Search results for: male mice

Authors: Seema Sharma Kaushik, Dhananjoy Shaw

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Various length dimensions of the body have been a variable of interest in the research areas of kinanthropometry. However the inclusion of length measurements in various studies remains restricted to reflect characteristics of a particular game/sport at a particular time. Hence, the present investigation was conducted to study various length dimensions correlates of a longitudinal physical conditioning program on Indian male youth. The study was conducted on 90 Indian male youth. The sample was equally divided into three groups namely, progressive load training (PLT), constant load training (CLT) and no load training (NL). The variables included sitting height, leg length, arm length and foot length. The study was conducted by adopting the multi group repeated measure design. Three different groups were measured four times after completion of each of the three meso-cycles of six-weeks duration each. The measurements were taken using the standard landmarks and procedures. Mean, standard deviation and analysis of co-variance were computed to analyze the data statistically. The post-hoc analysis was conducted for the significant F-ratios at 0.05 level. The study concluded that the followed longitudinal physical conditioning program had significant effect on various length dimensions of Indian male youth.

Keywords: Indian male youth, longitudinal, length dimensions, physical conditioning

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Authors: S. A. Nirmal, J. M. Ingale, G. S. Asane, S. C. Pal, Subhash C. Mandal

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The present work was undertaken to determine the effects of Amaranthus roxburghianus Nevski. (Amaranthaceae) root alone and in combination with piperine in treating ulcerative colitis (UC) in mice. Swiss albino mice were divided into seven groups (n = 6). Standard group received prednisolone (5 mg/kg, i.p.). Treatment groups received hydroalcoholic extract of roots of A. roxburghianus (50 and 100 mg/kg, p.o.) and a combination of hydroalcoholic extract of roots of A. roxburghianus (50 and 100 mg/kg, p.o.) and piperine (5 mg/kg, p.o.). Ulcer index, colitis severity, myeloperoxidase (MPO), malondialdehyde and glutathione were estimated from blood and tissue. Column chromatography of the extract was done and purified fractions were analyzed by gas chromatography-mass spectroscopy (GC-MS). Treatment with the combination of hydroalcoholic extract of A. roxburghianus and piperine showed minimal ulceration, hemorrhage, necrosis and leucocyte infiltration by histopathological observation. Acetic acid increased MPO levels in blood and colon tissue to 355 U/mL and 385 U/mg, respectively. The combination of hydroalcoholic extract (100 mg/kg) and piperine (5 mg/kg) significantly decreased MPO in blood and tissue to 182 U/mL and 193 U/mg, respectively. Similarly, this combination significantly reduced MPO and increased glutathione levels in blood and tissue. Various phytoconstituents were detected by GC-MS. The combination of hydroalcoholic extract and piperine is effective in the treatment of UC and the effects are comparable with the standard drug prednisolone. 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl, eugenol and benzene, and 1-(1,5-dimethyl-4-hexenyl)-4-methyl are reported having analgesic, anti-inflammatory, and antioxidant properties; they may play a role in the biological activity of A. roxburghianus root.

Keywords: Amaranthus roxburghianus, ulcerative colitis, anti-inflammatory, ulcerative colitis

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Authors: Ovidiu Anemtoaicei

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This paper offers a possible answer to the question of what it means to think about men and masculinities through the philosophy of sexual difference as developed by Luce Irigaray, employing Gilles Deleuze’s concept of 'critique' and arguing, at the same time, for a concept of 'becoming-man' as an expression of this answer. First, while examining the nature of the role of male bodies underlying the theorizing of men and masculinities in the field of the Critical Studies of Men and Masculinities, the paper argues for a turn to sexual difference theory as an answer to the 'gap' between the representations on male bodies and their participation in thought and masculine subjective production. Secondly, sharing Luce Irigaray’s critique of Western thought, the paper explores alternative morphological bodily 'locations' for rethinking male imaginary in relation to male embodiments, on the one hand, and in relation to the maternal and the feminine, on the other hand. Thirdly, the paper develops the idea that a phenomenologically-influenced approach towards male bodies might be productive, especially when thought through Irigaray’s sexual difference as a relational and experiential ontology. Finally, while showing that Irigaray and Deleuze share a similar critique of Western philosophical thought and of the masculine historical subject, it proposes a rethinking of the concept of 'becoming-man' as an assemblage meeting between Irigaray’s theory of sexual difference and Deleuze and Guattari’s nomadologic project, as a possibility of thinking change in men’s masculine subjective constitution in relation to both women and other men. As far as the ethical implications of such rethinking are concerned, the paper urges for the cultivation of a masculine culture of stepping back and its constitutive political, social and cultural practices so as to make possible the construction of new spaces that would allow for the becoming of at least two subjects based on the respect for their differences.

Keywords: feminist philosophy, male bodies, masculinities, phenomenology, sexual difference

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Authors: S. Kozlovski, S.W. Feigelson, R. Alon

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The b2 integrin ligands ICAM-1 ICAM-2 and the endothelial VLA-4 integrin ligand VCAM-1 are constitutively expressed on different lung vessels and on high endothelial venules (HEVs), the main portal for lymphocyte entry from the blood into lung draining lymph nodes. ICAMs are also ubiquitously expressed by many antigen-presenting leukocytes and have been traditionally suggested as critical for the various antigen-specific immune synapses generated by these distinct leukocytes and specific naïve and effector T cells. Loss of both ICAM-1 and ICAM-2 on the lung vasculature reduces the ability to patrol monocytes and Tregs to patrol the lung vasculature at a steady state. Our new findings suggest, however, that in terms of innate leukocyte trafficking into the lung lamina propria, both constitutively expressed and virus-induced vascular VCAM-1 can functionally compensate for the loss of these ICAMs. In a mouse model for influenza infection, neutrophil and NK cell recruitment and clearance of influenza remained normal in mice deficient in both ICAMs. Strikingly, mice deficient in both ICAMs also mounted normal influenza-specific CD8 proliferation and differentiation. In addition, these mice normally combated secondary influenza infection, indicating that the presence of ICAMs on conventional dendritic cells (cDCs) that present viral antigens are not required for immune synapse formation between these APCs and naïve CD8 T cells as previously suggested. Furthermore, long-lasting humoral responses critical for protection from a secondary homosubtypic influenza infection were also normal in mice deficient in both ICAM-1 and ICAM-2. Collectively, our results suggest that the expression of ICAM-1 and ICAM-2 on lung endothelial and epithelial cells, as well as on DCs and B cells, is not critical for the generation of innate or adaptive anti-viral immunity in the lungs. Our findings also suggest that endothelial VCAM-1 can substitute for the functions of vascular ICAMs in leukocyte trafficking into various lung compartments.

