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Protein-Based Adjuvants for Vaccines as Immunomodulators of the Innate and Adaptive Immune Response: Current Knowledge, Challenges, and Future Opportunities.

New-generation vaccines, formulated with subunits or nucleic acids, are less immunogenic than classical vaccines formulated with live-attenuated or inactivated pathogens. This difference has led to an intensified search for additional potent vaccine adjuvants that meet safety and efficacy criteria and confer long-term protection. This review provides an overview of protein-based adjuvants (PBAs) obtained from different organisms, including bacteria, mollusks, plants, and humans. Notably, despite structural differences, all PBAs show significant immunostimulatory properties, eliciting B-cell- a

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… The PBAs can interact at with TLR2 (e.g., porins FomA from Fusobacterium nucleatum and major outer membrane protein [MOMP] from Shigella dysenteriae , AB-type toxins from Vibrio cholerae, lipoprotein OMP 16 from Bordetella pertussis ); with TLR4 (e.g., high-mobility group box 1 [HMGB1], heat-shock-70 … In addition, the Vibrio cholerae porin OmpU mediates M1-polarization of macrophages/monocytes via TLR1/TLR2 activation [ 44 ]. …

Structure of the hypothetical Mycoplasma protein MPN555 suggests a chaperone function.

The crystal structure of the hypothetical protein MPN555 from Mycoplasma pneumoniae (gi|1673958) has been determined to a resolution of 2.8 Angstrom using anomalous diffraction data at the Se-peak wavelength. Structure determination revealed a mostly alpha-helical protein with a three-lobed shape. The three lobes or fingers delineate a central binding groove and additional grooves between lobes 1 and 3 and between lobes 2 and 3. For one of the molecules in the asymmetric unit, the central binding pocket was filled with a peptide from the uncleaved N-terminal affinity tag. The MPN555 structure

Estimated global and regional causes of deaths from diarrhoea in children younger than 5 years during 2000-21: a systematic review and Bayesian multinomial analysis.

BACKGROUND: Information on the causes of deaths from diarrhoea in children younger than 5 years is needed to design improved preventive and … arrhoea", "dysentery", "rotavirus", "Escherichia coli", "salmonella", "shigella", "campylobacter", "Vibrio cholerae", "cryptosporidium", "norovirus", "astrovirus", "sapovirus", and "adenovirus". To be included, studies had to have a patient population of children younger than 5 years who were hospitalised for diarrhoea (at least 90% of study participants), at lea …

The Roles of Inflammation, Nutrient Availability and the Commensal Microbiota in Enteric Pathogen Infection.

The healthy human intestine is colonized by as many as 1014 bacteria belonging to more than 500 different species forming a microbial ecosys … the Enterobacteriaceae (E. coli, Yersinia spp., Salmonella spp., Shigella spp.), the Vibrionaceae (Vibrio cholerae) and the Campylobacteriaceae (Campylobacter spp.). In general, members of these families (be it commensals or pathogens) only constitute a minority of the intestinal microbiota. However, proteobacterial "blooms" are a characteristic trait of an abno …

20 Years of Legislation - How Australia Has Responded to the Challenge of Regulating Genetically Modified Organisms in the Clinic.

•In contrast to the prior voluntary system, since 2001, gene technology in Australia has been regulated under a legislated national Gene Technology Regulatory Scheme which is administered by the Gene Technology Regulator.•The Scheme provides science-based assessment of the potential risks of gene technology to the health and safety of people and the environment.•It complements the role of the Australian Therapeutic Goods Administration which regulates all therapeutic products in Australia to ensure they are safe and effective.•Recent reforms to the Scheme contribute to, and anticipate, the con

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… cholera; Flavivirus, includes Yellow Fever and Dengue viruses; Paramyxoviridae, includes Bovine parainfluenza virus and Sendai virus . … Vaccines | Biocelect Vaxchora (PXVX0200) (previously Orochol) | AstraZeneca FluMist Indications | Cholera vaccine | Influenza vaccine Type | GM live attenuated Vibrio cholerae virus vaccine strain | GM live attenuated human Influenza A and B virus vaccine strains Administration | Per oral | Nasal spray …

Accidental Ixazomib Overdose in a Patient With Multiple Myeloma.

