PFKFB3 overexpression in monocytes of patients with colon but not rectal cancer programs pro-tumor macrophages and is indicative for higher risk of tumor relapse

Introduction: Circulating monocytes are main source for tumor-associated macrophages (TAMs) that control tumor growth, angiogenesis, metastasis and therapy resistance. We raised the questions how monocyte programming is affected by growing tumors localized in colon and rectal sections, and how treatment onsets affect monocyte programming in the circulation. Methods: Patients with rectal cancer and colon cancer were enrolled in the study. Peripheral blood monocytes were characterized by phenotypic analysis using flow cytometry, by transcriptomic analysis using RNA sequencing and by gene expression analysis using real-time RT-PCR. Phenotypic analysis was performed with IF/confocal microscopy. Spatial transcriptomic analysis was applied using GeoMX DSP-NGS. Results: In patients with rectal cancer, increased amount of CCR2+ monocytes was indicative for the absence of both lymphatic and hematogenous metastasis. In contrast, in patients with colon cancer CD163+ monocytes were indicative for LN metastasis. NGS analysis identified tumor-specific transcriptional programming of monocytes in all CRC patients compared to healthy individuals. The key transcriptional difference between monocytes of patients with colon and rectal cancer was increased expression of PFKFB3, activator of glycolysis that is currently considered as therapy target for major solid cancers. PFKFB3-expressing monocyte-derived macrophages massively infiltrated tumor in colon. Nanostring technology identified correlation of PFKFB3 with amount and tumor-promoting properties of TAMs in colon but not in rectal cancer. PFKFB3 was indicative for tumor relapse specifically in colon cancer. Discussion: Our findings provide essential argument towards CRC definition to cover two clinically distinct cancers – colon cancer and rectal cancer, that differentially interact with innate immunity

Experience of inulin use for correcting intestinal microbiota in patients suffering from recurrent vulvovaginal candidiasis: A prospective cohort comparative study

Aim. To evaluate the effectiveness of inulin for the adjustment of intestinal microflora in patients with recurrent vulvovaginal candidiasis (VVC). Materials and methods. A prospective cohort comparative study included 79 women aged 18 to 50 years. They were divided into three groups: the main group included 32 patients receiving complex treatment with a dietary supplement containing inulin derived from the "Extra" variety of Jerusalem artichoke root in combination with fluconazole; the comparison group included 27 patients receiving fluconazole only; and the control group included 20 healthy women. The patients were followed up for 12 months. Examination included stool culture for dysbiosis, complete blood count, urinalysis, blood chemistry (glucose, bilirubin, alanine aminotransferase, aspartate aminotransferase, total protein, urea, creatinine), examination of the vulva and vaginal mucosa, vaginal smear microscopy for microflora, Gram staining, real-time polymerase chain reaction for Mycoplasma hominis, Ureaplasma parvum, Trihomonas vaginalis, Chlamydia traсhomatis, Candida albicans. Subsequently, all subjects every three months underwent a bimanual examination, speculum examination of the cervical mucosa and vagina, Gram staining of vaginal mucosa and cervix swabs, a thorough interview, and history taking. At 12 months, stool was cultured for dysbiosis again, and the data were analyzed. Results. The VVC therapy in the group of inulin-containing dietary supplement was more effective: the recurrence rate was 3 times lower than with the standard treatment regimen. Conclusion. The use of dietary supplement containing inulin derived from the "Extra" variety of Jerusalem artichoke root in complex therapy for recurrent VVC can significantly improve the gut and vagina microflora condition and prevent the recurrence and normalization of stool in patients

Factors influencing the sexual drive of Russian women of reproductive age in the digital age

Aim. To assess the impact of age, number of sexual partners, having children, family income, and time spent with a smartphone or computer on the sexual drive of women of reproductive age in the era of information technology. Materials and methods. A study of the sexual drive of 79 women aged 18–35 in family (partner) relationships was conducted. The well-established international Female Sexual Function Index was used. Respondents also answered questions about some aspects of personality and social status. The results were evaluated using the methods of mathematical statistics: descriptive statistics, correlation, determination, and logit-regression analyses. Results. The intensity of sexual drive correlates with a woman's age, the number of sexual partners, and the family income. There was no correlation between the level of a woman's sexual drive and having children and the time women and their partners spend with computers and smartphones

Innovative Development of the Informatization of the Hotel Business in the Context of Globalization of the World Economy

The aim of the article is to study the identification of features of the international hotel business regulation using information technologies. There considered the influence of information technologies on management of the hotel, since it is directly related to the increase in the work efficiency of both an individual manager and the company as a whole, as well as their influence on the company competitiveness in today’s market. The use of computer networks, Internet and Internet technologies, software products of end-to-end automation of all hotel business processes, which today are not just a matter of leadership and creation of competitive advantages but also survival in the market in the near future, is analyzed. The conclusion is made on the need to use information technologies as a tool for regulating international business processes in the hotel sector

Search for additional tests for immunobiological evaluation of the candidate vaccines against African swine fever.

