Sex-dependent alterations of inflammatory factors, oxidative stress, and histopathology of the brain-gut axis in a VPA-induced autistic-like model of rats.

INTRODUCTION: In this study, we aimed to investigate the inflammatory factors, oxidative stress, and histopathological consequences of the brain-gut axis in male and female rats prenatally exposed to VPA. METHODS: Pregnant Wistar rats were randomly divided into two groups. The animals received saline, and valproic acid (VPA) (600 mg/kg, i.p.) on embryonic day 12.5 (E12.5). All offspring were weaned on postnatal day 21, and the experiments were done in male and female rats on day 60. The brain and intestine tissues were extracted to assess histopathology, inflammation, and oxidative stress. RESULTS: An increase of interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) and a decrease of interleukin-10 (IL-10) were observed in the two sexes and two tissues of the autistic rats. In the VPA-exposed animals, malondialdehyde (MDA) and protein carbonyl (PC) increased in the brain of both sexes and the intestines of only the males. The total antioxidant capacity (TAC), superoxide dismutase (SOD), and catalase (CAT) significantly decreased in both tissues of male and female autistic groups. Histopathological evaluation showed that the %apoptosis of the cortex in the autistic male and female groups was more than in controls whereas this parameter in the CA1 and CA3 was significant only in the male rats. In the intestine, histopathologic changes were seen only in the male autistic animals. CONCLUSION: The inflammatory and antioxidant factors were in line in the brain-gut axis in male and female rats prenatally exposed to VPA. Histopathological consequences were more significant in the VPA-exposed male animals.

The nongenomic neuroprotective effects of estrogen, E2-BSA, and G1 following traumatic brain injury: PI3K/Akt and histopathological study.

OBJECTIVES: Studies suggest that both genomic and nongenomic pathways are involved in mediating the salutary effects of steroids following traumatic brain injury (TBI). This study investigated the nongenomic effects of 17ß-estradiol (E2) mediated by the PI3K/p-Akt pathway after TBI. METHODS: Ovariectomized rats were apportioned to E2, E2-BSA (E2 conjugated to bovine serum albumin), G1 [G-protein-coupled estrogen receptor agonist (GPER)] or their vehicle was injected following TBI, whereas ICI (classical estrogen receptor antagonist), G15 (GPER antagonist), ICI + G15, and their vehicles were injected before the induction of TBI and injection of drugs. Diffuse TBI was induced by the Marmarou model. Evans blue (EBC, 5 h), brain water contents (BWC), histopathological changes, and brain PI3K and p-Akt protein expressions were measured 24 h after TBI. The veterinary comma scale (VCS) was assessed before and at different times after TBI. RESULTS: The results showed a reduction in BWC and EBC and increased VCS in the E2, E2-BSA, and G1 groups. Also, E2, E2-BSA, and G1 reduced brain edema, inflammation, and apoptosis. The ICI and G15 inhibited the beneficial effects of E2, E2-BSA, and G1 on these parameters. All drugs, following TBI, prevented the reduction of brain PI3K/p-Akt expression. The individual or combined use of ICI and G15 eliminated the beneficial effects of E2, E2-BSA, and G1 on PI3K/p-Akt expressions. CONCLUSIONS: These findings indicated that PI3K/p-Akt pathway plays a critical role in mediating the salutary effects of estradiol on histopathological changes and neurological outcomes following TBI, suggesting that GPER and classic ERs are involved in regulating the expression of PI3K/p-Akt.

Exercise training improves diabetic renal injury by reducing fetuin-A, oxidative stress and inflammation in type 2 diabetic rats.

