Identification and experimental validation of PYCARD as a crucial PANoptosis-related gene for immune response and inflammation in COPD.

Chronic inflammatory and immune responses play key roles in the development and progression of chronic obstructive pulmonary disease (COPD). PANoptosis, as a unique inflammatory cell death modality, is involved in the pathogenesis of many inflammatory diseases. We aim to identify critical PANoptosis-related biomarkers and explore their potential effects on respiratory tract diseases and immune infiltration landscapes in COPD. Total microarray data consisting of peripheral blood and lung tissue datasets associated with COPD were obtained from the GEO database. PANoptosis-associated genes in COPD were identified by intersecting differentially expressed genes (DEGs) with genes involved in pyroptosis, apoptosis, and necroptosis after normalizing and removing the batch effect. Furthermore, GO, KEGG, PPI network, WGCNA, LASSO-COX, and ROC curves analysis were conducted to screen and verify hub genes, and the correlation between PYCARD and infiltrated immune cells was analyzed. The effect of PYCARD on respiratory tract diseases and the potential small-molecule agents for the treatment of COPD were identified. PYCARD expression was verified in the lung tissue of CS/LPS-induced COPD mice. PYCARD was a critical PANoptosis-related gene in all COPD patients. PYCARD was positively related to NOD-like receptor signaling pathway and promoted immune cell infiltration. Moreover, PYCARD was significantly activated in COPD mice mainly by targeting PANoptosis. PANoptosis-related gene PYCARD is a potential biomarker for COPD diagnosis and treatment.

[Herbalogical study on olibanum(Ruxiang)].

As a representative foreign medicinal material, olibanum(Ruxiang) was imported to China since the Qin and Han Dynasties. Olibanum was first described as a medicinal by the name "Xunluxiang" in Miscellaneous Records of Famous Physicians(Ming Yi Bie Lu). This study investigated historical records on olibanum and conducted the herbalogical study. It was found that olibanum came from the resin mainly obtained from the bark of Pistacia lenticus before the Tang Dynasty. With the prosperity of the Maritime Silk Road, instead, the resin obtained from the bark of Boswellia carterii was mainly used as olibanum. In ancient time, the oleo-gum-resin secreted from the cut bark was collected in spring and summer, and the quality was judged based on transparency and shape. The processing methods of olibanum went through many evolutions, which changed from simple methods such as grinding and frying to complex methods such as levigating and grinding with wine, and now to frying and processing with vinegar. The usage of olibanum included alchemy, folk and religious incense, bathing, cosmetic and medicinal since ancient times. From the Song Dynasty, olibanum had been mainly used as medicinal because of its good effect to treat wounds. In traditional Chinese medicine, olibanum unblocks menstruation, relieves pain and reduces swelling and generated muscles. The medicinal efficacy of olibanum is not much different from ancient to modern. Only the efficacy of replenishing energy and promoting the movement of Qi was rarely mentioned in modern reference. In this article, the historical evolutions of olibanum about original plants, processing and medicinal efficacy were sorted out. The results could provide historical basis for the further development and clinical utilization of olibanum.

Preparation of MnOx Supported LiOH Activated Soybean Oil Sludge Catalyst and Its Analysis in Denitration Mechanism of Selective Catalytic Oxidation (SCO).

Treatment with selective catalytic oxidation (SCO) is an effective technology applied recently for conversion of nitrogen oxides pollution control. In order to solve the problems of high cost and difficulties in practical application of SCO catalyst, it was put forward using the solid waste sludge from soybean oil plant as catalyst carrier to prepare denitration catalyst. The sludge was treated by alkaline activation and then MnOx-based sludge was prepared by impregnation. Finally, MnOx-based sludge was calcined in the muffle furnace. The effects of activation and calcination conditions on catalyst activity were investigated. Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to characterize the activity of the sludge based denitration catalyst, and the structure and activity of the sludge based denitration catalyst were furtherly confirmed. According to the achieved results, (1) after activated by LiOH with a mass concentration of 15% for 4 hours, the surface of the sludge catalyst has more alkali functional groups, making the denitration of sludge catalyst the best; (2) the MnOx-based catalyst calcined in the muffle furnace with calcination temperature of 450 °C for 4 hours has obvious denitration efficiency.

Cooperative effect of random and time-periodic coupling strength on synchronization transitions in one-way coupled neural system: mean field approach.