The spread of African swine fever (ASF) in Eurasia has forced a return to the development of live vaccines based on naturally or experimentally attenuated strains of the virus including those resulting from genetic manipulations. This process includes evaluation of the immunomodulating properties of the vaccines. In this report we provide our assessment of two tests for immunobiological evaluation of a candidate live vaccine against ASF from the attenuated ASF virus (ASFV) strain KK-202: (i) investigation of the effect of the attenuated ASFV strain KK-202 on the protectiveness of the vaccine ASFV strain FK-32/135 and a vaccine against classical swine fever (CSF) from the strain LK-VNIIVViM; (ii) determination of the phagocytic activity of blood neutrophils in pigs inoculated with ASFV strains differing in virulence. A simultaneous or sequential inoculation of attenuated strain KK-202 (seroimmunotype II) and vaccine strain FK-32/135 (seroimmunotype IV) into pigs resulted in the loss of protection against the virulent strain France-32 (seroimmunotype IV). Following the simultaneous or sequential inoculations of the ASFV strain KK-202 and the CSF virus (CSFV) vaccine produced from the strain LK-VNIIVViM, the neutralizing antibody titers against the CSFV observed in the experimental groups (after vaccination and after the challenge infection with the virulent CSFV strain Shimen) were not different from those found in animals of the control group. The phagocytic activity of blood neutrophils was shown to increase from 30% in the norm to 50%-94% depending on the virulence of the ASFV strains inoculated into pigs. The results of this work demonstrate the ability of the attenuated ASFV strains to modulate the development of the cellular link of protective immunity without negative impact on the humoral immune response. The informative value of the described immunobiological tests in vivo and in vitro seems to be a more preferable alternative in comparison to the commonly used in vitro tests, which do not always correlate with the development of protection against ASF

The attenuated ASFV strains MK-200 and FK-32/135 as possible models for investigation of protective immunity by ASFV infection.

African swine fever (ASF) is an infectious disease of domestic and wild pigs of all breeds and ages, with the acute form of the disease being characterized by high fever, hemorrhages in the reticuloendothelial system and a high mortality rate. Registered safe and efficacious ASF vaccines are not available. The development of experimental ASF vaccines, particularly live attenuated, have considerably intensified in the last years. There is much variability in experimental approaches undertaken by laboratories attempting to develop first generation vaccines, rendering it difficult to interpret and make comparisons across trials. ASF virus (ASFV) genotyping does not fully correlate with available cross-protection data and may be of limited value in predicting cross-protective vaccine efficacy. Recently, ASFV strains were assigned to a respective nine groups by seroimmunotype (from I to IX): in vivo the grouping is based on results of cross protection of pigs survived after their infection with a virulent strain (bioassay), while in vitro this grouping is based on hemadsorption inhibition assay (HADIA) data. Here we demonstrate the antigenic and protective properties of two attenuated ASFV strains MK200 and FK-32/135. Pronounced differences in the HADIA and in immunological test in animals allow us to consider them and the corresponding reference virulent strains of the ASFV of Mozambique-78 (seroimmunotype III, genotype V) and France-32 (seroimmunotype IV, genotype I) as useful models for studying the mechanisms of protective immunity and evaluation of the candidate vaccines

TfOH-Promoted Reaction of 2,4-Diaryl-1,1,1-Trifluorobut-3-yn-2-oles with Arenes: Synthesis of 1,3-Diaryl-1-CF₃-Indenes and Versatility of the Reaction Mechanisms

The TfOH-mediated reactions of 2,4-diaryl-1,1,1-trifluorobut-3-yn-2-oles (CF3-substituted diaryl propargyl alcohols) with arenes in CH2Cl2 afford 1,3-diaryl-1-CF3-indenes in yields up to 84%. This new process for synthesis of such CF3-indenes is complete at room temperature within one hour. The synthetic potential, scope, and limitations of this reaction were illustrated by more than 70 examples. The proposed reaction mechanism invokes the formation of highly reactive CF3-propargyl cation intermediates that can be trapped at the two mesomeric positions by the intermolecular nucleophilic attack of an arene partner with a subsequent intramolecular ring closure

Acid-Promoted Reaction of Trifluoromethylated Allyl Alcohols with Arenes. Stereoselective Synthesis of CF₃‑Alkenes and CF₃‑Indanes

Reaction of 4-aryl-1,1,1-trifluorobut-3-en-2-ols [CF₃-allyl alcohols, ArCHCHCH­(OH)­CF₃] with arenes under activation with anhydrous FeCl₃ or FSO₃H was studied. We found that the transformation led to trifluoromethylated alkenes [Ar­(Ar′)­CHCHCHCF₃] or 1-trifluoromethylated indanes (CF₃-indanes). The formation of these two types of reaction products strongly depends on the nucleophilicity of the starting arene and the electrophilicity of cationic intermediates generated from CF₃-allyl alcohols under reaction conditions. Benzene, anisole, veratrole, and <i>ortho-</i>xylene lead exclusively to CF₃-alkenes with an <i>E-</i>configuration. More π-donating polymethylated arenes (pseudocumene, mesitylene) afford only CF₃-indanes with a predominantly <i>cis-</i>orientation of substituents at positions 1 and 3 of the indane ring. <i>Meta-</i> and <i>para-</i>xylenes show an intermediate behavior; they may form both CF₃-alkenes and/or CF₃-indanes. The mechanisms of the investigated transformations are discussed