Microfluidic systems for modeling digestive cancer: a review of recent progress.

Purpose. This review aims to highlight current improvements in microfluidic devices designed for digestive cancer simulation. The review emphasizes the use of multicellular 3D tissue engineering models to understand the complicated biology of the tumor microenvironment (TME) and cancer progression. The purpose is to develop oncology research and improve digestive cancer patients' lives.Methods. This review analyzes recent research on microfluidic devices for mimicking digestive cancer. It uses tissue-engineered microfluidic devices, notably organs on a chip (OOC), to simulate human organ function in the lab. Cell cultivation on modern three-dimensional hydrogel platforms allows precise geometry, biological components, and physiological qualities. The review analyzes novel methodologies, key findings, and technical progress to explain this field's advances.Results. This study discusses current advances in microfluidic devices for mimicking digestive cancer. Micro physiological systems with multicellular 3D tissue engineering models are emphasized. These systems capture complex biochemical gradients, niche variables, and dynamic cell-cell interactions in the tumor microenvironment (TME). These models reveal stomach cancer biology and progression by duplicating the TME. Recent discoveries and technology advances have improved our understanding of gut cancer biology, as shown in the review.Conclusion. Microfluidic systems play a crucial role in modeling digestive cancer and furthering oncology research. These platforms could transform drug development and treatment by revealing the complex biology of the tumor microenvironment and cancer progression. The review provides a complete summary of recent advances and suggests future research for field professionals. The review's major goal is to further medical research and improve digestive cancer patients' lives.

In silico design of a novel multi-epitope vaccine against HCV infection through immunoinformatics approaches.

Infection with the hepatitis C virus (HCV) is one of the causes of liver cancer, which is the world's sixth most prevalent and third most lethal cancer. The current treatments do not prevent reinfection; because they are expensive, their usage is limited to developed nations. Therefore, a prophylactic vaccine is essential to control this virus. Hence, in this study, an immunoinformatics method was applied to design a multi-epitope vaccine against HCV. The best B- and T-cell epitopes from conserved regions of the E2 protein of seven HCV genotypes were joined with the appropriate linkers to design a multi-epitope vaccine. In addition, cholera enterotoxin subunit B (CtxB) was included as an adjuvant in the vaccine construct. This study is the first to present this epitopes-adjuvant combination. The vaccine had acceptable physicochemical characteristics. The vaccine's 3D structure was predicted and validated. The vaccine's binding stability with Toll-like receptor 2 (TLR2) and TLR4 was confirmed using molecular docking and molecular dynamics (MD) simulation. The immune simulation revealed the vaccine's efficacy by increasing the population of B and T cells in response to vaccination. In silico expression in Escherichia coli (E. coli) was also successful.

Association between cytomegalovirus infection and neurological disorders: A systematic review.

Cytomegalovirus (CMV) belongs to the Herpesviridae family and is also known as human herpesvirus type 5. It is a common virus that usually doesn't cause any symptoms in healthy individuals. However, once infected, the virus remains in the host's body for life and can reactivate when the host's immune system weakens. This virus has been linked to several neurological disorders, including Alzheimer's disease, Parkinson's disease, Autism spectrum disorder, Huntington's disease (HD), ataxia, Bell's palsy (BP), and brain tumours, which can cause a wide range of symptoms and challenges for those affected. CMV may influence inflammation, contribute to brain tissue damage, and elevate the risk of moderate-to-severe dementia. Multiple studies suggest a potential association between CMV and ataxia in various conditions, including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, acute cerebellitis, etc. On the other hand, the evidence regarding CMV involvement in BP is conflicting, and also early indications of a link between CMV and HD were challenged by subsequent research disproving CMV's presence. This systematic review aims to comprehensively investigate any link between the pathogenesis of CMV and its potential role in neurological disorders and follows the preferred reporting items for systematic review and meta-analysis checklist. Despite significant research into the potential links between CMV infection and various neurological disorders, the direct cause-effect relationship is not fully understood and several gaps in knowledge persist. Therefore, continued research is necessary to gain a better understanding of the role of CMV in neurological disorders and potential treatment avenues.

PCL-based nanoparticles for doxorubicin-ezetimibe co-delivery: A combination therapy for prostate cancer using a drug repurposing strategy.

