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SummaryFertility preservation is one of the most important issues in assisted reproductive technology. Previous studies have shown that cytokines and growth factors can improve follicle growth. The endometrial stromal cells secrete various factors that are involved in maintaining the integrity of uterine and epithelial secretory function. The platelet-rich plasma contains a large assembly of platelets suspended in plasma that successfully improves the viability and growth of various cell lines. This work aimed to investigate the influences of conditioned medium (CM) and platelet-rich plasma (PRP) on the development of ovarian follicles in infertile mice due to cyclophosphamide (CYC) exposure. In this study, 65 healthy BALB/c female mice (∼28–30 g and 6-8 weeks old) in five groups were studied. Immunohistochemistry (IHC) was used to detect growth differentiation factor 9 (GDF9)-positive cells. The mRNA expression levels of SMAD1, SMAD2, and BMP15 was assessed using reverse transcription-polymerase chain reaction (RT-PCR) method. The expression levels of SMAD1, GDF9, BMP15, and SMAD2 in the CM+PRP group was significantly more than in the CM and PRP groups. In addition, live birth occurred in the CM+PRP group. Treatment with CM+PRP in infertile mice due to Cy exposure increased fertility and live-birth rate. In general, our study suggested that the CM and PRP combination could improve the growth of mice ovarian follicles in vivo.

Systemic arterial hypertension is an independent risk factor for coronary heart disease, stroke, heart failure, and chronic kidney diseases. Spirulina is microalgae with nutritious ingredients and has potential attenuating effects on chronic diseases including hypertension. Spirulina can be added to food products in order to develop functional foods. The aim of this study was to assess the effects of 8-week consumption of a salad dressing containing 2 g of spirulina platensis powder versus a placebo dressing on patients with hypertension. In this triple-blind randomized clinical trial, 48 patients with hypertension were enrolled to receive daily either spirulina-fortified dressing or placebo for 2 months. A total of 41 patients completed this study. We observed that the consumption of spirulina dressing significantly reduced systolic blood pressure (p = .02), diastolic blood pressure (p = .03), serum triglyceride (p = .01), total cholesterol, and low-density lipoprotein (LDL) levels, compared to nonsignificant changes in the placebo group. Significant changes in TAC and hs-CRP levels were observed in none of the groups. According to our findings, spirulina-fortified dressing as a functional food can be used a supportive treatment for patients with hypertension along with standard antihypertensive drugs. However, further investigations are required for a more comprehensive conclusion.

Rock excavation using drill and blast method is commonly used in tunneling world-wide. Drill and blast method has inherent disadvantage of deteriorating surrounding rock mass due to development of a blast-induced damage zone with reduced strength and stiffness parameters and increased permeability. Traditional tunnel analysis adopts same parameters for the entire rock mass, leading to the underestimation of tunnel stability. The blast damage zone with finite thickness is significant in tunnel stability. Tunneling below the groundwater table affects the hydraulic equilibrium. This will, in turn, cause seepage into the tunnel through the pores and discontinuities in the rock masses. The developed seepage force should be considered as an additional body force acting on both damaged and undamaged rock masses. This study presents a new analytical closed-form solution for the determination of stresses, strains, and displacements around a circular deep underwater tunnel with the consideration of the seepage forces and the damaged zone. The solutions are presented for tunnels excavated in pervious elastic–brittle–plastic rock masses with Mohr–Coulomb failure criterion. The damaged zone is assumed to have cylindrical shape with finite radius. The plastic zones may be formed in both damaged and undamaged rock masses, independently. In order to solve the proposed problem, three different paths for plasticity evolution including six different states that can possibly be encountered in the problem are considered. The results indicate that the seepage and the damaged zone have significant effects on the tunnel convergence and the distribution of stresses in the rock mass.