Keywords: emigration, ICAM-1, lymph nodes, VCAM-1

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Authors: Tara Panday, Despina Learmonth

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Sex work is often constructed as being an interaction between male clients and female sex workers. As a result, street-based male sex workers are continuously overlooked in the South African literature. This qualitative study explored male sex workers’ subjective experiences and constructions of their male clients’ identities and the client-sex worker relationship. This research was conducted from a social-constructionist perspective, which allowed for a deeper understanding of the reasons and context driving the choices and actions of male sex workers. Semi-structured face-to-face interviews were conducted with 10 South African men working as sex workers in Cape Town. Data was analysed through thematic analysis. The findings of the study construct the client-sex worker relationship in terms of a professional relationship, constrained choice, sexual identity and need, as well as companionship for pay, potentially highlighting underlying reasons for supply and demand. The data which emerged around the client-sex worker relationship and the clients’ identities also served to illuminate the power-dynamics in the client-sex worker relationship. This data increases insight into the exploitation and disempowerment experienced by male sex workers through verbal abuse, physical and sexual violence, and unfairly enforced laws and regulations. The findings of this study suggest that, in the context of South Africa, male sex workers' experiences of the client-sex worker relationship cannot be completely understood without considering the intersectionality of the triple stigmatisation of: the criminality of sex work, race, and the lack of economic power, which systematically maintains marginalization. Motivating for the Law Reform Commission to continue to review all emerging research may assist with guiding related policy and thereby, the provision of equal human rights and adequate health and social interventions for all sex workers in South Africa.

Keywords: human rights, prostitution, power relations, sex work

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Authors: Minu Lakra

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The present study was done on 100 (male=50 and female=50) teachers of physical education at tertiary level from Varanasi city. They were chosen according to the stratified sampling method. Data collection tool was Perceived Stress Scale: 14 items (Cohen, Kamarck and mermelstain 1983) and Quality of Life was developed by THE WHOQOL GROUP in 1991. Data was analyzed with the help of correlation. Findings explore that perceived stress and quality of life has been positively correlated in female teachers of higher education from physical education whereas in male teachers the relationship was found insignificant.

Keywords: higher education, male and female teachers , percieved stress, quality of life

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Authors: Muneeba Butt

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One of the most important physical evidence which leaves suspects at the crime scene is footprints. Analysis of footprints, which can provide useful information for personal identification, is helpful in crime scene investigation. For the current study, 200 samples collected (144 male and 56 female) from Pakistani population with a consent form. The footprints were collected by using black ink with an ink pad. The entire samples were photographed, and then the magnifying glass was used for visualization of individual characteristics including detail of toes, humps, phalange mark, and flat foot cracks in footprint patterns. The descriptive results of individualizing characteristics features were presented in tabular form with respective frequency and percentage. In the result in the male population, the prevalence of tibialis type (T-type) is highest. In the female population, the prevalence of midularis type (M-type) is highest. Humps on the first toe are more found in the male population rather than other humps. In the female population, humps on the third toe are more found rather than other humps. In the male population, the prevalence of phalange mark by toe 1 is highest followed by toe 3, toe 5, toe 2, toe 4 and in female population the prevalence of phalange mark by toe 1 is highest followed by toe 5, 4, 3 and 2. Creases marks are found highest in male population as compared to the female population.

Keywords: foot prints, toes, humps, cracks

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Authors: Subas Chandra Biswas, Kazi Sameen Naser, Farzana Misha

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Little is known about the sexual behavior of male youth, particularly unmarried young men in Bangladesh as most of the sexual and reproductive health and rights-related research and intervention are mainly focused on females and married couples. To understand the unmarried youth’s sexual behavior, data from a nationwide survey conducted in all 64 districts of Bangladesh were analyzed. Using multistage systematic random sampling, a survey was conducted among 11,113 male youth aged 15-24 years from May-August, 2019. This article analyzed and presented findings of the sexual behavior of unmarried respondents based on the data collected from 10,026 unmarried male youth. Findings showed that 18% had ever experience of sexual relationship, and the reported mean age of first sexual intercourse was 16.5years. For unmarried male youth, those who had a sexual experience, their first sexual partners were female friends/classmate (57%), female neighbors (16%), and female sex workers (12%), relatives (6%) and girlfriends with whom they had love relationship (4%). However, about 36% reported that they had a love relationship with girlfriends, and among them, 23% reported that they had sexual intercourse with their girlfriend. Those who had sexual relations with their girlfriend, 47% reported that they did not use the condom in their last sex with their girlfriend. Furthermore, 29% reported that they had sexual relationships with others besides their girlfriends. Other reported partners were female sex workers (32%), neighbors (29%), female friends (19%), relatives (12%), and cousins (5%). Also, 46% reported that they did not even use the condom during sex with other partners. About 9% used some sort of sexual stimulant to increase their libido. Among the respondents, 376 reported that they bought sex in the last six months, and the mean expenditure of buying sex for the respondent was 1,140 Taka (13.46 US Dollar). Though premarital sexual relations are not socially accepted, findings showed a large portion of male youth are engaged in these relationships and risky sexual behavior. Lack of awareness of sexual and reproductive health, unprotected sexual intercourse, use of the drug during sexual intercourse also increase the threats to health. Thus these findings are important to understand the sexual behavior of male youth in policy and programmatic implications. Therefore, to ensure a healthy sexual life and wellbeing, an immediate and culturally sensitive sexual health promotion intervention is needed for male youth in Bangladesh.

