Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma

BACKGROUND: Microbial intestinal colonization in early in life is regarded to play a major role for the maturation of the immune system. Application of non-pathogenic probiotic bacteria during early infancy might protect from allergic disorders but underlying mechanisms have not been analysed so far. OBJECTIVE: The aim of the current study was to investigate the immune effects of oral application of probiotic bacteria on allergen-induced sensitization and development of airway inflammation and airway hyper-reactivity, cardinal features of bronchial asthma. METHODS: Newborn Balb/c mice received orally 10(9) CFU every second day either Lactobacillus rhamnosus GG or Bifidobacterium lactis (Bb-12) starting from birth for consecutive 8 weeks, during systemic sensitization (six intraperitoneal injections, days 29-40) and airway challenge (days 54-56) with ovalbumin. RESULTS: The administration of either Bb-12 or LGG suppressed all aspects of the asthmatic phenotype: airway reactivity, antigen-specific immunoglobulin E production and pulmonary eosinophilia (mean: 137 vs. 17 and 13 cellsx10(3)/mL, respectively). Antigen-specific recall proliferation by spleen cells and T-helper type 2 cytokine production (IL-4, IL-5 and IL-10) by mesenteric lymph node cells also showed significant reduction, while TGF production remained unchanged. Oral LGG administration particularly suppressed allergen-induced proliferative responses and was associated with an increase in numbers of TGF-beta-secreting CD4+/CD3+ T cells in mesenteric lymph nodes (6.5, 16.7%) as well as nearly 2-fold up-regulation of Foxp3-expressing cells in peribronchial lymph nodes. CONCLUSIONS: Neonatal application of probiotic bacteria inhibits subsequent allergic sensitization and airway disease in a murine model of asthma by induction of T regulatory cells associated with increased TGF-beta production.     

PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted,but Functional in Patients with COVID-19

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Sequential production and activation of matrix-metalloproteinase-9 (MMP-9) with breast cancer progression

The degradation of the basement membrane by matrix-metalloproteinase(MMP) and serine protease is a critical pointin tumor invasion and metastasis. We measured theactivity of MMP-9 from 28 normal, 12 benignand 126 breast cancer tissues using gelatin zymographywith an image analysis system. ProMMP-9 was expressedin 17.5% of the cancer patients compared to2.5% in 40 non-cancerous tissues (p=0.014).The mature form of MMP-9 (82 kD) wasexpressed only in T2–T4 stages. During the earlyphase of breast cancer (DCIS and T1 stage)progression, only production of proMMP-9 increased. However, asthe cancer grew or invaded skin (T2–T4), orwith lymphovascular permeation, both production and activation ofMMP-9 increased. In conclusion, proMMP-9 production was themain cause of increased MMP-9 activity during theearly phase, while both production and activation increasedin the late phase of breast cancer.     

Clinical safety of drug-eluting stents in the Korea acute myocardial infarction registry.

BACKGROUND: Percutaneous coronary intervention (PCI) with drug-eluting stents (DES) may be useful in patients with acute myocardial infarction (AMI), but safety issues still need to be solved. This study was undertaken to investigate the incidence of major adverse cardiac events (MACE) and stent thrombosis in DES-implanted AMI patients in real-life clinical practice. METHODS AND RESULTS: On-line registry of AMI cases at the web site www.kamir.or.kr has been performed in 41 primary PCI centers in Korea and between November 2005 and September 2006, 1,541 surviving patients who had been implanted with either Cypher or Taxus stents were enrolled for analysis during a 6-month clinical follow-up. There were 2 groups: group I [834 patients, 61.9+/-11.9 years: sirolimus-eluting stent (Cypher)], group II [707 patients, 62.9+/-12.0 years: paclitaxel-eluting stent (Taxus)]. At both 1 and 6 months the incidence of MACE was not significantly different between the 2 groups. There were 17 cases of stent thrombosis, but the incidence of stent thrombosis was not significantly different between the 2 groups (group I:II=9 (1.1%):8 (1.1%), p=1.000). The stent type, length, number, lesion complexity and diabetes were not significant for the incidence of MACE or stent thrombosis after adjustment. CONCLUSION: MACE and stent thrombosis rates did not differ between 2 types of DES identified in Korea Acute Myocardial Infarction Registry (KAMIR). DES can be used in patients with AMI with a relatively low 6-month MACE rate.