Piperine mitigates oxidative stress, inflammation, and apoptosis in the testicular damage induced by cyclophosphamide in mice.

Although cyclophosphamide (CP) has been approved as an anticancer drug, its toxic effect on most organs, especially the testis, has been established. Piperine (PIP) is an alkaloid that has antioxidant, antiapoptotic, and anti-inflammatory activities. This study was investigated the protective effects of PIP on CP-induced testicular toxicity in the mice. In this experimental study, 48 adult male BALB/c mice (30-35 g) were divided into six groups (n = 8), receiving normal saline (C), 5 mg/kg of PIP (PIP5), 10 mg/kg of PIP (PIP10), 200 mg/kg of CP, 200 mg/kg of CP + PIP5, and 200 mg/kg of CP + PIP10. On the eighth day of the study, blood and testis samples were prepared for serum testosterone hormone quantification, sperm analysis, histological, and immunohistochemical assays. The results of this study showed that CP induced testicular toxicity with the decrease of sperm count, motility, and viability. Also, CP treatment caused histological structure alterations in the testis, including exfoliation, degeneration, vacuolation of spermatogenic cells, and reducing the thickness of the epithelium and the diameter of the seminiferous tubule. In addition, CP decreased glutathione (GSH) levels, increased malondialdehyde (MDA) levels, Caspase-3, and NF-κB. At the same time, PIP treatment reduced testicular histopathological abnormalities, oxidative stress, and apoptosis that were induced by CP. These results showed that PIP improved CP-induced testicular toxicity in mice, which can be related to its antioxidant, antiapoptotic, and anti-inflammatory activities.

Tyrosol and Olive Oil Ameliorate Sodium Arsenate-Induced Nephrotoxicity by Modulating of Oxidative Stress and Histological Changes in Mice.

Background: Sodium arsenate (Na 3As0 4, Sodium As) is an important toxic substance that leads to nephrotoxicity. Due to having bioactive molecules, such as polyphenols and tyrosol, olive oil plays a significant role in scavenging free radicals. This study aimed to investigate the effects of olive oil and tyrosol on As-induced nephrotoxicity. Methods: In our study, 42 adult male BALB/c mice were randomly divided into six groups: control (normal saline), olive oil (0.4 ml/d, gavage), tyrosol (5 mg/kg/d), Sodium As (15 mg/kg), olive oil + Sodium As, and tyrosol + Sodium As (olive oil and tyrosol received one hour before Sodium As). Drugs were administreted once daily for 30 consecutive days. On the 31st day of the study, oxidative stress parameters in kidney tissue, FRAP in plasma, renal function parameters in serum, and histopathological assays were performed. Results: Sodium As-induced renal damage as characterized by a significant increase of creatinine and BUN (P < 0.001) and histopathological changes. Also, Sodium As markedly altered oxidative stress biomarkers such as a significant increase in MDA (P < 0.001) and significantly decreased in FRAP and GSH (P < 0.01). Olive oil and tyrosol administration significantly improved the renal antioxidant defense system and decreased MDA concentration, markedly preserving the tissue structure and functional markers of kidney. However, these effects were more effective for tyrosol than olive oil. Conclusions: Our results suggest that olive oil and tyrosol can be used as a protective agent in preventing Sodium As-induced nephrotoxicity due to antioxidant property.

Sinapic acid attenuates cyclophosphamide-induced liver toxicity in mice by modulating oxidative stress, NF-κB, and caspase-3.

Objectives: Cyclophosphamide (CP) as an antineoplastic drug is widely used in cancer patients, and liver toxicity is one of its complications. Sinapic acid (SA) as a natural phenylpropanoid has anti-oxidant, anti-inflammatory, and anti-cancer properties. Materials and Methods: The purpose of the current study was to determine the protective effect of SA versus CP-induced liver toxicity. In this research, BALB/c mice were treated with SA (5 and 10 mg/kg) orally for one week, and CP (200 mg/kg) was injected on day 3 of the study. Oxidative stress markers, serum liver-specific enzymes, histopathological features, caspase-3, and nuclear factor kappa-B cells were then checked. Results: CP induced hepatotoxicity in mice and showed structural changes in liver tissue. CP significantly increased liver enzymes and lipid peroxidation, and decreased glutathione. The immunoreactivity of caspase-3 and nuclear factor kappa-B cells was significantly increased. Administration of SA significantly maintained histochemical parameters and liver function enzymes in mice treated with CP. Immunohistochemical examination showed SA reduced apoptosis and inflammation. Conclusion: The data confirmed that SA with anti-apoptotic, anti-oxidative, and anti-inflammatory activities was able to preserve CP-induced liver injury in mice.

