Evaluation of the Effect of Artemisia Absinthium L. Eye-Cream on Infra-Orbital Dark Circle: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: The relative darkening of the lower eyelid skin, which is often linked with dark circles, may make you seem fatigued and older than your real age. Considering the recommendations in the sources of Persian medicine regarding Artemisia absinthium L., the purpose of this clinical trial is investigating the effectiveness of cream prepared from the aqueous extraction of A.absinthium to remove periorbital dark circles. MATERIALS AND METHODS: The eye cream is made with 20% of aqueous extract of A.absinthium in the base of the cream. It was standardized based on Artemisinin via HPLC method. For the clinical trial, 60 patients equally enrolled in two drug and placebo groups. Erythema and Pigmentation were evaluated via a mexameter instrument. RESULTS: The cream is standardized, including 1.29±0.02 µg/mg Artemisinin in the product. Finally, 21 and 24 patients reached the end of study in drug and placebo groups, respectively. In these groups, the difference in the mean (SD) DE, DL, Erythema and Melanin factors before and after the research were significant (p0.05). However, the rate of reduction of DE, Erythema, and Melanin and rise of DL is greater in the treatment group than in the placebo group. Furthermore, the mean value of DE and DL factors before the research were significantly different in two groups (p0.001), but after the research did not show a significant difference. The mean value of Erythema factor in the two groups before (p=0.25) and after (p=0.5) did not show a significant difference. The mean value of Melanin after the research between two groups showed a significant difference (p=0.01). CONCLUSION: The results show that the cream prepared from the herbal composition of Persian medicine improves Infra Orbital Dark circle around the eyes.

Plumbagin attenuates Bleomycin-induced lung fibrosis in mice.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disease with limited treatment options. Plumbagin (PL) is an herbal extract with diverse pharmacological effects that have been recently used to treat various types of cancer. This study aims to explore the anti-fibrotic effect of PL and possible underlying mechanisms in IPF. METHODS: We used a bleomycin-induced experimental mouse model of lung fibrosis to assess the potential anti-fibrotic effect of PL. Histological analysis of lung tissue samples by H&E and Masson's trichrome staining and hydroxyproline assay was performed to evaluate the fibrotic alterations. ELISA and real-time quantitative PCR were conducted to determine the amount of tumor necrosis factor-alpha (TNFα), tumor growth factor-beta (TGF-ß), connective tissue growth factor (CTGF), and endothelin-1 (ET-1). RESULTS: Bleomycin exposure induced lung fibrosis, which was indicated by inflammation, collagen deposition, and structural damage. PL remarkably prevented bleomycin-induced lung fibrosis. Furthermore, PL significantly inhibited TNF-α and TGF-ß production. PL also diminished the upregulated expression of CTGF and ET-1 induced by bleomycin. CONCLUSION: Overall, our findings suggest PL as an anti-fibrotic agent acting via down-regulation of TGF-ß/CTGF or ET-1 axis, as well as TNF-α, to improve lung fibrosis.

Modulation of autophagy by melatonin via sirtuins in stroke: From mechanisms to therapies.

Sirtuins perform an important effect on the neural cell fate following stroke. Several mechanisms that have been correlated with stroke are oxidative stress, apoptosis, necrosis and autophagy. Autophagy is usually regarded as unitary of the neural cell survival mechanisms. Recently, the importance of the sirtuins effect on autophagy by antioxidant agents for stroke treatment mentioned in various studies. One of these agents is melatonin. Melatonin can modulate autophagy by changing on sirtuin pathways. Melatonin and its metabolites adjust various sirtuins pathways related to apoptosis, proliferation, metastases, autophagy and inflammation in case of stroke. In this review, we will discuss about the modulation of autophagy by melatonin via sirtuins in stroke.

Integrated genomic sequencing in myeloid blast crisis chronic myeloid leukemia (MBC-CML), identified potentially important findings in the context of leukemogenesis model.

