Area postrema neurons mediate interleukin-6 function in cancer cachexia.

Interleukin-6 (IL-6) has been long considered a key player in cancer cachexia. It is believed that sustained elevation of IL-6 production during cancer progression causes brain dysfunctions, which ultimately result in cachexia. However, how peripheral IL-6 influences the brain remains poorly understood.

The distribution of self-incompatibility systems in angiosperms: the relationship between mating system diversity, life span, growth habit and latitude in a changing global environment.

Background And Aims: There is ample theoretical and experimental evidence that angiosperms harbouring self-incompatibility (SI) systems are likely to respond to global changes in unique ways relative to taxa with other mating systems. In this paper, we present an updated database on the prevalence of SI systems across angiosperms and examine the relationship between the presence of SI and latitude, biomes, life-history traits and management conditions to evaluate the potential vulnerability of SI taxa to climate change and habitat disturbance.

Methods: We performed literature searches to identify studies that employed controlled crosses, microscopic analyses and/or genetic data to classify taxa as having SI, self-compatibility (SC), partial self-compatibility (PSC) or self-sterility (SS).

Corrigendum: Geographical and life-history traits associated with low and high species richness across angiosperm families.

[This corrects the article DOI: 10.3389/fpls.2023.

Geographical and life-history traits associated with low and high species richness across angiosperm families.

Introduction: The phenomenal expansion of angiosperms has prompted many investigations into the factors driving their diversification, but there remain significant gaps in our understanding of flowering plant species diversity.

Methods: Using the crown age of families from five studies, we used a maximum likelihood approach to classify families as having poor, predicted or high species richness (SR) using strict consensus criteria. Using these categories, we looked for associations between family SR and i) the presence of an inferred familial ancestral polyploidization event, ii) 23 life history and floral traits compiled from previously published datasets and papers, and iii) sexual system (dioecy) or genetically determined self-incompatibility (SI) mating system using an updated version of our own database and iv) geographic distribution using a new database describing the global distribution of plant species/families across realms and biomes and inferred range.

Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy.

Cystatin C (CyC), a secreted cysteine protease inhibitor, has unclear biological functions. Many patients exhibit elevated plasma CyC levels, particularly during glucocorticoid (GC) treatment. This study links GCs with CyC's systemic regulation by utilizing genome-wide association and structural equation modeling to determine CyC production genetics in the UK Biobank.

Ketogenic diet promotes tumor ferroptosis but induces relative corticosterone deficiency that accelerates cachexia.

Glucose dependency of cancer cells can be targeted with a high-fat, low-carbohydrate ketogenic diet (KD). However, in IL-6-producing cancers, suppression of the hepatic ketogenic potential hinders the utilization of KD as energy for the organism. In IL-6-associated murine models of cancer cachexia, we describe delayed tumor growth but accelerated cachexia onset and shortened survival in mice fed KD.

Tumor Cytokine-Induced Hepatic Gluconeogenesis Contributes to Cancer Cachexia: Insights from Full Body Single Nuclei Sequencing.

A primary cause of death in cancer patients is cachexia, a wasting syndrome attributed to tumor-induced metabolic dysregulation. Despite the major impact of cachexia on the treatment, quality of life, and survival of cancer patients, relatively little is known about the underlying pathogenic mechanisms. Hyperglycemia detected in glucose tolerance test is one of the earliest metabolic abnormalities observed in cancer patients; however, the pathogenesis by which tumors influence blood sugar levels remains poorly understood.

Cachexia: A systemic consequence of progressive, unresolved disease.

Cachexia, a systemic wasting condition, is considered a late consequence of diseases, including cancer, organ failure, or infections, and contributes to significant morbidity and mortality. The induction process and mechanistic progression of cachexia are incompletely understood. Refocusing academic efforts away from advanced cachexia to the etiology of cachexia may enable discoveries of new therapeutic approaches.

Ketogenic diet promotes tumor ferroptosis but induces relative corticosterone deficiency that accelerates cachexia.

The dependency of cancer cells on glucose can be targeted with high-fat low-carbohydrate ketogenic diet (KD). However, hepatic ketogenesis is suppressed in IL-6 producing cancers, which prevents the utilization of this nutrient source as energy for the organism. In two IL-6 associated murine models of cancer cachexia we describe delayed tumor growth but accelerated onset of cancer cachexia and shortened survival when mice are fed KD.

Area postrema neurons mediate interleukin-6 function in cancer-associated cachexia.

