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Background: Cerebral palsy (CP), a complex syndrome with multiple etiologies, is characterized by a range of movement disorders within the hypokinetic and hyperkinetic spectrum (dystonia or choreoathetosis). CP is often accompanied by neurological and psychiatric signs, such as spasticity, ataxia, and cognitive disorders. Although current treatment options for CP include pharmacological interventions, rehabilitation programs, and spasticity relief surgery, their effectiveness remains limited. Deep brain stimulation (DBS) has demonstrated significant effectiveness in managing dyskinesia; however, its potential therapeutic effect on CP remains determined. Methods: We present a case of a 44-year-old Asian female who was born as a twin with neonatal ischemic-hypoxic encephalopathy due to prolonged labor and delivery. She was diagnosed with CP at the age of 1 year. The patient exhibited delayed development compared to her peers and presented with various symptoms, including slurred speech, broad-based gait, horseshoe inversion of the right lower extremity, involuntary shaking of the upper extremities bilaterally, and hypotonia and showed no improvement with levodopa therapy. Two years ago, she developed progressive head tremors, which worsened during periods of tension and improved during sleep. As medical treatments proved ineffective and there were no contraindications to surgery, we performed bilateral globus pallidus interna DBS (GPi-DBS) to alleviate her motor dysfunction. Results: Following a 6-month follow-up, the patient demonstrated significant improvements in motor symptoms, including head and limb tremors and dystonia. In addition, significant improvement was observed in her overall psychological well-being, as evidenced by reduced anxiety and depression levels. Conclusion: DBS is an effective treatment for dyskinesia symptoms associated with CP in adults. Moreover, its effectiveness may continue to increase over time. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect and safety of Huannao Yicong Formula (还脑益聪方, HYF) in the treatment of patients with mild-to-moderate Alzheimer's disease (AD). Methods: Sixty patients with mild-tomoderate AD were evenly randomized into HYF group and donepezil group with the random number method. Patients in the HYF group took 5 g of HYF granules twice daily and 5 mg placebo of donepezil once daily. Patients in the donepezil group took 5 mg donepezil once daily and 5 g placebo of HYF granules twice daily. The intervention lasted for 6 months. Clinical researchers, participants and statisticians were blinded to the treatment assignment throughout the study. The primary outcomes were scores of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Chinese Medicine Symptom Scale (CM-SS). The secondary outcomes were scores of Montreal Cognitive Assessment (MoCA) test and Mini-Mental State Exam (MMSE). The serum levels of acetylcholinesterase (AchE) and amyloid-β protein 42 (Aβ42) were detected with enzymelinked immunosorbent assay kits. The scale assessments were conducted at baseline, the 3rd and 6th months of treatment, respectively. Biochemistry tests were conducted at baseline and the 6th month of treatment. Results: A total of 52 patients completed the trial, 28 in HYF group and 24 in donepezil group. Compared with the baseline, HYF and donepezil signifificantly decreased the total scores of ADAS-Cog and CM-SS, and signifificantly increased the scores of MoCA and MMSE after 6-month treatment (all P<0.01). Both treatments remarkably reduced the serum levels of AchE and Aβ42 (both P<0.05). The CM-SS total effective rate of HYF was signifificantly higher than donepezil [75.00% (21/28) vs. 54.17% (13/24), P<0.05]. No severe adverse events were observed in both groups. Conclusion: HYF is effective and safe for improving the cognitive function in mildto-moderate AD patients. [Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-IOR-17011746)] [ABSTRACT FROM AUTHOR]

