The role of PHF5A in cancer: A review and update

PHF5A is a member of the zinc-finger proteins. To advance knowledge on their role in carcinogenesis, data from experimental studies, animal models and clinical studies in different tumorigenesis have been reviewed. Furthermore, PHF5A as an oncogenic function, is frequently expressed in tumor cells and a potential prognostic marker for different cancers. PHF5A is implicated in the regulation of cancer cell proliferation, invasion, migration and metastasis. Knockdown of PHF5A prevented the invasion and metastasis of tumor cells. Here, the role of PHF5A in different cancers and their possible mechanism in relation to recent literature is reviewed and discussed. However, there is an open promising perspective to their therapeutic management for different cancer types.Comment: 18 pages, 1 figure, 2 table

Chronic and moderate consumption of reduced-alcohol wine confers cardiac benefits in a rat model of pulmonary arterial hypertension

Objectives In pulmonary arterial hypertension (PAH), right ventricular (RV) dysfunction develops via mechanisms involving oxidative stress. Moderate and chronic red wine (RW) consumption reduces oxidative stress and confers cardioprotection but its effect on PAH is unknown. We evaluated whether moderate and chronic consumption of reduced-alcohol RW (RARW) confers cardioprotection in a monocrotaline (MCT)-induced PAH rat model. Results Rats were randomly grouped: control; MCT; RARW; MCT + RARW. Wine was diluted to mimic moderate intake for humans, and consumed from 7 days before, until 28 days after MCT-injection. Echocardiography measured pulmonary artery acceleration time (PAAT) and RV thickness. Conjugated dienes (CD), and thiobarbituric acid reactive substances (TBARS) concentrations were assessed. MCT induced RV thickness and decreased PAAT compared to controls [1.22 ± 0.09 mm vs 0.46 ± 0.02 mm and 14 ± 1 vs 23 ± 2 m/s, respectively (p < 0.001)]. Chronic RARW consumption limited MCT-induced RV hypertrophy and increased PAAT. CD and TBARS increased in MCT-treated animals compared to controls (672 ± 43 nmol/L vs 453 ± 35 nmol/L; p < 0.01 and 13 ± 2 µmol/L vs 4 ± 0.3 µmol/L; p < 0.01). RARW reduced MCT-induced CD (472 ± 27 nmol/L vs 672 ± 43 nmol/L; p < 0.01). Conclusion Chronic and moderate intake of RARW ameliorates MCT-induced PAH in rats, which may be partly attributable to reduction of lipid peroxidation

Impact of exercise intensity on oxidative stress and selected metabolic markers in young adults in Ghana

Objective This study aimed to evaluate the effect of different levels of exercise on markers of oxidative stress and selected metabolic parameters in Ghanaian young adults. Results Significant increases in a marker of oxidative stress malondialdehyde and antioxidants such as superoxide dismutase and uric acid were observed in the exercisers compared with the inactive group (p < 0.05). Total cholesterol and high density lipoprotein levels were significantly different (p < 0.05) between the two groups. Positive associations between exercise intensity, antioxidant concentration and malondialdehyde were observed within the exercise group for vigorous exercise with regards to uric acid, superoxide dismutase and malondialdehyde (r = 0.512, p = 0.004; r = 0.810, p = 0.001; r = 0.715, p = 0.001) respectively and moderate exercise vs malondialdehyde (r = 0.841, p = 0.001) compared to the inactive group. Exercise participants performed more vigorous exercise (p < 0.001), moderate exercise (p < 0.001) and more walking (p < 0.001) compared with the inactive group while the inactive group exhibited more sitting (p < 0.001). The study provides a first report on the risk associated with increase in oxidative stress and the importance of walking as a health promotion intervention among young Ghanaian adults

Potential cardioprotective effect of chronic, moderate consumption of reduced-alcohol wine in a rat model of pulmonary hypertension

