Preventive Vaccine Research Articles

Cost-effectiveness of bivalent respiratory syncytial virus prefusion F vaccine for prevention of respiratory syncytial virus among older adults in Germany

ABSTRACT Introduction Among older adults, lower respiratory tract infection (LRTI) caused by respiratory syncytial virus (RSV) is common. We evaluated the cost-effectiveness of bivalent RSV prefusion F protein-based vaccine (RSVpreF) for prevention of RSV-LRTI among older adults in Germany. Research design and methods A static cohort model was developed to estimate lifetime health and economic outcomes of RSV-LRTI among adults aged 60–99 years in Germany, with (vs. without) use of RSVpreF. Vaccine uptake ranged from 27% to 54%. Vaccine effectiveness was derived from trial data and was assumed to last over 3 years, with some waning, following vaccination. Base case analyses were conducted from the societal perspective (costs/benefits discounted 3% annually); sensitivity analyses also were conducted. Results Among adults aged 60–99 years (N = 25.3 M), RSVpreF prevented 117,360 cases of hospitalized RSV-LRTI, 100,433 cases of ambulatory RSV-LRTI, and 9,298 RSV-LRTI-related deaths over a lifetime horizon. With total overall costs higher by 1.8 € billion and 49,576 quality-adjusted life-years (QALYs) gained, cost-effectiveness of RSVpreF was 36,064 €/QALY. In probabilistic sensitivity analyses, the mean cost-effectiveness ratio was 36,518 €/QALY; 925 of 1,000 replications yielded ratios <50,000 €/QALY. Conclusions RSVpreF has the potential to greatly reduce the public health and economic burden of RSV among older adults in Germany.

LADS: a powerful vaccine platform for cancer immunotherapy and prevention

BackgroundThe intracellular bacterium Listeria monocytogenes is an attractive vector for cancer immunotherapy as it can effectively deliver tumor antigens to antigen-presenting cells, leading to a robust antitumor response.ResultsIn this study, we developed a novel vaccine platform called Listeria-based Live Attenuated Double Substitution (LADS), which involves introducing two amino acid substitutions (N478AV479A) into the virulence factor listeriolysin O (LLO). LADS is a safe vaccine platform, with an attenuation of nearly 7000-fold, while retaining complete immunogenicity due to the absence of deletion of any virulence factors. We developed two LADS-based vaccines, LADS-E7 and LADS-AH1, which deliver the human papillomavirus (HPV) type 16 E7 oncoprotein and murine colon carcinoma immunodominant antigen AH1, respectively. Treatment with LADS-E7 or LADS-AH1 significantly inhibited and regressed established tumors, while also dramatically increasing the populations of tumor-infiltrated antigen-specific CD8+ T cells. RNA-sequencing analysis of tumor tissue samples revealed that LADS-E7 altered the expression of genes related to the immune response. Moreover, intratumoral injection of LADS-based vaccines induced strong antitumor responses, generating systemic antitumor responses to control distant tumor growth. Encouragingly, LADS-E7 or LADS-AH1 immunization effectively prevented tumor formation and growth.ConclusionsOur findings demonstrate that LADS-based vaccines represent a more powerful platform for the development of immunotherapeutic and preventive vaccines against cancers and infectious diseases.

HPV genotypes in invasive cervical cancer: prevalence, risk attribution, and optimized vaccine strategies in western China

