Investigating the Therapeutic Effects of Nimodipine on Vasogenic Cerebral Edema and Blood-Brain Barrier Impairment in an Ischemic Stroke Rat Model.

Vasogenic brain edema, a potentially life-threatening consequence following an acute ischemic stroke, is a major clinical problem. This research aims to explore the therapeutic benefits of nimodipine, a calcium channel blocker, in mitigating vasogenic cerebral edema and preserving blood-brain barrier (BBB) function in an ischemic stroke rat model. In this research, animals underwent the induction of ischemic stroke via a 60-minute blockage of the middle cerebral artery and treated with a nonhypotensive dose of nimodipine (1 mg/kg/day) for a duration of five days. The wet/dry method was employed to identify cerebral edema, and the Evans blue dye extravasation technique was used to assess the permeability of the BBB. Furthermore, immunofluorescence staining was utilized to assess the protein expression levels of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). The study also examined mitochondrial function by evaluating mitochondrial swelling, succinate dehydrogenase (SDH) activity, the collapse of mitochondrial membrane potential (MMP), and the generation of reactive oxygen species (ROS). Post-stroke administration of nimodipine led to a significant decrease in cerebral edema and maintained the integrity of the BBB. The protective effects observed were associated with a reduction in cell apoptosis as well as decreased expression of MMP-9 and ICAM-1. Furthermore, nimodipine was observed to reduce mitochondrial swelling and ROS levels while simultaneously restoring MMP and SDH activity. These results suggest that nimodipine may reduce cerebral edema and BBB breakdown caused by ischemia/reperfusion. This effect is potentially mediated through the reduction of MMP-9 and ICAM-1 levels and the enhancement of mitochondrial function.

Nicotine promotes development of bile duct ligation-induced liver fibrosis by increasing expression of nicotinic acetylcholine receptors in rats.

Aim of the study: Liver fibrosis and cigarette smoking seem to be directly linked. Nicotine, as an agonist of nicotinic acetylcholine receptors (nAChRs), induces many downstream signaling pathways. The pathways through which nicotine affects the process of liver fibrosis have not been clarified. The present study aimed to investigate the nicotine-induced effects on fibrosis progression in cholestatic rats. Material and methods: First, the Wistar rats were subjected to sham or bile duct ligation (BDL) surgery. The rats were treated with low and high doses of nicotine (1 or 10 mg/kg) for three weeks. They were monitored for their body weights before and 21 days after BDL. Also, spleens were weighed to calculate the spleen/body weight ratio. Ductular proliferation and fibrosis were evaluated using hematoxylin and eosin (H&E) as well as Masson's trichrome staining. The mRNA expression of α4nAChR, α7nAChR, and fibrosis gene α-smooth muscle actin (α-SMA) was measured by real-time PCR. Results: The findings showed that nicotine promotes the development of BDL-induced liver fibrosis. The ratio of spleen/body weight was significantly affected by nicotine exposure. H&E and Masson's trichrome staining showed that the level of liver fibrosis was higher in the cholestatic BDL groups, and this effect was significantly augmented in the nicotine-treated rats. Also, α4nAChR, α7nAChR, and α-SMA expression was observed in the BDL rats and increased following nicotine treatment. Conclusions: The activation of nAChR triggers biliary proliferation and liver fibrosis. Studying the intracellular mechanism of nicotine and alteration in the expression of nicotinic receptors following nicotine exposure can be useful both in diagnosing nicotine-related diseases and finding new treatment strategies.

Effects of nicotine on microRNA-124 expression in bile duct ligation-induced liver fibrosis in rats.

