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Part of fraction 1 (33.6 g) was subjected to silica gel chromatography by eluting with I n i -hexane-acetone (50:1), enriched with acetone, to furnish four further fractions (1-1-1-4). Fraction 2-3 (12.1 g) was subjected to silica gel chromatography, eluting with CH SB 2 sb Cl SB 2 sb -MeOH (100:1), and enriched gradually with MeOH, to obtain three fractions (2-3-1-2-3-3). Part of fraction 2 (29.7 g) was subjected to silica gel chromatography by eluting with I n i -hexane-acetone (40:1), enriched with acetone to furnish three further fractions (2-1-2-3). Part of fraction 5 (10.2 g) was subjected to silica gel chromatography by eluting with CH SB 2 sb Cl SB 2 sb -MeOH (70:1), enriched with MeOH, to furnish three fractions (5-1-5-3). [Extracted from the article]

Background: The risk of peripheral artery occlusive disease (PAOD) in patients with lower leg fracture who underwent fixation procedures is not yet completely understood. Therefore, the current study aimed to examine the risk of subsequent PAOD in patients with lower leg fracture who received fixation and non-fixation treatments. Methods: We included 6538 patients with lower leg fracture who received non-fixation treatment and a matched cohort comprising 26152 patients who received fixation treatment from the National Health Insurance Database. Patients were frequency matched according to age, sex, and index year. The incidence and risk of PAOD in patients with lower leg fracture who received fixation and non-fixation treatments were evaluated via the stratification of different characteristics and comorbidities. Results: Non-fixation treatment, male sex, older age (≥ 50 years old), diabetes mellitus, and gout were associated with a significantly higher risk of lower extremity PAOD compare to each comparison group, respectively. Moreover, there was a significant correlation between fixation treatment and a lower risk of lower extremity PAOD in women (adjusted hazard ratio [aHR] = 0.58, 95% confidence interval [CI] = 0.38–0.90), women aged > 50 years (aHR = 0.61, 95% CI = 0.38–0.96), and patients with coronary artery disease (aHR = 0.43, 95% CI = (0.23–0.81). Further, patients with fixation treatment had a significantly lower risk of lower extremity PAOD within 2 years after trauma (aHR = 0.57, 95% CI = 0.34–0.97). The Kaplan–Meier analysis showed that the cumulative incidence of PAOD was significantly higher in the non-fixation treatment group than in the fixation treatment group at the end of the 10-year follow-up period (log-rank test: P = 0.022). Conclusion: Patients with lower leg fracture who received non-fixation treatment had a significantly higher risk of PAOD than those who received fixation treatment. Moreover, the risk of PAOD was higher in women aged > 50 years, as well as in coronary artery disease patients who received non-fixation treatment than in those who received fixation treatment. Therefore, regular assessment of vessel patency are recommended for these patients. Nevertheless, further studies must be conducted to validate the results of our study. [ABSTRACT FROM AUTHOR]