BackgroundUnderstanding the HPV genotype distribution in invasive cervical cancer (ICC) is essential for vaccine optimization. This study presents a comprehensive analysis of HPV genotypes in ICC tissues from patients in western China, with the aim of informing regional vaccine policy and prevention strategies.MethodsDNA was extracted from 1,908 paraffin-embedded ICC samples, and 23 HPV genotypes were detected via PCR and reverse dot hybridization gene chip assays. The genotypic distribution of HPV infections was analyzed, the attribution of each HPV genotype found in multiple infection cases was calculated using the fractional contribution approximation. Furthermore, the cumulative attribution rates of HPV genotypes included in each vaccine combination were totaled to estimate the potential vaccination coverage of ICC across various histologic types and age groups.ResultsThe overall prevalence of HPV infection was 94.9% (95% CI 93.8–95.8) among 1,908 women with ICC. HPV genotypes 16 and 18 were detected in 1645 of 1810 HPV-positive patients (90.9, 95% CI 89.5–92.1) of ICC. HPV16, 18, 33, 52, and 58 were detected in 1,749 patients (96.6, 95% CI 95.7–97.4), the five most common genotypes in different age groups. HPV genotypes contained in the 9-valent vaccine were detected in 1776 patients (98.1, 95% CI 97.4–98.7). By weighted imputation analysis, the cumulative attribution rates of the bivalent vaccine was 83.4%, and that of the nine-valent vaccine was 89.8%. Optimization group A included the five genotypes with the highest prevalence, HPV16, 18, 33, 52, and 58, with a cumulative attribution rates of 88.5%, and optimization group B included the nine most common HPV genotypes, HPV16, 18, 31, 33, 35, 45, 52, 58, and 59, with a cumulative attribution rates of 90.5%.ConclusionOur comprehensive postsurgical analysis of HPV in ICC patients in western China revealed that the incorporation of the bivalent vaccine into the national program is cost-effective, with group A optimization closely matching the vaccination coverage of the 9-valent vaccine, which can be used to guide future prevention strategies.

Development, effectiveness, and future directions of HPV vaccines

Human papillomavirus (HPV) vaccines are vaccines used to prevent sexually transmitted diseases caused by HPV. HPV infection is the leading causation that causing the cervical cancer. Specifically, high-risk-type, for instance, HPV-16 and HPV-18, are also connected with some other cancers. This article summarizes the development mechanism, availability, clinical trials, and problems faced by HPV vaccines. Currently, there were three approved HPV vaccines, including bivalent vaccine, quadrivalent vaccine, and nine-valent vaccine, which can prevent different types of HPV infection. The widely utilization of HPV vaccines has notably diminished the occurrence of diseases that are connected with HPV, especially to guard against cervical cancer. However, research on therapeutic HPV vaccines is still in its early stages, and the results of existing studies in terms of effectiveness and side effects are not ideal. Despite this, therapeutic vaccines remain a promising area in HPV research. This article summarizes the mechanism and effect of preventive HPV vaccines, explores the current status of therapeutic vaccine development, and provides basic information for future HPV vaccine research. Future research should focus on developing more targeted therapeutic vaccines and continue to improve preventive vaccines to cover more high-risk HPV types.

Understanding student engagement in vaccination education: an interview-based multi-stakeholder study

The COVID-19 pandemic has underscored the importance of informed decision-making, especially concerning vaccination for disease prevention. This highlights the need for scientific literacy, trust, and understanding of relevant concepts such as pathogens, immune responses, and transmission pathways. Additionally, societal and ethical considerations are integral for a comprehensive approach. While collaborating with medical professionals and fostering argumentation and decision-making skills hold promise for enhancing engagement with these topics in educational settings, understanding students’ perspectives is essential for maintaining their motivation to learn and their interest in such complex subjects. Therefore, a qualitative study involving interviews with secondary school students, experienced educators, and vaccination experts familiar with school environments was conducted to identify factors fostering student engagement and interest in immunobiology and vaccines. The findings highlight focal areas of student interest in the topic and the value of involving students in lesson planning. They also underscore the importance of real-world relevance and the need for clear, student-centered communication with medical professionals. Recommendations for educators include integrating interactive learning activities, real-world examples, and case studies.

Epstein-Barr virus and immunity.

