Bioengineering scalable and drug-responsive in vitro human multicellular non-alcoholic fatty liver disease microtissues encapsulated in the liver extracellular matrix-derived hydrogel.

Non-alcoholic fatty liver disease (NAFLD) is a high-prevalence and progressive disorder. Due to lack of reliable in vitro models to recapitulate the consecutive phases, the exact pathogenesis mechanism of this disease and approved therapeutic medications have not been revealed yet. It has been proven that the interplay between multiple hepatic cell types and liver extracellular matrix (ECM) are critical in NAFLD initiation and progression. Herein, a liver microtissue (LMT) consisting of Huh-7, THP-1, and LX-2 cell lines and human umbilical vein endothelial cells (HUVEC), which could be substituted for the main hepatic cells (hepatocyte, Kupffer, stellate, and sinusoidal endothelium, respectively), encapsulated in liver derived ECM-Alginate composite, was bioengineered. When the microtissues were treated with free fatty acids (FFAs) including Oleic acid (6.6×10-4M) and Palmitic acid (3.3×10-4M), they displayed the key features of NAFLD, including similar pattern of transcripts for genes involved in lipid metabolism, inflammation, insulin-resistance, and fibrosis, as well as pro-inflammatory and pro-fibrotic cytokines' secretions and intracellular lipid accumulation. Continuing FFAs supplementation, we demonstrated that the NAFLD phenomenon was established on day 3 and progressed to the initial fibrosis stage by day 8. Furthermore, this model was stable until day 12 post FFAs withdrawal on day 3. Moreover, administration of an anti-steatotic drug candidate, Liraglutide (15 µM), on the NAFLD microtissues significantly ameliorated the NAFLD phenomenon. Overall, we bioengineered a drug-responsive, cost-benefit liver microtissues which can simulate the initiation and progression of NAFLD. It is expected that this platform could potentially be used for studying molecular pathogenesis of NAFLD and high-throughput drug screening. See also the graphical abstract(Fig. 1).

Diminution of STING Expression in the Blood of Patients with Severe or Critical COVID-19 Pneumonia.

INTRODUCTION: Cytokine storm and critical COVID-19 pneumonia are caused in at least 10% of patients by inborn errors of or auto-Abs to type I IFNs. The pathogenesis of life-threatening COVID-19 pneumonia in other patients remains unknown. METHODS: This study was conducted at Masih Daneshvari Hospital, Tehran, Iran. In the period of study, 75 confirmed cases of COVID-19 with presentations ranging from mild upper respiratory tract infection to lower respiratory tract infection, including moderate, severe, and critical disease, were recruited. Expression of STING mRNA was measured in peripheral blood mononuclear cells (PBMCs) and compared between patients with different severity and outcome. RESULTS: There was a significant negative correlation between age and STING expression level (p value = 0.010). Patients with "severe to critical" illness had a 20-fold lower STING expression level compared to the "mild to moderate" group (p value = 0.001). Also, the results showed lower expressions of STING in the patients admitted to the ICU (p value = 0.015). Patients who finally died had lower expression of STING at the time of sampling (p value = 0.041). CONCLUSION: STING mRNA expression in PBMCs was significantly lower in older COVID-19 cases, the patients with more severe illness, who needed intensive care, and who eventually died.

The role of angiotensin I converting enzyme insertion/deletion polymorphism in the severity and outcomes of COVID-19 patients.

The pandemic of coronavirus disease in 2019 has led to a global crisis. COVID-19 shows distinct clinical manifestations of the severity of symptoms. Numerous patients with no associated risk factors demonstrate acute respiratory distress syndrome (ARDS). The role of genetic factors in determining the severity and outcome of the disease remains unresolved. The purpose of this study was to see if a correlation exists between Angiotensin I Converting Enzyme (ACE) insertion/deletion (I/D) polymorphism and the severity of COVID-19 patients' symptoms. 120 COVID-19 patients admitted to Masih Daneshvari Hospital in Tehran with their consent to participate entered the study. Based on the World Health Organization classification, patients were divided into moderate and severe groups, which were primarily affected by O2 saturation levels. The effects of the patients' ACE insertion/deletion polymorphism, background disease, Angiotensin receptor blocker (ARB) drug consumption, and demographic parameters on the severity risk were calculated statistically. The ACE D allele was associated with an increased risk of disease severity (OR = 6.766, p = 0.012), but had no effect on mortality.

