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Background: Hyperglycemia-induced oxidative stress can damage the liver and lead to diabetes complications. Coenzyme Q10 (CoQ-10) reduces diabetes-related oxidative stress. However, its molecular mechanisms are still unclear. This study aimed to examine CoQ-10's antioxidant capabilities against hyperglycemia-induced oxidative stress in the livers of diabetic rats, specifically targeting the Nrf2/Keap1/ARE signaling pathway. Methods: This study was conducted between 2020-2021 at Arak University of Medical Sciences. A total of 30 male adult Wistar rats (8 weeks old) weighing 220-250 g were randomly assigned to five groups (n=6 in each group): control healthy, sesame oil (CoQ-10 solvent), CoQ-10 (10 mg/Kg), diabetic, and diabetic+CoQ-10. Liver oxidative stress indicators, including malondialdehyde, catalase, glutathione peroxidase, and glutathione, were estimated using the spectrophotometry method. Nrf2, Keap1, HO-1, and NQO1 gene expressions were measured using real-time PCR tests in the liver tissue. All treatments were conducted for 6 weeks. Statistical analysis was performed using SPSS software. One-way ANOVA followed by LSD's or Tukey's post hoc tests were used to compare the results of different groups. P<0.05 was considered statistically significant. Results: The findings showed that induction of diabetes significantly increased Keap1 expression (2.1±0.9 folds, P=0.01), and significantly inhibited the mRNA expression of Nrf2 (0.38±0.2 folds, P=0.009), HO-1 (0.27±0.1 folds, P=0.02), and NQO1 (0.26±0.1 folds P=0.01), compared with the healthy group. In the diabetic group, the activity of glutathione peroxidase, catalase enzymes, and glutathione levels was decreased with an increase in malondialdehyde level. CoQ-10 supplementation significantly up-regulated the expressions of Nrf2 (0.85±0.3, P=0.04), HO-1 (0.94±0.2, P=0.04), NQO1 (0.88±0.5, P=0.03) genes, and inhibited Keap1 expression (1.1±0.6, P=0.02). Furthermore, as compared to control diabetic rats, CoQ-10 ameliorated oxidative stress by decreasing malondialdehyde levels and increasing catalase, glutathione peroxidase activities, and glutathione levels in the liver tissues of the treated rats in the treatment group. Conclusion: The findings of this study revealed that CoQ-10 could increase the antioxidant capacity of the liver tissue in diabetic rats by modulating the Nrf2/Keap1/HO-1/NQO1 signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Exposure to ionizing radiation induces reactive oxygen species (ROS), which leads to oxidative stress in the involved tissues. The oxidative stress may be minimized by using natural antioxidant products, such as Zingiber officinale. This study aimed to investigate the protective and antioxidant effects of ginger extract on the inhibition of oxidative stress in the serum and liver tissue of rats after exposure to X-ray irradiation. Methods: Thirty-six Sprague Dawley rats were divided into six groups. Groups 1 and 2 received normal saline and dimethyl sulfoxide, respectively; group 3 was placed in a turned-off X-ray device; group 4 was treated with ginger extract (100 mg/kg); groups 5 and 6 received X-radiation (4 Gy) and X-radiation + ginger extract, respectively. All treatments were orally administered once daily for four weeks. The total antioxidant capacity (TAC), total oxidant status (TOS), and malondialdehyde (MDA) levels were measured in the serum and liver tissues of the animals. Results: X-ray radiation significantly increased the levels of MDA and TOS and decreased TAC in the serum and liver tissues of irradiated rats compared to those of the control group. Ginger pre-treatment prior to X-ray significantly decreased the MDA and TOS levels and increased the TAC levels in the serum and liver samples of the rats compared to the rats irradiated with X-ray alone. Conclusion: This study demonstrated that ginger acted as a protector against X-ray radiation by suppressing oxidative stress in the rats' liver and serum samples. [ABSTRACT FROM AUTHOR]

