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Abstract Despite the tremendous advancements in the knowledge of the pathophysiology and clinical aspects of SARS-CoV-2 infection, still many issues remain unanswered, especially in the long-term effects. Mounting evidence suggests that pulmonary fibrosis (PF) is one of the most severe complications associated with COVID-19. Therefore, understanding the molecular mechanisms behind its development is helpful to develop successful therapeutic strategies. Epithelial to mesenchymal transition (EMT) and its cell specific variants endothelial to mesenchymal transition (EndMT) and mesothelial to mesenchymal transition (MMT) are physio-pathologic cellular reprogramming processes induced by several infectious, inflammatory and biomechanical stimuli. Cells undergoing EMT acquire invasive, profibrogenic and proinflammatory activities by secreting several extracellular mediators. Their activity has been implicated in the pathogenesis of PF in a variety of lung disorders, including idiopathic pulmonary fibrosis (IPF) and COVID-19. Aim of this article is to provide an updated survey of the cellular and molecular mechanisms, with emphasis on EMT-related processes, implicated in the genesis of PF in IFP and COVID-19.

In this article published in Cell J, Vol 18, No 2, Jul-Sep (Summer) 2016, on pages 179-188, the authors found thatFigure 2A was the same as the one that has already been published and it was confusing. The following figure’s legendis corrected in reference 9.The authors would like to apologies for any inconvenience caused.

Hemojuvelin (HJV), a BMP co-receptor promoting hepcidin expression in the liver, has a hepatoprotective function and its deficiency in mice triggers mitochondrial dysfunction and hepatocarcinogenesis.

The liver is an organ that is particularly exposed to reactive oxygen species (ROS), which not only arise during metabolic functions but also during the biotransformation of xenobiotics. The disruption of redox balance causes oxidative stress, which affects liver function, modulates inflammatory pathways and contributes to disease. Thus, oxidative stress is implicated in acute liver injury and in the pathogenesis of prevalent infectious or metabolic chronic liver diseases such as viral hepatitis B or C, alcoholic fatty liver disease, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Moreover, oxidative stress plays a crucial role in liver disease progression to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Herein, we provide an overview on the effects of oxidative stress on liver pathophysiology and the mechanisms by which oxidative stress promotes liver disease.

Abstract Background Identification of molecular markers, such as miRNAs is promising for the diagnosis of asthma and its clinical phenotypes. The aim of this study was to examine the changes in the expression of selected microRNAs in plasma exosomal fractions of severe asthma patients. The expression of miRNAs was determined in relation to the changes in inflammatory markers. Method Severe asthma patients (n = 30) and healthy subjects (n = 30) were selected among the individuals referred to asthma and allergy clinic. Blood was collected from each participant to determine the serum high-sensitive C-reactive protein (hs-CRP) and total IgE. The exosomal fraction of plasma was isolated and processed for quantitation of miR-124, miR-125b, miR-133b, miR-130a and miR-125b-1-3p expression using quantitative real time-PCR (qRT-PCR). Results Serum hs-CRP and total IgE were significantly higher in asthma patients compared to controls. Expression of miR-124, miR-133b, and miR-130a was down-regulated in asthma patients as compared to controls (p

Objective(s): Autophagy is an intracellular degradation system of damaged proteins and organelles; however, the role of autophagy in the progression of cancer remains unclear. In recent years, mesenchymal stem cell (MSC)-based approaches have attracted considerable attention for anti-cancer therapy. The present study aimed to examine the interaction of MSCs with the breast cancer cells under autophagy-induced conditions. Materials and Methods: In this study, MSCs isolated from human adipose tissue were co-cultured with MDA-MB 231, a breast cancer cell line, and the autophagy process was induced by tunicamycin treatment. The cell viability was monitored by the MTT assay, and the cells were recovered at different time intervals (24 or 48 hours) to determine autophagy markers such as Beclin, mTOR and the ratio of LC3II/I expression. Additionally, the animal study was conducted using a mouse model of breast cancer treated with isogenic adipose-derived MSCs, and the expression of Beclin and Ki67 was determined using immunohistochemistry in breast tumor tissue.Results: In cancer cells co-cultured with MSCs, the cell proliferation was increased, the Beclin expression and the LC3II/I protein ratio were decreased, and the mTOR expression was increased in MDA-MB 231 upon co-cultured with MSCs. Direct injection of MSCs to a mouse model of breast cancer showed an increase in tumor volume, an increase in the accumulation of Ki67 and a decrease in the Beclin expression in tumor tissues. Conclusion: The data may suggest that suppressed autophagy in breast cancer cells is probably a mechanism by which MSCs can induce cancer cell proliferation.