Chronic myeloid leukemia (CML) is a model of leukemogenesis in which the exact molecular mechanisms underlying blast crisis still remained unexplored. The current study identified multiple common and rare important findings in myeloid blast crisis CML (MBC-CML) using integrated genomic sequencing, covering all classes of genes implicated in the leukemogenesis model. Integrated genomic sequencing via Whole Exome Sequencing (WES), Chromosome-seq and RNA-sequencing were conducted on the peripheral blood samples of three CML patients in the myeloid blast crisis. An in-house filtering pipeline was applied to assess important variants in cancer-related genes. Standard variant interpretation guidelines were used for the interpretation of potentially important findings (PIFs) and potentially actionable findings (PAFs). Single nucleotide variation (SNV) and small InDel analysis by WES detected sixteen PIFs affecting all five known classes of leukemogenic genes in myeloid malignancies including signaling pathway components (ABL1, PIK3CB, PTPN11), transcription factors (GATA2, PHF6, IKZF1, WT1), epigenetic regulators (ASXL1), tumor suppressor and DNA repair genes (BRCA2, ATM, CHEK2) and components of spliceosome (PRPF8). These variants affect genes involved in leukemia stem cell proliferation, self-renewal, and differentiation. Both patients No.1 and No.2 had actionable known missense variants on ABL1 (p.Y272H, p.F359V) and frameshift variants on ASXL1 (p.A627Gfs*8, p.G646Wfs*12). The GATA2-L359S in patient No.1, PTPN11-G503V and IKZF1-R208Q variants in the patient No.3 were also PAFs. RNA-sequencing was used to confirm all of the identified variants. In the patient No. 3, chromosome sequencing revealed multiple pathogenic deletions in the short and long arms of chromosome 7, affecting at least three critical leukemogenic genes (IKZF1, EZH2, and CUX1). The large deletion discovered on the short arm of chromosome 17 in patient No. 2 resulted in the deletion of TP53 gene as well. Integrated genomic sequencing combined with RNA-sequencing can successfully discover and confirm a wide range of variants, from SNVs to CNVs. This strategy may be an effective method for identifying actionable findings and understanding the pathophysiological mechanisms underlying MBC-CML, as well as providing further insights into the genetic basis of MBC-CML and its management in the future.

To use or not to use? an ethical analysis of access to data and samples of a deceased patient for genetic diagnostic and research purposes.

Using genetic tests on deceased patients' samples for diagnostic purposes affects the family members' health and lives but raises some ethical issues in today's practice of medicine and research. In this paper, we address a common ethical dilemma of clinicians regarding whether to perform genetic tests on a deceased patient's sample upon a request from first-degree relatives against the patient's wishes in the last days of life. In this paper, a real case scenario is presented that echoes the above-mentioned ethical challenge. Reviewing the genetic basis of the case, the ethical arguments for and against the reuse of genetic material in a clinical context are discussed. An ethico-legal analysis of the case is proposed based on Islamic medical ethics resources. As reusing stored samples of expired patients without their consent also challenges the researchers in the field of genetics, a debate is included on the post-mortem use of genetic data and samples for research. Finally, defining the special features of the presented case and positive benefit-risk ratio, it is concluded that reusing the patient's sample may be justified if the first-degree family members insist on genetic testing and are comprehensively informed about the benefits and harms.

Progesterone Aggravates Lung Fibrosis in a Mouse Model of Systemic Sclerosis.

Background: Gender-related factors have explained the higher prevalence of autoimmune diseases in women. Sex hormones play a key role in the immune system and parenchymal cells function; therefore, these hormones can be important in the pathogenesis of autoimmune diseases as a risk or beneficial factor. Lung fibrosis is the main cause of mortality in systemic sclerosis, a female predominant autoimmune disease. The objective of this study was to examine the effect of progesterone on lung fibrosis in a mouse model of systemic sclerosis. Methods: Mice with bleomycin-induced lung fibrosis treated with progesterone subcutaneously for 21 and 28 days. Blood was collected for hormone and cytokine measurement at the end of treatment then, skin and lung tissues were harvested for histological assessment, gene expression, cytokine, hydroxyproline, and gelatinase measurement. Results: Trichrome staining and hydroxyproline measurements showed that progesterone treatment increased the content of collagen in fibrotic and normal lung tissues. Progesterone increased α-SMA (P < 0.01), TGF- ß (P < 0.05) and decreased MMP9 (P < 0.05) in fibrotic lung tissues. Also progesterone treatment decreased the gene expression of Col1a2 (P <0.05), Ctgf (P <01), End1 (0.001) in bleomycin- injured lung tissues. The serum level of TNF-α was decreased, but the serum level of cortisol was increased by progesterone treatment in fibrotic mice (P< 0.05). Conclusion: Our results showed that progesterone aggravates lung fibrosis in a mouse model of systemic sclerosis.