Background: Diabetic kidney disease (DKD) stands as a primary contributor to end-stage renal disease, associated with heightened mortality in cardiovascular diseases. This study aimed to explore the impact of an eight-week high-intensity interval training (HIIT) on renal injury in diabetic rats. Methods: Twenty-eight male Wistar rats were randomly allocated into four groups: healthy control (CTL), diabetic control (DC), exercise (EX), and diabetes-exercise (D + EX). Induction of diabetes in the DC and D + EX groups occurred through a two-month high-fat diet followed by a single dose of 35 mg/kg streptozotocin (STZ). Rats in the EX and D + EX groups underwent 4-10 intervals of HIIT (80-100% Vmax) over 8 weeks. Subsequently, pathological and biochemical parameters were assessed in the serum and kidney tissue of the experimental groups. Results: In the DC group, diabetes led to elevated kidney damage, glomerulosclerosis, fasting blood glucose (FBG), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index, animal weight, kidney dysfunction, albuminuria, and glomerular filtration rate. Additionally, serum and kidney levels of fetuin-A increased, along with kidney levels of KIM-1. Mechanistically, diabetes induction resulted in kidney inflammation by elevating levels of tumor necrosis factor-alpha (TNF-α), transforming growth factor beta (TGF-ß), and interleukin 6 (IL-6), while reducing IL-10 levels and increasing the IL-6/IL-10 ratio. Furthermore, diabetes triggered renal oxidative stress, evidenced by increased Malondialdehyde (MDA) levels and decreased levels of glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD). HIIT mitigated the adverse effects of diabetes in the D + EX group compared to the DC group. Conclusion: Our findings suggest that HIIT ameliorates type 2 diabetes (T2D)-induced kidney damage by mitigating inflammation, lowering serum levels of fetuin-A, and bolstering antioxidant defenses. This study highlights the potential of HIIT as a time-efficient intervention for diabetic nephropathy.

Preparation and Evaluation of Preventive Effects of Inhalational and Intraperitoneal Injection of Myrtenol Loaded Nano-Niosomes on Lung Ischemia-Reperfusion Injury in Rats.

INTRODUCTION: Ischemia-reperfusion injury (IRI) is directly related to forming reactive oxygen species, endothelial cell injury, increased vascular permeability, and the activation of neutrophils and cytokines. Niosomes are nanocarriers and an essential part of drug delivery systems. We aimed to investigate the effects of myrtenol's inhaled and intraperitoneal niosomal form, compared to its simple form, on lung ischemia reperfusion injury (LIRI). MATERIAL AND METHOD: Wistar rats were divided into ten groups. Simple and niosomal forms of myrtenol were inhaled or intraperitoneally injected daily for one week prior to LIRI. We evaluated oxidative stress, apoptotic, and inflammatory indices, nitric oxide, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) and histopathological indices. RESULTS: Pretreatment with simple and niosomal forms of myrtenol significantly inhibited the indices of pulmonary edema, pro-inflammatory cytokines and proteins, oxidant agents, nitric oxide, iNOS, apoptotic proteins, congestion of capillaries, neutrophil infiltration, and bleeding in the alveoli. Furthermore, myrtenol increased anti-inflammatory cytokines, anti-oxidants agents, eNOS, anti-apoptotic proteins and the survival time of animals. The niosomal form of myrtenol showed a more ameliorative effect than its simple form. CONCLUSION: The results showed the superior protective effect of the inhalation of myrtenol niosomal form against LIRI compared to its simple form and systemic use.

Ameliorating effects of Acacia arabica and Ocimum basilicum on acetic acid-induced ulcerative colitis model through mitigation of inflammation and oxidative stress.

Introduction: Ulcerative colitis (UC) is a chronic recurrent inflammatory disease of the large intestine and rectum. The disease is characterized by oxidative stress and severe inflammation. Research has shown the anti-oxidative and anti-inflammatory effects induced by consuming the Acacia arabia and Ocimum basilicum. The present study aimed to evaluate the effect of treatment with O. basilicum together with A. arabica on healing, inflammation, and oxidative stress in the course of experimental colitis in rats. Methods: A total number of 50 male rats were selected and randomly assigned to five groups of 10 rats each. Colitis was induced in rats by enemas with a 4 % acetic acid solution. Four days after the colitis induction, the rats were orally treated for the next 4 days with saline or a combination of A. arabica and O. basilicum (1000 mg/kg) or sulfasalazine (100 mg/kg). Results: Acetic acid-induced colitis increased the colon's macroscopic and histopathological damage scores; increased colon levels of MDA (Malondialdehyde), MPO (Myeloperoxidase), TNF-α (Tissue necrosis factor α), IL6 (Interleukin 6), and IL17 (Interleukin 17); and decreased SOD (Superoxide Dismutase), GPx (Glutathione Peroxidase), and IL10 (Interleukin 10) levels in the treated rats compared with the control group (P < 0.001). Overall, a combination of A. arabica and O. basilicum reduced macroscopic and histopathological damage scores (P < 0.01) of the colon, and MDA, MPO, TNF-α, IL6 (P < 0.001), and IL17 (P < 0.01) levels of the colon. Furthermore, it increased SOD, GPx, and IL10 levels compared to the colitis group (P < 0.01). Conclusion: A. arabica and O. basilicum have improving effects on UC by reducing inflammation and oxidative stress.