Objectives: Chronic inflammation in urothelial tissues can lead to DNA damage and cancer formation. Inflammatory reactions in bladder cancer (BC) probably depend on the stages and grades of tumors. The aim of this research was to find out if there is a relationship between the serum levels of selected inflammatory factors and the pathological grades/stages of tumors in new cases of non-muscle invasive urothelial bladder carcinoma patients. Materials and Methods: Blood samples were collected from 40 newly diagnosed non-muscle invasive urothelial bladder carcinoma patients (before the surgery) and 40 normal individuals without the signs of acute and chronic diseases or cancer. All patients had proven BC and were sampled prior to the initial transurethral resection of bladder tumor and any medical intervention. Finally, the levels of selected inflammatory factors such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured using enzyme-linked immunosorbent assay kits. Results: Based on the results, the levels of IL-6 (3.041.32± vs. 0.76±0.23), TNF-α (18.5±5.24 vs. 10.52±2.67), and CRP (807.09±564.86 vs. 132.08±53.76) were significantly higher in samples obtained from cancer patients compared to the control group, respectively (P

Introduction: MicroRNAs (miRs) are a group of endogenous, non-coding, 18-24 nucleotide length single-strand RNAs that mediate gene expression at the post-transcriptional level through mRNA degradation or translational repression. They are involved in regulating diverse cellular biological processes such as cell cycle, differentiation, and apoptosis. The deregulation of miRs affects normal biological processes, leading to malignancies, including oral squamous cell carcinoma (OSCC). This study evaluates the expression level of miR-21-5p and miR-429 genes in biopsy samples from patients with OSCC and performs a comparison with controls. Materials and Methods: In this study, tissue samples were obtained from 40 individuals (20 OSCC patients and 20 healthy controls) to determine miR-21-5p and miR-429 expression using the ΔCT method and analyzed by the Mann–Whitney test. Results: The mean age of subjects in the control and patient groups was 47.15 and 53.8 years, respectively. According to the Mann–Whitney test, significant differences were observed in miR-21-5p (p < 0.0001) and miR-429 (p = 0.0191) expression levels between the two groups (p < 0.05). Conclusions: The expression of miR-21-5p, miR-429, and combined miRNAs in the OSCC group was significantly higher compared to the control group. As a result, changes in the expression of these biomarkers in cancerous tissues could potentially be considered as a marker for the early diagnosis of OSCC.

N-acetylcysteine (NAC) as a glutathione inducer is known for its anti-inflammatory effects in inflammatory conditions. The aim of the present study was to know if supplementation of the culture medium with NAC can improve anti-inflammatory activities of hepatocytes during their differentiation from mesenchymal stem cells (MSCs). For this, in vitro hepatic differentiation of MSCs was performed in culture medium supplemented with NAC and selected pro- and anti-inflammatory factors were monitored for two weeks. Treatment of the MSCs undergoing hepatic differentiation with NAC (0.1 and 1.0 mM) caused a significant (~5-fold) increase in proliferation rate of MSCs, whereas the rate of hepatic differentiation was declined in NAC-treated cells as compared to those untreated with NAC. Under these circumstances, NAC caused a significant increase in total glutathione in cell lysate during 2 weeks of differentiation as compared to untreated group. NAC-related increase in glutathione was associated with significant alterations in tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8 and IL-10 levels secreted in the culture medium. A substantial decrease in the IL-6, IL-8 and TNF-α levels in the culture medium supplemented with NAC was obvious in hepatocytes recovered 14 days after differentiation. In contrast, the secretary IL-10 was significantly increased as a result of NAC treatments. These data suggest that NAC supplementation can improve anti-inflammatory activities of the hepatocytes derived from MSCs. NAC function mediated by glutathione synthesis can also help in modulation of proliferation of the stem cells and their differentiation into hepatocyte-like cells.

