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1.
Photodiagnosis Photodyn Ther ; 42: 103606, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37187270

ABSTRACT

Autoimmune diseases (AIDs) are poorly understood clinical syndromes due to breakdown of immune tolerance towards specific types of self-antigens. They are generally associated with an inflammatory response mediated by lymphocytes, autoantibodies or both. Ultimately, chronic inflammation culminates in tissue damages and clinical manifestations. AIDs affect 5% of the world population, and they represent the main cause of fatality in young to middle-aged females. In addition, the chronic nature of AIDs has a devastating impact on the patient's quality of life. It also places a heavy burden on the health care system. Establishing a rapid and accurate diagnosis is considered vital for an ideal medical management of these autoimmune disorders. However, for some AIDs, this task might be challenging. Vibrational spectroscopies, and more particularly Fourier-transform infrared (FTIR) spectroscopy, have emerged as universal analytical techniques with promising applications in the diagnosis of various types of malignancies and metabolic and infectious diseases. The high sensitivity of these optical sensing techniques and their minimal requirements for test reagents qualify them to be ideal analytical techniques. The aim of the current review is to explore the potential applications of FTIR spectroscopy in the diagnosis and management of most common AIDs. It also aims to demonstrate how this technique has contributed to deciphering the biochemical and physiopathological aspects of these chronic inflammatory diseases. The advantages that can be offered by this optical sensing technique over the traditional and gold standard methods used in the diagnosis of these autoimmune disorders have also been extensively discussed.


Subject(s)
Autoimmune Diseases , Photochemotherapy , Middle Aged , Female , Humans , Spectroscopy, Fourier Transform Infrared , Quality of Life , Photochemotherapy/methods , Photosensitizing Agents , Autoimmune Diseases/diagnosis , Autoimmune Diseases/therapy
2.
Photodiagnosis Photodyn Ther ; 42: 103505, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36965755

ABSTRACT

Chronic liver diseases (CLDs) are a major public health problem. Despite the progress achieved in fighting against viral hepatitis, the emergence of non-alcoholic fatty liver disease might pose a serious challenge to the public's health in the coming decades. Medical management of CLDs represents a substantial burden on the public health infrastructures. The health care cost of these diseases is an additional burden that weighs heavily on the economies of developing countries. Effective management of CLDs requires the adoption of reliable and cost-effective screening and diagnosing methods to ensure early detection and accurate clinical assessment of these diseases. Vibrational spectroscopies have emerged as universal analytical methods with promising applications in various industrial and biomedical fields. These revolutionary analytical techniques rely on analyzing the interaction between a light beam and the test sample to generate a spectral fingerprint. This latter is defined by the analyte's chemical structure and the molecular vibrations of its functional groups. Raman spectroscopy and surface-enhanced Raman spectroscopy have been used in combination with various chemometric tests to diagnose a wide range of malignant, metabolic and infectious diseases. The aim of the current review is to cast light on the use of these optical sensing methods in the diagnosis of CLDs. The vast majority of research works that investigated the potential application of these spectroscopic techniques in screening and detecting CLDs were discussed here. The advantages and limitations of these modern analytical methods, as compared with the routine and gold standard diagnostic approaches, were also reviewed in details.


Subject(s)
Liver Diseases , Photochemotherapy , Humans , Spectrum Analysis, Raman/methods , Photochemotherapy/methods , Photosensitizing Agents , Liver Diseases/diagnosis , Vibration
3.
Int J Legal Med ; 136(6): 1717-1736, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36050421

