Evaluation of photobiomodulation therapy (117 and 90s) on pain, regeneration, and epigenetic factors (HDAC 2, DNMT3a) expression following spinal cord injury in a rat model.

BACKGROUND: Photobiomodulation therapy (PBMT), due to its anti-inflammatory, analgesic effects, and most importantly as a non-invasive procedure, has currently gained a special setting in pain relief and the treatment of Spinal cord injuries (SCI). However, the mechanism of action of the PBM is not yet completely understood. METHODS: In this study, SCI is induced by an aneurysm clip, and PBM therapy was applied by a continuous-wave (CW) laser with a wavelength of 660 nm. Adult male rats were divided into four groups: Control, SCI, SCI + PBMT 90s, and SCI + PBMT 117s. After 7 weeks, hyperalgesia, allodynia, and functional recovery were assessed. Fibroblasts infiltrating the spinal cord were counted after H&E staining. The expression of epigenetic factors (HDAC2, DNMT3a), protein relevant for pain (GAD65), and astrocytes marker (GFAP) after 4 weeks of daily PBMT (90 and 117s) was probed by western blotting. RESULTS: Both PBMTs (90 and 117s) significantly improved the pain and ability to move and fibroblast invasion was reduced. SCI + PBMT 90s, increased GAD65, HDAC2, and DNMT3a expression. However, PBMT 117s decreased GFAP, HDAC2, and DNMT3a. CONCLUSION: PBMT 90 and 117s improved the pain, and functional recovery equally. The regulation of epigenetic mechanisms appears to be a significant effect of PBMT117s, which emphasizes on impact of radiation duration and accumulative energy.

The potential of curcumin for treating spinal cord injury: a meta-analysis study.

INTRODUCTION: In this paper, we conducted a meta-analysis on the curcumin effect on functional recovery provided by the Basso, Beattie, Brenham (BBB) test for rats, and the Basso mouse scale (BMS) for mice after spinal cord injury (SCI) in animal models. METHOD: Data mining was performed, and the standard mean difference (SMD) between the treated and control (untreated) groups was calculated using the STATA software. Quality control and subgroup analysis were performed. RESULTS: The analysis includes 24 experimental studies that showed curcumin had a strong significance in improving functional recovery after SCI (SMD = 3.38; 95% CI: 2.54-4.22; p < 0.001). When curcumin was administered daily, it had a stronger effect than single-dose treatment or weekly administration. Despite the same effect in the follow-up time before and after 4 weeks post-injury, but later 9 weeks, curcumin had only a moderate effect. Curcumin also significantly reduced the expression of GFAP (Glial fibrillary acidic protein) marker compared to untreated groups. CONCLUSION: These findings suggest that daily administration of curcumin can be an effective approach to improving functional recovery after SCI.

Study of nerve cell regeneration on nanofibers containing cerium oxide nanoparticles in a spinal cord injury model in rats.

Since the CNS is unable to repair itself via neuronal regeneration in adult mammals, alternative therapies need to be found. The use of cerium oxide nanoparticles to repair nerve damage could be a promising approach for spinal cord reconstruction. In this study, we constructed a scaffold containing cerium oxide nanoparticles (Scaffold-CeO2) and investigated the rate of nerve cell regeneration in a rat model of spinal cord injury. The scaffold of gelatin and polycaprolactone was synthesized, and a gelatin solution containing cerium oxide nanoparticles was attached to the scaffold. For the animal study, 40 male Wistar rats were randomly divided into 4 groups (n = 10): (a) Control; (b) Spinal cord injury (SCI); (c) Scaffold (SCI + scaffold without CeO2 nanoparticles); (d) Scaffold-CeO2 (SCI + scaffold containing CeO2 nanoparticles). After creation of a hemisection SCI, scaffolds were placed at the site of injury in groups c and d, and after 7 weeks the rats were subjected to behavioral tests and then sacrificed for preparation of the spinal cord tissue to measure the expression of G-CSF, Tau and Mag proteins by Western blotting and Iba-1 protein by immunohistochemistry. The result of behavioral tests confirmed motor improvement and pain reduction in the Scaffold-CeO2 group compared to the SCI group. Decreased expression of Iba-1 and higher expression of Tau and Mag in the Scaffold-CeO2 group compared to the SCI group could be the result of nerve regeneration caused by the scaffold containing CeONPs as well as relief of pain symptoms.

