Treatment Of Infectious Diseases Research Articles

Advances in Coordination Chemistry of Schiff Base Complexes: A Journey from Nanoarchitectonic Design to Biomedical Applications.

Since the discovery of Schiff bases over one and a half centuries ago, there has been tremendous research activity in the design of various Schiff bases and examination of their diverse structures and versatile applications. This family of compounds has continued to captivate many research groups due to the simplicity of their synthesis through the condensation of amines with carbonyl compounds. While conventional synthesis has been the most widely used, green synthetic methodologies have been also explored for this reaction, including sonication, microwave-assisted, natural acid-catalyzed and mechanochemical syntheses as well as utilizing ionic liquid solvents or deep eutectic solvents. Schiff bases have been utilized as excellent ligands for coordination to transition metals and late transition metals (lanthanides and actinides). These Schiff base compounds can be mono-, di-, or polydentate ligands. The aim of this review is to examine the biological applications of Schiff base complexes over the past decade with particular focus on their antimicrobial, antiviral, anticancer, antidiabetic, and anti-inflammatory activity. Schiff base complexes have been found effective in combating bacterial and fungal infections with numerous examples in the literature. The review addressed this area by focusing on the very recent examples while using tables to summarize the vast breadth of research according to the metallic moieties. Viruses have continued to be a target of many researchers in light of their continuous mutations and impact on human health, and therefore some examples of Schiff base complexes with antiviral activity are described. Cancer continues to be among the leading causes of death worldwide. In this article, the use of Schiff base complexes for, and the mechanisms associated with, their anticancer activity are highlighted. The production of reactive oxygen species (ROS) or intercalation with DNA base pairs leading to cell cycle arrest were the main mechanisms described. While there have been some efforts made to use Schiff base complexes as antidiabetic or anti-inflammatory agents, there are limited examples when compared with antimicrobial and anticancer studies. The conclusion of this review highlights the emerging areas of research and future perspectives with an emphasis on the potential uses of Schiff bases in the treatment of infectious and noninfectious diseases.

Biofilm Inhibition: The Role of Fixed Oil from Caryocar coriaceum in Fighting Resistant Bacterial Communities

Biofilms, formed by microbial communities that increase resistance to antibiotics, are responsible for chronic infections, making their combat a therapeutic priority. Taking this into account, the fruit Caryocar coriaceum stands out for its potential in the treatment of infectious diseases. The different parts of this plant can be used, and the fixed oil extracted from its fruit, rich in fatty acids, is indicated as responsible for its biological activities. Thus, the objective of this study was to evaluate the chemical composition of the fixed oil extracted from the fruits of C. coriaceum (FOCC), in addition to analyzing its action in the inhibition and pre-formed biofilm disruption of bacteria. The fixed oil was extracted from the internal mesocarp through exhaustive extraction with n-hexane, resulting in a yield of 38.29%. For antibiofilm evaluation, multidrug-resistant bacterial strains were exposed to the oil, and the antibiofilm activity was verified through biofilm formation and pre-formed biofilm disruption assays. The chemical analysis of the fixed oil of C. coriaceum (FOCC) identified eight fatty acids, representing 98.2% of the total composition, with a predominance of oleic acid (60.1%) and palmitic acid (33.5%). FOCC demonstrated approximately 70% inhibition of Streptococcus mutans biofilm formation at a concentration of 10 mg/mL and approximately 60% inhibition against Staphylococcus aureus and Pseudomonas aeruginosa. In pre-formed biofilm disruption, FOCC showed low efficacy against S. mutans and P. aeruginosa but showed greater activity against Enterococcus faecalis and S. aureus. These results indicate that FOCC has the potential to prevent biofilms, but its pre-formed biofilm disruption capacity is still limited.

Click chemistry-enabled gold nanorods for sensitive detection and viability evaluation of copper(II)-reducing bacteria.

The rise of antibiotic resistance poses a significant and ongoing challenge to public health, with pathogenic bacteria remaining a persistent threat. Traditional culture methods, while considered the gold standard for bacterial detection and viability assessment, are time-consuming and labor-intensive. To address this limitation, we developed a novel point-of-care (POC) detection method leveraging citrate- and alkyne-modified gold nanorods (AuNRs) synthesized with click chemistry properties. These AuNRs exhibit superior biocompatibility and enhanced quantitative performance compared to conventional surfactant-modified AuNRs. Our method, termed AuNRs-bacteria-initiated click chemistry (AuNRs-BICC), detects CuII-reducing bacteria by quantifying AuNRs bound to a biosensing interface via bacteria-mediated CuII reduction to CuI and subsequent click chemistry with biosensing interface of azide modifications. Using dark-field microscopy (DFM), we demonstrated a strong linear correlation between AuNR counts and the logarithm of bacterial concentration for both Gram-negative Escherichia coli (including KPC-2-expressing antibiotic-resistant strains) and Gram-positive Staphylococcus aureus across a range of 101 to 107cells, achieving a remarkable detection limit of 101cells. The AuNRs-BICC biosensor exhibits high selectivity for target bacterial strains and provides rapid detection within 3h. Furthermore, it can assess bacterial viability in the presence of various antibiotics, including meropenem, ceftriaxone and tetracycline, suggesting its potential for rapid antibiotic susceptibility testing and facilitating timely clinical intervention for infectious diseases.