Nicotine and modafinil combination protects against the neurotoxicity induced by 3,4-Methylenedioxymethamphetamine in hippocampal neurons of male rats.

MDMA (3,4-Methylenedioxymethamphetamine) is a common recreational drug of abuse which causes neurodegeneration. Nicotine and modafinil provide antioxidant and neuroprotective properties and may be beneficial in the management of MDMA-induced neurotoxicity. The purpose of this study was to characterize how acute and chronic administration of nicotine and/or modafinil exert protective effects against the MDMA-induced impaired cognitive performance, oxidative stress, and neuronal loss. Adult male rats were divided into three groups, namely control, MDMA and treatment (modafinil and/or nicotine). MDMA (10 mg/kg) was administered intraperitoneally during a three-week schedule (two times/day for two consecutive days/week). The treated-groups were classified based on the acute or chronic status of treatment. In the groups which underwent acute treatments, nicotine (0.5 mg/kg) and/or modafinil (100 mg/kg) were injected just prior to the MDMA administration (acute nicotine (NA), acute modafinil (MA), and acute nicotine and modafinil (NMA)). In the rats which received chronic treatments, nicotine (0.5 mg/kg) and/or modafinil (100 mg/kg) were injected every day during the three week-schedule administration of MDMA (chronic nicotine (NC), chronic modafinil (MC), and chronic nicotine and modafinil (NMC)). Learning and memory performance, as well as avoidance response, were assessed by Morris water maze and Shuttle box, respectively. Our findings indicate enhanced learning and memory and avoidance response in the NMC group. By TUNEL test and Cresyl Violet staining we evaluated neuronal loss and apoptosis in the hippocampal CA1 and found increased neuronal viability in the NMC group. On the other hand, chronic administration of modafinil and nicotine significantly down-regulated the caspase 3 and up-regulated both BDNF and TrkB levels in the MDMA-received rats. The serum levels of glutathione peroxidase (GPx) and total antioxidant capacity (TAC) were evaluated and we found that the alterations of serum levels of GPx and TAC were considerably prevented in the NMC group. The overall results indicate that nicotine and modafinil co-administration rescued brain from MDMA-induced neurotoxicity. We suggest that nicotine and modafinil combination therapy could be considered as a possible treatment to reduce the neurological disorders induced by MDMA.

The importance of CDC27 in cancer: molecular pathology and clinical aspects.

BACKGROUND: CDC27 is one of the core components of Anaphase Promoting complex/cyclosome. The main role of this protein is defined at cellular division to control cell cycle transitions. Here we review the molecular aspects that may affect CDC27 regulation from cell cycle and mitosis to cancer pathogenesis and prognosis. MAIN TEXT: It has been suggested that CDC27 may play either like a tumor suppressor gene or oncogene in different neoplasms. Divergent variations in CDC27 DNA sequence and alterations in transcription of CDC27 have been detected in different solid tumors and hematological malignancies. Elevated CDC27 expression level may increase cell proliferation, invasiveness and metastasis in some malignancies. It has been proposed that CDC27 upregulation may increase stemness in cancer stem cells. On the other hand, downregulation of CDC27 may increase the cancer cell survival, decrease radiosensitivity and increase chemoresistancy. In addition, CDC27 downregulation may stimulate efferocytosis and improve tumor microenvironment. CONCLUSION: CDC27 dysregulation, either increased or decreased activity, may aggravate neoplasms. CDC27 may be suggested as a prognostic biomarker in different malignancies.

