Treatment with quercetin increases Nrf2 expression and neuronal differentiation of sub ventricular zone derived neural progenitor stem cells in adult rats.

BACKGROUND: The presence of neural precursor stem cells (NPSCs) in some parts of the adult brain and the potency of these types of cells with a therapeutic viewpoint, has opened up a new approach for the treatment and recovery of the defects of central nervous system (CNS). Quercetin, as an herbal flavonoid, has been extensively investigated and shown to have numerous restoratives, inhibitory, and protective effects on some cell-lines and disorders. The purpose of this study is to simultaneously investigate the effect of quercetin on the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) gene and the effect on the proliferation and differentiation of NPSCs derived from the subventricular zone (SVZ) of the brain of adult rats. METHODS AND RESULTS: The cell obtained from SVZ cultured for one week and treated with quercetin at the concentrations of 1, 5, and 15 µM to evaluate the Nrf2 expression, proliferation and differentiation of NSCs after one week. Cellular and genetic results was performed by RT-PCR, MTT assay test, quantification of images with Image-J and counting. The results indicated that the quercetin increases expression of Nrf2 at concentration above 5 µM. Also differentiation and proliferation rate of NSCs is affected by various concentrations of quercetin in a dose-dependent manner. CONCLUSION: These findings confirmed the dose-dependent effect of quercetin on proliferation and differentiation of cell. In addition, quercetin increased the expression of Nrf2 gene. By combining these two effects of quercetin, this substance can be considered an effective compound in the treatment of degenerative defects in CNS.

Encapsulated saponin by ferritin nanoparticles attenuates the murine pneumococcal pneumonia.

Streptococcus pneumonia is classified as a gram-positive bacterial pathogen that causes asymptomatic or symptomatic respiratory infections. This study aimed to evaluate the effects of designed encapsulated saponin by ferritin nanoparticles in the healing progression of experimental bacterial pneumonia. The saponin encapsulated by ferritin followed the disassembly-reassembly process. Pneumonia was induced by the preparation of Streptococcus pneumonia. A total of 50 NMRI mice were divided into control, pneumonia, pneumonia + ferritin, pneumonia + saponin, and pneumonia + encapsulated saponin by ferritin nanoparticles (Nano Saponin) groups. ELISA, Real-time PCR, and Western blotting were used to measure sera IL-4 level, tumor necrosis factor-alpha (Tnf-α), and protein cyclooxygenase-2 (COX-2) gene expression, respectively. COX-2 protein expression, Tnf-α gene expression, and serum levels of IL-4 reduced compared to the pneumonia group. The histopathology results revealed that the rates of inflammation, mucus secretion, pulmonary hemorrhage, thickening of the alveoli wall, and secretion of inflammatory cells were lower in the Nano Saponin group than in the other groups. This study suggests that Glycyrrhiza glabra saponin and encapsulated saponin by ferritin nanoparticles oral consumption with anti-Tnf-α effect besides decreasing protein expression of COX-2 allows mice with pneumonia to recover.

Expression of toll like receptors before and after coronary angiography with isomolar contrast among those with and without coronary atherosclerosis.

Angiography is a safe technique for the detection of and treatment of cardiovascular diseases. However, the effects of the technique on the molecular response of the immune system are yet to be clarified. Toll like receptors (TLRs) are the important molecule participate in the innate immunity responses and induction of inflammation. This project was designed to explore the effects of angiography on the expression of TLR1, TLR2, TLR3 and TLR4. Fifty-five participants, including three separate groups (without artery stenosis, with one artery stenosis and more than one artery stenosis), were assessed in this project. TLR1, TLR2, TLR3 and TLR4 expression levels were evaluated in peripheral blood immune cells by measuring mRNA before and after angiography using Real-Time PCR techniques. mRNA levels of TLR1, TLR2 and TLR3 were significantly increased following angiography. Expression of TLR4 did not change after angiography. Other criteria also showed no correlation on TLR expression after angiography. TLR4 mRNA levels had a positive correlation with age in the participants without artery stenosis. Angiography may induce inflammation in subjects without artery stenosis via up-regulation of TLR1, 2 and 3 which may lead to cardiovascular diseases related complications.