BACKGROUND: Nicotine, the main compound of smoking may exert its effects by changing the expression of microRNAs (miRNAs). This study was conducted to further investigate the molecular mechanisms of miRNA-dependent effects of nicotine in an animal model of liver fibrosis. METHODS: The bile duct ligation (BDL) approach was used to create a model of liver fibrosis. Twenty-four male Wistar rats were used in the study. The effects of nicotine administration on miRNA-124 expression, as well as alpha-smooth muscle actin (liver fibrosis marker) and chemokine ligand 2 (an inflammatory chemokine), were investigated using RT-qPCR. In addition, the mRNA and protein expression of signal transducer and activator of transcription 3 (STAT-3; as a potential target for miRNA-124) were investigated by RT-qPCR and immunofluorescence, respectively. Liver enzyme activity levels were measured using a colorimetric assay. In addition, the effects of nicotine on the process of liver fibrosis were investigated with histological studies. RESULTS: The development of liver fibrosis in BDL rats and nicotine administration led to a decrease in miRNA-124 expression. The decrease in the expression is accompanied by the increase in the expression of fibrotic and proinflammatory genes. Also, an increase in STAT-3 mRNA and protein expression was observed in the fibrotic rats that received nicotine. In addition, the significant increase in bilirubin and liver enzymes in fibrotic rats worsens with nicotine administration. The results of histological studies also confirm these results. CONCLUSION: Considering that miRNA-124 is an anti-inflammatory miRNA, it can be concluded that the decrease in its expression due to nicotine exposure leads to an increase in inflammatory processes and subsequently to an increase in liver fibrosis.

Comparison of modeling, optimization, and prediction of important parameters in the adsorption of cefixime onto sol-gel derived carbon aerogel and modified with nickel using ANN, RSM, GA, and SOLVER methods.

Today, the main goal of many researchers is the use of high-performance, economically and industrially justified materials, as well as recyclable materials in removing organic and dangerous pollutants. For this purpose, sol-gel derived carbon aerogel modified with nickel (SGCAN) was used to remove Cefixime from aqueous solutions. The influence of important parameters in the cefixime adsorption onto SGCAN was modeled and optimized using artificial neural network (ANN), response surface methodology (RSM), genetic algorithm (GA), and SOLVER methods. R software was applied for this purpose. The design range of the runs for a time was in the range of 5 min-70 min, concentration in the range of 5 mg L-1 to 40 mg L-1, amount of adsorbent in the range of 0.05 g L-1 to 0.15 g L-1, and pH in the range of 2.0-11. The results showed that the ANN model due to lower Mean Squared Error (MSE), Sum of Squared Errors (SSE), and Root Mean Squared Error (RMSE) values and also higher R2 is a superior model than RSM. Also, due to the superiority of ANN over the RSM model, the optimum results were calculated based on GA. Based on GA, the highest Cefixime adsorption onto SGCAN was obtained in pH, 5.98; reaction time, 58.15 min; initial Cefixime concentration, 15.26 mg L-1; and adsorbent dosage, 0.11 g L-1. The maximum adsorption capacity of Cefixime onto SGCAN was determined to be 52 mg g-1. It was found the pseudo-second-order model has a better fit with the presented data.

Chronic stress-induced anxiety-like behavior, hippocampal oxidative, and endoplasmic reticulum stress are reversed by young plasma transfusion in aged adult rats.

Objectives: Aging and stress synergistically induce behavioral dysfunctions associated with oxidative and endoplasmic reticulum (ER) stress in brain regions. Considering the rejuvenating effects of young plasma on aging brain function, in the current study, we examined the effects of young plasma administration on anxiety-like behavior, NADH oxidase, NADPH oxidase, and ER stress markers in the hippocampus of old male rats. Materials and Methods: Young (3 months old) and aged (22 months old) rats were randomly assigned into five groups: young control (Y), aged control (A), aged rats subjected to chronic stress for four weeks (A+S), aged rats subjected to chronic stress and treated with old plasma (A+S+OP), and aged rats subjected to chronic stress and treated with young plasma (A+S+YP). Systemic injection of (1 ml) young and old plasma was performed for four weeks (3 times/week). Results: Young plasma transfusion significantly improved anxiety-like behavior in aged rats and modulated oxidative stress in the hippocampus, evidenced by the increased NADH oxidase (NOX) activity and the reduced NADPH oxidase. In addition, the levels of C/EBP homologous protein (CHOP) and Glucose-Regulated Protein 78 (GRP-78), as ER stress markers, markedly reduced in the hippocampus following the administration of young plasma. Conclusion: These findings suggest that young plasma transfusion could reverse anxiety-like behavior in stress-exposed aged rats by modulating the hippocampal oxidative and ER stress markers.

Chronic Sustained Hypoxia Leads to Brainstem Tauopathy and Declines the Power of Rhythms in the Ventrolateral Medulla: Shedding Light on a Possible Mechanism.

