Polyketides with α-glucosidase inhibitory and neuroprotective activities from Aspergillus versicolor associated with Pedicularis sylvatica.

Aspergillus versicolor, an endophytic fungus associated with the herbal medicine Pedicularis sylvatica, produced four new polyketides, aspeversins A-D (1-2 and 5-6) and four known compounds, O-methylaverufin (2), aversin (3), varilactone A (7) and spirosorbicillinol A (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by calculated electronic circular dichroism (ECD) and Mo2(AcO)4-induced CD data. Compound 5 was found to exhibit α-glucosidase inhibitory activity with an IC50 value of 25.57 µM. An enzyme kinetic study indicated that 5 was a typical uncompetitive inhibitor toward α-glucosidase, which was supported by a molecular docking study. Moreover, compounds 1-3 and 5 also improved the cell viability of PC12 cells on a 1-methyl-4-phenylpyridinium (MPP+)-induced Parkinson's disease model, indicating their neuroprotective potential as antiparkinsonian agents.

Triterpenoids and meroterpenoids from the edible Ganoderma resinaceum and their potential anti-inflammatory, antioxidant and anti-apoptosis activities.

Ganoderma resinaceum, as a traditional edible mushroom, has been widely reported to improve neurodegenerative diseases characterized by oxidative stress and inflammation. In this study, five new terpenoids, including four lanostane triterpenoids, named ganoresinoid A-D (1-4) and one meroterpenoid, named ganoresinoid E (5), along with 27 known compounds (6-32), were isolated from the fruiting bodies of edible mushroom G. resinaceum. These structures were identified by NMR, HRESIMS data analysis. All metabolites were evaluated for anti-inflammatory, antioxidative and anti-apoptosis activities. Among them, ganoresinoid A showed notably restrained nitric oxide (NO), IL-1ß, IL-6 and TNF-α levels in LPS-activated BV-2 microglial cells via suppressing TLR-4/ NF-κB and MAPK signaling pathway. Simultaneously, ganoresinoid A remarkably alleviated LPS-induced apoptosis by means of the decrease of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). In addition, ganoresinoid A demonstrated antioxidant effects in H2O2-induced SH-SY5Y cells by activating the Akt/GSK-3ß/Nrf2 signaling pathway. Taken together, these results may provide a stronger theoretical basis for ganoresinoid A from G. resinaceum as nutrition intervention to alleviate neurodegenerative diseases.

Extracellular vesicles from human hepatic progenitor cells accelerate deep frostbite wound healing by promoting fibroblasts proliferation and inhibiting apoptosis.

Frostbites are cold tissue damages frequently observed at high altitudes and under extremely cold conditions. Though their incidence rate is low, the resulting impact in affected patients can be very serious, often leading to amputations. Clinical management and the prediction of outcome can be of utmost importance to frostbite patients. A possible use of stem cell-derived extracellular vesicles (EVs) has been suggested for cutaneous wound healing and we, therefore, tested their use for the treatment of deep frostbite wound. To this end, the impacts of hHPC-derived EVs were evaluated in an in vivo animal model comprising of Kunming female mice as well as studied in vitro for the mechanism. We first characterized the EVs and these hHPC-derived EVs, when applied to treat frostbite wounds, accelerated wound healing in the in vivo animal model, as assessed by wound closure, re-epithelization thickness, collagen density and the expression of Collagen I and α-SMA. The proliferation and migration of human skin fibroblasts was also found to be increased by EVs in the in vitro experiments. The H2O2-induced apoptosis cell model, established to simulate the post-frostbite injury, was inhibited by EVs, with concomitant increase in the expression of Bcl-2 and decreased expression of Bax, further confirming the findings. Our novel results indicate that the application of EVs might be a promising strategy for deep frostbite wound healing.

The study of Raddeanin A cerebrovascular endothelial cell trafficking through P-glycoprotein.