Background and objective: Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy. Expression patterns of microRNAs (miRNAs) can direct us in identifying valuable biomarkers for the prognosis of different neoplasms. Inappropriate regulation of miRNAs during physiological procedures can result in malignancies including OSCC. The aim of the present study was to evaluate the expression of miR-486-3p, miR-561-5p, miR-548-3p, and miR-509-5p in tissue biopsy samples with and without OSCC. Materials and methods: This case-control study was conducted on 17 healthy and 17 OSCC tissue biopsy samples. The expression of miRNAs was assessed using quantitative real-time PCR (q-RT-PCR) after RNA extraction from normal and cancer tissues and cDNA synthesis. Results: The means of miRNA-486-3p, miR-561-5p, and miR-548-3p expression were significantly different between OSCC and control groups (p < 0.001), but there was no significant difference in means of miR-509-5p expression between OSCC and control groups (p = 0.179). Conclusions: The findings of this study revealed that the expression of miR-486-3p and miR-561-5p was significantly lower in cancer samples compared to normal tissue samples. On the other hand, miR-548-3p expression increased in the OSCC group compared to the control group.

Multiple sclerosis (MS) is an inflammatory demyelinating disease, which is considered as a common autoimmune disorder in young adults. A growing number of evidences indicated that the impairment in non-neural tissues plays a significant role in pathology of MS disease. There are bidirectional relationship, metabolic activities and functional similarity between central nervous system (CNS) and kidneys which suggest that kidney tissue may exert remarkable effects on some aspects of MS disorder and CNS impairment in these patients compels the kidney to respond to central inflammation. Recently, it has been well documented that hormonal secretion possesses the important role on CNS abnormalities. In this regard, due to the functional similarity and significant hormonal and non-hormonal relationship between CNS and kidneys, we hypothesized that kidneys exert significant effect on initiation, progression or amelioration of MS disease which might be regarded as potential therapeutic approach in the treatment of MS patients in the future.

In recent years, a lot of attention has been paid to quantum dot (QD) nanoparticles as fluorescent sensors for sensitive and accurate detection of cancer biomarkers. Here, using a homemade specific monoclonal antibody against CA125 and QD525- or FITC-labeled probes, expression of this marker in an ovarian cancer cell line and cancer tissues were traced and optical properties of fluorophores were compared qualitatively and quantitatively. Our results clearly showed that besides lower background and exceptionally higher photobleaching resistance, QD525 exhibited higher fluorescent intensity for both ovarian cancer cell and tissues at different exposure times (p

Background: Acetaminophen (APAP) overdose causes renal and hepatic injury. It is also believed that oxidative stress has a pivotal role in APAP-induced renal injury. Therefore, protective effects of different antioxidants have been examined in APAP-induced renal and hepatic toxicity models. Stevia rebadiana is a plant with a high degree of natural antioxidant activity in its leaf extract. The aim of this study was to investigate the possible protective effects of rebadioside A; one of the main components of stevia extract, on APAP-induced oxidative stress in kidney of mice. Methods: Oxidative stress was induced in kidney of BALB/c mice by the intraperitoneal (i.p.) administration of a single dose of 300 mg/kg APAP. Some of these mice also received rebadioside A (700 mg/kg) (i.p.) 30 minutes after APAP injection. Two and six hours after APAP injection, all mice were sacrificed and malondialdehyde (MDA), glutathione (GSH), free APAP, and glutathione conjugated of APAP (APAP-GSH) were determined in the kidney tissue. Results: GSH depletion and MDA levels significantly (P

Objective: Multiple sclerosis (MS) is a chronic autoimmune disease due to demyelination of the central nervous system. It is believed that cytokines are involved in the pathogenesis of MS. The interleukin-2 (IL2) gene is powerful functional candidate that is involved in immune regulation and operation. In this study, for the first time, we investigated the effect of -475 A/T and -631 G/A IL2 polymorphisms on MS disease in Iranian patients.Materials and Methods: In this case-control study, 100 MS patients (mean age: 32.95 ± 6.51 years, age range: 20-42 years) selected according to McDonald criteria, and 100 ethnically, sex and age matched healthy controls (mean age: 29 ± 7.8 years, age range: 20-52 years) with no personal or family history of autoimmune diseases were studied. The restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method was applied to define different alleles and genotypes of IL2 promoter single nucleotide polymorphism -475 A/T as well as -631 G/A among individuals. χ2 was calculated and Fisher’s exact test was applied to analyze the obtained data. The value of p

