-
Journal of Oral and Maxillofacial... 2023Inflammatory cells and cytokines in the chronically injured mucosa promote fibrosis in the oral submucous fibrosis (OSF) fibrotic milieu. Osteopontin (OPN) is a...
BACKGROUND
Inflammatory cells and cytokines in the chronically injured mucosa promote fibrosis in the oral submucous fibrosis (OSF) fibrotic milieu. Osteopontin (OPN) is a wound-healing mediator that upregulates the inflammatory response and is involved in the malignancy and fibrosis of multiple organ systems.
OBJECTIVES
We investigated the expression of OPN in oral potentially malignant disorders (OPMDs) and oral squamous cell carcinomas (OSCCs) to determine its role in the malignant transformation and fibrosis of oral tissues. The expression of OPN in OPMDs and OSCCs was compared and correlated, and the role of OPN as a fibrotic mediator in OSF was explained.
STUDY DESIGN
A total of 30 cases of normal mucosa and OPMDs (mild dysplasia, severe dysplasia, OSF and OSCCs) were studied by purposive sampling. In these groups, OPN immunoreactivity was examined and correlated with clinical findings.
RESULTS
In mild dysplasia, OPN expression was restricted to the basal cell layer with moderate staining intensity. In severe dysplasia, it was extremely intense and extended throughout the epithelium. In the OSF, OPN expression was moderate in the perinuclear areas of the basal cell layer. The expression of OPN was very strong in OSCC. A flow diagram explaining the profibrotic role of OPN in OSF has been provided.
CONCLUSION
A positive role of OPN in both pathogenesis and malignant transformation of OPMDs and OSCC has been demonstrated.
PubMed: 38304518
DOI: 10.4103/jomfp.jomfp_492_22 -
International Journal of Biological... Mar 2024Effects of fermentation by Lactobacillus Plantarum NCU116 on the antihypertensive potential of black sesame seed (BSS) and structure characteristics of fermented black...
Effects of fermentation by Lactobacillus Plantarum NCU116 on the antihypertensive potential of black sesame seed (BSS) and structure characteristics of fermented black sesame seed protein (FBSSP) were investigated. Angiotensin-I-converting enzyme (ACE) inhibition and zinc chelating ability of fermented black sesame seed hydrolysate (FBSSH) reached the highest of 60.78 ± 3.67 % and 2.93 ± 0.04 mg/mL at 48 h and 60 h of fermentation, respectively. Additionally, the antioxidant activities of FBSSH and surface hydrophobicity of FBSSP were increased noticeably by fermentation. The α-helix and β-rotation of FBSSP tended to decrease and increase, respectively, during fermentation. Correlation analysis indicated strong positive relationships between β-turn and ACE inhibition activity as well as zinc chelating ability with correlation coefficients r of 0.8976 and 0.8932. Importantly, novel ACE inhibitory peptides LLLPYY (IC = 12.20 μM) and ALIPSF (IC = 558.99 μM) were screened from FBSSH at 48 h using in silico method. Both peptides showed high antioxidant activities in vitro. Molecular docking analysis demonstrated that the hydrogen bond connected with zinc ions of ACE mainly attributed to the potent ACE inhibitory activity of LLLPYY. The findings indicated that fermentation by Lactobacillus Plantarum NCU116 is an effective method to enhance the antihypertensive potential of BSS.
Topics: Antihypertensive Agents; Lactobacillus plantarum; Sesamum; Fermentation; Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Molecular Docking Simulation; Peptides; Zinc; Peptidyl-Dipeptidase A
PubMed: 38302018
DOI: 10.1016/j.ijbiomac.2024.129811 -
Integrative Medicine Research Mar 2024Herbal medicine Oryeongsan (ORS), also known as Wulingsan in Chinesehas been used for the treatment of impaired body fluid balance. However, the mechanisms involved are...
BACKGROUND
Herbal medicine Oryeongsan (ORS), also known as Wulingsan in Chinesehas been used for the treatment of impaired body fluid balance. However, the mechanisms involved are not clearly defined. The purpose of the present study was to identify the actions of ORS on the renal excretory function and blood pressure (BP) and to define the mechanisms involved in association with renin-angiotensin system (RAS) and natriuretic peptide system (NPS) in spontaneously hypertensive rats (SHR), an animal model of human essential hypertension.