Background: Testicular torsion is a surgical emergency leads to severe acute ischemia injuries, and may eventually cause male infertility. The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is involved in testicular torsion pathophysiology. The aim of this study was to evaluate the effects of nanocurcumin (nCur) on testicular tissue and the NLRP3 inflammasome components. Materials and Methods: In this experimental study, male Wistar rats (n=36) were randomly divided into six equal groups: controls, ischemia-reperfusion (I/R), I/R+nCur (50 or 100 mg/kg thirty minutes before reperfusion), and I/ R+nCur (50 or 100 mg/kg thirty minutes before reperfusion and continued for seven days). The left testis was rotated 720 (2x360) degrees counterclockwise to induce testicular torsion. After two hours of ischemia, detorsion was performed. At the end of treatment, an orchiectomy was carried out. The testis histopathology and the mRNA levels of NLRP3, apoptosis-associated speck-like protein (ASC), and Caspase-1 were evaluated. Results: Our results revealed that, testicular I/R had a detrimental effect on testis histology such as the number of spermatogonia (14.5 ± 0.57, P<0.001) and the seminiferous tubules epithelium thickness (28.5 ± 11.7, P=0.007). It also significantly increased the expression of the NLRP3 inflammasome components (P<0.001). Treatment with nCur (in both doses) improved testicular damage and significantly reduced the expression of NLRP3 (P=0.007), ASC (P=0.003), and Caspase-1 (P<0.001). Conclusion: These results imply that nCur might be a useful therapeutic strategy in the field of reproductive medicine to diminish the side effects of testicular I/R via its anti-inflammatory properties and may be employed as adjuvant therapy to lessen testicular torsion complications. [ABSTRACT FROM AUTHOR]

Background: Anabolic androgenic steroids (AAS), such as nandrolone (N), are commonly used in medicine to maximize anabolic effects while minimizing androgenic effects. On the other hand, illicit use of anabolic androgenic steroids is prevalent among adolescents and bodybuilders because of their anabolic proprieties and their capacity to increase tolerance to exercise. Exogenous testosterone (T) adversely affects spermatogenesis in fertile men, but discontinuation generally leads to recovery. Objectives: This study investigated the impact of short- and long-term administration of testosterone and nandrolone on testis histopathology and sperm parameters following exercise. Methods: The study consisted of two components: Short-term and long-term administration of T and ND. Thirty-six male NMRI mice were used for each component. Animals were divided into six groups: Control, exercise )E(, N )10 mg/kg(, T )0.1 mg/kg(, N + E, and T + E. The high-intensity interval training was used. The injection of N and T continued for 14 days for the short-term component and 36 days for the long-term component. Sperm parameters, testis histology, and stereological study were analyzed. Results: There were no differences between the control and exercise groups. Short-term and long-term treatment with N and T significantly reduced sperm quality (P < 0.05). Both short-term and long-term administration of N and T had deleterious effects on testicular histology and stereological indices (P < 0.05). Exercise was found to improve sperm parameters and testicular histopathology in both groups (P < 0.05). Conclusion: Nandrolone demonstrated more detrimental effects on testicular tissue compared to testosterone. However, the harmful effects of anabolic androgens on testicular tissue can be mitigated by exercise. These findings shed light on the potential impact of testosterone and nandrolone administration on male reproductive health and the potential benefits of exercise in counteracting their adverse effects. [ABSTRACT FROM AUTHOR]

Nrf2/Keap1 pathway, which prevents cellular damage against reactive oxygen species production, is disrupted in epididymis following cryptorchidism. In this study, we aimed to use curcumin (Cur) as an activator of Nrf2 to decrease the effects of disruption in this pathway caused by cryptorchidism. In this study, animals were randomly divided into following groups: control, sham‐surgery, sham‐vehicle, sham‐Cur50, sham‐Cur100, cryptorchidism, cryptorchidism‐vehicle, cryptorchidism‐Cur50 and cryptorchidism‐Cur100. For cryptorchidism induction, the left testicle was removed from the scrotum and sutured to the abdominal wall. Two weeks after surgery, Cur was given orally to animals. After 1 month, sperm parameters and testis histopathology were analysed. The expression of Nrf2, NQO1, HO1, and Keap1 genes was evaluated by real‐time polymerase chain reaction. Our data showed that Cur, especially at high doses, could improve sperm parameters and testis histopathology, which were damaged following cryptorchidism induction. The expression of HO1, NQO1, and Nrf2 genes, which had decreased in the cryptorchidism group, showed a significant increase after administration of Cur in a dose‐dependent manner. Cur, by inducing the expression of genes involved in the Nrf2/Keap1 pathway, could reduce the adverse effects of cryptorchidism and might be used as adjuvant therapy for decreasing cryptorchidism complications before surgery. [ABSTRACT FROM AUTHOR]

