Miracle-dz/UniFAR-FTUs huggingface dataset:
Melatonin protects against common deletion of mitochondrial DNA‐augmented mitochondrial oxidative stress and apoptosis

Abstract: Defected mitochondrial respiratory chain (RC), in addition to causing a severe ATP deficiency, often augments reactive oxygen species (ROS) generation in mitochondria (mROS) which enhances pathological conditions and diseases. Previously, we demonstrated a potent endogenously RC defect‐augmented mROS associated dose‐dependently with a commonly seen large‐scale deletion of 4977 base pairs of mitochondrial DNA (mtDNA), i.e. the common deletion (CD). As current treatments for CD‐associated diseases are rather supplementary and ineffective, we investigated whether melatonin, a potential mitochondrial protector, provides beneficial protection for CD‐augmented mitochondrial oxidative stress and apoptosis particularly upon the induction of a secondary oxidative stress. Detailed mechanistic investigations were performed by using laser scanning dual fluorescence imaging microscopy to provide precise spatial and temporal resolution of mitochondrial events at single cell level. We demonstrate, for the first time, that melatonin significantly prevents CD‐augmented mROS formation under basal conditions as well as at early time‐points upon secondary oxidative stress induced by H2O2 exposure. Thus, melatonin prevents mROS‐mediated depolarization of mitochondrial membrane potential (ΔΨm) and subsequent opening of the mitochondrial permeability transition pore (MPTP) and cytochrome c release. Moreover, melatonin prevents depletion of cardiolipin which appears to be crucial for postponing later MPTP opening, disruption of the mitochondrial membrane and apoptosis. Finally, the protection provided by melatonin is superior to those caused by the suppression of mitochondrial Ca2+ regulators including the mitochondrial Na+‐Ca2+ exchanger, the MPTP, and the mitochondrial Ca2+ uniporter and by antioxidants including vitamin E and mitochondria‐targeted coenzyme Q, MitoQ. As RC defect‐augmented endogenous mitochondrial oxidative stress is centrally involved in a variety of pathological conditions and diseases, melatonin thus may serve as a therapeutic drug to benefit many clinical conditions that involve malfunction of the mitochondria.
Intracellular HMGB1 transactivates the human IL1B gene promoter through association with an Ets transcription factor PU.1

High mobility group box 1 protein (HMGB1), originally described as a non‐histone, DNA binding protein, was recently identified as a late mediator of inflammation via its extracellular release from activated macrophages/monocytes. In the present study, we report that intracellular HMGB1 synergizes with a macrophage/monocyte‐specific E26 transformation‐specific sequence (Ets) transcription factor PU.1 to transactivate the promoter of the IL1B gene coding a 31‐kDa proIL‐1β protein. The −131 to +12 IL1B promoter, which possesses a PU.1 binding motif essential for its transactivation, was induced when HMGB1 expression vector was transfected into murine RAW264.7 macrophage cells. Our glutathione S‐transferase‐pulldown and coimmunoprecipitation assays demonstrated direct physical interaction of HMGB1 with PU.1. Deletion of the PU.1 winged helix‐turn‐helix DNA‐binding domain inhibited the association of the two proteins. In electrophoretic mobility shift assay using recombinant PU.1 protein, a ternary complex of PU.1, HMGB1 and PU.1‐binding element within the IL1B promoter was generated. The importance of PU.1 was further supported by our observation that induction of the IL1B promoter was obtained only after PU.1 expression in PU.1‐deficient murine EL4 thymoma cells. Thus, our data raise the possibility of a novel mechanism which sustains and amplifies inflammatory reactions through physical interaction of PU.1 with intracellular HMGB1 in macrophages/monocytes.
Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors

Traditional treatment of infectious diseases is based on compounds that kill or inhibit growth of bacteria. A major concern with this approach is the frequent development of resistance to antibiotics. The discovery of communication systems (quorum sensing systems) regulating bacterial virulence has afforded a novel opportunity to control infectious bacteria without interfering with growth. Compounds that can override communication signals have been found in the marine environment. Using Pseudomonas aeruginosa PAO1 as an example of an opportunistic human pathogen, we show that a synthetic derivate of natural furanone compounds can act as a potent antagonist of bacterial quorum sensing. We employed GeneChip® microarray technology to identify furanone target genes and to map the quorum sensing regulon. The transcriptome analysis showed that the furanone drug specifically targeted quorum sensing systems and inhibited virulence factor expression. Application of the drug to P.aeruginosa biofilms increased bacterial susceptibility to tobramycin and SDS. In a mouse pulmonary infection model, the drug inhibited quorum sensing of the infecting bacteria and promoted their clearance by the mouse immune response.
Immunohistochemical Localization of Some Neurotransmitters in Mole-rats (Spalax leucodon) Intestinal Plexus

The aim of this study was to investigate the presence of calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP) and serotonin immunoreactivity in the intestinal plexus of mole-rats (Spalax leucodon). Immunohistochemical methods were conducted on the ileum and colon of the small and large intestine. CGRP immunoreactive neuronal structures were detected in the form of enteric ganglia within the myenteric plexus of ileum and colon. SP immunoreactivity in both of muscle layer of these intestine regions were identified in the form of running nerve fibers and myenteric ganglia. Also, NPY immunoreactive nerve cell bodies and fibers were present in the lamina propria and myenteric plexus of ileum and colon. However, VIP and serotonin immunoreactive neuronal structures were not detected in any other region of the small and large intestines. In conclusion, this study demonstrated the presence of different neuronal populations in the mucosal and ganglionated plexuses in the small and large intestine of the mole rats.
Pilot Study

Abstract Poor nutrition may contribute to the incidence and complications of hip fractures. An interview survey was used to assess the nutrition knowledge and attitudes of 40 female and 10 male elderly subjects hospitalized with hip fractures at a local community hospital. Subjects were recruited from a sample of convenience able to respond appropriately. Ninety-two percent of the subjects were unaware of the potential role nutrition plays in recovery. Once counseled on the possible benefits, 80% of the participants were willing to implement some degree of nutrition therapy. While inferential statistics yielded no statistically significant correlations, the practical applications are of importance.
Role of oxidative stress in cardiovascular diseases

Objectives In view of the critical role of intracellular Ca2+-overload in the genesis of myocyte dysfunction and the ability of reactive oxygen species (ROS) to induce the intracellular Ca2+-overload, this article is concerned with analysis of the existing literature with respect to the role of oxidative stress in different types of cardiovascular diseases. Observations Oxidative stress in cardiac and vascular myocytes describes the injury caused to cells resulting from increased formation of ROS and/or decreased antioxidant reserve. The increase in the generation of ROS seems to be due to impaired mitochondrial reduction of molecular oxygen, secretion of ROS by white blood cells, endothelial dysfunction, auto-oxidation of catecholamines, as well as exposure to radiation or air pollution. On the other hand, depression in the antioxidant reserve, which serves as a defense mechanism in cardiac and vascular myocytes, appears to be due to the exhaustion and/or changes in gene expression. The deleterious effects of ROS are mainly due to abilities of ROS to produce changes in subcellular organelles, and induce intracellular Ca2+-overload. Although the cause–effect relationship of oxidative stress with any of the cardiovascular diseases still remains to be established, increased formation of ROS indicating the presence of oxidative stress has been observed in a wide variety of experimental and clinical conditions. Furthermore, antioxidant therapy has been shown to exert beneficial effects in hypertension, atherosclerosis, ischemic heart disease, cardiomyopathies and congestive heart failure. Conclusions The existing evidence support the view that oxidative stress may play a crucial role in cardiac and vascular abnormalities in different types of cardiovascular diseases and that the antioxidant therapy may prove beneficial in combating these problems.
Diagnosis and staging of hepatocellular carcinoma prior to transplantation: Expertise or failure