Introduction: Drug repurposing is an effective strategy for identifying the use of approved drugs for new therapeutic purposes. This strategy has received particular attention in the development of cancer chemotherapy. Considering that a growing body of evidence suggesting the cholesterol-lowering drug ezetimibe (EZ) may prevent the progression of prostate cancer, we investigated the effect of EZ alone and in combination with doxorubicin (DOX) on prostate cancer treatment. Methods: In this study, DOX and EZ were encapsulated within a PCL-based biodegradable nanoparticle. The physicochemical properties of drug containing nanoparticle based on PCL-PEG-PCL triblock copolymer (PCEC) have been exactly determined. The encapsulation efficiency and release behavior of DOX and EZ were also studied at two different pHs and temperatures. Results: The average size of nanoparticles (NPs) observed by field emission scanning electron microscopy (FE-SEM) was around 82±23.80 nm, 59.7±18.7 nm, and 67.6±23.8 nm for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively, which had a spherical morphology. In addition, DLS measurement showed a monomodal size distribution of around 319.9, 166.8, and 203 nm hydrodynamic diameters and negative zeta potential (-30.3, -6.14, and -43.8) mV for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively. The drugs were released from the NPs sustainably in a pH and temperature-dependent manner. Based on the MTT assay results, PCEC copolymer exhibited negligible cytotoxicity on the PC3 cell line. Therefore, PCEC was a biocompatible and suitable nano-vehicle for this study. The cytotoxicity of the DOX-EZ-loaded NPs on the PC3 cell line was higher than that of NPs loaded with single drugs. All the data confirmed the synergistic effect of EZ in combination with DOX as an anticancer drug. Furthermore, fluorescent microscopy and DAPI staining were performed to show the cellular uptake, and morphological changes-induced apoptosis of treated cells. Conclusion: Overall, the data from the experiments represented the successful preparation of the nanocarriers with high encapsulation efficacy. The designed nanocarriers could serve as an ideal candidate for combination therapy of cancer. The results corroborated each other and presented successful EZ and DOX formulations containing PCEC NPs and their efficiency in treating prostate cancer.

Comparison of Efficacy and Safety of Levetiracetam Versus Phenytoin for Post-craniotomy Seizure Prophylaxis.

Background: Superiority of levetiracetam over phenytoin for postcraniotomy seizure prophylaxis in patients with a supratentorial brain tumor is controversial. We aimed to evaluate the efficacy of levetiracetam versus phenytoin for postcraniotomy seizure prophylaxis in supratentorial brain tumor. Methods: In a randomized controlled trial study, 80 patients with a supratentorial brain tumor who underwent craniotomy were allocated to levetiracetam or phenytoin group, 40 patients each. Seizure prophylaxis was started 5 days before the surgery and continued until 90 days after surgery. Phenytoin group received 100 mg oral phenytoin 3 times a day. The levetiracetam group received 500 mg oral levetiracetam 2 times a day. The primary outcome was the incidence of postcraniotomy seizures. The secondary outcome measure was the safety profile of the drugs. Results: All patients of the phenytoin group and 39 patients of levetiracetam completed the study. Two seizures developed in the study population, 1 in the phenytoin group (2.5%) and 1 in the levetiracetam group (2.6%) (P = 0.710). Renal or hepatic dysfunction was not observed in any patients. Wound hematoma was seen in 5 patients (12.5%) of the phenytoin and 6 patients (15.4%) of the levetiracetam group (P = 0.481). Skin rash developed in 3 patients (7.5%) of the phenytoin group and no patient of the levetiracetam group (P = 0.132). Thrombocytopenia was detected in 1 patient of the phenytoin group (2.5%) and no patient of the levetiracetam group (P = 0.511). None of the adverse events led to drug withdrawal. Conclusion: These results reveal no superiority of levetiracetam over phenytoin for postcraniotomy seizure prophylaxis in supratentorial brain tumor.

The Novel Role of Crocus sativus L. in Enhancing Skin Flap Survival by Affecting Apoptosis Independent of mTOR: A Data-Virtualized Study.