Objective: Many studies have revealed the prominent roles of mast cells in wound healing, including inflammatory reactions, angiogenesis and extracellular matrix reabsorption. In the present study, we aimed to assess the probable therapeutic features of bromelain on wound contraction and mast cell degranulation in wound healing in experimental diabetic animals. Method: Male rats were grouped as control, vehicle and experiment. Skin wounds were generated in all groups. Treatments were applied with distilled water and with bromelain (BR) intraperitoneally in the vehicle and experimental groups, respectively. Following skin wound generation, animals were euthanised on days 3, 5, 7 and 15. We gathered 16,800 microscopic images to count the mast cells and degranulation level (Image J software). The wound contraction index was assessed both microscopically (Image J software) and macroscopically (time-lapse photography). The meshwork evaluation method was used to assess wound healing. Results: Time-lapse photography revealed that the BR significantly (p<0.05) accelerated wound contraction and healing. BR significantly (p<0.05) increased the total number of mast cells in all experimental groups on days 5 and 7. The count of grade III (degranulated) mast cells was reduced significantly (p<0.05) on days 5 and 7 in experimental groups compared to control and vehicle groups. Conclusion: In this study, the rate of wound healing was accelerated considerably following BR administration. In addition, this agent decreased the count of degranulated mast cells, leading to wound contraction and healing. [ABSTRACT FROM AUTHOR]

Despite the dramatic efficacy of EGFR‐TKIs, most of non‐small cell lung cancer patients ultimately develop resistance to these agents. In this study, we explored the effects of miRNA‐125a‐5p and miRNA‐145, alone or in combination, EGFR expression, cell growth and sensitivity of the NSCLC cells to erlotinib. The expression of EGFR was measured using RT‐qPCR and Western blotting. The effect of miRNAs and erlotinib on cell growth and survival was assessed by trypan blue assay and MTT assay, respectively. Apoptosis was measured using ELISA cell death assay. We found that transfection of miRNA‐125a‐5p and miRNA‐145 significantly inhibited the expression of EGFR mRNA and protein in a time‐dependent manner (p < 0.05 vs. blank control or negative control miRNA). ANOVA and Bonferroni's test were used to ascertain significant differences between groups. Other experiments indicated that upregulation of each of miRNA‐125a‐5p or miRNA‐145 inhibited cell growth, induced apoptosis, and markedly decreased the IC50 value of erlotinib in A549 lung cancer cells (p < 0.05). Moreover, the combination of two miRNAs showed a stronger effect on cells survival, apoptosis, and drug sensitivity, relative to single miRNA (p < 0.05). The results of our study indicate that the therapeutic delivery of miRNA‐145 and miRNA‐125a‐5p to lung cancer may inhibit cell proliferation, trigger apoptosis, and sensitize lung cancer cells to EGFR‐TKIs. [ABSTRACT FROM AUTHOR]

Background: Varicocele is a common cause of male infertility with multifactorial etiology. Inflammation is a characteristic pathological event that occurs in the testis tissue following the varicocele. The aim of this study was to investigate expression of nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome components and cytokines in semen of varicocele and control subjects. Materials and Methods: In this case-control study, seminal plasma was collected from 32 varicocele patients (with grades 2 and 3) and 20 fertile men as control group. Semen analysis was performed in all subjects. Concentrations of interleukin-1b (IL-1b), IL-18 and caspase-1 in seminal plasma were measured by enzyme-linked immunosorbent assay (ELISA). Apoptosis-associated speck-like protein containing a caspase activation and recruitment domain, in addition to NALP3 were identified in seminal plasma by Western blot. Statistical significance between the mean values was determined by student's t test. Results: According to our data, the level of IL-1b was significantly (P=0.03) increased in the seminal plasma of varicocele patients, compared to the control subjects. We analyzed amount of IL-18 in the both groups. The level of this interleukin was markedly (P=0.002) decreased in varicocele patients. No change was observed in the level of caspase-1 in both groups. Western blot analysis revealed that apoptosis associated speck-like protein (ASC, P=0.0002) and NLRP3 (P=0.005) were significantly elevated in the semen of varicocele patients. Conclusion: This study provides the first evidence of activation of NLRP3 components in semen of men with varicocele. [ABSTRACT FROM AUTHOR]