Time-dependent photobiomodulation management of neuropathic pain induced by spinal cord injury in male rats.

Neuropathic pain (NP) following spinal cord injury (SCI) often lasts for a long time and causes a range of problems that reduce the quality of life. Current treatments are not generally effective; however, photobiomodulation therapy (PBMT) has made some progress in this area. Due to the novelty of this treatment, standard therapeutic protocols have not yet been agreed upon. In the present study, we compare the analgesic effect of two PBMT protocols (2 and 4 weeks of radiation). A total of thirty-two adult male Wistar rats were divided into four groups: control, SCI, 2 W PBMT, and 4 W PBMT. SCI was induced by an aneurism clip and PBMT used a 660-nm, initiated 30 min post-SCI, and continued daily for 2 or 4 weeks. Functional recovery, hyperalgesia, and allodynia were measured weekly. At the end of the study, the Gad65, interleukin 1-alpha (IL1α), interleukin 10 (IL10), IL4, and purinergic receptor (P2xR and P2yR) expressions were measured. Data were analyzed by Prism6. The results showed PBM irradiation for 2 and 4 weeks had the same effects in improving hyperalgesia. In the case of allodynia and functional recovery, 4 W PBMT was more effective (p<0.01). 4 W PBMT increased the Gad65 expression (p <0.001) and reduced P2Y4R (p <0.05) compared to SCI animals. The effects of 2 and 4 W PBMT were the same for IL1α, IL10, and P2X3 receptors. 4 W PBMT was more effective in reducing the complications of SCI such as pain and disability. PBMT therapy is an effective method aimed at immune system function modulation to reduce NP and motor dysfunction.

The Role of Intraspinal Administration of Self-Assembled Peptide on Locomotion Recovery After Spinal Cord Injury: A Systematic Review and Meta-Analysis Study.

BACKGROUND: Spinal cord injury (SCI) treatment is still a challenge and new treatments that help these patients are being considered. Recent studies showed that the use of self-assembled peptide (SAP) can be useful in SCI treatment. MATERIALS AND METHODS: In this meta-analysis, we investigated the effect of SAP administration on locomotion recovery after SCI. Records were obtained from a comprehensive search of data bases. Articles were scrutinized for inclusion and exclusion criteria. Data were analyzed and results were reported as standardized mean difference (SMD) with 95% CI. Subgroup analysis was also performed. RESULTS: A total of 14 studies and 17 separate experiments were included in the final analysis. Treatment with SAP structures after SCI resulted in a significant improvement in animal motor function (SMD = 1.13; 95% CI: 0.68-1.58; p < 0.0001). SAP treatment facilitated axon sprouting (SMD = 0.76; 95% CI: 0.33-1.18; p < 0.0001) and reduction of glial scar (SMD = -1.02; 95% CI: -1.94 to -0.09; p = 0.03). The difference in SAP type, its concentration, follow-up time, and SCI model had no effect on SAP effectiveness. In addition, SAP administration had a similar effect on improving locomotion in all three immediate, acute, and subacute phases which gives the good news of using this treatment for patients who are in the chronic phase. CONCLUSION: SAP treatment can be considered as a potential treatment to help the motor recovery of SCI and axon regeneration.

Sustained delivery of chABC improves functional recovery after a spine injury.