Keywords: Bangladesh, male youth, sexual and reproductive health, sexual behavior

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Authors: Abeer Rababa'h, Ragad Bsoul, Mohammad Alkhatatbeh, Karem Alzoubi

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Introduction: Tobacco use is one of the main risk factors to cardiovascular diseases (CVD) and atherosclerosis in particular. WPS contains several toxic materials such as: nicotine, carcinogens, tar, carbon monoxide and heavy metals. Thus, WPS is considered to be as one of the toxic environmental factors that should be investigated intensively. Therefore, the aim of this study is to investigate the effect of WPS on several cardiovascular biological markers that may cause atherosclerosis in mice. The study also conducted to study the temporal effects of WPS on the atherosclerotic biomarkers upon short (2 weeks) and long-term (8 weeks) exposures. Methods: mice were exposed to WPS and heart homogenates were analyzed to elucidate the effects of WPS on matrix metalloproteinase (MMPs), endothelin-1 (ET-1) and, myeloperoxidase (MPO). Following protein estimation, enzyme-linked immunosorbent assays were done to measure the levels of MMPs (isoforms 1, 3, and 9), MPO, and ET-1 protein expressions. Results: our data showed that acute exposure to WPS significantly enhances the levels of MMP-3, MMP- 9, and MPO expressions (p < 0.05) compared to their corresponding control. However, the body was capable to normalize the level of expressions for such parameters following continuous exposure for 8 weeks (p > 0.05). Additionally, we showed that the level of ET-1 expression was significantly higher upon chronic exposure to WPS compared to both control and acute exposure groups (p < 0.05). Conclusion: Waterpipe exposure has a significant negative effect on atherosclerosis and the enhancement of the atherosclerotic biomarkers expression (MMP-3 and 9, MPO, and ET-1) might represent an early scavenger of compensatory efforts to maintain cardiac function after WP exposure.

Keywords: atherosclerotic biomarkers, cardiovascular disease, matrix metalloproteinase, waterpipe

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Authors: Djebbar Atmani, Aghiles Karim Aissat, Nadjet Debbache-Benaida, Nassima Chaher-Bazizi, Dina Atmani-Kilani, Meriem Rahmani-Berboucha, Naima Saidene, Malika Benloukil, Lila Azib

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Medicinal plants are believed to be an important source for the discovery of potential antioxidant, anti-inflammatory and anti-diabetic substances. The present study was designed to investigate the neuroprotective, anti-inflammatory, anti-diabetic and anti-hyperuricemic potential of Pistacia lentiscus, as well as the identification of active compounds. The antioxidant potential of plant extracts against known radicals was measured using various standard in vitro methods. Anti-inflammatory activity was determined using the paw edema model in mice and by measuring the secretion of the pro-inflammatory cytokine, whereas the anti-diabetic effect was assessed in vivo on streptozotocin-induced diabetic rats and in vitro by inhibition of alpha-amylase. The anti-hyperuricemic activity was evaluated using the xanthine oxidase assay, whereas neuroprotective activity was investigated using an Aluminum-induced toxicity test. Pistacia lentiscus extracts and fractions exhibited high scavenging capacity against DPPH, NO. and ABTS+ radicals in a dose-dependent manner and restored blood glucose levels, in vivo, to normal values, in agreement with the in vitro anti-diabetic effect. Oral administration of plant extracts significantly decreased carrageenan-induced mice paw oedema, similar to the standard drug, diclofenac, was effective in reducing IL-1β levels in cell culture and induced a significant increase in urinary volume in mice, associated to a promising anti-hyperuricemic activity. Plant extracts showed good neuroprotection and restoration of cognitive functions in mice. HPLC-MS and NMR analyses allowed the identification of known and new phenolic compounds that could be responsible for the observed activities. Therefore, Pistacia lentiscus could be beneficial in the treatment of inflammatory conditions and diabetes complications and the enhancement of cognitive functions.

Keywords: Pistacia lentiscus, anti-inflammatory, antidiabetic, flavanols, neuroprotective

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Authors: Therese Besnard

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Internationally in early childhood education (ECE), the great majority of teachers are women. Some groups believe that a greater male teacher presence in ECE would be beneficial for children, specifically for boys as it could offer a positive male model. It is a common belief that children would benefit from being exposed to both male and female models. Some believe that women are naturally better suited to offer quality care to young children comparatively to men. Some authors bring forth that after equivalent training, differences in the educational practices are purely individual and do not depend on the teacher’s gender. Others believe that a greater male presence in ECE would increase the risk of pedophilia or child abuse. The few scientific studies in this area suggest that differences could exist between male and female ECE teacher, in particular when it comes to play which is the mainstay of the ECE educational program. Male teachers describe themselves as being more playful and having a greater tendency to initiate physical and turbulent play comparatively to female teachers, who describe themselves as favoring games that are calmer and focused on social interaction. Observed directly, male teachers appear more actively engaged in play with children and propose more motor play than female teachers. Furthermore children who have both male and female teachers for one year show less behavior difficulties when compared to children with only female teachers. Despite a variety of viewpoints we don’t know if the educational practices of male ECE teachers, (emotional support, classroom organization or instructional support) are different than the educational practices of female teachers and if these practices are linked with children’s adaptation. This study compares the educational practices of 37 ECE teachers (57 % male) and analyses the link with children' social adaptation (n=221). Educational practices were assessed through observational measurements with the Classroom Assessment Scoring System (CLASS) in a natural class environment. Child social adaptation was assessed with the Social Competence and Behavior Evaluation (SCBE). Observational data reveals no differences between men's and women's scale of the CLASS. Results using Multilevel models analyses suggest that the ability to propose good classroom organization and give good instructional support are linked with better child' social adaptation, and that is always true for men and women teachers. The results are discussed on the basis of their potential impact on future educational interventions.