Association of S19W polymorphism in APOA5 gene and serum lipid levels in patients with type 2 diabetic nephropathy.

OBJECTIVES: Type 2 diabetic Mellitus (T2DM) is the most common systemic and endocrine disease in humans, and diabetic nephropathy is one of the most serious complications of this disorder. The polymorphisms in the apolipoprotein A5 (ApoA5) gene are strongly related to hypertriglyceridemia and are considered a predisposing factor for diabetic nephropathy. The current study proposed to examine the association of APOA5-S19W polymorphism with serum lipids levels in patients with type 2 diabetic nephropathy in Mazandaran province. METHODS: This case-control study was designed to determine the association of APOA5-S19W polymorphism with plasma lipid profile in 161 T2DM patients with nephropathy (DN+), without nephropathy (DN-), and in 58 healthy individuals. Lipid profile values were measured using Pars Azmoun commercial kits. S19W variant, one of the polymorphisms of the APOA5 gene, was determined by PCR-restriction fragment length polymorphism (PCR-RFLP) and Taq1 restriction enzyme. RESULTS: In comparison between the three groups, DN+ had a higher mean TG than DN- and the control group (p<0.001). The incidence of the G allele in DN+ was not significant compared to groups of DN-. Comparing the relationship between the mean of biochemical variables with CC and CG genotypes showed that the mean level of TG in people with CC genotype was increased compared to people with CG genotype in diabetic patients. However, this increase was not significant (p=0.19). CONCLUSIONS: There was no association between SNP APOA5 S19W and serum lipids in diabetic patients with and without nephropathy.

Differential gene expression analysis of common target genes for the detection of SARS-CoV-2 using real time-PCR.

COVID-19 currently is the main cause of the severe acute respiratory disease and fatal outcomes in human beings worldwide. Several genes are used as targets for the detection of SARS-CoV-2, including the RDRP, N, and E genes. The present study aimed to determine the RDRP, N, and E genes expressions of SARS-CoV- 2 in clinical samples. For this purpose, 100 SARS-CoV-2 positive samples were collected from diagnostic laboratories of Mazandaran province, Iran. After RNA extraction, the real-time reverse transcription PCR (real-time RT-PCR) assay was performed for differential gene expressions' analysis of N, E, and RDRP. The threshold cycle (Ct) values for N, RDRP, and E targets of 100 clinical samples for identifying SARS-CoV-2 were then evaluated using quantitative real-time PCR (qRT-PCR). This result suggests N gene as a potential target for the detection of the SARS-CoV-2, since it was observed to be highly expressed in the nasopharyngeal or oropharynges of COVID-19 patients (P < 0.0001). Herein, we showed that SARS-CoV- 2 genes were differentially expressed in the host cells. Therefore, to reduce obtaining false negative results and to increase the sensitivity of the available diagnostic tests, the target genes should be carefully selected based on the most expressed genes in the cells.

The microenvironment of silk/gelatin nanofibrous scaffold improves proliferation and differentiation of Wharton's jelly-derived mesenchymal cells into islet-like cells.

The use of umbilical cord-derived mesenchymal stem cells along with three-dimensional (3D) scaffolds in pancreatic tissue engineering can be considered as a treatment for diabetes. This study aimed to investigate the differentiation of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) into pancreatic islet-insulin producing cells (IPCs) on silk/gelatin nanofibers as a 3D scaffold. Mesenchymal markers were evaluated at the mesenchymal stem cells (MSCs) level by flow cytometry. WJ-MSCs were then cultured on 3D scaffolds and treated with a differential medium. Immunocytochemical assays showed efficient differentiation of WJ-MSCs into IPCs. Also, Real-time PCR results showed a significant increase in the expression of pancreatic genes in the 3D culture group compared to the two-dimensional (2D) culture group. Despite these cases, the secretion of insulin and C-peptide in response to different concentrations of glucose in the 3D group was significantly higher than in the 2D culture. The results of our study showed that silk/gelatin scaffold with WJ-MSCs could be a good option in the production of IPCs in regenerative medicine and pancreatic tissue engineering.