INTRODUCTION: Chondroitinase ABC (chABC) is an enzyme could improve regeneration and thereby improving functional recovery of spinal cord injury (SCI) in rodent models. Degradation of the active enzyme and diffusion away from the lesion are the causes of using hydrogels as a scaffold to deliver the chABC into the lesion site. In this meta-analysis, we investigated the effects of chABC embedded in a scaffold or hydrogel on the functional recovery after SCI. METHOD: Databases were searched based on keywords related to chABC and spinal cord injury (SCI). Primary and secondary screening was performed to narrow down study objectives and inclusion criteria, and finally the data were included in the meta-analysis. The standard mean difference of the score of the functional recovery that measured by Basso, Beattie, Bresnahan (BBB) test after SCI was used to analyze the results of the reported studies. Subgroup analysis was performed based on SCI model, severity of SCI, transplantation type, and the follow-up time. Quality control of articles was also specified. RESULTS: The results showed that embedding chABC within the scaffold increased significantly the efficiency of functional recovery after SCI in animal models (SMD = 1.95; 95% CI 0.71-3.2; p = 0.002) in 9 studies. SCI model, severity of SCI, injury location, transplantation type, and the follow-up time did not affect the overall results and in all cases scaffold effect could not be ignored. However, due to the small number of studies, this result is not conclusive and more studies are needed. CONCLUSION: The results could pave the way for the use of chABC embedded in the scaffold for the treatment of SCI and show that this method of administration is superior to chABC injection alone.

Effect of herbal compounds on coronavirus; a systematic review and meta-analysis.

BACKGROUND: The new coronavirus (COVID-19) has been transmitted exponentially. Numerous studies have been performed in recent years that have shown the inhibitory effect of plant extracts or plant-derived compounds on the coronavirus family. In this study, we want to use systematic review and meta-analysis to answer the question, which herbal compound has been more effective? MAIN BODY: The present study is based on the guidelines for conducting meta-analyzes. An extensive search was conducted in the electronic database, and based on the inclusion and exclusion criteria, articles were selected and data screening was done. Quality control of articles was performed. Data analysis was carried out in STATA software. CONCLUSION: Due to the variety of study methods, definitive conclusions are not possible. However, in this study, we attempted to gather all the available evidence on the effect of plant compounds on SARS-COV-2 to be used for the development and use of promising antiviral agents against this virus and other coronaviruses. Trypthantrin, Sambucus extract, S. cusia extract, Boceprevir and Indigole B, dioica agglutinin urtica had a good effect on reducing the virus titer. Also among the compounds that had the greatest effect on virus inhibition, Saikosaponins B2, SaikosaponinsD, SaikosaponinsA and Phillyrin, had an acceptable selectivity index greater than 10. Andrographolide showed the highest selectivity index on SARS-COV-2. Our study confirmed insufficient data to support alkaloid compounds against SARS-COV-2, and the small number of studies that used alkaloid compounds was a limitation. It is recommended to investigate the effect of more alkaloid compounds against Corona virus.

ERK/HIF-1α/VEGF pathway: a molecular target of ELABELA (ELA) peptide for attenuating cardiac ischemia-reperfusion injury in rats by promoting angiogenesis.

BACKGROUND: Myocardial ischemia-reperfusion (I/R) injury is caused by a chain of events such as endothelial dysfunction. This study was conducted to investigate protective effects of ELABELA against myocardial I/R in Wistar rats and clarify its possible mechanisms. METHODS AND RESULTS: MI model was established based on the left anterior descending coronary artery ligation for 30 min. Then, 5 µg/kg of ELA peptide was intraperitoneally infused in rats once per day for 4 days. Western blot assay was used to assay the expression of t-ERK1/2, and p-ERK1/2 in different groups. The amount of myocardial capillary density, the expression levels of VEGF and HIF-1α were evaluated using immunohistochemistry assay. Masson's trichrome staining was utilized to assay cardiac interstitial fibrosis. The results showed that establishment of MI significantly enhanced cardiac interstitial fibrosis and changed p-ERK1/2/ t-ERK1/2 ratio. Likewise, ELA post-treatment markedly increased myocardial capillary density, the expression of several angiogenic factors (VEGF-A, HIF-1α), and reduced cardiac interstitial fibrosis by activation of ERK1/2 signaling pathways. CONCLUSION: Collectively, ELA peptide has ability to reduce myocardial I/R injury by promoting angiogenesis and reducing cardiac interstitial fibrosis through activating ERK/HIF-1α/VEGF pathway.

Curcumin-coated gold nanoparticles attenuate doxorubicin-induced cardiotoxicity via regulating apoptosis in a mouse model.

