Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased poly(ADP-ribose) polymerase (PARP)-1 expression and activity are associated with inflammation but not goblet cell metaplasia in murine models of allergen-induced airway inflammation

ABSTRACT Inflammation plays a key role in lung injury and in the pathogenesis of asthma. Two murine models of allergic airway inflammation—sensitization and challenge to ovalbumin (OVA) and intratracheal exposure to interleukin-13 (IL13)—were used to evaluate the expression of poly(ADP-ribose) polymerase-1 (PARP-1) in allergic airway inflammation. Inflammation is prominent in OVA-induced allergic asthma, but this inflammation is greatly reduced by a PARP-1 inhibitor and almost eliminated when PARP-1 knockout mice are subjected to the OVA model. The present study temporally evaluated PARP-1 protein expression, localization, and activity, as well as inflammation and goblet cell metaplasia (GCM), in murine lungs following a single OVA challenge or IL13 exposure. Following OVA challenge PARP-1 protein expression and activity were greatly increased, being maximal at 3 to 5 days following OVA exposure and beginning to decrease by day 8. These changes correlated with the timing and degree of inflammation and GCM. In contrast, PARP-1 protein or activity did not change following single IL13 exposure, though GCM was manifested without inflammation. This study demonstrates that both PARP-1 protein and activity are increased by allergen-activated inflammatory mediators, excluding IL13, and that PARP-1 increase does not appear necessary for GCM, one of the characteristic markers of allergic airway inflammation in murine models.
Peroxiredoxin 6 differentially regulates acute and chronic cigarette smoke–mediated lung inflammatory response and injury

ABSTRACT Peroxiredoxin 6 (Prdx6) exerts its protective role through peroxidase activity against H2O2 and phospholipid hydroperoxides. We hypothesized that targeted disruption of Prdx6 would lead to enhanced susceptibility to cigarette smoke (CS)-mediated lung inflammation and/or emphysema in mouse lung. Prdx6 null (Prdx6−/−) mice exposed to acute CS showed no significant increase of inflammatory cell influx or any alterations in lung levels of proinflammatory cytokines compared to wild-type (WT) mice. Lung levels of antioxidant enzymes were significantly increased in acute CS-exposed Prdx6−/− compared to WT mice. Overexpressing (Prdx6+/+) mice exposed to acute CS showed significant decrease in lung antioxidant enzymes associated with increased inflammatory response compared to CS-exposed WT mice or air-exposed Prdx6−/− mice. However, chronic 6 months of CS exposure resulted in increased lung inflammatory response, mean linear intercept (Lm), and alteration in lung mechanical properties in Prdx6−/− when compared to WT mice exposed to CS. These data show that targeted disruption of Prdx6 does not lead to increased lung inflammatory response but is associated with increased antioxidants, suggesting a critical role of lung Prdx6 and several compensatory mechanisms during acute CS-induced adaptive response, whereas this protection is lost in chronic CS exposure leading to emphysema.
Transcatheter arterial embolization of acute gastrointestinal tumor hemorrhage with Onyx.

BACKGROUND Endovascular embolization has been used to control gastrointestinal tumor bleeding. Lots of embolic agents have been applied in embolization, but liquid embolic materials such as Onyx have been rarely used because of concerns about severe ischemic complications. AIM To evaluate the clinical efficacy and safety of transcatheter arterial embolization (TAE) with Onyx for acute gastrointestinal tumor hemorrhage. MATERIALS AND METHODS Between September 2011 and July 2013, nine patients were diagnosed as acute gastrointestinal tumor hemorrhage by clinical feature and imaging examination. The angiographic findings were extravasation of contrast media in the five patients. The site of hemorrhage included upper gastrointestinal bleeding in seven cases and lower gastrointestinal bleeding in two cases. TAE was performed using Onyx in all the patients, and the blood pressure and heart rate were monitored, the angiographic and clinical success rate, recurrent bleeding rate, procedure related complications and clinical outcomes were evaluated after therapy. The clinical parameters and embolization data were studied retrospectively. RESULTS All the patients (100%) who underwent TAE with Onyx achieved complete hemostasis without rebleeding and the patients were discharged after clinical improvement without a second surgery. No one of the patients expired during the hospital course. All the patients were discharged after clinical improvement without a second surgery. Postembolization bowel ischemia or necrosis was not observed in any of the patients who received TAE with Onyx. CONCLUSIONS TAE with Onyx is a highly effective and safe treatment modality for acute gastrointestinal tumor hemorrhage, even with pre-existing coagulopathy.
Structural and biochemical properties of Sept7, a unique septin required for filament formation