The Epstein-Barr virus has infected the vast majority of the world's population. EBV is the most common herpes virus in the human population. In childhood, viral infection is either asymptomatic or can lead to infectious mononucleosis. In a small proportion of latently infected people, especially in immunosuppressed patients, EBV causes lymphoid and epithelial malignancies and a number of autoimmune diseases, including one of the causes of the development of multiple sclerosis. Innate immunity is the first line of antiviral defense, which EBV evades using a number of strategies to achieve successful infection. EBV disrupts the innate immune signaling pathways activated by Toll-like, RIG-I-like, NOD-like and AIM2-like receptors, as well as cyclic GMP-AMP synthetase. EBV also antagonizes interferon production and signaling, including the TBK1-IRF3 and JAK-STAT pathways. Through differential modulation of proviral and antiviral mechanisms of action of caspases and other cellular life cycle regulators at different stages of infection, EBV actively interferes with apoptotic and inflammatory pathways to continue effective infection. By turning the activation of innate immunity to its advantage by triggering a pro-inflammatory reaction and proteolytic cleavage of caspases that exhibit proviral activity, the virus establishes latency or enters the lytic reactivation phase, which contributes to the development of serious life-threatening diseases, including oncogenesis. The outcome of EBV infection is regulated by a subtle interaction between innate, adaptive immunity, and viral replication. In the absence of licensed preventive vaccines, immunocorrection and antiviral therapy are the only possible ways to combat the virus and prevent diseases associated with it. Understanding the mechanisms of action of certain EBV genes involved in the life cycle at different stages of infection will help in the future to find the right approach to the development of preventive and therapeutic drugs against EBV.

Vaccines for cancer prevention: exploring opportunities and navigating challenges.

Improved understanding of cancer immunology has gradually brought increasing attention towards cancer-preventive vaccines as an important tool in the fight against cancer. The aim of this approach is to reduce cancer occurrence by inducing a specific immune response targeting tumours at an early stage before they can fully develop. The great advantage of preventive cancer vaccines lies in the potential to harness a less-compromised immune system in vaccine recipients before their immune responses become affected by the advanced status of the disease itself or by aggressive treatments such as chemotherapy. Successful implementation of immunoprevention against oncogenic viruses such as hepatitis B and papillomavirus has led to a dramatic decrease in virally induced cancers. Extending this approach to other cancers holds great promise but remains a major challenge. Here, we provide a comprehensive review of preclinical evidence supporting this approach, encouraging results from pioneering clinical studies as well as a discussion on the key aspects and open questions to address in order to design potent prophylactic cancer vaccines in the near future.

Comparative Effectiveness of Cell-Based Versus Egg-Based Influenza Vaccines in Prevention of Influenza Hospitalization During the 2022-2023 Season Among Adults 18-64 Years.

This retrospective cohort study evaluated the comparative vaccine effectiveness (cVE) of licensed standard-dose cell-based versus egg-based influenza vaccines in preventing influenza hospitalization among adults 18-64 years during the 2022-2023 season. The cohort included eligible Kaiser Permanente Southern California members who received ≥ 1 dose of influenza vaccine (n = 848,334). The adjusted cVE against influenza hospitalization was -10.1% (95% CI: -49.8%, 37.8%) in the 18- to 49-year-old cohort. In the 50- to 64-year-old cohort, the adjusted cVE was 14.9% (-33.8%, 52.1%). Cell-based and egg-based influenza vaccines conferred comparable protection against influenza hospitalization in adults 18-64 years of age in the 2022-2023 season.

Advances in human norovirus research: Vaccines, genotype distribution and antiviral strategies.

Norovirus, belonging to the Caliciviridae family, is a non-enveloped, positive-sense single-stranded RNA virus. It is widely acknowledged as a significant etiological agent responsible for non-bacterial acute gastroenteritis and considered a major cause thereof. Norovirus is primarily tranmitted via fecal-oral route, but can also be transmitted via airborne routes. Clinical manifestations often include symptoms associated with acute gastroenteritis, like nausea, vomiting, watery diarrhea, stomach cramps, and others. Due to the specific pathogenic mechanism of the virus, and genomic diversity, there are currently no preventive vaccines or effective antiviral drugs available for treating norovirus-induced acute gastroenteritis infections. The management of such infections mainly relies on oral rehydration therapy while prevention necessitates adherence to personal hygiene measures. The present paper discusses the nature, transmission route, clinical manifestations, immune response mechanism, and vaccine research of Norovirus. The objective of this review manuscript is to systematically gather, analyze, and summarize recent research and investigations on norovirus in order to enhance our understanding of its characteristics and pathogenesis. This not only facilitates subsequent researchers in acquiring a more expedited and comprehensive grasp of the existing knowledge about norovirus but also provides clearer directions and goals for future studies.