Cardioprotective effects of calorie restriction against inflammation and apoptosis in ovariectomized obese rats: Role of classical estrogen receptors and SIRT1.

AIM: Obesity is a metabolic complication linked with bad eating habits and a sedentary lifestyle, and the heart is one of the target organs damaged by it. Estrogen deficiency during menopause worsens the situation. Calorie restriction (CR) can contribute to reducing cardiovascular disease (CVD) in postmenopausal conditions. Thus, the effects of CR on inflammation and apoptosis in ovariectomized rats' hearts with obesity were studied. METHOD: Female Wistar rats were categorized into Sham and OVX (ovariectomized) groups and received a standard diet (SD) or high-fat diet (60%HFD) or calorie restriction (30% CR) for 16 weeks. The real-time PCR method was used to evaluate the inflammatory markers and estrogen receptors gene expression. Western-blot and ELISA methods were respectively used for the measurement of apoptosis and SIRT1 protein expression. RESULTS: HFD led to the elevation of body weight, IL-6 (interleukin-6) and TNF-α (tumor necrosis factor-α) and reduction of IL-10 (interleukin-10) gene expressions, and also an increment in protein levels of cleaved caspase-3, Bax and Bax/Bcl2 ratio and decrement in Bcl-2 in OVX rats (P < 0.001). Additionally, HFD reduced SIRT1 (sirtuin1) protein levels, ERα (estrogen receptor α), and ERß (estrogen receptor ß) gene expressions (P < 0.001). In contrast, CR declined body weight, IL-6 and TNF-α (P < 0.001), increased IL-10 expressions (P < 0.05), decreased cleaved caspase-3 (P < 0.001), Bax (P < 0.01), and Bax/Bcl2 ratio (P < 0.05), enhanced Bcl-2 (P < 0.001), increased SIRT1 (P < 0.05) and ERα (P < 0.001) and ERß (P < 0.01) expressions. CONCLUSION: CR through the SIRT1 regulation and estrogen receptors attenuate obesity-induced-cardiac inflammation and apoptosis. CR can be a cardioprotective candidate in postmenopausal conditions.

The administration of oral mucosal mesenchymal-derived stem cells improves hepatic inflammation, oxidative stress, and histopathology following traumatic brain injury.

BACKGROUND: The inflammatory mediators produced after traumatic brain injury (TBI) are reaching peripheral organs causing organ and tissue damage, including the liver. Our study assessed the effect of intravenous (i.v.) infusion of oral mesenchymal stem cells (OMSCs) on TBI-induced liver damage by measuring liver inflammatory factors and liver oxidative stress. METHODS: Twenty-eight adult male Wistar rats were divided into four groups: 1) sham control; 2) TBI alone (TBI); 3) TBI vehicle (Veh)-control; and 4) TBI with OMSC treatment (SC). OMSCs were obtained from oral mucosa biopsies. OMSCs were administered and administered i.v. at 1 and 24 h after TBI. Within 48 h after TBI, multiple parameters were analyzed, including inflammation, oxidative stress, and histopathological changes. RESULTS: In comparison to sham controls, the TBI alone showed in liver significantly increased levels of interleukin-1ß (IL-1ß; P < 0.001), interleukin-6 (IL-6; P < 0.001), malondialdehyde (MDA; P < 0.001), and protein carbonyl (PC; P < 0.001). At the same time the TBI alone decreased the liver levels of superoxide dismutase (SOD; P < 0.001), total antioxidant capacity (TAC; P < 0.001), catalase (CAT; P < 0.001), and interleukin-10 (IL-10; P < 0.001). In comparison to the TBI alone group, the therapeutic group treated with i.v. infusion of OMSCs demonstrated significantly reduced changes of IL-1ß (P < 0.001), IL-6 (P < 0.01), MDA (P < 0.01), PC (P < 0.05), SOD (P < 0.001), TAC (P < 0.01), CAT (P < 0.01), and IL-10 (P < 0.01). Histopathological evaluation showed in TBI alone group that the total score of liver tissue injury included extensive hydropic degeneration, lobular necrosis, inflammation as well as central vein congestion with subendothelial hemorrhage increased compared the sham group (P < 0.001). Administration of OMSC showed significantly smaller increase in the injury score compared to the TBI alone group (P < 0.001). CONCLUSION: Therapy with i.v. OMSCs administration after TBI reduces liver injury, as measured by inflammation and oxidative stress. The use of OMSCs can be considered for treatment of liver injury caused by TBI.