Abstract Septins constitute a family of conserved guanine nucleotide binding proteins found in a wide range of organisms from fungi to mammals. Members of the family share a canonical G-domain with N- and C-terminal extensions. G-domains assemble into hetero-oligomeric complexes which form non-polarised filaments or rings. Linear filaments are formed between the G-domains using either the guanine nucleotide binding site (G interface) or N- and C-terminal extensions (NC interface). Sept7 is a unique among the 13 human septins in that it occupies the ends of hexameric building blocks which assemble into non-polarised filaments. To gain insight into its particular properties we performed structural and biochemical studies on Sept7. We solved the crystal structure of a Sept7 dimer in the GDP-bound state. The structure and biochemistry of Sept7 provide new insights into the dynamics of the G interface and outline the differences in the properties of Sept7 compared to the members of group 2 septins.
Neuromodulation mediated by the tachykinin NK3-receptor agonist [MePhe7]-neurokinin B in the isolated perfused lung of nonsensitized nonchallenged and ovalbumin-sensitized and -challenged guinea pig

The neuromodulatory action of the tachykinin NK3-receptor agonist [MePhe7]-neurokinin B ([MePhe7]-NKB) was evaluated on vagal stimulation–induced bronchoconstriction in nonsensitized nonchallenged and ovalbumin (OVA)-sensitized and -challenged guinea pig using the isolated perfused lung preparation. Lungs were placed inside a warmed (37°C) glass chamber and suspended from a force displacement transducer (Grass FT-03) with both vagi connected to a stimulating electrode. Isolated lungs were stimulated at a constant voltage (20 V) and pulse duration (5 ms) with electrical stimulation frequencies ranging from 1 to 128 Hz. The authors demonstrated that vagal stimulation produced frequency-dependent bronchoconstriction and [MePhe7]-NKB, at a dose (0.1 μM) that does not produce bronchoconstriction by itself, potentiated the vagally induced bronchoconstriction at all frequencies in nonsensitized nonchallenged animals and to a greater extent in OVA-sensitized and -challenged guinea pigs; the potentiations were totally inhibited by the tachykinin NK3-receptor antagonist SR 142801 (1 μM). In a second set of experiments, [MePhe7]-NKB produced bronchoconstriction in a dose-dependent (1 to 300 μg/mL) manner with similar potencies and maximum responses in nonsensitized nonchallenged (EC50 = 8.6 ± 1.1 μM; EMax = 61.1 ± 3.5 mm Hg) and OVA-sensitized and -challenged (EC50 = 8.5 ± 1.3 μM; EMax = 63.5 ± 3.7 mm Hg) animals. In conclusion, these results demonstrated that [MePhe7]-NKB potentiated vagal stimulation–induced bronchoconstriction via the tachykinin NK3-receptors and OVA sensitization caused development of airway hyperresponsiveness in these potentiations. However, OVA sensitization had no effect on airway responsiveness of vagal stimulation–and [MePhe7]-NKB–induced bronchoconstrictions.
New twist in the regulation of cyclin D1

Abstract Among the cell cycle-related mammalian cyclins, cyclin D1 is more closely connected with cell proliferation in response to extracellular signals than the cell cycle clock itself. Because both its mRNA and protein are labile, the intracellular abundance of cyclin D1 is thought to be largely regulated at the level of transcription. However, recent findings suggest that, in certain cell types, cyclin D1 is post-translationally regulated, and a disturbance of this regulatory mechanism induces aberrant entry into the cell cycle and proliferation, sometimes leading to diseases such as cancer. In this review, we summarize recent findings and discuss the physiological role and cellular function of the novel mechanism of regulation of cyclin D1 in terms of the control of cell proliferation.
The synergetic effect of ambient PM2.5 exposure and rhinovirus infection in airway dysfunction in asthma: A pilot observational study from the central valley of california

