Multidisciplinary comprehensive treatment of massive hepatocellular carcinoma with hemorrhage: A case report and review of literature.

BACKGROUND: Hepatocellular carcinoma (HCC), a major contributor to cancer-related deaths, is particularly prevalent in Asia, largely due to hepatitis B virus infection. Its prognosis is generally poor. This case report contributes to the medical literature by detailing a unique approach in treating a large HCC through multidisciplinary collaboration, particularly in patients with massive HCC complicated by ruptured bleeding, a scenario not extensively documented previously. CASE SUMMARY: The patient presented with large HCC complicated by intratumoral bleeding. Treatment involved a multidisciplinary approach, providing individualized care. The strategy included drug-eluting bead transarterial chemoembolization, sorafenib-targeted therapy, laparoscopic partial hepatectomy, and standardized sintilimab monoclonal antibody therapy. Six months after treatment, the patient achieved complete radiological remission, with significant symptom relief. Imaging studies showed no lesions or recurrence, and clinical assessments confirmed complete remission. This report is notable as possibly the first documented case of successfully treating such complex HCC conditions through integrated multidisciplinary efforts, offering new insights and a reference for future similar cases. CONCLUSION: This study demonstrated effective multidisciplinary treatment for massive HCC with intratumoral bleeding, providing insights for future similar cases.

Phosphorescent acyclic cucurbituril solid supramolecular multicolour delayed fluorescence behaviour.

Organic photoluminescent macrocyclic hosts have been widely advanced in many fields. Phosphorescent hosts with the ability to bind organic guests have rarely been reported. Herein, acyclic cucurbituril modified with four carboxylic acids (ACB-COOH) is mined to present uncommon purely organic room-temperature phosphorescence (RTP) at 510 nm with a lifetime of 1.86 µs. Its RTP properties are significantly promoted with an extended lifetime up to 2.12 s and considerable quantum yield of 6.29% after assembly with a polyvinyl alcohol (PVA) matrix. By virtue of the intrinsic self-crimping configuration of ACB-COOH, organic guests, including fluorescence dyes (Rhodamine B (RhB) and Pyronin Y (PyY)) and a drug molecule (morphine (Mor)), could be fully encapsulated by ACB-COOH to attain energy transfer involving phosphorescent acyclic cucurbituril. Ultimately, as-prepared systems are successfully exploited to establish multicolor afterglow materials and visible sensing of morphine. As an expansion of phosphorescent acyclic cucurbituril, the host afterglow color can be readily regulated by attaching different aromatic sidewalls. This study develops the fabrication strategies and application scope of a supramolecular phosphorescent host and opens up a new direction for the manufacture of intelligent long-lived luminescent materials.

A Phase II Study of Neoadjuvant PLD/Cyclophosphamide and Sequential nab-Paclitaxel Plus Dual HER2 Blockade in HER2-Positive Breast Cancer.