Keywords: child social adaptation, early childhood education, educational practices, men teacher

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Authors: Huimin Zhao, Xiaoquan Liu, Haochen Liu

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The major challenge facing Alzheimer's Disease (AD) drug development is how to effectively improve cognitive function in clinical practice. Growing evidence indicates that stimulating hippocampal neurogenesis is a strategy for restoring cognition in animal models of AD. The mitogen-activated protein kinase (MAPK) pathway is a crucial factor in neurogenesis, which is negatively regulated by Dual-specificity phosphatase 16 (DUSP16). Transcriptome analysis of post-mortem brain tissue revealed up-regulation of DUSP16 expression in AD patients. Additionally, DUSP16 was involved in regulating the proliferation and neural differentiation of neural progenitor cells (NPCs). Nevertheless, whether the effect of DUSP16 on ameliorating cognitive disorders by influencing NPCs differentiation in AD mice remains unclear. Our study demonstrates an association between DUSP16 SNPs and clinical progression in individuals with mild cognitive impairment (MCI). Besides, we found that increased DUSP16 expression in both 3×Tg and SAMP8 models of AD led to NPC differentiation impairments. By silencing DUSP16, cognitive benefits, the induction of AHN and synaptic plasticity, were observed in AD mice. Furthermore, we found that DUSP16 is involved in the process of NPC differentiation by regulating c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, the increased DUSP16 may be regulated by the ETS transcription factor (ELK1), which binds to the promoter region of DUSP16. Loss of ELK1 resulted in decreased DUSP16 mRNA and protein levels. Our data uncover a potential regulatory role for DUSP16 in adult hippocampal neurogenesis and provide a possibility to find the target of AD intervention.

Keywords: alzheimer's disease, cognitive function, DUSP16, hippocampal neurogenesis

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Authors: Jaskarn Singh Sidhu

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The present study investigated the relationship of Empathy and Narcissism among university sports persons. Sample-The sample of the study consists of a total of 248 sportspersons and non-sports persons. Tools- To evaluate empathy, a 16-scale questionnaire was used and to evaluate narcissism, NPI-16 questionnaire was used. Statically-Two-Way Analysis of Variance used to analyse the data collected to establish the relationship. Results- In empathy male champion players shows more empathy than female counterparts the results also reveals that non champion females showed more empathy than non-champion male sports persons. In totality champion shows more empathy than non- champions. Results of Narcissism revealed that male champion sports persons were high on Narcissism scale then female counterparts. Non -champion males also indicate high narcissism then non champion female sports persons indicating female were less self -oriented then male sports persons. Conclusion- From the results it was concluded that no significant difference exists among sports persons in empathy and narcissism with reference to gender and sports performance.

Keywords: champion, narcissism, empathy, non champion players

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Authors: Divya Vohora, Md. Jamir Anwar

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Antiepileptic drugs (AEDs)-induced adverse consequences on bone are now well recognized. Despite this, there is limited data on the effect of anti-osteoporotic therapies on AEDs-induced bone loss. Both phenytoin (PHT) and sodium valproate (SVP) inhibit human aromatase enzyme and stimulate microsomal catabolism of oestrogens. Estrogen deficiency states are known to reduce the deposition of transforming growth factor-β (TGF-β3), a bone matrix protein, having anti-osteoclastic property. Thus, an attempt was made to investigate the effect of raloxifene, a selective oestrogen receptor modulator, in comparison with CVD supplementation, on PHT and SVP-induced alterations in bone in mice. Further, the effect of raloxifene on seizures and on the antiepileptic efficacy of AEDs was also investigated. Swiss strains of female mice were treated with PHT (35 mg/kg, p.o.) and SVP (300 mg/kg, p.o.) for 120 days to induce bone loss as evidenced by reduced bone mineral density (BMD) and altered bone turnover markers in lumbar bones (alkaline phosphatase, tartarate resistant acid phosphatase, hydroxyproline) and urine (calcium). The bone loss was accompanied by reduced serum estradiol levels and bone TGF-β3 content. Preventive and curative treatment with raloxifene ameliorated bony alterations and was more effective than CVD. Deprived estrogen levels (that in turn reduced lumbar TGF-β3 content) following PHT and SVP, thus, might represent one of the various mechanisms of AEDs-induced bone loss. Raloxifene preserved the bony changes without interfering with their antiepileptic efficacy, and hence raloxifene could be a potential therapeutic option in the management of PHT and SVP-induced bone disease if clinically approved.

Keywords: antiepileptic drugs, osteoporosis, raloxifene, TGF-β3

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Authors: Seunghwan Seo, Woo-Seok Lee, Ji-Sun Shin, Young Kyoung Rhee, Chang-Won Cho, Hee-Do Hong, Kyung-Tae Lee

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Doenjang, known as traditional Korean food, is product of a natural mixed fermentation process carried out by lactic acid bacteria (LAB). Lactobacillus sakei K040706 (K040706) has been accepted as the most populous LAB in over ripened doenjang. Recently, we reported the immunostimulatory effects of K040706 in RAW 264.7 macrophages and in a cyclophosphamide-induced mouse model. In this study, we investigated the ameliorative effects of K040706 in a dextran sulfate sodium (DSS)-induced colitis mouse model. We induced colitis using DSS in 5-week-ICR mice over 14 days with or without 0.1, 1 g/kg/day K040706 orally. The body weight, stool consistency, and gross bleeding were recorded for determination of the disease activity index (DAI). At the end of treatment, animals were sacrificed and colonic tissues were collected and subjected to histological experiments and myeloperoxidase (MPO) accumulation, cytokine determination, qRT-PCR and Western blot analysis. Results showed that K040706 significantly attenuated DSS-induced DAI score, shortening of colon length, enlargement of spleen and immune cell infiltrations into colonic tissues. Histological examinations indicated that K040706 suppressed edema, mucosal damage, and the loss of crypts induced by DSS. These results were correlated with the restoration of tight junction protein expression, such as, ZO-1 and occludin in K040706-treated mice. Moreover, K040706 reduced the abnormal secretions and mRNA expressions of pro-inflammatory mediators, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). DSS-induced mRNA expression of intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in colonic tissues was also downregulated by K040706 treatment. Furthermore, K040706 suppressed the protein and mRNA expression of toll-like receptor 4 (TLR4) and phosphorylation of NF-κB and signal transducer and activator of transcription 3 (STAT3). These results suggest that K040706 has an anti-colitic effect by inhibition of intestinal inflammatory responses in DSS-induced colitic mice.

