19 research outputs found
Cues to opening mechanisms from in silico electric field excitation of cx26 hemichannel and in vitro mutagenesis studies in HeLa transfectans
Connexin channels play numerous essential roles in virtually every organ by mediating solute exchange between adjacent cells, or between cytoplasm and extracellular milieu. Our understanding of the structure-function relationship of connexin channels relies on X-ray crystallographic data for human connexin 26 (hCx26) intercellular gap junction channels. Comparison of experimental data and molecular dynamics simulations suggests that the published structures represent neither fully-open nor closed configurations. To facilitate the search for alternative stable configurations, we developed a coarse grained (CG) molecular model of the hCx26 hemichannel and studied its responses to external electric fields. When challenged by a field of 0.06 V/nm, the hemichannel relaxed toward a novel configuration characterized by a widened pore and an increased bending of the second transmembrane helix (TM2) at the level of the conserved Pro87. A point mutation that inhibited such transition in our simulations impeded hemichannel opening in electrophysiology and dye uptake experiments conducted on HeLa tranfectants. These results suggest that the hCx26 hemichannel uses a global degree of freedom to transit between different configuration states, which may be shared among the whole connexin family
Effects of an high-fat diet enriched in lard or in fish oil on the hypothalamic amp-activated protein kinase and inflammatory mediators
The high fat diet (HFD) rich in lard induces obesity, inflammation and oxidative
stress, and the deregulation of hypothalamic nuclei plays an important role in this
mechanism. One important factor involved in the food intake and inflammation
is adenosine monophosphate-dependent kinase (AMPK), a serine/threonine kinase
activated by phosphorylation. Omega (&)3-polyunsaturated fatty acids (PUFA) are
dietary compounds known to attenuate the obesity-related diseases, although the
molecular mechanisms underlying their actions in the hypothalamus are not completely
understood. We hypothesized that the beneficial effects of PUFA may be mediated
by AMPK in the hypothalamus. To this aim, rats were fed a control diet (CD), or
isocaloric HFD containing either fish oil (FD; rich in &3-PUFA) or lard (LD) for 6
weeks, and the activation of AMPK, inflammatory state (IKKb, TNF-a) and oxidative
stress were analyzed in the hypothalamus. In addition, we also studied serum
lipid profile, homeostatic model assessment (HOMA) index, and pro-inflammatory
parameters. Our results showed, at the hypothalamic level of LD-fed rats, an increase
of AMPK activation, inflammation and oxidative stress, while no modifications were
detected in FD-fed animals compared to CD. In addition body weight gain, serum
lipid profile, pro-inflammatory parameters and insulin resistance were reduced in FD
animals compared to LD. In conclusion, our data indicate that the substitution of
saturated by unsaturated fatty acids in the diet has beneficial effects on modulation
of hypothalamic inflammation and function in obesity, underlying, at hypothalamic
level, the interaction among insulin and/or leptin resistance, AMPK activation and
hyperphagia
Effects of an high-fat diet enriched in lard or in fish oil on the hypothalamic amp-activated protein kinase and inflammatory mediators.