BACKGROUND: Neoadjuvant trastuzumab/pertuzumab (HP) plus chemotherapy for HER2-positive breast cancer (BC) achieved promising efficacy. The additional cardiotoxicity still existed. Brecan study evaluated the efficacy and safety of neoadjuvant pegylated liposomal doxorubicin (PLD)/cyclophosphamide and sequential nab-paclitaxel based on HP (PLD/C/HP-nabP/HP). PATIENTS AND METHODS: Brecan was a single-arm phase II study. Eligible patients with stages IIA-IIIC HER2-positive BC received 4 cycles of PLD, cyclophosphamide, and HP, followed by 4 cycles of nab-paclitaxel and HP. Definitive surgery was scheduled after 21 days for patients completing treatment or experiencing intolerable toxicity. The primary endpoint was the pathological complete response (pCR). RESULTS: Between January 2020 and December 2021, 96 patients were enrolled. Ninety-five (99.0%) patients received 8 cycles of neoadjuvant therapy and all underwent surgery with 45 (46.9%) breast-conserving surgery and 51 (53.1%) mastectomy. The pCR was 80.2% (95%CI, 71.2%-87.0%). Four (4.2%) experienced left ventricular insufficiency with an absolute decline in LVEF (43%-49%). No congestive heart failure and ≥grade 3 cardiac toxicity occurred. The objective response rate was 85.4% (95%CI, 77.0%-91.1%), including 57 (59.4%) complete responses and 25 (26.0%) partial responses. The disease control rate was 99.0% (95%CI, 94.3%-99.8%). For overall safety, ≥grade 3 AEs occurred in 30 (31.3%) and mainly included neutropenia (30.2%) and asthenia (8.3%). No treatment-related deaths occurred. Notably, age of >30 (P = .01; OR = 5.086; 95%CI, 1.44-17.965) and HER2 IHC 3+ (P = .02; OR = 4.398; 95%CI, 1.286-15.002) were independent predictors for superior pCR (ClinicalTrials.gov Identifier NCT05346107). CONCLUSION: Brecan study demonstrated the encouraging safety and efficacy of neoadjuvant PLD/C/HP-nabP/HP, suggesting a potential therapeutic option in HER2-positive BC.

New Interpretation of Neonatal Outcomes by Phenotypically Classified Preterm Syndrome: A Retrospective Cohort Study.

OBJECTIVE: The global aim to lower preterm birth rates has been hampered by the insufficient and incomplete understanding of its etiology, classification, and diagnosis. This study was designed to evaluate the association of phenotypically classified preterm syndromes with neonatal outcomes; to what extent would these outcomes be modified after the obstetric interventions, including use of glucocorticoid, magnesium sulfate, and progesterone. METHODS: This was a retrospective cohort study conducted at Tongji Hospital (composed of Main Branch, Optical Valley Branch and Sino-French New City Branch) in Wuhan. A total of 900 pregnant women and 1064 neonates were retrospectively enrolled. The outcomes were the distribution of different phenotypes among parturition signs and pathway to delivery, the association of phenotypically classified clusters with short-term unfavorable neonatal outcomes, and to what extent these outcomes could be modified by obstetric interventions. RESULTS: Eight clusters were identified using two-step cluster analysis, including premature rupture of fetal membranes (PPROM) phenotype, abnormal amniotic fluid (AF) phenotype, placenta previa phenotype, mixed condition phenotype, fetal distress phenotype, preeclampsia-eclampsia & hemolysis, elevated liver enzymes, and low platelets syndrome (PE-E&HELLP) phenotype, multiple fetus phenotype, and no main condition phenotype. Except for no main condition phenotype, the other phenotypes were associated with one or more complications, which conforms to the clinical practice. Compared with no main condition phenotype, some phenotypes were significantly associated with short-term adverse neonatal outcomes. Abnormal AF phenotype, mixed condition phenotype, PE-E&HELLP phenotype, and multiple fetus phenotype were risk factors for neonatal small-for gestation age (SGA); placenta previa phenotype was not associated with adverse outcomes except low APGAR score being 0-7 at one min; mixed condition phenotype was associated with low APGAR scores, SGA, mechanical ventilation, and grade HI-W intraventricular hemorrhage (IVH); fetal distress phenotype was frequently associated with neonatal SGA and mechanical ventilation; PE-E&HELLP phenotype was correlated with low APGAR score being 0-7 at one min, SGA and neonatal intensive care unit (NICU) admission; multiple fetus phenotype was not a risk factor for the outcomes included except for SGA. Not all neonates benefited from obstetric interventions included in this study. CONCLUSION: Our research disclosed the independent risk of different preterm phenotypes for adverse pregnancy outcomes. This study is devoted to putting forward the paradigm of classifying preterm birth phenotypically, with the ultimate purpose of defining preterm phenotypes based on multi-center studies and diving into the underlying mechanisms.