Ellagic acid reduces hepatic lipid contents through regulation of SIRT1 and AMPK in old rats.

OBJECTIVE: Ellagic acid is used in traditional medicine for the treatment of lipid disorders. In this study, the effects of ellagic acid on key regulators of lipid metabolism, and histopathological alterations in aged liver were examined. METHODS: A total of 21 male Wistar rats were divided into three groups, including young control, old control, and old ellagic acid. After one month of treatment with ellagic acid, the expression levels of hepatic SIRT1, AMPK, SREBP-1c, PPAR-α, and phosphorylated AMPK (p-AMPK) were evaluated. The levels of several serum biochemical factors, and hepatic triglyceride, and cholesterol contents were assessed. RESULTS: Ellagic acid elevated the levels of SIRT1, p-AMPK, and PPAR-α and reduced SREBP-1c level in the liver of old rats. It decreased triglyceride and cholesterol contents in the aged liver and improved histopathological changes. CONCLUSIONS: The results demonstrated that ellagic acid can exert protective effects against hepatic lipid metabolism disorders induced by ageing.

Carvacrol decreases blood-brain barrier permeability post-diffuse traumatic brain injury in rats.

Previously, we showed that Satureja Khuzestanica Jamzad essential oil (SKEO) and its major component, carvacrol (CAR), 5-isopropyl-2-methylphenol, has anti-inflammatory, anti-apoptotic, and anti-edematous properties after experimental traumatic brain injury (TBI) in rats. CAR, predominantly found in Lamiaceae family (Satureja and Oregano), is lipophilic, allowing diffusion across the blood-brain barrier (BBB). These experiments test the hypothesis that acute treatment with CAR after TBI can attenuate oxidative stress and BBB permeability associated with CAR's anti-edematous traits. Rats were divided into six groups and injured using Marmarou weight drop: Sham, TBI, TBI + Vehicle, TBI + CAR (100 and 200 mg/kg) and CAR200-naive treated rats. Intraperitoneal injection of vehicle or CAR was administered thirty minutes after TBI induction. 24 h post-injury, brain edema, BBB permeability, BBB-related protein levels, and oxidative capacity were measured. Data showed CAR 200 mg/kg treatment decreased brain edema and prevented BBB permeability. CAR200 decreased malondialdehyde (MDA) and reactive oxygen species (ROS) and increased superoxide dismutase (SOD) and total antioxidative capacity (T-AOC), indicating the mechanism of BBB protection is, in part, through antioxidant activity. Also, CAR 200 mg/kg treatment suppressed matrix metalloproteinase-9 (MMP-9) expression and increased ZO-1, occludin, and claudin-5 levels. These data indicate that CAR can promote antioxidant activity and decrease post-injury BBB permeability, further supporting CAR as a potential early therapeutic intervention that is inexpensive and more readily available worldwide. However, more experiments are required to determine CAR's long-term impact on TBI pathophysiology.

Evaluating the neuroprotective effects of progesterone receptors on experimental traumatic brain injury: The PI3K/Akt pathway.

BACKGROUND: Studies have confirmed the salutary effects of progesterone (P4) on traumatic brain injury (TBI). This study investigated the beneficial effects of P4 via its receptors on TBI, and also whether progesterone receptors (PRs) can modulate TBI through PI3K/Akt pathway. MATERIAL AND METHODS: Marmarou method was utilized to induce diffuse TBI in ovariectomized rats. P4 (1.7 mg/kg) or the vehicle (oil) was administered 30 min after TBI induction. Moreover, RU486 (PR antagonist) and its vehicle (DMSO) were injected before TBI induction and P4 injection. Brain Evans blue content, brain water content (WC), various oxidative stress parameters, IL-1ß levels, tumor necrosis factor-α (TNF-α), histopathological alterations, and also phosphorylated Akt (p-Akt) and PI3K expressions in the brain were assessed 24 h after TBI. The veterinary comma scale (VCS) was measured before and after TBI at different times. RESULTS: The findings revealed that P4 caused an increase in VCS and a decrease in brain WC, oxidative stress, TNF-α and IL-1ß levels. RU486 inhibited the beneficial effects of P4 on these indices. Moreover, RU486 prevented the reduction of brain edema, inflammation, and apoptosis caused by P4. Moreover, P4 following TBI increased the expression of PI3K/p-Akt protein in the brain. RU486 eliminated the effects of P4 on PI3K/p-Akt expression. CONCLUSION: According to these findings, PRs are acting as critical mediators for the neuroprotective properties of P4 on oxidative stress, pro-inflammatory cytokine levels, and neurological outcomes. PRs also play an important role in regulating the PI3K/p-Akt expression and nongenomic function of P4.