Background: Pulmonary arterial hypertension (PAH) is a severe disease which leads to right ventricular (RV) dysfunction and possibly death. The pathophysiological process of PAH remains unclear but oxidative stress is thought to contribute to arterial and ventricular dysfunction. Red wine has powerful antioxidant properties and is cardioprotective. However, side effects of alcohol may limit the use of wine as a therapeutic agent. The aim of this study was to test whether reduced-alcohol red wine (RARW) or regular red wine (RW) consumption would limit monocrotaline (MCT)-induced PAH in rats. Methods: Long Evans male rats (150-175g) were randomly assigned into 6 groups: (1) Control: no subcutaneous injection of MCT; (2) MCT; (3) RARW; (4) MCT-Treated with RARW: 5.5% alcohol red wine (5) RW and (6) MCT-Treated with RW: 15% alcohol red wine. The wines were diluted with water (1:7), to supply an equivalent of 2-3 glasses daily consumed in humans ad libitum for 7 days before MCT treatment and for 28 days after MCT treatment with 80mg/kg. The stability of the wine was determined for 4 weeks by analysing ORAC values, total phenolic concentration, anthocyanin and catechin concentrations. Prior to randomisation, and at day 28, echocardiography (VEVO 2100, Visualsonics Inc.) was performed to evaluate pulmonary artery acceleration time (PAAT), an accurate estimate of pulmonary artery pressure, PAAT/Ejection fraction and RV thickness as a marker of RV hypertrophy. Oxidative stress was evaluated by measuring lipid peroxidation markers (conjugated dienes (CD), thiobarbituric acid reactive substances (TBARS)) and antioxidant measures of oxygen radical absorbance capacity (ORAC), superoxide dismutase (SOD) and catalase (CAT) activities in blood plasma were analysed. Results: Baseline echocardiography showed similar cardiac function amongst all groups. MCT injection induced right ventricular hypertrophy compared to controls (1.22 ± 0.01 mm and 0.52 ± 0.04 mm; p< 0.0001). A decrease in PAAT was observed in the MCT group compared to controls (13.95 ± 0.95 vs 23.43 ± 1.64 ms, p< 0.001). However, MCT treatment with RARW ameliorated the trend in the MCT group (18.93 ± 1.80 vs 13.95 ± 0.95 ms, p=0.02). Similarly, PAAT/Ejection fraction in the MCT group was reduced compared to the control group (0.18 ± 0.02 ms and 0.32 ± 0.18 ms; p< 0.001). Chronic moderate treatment with RARW in PAH animals improved hypertrophy and PAAT/Ejection fraction (0.85 ± 0.07 mm; P< 0.001and 0.25 ± 0.30 ms, respectively; p=0.02 versus the MCT group). Oxidative stress markers showed an increase in CD amongst animals with MCT compared to controls (671.60 ± 42.53 nmol/L and 453.10 ± 34.76 nmol/L; p=0.004). Chronic moderate treatment with RARW reduced lipid peroxidation (CD: 471.60 ± 27.45 nmol/L; p=0.004 versus the MCT group). Plasma TBARS, ORAC, SOD and CAT were not significantly affected by the condition or the treatment. The RARW had a consistently higher antioxidant status than the RW for the duration of the study. The mean concentration of RARW to the RW after 4 weeks in the total phenol was (291.90 ± 10.42 vs 235.80 ± 9.22 mg/L, p=0.006), that of the anthocyanins was (190.00 ± 3.53 vs 172.20 ± 5.13 mg/L M-3-G, p=0.0008), that of catechin was (12.06 ± 0.31 vs 10.26 ± 0.19 mg/L, p=0.157), and that of ORAC was (32.55 ± 2.75 vs 26.55 ± 2.37 nmol/L trolox equivalents, p=0.983). Conclusion: This study suggests that a moderate and chronic treatment with RARW but not RW attenuates MCT-induced PAH in rats, an effect which may be mediated, at least in part, by reduction of lipid peroxidation. The use of RARW could be tested in a randomised controlled trial and may be more beneficial than RW. This simple, inexpensive treatment might represent a new therapeutic option for PA

Oxidative Stress, Antioxidants and Hypertension

As a major cause of morbidity and mortality globally, hypertension remains a serious threat to global public health. Despite the availability of many antihypertensive medications, several hypertensive individuals are resistant to standard treatments, and are unable to control their blood pressure. Regulation of the renin-angiotensin-aldosterone system (RAAS) controlling blood pressure, activation of the immune system triggering inflammation and production of reactive oxygen species, leading to oxidative stress and redox-sensitive signaling, have been implicated in the pathogenesis of hypertension. Thus, besides standard antihypertensive medications, which lower arterial pressure, antioxidant medications were tested to improve antihypertensive treatment. We review and discuss the role of oxidative stress in the pathophysiology of hypertension and the potential use of antioxidants in the management of hypertension and its associated organ damage

Oxidative Stress, Antioxidants and Hypertension

As a major cause of morbidity and mortality globally, hypertension remains a serious threat to global public health. Despite the availability of many antihypertensive medications, several hypertensive individuals are resistant to standard treatments, and are unable to control their blood pressure. Regulation of the renin-angiotensin-aldosterone system (RAAS) controlling blood pressure, activation of the immune system triggering inflammation and production of reactive oxygen species, leading to oxidative stress and redox-sensitive signaling, have been implicated in the pathogenesis of hypertension. Thus, besides standard antihypertensive medications, which lower arterial pressure, antioxidant medications were tested to improve antihypertensive treatment. We review and discuss the role of oxidative stress in the pathophysiology of hypertension and the potential use of antioxidants in the management of hypertension and its associated organ damage