The high fat diet (HFD) rich in lard induces obesity, inflammation and oxidative stress, and the deregulation of hypothalamic nuclei plays an important role in this mechanism. One important factor involved in the food intake and inflammation is adenosine monophosphate-dependent kinase (AMPK), a serine/threonine kinase activated by phosphorylation. Omega (ω)3-polyunsaturated fatty acids (PUFA) are dietary compounds known to attenuate the obesity-related diseases, although the molecular mechanisms underlying their actions in the hypothalamus are not completely understood. We hypothesized that the beneficial effects of PUFA may be mediated by AMPK in the hypothalamus. To this aim, rats were fed a control diet (CD), or isocaloric HFD containing either fish oil (FD; rich in ω3-PUFA) or lard for 6 weeks, and the activation of AMPK, inflammatory state (IKKβ, TNF-α) and oxidative stress were analyzed in the hypothalamus. In addition, we also studied serum lipid profile, homeostatic model assessment (HOMA) index, and pro-inflammatory parameters. Our results showed, at the hypothalamic level of LD-fed rats, an increase of AMPK activation, inflammation and oxidative stress, while no modifications were detected in FD-fed animals compared to CD. In addition body weight gain, serum lipid profile, pro-inflammatory parameters and insulin resistance were reduced in FD animals compared to LD. In conclusion, our data indicate that the substitution of saturated by unsaturated fatty acids in the diet has beneficial effects on modulation of hypothalamic inflammation and function in obesity, underlying, at hypothalamic level, the interaction among insulin and/or leptin resistance, AMPK activation and hyperphagia
Omic Approach in Non-Smoker Female with Lung Squamous Cell Carcinoma Pinpoints to Germline Susceptibility and Personalized Medicine
Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease
Appropriateness and Right Price: An Inseparable Binomial to Improve Care and Reduce Cost
Cues to Opening Mechanisms From in Silico Electric Field Excitation of Cx26 Hemichannel and in Vitro Mutagenesis Studies in HeLa Transfectans
Connexin channels play numerous essential roles in virtually every organ by mediating solute exchange between adjacent cells, or between cytoplasm and extracellular milieu. Our understanding of the structure-function relationship of connexin channels relies on X-ray crystallographic data for human connexin 26 (hCx26) intercellular gap junction channels. Comparison of experimental data and molecular dynamics simulations suggests that the published structures represent neither fully-open nor closed configurations. To facilitate the search for alternative stable configurations, we developed a coarse grained (CG) molecular model of the hCx26 hemichannel and studied its responses to external electric fields. When challenged by a field of 0.06 V/nm, the hemichannel relaxed toward a novel configuration characterized by a widened pore and an increased bending of the second transmembrane helix (TM2) at the level of the conserved Pro87. A point mutation that inhibited such transition in our simulations impeded hemichannel opening in electrophysiology and dye uptake experiments conducted on HeLa tranfectants. These results suggest that the hCx26 hemichannel uses a global degree of freedom to transit between different configuration states, which may be shared among the whole connexin family
Use of metronomic chemotherapy in oncology: results from a national Italian survey
Aims and background.Metronomic chemotherapy refers to the administration of low doses of cytotoxic agents over a prolonged period of time with no or only short drug-free intervals. It is designed to overcome acquired tumor resistance to chemotherapy and reduce neo-angiogenesis despite a lower toxicity than with standard chemother-apy. The role of metronomic chemotherapy remains controversial, and its optimal therapeutic use has not yet been defined. Methods and study design.The present survey was designed as a short questionnaire and was sent to the medical oncologists registered with Medikey, a national database listing all the Italian oncology specialists linked with the Italian Council of Medica
Lymphoepithelioma-like carcinoma of the ovary
Only one case of lymphoepithelioma-like carcinoma of the ovary has been reported so far. A new case is herein illustrated in a 69-year-old woman: an ovarian mass adherent to urinary bladder dome with peritoneal carcinomatosis. Histologically, undifferentiated carcinomatous areas were intermingled with abundant lymphoid tissue. Epstein-Barr virus has not been detected either in neoplastic or in lymphoid cells. © The Author(s) 2011
COVID-19 and the Pancreas: A Narrative Review
The outbreak of COVID-19, initially developed in China in early December 2019, has rapidly spread to other countries and represents a public health emergency of international concern. COVID-19 has caused great concern about respiratory symptoms, but it is worth noting that it can also affect the gastrointestinal tract. However, the data on pancreatic involvement during SARS-CoV-2 infection are limited. The prevalence and severity of pancreatic damage and acute pancreatitis, as well as its pathophysiology, are still under debate. Moreover, the possible implication of pancreatic damage as an apparent adverse effect of COVID-19 therapies or vaccines are issues that need to be addressed. Finally, the COVID-19 pandemic has generated delays and organizational consequences for pancreatic surgery, an element that represent indirect damage from COVID-19. This narrative review aims to summarize and analyze all the aspects of pancreatic involvement in COVID-19 patients, trying to establish the possible underlying mechanisms and scientific evidence supporting the association between COVID-19 and pancreatic disease