Eukaryotic initiation factor 3 (EIF3) is one of the largest and most complex translation initiation factors, which consists of 13 subunits named eukaryotic translation initiation factor 3 subunit A (EIF3a) to EIF3m. EIF3a is the largest subunit of EIF3. Previous studies suggested that EIF3a is a housekeeping gene, recent results have found that EIF3a is closely related to the tumorigenesis and drug resistance. Circular RNAs (circRNAs) derived from biologically important gene can play an important role in gene regulation. However, the mechanism underlying circRNAs' biological functions is not well understood yet. In this work, we screened 31 EIF3a‐derived circRNAs, in which two circEIF3as were identified to be correlated with cisplatin drug sensitivity in lung cancer. Two circEIF3as were found involved in RNA‐binding proteins‐mediated biological processes and may be related to translational regulation according to bioinformatics analyses. CircEIF3as, the transcriptional initiation factor EIF3a transcribed circRNAs, are associated with both drug sensitivity and translation regulation. These findings mean that they may have a functional synergy effect with EIF3a or be valuable therapeutic targets for treatment like EIF3a. This is the first study that exploits circRNAs screening from EIF3a in lung cancer, our findings provide a novel perspective on the function of EIF3a and circEIF3as in lung cancer. [ABSTRACT FROM AUTHOR]

Radiation-induced enteritis is one of the most common complications in patients under radiotherapy at abdominal or pelvic cavity. Up to 50% of patients treated with pelvic radiotherapy has been reported radiation-induced acute enteritis, and half of them developed chronic enteritis. Overproduction of free radicals, activation of inflammatory pathways and vascular endothelial dysfunction were considered as the primary mechanisms of radiation-induced enteritis. Because probiotics have been demonstrated as a promising potential candidate for treating intestinal diseases, it may be a safer and more effective radioprotector for the enteritis compared to conventional chemical agents with inherent toxicities. Here, we propose that a recombinant Lactobacillus sakei would decrease the complications or symptoms significantly through against different pathogenic mechanisms simultaneously. Therefore, application of higher radiation dose for tumor control would be feasible when co-treating with recombinant Lactobacillus sakei. [ABSTRACT FROM AUTHOR]

Urinary bladder cancer (UBC) is one of the most common urological cancer types. Muscle invasive bladder cancer possesses high propensity for metastasis with poor prognosis. Honokiol is a lignan isolated from Magnolia officinalis with high bioavailability and potent anticancer effects. The results of the present study demonstrated that honokiol significantly inhibited UBC cell migration and invasion in a dose-dependent manner compared with the vehicle-treated control group. In addition, honokiol treatment suppressed epithelial-mesenchymal transition by induction of E-cadherin and repression of N-cadherin. Honokiol was capable of significantly downregulating the expression of cell invasion-associated genes, steroid receptor coactivator-3 (SRC-3), matrix metalloproteinase (MMP)-2 and Twist1. Notably, the inhibition of UBC cell invasion by honokiol was reversed by reintroduction of oncoprotein SRC-3 expression, with the restoration of MMP-2 and Twist1, and reduction of E-cadherin expression. Furthermore, the results of the luciferase assay confirmed that SRC-3 could regulate Twist1 promoter activity. Taken together, the results of the present study suggest that honokiol is a promising agent against UBC cell invasion via downregulation of SRC-3 and its target genes. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The hemi-Mustard and bidirectional Glenn (BDG) procedures combined with the Rastelli procedure have been applied to selected cases of congenitally corrected transposition of the great arteries (ccTGA) for potential benefit over the classic atrial switch procedure. The aim of this study was to analyse our experience with the hemi-Mustard, BDG and Rastelli procedures as an anatomical correction for patients with ccTGA/left ventricular outflow tract obstruction (LVOTO) with positional heart anomalies. METHODS: In this retrospective study, 31 consecutive patients with corrected transposition underwent the hemi-Mustard/BDG procedures with the Rastelli operation between 2011 and 2015. The median age was 5.4 (range: 0.75-12) years. Positional anomalies were present in all patients. Eleven patients underwent BDG initially; they then had the second-stage hemi-Mustard and Rastelli procedures; 'one-stage repair' (hemi-Mustard/BDG and the Rastelli procedures) was performed in 20 cases. RESULTS: There were no in-hospital deaths, and 3 patients received a pacemaker. One patient had an atrial baffle obstruction that was observed in the early postoperative period; 7 patients had prolonged pleural effusions that developed more frequently in the one-stage repair group (7/20 vs 0/11, P=0.033). During the mean follow-up of 3.3 years, 1 late death was noted, and no conduit replacements were required. Twenty-five (83.3%) patients are in New York Heart Association classes I and II at the latest follow-up. CONCLUSIONS: Hemi-Mustard, BDG and the Rastelli procedures are technically feasible for correction of ccTGA/left ventricular outflow tract obstruction (LVOTO) and cardiac malposition. Nevertheless, postoperative pleural effusion is the most prevalent complication in the one-stage repair. Two-stage repair may reduce the risk of pleural effusion-related complications. [ABSTRACT FROM AUTHOR]