Interleukin-6 (IL-6) has been long considered a key player in cancer-associated cachexia . It is believed that sustained elevation of IL-6 production during cancer progression causes brain dysfunctions, which ultimately result in cachexia . However, how peripheral IL-6 influences the brain remains poorly understood.

Hidden Tenants: Microbiota of the Rhizosphere and Phyllosphere of Trees in Mayan Forests and Homegardens.

During domestication, the selection of cultivated plants often reduces microbiota diversity compared with their wild ancestors. Microbiota in compartments such as the phyllosphere or rhizosphere can promote fruit tree health, growth, and development. is a deciduous tree used by Maya people for its fruit and wood, growing, to date, in remnant forest fragments and homegardens (traditional agroforestry systems) in Yucatán.

Training the host organism to enhance anti-cancer immunity.

In this issue of Cancer Cell, Kurz et al. demonstrate in an orthotopic pancreatic cancer model that low-intensity exercise improves tumor control and response to immunotherapy in an IL-15-dependent manner. Combination therapy, IL-15 super-agonist, anti-PD-1 antibody and chemotherapy, strongly reduces tumor growth.

Early Neutrophilia Marked by Aerobic Glycolysis Sustains Host Metabolism and Delays Cancer Cachexia.

An elevated neutrophil-lymphocyte ratio negatively predicts the outcome of patients with cancer and is associated with cachexia, the terminal wasting syndrome. Here, using murine model systems of colorectal and pancreatic cancer we show that neutrophilia in the circulation and multiple organs, accompanied by extramedullary hematopoiesis, is an early event during cancer progression. Transcriptomic and metabolic assessment reveals that neutrophils in tumor-bearing animals utilize aerobic glycolysis, similar to cancer cells.

Oral famotidine versus placebo in non-hospitalised patients with COVID-19: a randomised, double-blind, data-intense, phase 2 clinical trial.

Objective: We assessed whether famotidine improved inflammation and symptomatic recovery in outpatients with mild to moderate COVID-19.

Design: Randomised, double-blind, placebo-controlled, fully remote, phase 2 clinical trial (NCT04724720) enrolling symptomatic unvaccinated adult outpatients with confirmed COVID-19 between January 2021 and April 2021 from two US centres. Patients self-administered 80 mg famotidine (n=28) or placebo (n=27) orally three times a day for 14 consecutive days.

A comparative analysis of immune privilege in pregnancy and cancer in the context of checkpoint blockade immunotherapy.

Despite their abilities to elicit immune responses, both syngeneic tumors and the half-mismatched placenta grow in the host, unlike a tissue allograft that is aggressively rejected. This is because of local and systemic factors that contribute to the immunologic privilege of tumors and the placenta. Checkpoint blockade immunotherapies subvert this privilege, with spectacularly beneficial outcomes in subsets of patients with certain types of cancer.

Self-sterility in flowering plants: preventing self-fertilization increases family diversification rates.

Background And Scope: New data are presented on the distribution and frequency of self-sterility (SS) - predominantly pre-zygotic self-incompatibility (SI) systems - in flowering plants and the hypothesis is tested that families with self-sterile taxa have higher net diversification rates (DRs) than those with exclusively self-compatible taxa using both absolute and relative rate tests.

Key Results: Three major forms of SI systems (where pollen is rejected at the stigmatic, stylar or ovarian interface) are found to occur in the oldest families of flowering plants, with times of divergence >100 million years before the present (mybp), while post-fertilization SS and heterostyly appear in families with crown ages of 81 and 87 mybp, respectively. It is also founnd that many (22) angiosperm families exhibit >1 SI phenotype and that the distribution of different types of SS does not show strong phylogenetic clustering, collectively suggesting that SS and SI systems have evolved repeatedly de novo in angiosperm history.

Effect of variation in self-incompatibility on pollen limitation and inbreeding depression in Flourensia cernua (Asteraceae) scrubs of contrasting density.

Background And Aims: Selection may favour a partial or complete loss of self-incompatibility (SI) if it increases the reproductive output of individuals in the presence of low mate availability. The reproductive output of individuals varying in their strength of SI may also be affected by population density via its affect on the spatial structuring and number of S-alleles in populations. Modifiers increasing levels of self-compatibility can be selected when self-compatible individuals receive reproductive compensation by, for example, increasing seed set and/or when they become associated with high fitness genotypes.