Hepatotoxicity in young adult rat offspring after prenatal exposure to benzo(a)pyrene, and protective effect of atorvastatin.

OBJECTIVES: Benzo[a]pyrene (BaP) is an environmental contaminant that interrupts the antioxidant defense and thus leads to oxidative stress and DNA damage in the liver. Atorvastatin (ATV) for reducing cholesterol has antioxidant and anti-apoptotic activities. This study investigated the effects of prenatal exposure of BaP on liver toxicity and the protective role of ATV in reducing liver toxicity. MATERIALS AND METHODS: In this study, rats were distributed randomly to seven groups: I. Saline control; II. ATV (10 mg/kg); III. Corn oil; IV and V. BaP (10 and 20 mg/kg); VI and VII. ATV + BaP (10 and 20 mg/kg). BaP and ATV were administrated from gestation day 7-16 (GD7-GD16), orally. Ten weeks after the birth, female offspring were examined for oxidative stress markers, liver enzymes, and histology. RESULTS: Data revealed that BaP significantly induced oxidative stress (decreased glutathione and increased malondialdehyde level), and disrupted the tissue structure of the liver. Moreover, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase increased in the offspring. ATV treatment along with BaP during gestation was able to bring the antioxidant status and serum liver enzymes levels relatively close to normal. As well as, histological findings showed that ATV was able to improve liver tissue structure caused by BaP. CONCLUSION: Based on the above studies we concluded that ATV at a low dose during gestation was able to reduce liver damage caused by BaP with antioxidant properties.

Synergistic neuroprotective effects of hyperbaric oxygen and methylprednisolone following contusive spinal cord injury in rat.

OBJECTIVE: Recent studies revealed the neuroprotective effects of hyperbaric oxygen (HBO) on spinal cord injury (SCI). Meanwhile, the use of methylprednisolone (MP) is one of the current protocols with limited effects in SCI patients. Accordingly, the aim of the present study was to investigate the effect of combined HBO and MP treatment on SCI. DESIGN: The present study was conducted on five groups of rats each as follows: Sham group (underwent laminectomy alone at T9 level vertebra); SCI group (underwent moderate contusive SCI); MP group (underwent SCI and received MP); HBO group (underwent SCI and received HBO); HBO + MP group (underwent SCI and simultaneously received MP and HBO). Blood serum and Spinal cord tissue samples were taken 48 h after SCI for analysis of serum ferric reducing antioxidant power (FRAP) and tissue malodialdehyde (MDA) levels as well as immunohistochemistry of caspase-3 and tumor necrosis factor-alpha (TNF-α). Neurological function was evaluated by the Basso-Beattie-Bresnehan (BBB) locomotion scores until the end of experiments. Additionally, histopathology was assessed at the end of the study. SETTING: Mazandaran University of Medical Sciences, Sari, Iran. RESULTS: Combination therapy with HBO and MP in the HBO + MP group significantly decreased MDA as well as increased FRAP levels compared to other treatment groups. Meanwhile, attenuated TNF-α and Caspase-3 expression could be significantly detected in the HBO + MP group. At the end of treatment, the neurological outcome was significantly improved and the extent of injured spinal tissue was also significantly reduced in the HBO + MP compared to other treatment groups. CONCLUSION: The results suggest that combined therapy with MP and HBO has synergistic effects on SCI treatment.

Effects of clozapine and risperidone antipsychotic drugs on the expression of CACNA1C and behavioral changes in rat 'Ketamine model of schizophrenia.

Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C) is one of the most important genes associated with schizophrenia. In this study, 45 male Wistar rats were divided into 5 groups of saline, control, ketamine, clozapine, and risperidone. Animals in ketamine, risperidone, and clozapine groups received ketamine (30 mg/kg-i.p.) for 10 days. After the last injection of ketamine, we started injecting clozapine (7.5 mg/kg-i.p.), risperidone (1 mg/kg-i.p.), up to 28 days. Twenty-four hours after the last injection, open field, social interaction, and elevated plus-maze tests and gene expression in hippocampus were performed. The results of the social interaction test revealed a significant decrease in cumulative time with ketamine, compared with the saline group, and an increase with clozapine and risperidone compared with the ketamine group. Moreover, results from the elevated plus-maze test demonstrated a critical decrease in open arm time and increase in close arm time with ketamine compared with saline, as well as increased in open arm time with risperidone compared with ketamine. Further results revealed a significant increase in rearing and grooming with ketamine compared to saline, as well as a decrease with risperidone and clozapine compared to ketamine. There were no significant differences in CACNA1C gene expression between groups in the rat hippocampus. In brief, the results of this study indicated that clozapine and risperidone could partially improve cognitive impairments in the rat. However, our findings demonstrated that this treatment is not related to CACNA1C gene expression.

Protective effects of sinapic acid against cyclophosphamide-induced testicular toxicity via inhibiting oxidative stress, caspase-3 and NF-kB activity in BALB/c mice.

Cyclophosphamide (CP), as a chemotherapeutic agent, with the generation of oxidative stress leads to testicular toxicity. Sinapic acid (SA), as a phenylpropanoid compound has therapeutic activities. This research was planned to evaluate the improving effects of SA versus testicular injury induced by CP. Forty-eight mice were distributed into six groups: untreated, SA (5 and 10 mg/kg), CP (200 mg/kg) and CP + SA (5 and 10 mg/kg). SA was administrated for 7 successive days and CP was administered intraperitoneally on the 3rd day of study. On the 10th day of research, testicular toxicity was evaluated by sperm parameters test, tissue (oxidative stress parameters) and serum (testosterone) biochemical, histopathological, and immunohistochemical (Caspase-3 and NF-kB) assays. The findings illustrated that CP induces atypical appearance in tissue structure, disorder of sperm parameters dysfunction, decrease of testosterone, oxidative stress (an increase of MDA and decrease of GSH), apoptosis and inflammation in testicular tissue. SA administration protected testis from oxidative stress and improves testosterone level and structure. Moreover, immunohistochemical findings also showed that SA can inhibit Caspase-3 and NF-kB activity. Data have confirmed that SA could protect testis structure and its functions against CP-induced injury through antioxidant, anti-inflammatory and anti-apoptotic activities.

Correlation between ELF-PEMF exposure and Human RPE Cell Proliferation, Apoptosis and Gene Expression.

PURPOSE: Emerging evidence implies that electromagnetic fields (EMFs) can negatively affect angiogenesis. In this regard, the effects of extremely low frequency pulsed electromagnetic field (ELF-PEMF) exposure on the relative expression level of angiogenic factors involved in the pathogenesis of ocular disorders were evaluated in human retinal pigment epithelial (hRPE) cells in order to investigate a noninvasive therapeutic method for patients with several ocular diseases associated with neovascularization. METHODS: After separating hRPE cells from globes, hRPE cells were exposed to 15 mT of ELF-PEMF (120 Hz) at 5, 10, and 15 min for seven days. Cell proliferation and apoptosis of treated cells were evaluated via ELISA assay. Moreover, relative expression changes of HIF-1α, CTGF, VEGFA, MMP-2, cathepsin D, and E2F3 were performed using real-time RT-PCR. RESULTS: ELF-PEMF exposure had no significant effects on the apoptosis and proliferation rate of hRPE cells. Expression level of HIF-1α, CTGF, VEGFA, MMP-2, cathepsin D, and E2F3 was downregulated following 5 min of ELF-PEMF exposure. CONCLUSION: As ELF-PEMF showed inhibitory effects on the expression of angiogenic genes in hRPE cells with no cytotoxic or proliferative side effects, it can be introduced as a useful procedure for managing angiogenesis induced by retinal pathogenesis, although more studies with adequate follow-up in animal models are needed.

Effect of prenatal exposure to Benzo[a]pyrene on ovarian toxicity and reproductive dysfunction: Protective effect of atorvastatin in the embryonic period.

