Dexmedetomidine alleviates the long-term neurodevelopmental toxicity induced by sevoflurane in the developing brain.

INTRODUCTION: Sevoflurane is an extensively used anesthetic for pediatric patients, however, numerous studies showed that sevoflurane (SEVO) may cause long-term neurodevelopmental toxicity. Dexmedetomidine (DEX) has been shown to be protective against SEVO-induced neurotoxicity, but the mechanism remains unclear. The effects and mechanisms of different DEX administration routes on SEVO-induced neurotoxicity and long-term cognitive defects were determined and further investigated the role of sex in these processes. METHODS: Male and female Sprague Dawley (SD) rats at postnatal day 7 (PND7) received an intraperitoneal injection of DEX (10 µg/kg) before or after exposure to 2.5% SEVO for 6 hours, or before and after SEVO exposure. The respiratory and mortality rates of the pups were recorded during anesthesia. Neuroapoptosis was evaluated by TdT-mediated dUTP Nick-End labeling (TUNEL) staining. Immunohistochemistry and immunofluorescence were employed to detect the expression of caspase-3 in neuronal cells and neurons. The expression of GSK-3ß and DISC1 were determined by Western blotting or RT-qPCR. Morris Water Maze (MWM) test was used to evaluate the learning and memory ability of rats until they were 3 weeks and 5 weeks old. RESULTS: Compared with the control group, exposure to 2.5% SEVO resulted in increased neuroapoptosis, and decreased the expression of DISC1 at levels of mRNA and protein and phosphorylated GSK-3ß in the developing brain. SEVO exposure during critical neurodevelopmental periods could cause persistent cognitive defects in adolescent male and female rats, and inhibited DISC1 and phosphorylated GSK-3ß protein expression. The neurotoxic impacts of SEVO were lessened by the administration of DEX (10 µg/kg) before or after exposure. CONCLUSION: Our findings suggest that DEX (10 µg/kg) mitigates the neurotoxic effects of SEVO on the developing rat brain as well as postnatal cognitive defects by regulating the DISC1/GSK-3ß signaling.

Propofol Inhibits Ferroptotic Cell Death Through the Nrf2/Gpx4 Signaling Pathway in the Mouse Model of Cerebral Ischemia-Reperfusion Injury.

Ferroptosis is characterized by excessive accumulation of iron and lipid peroxides, which are involved in ischemia, reperfusion-induced organ injury, and stroke. Propofol, an anesthetic agent, has neuroprotective effects due to its potent antioxidant, anti-ischemic, and anti-inflammatory properties. However, the relationship between propofol and ferroptosis is still unclear. In the current study, we elucidated the role of ferroptosis in the neuroprotective effect of propofol in mouse brains subjected to cerebral ischemia reperfusion injury (CIRI). Ferroptosis was confirmed by Western blotting assays, transmission electron microscopy, and glutathione assays. Propofol regulated Nrf2/Gpx4 signaling, enhanced antioxidant potential, inhibited the accumulation of lipid peroxides in CIRI-affected neurons, and significantly reversed CIRI-induced ferroptosis. Additionally, Gpx4 inhibitor RSL3 and Nrf2 inhibitor ML385 attenuated the effects of propofol on antioxidant capacity, lipid peroxidation, and ferroptosis in CIRI-affected neurons. Our data support a protective role of propofol against ferroptosis as a cause of cell death in mice with CIRI. Propofol protected against CIRI-induced ferroptosis partly by regulating the Nrf2/Gpx4 signaling pathway. These findings may contribute to the development of future therapies targeting ferroptosis induced by CIRI.