Background: Herpes simplex virus (HSV) is a common human pathogen that causes a variety of diseases, including oral-labial, genital lesions and life-threatening encephalitis. The antiviral nucleoside analogues such as acyclovir are currently used in anti-HSV therapies; however, clinical overuse of these drugs has led to the emergence of drug-resistant viral strains. Hence, there is an urgent need to develop new anti-HSV agents.Methods: To identify novel anti-HSV-1 compounds, we screened the LOPAC small scale library of 1280 bioactive compounds to identify inhibitors of HSV-1-induced necroptosis. Further experiments including western blot analysis, Q-PCR analysis and immunohistochemistry were performed to explore the antiviral mechanism of the compounds.Results: Here, we identified PHA767491 as a new inhibitor of HSV. PHA767491 potently blocked the proliferation of HSV in cells, as well as HSV induced cell death. Further, we found that PHA767491 strongly inhibited HSV infection post viral entry. Moreover, PHA767491 reduced the expression of viral genes required for DNA synthesis including UL30/42 DNA polymerase and UL5/8/52 helicase-primase complex. The essential immediate early (IE) genes such as ICP4 and ICP27 are critical for the expression of the early and late genes. Of note, PHA767491 inhibited the expression of all IE genes of both HSV-1 and HSV-2. Importantly, PHA767491 reduced viral titers in the tissues from the mice infected with HSV-1. Consistently, immunohistochemistry analysis showed that PHA767491 dramatically attenuated expression of viral protein gB in the livers.Conclusions: Taken together, PHA767491 has potent anti-HSV activity by inhibiting viral replication both in vitro and in mouse model. Thus, PHA767491 could be a promising agent for the development of new anti-HSV therapy. [ABSTRACT FROM AUTHOR]

Cleidocranial dysplasia (CCD) is a rare autosomal dominant condition that affects ossification. The dental abnormalities associated with CCD present an obstacle to orthodontic treatment planning. Early diagnosis is crucial to provide the patient with different treatment modalities that will suit the particular patient. In the present case, combined surgical and orthodontic treatment were performed to guide multiple impacted teeth. A single nucleotide missense variation was identified in exon 3 of runt-related transcription factor 2 (RUNX2) in this patient. The current results suggest a correlation between dental alterations and mutations in the runt domain of RUNX2 in CCD patients. Further clinical and genetic studies may required to confirm the association between phenotypes and genotypes in CCD and to identify other factors that may influence the clinical features of this disease. Patients with cleidocranial dysplasia require a team approach which demands good communication and cooperation from the patient. Timing of the intervention is critical, and numerous surgeries may be required. The patient in the present case report was treated by a team of practitioners, which involved several dental specialties to achieve an optimal result. [ABSTRACT FROM AUTHOR]

Background: Nowadays, treatments for cholestasis remain largely nonspecific and often ineffective. Recent studies showed that inflammatory injuries and oxidative stress occur in the liver with cholestasis. In this study, we would use corilagin to treat the animal model of acute cholestasis in order to define the activity to interfere with inflammation-related and oxidative stress pathway in cholestatic pathogenesis.Methods: Rats were administrated with alpha-naphthylisothiocyanate to establish model of cholestasis and divided into corilagin, ursodeoxycholic acid, dexamethasone, model and normal groups with treatment of related agent. At 24h, 48h and 72h time points after administration, living condition, serum markers of liver damage, pathological changes of hepatic tissue, nuclear factor (NF)-kappaB, myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) were examined and observed.Results: Compared to model group, corilagin had remarkable effect on living condition, pathological manifestation of liver tissue, total bilirubin, direct bilirubin, (P<0.01), but no effect on alanine aminotransferase (ALT) and aspartate aminotransferase (AST). With corilagin intervention, levels of MPO, MDA and translocation of NF-κB were notably decreased, and levels of SOD and NO were markedly increased (P<0.05 or P<0.01).Conclusions: It is shown that corilagin is a potential component to relieve cholestasis through inflammation-related and oxidation-related pathway. [ABSTRACT FROM AUTHOR]