Transmission electron microscopy study of suspected primary ciliary dyskinesia patients.

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive condition often presenting with chronic respiratory infections in early life. Transmission electron microscopy (TEM) is used to detect ciliary ultrastructural defects. In this study, we aimed to assess ciliary ultrastructural defects using quantitative methods on TEM to identify its diagnostic role in confirming PCD. Nasal samples of 67 patients, including 37 females and 30 males (20.3 ± 10.7 years old), with suspected PCD symptoms were examined by TEM. The most common presentations were bronchiectasis: 26 (38.8%), chronic sinusitis: 23 (34.3%), and recurrent lower respiratory infections: 21 (31.3%). Secondary ciliary dyskinesia, including compound cilia (41.4%) and extra-tubules (44.3%), were the most prevalent TEM finding. Twelve patients (17.9%) had hallmark diagnostic criteria for PCD (class 1) consisting of 11 (16.4%) outer and inner dynein arm (ODA and IDA) defects and only one concurrent IDA defect and microtubular disorganization. Also, 11 patients (16.4%) had probable criteria for PCD (class 2), 26 (38.8%) had other defects, and 18 (26.9%) had normal ciliary ultrastructure. Among our suspected PCD patients, the most common ultrastructural ciliary defects were extra-tubules and compound cilia. However, the most prevalent hallmark diagnostic defect confirming PCD was simultaneous defects of IDA and ODA.

Purinergic receptor ligands: the cytokine storm attenuators, potential therapeutic agents for the treatment of COVID-19.

The coronavirus disease-19 (COVID-19), at first, was reported in Wuhan, China, and then rapidly became pandemic throughout the world. Cytokine storm syndrome (CSS) in COVID-19 patients is associated with high levels of cytokines and chemokines that cause multiple organ failure, systemic inflammation, and hemodynamic instabilities. Acute respiratory distress syndrome (ARDS), a common complication of COVID-19, is a consequence of cytokine storm. In this regard, several drugs have been being investigated to suppress this inflammatory condition. Purinergic signaling receptors comprising of P1 adenosine and P2 purinoceptors play a critical role in inflammation. Therefore, activation or inhibition of some subtypes of these kinds of receptors is most likely to be beneficial to attenuate cytokine storm. This article summarizes suggested therapeutic drugs with potential anti-inflammatory effects through purinergic receptors.

Umbelliprenin Increases the M1/M2 Ratio of Macrophage Polarization and Improves the M1 Macrophage Activity in THP-1 Cells Cocultured with AGS Cells.

BACKGROUND: Gastric adenocarcinoma is the fifth most diagnosed malignancy in the world. The immune system consists of a heterogeneous mixture of macrophages that defense the body through phagocytosis and the production of different cytokines and chemokines. Tumors cause macrophages to polarize differently in the manner of their favorite growth and angiogenesis. Umbelliprenin, a natural sesquiterpene coumarin, has been shown to have anticancer properties against some tumors, including gastric adenocarcinoma. The aim of our study was to investigate the effect of umbelliprenin on the polarization of macrophages in addition to the measurement of some of the soluble factors they produce. METHOD: The values of IC5 and IC50 for umbelliprenin in the AGS and THP-1 cells were estimated using the MTT assay. THP-1 cells were treated with 10 µM umbelliprenin, either alone or cocultured with AGS cells. Flow cytometry analysis of treated THP-1 cells was performed for CD68, CD86, and CD206 markers to evaluate M0, M1, and M2 macrophages polarization, respectively. AGS cells were assessed for apoptosis and necrosis by flow cytometry after labeling with Annexin V-FITC and propidium iodide. Interleukin- (IL-) 10 and IL-12 contents were measured in the supernatant by the ELISA method. Griess Reaction assay technique was used to determine nitric oxide (NO) concentration. RESULTS: The results of the MTT showed lower toxicity of umbelliprenin in THP-1 (IC50 = 75.79) compared to the AGS cell line (IC50 = 48.81). Umbelliprenin significantly increased the M1/M2 ratio. IL-10 content decreased significantly in the supernatant of M1 and M2 cells after umbelliprenin treatment, while IL-12 increased in the supernatant of M1 cells and decreased in the supernatant of the M2 cells. Umbelliprenin caused an increase in the NO in the supernatant of the M1 cells. CONCLUSION: Umbelliprenin alters the macrophage's secretions and its phenotypes in favor of tumor suppression.