Standardization, Characterization and Potential Biological Activity of Ozonized Sunflower Vegetable Oil

Objective: The ozone molecule, composed of three oxygen atoms, possesses high oxidizing power and is widely utilized for various applications, including therapeutic treatments involving the administration of medicinal ozone to combat various diseases. The standardization of ozonized oil is essential to ensure patient safety. The objective of this study was to develop protocols for the standardization and characterization of ozonized oil using analytical techniques such as gas chromatography-mass spectrometry (GC-MS) and to evaluate its biological activity through microbiological and cytotoxic assays. Methods: Standardization and characterization were carried using gas chromatography coupled to mass spectrometry (CG-MS), and microbiological tests including agar diffusion, time-kill and MIC and cytotoxic tests were employed in bacterial cells. Results: The obtained results indicated that after 480 minutes of ozonization in 100 mL of sunflower oil (OG), a significant antimicrobial potential was observed, leading to the formation of ozonides. Antibacterial and antifungal activity assays, conducted using the ‘time kill’ method, agar diffusion, and Minimum Inhibitory Concentration (MIC) tests, demonstrated activity against Staphylococcus aureus, Escherichia coli, Salmonella choleraesuis, Pseudomonas aeruginosa, Candida albicans, Aspergillus brasiliensis, and Malassezia furfur. Conclusion: Results demonstrate the therapeutic potential of the application of ozonized oil in the treatment of topic infectious diseases. In summary, the standardization of the ozonization process of sunflower oil showed to be promising, providing a product exerting antimicrobial activity and therapeutic potential, opening perspectives for its application in various areas of medicine.

P-1799. Impact of coronavirus disease 2019 on infectious disease treatment and infection control: Multicenter study in Japan

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic impacted infection control practices such as hand hygiene and antimicrobial use, but its specific effects remain unclear. Thus, in this multicenter study, we aimed to determine the pandemic's effect on these factors by comparing pre- and post-COVID-19 periods. (A) The number of inpatients by month during the study period. (B) The amount of hand sanitizer used per inpatient by month during the study period. The two solid lines show the regression lines in the pre- and post-COVID-19 periods. The dashed line in the post-COVID-19 period is an extension of the regression line in the pre-COVID-19 period. Methods Data on hand sanitizer use, antimicrobial use, positive blood cultures, and antimicrobial-resistant (AMR) organism detections were collected monthly from April 2015 to March 2023 at four Japanese hospitals. The pre-COVID-19 period data (April 2015 to March 2020) were compared to the post-COVID-19 period data (April 2020 to March 2023). Results Compared to pre-COVID-19, hand sanitizer use per inpatient and antimicrobial use, particularly broad-spectrum antimicrobials, increased significantly post-COVID-19. The proportion of positive blood cultures increased, but AMR organism detections remained unchanged, suggesting increased contamination rather than infection. Conclusion Ongoing antimicrobial use monitoring, hand hygiene education, and promotion of effective infection control and antimicrobial stewardship by infection control teams are crucial for prevention of future pandemics. (A) Total DOT (combined with all antimicrobials extracted in this study) by month. (B–F) DOT of individual antimicrobial agents by month. The two solid lines show the regression lines in the pre- and post-COVID-19 periods. Other antimicrobial agents are shown in Appendix Figure A.1. Abbreviations: CFPM, cefepime; CI, confidence interval; CTRX, ceftriaxone; DOT, days of therapy; MEPM, meropenem; SBT/ABPC, sulbactam/ampicillin; TAZ/PIPC, tazobactam/piperacillin. Disclosures Hiroshi Kakeya, MD, PhD, Asahikasei Phrma: Honoraria|GSK: Honoraria|MSD: Honoraria|Pfizer: Honoraria|Shionogi: Honoraria|Sumitomo Parma: Honoraria

P-1306. Establishing Respiratory Syncytial Virus (RSV) Surveillance Methodology within the Indian Health Service