BACKGROUND: Despite the improvements to enhance skin flap viability, the effects of ischemia-reperfusion (IR), oxidative stress, necrosis, and apoptosis are still challenging. Crocus sativus L. (Saffron) is highly noticeable due to its tissue-protective and antioxidant properties. So, we aimed to investigate its effects on skin flap viability, oxidative stress, apoptosis markers, histopathological changes, and mTOR/p-mTOR expression. MATERIALS AND METHODS: 40 Sprauge-Dawley rats, weighting 200-240 g, were divided into four groups including: (1) Sham (8 × 3 cm skin cut, without elevation); (2) Flap Surgery (8 × 3 cm skin flap with elevation from its bed); (3) Saffron 40 mg/kg + Flap Surgery; and (4) Saffron 80 mg/kg + Flap Surgery. Saffron was administrated orally for 7 days. At day 7, flap necrosis percentage, histopathological changes, malondialdehyde level, Myeloperoxidase and superoxide dismutase activity, Bax, Bcl-2, mTOR, and p-mTOR expression were measured. Protein expressions were controlled by ß-Actin. RESULTS: Saffron administration decreased flap necrosis percentage (p < 0.01), which was not dose-dependent. Treatment groups showed significant histological healing signs (Neovascularization, Fibroblast migration, Epithelialization, and Epithelialization thickness), decreased MDA content (p < 0.01), increased SOD (p < 0.01) and decreased MPO activity (p < 0.01). Bax and Bcl-2 expression, decreased and increased respectively in treated groups (p < 0.0001). mTOR and p-mTOR expression were not changed significantly in Saffron treated groups. CONCLUSION: Saffron could increase skin flap viability, alleviate necrosis, decrease oxidative stress and decrease apoptotic cell death, after skin flap surgery, but it acts independent of the mTOR pathway. So, Saffron could potentially be used clinically to enhance skin flap viability. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. https://www.springer.com/00266.

In silico design of a multi-epitope vaccine against HPV16/18.

BACKGROUND: Cervical cancer is the fourth most common cancer affecting women and is caused by human Papillomavirus (HPV) infections that are sexually transmitted. There are currently commercially available prophylactic vaccines that have been shown to protect vaccinated individuals against HPV infections, however, these vaccines have no therapeutic effects for those who are previously infected with the virus. The current study's aim was to use immunoinformatics to develop a multi-epitope vaccine with therapeutic potential against cervical cancer. RESULTS: In this study, T-cell epitopes from E5 and E7 proteins of HPV16/18 were predicted. These epitopes were evaluated and chosen based on their antigenicity, allergenicity, toxicity, and induction of IFN-γ production (only in helper T lymphocytes). Then, the selected epitopes were sequentially linked by appropriate linkers. In addition, a C-terminal fragment of Mycobacterium tuberculosis heat shock protein 70 (HSP70) was used as an adjuvant for the vaccine construct. The physicochemical parameters of the vaccine construct were acceptable. Furthermore, the vaccine was soluble, highly antigenic, and non-allergenic. The vaccine's 3D model was predicted, and the structural improvement after refinement was confirmed using the Ramachandran plot and ProSA-web. The vaccine's B-cell epitopes were predicted. Molecular docking analysis showed that the vaccine's refined 3D model had a strong interaction with the Toll-like receptor 4. The structural stability of the vaccine construct was confirmed by molecular dynamics simulation. Codon adaptation was performed in order to achieve efficient vaccine expression in Escherichia coli strain K12 (E. coli). Subsequently, in silico cloning of the multi-epitope vaccine was conducted into pET-28a ( +) expression vector. CONCLUSIONS: According to the results of bioinformatics analyses, the multi-epitope vaccine is structurally stable, as well as a non-allergic and non-toxic antigen. However, in vitro and in vivo studies are needed to validate the vaccine's efficacy and safety. If satisfactory results are obtained from in vitro and in vivo studies, the vaccine designed in this study may be effective as a therapeutic vaccine against cervical cancer.

Role of Polyphenols on Gut Microbiota and the Ubiquitin-Proteasome System in Neurodegenerative Diseases.

Today, neurodegenerative diseases have become a remarkable public health challenge due to their direct relation with aging. Accordingly, understanding the molecular and cellular mechanisms occurring in the pathogenesis of them is essential. Both protein aggregations as a result of the ubiquitin-proteasome system (UPS) inefficiency and gut microbiota alternation are the main pathogenic hallmarks. Polyphenols upregulating this system may decrease the developing rate of neurodegenerative diseases. Most of the dietary intake of polyphenols is converted into other microbial metabolites, which have completely different biological properties from the original polyphenols and should be thoroughly investigated. Herein, several prevalent neurodegenerative diseases are pinpointed to explain the role of gut microbiota alternations and the role of molecular changes, especially UPS down-regulation in their pathogenesis. Some of the most important polyphenols found in our diet are explained along with their microbial metabolites in the body.

