogenic effect of GJFE. In conclusion, GJFE induces thermogenic action by activating mitochondrial function via PPARγ activation. Through these findings, we suggest GJFE as a potential anti-obesity agent with a novel mechanism involving thermogenic action in white adipocytes.

Ellagic acid induces beige remodeling of white adipose tissue by controlling mitochondrial dynamics and SIRT3.

To determine whether ellagic acid (EA) induces the "beige remodeling" of white adipose tissue (WAT), we treated cold-exposed mice and mouse stromal vascular fraction (SVF) cells with EA, a phytochemical abundant in fruits and vegetables, in particular berries. We then investigated the mechanism of EA in beige remodeling with a particular focus on DRP1-mediated mitochondrial fission and SIRT3. EA induced the trans-differentiation of white adipocytes to beige adipocytes by promoting the expression of UCP1 and other brown and beige adipocytes/fat factors (PRDM16, UCP1, PGC1α, CD137, and TBX1) and mitochondrial dynamics-related factors (SIRT3, NRF1, CPT1ß, DRP1, and FIS1) in 3T3-L1/SVF cells, and these were confirmed in the inguinal WAT of a cold-exposed mouse model. The browning effect of EA was abolished by a potent DRP1 inhibitor Mdivi-1 or SIRT3 knockdown, suggesting that EA induces beige remodeling of WAT by regulating the mitochondrial dynamics and SIRT3.

Comparison of remifentanil concentrations with and without dexmedetomidine for the prevention of emergence cough after nasal surgery: a randomized double-blinded trial.

BACKGROUND: Preventing emergence cough after nasal surgery is critical. Emergence cough can provoke immediate postoperative bleeding, which leads to upper airway obstruction. In the present study, we compared the effect-site concentration (Ce) of remifentanil to prevent emergence cough after propofol anesthesia for nasal surgery when remifentanil was or was not combined with dexmedetomidine. METHODS: Forty-seven patients with propofol-remifentanil anesthesia for nasal surgery were randomly assigned to a dexmedetomidine group (Group D, n = 23) or a saline group (Group S, n = 24). Group D and Group S were infused with dexmedetomidine (0.5 µg/kg) and saline, respectively, for 10 min before the completion of surgery. A predetermined Ce of remifentanil was infused until extubation. Remifentanil Ce to prevent cough in 50 and 95% of patients (EC50 and EC95) was estimated using modified Dixon's up-and-down method and isotonic regression. Hemodynamic and recovery parameters were recorded. RESULTS: The EC50 of remifentanil Ce was significantly lower in Group D than in Group S (2.15 ± 0.40 ng/mL vs. 2.66 ± 0.36 ng/mL, p = 0.023). The EC95 (95% CI) of remifentanil Ce was also significantly lower in Group D [2.75 (2.67-2.78) ng/mL] than in Group S [3.16 (3.06-3.18) ng/mL]. Emergence and recovery variables did not differ between the two groups. CONCLUSION: The remifentanil EC50 to prevent cough after propofol-remifentanil anesthesia was significantly lower (approximately 19%) when a combination of remifentanil and 0.5 µg/kg dexmedetomidine was used than when remifentanil infusion alone was used in patients undergoing nasal surgery. Therefore, the Ce of remifentanil may be adjusted to prevent emergence cough when used in combination with dexmedetomidine. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03622502 , August 9, 2018).