The cooperative effect of random coupling strength and time-periodic coupling strengh on synchronization transitions in one-way coupled neural system has been investigated by mean field approach. Results show that cooperative coupling strength (CCS) plays an active role for the enhancement of synchronization transitions. There exist an optimal frequency of CCS which makes the system display the best CCS-induced synchronization transitions, a critical frequency of CCS which can not further affect the CCS-induced synchronization transitions, and a critical amplitude of CCS which can not occur the CCS-induced synchronization transitions. Meanwhile, noise intensity plays a negative role for the CCS-induced synchronization transitions. Furthermore, it is found that the novel CCS amplitude-induced synchronization transitions and CCS frequency-induced synchronization transitions are found.

Peroxisome Proliferator-Activated Receptor α Activation Suppresses Cytochrome P450 Induction Potential in Mice Treated with Gemfibrozil.

Gemfibrozil, a peroxisome proliferator-activated receptor α (PPARα) agonist, is widely used for hypertriglyceridaemia and mixed hyperlipidaemia. Drug-drug interaction of gemfibrozil and other PPARα agonists has been reported. However, the role of PPARα in cytochrome P450 (CYP) induction by fibrates is not well known. In this study, wild-type mice were first fed gemfibrozil-containing diets (0.375%, 0.75% and 1.5%) for 14 days to establish a dose-response relationship for CYP induction. Then, wild-type mice and Pparα-null mice were treated with a 0.75% gemfibrozil-containing diet for 7 days. CYP3a, CYP2b and CYP2c were induced in a dose-dependent manner by gemfibrozil. In Pparα-null mice, their mRNA level, protein level and activity were induced more than those in wild-type mice. So, gemfibrozil induced CYP, and this action was inhibited by activated PPARα. These data suggested that the induction potential of CYPs was suppressed by activated PPARα, showing a potential role of this receptor in drug-drug interactions and metabolic diseases treated with fibrates.

Gemfibrozil not fenofibrate decreases systemic glucose level via PPARα.

BACKGROUND: Concurrence of high glucose or diabetes in patients with dyslipidemia is presenting major challenges for clinicians. Although sporadically reported, a rational basis for the use of fibrates for the treatment of dyslipidemia with concurrent metabolic syndrome has not been established. METHODS: In this study, wild-type (WT) and Ppara-null (KO) mice were fed a serial gemfibrozil- and fenofibrate-containing diet under the same experimental conditions for 14 days. Glucose level in the blood, glycogen storage in the liver tissues, and the potential toxic responses were assayed. Genes involved in glucose metabolism were determined by quantitative polymerase chain reaction analysis. RESULTS: Both the blood glucose level and the glycogen content in the liver were down-regulated by gemfibrozil but not by fenofibrate in WT mice, in a dose-dependent manner. This decrement did not occur in KO mice for either fibrate agent. Secondary regulation on the transcription of pyruvate kinase, and gluconolactonase were observed following gemfibrozil treatment, which was differential between WT mice and KO mice. CONCLUSIONS: Gemfibrozil, not fenofibrate, down-regulates systemic glucose level and glycogen storage in the liver dependent on PPARα, suggesting its potential value for treatment of dyslipidemia with concurrent diabetes or high glucose levels.

[Identification of susceptibility to acute mountain sickness by detecting vascular tone using a photoplethysmographic sensor].

OBJECTIVE: Vascular tone had shown the potential susceptibility to acute mountain sickness (AMS), however the detailed tendency has not been studied. METHODS: Vascular tone, SpO2 and Rate pressure product (RPP) were studied in seventeen healthy subjects before and after rapid ascent from sea level to 3658 m. Human acute mountain sickness was evaluated by the Lake Louise Score (LLS). RESULTS: Nine of the seventeen participants were diagnosed with AMS. On initial exposure, there was a significant decrease in vascular tone between subjects with and without AMS. Significance was also found in the decrease of SpO2 before and after rapid ascent but the differences between subjects with and without AMS did not reach significance during the initial phase. CONCLUSIONS: s:Vascular tone on initial exposure in response to rapid ascent is a possible sign of susceptibility to AMS. Conclusion: measurement of vascular tone using a wearable sensor throughout the acute phase response will provide numerical values of pathophysiology throughout the development of AMS.

An outbreak of hepatitis A associated with a contaminated well in a middle school, Guangxi, China.