Correlation between perioperative parecoxib use and postoperative acute kidney injury in patients undergoing radical mastectomy: a retrospective cohort analysis.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed drugs worldwide. However, the effect of NSAIDS on postoperative renal function is still unclear. Few studies have assessed the effects of parecoxib on renal function. Our aim is to investigate a correlation between parecoxib and the presence or absence of AKI postoperatively after a breast cancer surgery operation. METHODS: This was a retrospective cohort study that we performed on our hospitalized database. From January 2012 to August 2021, 3542 female patients undergoing radical mastectomy were enrolled, all data including the patients' information and laboratory results were obtained from electronic medical system. The main outcome was the incidence of AKI postoperatively. AKI was defined in accordance with the KDIGO criteria. Study groups were treated with or without parecoxib. Univariable and multivariable logistic regression analyses were performed. RESULTS: In our study, about 5.76% experienced AKI. The incidence rate of postoperative AKI (3.49%) within 7 days in the parecoxib group was lower than that in the control group (6.00%, P = 0.05). Compared to the control group, the AKI's incidence was reduced by 49% (OR = 0.46; 95%CI 0.27-0.97) in parecoxib group in multivariable logistic regression analysis. There was a reduction in the incidence of postoperative AKI in other three subgroups: preoperative eGFR < 90 mL/min·1.73/m2 (OR = 0.52; 95%CI 0.27-0.97), blood loss < 1000 ml (OR = 0.48; 95%CI 0.24-0.96) and non-diabetes (OR = 0.51; 95%CI 0.26-0.98). CONCLUSIONS: Parecoxib was associated with incidence of postoperative acute kidney injury.

Intestinal Flora Dysbiosis Aggravates Cognitive Dysfunction Associated With Neuroinflammation in Heart Failure.

BACKGROUND: Cognitive dysfunction after heart failure (HF) is characterized by neuroinflammation, which plays an important role in the occurrence and development of cognitive dysfunction. Recent studies have shown that an intestinal flora imbalance may also trigger neuroinflammation in Alzheimer's disease. The present study was designed to reveal that intestinal flora dysbiosis caused by HF aggravates neuroinflammation-associated cognitive impairment. METHODS AND RESULTS: Adult male Sprague-Dawley rats were fed daily for 2 weeks with probiotics or placebo until the day of surgery. HF was then triggered by 8 weeks of sustained coronary artery occlusion. 16S rDNA sequencing was used to confirm intestinal flora dysbiosis after HF and demonstrate that the changes paralleled intestinal pathology scores. The permeability of the blood-brain barrier was increased after HF, and such an increase in permeability may increase the levels of inflammatory cytokines caused by intestinal flora disorders. The changes in the intestinal flora caused by probiotics significantly reduced the level of neuroinflammation. In addition, probiotic administration considerably improved the impaired spatial memory in HF rats. CONCLUSIONS: We conclude that intestinal flora dysbiosis plays a potential role in aggravating the impaired cognition associated with neuroinflammation and that these effects may be attenuated by probiotics.

Impact of echocardiographic wall motion abnormality and cardiac biomarker elevation on outcome after subarachnoid hemorrhage: a meta-analysis.

Cardiac abnormalities (echocardiographic wall motion abnormality (WMA), biomarker elevation of cardiac troponin (cTn), B-type natriuretic peptide (BNP), or N-terminal prohormone of B-type natriuretic peptide (NT-proBNP)) frequently occur after subarachnoid hemorrhage (SAH). The clinical significance of cardiac abnormalities after SAH remains controversial. This meta-analysis was performed to assess the association between cardiac abnormalities and patient outcomes, including delayed cerebral ischemia (DCI), poor outcome, and death in SAH patients. PubMed and Embase were searched for observational studies reporting an association between cardiac abnormalities and outcome after SAH that were published before 31 December 2017. We extracted data regarding patient characteristics, cardiac abnormalities, and outcome measurements (DCI, poor outcome, or death). Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Twenty-six studies involving 3917 patients were included in our data analysis. WMA showed significant associations with higher rates of DCI (RR, 2.03; 95% CI, 0.99-4.15), poor outcome (RR, 1.45; 95% CI, 1.08-1.93), and death (RR, 2.54; 95% CI, 1.59-4.05). cTn elevation was associated with an increased risk of DCI (RR, 1.48; 95% CI, 1.23-1.79), poor outcome (RR, 1.85; 95% CI, 1.49-2.30), and death (RR, 2.68; 95% CI, 2.19-3.27). Elevation of BNP or NT-proBNT was significantly associated with higher rates of DCI (RR, 1.87; 95% CI, 1.16-3.02). WMA and elevation of cTn, BNP, and NT-proBNP in SAH patients are associated with an increased risk of DCI, poor outcome, and death after SAH.