METHODS
Changes in urine volume (UV), excretion of electrolytes including Na (urinary excretion of Na (UV)) were measured. RT-PCR was performed to trace the changes in expression of RAS, NPS and sodium (Na)-hydrogen (H) exchanger 3 (NHE3) in the renal cortex.
RESULTS
In the SHR treated with vehicle (SHR-V) group, UV and UV were suppressed and the Na balance was maintained at the higher levels leading to an increase in BP compared to WKY-V group. These were accompanied by an increase in NHE3 expression with an accentuation of angiotensin I converting enzyme-angiotensin II type 1 (ACE-AT) receptor and concurrent suppression of angiotensin II type 2 (AT) receptor/ACE2-Mas receptor expression in the renal cortex. Chronic treatment with ORS increased UV and UV, and decreased the Na and water balance with a decrease in BP in the ORS-treated SHR-ORS group compared to SHR-V. These were accompanied by a decrease in NHE3 expression with a suppression of ACE-AT receptor and concurrent accentuation of AT/ACE2-Mas receptor.
CONCLUSION
The present study shows that ORS reduced BP with a decrease in Na and water retention by a suppression of NHE3 expression via modulation of RAS and NPS in SHR. The present study provides pharmacological rationale for the treatment of hypertension with ORS in SHR.
PubMed: 38298863
DOI: 10.1016/j.imr.2023.101007 -
Cureus Dec 2023The growing research regarding the implementation of angiotensin-converting enzyme-2 inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in the treatment of... (Review)
Review
Clinical Outcomes of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in COVID-19 Patients With Pre-existing Cardiac Comorbidities: A Literature Review.
The growing research regarding the implementation of angiotensin-converting enzyme-2 inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in the treatment of COVID-19 in patients with pre-existing cardiac comorbidities has become a large topic of discussion since the onset of the pandemic. Previous research primarily associates positive outcomes to the use of these drug classes due to their mechanism of action, which involves the downregulation of angiotensin I-converting enzyme 2 (ACE2) in the renin-angiotensin-aldosterone-system (RAAS) pathway, inflammatory mediators, and cytokines. Thus, these medications can convey preventative and protective effects in patients suffering from a SARS-CoV-2 infection. While we explored the studies that supported the positive outcomes of the use of these drugs in the first half of this review, we also expanded on the limitations of these studies in the latter portion. We also further explored the contradictory studies that indicated that using these antihypertensives can paradoxically increase the severity of COVID-19 infection as well. The studies in support of the use of these medications should consider epigenetic variations, ACE2 variants and acknowledge inherent genetic variations in certain ethnic groups as some have a predisposition for a severe COVID-19 infection. Additionally, mortality rates need to be taken into consideration in these studies as they naturally differ throughout the trajectory of the COVID-19 pandemic. While some studies are in support of the use of these antihypertensives despite other studies suggesting otherwise, further research is needed to explore the long-term effects of these antihypertensives and observe whether they are truly beneficial or not in reducing the severity of COVID-19 infections.
PubMed: 38283421
DOI: 10.7759/cureus.51244 -
The Journal of General and Applied... Jan 2024To enhance the value of surimi, efforts have been made to develop a fermentation method with lactic acid bacteria (LAB) to proteolyze fish protein. However, fermenting...
To enhance the value of surimi, efforts have been made to develop a fermentation method with lactic acid bacteria (LAB) to proteolyze fish protein. However, fermenting unheated surimi poses a spoilage risk due to its high bacterial content. Surimi heat treatment can prevent spoilage, but gel formation induced by heating introduces another technical issue: it hinders uniform fermentation. Thus, this study aims to observe the proteolysis and enhance the functionality of seafood product through lactic acid fermentation of kamaboko, a heated surimi. Upon analyzing the kamaboko fermented with Lactobacillus helveticus JCM1004, we observed that LAB produced protease, resulting in the degradation of myosin heavy chain and actin during fermentation. Lactic acid fermentation significantly augmented the peptide content of kamaboko, subsequently elevating the angiotensin Ⅰ-converting enzyme (ACE) inhibitory activity in 200-fold diluted extract of fermented kamaboko to approximately 70% and higher. Notably, our investigation revealed that proteolysis was confined to the surface of kamaboko, as evidenced by SDS-PAGE analysis. This observation implies that the surface area of kamaboko influences the ACE inhibitory activity. Through a comparative analysis of various bacterial strains, we demonstrated that the increase in ACE inhibitory activity is contingent on the protease generated by LAB. These results suggest that LAB-mediated proteolysis of fish proteins liberates bioactive peptides, thereby manifesting in the ACE inhibitory activity. In summary, this study underscores that the fermentation of kamaboko employing proteolytic LAB holds promise in the development of novel functional seafood products.
