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Graphical abstract, Diabetes mellitus is a well-known danger element for the progression of male reproductive dysfunctions. Available evidence supports oxidative stress to be the underlying mechanism for the manifestation of testicular dysfunctions during diabetes, and this relation represents an attractive target to antagonize these complications. Artemisia judaica L. is known to have antidiabetic and antioxidant characteristics. The possible protective effect of Artemisia judaica against diabetes-induced testicular disorders was not explored. In this investigation, we planned to estimate the possible protective effect of Artemisia judaica extract against diabetes-induced testicular disorders in male rats. The blood levels of insulin, glucose, glycosylated hemoglobin, testosterone, luteinizing hormone and follicle stimulating hormone were evaluated in rats after 12 weeks of Artemisia judaica treatment. Further, oxidative stress markers were determined in their testicular tissue. Epididymal fluid and testicular histological changes were also assessed. Expression of proliferating cell nuclear antigen has been evaluated in testis. Testicular mRNA expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 as the significant transcription factors in controlling antioxidant system were evaluated by real-time polymerase chain reaction. Artemisia judaica extracts have the ability to ameliorate the elevation in the serum glucose and blood glycosylated hemoglobin and the reduction in insulin, testosterone, follicle stimulating hormone and luteinizing hormone caused by streptozotocin-induced diabetes. It induced a significant recovery of the testicular oxidative stress markers, sperm characteristics and improved histopathological findings of the testes. Treatment with Artemisia judaica extracts led to an increase in proliferating cell nuclear antigen protein expression. Reduction of testicular oxidative stress potential in streptozotocin-treated groups was confirmed by upregulation of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1.

Non-alcoholic steatohepatitis (NASH) is a chronic metabolic syndrome and the CFLAR-JNK pathway can reverse the process of NASH. Although silibinin is used for the treatment of NASH in clinical, its effect on CFLAR-JNK pathway in NASH remains unclear. This study aimed to investigate the effect of silibinin on CFLAR-JNK pathway in NASH models both in vivo and in vitro. The in vivo study was performed using male C57BL/6 mice fed with methionine– choline-deficient diet and simultaneously treated with silibinin for 6 weeks. The in vitro study was performed by using mouse NCTC-1469 cells which were respectively pretreated with oleic acid plus palmitic acid, and adenovirus-down Cflar for 24 h, then treated with silibinin for 24 h. After the drug treatment, the key indicators involved in CFLAR-JNK pathway including hepatic injury, lipid metabolism and oxidative stress were determined. Silibinin significantly activated CFLAR and inhibited the phosphorylation of JNK, up-regulated the mRNA expression of Pparα, Fabp5, Cpt1α, Acox, Scd-1, Gpat and Mttp, reduced the activities of serum ALT and AST and the contents of hepatic TG, TC and MDA, increased the expression of NRF2 and the activities of CAT, GSH-Px and HO-1, and decreased the activities and expression of CYP2E1 and CYP4A in vivo. These effects were confirmed by the in vitro experiments. Silibinin prevented NASH by regulating CFLAR-JNK pathway, and thereby on one hand promoting the β-oxidation and efflux of fatty acids in liver to relieve lipid accumulation, and on the other hand inducing antioxidase activity (CAT, GSH-Px and HO-1) and inhibiting pro-oxidase activity (CYP2E1 and CYP4A) to relieve oxidative stress., Graphical abstract Silibinin could regulate CFLAR-JNK pathway to ameliorates hepatic lipid accumulation, insulin resistence and oxidative stress in C57BL/6 mice treated by methionine- and choline-deficient diet, and NCTC-1469 cells treated by the mixture of oleic acid and palmitic acid and adenovirus-down Cflar.fx1

Background Coronavirus disease-2019 (COVID-19) caused by infection with severe acute respiratory coronavirus-2 (SARS-CoV-2) has been spreading rapidly throughout China and in other countries since the end of 2019. The World Health Organization (WHO) has declared that the epidemic is a public health emergency of international concerns. The timely and appropriate measures for treating COVID-19 in China, which are inseparable from the contribution of traditional Chinese medicine (TCM), have won much praise of the world. Purpose This review aimed to summarize and discuss the essential role of TCM in protecting tissues from injuries associated with COVID-19, and accordingly to clarify the possible action mechanisms of TCM from the perspectives of anti-inflammatory, antioxidant and anti-apoptotic effects. Methods Electronic databases such as Pubmed, ResearchGate, Science Direct, Web of Science, medRixv and Wiley were used to search scientific literatures. Results The present review found that traditional Chinese herbs commonly used for the clinical treatment of organ damages caused by COVID-19, such as Scutellaria baicalensis, Salvia miltiorrhizaSalvia miltiorrhiza, and ginseng, could act on multiple signaling pathways involved in inflammation, oxidative stress and apoptosis. Conclusion TCM could protect COVID-19 patients from tissue injuries, a protection that might be, at least partially, attributed to the anti-inflammatory, antioxidant and anti-apoptotic effects of the TCM under investigation. This review provides evidence and support for clinical treatment and novel drug research using TCM.