Oxidative stress is a major complication in diabetes mellitus. The aim of this study was to investigate potential antioxidant activity of coenzyme Q10 (Co Q10) against hyperglycemia-induced oxidative stress in diabetic rat and unraveling its mechanism of action by focusing on silent information regulator 1 (Sirt1) and nuclear factor E2-related factor 2 (Nrf2) mRNA expression level. Furthermore, the activity of two Nrf2-dependent antioxidant enzymes (superoxide dismutase and catalase) in the liver of diabetic rats was studied. After induction of diabetes in rats using streptozotocin (55 mg/kg), rats were divided into five groups of six each. Groups 1 and 2 (healthy control groups) were injected with isotonic saline or sesame oil; group 3 received Co Q10 (10 mg /Kg /day), group 4, as a diabetic control, received sesame oil; and group 5 was diabetic rats treated with Co Q10. Afterwards, serum and liver samples were collected, and oxidative stress markers, lipid profile, as well as the expression of Sirt1 and Nrf2 genes were measured. Diabetes induction significantly reduced expression level of Sirt1 and Nrf2 mRNAs and also declined catalase, superoxide dismutase activities, and total thiol groups levels in diabetic group in comparison to healthy controls, while a significant increase was found in the levels of malondialdehyde and lipid profile. Co Q10 treatment significantly up-regulated Sirt1 and Nrf2 mRNA levels along with an increase in catalase activity in diabetic group as compared with untreated diabetic rats. Furthermore, Co Q10 caused a marked decrease in malondialdehyde levels and significantly improved lipid profile. Our data demonstrated that Co Q10 may exert its antioxidant activity in diabetes through the induction of Sirt1/Nrf2 gene expression. [ABSTRACT FROM AUTHOR]

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) such as Aspirin may have anticancer properties, and can be effective as a novel strategy for the treatment of colorectal cancer (CRC). The aim of this study was to assess the cytotoxic effects of Aspirin drug in CRC cell lines compared with Oxaliplatin drug in vitro. Methods: Cell viability was assessed after treatment of SW742 and SW480 cells with Aspirin and Oxaliplatin by MTT assay, and the amount of IC50 was determined. Statistical analysis was performed through one-way ANOVA and Tukey multiple range analysis (SPSS 19.0 software (P <0.05). Results: Aspirin and Oxaliplatin considerably inhibited the growth of SW742 and SW480 cell lines. SW742 cell line was more sensitive to Aspirin than SW480 cell line. The cytotoxic effect of Oxaliplatin was higher than Aspirin in both cell lines. Conclusions: This study demonstrated that both Aspirin and Oxaliplatin have cytotoxic effects on SW742 and SW480 cell lines in vitro. Thus, Aspirin may be considered as a therapeutic agent in CRC, however, further in vivo investigations are required to fully establish this effect. [ABSTRACT FROM AUTHOR]

Background: Berberine and Nano-curcumin are two herbal medicines with strong anti-cancer effects on tumor cells, but low toxicity on normal cells, when used alone. Breast cancer is known as the most common cancer in women and second deadly one. In this study, we evaluated the cytotoxicity effects of combination Berberine and Nano-curcumin in breast cancer cell line to see whether they have further synergism cytotoxicity on MCF-7 breast cancer cell line. Methods: The cytotoxicity effects of Berberine and Nano-curcumin alone and in combination, were evaluated in MCF-7 cell lines using MTT cytotoxicity test. Statistical analysis is done through one-way ANOVA and Tukey multiple range tests. Results: Analyzing results of this study showed that cytotoxicity of Nano-curcumin was higher than Berberine in a dose-dependent manner. The IC50 of combination Berberine and Nanocurcumin was lower and showed higher cytotoxicity in MCF-7 cells compared with the time we use each of these drugs alone. Conclusion: In this study co-treatment of Berberine and Nano-curcumin significantly inhibited the growth of MCF-7 breast cancer cell line and resulted in synergism cytotoxicity effects. These results indicated on their potency to further combination of these two drugs with other agents and common chemotherapies to improve breast cancer outcomes. [ABSTRACT FROM AUTHOR]

Objective(s): Varicocele is an abnormal dilation in the testicular vein, which can cause hypoxia, reactive oxygen species accumulation, elevation in testicular temperature, and promote apoptosis and increase proinflammatory cytokine production. According to the varicocele pathophysiology, it is possible that a group of cytosolic receptors called nucleotide oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes also involve in varicocele pathogenesis. Due to the important role of antioxidant in decreasing the testis tissue damage, in this study we investigated the protective effect of resveratrol (RES) on NLRP3 complex and apoptosis in experimental varicocele rats. Materials and Methods: In this study, 40 male Wistar rats were randomly divided into 5 groups (8 rats in each group): Control, experimental left varicocele (ELV), ELV + ethanol, ELV + 20 mg/kg RES and ELV + 50 mg/kg RES. Varicocele was induced by partial ligation of the left renal vein. Three months after varicocele induction, RESwas orally administered to rats for 1 month. The expression levels of NLRP3, apoptosis associated specklike protein (ASC), caspase-1, Bax and Bcl2 were analyzed using real time PCR. Results: Our results showed that RESat both doses significantly (P≤ 0.05) decreased the gene expression levels of ASC, NLRP3, caspase-1 and Bax and increased Bcl2 gene expression at high dose. Conclusions: RESby reducing inflammatory factors and decreasing apoptosis might be used as adjuvant therapy to reduce varicocele complication. [ABSTRACT FROM AUTHOR]