Doxorubicin (DOX) is one of the most widely used chemotherapy agents; however, its nonselective effect causes cardiotoxicity. Curcumin (Cur), a well known dietary polyphenol, could exert a significant cardioprotective effect, but the biological application of this substance is limited by its chemical insolubility. To overcome this limitation, in this study, we synthesised gold nanoparticles based on Cur (Cur-AuNPs). Ultraviolet-visible (UV-Vis) absorbance spectroscopy and transmission electron microscopy (TEM) were performed for the characterisation of synthesised NPs, and Fourier transform infrared (FTIR) spectroscopy were applied to detect Cur on the surface of AuNPs. Its cytotoxicity effect on H9c2 cells was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The biological efficacy of Cur-AuNPs was assessed after acute cardiotoxicity induction in BALB/c mice with DOX injection. The serum biomarkers, myocardial histological changes, and cardiomyocyte apoptosis were then measured. The results revealed that the heart protection by Cur-AuNPs is more effective than Cur alone. Heart protective effect of Cur-AuNPs was evident both in the short-term (24 hours) and long-term (14 days) study. The results of Cur-AuNPs400 after 24 hours of toxicity induction displayed the reduction of the cardiac injury serum biomarkers (LDH, CK-MB, cTnI, ADT, and ALT) and apoptotic proteins (Bax and Caspase-3), as well as increase of Bcl-2 anti-apoptotic proteins without any sign of interfibrillar haemorrhage and intercellular spaces in the heart tissue microscopic images. Our long-term study signifies that Cur-AuNPs400 in DOX-intoxicated mice could successfully inhibit body and heart weight loss in comparison to DOX group.

Mechanistic aspects of photobiomodulation therapy in the nervous system.

Photobiomodulation therapy (PBMT) previously known as low-level laser therapy (LLLT) has been used for over 30 years, to treat neurological diseases. Low-powered lasers are commonly used for clinical applications, although recently LEDs have become popular. Due to the growing application of this type of laser in brain and neural-related diseases, this review focuses on the mechanisms of laser action. The most important points to consider include the photon absorption by intracellular structures; the effect on the oxidative state of cells; and the effect on the expression of proteins involved in oxidative stress, inflammation, pain, and neuronal growth.

Antibacterial effect of cerium oxide nanoparticle against Pseudomonas aeruginosa.

BACKGROUND: Antibiotics have been widely used for the treatment of bacterial infections for decades. However, the rapid emergence of antibiotic-resistant bacteria has created many problems with a heavy burden for the medical community. Therefore, the use of nanoparticles as an alternative for antibacterial activity has been explored. In this context, metal nanoparticles have demonstrated broad-spectrum antimicrobial activity. This study investigated the antimicrobial activity of naked cerium oxide nanoparticles dispersed in aqueous solution (CNPs) and surface-stabilized using Pseudomonas aeruginosa as a bacterial model. METHODS: Gelatin-polycaprolactone nanofibers containing CNPs (Scaffold@CNPs) were synthesized, and their effect on P. aeruginosa was investigated. The minimum inhibitory and bactericidal concentrations of the nanoparticls were determined in an ATCC reference strain and a clinical isolate strain. To determine whether the exposure to the nanocomposites might change the expression of antibiotic resistance, the expression of the genes shv, kpc, and imp was also investigated. Moreover, the cytotoxicity of the CNPs was assessed on fibroblast using flow cytometry. RESULTS: Minimum bactericidal concentrations for the ATCC and the clinical isolate of 50 µg/mL and 200 µg/mL were measured, respectively, when the CNPs were used. In the case of the Scaffold@CNPs, the bactericidal effect was 50 µg/mL and 100 µg/mL for the ATCC and clinical isolate, respectively. Interestingly, the exposure to the Scaffold@CNPs significantly decreased the expression of the genes shv, kpc, and imp. CONCLUSIONS: A concentration of CNPs and scaffold@CNPs higher than 50 µg/mL can be used to inhibit the growth of P. aeruginosa. The fact that the scaffold@CNPs significantly reduced the expression of resistance genes, it has the potential to be used for medical applications such as wound dressings.