Behavioral Changes in Combination Therapy of Ethanol and Modafinil on Rats Focal Cerebral Ischemia.

INTRODUCTION: Ethanol is considered as an effective agent in reducing brain stroke injury. In this study, we assessed the effects of modafinil along with ethanol as a combination therapy on behavioral function in Wistar rats. METHODS: The right Middle Cerebral Artery Occlusion (MCAO) was performed and the rats were divided into nine groups (n=8 per group). The animal groups in this study were as follows: 1. MCAO control group (ischemia without treatment); 2. Vehicle group; 3. Modafinil group that was randomly subdivided into three groups receiving different doses of modafinil (10, 30, and 100 mg/kg) for 7 days before MCAO; 4. Ethanol group receiving 1.5 g/kg ethanol at the time of reperfusion; 5. Modafinil + ethanol group that was further subdivided into three groups receiving modafinil at different doses (10, 30, and 100 mg/kg) for 7 days before MCAO and ethanol at the time of reperfusion. The motor behavior was measured using the Garcia test 24, 48, and 72 h after the ischemia, and the elevated body swing test was performed 48 and 72 h after the ischemia. The anxiety and locomotor activity were analyzed by open field test 48 and 72 h post-ischemia. RESULTS: The results showed that the neurological deficit score, locomotor activity, and unexpected thigmotaxis (anxiety) in the ethanol, modafinil (in a dose-dependent manner), and ethanol+modafinil treatment groups were significantly higher than the MCAO control group. CONCLUSION: It seems that the combination therapy of modafinil (100 mg/kg) and ethanol (1.5 g/kg) significantly enhanced neuroprotection via an improvement in locomotor activity and neurological functions.

Oxytocinergic system mediates the proconvulsant effects of sildenafil: The role of calcineurin.

Sildenafil is a phosphodiesterase type 5 inhibitor used to treat male erectile dysfunction and pulmonary hypertension. A potential side effect of sildenafil is a noticeable decrease in seizure threshold. Oxytocin (OXT) secretion and the subsequent cAMP-responsive element-binding (CREB) phosphorylation are involved in proconvulsant effects of sildenafil in experimental models. The aim of the present study was to investigate the potential role of OXT receptors and their downstream calcineurin (CN)/inducible nitric oxide synthase (iNOS) pathways in proconvulsant effects of sildenafil. The pentylenetetrazole (PTZ)-induced seizure was used as a standard convulsion model in this study. Cortical CN activity, hippocampal nitrite levels, and proinflammatory cytokine content were measured. Our results indicated that following PTZ administration, sildenafil significantly increased CN activity at 40 mg/kg, respectively, in the control group. The combination of sildenafil and OXT receptor antagonist, atosiban (10 µg/kg, i.c.v) 30 min before sildenafil administration significantly reduced the CN activity. Also, the subeffective dose of CN inhibitor cyclosporine (5 mg/kg) 30 min before the administration of effective dose of sildenafil (40 mg/kg) reversed proconvulsant actions of sildenafil. This effect was iNOS-dependent because pretreatment of a low dose of aminoguanidine (20 mg/kg) 15 min before the administration of a low dose of cyclosporine (1 mg/kg) reversed the proconvulsant action of sildenafil (40 mg/kg). Finally, sildenafil induced the elevation of tumor necrosis factor alpha (TNF-α) and the nitrite level was blocked by the administration of cyclosporine in PTZ-treated mice. Collectively, our data provide insights into the role of OXT receptor/CN/iNOS pathway in the proconvulsant aspect of sildenafil.

Suppression of nicotinamide phosphoribosyltransferase expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin.