Background and purpose: Early soluble epoxide hydrolase inhibitors (sEHIs) such as 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) are effective anti-hypertensive and anti-inflammatory agents in various animal models. However, their poor metabolic stability and limited water solubility make them difficult to use pharmacologically. Here we present the evaluation of four sEHIs for improved pharmacokinetic properties and the anti-inflammatory effects of one sEHI. Experimental approach: The pharmacokinetic profiles of inhibitors were determined following p.o. (oral) administration and serial bleeding in mice. Subsequently the pharmacokinetics of trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid ( t-AUCB), the most promising inhibitor, was further studied following s.c. (subcutaneous), i.v. (intravenous) injections and administration in drinking water. Finally, the anti-inflammatory effect of t-AUCB was evaluated by using a lipopolysaccharide (LPS)-treated murine model. Key results: Better pharmacokinetic parameters (higher Cmax, longer t1/2 and greater AUC) were obtained from the tested inhibitors, compared with AUDA. Oral bioavailability of t-AUCB (0.1 mg·kg−1) was 68 ± 22% ( n = 4), and giving t-AUCB in drinking water is recommended as a feasible, effective and easy route of administration for chronic studies. Finally, t-AUCB (p.o.) reversed the decrease in plasma ratio of lipid epoxides to corresponding diols (a biomarker of soluble epoxide hydrolase inhibition) in lipopolysaccharide-treated mice. The in vivo potency of 1 mg·kg−1 of t-AUCB (p.o.) was better in this inflammatory model than that of 10 mg·kg−1 of AUDA-butyl ester (p.o) at 6 h after treatment. Conclusions and implications: t-AUCB is a potent sEHI with improved pharmacokinetic properties. This compound will be a useful tool for pharmacological research and a promising starting point for drug development. Mandarin translation of abstract [ABSTRACT FROM AUTHOR]

N,N ′-disubstituted urea-based soluble epoxide hydrolase (sEH) inhibitors are promising therapeutics for hypertension, inflammation, and pain in multiple animal models. The drug absorption and pharmacological efficacy of these inhibitors have been reported extensively. However, the drug metabolism of these inhibitors is not well described. Here we reported the metabolic profile and associated biochemical studies of an N -adamantyl urea-based sEH inhibitor 1-adamantan-1-yl-3-(5-(2-(2-ethoxyethoxy)ethoxy)pentyl)urea (AEPU) in vitro and in vivo . The metabolites of AEPU were identified by interpretation of liquid chromatography–mass spectrometry (LC–MS), liquid chromatography–tandem mass spectrometry (LC–MS/MS) and/or NMR. In vitro , AEPU had three major positions for phase I metabolism including oxidations on the adamantyl moiety, urea nitrogen atoms, and cleavage of the polyethylene glycol chain. In a rodent model, the metabolites from the hydroxylation on the adamantyl group and nitrogen atom were existed in blood while the metabolites from cleavage of polyethylene glycol chain were not found in urine. The major metabolite found in rodent urine was 3-(3-adamantyl-ureido)-propanoic acid, a presumably from cleavage and oxidation of the polyethylene glycol moiety. All the metabolites found were active but less potent than AEPU at inhibiting human sEH. Furthermore, cytochrome P450 (CYP) 3A4 was found to be a major enzyme mediating AEPU metabolism. In conclusion, the metabolism of AEPU resulted from oxidation by CYP could be shared with other N -adamantyl-urea-based compounds. These findings suggest possible therapeutic roles for AEPU and new strategies for drug design in this series of possible drugs. [ABSTRACT FROM AUTHOR]