The Role of Inhaled Estradiol and Myrtenol, Alone and in Combination, in Modulating Behavioral and Functional Outcomes Following Traumatic Experimental Brain Injury: Hemodynamic, Molecular, Histological and Behavioral Study.

BACKGROUND: Traumatic brain injury (TBI) is an important and growing cause of disability worldwide, and its cognitive consequences may be particularly significant. This study assessed the neuroprotective impacts of estradiol (E2), myrtenol (Myr), and the combination of the two on the neurological outcome, hemodynamic parameters, learning and memory, brain-derived neurotrophic factor (BDNF) level, phosphoinositide 3-kinases (PI3K/AKT) signaling, and inflammatory and oxidative factors in the hippocampus after TBI. METHODS: Eighty-four adult male Wistar rats were randomly divided into 12 groups with seven rats in each (six groups to measure intracranial pressure, cerebral perfusion pressure, brain water content, and veterinary coma scale, and six groups for behavioral and molecular studies): sham, TBI, TBI/vehicle, TBI/Myr, TBI/E2, and TBI/Myr + E2 (Myr 50 mg/kg and E2 33.3 µg/kg via inhalation for 30 min after TBI induction). Brain injury was induced by using Marmarou's method. Briefly, a 300-g weight was dropped down from a 2-m height through a free-falling tube onto the head of the anesthetized animals. RESULTS: Veterinary coma scale, learning and memory, brain water content, intracranial pressure, and cerebral perfusion pressure were impaired following TBI, and inflammation and oxidative stress were raised in the hippocampus after TBI. The BDNF level and PI3K/AKT signaling were impaired due to TBI. Inhalation of Myr and E2 had protective effects against all negative consequences of TBI by decreasing brain edema and the hippocampal content of inflammatory and oxidant factors and also by improving BDNF and PI3K/AKT in the hippocampus. Based on these data, there were no differences between alone and combination administrations. CONCLUSIONS: Our results propose that Myr and E2 have neuroprotective effects on cognition impairments due to TBI.

Protective effects of calorie restriction and 17-ß estradiol on cardiac hypertrophy in ovariectomized obese rats.

Obesity and menopause lead to cardiovascular diseases. Calorie restriction (CR) can modulate estrogen deficiency and obesity-related cardiovascular diseases. The protective effects of CR and estradiol on cardiac hypertrophy in ovariectomized obese rats were explored in this study. The adult female Wistar rats were divided into sham and ovariectomized (OVX) groups that received a high-fat diet (60% HFD) or standard diet (SD) or 30% CR for 16 weeks, and then, 1mg/kg E2 (17-ß estradiol) was injected intraperitoneally every 4 days for four weeks in OVX-rats. Hemodynamic parameters were evaluated before and after each diet. Heart tissues were collected for biochemical, histological, and molecular analysis. HFD consumption led to weight gain in sham and OVX rats. In contrast, CR and E2 led to body weight loss in these animals. Also, heart weight (HW), heart weight/body weight (HW/BW) ratio, and left ventricular weight (LVW) were enhanced in OVX rats that received SD and HFD. E2 reduced these indexes in both diet conditions but reduction effects of CR were seen only in HFD groups. HFD and SD feeding increased hemodynamic parameters, ANP (atrial natriuretic peptide) mRNA expression, and TGF-ß1(transforming growth factor-beta 1) protein level in the OVX animals, while CR and E2 reduced these factors. Cardiomyocyte diameter and hydroxyproline content were increased in the OVX-HFD groups. Nevertheless, CR and E2 decreased these indicators. The results showed that CR and E2 treatment reduced obesity-induced-cardiac hypertrophy in ovariectomized groups (20% and 24% respectively). CR appears to have almost as reducing effects as estrogen therapy on cardiac hypertrophy. The findings suggest that CR can be considered a therapeutic candidate for postmenopausal cardiovascular disease.