Abstract Background American Indian and Alaska Native (AI/AN) populations have high rates of Respiratory Syncytial Virus (RSV)-associated hospitalizations among both infants and older populations. Due to underrepresentation, most national surveillance reports do not adequately describe the burden of disease in the AI/AN population. Currently, there is no standardized approach for RSV surveillance within the IHS. This work explores establishing RSV surveillance using IHS-specific electronic medical records (EMR) data. Additionally, this work aims to implement a standardized surveillance methodology across IHS for RSV and adaptable for other infectious diseases. The objective of this abstract is to describe the process of RSV surveillance methodology within the IHS. Venn diagram of ICD and LOINC datasets The above image is a representation of the Venn diagram of ICD and LOINC datasets. The two datasets are merged together to identify the overlapped records and unique ICD and LOINC records for RSV. Methods We investigated the utility of using administrative data from Federal, Tribal, and Urban Indian health facilities for RSV surveillance among AI/AN population for Fiscal Year (FY) 2023. We evaluated RSV administrative codes, such as Logical Observation Identifiers Names and Codes (LOINC), International Classification of Diseases (ICD) 9 and 10, to develop an algorithm for RSV records. The records that contained either an ICD 9 or ICD 10 code for RSV came from the ICD dataset; records that contained RSV-specific LOINC code came from the LOINC dataset. Final set of records were flagged as positive and negative RSV records.Table 1.Distribution of unique LOINC records by the type of tests The table shows the distribution of the unique LOINC records by the four categories of type of tests. The categories include PCR, Antigen, Antibody and Culture tests. Results In FY 2023, 16396 records came from the ICD dataset and 151542 records came from the LOINC dataset. On merging ICD and LOINC datasets, 4623 records overlapped, 11830 records were unique to ICD dataset and 146959 records were unique to LOINC dataset. Of the records unique to LOINC dataset (146959), 81% (n=119698) represent PCR tests while antigen (n=13722) and antibody (n=13384) tests represent 9% respectively. Conclusion This study highlights the importance of using both ICD and LOINC codes for identifying RSV cases in EMR. It aids in understanding trends and burden among AI/AN population. Currently, we are conducting site validations to evaluate the surveillance methods across IHS. Additionally, surveillance reports and epidemiological studies generated using this standard approach could help target interventions for RSV and other infectious diseases. Disclosures All Authors: No reported disclosures

P-898. Reproducible profiling of eight Brazilian infectious diseases specialist training sites through open databases

Abstract Background Many factors influence the choice of a specialty and a residency training site after essential medical education, including hospital characteristics. We set out to explore characteristics of infectious diseases (ID) and pediatric ID training sites in one Brazilian state, aiming to provide a data-driven input into residency site choice. Number of hospitalizations and age and sex of patients (A) Absolute number of hospitalizations per institution in the 10-year period, and (B) proportion of hospitalizations in each institution along the years. (C) Violin plots of ages for each institution with the same maximum width, and inner boxplots with width proportional to hospitalization count. (D) Frequency plots of male and female patients hospitalized in each institution, with (E) corresponding area plots adding to 100% for every age. Methods We performed a retrospective, descriptive study of hospitalizations in institutions which offer ID and/or peds ID medical training, using Ministry of Health openly available hospitalization databases as sources. We used R software version 4.3.1 for analysis to ensure reproducibility. Procedures performed, length of hospital stay and intensive care unit costs per institution (A) Proportion of diagnostic, clinical, surgical and transplant procedures carried out in each hospital. (B) Proportion of specialty associated with hospital bed used for each hospitalization. (C) Violin plots of days of hospital stay for each institution. (D) Violin plots of total ICU costs (US dollars, log scale) in each hospitalization for each hospital; (E) the same plot, after removing COVID hospitalizations. Results Eight institutions from Rio de Janeiro (RJ) fit the criteria and had available data. From January 2013 to December 2022, they carried out 583,362 hospitalizations. Two hospitals (HGNI, HUPE) accounted for 56.6% of these. The hospitals with peds ID positions (IPPMG, IFF) have different age distributions because one also admits birthing mothers. Most admissions were due to clinical or surgical procedures, with a minority cataloged as diagnostic procedures or cell, tissue and organ transplants. Most patients were discharged within 7 days. HUCFF had the highest proportion of diagnostic and transplant procedures (1.88% and 2.12%, respectively). On average, university hospitals are paid 2∼3 times as much as other institutions per hospitalization. Overall disease burden was diverse, but INI stood out as a center for HIV care. Proportions of ICD-10 chapters or subchapters as leading causes of hospitalization Heatmaps with unsupervised clustering of ICD-10 chapter or subchapter frequency as leading cause of hospitalization, for all hospitalizations (A), for hospitalizations filed under “clinical treatment of infectious and parasitic diseases” or “clinical treatment of HIV/AIDS” (B), or for hospitalizations filed under ICD-10 chapters I or VI (C). Conclusion Hospitals in RJ with ID and peds ID residency spots have distinct workloads, patient profiles, disease burden and government-paid income. Residents from these programs might express similar views, but they do not necessarily reflect the widest picture, and might not be accessible to all interested candidates. Although subjectivity should not be discarded when choosing a training site, open data can inform more precise, transparent distinctions. For example, candidates interested in transplant ID could be more inclined to choose HUCFF, while candidates interested in less complex care could opt for HGNI. The framework we provide can also be employed to analyze other programs and hospitals, such as surgical residencies. Not all hospitals with residency positions feed these databases, thus limiting our analysis. Disclosures All Authors: No reported disclosures

