Alterations of methionine cycle in steatohepatitis, cirrhosis, and hepatocellular carcinoma induce MAT1A decrease and MAT2A increase expressions with the consequent decrease of ...S-adenosyl-L-methionine (SAM). This causes non-alcoholic fatty liver disease (NAFLD). SAM administration antagonizes pathological conditions, including galactosamine, acetaminophen, and ethanol intoxications, characterized by decreased intracellular SAM. Positive therapeutic effects of SAM/vitamin E or SAM/ursodeoxycholic acid in animal models with NAFLD and intrahepatic cholestasis were not confirmed in humans. In in vitro experiments, SAM and betaine potentiate PegIFN-alpha-2a/2b plus ribavirin antiviral effects. SAM plus betaine improves early viral kinetics and increases interferon-stimulated gene expression in patients with viral hepatitis non-responders to pegIFNα/ribavirin. SAM prevents hepatic cirrhosis, induced by CCl4, inhibits experimental tumors growth and is proapoptotic for hepatocellular carcinoma and MCF-7 breast cancer cells. SAM plus Decitabine arrest cancer growth and potentiate doxorubicin effects on breast, head, and neck cancers. Furthermore, SAM enhances the antitumor effect of gemcitabine against pancreatic cancer cells, inhibits growth of human prostate cancer PC-3, colorectal cancer, and osteosarcoma LM-7 and MG-63 cell lines; increases genomic stability of SW480 cells. SAM reduces colorectal cancer progression and inhibits the proliferation of preneoplastic rat liver cells in vivo. The discrepancy between positive results of SAM treatment of experimental tumors and modest effects against human disease may depend on more advanced human disease stage at moment of diagnosis.
Integral estimates for weak solutions to a class of Dirichlet problems for nonlinear, fully anisotropic, elliptic equations with a zero order term are obtained by symmetrization techniques. The ...anisotropy of the principal part of the operator is governed by a general n-dimensional Young function of the gradient which is not necessarily of polynomial type and need not satisfy the Δ2-condition.
Summary
Background
Current management of egg allergy relies on egg elimination from the diet. It does not protect patients from reactions after accidental ingestion of the food and it has a negative ...influence on quality of life. To solve these problems, some desensitization protocols have been described that are safe and effective, but only one study of a rush regimen for egg with a small patient sample has been published.
Objective
To evaluate the safety, efficacy and immunologic effects of an oral rush desensitization protocol for immediate egg allergy.
Methods
Subjects aged 5 years or older with symptomatic IgE‐mediated allergy to hen's egg underwent a 5‐day oral tolerance induction regimen and were subsequently maintained on a regular egg intake. The variables studied were the reactions that occurred during the induction regimen and follow‐up and the duration of desensitization. Prick test weal size and egg white‐specific IgE and IgG concentrations were monitored.
Results
Twenty‐three patients between 5 and 17 years of age entered the protocol. Twenty (86.9%) achieved the daily intake of a whole cooked egg, 14 of them within the scheduled 5 days. One abandoned the protocol and two were changed to a slower regimen because of repeated reactions. Allergic reactions were frequent but in general were mild. No severe reactions occurred. During follow‐up of at least 6 months, egg was well tolerated by all patients. Compared with baseline, skin prick test weal size and egg white‐sIgE levels had fallen at 3 months, although the differences were only significant at 6 months.
Conclusions and Clinical Relevance
The rush protocol described is useful and safe for achieving tolerance to egg within a few days but it should always be performed in a highly supervised setting. A high proportion of patients allergic to egg can effectively be desensitized using the described schedule, with the advantage of shortening the time to become protected from reactions after inadvertent ingestion of egg, with no increase in the risk compared with the earlier reported slower protocols.
Cite this as: R. García Rodríguez, J. M. Urra, F. Feo‐Brito, P. A. Galindo, J. Borja, E, Gómez, P. Lara and F. Guerra, Clinical & Experimental Allergy, 2011 (41) 1289–1296.
