COVID-19 and the role of cytokines in this disease.

Studies have shown that SARS-CoV-2 has the ability to activate and mature proinflammatory cytokines in the body. Cytokine markers are a group of polypeptide signalling molecules that can induce and regulate many cellular biological processes by stimulating cell receptors at the surface. SARS-CoV-2 has been shown to be associated with activation of innate immunity, and an increase in neutrophils, mononuclear phagocytes, and natural killer cells has been observed, as well as a decrease in T cells including CD4+ and CD8. It is noteworthy that during the SARS-CoV-2 infection, an increase in the secretion or production of IL-6 and IL-8 is seen in COVID-19 patients along with a decrease in CD4+ and CD8+ and T cells in general. SARS-CoV-2 has been shown to significantly increase Th2, Th1/Th17 cells and antibody production in the body of patients with COVID-19. Specific immune profiles of SARS-CoV-2 infection can lead to secondary infections and dysfunction of various organs in the body. It has been shown that Interleukins (such as IL-1, IL-4, IL-6, IL-7, IL-10, IL-12, IL-17, and IL-18), IFN-γ, TNF-α,TGF-ß and NF-κB play major roles in the body's inflammatory response to SARS-CoV-2 infection. The most important goal of this review is to study the role of inflammatory cytokines in COVID-19.

The role of AMPK-dependent pathways in cellular and molecular mechanisms of metformin: a new perspective for treatment and prevention of diseases.

Metformin can suppress gluconeogenesis and reduce blood sugar by activating adenosine monophosphate-activated protein kinase (AMPK) and inducing small heterodimer partner (SHP) expression in the liver cells. The main mechanism of metformin's action is related to its activation of the AMPK enzyme and regulation of the energy balance. AMPK is a heterothermic serine/threonine kinase made of a catalytic alpha subunit and two subunits of beta and a gamma regulator. This enzyme can measure the intracellular ratio of AMP/ATP. If this ratio is high, the amino acid threonine 172 available in its alpha chain would be activated by the phosphorylated liver kinase B1 (LKB1), leading to AMPK activation. Several studies have indicated that apart from its significant role in the reduction of blood glucose level, metformin activates the AMPK enzyme that in turn has various efficient impacts on the regulation of various processes, including controlling inflammatory conditions, altering the differentiation pathway of immune and non-immune cell pathways, and the amelioration of various cancers, liver diseases, inflammatory bowel disease (IBD), kidney diseases, neurological disorders, etc. Metformin's activation of AMPK enables it to control inflammatory conditions, improve oxidative status, regulate the differentiation pathways of various cells, change the pathological process in various diseases, and finally have positive therapeutic effects on them. Due to the activation of AMPK and its role in regulating several subcellular signalling pathways, metformin can be effective in altering the cells' proliferation and differentiation pathways and eventually in the prevention and treatment of certain diseases.

Risperidone attenuates acetic acid-induced colitis in rats through inhibition of TLR4/NF-kB signaling pathway.

AIM: The purpose of the present study is to explore the anti-inflammatory potential of risperidone in acetic acid-induced rat colitis through inhibition of TLR4/NF-kB pathway. METHODS: Acute colitis induction was done by intra-rectal administration of 2 mL of 4% diluted acetic acid solution. Two h after colitis induction, dexamethasone (2 mg/kg) as standard drugorrisperidone (2, 4 and 6 mg/kg) were administered orally to wistar rats for five consecutive days. 24 h after the last treatment, animals were sacrificed by cervical dislocation. Macroscopic and microscopic damage evaluation was done. Biochemical and ELISA methods were used to assess myeloid peroxidase (MPO) enzyme activity and tumor necrosis factor-α (TNF-α) level respectively. Moreover, immunohistochemistry (IHC) was performed to detect the expression of TLR4 and pNF-kBproteins. RESULTS: Dexamethasone (2 mg/kg) or risperidone (2, 4 and 6 mg/kg) improved acetic acid-induced macroscopic (p < .001) and microscopic lesions. Additionally, risperidone (2, 4 and 6 mg/kg) inhibited the activity of MPO and TNF-α (p < .01, p < .001) in the colon tissue compared to acetic acid group. Furthermore, bothdexamethasone and risperidone (2, 4 and 6 mg/kg) significantly reduced acetic acid-induced expression of TLR4and pNF-kB proteins (p < .05, p < .01, p < .001). CONCLUSION: The anti-inflammatory effect of risperidone on acetic acid-induced colitis in rats may involve inhibition of TLR4 and NF-kB signaling pathway.