BACKGROUND: Nicotinamide phosphoribosyltransferase (NAMPT) enzyme acts as the major enzyme in the nicotinamide adenine dinucleotide (NAD) synthesis salvage pathway. Deregulation of NAD could be associated with progression of several cancers such as breast cancer. Here, the consequence of NAMPT inhibition by miR-154 was investigated on breast cancer cells. METHODS: MDA-MB-231 and MCF-7 cancer cell lines were transfected with the mimic and inhibitors of miR-154-5p and their corresponding negative controls. Consequently, levels of NAMPT and NAD were assayed employing qRT-PCR, Western blotting and enzymatic method, respectively. Subsequently, flow cytometry and colorimetric methods were performed to evaluate apoptosis and cell viability. Bioinformatics analyses as well as luciferase assay were done to investigate whether the 3'-UTR of NAMPT is directly targeted by miR-154. RESULTS: According to the obtained results, NAMPT was recognized as a target for binding of miR-154 and the levels of this miRNA was inversely associated with both mRNA and protein levels of NAMPT in breast cancer cell lines. Functionally, miR-154 inhibited the NAD salvage pathway leading to a remarkable decrease in cell viability and increased rate of cell death. When breast cancer cells were simultaneously treated with doxorubicin and miR-154 mimic, cell viability was considerably reduced compared to treatment with doxorubicin alone in both cell lines. CONCLUSIONS: It was concluded that the inhibition of NAD production by miR-154 might be introduced as an appropriate therapeutic approach in order to improve breast cancer outcome either alone or in combination with other conventional chemotherapeutic agents.

Up-regulation of miR-381 inhibits NAD+ salvage pathway and promotes apoptosis in breast cancer cells.

Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme involved in nicotinamide adenine dinucleotide (NAD) salvage pathway, is overexpressed in many human malignancies such as breast cancer. This enzyme plays a critical role in survival and growth of cancer cells. MicroRNAs (miRNAs) are among the most important regulators of gene expression, and serve as potential targets for diagnosis, prognosis, and therapy of breast cancer. Therefore, the aim of this study was to assess the effect of NAMPT inhibition by miR-381 on breast cancer cell survival. MCF-7 and MDA-MB-231 cancer cell lines were transfected with miR-381 mimic, inhibitor, and their corresponding negative controls (NCs). Subsequently, the level of NAMPT and NAD was assessed using real-time PCR, immuno-blotting, and enzymatic methods, respectively. In order to evaluate apoptosis, cells were labelled with Annexin V-FITC and propidium iodide and analyzed by flow cytometry. Bioinformatics analysis was performed to recognize whether NAMPT 3'-untranslated region (UTR) is a direct target of miR-381 and the results were authenticated by the luciferase reporter assay using a vector containing the 3'-UTR sequence of NAMPT. Our results revealed that the 3'-UTR of NAMPT was a direct target of miR-381 and its up-regulation decreased NAMPT gene and protein expression, leading to a notable reduction in intracellular NAD and subsequently cell survival and induction of apoptosis. It can be concluded that miR-381 has a vital role in tumor suppression by down-regulation of NAMPT, and it can be a promising candidate for breast cancer therapy.

Melatonin regulates neuroinflammation ischemic stroke damage through interactions with microglia in reperfusion phase.

Even today, ischemic stroke is a major cause of death and disabilities because of its high incidence, limited treatments and poor understanding of the pathophysiology of ischemia/reperfusion, neuroinflammation and secondary injuries following ischemic stroke. The function of microglia as a part of the immune system of the brain following ischemic stroke can be destructive or protective. Recent surveys indicate that melatonin, a strong antioxidant agent, has receptors on microglial cells and can regulate them to protective form; yet, more findings are required for better understanding of this mechanism, particularly in the reperfusion phase. In this study, we initially aimed to evaluate the therapeutic efficacy of melatonin intra-arterially and to clarify the underlying mechanisms. After that by using an in vitro approach, we evaluated the protective effects of melatonin on microglial cells following the hypoxia condition. Our results proved that a single dose of melatonin at the beginning of reperfusion phase improved structural and behavioral outcomes. Melatonin increased NeuN and decreased GFAP, Iba1 and active caspase-3 at protein level. Furthermore, melatonin elevated BDNF, MAP2, HSPA1A and reduced VEGF at mRNA level. We also showed that melatonin receptor 1B highly expressed in microglial cells after 3 h hypoxia. Besides, melatonin increased the ratio of TREM2/iNOS as a marker of the most protective form of microglia (M2). In summary, our data suggest that melatonin has the possibility to serve as targeting microglial action for preventing secondary injury of reperfusion phase after ischemic stroke.