Multiple myeloma is the second most common hematological malignancy. Ixazomib is the first oral proteasome inhibitor approved in the United States for the management of multiple myeloma who have received at least one prior treatment. The availability of oral chemotherapeutic agents for the management of multiple myeloma has made it easier for patients who do not have to come to the hospital for chemotherapy infusions. However, many barriers are associated with oral chemotherapy, and one of them is a misinterpretation of instruction which can have deleterious effects. In this case report, we pr

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… Test performed | Polymerase chain reaction result Campylobacter spp | Not detected Clostridium difficile toxin A/B genes | Not detected Plesiomonas shigelloides | Not detected Salmonella spp | Not detected Vibrio spp | Not detected Vibrio cholerae | Not detected Yersinia enterocolotica | Not detected …

Characterization of the Pseudomonas aeruginosa NQR complex, a bacterial proton pump with roles in autopoisoning resistance.

Pseudomonas aeruginosa is a Gram-negative bacterium responsible for a large number of nosocomial infections. The P. aeruginosa respiratory chain contains the ion-pumping NADH:ubiquinone oxidoreductase (NQR). This enzyme couples the transfer of electrons from NADH to ubiquinone to the pumping of sodium ions across the cell membrane, generating a gradient that drives essential cellular processes in many bacteria. In this study, we characterized P. aeruginosa NQR (Pa-NQR) to elucidate its physiologic function. Our analyses reveal that Pa-NQR, in contrast with NQR homologues from other bacterial s

Mucosal-Associated Invariant T Cells in Health and Disease.

Mucosal-associated invariant T (MAIT) cells are a population of evolutionarily conserved, unconventional innate-like T lymphocytes that are restricted by major histocompatibility complex Class I-related (MR1) molecules. They can be activated either in a T-cell receptor-MR1- or cytokine-dependent manner. Activated MAIT cells play crucial roles in maintaining homeostasis and the fine regulation of the immune system. This review presents a systematic exploration of the development, biological characteristics, and multiple effects of MAIT cells in health and various diseases. In healthy individual

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… Abbreviations : Mtb , Mycobacterium tuberculosis ; S. aureus , Staphylococcus aureus ; M. abscessus , Mycobacterium abscessus ; L. longbeachae , Legionella longbeachae ; H. pylori , Helicobacter pylori ; V. cholerae , Vibrio cholerae ; C. albicans , Candida albicans ; S. cerevisiae , Saccharomyces cerevisiae … Vibrio Cholerae Vibrio cholerae ( V. cholerae ) is the causative agent of cholera, a severe diarrheal disease transmitted through contaminated water, food, and contact with infected individuals. Untreated patients may quickly die following V. cholerae infection [ 86 ]. …

Evaluation of a multiplex panel for the diagnosis of acute infectious diarrhea in immunocompromised hematologic patients.

IntroductionDiarrhea is a frequent complication in hematologic patients, being an infectious cause frequently suspected. Rapid and accurate detection of gastrointestinal pathogens is vital in immunocompromised hosts. The aim of this study was to compare routine diagnostic methods versus a multiplex polymerase chain reaction (PCR) assay for the diagnosis of infectious diarrhea in immunocompromised hematologic patients.Material and methodsWe conducted a prospective observational study from March 2015 to January 2016 to compare conventional methods for the diagnosis of infectious diarrhea with FI

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… This panel includes a total of 22 targets, including bacteria ( Campylobacter jejuni , Campylobacter coli , Campylobacter upsaliensis , Clostridium difficile (toxin A/B), Plesiomonas shigelloides , Salmonella , Yersinia enterocolitica , Vibrio parahaemolyticus , Vibrio vulnificus , Vibrio cholerae and …

Opportunistic Pathogens in Drinking Water Distribution Systems-A Review.

