Mesenchymal stem cells shift the pro-inflammatory phenotype of neutrophils to ameliorate acute lung injury.

BACKGROUND: Mesenchymal stem cell (MSC) treatment plays a major role in the management of acute lung injury (ALI), and neutrophils are the initial line of defense against ALI. However, the effect of MSCs on neutrophils in ALI remains mostly unknown. METHODS: We investigated the characteristics of neutrophils in lung tissue of ALI mice induced by lipopolysaccharide after treatment with MSCs using single-cell RNA sequencing. Neutrophils separated from lung tissue in ALI were co-cultured with MSCs, and then samples were collected for reverse transcription-polymerase chain reaction and flow cytometry. RESULTS: During inflammation, six clusters of neutrophils were identified, annotated as activated, aged, and circulatory neutrophils. Activated neutrophils had higher chemotaxis, reactive oxygen species (ROS) production, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase scores than aged neutrophils. Circulatory neutrophils occurred mainly in healthy tissue and were characterized by higher expression of Cxcr2 and Sell. Activated neutrophils tended to exhibit higher expression of Cxcl10 and Cd47, and lower expression of Cd24a, while aged neutrophils expressed a lower level of Cd47 and higher level of Cd24a. MSC treatment shifted activated neutrophils toward an aged neutrophil phenotype by upregulating the expression of CD24, thereby inhibiting inflammation by reducing chemotaxis, ROS production, and NADPH oxidase. CONCLUSION: We identified the immunosuppressive effects of MSCs on the subtype distribution of neutrophils and provided new insight into the therapeutic mechanism of MSC treatment in ALI.

Financial Health of People Living With Dementia and Their Informal Care Partners: Protocol for a Mixed Methods Study.

BACKGROUND: There is a growing body of academic literature focusing on the significant financial burdens placed on people living with cancer, but little evidence exists on the impact of rising costs of care in other vulnerable populations. This financial strain, also known as financial toxicity, can impact behavioral, psychosocial, and material domains of life for people diagnosed with chronic conditions and their care partners. New evidence suggests that populations experiencing health disparities, including those with dementia, face limited access to health care, employment discrimination, income inequality, higher burdens of disease, and exacerbating financial toxicity. OBJECTIVE: The three study aims are to (1) adapt a survey to capture financial toxicity in people living with dementia and their care partners; (2) characterize the degree and magnitude of different components of financial toxicity in this population; and (3) empower the voice of this population through imagery and critical reflection on their perceptions and experiences relating to financial toxicity. METHODS: This study uses a mixed methods approach to comprehensively characterize financial toxicity among people living with dementia and their care partners. To address aim 1, we will adapt elements from previously validated and reliable instruments, including the Comprehensive Score for Financial Toxicity and Patient-Reported Outcomes Measurement Information System, to develop a financial toxicity survey specific to dyads of people living with dementia and their care partners. A total of 100 dyads will complete the survey, and data will be analyzed using descriptive statistics and regression models to address aim 2. Aim 3 will be addressed using the process of "photovoice," which is a qualitative, participatory research method that combines photography, verbal narratives, and critical reflection by groups of individuals to capture aspects of their environment and experiences with a certain topic. Quantitative results and qualitative findings will be integrated using a validated, joint display table mixed methods approach called the pillar integration process. RESULTS: This study is ongoing, with quantitative findings and qualitative results anticipated by December 2023. Integrated findings will enhance the understanding of financial toxicity in individuals living with dementia and their care partners by providing a comprehensive baseline assessment. CONCLUSIONS: As one of the first studies on financial toxicity related to dementia care, findings from our mixed methods approach will support the development of new strategies for improving the costs of care. While this work focuses on those living with dementia, this protocol could be replicated for people living with other diseases and serve as a blueprint for future research efforts in this space. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47255.

Long non-coding RNA SNHG16 promotes human placenta-derived mesenchymal stem cell proliferation capacity through the PI3K/AKT pathway under hypoxia.

BACKGROUND: The effect of hypoxia on mesenchymal stem cells (MSCs) is an emerging topic in MSC biology. Although long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) are reported to play a critical role in regulating the biological characteristics of MSCs, their specific expression and co-expression profiles in human placenta-derived MSCs (hP-MSCs) under hypoxia and the underlying mech anisms of lncRNAs in hP-MSC biology are unknown. AIM: To reveal the specific expression profiles of lncRNAs in hP-MSCs under hypoxia and initially explored the possible mechanism of lncRNAs on hP-MSC biology. METHODS: Here, we used a multigas incubator (92.5% N2, 5% CO2, and 2.5% O2) to mimic the hypoxia condition and observed that hypoxic culture significantly promoted the proliferation potential of hP-MSCs. RNA sequencing technology was applied to identify the exact expression profiles of lncRNAs and mRNAs under hypoxia. RESULTS: We identified 289 differentially expressed lncRNAs and 240 differentially expressed mRNAs between the hypoxia and normoxia groups. Among them, the lncRNA SNHG16 was upregulated under hypoxia, which was also validated by reverse transcription-polymerase chain reaction. SNHG16 was confirmed to affect hP-MSC proliferation rates using a SNHG16 knockdown model. SNHG16 overexpression could significantly enhance the proliferation capacity of hP-MSCs, activate the PI3K/AKT pathway, and upregulate the expression of cell cycle-related proteins. CONCLUSION: Our results revealed the specific expression characteristics of lncRNAs and mRNAs in hypoxia-cultured hP-MSCs and that lncRNA SNHG16 can promote hP-MSC proliferation through the PI3K/AKT pathway.