Empedoclean Epistemology

Presocratic, and particularly Empedoclean, epistemology has long been the object of intense debate. Unbridgeable (or apparently so) contrasts emerge in the large output of the Agrigentine philosopher, as far as epistemology is concerned. They may partially overlap with the differences among the poems ascribed to him. But sometimes such discrepancies can be traced even inside one and the same work. An obvious example of the first kind is the contradiction between frr. 2–3 D.–K., on one hand, which belongs to the περὶ φύσεως and supports a cautious empiricism, and, on the other hand, frr. 131–134 D.–K. (especially frr. 133–134), which belong to an undetermined poem, but surely convey a much greater confidence in Empedocles’ own capacity of possessing and imparting reliable theological knowledge, although such knowledge is unattainable through the senses. An example of the second kind concerns the contradiction between fr. 2, which insists on the poorness of human means of knowledge, and fr. 3, which recalls religious limits imposed on human knowledge but also encourages investigation through each of the senses. This contribution will clarify the terms of such contrasts, and try to explain their meaning. Another crucial aspect of Empedoclean epistemology will be taken into consideration — i. e. the relationship between thought and perception; and the author will argue against any straight identification between the two.Attention will be dedicated to specific connections of epistemology with different works by Empedocles, including the lost Proem to Apollo.                                      

Un fragmento desatendido de Alceo: el fr. 369 Voigt = 369 Liberman

Alcaeus fr. 369 Voigt (= 369 Liberman) has received scarce attention. Athenaeus of Naucratis has preserved it, and its content is summarized by Eustathius of Thessalonica. These two witnesses take this fragment to mean that sometimes drinking wine sweetens our temper, sometimes it makes it sour. But neither Athenaeus nor Eustathius are likely to have ever read the complete poem from which the fragment is extracted. Interpretations put forward by modern scholars (Page, Liberman) are to be rejected too, because they do not take into account the alternation expressed by the parallel ἄλλοτα μὲν..., ἄλλοτα δ᾽... . And also literal interpretation should be denied, because it is absurd to imagine that people of Alcaeus’ environment might drink sour wine. An allegoric interpretation is suggested in the light of B. Snell’s and J. Krause’s «law of eternal change» or «law of alternation»: sometimes man meets with good days, sometimes with ill days.Alceo fr. 369 Voigt (= 369 Liberman) ha recibido poca atención. Ateneo de Náucratis lo conservó y Eustacio de Tesalónica sintetizó su contenido. Estos dos escritores suponen que el fr. 369 significa que a veces beber vino suaviza el carácter y a veces lo exacerba. Pero es probable que ni Ateneo ni Eustacio leyeran nunca el poema completo de donde proviene el fragmento. Hay que rechazar tambien las interpretaciones que han propuesto los estudiosos modernos (Page, Liberman), porque no tienen en consideración la alternancia expresada en el paralelo ἄλλοτα μὲν..., ἄλλοτα δ᾽... . Además, hay que rechazar una interpretación literal del fragmento, ya que es absurdo imaginar que hombres del ambiente de Alceo pudiesen beber vino malo o vinagre. El autor del presente artículo sugiere una interpretación alegórica a la luz de la «ley de la mutación eterna» o «ley de la alternancia»: a veces se encuentran días afortunados, a veces días infaustos

MiR200 and MiR302: Two big families influencing stem cell behavior

In this review, we described different factors that modulate pluripotency in stem cells, in particular we aimed at following the steps of two large families of miRNAs: the miR-200 family and the miR-302 family. We analyzed some factors tuning stem cells behavior as TGF-\uce\ub2, which plays a pivotal role in pluripotency inhibition together with specific miRNAs, reactive oxygen species (ROS), but also hypoxia, and physical stimuli, such as ad hoc conveyed electromagnetic fields. TGF-\uce\ub2 plays a crucial role in the suppression of pluripotency thus influencing the achievement of a specific phenotype. ROS concentration can modulate TGF-\uce\ub2 activation that in turns down regulates miR-200 and miR-302. These two miRNAs are usually requested to maintain pluripotency, while they are down-regulated during the acquirement of a specific cellular phenotype. Moreover, also physical stimuli, such as extremely-low frequency electromagnetic fields or high-frequency electromagnetic fields conveyed with a radioelectric asymmetric conveyer (REAC), and hypoxia can deeply influence stem cell behavior by inducing the appearance of specific phenotypes, as well as a direct reprogramming of somatic cells. Unraveling the molecular mechanisms underlying the complex interplay between externally applied stimuli and epigenetic events could disclose novel target molecules to commit stem cell fate

Stem cell senescence: effects of REAC technology on telomerase-independent and telomerase-dependent pathways

Decline in the gene expression of senescence repressor Bmi1, and telomerase, together with telomere shortening, underlay senescence of stem cells cultured for multiple passages. Here, we investigated whether the impairment of senescence preventing mechanisms can be efficiently counteracted by exposure of human adipose-derived stem cells to radio electric asymmetrically conveyed fields by an innovative technology, named Radio Electric Asymmetric Conveyer (REAC). Due to REAC exposure, the number of stem cells positively stained for senescence associated ß-galactosidase was significantly reduced along multiple culturing passages. After a 90-day culture, REAC-treated cells exhibited significantly higher transcription of Bmi1 and enhanced expression of other stem cell pluripotency genes and related proteins, compared to unexposed cells. Transcription of the catalytic telomerase subunit (TERT) was also increased in REAC-treated cells at all passages. Moreover, while telomere shortening occurred at early passages in both REAC-treated and untreated cells, a significant rescue of telomere length could be observed at late passages only in REAC-exposed cells. Thus, REAC-asymmetrically conveyed radio electric fields acted on a gene and protein expression program of both telomerase-independent and telomerase-dependent patterning to optimize stem cell ability to cope with senescence progression