Keywords: Lactobacillus sakei, NF-κB, STAT3, ulcerative colitis

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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Authors: Lian Zeng

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Double-Spear 1-H2-1 (DS1-H2-1) is an oncolytic virus and an innovative biological drug candidate. The chemical composition of the drug product is a live attenuated West Nile virus (WNV) containing the human T cell costimulator (CD86) gene. After intratumoral injection, the virus can rapidly self-replicate in the injected site and lyse/kill the tumor by repeated infection among tumor cells. We also established xenograft tumor models in mice to evaluate the drug candidate's efficacy on those tumors. The results from preclinical studies on transplanted tumors in immunodeficient mice showed that DS1-H2-1 had significant oncolytic effects on human-origin cancers: it completely (100%) shrieked human glioma; limited human neuroblastoma growth reached as high as 95% growth inhibition rate (%TGITW). The safety data of preclinical animal experiments confirmed that DS1-H2-1 is safe as a biological drug for clinical use. In the preclinical drug efficacy experiment, virus-drug administration with different doses did not show abnormal signs and disease symptoms in more than 300 tested mice, and no side effects or death occurred through various administration routes. Intravenous administration did not cause acute infectious disease or other side effects. However, the replication capacity of the virus in tumor tissue via intravenous administration is only 1% of that of direct intratumoral administration. The direct intratumoral administration of DS1-H2-1 had a higher rate of viral replication. Therefore, choosing direct intratumoral injection can ensure both efficacy and safety.

Keywords: oncolytic virus, WNV-CD86, immunotherapy drugs, glioma, neuroblastoma

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Authors: Andriana E. Tran, Anna Chur-Hansen

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Sexual health is an important aspect of overall wellbeing. This study aimed to explore the sexual health experiences of men aged 50 years and over from the perspective of health care professional participants who were specializing in sexual health care and who consulted with older men. A total of ten interviews were conducted. Eleven themes were identified regarding men’s experiences with sexual health care as reported by participants. 1) Biologically focused: older male clients focus largely on the biological aspect of their sexual health without consideration of other factors which might affect their functioning. 2) Psychological concerns: there is an interaction between mental and sexual health but older male clients do not necessarily see this. 3) Medicalization of sexual functioning: advances in medicine that aid with erectile difficulties which consequently mean that older men tend to favor a medical solution to their sexual concerns. 4) Masculine identity: sexual health concerns are linked to older male clients’ sense of masculinity. 5) Penile functionality: most concerns that older male clients have center on their penile functionality. 6) Relationships: many male clients seek sexual help as they believe it improves relationships. Conversely, having supportive partners may mean older male clients focus less on the physicality of sex. 7) Grief and loss: men experience grief and loss – the loss of their sexual functioning, grief from loss of a long-term partner, and loss of intimacy and privacy when moving from independent living to residential care. 8) Social stigma: older male clients experience stigma around aging sexuality and sex in general. 9) Help-seeking behavior: older male clients will usually seek mechanistic solution for biological sexual concerns, such as medication used for penile dysfunction. 10) Dismissed by health care professionals: many older male clients seek specialist sexual health care without the knowledge of their doctors as they feel dismissed due to lack of expertise, lack of time, and the doctor’s personal attitudes and characteristics. Finally, 11) Lack of resources: there is a distinct lack of resources and training to understand sexuality for healthy older men. These findings may inform future research, professional training, public health campaigns and policies for sexual health in older men.

Keywords: ageing, biopsychosocial model, men's health, sexual health

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Authors: Soumeya Krimat, Tahar Dob, Aicha Kesouri, Ahmed Nouasri, Hafidha Metidji

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Lavandula antineae Maire is an endemic medicinal plant of Algeria which is traditionally used for the treatment of chills, bruises, oedema and rheumatism. The objective of this study is to evaluate the anti-inflammatory of hydromethanolic aerial parts extract of Lavandula antineae for the first time using carrageenan-paw edema and croton oil-ear odema models. The plant extract, at the dose of 200 mg/kg, showed a significant anti-inflammatory activity (P˂0.05) in the carrageenan induced edema test in mice, showing 80.74% reduction in the paw thikness comparable to that produced by the standard drug aspirin 83.44% at 4h. When it was applied topically at a dosage of 1 and 2 mg per ear, the percent edema reduction in treated mice was 29.45% and 74.76%, respectively. These results demonstrate that Lavandula antineae Maire extract possess remarkable anti-inflammatory activity, supporting the folkloric usage of the plant to treat various inflammatory and pain diseases.

Keywords: lavandula antineae maire, medicinal plant, anti-inflammatory activity, carrageenan-paw edema, croton oil-ear edema

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Authors: Marcela Parra-Vargas, Ana Sandoval-Rodriguez, Roberto Rodriguez-Echevarria, Jose Dominguez-Rosales, Juan Armendariz-Borunda

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Non-alcoholic fatty liver disease (NAFLD) is characterized by an excess of hepatic lipids, and it is to author’s best knowledge, the most prevalent chronic liver disorder. Anthocyanin-rich food consumption is linked to health benefits in metabolic disorders associated with obesity and NAFLD, although the precise functional role of anthocyanidin delphinidin (Dp) has yet to be established. The aim of this study was to investigate the effect of the Dp in NAFLD metabolic alterations by evaluating prevention or amelioration of hepatic lipid accumulation, as well as molecular mechanisms in two experimental obesity-related models of NALFD. In vitro: HepG2 cells were incubated with sodium palmitate (PA, 1 mM) to induce lipotoxic damage, and concomitantly treated with Dp (180 uM) for 24 h. Subsequently, total lipid accumulation was measured by colorimetric staining with Oil Red O, and total intrahepatic triglycerides were determined by an enzymatic assay. To assess molecular mechanisms, cells were pre-treated with PA for 24 h and then exposed to Dp for 1 h. In vivo: four-week-old male C57BL/6Nhsd mice were allocated in two main groups. Mice were fed with standard diet (control) or high-fat and high-carbohydrate diet (45% fat, HFD) for 16 wk to induce NAFLD. Then HFD was divided into subgroups: one treated orally with Dp (15 mg/kg bw, HFD-Dp) every day for 4 wk, while HFD group treated with vehicle (DMSO). Weight and fasting glucose were recorded weekly, while dietary ingestion was measured daily. Insulin tolerance test was performed at the end of treatment. Liver histology was evaluated with H&E and Masson’s trichrome stain. RT-PCR was used to evaluate gene expression and Western Blot to determine levels of protein in both experimental models. Parametric data were analyzed with one-way ANOVA and Tukey’s post-hoc test. Kruskal-Wallis and Mann-Whitney U test for non-parametric data, and P < 0.5 were considered significant. Dp prevented hepatic lipid accumulation by PA in HepG2 hepatocytes. Furthermore, Dp down-regulated gene expression of SREBP1c, FAS, and CPT1a without modifying AMPK phosphorylation levels. In vivo, Dp oral administration did not ameliorate lipid metabolic alterations raised by HFD. Adiposity, dietary ingestion, fasting glucose, and insulin sensitivity after Dp treatment remained similar to HFD group. Histological analysis showed hepatic damage in HFD groups and no differences between HFD and HFD-Dp groups were found. Hepatic gene expression of ACC and FAS were not altered by HFD. SREBP1c was similar in both HFD and HFD-Dp groups. No significant changes were observed in SREBP1c, ACC, and FAS adipose tissue gene expression by HFD or Dp treatment. Additionally, immunoblotting analysis revealed no changes in pathway SIRT1-LKB-AMPK and PPAR alpha by both HFD groups compared to control. In conclusion, the antioxidant Dp may provoke beneficial effects in the prevention of hepatic lipid accumulation. Nevertheless, the oral dose administrated in mice that simulated the total intake of anthocyanins consumed daily by humans has no effect as a treatment on hepatic lipid metabolic alterations and histological abnormalities associated with exposure to chronic HFD. A healthy lifestyle with regular intake of antioxidants such as anthocyanins may prevent metabolic alterations in NAFLD.

