Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system

The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.

Renin-angiotensin system inhibitors prescriptions in Chinese hospitalized chronic kidney disease patients

BACKGROUND Many guidelines have recommended renin-angiotensin system inhibitors(RASI)as the first-line treatment for patients with chronic kidney disease(CKD).We studied RASI prescription trends from 2010 to 2019,and analyzed the characteristics associated with RASI prescription in Chinese hospitalized CKD patients.AIM To study the prescription of renin angiotensin system inhibitors in hospitalized patients with CKD in China.METHODS It was retrospectively,cross-sectional reviewed RASI prescriptions in hospitalized CKD patients in China from 2010 to 2019.RASI prescribing trends were analyzed from 2010 to 2019,and bivariate and multivariate logistic regression analyses were conducted to identify characteristics associated with RASI prescription.RESULTS A total of 35090 CKD patients were included,with 10043(28.6%)RASI prescriptions.Among these patients,18919(53.9%)met the criteria for RASI treatments based on the 2012 kidney disease:Improving global outcomes guidelines.Of these,7246(38.3%)patients received RASI prescriptions.RASI prescriptions showed an initial rapid increase from 2011 to 2012,reached its peak around 2015 and 2016,and then exhibited a subsequent slight decreasing trend.Both bivariate and multivariate analyses showed that several characteristics,including the male gender,age less than 60-year-old,nephrology department admission,lower CKD stage,history of hypertension or diabetes,proteinuria,glomerulonephritis as the CKD etiology,and non-acute kidney injury were associated with RASI prescriptions.CONCLUSION The frequency of RASI prescriptions showed an initial increase but a slight decreasing trend in more recent years.CKD patients with certain characteristics such as elderly age,advanced disease stage,surgery department admission,or acute kidney injury were less likely to receive RASI prescriptions.In the application of RASI in hospitalized CKD patients is insufficient.The actual clinical practice needs to be improved.The development of related research is helpful to guide the correct choice of clinical treatment strategy.

Angiotensin-converting enzyme 2 and AMPK/mTOR pathway in the treatment of liver fibrosis:Should we consider further implications?

This editorial contains comments on the article by Zhao et al in print in the World Journal of Gastroenterology.The mechanisms responsible for hepatic fibrosis are also involved in cancerogenesis.Here,we recapitulated the complexity of the renin-angiotensin system,discussed the role of hepatic stellate cell(HSC)autophagy in liver fibrogenesis,and analyzed the possible implications in the development of hepatocarcinoma(HCC).Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers definitively contribute to reducing hepatic fibrogenesis,whereas their involvement in HCC is more evident in experimental conditions than in human studies.Angiotensin-converting enzyme 2(ACE2),and its product Angiotensin(Ang)1-7,not only regulate HSC autophagy and liver fibrosis,but they also represent potential targets for unexplored applications in the field of HCC.Finally,ACE2 overexpression inhibits HSC autophagy through the AMP-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)pathway.In this case,Ang 1-7 acts binding to the MasR,and its agonists could modulate this pathway.However,since AMPK utilizes different targets to suppress the mTOR downstream complex mTOR complex 1 effectively,we still need to unravel the entire pathway to identify other potential targets for the therapy of fibrosis and liver cancer.

What have we learned about the kallikrein-kinin and renin-angiotensin systems in neurological disorders?

The kallikrein-kinin system(KKS) is an intricate endogenous pathway involved in several physiological and pathological cascades in the brain. Due to the pathological effects of kinins in blood vessels and tissues, their formation and degradation are tightly controlled. Their components have been related to several central nervous system diseases such as stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy and others. Bradykinin and its receptors(B1R and B2R) may have a role in the pathophysiology of certain central nervous system diseases. It has been suggested that kinin B1R is up-regulated in pathological conditions and has a neurodegenerative pattern, while kinin B2R is constitutive and can act as a neuroprotective factor in many neurological conditions. The renin angiotensin system(RAS) is an important blood pressure regulator and controls both sodium and water intake. AngⅡ is a potent vasoconstrictor molecule and angiotensin converting enzyme is the major enzyme responsible for its release. AngⅡ acts mainly on the AT1 receptor, with involvement in several systemic and neurological disorders. Brain RAS has been associated with physiological pathways, but is also associated with brain disorders. This review describes topics relating to the involvement of both systems in several forms of brain dysfunction and indicates components of the KKS and RAS that have been used as targets in several pharmacological approaches.

