Temporal expression of growth factors triggered by epiregulin regulates inflammation development.

In this study, we investigated the relationship between several growth factors and inflammation development. Serum concentrations of epiregulin, amphiregulin, betacellulin, TGF-α, fibroblast growth factor 2, placental growth factor (PLGF), and tenascin C were increased in rheumatoid arthritis patients. Furthermore, local blockades of these growth factors suppressed the development of cytokine-induced arthritis in mice by inhibiting chemokine and IL-6 expressions. We found that epiregulin expression was early and followed by the induction of other growth factors at different sites of the joints. The same growth factors then regulated the expression of epiregulin at later time points of the arthritis. These growth factors were increased in patients suffering from multiple sclerosis (MS) and also played a role in the development of an MS model, experimental autoimmune encephalomyelitis. The results suggest that the temporal expression of growth factors is involved in the inflammation development seen in several diseases, including rheumatoid arthritis and MS. Therefore, various growth factor pathways might be good therapeutic targets for various inflammatory diseases.

Association between a malnutrition screening tool and mealtime observation checklist items in older people receiving oral intake support: A cross-sectional study of four long-term care facilities.

BACKGROUND: Multiple nutritional screening tools are available for older people; however, few screening tools include specific eating behaviours as risk factors that could lead to poor food intake. The 24-item mealtime observation checklist (MOCL), developed by the Japanese Ministry of Health, Labour and Welfare in 2015, comprises signs, symptoms and conditions during mealtime that reflect eating and swallowing functions and oral conditions. OBJECTIVES: To examine factors associated with malnutrition among the MOCL items in older people. METHODS: A cross-sectional study was conducted using data from a retrospective cohort study conducted at four long-term care facilities in Japan. Among the older people residing in the facilities, 198 who received oral intake support were included in the analyses. Nutritional status was assessed using the Mini Nutritional Assessment-Short Form (MNA®-SF), and comparisons were made between 'malnutrition' and 'at-risk or well-nourished'. The association between each MOCL item and malnutrition was assessed using multivariable logistic regression analysis. RESULTS: Of the 198 participants, 98 (49.5%) were classified as 'malnutrition', 98 (49.5%) as 'at-risk' and 2 (1%) as 'well-nourished' by MNA®-SF. After adjusting for participant characteristics such as age and sex, significant associations with malnutrition were observed for four items from the 24-item MOCL: 'Has fatigue due to extended mealtime (odds ratio [OR] = 3.20, 95% confidence interval [CI]: 1.36-7.53)', 'Food residues in the oral cavity are conspicuous (OR = 2.77, 95% CI: 1.38-5.52)', 'Has difficulty swallowing food and takes time to swallow (OR = 3.78, 95% CI: 1.45-9.84)' and 'Assisted feeding is required (OR = 3.70, 95% CI: 1.73-7.91)'. CONCLUSIONS: The four signs, symptoms and conditions during mealtime identified in this study may be associated with malnutrition in older people. IMPLICATIONS FOR PRACTICE: These may indicate the potential eating problems that can lead to malnutrition. By incorporating them into early intervention and prevention measures, health care providers may help prevent malnutrition and improve the nutritional status of older people.

Validation of the applicability of the mealtime observation checklist in predicting the risk of aspiration pneumonia in older adults receiving oral intake support: A retrospective cohort study of four long-term care facilities.

AIM: In Japan, a 24-item mealtime observation checklist (MOCL) was developed in 2015 to support oral intake and prevent aspiration in older adults. The MOCL consists of signs/symptoms/conditions that reflect eating and swallowing functions and oral conditions. This study aimed to examine the association between each MOCL item and the onset of aspiration pneumonia (AP). METHODS: This retrospective cohort study included 199 older adults with difficulties in oral intake residing in four long-term care facilities. The association between the time to the onset of AP (6 months follow-up) and each MOCL item was examined using Cox proportional hazards models. RESULTS: The median (25th, 75th percentiles) age of the participants was 87 (82, 91.5) years; 131 (65.8%) were women; and 24 developed AP during the study period. After adjusting for the characteristics of participants, six items were significantly associated with the onset of AP: "Has difficulty maintaining a sitting position" (hazard ratio [HR] = 3.29, 95% confidence interval [CI]: 1.37-7.88), "Sleep while eating" (HR = 3.45, 95% CI: 1.12-10.59), "Has difficulty starting to eat, frequently interrupts eating even after starting to eat, and has difficulty concentrating on eating" (HR = 2.51, 95% CI: 1.10-5.72), "Has fatigue because additional time is needed to eat" (HR = 3.08, 95% CI: 1.32-7.20), "Dry mouth" (HR = 2.84, 95% CI: 1.21-6.67), and "Assisted feeding is required" (HR = 2.90, 95% CI: 1.21-6.93). CONCLUSIONS: Of the 24 items on the MOCL, we found six items that might contribute to screening older adults at a high risk of AP onset. Geriatr Gerontol Int 2023; 23: 376-382.

The Gateway Reflex, which is mediated by the inflammation amplifier, directs pathogenic immune cells into the CNS.

The brain-blood barrier (BBB) tightly limits immune cell migration into the central nervous system (CNS), avoiding unwanted inflammation under the normal state. However, immune cells can traverse the BBB when inflammation occurs within the CNS, suggesting a certain signal that creates a gateway that bypasses the BBB might exist. We revealed the inflammation amplifier as a mechanism of this signal, and identified dorsal vessels of the fifth lumber (L5) spinal cord as the gateway. The inflammation amplifier is driven by a simultaneous activation of NF-κB and STATs in non-immune cells, causing the production of a large amount of inflammatory chemokines to open the gateway at L5 vessels. It was found that the activation of the amplifier can be modulated by neural activation and artificially operated by electric pulses followed by establishment of new gateways, Gateway Reflex, at least in mice. Furthermore, genes required for the inflammation amplifier have been identified and are highly associated with various inflammatory diseases and disorders in the CNS. Thus, physical and/or pharmacological manipulation of the inflammation amplifier holds therapeutic value to control neuro-inflammation.

Disease-association analysis of an inflammation-related feedback loop.

The IL-6-triggered positive feedback loop for NFκB signaling (or the IL-6 amplifier/Inflammation amplifier) was originally discovered as a synergistic-activation signal that follows IL-17/IL-6 stimulation in nonimmune cells. Subsequent results from animal models have shown that the amplifier is activated by stimulation of NFκB and STAT3 and induces chemokines and inflammation via an NFκB loop. However, its role in human diseases is unclear. Here, we combined two genome-wide mouse screens with SNP-based disease association studies, revealing 1,700 genes related to the IL-6 amplifier, 202 of which showed 492 indications of association with ailments beyond autoimmune diseases. We followed up on ErbB1 from our list. Blocking ErbB1 signaling suppressed the IL-6 amplifier, whereas the expression of epiregulin, an ErbB1 ligand, was higher in patients with inflammatory diseases. These results indicate that the IL-6 amplifier is indeed associated with human diseases and disorders and that the identified genes may make for potential therapeutic targets.