Keywords: anthocyanins, antioxidants, delphinidin, non-alcoholic fatty liver disease, obesity

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Authors: Md. M. Hossain, Regan Roat, Jenica Christopherson, Colette Free, Zhiguang Guo

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Long noncoding RNA (lncRNA) mediated post-transcriptional gene regulation, and their epigenetic landscapes have been shown to be involved in many human diseases. However, their regulation in diabetes through governing islet’s β-cell function and survival needs to be elucidated. Due to the technical and ethical constraints, it is difficult to study their role in β-cell function and survival in human under in vivo condition. In this study, humanized mice have been developed through transplanting human pancreatic islet under the kidney capsule of NOD.SCID mice and induced β-cell death leading to diabetes condition to study lncRNA mediated regulation. For this, human islets from 3 donors (3000 IEQ, purity > 80%) were transplanted under the kidney capsule of STZ induced diabetic NOD.scid mice. After at least 2 weeks of normoglycecemia, lymphocytes from diabetic NOD mice were adoptively transferred and islet grafts were collected once blood glucose reached > 200 mg/dl. RNA from human donor islets, islet grafts from humanized mice with either adoptive lymphocyte transfer (ALT) or PBS control (CTL) were ribodepleted; barcoded fragment libraries were constructed and sequenced on the Ion Proton sequencer. lncRNA expression in isolated human islets, islet grafts from humanized mice with and without induced β-cell death and their regulation in human islets function in vitro under glucose challenge, cytokine mediated inflammation and induced apoptotic condition were investigated. Out of 3155 detected lncRNAs, 299 that highly expressed in islets were found to be significantly downregulated and 224 upregulated in ALT compared to CTL. Most of these are found to be collocated within 5 kb upstream and 1 kb downstream of 788 up- and 624 down-regulated mRNAs. Genomic Regions Enrichment of Annotations Analysis revealed deregulated and collocated genes are related to pancreas endocrine development; insulin synthesis, processing, and secretion; pancreatitis and diabetes. Many of them, that found to be located within enhancer domains for islet specific gene activity, are associated to the deregulation of known islet/βcell specific transcription factors and genes that are important for β-cell differentiation, identity, and function. RNA sequencing analysis revealed aberrant lncRNA expression which is associated to the deregulated mRNAs in β-cell function as well as in molecular pathways related to diabetes. A distinct set of candidate lncRNA isoforms were identified as highly enriched and specific to human islets, which are deregulated in human islets from donors with different BMIs and with type 2 diabetes. These RNAs show an interesting regulation in cultured human islets under glucose stimulation and with induced β-cell death by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the media of islets cultured with cytokines. Results of this study suggest that the islet specific lncRNAs are deregulated in human islet with β-cell death, hence important in diabetes. These lncRNAs might be important for human β-cell function and survival thus could be used as biomarkers and novel therapeutic targets for diabetes.

Keywords: β-cell, humanized mouse, pancreatic islet, LncRNAs

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Authors: To Que Nga

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College-bound males may experience considerable maladjustment during the crucial developmental time between high school and college. By participating in stereotypically male actions, men may feel under pressure to "prove" their masculinity, which may be harmful to their general well-being. Although adherence to multidimensional male standards has been linked to worse mental health, no research has considered the impact of these norms on college men's potential depressive symptoms. A viable theoretical framework to explain within-group variation in depression symptomatology can be provided by longitudinally examining college men's adherence to multidimensional masculine standards. An overview of recent studies on the connection between masculine norms and depression among Vietnamese men in college is given in this article. 208 males from different Hanoi colleges were included in the study. Male norms were evaluated at the start of their first semester. Six months following the initial round of data collection, depressive symptomatology was evaluated. Men who approved the male norms of Self-Reliance, Playboy, and Power Over Women showed a positive relationship between masculine norms and depression scores. The impact of multidimensional masculine norms on college men's depressive symptomatology was first examined in this study. The findings imply that professionals who interact with males should think about determining whether their clients conform to particular masculine standards and investigating how these could be affecting their present mental health.

Keywords: masculinity, conformity to masculinity, depression, psycho-social issues, men, college

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Authors: Rona Hanani Simamora, Bahagia Loebis, M. Surya Husada