As one of the natural triterpenoids isolated from Anemone Raddeana Regel, Raddeanin A (RA) has been confirmed to possess therapeutic effects against multiple tumorigeneses, especially for the onset of glioblastoma and growth in human brains. However, the mechanism by which this happens remains poorly understood in terms of the vascular endothelium trafficking routine of RA through the brain-blood barrier (BBB). To seek such answers, human brain microenvironment endothelial cells (HBMECs) were used to stimulate the microenvironment in vitro, and to explore the intracellular accumulation of RA. The results of this experiment illustrated that RA has a relative moderate transport affinity for such cells. The kinetic parameter Km was 37.01 ± 2.116 µM and Vmax was 9.412 ± 0.1375 nM/min/mg of protein. Interestingly, protein downregulation of P-glycoprotein (P-gp, ABCB1/MDR1) significantly activated RA transmembrane activity, which proves that P-gp is responsible for RA cellular trafficking. In addition, the selective non-specific inhibitor, LY335979 increased either RA or the classical substrate of P-gp, digoxin, intracellular accumulation by restricting the transporter's function but without jeopardizing cytomembrane proteins. Moreover, a decrease in the expression or activity of P-gp triggered RA drug resistance to HBMECs. In summary, our data showed that both the expression and function of P-gp are all necessary for RA transmembrane trafficking through cerebrovascular endothelial cells. This study provides significant evidence for the presence of a connection between RA transport and P-gp variation during drug BBB penetration. It is also suggesting some vital guidance on the RA pharmacodynamic effect in human brains.

Prognostic impacts of ß-blockers in acute coronary syndrome patients without heart failure treated by percutaneous coronary intervention.

BACKGROUND: The use of ß-blockers for acute coronary syndrome (ACS) patients without heart failure (HF) is controversial, and lacks of evidence in the era of reperfusion and intensive secondary preventions. This study aimed to investigate the prognostic impacts of ß-blockers on patients with ACS but no HF treated by percutaneous coronary intervention (PCI). METHODS: A total of 2397 consecutive patients with ACS but no HF treated by PCI were retrospectively recruited from January 2010 to June 2017. Univariable Cox regression was used to assess the prognostic impacts of ß-blockers, followed by adjusted analysis, one-to-one propensity score matching (PSM), and inverse probability treatment weighting (IPTW) analysis, in order to control for systemic between-group differences. The primary outcome was all-cause death. RESULTS: Among the included patients, 2060 (85.9%) were prescribed with ß-blockers at discharge. The median follow-up time was 727 (433-2016) days, with 55 (2.3%) cases of all-cause death. Unadjusted analysis showed that the use of ß-blockers was associated with lower risk of death (hazard ratio [HR]: 0.42, 95% confidence interval [CI]: 0.23-0.76, P = 0.004), which was sustained in adjusted analysis (HR: 0.53, 95% CI: 0.29-0.98, P = 0.044), PSM analysis (HR: 0.44, 95% CI: 0.20-0.96, P = 0.039) and IPTW analysis (HR: 0.49. 95% CI: 0.35-0.70, P < 0.001). Risk reduction was also seen in ß-blocker users for cardiac death, but not for major adverse cardiovascular events. CONCLUSIONS: The use of ß-blockers was associated with reduced long-term mortality for ACS-PCI patients without HF.

Claudin 14/15 play important roles in early wallerian degeneration after rat sciatic nerve injury.

PURPOSE: Wallerian degeneration (WD) is an antegrade degenerative process distal to peripheral nerve injury. Numerous genes are differentially regulated in response to the process. However, the underlying mechanism is unclear, especially the early response. We aimed at investigating the effects of sciatic nerve injury on WD via CLDN 14/15 interactions in vivo and in vitro. METHODS: Using the methods of molecular biology and bioinformatics analysis, we investigated the molecular mechanism by which claudin 14/15 participate in WD. Our previous study showed that claudins 14 and 15 trigger the early signal flow and pathway in damaged sciatic nerves. Here, we report the effects of the interaction between claudin 14 and claudin 15 on nerve degeneration and regeneration during early WD. RESULTS: It was found that claudin 14/15 were upregulated in the sciatic nerve in WD. Claudin 14/15 promoted Schwann cell proliferation, migration and anti-apoptosis in vitro. PKCα, NT3, NF2, and bFGF were significantly upregulated in transfected Schwann cells. Moreover, the expression levels of the ß-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK signaling pathways were also significantly altered. CONCLUSION: Claudin 14/15 affect Schwann cell proliferation, migration, and anti-apoptosis via the ß-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK pathways in vitro and in vivo. The results of this study may help elucidate the molecular mechanisms of the tight junction signaling pathway underlying peripheral nerve degeneration.

A new surgical approach of direct perineal wound full-thick closure for perineal wound of abdominoperineal resection for rectal carcinoma: A prospective cohort trial.