Association of Serum Vitamin D Concentration With Clinical Symptoms and Quality of Life in Patients With Irritable Bowel Syndrome.

OBJECTIVE: A high prevalence of vitamin D deficiency (VDD) in gastrointestinal (GI) disorders and the role of vitamin D in the function of the gut have been shown previously. Therefore, we aimed to evaluated the VDD and the possible association of the GI symptoms severity and quality of life (QoL) score with the serum levels of vitamin D in irritable bowel syndrome (IBS). METHODS: A total of 90 patients with IBS based on Rome III criteria enrolled in the study from the tertiary referral university hospital. In addition, 90 sex- and age-matched healthy controls (HCs) were recruited. To measure the serum levels of 25(OH)D3, blood samples were taken from all the participants. Severity of clinical symptoms, IBS quality of life (IBS-QoL), and IBS symptom severity score (IBSSS) were assessed. RESULTS: In 66.7% of IBS patients, serum 25(OH)D3 concentrations were <20 ng/mL. The mean serum 25(OH)D3 of IBS patients was statistically (p < 0.05) lower vs. HCs. When different subtypes were analyzed, the serum 25(OH)D3 concentrations in diarrhea-predominant IBS were statistically (p < 0.05) lower as compared to HCs. Furthermore, the lower serum concentrations of 25(OH)D3 were associated (p < 0.05) with higher severity of abdominal pain and distention, flatulence, overall GI symptoms, and IBSSS. However, a direct significant association was seen between IBS-QoL and serum 25(OH)D3. CONCLUSION: Results of this study showed a high prevalence of VDD in patients with IBS. In addition, VDD was associated with a higher severity of clinical symptoms and lower QoL in IBS.

Anticonvulsant effect of minocycline on pentylenetetrazole-induced seizure in mice: involvement of nitric oxide and N-methyl-d-aspartate receptor.

Anticonvulsant effects of minocycline have been explored recently. This study was designed to examine the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole-induced seizures in mouse considering the possible role of the nitric oxide/N-methyl-d-aspartate (NMDA) pathway. We induced seizure using intravenous administration of pentylenetetrazole. Our results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of subeffective doses of the nonselective nitric oxide synthase (NOS) inhibitor NG-l-arginine methyl ester (10 mg/kg) and the neuronal NOS inhibitor 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of subeffective doses of minocycline (40 mg/kg). We found that inducible NOS inhibitor aminoguanidine (100 mg/kg) had no effect on the antiseizure effect of minocycline. Moreover, l-arginine (60 mg/kg), as a NOS substrate, reduced the anticonvulsant effect of minocycline. We also demonstrated that pretreatment with the NMDA receptor antagonists ketamine (0.5 mg/kg) and MK-801 (0.05 mg/kg) increased the anticonvulsant effect of subeffective doses of minocycline. Results showed that minocycline significantly decreased the hippocampal nitrite level. Furthermore, co-administration of a neuronal NOS inhibitor like NMDA receptor antagonists augmented the effect of minocycline on the hippocampal nitrite level. In conclusion, we revealed that anticonvulsant effect of minocycline might be, at least in part, due to a decline in constitutive hippocampal nitric oxide activity as well as inhibition of NMDA receptors.

Inflammatory cytokines and oxidative stress biomarkers in irritable bowel syndrome: Association with digestive symptoms and quality of life.