Enhancing preventive and therapeutic cancer vaccine efficacy through biotherapeutic ligand-associated extracellular vesicles

Extracellular vesicles (EVs), secreted by almost all living cells, have gained significant attention for their role in intercellular communication and their potential as versatile carriers for biotherapeutics. However, the clinical translation of EV-based therapies faces significant challenges, primarily due to the lack of efficient methods for loading biotherapeutic agents into EVs. This study introduces a simple, reproducible strategy for the simultaneous incorporation of various biotherapeutics within EVs. The process is gentle and preserves the essential physicochemical and biological characteristics of EVs, thereby protecting labile ligands from premature degradation and elimination. The binding and uptake efficiency of EVs by target cells reached approximately 97 % within 24 h of incubation. Administration of EVs loaded with oligodeoxynucleotides (ODN) resulted in a 4-fold increase in IFNγ+ CD4+ T cells and a 5-fold increase in IFNγ+ CD8+ T cells in the spleens and lymph nodes. Additionally, the co-administration of EVs with ODN and ovalbumin (OVA) induced elevated Th1-biased antibody responses and antigen-specific cytotoxic T-cell responses, providing long-lasting complete protection in 60 % of mice against T-cell thymoma challenge. Furthermore, EVs associated with three different ligands (OVA, CpG-ODN, and α-GalCer) effectively regressed established murine melanoma and significantly improved survival rates in mice. This study presents a powerful and promising approach to overcoming the limitations of EV-based cancer vaccines, advancing the development of effective cancer immunotherapies. SummaryImmunization with EVs that are co-associated with antigen and biotherapeutic cargo through a lyophilization-based technique elicits potent anti-cancer immunity.

Beyond Social Media: The Influence of News Consumption, Populism, and Expert Trust on Belief in COVID-19 Misinformation

The COVID-19 pandemic was accompanied by an unprecedented influx of misinformation often with adverse impact on the effectiveness of institutional responses to the health crisis. However, relatively little is still known about the factors that may have facilitated the proliferation and public acceptance of misinformation related to the virus or to the government’s anti-pandemic measures, particularly in comparative perspective. Utilizing data collected by a representative cross-country survey ( N = 5,000) in four countries led by populist leaders during the pandemic—Brazil, Poland, Serbia, and the United States—this study explores the links between three mutually interrelated factors, namely media usage across different platforms, affinity to populism, and trust in scientific expertise, and people’s beliefs in selected COVID-related misinformation. The findings show that preexisting attitudes, especially affinity to populism and mistrust in experts, are generally stronger predictors of people’s likelihood to endorse misinformation related to the pandemic than their news consumption patterns. Nevertheless, the analysis also indicates an important role played by exposure to specific media brands, particularly those promoting a skeptical stance toward preventive measures and COVID-19 vaccines, as well as messaging apps, which display stronger relationship with misinformation beliefs than social networking sites. The article concludes by discussing implications for practical efforts to combat misinformation, especially during a health crisis.

Inhibition of Neospora caninum activity by niclosamide: Evidence from in vitro and in vivo studies

Neosporosis caused by Neospora caninum (N. caninum) is one of the main causes of bovine miscarriage, but there are currently no effective drugs or vaccines for treatment and prevention. Our previous works have found that NLRP3 inflammasome activation participated in controlling N. caninum proliferation and niclosamide has been regarded as an NLRP3 inflammasome inducer. This study aimed to evaluate the resistance of niclosamide to N. caninum infection. Niclosamide-mediated NLRP3 inflammasome activation was determined by LDH and ELISA measurement of IL-1β release as a marker for inflammasome activation in a model of N. caninum-infected macrophages. The in vitro antiparasitic effect of niclosamide was further explored in Vero cells by plaque assays, qPCR, and Giemsa staining. The in vivo effects were investigated in N. caninum-infected mice by measuring parasite burden, histopathology, and survival. Results showed that niclosamide partially enhanced macrophage-mediated clearance of N. caninum via the NLRP3 inflammasome activation and displayed direct antiparasitic activity. Plaque assays confirmed significant inhibition of N. caninum growth, and niclosamide effectively reduced cell invasion and intracellular proliferation compared to toltrazuril. In vivo, after niclosamide treatment, the body weight was regained, survival rate was increased, tissue damage was reduced, and parasite burden in tissues was significantly decreased. The numerous vacuole formations were observed in niclosamide-treated N. caninum tachyzoites by electron microscopy. Mitochondrial membrane potential and ATP production of N. caninum tachyzoites were reduced considerably by niclosamide treatment. In conclusion, niclosamide showed strong potential as a therapeutic agent for N. caninum infection, offering a promising treatment option for neosporosis.

