Granulocyte colony-stimulating factor: Its role in gut-homing macrophage generation and colitis, and production by probiotics

The pleiotropic cytokine granulocyte-colony stimulatory factor (G-CSF) is mainly required for the generation of neutrophils, but its role in macrophage generation has also been reported. In addition, G-CSF is effective for the down-regulation of inflammatory cytokines and ameliorating gut disorders, such as colitis. However, the G-CSF function in macrophage generation and gut immunity remains unclear. The first focus of this thesis was to assess the role of G-CSF in macrophage generation and its contribution to gut immunity. G-CSF was found to promote the generation of Gr-1high/F4/80+ macrophages in macrophage (M)-CSF-treated bone marrow cells, most likely through suppressing cell death. Gr-1high macrophages showed anti- inflammatory/regulatory macrophage (M2)-like cytokine and surface marker profiles. G-CSF receptor deficient (G-CSFR-/-) mice harbored less gut macrophages, but had a similar number of neutrophils in the gut. In addition, adoptive transfer of G-CSF- treated bone marrow-derived macrophages (G-BMDM) showed a dominant gut- homing phenotype. G-CSFR-/- mice were also more susceptible to dextran sulfate sodium (DSS)-induced colitis than wild-type mice and adoptive transfer of G-BMDM protected these mice from DSS-induced colitis. The second focus of this thesis was to explore the signaling mechanism(s) controlling the preferential G-CSF production over inflammatory cytokines in probiotic bacteria-exposed BMDM. Lactobacillus rhamnosus GR-1 (GR-1) renders several immunomodulatory effects, at least in part, through preferentially inducing G-CSF in macrophages. However, the mechanism(s) by which GR-1 induces preferential G-CSF production in macrophages is still unknown. Among 84 genes tested, G-CSF was the cytokine induced at highest levels in GR-1-treated BMDM, but the induction of inflammatory cytokines, such as TNF-α, was minimal. The signaling pathway of GR-1-preferential G-CSF production was TLR2-, NF-κB-, ERKs- and PI3K/Akt-dependent. A secreted protein-like molecule(s) was found to be responsible for GR-1-preferential G-CSF production. Collectively, these results demonstrated the immune regulatory function of G-CSF on macrophages in gut immunity and a potential mechanism of action of certain probiotics

Robespierre-Kant: A Study of the Relationship between Absolute Freedom and Terror and Kant's Philosophy of Ethics Based on the Phenomenology of Hegel's spirit

In Phenomenology of the Spirit, Hegel depicts the dialectical structure of the history of European human consciousness. In all the transitions of consciousness to different outcomes, he has recognized the necessity and dialectical relation and follows it in all fields of history and fields of thought in different currents. In the chapter on the spirit, we encounter two very important currents in social history, namely the French Revolution, and in the history of thought, that is, Kant's philosophy of morality, which appear in two consecutive sections. And it's as if Hegel found a close connection between Robespierre's assassination rule and Kantian philosophy of morality. Where Robespierre's abstract freedom, in order to create absolute freedom in the realization of his generalized partial will, destroys any institution or detail as a factor in disrupting the realization of his free will, and begins a period of tyranny and terror. It is as if such a claim of a common will that tolerates no detail or opposition becomes the internal tyranny of Kant's general moral law (the realization of which is the only way to attain freedom) in order to destroy nature, desires, customs and objective institutions, and so on. And it creates fear and anxiety due to endless contradictions, and the moral person, like the revolutionary person, is trapped within his abstract will by the complete elimination of objectivity, which, according to Hegel, will have dangerous consequences

The Relationship between Kant’s Philosophy of Ethics and the Decline of Political Thought in His Philosophy