As an environmental contaminant, Benzo[a]pyrene (B[a]P; BaP) disrupts the antioxidant signaling and thus leads to the induction of oxidative stress and the damage of DNA in the ovary. low-dose atorvastatin (ATV) has antioxidant and anti-apoptotic properties. The present study aimed to survey the effects of prenatal exposure to BaP on ovarian toxicity and also to investigate the protective role of ATV in reducing ovarian toxicity. In this study, rats were divided into seven groups: control, ATV (10 mg/kg), oil, BaP (10 and 20 mg/kg), and ATV + BaP (10 and 20 mg/kg). BaP and ATV were administrated from gestation day 7-16 (GD7 to GD16), orally. 10 weeks after the birth, female offsprings were examined for oxidative stress markers, sex hormones, ovarian and tubular tissue structure, and the apoptosis markers. Data showed that BaP significantly reduced glutathione, increased malondialdehyde level, and disrupted the tissue structure of the ovary. Moreover, estrogen and progesterone levels significantly decreased in the offsprings rats. Also, BaP increased caspase-3 immunoreactivity. Atorvastatin treatment along with BaP in the embryonic period were able to bring the antioxidant status and sex hormones levels relatively close to normal. Besides, histological findings showed that atorvastatin was able to improve ovarian and oviduct abnormalities caused by BaP. Based on the above studies be concluded that atorvastatin in the embryonic during was able to reduce ovarian damage caused by BaP with antioxidant and anti-apoptotic properties.

Alleviation of cisplatin-induced hepatotoxicity by gliclazide: Involvement of oxidative stress and caspase-3 activity.

AIMS: Cisplatin (CP), as an effective alkylating agent, is widely used in cancer treatment, while hepatotoxicity is one of its side effects. Gliclazide (GLZ), as an oral hypoglycemic drug, has antioxidant and anti-inflammatory properties. This study was designed to investigate the protective effect of GLZ against CP-induced hepatotoxicity in mice. METHODS: In this experimental study, 64 adult male mice randomly were allocated into eight groups (8 mice/group). Control, GLZ (5, 10, and 25 mg/kg, orally), CP (10 mg/kg, single dose, intraperitoneally), and CP+GLZ (in three doses). GLZ was administrated for 10 consecutive days. CP was injected on the 7th day of the study. At the end of the experiment, hepatotoxicity was evaluated by serum and tissue biochemical, histopathological, and immunohistochemical assessments. RESULTS: The data were revealed that CP increased oxidative stress (increased MDA and reduced GSH), liver damage enzymes (ALT, AST, and ALP), and immunoreactivity of caspase-3 in liver tissue of CP-injected mice. Also, CP induced histopathological changes such as eosinophilic of hepatocytes, dilatation of sinusoids, congestion, and proliferation of Kupffer cells. GLZ administration significantly ameliorated serum functional enzyme and hepatic oxidative stress markers in CP-injected mice. In addition, the histological and immunohistochemical alterations were ameliorated in GLZ-treated mice. Of the three doses, 10 and 25 mg/kg were more effective. CONCLUSIONS: In conclusion, GLZ with its antioxidant, anti-inflammatory, and anti-apoptotic activities, can be suggested as a promising drug in the treatment of CP-induced hepatotoxicity.

Improved risk assessment of coronary artery disease by substituting paraoxonase 1 activity for HDL-C: Novel cardiometabolic biomarkers based on HDL functionality.