A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial of High-Dose, Short-Term Vitamin D Administration in the Prevention of Acute Kidney Injury after Cardiac Surgery.

BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is a relatively common complication affecting short- and long-term survival. The renoprotective effect of vitamin D (VitD) has been confirmed in several experimental models. This study was conducted to evaluate the effect of high-dose VitD administration in patients with VitD insufficiency on the incidence of postoperative AKI, the urinary level of tubular biomarkers, and serum anti-inflammatory biomarker after coronary artery bypass graft. DESIGN AND METHOD: In this randomized double-blind controlled clinical trial, the patients were randomly allocated to either the VitD group (n = 50), receiving 150,000 IU VitD tablets daily for 3 consecutive days before surgery or the control group (n = 61), receiving placebo tablets. RESULTS: There was no difference in the incidence of postoperative AKI between the groups. Both of the urinary levels of interleukin-18 and kidney injury molecule-1 were significantly increased after the operation (p < 0.001, for both). Also, the serum level of interleukin-10 was increased after 3 days of VitD supplementation (p = 0.001). In comparison with the control group, it remained on a higher level after the operation (p < 0.001) and the next day (p = 0.03). The patients with AKI had more postoperative bleeding and received more blood transfusion. CONCLUSION: VitD pretreatment was unable to impose any changes in the incidence of AKI and the urinary level of renal biomarkers. However, high-dose administration of VitD may improve the anti-inflammatory state before and after the operation. Further studies are needed to assess the renoprotective effect of VitD on coronary surgery patients.

ACE2: Its potential role and regulation in severe acute respiratory syndrome and COVID-19.

COVID-19, a new disease caused by the 2019-novel coronavirus (SARS-CoV-2), has swept the world and challenged its culture, economy, and health infrastructure. Forced emergence to find an effective vaccine to immunize people has led scientists to design and examine vaccine candidates all over the world. Until a vaccine is developed, however, effective treatment is needed to combat this virus, which is resistant to all conventional antiviral drugs. Accordingly, more about the structure, entry mechanism, and pathogenesis of COVID-19 is required. Angiotensin-converting enzyme 2 (ACE2) is the gateway to SARS-CoV and SARS-CoV-2, so our knowledge of SARS-CoV-2 can help us to complete its mechanism of interaction with ACE2 and virus endocytosis, which can be interrupted by neutralizing small molecules or proteins. ACE2 also plays a crucial role in lung injury.

Correlation Between Low-Dose Chest Computed Tomography and RT-PCR Results for the Diagnosis of COVID-19: A Report of 27,824 Cases in Tehran, Iran.