In contrast to "frank" pathogens, like Salmonella entrocolitica, Shigella dysenteriae, and Vibrio cholerae, that always have a probability of disease, "opportunistic" pathogens are organisms that cause an infectious disease in a host with a weakened immune system and rarely in a healthy host. Historically, drinking water treatment has focused on control of frank pathogens, particularly those from human or animal sources (like Giardia lamblia, Cryptosporidium parvum, or Hepatitis A virus), but in recent years outbreaks from drinking water have increasingly been due to opportunistic pathogens. C…

Human Health and Ocean Pollution.

BACKGROUND: Pollution - unwanted waste released to air, water, and land by human activity - is the largest environmental cause of disease in the world today. It is responsible for an estimated nine million premature deaths per year, enormous economic losses, erosion of human capital, and degradation of ecosystems. Ocean pollution is an important, but insufficiently recognized and inadequately controlled component of global pollution. It poses serious threats to human health and well-being. The nature and magnitude of these impacts are only beginning to be understood. GOALS: (1) Broadly examin

The pathological anatomical collection of the Natural History Museum Vienna.

The pathological anatomical collection Vienna (Pathologisch-Anatomische Sammlung Wien; PASW) is a living and still growing research collection. It was established as early as 1796 as part of the Medical University of Vienna, acquired the status of an independent federal museum in 1971, and was assigned to the Natural History Museum Vienna in 2012. It houses a wide range of human wet and dry specimens and further objects, such as moulages, medical devices, microbiological and histological specimens, and a photo archive (approximately 50,000 objects), which, as a meaningful source, may contribut

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… It is caused by bacterial infection (Vibrio cholerae ); symptoms of this disease include diarrhea which may lead to severe dehydration and—in the worst case—even death within a very short time. The epidemic reached Vienna in mid-August 1831. …

Новальная граница в исследовании оксиса Гут-Брэйна: трансплантация фекалий микробиота в неевродегенеративных расстройствах.

Ось кишечника (GBA) представляет собой сложную двунаправленную систему связи, соединяющую центральную нервную систему (CNS) и желудочно-кишечный тракт (GI). Такое взаимодействие происходит главным образом через нейронные, иммунные и метаболические пути. Дисбиоз в кишечной микробиоте связан с многочисленными нейродегенеративными заболеваниями, такими, как болезнь Паркинсона (PD), болезнь Альцгеймера (AD), множественный склероз (MS) и амиотропический боковой склероз (ALS). В последние годы в качестве новаторского терапевтического подхода к трансплантации фекальной микробиоты (ФМТ) была привлечен

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… Additional considerations include testing for Aeromonas , Plesiomonas , Listeria monocytogenes , Yersinia , Vibrio cholerae , and Vibrio parahaemolyticus . (2) Viruses: Key pathogens screened include Rotavirus and Norovirus . (3) Parasites: Tests are performed for Cryptosporidium , Cyclospora …

Current Status of COVID-19 Therapies and Drug Repositioning Applications.

The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in dru

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… Introduction Over the past few centuries, outbreaks caused by bacteria like Yersinia pestis and Vibrio cholerae (the causative agents of plague and cholera, respectively, Cohn and Kutalek, 2016 ; Pechous et al., 2016 ) and also by viral infectious agents such as influenza viruses, Ebola viruses, SARS-CoV …

Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma.

BACKGROUND: Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR T) therapy showed remarkable efficacy in patients with relapsed or refractory multiple myeloma (RRMM). This phase 1 dose-escalation and expansion study developed C-CAR088, a novel second-generation humanized anti-BCMA CAR T-cell therapy, and assessed the safety and efficacy of three dosages of C-CAR088 in patients with RRMM. METHODS: Patients received lymphodepletion with three doses of cyclophosphamide (300 mg/m2) and three doses of fludarabine (30 mg/m2) on days -5, -4, and -3, followed by an infusion of

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… One patient discontinued treatment on week 2, one patient died of septic shock caused by Vibrio cholerae infection on day 3 after C-CAR088 infusion, and one patient was not evaluable. Among 28 evaluable patients, the ORR was 96.4% (13 sCR, 3 CR, 9 VGPR). …

Antibiotics: Conventional Therapy and Natural Compounds with Antibacterial Activity-A Pharmaco-Toxicological Screening.