ABSTRACT Background: Elevated levels of particulate matter PM2.5 and rhinovirus infection have been known to exacerbate asthma. However, the combined effect of rhinovirus infection and high PM2.5 has not been investigated. Purpose: To investigate the effect of PM2.5 and concomitant rhinovirus infection on airway function in asthma in an area with high PM2.5 concentration. Methods: Asthmatics and their matched controls were monitored for lung function, exhaled nitric oxide (eNO) and respiratory symptoms on days with varying levels of PM2.5. As the study was a repeated measure design, repeated clinical findings, and laboratory data were used in the mixed model analysis. Results: Wheezing and dyspnea in asthmatics were worsened with increasing ambient PM2.5. Increasing PM2.5 decreased FEV1% predicted (–0.51, –0.79 to –0.23) and FEF25–75% predicted (–0.66, –1.07 to –0.24) in subjects with asthma (all P < .01). Rhino viral infection reduced FEF25–75% predicted in subjects with asthma (–11.7, –20 to –2.9). The reductions in FEV25–75 and FEV1 per 10 μg/m3 increase in ambient PM2.5 were 6% and 5% respectively. A significant interaction was observed between presence of rhinovirus infection and elevated PM2.5 in asthmatics causing a 4-fold decrease in FEF25–75 (P = .01) and a 2-fold decrease in FEV1% predicted values (P = .01) compared with asthmatics with no rhino viral infection. Conclusions: Increasing ambient PM2.5 and low temperature independently worsened airway function in asthma. The interaction between rhinovirus and PM2.5 significantly impairs airway function in asthma. A larger sample size study is suggested to investigate these observations.
Epigenetherapy, a new concept

Abstract Small RNAs have been shown to regulate gene transcription by interacting with the promoter region and modifying the histone code. The exact mechanism of function is still unclear but the feasibility to activate or repress endogenous gene expression with small RNA molecules has already been demonstrated in vitro and in vivo. In traditional gene therapy non-mutated or otherwise useful genes are inserted into patient's cells to treat a disease. In epigenetherapy the action of small RNAs is utilized by delivering only the small RNAs to patient's cells where they then regulate gene expression by epigenetic mechanisms. This method could be widely useful not only for basic research but also for clinical applications of small RNAs.
Does extended lymph node dissection affect the lymph node density and survival after radical cystectomy?

BACKGROUND Diagnostic and therapeutic importance of pelvic lymph node (LN) dissection (PLND) in radical cystectomy (RC) has gained recent attention. A method of pathological analysis of LN affects total number of LN removed, number of LN involved, and LN density. OBJECTIVE To compare extended lymphadenectomy to standard lymphadenectomy in terms of LN yield, density, and effect on survival. MATERIALS AND METHODS From Jan 2004 - July 2009, 78 patients underwent RC whose complete histopathological report was available for analysis. All were transitional cell carcinoma. From July 2007 onward extended LN dissection was started and LNs were sent in six packets. Twenty-eight patients of standard PLND kept in group I. Group II had 23 patients of standard PLND (LN sent in four packets), and group III had 23 patients of extended PLND (LN sent in six packets). SPSS 15 software used for statistical calculation. RESULTS Distribution of T-stage among three groups is not statistically significant. Median number of LN harvested were 5 (range, 1-25) in group I, 9 (range, 3-28) in group II, and 16 (range, 1-25) in group III. Although this is significant, we did not find significant difference in number of positive LN harvested. We did not find any patient with skip metastasis to common iliac LN in group 3. CONCLUSIONS Separate package LN evaluation significantly increased the total number of LN harvested without increasing the number of positive LN and survival.
Knockdown of Drosha in human alveolar type II cells alters expression of SP-A in culture: A pilot study