P-511. Missed Opportunities for Pre-Exposure Prophylaxis Initiation in Hospitalized Persons with Opioid Use Disorder and Infectious Diseases

Abstract Background Hospitalizations are increasing among persons with opioid use disorder (OUD) secondary to overdose as well as infections. Hospital settings are a reachable moment not only to offer treatment for OUD and co-occurring infections, but also to offer HIV testing and link to antiretroviral therapy to treat and prevent HIV. Pre-exposure prophylaxis (PrEP) prevents HIV acquisition through both sharing injection drug use equipment and condomless sexual intercourse. Unfortunately, few persons who use drugs including those with OUD are offered PrEP. This descriptive analysis sought to examine patients’ knowledge and attitude about PrEP to better understand if PrEP initiation at time of hospital contact could be used as a way to increase PrEP uptake in patients with OUD.Figure 1.Participants’ perceived risk of HIV on hospital discharge. Methods A retrospective data analysis was performed from the ongoing parent study, Project COMMIT (Coordinated Medical Treatment of Opioid Use Disorder and Infectious Disease). Adult patients (N = 144) hospitalized with bacterial, viral, or fungal infection with moderate to severe OUD were recruited upon admission to hospital and randomized 1:1 to either: 1) infectious disease management of OUD with long-acting injectable buprenorphine vs. 2) treatment as usual. Of the 144, 73 participants who did not report HIV infection, completed a supplemental questionnaire assessing beliefs in PrEP. Basic demographic information, sexual and HIV risk factors, and opioid use risk factors and beliefs about PrEP were reported as frequencies and percentages. Results When exploring HIV risk behavior in the past 30 days, 46 (63%) used injection drugs, 26 (35.6%) had condomless sex, 3 (4.1%) knew of their sexual partner being HIV positive or of unknown status, and 12 (16.4%) shared works. Of the 73 who completed the survey, 29 (39.7%) had never heard of PrEP, and none (n=0, 0.0%) had taken PrEP before. When asked about perceived risk of HIV, on a 4-point scale (high, medium, low or no risk), a majority of participants 64 (87.7%) thought they had no or low risk of HIV infection. Conclusion This study identified the need for increased education about risk for HIV and PrEP among people who use drugs and attention to acute hospitalization as a reachable moment for engaging them in HIV prevention care. Disclosures Sheela Shenoi, MD MPH, Merck Pharmaceuticals: Stocks/Bonds (Private Company) Frances Levin, MD, Aelis Pharmaceuticals: Grant/Research Support|Indivior: Medication for Research|Major League Baseball: Advisor/Consultant|NCATS: Grant/Research Support|NIDA: Grant/Research Support|NYSPI: Salary Support|SAMSHA: Grant/Research Support|US World Meds: Grant/Research Support Edward Nunes, MD, Alkermes: Advisor/Consultant|Alkermes: donated medication or digital therapeutics|Braeburn: donated medication or digital therapeutics|Camurus: Advisor/Consultant|Camurus: donated medication or digital therapeutics|Chess Health: donated medication or digital therapeutics|Indivior: Advisor/Consultant|Indivior: donated medication or digital therapeutics|Pear Therapeutics: Advisor/Consultant|Pear Therapeutics: donated medication or digital therapeutics Alain H. Litwin, MD, MPH, MS, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Merck Pharmaceuticals: Advisor/Consultant Sandra Ann Springer, MD, Alkermes Inc: Honoraria|Alkermes Inc: In kind study drug donation for NIH sponsored research|Indivior Pharmaceutical company: In kind study drug donation for NIH sponsored research

Roles of mobile teams in tracing lost to follow–up clients: evidence from the optimization of COVID-19 vaccination uptake and routine immunization in Ekiti State