RATIONALE AND OBJECTIVES: Real-time polymerase chain reaction (RT-PCR) remains the gold standard for confirmation of Coronavirus Disease 2019 (COVID-19) despite having many disadvantages. Here, we investigated the diagnostic performance of chest computed tomography (CT) as an alternative to RT-PCR in patients with clinical suspicion of COVID-19 infection. METHODS: In this descriptive cross-sectional study, 27,824 patients with clinical suspicion of COVID-19 infection who underwent unenhanced low-dose chest CT from 20 February, 2020 to 21 May, 2020 were evaluated. Patients were recruited from seven specifically designated hospitals for patients with COVID-19 infection affiliated to Shahid Beheshti University of Medical Sciences. In each hospital, images were interpreted by two independent radiologists. CT findings were considered as positive/negative for COVID-19 infection based on RSNA diagnostic criteria. Then, the correlation between the number of daily positive chest CT scans and number of daily PCR-confirmed cases and COVID-19-related deaths in Tehran province during this three-month period was assessed. The trends of admission rate and patients with positive CT scans were also evaluated. RESULTS: A strong positive correlation between the numbers of daily positive CT scans and daily PCR-confirmed COVID-19 cases (r = 0.913, p < 0.001) was observed. Furthermore, in hospitals located in regions with a lower socioeconomic status, the admission rate and number of positive cases within this three-month period was higher as compared to other hospitals. CONCLUSION: Low-dose chest CT is a safe, rapid and reliable alternative to RT-PCR for the diagnosis of COVID-19 in high-prevalence regions. In addition, our study provides further evidence for considering patients' socioeconomic status as an important risk factor for COVID-19.

Pyrvinium pamoate induces in-vitro suppression of IL-6 and IL-8 produced by human endometriotic stromal cells.

Endometriosis, a chronic inflammatory disease, is identified by the presence of endometrial tissue outside the uterus. The prevalence of this disease among reproductive-age women is almost 10-15%. High levels of IL-6 and IL-8 have been found in the peritoneal fluid (PF) of women with endometriosis and are involved in its pathogenesis. Isolated stromal cells from 12 ectopic and eutopic endometrial biopsies of women with ovarian endometrioma and also 12 endometrial biopsies of nonendometriotic controls were treated with 1.1 µM pyrvinium pamoate, a Wnt/ß-catenin signaling pathway inhibitor, for 72 hrs. Before treatment, mRNA gene expression and secretion of IL-6 and IL-8 were significantly higher in ectopic (EESCs) than eutopic (EuESCs) and control (CESCs) endometrial stromal cells. After treatment, mRNA gene expression and also secretion of IL-6 and IL-8 were significantly reduced. Our Findings showed that pyrvinium pamoate suppresses the mRNA gene expression and secretion of IL-6 and IL-8 in human endometriotic stromal cells. Additional investigations on this compound are required before clinical application.

Anti-Leishmanial Effects of Chitosan-Polyethylene Oxide Nanofibers Containing Berberine: An Applied Model for Leishmania Wound Dressing.

BACKGROUND: Leishmaniasis is the most important parasitic disease in Iran and is the third highest rate of rural cutaneous leishmaniasis in the world. Chitosan-polyethylene oxide nanocomposite fibers can be a suitable replacement for ordinary bandages. For the first time, in the absence of any published reports, the present in vitro study aimed to evaluate the anti-leishmanial effects of chitosan (CS)-polyethylene oxide (PEO)-berberine nanofibers on Leishmania major. METHODS: The present experimental study was conducted in 2018 in Tehran, Iran. The CS-PEO nanofibers containing berberine, as a natural anti-parasitic agent, were prepared using the electrospinning technique. Biocompatibility and fibroblast proliferation on nanofibers were investigated. In addition, the anti-leishmanial activity of CS-PEO nanofibers in both the promastigote and amastigote stages of Leishmania major was evaluated after parasite vital staining and MTT assay and compared to a control group. Statistical analysis was performed using SPSS software (version 18.0). Statistically significant differences were determined using the one-way ANOVA. The Duncan and Dunnett post hoc tests were used for within-group comparisons. P<0.05 was considered statistically significant. RESULTS: The results showed that nanofiber scaffolds with a mean diameter of 77.5±19.5 nm were perfect, regular, bead-free, and non-toxic, on which fibroblast cells grew well and proliferated. In addition, the optical density indicated that berberine 20% (w/v) significantly prevented promastigotes growth (IC50=0.24 µg/mL) and amastigotes death (IC50=0.91 µg/mL) compared with other concentrations and the control group. CONCLUSION: The study on the cytotoxic effects showed that CS-PEO-berberine nanofibers had strong lethal effects on Leishmania major in promastigote and amastigote stages in vitro. Further studies are required to investigate the effects of this nanofiber on leishmanial ulcers in laboratory animals and clinical cases.