Beneficial effects of time and energy restriction diets on the development of experimental acute kidney injury in Rat: Bax/Bcl-2 and histopathological evaluation.

People's lifestyles and, especially, their eating habits affect their health and the functioning of the organs in their bodies, including the kidneys. One's diet influences the cells' responses to stressful conditions such as acute kidney injury (AKI). This study aims to determine the preconditioning effects of four different diets: energy restriction (ER) diet, time restriction (TR) eating, intermittent fasting (IF), and high-fat diet (HF) on histopathological indices of the kidney as well as the molecules involved in apoptosis during AKI. Adult male rats underwent ER, TR, IF, and HF diets for eight weeks. Then, AKI was induced, and renal function indices, histopathological indices, and molecules involved in apoptosis were measured. In animals with AKI, urinary albumin excretion, serum urea, creatinine and, Bax/Bcl-2 ratio increased in the kidney, while renal eGFR decreased. ER and TR diets improved renal parameters and prevented an increase in the Bax/Bcl-2 ratio. The IF diet improved renal parameters but had no effect on the Bax/Bcl-2 ratio. On the other hand, the HF diet worsened renal function and increased the Bax/Bcl-2 ratio. Histopathological examination also showed improved kidney conditions in the ER and TR groups and more damage in the HF group. This study demonstrated that ER and TR diets have renoprotective effects on AKI and possibly cause the resistance of kidney cells to damage by reducing the Bax/Bcl-2 ratio and improving apoptotic conditions.

Satureja khuzistanica Jamzad essential oil and pure carvacrol attenuate TBI-induced inflammation and apoptosis via NF-κB and caspase-3 regulation in the male rat brain.

Traumatic brain injury (TBI) causes progressive dysfunction that induces biochemical and metabolic changes that lead to cell death. Nevertheless, there is no definitive FDA-approved therapy for TBI treatment. Our previous immunohistochemical results indicated that the cost-effective natural Iranian medicine, Satureja khuzistanica Jamzad essential oil (SKEO), which consists of 94.16% carvacrol (CAR), has beneficial effects such as reducing neuronal death and inflammatory markers, as well as activating astrocytes and improving neurological outcomes. However, the molecular mechanisms of these neuroprotective effects have not yet been elucidated. This study investigated the possible mechanisms involved in the anti-inflammatory and anti-apoptotic properties of SKEO and CAR after TBI induction. Eighty-four male Wistar rats were randomly divided into six groups: Sham, TBI, TBI + Vehicle, TBI + CAR (100 and 200 mg/kg), and TBI + SKEO (200 mg/kg) groups. After establishing the "Marmarou" weight drop model, diffuse TBI was induced in the rat brain. Thirty minutes after TBI induction, SKEO & CAR were intraperitoneally injected. One day after TBI, injured rats exhibited significant brain edema, neurobehavioral dysfunctions, and neuronal apoptosis. Western blot results revealed upregulation of the levels of cleaved caspase-3, NFκB p65, and Bax/Bcl-2 ratio, which was attenuated by CAR and SKEO (200 mg/kg). Furthermore, the ELISA results showed that CAR treatment markedly prevents the overproduction of the brain pro-inflammatory cytokines, including IL-1ß, TNF-α, and IL-6. Moreover, the neuron-specific enolase (NSE) immunohistochemistry results revealed the protective effect of CAR and SKEO on post-TBI neuronal death. The current study revealed that the possible neuroprotective mechanisms of SKEO and CAR might be related to (at least in part) modulating NF-κB regulated inflammation and caspase-3 protein expression. It also suggested that CAR exerts more potent protective effects than SKEO against TBI. Nevertheless, the administration of SKEO and CAR may express a novel therapeutic approach to ameliorate TBI-related secondary phase neuropathological outcomes.

The effect of combining basil seeds and gum Arabic on the healing process of experimental acetic acid-induced ulcerative colitis in rats.