Chlorogenic acid induces 4T1 breast cancer tumor's apoptosis via p53, Bax, Bcl-2, and caspase-3 signaling pathways in BALB/c mice.

Despite all the new treatments, metastatic breast cancer (BC) causes many deaths. Chlorogenic acid (CGA) is a polyphenol compound with various pharmacological traits, such as anticancer properties. Targeting apoptotic death pathways has been propounded as the most effective therapeutic method in various cancers. In the current study, apoptotic agents such as p53, Bax, Bcl-2, and caspase-3 have been investigated. The experimental groups included saline, BC, CGA, protective (PR), and treatment (TM) groups. First, 4T1 mouse BC was established and then the effects of treatment with CGA were investigated through measurement of tumor weight and volume, metastatic nodules, liver biochemical tests, hematoxylin and eosin (H&E), immunohistochemistry (IHC) staining, and real-time reverse transcription-polymerase chain reaction (RT-PCR) in experimental groups. The findings showed that CGA reduced tumor weight and volume in the PR group (P < .05) and in the TM group (P < .001). Surprisingly, it eliminated the tumors in the TM group. Metastatic nodules in the PR and TM groups were significantly reduced as compared with the BC group (P < .001). The evaluation by H&E staining showed cell apoptosis in both the PR and TM groups. The results of real-time RT-PCR showed that CGA therapy increased the expression ratio of Bax/Bcl-2 (P < .001 and P < .05, respectively) and the expression of p53 (P < .001 and P < .05, respectively) and caspase-3 genes (P < .01) in the PR and TM groups. The IHC data regarding the Bax/Bcl-2 ratio confirmed the other results (P < .001). The findings demonstrate that CGA plays a significant role in the induction of apoptosis and the treatment of 4T1 BC tumors in BALB/c mice.

Effect of memantine on expression of Bace1-as and Bace1 genes in STZ-induced Alzheimeric rats.

Recent studies have showed that the long non-coding RNAs (lncRNAs) expression is dysregulated in different neurodegenerative disorders like Alzheimer's disease (AD). In the present study, the effects of memantine on the level of Bace1-as and Bace1 genes' expression in streptozotocin (STZ)-induced Alzheimer's and memantine treated rats were investigated. The male Wistar rats were randomly divided into four groups: 1-Normal control, 2-Sham-operated control, 3- Alzheimer'scontrol rats (ICV-STZ), 4-Experimental group rats treated by memantine in a dose of 30 mg/kg/day for 28 days in ICV-STZ rats. The expression of Bace1-as and Bace1 genes was measured by quantitative-PCR in the brain and blood tissues. ELISA was used to analyze Bace1 and Aß proteins. Expression of Bace1-as was significantly increased in the brain and blood tissues of the experimental group (p = 0.032 and p = 0.034, respectively). The expression of Bace1 gene showed no significant changes in the brain. Furthermore, the ELISA analysis revealed that Bace1 protein was significantly increased in the plasma of the Alzheimer's control group (p = 0.000) and in the brain tissue of the experimental group (p = 0.000). Additionally, Aß levels had no significant changes between all groups studied. The Bace1 protein may be used as a prognostic biomarker in plasma, or before using memantine as a treatment. Furthermore, Bace1-as gene expression may play a role in monitoring the progression of AD.

DNA methylation changes of apoptotic genes in organogenesis stage of mice embryos by maternal chlorpyrifos induction.

The continued use of pesticides is one of the requirements of modern agriculture. Investigations have shown that pesticides can alter gene methylation and expression and subsequently may lead to abortion or birth of embryos with teratogenic disorders. In present study, 30 female NMRI mouse were divided in three experimental groups which in the CPF group, intraperitoneal chlorpyrifos was injected, in the sham group, DMSO was injected, and the control group without injection. The mice were mated and utinized 10 days' post gestation. The number of embryos in each fertilized female, maternal weight, and liver fibrosis was evaluated. The apoptosis pathway genes (caspase3, caspase9) and protein expressions (pro-caspase3, caspase3) of the embryos were evaluated with qRT-PCR and western blot, respectively. The DNA methylation of caspase3 and caspase9 were also assessed. The number of embryos and obtained maternal weight from the CPF group was significantly lower than other two groups. The mRNA expression of Caspase3 and Caspase9 were significantly higher in the CPF group. The protein expression evaluation confirmed the results achieved at the mRNA level. The percentage of Caspase9 DNA methylation in embryos collected from the CPF group was higher compared to the others. It can be considered that consumption of chlorpyrifos toxin can alter the DNA methylation and increase the expression of apoptotic genes. Therefore, continuous use of chlopyrifos may affect pregnancy by increasing the apoptosis pathway in the developing embryos which may lead to abortion or teratogenic disorders in newborn infants.