Renin-angiotensin system in the kidney: What is new?

The renin-angiotensin system （RAS） has been known for more than a century as a cascade that regulates body fuid balance and blood pressure. Angiotensin Ⅱ（Ang Ⅱ） has many functions in different tissues; how-ever it is on the kidney that this peptide exerts its main functions. New enzymes, alternative routes for Ang Ⅱformation or even active Ang Ⅱ-derived peptides have now been described acting on Ang Ⅱ AT1 or AT2 recep-tors, or in receptors which have recently been cloned, such as Mas and AT4. Another interesting observation was that old members of the RAS, such as angioten-sin converting enzyme （ACE）, renin and prorenin, well known by its enzymatic activity, can also activate intra-cellular signaling pathways, acting as an outside-in sig-nal transduction molecule or on the renin/（Pro）renin re-ceptor. Moreover, the endocrine RAS, now is also known to have paracrine, autocrine and intracrine action on different tissues, expressing necessary components for local Ang Ⅱ formation. This in situ formation, especially in the kidney, increases Ang Ⅱ levels to regulate blood pressure and renal functions. These discoveries, such as the ACE2/Ang-（1-7）/Mas axis and its antangonistic effect rather than classical deleterious Ang Ⅱ effects, improves the development of new drugs for treating hypertension and cardiovascular diseases.

The renin-angiotensin system,mood,and suicide:Are there associations?

Available evidence points to a possible role of the renin-angiotensin system(RAS)in the pathophysiology of mood disorders and suicide.We carried out a critical analysis of literature data regarding this role,with a focus on the proposed association between RAS dysfunction and suicidal behavior.Epidemiological,genetic,and biochemical findings are described,and the pathophysiological hypothesis aiming at explaining the possible relationship between RAS and suicide are discussed.Available findings do support the involvement of the RAS in the neurobiology of suicide,although the exact mechanisms underlying this involvement are still unknown.

Renin-angiotensin system blockers-SGLT2 inhibitorsmineralocorticoid receptor antagonists in diabetic kidney disease:A tale of the past two decades!

Several pharmacological agents to prevent the progression of diabetic kidney disease(DKD)have been tested in patients with type 2 diabetes mellitus(T2DM)in the past two decades.With the exception of renin-angiotensin system blockers that have shown a significant reduction in the progression of DKD in 2001,no other pharmacological agent tested in the past two decades have shown any clinically meaningful result.Recently,the sodium-glucose cotransporter-2 inhibitor(SGLT-2i),canagliflozin,has shown a significant reduction in the composite of hard renal and cardiovascular(CV)endpoints including progression of end-stage kidney disease in patients with DKD with T2DM at the top of reninangiotensin system blocker use.Another SGLT-2i,dapagliflozin,has also shown a significant reduction in the composite of renal and CV endpoints including death in patients with chronic kidney disease(CKD),regardless of T2DM status.Similar positive findings on renal outcomes were recently reported as a top-line result of the empagliflozin trial in patients with CKD regardless of T2DM.However,the full results of this trial have not yet been published.While the use of older steroidal mineralocorticoid receptor antagonists(MRAs)such as spironolactone in DKD is associated with a significant reduction in albuminuria outcomes,a novel non-steroidal MRA finerenone has additionally shown a significant reduction in the composite of hard renal and CV endpoints in patients with DKD and T2DM,with reasonably acceptable side effects.