PubMed: 38281752
DOI: 10.2323/jgam.2024.01.003 -
Cell Biochemistry and Function Jan 2024The liver is an important organ, and hepatic ischemia-reperfusion (IR) injury is a frequent pathophysiological process that can cause significant morbidity and...
The liver is an important organ, and hepatic ischemia-reperfusion (IR) injury is a frequent pathophysiological process that can cause significant morbidity and mortality. Thus, our study aimed to investigate the effect of targeting PI3K/p-Akt/eNOS (phosphoinositide 3-kinase/phospho-protein kinase B/endothelial nitric oxide synthase), Nrf2/HO-1 (nuclear factor-erythroid 2-related factor-2/heme oxygenase-1), and NF-κB/p53 (nuclear factor-κB/tumor protein 53) signaling pathways by using angiotensin (1-7) [ang-(1-7)] against hepatic injury induced by IR. Thirty-two male rats were included in sham group, ang-(1-7)-treated group, hepatic IR group, and hepatic IR group treated with ang-(1-7). The levels of hepatic ang-(1-7), angiotensin II (Ang II), angiotensin-converting enzyme 2 (ACE2), HO-1, malondialdehyde (MDA), PI3K, and p-Akt were assessed. The expressions of eNOS and B-cell leukemia/lymphoma-2 (BCL-2) in the liver were determined. Histological assessment and immunohistochemical expression of NF-κB, p53, and Nrf2 were carried out. The levels of reduced glutathione (GSH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in serum were estimated. Results showed that administration of ang-(1-7) to hepatic IR rats led to significant amelioration of hepatic damage through a histological evaluation that was associated with significant upregulation of the expressions of PI3K/p-Akt/eNOS and Nrf2/HO-1 with downregulation of NF-κB/p53 signaling pathways. In conclusion, PI3K/p-Akt/eNOS and Nrf2/HO-1 signaling pathways are involved in the protective effects of ang-(1-7) against hepatic damage induced by IR. Therefore, ang-(1-7) can be used to prevent hepatic IR, which occurs in certain conditions such as liver transplantation, hemorrhagic shock, and severe infection.
Topics: Male; Animals; Rats; NF-kappa B; Phosphatidylinositol 3-Kinases; NF-E2-Related Factor 2; Proto-Oncogene Proteins c-akt; Tumor Suppressor Protein p53; Nitric Oxide Synthase Type III; Liver; Ischemia; Reperfusion; Reperfusion Injury; Signal Transduction; Angiotensin I; Peptide Fragments
PubMed: 38269514
DOI: 10.1002/cbf.3938 -
Frontiers in Endocrinology 2023Twin gestation is related to a higher risk of hypertensive disorders in pregnancy with possible risk stratification depending on chorionicity. It may be related to... (Observational Study)
Observational Study
INTRODUCTION
Twin gestation is related to a higher risk of hypertensive disorders in pregnancy with possible risk stratification depending on chorionicity. It may be related to differences in plasma renin-angiotensin-aldosterone components between monochorionic and dichorionic twin pregnancies. The study aimed to analyze the plasma ANG II and ANG 1-7 concentrations in women with monochorionic and dichorionic twin gestation.
METHODS
A prospective observational study included 79 women between 32 and 34 weeks of gestation with twin pregnancy (31 with monochorionic gestation and 48 with dichorionic gestation). Angiotensin II and angiotensin 1-7 concentrations were measured in the collected blood samples.
RESULTS
No significant differences were observed in angiotensin II concentrations between the dichorionic and monochorionic group with significantly higher levels of angiotensin 1-7 being observed in the dichorionic group. Angiotensin 1-7 level was higher than angiotensin II in 20 women (64.5%) in the monochorionic group and in 42 women (87.5%, p=0.01) in the dichorionic group. Higher plasma concentrations of angiotensin II and lower concentrations of angiotensin 1-7 were found in 5 women with gestational hypertension and in 3 with preeclampsia compared to normotensive women.
DISCUSSION
It is the first study investigating angiotensin II and angiotensin 1-7 in twin pregnancies regarding chorionicity. Our results showed that plasma angiotensin 1-7 concentration was related to chorionicity, while plasma angiotensin II level was not. In most women with twin gestation angiotensin 1-7 concentration exceeded the concentration of angiotensin II. A switch in the relation between angiotensin II and angiotensin 1-7 was observed in hypertensive pregnant women.
