嚢胞性線維症

Pseudomonas aeruginosa is a highly diverse, adaptable Gram-negative bacterium that thrives in many environments and is a frequent cause of chronic opportunistic infections in people with cystic fibrosis (CF). P. aeruginosa adapts over time of colonization to facilitate chronic infection, including loss of virulence factors; however, proteomic analyses of the adaptation to chronic infection have been limited. We previously assembled and characterized an international panel of P. aeruginosa strains from diverse clinical and geographical sources, including three sets of sequential CF isolates, enabling identification of conserved adaptations linked to chronic CF lung colonization. We compared the proteomes of eight strains (three early and five late infection) to assess whether common proteomic changes emerged during colonization across the sequential isolates. We identified 11 proteins showing increased abundance in late isolates in all three series, many of which are associated with virulence, regulation of virulence, or response to hypoxia. These include CF inhibitory factor repressor (CifR); WspR; 2 two-component response regulators (PA2572 and PA3702), and transcriptional regulator (PA2551). Moreover, we identified three proteins (PA2572, PA3819, and PA5028) that showed increased abundance in all five late isolates. The probability of this being random is 5.06 × 10-53 and therefore, strong evidence of positive selection. The increased abundance of PA2573 and PA3819 appears to improve the fitness of P. aeruginosa in response to antibiotics and oxidative stress. All three proteins share a tyrosine phosphorylation motif, suggesting a common regulatory mechanism. Overall, despite substantial diversity across P. aeruginosa, common adaptations occur in the CF lung.

OBJECTIVES: Deoxyribonuclease (DNase) is widely used in treating obstructed purulent sputum drainage caused by bronchiectasis, lung abscess, cystic fibrosis, and atelectasis and inhibits biofilm formation. METHODS: This study optimized the earthworm DNase extraction process. Tissue homogenates were prepared using mechanical homogenization, followed by isoelectric precipitation and acetone precipitation. Crude earthworm extracts (EWE) were purified by ion exchange chromatography. DNase activity was evaluated by Bradford assay and UV absorption method. RESULTS: Method 1 took 42-45 h, while method 2 took 15-18 h. The specific activity of EWE1 was 677.48 ± 52.84 U/mg. The specific activity of EWE2 was 622.03 ± 49.76 U/mg. Following weak cation exchange chromatography and heparin affinity chromatography, the enzyme activity of the extract was 4443.33 ± 266.59 U/mg. The minimum working concentration was 1.88 µg/mL. CONCLUSION: The improved extraction process markedly reduced the preparation time and enhanced DNase specific activity of earthworm extract.

Ring finger protein 5 (RNF5), a membrane-associated RING-type E3 ubiquitin ligase, serves as a critical regulator of cellular homeostasis by controlling protein stability, metabolic adaptation, and immune signaling. This review provides a comprehensive overview of the multifaceted functions of RNF5, with particular emphasis on its context-dependent roles in cancer progression, antiviral immunity, and non-neoplastic diseases. In cancer, RNF5 exhibits highly context-dependent and sometimes paradoxical functions that are influenced by cellular environments, disease stages, and substrate availability. RNF5 regulates tumor-associated metabolic reprogramming by targeting glutamine transporters and key regulators of lipid metabolism. Moreover, through interactions with autophagy-related proteins and Ephrin receptors, RNF5 modulates tumor growth, therapeutic resistance, and antitumor immune responses. These findings highlight RNF5 as a complex regulator of tumor biology with both oncogenic and tumor-suppressive potential. During viral infections, RNF5 demonstrates dual regulatory activities in host-pathogen interactions. On one hand, RNF5 can suppress antiviral innate immune signaling by promoting the ubiquitination and degradation of key immune adaptors, including STING and MAVS. On the other hand, RNF5 may restrict viral replication by directly targeting viral components, such as the SARS-CoV-2 envelope protein and foot-and-mouth disease virus VP1, for ubiquitination and degradation. Thus, RNF5 functions as a versatile modulator of antiviral defense, with effects determined by the specific viral context and host signaling landscape. Beyond cancer and viral infection, emerging evidence implicates RNF5 in a variety of non-neoplastic disorders. RNF5 contributes to protein quality control in neurodegenerative diseases by facilitating the clearance of pathological tau through the ERAD pathway. In addition, genetic inhibition of RNF5 ameliorates intestinal pathological phenotypes in a mouse model of cystic fibrosis, while RNF5 has also been associated with hepatic and cardiovascular injury responses through regulation of cellular stress pathways. From a therapeutic perspective, RNF5-targeting strategies, including small-molecule inhibitors and pathway modulators, have emerged as potential approaches for manipulating RNF5-associated biological processes. However, substantial challenges remain, including achieving target specificity, understanding the context-dependent consequences of RNF5 modulation, minimizing potential disruptions to proteostasis and innate immune regulation, and developing clinically feasible therapeutic interventions. This review summarizes the complex regulatory network governed by RNF5 and discusses future opportunities and challenges in translating mechanistic insights into therapeutic applications while carefully considering potential risks associated with RNF5 targeting.

Exophiala dermatitidis is an opportunistic pathogen belonging to the so-called black yeasts, a group of fungi capable of causing a wide range of infections. Here we systematically reviewed 77 global cases of E. dermatitidis infections reported between 1989 and 2024. Most cases were reported from Japan (19/77), United States (16/77) and China (10/77), with 64.9% (50/77) cases reported since 2010, indicating an increasing global awareness of this fungus. Our results indicated that reported E. dermatitidis infections occurred in both immunocompromised (54.55%; 42/77) and apparently immunocompetent hosts (45.45%; 35/77), with deep-seated infections being the most common (76.62%; 59/77). Infections are associated with a high mortality rate, especially those affecting the central nervous system (63.63%; 7/11). Leukemia, nephropathy, diabetes, cystic fibrosis and CARD9 deficiency were identified as important predisposing factors for E. dermatitidis infection. All included cases were culture-confirmed, with a subset additionally supported by histopathological examination and/or molecular identification. Although there is currently no consensus about antifungal treatment for E. dermatitidis infections, our findings suggest that voriconazole was the most frequently used antifungal agent among the reviewed cases.