The possible role of nitric oxide in anti-convulsant effects of Naltrindole in seizure-induced by social isolation stress in male mice.

Social isolation stress (SIS) as a chronic model of early-life stress could induce proconvulsant effects in mice. In the current study, we evaluated the role of opioid receptors (OPRs) agonists and antagonists in pro-conversant effects of SIS and the common pathway between delta-opioid receptors (DORs) and nitric oxide (NO) in stress-induced seizure. For reaching to this goal, we used pentylenetetrazol (PTZ) model of clonic-seizure to measure seizure threshold and administrated selective and non-selective OPRs agonists and antagonists in both social condition (SC) and isolated condition (IC) animals. In the next step, we administrated sub effective dose of naltrindole (NLT, 0.3 mg/kg) with sub-effective doses of nitric oxide synthesis (NOS) inhibitors including L-NAME (10 mg/kg), aminoguanidine (50 mg/kg) and 7-NI (15 mg/kg). Also, we co-administrated sub-effective dose of SNC80 (0.5 mg/kg) with sub-effective dose of l-arg (25 mg/kg) to assess the seizure threshold. In addition, we measured nitrite levels of hippocampus following administration of mentioned drugs in both SC and IC mice. Our findings showed that L-NAME and 7-NI (but not AG) increased anti-convulsant activity of NLT and l-arg increased proconvulsant effects of SNC80 in IC animals. Nitrite assay showed that co-administration of NLT plus sub-effective doses of L-NAME and 7-NI (but not AG) decreased and co-administration of SNC80 with sub-effective dose of l-arg increased nitrite levels of hippocampus in IC mice. This study suggests the role of n-NOS in anti-convulsant effects of NLT and pro-convulsant effects of SNC80 in stress-induced seizure.

The renin-angiotensin system in cutaneous hypertrophic scar and keloid formation.

Hypertrophic scar and keloid are two types of fibroproliferative conditions that result from excessive extracellular matrix production. The underlying pathological mechanism is not entirely clear. Activation of the renin-angiotensin system (RAS) is associated with fibrosis in various organs. RAS components including angiotensin II (Ang II), angiotensin AT1 and AT2 receptors, and angiotensin-converting enzyme (ACE) are expressed in the skin and act independently from the plasma RAS. AT1 receptors, which are usually the dominating receptor subtype, promote fibrosis and scar formation, while AT2 receptors inhibit the aforementioned AT1 receptor-coupled effects. Elevated angiotensin II (Ang II) levels acting on the AT1 receptor contribute to skin scar formation through increased expression of inflammatory factors such as interleukin-6 (IL-6), angiogenic factors such as vascular endothelial growth factor (VEGF) and fibrinogenic factors such as transforming growth factor-ß1 (TGF-ß1) and connective tissue growth factor (CTGF), while at the same time suppressing the anti-fibrotic tissue inhibitors of matrix metalloproteinase (TIMPs). First, small clinical trials have provided evidence that inhibition of the ACE/Ang II/ AT1 receptor axis may be effective in the treatment of hypertrophic scars/keloids. This review provides a detailed overview of the current literature on the RAS in skin, wound healing and scar formation and discusses the translational potential of targeting this hormonal system for treatment and prevention of hypertrophic scars and keloids.

Chitosan-based nano-scaffolds as antileishmanial wound dressing in BALB/c mice treatment: Characterization and design of tissue regeneration.