Electrical stimulation mPFC affects morphine addiction by changing glutamate concentration in the ventral tegmental area.

Morphine addiction is known as a serious social problem. Medial prefrontal cortex (mPFC) and ventral tegmental area (VTA) are two important sites of the brain that contribute to this type of addiction, and a complicated relation exists in between. In addition, neurotransmitters like glutamate and γ--Amino Butyric Acid (GABA) play an important role in the formation of these relations. Thus, the present study was undertaken to investigate these relations by evaluating the level of associated changes in the indicated neurotransmitters in the VTA, using HPLC method. This was performed after electrical stimulation and inducing lesion of mPFC and through microinjections of N-Methyl-D-Aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, respectively AP5 and CNQX, into the VTA of addicted rats. Our results showed that intra-peritoneal (i.p.) administration of morphine in 9 days in the morphine group, and also electrical stimulation (100 µA) of mPFC, receiving (i.p.) morphine, caused an increase in the glutamate release in the VTA, compared to the control group, but the increase of glutamate levels in the VTA in the morphine-stimulation group was not significant, compared to the morphine group. Moreover, GABA release into this area was decreasing in morphine and morphine- stimulation groups, compared to the control group. Our findings also showed that electrical lesion (0.4 mA) of mPFC, and also microinjection of glutamate antagonists into the VTA, receiving (i.p.) morphine in rats, caused a decrease of glutamate in the VTA. Therefore, it could be concluded that the relation between mPFC and VTA is highly effective in the formation of reward system.

Effect of cerebrolysin on bladder function after spinal cord injury in female Wistar rats.

OBJECTIVES: To study the effect of cerebrolysin on bladder function after spinal cord injury using functional measurements in rats. METHODS: A total of 60 female rats were enrolled in this study. After induction of complete transection at T9-T10 spinal vertebrae, cerebrolysin was injected intraperitoneally, and daily in three dosages until 7 days (1 week) and continued until 28 days (4 weeks) in three groups to show the impact of that on the bladder function. Urodynamic parameters were measured in the different groups. RESULTS: Cerebrolysin injection in a dose of 1 mL/kg for 1 week showed a slight improvement in urodynamic parameters. However, infusion of 2.5 and 5 mL/kg cerebrolysin for 1 week caused an elevation in contractions and a decrease in compliance. In long-term 2.5 mL/kg cerebrolysin injection, an improvement in compliance was observed, despite relative contractions. Furthermore, the bladder pressure pattern in the 2.5 mL/kg infused rats for 4 weeks was similar to the control group, but in the group receiving 5 mL/kg cerebrolysin for 4 weeks, reduced bladder contractions and function were observed. CONCLUSIONS: Our findings suggest that cerebrolysin might be able to inhibit the emergence of neurogenic detrusor overactivity in spinal cord injured female rats.

Effect of sinapic acid on memory deficits and neuronal degeneration induced by intracerebroventricular administration of streptozotocin in rats.

The present study aimed to elucidate the neuroprotective effect of sinapic acid on intracerebroventricular streptozotocin (ICV-STZ) induced neuronal loss and memory impairment. To test this hypothesis, male Wistar rats were randomly divided into 11 groups: normal control, sham-operated control, sinapic acid (2.5, 5, 10, and 20 mg/kg bw intragastrically, daily) alone, Alzheimer control rats (ICV-STZ, 3 mg/kg bw), sinapic acid (2.5, 5, 10, and 20 mg/kg bw intragastrically, daily) together with STZ, and the treatment was performed accordingly. After 28 days of ICV-STZ administration, the animals were assessed for cognitive performance using passive avoidance test and then sacrificed for biochemical and histopathological examinations. Sinapic acid was found to be effective in improving antioxidant status and preventing memory loss in Alzheimer rats. Moreover, TNF-α level in the hippocampus was significantly decreased by sinapic acid. Also, administration of sinapic acid significantly increased the levels of antioxidant enzymes and decreased malondialdehyde level in the hippocampus. Histopathological examination showed that sinapic acid reduced cell loss in the cerebral cortex and hippocampus in Alzheimer's rats. The present study suggests that sinapic acid is effective in the prevention of memory loss and improvement of oxidative stress and might be beneficial in the treatment of Alzheimer's disease.