Background: Peripheral arterial occlusive disease (PAOD) is a challenge in peripheral vascular disease. Clinical observations show reperfusion of occluded vessels may cause compartment syndrome or remote organ injury. Less well known is the role of vitamin D3 in tissue injury; therefore, we attempted to determine whether vitamin D3 could alleviate local and remote organ injury induced by reperfusion of occluded vessels in animal models. Methods: Twenty-four male Sprague-Dawley rats were randomized into four groups: saline + sham, saline + I/R, vitamin D3 + sham, and vitamin D3 + I/R group. After pretreatment for 5 d, the animals designed to I/R injury were subjected to 3 h of ischemia induced by bilateral femoral arteries clamp, followed by reperfusion of the vessels for 3 h on d 6. Left lung and left anterior tibial muscle tissue were harvested for wet/dry weight ratio and histopathologic analysis. Blood was collected for analysis of urea nitrogen (BUN), creatinine (Cr), aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), ionized calcium levels, and heme oxygenase-1 (HO-1). Results: Compared with the saline + sham group, there was a significant increase in plasma IL-6 level in both saline + I/R and vitamin D3 + I/R groups and muscle, lung wet/dry weight ratio in the saline + I/R group (P < 0.05). Compared with the saline + I/R group, there was a significant decrease in plasma IL-6 level, muscle and lung wet/dry weight ratio in both vitamin D3 + sham and vitamin D3 + I/R groups, and leukocyte HO-1 expression in vitamin D3 + sham group (P < 0.05). Compared with the vitamin D3 + sham group, there was a significant increase in plasma IL-6 levels in the vitamin D3 + I/R group, and leukocyte HO-1 expression in vitamin D3 + sham group (P < 0.05). BUN, Cr, AST, ALT, TNF-α, ionized calcium levels did not differ significantly among the groups. Conclusions: Pretreatment of vitamin D3 ameliorates the systemic IL-6 levels, lung and muscle injury induced by ischemia followed by reperfusion of bilateral occluded vessels in a rat model. [Copyright &y& Elsevier]

Accumulation of abnormal chondroitin sulfate (CS) chains in breast cancer tissue is correlated with poor prognosis. However, the biological functions of these CS chains in cancer progression remain largely unknown, impeding the development of targeted treatment focused on CS. Previous studies identified chondroitin polymerizing factor (CHPF; also known as chondroitin sulfate synthase 2) is the critical enzyme regulating CS accumulation in breast cancer tissue. We then assessed the association between CHPF‐associated proteoglycans (PGs) and signaling pathways in breast cancer datasets. The regulation between CHPF and syndecan 1 (SDC1) was examined at both the protein and RNA levels. Confocal microscopy and image flow cytometry were employed to quantify macropinocytosis. The effects of the 6‐O‐sulfated CS‐binding peptide (C6S‐p) on blocking CS functions were tested in vitro and in vivo. Results indicated that the expression of CHPF and SDC1 was tightly associated within primary breast cancer tissue, and high expression of both genes exacerbated patient prognosis. Transforming growth factor beta (TGF‐β) signaling was implicated in the regulation of CHPF and SDC1 in breast cancer cells. CHPF supported CS–SDC1 stabilization on the cell surface, modulating macropinocytotic activity in breast cancer cells under nutrient‐deprived conditions. Furthermore, C6S‐p demonstrated the ability to bind CS‐SDC1, increase SDC1 degradation, suppress macropinocytosis of breast cancer cells, and inhibit tumor growth in vivo. Although other PGs may also be involved in CHPF‐regulated breast cancer malignancy, this study provides the first evidence that a CS synthase participates in the regulation of macropinocytosis in cancer cells by supporting SDC1 expression on cancer cells. [ABSTRACT FROM AUTHOR]

Abstract: Background: Lung ischemia-reperfusion (I/R) injury plays an important role in lung transplantation. Less well known is the role of sildenafil in lung I/R injury; therefore, we attempted to determine whether sildenafil could alleviate lung apoptosis and tissue injury in a rat model. Methods: Forty male Sprague-Dawley rats were randomized into four groups: saline + sham, saline + I/R, sildenafil + sham, and sildenafil + I/R groups. Three hours before the operation, each rat received normal saline or sildenafil (10 mg/kg) by lavage. The animals designed to I/R injury were subjected to 2 h of ischemia induced by occlusion of left pulmonary artery, veins, and bronchus, followed by reperfusion for 2 h. The lung tissue was harvested for the analysis of the expression of Bax, Bcl-2, p53, caspase 3, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and wet/dry (W/D) weight ratio. Results: Compared with the saline + sham group, the saline + I/R group had significant increases in Bax, p53, Bax/Bcl-2 ratio, caspase 3, IL-6, TNF-α, and W/D weight ratio but a decrease in Bcl-2 (P < 0.05). Compared with the saline + I/R group, sildenafil + I/R group had significant decreases in Bax, p53, Bax/Bcl-2 ratio, caspase 3, IL-6, TNF-α level, and W/D weight ratio but an increase in Bcl-2 expression (P < 0.05). Compared with the sildenafil + sham group, there were significant increases in p53 and TNF-α expression in the sildenafil + I/R group (P < 0.05). Conclusions: Pretreatment with sildenafil alleviates lung apoptosis and tissue injury in a rat model. [Copyright &y& Elsevier]