Chemoprevention of Prostate Cancer Cells by Vitamin C plus Quercetin: role of Nrf2 in Inducing Oxidative Stress.

To assess the effect of sequential treatment with Vitamin C (VC) and Quercetin (Q) on Nrf2-related oxidative stress in PC3 and DU145 cells, viability was measured by MTT assay. Intracellular ROS levels were determined, using 2'-7'-dichlorodihydrofluorescein diacetate fluorescent as a probe. Nrf2 gene expression was investigated by quantitative reverse transcription polymerase chain reaction, and Nrf2 protein levels were defined by western blot analysis. The activity of glutathione peroxidase (GPx), glutathione reductase (GR), nicotinamide adenine dinucleotide phosphate dehydrogenase quinone 1 (NQO1) and hemeoxygenase 1 (HO-1) enzymes were measured. The IC50 values for VC + Q were 263.03-372.1 µM and 144.2-194.1 µM respectively and 200 µM VC + 50 µM Q (dose no.1) and 100 µM VC + 75 µM Q (dose no.2) were selected. Sequential treatment of PC3 cells led to a significant reduction of Nrf2 mRNA expression and protein levels in addition to a significant reduction of GPx, GR and NQO1 enzymatic activity. Although the data was slightly different for DU145 cells after the treatments, in terms of Nrf2 gene expression, we obtained the same results. Our study revealed the significant effects of sequential treatment with VC + Q on Nrf2 suppression in prostate cancer cells.

The Toxic Effect of Silver Nanoparticles on Nerve Cells: A Systematic Review and Meta-Analysis.

Despite the increasing use of silver nanoparticles in medical sciences, published studies on their interaction with nerve cells and evaluation of risks are dispersed. This systematic review and meta-analysis could be used to devise safety guidelines for the use of silver nanoparticles in industry and medicine to reduce adverse effects on the CNS.After extensive searches, the full text of 30 related studies was reviewed and data mining completed. Data were analyzed by calculating the mean of different ratios between treated and untreated groups. Linear regression between variables was evaluated by meta-regression. Subgroup analysis was also performed due to heterogeneity.Treatment with silver nanoparticles significantly reduced cell viability (SMD = -1.79%; 95% CI: -2.17 to -1.40; p < 0.0001). Concentration > 0.1 µg/mL could kill neurons, while lower concentration would not (SMD -0.258; 95% CI: -0.821 to 0.305; p = 369). In addition to the concentration, the coating, size of the nanoparticles, and cell type are also factors that influence SNP nerve cell toxicity. Measurement of apoptosis (SMD = 2.21; 95% CI: 1.62 to 2.80; p=0.001) and lactate dehydrogenase release rate (SMD = 0.9; 95% CI: 0.33 to 1.47; p < 0.0001) also confirmed the destructive effect of silver nanoparticles on nerve cells.

Necroptosis and RhoA/ROCK pathways: molecular targets of Nesfatin-1 in cardioprotection against myocardial ischemia/reperfusion injury in a rat model.

Nesfatin-1 as a new energy-regulating peptide has been known to display a pivotal role in modulation of cardiovascular functions and protection against ischemia/reperfusion injury. However, the detailed knowledge about molecular mechanisms underlying this protection has not been completely investigated yet. This study was designed to clarify the molecular mechanisms by which nesfatin-1 exert cardioprotection effects against myocardial ischemia-reperfusion (MI/R). Left anterior descending coronary artery (LAD) was ligated for 30 min to create a MI/R model in rats. MI/R rats were treated with three concentrations of nesfatin-1 (10, 15 and 20 µg/kg) then expression of necroptosis and necrosis mediators were measured by western blotting assay. Fibrosis, morphological damages, cardiac function, myocardial injury indictors and oxidative stress factors were evaluated as well. Induction of MI/R model resulted in cardiac dysfunction, oxidative stress, increased activity of RIPK1-RIPK3-MLKL axis and RhoA/ROCK pathway, extension of fibrosis and heart tissue damage. Highest tested concentration of nesfatin-1 markedly improved cardiac function. Moreover, it reduced oxidative stress, collagen deposition, and morphological damages, through inhibiting the expression of necroptosis mediators and also, necrosis including RIPK1, RIPK3, MLKL, ROCK1, and ROCK2 proteins. The lowest and middle tested concentrations of nesfatin-1 failed to exert protective effects against MI/R. These findings have shown that nesfatin-1 can exert cardioprotection against MI/R in a dose dependent manner by suppressing necroptosis via modulation of RIPK1-RIPK3-MLKL axis and RhoA/ROCK/RIP3 signaling pathway.