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Background: The exact cause of schizophrenia is not known, although several etiology theories have been proposed for the disease, including immune dysfunction or autoimmune mechanisms. Cytokines including Tnf-α has an important role in the pathophysiology of schizophrenia and the effects of pharmacological treatment with antipsychotics. Nicotine is widespread effects on the brain, immune system and cytokine levels. Smoking among schizophrenic patients could play a role in the altered cytokine profiles of schizophrenia such as Tnf-α. Aims: To determine differences of serum Tnf-α levels between schizophrenic patients with smoking in male and healthy control. Methods: This study was a comparative analytic study, divided into two groups: 1) group of male schizophrenic patients with smoking (n1=30) with inclusion criteria were patients who have been diagnosed schizophrenic based PPDGJ-III, 20-60 years old, male, smoking, chronic schizophrenic patients in the stable phase and willing to participate this study. Exclusion criteria were having other mental disorders and comorbidity with other medical illnesses. 2) healthy control group (n2=30) with inclusion criteria were 20-60 years old, male, smoking, willing to participate this study. Exclusion criteria were having mental disorder, a family history of psychiatric disorders, the other medical illnesses, a history of alcohol and other substances abuse (except caffeine and nicotine). Serum Tnf-α were analyzed using the Quantikine HS Human Tnf –α Immunoassay. Results: Serum Tnf-α level measure in patient schizophrenia male with smoking and compared with the healthy control subjects. Tnf-α levels were significantly higher in patients schizophrenic male with smoking (25,79±27,96) to healthy control subjects (2,74±2,19), by using the Mann Whitney U test showed a statistically significant difference was observed for serum Tnf-α level (p < 0,001). Conclusions: Schizophrenia is a highly heterogeneous disorder, and this study shows an increase Tnf-α as pro-inflammation cytokines in schizophrenics. These results suggest an immune abnormalities may be involved in the etiology and pathophysiology of schizophrenia.

Keywords: male, schizophrenic, smoking, Tnf Alpha

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Authors: Mrinal Gupta, Mohammad Rumman, Babita Singh Abbas Ali Mahdi, Shivani Pandey

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Introduction: Berberine (BBR), a bioactive compound isolated from Coptidis Rhizoma, possesses diverse pharmacological activities, including anti-bacterial, anti-inflammatory, antitumor, hypolipidemic, and anti-diabetic. However, its role as an anti-diabetic agent in animal models of dexamethasone (Dex)-induced diabetes remains unknown. Studies have shown that natural compounds, including aloe, caper, cinnamon, cocoa, green and black tea, and turmeric, can be used for treating Type 2 diabetes mellitus (DM). Compared to conventional drugs, natural compounds have fewer side effects and are easily available. Herein, we studied the anti-diabetic effects of BBR in a mice model of Dex-induced diabetes. Methods: HepG2 cell line was used for glucose release and glycogen synthesis studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. For animal studies, mice were treated with Dex (2 mg/kg, i.m.) for 30 days and the effect of BBR at the doses 100, 200, and 500 mg/kg (p.o.) was analyzed. Glucose, insulin, and pyruvate tests were performed to evaluate the development of the diabetic model. An echo MRI was performed to assess the fat mass. Further, to elucidate the mechanism of action of BBR, mRNA expression of genes regulating gluconeogenesis, glucose uptake, and glycolysis were analyzed. Results: In vitro BBR had no impact on cell viability up to a concentration of 50μM. Moreover, BBR suppressed the hepatic glucose release and improved glucose tolerance in HepG2 cells. In vivo, BBR improved glucose homeostasis in diabetic mice, as evidenced by enhanced glucose clearance, increased glycolysis, elevated glucose uptake, and decreased gluconeogenesis. Further, Dex treatment increased the total fat mass in mice, which was ameliorated by BBR treatment. Conclusion: BBR improves glucose tolerance by increasing glucose clearance, inhibiting hepatic glucose release, and decreasing obesity. Thus, BBR may become a potential therapeutic agent for treating glucocorticoid-induced diabetes and obesity in the future.

Keywords: glucocorticoid, hyperglycemia, berberine, HepG2 cells, insulin resistance, glucose

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Authors: Leila Yazdanpanah, Hajieh Shahbazian, Seyed Mahmoud Latifi, Armaghan Moravej Aleali, Saeed Ghanbari

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Introduction: This study was designed to determine the prevalence of diabetes in people aged over 20 years in Ahvaz, Iran. Material and Methods: The study population selected by cluster sampling. Fasting blood sugar (FBS) assessed after minimum 8 hours night fasting. A questionnaire included: age, sex, weight, height, blood pressure, waist circumference and previous history of diabetes were completed for each patient. FBS≥126mg/dl and/or oral hypoglycemic treatment and/or insulin was defined as diabetes, FBS=100-125 mg/dl as impaired fasting glucose (IFG) and FBS<100mg/dl as normal. Results: Study population was 936 persons (47.2 % male and 52.8% female). The mean age of a population was 42.2±14 years. Diabetes was detected in 15.1 % of population. Only 57cases(6.1%) were aware of their disease and 9% had unknown diabetes. Diabetes was detected in 14.5% of male (11.3% unknown and 3.2 % known diabetes) and in 11.7% of female (7% unknown and 4.7% known diabetes). Prevalence of diabetes had no significant difference (P=0.21) in male and female but unknown diabetes was significantly higher in male (P=0.025). Prevalence of diabetes was increased with rising of age between 20-60 years old but decreasing after 60 years old. Diabetes was related to age, waist circumference and systolic and diastolic blood pressure, TG level and BMI in both sex (P=0.0001). Conclusion: More than half of female and three-fourth of male diabetic patients are unaware of their disease in South of Iran. Diabetes screening should be intensified in this population.

Keywords: diabetes, prevalence, risk factor, awareness

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Authors: Reva Sharan Thakur, Mrinalini Tiwari, Jyoti das

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Cerebral malaria-associated over expression of pro-inflammatory cytokines and chemokines ultimately results in the up-regulation of adhesion molecules in the brain endothelium leading to sequestration of mature parasitized RBCs in the brain. The high-parasitic load subsequently results in increased mortality or development of neurological symptoms within a week of infection. Studies in the human and experimental cerebral malaria have implicated the breakdown of the integrity of blood-brain barrier during the lethal course of infection, cerebral dysfunction, and fatal organ pathologies that result in multi-organ failure. In the present study, using Plasmodium berghei Anka as a mouse model and in vitro conditions, we have investigated the effect of MSCs to attenuate cerebral malaria pathogenesis by diminishing the effect of inflammation altered organ morphology, reduced parasitemia, and increased survival of the mice. MSCs are also validated for their role in preventing BBB dysfunction and reducing malarial toxins. It was observed that administration of MSCs significantly reduced parasitemia and increased survival in Pb A infected mice. It was further demonstrated that MSCs play a significant role in reversing neurological complexities associated with cerebral malaria. Infusion of MSCs in infected mice decreased hemozoin deposition; oedema, and haemorrhagic lesions in vascular organs. MSCs administration also preserved the integrity of the blood-brain barrier and reduced neural inflammation. Taken together, our results demonstrate the potential of MSCs as an emerging anti-malarial candidate.