Universal cooling patterns of the butterfly wing scales hierarchy deduced from the heterogeneous thermal and structural properties of Tirumala limniace (Lepidoptera: Nymphalidae, Danainae).

The radiative cooling of butterfly wing scales hierarchy has great value in understanding how poikilotherms adapt to the environment and developing bionic materials. However, it remains unclear what the cooling system is like and how the variation of hierarchy affects the cooling efficiency. Therefore, the correlation between the variations of the structure and emissivity of scale hierarchy is thoroughly investigated in Tirumala limniace (Cramer, 1775), whose thermal properties are highly heterogeneous among different wings and regions but similar between males and females. Patterns were deduced from the biological and model simulation experiments. The scale hierarchy varies at the micro- to nanolevel on both surface and section, corresponding to the variating emissivity. Scales on wing veins and margins have large nanostructured units with small lumens and are distinctly thickened, which bring extraordinarily high emissivity. The variations of light and dark scales, respectively, lead to the high emissivity of the middle region of wings and the front wings. Generally, the elevation of the inner surface area and the thickness of the chitin is the key to enhancing the cooling efficiency. For the first time, the effects of the variation of hierarchy toward emissivity of the mid-infrared spectrum are systematically clarified. It is demonstrated that wing scales integrally differentiate in coping with the heterogeneous cooling needs, which may benefit in balancing multifunctions and the development toward the adaptation to the abiotic environment. The study provides insights into the comprehensive thermoregulation system of butterflies and the further development of radiative cooling materials.

Interaction between working memory load and the ability to resist interference from negative distractors in dysphoria.

Although the relationship between emotional working memory (WM) and depressive symptoms has been well established in clinical samples, research in the subclinical population has produced mixed results. The present study tested the effect of WM load on control of interference from emotional (positive, negative, neutral) distractors in dysphoria. Dysphoric (n = 32) and non-dysphoric (n = 35) university students were administered the emotional 2-back (lower WM load) and 3-back (higher WM load) tasks. Results showed that resisting negative distractors was more difficult for the dysphoric group than the non-dysphoric group, but only in the 3-back task. The results demonstrate that dysphoria is associated with greater interference from negative distractors under high WM load. We conclude that both WM load and emotional valence have an effect on WM performance in dysphoria, and the poor ability to resist interference from negative distractors in WM might be a key cognitive vulnerability factor for depression.

The role of prepotent response inhibition and interference control in depression.

INTRODUCTION: The ability to suppress inappropriate prepotent response and to overcome the interference of irrelevant information are two important components of inhibitory control. Little is known, however, about the relevant contributions in these two components of inhibitory control to depression. The aim of the present study was to assess the prepotent response inhibition and interference control simultaneously in a group of patients diagnosed with major depression disorder (MDD). METHODS: A clinical group of patients with MDD (n = 41) and a control group of healthy volunteers (n = 39) were recruited and assessed using the stop-signal task and the Flanker task respectively. RESULTS: The results showed longer stop-signal reaction time in patients with MDD in the stop-signal task. Regarding the interference control function, the analysis showed the response accuracy under the incongruent condition was significantly lower in patients with MDD than healthy individuals. CONCLUSIONS: In conclusion, patients with MDD showed impairments both in prepotent response inhibition and interference control. The present findings provide a better understanding of the mechanism of depression-related deficits in inhibition and have great implications for the development of cognitive training programmes to remediate cognitive dysfunction in depression.

A Participant-assigned Interventional Research of Precesarean Internal Iliac Artery Balloon Catheterization for Managing Intraoperative Hemorrhage of Placenta Previa and Placenta Accreta Spectrum Disorders After Cesarean Section.