Ubiquitin-proteasome system and the role of its inhibitors in cancer therapy.

Despite all the other cells that have the potential to prevent cancer development and metastasis through tumour suppressor proteins, cancer cells can upregulate the ubiquitin-proteasome system (UPS) by which they can degrade tumour suppressor proteins and avoid apoptosis. This system plays an extensive role in cell regulation organized in two steps. Each step has an important role in controlling cancer. This demonstrates the importance of understanding UPS inhibitors and improving these inhibitors to foster a new hope in cancer therapy. UPS inhibitors, as less invasive chemotherapy drugs, are increasingly used to alleviate symptoms of various cancers in malignant states. Despite their success in reducing the development of cancer with the lowest side effects, thus far, an appropriate inhibitor that can effectively inactivate this system with the least drug resistance has not yet been fully investigated. A fundamental understanding of the system is necessary to fully elucidate its role in causing/controlling cancer. In this review, we first comprehensively investigate this system, and then each step containing ubiquitination and protein degradation as well as their inhibitors are discussed. Ultimately, its advantages and disadvantages and some perspectives for improving the efficiency of these inhibitors are discussed.

Amniotic Membrane-Derived Mesenchymal Stem Cells for Heart Failure: A Systematic Review and Meta-Analysis of the Published Preclinical Studies.

Background: Ischemic cardiomyopathies are the leading causes of mortality and morbidity. Stem cell therapy using amniotic membrane mesenchymal stem cells have emerged as a promising cardiac regeneration modality. They have shown great immunological advantage when used in allogeneic or xenogeneic transplantation. The aim of the current study is to accumulate evidence from published preclinical studies on the application of amniotic membrane derived mesenchymal stem cells (AMSCs) in the treatment of ischemic cardiomyopathies including myocardial ischemia and heart failure. The aim is to define if there is enough high-quality current evidence to support starting the use of these cells in clinical trials. Methods: PubMed, SCOPUS, EMBASE, and ISI Web of Science databases were searched without temporal and language restrictions. Data were extracted from selected studies. The primary outcomes were left ventricular ejection fraction (LVEF) and LV fibrosis. The risk of bias (ROB) assessment was performed using SYRCLE's ROB tool. After qualitative synthesis, provided that data meets the criteria for quantitative analysis, a meta-analysis was performed using Stata software V12 to investigate the heterogeneity of the data and to get an overall estimate of the effect size of the treatment on each outcome. Results: On primary search, 438 citations were retrieved. After screening, three studies were selected for quantitative analysis of each of the outcomes LVEF and LV fibrosis. Their administration in acute and chronic MI alleviates heart failure and improves LVEF (SMD=3.56, 95% CI: 2.24-4.87, I-squared=83.1%, p=0.003) and reduces infarct size (SMD= -4.41, 95% CI: (-5.68)-(-3.14), I-squared=79.0%, p=0.009). These observations were achieved in the acute MI model, HF following ischemia due to coronary artery stenosis and coronary artery occlusion with the early restoration of the perfusion. Conclusion: Present low and medium quality evidence from preclinical studies confirm the efficacy of the AMSCs in the preclinical models of acute MI and HF following ischemia due to coronary artery stenosis and permanent/temporary coronary artery occlusion. High-quality preclinical studies are indicated to bridge the gaps in translation of the current findings of AMSCs research for the treatment of patients with acute and chronic myocardial ischemia and heart failure.

Significant effect of simvastatin and/or ezetimibe-loaded nanofibers on the healing of femoral defect: An experimental study.

BACKGROUND: Fracture healing complications are associated with significant healthcare and economic burden. In this study, we aimed to investigate how the combined administration of local simvastatin and ezetimibe into the femoral defect of the animal model affects the bone-healing process in comparison with their monotherapy. METHODS: A total of 32 four-month-old adult male Wistar rats were randomized into the four study groups: simvastatin + ezetimibe-loaded nanofibers (group 1), simvastatin-loaded nanofibers (group 2), ezetimibe-loaded nanofibers (group 3), and non-loaded nanofibers (group 4). After the generation of femoral defects, the predesigned nanofibers were locally administered into the defect site. The healing measures were serum and bone osteoprotegerin (OPG) expression, pathologic evaluation of union (Allen's fracture healing scores), and radiographic evaluation of bone density (Hounsfield scale) at weeks 2 and 4. RESULTS: The improvement of all evaluated healing measures was remarkably superior in rats that were treated with loaded nanofibers in comparison with the control group. Also, the improvement of all evaluated healing measures was considerably more in the simvastatin-ezetimibe combination therapy group compared to their monotherapy. All the evaluated measures were superior in the ezetimibe monotherapy group compared to the simvastatin monotherapy group. CONCLUSION: The cumulative effect of simvastatin and ezetimibe on the induction of bone healing is more significant than the individual effect of these drugs. Therefore, local administration of nanofibers loaded with simvastatin and ezetimibe could be regarded as a promising osteoinductive compound for the acceleration of bone repair.