Janus kinase 3 (JAK3) est un membre de la famille JAK de protéines tyrosine kinase impliquées dans la transduction du signal intracellulaire médiée par les récepteurs de cytokines via la voie de signalisation JAK/STAT. JAK3 s'est avéré exprimé de manière différentielle dans les cellules de la granulosa (GC) des follicules pré-ovulatoires bovins et régulé à la baisse par l'hormone lutéinisante. Ces observations suggèrent que la régulation de JAK3 pourrait moduler la prolifération des GC, l'activité stéroïdienne et l'activation/l'inhibition des cibles en aval. Pour étudier les mécanismes des actions de JAK3 dans GC, nous avons utilisé JANEX-1, un inhibiteur pharmacologique de JAK3, et des traitements FSH et analysé des marqueurs de prolifération, des enzymes stéroïdogènes et la phosphorylation de protéines cibles, y compris STAT3 et les partenaires JAK3 précédemment identifiés CDKN1B/p27Kip1 et MAPK8IP3/JIP3. Les GC en culture ont été traités avec ou sans FSH en présence ou non de JANEX-1. L'ARN total et les protéines ont été extraits et analysés par RT-qPCR, western blot et UHPLC-MS/MS. L'expression de l'enzyme stéroïdogène CYP11A1, mais pas du CYP19A1, était significativement régulée à la hausse dans les GC traités avec la FSH et les deux étaient significativement diminuées lorsque JAK3 était inhibé par rapport au contrôle. Les marqueurs de prolifération CCND2 et PCNA ont été significativement réduits dans les GC traités au JANEX-1 et régulés positivement par la FSH. Les analyses Western blots ont montré que le traitement JANEX-1 réduisait de manière significative les quantités de pSTAT3 tandis que la surexpression de JAK3 augmentait pSTAT3. De même, le traitement à la FSH a augmenté pSTAT3 même dans les GC traités au JANEX-1. Les analyses UHPLC-MS/MS ont montré une phosphorylation et des modifications supplémentaires de résidus d'acides aminés spécifiques dans JAK3 ainsi que ses partenaires de liaison CDKN1B et MAPK8IP3 révélant une activation ou une inhibition possible de JAK3 après des traitements FSH ou JANEX-1, respectivement. L'abondance de la protéine totale JAK3 a augmenté après le traitement par FSH et a diminué de manière significative, avec MAPK8IP3, dans le GC traité par JANEX-1, tandis que l'abondance totale de CDKN1B a été modifiée après FSH et augmentée après JANEX-1. Nous montrons que JAK3 influence l'activité GC par la phosphorylation de protéines cibles en réponse à des stimulations telles que la FSH, ce qui conduit à l'activation de JAK/STAT et module probablement d'autres voies de signalisation impliquant CDKN1B et MAPK8IP3., Janus kinase 3 (JAK3) is a member of the JAK family of tyrosine kinase proteins involved in cytokine receptor-mediated intracellular signal transduction through the JAK/STAT signaling pathway. JAK3 was shown as differentially expressed in granulosa cells (GC) of bovine preovulatory follicles and downregulated by the luteinizing hormone. These observations suggested JAK3 regulation could modulate GC proliferation, steroidogenic activity and activation/inhibition of downstream targets. To investigate the mechanisms of JAK3 actions in GC, we used JANEX-1, a pharmacological JAK3 inhibitor, and FSH treatments and analyzed proliferation markers, steroidogenic enzymes and phosphorylation of target proteins including STAT3 and previously identified JAK3 partners CDKN1B/p27Kip1 and MAPK8IP3/JIP3. Cultured GCs were treated with or without FSH in the presence or not of JANEX-1. Total RNA and proteins were extracted and analyzed by RT-qPCR, western blotting and UHPLC-MS/MS. Expression of steroidogenic enzyme CYP11A1, but not CYP19A1, was significantly upregulated in GC treated with FSH and both were significantly decreased when JAK3 was inhibited as compared to control. Proliferation markers CCND2 and PCNA were significantly reduced in JANEX-1-treated GC and upregulated by FSH. Western blots analyses showed that JANEX-1 treatment significantly reduced pSTAT3 amounts while JAK3 overexpression increased pSTAT3. Similarly, FSH treatment increased pSTAT3 even in JANEX-1-treated GC. UHPLC-MS/MS analyses showed phosphorylation and additional modifications of specific amino acid residues within JAK3 as well as its binding partners CDKN1B and MAPK8IP3 revealing possible activation or inhibition of JAK3 following FSH or JANEX-1 treatments, respectively. Abundance of JAK3 total protein was increased post-FSH treatment and significantly decreased, along with MAPK8IP3, in JANEX-1-treated GC while CDKN1B total abundance was altered post-FSH and increased post-JANEX-1. We show that JAK3 influences GC activity through phosphorylation of target proteins in response to stimulations such as FSH, which leads to the activation of JAK/STAT and likely modulating other signaling pathways involving CDKN1B and MAPK8IP3.