High-intensity interval training increases myocardial levels of Klotho and protects the heart against ischaemia-reperfusion injury.

NEW FINDINGS: What is the central question of this study? Can short-term high-intensity interval training (HIIT) contribute to the reduction of ischaemia-reperfusion (IR) injury by enhancing the levels of Klotho and its related axes, including myocardial TRPC6 expression, and antioxidant defence as novel possible mechanisms of exercise-induced cadioprotection (EICP) against IR injury? What is the main finding and its importance? The increase of plasma and myocardial levels of Klotho as a result of preconditioning with HIIT and prevention of a significant reduction of Klotho during IR injury can promote cardioprotection and reduce damage by attenuating myocardial TRPC6 expression and increasing antioxidant defence. The present findings may provide a new mechanism in EICP and IR injury, and provide the knowledge to develop preventive and therapeutic approaches. ABSTRACT: Cardiovascular disease, especially coronary artery disease, remains a major cause of morbidity and mortality in the world, and ischaemia-reperfusion (IR) insult is the main pathological cause leading to death. Exercise training is associated with a reduced risk of cardiovascular disease and the development of cardioprotection against IR injury. Therefore, the purpose of this study was to investigate the effect of preconditioning with high-intensity interval training (HIIT) on myocardial and plasma levels of Klotho and its related axes as novel mechanisms of exercise-induced cardioprotection against IR injury. Seventy male Wistar rats were randomly divided into five groups of control, HIIT, sham, IR and HIIT group that underwent IR injury (H-IR). The training group performed five sessions of HIIT on the treadmill. The cardiac IR injury was induced by ligation of the left anterior descending coronary artery for 30 min followed by 24 h reperfusion. Infarct size and histopathological assessment of cardiac tissues were determined through Evans Blue-triphenyltetrazolium chloride and haematoxylin-eosin staining, respectively. We investigated lipid peroxidation and markers of cardiac injury, antioxidant enzymes and the plasma levels of Klotho using enzyme-linked immunosorbent assays. Also, myocardial levels of Klotho and TRPC6 expression were determined by western blot assays. The results demonstrated a significant increase in myocardial and plasma levels of Klotho following HIIT and a significant decrease during IR injury. Myocardial TRPC6 channel expression increased following IR. HIIT also prevented a significant reduction of Klotho during IR and consequently reduced the expression of the TRPC6 channel in the H-IR group compared with the IR group. Furthermore, HIIT decreased the infarct size, cardiac injury, lipid peroxidation, lactate dehydrogenase, creatine kinase myocardial band and cardiac troponin-I, and improved total antioxidant capacity and catalase, superoxide dismutase and glutathione peroxidase activities following IR injury. The findings of the present study suggest that HIIT improves cardioprotection against IR injury and reduces cardiac damages through an increase in myocardial and plasma levels of Klotho and its related axes (TRPC6 and antioxidant defence). These findings can help to develop preventive and therapeutic approaches.

Application of ɑ-Tocotrienol-Loaded Biocompatible Precirol in Attenuation of Doxorubicin Dose-Dependent Behavior in HUH-7 Hepatocarcinoma Cell Line.