Allergic rhinitis affects the quality of life of millions of people worldwide. Air pollution not only causes morbidity, but nearly 3 million people per year die from unhealthy indoor air exposure. Furthermore, allergic rhinitis and air pollution interact. This report summarizes the discussion of an International Expert Consensus on the management of allergic rhinitis aggravated by air pollution. The report begins with a review of indoor and outdoor air pollutants followed by epidemiologic evidence showing the impact of air pollution and climate change on the upper airway and allergic rhinitis. Mechanisms, particularly oxidative stress, potentially explaining the interactions between air pollution and allergic rhinitis are discussed. Treatment for the management of allergic rhinitis aggravated by air pollution primarily involves treating allergic rhinitis by guidelines and reducing exposure to pollutants. Fexofenadine a non-sedating oral antihistamine improves AR symptoms aggravated by air pollution. However, more efficacy studies on other pharmacological therapy of coexisting AR and air pollution are currently lacking. Keywords: Allergic rhinitis, Occupational rhinitis, Air pollution, Climate change, Air pollutants, Indoor air quality, Oxidative stress, Antioxidant enzymes

Clinical application of doxorubicin (DOX) is limited because of its cardiotoxicity. Thus, exploration of effective lead compounds against DOX-induced cardiotoxicity is necessary. The aim of the present study was to investigate the effects and possible mechanisms of dioscin against DOX-induced cardiotoxicity. The in vitro model of DOX- treated H9C2 cells and the in vivo models of DOX-treated rats and mice were used in this study. The results showed that discoin markedly increased H9C2 cell viability, decreased the levels of CK, LDH, and improved histopathological and electrocardio- gram changes in rats and mice to protect DOX-induced cardiotoxicity. Furthermore, dioscin significantly inhibited myocardial oxidative insult through adjusting the levels of intracellular ROS, MDA, SOD, GSH and GSH-Px in vitro and in vivo. Our data also indicated that dioscin activated Nrf2 and Sirt2 signaling pathways, and thereby affected the expression levels of HO-1, NQO1, Gst, GCLM, Keap1 and FOXO3a through decreasing miR-140-5p expression level. In addition, the level of intracellular ROS was significantly increased in H9C2 cells treated by DOX after miR-140-5p mimic transfection, as well as the down-regulated expression levels of Nrf2 and Sirt2, which were markedly reversed by dioscin. In conclusion, our data suggested that dioscin alleviated DOX-induced cardiotoxicity through modulating miR-140-5p-mediated myocardial oxidative stress. This natural product should be developed as a new candidate to alleviate cardiotoxicity caused by DOX in the future., Graphical abstract fx1, Highlights • Dioscin significantly alleviated DOX-induced cardiotoxicity. • Dioscin markedly inhibited myocardial oxidative stress. • Dioscin significantly decreased the levels of miR-140-5p in vitro and in vivo. • Dioscin activated Nrf2 and Sirt2 signal pathways in vitro and in vivo. • Dioscin may be a new potential candidate for DOX-induced cardiotoxicity.