Placenta accreta spectrum disorder (PASD) and placenta previa (PP) are two of the most hideous obstetric complications which are usually associated with a history of cesarean section (CS). Moreover, women with PASD, PP and/or a cesarean scarred uterus are more likely to have adverse pregnancy outcomes, including blood transfusion, hysterectomy, pelvic organs damage, postpartum hemorrhage, disseminated intravascular coagulation, multi-organ dysfunction syndrome and even maternal or fetal death. This study aimed to investigate the efficacy of precesarean internal iliac artery balloon catheterization (BC) for managing severe hemorrhage caused by PASD and PP with a history of CS. This participant-assigned interventional study was conducted in Tongji Hospital. We recruited 128 women with suspected PASD, PP and a history of CS. Women in the BC group accepted precesarean BC of bilateral internal iliac arteries before the scheduled cesarean delivery. Women in the control group underwent a conventional cesarean delivery. Intraoperative hemorrhage, transfusion volume, radiation dose, exposure time, complications and neonatal outcomes were discussed. There were significant differences in calculated blood loss (CBL) between BC group and control group (1015.0±144.9 vs. 1467.0±171.0 mL, P=0.04). Precesarean BC could reduce intraoperative red blood cell (RBC) transfusion as compared with control group (799.5±136.1 vs. 1286.0±161.6 mL, P=0.02) and lessen the rate of using blood products (57.1% vs. 76.4%, P=0.02). The incidence of hysterectomy was also lower in BC group than in control group. Postpartum outcomes showed no significant differences between the two groups, except that postoperation hospitalization was longer in BC group than in control group (6.7±0.4 vs. 5.8±0.2 days, P=0.03). Precesarean BC of internal iliac artery is an effective method for managing severe hemorrhage caused by PASD and PP with a cesarean scarred uterus, as it could reduce intraoperative blood loss, lessen intraoperative RBC transfusions and potentially decrease hysterectomies.

Predictive and prognostic values of preoperative platelet parameters in patients with gynecological tumors.

BACKGROUND: Platelets play a role in tumor cell growth, metastasis, and angiogenesis, and the present study aimed to evaluate diagnostic and prognostic values of platelet parameters in patients with gynecological tumors. METHODS: A total of 1062 women were included. Differences of platelet parameters (platelet count [PLT], plateletcrit [PCT], mean platelet volume [MPV], platelet-large cell rate [P-LCR], and platelet distribution width [PDW]) between different categories were analyzed by nonparametric test. The optimal cutoff value was calculated with receiver operating characteristic analysis. Overall survivals were analyzed with Kaplan-Meier method and log-rank tests for univariate analysis. RESULTS: Platelet count and PCT were significantly increased, and MPV and P-LCR were significantly reduced in malign and benign gynecological tumor groups compared with the controls (P < .001); PDW had no significant differences. There were no significant differences in PLT, PCT, MPV, P-LCR, and PDW between different tumor locations and pathologic types. The optimal cutoff values of PLT, PCT, MPV and P-LCR were 274, 0.26, 10.08, and 24.8 (AUC: 0.661, 0.643, 0.593, 0.562), and PCT had preferable sensibility and specificity (50.84% and 70.42%) in predicting the presence of gynecological tumors. According to survival analysis, increased PLT (≥274 × 109 /L) and PCT (≥0.26), and induced MPV (<10.08 fL) and P-LCR (<24.8%) were associated with shorter overall survival. CONCLUSIONS: Platelet count, PCT, MPV, and P-LCR can be used as preferable auxiliary parameters for predicting the presence of gynecological tumors. Increased PLT and PCT, or decreased MPV and P-LCR indicated a heavier tumor burden and shorter overall survival.

[Genetic Diagnosis and Phenotype Analysis for 3 Patients with Hereditary Coagulation Factor â ¦ Deficiency].