Liver transplantation is an effective treatment for hepatocellular carcinoma (HCC), and for years there has been a major effort to define which patients were the optimal candidates for this intervention. Several studies conducted in the early years of transplantation evidenced that patients with advanced HCC (defined as large/multifocal tumors or by the presence of vascular invasion) should be excluded from the procedure because of almost universal recurrence in the short term. The seminal work by Mazzaferro et al., together with data from Paris, Barcelona, and Berlin, as well as from other groups, demonstrated that the best results in terms of survival with minimal recurrence were achieved in patients with tumors diagnosed at an early stage and defined as single HCC 5 cm in diameter or up to 3 nodules 3 cm in diameter. This definition is currently the accepted criteria for candidate selection in most countries. Proposals for expansion have been raised, but new limits have not been properly validated in enough number of cases prospectively recruited. Larger size is associated with a high rate of vascular invasion and, ultimately, tumor recurrence. In addition, recent data on live donation show that expansion should be carefully defined to avoid less than optimal results. In any case, the current clinical challenge is not howmanymore patients could be enlisted for transplantation, but how to accurately diagnose HCC, how to define the extent of the disease and, finally, how to establish priorities to guarantee a fair and equative distribution of the scarce number of available livers. Fortunately, the clinical research conducted up to now has been fruitful in exposing the successes and failures of different strategies and allowed a steady improvement of our knowledge of the disease. Thus, several studies have pointed out which concepts or approaches should be abandoned or at least largely improved. The manuscripts by Kemmer et al. and by Freeman et al. published in this issue of Liver Transplantation are important additions in that regard. Kemmer et al. analyzed the United Network for Organ Sharing (UNOS) database to assess whether a concentration of alpha-fetoprotein (AFP) increasing beyond 500 ng/mL is a valid criterion to indicate liver transplantation because of HCC suspicion, even if imaging techniques are negative. Such a scenario depicts a stressful clinical dilemma that several transplant groups have faced: Is it justified to transplant a cirrhotic patient for whom the HCC suspicion may not be confirmed, or it is better to adopt a “wait and see” approach that may finally demonstrate a massive HCC not suitable for transplantation? The reduced sensitivity of old imaging techniques could have justified the proposal of transplantation because of increasing AFP in the absence of positive imaging findings. At the time of old imaging techniques, the majority of patients with increased AFP would ultimately have been proven to bear HCC if explored by laparoscopy or necropsy. Today, however, the sensitivity of imaging techniques for
“Do-Live-Well”: A Canadian framework for promoting occupation, health, and well-being

Background. Occupational therapists can bring a unique and valuable perspective to the national dialogue on health promotion. Current approaches have a narrow focus on diet and exercise; a broader focus on occupation has the potential to enrich understanding regarding forces that contribute to health and well-being. Purpose. A new “Do-Live-Well” framework will be presented that is grounded in evidence regarding the links between what people do every day and their health and well-being. Key Issues. Elements of the framework include eight different dimensions of experience and five key activity patterns that impact health and well-being outcomes. Personal and social forces that shape activity engagement also affect the links to health and well-being. Implications. The framework is designed to facilitate individual reflection, community advocacy, and system-level dialogue about the impact of day-to-day occupations on the health and well-being of Canadians.
The Effects of Multiple Administrations of Sevoflurane to Cynomolgus Monkeys: Clinical Pathologic, Hematologic, and Pathologic Study

The effect of multiple administrations of sevoflurane was evaluated by several measures of toxicity.Cynomolgus monkeys assigned to a control group and three treatment groups were anesthetized with sevoflurane at 1.0, 1.6, and 2.0 times the minimum alveolar anesthetic concentration (MAC) for 3 h/day, 3 days/wk for 8 wk. Reductions in total erythrocyte and leukocyte counts and increases in serum enzymes were the only changes noted. The increases in the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactic dehydrogenase (LDH), and creatinine kinase (CK), occurred at Week 1 at all three concentrations of sevoflurane. These increases were dose-related, and returned to baseline by Week 2 for 1.0 MAC. All serum enzyme concentrations had returned to baseline by the end of the study. There were no gross pathologic, histopathologic, or ultrastructural differences found in any of the four groups of monkeys. At 2.0 MAC, three deaths occurred. The multiple administrations of 1.0 and 1.6 MAC sevoflurane anesthesia were well tolerated by the monkeys. The techniques of this study did not detect adverse effects from the above enzyme changes. (Anesth Analg 1995;81:347-52)
Evaluation of Some Methods of Histamine Determination to be used in HACCP System Implementation of Sardine Canning Process.