Primary and secondary hypertension is associated with kidney redox imbalance resulting in enhanced reactive oxygen species (ROS) and enzymes dependent phospholipid metabolism. The fatty acid amide hydrolase inhibitor, URB597, modulates the levels of endocannabinoids, particularly of anandamide, which is responsible for controlling blood pressure and regulating redox balance. Therefore, this study aimed to compare the effects of chronic URB597 administration to spontaneously hypertensive rats (SHR) and rats with secondary hypertension (DOCA-salt rats) on the kidney metabolism associated with the redox and endocannabinoid systems. It was shown fatty acid amide hydrolase (FAAH) inhibitor decreased the activity of ROS-generated enzymes what resulted in a reduction of ROS level. Moreover varied changes in antioxidant parameters were observed with tendency to improve antioxidant defense in SHR kidney. Moreover, URB597 administration to hypertensive rats decreased pro-inflammatory response, particularly in the kidneys of DOCA-salt hypertensive rats. URB597 had tendency to enhance ROS-dependent phospholipid oxidation, estimated by changes in neuroprostanes in the kidney of SHR and reactive aldehydes (4-hydroxynonenal and malondialdehyde) in DOCA-salt rats, in particular. The administration of FAAH inhibitor resulted in increased level of endocannabinoids in kidney of both groups of hypertensive rats led to enhanced expression of the cannabinoid receptors type 1 and 2 in SHR as well as vanilloid receptor 1 receptors in DOCA-salt rats. URB597 given to normotensive rats also affected kidney oxidative metabolism, resulting in enhanced level of neuroprostanes in Wistar Kyoto rats and reactive aldehydes in Wistar rats. Moreover, the level of endocannabinoids and cannabinoid receptors were significantly higher in both control groups of rats after URB597 administration. In conclusion, because URB597 disturbed the kidney redox system and phospholipid ROS-dependent and enzymatic-dependent metabolism, the administration of this inhibitor may enhance kidney disorders depending on model of hypertension, but may also cause kidney disturbances in control rats. Therefore, further studies are warranted., Graphical abstract fx1, Highlights • URB597 has tendency to decrease kidney oxidative conditions. • URB597 differentiates Nrf2 pathway response in kidney of SHR and DOCA-salt rats. • URB597 enhances level of phospholipid peroxidation products and endocannabinoids. • URB597 reduces pro-inflammatory response particularly in kidney of DOCA-salt rats.

Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are characterised by immunodeficiency, extreme radiosensitivity, higher cancer susceptibility, premature aging, neurodegeneration and insulin resistance. Some of these functional abnormalities can be explained by aberrant DNA damage response and chromosomal instability. It has been suggested that one possible common denominator of these conditions could be chronic oxidative stress caused by endogenous ROS overproduction and impairment of mitochondrial homeostasis. Recent studies indicate new, alternative sources of oxidative stress in A-T, BS and NBS cells, including NADPH oxidase 4 (NOX4), oxidised low-density lipoprotein (ox-LDL) or Poly (ADP-ribose) polymerases (PARP). Mitochondrial abnormalities such as changes in the ultrastructure and function of mitochondria, excess mROS production as well as mitochondrial damage have also been reported in A-T, BS and NBS cells. A-T, BS and NBS cells are inextricably linked to high levels of reactive oxygen species (ROS), and thereby, chronic oxidative stress may be a major phenotypic hallmark in these diseases. Due to the presence of mitochondrial disturbances, A-T, BS and NBS may be considered mitochondrial diseases. Excess activity of antioxidant enzymes and an insufficient amount of low molecular weight antioxidants indicate new pharmacological strategies for patients suffering from the aforementioned diseases. However, at the current stage of research we are unable to ascertain if antioxidants and free radical scavengers can improve the condition or prolong the survival time of A-T, BS and NBS patients. Therefore, it is necessary to conduct experimental studies in a human model., Graphical abstract fx1

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and progressive joint destruction and is a primary cause of disability worldwide. Despite the existence of numerous anti-rheumatic drugs, a significant number of patients with RA do not respond or are intolerant to current treatments. Mesenchymal stem/stromal cell (MSCs) therapy represents a promising therapeutic tool to treat RA, mainly attributable to the immunomodulatory effects of these cells. This review comprises a comprehensive analysis of the scientific literature related to preclinical studies of MSC-based therapy in RA to analyse key aspects of current protocols as well as novel approaches which aim to improve the efficacy of MSC-based therapy.

Highlights • Patchouli alcohol (PA) is a bioactive component in essential oil extracted from Pogostemon cablin. • The present review provides the scientific mechanisms for health beneficial activities of PA in diverse disease models. • PA possesses diverse health beneficial activities., Patchouli alcohol (PA), a tricyclic sesquiterpene, is a dominant bioactive component in oil extracted from the aerial parts of Pogostemon cablin (patchouli). Diverse beneficial activities have been reported, including anti-influenza virus, anti-depressant, anti-nociceptive, vasorelaxation, lung protection, brain protection, anti-ulcerogenic, anti-colitis, pre-biotic-like, anti-inflammatory, anti-cancer and protective activities against metabolic diseases. However, detailed mechanistic studies are required to explore the possibility of developing PA as a functional food material or promising drug for the prevention and treatment of human diseases. This review highlights multiple molecular targets and working mechanisms by which PA mediates health benefits.