In this article, the author claims that Kant’s political thought is formed both in the break from his moral thought and in the continuation and decline of his moral thought in politics. Kant has previously struggled in the field of ethics to realize autonomy in external and internal nature, as well as in institutions, on the premise that man is evil and that the world of phenomena or experience lacks rationality. And to escape from this problem, he either seeks refuge in the unknown future or in God and theoretically never has a theory to establish a relationship between the world of phenomena and phenomena, or in other words, the subjective and objective. In such a state, the person stands outside nature with his free inside, and the experience or object appears to him as something threatening. Kant brings all these problems with him to his world of understanding of politics. And because it has already created a disconnect between the two realms of subject and object, this continues also in political thought, because it cannot use the capacity of its new understanding of human freedom to achieve the theory of public will and its embodiment outside. Instead, it seeks to establish the government of law and ensure it by forcing the state to achieve good citizenship for society. Thus Kant’s political thought separated from the freedom of autonomy and it falls into utilitarian thought.In this article, the author not only believes that there is a gap between freedom and autonomy in Kant’s moral thought and his political philosophy but also believes that Kant’s theoretical decline in political thought is due to the weakness of his moral thought. That is, not establishing a relationship with the real world or phenomena or experience in Kant’s moral thought and not realizing his autonomy outside, whether on the basis of anthropology based on man’s evil or on the irrationality of the outside world and also not accepting its institutions which is the embodiment of human desires and wishes; all of these have had an inevitable impact on his political thought. in such a way that whenever Kant speaks of politics in the real world, he can never speak of the transcendental freedom embodied in it. Thus, that conflict between subject and object or morality and nature or human desires with social institutions in politics has been reproduced again. In such a situation, as Kant has not been able to bring that abstract moral man into the realm of politics and in concrete cases, explain the conditions of its realization in case of public will, inevitably, one must turn to the government for the realization of both private and public will in the field of politics which is not at all the embodiment of the public will of individuals, but a master who prepares man for social life by coercion and its metaphysical repression. Thus, autonomy is not realized in politics as in ethics in the external sphere, and empirical coercion in the form of government will impose itself on the abstraction of autonomy like God in Kant’s moral thought