Background: Noise induced hearing loss is one of the top ten occupational diseases in worldwide and carbon monoxide (CO) can potentiate this disorder. Oxidative stress have been implicated in cochlear damage resulting from exposure to noise ,but mechanisms underlying auditory impairment following exposure to noise plus CO are not well known. This study was performed to evaluate the effect of noise and CO exposure on blood antioxidant and blood glutathione (GSH) status in rabbits. Methods: In this experimental study, 24 male adult white rabbits are divided to four groups: control group, noise exposure group, noise plus carbon monoxide exposure group and CO exposure group. Ferric reducing ability of plasma (FRAP assay) and total blood GSH of groups were determined before and after exposure. Results: Mean of total antioxidant ability of plasma after exposure to noise and CO were 707.5± 31.7 and 811.3± 51.8 µmol/lit. Blood GSH of these groups were 1.39± 0.09 and 1.79±0.08 mg/dl RBCs respectively. These values were less than the values in control group significantly ( p value

Objective: The aim of this study was to determine the oxidative stress; serum level of Total Antioxidant Capacity (TAC)and Malondialdehyde (MDA) level and the depression score among the depressed rotational shift workers in Shahid Tondgouyan Refinery in Tehran (Iran). Methods: A cross-sectional study was conducted among all the 189 shift workers in Shahid Tondgouyan oil refinery who were eligible to participate in the study. They did not take any antidepressants for two months or any supplements for two weeks prior to the study entry. Written consent was obtained from the participants. 21- Item Beck Depression Inventory was used to measure the depression level. Furthermore, body weight, height and systolic and diastolic blood pressure were collected from all the participants. The levels of Total Antioxidant Capacity (TAC) and Malondialdehyde (MDA) were measured by 8 ml fasting blood sample. MDA was determined by thiobarbituric acid reaction. Serum total antioxidants were measured using the spectrophotometric BTS. In the ABTS test, 2,2’-azinobis (3-ethylbenzthiazoline-6-acid) (ABTS) is converted into its radical cation (ABTS•+) by addition of sodium persulphate. This blue-green radical cation absorbs light at 734 nm. ABTS•+ is reactive towards most antioxidants. Descriptive statistics, ANOVA, ANCOVA and regression tests and correlation were used to analyze the data using SPSS software version 16. Results: The age of the participants ranged from 21 to 52 years. The mean age of the participants was 30.58 year (±6.97yr). Of all the participants, 28% (n= 53) had no depression symptoms (depression score between 0 and 9), 65.1% (n=123) were categorized as having mild depression (depression score between 10 and 18) and 6.9% (n=13) were categorized as having moderate depression (depression score between 19 and 29). The participants’ BMI ranged from 15.9 to 34.3; the mean BMI of the participants was 24.82 kg/m2 (+ 3.81 kg/m2). The mean of the serum TAC level was 2.51 (± 0.56) mg/dl, and the mean serum MDA level was 3.67(± 1.08) μmol/l. There was a significant difference in the mean TAC concentration between the non-depressed group and the group with mild depression (p=0.029). Conclusion: Depression was associated with reduced mean TAC concentration and an increase in MDA level. There was a linear relationship between the depression score and shift work experience among the rotational shift workers, which showed a high level of stress and depression among the shift-workers.

