Preparation of mitochondrial damage-associated molecular patterns from mouse liver tissue.

Mitochondrial damage-associated molecular patterns (mitoDAMPs) are released from cells dying uncontrolled, non-apoptotic deaths, usually secondary to disease or trauma. Here, we describe preparation of mitoDAMPs from mouse liver, but this protocol can be adapted for preparation of mitoDAMPs from other species and tissues. Tissues are dissociated and then processed to isolate mitochondria. Mitochondria are then sonicated and mitoDAMPs are collected by ultracentrifugation. This procedure produces µg quantities of mitoDAMPs and facilitates research to understand their impacts in health and disease. For complete details on the use and execution of this protocol, please refer to Westhaver et al. (2022).

Mitochondrial damage-associated molecular patterns trigger arginase-dependent lymphocyte immunoregulation.

Tissue damage leads to loss of cellular and mitochondrial membrane integrity and release of damage-associated molecular patterns, including those of mitochondrial origin (mitoDAMPs). Here, we describe the lymphocyte response to mitoDAMPs. Using primary cells from mice and human donors, we demonstrate that natural killer (NK) cells and T cells adopt regulatory phenotypes and functions in response to mitoDAMPs. NK cell-mediated cytotoxicity, interferon gamma (IFN-γ) production, T cell proliferation, and in vivo anti-viral T cell activation are all interrupted in the presence of mitoDAMPs or mitoDAMP-rich irradiated cells in in vitro and in vivo assays. Mass spectrometry analysis of mitoDAMPs demonstrates that arginase and products of its enzymatic activity are prevalent in mitoDAMP preparations. Functional validation by arginase inhibition and/or arginine add-back shows that arginine depletion is responsible for the alteration in immunologic polarity. We conclude that lymphocyte responses to mitoDAMPs reflect a highly conserved mechanism that regulates inflammation in response to tissue injury.

NK cell infiltration is associated with improved overall survival in solid cancers: A systematic review and meta-analysis.

The immune landscape of a tumor is highly connected to patient prognosis and response to treatment, but little is known about how natural killer (NK) cells predict overall survival (OS) among patients with solid tumors. We present the first meta-analysis on NK cell infiltration into solid tumors as a prognostic indicator for OS, considering cancer types independently, and together. Samples were collected from 1973 to 2016 with results published between 1989 and 2020. From 53 studies, we found that NK cell infiltration corresponds with decreased risk of death (HR=0.34, 95% CI: 0.26-0.46; p<0.0001). Among studies that investigated the prognostic potential of NK cells in specific regions of the tumor, intraepithelial infiltration was better predictive of OS than NK infiltration in the tumor-adjacent stroma. Generally, NK cell infiltration is lower in advanced-stage and lower-grade tumors; nevertheless, it remains prognostically beneficial. This meta-analysis highlights an important prognostic role of NK cells in solid tumors, but exposes that few studies have considered the contributions of NK cells. Toward NK cell-based immunotherapies, it will be important to understand the conditions under which NK cells can be effective agents of tumor control.

Body image in older breast cancer survivors: A systematic review.

OBJECTIVE: Breast cancer is the most common cancer among women world-wide. In North America survival rates are >80%, resulting in a large population of survivors. The goal of this review was to systematically explore the literature to identify the status of body image and factors that can impact the body image of older breast cancer survivors. METHODS: A systematic review of the literature was conducted and registered with PROSPERO (CRD42019133617). EMBASE and PubMed were searched for articles including terms related to "body image" and "breast cancer." Duplicates were removed and the remaining 322 abstracts were screened. Articles published before 2000, were off-topic, or those that were non-primary research articles were excluded. Sixty-nine remaining full-length articles were screened for language, gender and location. Seven articles underwent quality assessment of which five passed and were reviewed in depth. The remaining two articles were briefly discussed. RESULTS: The literature review suggests that body image is considered important in older BCS and that body image may impact or be impacted by several factors including age, menopausal status, mental health, treatment modality and exercise. Additionally, themes of dealing with physical changes and the length of time women are impacted following treatment were explored. CONCLUSION: Our findings highlight that older women may be at an advantage in terms of being post-menopausal, however concerns surrounding physical and emotional changes affecting body image are indeed present. Future studies on breast cancer survivorship should consider the inclusion of body image as an outcome measure in addition to including individuals representing a wide range of ages.

Ligictaluridus michaelalicea n. sp. (Monogenea: Dactylogyridae) from flathead catfish (Pylodictis olivaris) in the upper Mississippi River, including remarks on taxonomy influencing monogenean treatment regulation in the United States.

Ligictaluridus michaelalicea n. sp. (Monogenea: Dactylogyridae, Ancyrocephalinae) is described from the gills of Pylodictis olivaris (Siluriformes: Ictaluridae) from Wisconsin and Iowa portions of the upper Mississippi River. Diagnostic features include a relatively large, strongly curved tubular cirrus with minor terminal flare; an accessory piece with a prominent basal lobe and a simple, thick terminal limb featuring a thin lateral flange and blunt distal tip devoid of recurved hooks. The sinistral vagina, two prostatic reservoirs, and a terminal seminal vesicle of the vas deferens are prominent. The anchors, ventral and dorsal bars, and hooks are similar in overall form to those of other members of the genus. The description includes sequence data for the 18S rRNA gene, which aligned most closely with species of ancyrocephaline monogeneans, with the highest similarity being with Ligictaluridus pricei (Mueller, 1936). Other monogenean species identified from the flathead catfish examined included L. pricei and Ligictaluridus mirabilis (Mueller, 1937). L. michaelalicea n. sp. is the fourth species to be described from P. olivaris within its natural range in central and eastern North America. Implications resulting from taxonomic name changes, including species of Ligictaluridus, and United States Food and Drug Administration treatment regulations are discussed. An updated key to species of the genus Ligictaluridus is presented.