OBJECTIVES: Rapid healing of cutaneous leishmaniasis as one of the most important parasitic diseases leads to the decrease of scars and prevention of a great threat to the looks of the affected people. Today, the use of nano-scaffolds is rapidly increasing in tissue engineering and regenerative medicine with structures similar to the target tissue. Chitosan (CS) is a bioactive polymer with antimicrobial and accelerating features of healing wounds, which is commonly used in biomedicine. This study aimed to investigate the effects of CS/polyethylene oxide (PEO)/berberine (BBR) nanofibers on the experimental ulcers of Leishmania major in BALB/c mice. MATERIALS AND METHODS: CS/PEO/BBR nanofibers were prepared by the electrospinning method, and their morphology was examined by SEM, TEM, and AFM. Then, water absorption, stability, biocompatibility, porosity, and drug release from nano-scaffolds were explored. Afterward, 28 BALB/c mice infected with the parasite were randomly divided into control and experimental groups, and their wounds were dressed with the produced nano-scaffolds. Finally, the effect of nanobandage on the animals was investigated by macroscopic, histopathologic, and in vivo imaging examinations. RESULTS: The prepared nanofibers were completely uniform, cylindrical, bead-free, and biocompatible with an average diameter of 94±12 nm and had appropriate drug release. In addition, the reduced skin ulcer diameter (P=0.000), parasite burden (P=0.003), changes in the epidermis (P=0.023), and dermis (P=0.032) indicated significantly strong effectiveness of the produced nano-scaffolds against leishmania ulcers. CONCLUSION: Studies showed that CS/PEO/BBR nanofibers have a positive effect on the rapid healing of leishmania ulcers. Future studies should focus on other chronic ulcers treatment.

Chitosan/PVA/Doxycycline Film and Nanofiber Accelerate Diabetic Wound Healing in a Rat Model.

In this study, we evaluated the effects of nanofiber and film polymers with doxycycline for treating a wound in a diabetic rat model. 108 male rats were divided into six groups, the control group, the diabetic control, and the groups were diabetic rats receiving different wound dressing. At the 3rd, 7th, and 14th days, macroscopic/histologic imaging and tissue sampling were performed. Tissues were analyzed for IL-1ß, TNF-α, IL-10, TIMP-1, and MMP-2 by using ELISA. Dressings of chitosan, polyvinyl alcohol, and doxycycline increased the rate of wound closure, the volume of collagen, dermal, and epidermis. In addition, it increased the number of fibroblasts and basal cell epidermis cells, vascular length, and decreased the number of neutrophil cells. Inflammatory cytokines and MMP-2 were decreased, and anti-inflammatory IL-10 and TIMP-1 were increased. It was ultimately attained that the combination of chitosan/ polyvinyl alcohol /doxycycline could be a useful dressing for the healing of diabetic wounds.

Protective Effect of Gallic Acid on Testicular Tissue, Sperm Parameters, and DNA Fragmentation against Toxicity Induced by Cyclophosphamide in Adult NMRI Mice.

PURPOSE: This study aimed to investigate the protective effect of Gallic acid (GA) on the Cyclophosphamide (CP) toxicity induced in the reproductive system. MATERIALS AND METHODS: After a pilot study for dose responses of Gallic acid ,Forty adult male NMRI mice were divided into 5 groups (n=8): control, sham (NaCl Serum: 0.2mL per day), CP (15 mg kg-1 per week; IP), GA (12.5 mg kg-1 per day ; IP) and GA (12.5 mg kg-1 per day ; IP) +CP(15 mg kg-1 per week; IP). After treatment, the left testis was detached and used for Histological examination and right testis used for Malondialdehyde (MDA) measures. Left caudal epididymis was placed in the Ham's F10 medium and released spermatozoa were used in order to analyze sperm parameters. Sperm DNA fragmentation was assessed by Sperm Chromatin Dispersion (SCD) method. RESULTS: In the CP group, there was a significant increase in the sperm DNA fragmentation (% 57.89 ± 23.91) compared with control group (% 24.52 ± 10.27). That was significantly improved by GA  (12.5 mg kg-1 per day ; IP)  in GA+CP group (% 28.4 ± 8.85) compared to CP group (p< .001).A significant increase was reported about MDA levels in CP group (6.26 ± 2.59) in compared with the control group (4.30 ± 2.05), But GA (3.24 ± 1.33) decreased it in GA+ CP group (p< .01).  The histopathological investigation revealed marked testicular atrophy in CP group, whereas GA diminished these deviations (P< .05). CONCLUSION: Gallic acid can modify the reproductive toxicity of cyclophosphamide in NMRI mice and increase the antioxidant capacity of testis tissue.