Antinociceptive and anti-inflammatory effects of the aerial parts of Artemisia dracunculus in mice.

CONTEXT: Tarragon (Artemisia dracunculus L., Asteraceae) is an ancient herb, which is widely used as a medicine, flavoring, or fragrance. OBJECTIVE: To determine the antinociceptive and anti-inflammatory effects of aerial parts of tarragon, we investigated the effects of ethanolic extract of the plant in adult male Balb/c mice. MATERIALS AND METHODS: Antinociceptive activity was determined using formalin, hot-plate, and writhing tests. The effect of the ethanolic extract on acute inflammation was evaluated by xylene-induced ear edema in mice. The ethanolic extract was administered at doses of 5, 10, 50, and 100 mg/kg, i.p. The control group received saline as vehicle of ethanolic extract. RESULTS: Our results showed that the ethanolic extract (50 and 100 mg/kg) decreased both phases of pain in the formalin test (ED50 = 109.66 and 87.13 mg/kg, respectively). In the hot-plate test, the extract (50 and 100 mg/kg) increased pain threshold during 60 min (ED50 = 81.03 mg/kg). The extract (50 and 100 mg/kg) exhibited antinociceptive activity against acetic acid-induced writhing (ED50 = 66.99 mg/kg). The extract (50 and 100 mg/kg) showed significant activity in the xylene ear edema test (ED50 = 78.20 mg/kg). Pretreatment of the animals with naloxone decreased the analgesia induced by the extract in hot-plate and formalin tests; therefore, opioid receptors may be involved, at least partly, in the analgesic effect of tarragon extract. DISCUSSION AND CONCLUSION: The results suggested that tarragon have significant analgesic and anti-inflammatory effects in mice, and, therefore, further studies are required to evaluate these effects and additional potential of the plant.

The neuroprotective potential of sinapic acid in the 6-hydroxydopamine-induced hemi-parkinsonian rat.

Parkinson's disease (PD) is a neurodegenerative movement disorder due to selective loss of dopaminergic neurons of mesencephalic substantia nigra pars compacta (SNC) with debilitating motor symptoms. Current treatments for PD afford symptomatic relief with no prevention of disease progression. Due to the antioxidant and neuroprotective potential of sinapic acid, this study was conducted to evaluate whether this agent could be of benefit in an experimental model of early PD in rat. Unilateral intrastriatal 6-hydroxydopamine (6-OHDA)-lesioned rats were pretreated p.o. with sinapic acid at doses of 10 or 20 mg/kg. One week after surgery, apomorphine caused significant contralateral rotations, a significant reduction in the number of Nissl-stained and tyrosine hydroxylase (TH)-positive neurons and a significant increase of iron reactivity on the left side of SNC. Meanwhile, malondialdehyde (MDA) and nitrite levels in midbrain homogenate significantly increased and activity of superoxide dismutase (SOD) significantly reduced in the 6-OHDA-lesioned group. In addition, sinapic acid at a dose of 20 mg/kg significantly improved turning behavior, prevented loss of SNC dopaminergic neurons, lowered iron reactivity, and attenuated level of MDA and nitrite. These results indicate the neuroprotective potential of sinapic acid against 6-OHDA neurotoxicity that is partially due to the attenuation of oxidative stress and possibly lowering nigral iron level.

Effects of folic acid on dyslipidemia and serum homocysteine in a rat model of cholestasis and hepatic fibrosis.