ALDH2 Protects Against Ischemic Stroke in Rats by Facilitating 4-HNE Clearance and AQP4 Down-Regulation.

Aldehyde dehydrogenase 2 (ALDH2) is a new therapeutic target in the central nervous system. However, the association between ALDH2 and brain edema following ischemic stroke (IS) remains unclear. The present study was investigated to whether active ALDH2 can attenuate brain edema by using a rat model of IS, with the aim of clarifying the underlying mechanisms involved. Rats were administered the ALDH2 agonist Alda-1, vehicle or the ALDH2 inhibitor cyanamide (CYA) 15 min prior to a 1.5 h middle cerebral artery occlusion (MCAO) surgery. The effects of ALDH2 were subsequently investigated 24 h after reperfusion by evaluating neurological function, infarct sizes, brain edema volumes, 4-hydroxy-2-nonenal (4-HNE) levels, and aquaporin 4 (AQP4) protein expression. The results demonstrated that increasing ALDH2 activity significantly improved neurological deficits, reduced infarct sizes, and attenuated brain edema after MCAO. Alda-1 administration led to decreased 4-HNE levels and inhibited AQP4 protein expression in the peri-infarct section of the brain. Whereas, CYA administration increased 4-HNE levels, AQP4 expression, and simultaneously aggravated brain edema following MCAO. In conclusion, increasing ALDH2 activity can improve brain edema, infarct volumes, and reduce neurological impairment in a rat IS model. The therapeutic benefits of ALDH2 are related to 4-HNE clearance and AQP4 down-regulation.

Propofol Prevents Oxidative Stress by Decreasing the Ischemic Accumulation of Succinate in Focal Cerebral Ischemia-Reperfusion Injury.

Oxidative stress caused by mitochondrial dysfunction during reperfusion is a key pathogenic mechanism in cerebral ischemia-reperfusion (IR) injury. Propofol (2,6-diisopropylphenol) has been proven to attenuate mitochondrial dysfunction and reperfusion injury. The current study reveals that propofol decreases oxidative stress injury by preventing succinate accumulation in focal cerebral IR injury. We evaluated whether propofol could attenuate ischemic accumulation of succinate in transient middle cerebral artery occlusion in vivo. By isolating mitochondria from cortical tissue, we also examined the in vitro effects of propofol on succinate dehydrogenase (SDH) activity and various mitochondrial bioenergetic parameters related to oxidative stress injury, such as the production of reactive oxidative species, membrane potential, Ca2+-induced mitochondrial swelling, and morphology via electron microscopy. Propofol significantly decreased the ischemic accumulation of succinate by inhibiting SDH activity and inhibited the oxidation of succinate in mitochondria. Propofol can decrease membrane potential in normal mitochondria but not in ischemic mitochondria. Propofol prevents Ca2+-induced mitochondrial swelling and ultrastructural changes to mitochondria. The protective effect of propofol appears to act, at least in part, by limiting oxidative stress injury by preventing the ischemic accumulation of succinate.

Weaponized Health Communication: Twitter Bots and Russian Trolls Amplify the Vaccine Debate.

OBJECTIVES: To understand how Twitter bots and trolls ("bots") promote online health content. METHODS: We compared bots' to average users' rates of vaccine-relevant messages, which we collected online from July 2014 through September 2017. We estimated the likelihood that users were bots, comparing proportions of polarized and antivaccine tweets across user types. We conducted a content analysis of a Twitter hashtag associated with Russian troll activity. RESULTS: Compared with average users, Russian trolls (χ2(1) = 102.0; P < .001), sophisticated bots (χ2(1) = 28.6; P < .001), and "content polluters" (χ2(1) = 7.0; P < .001) tweeted about vaccination at higher rates. Whereas content polluters posted more antivaccine content (χ2(1) = 11.18; P < .001), Russian trolls amplified both sides. Unidentifiable accounts were more polarized (χ2(1) = 12.1; P < .001) and antivaccine (χ2(1) = 35.9; P < .001). Analysis of the Russian troll hashtag showed that its messages were more political and divisive. CONCLUSIONS: Whereas bots that spread malware and unsolicited content disseminated antivaccine messages, Russian trolls promoted discord. Accounts masquerading as legitimate users create false equivalency, eroding public consensus on vaccination. Public Health Implications. Directly confronting vaccine skeptics enables bots to legitimize the vaccine debate. More research is needed to determine how best to combat bot-driven content.