Hypoxia, especially the chronic type, leads to disruptive results in the brain that may contribute to the pathogenesis of some neurodegenerative diseases such as Alzheimer's disease (AD). The ventrolateral medulla (VLM) contains clusters of interneurons, such as the pre-Bötzinger complex (preBötC), that generate the main respiratory rhythm drive. We hypothesized that exposing animals to chronic sustained hypoxia (CSH) might develop tauopathy in the brainstem, consequently changing the rhythmic manifestations of respiratory neurons. In this study, old (20-22 months) and young (2-3 months) male rats were subjected to CSH (10 ± 0.5% O2) for ten consecutive days. Western blotting and immunofluorescence (IF) staining were used to evaluate phosphorylated tau. Mitochondrial membrane potential (MMP or ∆ψm) and reactive oxygen species (ROS) production were measured to assess mitochondrial function. In vivo diaphragm's electromyography (dEMG) and local field potential (LFP) recordings from preBötC were employed to assess the respiratory factors and rhythmic representation of preBötC, respectively. Findings showed that ROS production increased significantly in hypoxic groups, associated with a significant decline in ∆ψm. In addition, tau phosphorylation elevated in the brainstem of hypoxic groups. On the other hand, the power of rhythms declined significantly in the preBötC of hypoxic rats, parallel with changes in the respiratory rate, total respiration time, and expiration time. Moreover, there was a positive and statistically significant correlation between LFP rhythm's power and inspiration time. Our data showed that besides CSH, aging also contributed to mitochondrial dysfunction, tau hyperphosphorylation, LFP rhythms' power decline, and changes in respiratory factors.

Aging impairs recovery from stress-induced depression in male rats possibly by alteration of microRNA-101 expression and Rac1/RhoA pathway in the prefrontal cortex.

Along with altering brain responses to stress, aging may also impair recovery from depression symptoms. In the present study, we investigated depressive-like behaviors in young and aged rats and assayed the levels of microRNA-101 (miR-101), Rac1/RhoA, PSD-95, and GluR1 in the prefrontal cortex (PFC) after stress cessation and after a recovery period. Young (3 months old) and aged (22 months old) male Wistar rats were divided into six groups; Young control (YNG), young rats received chronic stress for four weeks (YNG + CS), young rats received chronic stress for four weeks followed by a 6-week recovery period (YNG + CS + REC), Aged control (AGED), aged rats received chronic stress for four weeks (AGED + CS), and aged rats received chronic stress for four weeks followed by a 6-week recovery period (AGED + CS + REC). Stress-induced depression, evaluated by the sucrose preference test (SPT) and forced swimming test (FST), was yet observed after the recovery period in aged but not in young rats, which were accompanied by unchanged levels of miR-101, Rac1/RhoA, GluR1, and PSD-95 in the PFC of aged rats. These data suggested that impaired synaptic plasticity of glutamatergic synapses via the miR-101/Rac1/RhoA pathway may contribute to the delayed behavioral recovery after stress exposure observed in aging animals.

The role of microRNAs in nicotine signaling.

Cigarette smoking is a harmful habit that is widespread around the world. It is among the well-known lifestyle-related risk factors for many diseases. Nicotine, as its principal constituent, has various detrimental, and beneficial functions. Nicotinic acetylcholine receptors (nAChRs), which are present in nearly all body cells, are how nicotine works. Numerous investigations have demonstrated that nicotine causes abnormal microRNA expression (miRNAs). These short sequences of RNAs are known to regulate gene expression post-transcriptionally. A wide range of miRNAs are modulated by nicotine, and nicotine-induced miRNA changes could subsequently mediate nicotine's effect on gene expression regulation. We will focus on the reciprocal interaction between nAChRs and miRNAs and describe the essential targets of these dysregulated miRNAs after nicotine exposure and activation of nAChRs. It appears that crucial subcellular mechanisms implicated in nicotine's effects are miRNA-related pathways. It is crucial to investigate the molecular mechanism underlying the effects of nicotine as well as the dysregulation of miRNA following nAChR activation. The finding about epigenetic mechanisms of nicotine-induced effects may shed light on the establishment of new treatment strategies to prevent the harmful effects of nicotine and perhaps may augment the beneficial effects in diverse smoking-related diseases.