We have recently reported that antioxidant supplements enhance the efficacy of cryopreserved spermatogonial stem cells. Melatonin is considered a free radical scavenger which has direct and indirect antioxidant effects inin vitroandin vivomicroenvironments. Due to the anti-apoptotic properties of melatonin, researchers have proposed that melatonin may improve the efficiency of spermatogonial stem cell (SSC) transplantation. However, the appropriate methodology which facilitates SSC proliferation remains to be determined. Identification of a proper propagation system is essential for the future application of SSCs in the field of infertility. The aim of the present study was to investigate the effects of melatonin on the colonization of SSCs. SSCs were isolated from the testes of three to six day old mice, and their purities were assessed by cytometry using Plzfantibody. Isolated testicular cells were cultured in the absence or presence of melatonin extract for two weeks. Suppression of differentiation and maintenance of spermatogonial stem cells was confirmed by alkaline phosphatase staining and immunocytochemistry usingPlzfantibody. The number and diameter of the colonies of SSCs were assessed during the 7thand 14thdays of culture, and the expression ofId4, Plzf, andC-kitwere evaluated using real-time PCR at the end of the culture period. The survival rate of the cultured cells in the presence of melatonin was significantly higher than the control group. The number and diameter of colonies also increased in the cells treated with melatonin. The results of our study suggest that culture of SSCs with 100 μM melatonin supplementation can increase SSCs proliferation significantly. [ABSTRACT FROM AUTHOR]

Objective(s): Vascular endothelial growth factor (VEGF) is one of the most effective proteins in angiogenesis, mesenchymal stem cells (MSCs) differentiation and wound healing. These abilities are therapeutic potential of VEGF in diabetic retinopathy, nephropathy and other tissue damage circumstances. In this study, recombinant VEGF was produced in Escherichia coli (E. coli) sys tem and then biological activity of this protein was evaluated in animal wound healing. Materials and Methods: E. coli BL21 (DE3) competent cells were transformed with pET32a-VEGF clone and induced by isopropyl-β-D-thio-galactoside (IPTG). The recombinant protein was purified by affinity chromatography. Recombinant VEGF-A-based ointment (VEGF/Vaseline 0.8 mg/100 w/w) was used for external wound (25×15mm thickness) healing in animal model. In vivo activity of ointment was evaluated by clinical evidences and cytological microscopic assessment. Results: The recombinant protein with molecular weight of 45 kilodaltons (kDa) and concentration of 0.8 mg/ml was produced. Immunoblotting data showed that the antigenic region of VEGF can be expressed in E. coli and the recombinant protein has similar epitopes with close antigenic properties to the natural form. Macroscopic findings and microscopic data showed that the recombinant VEGF-A ointment was effective on excisional wound healing. Conclusion: Recombinant VEGF-A produced by pET32a in E. coli, possesses acceptable structure and has wound healing capability. [ABSTRACT FROM AUTHOR]

Cryopreservation of spermatogonial stem cells is considered as a useful procedure for preserving fertility in children with testis cancer. SSCs were isolated from testes mice, and then antioxidant was added to the freezing medium. The Bax expression level in antioxidant groups was significantly (P ≤ 0.05) lower than the control group and a significant rise of Bcl2 expression was detected in the antioxidant groups. ROS production with antioxidant was significantly lower compared with the control group. Cryopreservation with the addition of the antioxidants can help increase the number of SSCs and improve the quality and viability of these cells after cryopreservation. [ABSTRACT FROM AUTHOR]

Stem cells are self-renewing and undifferentiated cell types that can be differentiate into functional cells. Stem cells can be classified into two main types based on their source of origin: Embryonic and Adult stem cells. Stem cells also classified based on the range of differentiation potentials into Totipotent, Pluripotent, Multipotent, and Unipotent. Multipotent stem cells have the ability to differentiate into all cell types within one particular lineage. There are plentiful advantages and usages for multipotent stem cells. Multipotent Stem cells act as a significant key in procedure of development, tissue repair, and protection. Multipotent Stem cells have been applying in treatment of different disorders such as spinal cord injury, bone fracture, autoimmune diseases, rheumatoid arthritis, hematopoietic defects, and fertility preservation. [ABSTRACT FROM AUTHOR]