Graphical abstract, Highlights • Decocting YPS and FSI together can better extract flavonoids and polysaccharides • DPPH assay confirmed that MYP had the synergistic antioxidant effect in vitro • Measuring the level of oxidation factors can determine the antioxidant ability of MYP • MYP had a better free radical scavenging effect in vivo than YPS, Objective This study aimed to determine the optimal extraction process and examine whether the combination ofFlos Sophorae Immaturus (FSI) and Yupingfeng san (YPS) has a synergistic effect on free radical scavenging capacity. Design and methods The time of immersion and extraction and the ratios (material/solvent) of the combination of YPS and FSI were optimized on the basis of polysaccharide and flavonoid yields via orthogonal design. The optimal result was used in the 1,1-diphenyl-1-picrylhydrazyl (DPPH) assay and animal experiments to test the antioxidant activity, which is reflected by superoxide dismutase, malondialdehyde, glutathione peroxidase, and total antioxidant capacity serum levels. The optimal extraction process was determined using various ingredients to obtain complex extracts with high active ingredient content and antioxidant activity. DPPH assay results showed that the optimized ingredients have antioxidant effects, and the combination had better antioxidation function than YPS in vitro. The combination also showed synergistic antioxidant activity compared with YPS in vivo. Conclusions The combination of YPS and FSI had a synergistic antioxidant effect in vitro. The optimized extracts had antioxidant effects in vivo. These results indicated that YPS could be used with FSI to improve its antioxidant capacity in the body on the basis of free radical scavenging capacity.

Graphical abstract, Highlights • Capsaicinoids (CAPs) are active compounds in Capsicum fruits. • CAPs have anti-inflammatory and antioxidant properties. • CAPs with regular exercise may enhance lipid metabolism. • CAPs down-regulate muscle SREBP-1c, LXRs, ACLY, FAS in exercised rats., The purpose of this study was to investigate the effects of capsaicinoids (CAPs) on lipid metabolism, inflammation, antioxidant status and the changes in gene products involved in these metabolic functions in exercised rats. A total of 28 male Wistar albino rats were randomly divided into four groups (n = 7) (i) No exercise and no CAPs, (ii) No exercise + CAPs (iii) Regular exercise, (iv) Regular exercise + CAPs. Rats were administered as 0.2 mg capsaicinoids from 10 mg/kg BW/day Capsimax® daily for 8 weeks. A significant decrease in lactate and malondialdehyde (MDA) levels and increase in activities of antioxidant enzymes were observed in the combination of regular exercise and CAPs group (P < 0.0001). Regular exercise + CAPs treated rats had greater nuclear factor-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) levels in muscle than regular exercise and no exercise rats (P < 0.001). Nevertheless, regular exercise + CAPs treated had lower nuclear factor kappa B (NF-κB) and IL-10 levels in muscle than regular exercise and control rats (P < 0.001). Muscle sterol regulatory element-binding protein 1c (SREBP-1c), liver X receptors (LXR), ATP citrate lyase (ACLY) and fatty acid synthase (FAS) levels in the regular exercise + CAPs group were lower than all groups (P < 0.05). However, muscle PPAR-γ level was higher in the regular exercise and CAPs alone than the no exercise rats. These results suggest CAPs with regular exercise may enhance lipid metabolism by regulation of gene products involved in lipid and antioxidant metabolism including SREBP-1c, PPAR-γ, and Nrf2 pathways in rats.