Preparation, characterization, and evaluation of the anticancer activity of artemether-loaded nano-niosomes against breast cancer.

BACKGROUND: The aim of this study was to develop nonionic surfactant vesicles (niosomes) as a promising nanocarrier to enhance the anticancer activity of artemether. METHODS: The niosomes were prepared by thin-film hydration method containing a mixture of Span, Tween and cholesterol (Chol) in different molar ratios. All formulations were characterized in terms of size, entrapment efficiency (%EE), release profile and morphology. The optimized niosomal formulation (F7), artemether and phosphate buffered saline (PBS) were intratumorally administrated to mice as the nano-niosome group, the free drug group and the control group, respectively (n = 4 per group). Tumor volume was measured during the 12-day experiment, then mice were sacrificed to evaluate the necrosis, angiogenesis, and cell proliferation of tumor tissues by H&E, CD34 and Ki-67 immunostaining, respectively. RESULTS: Both artemether and nano-niosome groups could decrease angiogenesis and proliferation of tumor cells. However, in nano-niosome group superior tumor necrosis and smaller tumor volume were observed compared to both artemether and control groups. CONCLUSIONS: The niosomal formulation could be a promising carrier for breast cancer treatment.

The effect of chrysin-curcumin-loaded nanofibres on the wound-healing process in male rats.

AIM: The aim of the present study was to produce chrysin-curcumin-loaded PCL-PEG nanofibres by an electrospinning technique and to evaluate the biological activity of the chrysin-curcumin-loaded PCL-PEG fibres for wound healing and its related genes using in vivo methods. MATERIALS AND METHODS: The electrospinning method was carried out for the preparation of the chrysin, curcumin and chrysin-curcumin-loaded PCL-PEG nanofibres with different concentrations. FTIR and SEM were performed to characterize the chemical structures and morphology of the nanofibres. In vitro drug release, as well as in vivo wound-healing studies were investigated in male rats. The expressions of genes related to the wound-healing process were also evaluated by real-time PCR. RESULTS: Our study showed that the chrysin-curcumin-loaded nanofibres have anti-inflammatory properties in several stages of the wound-healing process by affecting the IL-6, MMP-2, TIMP-1, TIMP-2 and iNOS gene expression. Our results demonstrated that the effect of the chrysin-loaded nanofibre, the curcumin-loaded nanofibre and the chrysin-curcumin-loaded nanofibre in the wound-healing process is dose dependent and in accordance with the obtained results in that it might affect the inflammation phase more than the other stages of the wound-healing process. CONCLUSION: We have introduced chrysin-curcumin-loaded PCL-PEG nanofibres as a novel compound for shortening the duration of the wound-healing process.

Development and characterization of a novel conductive polyaniline-g-polystyrene/Fe3O4 nanocomposite for the treatment of cancer.

The goal of this study is to synthesize, characterize and investigate some physicochemical properties of conductive polyaniline-g-polystyrene/Fe3O4 (Fe3O4/PSt-g-PANi) nanocomposites. For this purpose, initially, Fe3O4 nanoparticles were synthesized by a co-precipitation method. Then, the desired nanocomposite was synthesized in two steps. First, the atom transfer radical polymerization (ATRP) of styrene was performed using an ATRP initiator attached to the surface of Fe3O4 nanoparticles, followed by functionalization of the Fe3O4-PSt with amine groups (-NH2). Second, surface oxidative graft copolymerization of aniline was accomplished using the -NH2 moieties on the Fe3O4/PSt-NH2 as the anchoring sites. The prepared materials were characterized by various instruments, including TEM, SEM, TGA, EDX, FT-IR, XRD and conductivity measurements. The results indicated that the synthesized conductive polymer/Fe3O4 nanocomposites had higher electrical conductivity and thermal resistance than those of the corresponding homopolymers.