A combination therapy of nanoethosomal piroxicam formulation along with iontophoresis as an anti-inflammatory transdermal delivery system for wound healing.

Inflammation accounts as one of the major phases in wound healing, while prolonged and chronic inflammation may lead to adverse pathological conditions. Therefore, transdermal delivery of nonsteroidal anti-inflammatory (NSAIDs) such as encapsulated piroxicam into a nanocarrier seems to be promising. For the first time, a nanoethosomal piroxicam of <200 nm was prepared and combined with iontophoresis. Results showed that there was a critical point at the concentration of 5 mg lecithin with the smallest particle size. Besides, lecithin concentration had direct and inverse linear relationships with turbidity and pH of nanocarriers, respectively. Moreover, as there was no linear relationship between the lecithin concentration and particle size, the effect of lecithin concentration was dominant on turbidity compared with particle size. It seems that a pH higher than 5.5 disturbed the linear relationship of pH and entrapment efficacy percentage (EE%) while at the pH range of 4 to 5.5, the relationship was linear and EE% gradually decreased with increasing pH. These data showed that an optimised nanocarrier with special physicochemical properties is dominant to the just particle size. Besides, ex vivo permeation studies in rat skin showed that there was no significant difference between the permeation of free drug and ethosomal ones. However, iontophoresis significantly enhanced ethosomal piroxicam permeation compared with the free drug. Overall, these data emphasise the superiority of iontophoresis for the transdermal delivery of nanoethosomal medications while nanoethosomal delivery without iontophoresis did not show significant transdermal potential. To sum up, transdermal nanoethosomal piroxicam along with iontophoresis seems to be promising in wound healing.

Gelatinases Increase in Bleomycin-induced Systemic Sclerosis Mouse Model.

Systemic sclerosis is a fibrotic autoimmune disease in which aberrant remodeling of the extracellular matrix in organs disturbs their functionalities. The aim of this study was to investigate the expression of gelatinases on systemic sclerosis. Consequently, a mouse model of systemic sclerosis was employed and the gelatinolytic activity of gelatinases was evaluated on the fibrotic tissues of this model. Two groups of ten mice were considered in this work: a group of systemic sclerosis model and control group. For the generation of systemic sclerosis model, mice received bleomycin, while the control group was subjected to phosphate buffered saline (PBS) reception. Mice were tested for fibrosis by using trichrome staining, hydroxyproline measurement and α-SMA detection in tissue sections. Additionally, the gelatinolytic activity of matrix metalloproteinase 2 and matrix metalloproteinase 9 were measured using gelatin zymography in lungs and skin tissue homogenates. The obtained results indicated that subcutaneous injection of bleomycin-induced fibrosis in skin and lung tissues of mice. Pro and active forms of matrix methaloproteinase 9 were increased in fibrotic lung tissues (p<0.05 and p<0.01, respectively), while, the gelatinolytic activity of MMP2 was unaffected in these tissues. Additionally, in skin tissues of bleomycin-treated animals, both pro and active forms of MMP9 and MMP2 were increased (p<0.05). Pro and active forms of gelatinases increase differently in skin and lung tissues of bleomycin-induced scleroderma.

The Role of Progesterone in Cellular Apoptosis of Skin and Lung in a Bleomycin-injured Mouse Model.