Epistemic Luck and Anti-Luck Epistemology in the View of Duncan Pritchard

The problem of epistemic luck arises when a person has a true belief that is only true by luck. Before Gettier, it was believed that the element of justification would be sufficient for knowledge; but he showed that it is possible to have a justified true belief that is not an example of knowledge because of the intrusion of luck. Duncan Pritchard has examined epistemic luck in an extensive and detailed manner. He offers a modal account of luck based on two elements: a possible-worlds analysis of counterfactual conditions and a significance condition for the factors that make the truth of the belief lucky. Pritchard argues for the superiority of this account to those that focus on whether the truth of the belief is “accidental” and on whether the believer has sufficient control over the belief. Epistemic luck may be “reflective” or “veritic”. Both undermine knowledge claims, although Pritchard gives the central role to veritic luck in his anti-luck epistemology, which is based on two elements: a safety principle and a condition to ensure that the cognitive faculties of the agent are not impaired. In this article, we will describe, analyze, and subsequently, evaluate the viewpoint of Pritchard. In addition to the critiques offered by others, ambiguities in his counterfactual account of luck and other components of his theory detract from his theory. IntroductionThe problem of epistemic luck in post-Gettier philosophical literature refers to the insufficiency of the tripartite definition of knowledge. Examples in which we have justified true belief that are not instances of knowledge are now well known. In these examples, luck plays a central role in the process of acquiring true belief. Duncan Pritchard has examined this topic extensively and in detail. His analysis is presented in four stages: anti-luck epistemology, anti-luck virtue epistemology, anti-risk epistemology, and anti-risk virtue epistemology. The aim of this article is to examine the first two stages analytically and critically. Pritchard’s turn from luck to risk will be studied in another article. We conclude that the ambiguity of some of his statements and key concepts are liabilities for his theory.Modal account of luckPritchard, after criticizing rival accounts, defends a modal account of luck. This account is based on two principles: 1) the principle of possible worlds, for which Pritchard is indebted to David Lewis. There are many ways things could have been besides the way they actually are. He identifies possible worlds with “ways things could have been”. Possible worlds are counterfactual ways things could be that are more or less similar to the actual world and are considered to be closer or further from the actual world, respectively. So, a lucky event like a lottery win occurs in the actual world but does not occur in a wide class of the nearby possible worlds where the relevant initial conditions for the event are the same. This makes the win “lucky”. After reviewing the conception of possible worlds, this article draws attention to the degree of luck of an event. Pritchard (2005) holds that the degree of luck is determined by the proportion of close possible worlds in which it would fail to occur. In another article (2014), he takes a different position and says that the degree of luck involved varies in line with the modal closeness of the world in which the target event fails to occur. 2) The significance condition, which Pritchard has explicated in three different ways over the course of his writing on this topic. First, in (2004) he adds this condition to his modal account and states that there should be an agent who is affected by a lucky event so that good luck or bad luck can be attributed to him. Then, in (2014), he omits the significance condition from his modal account and takes luck to be a metaphysical and objective phenomenon independent of subjective factors such as significance. Finally, in (2020), he settles on a minimal account of significance.The modal account by Pritchard, even though some elements of it have changed through the years, can be articulated as follows: a significant event E is lucky for an agent S at time t if, and only if, E occurs in the actual world at t but does not occur at t in a wide proportion of close possible worlds in which the relevant initial conditions for E are the same as in the actual world.Types of epistemic luckCompatible types of epistemic luck may be categorized on the basis of whether luck is relevant to the content, capacity, or evidential weight of the belief. These types are obtained inductively and more can be found. They are epistemically harmless and are concerned with luck in the preconditions for knowledge. Forms of luck that are incompatible with knowledge are veritic and reflective, and they infect the core epistemic relation between an agent and a true proposition which is pivotal to knowledge possession. The concentration of Pritchard’s ant-luck virtue epistemology is to omit veritic epistemic luck which is of two types: intervening and environmental. Environmental epistemic luck is something about which Sosa and Pritchard differ. According to Sosa’s point of view, environmental epistemic luck has no effect on the justification or formation of a belief.Anti-luck virtue epistemologyAfter defining epistemic luck and getting familiar with its types, Pritchard presents his anti-luck epistemology, the main principle of which is safety. But because this principle is not sufficient for removing veritic epistemic luck, he proposes an anti-luck virtue epistemology that has two main elements: the safety principle and the ability intuition. Pritchard believes that this epistemology can deal with Gettier cases and the like which are undermined by the intrusion of luck. His anti-luck virtue epistemology is influenced by Greco and Sosa and his view has affinities to reliabilism.We can articulate the final version of his safety principle as follows: if an agent A knows a contingent proposition P, then in nearly all possible worlds in which he forms his belief about P in the same way as he forms his belief in the actual world, that agent only believes that P when P is true.About the ability intuition, he thinks of it in terms of dispositions that should be both reliable and suitably integrated with the agent’s other belief-forming dispositions.DiscussionFor evaluating Pritchard’s point of view, first remember that in virtue epistemology, knowledge is a skillful achievement that is achieved through cognitive abilities and leaves no room for the influence of luck. But, as Hales implies, there are cases of skillful achievements that are lucky. Second, as Bricker demonstrates, cognitive neuroscience and a number of recent EEG studies can introduce a new challenge to this account, especially to the counterfactual principle. Third, a general problem with his view is that his modal account and his epistemology and their elements are not free from ambiguity. It is natural and logical that a philosopher changes and completes his position over time, but it seems that Pritchard has chosen his path with more ambiguity in some cases. For example, a counterfactual theory is one of the most important elements of his modal account, but the metric that determines the distance from the actual world is notoriously unclear. His view has wavered about whether the relevant possible worlds are the nearest ones, or all those that are nearby, or any possible world sufficiently near. There are also unanswered questions about the number of possible worlds and other components of his theory.ConclusionWe conclude that, despite his commendable efforts, the ambiguities of some of his statements and key concepts are liabilities his position has been unable to remove