Long-term resveratrol administration improves diabetes-induced pancreatic oxidative stress, inflammatory status, and ß cell function in male rats

Abstract Diabetes is a metabolic disorder caused by insulin resistance or a defect in the pancreatic beta cells in insulin secretion. The aim of this study was to evaluate the possible effectiveness of long-term administration of resveratrol on inflammatory and oxidative stress markers in the pancreatic tissue of diabetic rats. Male Wistar rats (n = 24) were randomly divided into four groups of six animals, namely a healthy group, a healthy group receiving resveratrol, a diabetic control group, and a diabetic group receiving resveratrol. Diabetes was induced by single dose injection of streptozotocin (50 mg/kg; ip), 15 min after injection of nicotinamide (110 mg/kg; ip). Resveratrol was also administered by gavage (5 mg/kg/day) for 4 months. Administration of resveratrol alleviated hyperglycemia, weight loss and pancreatic ß cell function measured by HOMA-ß. Resveratrol improved oxidative stress (nitrate/nitrite, 8-isoprostane and glutathione) and proinflammatory markers (tumor necrosis factor α, cyclooxygenase 2, interleukin 6 and nuclear factor kappa B) in the pancreatic tissue of diabetic rats. Resveratrol administration had no significant effect on the activity of superoxide dismutase and catalase enzyme. These observations indicate that resveratrol administration may be effective as a beneficial factor in improving pancreatic function and reducing the complications of diabetes

The role of microRNAs in hepatocellular carcinoma: Therapeutic targeting of tumor suppressor and oncogenic genes.

Hepatocellular carcinoma (HCC) is a severe malignant liver cancer with a poor prognosis and a high mortality rate. This carcinoma is a multistage process that begins with chronic hepatitis and progresses to cirrhosis, dysplastic nodules, and eventually HCC. However, the exact molecular etiology remains unclear. MicroRNAs (miRs) are small non-coding RNAs that modulate the expression of numerous genes. These molecules have become significant participants in several functions, including cell proliferation, differentiation, development, and tumorrelated properties. They have a pivotal role in carcinogenesis as oncogenes or tumor suppressor genes. Furthermore, some investigations have shown that particular miRs might be used as predictive or diagnostic markers and therapeutic targets in HCC therapy. This review study summarizes the current level of knowledge on the role of miRs in the initiation and progression of HCC.

Intersection of hippocampus and spinal cord: a focus on the hippocampal alpha-synuclein accumulation, dopaminergic receptors, neurogenesis, and cognitive function following spinal cord injury in male rats.

BACKGROUND: Following Spinal Cord Injury (SCI), innumerable inflammatory and degenerative fluctuations appear in the injured site, and even remotely in manifold areas of the brain. Howbeit, inflammatory, degenerative, and oscillatory changes of motor cortices have been demonstrated to be due to SCI, according to recent studies confirming the involvement of cognitive areas of the brain, such as hippocampus and prefrontal cortex. Therefore, addressing SCI induced cognitive complications via different sights can be contributory in the treatment approaches. RESULTS: Herein, we used 16 male Wistar rats (Sham = 8, SCI = 8). Immunohistochemical results revealed that spinal cord contusion significantly increases the accumulation of alpha-synuclein and decreases the expression of Doublecortin (DCX) in the hippocampal regions like Cornu Ammonis1 (CA1) and Dentate Gyrus (DG). Theses degenerative manifestations were parallel with a low expression of Achaete-Scute Family BHLH Transcription Factor 1 (ASCL1), SRY (sex determining region Y)-box 2 (SOX2), and dopaminergic receptors (D1 and D5). Additionally, based on the TUNEL assay analysis, SCI significantly increased the number of apoptotic cells in the CA1 and DG regions. Cognitive function of the animals was assessed, using the O-X maze and Novel Object Recognition (NORT); the obtained findings indicted that after SCI, hippocampal neurodegeneration significantly coincides with the impairment of learning, memory and recognition capability of the injured animals. CONCLUSIONS: Based on the obtained findings, herein SCI reduces neurogenesis, decreases the expression of D1 and D5, and increases apoptosis in the hippocampus, which are all associated with cognitive function deficits.