Topics: Pregnancy; Female; Humans; Pregnancy, Twin; Angiotensin II; Pregnancy Trimester, Third; Peptide Hormones; Hypertension, Pregnancy-Induced; Angiotensin I; Peptide Fragments
PubMed: 38260128
DOI: 10.3389/fendo.2023.1329025 -
Biomedicines Jan 2024We hypothesized that subjects with heterozygous loss-of-function (LoF) mutations are at risk for Alzheimer's disease because amyloid Aβ42, a primary component of the...
We hypothesized that subjects with heterozygous loss-of-function (LoF) mutations are at risk for Alzheimer's disease because amyloid Aβ42, a primary component of the protein aggregates that accumulate in the brains of AD patients, is cleaved by ACE (angiotensin I-converting enzyme). Thus, decreased ACE activity in the brain, either due to genetic mutation or the effects of ACE inhibitors, could be a risk factor for AD. To explore this hypothesis in the current study, existing SNP databases were analyzed for LoF mutations using four predicting tools, including PolyPhen-2, and compared with the topology of known mutations already associated with AD. The combined frequency of >400 of these LoF-damaging mutations in the general population is quite significant-up to 5%-comparable to the frequency of AD in the population > 70 y.o., which indicates that the contribution of low ACE in the development of AD could be under appreciated. Our analysis suggests several mechanisms by which ACE mutations may be associated with Alzheimer's disease. Systematic analysis of blood ACE levels in patients with all mutations is likely to have clinical significance because available sequencing data will help detect persons with increased risk of late-onset Alzheimer's disease. Patients with transport-deficient mutations (about 20% of damaging ACE mutations) may benefit from preventive or therapeutic treatment with a combination of chemical and pharmacological (e.g., centrally acting ACE inhibitors) chaperones and proteosome inhibitors to restore impaired surface ACE expression, as was shown previously by our group for another transport-deficient ACE mutation-Q1069R.
PubMed: 38255267
DOI: 10.3390/biomedicines12010162 -
Inflammation Jun 2024Sepsis-induced acute liver injury (ALI) is common in intensive care units. Angiotensin-converting enzyme 2 (ACE2) plays a vital role in hepatic fibrosis and steatosis;...
Sepsis-induced acute liver injury (ALI) is common in intensive care units. Angiotensin-converting enzyme 2 (ACE2) plays a vital role in hepatic fibrosis and steatosis; however, its role in sepsis-induced ALI remains unclear. This study found that hepatic ACE2 expression in cecal ligation and puncture (CLP)-treated mice significantly decreased 24 h after CLP. ACE2-transgenic (TG) mice exhibited a significant improvement in CLP-induced ALI, accompanied by the inhibition of hepatocyte apoptosis, oxidative stress, and inflammation, while ACE2-knockout mice demonstrated an opposite trend. During sepsis-induced ALI, ACE2-TG could also elevate the Ang-(1-7) and Mas receptor (MasR) levels in liver tissues. Interestingly, the MasR inhibitor A779 abrogated the favorable effects of ACE2 on CLP-induced ALI. In a bone marrow transplantation experiment, the ACE2-TG transplantation group showed significantly improved inflammation and liver dysfunction, less hepatocyte apoptosis, and reduced oxidative stress after CLP compared with the wild-type transplantation group. In contrast, the ACE2-knockout group showed poor inflammatory response and liver dysfunction, significantly more hepatocyte apoptosis, and elevated oxidative stress than the wild-type transplantation group after CLP. ACE2 protects against sepsis-induced ALI by inhibiting hepatocyte apoptosis, oxidative stress, and inflammation via the Ang-(1-7)-Mas receptor axis. Thus, targeting ACE2 may be a promising novel strategy for preventing and treating sepsis-induced ALI.
Topics: Animals; Angiotensin-Converting Enzyme 2; Sepsis; Angiotensin I; Receptors, G-Protein-Coupled; Mice; Peptide Fragments; Proto-Oncogene Proteins; Proto-Oncogene Mas; Myeloid Cells; Apoptosis; Mice, Knockout; Oxidative Stress; Peptidyl-Dipeptidase A; Mice, Transgenic; Hepatocytes; Liver
PubMed: 38240986
DOI: 10.1007/s10753-023-01949-5