Ocular renin-angiotensin system with special reference in the anterior part of the eye

The renin-angiotensin system(RAS) regulates blood pressure(BP) homeostasis, systemic fluid volume and electrolyte balance. The RAS cascade includes over twenty peptidases, close to twenty angiotensin peptides and at least six receptors. Out of these, angiotensin Ⅱ, angiotensin converting enzyme 1 and angiotensin Ⅱ type 1 receptor(AngⅡ-ACE1-AT1R) together with angiotensin(1-7), angiotensin converting enzyme 2 and Mas receptor(Ang(1-7)-ACE2-Mas R) are regarded as the main components of RAS. In addition to circulating RAS, local RA-system exists in various organs. Local RA-systems are regarded as tissue-specific regulatory system accounting for local effects and long term changes in different organs. Many of the central components such as the two main axes of RAS: AngⅡ-ACE1-AT1 R and Ang(1-7)-ACE2-Mas R, have been identified in the human eye. Furthermore, it has been shown that systemic antihypertensive RAS- inhibiting medications lower intraocular pressure(IOP). These findings suggest the crucial role of RAS not only in the regulation of BP but also in the regulation of IOP, and RAS potentially plays a role in the development of glaucoma and antiglaucomatous drugs.

Effect of cydosporin on renin-angiotensin system in a rat model of chronic cyclosporine nephropathy

Objective To explore the mechanisms of cyclosporin-induced chronic nephrotoxicity. Methods Radioimmunoassay was used to study the changes of plasma renin activity (PRA) ,plasma angiotensin Ⅱ(Ang Ⅱ),and Aldosterone after rats were given low salt diet and 30 mg?kg-1?d-1of CsAfor 28 days. The protective effects of Radix Salviae Miltiorrhizae or benazepril on these changes were also studied. Results In CsA-treated rats, PRA and Ang Ⅱ levels were significantly elevated as compared with control groups. The elevation was not influenced by injection of Radix Salviae Miltiorrhizae,but could be blocked markedly by benazepril. There was significant difference in Aldosterone levels among the groups except benazepril-treated group showing a decreased Aldosterone level. Conclusion Chronic cyclosporone nephropathy may be related to activation of renin-angiotensin system, especially to the elevation of Ang Ⅱ levels. The different effects of Radix Salviae Miltiorrhizae or benazepril on RAS suggest the different

Integrated Chinese and Western medicine in the treatment of a patient with podocyte infolding glomerulopathy:A case report

BACKGROUND Podocyte infolding glomerulopathy(PIG)is a newly described and rare glomerular disease.To date,only approximately 40 cases have been reported globally.CASE SUMMARY A 26-year-old female patient presented to our hospital with a complaint of intermittent edema of both lower limbs over the past 2 years.The patient was diagnosed with PIG.She was prescribed corticosteroid therapy in other hospitals during the initial stage,to which she had responded poorly and had developed femoral head necrosis.Therefore,we administered immunosuppressants,reninangiotensin system inhibitors,combined with traditional Chinese medicine.The patient was followed for 1 year,during which her clinical condition improved.CONCLUSION Integrated Chinese and Western medicine may be effective for PIG treatment,which requires active intervention to improve prognosis.

MicroRNA-155 mediates endogenous angiotensin II type 1 receptor regulation:implications for innovative type 2 diabetes mellitus management

Type 2 diabetes mellitus(T2DM)is a lifelong condition and a threat to human health.Thorough understanding of its pathogenesis is acutely needed in order to devise innovative,preventative,and potentially curative pharmacological interventions.MicroRNAs(miRNA),are small,non-coding,one-stranded RNA molecules,that can target and silence around 60%of all human genes through translational repression.MiR-155 is an ancient,evolutionarily well-conserved miRNA,with distinct expression profiles and multifunctionality,and a target repertoire of over 241 genes involved in numerous physiological and pathological processes including hematopoietic lineage differentiation,immunity,inflammation,viral infections,cancer,cardiovascular conditions,and particularly diabetes mellitus.MiR-155 Levels are progressively reduced in aging,obesity,sarcopenia,and T2DM.Thus,the loss of coordinated repression of multiple miR-155 targets acting as negative regulators,such as C/EBPβ,HDAC4,and SOCS1 impacts insulin signaling,deteriorating glucose homeostasis,and causing insulin resistance(IR).Moreover,deranged regulation of the renin angiotensin aldosterone system(RAAS)through loss of Angiotensin II Type 1 receptor downregulation,and negated repression of ETS-1,results in unopposed detrimental Angiotensin II effects,further promoting IR.Finally,loss of BACH1 and SOCS1 repression abolishes cytoprotective,anti-oxidant,anti-apoptotic,and anti-inflam matory cellular pathways,and promotesβ-cell loss.In contrast to RAAS inhibitor treatments that further decrease already reduced miR-155 Levels,strategies to increase an ailing miR-155 production in T2DM,e.g.,the use of metformin,mineralocorticoid receptor blockers(spironolactone,eplerenone,finerenone),and verapamil,alone or in various combinations,represent current treatment options.In the future,direct tissue delivery of miRNA analogs is likely.