Abstract: Synthesis and anti-inflammatory effects of certain furo[3′,2′:3,4]naphtho[1,2-d]imidazole derivatives 12–18 were studied. These compounds were synthesized from naphtho[1,2-b]furan-4,5-dione (10) which in turn was prepared from the known 2-hydoxy-1,4-naphthoquinone (7) in a one pot reaction. Furo[3′,2′:3,4]naphtho[1,2-d]imidazole (12) was inactive (IC50 value of >30μM) while its 5-phenyl derivative 13, with an IC50 value of 16.3 and 11.4μM against lysozyme and β-glucuronidase release, respectively, was comparable to the positive trifluoperazine. The same potency was observed for 5-furan derivative 16 with an IC50 value of 19.5 and 11.3μM against lysozyme and β-glucuronidase release, respectively. An electron-withdrawing NO2 substituted on 5-phenyl or 5-furanyl group led to the devoid of activity as in the cases of 14 and 17. Among them, compound 15 exhibited significant inhibitory effects, with an IC50 value of 7.4 and 5.0μM against lysozyme and β-glucuronidase release, respectively. For the LPS-induced NO production, the phenyl derivatives 12–15 were inactive while the nitrofuran counterparts 17 and 18 suppress LPS-induced NO production significantly, with an IC50 value of 1.5 and 1.3μM, respectively, which are more active than that of the positive 1400W. Compounds 16–18 were capable of inhibiting LPS-induced iNOS protein expression at a dose-dependent manner in which compound 18, with an IC50 of 0.52μM in the inhibition of iNOS expression, is approximately fivefold more potent than that of the positive 1400W. In the CLP rat animal model, compound 18 was found to be more active than the positive hydrocortisone in the inhibition of the iNOS mRNA expression in rat lung tissue. The sepsis-induced PGE2 production in rat serum decreased 150% by the pretreatment of 18 in a dose of 10mg/kg. [Copyright &y& Elsevier]

Few studies have discussed the development of post-traumatic headache (PTH) after zygoma fracture. This research aimed to examine the association between zygoma fracture and PTH and its other associated factors. A total of 3043 patients with zygoma fracture and 3043 patients with non-fracture were included in this analysis. They were matched to a non-fracture cohort from the National Health Insurance database according to age, sex, and index year. The incidence of PTH and its association with zygoma fracture were assessed. The zygoma fracture cohort had a significantly higher cumulative incidence of PTH than the non-fracture cohort in a 10-year follow-up. The confounding risk factors of PTH included zygoma fracture, female sex, and comorbidities, including obesity and depression. Female patients under 40 years old who had zygoma fractures had a higher incidence of PTH than the non-fracture group. Moreover, patients with zygoma fractures commonly developed PTH within three months after injury. Female patients under 40 years old with precedent zygoma fractures had a higher incidence rate of PTH than those without fractures. Moreover, patients with zygoma fractures commonly developed PTH within three months after injury. Nevertheless, before widely applying our results, a prospective study must be conducted to verify the risk factors found in this study. [ABSTRACT FROM AUTHOR]