Wheat is the most important cereal produced in Iran. A mycological survey was carried out for the first time, on the stored wheat samples in Tehran, East Azarbayejan and Mazandaran provinces in 2007. Exogenous and endogenous fungi, were isolated by the method of flotation with Malachite green agar (MGA 0.25) and Freeze blotter techniques respectively. In this study, 46 species belonging to 23 different genera were isolated. Cladosporium spp. (57.1–89.2%) and Alternaria spp. (82.4–100%) species were the predominant fungal species identified as endogenous mycoflora. The predominant exogenous fungi were Penicillium spp. (78.4–92.8%) and Aspergillus spp. (71.4–85.7%) species. Fusarium proliferatum was the most prevalent species of Fusarium isolates. Aspergillus niger (39.4%) and Aspergillus flavus (36.7%) were the predominant Aspergillus species identified as exogenous mycoflora. Aspergillus flavus (26.6%) was the predominant Aspergillus species identified as endogenous mycoflora. Flotation method with MGA 0.25 recommended for isolating of hyaline fungi from wheat cereals. In this study one isolate from Fusarium species was isolated on the basis of morphology and ribosomal internal transcribed spacer classified as Fusarium langsethiae but on the basis of partial translation elongation factor-1alpha gene grouped with Fusarium sporotrichioides. To our knowledge, this is the first report about F. cf. langsethiae in Iran and Asia. [ABSTRACT FROM AUTHOR]

Abstract  In this study, two techniques were used to compare the specific activity and total concentration of mycelial glutathione S-transferase (GST) in fungal strains isolated from natural sources. The fungi identified as Aspergillus parasiticus and Aspergillus flavus have been divided into two groups based on their ability to produce aflatoxins. Altogether 26 fungi were isolated, among which 12 were capable of producing varying levels of aflatoxin and 14 were proved to be non-toxigenic. GST specific activity in mycelial preparation was measured spectrophotometrically using 2,1-chloro-2,4-dinitrobenzene as the substrate. The results showed that the mean GST activity in toxigenic isolates was 25.06 ± 9.8 μmol/mg protein/min which was 2.8-fold greater than that measured in non-toxigenic isolates (8.84 ± 5.5 μmol/mg protein/min). Moreover, the GST concentration was compared in toxigenic and non-toxigenic isolates using an Enzyme Linked Immunosorbent Assay based on antigen (fungal preparation) and antibody (antibody produced against fungal GST in rabbit). The results of ELISA showed that the mean GST level in toxigenic and non-toxigenic fungi was 1.17 ± 0.55 and 0.40 ± 0.24, respectively. These results further confirm that the aflatoxin production in the fungal strains is correlated with GST expression and using ELISA, it is possible to discriminate aflatoxin-producing fungi from their non-toxigenic counterparts. [ABSTRACT FROM AUTHOR]

Soil isolates of Aspergillus section Flavi from Mazandaran and Semnan provinces with totally different climatic conditions in Iran were examined for aflatoxins (AFs; B and G types), cyclopiazonic acid (CPA) and sclerotia production. A total of 66 Aspergillus flavus group strains were identified from three species viz. Aspergillus flavus, Aspergillus parasiticus and Aspergillus nomius in both locations. A. flavus (87.9%) was found to be the prominent species followed by A. nomius (9.1%) and A. parasiticus (3.0%). Only 27.5% of A. flavus isolates were aflatoxigenic (B1 or B1 and B2), out of which approximately 75% were capable to producing CPA. All the A. parasiticus and A. nomius isolates produced AFs of both B (B1 and B2) and G (G1 and G2) types, but did not produce CPA. Sclerotia production was observed in only 4 isolates of A. flavus among all 66 isolates from three identified species. A. flavus isolates were classified into various chemotypes based on the ability to produce aflatoxins and CPA. In this study, a new naturally occurring toxigenic A. flavus chemotype comprising of two strains capable of producing more AFB2 than AFB1 has been identified. A relatively larger proportion of aflatoxigenic A. flavus strains were isolated from corn field soils of Mazandaran province which indicate a possible relationship between high levels of relative humidity and the incidence of aflatoxin-producing fungi. The importance of incidence of Aspergillus section Flavi in corn field soils regard to their mycotoxin production profiles and crop contamination with special reference to climatic conditions is discussed. [ABSTRACT FROM AUTHOR]