BackgroundEvidence from literature has established that tracing lost to follow-up clients is an effective strategy for complementing other mechanisms for infectious disease control like human immunodeficiency virus (HIV), tuberculosis, and other diseases such as Ebola. As a long-standing successful public health method of optimizing acceptance and/or adherence to infectious disease treatment tracing lost to follow-up clients is usually carried out by manually investigating individuals who absconded or are absent from treatments designed to manage and/or promote their health status. This study seeks to explore the role of mobile teams in tracing clients lost to follow-up for immunization.MethodsThis study was premised on a qualitative research approach to elicit information from purposively selected populations across 9 local government areas (LGA) in Ekiti state, Nigeria. Focus group discussions, in-depth interviews, and key informant interviews were the selected methods of data collection on the roles of mobile teams in tracing lost to follow–up clients for the optimization of COVID-19 and routine immunization in Ekiti state.ResultsA total of 107 healthcare workers across Ekiti state were selected to participate in this study. Our study found tracing lost to follow-up clients resulted in two major successes for health workers. These are increased awareness of COVID-19 vaccination and routine immunization, and improved vaccination coverage for both categories of vaccinees. Distance between communities, and transportation, were interdependent issues reported by health workers as challenges in the course of their duties.ConclusionOur study emphasizes the importance of onboarding and/or training health workers across all categories that are involved in the implementation of a public health program, irrespective of the existing knowledge that they may have on the concept. This study recommends that health workers across all levels, in collaboration with key players and stakeholders employ human-centered designed approaches to improve the sensitization of caregivers, and community populace on the values, benefits, and significance of the COVID-19 vaccination and routine immunization uptake.

Current pathogenicity factors of viral and bacterial pathogens of young cattle

Infectious pathologies of animals remain the main problem on the path of high productivity, preservation and, as a result, productive longevity of animals and ultimately determines the profitability of agricultural industrial production of animal products. The possibility of developing pathologies is caused by specific substances of predominantly organic origin (proteins, enzymes, toxins, glycopeptides, etc.), which cause a set of highly specific pathogenic properties of microorganisms. In this connection, there is a growing interest and need to study the pathogenic properties of viruses and bacteria, which cause a number of mechanisms that ensure the neutralization of protective immune mechanisms of animals (adhesive, anti-complementary, anti-lactoferin, antihemoglobin, anti-lysozyme activity, biofilm formation, antibiotic resistance, etc.). The study and development of effective methods to counteract these pathogenicity factors is possible only taking into account the study and search for the practical application of specific substances in the form of vaccines and drugs. Numerous studies of infectious agents causing pathology of the gastrointestinal tract with diarrhea syndrome in calves, according to statistics, distinguish the most common bovine rotavirus, bovine coronavirus, bovine viral diarrhea virus, bovine calicivirus and bovine torovirus, as well as bacteria Salmonella spp., E. coli, C. perfringens and C. parvum. The data from the review of the pathogenicity factors of bacteria and viruses show their diversity, which causes various forms of the course and manifestations of infectious pathologies. Monitoring and further study of the antigenic profile of infectious pathogens allows timely development of relevant diagnostic methods for their identification. The study of protein antigenic proteins makes it possible to develop means for the treatment and prevention of infectious animal diseases.

Causal Estimands for Analyses of Averted and Avertible Outcomes due to Infectious Disease Interventions.

During the coronavirus disease (COVID-19) pandemic, researchers attempted to estimate the number of averted and avertible outcomes due to vaccination campaigns to quantify public health impact. However, the estimands used in these analyses have not been previously formalized. It is also unclear how these analyses relate to the broader framework of direct, indirect, total, and overall causal effects under interference. Here, using potential outcome notation, we adjust the direct and overall effects to accommodate analyses of averted and avertible outcomes. We use this framework to interrogate the commonly held assumption that vaccine-averted outcomes via direct impact among vaccinated individuals (or vaccine-avertible outcomes via direct impact among unvaccinated individuals) is a lower bound on vaccine-averted (or -avertible) outcomes overall. To do so, we describe a susceptible-infected-recovered-death model stratified by vaccination status. When vaccine efficacies wane, the lower bound fails for vaccine-avertible outcomes. When transmission or fatality parameters increase over time, the lower bound fails for both vaccine-averted and -avertible outcomes. Only in the simplest scenario where vaccine efficacies, transmission, and fatality parameters are constant over time, outcomes averted via direct impact among vaccinated individuals (or outcomes avertible via direct impact among unvaccinated individuals) is a lower bound on overall impact. In conclusion, the lower bound can fail under common violations to assumptions on time-invariant vaccine efficacy, pathogen properties, or behavioral parameters. In real data analyses, estimating what seems like a lower bound on overall impact through estimating direct impact may be inadvisable without examining the directions of indirect effects.