A growing body of evidence suggests a possible role for low-grade inflammation in the pathogenesis of irritable bowel syndrome (IBS). The objectives of this study were to measure serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-17, interleukin (IL)-10, malondialdehyde (MDA) and total antioxidant capacity (TAC) in IBS patients and healthy controls (HCs), and to evaluate possible correlations of such markers with gastrointestinal (GI) symptoms and quality of life (QoL). Ninety Rome III positive IBS patients and 90 sex and age matched HCs were recruited. GI symptoms, IBS-QoL, IBS severity score system (IBSSS), and the serum levels of inflammatory cytokines and oxidative stress biomarkers were evaluated. In IBS patients, TNFα, IL-17 and MDA cytokines were significantly (P<0.05) higher, and IL-10 cytokine and TAC were significantly (P<0.05) lower vs. HCs. When comparing IBS subtypes, TNFα and IL-17 were significantly (P<0.05) higher, and IL-10 was significantly (P<0.05) lower in diarrhea predominant IBS (IBS-D) compared to HCs, whereas the inflammatory cytokine profile of other subtypes more closely resembled that of HCs. The serum levels of MDA and TAC were significantly different (P<0.05) in all the subtypes vs. HCs. All the inflammatory cytokines had significant (P<0.05) correlations with GI symptoms, IBSSS and IBS-QoL, whereas no significant association was found between oxidative stress biomarkers and these symptoms. IBS-D patients display increased pro-inflammatory cytokines and decreased anti-inflammatory cytokines. Present study demonstrated a correlation between inflammatory cytokines and both IBS symptoms and QoL.

Anti-inflammatory effect of AMPK signaling pathway in rat model of diabetic neuropathy.

Diabetic neuropathy (DN) is characterized as Hyperglycemia activates thdisturbed nerve conduction and progressive chronic pain. Inflammatory mediators, particularly cytokines, have a determinant role in the pathogenesis of neuropathic pain. The activity of adenosine monophosphate protein kinase (AMPK), an energy charge sensor with neuroprotective properties, is decreased in diabetes. It has been reported that activation of AMPK reduces the systemic inflammation through inhibition of cytokines. In this study, we aimed to investigate the probable protective effects of AMPK on DN in a rat of diabetes. DN was induced by injection of streptozotocin (65 mg/kg, i.p.). Motor nerve conduction velocities (MNCV) of the sciatic nerve, as an electrophysiological marker for peripheral nerve damage, were measured. Plasma levels of IL-6, TNF-α, CRP were assessed as relevant markers for inflammatory response. Also, the expression of phosphorylated AMPK (p-AMPK) and non-phosphorylated (non-p-AMPK) was evaluated by western blotting in the dorsal root ganglia. Histopathological assessment was performed to determine the extent of nerve damage in sciatic nerve. Our findings showed that activation of AMPK by metformin (300 mg/kg) significantly increased the MNCV and reduced the levels of inflammatory cytokines. In addition, we showed that administration of metformin increased the expression of p-AMPK as well as decline in the level of non p-AMPK. Our results demonstrated that co-administration of dorsomorphin with metformin reversed the beneficial effects of metformin. In conclusion, the results of this study demonstrated that the activation of AMPK signaling pathway in diabetic neuropathy might be associated with the anti-inflammatory response.

The protective potential of metformin against acetaminophen-induced hepatotoxicity in BALB/C mice.