BACKGROUND: In May 2012, an outbreak of viral hepatitis A was reported to the Guangxi Center for Disease Control and Prevention from a middle school in Liujiang County. An investigation was conducted to identify the cause and mode of transmission and to recommend control and prevention measures. METHODS: A case was defined as any person from the middle school with onset of fatigue, anorexia, abdominal pain, diarrhoea or jaundice from 20 February to 20 May 2012. We compared attack rates (AR) between boys and girls, assuming that only boys used well water and girls used pipeline water. We then selected 133 students from three classes in each of the three grades to compare AR by reported water source and drinking history. RESULTS: There were 22 cases, an AR of 3.8% (21/553) for students and 1.5% for teachers (1/65). Those who used well water were 8.7 (95% confidence interval [CI] = 2.1-37.2) times more likely to be ill than those using pipeline water. The cohort study showed that students who reported using well water daily were 5.2 (95% CI = 0.7-41.8) times more likely to be ill than those that reported using the pipeline water daily. Eighteen cases were confirmed as hepatitis A. CONCLUSION: This hepatitis A outbreak was potentially caused by a contaminated school well. We recommended that the school discontinue using the well and that the students should drink boiled water. As there is a vaccine for hepatitis A, we recommended that several doses of the vaccine be stored for controlling outbreaks and for immunizing susceptible populations in future outbreaks.

New candidate tumor-suppressor gene KLF6 and its splice variant KLF6 SV2 counterbalancing expression in primary hepatocarcinoma.

BACKGROUND/AIMS: This study aimed to detect the expression of newly discovered zinc finger transcriptional factor KLF6 and its splice variant KLF6 SV2 in primary hepatocarcinoma (PHC) tissues and hepatoma cell strains, and to evaluate their clinicopathologic relationship with PHC. METHODOLOGY: Wild-type KLF6 and KLF6 SV2 mRNA expression was determined by RTPCR in 27 cases of PHC tissues and cell strains of HepG2, SMMC7721 and LO2. Western blotting and immunohistochemical staining were adopted to detect KLF6 protein expression. Positive area ratio of wild-type KLF6 protein expression and its relationship with clinicopathological parameters of PHC was analyzed. RESULTS: Wild-type KLF6 expression in PHC tissues was lower than that in paracancerous tissues. In contrast, KLF6 SV2 mRNA expression was higher in PHC tissues and hepatoma cell strains (p<0.05). Positive area ratio of wild-type KLF6 protein expression was positively correlated with cellular differentiation degree of PHC (p<0.01), but negatively correlated not only with liver cirrhosis, tumor size and extrahepatic metastases (p<0.01), but also with portal vein thrombus and the number of lymph nodes with metastasis (p<0.05). CONCLUSIONS: Wild-type KLF6 deletion and inactivation was involved in the growth, cell differentiation and other physiological processes of PHC. The upregulation of KLF6 splice variant might counterbalance the wildtype KLF6 and contribute to the occurrence and development of PHC.

Clinicopathological and prognostic significance of Bmi-1 expression in human cervical cancer.

OBJECTIVE: To investigate the clinical significance of Bmi-1 expression as a prognostic marker for cervical cancer. Design. Retrospectively collected data from a population-based cohort. SETTING: Jiangsu Province Hospital. Population. Eighty-eight women diagnosed with cervical carcinoma between 2000 and 2003. METHODS: RT-PCR assay was performed to determine Bmi-1 mRNA expression in 18 cervical cancer and noncancerous tissue samples and immunohistochemistry to detect Bmi-1 protein expression in 88 cervical cancer samples. The correlation between Bmi-1 expression and clinicopathological factors was analyzed. Additionally, statistical analyses were applied to test for prognostic associations. RNA interference was used to downregulate Bmi-1 expression in a cervical cancer cell line (HeLa). In vitro cytotoxicity was measured by the methylthiazoletetrazolium and colony formation assays. Effects of Bmi-1 inhibition on in vivo growth of cancer cells was detected by the tumorigenicity assay. Cell cycle distribution and cell apoptosis were measured by flow cytometry. MAIN OUTCOME MEASURES: The levels of Bmi-1 mRNA and protein expression in tissues were evaluated by RT-PCR and Western Blot assays. RESULTS: The level of Bmi-1 mRNA expression in cervical cancer tissues was significantly higher than that in corresponding noncancerous tissues. High Bmi-1 expression was significantly correlated with poor tumor differentiation, advanced International Federation of Gynecology and Obstetrics stage and positive lymph node metastasis. Patients with high Bmi-1 expression showed shorter overall survival than those with low expression. Univariate and multivariate analyses showed that high Bmi-1 expression was an independent prognostic factor. CONCLUSIONS: RNA interference-mediated Bmi-1 inhibition could inhibit in vitro and in vivo growth, enhance apoptosis and induce cell cycle arrest of cervical cancer cells. Bmi-1 might be an independent prognostic marker for cervical cancer patients.

Pharmacologic vitreolysis with plasmin and hyaluronidase in diabetic rats.