OBJECTIVE: To investigate the gene mutations types and the clinical characteristics in 3 patients with hereditary coagulation factor Ⅶ deficiency. METHODS: The phenotype diagnosis was validated by detecting the coagulation parameters including prothrombin time (PT)，activated partial thromboplastin time (APTT), fibrinogen (FIB), FⅦ activity (FⅦ: C) and specific antigens (FⅦ: Ag) of proband and its family members. All exons, exon-intron boundaries, 5＇ untranslated regions and 3＇ untranslated regions of F7 gene were amplified with PCR. Potential mutations were detected by direct sequencing of purified PCR products. Suspected mutations were confirmed by sequencing of the opposite strand. RESULTS: A total of 5 different mutations were identified in 3 patients with hereditary coagulation factor Ⅶ deficiency and family members, including 4 misssense mutations and 1 splice site mutation. Out of 3 cases of hereditary coagulation factor Ⅶ deficiency 2 had double heterozygous mutation, I had homozygous mutations. Patient 1 had p.His408Gln with p.Arg413Gln double heterozygous mutations, her sister had p.His408Gln with p.Arg413Gln double heterozygous mutations, another one had p.His408Gln mono-heterozygous mutation, their correspo FⅦ: C were 5%, 3%, 75%. Patient 2 had p.Arg364Gln with p.His408Gln double heterozygous mutations, her brother had p.Arg364Gln with IVS6-1G＞A double heterozygous mutations, their corresponding FⅦ: C were 2.0%, 2.0%. Patient 3 had p.Arg337Cys homozygous mutation, FⅦ: C was 3.0%. CONCLUSION: A total of 5 different mutations were identified in 3 patients with hereditary coagulation factor Ⅶ deficiency, the p.His408Gln is a common mutation, the FⅦ: C and FⅦ: Ag have no correlation with clinical phenotypes.

Interaction with adipocytes induces lung adenocarcinoma A549 cell migration and tumor growth.

Adipocytes have been demonstrated to promote the progression of various tumors through modulation of cancer cell metabolism. However, their role in lung cancer progression remains undetermined. In the present study, adipocytes and lung adenocarcinoma A549 cells were cultured in a Transwell co­culture system. Cancer cells were additionally cultured in conditioned medium, obtained from adipocytes or co­cultured cells. A MTT and colony formation assay were performed to assess A549 cell proliferation. The expression of epithelial­mesenchymal transition protein markers E­cadherin and vimentin were measured by western blotting. A549 cell migration and invasion was determined with wound healing, Transwell and Matrigel assays. Oil Red­O staining was used to evaluate intracellular lipid content. Colorimetric assays were utilized to detect free fatty acid, glucose uptake, lactate production and triglyceride content in cells. The results revealed a reciprocal interaction between adipocytes and A549 cells, which significantly enhanced A549 cell proliferation and metastasis; whereas, the expression of E­cadherin was decreased and vimentin was increased in A549 cells. Additionally, A549 cells exhibited metabolic reprogramming in vitro following co­culture with adipocytes. It was demonstrated that lipid droplets accumulation, glucose consumption and lactate production increased in tumor cells exposed to adipocytes. Furthermore, adipocytes co­cultured with A549 cells exhibited a decrease in the number and size of lipid droplets, a decrease in the intracellular triglyceride content and a significant increase in the release of free fatty acids. These findings highlighted the crucial role of adipocytes in the modulation of lung adenocarcinoma A549 cell metabolism and suggested the involvement of adipocytes in lung cancer progression.

Anti-NY-ESO-1 autoantibody may be a tumor marker for intrahepatic cholangiocarcinoma.

Anti-NY-ESO-1 antibody is observed in a multitude of malignancies. This study was aimed to evaluate the expression of serum anti-NY-ESO-1 antibodies and its prognostic value in intrahepatic cholangiocarcinoma. A total of 103 patients with intrahepatic cholangiocarcinoma were enrolled in the study. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum level of anti-NY-ESO-1 antibody. Western blotting was performed to assess the NY-ESO-1 expression in tumor and adjacent tissues. The serum NY-ESO-1 antibody was detected in 18.4% of patients with intrahepatic cholangiocarcinoma, a value that was significantly higher than that in patients with chronic Hepatitis B. Serum NY-ESO-1 antibody was positively correlated with tumor differentiation, lymphatic metastasis, cTNM stage and abdominal pain. Finally, there was a higher cumulative survival rate in patients with serum NY-ESO-1 positivity than in those with serum NY-ESO-1 negativity among the patients with stage III + IV. Our data uncovered that NY-ESO-1 antibody might be a helpful tumor marker and prognostic predictor in intrahepatic cholangiocarcinoma.