Systemic sclerosis is a female predominant, a fibrotic autoimmune disease in which disturbance in tissue homeostasis and cell turnover including cell apoptosis are central events in pathogenesis. Sex hormones are known as the important players in sexual dimorphism of autoimmune diseases and in tissue homeostasis. Progesterone influences autoimmune disease via its immunomodulatory effect or by its direct action on parenchymal cell function. On the other hand, this hormone impacts tissue homeostasis by acting on cell apoptosis in a different situation. The objective of this study was to examine the effect of progesterone on cellular apoptosis of skin and lung tissues in a mouse model of scleroderma. Four group of mice were involved in this study with 10 mice in each. The fibrotic model was induced by daily subcutaneous injection of bleomycin for 28 days. One week after initiation of fibrosis induction, mice received subcutaneous progesterone alone or with bleomycin for 21 days. Control group received only Phosphate buffered saline PBS. After 28 days, under lethal anesthesia skin and lung tissues were harvested for histological assessment and hydroxyproline measurement. Apoptosis in tissue sections was detected by TUNEL assay technique. Bleomycin administration induced fibrosis in skin and lung tissues. Severe apoptosis was seen in skin and lung tissues of the bleomycin-treated group (p<0.001 in the skin and p<0.05 in the lung). Progesterone injection either in the skin (p>0.05) or in the lung (p>0.05) did not alter apoptosis in bleomycin-treated animals. Our data confirm the role of apoptosis in the pathogenesis of fibrosis in this model; however, progesterone does not affect cellular apoptosis in skin and lung tissues of bleomycin-injured animals.

Gold nanorods reinforced silk fibroin nanocomposite for peripheral nerve tissue engineering applications.

Nowadays, regenerating peripheral nerves injuries (PNIs) remain a major clinical challenge, which has gained a great attention between scientists. Here, we represent a nanocomposite based on silk fibroin reinforced gold nanorods (SF/GNRs) to evaluate the proliferation and attachment of PC12 cells. The morphological characterization of nanocomposites with transmission electron microscopy (TEM) and Scanning electron microscopy (SEM) showed that the fabricated scaffolds have porous structure with interconnected pores that is suitable for cell adhesion and growth. GNRs significantly improved the poor electrical conductivity of bulk silk fibroin scaffold. Evaluating the morphology of PC12 cells on the scaffold also confirmed the normal morphology of cells with good rate of adhesion. SF/GNRs nanocomposites showed better cellular attachment, growth and proliferation without any toxicity compared with bulk SF scaffold. Moreover, immunostaining studies represented the overexpression of neural specific proteins like nestin and neuron specific enolase (NSE) in the cells cultured on SF/GNRs nanocomposites in comparison to neat SF scaffolds.

Neuroprotective effect of ethanol and Modafinil on focal cerebral ischemia in rats.

Ethanol is known as an effective agent against cerebral lesions after ischemia. Modafinil is a stimulant of the central nervous system (CNS) with antioxidant properties. We assessed the neuroprotective effect of modafinil in combination with ethanol after focal cerebral ischemia. Male wistar rats weighing 280-300 g were divided into nine groups (n = 12 each group): The groups consisted of the MCAO (middle cerebral artery occlusion) group (i.e. ischemia without treatment); the vehicle group(Dimethylsulfoxide); the modafinil group including three subgroups which pretreated with Modafinil (10, 30, 100 mg/kg), respectively, for seven days prior to the induction of MCAO; the ethanol group which received 1.5g/kg ethanol at the time of reperfusion; and modafinil+ethanol group which was divided into three subgroups that received three doses of modanifil (10, 30,100 mg/kg), respectively, for seven days prior to MCAO as well as ethanol at the time of reperfusion. Transient cerebral ischemia was induced by 60-min intraluminal occlusion of the right middle cerebral artery. Edema, infarct volume, glial scar formation (gliosis) and apoptosis were analyzed. The ethanol alone treatment (with a less significant effect), modafinil (in a dose-dependent way), and the combination of modafinil and ethanol significantly decreased the brain infarct volume, edema, apoptosis, and gliosis (P ≤ 0.05). Additionally, modafinil+ethanol mediated the restoration of aerobic metabolism and hyper-glycolysis suppress, thereby resulting in an increase in pyruvate dehydrogenase and a decrease in lactate dehydrogenase activity, respectively, which ultimately reduced oxidative reperfusion injury. These results demonstrate that pretreatment with modafinil (100 mg/kg) and modafinil+ethanol(1.5 g/kg) may prevent ischemic brain injuries.