IgA Nephropathy: Are We Doing Enough?

Immunoglobulin A nephropathy (IgAN) was first identified and described as a disease by Berger and Hinglais in 1968. It is the most common primary glomerulopathy worldwide [1], most prevalent in East Asians and Caucasians and rare in black individuals. There are four key elements that contribute to IgAN, which determine the severity, course, and prognosis of the disease: circulating IgA immunocomplexes that favor mesangial deposition, the efficiency of the reticuloendothelial system, mesangial cell affinity and reaction to mesangial accumulation of poorly glycosylated IgA1, and the renal tendency to glomerulosclerosis and interstitial fibrosis. Clinical manifestations among patients with IgAN include hematuria, approximately 40% to 50% of cases present with one or more episodes of hematuria, usually preceded by upper respiratory tract infections. Between 30% and 40% present with hematuria and non-nephrotic range proteinuria that may be associated with arterial hypertension and impaired renal function. The TESTING study reveal a significant decrease in outcomes such as the risk of a 40% decrease in glomerular filtration rate or the need for renal replacement therapy in the group treated with steroids. The decrease in renal function compared to the group treated in the previously mentioned STOP-IgAN trial was 4 times less than in the TESTING study. Are we doing enough? Obviously, more trials are required with the use of adequate nephroprotection measures. We present 3 patients with a diagnosis of IgA nephropathy who attend the follow-up consultation and voluntarily decide to take part in the review.

基于GPS和GIS的精细农业信息处理系统研究

为了解决精细农业中空间信息的快速获取与分析处理问题 ,研究了一种用 Map Objects实现 GIS与 GPS有机结合的信息处理系统 ,具有空间数据可视化分析处理 ,实时测定和显示动点轨迹 ,并具有计算面积等功能 ,能很好地与专家系统和决策支持系统等结合。为展开精细农业的研究 。

ACE/AngⅡ/AT1轴和ACE2/Ang(1-7)/Mas轴对脂肪组织糖脂代谢的影响

肾素-血管紧张素系统(RAS)存在两条相互拮抗的轴:血管紧张素转化酶(ACE)-血管紧张素Ⅱ(AngⅡ)-AT1轴和血管紧张素转化酶2(ACE2)-血管紧张素(1-7)[Ang(1-7)]-Mas轴。RAS可作用于脂肪组织对糖脂代谢进行调节。ACE/AngⅡ/AT1轴引起脂肪组织糖代谢异常,而ACE2/Ang(1-7)/Mas轴能改善脂肪组织糖代谢。RAS在肥胖患者被过度激活,与肥胖、脂代谢紊乱和胰岛素抵抗存在潜在的联系。深入研究ACE/AngⅡ/AT1轴和ACE2/Ang(1-7)/Mas轴对脂肪组织糖脂代谢的影响,有可能为改善糖脂代谢发现新的治疗靶点。

Inflammation, oxidative stress and renin angiotensin system in atherosclerosis

Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.

The regulatory role of AT 1 receptor on activated HSCs in hepat,c fibrogenesis,effects of RAS inhibitors on hepatic fibrosis induced by CCl_4

