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Here we report a recombinant baculoviral vector-based DNA vaccine system against Middle East respiratory syndrome coronavirus (MERS-CoV) and the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2). A non-replicating recombinant baculovirus expressing the human endogenous retrovirus envelope gene (AcHERV) was constructed as a DNA vaccine vector for gene delivery into human cells. For MERS-CoV vaccine construction, DNA encoding MERS-CoV S-full, S1 subunit, or receptor-binding domain (RBD) was inserted into the genome of AcHERV. For COVID19 vaccine construction, DNA encoding SARS-CoV2 S-full or S1 or a MERS-CoV NTD domain-fused SARS-CoV2 RBD was inserted into the genome of AcHERV. AcHERV-DNA vaccines induce high humoral and cell-mediated immunity in animal models. In challenge tests, twice immunized AcHERV-MERS-S1 and AcHERV-COVID19-S showed complete protection against MERS-CoV and SARS-CoV2, respectively. Unlike AcHERV-MERS vaccines, AcHERV-COVID19-S provided the greatest protection against SARS-CoV2 challenge. These results support the feasibility of AcHERV-MERS or AcHERV-COVID19 vaccines in preventing pandemic spreads of viral infections.

Abstract:Objective: Diabetes, including type 1 and type 2, is associated with the hypercoagulable state. The aim of this study is to evaluate the concentration of selected hemostatic parameters and vascular endothelial growth factor-A (VEGF-A) in diabetic subjects. Methods: The study was conducted in 62 patients with diabetes. Group I consisted of 27 patients having uncontrolled diabetes with microalbuminuria and Group II included 35 well-controlled diabetic patients. The control group was made up of 25 healthy volunteers. In the citrate plasma, the concentrations of tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombin-antithrombin (TAT) complexes, and D-dimer were assayed. Serum concentrations of VEGF-A, lipid profile, creatinine, and plasma fasting glucose were measured and in the versene plasma the concentration of HbA1c was determined. Results: In the patients with uncontrolled diabetes, higher concentrations of TF, TFPI, and VEGF-A were observed, as compared with the well-controlled diabetics group and the control group. A significantly lower activity of antiplasmin was reported in patients from Group I as compared with the control group. In Group I, using the multivariate regression analysis, the glomerular filtration rate was independently associated with VEGF-A and dependently associated with total cholesterol. Conclusions: The study showed higher concentrations of TF and TFPI in the patients with uncontrolled diabetes with microalbuminuria, which is associated with rapid neutralization of the thrombin formation, since TFPI inhibits the complex of TF/VIIa/Ca 2+ . The manifestation of the above suggestions is the correct TAT complexes and D-dimer, which indicates a low grade of prothrombotic risk in this group of patients, but a higher risk of vascular complications.

Background and Objectives: Endometriosis is a hormone-dependent chronic inflammatory disease with serious reproductive and general health consequences. It is viewed as a multifactorial problem, consisting of matters related to altered immunity and genetics. In this study, we determined the correlation between endometriosis and allergic and autoimmune diseases in patients at reproductive age. Materials and Methods: Online surveys distributed through websites related to gynecological problems. The questionnaire was composed of 63 single and multiple-choice questions concerning the course of endometriosis, diet, and allergic and autoimmune diseases. The obtained data were assessed using statistical tests. Results: 501 female patients (mean age 31.1 SD = 6.8) were included in the study. The control group (n = 155) consisted of healthy females, whereas the study group (n = 346) consisted of female patients with endometriosis; each group was subdivided according to allergy status. There were statistically significant differences between groups for the following: positive family history of endometriosis (p = 0.0002), onset of allergic symptoms (p = 0.0003), frequency and duration of abdominal pain (p = 0.00625), and defecation disorders (p = 0.0006). Asthma was less common in the study group (p = 0.00611). The group of patients with endometriosis and allergies had a high median of consumption of red meat (p = 0.0143), fish (p = 0.0016), and dairy products (p = 0.0001). Conclusions: Endometriosis did not affect autoimmune diseases and their courses. Patients with diagnosed endometriosis presented allergy symptoms much earlier than the healthy patients. The consumption of dietary products such as soya products, red meat, and alcohol had an influence on the occurrence of endometriosis.

