RESUMEN
Burkholderia pseudomallei, an intracellular pathogen, is responsible for melioidosis, a zoonotic disease. Its pathogenesis involves several virulence factors, among which lipopolysaccharide (LPS) plays a crucial role. Our research reveals that the O antigen present within the LPS significantly regulates the host immune response. In a previous study, we obtained a B. pseudomallei mutant strain ΔwbiI. Here, the purification of LPS from ΔwbiI and a gas chromatography-mass spectrometry (GC-MS) analysis were conducted. The results confirmed the absence of specific sugar 6-deoxy-Talp, which is a typical component of the O antigen in the wild type B. pseudomallei. Our findings underscore the potent impact the O antigen exerts on the virulence of B. pseudomallei. The ΔwbiI strain displayed significantly increased invasiveness and cytotoxicity in vitro. This enhanced cytotoxicity seems to be related to the exposure of lipid A and an increased cell membrane hydrophobicity resulting from the deletion of the O antigen. Additionally, in mouse models, the ΔwbiI strain resulted in a heightened host lethality and an excessive inflammatory response in mice. These findings indicate that the O-antigenic polysaccharide moiety of B. pseudomallei plays a role in its pathogenicity in vitro and in vivo.
Asunto(s)
Burkholderia pseudomallei , Ratones , Animales , Antígenos O/genética , Lipopolisacáridos , Virulencia , MutaciónRESUMEN
Human immunodeficiency virus (HIV)-infected people's livelihoods are gradually being prolonged with the use of combined antiretroviral therapy (ART). Conversely, despite viral suppression by ART, the symptoms of HIV-associated neurocognitive disorder (HAND) endure. HAND persists because ART cannot really permanently confiscate the virus from the body. HAND encompasses a variety of conditions based on clinical presentation and severity level, comprising asymptomatic neurocognitive impairment, moderate neurocognitive disorder, and HIV-associated dementia. During the early stages of HIV infection, inflammation compromises the blood-brain barrier, allowing toxic virus, infected monocytes, macrophages, T-lymphocytes, and cellular products from the bloodstream to enter the brain and eventually the entire central nervous system. Since there are no resident T-lymphocytes in the brain, the virus will live for decades in macrophages and astrocytes, establishing a reservoir of infection. The HIV proteins then inflame neurons both directly and indirectly. The purpose of this review is to provide a synopsis of the effects of these proteins on the central nervous system and conceptualize avenues to be considered in mitigating HAND. We used bioinformatics repositories extensively to simulate the transcription factors that bind to the promoter of the HIV-1 protein and possibly could be used as a target to circumvent HIV-associated neurocognitive disorders. In the same vein, a protein-protein interaction complex was also deduced from a Search Tool for the Retrieval of Interacting Genes. In conclusion, this provides an alternative strategy that could be used to avert HAND.
Asunto(s)
Infecciones por VIH , Sistema Nervioso Central , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Proteínas del Virus de la Inmunodeficiencia Humana/uso terapéutico , Humanos , Factores de Transcripción , Carga ViralRESUMEN
Mesenchymal stem cells play an important role in tissue damage and repair. This role is mainly due to a paracrine mechanism, and extracellular vesicles (EVs) are an important part of the paracrine function. EVs play a vital role in many aspects of cell homeostasis, physiology, and pathology, and EVs can be used as clinical biomarkers, vaccines, or drug delivery vehicles. A large number of studies have shown that EVs derived from mesenchymal stem cells (MSC-EVs) play an important role in the treatment of various diseases. However, the problems of low production, low retention rate, and poor targeting of MSC-EVs are obstacles to current clinical applications. The engineering transformation of MSC-EVs can make up for those shortcomings, thereby improving treatment efficiency. This review summarizes the latest research progress of MSC-EV direct and indirect engineering transformation from the aspects of improving MSC-EV retention rate, yield, targeting, and MSC-EV visualization research, and proposes some feasible MSC-EV engineering methods of transformation.