Protective Role of trans-Chalcone against the Progression from Simple Steatosis to Non-alcoholic Steatohepatitis: Regulation of miR-122, 21, 34a, and 451.

Purpose: Non-alcoholic steatohepatitis (NASH) is an inflammatory disorder and an aggressive form of fatty liver disease. Certain microRNAs, including miR-122, 21, 34a, and 451, are involved in the transition from steatosis to NASH. This study examined how trans-chalcone (the core of chalcone derivatives) affects NAFLD progression by regulating miRNAs. Methods: Male rats were divided into three groups (n = 7/group) as follows: control, rats were gavaged with 10% tween 80 (for two weeks); NASH, rats were gavaged with a high-fat liquid diet (HFD; for six weeks) and 10% tween 80 (for two weeks); NASH + Chal, rats were gavaged with the HFD (for six weeks) and trans-chalcone (for two weeks). Hepatic expression levels of miR-122, 21, 34a, and 451 were determined. Results: trans-Chalcone reversed histological abnormalities, reduced liver injury markers, and attenuated insulin resistance in HFD-fed rats. In the liver, HFD-induced NASH increased the expression level of miR-34a and decreased expression levels of miR-122, 21, and 451. However, trans-chalcone inhibited HFD-induced changes in expression levels of these miRNAs. Conclusion: trans-Chalcone could inhibit the transition from steatosis to NASH through the modulation of miR-122, 21, 34a, and 451 expression levels in the liver.

Altered gene expression levels of IL-17/TRAF6/MAPK/USP25 axis and pro-inflammatory cytokine levels in lung tissue of obese ovalbumin-sensitized rats.

AIMS: The association between asthma and obesity has been shown but its accurate mechanism is unknown. In the current study, we sought to investigate the gene expression levels of IL-17/TRAF6/MAPK/USP25 axis and pro-inflammatory cytokine level (IL-6, IL-1ß, and TNF-α) in obese Ovalbumin (OVA)-sensitized female and male Wistar rats lung tissue. MAIN METHODS: Animals in both males and females were divided into eight groups (four groups in each sex) based on diet and OVA-sensitization: normal diet, a normal diet with OVA-sensitization, high-fat diet (HFD), and OVA-sensitization with an HFD. KEY FINDINGS: In both sexes, obese OVA-sensitized rats, the methacholine concentration-response curve shifted to the left and EC50 methacholine decreased. Increased pro-inflammatory cytokines as well as elevated IL-17/TRAF6/MAPK axis genes and decreased USP25 gene expression were identified in obese OVA-sensitized groups. SIGNIFICANCE: The results indicate that in obese OVA-sensitized rats, the IL-17 axis were involved in the pathogenesis of the disease and can be considered as a therapeutic target in subjects with obesity-related asthma.

Effect of ghrelin on hypoxia-related cardiac angiogenesis: involvement of miR-210 signalling pathway.

OBJECTIVE: Hypoxia is the main stimulus for angiogenesis. Hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), and miR-210 are involved in the hypoxia-induced angiogenesis. This study examined the effects of hypoxia and/or ghrelin on miR-210, HIF-1α, and VEGF levels in the heart of rats. METHODS: Wistar rats were randomly divided into 4 groups (n = 6): control; ghrelin, received daily intraperitoneal injections of ghrelin; hypoxia, was exposed to hypoxic condition; hypoxia + ghrelin, was exposed to hypoxic condition and received intraperitoneal injections of ghrelin, for 2 weeks. Myocardial angiogenesis, the expression level of miR-210, and protein levels of HIF-1α and VEGF were assayed in the heart samples. RESULTS: Hypoxia increased myocardial angiogenesis and cardiac levels of miR-210, HIF-1α, and VEGF. However, ghrelin inhibited these hypoxia-induced changes. Interestingly, ghrelin had no significant effect on miR-210, HIF-1α, and VEGF levels in normoxic condition. CONCLUSION: Ghrelin may be useful as an anti-angiogenic factor.

trans-Chalcone inhibits transforming growth factor-ß1 and connective tissue growth factor-dependent collagen expression in the heart of high-fat diet-fed rats.