Construction and evaluation of glycoprotein-based nucleic acid vaccines for Marburg virus.

Marburg virus (MARV) is a zoonotic virus that can infect humans and non-human primates (NHPs) and lead to a fatal Marburg hemorrhagic fever (MHF), while there is no approved vaccine or antiviral treatment for MHF. The nucleic acid vaccine has unique advantages, including fast and simple preparation, easy to follow the virus mutation situation, and less adverse reactions. Therefore, we constructed the DNA and mRNA candidate vaccines based on codon-optimized MARV glycoprotein sequence, and evaluated the immune effect in mice through ELISA, ELISpot, and Flow cytometry. After the second booster immunization, both of the candidate vaccines induced strong humoral immune response, enhanced T cell response, and elicited neutralizing antibodies. Notably, DNA candidate vaccine induced stronger humoral immune response, while mRNA candidate vaccine elicited higher levels of IFN-γ and IL-4. In addition, transcriptome analysis revealed that the candidate vaccines activated immune response related pathways. Our study shed new light on the nucleic acid vaccines for MARV and further confirmed the potential of nucleic acid vaccine for future MHF prevention and control.

Asymmetric polarization by vaccination status identification during the COVID-19 pandemic.

COVID-19 prevention measures and vaccine policies have led to substantial polarization across the world. I investigate whether and how vaccination status and vaccination status identification affect the sympathy and prejudice for vaccinated and unvaccinated individuals. Drawing on a preregistered vignette survey experiment in a large representative sample from Germany (n = 6,100) in December 2021, I show that prejudice was greater among the vaccinated towards the unvaccinated than vice versa. Furthermore, I find that differences in sympathy ratings are strongly subject to vaccination status identification. If individuals do not identify with their vaccination status, there are no differences in the evaluation of the in- and outgroups. Stronger vaccination status identification is, however, associated with greater prejudice among the vaccinated towards the unvaccinated but not for the unvaccinated towards the vaccinated. The results therefore show a stronger polarization on the side of the vaccinated that increases with the identification of one's vaccination status.

Recent Advances in the Development of Mincle-Targeting Vaccine Adjuvants

The Macrophage-inducible C-type lectin (Mincle) is a pattern-recognition receptor (PRR), which has shown much promise as a molecular target for the development of TH1/TH17-skewing vaccine adjuvants. In 2009, the first non-proteinaceous Mincle ligands, trehalose dimycolate (TDM) and trehalose dibehenate (TDB), were identified. This prompted a search for other Mincle agonists and the exploration of Mincle agonists as vaccine adjuvants for both preventative and therapeutic (anti-cancer) vaccines. In this review, we discuss those classes of Mincle agonists that have been explored for their adjuvant potential. These Mincle agonists have been used as stand-alone adjuvants or in combination with other pathogen-associated molecular patterns (PAMPs) or immunomodulatory agents. We will also highlight recently identified Mincle ligands with hitherto unknown adjuvanticity. Conjugate vaccines that contain covalently linked adjuvants and/or adjuvant–antigen combinations are also presented, as well as the different formulations (e.g., oil-in-water emulsions, liposomes, and particulate delivery systems) that have been used for the codelivery of antigens and adjuvants. Insofar the reader is presented with a thorough review of the potential of Mincle-mediated vaccine adjuvants, including historical context, present-day research and clinical trials, and outstanding research questions, such as the role of ligand presentation and Mincle clustering, which, if better understood, will aid in the development of the much-needed TH1/TH17-skewing vaccine adjuvants.