CONTEXT: Acetaminophen overdose is regarded to a common cause of acute liver failure. The hepatotoxicity leads to mitochondrial oxidative stress and subsequent necrotic hepatocellular death. OBJECTIVE: This study examines the protective effect of metformin on acetaminophen-induced oxidative stress, inflammation and subsequent hepatotoxicity in mice. MATERIALS AND METHODS: Male BALB/c mice were orally administered to acetaminophen (250 mg/kg/d) for a 7-day period. The mice received metformin (100 and 200 mg/kg/d, p.o.) for 21 days. To evaluate acetaminophen-induced oxidative stress, liver tissue level of malodialdehyde (MDA), end product of membrane lipid peroxidation, and activities of superoxide dismutase (SOD) and glutathione (GSH) were measured. Histological analysis and measurement of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were performed. Moreover, tissue concentrations of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), along with, C-reactive protein (CRP) were assessed. RESULTS: Acetaminophen caused focal hepatocyte necrosis, inflammation and fatty degeneration, as well as increased tissue levels of AST, ALT, ALP and MDA, and also decreased GSH and SOD activities. Moreover, IL-6, TNF-α and CRP levels were increased following acetaminophen hepatotoxicity. Metformin (200 mg/kg/d) significantly normalized MDA, SOD and GSH levels (p < 0.001), and exerted a hepatoprotective effect by significant decreasing ALT, AST and ALP concentrations (p < 0.001). The tissue levels of IL-6, TNF-α and CRP were markedly decreased by 21-day treatment with metformin (200 mg/kg/d) (p < 0.001). DISCUSSION: The results suggest metformin protects hepatocytes against acute acetaminophen toxicity. Metformin is indicated to diminish oxidative stress, proinflammatory cytokines, and hepatocyte necrosis.

Designing a T-cell epitope-based vaccine using in silico approaches against the Sal k 1 allergen of Salsola kali plant.

Allergens originated from Salsola kali (Russian thistle) pollen grains are one of the most important sources of aeroallergens causing pollinosis in desert and semi-desert regions. T-cell epitope-based vaccines (TEV) are more effective among different therapeutic approaches developed to alleviate allergic diseases. The physicochemical properties, and B as well as T cell epitopes of Sal k 1 (a major allergen of S. kali) were predicted using immunoinformatic tools. A TEV was constructed using the linkers EAAAK, GPGPG and the most suitable CD4+ T cell epitopes. RS04 adjuvant was added as a TLR4 agonist to the amino (N) and carboxyl (C) terminus of the TEV protein. The secondary and tertiary structures, solubility, allergenicity, toxicity, stability, physicochemical properties, docking with immune receptors, BLASTp against the human and microbiota proteomes, and in silico cloning of the designed TEV were assessed using immunoinformatic analyses. Two CD4+ T cell epitopes of Sal k1 that had high affinity with different alleles of MHC-II were selected and used in the TEV. The molecular docking of the TEV with HLADRB1, and TLR4 showed TEV strong interactions and stable binding pose to these receptors. Moreover, the codon optimized TEV sequence was cloned between NcoI and XhoI restriction sites of pET-28a(+) expression plasmid. The designed TEV can be used as a promising candidate in allergen-specific immunotherapy against S. kali. Nonetheless, effectiveness of this vaccine should be validated through immunological bioassays.

Protective assessment of progesterone and its receptor on experimental diabetic neuropathy: Antioxidant and anti-inflammatory effects.

Diabetes induces a disorder in mitochondrial activity, which causes damage to the nuclear and mitochondrial DNA and ultimately increases the release of inflammatory cytokines and damages the sciatic nerve and dorsal root ganglion and induces neuropathy. It has been shown that progesterone has anti-inflammatory and antioxidative effects and prevents nerve cell damage. Therefore, the aim of this experiment was to investigate the effect of progesterone receptor neuroprotection on diabetic neuropathy. Forty male Sprague-Dawley rats were divided into four groups, including control group, diabetic control group, diabetic control group + progesterone (30 mg/kg), and diabetic control group + combination of progesterone (30 mg/kg) and RU486 (10 mg/kg). After the induction of diabetes, blood glucose level, body weight, behavioral tests, electrophysiological tests, oxidative and inflammatory factors, and histological parameters were measured. Progesterone treatment significantly reduced the level of sensitivity to hot plate without significant effect on glucose level, and significant changes were also observed in the results of tail flick test. In addition, the results showed that the administration of progesterone can improve MNCV and significantly reduce the serum levels of oxidative stress and inflammatory factors, as well as inflammation and edema around the sciatic nerve. However, RU486 inverted the beneficial effects of progesterone. Progesterone can be considered as a protective agent in reducing DN because of its ability to reduce inflammation and nerve damage. In addition, RU486, a progesterone receptor blocker, inhibits the beneficial effects of progesterone on the DN; thus, progesterone receptors play an important role in the neuroprotective effect of progesterone.