A method for addressing right upper lobe obstruction with right-sided double-lumen endobronchial tubes during surgery: a randomized controlled trial.

BACKGROUND: A right-sided double-lumen tube (R-DLT) tends to obstruct the right upper lobe intraoperatively due to anatomical distortion during surgery. If the R-DLT is poorly matched with the patient's airway anatomy, it will not be possible to correctly replace the tube with a fiberoptic bronchoscope (FOB). In our study, we aimed to explore an efficient method for difficult repositioning caused by right upper lobe occlusion during surgery: repositioning the R-DLT from the right main bronchus into the left main bronchus. The current study was designed to assess the efficacy and safety of this method. METHODS: Sixty adult patients scheduled to undergo left-sided thoracic surgery were randomly assigned to two groups. With the patient in the right lateral position during surgery, the R-DLT was pulled back to the trachea while being rotated 90° clockwise; it was then either rotated 90° clockwise for placement into the left main bronchus (Group L) or rotated 90° anticlockwise and returned to the right main bronchus (Group R) using FOB guidance. The primary outcomes included clinical performance, which was measured by intubation time, and the quality of lung collapse. A secondary outcome was safety, which was determined according to bronchial injury and vocal cord injury. RESULTS: The median intubation time (IQR [range]) required for placement of a R-DLT into the left main bronchus was shorter than the time required for placement into the right main bronchus (15.0 s [IQR, 12.0 to 20.0 s]) vs 23.5 s [IQR, 14.5 to 65.8 s], P = 0.005). The groups showed comparable overall results for the quality of lung collapse during the total period of one-lung ventilation (P = 1.000). The numbers of patients with bronchial injuries or vocal cord injuries were also comparable between groups (Group R, 11/30 vs. Group L 8/30, P = 0.580 for bronchus injuries; Group R, 15/30 vs. Group L 13/30, P = 0.796 for vocal cord injuries). CONCLUSIONS: Repositioning a R-DLT from the right main bronchus into the left main bronchus had good clinical performance without causing additional injury. This may be an efficient method for the difficult repositioning of a R-DLT due to right upper lobe occlusion during surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-15006933 , registered on 15 August 2015.

Electrocardiographic Abnormalities Predict Adverse Clinical Outcomes in Patients with Subarachnoid Hemorrhage.

BACKGROUND: We conducted a retrospective cohort study of a large sample to assess whether electrocardiographic (ECG) abnormalities are independently associated with the occurrence of neurogenic pulmonary edema (NPE), delayed cerebral ischemia (DCI), and in-hospital death after nontraumatic subarachnoid hemorrhage (SAH). METHODS: In this retrospective observational study, patients who were admitted within 72 hours of SAH symptom onset between 2013 and 2015 were enrolled. Twelve-lead ECG findings obtained within 72 hours after SAH and the presence of NPE, DCI, and in-hospital death were collected based on the results reported in the medical records. RESULTS: We included 834 patients. NPE occurred in 192 patients (23%). The median delay from SAH onset to NPE was 3 days (interquartile range [IQR]: 5 days). DCI occurred in 223 patients (27%; median delay to DCI, 4 days; IQR: 5 days). In total, 141 patients (17%) died in the hospital (median time to death, 12 days; IQR: 18 days). The frequency of ECG abnormalities for all enrolled patients was 65%. Corrected QT prolongation had an adjusted risk ratio (RR) of 1.5 (1.1-2.2) for NPE and 1.8 (1.3-2.4) for DCI. ST depression had an adjusted RR of 3.0 (1.2-7.5) for in-hospital death. NSSTTCs (nonspecific ST- or T-wave changes) had an adjusted RR of 2.7 (1.8-4.2) for NPE, 2.8 (1.9-4.3) for DCI, and 2.2 (1.3-3.5) for in-hospital death. All RRs were adjusted for age and Hunt-Hess scores. CONCLUSIONS: ECG abnormalities assessed within 72 hours after SAH using a standard 12-lead ECG are independently associated with an increased risk of adverse clinical outcomes in patients with nontraumatic SAH.