JAK3 is a member of the JAK family of tyrosine kinase proteins involved in cytokine receptor-mediated intracellular signal transduction through the JAK/STAT signaling pathway. JAK3 was shown as differentially expressed in granulosa cells (GC) of bovine pre-ovulatory follicles suggesting that JAK3 could modulate GC function and activation/inhibition of downstream targets. We used JANEX-1, a JAK3 inhibitor, and FSH treatments and analyzed proliferation markers, steroidogenic enzymes and phosphorylation of target proteins including STAT3, CDKN1B/p27Kip1 and MAPK8IP3/JIP3. GC were treated with or without FSH in the presence or not of JANEX-1. Expression of steroidogenic enzyme CYP11A1, but not CYP19A1, was upregulated in GC treated with FSH and both were significantly decreased when JAK3 was inhibited. Proliferation markers CCND2 and PCNA were reduced in JANEX-1-treated GC and upregulated by FSH. Western blots analyses showed that JANEX-1 treatment reduced pSTAT3 amounts while JAK3 overexpression increased pSTAT3. Similarly, FSH treatment increased pSTAT3 even in JANEX-1-treated GC. UHPLC-MS/MS analyses revealed phosphorylation of specific amino acid residues within JAK3 as well as CDKN1B and MAPK8IP3 suggesting possible activation or inhibition post-FSH or JANEX-1 treatments. We show that FSH activates JAK3 in GC, which could phosphorylate target proteins and likely modulate other signaling pathways involving CDKN1B and MAPK8IP3.

Variations of the vertebral artery origin are congenital abnormalities that occur during embryonic development. The vertebral artery origins from the superior part of the first part of the subclavian artery and it provides the main blood supply of the posterior cranial fossa structures. Several variations in the vertebral artery origin and its entry to the transverse foramen have been reported in advance. However, mention to the variation of the right vertebral artery origin and its entrance to the transverse foramen is rare. By describing dissection of an old man cadaver, two vertebral arteries were observed which were arised from the first part of the subclavian artery at the right side, and they follow a different direction to enter the transverse foramen. One of the arteries rises in its natural direction and enters into the transverse foramen of C6, and the other arteries take an abnormal direction upwards and then enter the higher level surface into the transverse foramen of C4. It is necessary to mention, the artery on the left was in its normal state. Regarding neck root surgery, knowing these variations reduces arterial injury during surgery and angiography.

In tunnels, convergences of sidewalls, roof and floor may be different, because of weight of the failed or plastic rock mass. In this paper, a closed-form analytical solution for a deep tunnel excavated in an elastoplastic rock mass is proposed. Using the proposed solution, the effects of the weight of the plastic or failed region developed around the tunnel are investigated. In the proposed method, brittle–plastic or elastic–perfectly plastic behavior and Mohr–Coulomb yield criterion and plastic potential function are used for the ground medium. The gravitational loading is considered as a radial body force being applied to the ground medium. Illustrative examples are given to demonstrate the performance of the proposed method and to examine the effects of the gravity loads. The results obtained by the proposed method show that the gravity loading may affect the tunnel convergence, considerably.