Down‐regulation of the liver‐specific MAT1A gene, encoding S‐adenosylmethionine (SAM) synthesizing isozymes MATI/III, and up‐regulation of widely expressed MAT2A, encoding MATII isozyme, known as ...MAT1A:MAT2A switch, occurs in hepatocellular carcinoma (HCC). Here we found Mat1A:Mat2A switch and low SAM levels, associated with CpG hypermethylation and histone H4 deacetylation of Mat1A promoter, and prevalent CpG hypomethylation and histone H4 acetylation in Mat2A promoter of fast‐growing HCC of F344 rats, genetically susceptible to hepatocarcinogenesis. In HCC of genetically resistant BN rats, very low changes in the Mat1A:Mat2A ratio, CpG methylation, and histone H4 acetylation occurred. The highest MAT1A promoter hypermethylation and MAT2A promoter hypomethylation occurred in human HCC with poorer prognosis. Furthermore, levels of AUF1 protein, which destabilizes MAT1A messenger RNA (mRNA), Mat1A‐AUF1 ribonucleoprotein, HuR protein, which stabilizes MAT2A mRNA, and Mat2A‐HuR ribonucleoprotein sharply increased in F344 and human HCC, and underwent low/no increase in BN HCC. In human HCC, Mat1A:MAT2A expression and MATI/III:MATII activity ratios correlated negatively with cell proliferation and genomic instability, and positively with apoptosis and DNA methylation. Noticeably, the MATI/III:MATII ratio strongly predicted patient survival length. Forced MAT1A overexpression in HepG2 and HuH7 cells led to a rise in the SAM level, decreased cell proliferation, increased apoptosis, down‐regulation of Cyclin D1, E2F1, IKK, NF‐κB, and antiapoptotic BCL2 and XIAP genes, and up‐regulation of BAX and BAK proapoptotic genes. In conclusion, we found for the first time a post‐transcriptional regulation of MAT1A and MAT2A by AUF1 and HuR in HCC. Low MATI/III:MATII ratio is a prognostic marker that contributes to determine a phenotype susceptible to HCC and patients' survival. Conclusion: Interference with cell cycle progression and I‐kappa B kinase (IKK)/nuclear factor kappa B (NF‐κB) signaling contributes to the antiproliferative and proapoptotic effect of high SAM levels in HCC. (HEPATOLOGY 2012;56:165–175)
•GNMT gene expression contributes to determine hepatocellular carcinoma (HCC) prognosis.•GNMT expression is genetically determined.•Nuclear GNMT binds to CYP1A1, PREX2, PARP1, and NFKB gene promoters ...and strongly inhibits their expression.
GNMT (glycine N-methyltransferase) is a tumor suppressor gene, but the mechanisms mediating its suppressive activity are not entirely known.
We investigated the oncosuppressive mechanisms of GNMT in human hepatocellular carcinoma (HCC). GNMT mRNA and protein levels were evaluated by quantitative RT-PCR and immunoblotting. GNMT effect in HCC cell lines was modulated through GNMT cDNA induced overexpression or anti-GNMT siRNA transfection.
GNMT was expressed at low level in human HCCs with a better prognosis (HCCB) while it was almost absent in fast-growing tumors (HCCP). In HCCB, the nuclear localization of the GNMT protein was much more pronounced than in HCCP. In Huh7 and HepG2 cell lines, GNMT forced expression inhibited the proliferation and promoted apoptosis. At the molecular level, GNMT overexpression inhibited the expression of CYP1A (Cytochrome p450, aromatic compound-inducible), PREX2 (Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2), PARP1 Poly (ADP-ribose) polymerase 1, and NFKB (nuclear factor-kB) genes. By chromatin immunoprecipitation, we found GNMT binding to the promoters of CYP1A1, PREX2, PARP1, and NFKB genes resulting in their strong inhibition. These genes are implicated in hepatocarcinogenesis, and are involved in the GNMT oncosuppressive action.