Effects of PCSK9 Targeting: Alleviating Oxidation, Inflammation, and Atherosclerosis

Characterized as a chronic inflammatory disease of the large arteries, atherosclerosis is the primary cause of cardiovascular disease, the leading contributor of morbidity and mortality worldwide. Elevated plasma cholesterol levels and chronic inflammation within the arterial plaque are major mediators of plaque initiation, progression, and instability. In 2003, the protein PCSK9 (proprotein convertase subtilisin/kexin 9) was discovered to play a critical role in cholesterol regulation, thus becoming a key player in the mechanisms behind atherosclerotic plaque development. Emerging evidence suggests that PCSK9 could potentially have effects on atherosclerosis that are independent of cholesterol levels. The objective of this review was to discuss the role on PCSK9 in oxidation, inflammation, and atherosclerosis. This function activates proinflammatory cytokine production and affects oxidative modifications within atherosclerotic lesions, revealing its more significant role in atherosclerosis. Although a variety of evidence demonstrates that PCSK9 plays a role in atherosclerotic inflammation, the direct mechanism of involvement is still unknown, driving a gap in knowledge to such a predominant player in cardiovascular disease. Investigation of proteins structurally related to PCSK9 may interestingly be the link in unveiling the mechanistic role of this protein’s involvement in oxidation and inflammation. Importantly, the unique structure of PCSK9 bears structural homology to a one‐of‐a‐kind domain found in the metabolic protein resistin, which is responsible for many of the same inflammatory outcomes as PCSK9. Closing this gap in knowledge of PCSK9`s role in atherosclerotic oxidation and inflammation will provide fundamental information for understanding, preventing, and treating cardiovascular disease

Chronic and moderate consumption of reduced-alcohol wine confers cardiac benefits in a rat model of pulmonary arterial hypertension

Objectives!#!In pulmonary arterial hypertension (PAH), right ventricular (RV) dysfunction develops via mechanisms involving oxidative stress. Moderate and chronic red wine (RW) consumption reduces oxidative stress and confers cardioprotection but its effect on PAH is unknown. We evaluated whether moderate and chronic consumption of reduced-alcohol RW (RARW) confers cardioprotection in a monocrotaline (MCT)-induced PAH rat model.!##!Results!#!Rats were randomly grouped: control; MCT; RARW; MCT + RARW. Wine was diluted to mimic moderate intake for humans, and consumed from 7 days before, until 28 days after MCT-injection. Echocardiography measured pulmonary artery acceleration time (PAAT) and RV thickness. Conjugated dienes (CD), and thiobarbituric acid reactive substances (TBARS) concentrations were assessed. MCT induced RV thickness and decreased PAAT compared to controls [1.22 ± 0.09 mm vs 0.46 ± 0.02 mm and 14 ± 1 vs 23 ± 2 m/s, respectively (p &amp;lt; 0.001)]. Chronic RARW consumption limited MCT-induced RV hypertrophy and increased PAAT. CD and TBARS increased in MCT-treated animals compared to controls (672 ± 43 nmol/L vs 453 ± 35 nmol/L; p &amp;lt; 0.01 and 13 ± 2 µmol/L vs 4 ± 0.3 µmol/L; p &amp;lt; 0.01). RARW reduced MCT-induced CD (472 ± 27 nmol/L vs 672 ± 43 nmol/L; p &amp;lt; 0.01).!##!Conclusion!#!Chronic and moderate intake of RARW ameliorates MCT-induced PAH in rats, which may be partly attributable to reduction of lipid peroxidation

Cross-Talk of NADPH Oxidases and Inflammation in Obesity

Obesity is a major risk factor for cardiovascular and metabolic diseases. Multiple experimental and clinical studies have shown increased oxidative stress and inflammation linked to obesity. NADPH oxidases are major sources of reactive oxygen species in the cardiovascular system and in metabolically active cells and organs. An impaired balance due to the increased formation of reactive oxygen species and a reduced antioxidative capacity contributes to the pathophysiology of cardiovascular and metabolic diseases and is linked to inflammation as a major pathomechanism in cardiometabolic diseases. Non-alcoholic fatty liver disease is particularly characterized by increased oxidative stress and inflammation. In recent years, COVID-19 infections have also increased oxidative stress and inflammation in infected cells and tissues. Increasing evidence supports the idea of an increased risk for severe clinical complications of cardiometabolic diseases after COVID-19. In this review, we discuss the role of oxidative stress and inflammation in experimental models and clinical studies of obesity, cardiovascular diseases, COVID-19 infections and potential therapeutic strategies