Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks expression of the nuclear steroid receptors that bind estrogens (ER) and progestogens (PRs) and does not exhibit HER2 (Human epidermal growth factor 2) receptor overexpression. Even in the face of initially effective chemotherapies, TNBC patients often relapse. One primary cause for therapy-resistant tumor progression is the activation of cellular stress signaling pathways. The glucocorticoid receptor (GR), a corticosteroid-activated transcription factor most closely related to PR, is a mediator of both endocrine/host stress and local tumor microenvironment (TME)-derived and cellular stress responses. Interestingly, GR expression is associated with a good prognosis in ER+ breast cancer but predicts poor prognosis in TNBC. Classically, GR\'s transcriptional activity is regulated by circulating glucocorticoids. Additionally, GR is regulated by ligand-independent signaling events. Notably, the stress-activated protein kinase, p38 MAP kinase, phosphorylates GR at serine 134 (Ser134) in response to TME-derived growth factors and cytokines, including HGF and TGFβ1. Phospho-Ser134-GR (p-Ser134-GR) associates with cytoplasmic and nuclear signaling molecules, including 14-3-3ζ, aryl hydrocarbon receptors (AhR), and hypoxia-inducible factors (HIFs). Phospho-GR/HIF-containing transcriptional complexes upregulate gene sets whose protein products include the components of inducible oncogenic signaling pathways (PTK6) that further promote cancer cell survival, chemoresistance, altered metabolism, and migratory/invasive behavior in TNBC. Recent studies have implicated liganded p-Ser134-GR (p-GR) in dexamethasone-mediated upregulation of genes related to TNBC cell motility and dysregulated metabolism. Herein, we review the tumor-promoting roles of GR and discuss how both ligand-dependent and ligand-independent/stress signaling-driven inputs to p-GR converge to orchestrate metastatic TNBC progression.

UNASSIGNED: The ongoing global expansion of salt-affected land is a significant factor, limiting the growth and yield of crops, particularly rice (Oryza sativa L). This experiment explores the mitigation of salt-induced damage in rice (cv BRRI dhan100) following the application of plant growth-promoting rhizobacteria (PGPR).
UNASSIGNED: Rice seedlings, at five- and six-weeks post-transplanting, were subjected to salt stress treatments using 50 and 100 mM NaCl at seven-day intervals. Bacterial cultures consisting of endophytic PGPR (Bacillus subtilis and B. aryabhattai) and an epiphytic PGPR (B. aryabhattai) were administered at three critical stages: transplantation of 42-day-old seedlings, vegetative stage at five weeks post-transplantation, and panicle initiation stage at seven weeks post-transplantation.
UNASSIGNED: Salt stress induced osmotic stress, ionic imbalances, and oxidative damage in rice plants, with consequent negative effects on growth, decrease in photosynthetic efficiency, and changes in hormonal regulation, along with increased methylglyoxal (MG) toxicity. PGPR treatment alleviated salinity effects by improving plant antioxidant defenses, restoring ionic equilibrium, enhancing water balance, increasing nutrient uptake, improving photosynthetic attributes, bolstering hormone synthesis, and enhancing MG detoxification.
UNASSIGNED: These findings highlight the potential of PGPR to bolster physiological and biochemical functionality in rice by serving as an effective buffer against salt stress-induced damage. B. subtilis showed the greatest benefits, while both the endophytic and epiphytic B. aryabhattai had commendable effects in mitigating salt stress-induced damage in rice plants.

Systemic acquired acclimation and resistance are vital physiological mechanisms, essential for plants to survive challenging conditions, including herbicide stress. Harmonizing this adaptation involves a series of complex communication pathways. Hydrogen peroxide (H2O2) metabolism might play pivotal roles in orchestrating weeds\' acclimation and defense responses. In the context of herbicide resistance, the interaction between H2O2 and key stress signaling pathways is crucial in understanding weed physiology and developing effective management strategies. This dynamic interplay might significantly influence how weeds develop resistance to the various challenges posed by herbicides. Moreover, the production and eradication of H2O2 can be highly compartmentalized, depending on the type of herbicide exposure. Till date there have been no studies aiming to explore/discuss these possibilities. Therefore, in this mini-review, our objective is to delve into the potentialities and recent advancements regarding H2O2-mediated signaling of transcriptomic changes during herbicide stress.

The tomato is a fruit vegetable rich in nutritional and medicinal value grown in greenhouses and fields worldwide. It is severely sensitive to heat stress, which frequently occurs with rising global warming. Predictions indicate a 0.2 °C increase in average surface temperatures per decade for the next three decades, which underlines the threat of austere heat stress in the future. Previous studies have reported that heat stress adversely affects tomato growth, limits nutrient availability, hammers photosynthesis, disrupts reproduction, denatures proteins, upsets signaling pathways, and damages cell membranes. The overproduction of reactive oxygen species in response to heat stress is toxic to tomato plants. The negative consequences of heat stress on the tomato have been the focus of much investigation, resulting in the emergence of several therapeutic interventions. However, a considerable distance remains to be covered to develop tomato varieties that are tolerant to current heat stress and durable in the perspective of increasing global warming. This current review provides a critical analysis of the heat stress consequences on the tomato in the context of global warming, its innate response to heat stress, and the elucidation of domains characterized by a scarcity of knowledge, along with potential avenues for enhancing sustainable tolerance against heat stress through the involvement of diverse advanced technologies. The particular mechanism underlying thermotolerance remains indeterminate and requires further elucidatory investigation. The precise roles and interplay of signaling pathways in response to heat stress remain unresolved. The etiology of tomato plants\' physiological and molecular responses against heat stress remains unexplained. Utilizing modern functional genomics techniques, including transcriptomics, proteomics, and metabolomics, can assist in identifying potential candidate proteins, metabolites, genes, gene networks, and signaling pathways contributing to tomato stress tolerance. Improving tomato tolerance against heat stress urges a comprehensive and combined strategy including modern techniques, the latest apparatuses, speedy breeding, physiology, and molecular markers to regulate their physiological, molecular, and biochemical reactions.