Macrophylogenetic analyses of the gain and loss of self-incompatibility in the Asteraceae.

The self-incompatibility (SI) status of 571 taxa from the Asteraceae was identified and the taxa were scored as having SI, partial SI or self-compatibility (SC) as their breeding system. A molecular phylogeny of the internal transcribed spacer (ITS) region was constructed for 211 of these taxa. Macrophylogenetic methods were used to test hypotheses concerning the ancestral state of SI in the Asteraceae, the gain and loss of SI, the irreversibility of the loss of SI and the potential for partial SI or SC to be terminal states.

Evidence for subcomplexes in the Fanconi anemia pathway.

Fanconi anemia (FA) is a genomic instability disorder, clinically characterized by congenital abnormalities, progressive bone marrow failure, and predisposition to malignancy. Cells derived from patients with FA display a marked sensitivity to DNA cross-linking agents, such as mitomycin C (MMC). This observation has led to the hypothesis that the proteins defective in FA are involved in the sensing or repair of interstrand cross-link lesions of the DNA.

The nuclear accumulation of the Fanconi anemia protein FANCE depends on FANCC.

The Fanconi anemia (FA) protein FANCE is an essential component of the nuclear FA core complex, which is required for monoubiquitination of the downstream target FANCD2, an important step in the FA pathway of DNA cross-link repair. FANCE is predominantly localized in the nucleus and acts as a molecular bridge between the FA core complex and FANCD2, through direct binding of both FANCC and FANCD2. At present, it is poorly understood how the nuclear accumulation of FANCE is regulated and therefore we investigated the nuclear localization of this FA protein.

Identification of multiple nuclear export sequences in Fanconi anemia group A protein that contribute to CRM1-dependent nuclear export.

The Fanconi anemia (FA) pathway plays an important role in maintaining genomic stability, and defects in this pathway cause cancer susceptibility. The FA proteins have been found to function primarily in a nuclear complex, although a cytoplasmic localization and function for several FA proteins has also been reported. In this study, we investigated the possibility that FANCA, FANCC and FANCG are subjected to active export out of the nucleus.

FANCD2 expression in advanced non-small-cell lung cancer and response to platinum-based chemotherapy.

Fanconi's anemia (FA) is a genetically heterogeneous disease characterized by cancer susceptibility and hypersensitivity to cross-linking agents such as cisplatin. Recently, inactivation of the FA pathway has been proposed to contribute to genomic instability and an increased sensitivity to cisplatin-based therapy in a subset of ovarian tumors. Platinum-based chemotherapy constitutes standard systemic therapy for advanced non-small-cell lung cancer (NSCLC), but resistance to platinum chemotherapy is common.

Genetic structure and outcrossing rates in Flourensia cernua (Asteraceae) growing at different densities in the South-western Chihuahuan Desert.

Backgrounds And Aims: Flourensia cernua is a partially self-incompatible, wind-pollinated shrub that grows in two scrub types of contrasting densities. It was anticipated that differences in plant density would affect the amount of genotype availability, and thus higher outcrossing rates and less genetic differentiation would be found at high-density sites.

Methods: At five high-density sites and at five low-density sites, 11 allozyme loci were analysed in adults.

Chemosensitizing tumor cells by targeting the Fanconi anemia pathway with an adenovirus overexpressing dominant-negative FANCA.

Fanconi anemia (FA) is a rare genetic disorder characterized by bone-marrow failure and cellular hypersensitivity to crosslinking agents, including cisplatin. Here, we studied the use of the FA pathway as a possible target for cancer gene therapy with the aim to sensitize tumor cells for cisplatin by interfering with the FA pathway. As proof-of-principle, FA and non-FA lymphoblast-derived tumors were grown subcutaneously in scid mice and treated with two different concentrations of cisplatin.

Cisplatin triggers apoptotic or nonapoptotic cell death in Fanconi anemia lymphoblasts in a concentration-dependent manner.

Cells derived from Fanconi anemia (FA) patients are hypersensitive for cross-linking agents, such as cisplatin, that are potent inducers of programmed cell death (PCD). Here, we studied cisplatin hypersensitivity in FA in relation to the mechanism of PCD in lymphoblastoid cells representing FA groups A and C. In FA cells, a low concentration of cisplatin caused chromatin condensation, phosphatidylserine (PS) externalization, and the expression of an 18-kDa variant of Bax, all indicators of apoptotic cell death, and the latter suggesting the involvement of a mitochondrial route.