Association between deficient levels of circulating vitamin D, dietary intake of vitamin D, calcium and retinol, and risk of colorectal cancer in an Iranian population: A case control study.

AIM: We aimed to assess the association between deficient levels of circulating vitamin D, dietary intake of vitamin D, calcium and retinol, and risk of colorectal cancer in an Iranian population. METHODS: In this retrospective case-control study that was conducted between 2012 and 2015, 278 first incident colorectal cancer cases (colon cancer = 103; rectal cancer = 175), and 278 sex and age matched healthy controls (HCs) were recruited. Serum 25(OH)D, dietary vitamin D, and calcium intake were assessed. Logistic regression was used to estimate the odds ratio (OR) between studied factors and colorectal cancer. Estimates of OR were calculated according to both bivariate analyses based on the matching factors and multivariate analyses, with additional adjustment for potential confounders. RESULTS: A strong inverse linear dose-response association was seen between serum 25(OH)D and colorectal cancer (P for trend = .002). In comparison to serum 25(OH)D more than 40 nmol/L, lower serum concentrations were significantly associated with an increased OR of colorectal cancer. When analyzing anatomical subsites separately, lower circulating 25(OH)D was associated with higher OR for both colon and rectum cancers. Dietary vitamin D and calcium intake were not associated with colorectal cancer. Interaction analysis between serum 25(OH)D and the amount of calcium intake demonstrated that the lowest level of both factors was associated with an increased OR of colorectal cancer. The highest OR of colorectal cancer that was associated with lowest circulating 25(OH)D was stronger at the highest retinol intakes. CONCLUSION: This study demonstrated an inverse strong association between 25(OH)D concentration and colorectal cancer in an Iranian population.

Neuroprotective and Anti-inflammatory Role of Atorvastatin and Its Interaction with Nitric Oxide (NO) in Chronic Constriction Injury-induced Neuropathic Pain.

Prevention and treatment of neuropathic pain (NP) is one of the most difficult problems in clinical practice since the underlying mechanism of NP is unclear. In previous studies, the increased production of nitric oxide (NO) has been closely linked to the induced NP. In this study, we assessed the effect of atorvastatin through NO mechanism, on inflammation, thermal hyperalgesia, thermal allodynia, and mechanical allodynia as well as sciatic nerve histological score in rat with chronic constriction injury (CCI) model. Finally, we specified the role of cytokines such as TNF-α and IL-6 in the spinal cord. Treatment with atorvastatin and L-NAME (NO inhibitor) attenuated the thermal hyperalgesia, thermal allodynia and mechanical allodynia induced by CCI. The antinociceptive consequence was better elevated with a combination of atorvastatin and L-NAME in comparison with the other groups. In addition, the treatment with these drugs also attenuated the CCI-induced TNF-α and IL-6 level in the spinal cord. Furthermore, the histological analysis showed a low level of inflammation in the sciatic nerve in the CCI rats co-treated with atorvastatin and L-NAME. Findings of our study in NP-induced CCI in the rat model demonstrate that inhibition of NO displays antinociceptive and anti-neuroinflammatory effects of atorvastatin in peripheral and central nervous system. In addition, we found that inhibition of the NO by atorvastatin could be one of the most important anti-inflammatory pathways of atorvastatin effect.

Bupropion Ameliorates Acetic Acid-Induced Colitis in Rat: the Involvement of the TLR4/NF-kB Signaling Pathway.