The liver is the major site for storage and metabolism of folate. Folate deficiency is common in many liver diseases and causes severe effects on cellular metabolism and increases oxidative stress and the homocysteine (Hcy) level. The objective of this research was to investigate the effects of folic acid on dyslipidemia and serum Hcy concentrations in an experimental rat model of cholestasis. Eighty-one male Wistar rats were divided into nine groups: control, sham-operated, folic acid control, bile duct-ligated (BDL), and BDL+ folic acid groups. In folic acid treated groups, folic acid (1, 5, and 10 mg/kg body weight) was given orally for 28 days. After taking blood and liver samples, plasma lipid profiles and Hcy and hepatic reduced and oxidized glutathione concentrations were measured. Histopathological features of cholestasis were assessed by Masson's trichrome staining. Treatment of folic acid in BDL rats significantly prevented the progression of hepatic fibrosis and improved the serum and liver biochemical changes. These results suggest that folic acid protects the liver against cholestasis by reducing serum Hcy and by its antioxidant properties. Folic acid can be an important therapeutic intervention in dyslipidemia caused by cholestasis.

Hepatoprotective effects of Portulaca oleracea extract against CCl4-induced damage in rats.

CONTEXT: Purslane (Portulaca oleracea L., Portulacaceae) has been traditionally used in folk medicine to afford protection against liver injury, although its actual efficacy remains uncertain. OBJECTIVE: To evaluate purslane as a hepatoprotective agent, we investigated the protective effect of its ethanol extract against carbon tetrachloride (CCl4)-induced hepatic toxicity in rats. MATERIALS AND METHODS: A total of 108 male Wistar rats were randomly divided into 12 groups. The first group was maintained as normal control, whereas CCl4 (0.5 ml/kg bw, 50% CCl4 in olive oil, i.p.), purslane extract (0.005, 0.01, 0.05, 0.1, and 0.15 g/kg bw, intragastrically), and purslane extract (five doses as above) along with CCl4 were administered to the Groups II, III-VII, and VIII-XII, respectively. The rats were sacrificed on the 30th day, and blood was withdrawn by cardiac puncture. Liver damage was assessed by measuring hepatic marker enzymes (ALT, AST, ALP, GGT, and SOD) and histopathological observation. RESULTS: Treatment with CCl4 resulted in increased serum activities of marker enzymes with a concomitant decrease in SOD. Histological alterations were also observed in the liver tissue upon CCl4 treatment. Administration of purslane extract (0.01, 0.05, 0.1, and 0.15 g/kg b.w.) significantly showed a marked tendency towards normalization of all measured biochemical parameters in CCl4-treated rats. Histopathological changes also paralleled the detected alteration in markers of liver function. DISCUSSION AND CONCLUSION: These results demonstrate that purslane exerts protective effects against CCl4-induced damage in rat liver and supports a potential therapeutic use of purslane as an alternative for patients with liver diseases.

Relationship between serum IL10 level and p38MAPK enzyme activity on behavioral and cellular aspects of variation of hyperalgesia during different stages of arthritis in rats.

OBJECTS AND DESIGN: Regarding to anti-inflammatory role of interleukin (IL) 10, its inhibitory effects on p38MAPK activity and, different pro and anti-inflammatory roles of activated p38MAPK in cells, this study was aimed to investigate relationship between serum IL10 level and p38MAPK enzyme activity on behavioral and cellular aspects variation of hyperalgesia during different stages of arthritis in rats. MATERIALS AND METHODS: Adjuvant arthritis (AA) was induced by a single subcutaneous injection of complete Freund's adjuvant into the rats' hind paw. Behavioral and inflammatory responses were assessed at 0, 3, 7, 14, and 21 days of study. Receptor and other protein enzyme expression variations were detected by western blotting. Anti-IL10 and p38MAPK inhibitor were administered daily during the 21 days of study. RESULT: Daily treatment with anti-IL10 antibody significantly increased paw edema and hyperalgesia in the AA group compared with the AA control group. Administration of anti-IL10 antibody caused significant increase in the ratio of phosphorylated p38 to p38MAPK enzyme level expression on 14th and 21st days of study compared with the AA control group. CONCLUSION: Our study confirmed that a part of anti- inflammatory effects of serum IL10 during AA inflammation was mediated via inhibition of p38MAPK enzyme phosphorylation. Moreover, these findings suggest that increase in the level of spinal mu opioid receptor expression during AA inflammation is not mediated via the direct effect of serum IL10 on spinal p38MAPK.

Nanoselenium attenuates renal ischemia-reperfusion injury in rats.