The primary cilium is a characteristic feature of most non-immune cells and functions as an environmental signal transduction sensor. The defects in primary cilium have profound effects on the developmental program, including the maturation of retinal epithelium. The ciliary length is tightly regulated during ciliogenesis, but the impact of inflammation on ciliary length remains elusive. The current study investigates the outcome of inflammatory stimuli for the primary cilium length in retinal epithelium cells and mouse embryonic fibroblasts. Here, we report that exposure to the pro-inflammatory cytokine TNF-alpha elongates cilia in a mixed-lineage kinase (MLK)-dependent manner. Pro-inflammatory stimuli such as bacterial LPS and interferon-gamma have similar effects on ciliary length. In contrast, febrile condition-mimicking heat stress dramatically reduced the number of ciliated cells regardless of TNF-alpha exposure but did not shorten TNF-induced elongation, suggesting distinct but rapid effects of inflammatory stresses on ciliogenesis.

Intervertebral disc degeneration (IDD) is a major cause of lower back pain. The pathophysiological development of IDD is closely related to the stimulation of various stressors, including proinflammatory cytokines, abnormal mechanical stress, oxidative stress, metabolic abnormalities, and DNA damage, among others. These factors prevent normal intervertebral disc (IVD) development, reduce the number of IVD cells, and induce senescence and apoptosis. Stress-activated protein kinases (SAPKs), particularly, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK), control cell signaling in response to cellular stress. Previous studies have shown that these proteins are highly expressed in degenerated IVD tissues and are involved in complex biological signal-regulated processes. Therefore, we summarize the research reports on IDD related to JNK and p38 MAPK. Their structure, function, and signal regulation mechanisms are comprehensively and systematically described and potential therapeutic targets are proposed. This work could provide a reference for future research and help improve molecular therapeutic strategies for IDD.

Alcohol-associated liver disease (ALD) is a leading factor of liver-related death worldwide. ALD has various manifestations that include steatosis, hepatitis, and cirrhosis and is currently without approved pharmacotherapies. The Src homology phosphatase 2 (Shp2) is a drug target in some cancers due to its positive regulation of Ras-mitogen-activated protein kinase signaling and cell proliferation. Shp2 pharmacological inhibition yields beneficial outcomes in animal disease models, but its impact on ALD remains unexplored. This study aims to investigate the effects of Shp2 inhibition and its validity using a preclinical mouse model of ALD. We report that the administration of SHP099, a potent and selective allosteric inhibitor of Shp2, partially ameliorated ethanol-induced hepatic injury, inflammation, and steatosis in mice. Additionally, Shp2 inhibition was associated with reduced ethanol-evoked activation of extracellular signal-regulated kinase (ERK), oxidative, and endoplasmic reticulum (ER) stress in the liver. Besides the liver, excessive alcohol consumption induces multi-organ injury and dysfunction, including the intestine. Notably, Shp2 inhibition diminished ethanol-induced intestinal inflammation and permeability, abrogated the reduction in tight junction protein expression, and the activation of ERK and stress signaling in the ileum. Collectively, Shp2 pharmacological inhibition mitigates the deleterious effects of ethanol in the liver and intestine in a mouse model of ALD. Given the multifactorial aspects underlying ALD pathogenesis, additional studies are needed to decipher the utility of Shp2 inhibition alone or as a component in a multitherapeutic regimen to combat this deadly malady.

Heavy metal pollution threatens plant growth and development as well as ecological stability. Here, we synthesize current research on the interplay between plants and their microbial symbionts under heavy metal stress, highlighting the mechanisms employed by microbes to enhance plant tolerance and resilience. Several key strategies such as bioavailability alteration, chelation, detoxification, induced systemic tolerance, horizontal gene transfer, and methylation and demethylation, are examined, alongside the genetic and molecular basis governing these plant-microbe interactions. However, the complexity of plant-microbe interactions, coupled with our limited understanding of the associated mechanisms, presents challenges in their practical application. Thus, this review underscores the necessity of a more detailed understanding of how plants and microbes interact and the importance of using a combined approach from different scientific fields to maximize the benefits of these microbial processes. By advancing our knowledge of plant-microbe synergies in the metabolism of heavy metals, we can develop more effective bioremediation strategies to combat the contamination of soil by heavy metals.

暂无摘要。

Membrane lipidomes are dynamic and their changes generate lipid mediators affecting various biological processes. Phosphatidic acid (PA) has emerged as an important class of lipid mediators involved in a wide range of cellular and physiological responses in plants, animals, and microbes. The regulatory functions of PA have been studied primarily outside the nuclei, but an increasing number of recent studies indicates that some of the PA effects result from its action in nuclei. PA levels in nuclei are dynamic in response to stimuli. Changes in nuclear PA levels can result from activities of enzymes associated with nuclei and/or from movements of PA generated extranuclearly. PA has also been found to interact with proteins involved in nuclear functions, such as transcription factors and proteins undergoing nuclear translocation in response to stimuli. The nuclear action of PA affects various aspects of plant growth, development, and response to stress and environmental changes.