Overall, the present data indicate that GNMT exerts a multifaceted suppressive action by interacting with various cancer-related genes and inhibiting their expression.
We obtain a comparison result for a class of Dirichlet problems for the operator
−
div
γ
(
A
(
x
)
∇
w
)
in an infinite dimensional separable Hilbert space
X
with the Gauss measure
γ
and a suitable ...differentiable structure.
The role of inflammatory responses in predicting outcomes in oncological thoracic surgery is still unclear. The aim of this study was to evaluate a series of blood count inflammation indexes as ...predicting factors for postoperative complications. We retrospectively studied 249 patients undergoing elective thoracic surgery in our institution between 2008 and 2020. A total of 184 patients underwent open surgery, and 65 underwent VATS. The neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios, Systemic Inflammation Response Index (SIRI) were calculated preoperatively and on the first and fourth postoperative days, as well as a new derivative index, the Aggregate Inflammation Systemic Index (AISI). Univariate correlations evidenced a statistically significant association between the NLR at the fourth postoperative day and the occurrence of surgical complications in the global cohort (rho = 0.15,
= 0.03). A similar significant association with MLR on the fourth postoperative day is found in the open group (rho = -0.15,
= 0.048). NLR and LMR on the fourth postoperative day are associated with postoperative complications in the whole and open groups, respectively. Simple, easy-to-perform and inexpensive, blood cell count indexes may be useful in predicting complications in oncological thoracic surgery. A greater number of broader, prospective, randomized studies are necessary to confirm these findings.
Allergy diagnosis in patients exposed to multiple pollen species is complex and misdiagnosis is often a cause for unsuccessful specific immunotherapy. We studied the sensitization profile of ...individual allergens (major, minor and pan-allergens) in pollen-sensitized patients in a region with high exposure to olive pollen by investigating the influence of minor allergens on allergic disease and the association between pan- and minor allergen sensitizations. A panel of 13 purified allergens, which included the most relevant allergens in the area, as well as minor olive allergens and pan-allergens, were screened using a high-capacity technology (ADVIA-Centaur®) in 891 patients. Olive allergy as measured by specific IgE to Ole e 1 was the leading pollinosis in the area. The minor olive allergens Ole e 7 and Ole e 9 were markers of more severe allergic illness. Profilin sensitization was associated mainly with grass allergy, the second most prevalent pollinosis. Salsola kali pollen allergy was the third most common cause of pollinosis in the area. The prevalence of sensitization to the peach allergen Pru p 3, a nonspecific lipid-transfer protein, was notable. Epidemiological analysis by component-resolved diagnosis is a new method, which elucidates the interaction between allergen exposure gradient and patient sensitization. High exposure leads to differential sensitization profiles some of which are associated with more severe allergic conditions. Profilin sensitization, related mainly to grass pollinosis, was a marker of more severe grass pollen sensitization.
To examine the possible role of the soluble factor in fibromyalgia (FM) by studying the correlation of cytokine levels with the patients' clinical and psychiatric profile.
Eighty FM patients ...underwent clinical and psychiatric evaluations, and plasma levels of cytokines (IL-1, IL-6, IL-8, IL-10, TNF-alpha), aspecific markers of inflammation, rheumatoid factor (RF), anti-extractable nuclear antigen (ENA) antibodies, and anti-nuclear factor (FAN) were measured.
Higher levels of IL-10, IL-8 and TNF-alpha were found in FM patients than in controls. Significant correlations between the biochemical parameters and clinical data were found.
The higher levels of cytokines found in FM patients suggest the presence of an inflammatory response system (IRS) and highlight a parallel between the clinical symptoms and biochemical data. They support the hypothesis that cytokines may play a role in the clinical features of fibromyalgia. In addition, the similar cytokine patterns found in FM patients with different psychiatric profiles suggests that IRS impairment may play a specific role in the disease.
PDF