Objective: Non-alcoholic fatty liver disease (NAFLD) is one of the main risk factors for cardiovascular mortality and morbidity. This study, for the first time, explored the effects of trans-chalcone on cardiac expressions of myocardial fibrosis-related genes, including transforming growth factor -ß1 (TGF-ß1), connective tissue growth factor (CTGF/CCN2), and collagen type I.Materials and methods: Twenty-eight rats were randomly divided into four groups: control, received 10% tween 80; chalcone, received trans-chalcone; HFD, received high-fat diet (HFD) and 10% tween 80; HFD + chalcone, received HFD and trans-chalcone, by once-daily gavage for 6 weeks. Finally, cardiac expression levels of TGF-ß1, CTGF, and collagen type I were determined.Results: HFD feeding increased mRNA levels of collagen type I, TGF-ß1, and CTGF in the heart of rats. However, trans-chalcone inhibited HFD-induced changes.Conclusions: trans-Chalcone can act as a cardioprotective compound by inhibiting TGF-ß1 and CTGF-dependent stimulation of collagen type I synthesis in the heart of HFD-fed rats.

Young Plasma Induces Antidepressant-Like Effects in Aged Rats Subjected to Chronic Mild Stress by Suppressing Indoleamine 2,3-Dioxygenase Enzyme and Kynurenine Pathway in the Prefrontal Cortex.

Pathophysiology of depression in elderlies is linked to aging-associated increase in indoleamine 2,3-dioxygenase (IDO) levels and activity and kynurenine (Kyn) metabolites. Moreover, these aging-induced changes may alter the brain's responses to stress. Growing evidence suggested that young plasma can positively affect brain dysfunctions in old age. The present study aimed to investigate whether the antidepressant effects of young plasma administration in aged rats subjected to chronic unpredictable mild stress (CUMS) and underlying mechanisms, focusing on the prefrontal cortex (PFC). Young (3 months old) and aged (22 months old) male rats were divided into five groups; young control, aged control, aged rats subjected to CUMS (A + CUMS), aged rats subjected to CUMS and treated with young plasma (A + CUMS + YP), and aged rats subjected to CUMS and treated with old plasma (A + CUMS + OP). Plasma was injected (1 ml, intravenously) three times per week for four weeks. Young plasma significantly improved CUMS-induced depressive-like behaviors, evidenced by the increased sucrose consumption ratio in the sucrose preference test and the reduced immobility time in the forced swimming test. Furthermore, young plasma markedly reduced the levels of interferon-gamma (IFN-γ), IDO, Kyn, and Kyn to tryptophan (Kyn/Trp) ratio in PFC tissue. Expression levels of the serotonin transporter and growth-associated protein (GAP)-43 were also significantly increased after chronic administration of young plasma. These findings provide evidence for the antidepressant effect of young plasma in old age; however, whether it improves depressive behaviors or faster recovery from stress-induced deficits is required to be elucidated.

The detection of SARS-CoV-2 RNA in indoor air of dental clinics during the COVID-19 pandemic.

In the indoor environment of dental clinics, dental personnel and patients are exposed to a risk of infection because of the transmission of SARS-CoV-2 via particles or droplets. This study investigated the presence of SARS-CoV-2 RNA in indoor air of dental clinics in Tehran, Iran. Air sampling was done (n = 36) collecting particulate samples on PTFE filters at flow rates of 30 to 58 L/min. The samples were analyzed with novel coronavirus nucleic acid diagnostic real-time PCR kits. Only 13 out of 36 samples were positive for SARS-CoV-2 RNA. Logistic regression showed that sampling site's volume, PM2.5 concentration, number of people, and number of active patient treatment units were significantly positively related with the presence of SARS-CoV-2 RNA. Thus, strategies to control the spread of COVID-19 should include reducing the number of infected people in dental clinics, adding filtration systems, and/or improving ventilation conditions.

Epidemiological data of national Kawasaki disease registry in Iran, 2007-2019.