Inflammatory bowel disease composed of ulcerative colitis and Crohn's disease is a disorder that may involve entire gastrointestinal tract. Its pathogenesis is mainly an immune-mediated inflammation. Recently, it has been indicated that bupropion possesses anti-inflammatory properties; hence, the objective of this experiment is the investigation of the anti-inflammatory influence of bupropion on colonic lesions that emerged following the intrarectal administration of acetic acid. Thirty-six male Wistar rats were allocated randomly into six groups, including control, acetic acid, dexamethasone (2 mg/kg), and bupropion (40, 80, and 160 mg/kg). Colitis was induced by intrarectal administration of acetic acid in all study groups except control group, and animals were treated by oral administration of dexamethasone and bupropion. While macroscopic and microscopic lesions were observed after colitis induction, administration of dexamethasone and bupropion 160 mg/kg led to the remarkable improvement in lesions. In addition, the expression of TLR4 and NF-ĸB was decreased after colitis induction; however, treatment with dexamethasone (2 mg/kg) and bupropion (160 mg/kg) resulted in a significant decrease in their expression. Regarding biochemical factors, following colitis induction, TNF-α level and MPO activity were increased; nevertheless, dexamethasone (2 mg/kg) and bupropion (160 mg/kg) decreased the TNF-α and MPO activity. In conclusion, bupropion exerts anti-inflammatory influence through suppressing the TLR4 and NF-ĸB expression in the rat model of acute colitis.

Effect of Synbiotic on the Treatment of Jaundice in Full Term Neonates: A Randomized Clinical Trial.

PURPOSE: Jaundice accounts for most hospital admissions in the neonatal period. Nowadays, in addition to phototherapy, other auxiliary methods are used to reduce jaundice and the length of hospitalization. This study aimed to investigate the effect of probiotics on the treatment of hyper-bilirubinemia in full-term neonates. METHODS: In this randomized clinical trial, 83 full-term neonates, who were admitted to the hospital to receive phototherapy in the first 6 months of 2015, were randomly divided into two groups: synbiotic (SG, n=40) and control (CG, n=43). Both groups received phototherapy but the SG also received 5 drops/day of synbiotics. Serum bilirubin, urine, stool, feeding frequency, and weight were measured daily until hospital discharge. A p-value<0.05 was considered statistically significant. RESULTS: The mean total serum bilirubin in the SG was lower than that in the CG (9.38±2.37 and 11.17±2.60 mg/dL, respectively). The urine and stool frequency in the SG was significantly higher than that in the CG (p<0.05). The duration of hospitalization in the SG was shorter than that in the CG. CONCLUSION: Use of synbiotics as an adjuvant therapy had a significant treatment effect on jaundice in full-term neonates. Further studies including larger samples with long follow-up periods are essential to confirm the benefits of routine use of synbiotics in neonatal patients with jaundice.

Protective effects of persian honey, Apis Mellifera Meda Skorikov on side effects of chemotherapy and ischemia/reperfusion induced testicular injury.

Introduction The aim of the present study was to survey the protective effect of pretreatment with Persian honey on amelioration of side effects of chemotherapy and ischemia/reperfusion induced testicular injury. Materials and methods Forty adult's male wistar rats were divided into four groups of ischemia-reperfusion (IR), honey + ischemia-reperfusion (HIR), Busulfan (B) and Busulfan intraperitoneally+ honey (BH). The seminiferous tubules were rated for their modified spermatogenesis index (SI) by Johnsons score. Detection of single- and double-stranded DNA breaks at the early stages of apoptosis was performed using the in-situ cell death detection kit. Total serum concentration of Follicle-stimulating hormone (FSH) , Luteinizing hormone (LH) and testosterone was measured using ELISA. All data were expressed as mean ± SD and significance was set at p≤0.05. Results Honey improved SI in the HIR and BH groups and serum levels of FSH and LH in the BH and HIR groups (p<0.001). Also, serum levels of testosterone were significantly higher in BH and HIR groups. But, apoptotic cells in IR and B groups significantly increased (p<0.001), while in HIR and BH groups, the number of apoptotic cells decreased and the positive cells of TUNEL (TdT-mediated dUTP-X nick end labelling) staining were detected in spermatocytes and spermatid. Discussion Pretreatment with honey protect testis against chemotherapy and testicular IR injury, increase FSH and LH and testosterone and decrease the cellular damage and apoptosis. Honey can decrease the side effects of chemotherapy on reproductive system and prevent sterility.