The Impact of Vaccinations Against Respiratory Infections on the Prognosis in Heart Failure Patients

Heart failure (HF) affects 64 million people worldwide and is one of the most prevalent causes of hospitalization in adults. Infection is believed to be one of the potential triggers that may facilitate HF decompensation and the need for hospitalization. Therefore, it seems crucial to safeguard against such a situation. Vaccinations seem to be a very reasonable option. However, this remains an underutilized solution among HF patients. This review investigates the impact of available vaccinations, including influenza, COVID-19, pneumococcal, and RSV, on prognosis in specific HF populations only, as there are pathophysiological reasons to believe that this population of patients may benefit the most from the intervention. It will provide information about the safety profile of these vaccines and summarize the available evidence on their impact on hard clinical outcomes. In summary, this article will discuss the impact of preventive vaccinations against seasonal infections in the HF population.

Three-dimensional liver organoids as a novel platform for studying hepatitis B virus infection

Hepatitis B virus (HBV) infection is a major global health problem that contributes to chronic liver diseases, such as cirrhosis and hepatocellular carcinoma. Despite advances in antiviral therapy and the availability of preventive vaccines, current treatments often do not completely eradicate the virus, particularly in chronic HBV carriers, and the incidence of liver cancer due to chronic HBV infection remains high. A major obstacle to HBV research is the lack of infection models that can accurately recapitulate the complex interactions between HBV and the host. Existing models, such as hepatoma cell lines and animal models, are limited by species-specific barriers and the lack of support for the complete viral life cycle. These limitations pose significant challenges to the study of HBV pathogenesis and the development of therapies aimed at complete eradication of HBV. In recent years, 3-dimensional (3D) liver organoids have emerged as promising in vitro model systems to study HBV infection and HBV-mediated liver disease. These organoids serve as a suitable physiologically relevant platform for investigating HBV pathogenesis, including the ability of HBV to promote liver tumorigenesis. Furthermore, liver organoids can be genetically modified, patient-derived, expanded, and biobanked, providing a powerful tool for studying HBV pathogenesis and personalized medicine, drug discovery, and screening. In this review, we explore the utilization of 3D liver organoids as a research model for studying HBV infection and HBV-associated liver cancer, highlighting their advantages over conventional models.

Analysis of the incidence of influenza and acute upper respiratory tract infections under conditions of routine influenza vaccination

Background. Acute upper respiratory tract infections and influenza, while maintaining high epidemiological, social and economic significance, have a major effect on the public health of countries and individual regions.The aim. To study the impact of influenza vaccination on the manifestations of the epidemic process of influenza and acute upper respiratory tract infections in the Irkutsk region.Materials and methods. Epidemiological analysis of the incidence of acute upper respiratory tract infections and influenza, analysis of influenza mortality and the impact of vaccination on these infections were performed using continuous samples of statistical data from the Directorate of Rospotrebnadzor in the Irkutsk Region for the period of 2003–2022 (forms 2, 5).Results. The intensity of the epidemic process of acute upper respiratory tract infections among the general population, children and adults during the observation period was characterized by an uneven course with a tendency towards increase. The dynamics of the incidence of acute upper respiratory tract infections in children and adults demonstrates multidirectional trends over the compared periods. The incidence of influenza in the general population had a steady downward trend, the decrease rate was –8.4 %. At the same time, there are significant changes in the intensity of the epidemic process in the compared periods. The proportion of adults increased in the structure of cases of acute upper respiratory tract infections, and the proportion of children increased in the structure of cases of influenza. Significant changes in the epidemic seasons of influenza are shown. Since the beginning of routine influenza vaccination in the region, the number of vaccinated people has increased annually – from 23.6 to 61.7 % of the population. Against the background of the influenza vaccination campaign, a statistically significant decrease in the incidence of acute upper respiratory tract infections among the general population and children under 14 years of age was registered (p &lt; 0.01).Conclusion. In the Irkutsk region, the epidemiological disadvantage for the studied infections persists. Increasing the regulated indicators of population coverage with preventive influenza vaccinations (75 % and more) will help reduce the incidence rate.