ABSTRACT Human surfactant protein A (SP-A) plays an important role in surfactant metabolism and lung innate immunity. SP-A is synthesized and secreted by alveolar type II (ATII) cells, one of the two cell types of the distal lung epithelium (ATII and ATI). We have shown that miRNA interactions with sequence polymorphisms on the SP-A mRNA 3'UTRs mediate differential expression of SP-A1 and SP-A2 gene variants in vitro. In the present study, we describe a physiologically relevant model to study miRNA regulation of SP-A in human ATII. For these studies, we purified and cultured human ATII on an air-liquid interface matrix (A/L) or plastic wells without matrix (P). Gene expression analyses confirmed that cells cultured in A/L maintained the ATII phenotype for over 5 days, whereas P-cultured cells differentiated to ATI. When we transfected ATII with siRNAs to inhibit the expression of Drosha, a critical effector of miRNA maturation, the levels of SP-A mRNA and protein increased in a time dependent manner. We next characterized cultured ATII and ATI by studying expression of 1,066 human miRNAs using miRNA PCR arrays. We detected expression of >300 miRNAs with 24 miRNAs differentially expressed in ATII versus ATI, 12 of which predicted to bind SP-A 3'UTRs, indicating that these may be implicated in SP-A downregulation in ATI. Thus, miRNAs not only affect SP-A expression, but also may contribute to the maintenance of the ATII cell phenotype and/or the trans-differentiation of ATII to ATI cells, and may represent new molecular markers that distinguish ATII and ATI.
Determinants of culture success in an airway epithelium sampling program of young children with cystic fibrosis

ABSTRACT Aim of the study: The bronchial brushing technique presents an opportunity to establish a gold standard in vitro model of Cystic Fibrosis (CF) airway disease. However, unique obstacles exist when establishing CF airway epithelial cells (pAECCF). We aimed to identify determinants of culture success through retrospective analysis of a program of routinely brushing children with CF. Materials and methods: Anaesthetised children (CF and non-CF) had airway samples taken which were immediately processed for cell culture. Airway data for the CF cohort was obtained from clinical records and the AREST CF database. Results: Of 260 brushings processed for culture, 114 (43.8%) pAECCF successfully cultured to passage one (P1) and 63 (24.2% of total) progressed to passage two (P2). However, >80% of non-CF specimens (pAECnon-CF) cultured to P2 from similar cell numbers. Within the CF cohort, specimens successfully cultured to P2 had a higher initial cell count and lower proportion of severe CF mutation phenotype than those that did not proliferate beyond initial seeding. Elevated airway IL-8 concentration was also negatively associated with culture establishment. Contamination by opportunistic pathogens was observed in 81 (31.2% of total) cultures and brushings from children with lower respiratory tract infections were more likely to co-culture contaminating flora. Conclusions: Lower passage rates of pAECCF cultures uniquely contrasts with pAECnon-CF despite similar cell numbers. An equivalent establishment rate of CF nasal epithelium reported elsewhere, significant associations to CFTR mutation phenotype, elevated airway IL-8 and opportunistic pathogens all suggest this is likely related to the CF disease milieu.
Psychological disorders in women undergoing postoperative radiation and chemotherapy for breast cancer in India.

Indian Journal of Cancer | October-December 2011 | Volume 48 | Issue 4 glands and vague acini were seen. The cells were large, round to oval with moderate cytoplasm and vesicular nuclei with prominent nucleoli and occasional mitosis [Figure 4]. Many large glands were seen lined by cuboidal to columnar epithelial cells at the periphery, and the central area showed spindle-shaped cells in whorls, papillary pattern suggestive of PLGA [Figure 5]. A subtotal maxillectomy was performed and the defect was restored with an obturator [Figure 6].
Latrophilins updated

Abstract Latrophilins (LPHN) are part of a yet unexplored family of receptors comprising three isoforms, LPHN1-3, and belonging to a unique branch of G protein-coupled receptors (GPCR) named adhesion GPCR (aGPCR). LPHN are considered to be prototypical models for the study of aGPCR as they are one of the most evolutionary conserved members. Previously described as the target for a potent neurotoxin from the black widow spider venom, LPHN are now being studied under a whole new perspective. Indeed, recent advances have provided a better understanding of different aspects of this prototypical family of receptors: 1) elucidation of LPHN ectodomain organization by crystallography has unveiled a new functional domain with great repercussion on all the other members of the aGPCR family, 2) proteomic approaches have opened the gate to unsuspected functional characteristics of LPHN cellular role, and 3) genetic approaches have provided hints into the physiological functions of LPHN in specific systems and organisms. Moreover, genomic linkage studies screening human patients from diverse genetic backgrounds have involved LPHN gene defects in human disorders such as attention-deficit hyperactivity disorder and cancer. In this review, we will provide a historical perspective addressing experimental research on these receptors while highlighting the new advances and discoveries concerning LPHN functions. As GPCR still represent the most studied targets for the development of pharmacological approaches aiming at alleviating human disorders, the relevance of studying LPHN retains a high pertinence to better understand these receptors for the treatment of human diseases.
The emerging role of the first 17 amino acids of huntingtin in Huntington’s disease