Hesperidin improves the follicular development in 3D culture of isolated preantral ovarian follicles of mice.

IMPACT STATEMENT: It has been stated that hesperidin has many pharmacological effects, such as anti-inflammatory and antioxidant effects, antimicrobial activity, and anti-carcinogenic activity; but hesperidin and its derivatives have been under investigation as anti-fertility factors for a very long time. However, our results show that hesperidin can improve mice follicular growth and maturation during in vitro 3D culture. Hesperidin as an antioxidant factor could enhance the mRNA expression levels of two important genes involved in folliculogenesis, PCNA, and FSH-R. Our results prove for the first time that hesperidin not only has deleterious effects on follicular development but can also increase rates of in vitro fertilization and embryo development.

Evaluation of inflammatory response in patients undergoing surgical treatment for early and delayed femoral fractures.

INTRODUCTION: It has been shown that long bone fractures are correlated with the inflammatory response. In the initial injury, surgical reduction and fixation of fractures induce the immunoinflammatory response. This study aimed to evaluate serum variation of inflammatory markers in patients undergoing surgical treatment for early and delayed femoral fractures. MATERIAL AND METHODS: This study aimed to evaluate serum variation of inflammatory markers in patients undergoing surgical treatment for early and delayed femoral fractures. The patients were randomly divided into two groups using the method of block randomization including early surgery (within 24 h) and delayed surgery (after 48 h). Serum levels of inflammatory markers in both groups including interleukin (IL)-1, 5, 6, tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) were determined using specific kits. From each patient 10 ml blood was collected for cytokine assay in their serum. RESULTS: Our findings suggest that serum levels of IL-8 were markedly decreased from 12 h until 48 h postoperatively (p < 0.05). Moreover, the results indicated that serum levels of TNF-α were significantly increased in the early hours, but after 48 h a decreasing trend was detected (p < 0.05). Furthermore, serum levels of IL-10, IFN-γ, and IL-6 were significantly increased from 12 h until 48 h postoperatively (p < 0.05). CONCLUSIONS: The inflammatory status of the patient may be a useful adjunct in clinical decisions. With an improved understanding of the molecular basis of the inflammatory response, and by identifying relevant clinical markers of inflammation, surgeons can better manage the timing of surgical stabilization.

Lavender oil (Lavandula angustifolia) attenuates renal ischemia/reperfusion injury in rats through suppression of inflammation, oxidative stress and apoptosis.

Renal ischemia/reperfusion (I/R) injury following kidney transplantation has been found to be a great clinical problem owing to initiation of acute inflammatory responses and subsequently rapid loss of kidney function. It is well known that lavender oil exhibits an extensive spectrum of pharmacological and biochemical activities. The purpose of this study was to clarify molecular targets of lavender in treatment of this disease. Male Wistar rats weighing 200-250 g were divided into three major groups: sham, I/R, and I/R + different doses of lavender oil (L1:50 mg/kg, L2: 100 mg/kg, and L3: 200 mg/kg). A rat model of renal I/R (45 min ischemia and 24 h reperfusion) was created and lavender was administrated at 1 h after the beginning of reperfusion (i.p). Activities of antioxidant enzymes such as SOD, GPX, and CAT, and lipid peroxidation were evaluated. The expression of inflammatory cytokines such as TNFα, IL1ß, and IL10 was determined by IHC and ELISA assay. Apoptosis activity and tissue damage were evaluated by TUNEL and H & E staining, respectively. Our results showed that lavender oil markedly restored activities of antioxidant enzymes and reduced lipid peroxidation (P < 0.05). Lavender significantly decreased levels of TNFα and IL1ß and increased level of IL10 in a dose-dependent manner (P < 0.05). Lavender reduced TUNEL positive cells in a dose-dependent manner. However, lavender reduced damage to peritubular capillaries and contributed to preservation of normal morphology of renal cells. In sum, our findings establish a fundamental foundation for future drug industry to decrease the rates of rejection in kidney transplant patients.

Capsaicin protects against testicular torsion injury through mTOR-dependent mechanism.