Background: Fibrinogen-like protein 2 (FGL2) may promote glioblastoma multiforme (GBM) cancer development by inducing multiple immune-suppression mechanisms. Methods: The biological significance of FGL2 expression was assessed using the The Cancer Genome Atlast (TCGA) glioma database and tumor lysates analysis. The therapeutic effects of an anti-Fgl2 antibody and the role of immune suppression regulation by Fgl2 were determined in immune-competent, NOD-scid IL2Rgammanull (NSG), and FcγRIIB-/- mice (n = 3-18 per group). Data were analyzed with two-way analysis of variance, log-rank survival analysis, and Pearson correlation. All statistical tests were two-sided. Results: In low-grade gliomas, 72.5% of patients maintained two copies of the FGL2 gene, whereas 83.8% of GBM patients had gene amplification or copy gain. Patients with high levels of FGL2 mRNA in glioma tissues had a lower overall survival (P = .009). Protein levels of FGL2 in GBM lysates were higher relative to low-grade glioma lysates (11.48 ± 5.75 ng/mg vs 3.96 ± 1.01 ng/mg, P = .003). In GL261 mice treated with an anti-FGL2 antibody, median survival was 27 days compared with only 17 days for mice treated with an isotype control antibody (P = .01). The anti-FGL2 antibody treatment reduced CD39+ Tregs, M2 macrophages, programmed cell death protein 1 (PD-1), and myeloid-derived suppressor cells (MDSCs). FGL2- induced increases in M2, CD39, and PD-1 were ablated in FcγRIIB-/- mice. Conclusions: FGL2 augments glioma immunosuppression by increasing the expression levels of PD-1 and CD39, expanding the frequency of tumor-supportive M2 macrophages via the FcγRIIB pathway, and enhancing the number of MDSCs and CD39+ regulatory T cells. Collectively, these results show that FGL2 functions as a key immune-suppressive modulator and has potential as an immunotherapeutic target for treating GBM. [ABSTRACT FROM AUTHOR]

Aim: BIM deletion polymorphism was deemed to be associated with downregulation of BIM, resulting in a decreased apoptosis induced by epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutation-positive non-small cell lung cancer (NSCLC). However, accumulating evidences concerning the association between BIM deletion polymorphism and efficacy of EGFR-TKI and survival in EGFR-mutation-driven NSCLC patient reported contradictory results. Materials and Methods: A meta-analysis was conducted by combing six original eligible studies including 871 NSCLC patients. Results: Our study showed that BIM deletion polymorphism was significantly associated with poor response to EGFR-TKI therapy in mutant EGFRNSCLC patients (Ph = 0.309, Pz = 0.001, OR = 0.39, 95% confidence interval (CI) = 0.23-0.67). Disease control rate (DCR) in mutant EGFRNSCLC patient with treatment of EGFR-TKI was significantly decreased in patients with BIM deletion polymorphism comparing to patients harbored BIM wild variant (Ph = 0.583, PZ = 0.007, OR = 0.46, 95%CI = 0.25-0.85). EGFR mutation-derived NSCLC patient carrying BIM deletion polymorphism had a shorter progression-free survival (PFS; Ph < 0.001, Pz < 0.001, hazard ratio (HR) = 1.37, 95%CI = 1.09-1.71) and overall survival (OS; Ph = 0.90, Pz = 0.003, HR = 1.25, 95%CI = 1.08-1.45), than those harbored BIM wild variant. Conclusion: These results suggested that BIM deletion polymorphism might be a cause that contributes to primary EGFR-TKI resistance, and it could be used as a genetic predictor for EGFR-TKI outcome and an independent prognostic factor of EGFR mutation-driven NSCLC patient. [ABSTRACT FROM AUTHOR]

Aims. This study aimed to assess the differential expression of specific B cell subtypes in patients with chronic viral hepatitis. Methods. The frequencies of differential expression of specific B cell subtypes in patients with chronic viral hepatitis and healthy controls were assessed by flow cytometry using monoclonal antibodies specific for CD38, CD27, CD86, CD95, TLR-9, and IgD. The effect of adefovir treatment on B cell subsets in HBV patients was determined. The values of clinical parameters in the patients were also measured. Results. The frequency of CD86+ B cells was not significantly different in chronic HBV patients but was higher in HCV patients compared with that in healthy controls. CD95 and IgD levels were lower in HBV and HCV patients than in healthy controls. A significant negative correlation occurred between the proportion of CD95+ B cells and HBV DNA viral load. The frequency of TLR-9 on the B cells in HBV and HCV patients was higher compared with that of healthy controls. After treatment with adefovir, the frequency of CD95 and IgD expressed on B cells was increased in HBV patients. Conclusions. Activated B cells and exhausted B cells homeostasis were commonly disturbed in HBV and HCV patients. [ABSTRACT FROM AUTHOR]