Cardiac Troponin Elevation and Outcome after Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis.

BACKGROUND: Cardiac abnormalities frequently occur after subarachnoid hemorrhage (SAH). Cardiac troponin (cTn) is a preferred biomarker for the diagnosis of cardiac damage, and the clinical significance of cTn elevation after SAH remains controversial. This meta-analysis was performed to assess the association between cTn elevation and patient outcomes, including delayed cerebral ischemia (DCI), poor outcome (death or dependency), and death in SAH patients. METHODS: PubMed, Embase, and the Cochrane Library were searched for observational studies reporting an association between cTn elevation and outcome after SAH that were published before December 31, 2014. We extracted data regarding patient characteristics, cTn elevation, and outcome measurements (DCI, poor outcome, or death). Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Twelve studies involving 2214 patients were included in data analysis. Elevation of cTn was observed in 30% of the patients. The cTn elevation was associated with an increased risk of DCI (RR, 1.48; 95% CI, 1.23-1.79), poor outcome (RR, 1.91; 95% CI, 1.51-2.40), and death (RR, 2.53; 95% CI, 2.04-3.12). At the 3- and 12- month follow-ups, cTn elevation was associated with higher rates of DCI (RR, 1.51; 95% CI, 1.11-2.07), poor outcome (RR, 1.91; 95% CI, 1.51-2.40), and death (RR, 2.78; 95% CI, 1.80-4.29). At in-hospital follow-ups, cTn elevation was also associated with the higher rate of death (RR, 2.33; 95% CI, 1.76-3.07). CONCLUSIONS: cTn elevation in SAH patients is associated with an increased risk of DCI, poor outcome, and death after SAH.

Role of Microglial Mitophagy in Alleviating Postoperative Cognitive Dysfunction: a Mechanistic Study.

Postoperative cognitive dysfunction (POCD), a common complication following anesthesia and surgery, is influenced by hippocampal neuroinflammation and microglial activation. Mitophagy, a process regulating inflammatory responses by limiting the accumulation of damaged mitochondria, plays a significant role. This study aimed to determine whether regulating microglial mitophagy and the cGAS-STING pathway could alleviate cognitive decline after surgery. Exploratory laparotomy was performed to establish a POCD model using mice. Western blotting, immunofluorescence staining, transmission electron microscopy, and mt-Keima assays were used to examine microglial mitophagy and the cGAS-STING pathway. Quantitative polymerase chain reaction (qPCR) was used to detect inflammatory mediators and cytosolic mitochondrial DNA (mtDNA) levels in BV2 cells. Exploratory laparotomy triggered mitophagy and enhanced the cGAS-STING pathway in mice hippocampi. Pharmacological treatment reduced microglial activation, neuroinflammation, and cognitive impairment after surgery. Mitophagy suppressed the cGAS-STING pathway in mice hippocampi. In vitro, microglia-induced inflammation was mediated by mitophagy and the cGAS-STING pathway. Small interfering RNA (siRNA) of PINK1 hindered mitophagy activation and facilitated the cytosolic release of mtDNA, resulting in the initiation of the cGAS-STING pathway and innate immune response. Microglial mitophagy inhibited inflammatory responses via the mtDNA-cGAS-STING pathway inducing microglial mitophagy and inhibiting the mtDNA-cGAS-STING pathway may be an effective therapeutic approach for patients with POCD.

Fast-track rehabilitation program and conventional care after esophagectomy: a retrospective controlled cohort study.

PURPOSE: The purpose of this article is to evaluate fast-track rehabilitation program and conventional care after esophagectomy using a retrospective controlled cohort study in esophageal cancer patients. METHODS: Fifty-five patients underwent fast-track rehabilitation program and 57 patients underwent conventional care after esophagectomy. Fast-track rehabilitation program was performed to patients who have early movement, epidural analgesia control, fluid infusion volume control and enteral nutrition for early discharge. The other 57 patients underwent conventional care after esophagectomy. The average of hospital stay and complications were calculated in the patients between the two groups. RESULTS: The median length of hospital stay in the patients was significantly shorter after fast-track rehabilitation program than after conventional care (7.7 vs 14.8 day, P < 0.01). The percentage of patients who developed complications was significantly lower 30 day after fast-track rehabilitation program than after conventional care (29.1 vs 47.4%, P < 0.05). 87.3% in patients of the fast-track rehabilitation program group and 54.4% in those of the conventional care group reported excellent to very good satisfaction with their pain control (P = 0.000). CONCLUSIONS: The fast-track rehabilitation program results in fewer complications, less postoperative pain, a reduction in the hospital length of stay, and quicker return to work and normal activities after esophagectomy.