AIM To assess the effect of ACE inhibitor andAng Ⅱ type Ⅰ（AT1）receptor antagonist inpreventing hepatic fibrosis caused by CCl4administration in rats;to investigate whether ornot there are expression of AT 1 receptors onhepatic stellate cells;and to observe the effectof Ang Ⅱ on proliferation and ECM synthesis ofcultured HSCs.METHODS Studies were conducted in maleSprague-Dawley rats.Except for thehepatofibrotic model group and the controlgroup,in three treated groups,either enalapril（5 mg/kg）,or Iosartan（10 mg/kg）,or enalapril+Iosartan were given to the fibrotic rats bydaily gavage,and saline vehicle was given tomodel and normal control rats.After 6 weeks,liver fibrosis was assessed directly by hepaticmorphometric analysis,which has beenconsidered the gold standard for thequantification of fibrosis.The expressions of AT1 receptors and（α-mooth muscle actin,α-SMA）in liver tissue or isolated hepatic stellate cells（HSCs）were detected by immunohistochemicaltechniques.The effect of Ang Ⅱ on HSCproliferation was determined by MTT method.Effect of Ang Ⅱ on collagen synthesis of HSCswas determined by 3H-proline incorporation.RESULTS Contrasted to the fibrosis in rats ofthe model group,groups of rats treated with either enalapril or Iosartan,or a combination oftwo drugs showed a limited expansion of theinterstitium（4.23±3.70 vs 11.22±4.79,P【0.05）,but no difference was observedamong three treated groups（5.38±3.43,4.96±2.96,4.23±2.70,P】0.05）.Expression of AT 1receptors was found in fibrotic interstitium offibrotic rats,whereas in normal control rats theywere limited to vasculature only to a very slightdegree.AT 1 receptors were also expressed onactivated HSCs in the culture.At concentrationsfrom 10-9to 10-5mol/L,Ang Ⅱ stimulated HSCproliferation in culture in a dose-dependentmanner.Increasing Ang Ⅱ concentrationsproduced corresponding increases in 3H-prolineincorporation.Differences among groups were significant.CONCLUSION Angiotensin-converting enzyme inhibitors and AT I blocker may slow the progression of hepatic fibrosis; activated HSCs express AT 1 receptors, and Ang Ⅱ can stimulate the proliferation and collagen synthesis of HSCs in a dose-dependent manner; and activation of RAS may be related to hepatic fibrogenesis induced by CCI4.

Prehypertension: Underlying pathology and therapeutic options

Prehypertension(PHTN) is a global major health risk that subjects individuals to double the risk of cardiovascular disease(CVD) independent of progression to overt hypertension. Its prevalence rate varies considerably from country to country ranging between 21.9% and 52%. Many hypotheses are proposed to explain the underlying pathophysiology of PHTN. The most notable of these implicate the renin-angiotensin system(RAS) and vascular endothelium. However, other processes that involve reactive oxygen species, the inflammatory cytokines, prostglandins and C-reactive protein as well as the autonomic and central nervous systems are also suggested. Drugs affecting RAS have been shown to produce beneficial effects in prehypertensives though such was not unequivocal. On the other hand, drugs such as β-adrenoceptor blocking agents were not shown to be useful. Leading clinical guidelines suggest using dietary and lifestyle modifications as a first line interventional strategy to curb the progress of PHTN; however, other clinically respected views call for using drugs. This review provides an overview of the poten-tial pathophysiological processes associated with PHTN, abridges current intervention strategies and suggests investigating the value of using the "Polypill" in prehypertensive subjects to ascertain its potential in delaying(or preventing) CVD associated with raised blood pressure in the presence of other risk factors.

Effects of AT1 receptor antagonist,Iosartan,on rat hepatic fibrosis induced by CCl_4