Traditionally, hydrogen sulfide (H2S) was simply considered as a toxic and foul smelling gas, but recently H2S been brought into the spot light of cardiovascular research and development. Since the 1990s, H2S has been mounting evidence of physiological properties such as immune modification, vascular relaxation, attenuation of oxidative stress, inflammatory mitigation, and angiogenesis. H2S has since been recognized as the third physiological gaseous signaling molecule, along with CO and NO [65,66]. H2S is produced endogenously through several key enzymes, including cystathionine β-lyase (CBE), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST)/cysteine aminotransferase (CAT). These specific enzymes are expressed accordingly in various organ systems and CSE is the predominant H2S-producing enzyme in the cardiovascular system.The cystathionine γ-lyase (CSE)/H2S pathway has demonstrated various cardioprotective effects, including anti-atherosclerosis, anti-hypertension, pro-angiogenesis, and attenuation of myocardial ischemia–reperfusion injury. CSE exhibits its anti-atherosclerotic effect through 3 mechanisms, namely reduction of chemotactic factor inter cellular adhesion molecule-1 (ICAM-1) and CX3CR1, inhibition of macrophage lipid uptake, and induction of smooth muscle cell apoptosis via MAPK pathway. The CSE/H2S pathway's anti-hypertensive properties are demonstrated via aortic vasodilation through several mechanisms, including the direct stimulation of KATP channels of vascular smooth muscle cells (VSMCs), induction of MAPK pathway, and reduction of homocysteine buildup. Also, CSE/H2S pathway plays an important role in angiogenesis, particularly in increased endothelial cell growth and migration, and in increased vascular network length. In myocardial ischemia–reperfusion injuries, CSE/H2S pathway has shown a clear cardioprotective effect by preserving mitochondria function, increasing antioxidant production, and decreasing infarction injury size.However, CSE/H2S pathway's role in inflammation mitigation is still clouded, due to both pro and anti-inflammatory results presented in the literature, depending on the concentration and form of H2S used in specific experiment models.

Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica, and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage., Graphical abstract TCM preparation, Chinese materia medica and their active compounds show potential to ameliorate I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage with anti-inflammation, anti-oxidation, anti-apoptosis, anti-excitoxicity and pro-neurogenesis as the major underlying mechanisms.

4-Nitrophenol (PNP), is generally regarded as an environmental endocrine disruptor (EED). Phytosterin (PS), a new feed additive, possesses highly efficient antioxidant activities. The transcription factor, nuclear factor-erythroid 2-related factor 2 (Nrf2), is an important regulator of cellular oxidative stress. Using rats, this study examined PNP-induced testicular oxidative damage and PS-mediated protection against that damage. The generation of MDA and H2O2 upon PNP and PS treatment was milder than that upon treatment with PNP alone. This mitigation was accompanied by partially reversed changes in SOD, CAT, GSH and GSH-Px. Moreover, PNP significantly reduced the caudal epididymal sperm counts and serum testosterone levels. Typical morphological changes were also observed in the testes of PNP-treated animals. PNP reduced the transcriptional level of Nrf2, as evaluated by RT-PCR, but it promoted the dissociation from the Nrf2 complex, stabilization and translocation into the nucleus, as evaluated by immunohistochemistry and Western blotting. In addition, PNP enhanced the Nrf2-dependent gene expression of heme oxygenase-1 (HO-1) and glutamate–cysteine ligase catalytic subunit (GCLC). These results suggest that the Nrf2 pathway plays an important role in PNP-induced oxidative damage and that PS possesses modulatory effects on PNP-induced oxidative damage in rat testes.

Clinical application of doxorubicin (DOX), an anthracycline antibiotic with potent anti- tumor effects, is limited because of its cardiotoxicity. However, its pathogenesis is still not entirely understood. The aim of this paper was to explore the mechanisms and new drug targets to treat DOX-induced cardiotoxicity. The in vitro model on H9C2 cells and the in vivo models on rats and mice were developed. The results showed that DOX markedly decreased H9C2 cell viability, increased the levels of CK, LDH, caused histopathological and ECG changes in rats and mice, and triggered myocardial oxidative damage via adjusting the levels of intracellular ROS, MDA, SOD, GSH and GSH-Px. Total of 18 differentially expressed microRNAs in rat heart tissue caused by DOX were screened out using microRNA microarray assay, especially showing that miR-140-5p was significantly increased by DOX which was selected as the target miRNA. Double-luciferase reporter assay showed that miR-140-5p directly targeted Nrf2 and Sirt2, as a result of affecting the expression levels of HO-1, NQO1, Gst, GCLM, Keap1 and FOXO3a, and thereby increasing DOX-caused myocardial oxidative damage. In addition, the levels of intracellular ROS were significantly increased or decreased in H9C2 cells treated with DOX after miR-140-5p mimic or miR-140-5p inhibitor transfection, respectively, as well as the changed expression levels of Nrf2 and Sirt2. Furthermore, DOX- induced myocardial oxidative damage was worsened in mice treated with miR-140-5p agomir, and however the injury was alleviated in the mice administrated with miR-140-5p antagomir. Therefore, miR-140-5p plays an important role in DOX-induced cardiotoxicity by promoting myocardial oxidative stress via targeting Nrf2 and Sirt2. Our data provide novel insights for investigating DOX-induced heart injury. In addition, miR-140-5p/ Nrf2 and miR-140-5p/Sirt2 may be the new targets to treat DOX-induced cardiotoxicity., Graphical abstract fx1, Highlights • DOX significantly increased the levels of miR-140-5p in vitro and in vivo. • MiR-140-5p aggravated DOX-induced cardiotoxicity. • MiR-140-5p promoted myocardial oxidative stress. • MiR-140-5p directly targeted Nrf2 and Sirt2. • MiR-140-5p may be the new target of DOX-induced cardiotoxicity.