Background & aim: Ulcerative colitis (UC) is a chronic recurrent inflammatory disease of the large intestine and rectum that oxidative stress and severe inflammation are the main features of this disease. Previous studies have shown that separate consumption of basil and gum arabic can reduce inflammation and oxidative stress. The aim of the study was evaluating the effect of treatment with basil seeds given together with gum arabic on healing, inflammation and oxidative stress in the course of experimental colitis in rats. Experimental procedure: A total number of 50 male rats were used, randomly assigned to five groups of 10 rats each. Colitis was induced in rats by enemas with 4% solution od acetic acid. Four days after induction of colitis, rats were treated for next 4 days with saline or combination of basil seeds plus gum arabic (1 mg/kg) or sulfasalazine (100 mg/g) rectally. The experiment was terminated after last dose of treatment. Rats without induction of colitis were used as a sham group. Results: Acetic acid-induced colitis increased the macroscopic and histopathological damage scores of the colon as well as colon levels of MDA(Malondialdehyde), MPO(Myeloperoxidase), TNFα(Tissue necrosis factor α), IL6 (Interleukin 6)and IL17(Interleukin 17) and decreased SOD(Superoxide Dismutase), GPx (Glutathione Peroxidase) and IL10 (Interleukin 10) levels compared with the control group(P < 0.001). Treatment with basil and gum arabic reduced macroscopic and histopathological damage scores (P < 0.01) of the colon, MDA, MPO, TNFα, IL6(P < 0.001) and IL17 (P < 0.01) levels of the colon and increased SOD, GPx and IL10 levels compared to the colitis group (P < 0.01). Conclusion: Rectal administration of combination of basil seeds plus gum arabic after induction of colitis, exhibits antioxidant and anti-inflammatory effects, and accelerates the healing of the colon in experimental colitis evoked by acetic acid.

Protective effects of early exercise on neuroinflammation, and neurotoxicity associated by traumatic brain injury: a behavioral and neurochemical approach.

OBJECTIVE: The benefits of exercise in TBI have been proven. However, the time-dependent effects of exercise initiation and the involved mechanisms are controversial. We investigated the effects of preconditioning, continuous, early, and delayed treadmill exercise on motor behavior, brain edema, inflammation, and oxidative stress in experimental traumatic brain injury (TBI). MATERIALS AND METHODS: 48 male rats were assigned into two groups: sedentary control (Sham and TBI) and exercise groups: 1MB (preconditioning, initiation beginning at 1 month before trauma), 1MBA (continuous, initiation beginning at 1 month before and continuing 1 month after trauma), 24hA (early, initiation beginning at 24 h after trauma), and 1WA (delay, initiation beginning at 1 week after trauma). The rats in exercise groups were forced to run on a treadmill five days a week for 30 min per day. Rotarod and open file were used to assess motor behavior. ELISA was also used to measure total antioxidant capacity (TAC), tumor necrosis factor-alpha (TNF-α), and malondialdehyde (MDA) in serum and CSF. RESULTS: Exercise significantly decreased neurological impairments, motor deficits, and apoptosis compared with the sedentary group. Early (within 24 h) and ongoing (1 MBA) exercise significantly improved motor behavior after TBI. In addition, these exercise programs inhibited brain edema and the number of apoptotic cells. MDA and TNF-α levels increased in all exercise groups, but the effects were greater after early exercise than after delayed exercise, resulting in a significant decrease in TAC levels in serum and CSF. We discovered a positive correlation between MDA, TAC, and TNF-α concentration in serum and CSF. CONCLUSION: Our finding suggests that early exercise (24hA) and 1MBA groups afford neuroprotection and reduce the second injury consequence, probably by reducing neuronal apoptosis and oxidative stress.

The Prescription of Oral Mucosal Mesenchymal Stem Cells post-Traumatic Brain Injury Improved the Kidney and Heart Inflammation and Oxidative Stress.

Background: In the last years, mesenchymal stem cells (MSCs) have been considered as a useful strategy to treat many diseases such as traumatic brain injury (TBI). The production of inflammatory agents by TBI elicits an inflammatory response directed to other systems of body, such as the heart and the kidneys. In this study, the efficacy of oral mucosal mesenchymal stem cells (OMSCs) prescription after TBI in inflammation and oxidative stress of the heart and kidneys was evaluated. Methods: Twenty-four male rats were located in groups as follows: sham, TBI, vehicle (Veh), and stem cell (SC). OMSCs were injected intravenously 1 and 24 hours after TBI. Inflammatory, oxidative stress, and histopathological outcomes of the heart and kidney tissues were investigated 48 hours after TBI. Results: TBI caused an increase in the level of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), malondialdehyde (MDA), and carbonyl protein (PC) of the heart and kidney compared to the sham group. Superoxide dismutase (SOD), total antioxidant capacity (TAC), catalase (CAT), and interleukin-10 (IL-10) of the heart and kidney decreased after TBI. The use of OMSCs after TBI reduced the changes of these factors in both the heart and the kidney. Conclusion: Application of OMSCs after TBI can decrease inflammation and oxidative stress of the heart and kidney tissues leading to the reduction of damage. Therefore, this method can be evaluated in the TBI patients in future studies.