Potentials of N-Acyl hydrazones Against Colorectal Cancer: A Mini Review.

Colorectal cancer (CRC) is a malignant gastrointestinal tract disorder with high occurrence and mortality index and showing an upsurge. Standard therapies for treating CRC are surgery and chemotherapy. Despite great effort in developing effective treatments, the progress is limited due to its relapse and recurrence. Prognosis of metastatic CRC is always complicated. This condition can be evaded by a novel approach i.e., targeted therapy which increases the survival rate in CRC patients by blocking important pathways and acting on immune checkpoints. Drugs with N-acyl hydrazones (NAH) are currently being employed treatment of infectious diseases and disorders. NAH in combination with diverse heterocycles, natural product isolates are identified as interesting CRC inhibitors under-explored. This review provides an overview of the existing CRC targeted compounds having acyl hydrazones, hydrazine, hydrazides moieties, and their underlying mechanisms towards different CRC cell lines, together with a discussion of their limitations and future trends.

Standardized Residue Numbering and Secondary Structure Nomenclature in the Class D β-Lactamases.

Over 1370 class D β-lactamases are currently known, and they pose a serious threat to the effective treatment of many infectious diseases, particularly in some pathogenic bacteria where evolving carbapenemase activity has been reported. Detailed understanding of their molecular biology, enzymology and structural biology are critically important but the lack of a standardized residue numbering scheme and inconsistent secondary structure annotation has made comparative analyses sometimes difficult and cumbersome. Compounding this, in the post-AlphaFold world where we currently find ourselves, an extraordinary wealth of detailed structural information on these enzymes is literally at our fingertips, therefore it is vitally important that a standard numbering system is in place to facilitate the accurate and straightforward analysis of their structures. Here we present a residue numbering and secondary structure scheme for the class D enzymes and apply it to test targets to demonstrate ease at which it can be used.

REGULATION OF IMMUNE RESPONSE BY PERMAFROST MICROORGANISM METABOLITES VIA EFFECTOR T-LYMPHOCYTES

Infectious agents have closely interacted with the human immune system, acquiring a set of highly sophisticated mechanisms for modulating immunity. One of the survival strategies for viruses, bacteria, protozoa, helminths and fungi is to target the regulatory T cell network (Treg: CD4+CD25hiCD127-) that controls immunopathogenic responses in many infections. Not only pathogens but also commensals are able to directly induce the conversion of naive T cells into suppressive Foxp3-expressing Tregs, while others activate pre-existing natural Tregs, in both cases suppressing pathogen-specific effector responses. However, Tregs can also contribute to immunity under certain conditions, such as at the initial stages of infection when effector cells must gain access to the site of infection, and subsequently in ensuring the generation of effector memory cells. It is noteworthy that currently little information on whether infections selectively drive pathogen-specific Tregs, and if so, whether such cells are also reactive to autoantigens are available. Further analysis of Treg subset specificity, along with a clearer picture of relative dynamics during the disease, should lead to rational strategies of immune intervention to optimize immunity and eliminate the infectious process. Thus, restoration of Treg function is important in the treatment of infectious, autoimmune and other diseases and can serve as a marker of their successful treatment. The article assesses the effect of exometabolites of derived from permafrost Bacillus bacteria obtained at different temperature conditions of their cultivation on the activity of Treg and effector T lymphocyte differentiation. Significant differences were established: secondary microbial exometabolites affect Treg (CD4+CD25hiCD127-) differentiation and expression of activation markers (CD69, CD25, HLA-DR) on CD4+ and CD8+ T lymphocytes. This effect is regulated by the type of metabolites obtained at different temperatures - "cold" (obtained at 5°C of bacterial incubation), "medium-temperature" (at 22°C) and "heat" (at 37°C) metabolites. In this case, an increase in the Treg level is associated with lower differentiation activity of CD4+ T-lymphocytes exposed to “cold” secondary exometabolites, a decrease in the differentiation activity of CD8+ T-lymphocytes treated with “warm” secondary exometabolites, and a roughly equivalent effect on the differentiation activity of CD4+ and CD8+ T-lymphocytes acted upon by “medium-temperature” secondary exometabolites.