Using selenium (Se) nanoparticles has received attention in recent years because of their therapeutic benefits due to their anticancer, antioxidant, anti-inflammatory, and anti-diabetic effects. This research was conducted to evaluate the possible protective impact of nano-Se on renal unilateral ischemia/reperfusion injury (uIRI) in adult male Wistar rats. Using clamping of the left renal pedicle within 45 min uIRI was induced. The animals were randomly divided into nine groups of control, nano-Se (0.25, 0.5, and 1 mg/kg bw/day) alone, uIRI control, and uIRI rats administrated with nano-Se. At 30 days after treatment, the animals were sacrificed to be assessed biochemically and histopathologically. Nano-Se in uIRI groups have significantly decreased serum creatinine, urea levels, renal histological damage, and increased antioxidant status. Also, our findings demonstrated that the administration of nano-Se caused a significant decrease in the immunoreactivity level of the epidermal growth factor (EGF) and EGFR expression (EGF receptor) in the renal tissue of the uIRI rats. Therefore, nano-Se possesses renoprotective effects, and this effect might be attributable to its antioxidant and free radical scavenger effects. These renoprotective effects may depend on the decreased EGF immunoreactivity level and EGFR expression in the kidney tissue and improve the structure of the kidney tissue. Thus, our research provided biochemical and histological data supporting the potential clinical use of nano-Se for the treatment of certain kidney disorders.

Effect of Exosomes Derived from Bone Marrow Mesenchymal Stem Cells on Ovarian Granulosa Cells of Immature NMRI Mice.

OBJECTIVE: In recent years, in vitro maturation (IVM) has become the focus of fertility maintenance, and infertility treatment. The aim of this study is development of oocytes during folliculogenesis and oogenesis is greatly influenced by the presence of BMP-7, BMP-15, and GDF-9 genes, which are present in exosomes generated from bone marrow stem cells. MATERIALS AND METHODS: In the experimental study, we investigated how exosomes obtained from bone marrow stem cells affected development and expansion of ovarian granulosa cells (GCs) in NMRI mice. In this in vitro experiment, bone marrow stem cells were isolated from mice's bone marrow, and after identification, exosomes were recovered. Exosome doses of 100, 50, and 25 µg/ml were applied to GCs before using MTT assay to measure survival rates and quantitative reverse-transcription polymerase chain reaction (PCR) to measure expression of the BMP-7, BMP-15, and GDF-9 genes. RESULTS: The results showed that the GCs treated with exosomes concentrations of 25, 50, and 100 µg/ml significantly increased bioavailability, growth and proliferation and it also increased expression level of BMP-7, BMP-15, and GDF-9 genes compared to the controls. CONCLUSION: Findings of this study indicated that exosomes derived from bone marrow stem cells improved growth of GCs in NMRI mice and they were a good candidate for further clinical studies to improve quality of the assisted reproductive techniques.

Ameliorative mechanism of dietary vitamin d and magnesium on newborn's pulmonary toxicity induced by cadmium.