Tumor-targeted nanoparticle delivery system has been known as a substitute and capable achievement in cancer treatment compared to conventional methods. In this study, we examined potential application of ɑ-tocotrienol-Precirol formulation to enhance efficiency of doxorubicin (DOX) in induction of apoptosis in HUH-7 hepatocarcinoma cells. ɑ-tocotrienol-loaded nanoparticles were characterized at the point of zeta potential, particle size, scanning electron microscope (SEM), and cell internalization. To evaluate antiproliferative effects of formulation, apoptosis, cell cycle procedure, flow cytometry, and MTT assays were employed. Optimum size of the ɑ-tocotrienol formulation revealed narrow size distribution with mean average of 78 ± 3 nm. IC50 values for ɑ-tocotrienol and ɑ-tocotrienol-nano structured lipid carriers after 24 h were 15 ± 0.6 and 10 ± 0.03 µM, respectively. After incubation of cells with ɑ-tocotrienol-loaded careers, the rate of cell proliferation decreased from 53 ± 6.1 to 34 ± 7.1% (P < 0.05). A significant improvement in the apoptosis percentage was revealed after treatment of the HUH-7 cell line with DOX and ɑ-tocotrienol careers (P < 0.05). Gene expression results demonstrated a marked decrease in survivin and increase in Bid and Bax levels. Our findings suggest that ɑ-tocotrienol-loaded nanoparticles elevate DOX efficacy in HUH-7 hepatocarcinoma cell.

The effect of preconditioning with high-intensity training on tissue levels of G-CSF, its receptor and C-kit after an acute myocardial infarction in male rats.

BACKGROUND: Exercise training is known as a practical way to increase cardioprotection against stress, and it seems that stem cell recruitment is one of its mechanisms. The purpose of the present study was to investigate the effect of preconditioning with High-intensity interval training (HIIT) on tissue levels of G-CSF, its receptor and C-Kit following acute myocardial infarction in male rats. METHODS: Twenty Male Wistar rats were randomly divided into 4 groups of control, MI, HIIT, and HIIT+MI. Training groups performed 2 weeks of high intensity interval training in 4 sections. The first section consisted training in 3 days and 2 sessions in each day (4 × 2 min with 35-40 m/min and 3 × 2 min with 25-30 m/min between high intervals. The second part included 2 days of training (4 × 2 min with 40 to 45 m/min and 3 × 2 min with 28 to 32 m /min). The third part was performed in 3 days with one more repetition. The fourth section consisted 2 days of training and with one more repetition compared to section 3. For induction of myocardial infarction, subcutaneous injection of isoprenaline was used. CK, total CK, LDH, and troponin T were measured in serum and G-CSF, G-CSFR and C-Kit proteins were measured by the Western Blot method in the heart tissue. RESULTS: The results of this study showed that enzymes of CK, total CK, LDH, troponin T had a significant increase in both MI and HIIT+MI groups compared to the other two groups (P < 0.001) and these indices in the MI group were significantly higher than the HIIT+MI group. Also, the results demonstrated that G-CSF, G-CSFR and C-Kit protein expression in the heart tissue significantly increased after MI. As well as, 2 weeks of HIIT training significantly increased G-CSF and C-kit in the training group compared to the control group, but the training caused that these proteins does not increase in HIIT+MI group as much as MI group. CONCLUSIONS: Along with other protective pathways, high intensity interval training can increase cardioprotection and decrease heart injuries through the increase in G-CSF, G-CSFR and C-kit level.

Identification of Nrf2/STAT3 axis in induction of apoptosis through sub-G 1 cell cycle arrest mechanism in HT-29 colon cancer cells.

We investigated the role of stattic as an adjuvant molecule to increase the cytotoxicity of 5-fluorouracil (5-FU) through specific inhibition of molecular targets, signal transducer and activator of transcription 3 (STAT3) and nuclear factor erythroid 2-related factor 2 (Nrf2) in HT-29 colon cancer cells. Cytotoxicity and apoptotic effects were investigated by methylthiazolyldiphenyl-​tetrazolium bromide assay and flow cytometry analysis, respectively. Real-time polymerase chain reaction was applied to assess the messenger RNA (mRNA) level of STAT3, Nrf2, and apoptotic genes including Bax, Bcl-xl, and Bcl-2. The antitumor effect of 5-FU in combination with stattic induced synergistic effect in HT-29 cells with combination indexes (CIs) 0.49. Flow cytometric results related to apoptotic confirmed that there was up to 40% increase in the population of apoptotic cells in HT-29 colon cancer cells incubated with 5-FU and stattic compared with control groups. Our data from gene expression determined a substantial diminish in the mRNA levels of the Nrf2 and antiapoptotic gene Bcl-2 along with a noticeable increase in the level of the proapoptotic Bax in HT-29 colon cells that underwent cotreatment with 5-FU and stattic (P < 0.05). Moreover, the results exhibited that stattic can be used as adjuvant chemotherapy besides the 5-FU. This therapeutic approach in colon cancer could mediate 5-FU chemoresistance via modulating therapeutic targets (ie, STAT3 and Nrf2 pathways) and decreased 5-FU-related adverse effects.