The current pandemic and the possible emergence of new viruses urgently require the rapid development of antiviral vaccines and therapeutics. However, some viruses or newly generated variants are difficult to culture in common cell types or exhibit low viral susceptibility in vivo, making it difficult to manufacture viral vector-based vaccines and understand host–virus interactions. To address these issues, we established new cell lines deficient in both type I and type II interferon responses, which are essential for host immunity and interference with virus replication. These cell lines were generated by developing an integrated CRISPR-Cas9 system that simultaneously expresses dual-guide RNA cassettes and Cas9 nuclease in a single plasmid. Using this highly efficient gene-editing system, we successfully established three cell lines starting from IFN-α/β-deficient Vero cells, deleting the single interferon-gamma (IFNG) gene, the IFNG receptor 1 (IFNGR1) gene, or both genes. All cell lines clearly showed a decrease in IFN-γ-responsive antiviral gene expression and cytokine production. Moreover, production of IFN-γ-induced cytokines remained low, even after HSV-1 or HCoV-OC43 infection, while expression of the receptor responsible for viral entry increased. Ultimately, knockout of IFN-signaling genes in these cell lines promoted cytopathic effects and increased apoptosis after viral infection up to three-fold. These results indicate that our integrated CRISPR-Cas9-mediated IFNG- and IFNGR1-knockout cell lines promote virus replication and will be useful in viral studies used to design novel vaccines and therapies.

Notre communication s'intéressera à l'acte réactif dialogal de la réponse de l'interviewé politique à un certain type de question, fréquent, que nous définirons en termes de question médiée, dans l'interview politique, et plus précisément aux stratégies discursives employées, afin d'éviter une réponse franche et directe qui pourrait exposer sa face, sur la scène médiatique. Le genre interview politique peut très grossièrement se définir comme relevant de l'hypergenre des interactions verbales, qu'il spécifie de la façon suivante : l'interaction s'organise entre deux parties :-le (ou les) intervieweur(s) : un journaliste, dont le rôle est de poser des questions ; -le (ou les) interviewé(s) : une personnalité politique, dont le rôle est de répondre aux questions qui lui sont posées.L'interview est centrée sur la parole de l'interviewé, ses prises de position etc, devant lesquelles l'intervieweur doit s'effacer, il doit n'en être qu'un pur médiateur. Le journaliste intervieweur est là pour faire parler l'invité politique, pour tenter de faire sortir le renard de sa tanière, en questionnant sur ce qui fait problème. Les questions médiées se signalent par deux traits : (i) elles manifestent fréquemment une médiation énonciative, à savoir qu'elles se présentent comme rapportant, de différentes manières, un propos tenu antérieurement par un autre locuteur, qui appartient le plus souvent à la sphère politique ou syndicale ; (ii) ce propos est presque toujours contrediscursif, voire franchement polémique, ce qui donne à la question un tour offensif. La convocation d'autres discours permet au journaliste (i) d'être le « porteparole », le locuteur, le relais de questions qui se posent ; et (ii) de poser des questions offensives, sinon offensantes, en s'abritant derrière la médiation de la parole rapportée. Nous appellerons questions médiées toutes celles qui s'appuient de différentes manières sur le discours rapporté. La structure de la question médiée peut être décrite (en appui sur Nowakowska et Bres 2009), selon un module à 4 éléments:(i) thème général (avec parfois appui sur le dire immédiat de l'interviewé)(ii) jugement (offert à la mise en débat de la verbalisation de l'intervieweur) (iii) médiation énonciative de ce jugement (iv) interrogation peut porter directement sur le jugement : "est-ce que ii" ou se développer comme demande d'évaluation de ce jugement Soit l'exemple suivant :(1) Interview de J.-F. Copé par O. Galzi, dans Les quatre vérités, le 9 décembre 2008 OG29 -dernière question Xavier Bertrand va prendre la tête de l'UMP / vous êtes le chef de groupe UMP à l'assemblée (i) / on dit de lui (iii) que c'est votre meilleur ennemi (ii)// c'est vrai ? (iv) La forme de la question médiée de l'intervieweur correspond, dans ce cas, à la structure : thème (i), jugement rapporté médié (iii+ii) + interrogation (iv).