The hazard of subsequent arterial embolism and thrombosis (SAET) in patients with lower leg fractures is not yet well demonstrated. The purpose of this study is to determine the correlation between lower leg fracture and SAET in Taiwan. A total of 134,844 patients with lower leg fractures (ICD-9-CM: 823) and chronological diagnosis as SAET (ICD-9-CM: 444.22) was matched (1:1) to the non-fracture cohort according to their propensity score (data coming from the National Health Insurance database between January 2000 to December 2012). Patients were matched by age, gender, and comorbidities. The incidence of SAET and correlation between SAET development and lower leg fracture was statistically analyzed, and subgroup analysis categorized by characteristics and comorbidities was conducted as well. The cumulative incidence of SAET was calculated by Kaplan–Meier analysis. Kaplan–Meier analysis plot showed that, by the end of the ten-year follow-up period, the cumulative incidence of SAET was significantly higher for the lower leg fracture cohort than for the non-fracture cohort (log-rank test: p < 0.001). The lower leg fracture, male, elder age (45–64-year-old; ≥65-year-old), hypertension, diabetes mellitus, and gout were significantly associated with lower extremity SAET risk compared with the matched group. There was an inseparable correlation between the lower leg fracture group and the risks of SAET; subgroup analysis by gender (male, female), age (age < 40 years, age 40–64 years, and age > 65 years) and comorbidities (hypertension, diabetes mellitus, and gout) show compatible results as well. Patients with lower leg fracture have a significantly increased risk of SAET since then two years after the fracture. The hazard of SAET was significantly higher in patients with lower leg fracture than in the non-fracture cohort, and the high incidence was found since then two years after fracture. Further studies are warranted. [ABSTRACT FROM AUTHOR]

Abstract: Asthma occurs in more than 5% of the population in industrialized countries and is now characterized as a chronic inflammatory disease. The chronic aspiration of gastric fluid is considered by many investigators to be a primary inflammatory factor exacerbating or predisposing patients to asthma, with more than 50 medical papers per year linking asthma with gastroesophageal reflux disease (GERD), which can lead to aspiration events. However, the mechanisms involved in the inflammatory effects caused by gastric-fluid aspiration are not clear at the present time. The role of macrophages in the pathogenesis of disease seems likely given the involvement of those cells in a variety of chronic inflammatory diseases. To investigate the potential role of gastric fluid and the mechanisms potentially underlying chronic aspiration-associated pathogenesis, we examined the activation of murine macrophages (Raw 264.7 cell line) with gastric fluid. Inflammatory cytokine production and activation of the NF-κB signaling pathway were observed. Toll-like receptor (TLR)-4-dependent activation was observed under some conditions, indicating that bacterial components within the gastric fluid are involved in macrophage activation. Matrix metalloproteinase-9 (MMP-9) expression by macrophages was enhanced by gastric fluid, suggesting a potential mechanism by which remodeling of airways might be induced by gastric-fluid aspiration. [Copyright &y& Elsevier]

Because of limitations caused by unique complications of free flap reconstruction, the Clavien–Dindo classification was modified to include grade "IIIc" for "partial or total free flap failure." From 2013 to 2018, 116 patients who had undergone free flap reconstruction for head and neck cancer with grade III or higher postoperative complications were grouped using the "Modified" Clavien–Dindo classification. Alcoholism displayed significant predictive effects between grade IIIb and IIIc (72.7% vs. 50%, p = 0.028). Significant differences were observed between grade IIIb and IIIc in the duration of hospital stay (23.1 ± 10.1 vs. 28.6 ± 11.9 days, p = 0.015), duration of intensive care unit stay (6.0 ± 3.4 vs. 8.7 ± 4.3 days, p = 0.001), reoperation times during the current hospitalization (1.4 ± 0.8 vs. 2.0 ± 1.0 times, p < 0.001), and wound infection rate (29.9% vs. 62.5%, p = 0.002). The severity levels were significantly positively correlated with reoperation times during the current hospitalization (p < 0.001), ICU stay (p = 0.001), and hospital stay (p < 0.001). The modified Clavien–Dindo classification with grade IIIc describes the perioperative complications of head and neck free flap reconstruction to predict clinical outcomes based on severity. [ABSTRACT FROM AUTHOR]