BACKGROUND AND AIMS: Developing laboratory assays to evaluate HDL functions and improve cardiovascular disease (CVD) risk assessment has recently emerged as a challenge. The present study was conducted to help predict the risk of coronary artery disease (CAD) by investigating new cardiometabolic risk factors based on substituting paraoxonase 1 (PON1) as a critical enzyme in the functionality of HDL for that of HDL-C. METHODS AND RESULTS: The present study recruited 274 subjects undergoing diagnostic coronary angiography, 92 without significant CAD (non-CAD), and 182 with a severe CAD. The diagnostic accuracy of the new biomarkers in non-CAD versus multi-vessel disease was obtained in descending order of AUC as 0.72 (P < 0.001) for log (TG/PON1), 0.70 (P < 0.001) for nonHDL-C/PON1, and 0.67 (P < 0.001) for LDL-C/PON1. After performing a multivariate adjustment for age, gender, BMI, statin therapy, and diabetes mellitus, the increased odds of CAD remained significant for the new cardiometabolic ratios as independent variables [adjusted OR = 1.47 (1.15-1.88), p = 0.002 for LDL-C/PON1; adjusted OR = 2.15 (1.41-3.5), p = 0.009 for nonHDL-C/PON1; adjusted OR = 5.03 (2.14-13.02), p = 0.004 for log (TG/PON1)]. CAD was diagnosed with an optimal discriminating cutoff of 1.84 for LDL-C/PON1, 2.8 for nonHDL-C/PON1, and 0.48 for log (TG/PON1). CONCLUSIONS: To improve CAD's risk assessment, the PON1 activity was proposed as an alternative to HDL-C in the commonly used atherogenic lipid ratios. Substituting the PON1 activity for the HDL-C concentration can provide an index of the HDL activity. The present study sought to exploit the lipoprotein-related risk factors of CAD from a more effective perspective.

Assessment of the neuroprotective effects of (-)-epigallocatechin-3-gallate on spinal cord ischemia-reperfusion injury in rats.

Objective: Paraplegia or paraparesis due to spinal cord ischemia is one of the complications following thoracoabdominal aortic surgery. Recent studies revealed the neuroprotective effects of (-)-epigallocatechin-3-gallate (EGCG) on a variety of neurological disorders. The purpose of this study was to determine the neuroprotective effects of EGCG following spinal cord ischemia-reperfusion injury (IRI).Design: The present study was conducted on four groups of rats each as follows: Sham-operated group (laparotomy alone); Control group (with IRI); EGCGI group (50-mg/kg, i.p., before IRI), and EGCGII group (50-mg/kg, i.p., after IRI). Neurological function evaluated with motor deficit index (MDI) test. Spinal cord samples were taken 48 h after IRI and studied for determination of malodialdehyde (MDA) level, histopathology, and immunohistochemistry of caspase-3, TNF-α, and iNOS.Setting: Mazandaran University of Medical Sciences, Sari, Iran.Results: The level of MDA was significantly decreased in EGCG-treated rats. Attenuated caspase-3, TNF-α, and iNOS expression could be significantly detected in the EGCG-treated rats. Also, EGCG reduced the extent of degeneration of the spinal cord neurons, in addition to a significant reduction of MDI.Conclusion: The results suggest that pre- and post-treatment with EGCG may be effective in protecting spinal cord from IRI.

Synthesis and biological assessment of ciprofloxacin-derived 1,3,4-thiadiazoles as anticancer agents.

The quinolone-3-carboxylic acid scaffold is essential structure for antibacterial activity of fluoroquinolones such as ciprofloxacin. Modification of 3-carboxylic functionality in this structure can be used for switching its activity from antibacterial to anticancer. Accordingly, a series of C-3 modified ciprofloxacin derivatives containing N-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-carboxamide moiety was synthesized as novel anticancer agents. Most of compounds showed significant activity against MCF-7, A549 and SKOV-3 cancer cells in the MTT assay. In particular, compounds 13a-e and 13g were found to be as potent as standard drug doxorubicin against MCF-7 cell line (IC50s = 3.26-3.90 µM). Furthermore, the 4-fluorobenzyl derivatives 13h and 14b with IC50 values of 3.58 and 2.79 µM exhibited the highest activity against SKOV-3 and A549 cells, being as potent as doxorubicin. Two promising compounds 13e and 13g were further tested for their apoptosis inducing activity and cell cycle arrest. Both compounds could significantly induce apoptosis in MCF-7 cells, while compound 13e was more potent apoptosis inducer resulting in an 18-fold increase in the proportion of apoptotic cells at the IC50 concentration in MCF-7 cells. The cell cycle analysis revealed that compounds 13e and 13g could increase cell portions in the sub-G1 phase, inducing oligonucleosomal DNA fragmentation and apoptosis confirmed by comet assay.

Gliclazide attenuates cisplatin-induced nephrotoxicity through inhibiting NF-κB and caspase-3 activity.