Abstract Huntington’s disease (HD) is caused by a polyglutamine (polyQ) domain that is expanded beyond a critical threshold near the N-terminus of the huntingtin (htt) protein, directly leading to htt aggregation. While full-length htt is a large (on the order of ∼350 kDa) protein, it is proteolyzed into a variety of N-terminal fragments that accumulate in oligomers, fibrils, and larger aggregates. It is clear that polyQ length is a key determinant of htt aggregation and toxicity. However, the flanking sequences around the polyQ domain, such as the first 17 amino acids on the N terminus (Nt17), influence aggregation, aggregate stability, influence other important biochemical properties of the protein and ultimately its role in pathogenesis. Here, we review the impact of Nt17 on htt aggregation mechanisms and kinetics, structural properties of Nt17 in both monomeric and aggregate forms, the potential role of posttranslational modifications (PTMs) that occur in Nt17 in HD, and the function of Nt17 as a membrane targeting domain.
Invasive Fungal Infections in the Critically Ill Patient

Invasive fungal infections have become an increasingly prevalent and disturbing problem in critically ill patients. The advent of broad-spectrum antibacterial therapy and immunosuppressant therapy, among other factors such as mechanical ventilation, places the intensive care patient at significant risk for infection with pathogenic fungi. Most patients who become infected with invasive fungi, especially Candida species, have been previously colonized with the offending organism, lending to the notion that colonization precedes infection inmany cases. Despite an ever-increasing array of antifungal therapy for these infections, mortality rates remain extremely high, especially when the bloodstream is the primary site of infection. In addition, a shift toward more resistant pathogens such asCandida glabrata, Candida krusei, and moldswill provide clinicianswith therapeutic challenges for many years. The wide variation in acquisition cost across antifungal agents adds an additional layer of complexity to clinical decision making. Newer antifungal agents, each with its own advantages and disadvantages, have become available in recent years. Placing each agent in its appropriate niche is a dilemma that has yet to be solved.
Mercury and health care

Mercury is toxic heavy metal. It has many characteristic features. Health care organizations have used mercury in many forms since time immemorial. The main uses of mercury are in dental amalgam, sphygmomanometers, and thermometers. The mercury once released into the environment can remain for a longer period. Both acute and chronic poisoning can be caused by it. Half of the mercury found in the atmosphere is human generated and health care contributes the substantial part to it. The world has awakened to the harmful effects of mercury. The World Health Organization and United Nations Environmental Programme (UNEP) have issued guidelines for the countries’ health care sector to become mercury free. UNEP has formed mercury partnerships between governments and other stakeholders as one approach to reducing risks to human health and the environment from the release of mercury and its compounds to the environment. Many hospitals are mercury free now.
Occupational risk assessment of paint industry workers

Background: Thousands of chemical compounds are used in paint products, like pigments, extenders, binders, additives, and solvents (toluene, xylene, ketones, alcohols, esters, and glycol ethers). Paint manufacture workers are potentially exposed to the chemicals present in paint products although the patterns and levels of exposure to individual agents may differ from those of painters. The aim of the present study was to evaluate genome damage induced in peripheral blood lymphocytes and oral mucosa cells of paint industry workers. Materials and Methods: Genotoxicity was evaluated using the alkaline Comet assay in blood lymphocytes and oral mucosa cells, and the Micronucleus test in oral mucosa cells. For the micronucleus test in exfoliated buccal cells, no significant difference was detected between the control and paint industry workers. Results: The Comet assay in epithelia buccal cells showed that the damage index (DI) and damage frequency (DF) observed in the exposed group were significantly higher relative to the control group (P≤0.05). In the same way, the Comet assay data in peripheral blood leukocytes showed that both analysis parameters (DI and DF) were significantly greater than that for the control group (P≤0.05). Conclusions: Chronic occupational exposure to paints may lead to a slightly increased risk of genetic damage among paint industry workers.