Perineal wound complications after APR have high morbidity in the colorectal surgical department. Although some approaches have been figured out to solve this clinical focus, the outcomes are still not satisfied. Herein, this prospective comparative clinical trial has been designed to evaluate a new surgical procedure of direct perineal wound full-thick closure (DPWC), compared with conventional perineal wound closure (CPWC), with hopes of making wound healing with less complications. In addition, an evaluation of an incision negative wound pressure therapy, as another focus in this field, was also analysed in the DPWC group. A total of 44 participants in our department were recruited from March 2018 to March 2020, divided into two groups randomly, CPWC group and DPWC group. The patients' characteristics, such as age, gender, BMI, smoking, alcohol consumption, comorbidities, CEA level, and high-risk of invasion, were recorded without statistical significance between the CPWC group and DPWC group. After the same standard abdominal phase, these two groups were performed in different perineal phases. And then, operative and postoperative outcomes were analysed with different statistical methods. Data on wound healing time and length of stay in the DPWC group were shorter than those in the CPWC group (P < .05). Furthermore, cases of wound infection within 30 days in the DPWC group were also less than that in the CPWC group (P < .05). However, no difference was found between the incisional negative pressure wound therapy assisted group (NPA group) and non- incisional negative pressure wound therapy assisted group (non-NPA group). During this study, hypoalbuminemia, as an independent high-risk factor, impacted perineal wound healing. (P = .0271) In conclusion, DPWC is a new surgical approach, which can lead to a better outcome than DPWC, and it can be another surgical procedure for clinicians. In addition, hypoalbuminemia should be interfered for avoiding perineal wound complications.

Comparative analysis on the effect of Z-plasty versus conventional simple excision for the treatment of sacrococcygeal pilonidal sinus: A retrospective randomised clinical study.

Sacrococcygeal pilonidal sinus is one of common diseases in general department. However, it is characterised, for surgeons, by high post-surgical recurrence and high incidence of post-surgical wound complications. Due to that fact, this retrospective randomised clinical study was designed to evaluate the surgical procedure effect of Z-plasty (ZP), compared with convention simple excision (SE). A total of 67 patients from May 2015 to May 2019 in our department were studied into two groups randomly, the group of ZP and the group of SE. The patients' characteristics, surgical data, hospital length of stay (LOS), and post-surgery complications were recorded. Statistical approaches were proceed with P-value analysis. The results are as follows. No significant differences were found between these two groups of the ages, gender distribution, Body Mass Index (BMI), smoking history, diabetes mellitus, and blood hypertension. The estimated blood loss, specimen volume, distance to anus, and drain output on the first day of post-surgery between the two groups were not statistically significant, either. However, surgical time in the ZP group was longer than that in the SE group (P < .0001). LOS in the ZP group was obviously shorter than that in the SE group (P = .0051). Furthermore, the patients of the ZP group were tending to suffer from fewer post-surgical complications than the ones of the SE group. In a conclusion, we hold the point view that the surgical procedure of ZP can lead a better outcome than SE because it demonstrated shortened LOS and fewer post-surgical complications.

Deglycosylation influences the oxidation activity and antigenicity of myeloperoxidase.

AIM: Myeloperoxidase (MPO) is pathogenic in ANCA associated vasculitis. It also acts as bactericidal agent. MPO has five N-linked glycosylation sites on its heavy chains. The effect of glycosylation pattern to the functions of MPO is barely known. METHODS: We used eight glycosidases to remove different glycans on MPO separately. The chlorination activity of MPO, the binding between ceruloplasmin and MPO, and the reversing effect of MPO-ANCA to this binding were measured. Three de-glycosylated MPOs were used to assay the influence of deglycosylation on microbicidal effect of MPO. RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of ß-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance. Deglycosylation reduced the binding capacity between MPO and its physiological inhibitor-ceruloplasmin, with the most significance on the removal of innermost GlcNAc (0.37 ± 0.04 vs. 1.06 ± 0.11, P < 0.001). Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002). Removal of innermost GlcNAc, ß-galactopyranoside and α-neuraminidase could weaken the bactericidal effect of MPO, especially the removal of α-neuraminidase (P < 0.001). CONCLUSIONS: Deglycosylation decreased oxidation activity of MPO and its binding with ceruloplasmin. Deglycosylation could also decrease the microbicidal effect of MPO, which might contribute to more severe infections and inflammation. Deglycosylated MPO presented less antigenicity to MPO-ANCA, which indicated the contribution of glycans to MPO epitopes.

