Protective Effect of a Novel RIPK1 Inhibitor, Compound 4-155, in Systemic Inflammatory Response Syndrome and Sepsis.

Excessive inflammatory response is a critical pathogenic factor for the tissue damage and organ failure caused by systemic inflammatory response syndrome (SIRS) and sepsis. In recent years, drugs targeting RIPK1 have proved to be an effective anti-inflammatory strategy. In this study, we identified a novel anti-inflammatory lead compound 4-155 that selectively targets RIPK1.

iTRAQ-based proteomics revealed baicalein enhanced oxidative stress of Candida albicans by upregulating CPD2 expression.

Baicalein could inhibit the growth and biofilm formation of Candida albicans, the most common clinical fungal pathogen. However, the antifungal mechanism of baicalein has not been elucidated. In this study, isobaric tags for relative and absolute quantification (iTRAQ) was used to verify the mechanism of antifungal fluconazole and baicalein.

E3 ligase c-Cbl regulates intestinal inflammation through suppressing fungi-induced noncanonical NF-κB activation.

Intestinal fungi are critical for modulating host immune homeostasis and underlying mechanisms remain unclear. We show that dendritic cell (DC)-specific deficiency of casitas B-lineage lymphoma (c-Cbl) renders mice susceptible to dextran sodium sulfate (DSS)-induced colitis. Mechanistically, we identify that c-Cbl functions downstream of Dectin-2 and Dectin-3 to mediate the ubiquitination and degradation of noncanonical nuclear factor κB subunit RelB.

Priming with FLO8-deficient Candida albicans induces Th1-biased protective immunity against lethal polymicrobial sepsis.

The morphological switch between yeast and hyphae of Candida albicans is essential for its interaction with the host defense system. However, the lack of understanding of host-pathogen interactions during C. albicans infection greatly hampers the development of effective immunotherapies.

A New Antifungal Agent (4-phenyl-1, 3-thiazol-2-yl) Hydrazine Induces Oxidative Damage in .

A gradual rise in immunocompromised patients over past years has led to the increasing incidence of invasive fungal infections. Development of effective fungicides can not only provide new means for clinical treatment, but also reduce the occurrence of fungal resistance. We identified a new antifungal agent (4-phenyl-1, 3-thiazol-2-yl), hydrazine (numbered as 31C) which showed high-efficiency, broad-spectrum and specific activities.

New Triazole NT-a9 Has Potent Antifungal Efficacy against Cryptococcus neoformans and .

In the past decades, the incidence of cryptococcosis has increased dramatically, which poses a new threat to human health. However, only a few drugs are available for the treatment of cryptococcosis. Here, we described a leading compound, NT-a9, an analogue of isavuconazole, that showed strong antifungal activities and NT-a9 showed a wide range of activities against several pathogenic fungi , including , , , , , , and , with MICs ranging from 0.

SDH2 is involved in proper hypha formation and virulence in Candida albicans.

Aim: To investigate the role of SDH2 in Candida albicans filamentation and virulence.

Materials & Methods: Caenorhabditis elegans and mouse candidiasis models were used to assess the virulence of a sdh2Δ/Δ mutant. Various hypha-inducing media were used to evaluate the hyphal development of C.

CARD9 facilitates the production of IL-5 by alveolar macrophages for the induction of type 2 immune responses.

The adaptor CARD9 functions downstream of C-type lectin receptors (CLRs) for the sensing of microbial infection, which leads to responses by the T1 and T17 subsets of helper T cells. The single-nucleotide polymorphism rs4077515 at CARD9 in the human genome, which results in the substitution S12N (CARD9), is associated with several autoimmune diseases. However, the function of CARD9 has remained unknown.

() Encoding Protein Controls Sensitivity of to Azoles through Regulating the Synthesis of C14-Methylated Sterols.

Antifungal azole drugs inhibit the synthesis of ergosterol and cause the accumulation of sterols containing a 14α-methyl group, which is related to the properties of cell membrane. Due to the frequent recurrence of fungal infections and clinical long-term prophylaxis, azole resistance is increasing rapidly. In our research, Nsg2p, encoded by the in , is found to be involved in the inhibition of 14α-methylated sterols and resistance to azoles.

Chemogenomic Profiling of the Fungal Pathogen Candida albicans.

There is currently a small number of classes of antifungal drugs, and these drugs are known to target a very limited set of cellular functions. We derived a set of approximately 900 nonessential, transactivator-defective disruption strains from the tetracycline-regulated GRACE collection of strains of the fungal pathogen This strain set was screened against classic antifungal drugs to identify gene inactivations that conferred either enhanced sensitivity or increased resistance to the compounds. We examined two azoles, fluconazole and posaconazole; two echinocandins, caspofungin and anidulafungin; and a polyene, amphotericin B.

The synthesis, regulation, and functions of sterols in Candida albicans: Well-known but still lots to learn.

Sterols are the basal components of the membranes of the fungal pathogen Candida albicans, and these membranes determine the susceptibility of C. albicans cells to a variety of stresses, such as ionic, osmotic and oxidative pressures, and treatment with antifungal drugs. The common antifungal azoles in clinical use are targeted to the biosynthesis of ergosterol.

The Role of Mms22p in DNA Damage Response in Candida albicans.

To ensure correct DNA replication, eukaryotes have signaling pathways that respond to replication-associated DNA damage and trigger repair. In both Saccharomyces cerevisiae and Schizosaccharomyces pombe, a complex of proteins, including the cullin protein Rtt101p and two adapter proteins Mms22p and Mms1p, is important for proper response to replication stress. We have investigated this system in Candida albicans.

Molecular genetic techniques for gene manipulation in Candida albicans.

Candida albicans is one of the most common fungal pathogen in humans due to its high frequency as an opportunistic and pathogenic fungus causing superficial as well as invasive infections in immunocompromised patients. An understanding of gene function in C. albicans is necessary to study the molecular basis of its pathogenesis, virulence and drug resistance.