Cisplatin (CP), as a chemotherapeutic drug, causes nephrotoxicity that has limited the clinical utility of CP. Gliclazide (GLZ), as an antihyperglycemic drug, at low dose has antioxidant property. In this study, we aimed to investigate the protective effect of GLZ against CP-induced acute renal injury. Sixty-four BALB/c mice were randomly divided into eight groups. The groups were included as control, GLZ (5, 10, and 25 mg/kg), CP, and GLZ (5, 10, and 25 mg/kg) + CP. Renal function markers (serum creatinine and blood urea nitrogen), oxidative stress markers (malondialdehyde and glutathione), apoptotic marker (caspase-3), and NF-κB were histopathologically evaluated. The results of our study showed that increased urea and creatinine were evidence of CP-induced nephrotoxicity. Histopathological examination revealed tubular epithelial and Bowman degeneration, edema, and cytoplasmic vacuolation in renal tissue structure. Administration of GLZ reduced oxidative stress, caspase-3, and NF-κB activity, and improved kidney function markers in CP-treated mice compared with CP alone group. Also, we observed that the histological tissue structure of the kidney was maintained. GLZ at dose of 25 mg/kg had higher protective effect as compared with other doses. Overall, our study suggests that GLZ with antioxidant, antiapoptotic, and anti-inflammatory properties may be a promising new therapeutic agent to prevent CP-induced nephrotoxicity.

MicroRNAs in the anticancer effects of celecoxib: A systematic review.

Cyclooxygenase-2 (COX-2) is known as an important enzyme in the inflammation process that has tumorigenesis function in various cancers through the induction of epithelial-to-mesenchymal transition (EMT), cell proliferation, migration, and invasion that lead to metastasis. Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that can selectively target COX-2, suppress downstream pathways, and finally lead to anticancer potentiality. microRNAs (miRNAs), as a class of small noncoding RNAs, play pivotal roles in cancers through the tumor-suppressive or oncogenic effects, by post-transcriptional regulation of their target genes. In this regard, shreds of evidence have shown that, COX-2 reveals its action through miRNA regulation. So, in this systematic review, we aimed to highlight the tumorigenic role of COX-2 in cancer development and the therapeutic effects of celecoxib, as a selective COX-2 drug, through the regulation of miRNAs.

Therapeutic applications of AS1411 aptamer, an update review.

Nucleolin or C23, is one of the most abundant non-ribosomal phosphoproteins of nucleolus. However, in several cancers, nucleolin is highly expressed both intracellularly and on the cell surface. So, it is considered as a potential target for the diagnosis and cancer therapy. Targeting nucleolin by compounds such as AS1411 aptamer can reduce tumor cell growth. In this regard, interest has increased in nucleolin as a molecular target for overcoming cancer therapy challenges. This review paper addressed recent progresses in nucleolin targeting by the G-rich AS1411 aptamer in the field of cancer therapy mainly over the past three years.

A panel of noncoding RNAs in non-small-cell lung cancer.

Non-small-lung cancer (NSCLC) is the leading cause of cancer death. Early detection of NSCLC could pave the way for effective therapies. Analysis of molecular genetic biomarkers in biological fluids has been proposed as a useful tool for cancer diagnosis. Here, we aimed to develop a panel of noncoding RNAs (ncRNAs) in sputum for NSCLC early detection. Expression of 11 ncRNAs were analyzed by real-time polymerase chain reaction in sputum samples of 30 NSCLC patients and 30 sex- and age-matched cancer-free controls. Stability of endogenous microRNAs (miRNAs) in sputum was evaluated after 3 and 6 days at 4°C, 6 months, and 1 year at -80°C. Nine ncRNAs showed significant differences of their expression in sputum between NSCLC patients and controls. A logistic regression model with the best prediction was built based on miR-145, miR-126, and miR-7. The composite of the three miRNAs produced 90% sensitivity and specificity in distinguishing NSCLC patients from the controls. Results indicate that miRNAs could be useful biomarkers based on their stability under various storage conditions and maintain differential changes between cancer and control groups. Moreover, measurement of miRNAs in sputum could be a noninvasive approach for detection of lung cancer.