Altered Lipid Metabolism in Blood Mononuclear Cells of Psoriatic Patients Indicates Differential Changes in Psoriasis Vulgaris and Psoriatic Arthritis

The aim of this study was to investigate possible stress-associated disturbances in lipid metabolism in mononuclear cells, mainly lymphocytes of patients with psoriasis vulgaris (Ps, n = 32) or with psoriatic arthritis (PsA, n = 16) in respect to the healthy volunteers (n = 16). The results showed disturbances in lipid metabolism of psoriatic patients reflected by different phospholipid profiles. The levels of non-enzymatic lipid metabolites associated with oxidative stress 8- isoprostaglandin F2α (8-isoPGF2α) and free 4-hydroxynonenal (4-HNE) were higher in PsA, although levels of 4-HNE-His adducts were higher in Ps. In the case of the enzymatic metabolism of lipids, enhanced levels of endocannabinoids were observed in both forms of psoriasis, while higher expression of their receptors and activities of phospholipases were detected only in Ps. Moreover, cyclooxygenase-1 (COX-1) activity was enhanced only in Ps, but cyclooxygenase-2 (COX-2) was enhanced both in Ps and PsA, generating higher levels of eicosanoids: prostaglandin E1 (PGE1), leukotriene B4 (LTB4), 13-hydroxyoctadecadienoic acid (13HODE), thromboxane B2 (TXB2). Surprisingly, some of major eicosanoids 15-d-PGJ2 (15-deoxy-∆12, 14- prostaglandin J2), 15-hydroxyeicosatetraenoic acid (15-HETE) were elevated in Ps and reduced in PsA. The results of our study revealed changes in lipid metabolism with enhancement of immune system- modulating mediators in psoriatic mononuclear cells. Evaluating further differential stress responses in Ps and PsA affecting lipid metabolism and immunity might be useful to improve the prevention and therapeutic treatments of psoriasis

The Appearance of 4-Hydroxy-2-Nonenal (HNE) in Squamous Cell Carcinoma of the Oropharynx

Tumor growth is associated with oxidative stress, which causes lipid peroxidation. The most intensively studied product of lipid peroxidation is 4- hydroxy-2-nonenal (HNE), which is considered as a “second messenger of free radicals” that binds to proteins and acts as a growth-regulating signaling factor. The incidence of squamous cell carcinoma of the oropharynx is associated with smoking, alcohol and infection of human papilloma virus (HPV), with increasing incidence world-wide. The aim of this retrospective study involving 102 patients was to determine the immunohistochemical appearance of HNE-protein adducts as a potential biomarker of lipid peroxidation in squamous cell carcinoma of the oropharynx. The HNE-protein adducts were detected in almost all tumor samples and in the surrounding non-tumorous tissue, while we found that HNE is differentially distributed in squamous cell carcinomas in dependence of clinical stage and histological grading of these tumors. Namely, the level of HNE-immunopositivity was increased in comparison to the normal oropharyngeal epithelium in well- and in moderately- differentiated squamous cell carcinoma, while it was decreasing in poorly differentiated carcinomas and in advanced stages of cancer. However, more malignant and advanced cancer was associated with the increase of HNE in surrounding, normal tissue. This study confirmed the onset of lipid peroxidation, generating HNE-protein adducts that can be used as a valuable bioactive marker of carcinogenesis in squamous cell carcinoma of the oropharynx, as well as indicating involvement of HNE in pathophysiological changes of the non-malignant tissue in the vicinity of cancer

Positron emission tomography-computed tomography and 4-hydroxynonenal-histidine immunohistochemistry reveal differential onset of lipid peroxidation in primary lung cancer and in pulmonary metastasis of remote malignancies

The Aim of the study was to reveal if PET-CT analysis of primary and of secondary lung cancer could be related to the onset of lipid peroxidation in cancer and in surrounding non-malignant lung tissue

Nova metoda za dokazivanje HNE-histidinskih konjugata u {takorskim upalnim stanicama