The greater effect of high-intensity interval training versus moderate-intensity continuous training on cardioprotection against ischemia-reperfusion injury through Klotho levels and attenuate of myocardial TRPC6 expression.

BACKGROUND: Myocardial ischemia-reperfusion (IR) injury is a leading cause of death all over the world, so developing practical approaches to promote cardioprotection against IR injury is essential. Exercise training is an effective strategy to improve cardioprotection. Hence, the purpose of this study was to investigate the effect of short-term preconditioning with two types of high-intensity interval training (HIIT) and moderate intensity continuous training (MICT) on klotho and TRPC6 mechanisms in cardioprotection. METHODS: Eighty Male Wistar rats (250-300 g) were randomly divided into 7 groups, including Control, HIIT, MICT, Sham, IR, HIIT+IR, and MICT+IR. Training was performed in 5 consecutive days. HIIT protocol consisted of running on the treadmill at intervals 85-90% vo2max that separated by slow intensity periods at 50-60% vo2max. MICT program was performed at 70% VO2max at the same running distance with HIIT groups. The cardiac IR injury was induced by LAD occlusion followed by reperfusion. ELISA kit was used in order to measure the plasma levels of klotho, LDH and CK-MB, and TRPC6 expression was determined using the western blot technique. Data were analyzed using one way ANOVA and Tukey's post hoc tests. RESULTS: The results of this study showed that both types of exercise training programs significantly increase plasma levels of klotho and reduce the infarct size and heart injury. In addition, the exercise training decreased the amount of TRPC6 channels expression during IR. However, the effect of HIIT on increasing the klotho and cardioprotection was greater compared to MICT. CONCLUSIONS: Based on the results, even a short-term of aerobic exercise training, especially HIIT, promotes cardioprotection against IR injury and decreases infarct size via an increase in klotho and attenuate of protein expression of myocardial TRPC6 during IR.

Combination Effect of Caffeine and Caffeic Acid Treatment on the Oxidant Status of Ectopic Endometrial Cells Separated from Patients with Endometriosis.

BACKGROUND: Endometriosis is a common gynecological disease in which oxidative stress is a potential factor. Caffeine and caffeic acid are present in various foods and beverages with anti-oxidant, anti-inflammatory, and anti-carcinogenic properties. In this study, we aimed to investigate the ameliorative effects of caffeine, caffeic acid, and caffeine+caffeic acid treatments on oxidative stress in ectopic endometrial cells taken from patients and eutopic ones from women without endometriosis. METHODS: In this experimental study, eutopic and ectopic endometrial cells were obtained from biopsies of women free of disease (n=10) and patients with endometriosis (n=10) who referred to Shiraz reference hospitals (2017-2018). Both eutopic and ectopic endometrial cells were divided into four groups: Treated with caffeine, with caffeic acid, with caffeine+caffeic acid, and the control. Also, antioxidant enzyme activities and the levels of glutathione (GSH) and malondialdehyde (MDA) were determined in each group. The data were analyzed using independent sample t test and one-way ANOVA followed by Tukey post-hoc test. RESULTS: Caffeic acid, but not caffeine treatment demonstrated a decrease in MDA level (P<0.001) as well as an increase in GSH level (P<0.001) and antioxidant enzyme activities in ectopic endometrial cells. Also, the treatment of the cells with caffeine+caffeic acid caused similar effects as those ectopic cells treated with caffeic acid. CONCLUSION: According to the findings of the present study, caffeic acid reduced oxidative stress which may alleviate the complications associated with endometriosis. However, more investigations are needed for evaluating the efficiency and safety of caffeic acid.