SCOPE: Testicular torsion and subsequent release of reactive oxygen species (ROS) can cause infertility in adults. Oxidative stress following testicular torsion plays an important role in the ýonset and development of apoptotic cell death through dysregulation of the cellular signaling pathways. Anti-inflammatory and antioxidant properties of capsaicin, a bioactive composition present in red peppers, has already been exploited for treatment of the cancer and pain relief. In present work, we evaluated the role of the mammalian target of rapamycin (mTOR) in antioxidant effect of capsaicin against reperfusion injury following testicular torsion. METHODS: Male Wistar rats weighing 200-220 g were randomly assigned into four major groups: (i) a sham operated group, (ii) a testicular torsion (TT) group, (iii) three groups treated with different doses of capsaicin (TT + 100, 500 and 1000 µg/ml Cap), and (iv) three groups of healthy rats treated with different doses of capsaicin (100, 500 and 1000 µg/ml). Western blotting assay was used to examine the anti-apoptotic effects of capsaicin in testicular cells following torsion. H&E and TUNEL methods were used to evaluate testicular morphology and apoptosis activity. RESULTS: Compared to control group, phosphorylation of mTOR was significantly increased in the TT groups. Capsaicin administration remarkably decreased the phosphorylation of mTOR at the highest dose (P < 0.05). Capsaicin decreased apoptosis and preserved tubular morphology in testes. CONCLUSION: Our results showed that antioxidant properties of capsaicin minimizes cell death and reperfusion injury following testicular torsion.

Activation of mitochondrial KATP channels mediates neuroprotection induced by chronic morphine preconditioning in hippocampal CA-1 neurons following cerebral ischemia.

PURPOSE: Pharmacologic preconditioning, through activating several mechanisms and mediators, can increase the tolerance of different tissues against ischemia/reperfusion (I/R) injury. Recent studies have shown that morphine preconditioning has protective effects in different organs, especially in the heart. Nevertheless, its mechanisms are not well elucidated in the brain. The present study aimed to clarify whether the activation of mitochondrial KATP (mKATP) channels in chronic morphine (CM) preconditioning could decrease hippocampus damage following I/R injury. MATERIALS AND METHODS: CM preconditioning was performed by the administration of additive doses of morphine for 5days before I/R injury induction. I/R injury was induced by the occlusion of bilateral common carotid arteries. The possible role of mKATP channels was evaluated by the injection of 5-hydroxydecanoate (5-HD) before I/R injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was performed to detect apoptosis in hippocampal neurons. The expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (BAX) and levels of malondialdehyde (MDA) and catalase (CAT) enzymes were assessed. RESULTS: CM attenuated apoptosis in the hippocampal CA1 neurons (P<0.001 vs I/R), and mKATP channel blocking with 5-HD significantly increased apoptosis (P<0.001 vs CM+I/R). CM increased CAT activity (P<0.05 vs I/R) and Bcl-2 protein expression (P<0.01 vs I/R), while it decreased MDA level (P<0.05 vs I/R) and BAX protein expression (P<0.05 vs I/R). Pretreatment with 5-HD abolished all the above-mentioned effects of CM. CONCLUSIONS: These findings describe novel evidence whereby CM preconditioning in hippocampal CA1 neurons can improve oxidative stress and apoptosis through the activation of mKATP channels and eventually protect the hippocampal tissue against I/R injury.

Targeting signal transducers and activators of transcription (STAT) in human cancer by dietary polyphenolic antioxidants.

Over the course of the last three decades, a large body of evidence has shown that polyphenols, the secondary metabolites occurring in plant foods and beverages, exert protective effects due to their antioxidant activity mediated through different mechanisms ranging from direct radical scavenging and metal chelating activities, to the capacity to inhibit pro-oxidant enzymes and to target specific cell-signalling pathways. In the last decade, dietary components, and polyphenols in particular have gained considerable attention as chemopreventive agents against different types of cancer. The signal transducers and activators of transcription (STAT) family is a group of cytoplasmic transcription factors which interact with specific sequences of DNA, inducing the expression of specific genes which in turn give rise to adaptive and highly specific biological responses. Growing evidence suggests that, of the seven STAT members identified, STAT3 is over-expressed in many human tumors (i.e. solid tumors and hematological malignancies) promoting the onset and development of cancer in humans by inhibiting apoptosis or by inducing cell proliferation, angiogenesis, invasion, and metastasis. This review article aims to assess the most recent studies on the role of STATs, with focus on STAT3, in oncogenesis, and the promising effects of some polyphenols on STAT expression. Moreover, the mechanisms behind the anti-inflammatory and antioxidant activities of polyphenols which have an influence on STAT expression are discussed, with a focus on their ability to target specific cell-signalling pathways.