Fabrication of MoS2@Fe3O4 Magnetic Catalysts with Photo-Fenton Reaction for Enhancing Tetracycline Degradation

Tetracycline (TCs) is widely used in the treatment of human and animal infectious disease. TCs gives rise to a growing threat to the human health and environment protection due to its overuse. Therefore, it is important to remove TCs contaminants from waste effluents. In this work, MoS2@Fe3O4 catalytic material was fabricated by the simple hydrothermal method, which was applied in the photo-Fenton system to degrade TCs. The crystal structure, surface morphology, elemental composition, chemical state, electrochemical properties, and separability of MoS2@Fe3O4 catalytic materials were analyzed by X-ray diffraction (XRD), scanning electron microscope (SEM), conventional and high-resolution transmission electron microscopy (TEM/HRTEM), X-ray photoelectron spectroscopy (XPS), electrochemical impedance spectroscopy (EIS), and vibrating sample magnetometry (VSM). Furthermore, MoS2@Fe3O4 could degrade 98.6% of TCs within 60 min under the optimum reaction conditions (the catalyst dosage of 3 g/L, H2O2 concentration of 5 mmol/L, the initial TCs concentration of 50 mg/L, and the initial pH of 5), which was a significant increase compared with pure Fe3O4. MoS2 can accelerate the Fe3+/Fe2+ cycle through electron transfer from Mo4+ to Fe3+, resulting in the improvement in the degradation efficiency of TCs. The quenching and electron paramagnetic resonance (EPR) results showed that OH• and photogenic hole h+ was the main active species in the photo-Fenton system. What is more, MoS2@Fe3O4 catalytic materials had remarkable stability and reusability, and can be handily regained via magnetic separation technology in a real scenario.

Synergistic and off-target effects of bacteriocins in a simplified human intestinal microbiome: implications for Clostridioides difficile infection control

ABSTRACT Clostridioides difficile is a major cause of nosocomial diarrhea. As current antibiotic treatment failures and recurrence of infections are highly frequent, alternative strategies are needed for the treatment of this disease. This study explores the use of bacteriocins, specifically lacticin 3147 and pediocin PA-1, which have reported inhibitory activity against C. difficile. We engineered Lactococcus lactis strains to produce these bacteriocins individually or in combination, aiming to enhance their activity against C. difficile. Our results show that lacticin 3147 and pediocin PA-1 display synergy, resulting in higher anti-C. difficile activity. We then evaluated the effects of these L. lactis strains in a Simplified Human Intestinal Microbiome (SIHUMI-C) model, a bacterial consortium of eight diverse human gut species that includes C. difficile. After introducing the bacteriocin-producing L. lactis strains into SIHUMI-C, samples were collected over 24 hours, and the genome copies of each species were assessed using qPCR. Contrary to expectations, the combined bacteriocins increased C. difficile levels in the consortium despite showing synergy against C. difficile in agar-based screening. This can be rationally explained by antagonistic inter-species interactions within SIHUMI-C, providing new insights into how broad-spectrum antimicrobials might fail to control targeted species in complex gut microbial communities. These findings highlight the need to mitigate off-target effects in complex gut microbiomes when developing bacteriocin-based therapies with potential clinical implications for infectious disease treatment.

Application and Prospect of Bio-antibiotics and mRNA Vaccines in the Prevention and Treatment of Bacterial Infections and Infectious Diseases

This paper delves into the application and prospects of bio-antibiotics and mRNA vaccines in preventing and treating bacterial infections and infectious diseases. Against the backdrop of the increasingly serious antibiotic resistance issue, the effectiveness of traditional antibiotic treatments is challenged, while bio-antibiotics and mRNA vaccines, as novel treatment methods, are emerging. Bio-antibiotics, derived from organisms or bioengineered, possess advantages such as antibacterial activity, biocompatibility, low toxicity, and reduced resistance risk, showing broad prospects in treating multi-drug-resistant bacteria infections, special types of infections, and preventive medication. mRNA vaccines, by introducing mRNA encoding pathogen antigens to stimulate the human immune response, are characterized by rapid development, high efficiency, and safety, playing a crucial role in infectious disease prevention and control, especially during the COVID-19 pandemic when the successful development and widespread application of mRNA vaccines significantly reduced the infection rate and mortality. The article also analyzes successful cases of bio-antibiotics and mRNA vaccines in practical applications and the challenges they face, such as extraction and purification techniques, stability, delivery systems, long-term safety, and regulatory policies, and proposes future research directions and prospects. In conclusion, bio-antibiotics and mRNA vaccines, as novel treatment, have great application potential and will bring new hope and opportunities to the global public health field.

Characterization, Bioactive Profiling and Evaluation of the Pharmacological Activities of Ethanol Extract of Lannea welwitschii (Hiern) Engl.