Involvement of dysregulated IKCa and SKCa channels in preeclampsia.

INTRODUCTION: Excessive constriction of placental chorionic plate arteries (CPAs) may be associated with preeclampsia (PE). Nitric oxide (NO) as well as intermediate and small Ca2+-activated K+ channels (IKCa and SKCa) plays vital roles in vasodilation of CPAs. We hypothesized that dysregulated IKCa and SKCa channels may be involved in the pathogenesis of PE mediated by the impaired NO system on CPAs. METHODS: The location of IKCa and SKCa channels, activities of NO synthases (NOS), and expression levels of these molecules were studied on CPAs from 30 normal pregnancies and 30 PE. The vasodilating function of CPAs was measured under openers or blockers of IKCa/SKCa channels in the presence or absence of NO donor or inhibitor. RESULTS: IKCa and SKCa channels were located both on endothelium and on smooth muscles of CPAs and the expressions of them were downregulated in PE women comparing to those in normal pregnant women. The protein expressions of endothelial NOS (eNOS) and inducible NOS (iNOS) were downregulated on CPAs in PE accompanied by decreased activity of eNOS. Notably, the vasodilatory functions mediated by IKCa/SKCa channels and by NO were aberrant on preeclamptic CPAs. In addition, IKCa and SKCa channels were responsible for nitric oxide (NO)-attributable vasorelaxation and activity modulation of NO synthases. CONCLUSIONS: This study provides evidence that dysregulated IKCa and SKCa channels might contribute to fetal pathogenesis of PE through direct promotion of vascular constriction of CPAs and through affecting functions of NO and activities of NOS.

Up-regulated expression of Tim-3/Gal-9 at maternal-fetal interface in pregnant woman with recurrent spontaneous abortion.

The relationship between T cell immunoglobulin domain and mucin domain protein 3 (Tim-3)/Galectin (Gal)-9 pathway and recurrent spontaneous abortion (RSA) was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin (IL)-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non-pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05), but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05). It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA.

Promoter methylation of DAPK gene may contribute to the pathogenesis of nonsmall cell lung cancer: a meta-analysis.

We performed a meta-analysis of cohort studies to determine whether promoter methylation of the death-associated protein kinase (DAPK) gene contributes to the pathogenesis of nonsmall cell lung cancer (NSCLC). A range of electronic databases were searched: MEDLINE (1966 ∼ 2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980 ∼ 2013), CINAHL (1982 ∼ 2013), Web of Science (1945 ∼ 2013), and the Chinese Biomedical Database (CBM; 1982 ∼ 2013) without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated. Our meta-analysis integrated results from 12 clinical cohort studies that met all inclusion criteria with a total of 1,027 NSCLC patients. We observed that the frequency of DAPK gene methylation in cancer tissues were significantly higher than that in the adjacent normal and benign tissues (cancer tissues vs. benign tissues: OR=8.50, 95 % CI=5.88 ∼ 12.28, P<0.001; cancer tissues vs. adjacent tissues: OR=5.95, 95 % CI=4.11 ∼ 8.60, P<0.001; cancer tissues vs. normal tissues: OR=4.75, 95 % CI=3.28 ∼ 6.87, P<0.001; respectively). Subgroup analysis by ethnicity demonstrated that DAPK gene methylation was closely associated with the development and progression of NSCLC among both Asians and Caucasians (all P<0.05). Furthermore, we conducted a subgroup analysis based on sample source and discovered that DAPK gene methylation was implicated in the pathogenesis of NSCLC in both blood and tissue subgroups (all P<0.05). Our results suggest that DAPK promoter methylation may be involved in NSCLC carcinogenesis. Thus, the detection of aberrant DAPK methylation may be helpful in the diagnosis and prognosis of NSCLC.