Luteolin and triptolide: Potential therapeutic compounds for post-stroke depression via protein STAT.

Post stroke depression (PSD) is a common neuropsychiatric complication following stroke closely associated with the immune system. The development of medications for PSD remains to be a considerable challenge due to the unclear mechanism of PSD. Multiple researches agree that the functions of gene ontology (GO) are efficient for the investigation of disease mechanisms, and DeepPurpose (DP) is extremely valuable for the mining of new drugs. However, GO terms and DP have not yet been applied to explore the pathogenesis and drug treatment of PSD. This study aimed to interpret the mechanism of PSD and discover important drug candidates targeting risk proteins, based on immune-related risk GO functions and informatics algorithms. According to the risk genes of PSD, we identified 335 immune-related risk GO functions and 37 compounds. Based on the construction of the GO function network, we found that STAT protein may be a pivot protein in underlying the mechanism of PSD. Additionally, we also established networks of Protein-Protein Interaction as well as Gene-GO function to facilitate the evaluation of key genes. Based on DP, a total of 37 candidate compounds targeting 7 key proteins were identified with a potential for the therapy of PSD. Furthermore, we noted that the mechanisms by which luteolin and triptolide acting on STAT-related GO function might involve three crucial pathways, including specifically hsa04010 (MAPK signaling pathway), hsa04151 (PI3K-Akt signaling pathway) and hsa04060 (Cytokine-cytokine receptor interaction). Thus, this study provided fresh and powerful information for the mechanism and therapeutic strategies of PSD.

NCBP1 Improves Cognitive Function in Mice by Reducing Oxidative Stress, Neuronal Loss, and Glial Activation After Status Epilepticus.

Status epilepticus (SE) is a severe manifestation of epilepsy which can cause neurologic injury and death. This study aimed to identify key proteins involved in the pathogenesis of epilepsy and find a potential drug target for SE treatment. Tandem mass tag (TMT)-based quantitative proteomic analysis was applied to screen differentially expressed proteins (DEPs) in epilepsy. The adeno-associated virus was employed to overexpress candidate DEP in mice, and kainic acid (KA) was used to generate a mouse model of epilepsy. Then histopathological examination of the hippocampal tissue was performed, and the inflammatory factors levels in serum and hippocampus were measured. The IP-MS analysis was carried out to identify the interacting protein of nuclear cap-binding protein 1 (NCBP1). The results were that NCBP1 was downregulated in the epileptic hippocampus. NCBP1 overexpression alleviated KA-induced cognitive impairment in mice and reduced the apoptosis and damage of hippocampal neurons. Additionally, overexpressed NCBP1 increased the expression of NeuN and reduced the expression of GFAP and IBA-1 in the hippocampus of the mice. Further study indicated that NCBP1 overexpression inhibited the expression of IL-6, IL-1ß, and IFN-γ in serum and hippocampus as well as MDA and LDH in the hippocampus, whereas it increased the SOD levels, suggesting that overexpression of NCBP1 could diminish KA-induced inflammatory responses and oxidative stress. The IP-MS analysis identified that ELAVL4 was the NCBP1-interacting protein. In conclusion, this finding suggests that NCBP1 may potentially serve as a drug target for the treatment of epilepsy.

Knowledge mapping of research on the mitochondrial unfolded protein response: a bibliometric and visual analysis.