Deglycosylation of myeloperoxidase uncovers its novel antigenicity.

Myeloperoxidase (MPO) is a common target antigen of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and is recognized in one-third of patients with anti-glomerular basement membrane (GBM) disease. Our previous study identified over 60% of patients with anti-GBM disease recognizing linear peptides of MPO heavy chain. Here we tested whether aberrant glycosylation alters MPO antigenicity through exposure of neo-epitopes on MPO molecules. Atypical glycosylated MPO molecules, including all possible glycosylation types, were prepared by exoglycosidase and endoglycosidase treatments. Antibodies were detected from the sera of 40 patients with anti-GBM disease without the coexistence of MPO-ANCA. Circulating antibodies against aberrant glycosylated MPO existed in 21 of these patients. Non-glycan MPO and MPO with only N-acetylglucosamine had high frequencies of recognition (16 and 15 patients, respectively). Antibodies binding to aberrant glycosylated MPO could not be inhibited by intact MPO or GBM antigen. When applied to ethanol-fixed neutrophils from normal individuals, these antibodies yielded a typical cytoplasmic staining pattern (c-ANCA). Antigen specificity was detected in 90% of the antibodies using five peptides containing one of the five N-glycosylation sites each, mostly on N323, N355, and N391. The antibodies were restricted to IgG1 subclass, could activate complement, and induce neutrophil degranulation in vitro. Thus, aberrant glycosylated MPO exposed neo-epitopes and was recognized by half of the patients with anti-GBM disease. Their antibodies possessed pathogenic characteristics and may be associated with kidney injury.

Synergy of Raddeanin A and cisplatin induced therapeutic effect enhancement in human hepatocellular carcinoma.

Cisplatin is a main compound for human hepatocellular carcinoma (HCC) chemotherapies, but it has certain cytotoxicity during applications. To release that, combining with other drugs are being as a regular plan in clinic. In our present study, we are focusing on one of active monomers extracted from Anemone Raddeana Regel, Raddeanin A (RA), which is on behalf of the same character like cisplatin in the tumor remedies. In order to investigate whether combination usage of RA and cisplatin can be priority to the later drug's effect development and its toxicity reduction in HCC, both of two drugs were treated 24 h or 48 h in QGY-7703 cells for estimating their abilities in tumor cell proliferation inhibition. Results show RA makes synergistic functions with cisplatin after measuring and analyzing their combination index (CI) values. Meanwhile it can strengthen cisplatin's effect through arresting the tumor cells in G0/G1 cycle and further promoting their apoptosis. Interestingly, the molecule signals correlated to tumor cell apoptosis containing both of p53 and bax are simultaneously activated, but bcl-2 and survivin are all depressed in mRNA level. Meanwhile, combining usage with RA can even raise the intracellular productions of reactive oxygen species (ROS). All these consequences reflect RA plays an important role in enhancing the therapeutic effect of cisplatin in HCC. This finding may guide for the drug usage of cisplatin in clinic practice.

Thrombin Stimulated Platelet-Derived Exosomes Inhibit Platelet-Derived Growth Factor Receptor-Beta Expression in Vascular Smooth Muscle Cells.

BACKGROUND/AIMS: It is difficult to predict acute thrombotic cardiovascular events in the clinic. Few studies have reported the presence of plasma exosomes containing microRNAs (miRNAs) in cardiovascular events. Therefore, we aimed to investigate the levels of miR-223, miR-339 and miR-21 in plasma exosomes before thrombosis in mouse models of carotid tandem stenosis, as well as the mechanisms underlying the origin and function of these exosomal miRNAs. METHODS: Plasma samples were collected from the carotid tandem stenosis and sham control groups of our successfully developed atherothrombosis mouse models before thrombosis. Platelets from healthy volunteers and mice were purified to obtain thrombin stimulated platelet-derived exosomes. Exosomes were isolated via differential ultracentrifugation, and western blotting and transmission electron microscopy were used for their identification. The total RNA was extracted, and quantitative real-time PCR was performed to determine the expression levels of miR-223, miR-339 and miR-21. DAVID Tools were used to analyze the pathways that were enriched among the miRNA target genes. Immuno-fluorescence staining was performed to identify the protein expression levels of platelet-derived exosome target genes in vascular smooth muscle cells (SMCs) in vitro and in vivo. RESULTS: The levels of miR-223, miR-339 and miR-21, which are associated with platelet activation, were elevated in pooled mouse plasma exosomes before thrombosis and enriched in thrombin-stimulated platelet-derived exosomes in vitro. Platelet-derived growth factor receptor-beta (PDGFRß) was a target of these miRNAs, and PDGFRß expression in vascular smooth muscle cells (SMCs) was inhibited following incubation with platelet-derived exosomes. Platelet-derived exosomes could also inhibit PDGF-stimulated SMC proliferation. Furthermore, a decrease in PDGFRß expression was observed in vascular SMCs around thrombotic areas in vivo. CONCLUSIONS: Our data indicate that activated platelet-derived exosomes containing miR-223, miR-339 and miR-21 could be transferred into SMCs and inhibit PDGFRß expression; these exosomal miRNAs may be a biomarker for predicting atherothrombosis.