Semi-IPN Films and Electrospun Nanofibers Based on Chitosan/PVA as an Antibacterial Wound Dressing.

The antimicrobial activity of a wound dressing is a key factor for preventing and treating wound infection. The current study evaluated the physiochemical properties and antimicrobial activities of semi-IPNs (interpenetrating polymer networks) based on chitosan/polyvinyl alcohol (PVA) films and nanofibers as candidates for wound dressings and investigated the effects of morphologies (nanofibrous mats and films), crosslinking conditions of chitosan chains (uncrosslinked and crosslinked with genipin), and the presence of antibacterial drug (doxycycline) on their physicochemical and antibacterial properties. The morphology, chemical structure, fluid uptake, water vapor transmission rate, antimicrobial activity, and doxycycline release profile were assayed using SEM, FTIR spectroscopy, swelling test, permeation test, agar diffusion antibiogram, and dissolution test, respectively. The results demonstrated that crosslinking chitosan with genipin reduced the diameter of nanofibers, fluid uptake, and drug release from both nanofiber mats and film samples. According to the results, wound dressings with film morphology have better antimicrobial activity than those with nanofiber. The chitosan/PVA/Doxycycline 1% film has the potential for use as an antimicrobial wound dressing.

Detection of Angiotensin II and AT1 Receptor Concentrations in Keloid and Hypertrophic Scar.

Background: Keloid and hypertrophic scars (HTS) are formed by excessive collagen formation. Angiotensin II, through the AT1 receptor, plays an important role in extracellular matrix production. However, less is known about angiotensin II and AT1 receptor concentrations in HTS and keloid tissues. Objective: The purpose of this study was to determine the angiotensin II and AT1 receptor concentrations in keloid, HTS, and normal skin tissues. Methods: Skin biopsy samples from patients with HTS (n=26), keloid (n=20), and normal (n=30) skin tissues were evaluated for angiotensin II and AT1 receptor concentrations by use of the enzyme-linked immunosorbent assay technique. Results: The angiotensin II concentration in patients with HTS was higher than that in the normal (P<0.0067) and keloid (P>0.9553) groups, while the AT1 receptor concentration in patients with keloid was higher than that in the HTS (P<0.0001) and normal (P<0.0048) groups. Conclusion: Angiotensin II and AT1 receptor concentrations could stimulate the formation of HTS and keloid. Angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors may be suitable compounds for the treatment of scar tissue.

Losartan ointment relieves hypertrophic scars and keloid: A pilot study.

Keloid and hypertrophic scars are two types of fibrosis caused by extracellular matrix overexpression, and angiotensin II via AT1 receptor is known to play a key role in stimulation of fibrosis. A pilot placebo controlled single blind study was carried out on patients with hypertrophic scars and keloids. A total of 37 adult volunteers were randomly assigned into losartan 5% or placebo treatment groups. The treatment was performed twice a day for three months and a 6-month follow-up. The treatment was evaluated using Vancouver scar scale method. Totally, 30 participants were analyzed (Losartan ointment n = 20; placebo ointment n = 10; seven placebo volunteers left the study because they thought the treatment was not effective for them). In the losartan group, VSS scores dropped significantly (p < 0.01) both in keloid and hypertrophic scar patients. Vascularity and pliability were significantly reduced by losartan treatment (p < 0.05). It can be concluded that losartan potassium ointment (5%) can alleviate the keloid and hypertrophic scar.