ABSTRACT

Contemporary criminal investigations are based on the statements made by the victim and the eyewitnesses. They also rely on the physical evidences found in the crime scene. These evidences, and more particularly biological ones, have a great judicial value in the courtroom. They are usually used to revoke the suspect's allegations and confirm or refute the statements made by the victim and the witnesses. Stains of body fluids are biological evidences highly sought by forensic investigators. In many criminal cases, the success of the investigation relies on the correct identification and classification of these stains. Therefore, the adoption of reliable and accurate forensic analytical methods seems to be of vital importance to attain this objective. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) is a modern and universal analytical technique capable of fingerprint recognition of the analyte using minimal amount of the test sample. The current systematic review aims to through light on the fundamentals of this technique and to illustrate its wide range of applications in forensic investigations. ATR-FTIR is a nondestructive technique which has demonstrated an exceptional efficiency in detecting, identifying and discriminating between stains of various types of body fluids usually encountered in crime scenes. The ATR-FTIR spectral data generated from bloodstains can be used to deduce a wealth of information related to the donor species, age, gender, and race. These data can also be exploited to discriminate between stains of different types of bloods including menstrual and peripheral bloods. In addition, ATR-FTIR has a great utility in the postmortem investigations. More particularly, in estimating the postmortem interval and diagnosing death caused by extreme weather conditions. It is also useful in diagnosing some ambiguous death causes such as fatal anaphylactic shock and diabetic ketoacidosis.


Subject(s)
Blood Stains , Body Fluids , Body Fluids/chemistry , Crime , Forensic Medicine , Humans , Spectroscopy, Fourier Transform Infrared/methods
4.
ACS Infect Dis ; 6(5): 939-946, 2020 05 08.
Article in English | MEDLINE | ID: mdl-32126763

ABSTRACT

Hospital-acquired bacterial infections are a significant burden on healthcare systems worldwide causing an increased duration of hospital stays and prolonged patient suffering. We show that polyurethane containing crystal violet (CV) and 3-4 nm zinc oxide nanoparticles (ZnO NPs) possesses excellent bactericidal activity against hospital-acquired pathogens including multidrug resistant Escherichia coli (E. coli), Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), and even highly resistant endospores of Clostridioides (Clostridium) difficile. Importantly, we used clinical isolates of bacterial strains, a protocol to mimic the environmental conditions of a real exposure in the healthcare setting, and low light intensity equivalent to that encountered in UK hospitals (∼500 lux). Our data shows that ZnO NPs enhance the photobactericidal activity of CV under low intensity light even with short exposure times, and we show that this involves both Type I and Type II photochemical pathways. Interestingly, polyurethane containing ZnO NPs alone showed significant bactericidal activity in the dark against one strain of E. coli, indicating that the NPs possess both light-activated synergistic activity with CV and inherent bactericidal activity that is independent of light. These new antibacterial polymers are potentially useful in healthcare facilties to reduce the transmission of pathogens between people and the environment.


Subject(s)
Anti-Infective Agents/pharmacology , Clostridioides difficile/drug effects , Escherichia coli/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Pseudomonas aeruginosa/drug effects , Anti-Bacterial Agents/pharmacology , Cross Infection/prevention & control , Drug Resistance, Multiple, Bacterial , Gentian Violet/pharmacology , Humans , Light , Microbial Sensitivity Tests , Nanoparticles , Polyurethanes , Zinc Oxide/pharmacology
5.
PLoS One ; 5(1): e8966, 2010 Jan 29.
Article in English | MEDLINE | ID: mdl-20126460

ABSTRACT

Francisella tularensis is a highly infectious bacterium causing the zoonotic disease tularaemia. During its infectious cycle, F. tularensis is not only exposed to the intracellular environment of macrophages but also resides transiently in extracellular compartments, in particular during its systemic dissemination. The screening of a bank of F. tularensis LVS transposon insertion mutants on chemically defined medium (CDM) led us to identify a gene, designated trkH, encoding a homolog of the potassium uptake permease TrkH. Inactivation of trkH impaired bacterial growth in CDM. Normal growth of the mutant was only restored when CDM was supplemented with potassium at high concentration. Strikingly, although not required for intracellular survival in cell culture models, TrkH appeared to be essential for bacterial virulence in the mouse. In vivo kinetics of bacterial dissemination revealed a severe defect of multiplication of the trkH mutant in the blood of infected animals. The trkH mutant also showed impaired growth in blood ex vivo. Genome sequence analyses suggest that the Trk system constitutes the unique functional active potassium transporter in both tularensis and holarctica subspecies. Hence, the impaired survival of the trkH mutant in vivo is likely to be due to its inability to survive in the low potassium environment (1-5 mM range) of the blood. This work unravels thus the importance of potassium acquisition in the extracellular phase of the F. tularensis infectious cycle. More generally, potassium could constitute an important mineral nutrient involved in other diseases linked to systemic dissemination of bacterial pathogens.