Furamidine-induced autophagy exerts an anti-mycobacterial effect in a SIRT1-pAMPK-FOXO3a-dependent manner by elevation of intracellular Ca2+ level expression

Mycobacterium tuberculosis (M. tb), the etiological agent of tuberculosis (TB), continues to be a major contributor to global mortality rates. To effectively combat this pandemic, TB control has to be enhanced in several areas, including point-of-care diagnostics, shorter and safer drug regimens, and preventative vaccination. The latest findings have highlighted autophagy as a host-defense mechanism that eradicates many invading bacteria, including M. tb. Thus, novel approaches like the stimulation of autophagy using various pharmaceutical drugs can be undertaken to deal with this noxious pathogen. The present study has been formulated to evaluate the anti-mycobacterial potential of Furamidine, a DNA minor groove binder (MGB). Initially, a non-cytotoxic concentration of Furamidine (10 µM) was used to assess its impact on the intracellular persistence of mycobacteria in differentiated THP-1 (dTHP-1) cells. Furamidine treatment compromised intracellular mycobacterial growth compared to control cells. Autophagy, a well-known host-defensive strategy, was investigated as a possible contributor to revealing the mechanism of action. Multiparametric approaches such as LC3-I to II conversion, protein level expression of different autophagic markers, and MDC staining were employed to study autophagic response that conclusively suggested the autophagy induction potential of Furamidine in dTHP-1 cells. Further, elevated LC3-II expression and increased autophagic vacuole accumulation under Baf-A1 treatment demonstrated the positive regulation of autophagic flux upon Furamidine treatment. Mechanistic investigations showed increased intracellular calcium (Ca2+) level expression, SIRT1, pAMPK, and FOXO3a activation upon its treatment. Inhibition of Ca2+ level expression suppressed Ca2+-mediated-FOXO3a level in Furamidine-treated cells. Furthermore, administering various inhibitors hampered the Furamidine-induced autophagy that impacted intracellular mycobacteria clearance. These results conclude that Furamidine triggered the Ca2+/pAMPK/SIRT1/FOXO3a pathway, causing less mycobacterial load in dTHP-1 cells.

Current epidemiological characteristics of cervical cancer in the Russian Federation

Background. The prevalence of cervical cancer (Cca) in Russian women makes it crucial to study modern epidemiological characteristics and adjust control measures accordingly.The aim. To analyze trends in the incidence of cervical cancer in the Russian Federation.Materials and methods. A retrospective epidemiological study was conducted on cervical cancer incidence in Russian Federation from 2008 to 2021. The materials of annual statistical data “Malignant neoplasms in Russia (morbidity and mortality)” and “Status of oncological assistance to the population of Russia” (2008–2022), data of the federal statistical reporting form No. 5 “Information about preventive vaccinations” (2021), data on the number of studies conducted (cytological study and HPV-test based on RT-PCR) in the clinical diagnostic laboratory of Central Research Institute of Epidemiology of Rospotrebnadzor (2013–2021) were used.Results and discussion. The trends of Cca incidence varied depending on the women’s age. Starting in 2016, there was a stabilization of the level of morbidity in women aged 30–49 with the subsequent decrease from 2019 due to the strengthening of secondary prevention measures, including the active introduction of HPV-test into the diagnostic schemes conducted in the Russian Federation. Increased control of cervical cancer caused a rise in the proportion of cases diagnosed at an early stage (carcinomas in situ and I–II stages Cca), the increase of detection rate of in situ carcinomas per 100 cases of Cca, the growth of the proportion of carcinomas in situ to I–II stages Cca, rise of the percentage of the cases detected actively, decrease of the number of Cca cases detected at later stages and one-year mortality index.Conclusion. The epidemiological analysis of cervical cancer incidence shows that preventive measures are effective and that there is a need to intensify and increase their coverage.