The comparison of plasma fibronectin in term and preterm delivery: A cross-sectional, descriptive-analytical study

Background: Preterm delivery is one of the main causes of infant death. Therefore, prediction of preterm delivery may eliminate a large number of prenatal complications. Objectives: The present study aimed to understand if preterm delivery can be predicted by assessing maternal plasma fibronectin concentration. Materials and Methods: Serum samples from 105 pregnant women participating in this study were collected. The plasma fibronectin were measured at 24-28 wk of gestation and again at 32-36 wk of gestation. Unfortunately, only 65 of the 105 pregnant women, returned for the second sampling. The plasma fibronectin was analyzed using ELISA method and its concentration in term and preterm deliveries was compared. The delivery dates of all the women were also recorded. Results: Out of 105 pregnant women, 28 delivered preterm (26.7%). The Plasma fibronectin concentrations in women with preterm delivery were higher than in those who delivered at term (p = 0.001). Accordingly, Plasma fibronectin concentrations were significantly higher in the second serum samples (p = 0.01). Plasma fibronectin concentrations was also higher in obese women and in those suffering from preeclampsia (p = 0.12) and gestational diabetes (p = 0.81). Conclusion: Plasma fibronectin concentrations test could be used as an optional screening test for preterm delivery at 28 to 34 wk of gestation in pregnant women who prefer to avoid vaginal sampling. Key words: Premature birth, Fibronectin, Maternal serum screening tests

Study of psychiatric disturbance in infertile women

Background: The experience of infertility can be extremely stressful and associated with a range of psychiatric problems in infertile women. Generally; some of the risk factors which may lead to psychiatric problem are repeated unsuccessful treatment of infertility, low socioeconomic status, lack of partner support, being female, life events, etc. Objective: In this study, we have analyzed the psychiatric problems of infertile women by means of primary health questionnaire (PHQ). Materials and methods: In a cross sectional study 100 infertile women were selected and advised to fill up PHQ. After obtaining their consents psychiatric problems such as somatoform, panic, other anxiety disorder major depressive and other depressive disorders, were assessed, and their results were analyzed and compared with these results from 98 fertile women. Results: According to PHQ results major depression and anxiety disorders were significantly more frequent in infertile women, but considering somatoform and panic disorder there was no significant difference between infertile and fertile women. Conclusions: Infertility may be considered as one of the major casual factor in major depressive and anxiety disorders in association with other social problems

The Protective Effects of Vitamins C and E on The Oxidative Stress Induced by Sodium Metabisulfite on The Kidney Tissue in Adult Rats

Background & Objective: Sodium metabisulfite which is used as a food preservative in the food industry, has adverse effects on body organs such as kidney and body grouth rate. In this research we have studied the protective effect of Vitamin C and E as antioxidants, on the kidney tissue damage after the consumption of Sodium metabisulfite. Materials & methods: Forty-eight Adult male Wistar rats of 150-200 grams were divided into 6 groups of 8 each. Rats in the experimental groups received Sodium metabisulfite (520 mg / kg body weight) by gavage feeding for 30 consecutive days. Also during this period, the experimental groups 2 and 3 received a daily dose of 100 mg / kg vitamins C and E, Respectively. The experimental group 4 received 50 mg / kg vitamin C plus 50 mg / kg of vitamin E by the same root. Control group received only normal diet and water. The placebo received vehicle (drug solvent) as well as normal diet and water. At the end of the exprimental period the body growth rate was measured between the groups. The histhopatological examination was performed on the kidney tissue sections. by light microscope Results: The results showed sodium metabisulfite in daily dietary could lead to the kidney tissue damage and reduced body weight in rats (p <0.05). However, vitamins C and E can reduce the kidney tissue damage and allow a normal growth weight (p <0.05). Conclusion: With this study we could conclude that the antioxidant effect of that vitamins C and E have a protective effect on renal damage induced by sodium metabisulfite consumptio