The Antinociceptive Effects of Rosuvastatin in Chronic Constriction Injury Model of Male Rats.

INTRODUCTION: According to studies, statins possess analgesics and anti-inflammatory properties. In the present study, we examined the antinociceptive, anti-inflammatory and antioxidative effects of rosuvastatin in an experimental model of Chronic Constriction Injury (CCI). METHODS: Our study was conducted on four groups; sham, CCI (the control group), CCI+rosuvastatin (i.p. 5 mg/kg), and CCI+rosuvastatin (i.p. 10 mg/kg). We performed heat hyperalgesia, cold and mechanical allodynia tests on the 3rd, 7th, 14th, and 21st after inducing CCI. Blood samples were collected to measure the serum levels of Tumor Necrosis Factor (TNF)-α, and Interleukin (IL)-6. Rats' spinal cords were also examined to measure tissue concentration of Malondialdehyde (MDA), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) enzymes. RESULTS: Our findings showed that CCI resulted in significant increase in heat hyperalgesia, cold and mechanical allodynia on the 7th, 14th and 21st day. Rosuvastatin use attenuated the CCI-induced hyperalgesia and allodynia. Rosuvastatin use also resulted in reduction of TNF-α, IL-6, and MDA levels. However, rosuvastatin therapy increased the concentration of SOD and GPx in the CCI+Ros (5 mg/kg) and the CCI+Ros (10 mg/kg) groups compared to the CCI group. CONCLUSION: Rosuvastatin attenuated the CCI-induced neuropathic pain and inflammation. Thus, antinociceptive effects of rosuvastatin might be channeled through inhibition of inflammatory biomarkers and antioxidant properties.

Minocycline through attenuation of oxidative stress and inflammatory response reduces the neuropathic pain in a rat model of chronic constriction injury.

OBJECTIVES: Several lines of evidence showed that minocycline possesses antioxidant and anti-inflammatory properties. This study aimed to demonstrate the effects of minocycline in rats subjected to chronic constriction injury (CCI). MATERIALS AND METHODS: In this study four groups (n = 6-8) of rats were used as follows: Sham, CCI, CCI + minocycline (MIN) 10 mg/Kg (IP) and CCI + MIN 30 mg/Kg (IP). On days 3, 7, 14, and 21 post-surgery hot-plate, acetone, and von Frey tests were carried out. Finally, Motor Nerve Conduction Velocity Evaluation (MNCV) assessment was performed and spinal cords were harvested in order to measure tissue concentrations of TNF_α, IL-1ß, Glutathione peroxidase (GPx), Superoxide dismutase (SOD) and Malondialdehyde (MDA). Extent of perineural inflammation and damage around the sciatic nerve was histopathologically evaluated. RESULTS: Our results demonstrated that CCI significantly caused hyperalgesia and allodynia twenty-one days after CCI. MIN attenuated heat hyperalgesia, cold and mechanical allodynia and MNCV in animals. MIN also decreased the levels of TNF_α and IL-1ß. Antioxidative enzymes (SOD, MDA, and GPx) were restored following MIN treatment. Our findings showed that MIN decreased perineural inflammation around the sciatic nerve. According to the results, the neuropathic pain reduced in the CCI hyperalgesia model using 30 mg/kg of minocycline. CONCLUSION: It is suggested that antinociceptive effects of minocycline might be mediated through the inhibition of inflammatory response and attenuation of oxidative stress.