Comparison of the effects of propofol and emulsified isoflurane alone or combined with dexmedetomidine on induction of anesthesia in dogs.

OBJECTIVE: To compare the respective effects of propofol and emulsified isoflurane administered alone and in combination with dexmedetomidine on the quality of induction of anesthesia, physiological variables and recovery in dogs. STUDY DESIGN: Prospective, randomized, experimental trial. ANIMALS: Thirty-six adult mixed-breed dogs. METHODS: Animals were randomly assigned to one of four induction protocols: propofol alone (group P); emulsified isoflurane alone (group EI); both propofol and dexmedetomidine (group PD), or both emulsified isoflurane and dexmedetomidine (group EID). Pulse rate (PR), respiratory rate (fR ), non-invasive arterial blood pressure and arterial blood gases were measured at baseline, before induction, immediately after intubation (time 0), and at 5 minute intervals until the dog began to swallow and the trachea was extubated. The quality of induction and recovery, and degree of ataxia were scored by a single investigator unaware of group assignment. The durations of anesthesia and recovery, and the incidence of adverse events were recorded. RESULTS: There were no clinically significant differences among the groups in induction quality. Systolic arterial pressure was lower in EID compared with P at 5 minutes. PR and fR were lower in PD and EID compared with P after induction. The PaCO2 at 5 minutes was higher than at baseline in group P. Ataxia score was lower in EID than in P. Time from induction to extubation and time from extubation to sternal recumbency were lower in EID compared with PD. CONCLUSIONS AND CLINICAL RELEVANCE: There were no clinically significant differences among the groups in induction quality. In PD and EID, but not in P, PR and fR were decreased after induction. The EID combination resulted in smooth and rapid induction and recovery and thus may be useful clinically for induction of anesthesia.

The prognostic value of glycerol-3-phosphate dehydrogenase 1-like expression in head and neck squamous cell carcinoma.

AIMS: In this study, we sought to determine the prognostic significance of glycerol-3-phosphate dehydrogenase 1-like (GPD1L) expression in head and neck squamous cell carcinoma (HNSCC). METHODS AND RESULTS: The mRNA levels of GPD1L were measured in 70 paired HNSCC and corresponding adjacent normal tissues using real-time PCR. GPD1L protein levels were evaluated in HNSCC from 135 patients using immunohistochemical staining. Correlations were analysed between GPD1L levels and local recurrence rate, regional recurrence rate, second primary malignancy rate), disease-free survival (DFS) and disease-specific survival (DSS). The results of real-time PCR showed that, compared with the paired normal tissues, mRNA levels of GPD1L were decreased significantly in HNSCC (P < 0.001). Patients whose tumours showed high GPD1L protein expression had a significantly better prognosis than those whose tumours showed low expression (61.3% versus 21.4%, P < 0.001 for DFS; 68% versus 39.3%, P = 0.001 for DSS). High GPD1L expression was associated with a lower local recurrence rate than low GPD1L expression (P = 0.049). Multivariate survival analysis also showed that GPD1L expression was an independent prognostic factor (P = 0.001). CONCLUSIONS: Our results indicate that the GPD1L expression is a strong predictor for local recurrence and survival in HNSCC.

Changes in plasma orexin-A levels in sevoflurane-remifentanil anesthesia in young and elderly patients undergoing elective lumbar surgery.