Recently we reported that ferric reducing ability of plasma (FRAP) assay, as an index of total antioxidant activity, increases in growing rats in response to high dose of vitamin K. In this study, it was found that acetaminophen (APAP) can cause elevation in FRAP in suckling and adult rats. This study was initiated to assess the contribution of individual antioxidant factors on elevation in FRAP. A surge in FRAP, 1 h after high dose APAP (250 or 450 mg/kg BW) administration was recorded in both young as well as adults. Whereas, low dose drug (25 mg/kg) failed to alter FRAP in both the age groups. Time-course studies show that drug-dependent elevation in FRAP begin rapidly, reaching a maximum at 1 h (> 500%). Increased FRAP was associated with a marked increase (∼14-fold) in plasma bilirubin, 6 h after drug administration at 450 mg/kg only in suckling rats. Similarly, APAP-related increase in superoxide dismutase activity in erythrocytes was limited to young rats of both the age groups. Other factors measured during this period viz., plasma uric acid, bilirubin and total protein together with catalase activity of erythrocytes remained unchanged in treated rats. Under these circumstances, APAP-related depletion in liver glutathione was almost similar in both the age groups. During a 12 h study, the concentration of lipid peroxidation products, in liver of treated groups remained within the levels of respective controls. The endpoint hepatotoxic effects of APAP was almost similar in both the age groups, suggesting that like adults, immature rats can cope with toxic effects of APAP owing to their drug-dependent induction in certain antioxidant factors. [ABSTRACT FROM AUTHOR]

Abstract The mode of action of the extracts prepared from neem plant i.e., Azadirachta indica on aflatoxin formation in toxigenic Aspergillus species is not well understood. Aflatoxin production by A. parasiticus was suppressed depending on the concentration of the plant aqueous extract (0, 1.56, 3.12, 6.25, 12.5, and 50% v/v) added to the culture media at the time of spore inoculation. Aflatoxin production in fungal mycelia grown for 96 h in culture media containing 50% neem leaf and seed extracts was inhibited by ~90 and ~65% respectively. Under similar conditions, culture media amended with 1.56% of leaf or seed extract caused 23 and 7% inhibition respectively. Mycelial samples exposed to selected concentrations of the plant extract (1.56 or 50% v/v) collected and processed for morphological studies. Semi-thin longitudinal and cross sections prepared from control (untreated) and treated mycelia (1.56% v/v) revealed that alterations are limited to the vacuolation of the mycelial cytoplasm. Nevertheless, exposure to high concentration i.e., 50% v/v of the extract resulted in vacuolation of the mycelial cytoplasm and vesicle deformation causing attenuation of cell wall at variable intervals. Herniation of the cytoplasmic contents that was protruding from the mycelium was associated with deformation of the mycelium. Some mycelia showed a cleft between the cell wall and cytoplasm. Association of aflatoxin production with morphological changes suggest that probably integrity of the cell barriers particularly cell wall is critical in regulation of aflatoxin production and excretion. [ABSTRACT FROM AUTHOR]

Background: Many attempts have done to improve cryopreservation of mammalian ovaries using simple, economical and efficient technique "vitrification". Objective: The aim of the present study was to compare the mouse ovaries cryopreservation by direct cover vitrification (DCV) using different concentrations of ethylene glycol (EG) with conventional vitrification methods (CV). Materials and Methods: Ninety NMRI mice were sacrificed by cervical dislocation; their ovaries were divided into three main experimental groups: control or non-vitrified group, CV group and DCV groups with 4, 6 and 8M EG as cryoprotectant. After vitrification-warming, the viability of mechanically isolated follicles and the morphology of ovarian follicles by light and electron microscopes were studied. Results: The normality of primary and preantral follicles in non-vitrified and CV groups were higher than those achieved by DCV groups (p<0.001). The survival rates of isolated follicles in non-vitrified, CV and DCV groups with 4M, 6M and 8M ethylene glycol were 98.32, 96.26, 84.10, 85.46 and 84.56 %, respectively and in DCV groups it was lower than other groups (p<0.001). The ultrastructure of ovarian follicles was well preserved in CV technique. The follicles in DCV groups appeared to have vacuolated oocyte with nuclear shrinkage and irregular distribution of cytoplasmic organelles. Their mitochondria were located mainly in the sub cortical part of the oocyte and the granulosa cells demonstrated some signs of degeneration. Conclusion: DCV of mouse ovarian tissue using only EG has induced some alteration on the fine structure of follicles. The integrity of mouse ovarian tissue was affected by DCV technique more than CV. [ABSTRACT FROM AUTHOR]