Histamine is the most important chemical hazards in fish and fishery products, where it is the main cause of histamine poisoning. The HACCP approach offers the advantage of in process control of histamine formation. This avoids the need for large scale terminal analysis of finished products which is time consuming and beyond the capabilities of many small canneries. In HACCP system, most monitoring procedures for critical control points should be done rapidly because the relation to on line processes. So, ELISA (Ridascreen R Histamine), ion exchange (Rida R Quick Histamine) and TLC techniques for histamine determination in sardine were evaluated and compared with HPLC methods as the most sensitive one (Detection limit, 1.2 ppm). Statistically, there were no significant differences between the results of TLC technique and those obtained by HPLC. In addition to histamine measurement, TLC also characterized by the possibility to analyse histamine potentiators (cadaverine, putrescine, tyramine) in 12 sardine samples at the same time on one plate. Although ELISA and ion exchange methods were characterized by simplicity and relatively low cost, its data were significantly higher than HPLC results. Receiving, sterilization and incubation period steps were established as CCPs during sardine canning. ELISA was recommended for the determination of histamine in sardine receiving step just as a screening technique. More study is required to identify an accurate and rapid technique for monitoring the histamine levels during sardine canning process. HPLC as well as TLC methods can be used in the verification step to ensure the efficiency of HACCP plan.
Association of Fc Gamma Receptor IIA Polymorphisms with Acute Renal-Allograft Rejection

Acute rejection is a leading cause of early renal-allograft failure. The human Fc gamma receptor IIA (Fc&ggr;RIIA) forms an essential link between the humoral branch and the effector cells of the immune system. In this study, we examined Fc&ggr;RIIA genotypes in renal-allograft recipients (rejectors) with acute graft rejection and in a number of control groups to investigate a possible association between Fc&ggr;RIIA polymorphism and acute renal-allograft rejection. The distribution of the genotypes in the study patient group differed from the control groups. The frequency of homozygosity for Fc&ggr;RIIA-R/R131 in the rejectors was significantly higher than that in the recipients (nonrejectors) with well-functioning renal allografts and in blood donors (P< 0.05). In comparison with the control groups, the rejectors displayed a higher R131 allele frequency (P< 0.05) and a lower H131 allele frequency (P< 0.05). These results reveal a significant association between Fc&ggr;RIIA-R/R131 and acute renal-graft rejection, and it is likely that Fc&ggr;RIIA polymorphisms could be useful markers for potential risk of rejection.
Expression of chemokine receptors CXCR4, CXCR5 and CCR7 on B and T lymphocytes from patients with primary antibody deficiency

The interaction of chemokines and their receptors directs lymphocyte migration, and is involved in the distribution and organization of lymphocytes within lymphoid tissues. We reasoned that abnormal chemokine receptor expression might give rise to defects of lymphocyte migration into and within lymphoid tissues, and consequently be associated with defective antibody production in primary antibody deficiencies. In this study, we have investigated the expression of chemokine receptors CXCR4, CXCR5 and CCR7 on lymphocyte subpopulations (naive and memory B cells; CD4+ and CD8+ T cells) in a cohort of patients with primary antibody deficiency (n = 23), and compared these with a group of healthy controls (n = 19). We show that there were significant differences in both the proportions of lymphocytes expressing, and the levels of expression of, specific chemokine receptors on individual lymphocyte subpopulations between patients and controls. Furthermore, these changes appeared more pronounced in patients with more severe antibody deficiency. These data support the hypothesis that abnormal lymphocyte trafficking may be involved in the pathogenesis of primary antibody deficiencies.
Local Morphology Predicts Functional Organization of the Dorsal Premotor Region in the Human Brain