BACKGROUND: Delayed emergence from general anesthesia frequently occurs in elderly patients, but the reason is not clear. Orexin has been shown to be involved in arousal from general anesthesia. In this study, we examined plasma orexin-A levels in both elderly and young patients during the anesthesia arousal cycle. METHODS: We recruited 41 patients scheduled for elective lumbar surgery and eventually evaluated 34 patients. Patients were divided into a young group (age 30-55, N = 16) and an elderly group (age 65-77, N = 18). Anesthesia with sevoflurane-remifentanil was titrated to maintain the Bispectral Index between 45 and 65. The times from stopping anesthesia to eyes opening and extubation were recorded. Arterial blood was collected, and plasma orexin-A was determined by radioimmunoassay at the following 4 time points: preanesthesia (T0), 1 hour after anesthesia induction (T1), emergence (5 minutes after tracheal extubation) (T2), and 30 minutes after tracheal extubation (T3). RESULTS: The times from stopping anesthesia to eyes opening and tracheal extubation were both significantly longer in the elderly group than in the young group (P = 0.004, P = 0.01, respectively). Basal (T0) orexin-A levels were higher in the elderly group than in the young group (T0, 26.13 ± 1.25 vs 17.9 ± 1.30 pg/mL, P < 0.0001). Plasma orexin-A levels did not change during induction of anesthesia in either group but significantly increased at T2 (vs T0, P <0.0001) in both elderly (35.0 ± 1.7 pg/mL) and young (29.2 ± 1.9 pg/mL) groups. Orexin-A levels were significantly higher in the elderly than in the young group at T1, T2, and T3. CONCLUSION: Plasma orexin-A levels are not responsible for the delayed emergence from general anesthesia in elderly patients.

Antagonism by salvianolic acid B of lipopolysaccharide-induced disseminated intravascular coagulation in rabbits.

The aim of the present study was to investigate the effects of salvianolic acid B on lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) in rabbits. Continuous infusion of LPS was used to induce a DIC model in rabbits. Treatment with salvianolic acid B (1, 3 or 6 mg/kg) was started simultaneously with LPS infusion (0.5 mg/kg LPS in 60 mL saline; 10 mL/h over a period of 6 h) through the contralateral marginal ear vein. Activated partial thromboplastin time (APTT), prothrombin time (PT), platelet count and fibrinogen concentration were determined, as were plasma levels of fibrin-fibrinogen degradation products (FDP), alanine aminotransferase (ALT), blood urea nitrogen (BUN), protein C activity, antithrombin III (ATIII) and tumour necrosis factor (TNF)-α concentration. The gradual impairment of haemostatic parameters was induced by continuous infusion of LPS. There were marked increases in APTT, PT, BUN, ALT and plasma TNF-α and marked decreases in the platelet count, fibrinogen, FDP, protein C and ATIII. The intravenous administration of 1, 3 or 6 mg/kg salvianolic acid B attenuated the increases in APTT, PT, BUN, ALT and plasma TNF-α and the decreases in fibrinogen, platelet, FDP, protein C and ATIII induced by LPS infusion. These observations indicate that salvianolic acid B has an effect against LPS-induced DIC in rabbits.

Supraomohyoid neck dissection in the management of oral squamous cell carcinoma: special consideration for skip metastases at level IV or V.

PURPOSE: The aim of this study was to evaluate the therapeutic safety and prognosis of supraomohyoid neck dissections for oral squamous cell carcinoma, with a special focus on the risk of skip metastases in level IV or V. MATERIALS AND METHODS: A retrospective study was conducted of 637 patients with oral squamous cell carcinoma who were admitted to the department of oral and maxillofacial surgery from September 1995 through July 2010. After completing a diagnostic evaluation, all patients underwent surgery (wide primary excision with supraomohyoid neck dissection, extended supraomohyoid neck dissection, or modified radical or radical neck dissection) and were followed periodically. RESULTS: Levels I, II, and III were the most common sites of occult metastasis. Skip metastases alone at level IV or V and any neck recurrence at level IV or V were not found. Three-year neck recurrence-free survival and disease-specific survival were not significantly different among the patients who underwent supraomohyoid neck dissection, extended supraomohyoid neck dissection, or modified radical or radical neck dissection owing to cN0 to cN(+) disease. CONCLUSIONS: The rate of skip metastasis at level IV or V is very rare and is very difficult to diagnose accurately. The results of this retrospective study show that supraomohyoid neck dissection for oral squamous cell carcinoma is an appropriate treatment.