[Effects and mechanism of osthole on intestinal ischemia-reperfusion injury in mice].

OBJECTIVE: To explore the protective role of osthole in intestinal ischemia-reperfusion (I/R) injury in mice and examine its underlying mechanism. METHODS: A murine model of intestinal I/R injury was established with clamping of superior mesenteric artery for 120 min and then clamping was relieved for 60 min. Forty-five SD male mice weighing 27-31 g were randomly divided into 3 groups (n = 15 each): sham group (S), I/R injury group (I/R) and I/R plus osthole treatment group (Ost+). Intestinal wet/dry weight ratio, superoxide dismutase (SOD), malondialdehyde (MDA) in serum were examined by colorimetric assay and diamine oxidase (DAO) was examined by automatic biochemical analyzer, the levels of tumor necrosis factor (TNF) -α, interleukin (IL)-1ß and IL-2 were examined by enzyme-linked immunosorbent assay (ELISA). Intestinal barrier permeability was detected by Evans blue (EB) test. One-way ANOVA was used to analyze all experimental data variance. RESULTS: Intestinal tissues wet/dry weight ratios, Evans blue content and Chiu's score of I/R group mice were significantly higher than those of S and Ost+ groups (0.80% ± 0.03% vs 0.77% ± 0.02% & 0.78% ± 0.02%, (0.11 ± 0.04) vs (0.05 ± 0.02) & (0.06 ± 0.02) µg/mg, 3.42 ± 0.73 vs 0.87 ± 0.35 & 2.63 ± 0.58, P < 0.05 or P < 0.01) . Serum level of DAO, MDA, IL-1ß & TNF-α of I/R group mice were significantly higher than those of S and Ost+ groups ( (18.9 ± 4.0) vs (14.5 ± 2.3) & (16.0 ± 2.6) U/L, (8.4 ± 1.2) vs (6.9 ± 1.7) & (6.1 ± 2.4) µmol/L, (93 ± 6) vs (51 ± 4) & (67 ± 5) ng/L, (467 ± 31) vs (235 ± 21) & (323 ± 30) ng/L, P < 0.01 or P < 0.05) . Serum SOD activity and IL-2 level were significantly lower than those of S and Ost+ groups ( (75 ± 7) vs (93 ± 16) & (89 ± 5) U/ml, (95 ± 16) vs (198 ± 14) & (139 ± 11) ng/L, all P < 0.05) . All parameters showed no significant difference between S and Ost+ groups (all P > 0.05). CONCLUSIONS: Treatment of osthole may protect murine intestinal tissue against intestinal I/R injury. And the mechanisms may be due to its actions of preventing oxygen stress and inflammatory responses.

[Pharmacokinetic/pharmacodynamic modeling of antipyretic and reducing plasma concentration of NO effects of Rheum palmatum in rat].