Antibiotics are considered as a cornerstone of modern medicine and their discovery offers the resolution to the infectious diseases problem. However, the excessive use of antibiotics worldwide has generated a critical public health issue and the bacterial resistance correlated with antibiotics inefficiency is still unsolved. Finding novel therapeutic approaches to overcome bacterial resistance is imperative, and natural compounds with antibacterial effects could be considered a promising option. The role played by antibiotics in tumorigenesis and their interrelation with the microbiota are sti

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… Small-molecule inhibitor of vibrio cholerae virulence and intestinal colonization Science 2005 310 670 674 10.1126/science.1116739 16223984 141. Chatterjee A. Ratner D.M. Ryan C.M. Johnson P.J. O’Keefe B.R. Secor W.E. Anderson D.J. Robbins P.W. Samuelson J. …

Contribution of Real-World Evidence in European Medicines Agency's Regulatory Decision Making.

Real-world data/evidence (RWD/RWE) may provide insightful information on medicines' clinical effects to guide regulatory decisions. While its contribution has been recognized for safety monitoring and disease epidemiology across medicines' life cycles, using RWD/RWE to demonstrate efficacy requires further evaluation. This study aimed to (i) characterize RWD/RWE presented by applicants to support claims on medicines' efficacy within initial marketing authorization applications (MAAs) and extension of indication applications (EoIs), and (ii) analyze the contribution of RWD/RWE to regulatory dec

Revealing the pharmacological effects of Remodelin against osteosarcoma based on network pharmacology, acRIP-seq and experimental validation.

Osteosarcoma (OS) is the most common primary malignant tumor of bone. Remodelin, an inhibitor of the N (4)-Acetylcytidine (ac4C) acetylation modifying enzyme N-acetyltransferase 10 (NAT10), has been shown to have therapeutic effects on cancer in several studies, and our previous studies have confirmed the inhibitory effect of Remodelin on OS cells, however, the mechanism of action has not yet been elucidated. We used network pharmacological analysis to quantify the therapeutic targets of Remodelin against OS. acRIP-seq and RNA-seq were performed to investigate the inhibitory activity of Remode

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… KEGG analysis revealed that differentially expressed genes were mainly associated with the following pathways: MAPK signaling pathway, Protein processing in endoplasmic reticulum, NOD-like receptor signaling pathway, Vibrio cholerae infection, ECM-receptor interaction (Fig. 5 D). …

The Role of Drug Repurposing in the Development of Novel Antimicrobial Drugs: Non-Antibiotic Pharmacological Agents as Quorum Sensing-Inhibitors.

Background: The emergence of multidrug-resistant organisms (MDROs) is a global public health issue, severely hindering clinicians in administering appropriate antimicrobial therapy. Drug repurposing is a drug development strategy, during which new pharmacological applications are identified for already approved drugs. From the viewpoint of the development of virulence inhibitors, inhibition of quorum sensing (QS) is a promising route because various important features in bacterial physiology and virulence are mediated by QS-dependent gene expression. Methods: Forty-five pharmacological agents,

Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases.

There are overwhelming reports on the promotional effect of hypoxia on the malignant behavior of various forms of cancer cells. This has been proposed and tested exhaustively in the light of cancer immunotherapy. However, there could be more interesting functions of a hypoxic cellular micro-environment than malignancy. There is a highly intricate crosstalk between hypoxia inducible factor (HIF), a transcriptional factor produced during hypoxia, and nuclear factor kappa B (NF-κB) which has been well characterized in various immune cell types. This important crosstalk shares common activating an

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… The Vibrio cholerae minor pilin TcpB mediates uptake of the cholera toxin phage CTXφ . J Biol Chem ( 2019 ) 294 ( 43 ): 15698–710 . doi: 10.1074/jbc.RA119.009980 PMC6816102 31471320 117 Kostic AD Xavier RJ Gevers D . …