Cadmium (Cd) exposure in mothers can cause respiratory issues in newborns, but the exact toxicity mechanisms are not fully understood. Vitamin D deficiency in Cd-exposed rats is associated with increased cadmium accumulation in tissues. Finding a cost-effective medication that is vital for the body while also reducing the effects of poisoning is crucial in treating poisonings. To investigate the mechanisms of Cd-induced lung toxicity, we examined the impact of prolonged Cd exposure in female rats before pregnancy on newborn lung health, focusing on sera TNF-α level, lung P53, Foxo1 mRNA, and lung VEGF, and BMP-4 protein level. A total of 50 rats were divided into control, Cd, Cd+Vitamin D, Cd+Mg, and Cd + Vitamin D+Mg groups. Cd exposure resulted in higher serum TNF-α levels and a significant rise in P53 mRNA levels. Additionally, the occurrence of hemorrhage, inflammatory cell infiltration, and thickening of alveolar walls decreased following treatment with vitamin D + Mg. Although Cd did not affect the newborns' body weight, it did impair their lung function. These findings suggest that the Cd-induced increase in the P53 gene expression could be alleviated by vitamin D and Mg, along with the elevation of VEGF and BMP-4 proteins and Foxo1 gene expression. The study revealed that environmental toxins can sometimes harm molecules and proteins, leading to damage in critical fetal tissues. However, these issues can be mitigated through essential supplements. STRUCTURED ABSTRACT: The increasing role of Cd in the erratic behavior of numerous biological and molecular entities, notably the development of fetal lung tissue, has made it beneficial to investigate the possible adverse effects of Cd exposure in pregnant mothers and fetal organ development, where instinctive molecular events occur. Researchers are encouraged to create new aspects of medications to reduce clinical symptoms and improve the quality of life due to exposure to metal toxins, particularly in industrialized countries. The present study aimed to evaluate histopathological and molecular modifications of fetal lungs caused by maternal Cd toxicosis and evaluate the possible ameliorating effects of vitamin D and Mg alone and in combination with fetal lung developmental abnormalities, followed by maternal toxin induction, which can be generalized to humans. Fifty female Wistar rats were purchased from the Pasteur Institute of Iran. To induce the model, cadmium at a dose of 2 mg/kg body weight was injected intraperitoneally into the female rats over 28 days before mating (5 days after injection in a week). Afterward, the female rats were randomly divided into type IV polycarbonate cages and mated with healthy male rats. The pregnancy was confirmed by observation of the vaginal plaque, which was subsequently observed, and the number of days of embryo formation was calculated. Subsequently, the pregnant rats were assigned to the following groups and received PBS, vitamin D, Mg, or vitamin D + Mg. At the end of the nine-day treatment period (the 6th day of pregnancy to the 14th day), the neonates were born vaginally, and their body weight and mortality were recorded. The P53 and Foxo1 gene expression levels in the left and right lobes of the homogenized lungs of the newborns in each group were assessed. TNF-alpha was detected in the sera collected from the newborns by ELISA. The isolated left and right lung tissues were homogenized in radioimmunoprecipitation assay (RIPA) buffer and the superior phase was collected to determine the total protein content by Lowry's method and VEGF and BMP-4 protein levels. The obtained lung samples from newborn rats were fixed in a 10% formalin solution for tissue processing. The fixed samples were embedded in paraffin, and serial paraffin sections were prepared for hematoxylin and eosin staining. This study is the first to examine how maternal Cd exposure affects fetal lung development and to estimate the impact of prescribing Mg and vitamin D during pregnancy. The present study assessed the effects of a repeated dose of Cd for 4 weeks before pregnancy on the lung development of newborn rats born to mothers treated with vitamin D and Mg. The results showed that the P53 gene was overexpressed in the model group, while Foxo1 gene expression was downregulated, negatively impacting the lung structure and developmental indices of the fetuses. Therefore, the intake of vitamin D and Mg may contribute to improving the various stages of Cd-induced lung injury by modulating lung inflammation and mucosal secretion while also positively influencing the number of surviving offspring.

Preparation of UiO-66 loaded Letrozole nano-drug delivery system: enhanced anticancer and apoptosis activity.

The use of drug delivery systems in targeting and achieving the targeting of drugs in treating diseases, especially cancer, has attracted the attention of researchers. Letrozole is one of the drugs for the treatment of breast cancer. In this study, the organic-metallic pharmaceutical porous nanostructure based on zirconium UiO-66 loaded letrozole was synthesized. Its cytotoxicity and effect on apoptosis and migration against breast cancer cell line were investigated. In this experimental study, the UiO-66 nanoparticle-loaded letrozole was synthesized using zirconium chloride (ZrCl4), dimethylformamide (DMF), and HCl. Its characteristics were determined by scanning electron microscopy, and its average size was determined by the DLS method. Also, the rate of letrozole drug release from the nanoparticle was investigated in 24, 48, and 72 h. In addition, its cytotoxicity effects were investigated using the MTT colorimetric method at concentrations of 3.125-100 µg/ml against the breast cancer cell line (MCF-7) in the periods of 48 and 72 h. Also, the expression level of apoptotic genes Bax and Bcl2 was investigated by the Real-Time PCR method. Also, the amount of cell migration was done by the migration assay method. The results showed that UiO-66 bound to letrozole had a spherical morphology and an average size of 9.2 ± 160.1. Also, the letrozole drug was loaded by 62.21 ± 1.80% in UiO-66 nanoparticles and had a slower release pattern than free letrozole in the drug release test, so within 72 h, 99.99% of free letrozole was released in If in UiO-66 containing letrozole, 57.55% of the drug has been released. Also, the cytotoxicity results showed that UiO-66 bound to letrozole has more significant cytotoxic effects than free letrozole (p < 0.05). Also, the results of Bax and Bcl2 gene expression showed that the treatment of MCF-7 cells with UiO-66 nanoparticles attached to letrozole increased the expression of Bax and Bcl2 genes compared to the reference gene Beta-actin in MCF-7 cell line, respectively. (p < 0.05) increased by 3.71 ± 0.42 and (p < 0.01) decreased by 0.636 ± 0.034 (p < 0.05). Cell migration results showed that the concentration of 50 µg/ml of UiO-66 bound to letrozole decreased the migration of MCF-7 cells. Generally, the results of this study showed that UiO-66 loaded letrozole can be used as a suitable drug carrier for cellular purposes, as it has increased the effects of cytotoxicity and the rate of apoptosis in breast cancer cell line (MCF-7), so it can be used with more studies used nanocarriers as a drug delivery system.