Many flavonoids have cardioprotection against myocardial ischemia/reperfusion (I/R) injury. Total flavones from Rhododendron simsii Planch flower (TFR) can protect myocardial ischemic injuries. However, its protective mechanism is still unknown. The present study was designed to investigate the mechanism of TFR on myocardial I/R and anoxia/reoxygenation (A/R) injuries. Rat model of myocardial I/R injury was made, and myocardial infarction was determined. A/R injury was induced in cultured rat cardiomyocytes; cellular damage was evaluated by measuring cell viability, LDH and cTnT releases, and MDA content. Expressions of ROCK1 and ROCK2 protein were examined by Western blot analysis, and K+ currents were recorded by using whole-cell patch clamp technique. TFR 20-80 mg/kg markedly reduced I/R-induced myocardial infarction. TFR 3.7-300 mg/L significantly inhibited A/R-induced reduction of cell viability, LDH and cTnT releases, and MDA production. Exposure to A/R significantly increased ROCK1 and ROCK2 expressions in rat cardiomyocytes, but TFR 33.3-300 mg/L obviously inhibited this increase. 300 mg/L TFR significantly augmented inward rectifier K+ current and other K+ currents in rat cardiomyocytes. These results indicate that TFR has a protective effect on rat cardiomyocytes A/R damage, and the protective mechanism may be engaged with the inhibition of ROCK1 and ROCK2 and activation of K+ channels. [ABSTRACT FROM AUTHOR]

Numerous previous studies have demonstrated that ghrelin promotes gastric motility when administered peripherally. This effect appears to be regulatory but not directly stimulatory, and therefore may involve a number of complex mechanisms. In the periphery, ghrelin may affect gastric motility through intercellular networks among interstitial cells of Cajal, myenteric nerve cells and smooth muscle cells. The aim of the present study was to investigate the effects and possible mechanisms underlying this hypothesis. The effects of ghrelin on the contraction force of gastric antrum smooth muscle strips of rats were studied in the presence or absence of carbachol (CCh), [D-Lys3]-GHRP-6, atropine, tetrodotoxin (TTX) and nimodipine in vitro. The expression of ghrelin receptors (GHS-Rs) on different cell types in gastric muscle layers was observed by means of immunofluorescence. Ghrelin enhanced smooth muscle strip contraction induced by CCh, but when CCh was absent, this effect was eliminated. Atropine and nimodipine eradicated the muscle strip contraction enhanced by ghrelin, while [D-Lys3]-GHRP-6 was only able to partly block this effect and TTX had no effect on muscle strip contraction. It was identified that ghrelin had no effect on the contractive rhythm of the strips. GHS-R1s were located differentially depending on the cell type, including myenteric nerve cells, interstitial cells of Cajal and smooth muscle cells. In conclusion the present study demonstrated that ghrelin may act as an adjuvant to regulate gastric smooth muscle contraction induced by CCh through GHS-R1s, which are expressed on myenteric nerve cells, Cajal cells and smooth muscle cells. Ghrelin may exert its effects by influencing the functional status of different cell types in the gastric muscle layer to subsequently enhance the contractive effect of cholinergic neurotransmitters and enhance gastric motility. [ABSTRACT FROM AUTHOR]