Introduction: Kawasaki disease(KD) is a vasculitis of childhood that tends to influence the coronary arteries. There is no national data about the prevalence of KD in Iran. This study aimed to perform a national registry in Iran for 13 years. Methods: In this retrospective study, the data for KD extracted from medical records of <19 year-old patients admitted to tertiary hospitals in Iran between 2007 and 2019 were recorded in the national KD registry system. Age, admission date, gender, location, and presence of KD criteria, laboratory and echocardiography findings, and treatment modalities were evaluated. Complete KD was considered if ≥4 clinical criteria of the KD existed and otherwise, incomplete KD was considered. Results: Data from 1,682 KD patients including 999(59.39%) boys and 683(40.61%) girls and male/female ratio of 1.46 were evaluated. The mean age was 3.08 ± 2.49 years and 1465(87%) were living in urban regions. The yearly incidence of the disease was between 2.62 to 3.03 from 2015 to 2019. The highest age-specific incidence was observed in children <1-year-old. Incomplete and resistant KD included 1,321(78.54%) and 9(0.54%) patients, respectively. Abnormal echocardiography was detected in 619(36.80%) patients. Leukocytosis, with dominancy of neutrophils, anemia, thrombocytosis and increased ESR and CRP were the most noticeable laboratory findings. No death due to KD disease was reported. Conclusion: Based on this study, most of the KD cases are presented with atypical presentation in Iran. So, increasing awareness of primary healthcare workers by educating and updating their data is very important in timely diagnosis and management of the disease.

Hepatoprotection of capsaicin in alcoholic and non-alcoholic fatty liver diseases.

Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are common causes of chronic liver disease that share the range of steatosis, steatohepatitis, fibrosis, cirrhosis, and finally, hepatocellular carcinoma. They are identified by the dysregulation of disease-specific signalling pathways and unique microRNAs. Capsaicin is an active ingredient of chilli pepper that acts as an agonist of transient receptor potential vanilloid subfamily 1. It seems that the protective role of capsaicin against NAFLD and ALD is linked to its anti-steatotic, antioxidant, anti-inflammatory, and anti-fibrotic effects. Capsaicin-induced inhibiting metabolic syndrome and gut dysbiosis and increasing bile acids production are also involved in its anti-NAFLD role. This review summarises the different molecular mechanisms underlying the protective role of capsaicin against NAFLD and ALD. More experimental studies are needed to clarify the effects of capsaicin on the expression of genes involved in hepatic lipid metabolism and hepatocytes apoptosis in NAFLD and ALD.

Young plasma administration mitigates depression-like behaviours in chronic mild stress-exposed aged rats by attenuating apoptosis in prefrontal cortex.

NEW FINDINGS: What is the central question of this study? Young plasma contains several rejuvenating factors that exert beneficial effects in ageing and neurodegenerative diseases: can repeated transfusion of young plasma improve depressive behaviour in aged rats? What is the main finding and its importance? Following chronic transfusion of young plasma, depressive behaviour was improved in the depression model of aged rats, which was associated with reduced apoptosis process in the prefrontal cortex. ABSTRACT: Brain ageing alters brain responses to stress, playing an essential role in the pathophysiology of late-life depression. Moreover, apoptotic activity is up-regulated in the prefrontal cortex in ageing and stress-related mood disorders. Considerable evidence suggests that factors in young blood could reverse age-related dysfunctions in organs, especially in the brain. Therefore, this study investigated the effect of young plasma administration on depressive behaviours in aged rats exposed to chronic unpredictable mild stress (CUMS), with a focus on the apoptosis process. Young (3 months old) and aged (22 months old) male rats were randomly assigned into four groups: young control (YC), aged control (AC), aged rats subjected to CUMS (A+CUMS) and aged rats subjected to CUMS and treated with young plasma (A+CUMS+YP). In the A+CUMS and A+CUMS+YP groups, CUMS was used to generate the depression rat model. Moreover, the A+CUMS+YP group received pooled plasma (1 ml, intravenously), collected from young rats, three times per week for 4 weeks. Young plasma administration significantly improved CUMS-induced depression-like behaviours, including decreased sucrose consumption ratio, reduced locomotor activity and prolonged immobility time. Importantly, young plasma reduced neuronal apoptosis in the prefrontal cortex that was associated with reduced TUNEL-positive cells and cleaved caspase-3 protein levels in the A+CUMS+YP compared with the A+CUMS group. Young plasma can partially improve the neuropathology of late-life depression through the apoptotic signalling pathways.