Hepatoprotective effects of Juglans regia extract against CCl4-induced oxidative damage in rats.

CONTEXT: Different parts of the walnut [Juglans regia L. (Juglandaceae)] have been used in folk medicine for protection against liver injury, although its actual efficacy remains uncertain. OBJECTIVE: The present study investigated the protective effect of walnut leaf extract against carbon tetrachloride (CCl4)-induced liver damage in rats. MATERIALS AND METHODS: The rats were randomly divided into seven groups: control, CCl4 (i.p., 0.5 mL/kg b.w., 50% CCl4 in olive oil), walnut extract (at dose level of 0.2 g/kg b.w.) alone, walnut extract (at dose levels of 0.05, 0.1, 0.2 and 0.4 g/kg b.w.) with CCl4, and treatment was carried out accordingly. On the 28th day, rats were sacrificed and blood was withdrawn by cardiac puncture. Liver damage was assessed by serum biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and albumin), antioxidant enzymes (superoxide dismutase and catalase) and histopathological observation. RESULTS: Administration of walnut leaf extract (ranging from 0.2 to 0.4 g/kg b.w.) significantly lowered serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels in CCl4-treated rats. Walnut leaf extract increased antioxidant enzymes, including superoxide dismutase and catalase. Histopathological examination of livers showed that walnut leaves extract reduced fatty degeneration, cytoplasmic vacuolization and necrosis in CCl4-treated rats. DISCUSSION AND CONCLUSION: These results suggest that walnut extract has a protective effect over CCl4-induced oxidative damage in rat liver. These results demonstrate that walnut extract acts as a good hepatoprotective and antioxidant agent in attenuating hepatocellular damage.

Abdominal Obesity May Play a Significant Role in inflammation Exacerbation in Polycystic Ovary Syndrome Patients.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is an endocrine disorder that seems to be pro-inflammatory at many levels, abdominal obesity (AO) is a prevalent pro-inflammatory phenotype in PCOS patients, and it seems to contribute to the initiation or worsening of inflammation in PCOS patients. In this study, we investigated the role of the AO phenotype in the occurrence of other obesity indicators (neck and arm) and augmentation of inflammation in the follicular fluid (FF) of PCOS patients. METHODS: 40 patients under the age of 35 were divided into four groups: PCOS with AO, PCOS without AO, non-PCOS with AO, and non-PCOS without AO. The FF samples were collected from each patient. Clinical and anthropometric characteristics of the participants, as well as tumor necrosis factor-α (TNF-α) concentration in the FF samples, were quantitatively assessed using enzyme-linked immunosorbent assays. The number of retrieved cumulus-oocyte complexes (COC) and their quality were scored. RESULTS: The PCOS+AO+ group had significantly increased neck circumference, compared to the other groups (p<0.001). The concentration of TNF-α was significantly higher in the PCOS+AO+ group than in the other groups (p<0.001). There were no significant differences in the number of retrieved COC per patient and the quality of oocytes between the groups (p>0.05). CONCLUSIONS: Given the significant role of inflammation in the development of PCOS, managing AO in PCOS patients may aid in reducing inflammation and could potentially help in the design of customized treatment approaches.