Methylene blue (MB), the first lead chemical structure of phenothiazine and other derivatives, is commonly used in diagnostic procedures and as a treatment for methemoglobinemia. We have previously demonstrated that MB could function as an alternative mitochondrial electron transfer carrier, enhance cellular oxygen consumption, and provide protection in vitro and in rodent models of Parkinson's disease and stroke. In the present study, we investigated the structure-activity relationships of MB in vitro using MB and six structurally related compounds. MB reduces mitochondrial superoxide production via alternative electron transfer that bypasses mitochondrial complexes I-III. MB mitigates reactive free radical production and provides neuroprotection in HT-22 cells against glutamate, IAA and rotenone toxicity. Distinctly, MB provides no protection against direct oxidative stress induced by glucose oxidase. Substitution of a side chain at MB's 10-nitrogen rendered a 1000-fold reduction of the protective potency against glutamate neurototoxicity. Compounds without side chains at positions 3 and 7, chlorophenothiazine and phenothiazine, have distinct redox potentials compared to MB and are incapable of enhancing mitochondrial electron transfer, while obtaining direct antioxidant actions against glutamate, IAA, and rotenone insults. Chlorophenothiazine exhibited direct antioxidant actions in mitochondria lysate assay compared to MB, which required reduction by NADH and mitochondria. MB increased complex IV expression and activity, while 2-chlorphenothiazine had no effect. Our study indicated that MB could attenuate superoxide production by functioning as an alternative mitochondrial electron transfer carrier and as a regenerable anti-oxidant in mitochondria. [ABSTRACT FROM AUTHOR]

PURPOSE: Retrospective analysis of the diagnosis and simultaneous treatment of midfacial fractures with traumatic cerebrospinal rhinorrhea. METHODS: One hundred and sixty three cases with contusion and laceration of brain, intracranial hematoma, primary brain-stem injury presented cerebrospinal rhinorrhea after reposition and fixation of the fractures from January 2003 to May 2011. They were analyzed in the respect of age, rate of blindness, length of stay in hospital, clinical characteristics, diagnosis and operation methods. RESULTS: 88.96% of the cerebrospinal rhinorrhea cured after 1 week, 10.43% cured after 2-3 weeks, and 1 patient died because of intracranial infection after 2 weeks, 4 cases with injury of temporal branch of facial nerve, 2 cases of numbness of scalp and paraesthesia with no syndrome after half a year, 13 cases had temporal fossa. The occlusion and mouth opening of all patients recovered and their faces were symmetrical depression. CONCLUSIONS: Treatment of facial trauma and cerebrospinal rhinorrhea simultaneously were consistent with the principle that cerebrospinal rhinorrhea reparation should do after 1 week of conservative therapy. The same incision can be used during operation, thus shortening the length of stay, reducing cost and complications, and promoting the resolution of cerebrospinal rhinorrhea. [ABSTRACT FROM AUTHOR]

. (J Card Surg 2011;26:130-134) [ABSTRACT FROM AUTHOR]

Abstract: Inflammation is a multi-staged process whose expansive phase is thought to be driven by acutely released arachidonic acid (AA) and its metabolites. Inhibition of cyclooxygenase (COX), lipoxygenase (LOX), or soluble epoxide hydrolase (sEH) is known to be anti-inflammatory. Inhibition of sEH stabilizes the cytochrome P450 (CYP450) products epoxyeicosatrienoic acids (EETs). Here we used a non-selective COX inhibitor aspirin, a 5-lipoxygenase activation protein (FLAP) inhibitor MK886, and a sEH inhibitor t-AUCB to selectively modulate the branches of AA metabolism in a lipopolysaccharide (LPS)-challenged murine model. We used metabolomic profiling to simultaneously monitor representative AA metabolites of each branch. In addition to the significant crosstalk among branches of the AA cascade during selective modulation of COX, LOX, or sEH, we demonstrated that co-administration of t-AUCB enhanced the anti-inflammatory effects of aspirin or MK886, which was evidenced by the observations that co-administration resulted in favorable eicosanoid profiles and better control of LPS-mediated hypotension as well as hepatic protein expression of COX-2 and 5-LOX. Targeted disruption of the sEH gene displayed a parallel profile to that produced by t-AUCB. These observations demonstrate a significant level of crosstalk among the three major branches of the AA cascade and that they are not simply parallel pathways. These data illustrate that inhibition of sEH by both pharmacological intervention and gene knockout enhances the anti-inflammatory effects of aspirin and MK886, suggesting the possibility of modulating multiple branches to achieve better therapeutic effects. [Copyright &y& Elsevier]