Oxidative stress, excessive production of reactive oxygen species, is considered an important part of different disorders, as well as of physiological processes (inflammation). The difference between physiological and pathological oxidative stress is often the occurrence of lipid peroxidation and its final toxic products, among which is 4-hydroxy-2-nonenal (HNE), a reactive aldehyde that forms protein conjugates. The aim of this study was to determine the distribution of HNE-histidine conjugates in leukocytes during systemic inflammation. We used genuine monoclonal antibodies against HNE-histidine conjugates for immuno-cytochemical, immuno- histochemical and immuno-electronmicroscopical analyses of HNE in inflammatory cells. Spleen tissue, leukocytes from blood and macrophages from the peritoneum of rats intraperitoneally (i.p.) injected with micronized zeolite (MZ) were analyzed. HNE-histidine conjugates were predominantly detected near cell membranes, phagosomes and macrophage granules. Immunodetection of HNE-histidine conjugates may be used as an analytical immunochemical method to study HNE formation in pathological and physiological processes and for pathomorphological diagnostic procedures.Oksidacijski stres, stanje prekomjernoga stvaranja reaktivnih kisikovih tvari, bitna je sastavnica različitih bolesti, ali i fizioloških procesa (upala). Često je razlika između fiziološkoga i patološkoga oksidacijskoga stresa pojava lipidne peroksidacije i njenih završnih toksičnih produkata, među kojima posebnu ulogu ima 4-hidroksi- 2-nonenal (HNE), reaktivni aldehid koji tvori konjugate s bjelančevinama. Cilj ovoga istraživanja bio je utvrditi distribuciju HNE-histidinskih konjugata u leukocitima tijekom nespecifične upalne reakcije. Rabili smo izvorna monoklonalna protutijela na HNE-histidinski konjugat, za imuno-citokemijsko, histokemijsko i elektronskomikroskopsko dokazivanje HNE-a u upalnim stanicama. Analizirano je tkivo slezene, leukociti iz krvi te makrofazi štakora kojima je intraperitonealno injiciran mikronizirani zeolit (MZ). HNE-histidinski konjugati pretežito su uočeni uz stanične membrane te pored fagosoma i makrofagnih granula. Imunodetekcija HNE-histidinskih konjugata mogla bi se stoga rabiti kao analitička imunokemijska metoda za istraživanja fizioloških i patoloških procesa te u patomorfološkim dijagnostičkim postupcima

Post-mortem findings of inflammatory cells and the association of 4-hydroxynonenal with systemic vascular and oxidative stress in lethal COVID-19

A recent comparison of clinical and inflammatory parameters, together with biomarkers of oxidative stress, in patients who died from aggressive COVID-19 and survivors suggested that the lipid peroxidation product 4-hydroxynonenal (4-HNE) might be detrimental in lethal SARS-CoV-2 infection. The current study further explores the involvement of inflammatory cells, systemic vascular stress, and 4-HNE in lethal COVID-19 using specific immunohistochemical analyses of the inflammatory cells within the vital organs obtained by autopsy of nine patients who died from aggressive SAR-CoV-2 infection. Besides 4-HNE, myeloperoxidase (MPO) and mitochondrial superoxide dismutase (SOD2) were analyzed alongside standard leukocyte biomarkers (CDs). All the immunohistochemical slides were simultaneously prepared for each analyzed biomarker. The results revealed abundant 4-HNE in the vital organs, but the primary origin of 4-HNE was sepsis-like vascular stress, not an oxidative burst of the inflammatory cells. In particular, inflammatory cells were often negative for 4-HNE, while blood vessels were always very strongly immunopositive, as was edematous tissue even in the absence of inflammatory cells. The most affected organs were the lungs with diffuse alveolar damage and the brain with edema and reactive astrocytes, whereas despite acute tubular necrosis, 4-HNE was not abundant in the kidneys, which had prominent SOD2. Although SOD2 in most cases gave strong immunohistochemical positivity similar to 4-HNE, unlike 4-HNE, it was always limited to the cells, as was MPO. Due to their differential expressions in blood vessels, inflammatory cells, and the kidneys, we think that SOD2 could, together with 4-HNE, be a potential link between a malfunctioning immune system, oxidative stress, and vascular stress in lethal COVID-19

Association of lipid peroxidation product 4-hydroxynonenal with post-traumatic stress disorder

Repeated activation of the hypothalamic-pituitary-adrenal axis system, sleep disturbances, and other symptoms related to posttraumatic stress disorder (PTSD) elevate reactive oxygen species, increase inflammation, and accelerate cellular aging, leading to neuroprogression and cognitive decline. However, there is no information about possible involvement of 4-hydroxynonenal (4-HNE), the product of lipid peroxidation associated with stress-associated diseases, in the complex etiology of PTSD. Therefore, the aim of this study was to compare the plasma levels of 4-HNE between war veterans with PTSD (n = 62) and age-, sex- and ethnicity- matched healthy control subjects (n = 58) in order to evaluate the potential of HNE-modified proteins as blood-based biomarker of PTSD. The genuine 4-HNE-Enzyme-Linked Immunosorbent Assay (HNE-ELISA), based on monoclonal antibody specific for HNE-histidine (HNE-His) adducts, was used to determine plasma HNE-protein conjugates. Our results revealed significantly elevated levels of 4-HNE in patients with PTSD. Moreover, the accumulation of plasma 4-HNE seems to increase with aging but in a negative correlation with BMI, showing specific pattern of change for individuals diagnosed with PTSD. These findings suggest that oxidative stress and altered lipid metabolism reflected by increase of 4-HNE might be associated with PTSD. If confirmed with further studies, elevated 4-HNE plasma levels might serve as a potential biomarker of PTSD