Background and Objectives: Uterine fibroids develop in 25–40% of women of childbearing age; however, there are discrepancies resulting from population and socioeconomic differences. The pathogenesis of fibroids is not clear. The aim of the study was to assess the potential connection between the use of oral contraceptives and the occurrence of uterine fibroids in women of childbearing age. Materials and Methods: In this prospective, survey, case–control study, data were collected from Caucasian female patients (mean age = 30) using a questionnaire concerning the onset, duration and form of hormonal contraception, and medical and obstetrical history. The questionnaires were handed personally to hospitalized patients as well as distributed through Google forms on social media. Results: In a study group (n = 140) of patients using hormonal contraception, 37.8% of them were diagnosed with uterine fibroids, whereas among the patients not using hormonal contraception (n = 206), uterine fibroids were diagnosed in 59.6% of the patients. The most common hormonal contraception was two-component hormonal tablets used by 93.3% of the patients. Taking contraceptives was a uterine fibroids protective factor (OR = 0.4, p = 0.007). In the study group, 5.5% of the patients were pregnant and 60.42% were diagnosed with uterine fibroids (OR = 4.4, p < 0.000001). Conclusion: Contraception was found to be a protective factor for uterine fibroids among the women surveyed. The presented data confirm the theory about the hormonal dependence of uterine fibroids.

Human papillomavirus (HPV) is a group of viruses that are extremely common worldwide. There are more than 100 types of HPV, including at least 14 cancer-causing viruses. Although the majority of infections cause no symptoms and are self-limiting, genital HPVs have become a major public health concern because persistent infection with certain types can cause cervical cancer, which kills about 311,000 women worldwide each year [1-3]. HPV serotypes 16 and 18 are reported to account for approximately 70% of cases, with the most common serotypes detected in women with cervical cancer [4]. Although commercial vaccines, including Gardasil and Cevarix, represent a remarkable improvement in the fight against cervical disease and other anogenital cancers, vaccinated individuals may remain infected with HPVs that are not targeted by the vaccines. Further, because the vaccines are relatively expensive, they may not be available to all women, especially those in developing countries [5, 6]. Currently no FDA-approved antiviral drugs are available to treat HPV infection [7, 8]. Recent studies investigating the prevention and treatment of HPV related to cervical cancer and other genital diseases are attracting increasing attention worldwide [8]. The study of inhibitors is focused on the oncogenic proteins E6 and E7, and the replication proteins E1 and E2 [9, 10]. The therapies for HPV-associated lesions, including cryotherapy, surgical excision, and topical application of cytotoxic agents, are mostly ablative and cytodestructive although genital warts can be treated by topical application of the immunomodulator imiquimod [11, 12]. Despite studies investigating the treatment of HPV-related lesions, effective drugs or treatments for HPV infection are imperative. Herbal medicine is considered one of the alternative approaches to the treatment of viral diseases (Ghanbari et al., 2019). Approximately 70,000 species of plants are used in herbal medicine, including the treatment of HPV infection [13, 14]. Green tea extract has been reported to regulate the genes involved in the pro-inflammatory response to HPV infection and inhibit the binding to receptors [15]. A recently approved Polyphenon ® E ointment found effective against HPV-related diseases was formulated with catechins extracted from green tea [16]. Pinus densiflora Sieb. et Zucc. has been reported to contain several phenolic compounds that exhibit biological activity, such as antibacterial and antioxidant effects, as well as potential anti-viral activity against the influenza A virus [17]. Among studies on the pharmacological action of pine needles, saponin is known to exhibit strong lethal Most cervical cancers are associated with high-risk human papillomavirus (HPV) infection. Currently, cervical cancer treatment entails surgical removal of the lesion, but treatment of infection and preventing tissue damage are issues that still remain to be addressed. Herbal medicine and biological studies have focused on developing anti-viral drugs from natural sources. In this study, we...