Pharmacokinetic-pharmacodynamic (PK-PD) modeling was used to characterize the antipyretic and anti-inflammatory effects in rats of Rhein, a major component in rhubarb. Twenty-four healthy male Sprague-Dawley (SD) rats were randomly into four groups, of 6 each. The rats in first group were injected intravenously with lipopolysaccharide (LPS, 100 microg x kg(-1)). The second group rats were given rhubarb decoction (RD, 1.54 g x kg(-1)) by oral administration alone. The rats belonging to third group were administered orally RD 30 min after LPS injection. The rest rats were given normal saline only as control group. Orbital sinus blood sampling was collected at different time points. The Rhein and NO concentration in plasma and body temperature (BT) were measured. Relevant data of PK-PD modeling were performed with Kinetica 5. 0. 11. RD could suppress the rise in BT and plasma NO concentration. The antipyretic and anti-inflammatory responses were best described by a Sigmod-E(max) model. Delay between exposure and response was accounted for by a transit compartment model with two parallel transit compartment chains. The results showed that some parameters such as t1/2, C(max) and AUC were significantly increased in rats treated with LPS, compared to those in rats treated with normal saline. The EC50 for antipyretic effect and decrease of plasma NO concentration was respectively equal to 114.1, 90.80 microg x L(-1). The E(max) for antipyretic effect was about 111% of that for increase in BT after LPS injection. The E(max) for anti-inflammatory action was close to 8.399% of that for elevated NO level after modeling. Meanwhile, there was a difference in pharmacokinetic process of Rhein between the impact of normal saline and LPS. So, it can be concluded that the targets of regulating NO production and BT after RD administration may be at the same location. Not only do that, the antipyretic effect induced by RD maybe completely manifest through reducing the plasma concentration of NO.

Polyunsaturated fatty acid relatively decreases cholesterol content in THP-1 macrophage-derived foam cell: partly correlates with expression profile of CIDE and PAT members.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) have positive effect on the regulation of plasma lipids. But the mechanism for them to modulate lipid homeostasis in macrophage is still unclear. In this study, we employed PUFA to pretreat macrophages and evaluated the variations of lipid droplet (LD) content, lipid composition, and expressions of LD-associated genes in macrophage-derived foam cells. METHOD: THP-1-derived macrophages or human peripheral blood monocyte-derived macrophages were pre-treated with four non-esterified fatty acids (NEFAs) separately: saturated fatty acid (SFA)-palmitic acid (PA), monounsaturated fatty acids (MUFAs)-oleic acid (OA), PUFAs-linoleic acid (LA) and eicosapentaenoic acid (EPA). Intracellular lipid content and cholesterol efflux were analyzed in THP-1 macrophage-derived foam cells. Related gene expressions were detected by quantitative real-time PCR. RESULTS: PUFA pre-treatment reduced cholesterol content in foam cells and increased cholesterol efflux to lipid-free apoAI in conditioned medium compared with PA or OA group. Cell death-inducing DFF45 like effector (CIDE) and Perilipin-Adipophilin-TIP47 (PAT) family members, as LD-associated proteins, showed specific gene expression profiles after PUFA pre-treatment. These results may help to explain the process of lipid metabolism within foam cells. CONCLUSION: PUFA (LA or EPA) had a potential protective effect against cholesterol accumulation. The specific expressions of CIDE and PAT genes may provide clues to explore the protective mechanism of PUFA in foam cells.

LSDP5 enhances triglyceride storage in hepatocytes by influencing lipolysis and fatty acid ß-oxidation of lipid droplets.

Lipid storage droplet protein 5 (LSDP5) is a lipid droplet-associated protein of the PAT (perilipin, adipophilin, and TIP47) family that is expressed in the liver in a peroxisome proliferator-activated receptor alpha (PPARα)-dependent manner; however, its exact function has not been elucidated. We noticed that LSDP5 was localized to the surface of lipid droplets in hepatocytes. Overexpression of LSDP5 enhanced lipid accumulation in the hepatic cell line AML12 and in primary hepatocytes. Knock-down of LSDP5 significantly decreased the triglyceride content of lipid droplets, stimulated lipolysis, and modestly increased the mitochondrial content and level of fatty-acid ß-oxidation in the mitochondria. The expression of PPARα was increased in LSDP5-deficient cells and required for the increase in the level of fatty acid ß-oxidation in LSDP5-deficient cells. Using serial deletions of LSDP5, we determined that the lipid droplet-targeting domain and the domain directing lipid droplet clustering overlapped and were localized to the 188 amino acid residues at the N-terminus of LSDP5. Our findings suggest that LSDP5, a novel lipid droplet protein, may contribute to triglyceride accumulation by negatively regulating lipolysis and fatty acid oxidation in hepatocytes.