Background: The mitochondrial unfolded protein response (UPRmt) is a mitochondria stress response, which exerts a crucial role in maintaining mitochondrial proteostasis during stress. However, there is no bibliometric analyses systematically studied this field which could comprehensively review research trends, evaluate publication performances and provide future perspectives. Methods: Articles investigating UPRmt published between 1994 and 2021 were downloaded from the Core Collection of the Web of Science (WOS). CiteSpace and VOSviewer bibliometric software were applied for bibliometric and visual analyses. Results: A total of 2,073 papers researching UPRmt were retrieved. According to the published number of papers, the field of UPRmt research has gone through its infancy (after 2000) and rapid growth (after 2021) phases. The United States and China contributed the most to UPRmt research. Regarding the distribution of institutions, Harvard University was the most influential institution. The most prolific authors are Johan Auwerx and CM Haynes. PLoS One is the most extensive journal in the field of UPRmt research, while the Cell Death and Differentiation journal had the greatest impact among the most-authored journals. Moreover, biochemistry/molecular biology, and cell biology are the largest subject areas. UPRmt research is mainly categorized as UPRmt, transcription, endoplasmic reticulum (ER) stress, lipotoxicity, mitophagy, inflammation, skeletal muscle, hypoxia, apoptosis, mitochondrial dysfunction, neurodegeneration, mitochondrial permeability transition, and integrated stress response. Conclusions: At present, research on UPRmt is booming. Further strengthening the cooperation and exchanges between countries, institutions, and authors in the future will surely promote the development of this field.

Inhibition of the expression of rgs-3 alleviates propofol-induced decline in learning and memory in Caenorhabditis elegans.

BACKGROUND: Exposure to anesthesia leads to extensive neurodegeneration and long-term cognitive deficits in the developing brain. Caenorhabditis elegans also shows persistent behavioral changes during development after exposure to anesthetics. Clinical and rodent studies have confirmed that altered expression of the regulators of G protein signaling (RGS) in the nervous system is a factor contributing to neurodegenerative and psychological diseases. Evidence from preclinical studies has suggested that RGS controls drug-induced plasticity, including morphine tolerance and addiction. This study aimed to observe the effect of propofol exposure in the neurodevelopmental stage on learning and memory in the L4 stage and to study whether this effect is related to changes in rgs-3 expression. METHODS: Caenorhabditis elegans were exposed to propofol at the L1 stage, and learning and memory abilities were observed at the L4 stage. The expression of rgs-3 and the nuclear distribution of EGL-4 were determined to study the relevant mechanisms. Finally, RNA interference was performed on rgs-3-expressing cells after propofol exposure. Then, we observed their learning and memory abilities. RESULTS: Propofol time- and dose-dependently impaired the learning capacity. Propofol induced a decline in non-associative and associative long-term memory, rgs-3 upregulation, and a failure of nuclear accumulation of EGL-4/PKG in AWC neurons. Inhibition of rgs-3 could alleviate the propofol-induced changes. CONCLUSION: Inhibition of the expression of rgs-3 alleviated propofol-induced learning and memory deficits in Caenorhabditis elegans.

Angiotensin receptor blockade attenuates glomerulosclerosis progression by promoting VEGF expression and bone marrow-derived cells recruitment.

BACKGROUND: Previous studies have demonstrated that angiotensin Type I receptor blockade (ARB) reduces proteinuria, reverses glomerular injury and glomerulosclerosis in rat models of diabetic nephropathy and glomerulonephritis. However, the cellular and molecular mechanisms are unclear. To investigate the role of cells of the bone marrow (BM) in glomerular repair seen during ARB administration, we induced progressive glomerulosclerosis in enhanced green fluorescent protein BM chimeric rats by a single injection of anti-Thy 1.1 monoclonal antibody, followed by unilateral nephrectomy. METHODS: Cohorts of rats received valsartan or no treatment from Week 2 to Week 8 after induction of disease. Renal function, urinary protein excretion and histological changes were examined 8 weeks after anti-Thy-1.1 monoclonal antibody injection. RESULTS: Valsartan administration improved renal function, reduced severity of glomerulosclrosis and markedly reduced mortality. Valsartan administration promoted regeneration of the glomerular tuft, lowered proteinuria and resulted in enhanced vascular endothelial growth factor (VEGF) expression in the cortex and glomerular tuft. In addition, valsartan promoted increased recruitment of BM-derived cells (BMDCs) many of which expressed VEGF and likely contributed directly to glomerular repair. Nearly all BMDCs recruited to the glomerulus expressed the monocyte/macrophage marker CD68. CONCLUSIONS: In conclusion, the data shows that ARB by valsartan prevents glomerulosclerosis progression by enhancing glomerular capillary repair which is associated with the recruitment of VEGF producing 'reparative' monocytes and macrophages from the BM.