OBJECTIVE: To evaluate the feasibility of inducing posterior vitreous detachment (PVD) with pharmacologic vitreolysis in diabetic rats. METHODS: Forty diabetic rats were randomly divided into four groups and treated with different drugs by intravitreous injection respectively as follows: Group A: hyaluronidase (5 U); Group B: plasmin (0.25 U); Group C: hyaluronidase (5 U) plus plasmin (0.25 U); and Group D: balanced salt solution (2 microL). Ten normal rats in Group E were used as controls and were treated with hyaluronidase (5 U) plus plasmin (0.25 U). Clinical observation, visual electrophysiology tests (electroretinogram), transmission electron microscopy, and scanning electron microscopy were performed on the rats 1 week after the injection. RESULTS: Scanning electron microscopy results showed that PVD did not occur at all with hyaluronidase alone (Group A, 0 of 10) and balanced salt solution alone (Group D, 0 of 10). Partial PVD was found in all eyes treated with plasmin alone (Group B, 10 of 10), whereas complete PVD was present in most but not all eyes treated with both hyaluronidase and plasmin (Group C, 8 of 10). All nondiabetic eyes treated with hyaluronidase and plasmin had total PVD (Group E, 10 of 10). No significant difference in electroretinogram was observed in each group before and after the injection (P < 0.05). CONCLUSION: Hyaluronidase (5 U) alone is ineffective, whereas plasmin (0.25 U) alone induces partial PVD, a very dangerous state for the diabetic eye. Combination of hyaluronidase and plasmin can induce complete PVD in 12-week old diabetic rats. However, it is more difficult to induce PVD in diabetic rats than in healthy rats. No obvious toxic reaction was observed in each group.

Intra subject 3D/3D kidney registration using local mutual information maximization.

One of the goal of the Nephron-Sparing Surgery properative planning is to delineate as exactly as possible the renal carcinoma and to specify its relations to the renal arterial, venous and collecting system anatomies. The classical preoperative imaging system is the Spiral CT Urography, which gives sucessive 3D acquisitions of complementary information The integration of this information within the a patient spacific anatomical referential can be achieved by intra-patient registration techniques. A local MI maximization registration method is proposed in this paper. The kidneys are extracted from the abdomen volumes and then the registration between the extracted kidneys is implemented by maximizing the MI between them. The experimental results demonstrates that this method is effective.

Cathepsin K in adipocyte differentiation and its potential role in the pathogenesis of obesity.

CONTEXT: The alteration of protein expression in white adipose tissue (WAT) may contribute to the pathogenesis of obesity. OBJECTIVE: The aim of the present study was to uncover proteins differentially expressed in the WAT of overweight/obese subjects and study the role of the identified proteins in adipocyte differentiation. DESIGN AND SETTING: Two-dimensional electrophoresis and matrix-assisted laser desorption ionization-time of flight-mass spectrometry were used to identify proteins differentially expressed in WAT between obese/overweight and control groups. Cathepsin K (CTSK), one of the proteins identified by the above methods, was highlighted to assess its effects on adipocyte differentiation through 3T3-L1 cell line. RESULTS: Human visceral adipose tissue of overweight/obese subjects displayed a differential protein expression profile, compared with that of normal-weight controls. CTSK was up-regulated in the WAT of overweight/obese subjects, and it had a significant positive correlation with body mass index. In vitro study showed that CTSK expression and its enzyme activity gradually increased in the process of adipocyte differentiation. Moreover, E-64, an inhibitor of CTSK, could prevent adipocyte differentiation in a dose-dependent manner, which was characterized by the absence of triglyceride accumulation and glycerol contents. CONCLUSIONS: CTSK, a cysteine protease involved in extracellular matrix remodeling, could be one of the determinants of adipocyte differentiation. CTSK may be involved in the pathogenesis of obesity by promoting adipocyte differentiation.

Fibronectin and neuroprotective effect of granulocyte colony-stimulating factor in focal cerebral ischemia.

Stroke is one of the leading causes of unnatural death and disability. No effective therapy is available. Recombinant human granulocyte colony-stimulating factor (rhG-CSF), as a mobilizing agent for bone marrow stem cells, can promote stem cell mobilization, homing to brain after cerebral ischemia. In the present study, the administration of G-CSF significantly increased number of CD34(+) cells in the marginal zone of the infarction. Rats receiving G-CSF had higher survival rate and lower infarction volume. Neurological behavior was improved, and the expression of fibronectin in the ischemic brain was increased, as compared to rats treated with vehicle. To mimic the ischemia-reperfusion injury in experimental animals, we employed hippocampal slice cultures that were first treated with oxygen and glucose deprivation (OGD) and then with oxygen-glucose resupply, finding that fibronectin significantly increased the neurite outgrowth of OGD hippocampal slices, upregulated the expression of Bcl-2 protein, and ameliorated the ultrastructure damage of OGD hippocampal slices.