Background The oxidative modifications of bioactive macromolecules have important roles in carcinogenesis. Of particular interest are lipid peroxidation products, which are involved in the activation of Nrf2 and endocannabinoids that affect cancer progression. Methods In lung cancer tissues (squamous cell lung carcinoma - SCC and adenocarcinoma - AC), the glutathione peroxidase and catalase activity and glutathione level, together with the expression of Nrf2 and its activators/inhibitors were estimated. The oxidative modifications of DNA (8-hydroxy-2′-deoxyguanosine and N7-methylguanine), endocannabinoids (anandamide and 2- arachidonylglyceriol), their receptors (CB1/2, TRV1, GPR55), phospholipid fatty acids (arachidonic, linoleic and docosahexaenoic), and reactive aldehydes (4-hydroxynonenal, 4-oxononenal and malondialdehyde) were determined. Results Tumour tissues showed lower antioxidant capacity than healthy tissues, which was accompanied by lower levels of fatty acids and higher levels of reactive aldehydes. Disturbances in antioxidant capacity and enhanced DNA oxidative modifications were observed in 88% of AC patients and 81% of SCC patients. The 4-hydroxynonenal-Histidine adducts were detected in the necrotic and stromal cells in all tumours. These findings were associated with the enhanced Nrf2 activity, especially in AC. The strong difference between the cancer subtypes was evident in the levels of endocannabinoids, with an increase in 89% of SCC and a decrease in 85% of AC patients being observed. Additionally, the increase in the expression of CB1/2 receptors was observed only in 82% of AC, while the expression of VR1 and GPR55 was enhanced in 79% of SCC and 82% of AC patients. Conclusions This study shows significant differences in the redox status, Nrf2 pathway and endocannabinoid system between SCC and AC tissues. Understanding the relation between the various lipid mediators and antioxidants in different lung cancer subtypes may be beginning for further research on the effective anticancer therapy., Graphical abstract fx1, Highlights • AC tissues show lower antioxidant capacity than SCC. • Nrf2/ARE pathway is activated stronger in AC than in SCC. • AC exhibits more lipid oxidative modifications than SCC. • HNE-protein adducts are detected in the necrotic and stromal cells in SCC and AC. • SCC exhibits increase in endocannabinoids level while in AC reverse effect is observed.

Background: Obstructive Jaundice (OJ) is associated with a significant risk of developing acute renal failure (ARF). The involvement of oxidative stress in the development of cholestasis has been demonstrated in different experimental models. However, its role in the morbidity of human cholestasis is far to be elucidated. The aim of the study was the evaluation of oxidative stress markers in blood from patients with OJ and its relation to complications and benign/malignant evolution of cholestasis. Methods: A prospective cross-sectional study of 105 patients with OJ and 34 control subjects were included. Several markers of liver function and oxidative stress, such as lipoperoxides (LPO), as well as reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were assessed. Results: The patients with OJ showed a marked increase in plasma levels of LPO, SOD and GSH, while GSH-Px levels were decreased. The increase in lipid peroxidation products and the depletion of SOD activity in blood were also related to renal dysfunction. The highest level of LPO was associated with malignant etiology of the disease. The logistic regression analysis showed that the age of the patient and the levels of LPO in blood were predictors of renal dysfunction in OJ patients. Conclusions: This study demonstrates a correlation between oxidative stress and renal dysfunction patients with OJ., Graphical abstract fx1, Highlights • Obstructive jaundice was associated to a decreased glomerular filtration rate. • Renal impairment was more frequent in jaundiced patients than in healthy subjects. • LPO levels were higher in jaundiced patients than in healhy subjects, with highest levels related to malignant ethiology. • Renal function was affected by the intensity of the biliary obstruction, and the balance between LPO and antioxidant defenses