Keywords: cerebral malaria, mesenchymal stem cells, erythropoesis, cell death

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Authors: Roberto Coppo, Francesca Orso, Daniela Dettori, Elena Quaglino, Lei Nie, Mehran M. Sadeghi, Daniela Taverna

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Malignant melanoma is currently the fifth most common cancer in the white population and it is fatal in its metastatic stage. Several research studies in recent years have provided evidence that cancer initiation and progression are driven by genetic alterations of the tumor and paracrine interactions between tumor and microenvironment. Scattered data show that the Endothelial and Smooth muscle cell-Derived Neuropilin-like molecule (ESDN) controls cell proliferation and movement of stroma and tumor cells. To investigate the role of ESDN in the tumor microenvironment during melanoma progression, murine melanoma cells (B16 or B16-F10) were injected in ESDN knockout mice in order to evaluate how the absence of ESDN in stromal cells could influence melanoma progression. While no effect was found on primary tumor growth, increased cell extravasation and lung metastasis formation was observed in ESDN knockout mice compared to wild type controls. In order to understand how cancer cells cross the endothelial barrier during metastatic dissemination in an ESDN-null microenvironment, structure, and permeability of lung blood vessels were analyzed. Interestingly, ESDN knockout mice showed structurally altered and more permeable vessels compared to wild type animals. Since cell surface molecules mediate the process of tumor cell extravasation, the expression of a panel of extravasation-related ligands and receptors was analyzed. Importantly, modulations of N-cadherin, E-selectin, ICAM-1 and VAP-1 were observed in ESDN knockout endothelial cells, suggesting the presence of a favorable tumor microenvironment which facilitates melanoma cell extravasation and metastasis formation in the absence of ESDN. Furthermore, a potential contribution of immune cells in tumor dissemination was investigated. An increased recruitment of macrophages in the lungs of ESDN knockout mice carrying subcutaneous B16-F10 tumors was found. In conclusion, our data suggest a functional role of ESDN in the tumor microenvironment during melanoma progression and the identification of the mechanisms that regulate tumor cell extravasation could lead to the development of new therapies to reduce metastasis formation.

Keywords: melanoma, tumor microenvironment, extravasation, cell surface molecules

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Authors: Zahra Safaeian, Shila Goldasteh, Rouhollah Radjabi

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Flowerflies of Syrphidae family is one of the largest families among the Diptera order that due to predatory habit of some species in larva stage has an important role for controlling aphids of the fields. In the present study, flowerflies fauna in the alfalfa fields of the north of Khouzestan were studied during 2012-2013. The species of the family were collected using appropriate methods including insect collecting sweeping net and Malaise traps. According to the fact that the shape of male genitalia in the male insect is important in identification of these species the male genitalia was separated from the body and microscopical slide was prepared then species identification was done considering the male genitalia, the patterns and figures on the abdomen and using available keys. Based on the finding four species of Sphaerophoria scripta, Sphaerophoria turkmenica, Melanostoma mellinu, Sphaerophoria ruppelli were collected and according to the abundance frequency of the collected species the most abundance was related to Sphaerophoria scripta, then Sphaerophoria turkmenica had the most abundance and the least abundance was related to Sphaerophoria ruppelli.

Keywords: syrphidae, fauna, alfalfa, Iran

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Authors: S. Zolghadri, M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani

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In this study, the absorbed dose of human organs after injection of ¹⁷⁷Lu-DOTATOC was studied based on the biodistribution of the complex in adenocarcinoma breast cancer bearing mice. For this purpose, the biodistribution of the radiolabelled complex was studied and compartmental modeling was applied to calculate the absorbed dose with high precision. As expected, ¹⁷⁷Lu-DOTATOC illustrated a notable specific uptake in tumor and pancreas, organs with high level of somatostatin receptor on their surface and the effectiveness of the radio-conjugate for targeting of the breast adenocarcinoma tumors was indicated. The elicited results of modeling were the exponential equations, and those are utilized for obtaining the cumulated activity data by taking their integral. The results also exemplified that non-target absorbed-doses such as the liver, spleen and pancreas were approximately 0.008, 0.004, and 0.039, respectively. While these values were so much lower than target (tumor) absorbed-dose, it seems due to this low toxicity, this complex is a good agent for therapy.

Keywords: ¹⁷⁷Lu, breast cancer, compartmental modeling, dosimetry

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Authors: Moustafa Elhamouly, Masayuki Shimada

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The production of competent oocytes is essential for reproductivity in mammals. Maintenance of mitochondrial efficiency is required to supply the ATP necessary for granulosa cell proliferation during the follicular development process. Treatment with Pyrroloquinoline quinone (PQQ) has been reported to increase the number of ovulated oocytes and pups per delivery in mice by maintaining healthy mitochondrial function. This study aimed to elucidate how PQQ maintains mitochondrial function during ovarian follicle growth. To do this, both in vitro and in vivo experiments were performed with granulosa cells from superovulated immature (3-week-old) mice that were pretreated with or without PQQ. The effects of PQQ on beta-oxidation, mitochondrial function, mitophagy, and mitochondrial biogenesis were examined. PQQ increased beta-oxidation-related genes and CPT1 protein content in granulosa cells and this was associated with a decreased phosphorylation of P38 signaling protein. Using the fatty acid oxidation assay on the flux analyzer, PQQ increased the reliance of beta-oxidation on the endogenous fatty acids and was associated with a mild UCP-dependant mitochondrial uncoupling, ATP production, mitophagy, and mitochondrial biogenesis. PQQ also increased the expression of endogenous antioxidant enzymes. Thus, PQQ induced beta-oxidation in growing granulosa cells relying on endogenous fatty acids. And reduced the Reactive oxygen species (ROS) production by inducing a mild mitochondrial uncoupling with keeping high mitochondrial function. Damaged mitochondria were recycled by the induced mitophagy and replaced by the increased mitochondrial biogenesis. Collectively, PQQ may enhance reproductivity by maintaining the efficiency of mitochondria to produce enough ATP required for normal folliculogenesis.

Keywords: granulosa cells, mitochondrial uncoupling, mitophagy, pyrroloquinoline quinone (PQQ), reactive oxygen species (ROS).

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