[Effects of dexmedetomidine combined with fentanyl in patients undergoing anesthesia induction by sevoflurane].

OBJECTIVE: To investigate the effects of dexmedetomidine combined with fentanyl in patients undergoing anesthesia induction by sevoflurane. METHOD: Eighty patients for elective endotracheal intubation under general anesthesia operations were randomly and double-blindly divided into Dex combined with fentanyl group (Group DF) and the fentanyl group (Group F) from April 2011 to September 2011 at the Fourth Affiliated Hospital of Harbin Medical University, and there were 40 cases in each group. The investigation was approved by all the patients and by the Ethics Committee of the hospital. In group DF, each patient was pumped in the 0.5 µg/kg Dex by vein before 10 minutes of anesthesia induction and group F were given the same amount of normal saline, and tidal volume method was used to induce anesthesia of sevoflurane. All the patients were given 2 µg/kg fentanyl and 0.1 mg/kg vecuronium by tracheal intubation and the MAP and HR and adverse reactions were observed before anesthesia induction (T(0)), before endotracheal intubation (T(1)), at the moment of tracheal intubation (T(2)), after 1 minutes of tracheal intubation (T(3)), after 3 minutes of tracheal intubation (T(4)) and after 5 minutes of tracheal intubation (T(5)). RESULT: The loss of eyelash reflex time of group DF is shorter (P < 0.05), adverse reaction is less (P < 0.05) and the number of adding atropine case is higher than that of group F (P < 0.05), the MAP of the two groups after induction of other moments are lower than that of T(0) (P < 0.05); MAP of group F at T(1) is lower than that of T(0), T(2), T(3) and group DF (P < 0.05); T(1) of group DF is lower than that of T(0) (P < 0.05), the HR after induction of group DF is lower than that of T(0) and F group (P < 0.05), and that of T(2) and T(4) are higher than that of T(1) (P < 0.05); HR of group F at T(1) is lower than that of T(2) and T(3) (P < 0.05). CONCLUSION: Dexmedetomidine in combination with fentanyl can inhibit stress response of tracheal intubation of sevoflurane induction efficiently and stabilize hemodynamics.

sVCAM1 in the Hippocampus Contributes to Postoperative Cognitive Dysfunction in Mice by Inducing Microglial Activation Through the VLA-4 Receptor.

Postoperative cognitive dysfunction (POCD) is a severe postsurgical complication, but its underlying mechanisms remain unclear. Neuroinflammation mediated by microglial activation plays a major role in POCD pathophysiology. Upregulation of vascular cell adhesion molecule 1 (VCAM1) on brain endothelial cells is closely correlated with microglial activation in the mouse hippocampus. However, the role of VCAM1 upregulation in microglial activation remains unknown. Soluble VCAM1 (sVCAM1) activates the very late antigen-4 (VLA-4) receptor under inflammatory conditions. Therefore, we hypothesized that sVCAM1 which is shed from VCAM1 contributes to POCD by triggering hippocampal microglial activation through the VLA-4 receptor. We found that VCAM1 and sVCAM1 expression in the mouse hippocampus was upregulated after surgery, and the upregulation was accompanied by hippocampal microglial activation. sVCAM1 levels in mouse and human serum were increased after surgery. Anti-VCAM1 treatment inhibited microglial activation, proinflammatory cytokine production, VLA-4 expression and P38 mitogen-associated protein kinase (MAPK) pathway activation and attenuated hippocampal-dependent cognitive dysfunction. In vitro, recombinant sVCAM1 promoted M1 polarization in BV2 cells, increased VLA-4 expression and activated the P38 MAPK pathway. These effects were reversed by VLA-4 receptor blockade. Anti-VLA-4 treatment ameliorated hippocampal-dependent cognitive dysfunction after surgery by inhibiting microglial activation, proinflammatory cytokine production and P38 pathway activation. In conclusion, increased sVCAM1 in the hippocampus is involved in microglial activation and cognitive dysfunction induced by surgery. Inhibiting the sVCAM1-VLA-4 interaction in microglia may be a therapeutic strategy for POCD.