Assessment of antibiotic resistance changes during the Covid-19 pandemic in northeast of Iran during 2020-2022: an epidemiological study.

BACKGROUND: The coronavirus disease 2019 seems to change antibiotic resistance pattern. Certain conditions in the Covid-19 era may be contributing to the rise of antimicrobial resistance (AMR). Due to the limited information on the impact of Covid-19 on antimicrobial resistance (AMR), the purpose of this research was to investigate the trend in antimicrobial resistance changes of E. coli, P. aeruginosa, K. pneumoniae, and A. baumannii in Hasheminezhad hospital. This hospital was a Corona center in Mashhad at the onset of this epidemic. METHODS: 1672 clinical samples were collected between January 21, 2020 and January 30, 2022from patients hospitalized at Hasheminezhad Hospital in Mashhad, Conventional microbiological procedures for identifying gram-negative bacteria and antibiotic susceptibility testing were used, according to the clinical and laboratory standards institute (CLSI) 2021. The two years of the pandemic, from the initial stage of the outbreak until the 6th peak, (January 2020 to and January 2022) were divided into 9 periods according to the seasons. RESULTS: Highest resistance rates were seen in E. coli (615 samples), K. pneumoniae (351 samples), P. aeruginosa (362 samples) and A. baumannii (344 samples) to Ampicillin (89.6%), Ampicillin (98%), Imipenem (91.8%), and Ceftazidime (94.6%), respectively. The largest change in antibiotic resistance was seen between Summer 2020 and Summer 2021 for K. pneumoniae with about a 30% rise in antibiotic resistance to Ceftriaxone. CONCLUSIONS: All 4 species evaluated in this study, have shown rising AMR rates during the first year of the pandemic in the northeast of Iran. This study revealed that E. coli, P. aeruginosa, K. pneumoniae, and A. baumannii strains in Northern Iran have a higher level of antibiotic resistance than what was measured in similar studies conducted before the pandemic. This will further restrict treatment choices and jeopardize global public health.

The effect of two types of diet on apoptosis indexes, lipid profile and histopathological outcome in acute kidney injury during exercise.

BACKGROUND: Exercise and some pre-AKI diets have been shown to improve injury, apoptosis, and lipid profile. In this study, the effect of two different diets along with exercise training on acute kidney injury (AKI) was investigated.  MATERIALS AND METHODS: Laboratory rats were randomly divided into four groups of control, standard diet + exercise, exercise + calorie restriction (CR) and exercise + time restriction (TR). Each group was divided into two subgroups of AKI and no AKI. The animals received endurance training and diet regimens before AKI. Fasting blood glucose, serum creatinine, Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl2) and histopathological outcome of renal tissue as well as serum lipid profile of animals were assessed 24 h after AKI.  RESULTS: The percentage of changes in renal Bcl2 and Bax after AKI in the group with previous exercise was lower than the group without previous exercise (p < 0.01). After induction of AKI, serum lipid profile changed in non-exercised rats (p < 0.001). Also, after injury, fasting blood glucose levels increased in non-exercised rats (p < 0.05). After injury, the start of both CR and TR diets during exercise caused less change in Bcl2 and Bax of non-exercised rats compared to exercised rats (p < 0.001). CR diet along with exercise improved lipid profile, and also CR diet along exercise decreased fasting blood glucose levels (p < 0.001). Also, both the CR and TR diets during exercise caused fewer changes in histopathological outcome after AKI. CONCLUSION: Exercise alone decreased changes in apoptotic and histopathological indexes, fasting blood glucose, as well as lipid profile of rats after AKI. Reduction of apoptosis and improvement of histopathological outcome after AKI appeared more when CR and TR diets were commenced during exercise. The reduction of lipid profile changes was more pronounced in the group that received CR diet during exercise.