Melatonin and Vitamin D Interfere with the Adipogenic Fate of Adipose-Derived Stem Cells

Adipose-derived stem cells (ADSCs) represent one of the cellular populations resident in adipose tissue. They can be recruited under certain stimuli and committed to become preadipocytes, and then mature adipocytes. Controlling stem cell differentiation towards the adipogenic phenotype could have a great impact on future drug development aimed at counteracting fat depots. Stem cell commitment can be influenced by different molecules, such as melatonin, which we have previously shown to be an osteogenic inducer. Here, we aimed at evaluating the effects elicited by melatonin, even in the presence of vitamin D, on ADSC adipogenesis assessed in a specific medium. The transcription of specific adipogenesis orchestrating genes, such as aP2, peroxisome proliferator-activated receptor \u3b3 (PPAR-\u3b3), and that of adipocyte-specific genes, including lipoprotein lipase (LPL) and acyl-CoA thioesterase 2 (ACOT2), was significantly inhibited in cells that had been treated in the presence of melatonin and vitamin D, alone or in combination. Protein content and lipid accumulation confirmed a reduction in adipogenesis in ADSCs that had been grown in adipogenic conditions, but in the presence of melatonin and/or vitamin D. Our findings indicate the role of melatonin and vitamin D in deciding stem cell fate, and disclose novel therapeutic approaches against fat depots

Mechanical Stimulation of Fibroblasts by Extracorporeal Shock Waves: Modulation of Cell Activation and Proliferation Through a Transient Proinflammatory Milieu

Extracorporeal shock waves (ESWTs) are "mechanical" waves, widely used in regenerative medicine, including soft tissue wound repair. Although already being used in the clinical practice, the mechanism of action underlying their biological activities is still not fully understood. In the present paper we tried to elucidate whether a proinflammatory effect may contribute to the regenerative potential of shock waves treatment. For this purpose, we exposed human foreskin fibroblasts (HFF1 cells) to an ESWT treatment (100 pulses using energy flux densities of 0.19 mJ/mm2 at 3 Hz), followed by cell analyses after 5 min, up to 48 h. We then evaluated cell proliferation, reactive oxygen species generation, ATP release, and cytokine production. Cells cultured in the presence of lipopolysaccharide (LPS), to induce inflammation, were used as a positive control, indicating that LPS-mediated induction of a proinflammatory pattern in HFF1 increased their proliferation. Here, we provide evidence that ESWTs affected fibroblast proliferation through the overexpression of selected cytokines involved in the establishment of a proinflammatory program, superimposable to what was observed in LPS-treated cells. The possibility that inflammatory circuits can be modulated by ESWT mechanotransduction may disclose novel hypothesis on their biological underpinning and expand the fields of their biomedical application

Melatonin and Vitamin D Orchestrate Adipose Derived Stem Cell Fate by Modulating Epigenetic Regulatory Genes

Melatonin, that regulates many physiological processes including circadian rhythms, is a molecule able to promote osteoblasts maturation in vitro and to prevent bone loss in vivo, while regulating also adipocytes metabolism. In this regard, we have previously shown that melatonin in combination with vitamin D, is able to counteract the appearance of an adipogenic phenotype in adipose derived stem cells (ADSCs), cultured in an adipogenic favoring condition. In the present study, we aimed at evaluating the specific phenotype elicited by melatonin and vitamin D based medium, considering also the involvement of epigenetic regulating genes. ADSCs were cultured in a specific adipogenic conditioned media, in the presence of melatonin alone or with vitamin D. The expression of specific osteogenic related genes was evaluated at different time points, together with the histone deacetylases epigenetic regulators, HDAC1 and Sirtuins (SIRT) 1 and 2. Our results show that melatonin and vitamin D are able to modulate ADSCs commitment towards osteogenic phenotype through the upregulation of HDAC1, SIRT 1 and 2, unfolding an epigenetic regulation in stem cell differentiation and opening novel strategies for future therapeutic balancing of stem cell fate toward adipogenic or osteogenic phenotype

Physical stimulation by REAC and BMP4/WNT-1 inhibitor synergistically enhance cardiogenic commitment in iPSCs

It is currently known that pluripotent stem cells can be committed in vitro to the cardiac lineage by the modulation of specific signaling pathways, but it is also well known that, despite the significant increase in cardiomyocyte yield provided by the currently available conditioned media, the resulting cardiogenic commitment remains a highly variable process. Previous studies provided evidence that radio electric fields asymmetrically conveyed through the Radio Electric Asymmetric Conveyer (REAC) technology are able to commit R1 embryonic stem cells and human adipose derived stem cells toward a cardiac phenotype. The present study aimed at investigating whether the effect of physical stimulation by REAC in combination with specific chemical inductors enhance the cardiogenic potential in human induced pluripotent stem cells (iPSCs). The appearance of a cardiac-like phenotype in iPSCs cultured in the presence of a cardiogenic medium, based upon BMP4 and a WNT-inhibitor, was consistently increased by REAC treatment used only during the early fate differentiation for the first 72 hours. REAC-exposed iPSCs exhibited an upregulation in the expression of specific cardiogenic transcripts and morphologically in the number of beating clusters, as compared to cells cultured in the cardiogenic medium alone. Our results indicate that physical modulation of cellular dynamics provided by the REAC offers an affordable strategy to mimic iPSC cardiac-like fates in the presence of a cardiogenic milieu