Introduction: Lannea welwitschii is a medicinal plant used in traditional medicine to treat various infectious diseases due to its plethora of bioactive compounds that possess various pharmacological activities. This study aimed to characterize and determine the phytochemical profile and the bioactive compounds responsible for their pharmacological activities. Methods: Phytochemical screening and Gas-Chromatography Mass Spectrometry (GC-MS) analysis were carried out on the ethanolic extract of L. welwitschii to determine the volatile compounds present. Characterization of the crude extract was carried out using Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), X-ray diffraction (XRD) and Energy Dispersive X-ray spectroscopy (EDX). The antioxidant potential of the extract was evaluated using methods such as 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric-reducing antioxidant Potential (FRAP). The antibacterial activities were determined using the macro-broth dilution technique. Results: Secondary metabolites such as saponins, tannins, alkaloids, reducing sugars, and cardiac glycoside were identified. The GC-MS analysis showed the presence of 48 bioactive compounds, out of which 12 had peak area percentages ≥ 1%. Some of the bioactive compounds identified include 2-butoxy-ethanol, Dodecanoic acid, Stigmasterol, Isopropenyl, and n-hexadecanoic acid, which have been reported with different biological activities. FTIR analysis revealed the presence of various functional groups which showed major compounds in the plant extract. The morphological features showed the spherical shape of the plant extract with several aggregates, while the EDX analysis identified elements such as silicon, oxygen, and silver. The extract demonstrated inhibitory potential against some of the bacterial isolates. However, Bacillus pumilus, Klebsiella quasipneumoniae, Klebsiella aerogenes, and Staphylococcus aureus are more susceptible with MIC of 0.313 and 0.625 mg/ml respectively. Conclusion: The presence of secondary metabolites and bioactive compounds revealed by the characterization and phytochemical analysis provided enough evidence for the usage of the plant in the treatment of infectious diseases and thus might be considered a therapeutic agent.

IPSC Technology Revolutionizes CAR-T Cell Therapy for Cancer Treatment.

Chimeric Antigen Receptor (CAR)-engineered T (CAR-T) cell therapy represents a highly promising modality within the domain of cancer treatment. CAR-T cell therapy has demonstrated notable efficacy in the treatment of hematological malignancies, solid tumors, and various infectious diseases. However, current CAR-T cell therapy is autologous, which presents challenges related to high costs, time-consuming manufacturing processes, and the necessity for careful patient selection. A potential resolution to this restriction could be found by synergizing CAR-T technology with the induced pluripotent stem cell (iPSC) technology. iPSC technology has the inherent capability to furnish an inexhaustible reservoir of T cell resources. Experimental evidence has demonstrated the successful generation of various human CAR-T cells using iPSC technology, showcasing high yield, purity, robustness, and promising tumor-killing efficacy. Importantly, this technology enables the production of clinical-grade CAR-T cells, significantly reducing manufacturing costs and time, and facilitating their use as allogeneic cell therapies to treat multiple cancer patients simultaneously. In this review, we aim to elucidate essential facets of current cancer therapy, delineate its utility, enumerate its advantages and drawbacks, and offer an in-depth evaluation of a novel and pragmatic approach to cancer treatment.

Pharmaceutical development of sangviritrin spray for the treatment of inflammatory diseases of the oral cavity

Introduction. One of the most common bacterial infections includes acute and chronic tonsillitis, affecting 10 to 15 % of adults and approximately 20–25 % of children worldwide, according to the World Health Organization. The focus of this study was an original substance, sangviritrin, containing no less than 96.5 % of the sum of bisulfates of two alkaloids: sanguinarine and chelerythrine. Given the high antimicrobial activity of sangviritrin, the research aimed to develop a local delivery system based on this medicinal substance.Aim. The aim of this work was to develop an oral medicinal form of sangviritrin.Materials and Methods. Sangviritrin, produced by the All-Russian Scientific Research Institute of Medicinal and Aromatic Plants, was used as the active pharmaceutical ingredient. The selection of auxiliary components was carried out in accordance with the methodologies specified in the State Pharmacopoeia XV edition. The organoleptic properties of the substance and spray samples were studied using A. I. Tenzova's method. The local irritant action of the spray was assessed using the conjunctival test method on chinchilla rabbits weighing 3.5–4.3 kg. Quantitative determination of sangviritrin in the medicinal form was performed using spectrophotometric methods at a wavelength of 321 ± 2 nm on a spectrophotometer SPECORD® 200 PLUS (Analytik Jena GmbH+Co. KG, Germany).Results and Discussion. Optimal auxiliary component compositions were selected based on measurements of spray technological parameters. A comprehensive approach was justified for correcting the organoleptic properties of the substance, involving the introduction of a minimal amount of sweeteners and additional use of β-cyclodextrin. Examination of the local irritant action indicated a "weak or absent" degree of local irritation.Conclusion. A local delivery system for sangviritrin has been developed for the treatment of infectious and inflammatory diseases of the oral cavity.