Subject(s)
Bacterial Proteins/physiology , Francisella tularensis/pathogenicity , Potassium/metabolism , Amino Acid Sequence , Animals , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Genes, Bacterial , Mice , Molecular Sequence Data , Mutation , Sequence Homology, Amino Acid
6.
Infect Immun ; 77(5): 1866-80, 2009 May.
Article in English | MEDLINE | ID: mdl-19223477

ABSTRACT

Francisella tularensis is a highly infectious pathogen that infects animals and humans, causing tularemia. The ability to replicate within macrophages is central for virulence and relies on expression of genes located in the Francisella pathogenicity island (FPI), as well as expression of other genes. Regulation of FPI-encoded virulence gene expression in F. tularensis involves at least four regulatory proteins and is not fully understood. Here we studied the RNA-binding protein Hfq in F. tularensis and particularly the role that it plays as a global regulator of gene expression in stress tolerance and pathogenesis. We demonstrate that Hfq promotes resistance to several cellular stresses (including osmotic and membrane stresses). Furthermore, we show that Hfq is important for the ability of the F. tularensis vaccine strain LVS to induce disease and persist in organs of infected mice. We also demonstrate that Hfq is important for stress tolerance and full virulence in a virulent clinical isolate of F. tularensis, FSC200. Finally, microarray analyses revealed that Hfq regulates expression of numerous genes, including genes located in the FPI. Strikingly, Hfq negatively regulates only one of two divergently expressed putative operons in the FPI, in contrast to the other known regulators, which regulate the entire FPI. Hfq thus appears to be a new pleiotropic regulator of virulence in F. tularensis, acting mostly as a repressor, in contrast to the other regulators identified so far. Moreover, the results obtained suggest a novel regulatory mechanism for a subset of FPI genes.


Subject(s)
Bacterial Proteins/physiology , Francisella tularensis/physiology , Gene Expression Regulation, Bacterial , Host Factor 1 Protein/physiology , Virulence Factors/biosynthesis , Amino Acid Sequence , Animals , Down-Regulation , Female , Gene Expression Profiling , Gene Order , Genomic Islands , Humans , Mice , Mice, Inbred BALB C , Molecular Sequence Data , Oligonucleotide Array Sequence Analysis , Sequence Alignment , Stress, Physiological , Survival Analysis , Tularemia/microbiology , Tularemia/pathology , Virulence
7.
PLoS Pathog ; 5(1): e1000284, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19158962

ABSTRACT

Francisella tularensis is a highly infectious bacterium causing the zoonotic disease tularemia. Its ability to multiply and survive in macrophages is critical for its virulence. By screening a bank of HimarFT transposon mutants of the F. tularensis live vaccine strain (LVS) to isolate intracellular growth-deficient mutants, we selected one mutant in a gene encoding a putative gamma-glutamyl transpeptidase (GGT). This gene (FTL_0766) was hence designated ggt. The mutant strain showed impaired intracellular multiplication and was strongly attenuated for virulence in mice. Here we present evidence that the GGT activity of F. tularensis allows utilization of glutathione (GSH, gamma-glutamyl-cysteinyl-glycine) and gamma-glutamyl-cysteine dipeptide as cysteine sources to ensure intracellular growth. This is the first demonstration of the essential role of a nutrient acquisition system in the intracellular multiplication of F. tularensis. GSH is the most abundant source of cysteine in the host cytosol. Thus, the capacity this intracellular bacterial pathogen has evolved to utilize the available GSH, as a source of cysteine in the host cytosol, constitutes a paradigm of bacteria-host adaptation.


Subject(s)
Cysteine/metabolism , Dipeptides/metabolism , Francisella tularensis/metabolism , Francisella tularensis/pathogenicity , Glutathione/metabolism , Microbial Viability , Animals , Cell Line , Cytosol/metabolism , Escherichia coli/genetics , Female , Francisella tularensis/genetics , Genes, Bacterial , Genetic Complementation Test , Macrophages/cytology , Macrophages/microbiology , Mice , Mice, Inbred BALB C , Mutation , Plasmids , Virulence , gamma-Glutamyltransferase/genetics , gamma-Glutamyltransferase/metabolism
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