Activation of RIG-I signaling in the early stage of Paragonimus proliferus infection causes lung injury via type I immune response in rat.

Paragonimiasis is a common zoonotic parasitic disease. The retinoic acid-inducible gene I (RIG-I) signaling is very important for the host to recognize invading pathogens (especially viruses and bacteria). However, the role of RIG-I signaling in the early stages of P. proliferus infection remains unclear. Therefore, in this study, Sprague-Dawley (SD) rat models with lung damage caused by P. proliferus were established. Experimental methods including Enzyme-linked Immuno Sorbent Assay (ELISA), real-time fluorescent quantitative polymerase chain reaction (PCR), western blotting, and hematoxylin and eosin (HE) staining were used to explore the mechanisms of lung injury caused by P. proliferus. As a result, the expression of the mRNA and proteins of RIG-I signal-related key target molecules, including RIG-I, tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6), interferon regulatory Factor 7 (IRF7), IPS-1, and downstream C-X-C chemokine ligand 10 (CXCL10), were significantly up-regulated immediately after infection, peaked at 3 or 7 days, and showed a downward trend on after 14 days. The levels of pro-inflammatory cytokines interleukin-1 (IL-1), interferon (IFN)-α, -ß, and -γ, which represent type 1 immune response, gradually increased and reached a peak by 14 days, which was consistent with the changes in the degree of inflammatory damage observed under HE staining of lung tissues. In conclusion, RIG-I signaling is activated in the early stage (before 14 days) of P. proliferus infection, it is inferred that the lung injury of the host may be related to the activation of RIG-I like signaling to induce type I immune response.

Measuring and explaining inequality of continuous care for people living with HIV receiving antiretroviral therapy in Kunming, China.

BACKGROUND: In the context of scaling up free antiretroviral therapy (ART), healthcare equality is essential for people living with HIV. We aimed to assess socioeconomic-related inequalities in uptake of continuous care for people living with HIV receiving ART, including retention in care in the last six months, routine toxicity monitoring, adequate immunological and virological monitoring, and uptake of mental health assessment in the last 12 months. We also determined the contributions of socioeconomic factors to the degree of inequalities. METHODS: A hospital-based cross-sectional survey was conducted among consecutive clients visiting an HIV treatment center in Kunming, China in 2019. Participants were 702 people living with HIV aged ≥18 years (median age: 41.0 years, 69.4% male) who had been on ART for 1-5 years. Socioeconomic-related inequality and its contributing factors were assessed by a normalized concentration index (CIn) with a decomposition approach. RESULTS: The uptake of mental health assessment was low (15%) but significantly higher among the rich (CIn 0.1337, 95% CI: 0.0140, 0.2534). Retention in care, toxicity, and immunological monitoring were over 80% but non-significant in favor of the rich (CIn: 0.0117, 0.0315, 0.0736, respectively). The uptake of adequate virological monitoring was 15% and higher among the poor (CIn = -0.0308). Socioeconomic status positively contributed to inequalities of all care indicators, with the highest contribution for mental health assessment (124.9%) and lowest for virological monitoring (2.7%). CONCLUSIONS: These findings suggest virological monitoring and mental health assessment be given more attention in long-term HIV care. Policies allocating need-oriented resources geared toward improving equality of continuous care should be developed.

The Protective Action of Piperlongumine Against Mycobacterial Pulmonary Tuberculosis in Its Mitigation of Inflammation and Macrophage Infiltration in Male BALB/c Mice.

INTRODUCTION: Piperlongumine (PL) is a bioactive alkaloid and medicinal compound of piperamide isolated from the long pepper (Piper longum Linn). It has demonstrated bactericidal action against Mycobacterium tuberculosis (MTB), the cause of pulmonary tuberculosis; nevertheless, immunomodulatory activity had not been identified for it in MTB-triggered granulomatous inflammation. This study investigated if piperlongumine could inhibit such inflammation. MATERIAL AND METHODS: Mycobacterium tuberculosis strain H37Rv was subjected to a broth microdilution assay. Piperlongumine at 5, 15, and 25 µg/mL, 0.2% dimethyl sulphoxide as control or 4 µM of dexamethasone were tested in vitro on MH-S murine alveolar macrophages. BALB/c mice were orally administered PL at 50, 100 and 150 mg/kg b.w. after trehalose-6,6-dimycolate (TDM) stimulation. Chemokine and cytokine concentrations were determined in lung supernatants. Flow cytometry and Western blot analysis were performed to determine phosphorylated spleen tyrosine kinase (Syk), c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways. RESULTS: Piperlongumine inhibited inflammatory mediators and adherence of lymphocyte function-associated antigen 1 to MH-S cells following TDM activation. It also improved macrophage clearance of MTB. In TDM-stimulated MH-S cells, PL significantly influenced the macrophage inducible Ca2+-dependent lectin receptor (Mincle)-Syk-ERK signalling pathway. Oral dosing of PL effectively suppressed the development of pulmonary granulomas and inflammatory reactions in the TDM-elicited mouse granuloma model. CONCLUSION: PL as an inhibitor of MTB-triggered granulomatous inflammation may be an effective complementary treatment for mycobacterial infection.

Inhibition of respiratory syncytial virus replication and suppression of RSV-induced airway inflammation in neonatal rats by colchicine.

The present study investigated the role of colchicine in the treatment of RSV infection. Treatment of BEAS-2B cells following RSV infection with colchicine caused a significant decrease in the number of viral plaques. In RSV-infected BEAS-2B cells' treatment with colchicine leads to a significant up-regulation of both IFN-ß1 and RIG-I genes. The levels of interleukin, NO, and MDA were suppressed in BEAS-2B cells infected with RSV by colchicine. The phosphorylation of Stat3, COX-2, and p38 was also suppressed significantly by colchicine. The phosphorylation of IkBα was promoted in RSV-infected BEAS-2B cells' oncolchicine treatment. In neonatal rats, replication of RSV was inhibited significantly by colchicine treatment which was evident by suppression of RSV-L gene expression. A significant decrease in the level of IL-6 and TNF-α was caused in neonatal rat BALF by colchicine treatment. The production of MDA, NO and MPO in the neonatal rat BALF was suppressed markedly by colchicine treatment. Treatment of the neonatal rats infected by RSV with colchicine suppressed the release of IκBα and COX-2 in the pulmonary epithelial cells. Colchicine treatment of the neonatal rats promoted the expression of IFN-α and IFN-ß1. In summary, the current study showed that colchicine inhibited RSV infection in neonatal rats through regulation of anti-oxidative factor production. The expression of IFN-ß1 and RIG-I genes was also up-regulated in the RSV-infected alveolar epithelial cells by treatment with colchicine. Therefore, colchicine may be developed as the therapeutic agent for the treatment of RSV infection.