AIM To investigate effect of losartan,an AT1receptor antagonist,on hepatic fibrosis induced byCCl;and to determine whether or not AT1receptors are expressed on hepatic stellate cells,METHODS AND RESULTS Fifty male Sprague-Dawley rats,weighing（180±20）g,wererandomized into five groups（control group,modelgroup,and three losartan treated groups）,inwhich all rats were given the subcutaneousinjection of 40% CCl4（every 3 days for 6 weeks）except for rats of control group.Rats of losartan-treated groups were treated with losartan（20 mg/kg,10 mg/kg,5 mg/kg,daily gavage）,After 6weeks liver tissue and serum samples of all ratswere examined.Serum hyaluronic acid（HA）,procollagen typeⅢ（PCⅢ）were detected byradioimmunoassays,van Giesion collagen stainingwas used to evaluate the extracellular matrix of ratswith liver fibrosis.The expression of AT1receptors,transforming growth factor-beta（TGF-β）,and alpha-smooth muscle actin（a-SMA）inliver tissue were determined byimmunohistochemical techniques.Compared withmodel group,serum ALT and AST of losartan-treated groups were significantly reduced（t=4.20,P【0.01 and t=4.57,P【0.01）.Serum HAand PCⅢalso had significant differences（t=3.53,P【0.01 and t=2.20,P【0.05）.Thedegree of fibrosis was improved by losartan and correlated with the expressions of AT1 receptors,TGF-β,and α-SMA in liver tissue.CONCLUSION AT1 receptor antagonist,losartan,could limit the progression of the hepatic fibrosisinduced by CCl4.The mechanism may be related tothe decrease in the expression of AT1 receptorsand TGF-β,ameliorating the injury of hepatocytes;activation of local renin-angiotensin system mightrelate to hepatic fibrosis;and during progressionof fibrosis,activated hepatic stellate cells mightexpress AT1 receptors.

Dynamic Variation of RAS on Silicotic Fibrosis Pathogenesis in Rats

The dynamic variation of renin-angiotensin system (RAS) in silicosis remains unclear.Seventy Wistar rats were divided into 7 groups including control group,silicosis groups (inhaling SiO2 for 2,4,8,16 and 24 weeks,respectively) and Captopril (Cap) group.Rat lung primary fibroblasts were divided into control group,SiO2-stimulated group (0,0.5,1,3,6,12,24 and 48 h) and Cap group.The silicotic nodules were formed and collagens were deposited gradually in silicosis group observed by haematoxylin and eosin (HE) staining and Van Gieson (VG) staining.Cap relieved the lung fibrosis and collagen deposition.Immunohistochemistry indicated the positive expression of α-smooth muscle actin α-SMA) was increased gradually in silicotic rat lung tissue.Western blotting revealed the expression of collagen type Ⅰ(Col Ⅰ) and α-SMA was up-regulated in silicotic rat lung tissue and fibroblasts stimulated by SiCh.Cap decreased the expression of Col Ⅰ and α-SMA in silicotic rat lung tissue and fibroblasts stimulated by SiCh.Western blotting also demonstrated the expression of angiotensin-converting enzyme (ACE) and angiotensin Ⅱ type 1 receptor (ATI) was increased,and the expression of ACE2 and Mas was decreased gradually in silicotic rat lung tissue and fibroblasts stimulated by SiCh.ELISA showed the serum levels of ACE and angiotensin Ⅱ(Ang Ⅱ) were also increased and ACE2 and Ang (1 -7) were decreased in the silicosis group.Treatment with Cap decreased the expression levels of ACE,Ang Ⅱ and ATI,and increased the expression levels of ACE2,Ang (1-7) and Mas.These findings suggested that an imbalance between ACE-Ang Ⅱ-AT1 axis and ACE2-Ang (l-7)-Mas axis may participate in the development of silicosis.

Clinical therapeutic strategies for early stage of diabetic kidney disease

Diabetic kidney disease(DKD) is the most common cause of chronic kidney disease, leading to end-stage renal disease and cardiovascular disease. The overall number of patients with DKD will continue to increase in parallel with the increasing global pandemic of type 2 diabetes. Based on landmark clinical trials, DKD has become preventable by controlling conventional factors, including hyperglycemia and hypertension, with multifactorial therapy; however, the remaining risk of DKD progression is still high. In this review, we show the importance of targeting remission/regression of microalbuminuria in type 2 diabetic patients, which may protect against the progression of DKD and cardiovascular events. To achieve remission/regression of microalbuminuria, several steps are important, including the early detection of microalbuminuria with continuousscreening, targeting HbA1c < 7.0% for glucose control, the use of renin angiotensin system inhibitors to control blood pressure, the use of statins or fibrates to control dyslipidemia, and multifactorial treatment. Reducing microalbuminuria is therefore an important therapeutic goal, and the absence of microalbuminuria could be a pivotal biomarker of therapeutic success in diabetic patients. Other therapies, including vitamin D receptor activation, uric acid-lowering drugs, and incretin-related drugs, may also be promising for the prevention of DKD progression.