A confusing picture of the functional organization of the dorsal premotor region of the human brain emerged when functional neuroimaging studies that either examined visuomotor hand conditional activity or attempted to localize the human frontal eye field reported activity increases at the same general location, namely the junction of the superior precentral sulcus with the superior frontal sulcus. The present functional magnetic resonance imaging study examined visuomotor hand conditional activity and the locus of the frontal eye field as defined by a standard task, on a subject-by-subject basis, to clarify their location and reveal relationships between the pattern of local morphology and functional activity. The results demonstrate that visuomotor hand conditional activity and the frontal eye field lie within distinct parts of the superior precentral sulcus, revealing an organization of the human premotor cortex consistent with that observed in experimental studies in the monkey.
The Role of Customer Trust and Commitment as Mediator for the Relation between Customer Satisfaction and Loyalty at Bank Rakyat Indonesia ( BRI ) Kendari Southeast Sulawesi

Banking firm and society are two components that arrange partnership and inter-dependent as well. The concept of “trust” has gained considerable importance in the field of marketing during the last decades and is seen as a key mediator of customer relationship marketing. But upon a closer look at the literature, the construct “trust” is conceptualized and measured very differently. Based on a literature review and theoretical work, the purpose of this paper is to develop a conceptual model of consumer trust and commitment in a service banking. More specific purpose is to test the role of customer trust and commitment as a mediator of relationship between customer satisfaction and loyalty at BRI Kendari Southeast Sulawesi, one of the leading government bank in Indonesia. The design of this study used the survey method with data collection through questionnaire. The data were obtained by distributing questionnaire for 200 respondents. Among that number, the response rate was 184 (92%); after some correction, the complete and useable questionnaires are 160 (80%). The data was analyzed with the Structural Equation Modeling (SEM). The results showed that customer satisfaction only affects loyalty if the satisfaction is supported by customer trust. In this research, it is proven that commitment is neither mediating variable for the customer satisfaction toward customer loyalty nor customer trust toward customer loyalty. An implication is that, when proposed model of customer trust prediction has the potential to help BRI Kendari managers to strengthen the customer-bank relationship and, ultimately, to enhance customer satisfaction, trust, commitment and loyalty ratios especially in the light of the credit crunch that most banks in the BRI Kendari are facing. Research limitation, findings are limited to the cross-sectional design of the study and the banking industry. Originality of research, this study makes a significant new contribution to theory and practice. The most crucial finding of this research is that trust is the key aspect to enhance customer loyalty. KeywordsCustomer Satisfaction, Commitment, Trust, Loyalty
Effects of a brief Valsalva manoeuvre on hemodynamic response to strength exercises

Strength training is a recommended measure against loss of strength and muscle mass because of age‐ or illness‐induced inactivity. Strength exercises may impose heavy cardiovascular load by increasing heart rate and blood pressure. To increase strength efficiently, a heavy load has to be applied; this, however, leads to a spontaneous Valsalva manoeuvre, which additionally raises blood pressure. Avoidance of this manoeuvre is recommended. If the additional rise in arterial blood pressure caused by Valsalva manoeuvre is smaller than intrathoracic or intracranial pressures during this manoeuvre, Valsalva manoeuvre may actually protect arteries located in the thorax and in the brain by diminishing transmural pressure acting across these vessels. Effect of controlled breathing or brief Valsalva manoeuvre on arterial pressure at rest and during knee extension against 15‐repetition maximum resistance was evaluated. In 12 healthy young men blood pressure was measured continuously and non‐invasively, knee angle, speed of respiratory air or mouth pressure (MP) were continuously registered. Each combination of respiratory and exercise manoeuvres was repeated six times, for every of last three repetitions peak and trough systolic and diastolic pressure were determined. Strength exercises elevated peak pressures more than trough pressures, systolic more than diastolic. Valsalva manoeuvre increased only peak systolic and peak diastolic pressure. This increase was in average lesser than MP, thus rendering an argument in favour of protective role of brief Valsalva manoeuvre because of decline in transmural pressure acting on thoracic and possibly cerebral arteries. However, there was strong individual variability, and in few instances, arterial pressure increased because of brief Valsalva manoeuvre more than MP; thus in some subjects, the manoeuvre might enhance transmural pressure acting on thorax arteries.