Maternal dietary nitrate intake and risk of neural tube defects: A systematic review and dose-response meta-analysis.

Despite growing evidence for the potential teratogenicity of nitrate, knowledge about the dose-response relationship of dietary nitrate intake and risk of specific birth defects such as neural tube defects (NTDs) is limited. Therefore, the aim of this meta-analysis was to synthesize the knowledge about the dose-response relation between maternal dietary nitrate intake and the risk of NTDs. We conducted a systematic search in PubMed, ISI Web of Science and Scopus up to February 2018 for observational studies. Risk ratios (RRs) and 95% confidence intervals (95% CI) were calculated using a random-effects model for highest versus lowest intake categories. The linear and non-linear relationships between nitrate intake and risk of NTDs were also investigated. Overall, 5 studies were included in the meta-analyses. No association was observed between nitrate intake and NTDs risk in high versus low intake (RR: 1.33; 95% CI: 0.89-1.99, p = 0.158) and linear dose-response (RR: 1.03; 95% CI: 0.99-1.07, p = 0.141) meta-analysis. However, there were positive relationships between nitrate intake and risk of NTDs in non-linear (pnon-linearity<0.05) model. Findings from this dose-response meta-analysis indicate that maternal nitrate intake higher than ∼3 mg/day is positively associated with NTDs risk.

Evaluation of selenium on kidney function following ischemic injury in rats; protective effects and antioxidant activity.

Introduction: Renal dysfunction is caused by ischemia-reperfusion (I/R) injury, which is a common problem in kidney surgery or kidney transplantation. The human body consists of enormous complex antioxidant systems, which inquires adequate selenium (Se) absorption for normal physiologic function. It is known that Se has some antioxidant effects. Objectives: In the present research, effects of the Se on damages caused by I/R injury investigated. Materials and Methods: In this experimental research, four groups of rats (weighing 220±10 g) used, include control group, I/R group, healthy group treated with Se for two weeks, and I/R group with two-week Se treatment. On the test day, I/R was treated in both right and left renal arteries for 45 minutes and the reperfusion was done for 24 hours. Results: In I/R group, the amount of urea and serum creatinine (Cr) was an injury indicator of the kidney cells which showed a significant increase compared with the control group. When the treatment with Se significantly reduced these indicators, glutathione (GSH) enzyme levels reduced significantly in the second group and the enzyme levels increased due to Se treatment in the fourth group. Furthermore, malondialdehyde (MDA) enzyme levels increased in I/R group due to the Se treatment in the fourth group which was significantly reduced. In addition, the tissue damage was reduced in the fourth group compared with I/R group. Conclusion: Se has a protective effect against the I/R injury. This effect might be due to the antioxidant properties of Se.

Double-button Fixation System for Management of Acute Acromioclavicular Joint Dislocation.

BACKGROUND: Surgical treatments for acromioclavicular (AC) joint dislocation present with some complications. The present study was designed to evaluate the double-button fixation system in the management of acute acromioclavicular joint dislocation. METHODS: This cross sectional study, done between February 2011 to June 2014, consisted of 28 patients who underwent surgical management by the double-button fixation system for acute AC joint dislocation. Age, sex, injury mechanism, dominant hand, side with injury, length of follow up, time before surgery, shoulder and hand (DASH), constant and visual analogue scale (VAS) scores, and all complications of the cases during the follow up were recorded. RESULTS: The mean age of patients was 33.23±6.7 years. Twenty four patients (85.71%) were male and four (14.28%) were female. The significant differences were observed between pre-operation VAS, constant shoulder scores and post-operation measurements. There were not any significant differences between right and left coracoclavicular, but two cases of heterotrophic ossifications were recorded. The mean follow-up time was 16.17±4.38 months. CONCLUSION: According to the results, the double-button fixation system for management of acute acromioclavicular joint dislocation has suitable results and minimal damage to the soft tissues surrounding the coracoclavicular ligaments.