Abstract: Aim of the study: This paper aimed to elucidate the anti-inflammatory effects of EtOAc fraction prepared from Melilotus suaveolens Ledeb ethanol extract with a cellular model of LPS-stimulated RAW 264.7 cell. Materials and methods: Some key pro-inflammatory cytokines and mediators including IL-1β, IL-6, NO, iNOS, COX-2 and TNF-α, two important anti-inflammatory cytokines and mediators IL-10 and HO-1, I-κB and NF-κB were studied by sandwich ELISA, real-time PCR, western blot analysis and immunocytochemistry. At last a HPLC fingerprint was taken to evaluate the fraction. Results: The EtOAc fraction could significantly inhibit the production of IL-1β, IL-6, NO, TNF-α, COX-2 in LPS-stimulated cell than that of single LPS-stimulated cell (p <0.01 or p <0.05), and the extract could increase the production of IL-10 and HO-1 than that of single LPS intervention cell (p <0.01 or p <0.05). Meanwhile, the extract also could inhibit the production of NF-κB compared to single LPS-stimulated cell. All the results showed that the extract had a good anti-inflammatory effect on LPS-stimulated RAW264.7 cell. Conclusions: Taken together, the anti-inflammatory actions of M. suaveolens Ledeb EtOAc fraction might be due to the down-regulation of IL-1β, IL-6, NO, TNF-α and COX-2 via the suppression of NF-κB activation, and another pathway was up regulating the production of IL-10 and HO-1. Meanwhile, the EtOAc fraction might be further studied to isolate the active anti-inflammatory ingredients besides coumarin. [Copyright &y& Elsevier]

Hypoxia-inducible factor (HIF) transcription factors respond to multiple environmental stressors, including hypoxia and hypoglycemia. We report that mice lacking the HIF family member HIF-2a (encoded by Epas1) have a syndrome of multiple-organ pathology, biochemical abnormalities and altered gene expression patterns. Histological and ultrastructural analyses showed retinopathy, hepatic steatosis, cardiac hypertrophy, skeletal myopathy, hypocellular bone marrow, azoospermia and mitochondrial abnormalities in these mice. Serum and urine metabolite studies showed hypoglycemia, lactic acidosis, altered Krebs cycle function and dysregulated fatty acid oxidation. Biochemical assays showed enhanced generation of reactive oxygen species (ROS), whereas molecular analyses indicated reduced expression of genes encoding the primary antioxidant enzymes (AOEs). Transfection analyses showed that HIF-2a could efficiently transactivate the promoters of the primary AOEs. Prenatal or postnatal treatment of Epas1-/- mice with a superoxide dismutase (SOD) mimetic reversed several aspects of the null phenotype. We propose a rheostat role for HIF-2a that allows for the maintenance of ROS as well as mitochondrial homeostasis. [ABSTRACT FROM AUTHOR]

BACKGROUND Axillary bromhidrosis is a distressing problem, which has a strong negative effect on one's social life. OBJECTIVE To evaluate the effects and complications of the surgical modality for the treatment of axillary bromhidrosis. METHODS One hundred fifteen patients with axillary bromhidrosis were treated. Two incisions were made transversely along the marked lines on the axillary crease. Subdermal undermining of the marked area with a depth of 0.3 to 0.5 cm and transverse detachment were performed, allowing the exposure of the skin flaps. Skin flaps were carefully separated from the skin. The apocrine glands, follicles, and fats were dissected, and the axillary superficial fascia was maintained. RESULTS All patients achieved good results in terms of malodor elimination during the follow-up period. All patients reported reduction in axillary sweating. Postoperative complications were minor, including small hematoma (3 cases), delayed wound healing (5 cases), pressure blister (5 cases), and slightly wound scar (2 cases). No infection, skin necrosis, malodor, or recurrence was observed. One hundred eleven patients (96.5%) were very satisfied and 4 (3.5%) patients satisfied with the procedure, with none regretful. CONCLUSION The procedure has the advantage of a high success rate in radical elimination of the malodor with minor complications. [ABSTRACT FROM AUTHOR]