Prognostic factors of squamous cell carcinoma of the buccal mucosa: a retrospective study of 168 cases in North China.

PURPOSE: Buccal mucosa squamous cell carcinoma (BSCC) is considered a rare and aggressive malignancy that has a high rate of locoregional recurrence. The aim of this study was to analyze the outcome of surgical therapy as a treatment for BSCC in a North Chinese population over a period of 14 years. MATERIALS AND METHODS: A retrospective study was performed by reviewing the records and pathologies of 168 patients with BSCC who were treated at the Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Peking University, from June 1999 to September 2013. RESULTS: The rates of local, regional, and locoregional recurrence were 47.3%, 13.5%, and 6.8%, respectively. The neck metastasis rate in patients classified as having cN0 was 28.4%, and the occult metastasis rate in patients with BSCC stages T2 to T4 was higher than 15%. Neck metastases were most common at levels I and II. The 3-year disease-free survival, overall survival, and disease-specific survival rates were 60.6%, 74.6%, and 78.0%, respectively. Gender, T stage, pathologic node status, and pathologic grade were significant factors in determining disease-specific survival. However, only pathologic node status (P = .002) was an independent predictive factor of 3-year disease-specific survival. CONCLUSIONS: Buccal carcinoma is an aggressive disease with high rates of local and regional recurrence. In seeking to offer better prognoses and quality of life, extensive resection of the primary tumor, supraomohyoid neck dissection, and preferred free flap reconstruction are the therapies that have been recommended and used in the authors' hospital during the past 10 years.

In vitro and in vivo anti-inflammatory properties of an active fucoidan fraction from Sargassum fusiforme and a fraction-based hydrogel.

In a previous study, we separated an active fucoidan (JHCF4) from acid-processed Sargassum fusiforme, then analyzed and confirmed its structure. In the present study, we investigated the potential anti-inflammatory properties of JHCF4 and a JHCF4-based hydrogel in vitro and in vivo. JHCF4 reliably inhibited nitric oxide (NO) production in LPS-induced RAW 264.7 macrophages, with an IC50 of 22.35 µg/ml. Furthermore, JHCF4 attenuated the secretion of prostaglandin E2, tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6, indicating that JHCF4 regulates inflammatory reactions. In addition, JHCF4 downregulated iNOS and COX-2 and inhibited the activation of the MAPK pathway. According to further in vivo analyses, JHCF4 significantly reduced the generation of reactive oxygen species (ROS), NO production, and cell death in an LPS-induced zebrafish model, suggesting that JHCF4 exhibits anti-inflammatory effects. Additionally, a JHCF4-based hydrogel was developed, and its properties were evaluated. The hydrogel significantly decreased inflammatory and nociceptive responses in carrageenan (carr)-induced mouse paws by reducing the increase in paw thickness and decreasing neutrophil infiltration in the basal and subcutaneous layers of the toe epidermis. These results indicate that JHCF4 exhibits potential anti-inflammatory activity in vitro and in vivo and that JHCF4-based hydrogels have application prospects in the cosmetic and pharmaceutical fields.

Ethylidene-Tethered Chromene-Pyrone Hybrids as Potential Plant-Growth Regulators from an Endolichenic Phaeosphaeria Species.

Phaeosphaeria sp., a lichen-associated fungus, produced six skeletally new dimeric spiciferones (1-6) and four known metabolites (7-10). The new structures were elucidated by spectroscopic analysis, and their absolute configurations were determined by electronic circular dichroism calculations. Compounds 1 and 3-6 represent the first examples of ethylidene-bridged dimers from the building blocks 4H-chromene-4,7(8H)-dione and α-pyrone, and 2 is a unique homodimer of spiciferone. Compounds 1, 2, and 5-9 significantly inhibited the growth of weed-like dicot Arabidopsis thaliana at 100.0 µM. Notably, 8 showed the strongest inhibitory activity against the fresh weight and root elongation of A. thaliana with the IC50 values of 32.04 and 26.78 µM, respectively, whereas 1, 8, and 9 stimulated the growth of A. thaliana at lower concentrations. Meanwhile, compounds 2 and 6 exhibited weak inhibitory effects on the root elongation of monocot rice, while 1 and 8 exhibited growth-promoting effects on the shoot and root elongation of rice in a roughly dose-dependent manner.