Organellophagy regulates cell death:A potential therapeutic target for inflammatory diseases.

BACKGROUND: Dysregulated alterations in organelle structure and function have a significant connection with cell death, as well as the occurrence and development of inflammatory diseases. Maintaining cell viability and inhibiting the release of inflammatory cytokines are essential measures to treat inflammatory diseases. Recently, many studies have showed that autophagy selectively targets dysfunctional organelles, thereby sustaining the functional stability of organelles, alleviating the release of multiple cytokines, and maintaining organismal homeostasis. Organellophagy dysfunction is critically engaged in different kinds of cell death and inflammatory diseases. AIM OF REVIEW: We summarized the current knowledge of organellophagy (e.g., mitophagy, reticulophagy, golgiphagy, lysophagy, pexophagy, nucleophagy, and ribophagy) and the underlying mechanisms by which organellophagy regulates cell death. KEY SCIENTIFIC CONCEPTS OF REVIEW: We outlined the potential role of organellophagy in the modulation of cell fate during the inflammatory response to develop an intervention strategy for the organelle quality control in inflammatory diseases.

The crosstalk between mitochondrial quality control and metal-dependent cell death.

Mitochondria are the centers of energy and material metabolism, and they also serve as the storage and dispatch hubs of metal ions. Damage to mitochondrial structure and function can cause abnormal levels and distribution of metal ions, leading to cell dysfunction and even death. For a long time, mitochondrial quality control pathways such as mitochondrial dynamics and mitophagy have been considered to inhibit metal-induced cell death. However, with the discovery of new metal-dependent cell death including ferroptosis and cuproptosis, increasing evidence shows that there is a complex relationship between mitochondrial quality control and metal-dependent cell death. This article reviews the latest research results and mechanisms of crosstalk between mitochondrial quality control and metal-dependent cell death in recent years, as well as their involvement in neurodegenerative diseases, tumors and other diseases, in order to provide new ideas for the research and treatment of related diseases.

Development of a nomogram to predict 30-day mortality of sepsis patients with gastrointestinal bleeding: An analysis of the MIMIC-IV database.

Background: We aimed to establish and validate a prognostic nomogram model for improving the prediction of 30-day mortality of gastrointestinal bleeding (GIB) in critically ill patients with severe sepsis. Methods: In this retrospective study, the current retrospective cohort study extracted data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, then partitioned the cohort randomly into training and validation subsets. The cohort was partitioned into training and validation subsets randomly. Our primary endpoint was 30-day all-cause mortality. To reduce data dimensionality and identify predictive variables, the least absolute shrinkage and selection operator (LASSO) regression was employed. A prediction model was constructed by multivariate logistic regression. Model performance was evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Results: The analysis included 1435 total patients, comprising 1005 in the training cohort and 430 in the validation cohort. We found that age, smoking status, glucose, (BUN), lactate, Sequential Organ Failure Assessment (SOFA) score, mechanical ventilation≥48h (MV), parenteral nutrition (PN), and chronic obstructive pulmonary disease (COPD) independently influenced mortality in sepsis patients with concomitant GIB. The C-indices were 0.746 (0.700-0.792) and 0.716 (0.663-0.769) in the training and validation sets, respectively. Based on the area under the curve (AUC) and DCA, the nomogram exhibited good discrimination for 30-day all-cause mortality in sepsis with GIB. Conclusions: For sepsis patients complicated with GIB, we created a unique nomogram model to predict the 30-day all-cause mortality. This model could be a significant therapeutic tool for clinicians in terms of personalized treatment and prognosis prediction.

Ferritinophagy: A novel insight into the double-edged sword in ferritinophagy-ferroptosis axis and human diseases.

Nuclear receptor coactive 4 (NCOA4), which functions as a selective cargo receptor, is a critical regulator of the particularly autophagic degradation of ferritin, a process known as ferritinophagy. Mechanistically, NCOA4-mediated ferritinophagy performs an increasingly vital role in the maintenance of intracellular iron homeostasis by promoting ferritin transport and iron release as needed. Ferritinophagy is not only involved in iron-dependent responses but also in the pathogenesis and progression of various human diseases, including metabolism-related, neurodegenerative, cardiovascular and infectious diseases. Therefore, ferritinophagy is of great importance in maintaining cell viability and function and represents a potential therapeutic target. Recent studies indicated that ferritinophagy regulates the signalling pathway associated with ferroptosis, a newly discovered type of cell death characterised by iron-dependent lipid peroxidation. Although accumulating evidence clearly demonstrates the importance of the interplay between dysfunction in iron metabolism and ferroptosis, a deeper understanding of the double-edged sword effect of ferritinophagy in ferroptosis has remained elusive. Details of the mechanisms underlying the ferritinophagy-ferroptosis axis in regulating relevant human diseases remain to be elucidated. In this review, we discuss the latest research findings regarding the mechanisms that regulate the biological function of NCOA4-mediated ferritinophagy and its contribution to the pathophysiology of ferroptosis. The important role of the ferritinophagy-ferroptosis axis in human diseases will be discussed in detail, highlighting the great potential of targeting ferritinophagy in the treatment of diseases.

Publication trends of research on sepsis and programmed cell death during 2002-2022: A 20-year bibliometric analysis.

Background: Sepsis is considered an intractable dysfunction that results from the disordered host immune response to uncontrolled infection. Even though the precise mechanism of sepsis remains unclear, scientific advances have highlighted the key role of various programmed cell death processes in the pathophysiology of sepsis. The current study aims to explore the worldwide research trend on programmed cell death in the setting of sepsis and assesses the achievements of publications from various countries, institutions, journals, and authors globally. Material and methods: Associated publications during 2002-2022 with the topical subject of sepsis and programmed cell death were extracted from the Web of Science. VOSviewer was utilized to evaluate and map the published trend in the relevant fields. Results: All 2,037 relevant manuscripts with a total citation of 71,575 times were screened out by the end of 1 January 2022. China accounted for the largest number of publications (45.07%) and was accompanied by corporate citations (11,037) and H-index (48), which ranked second globally. The United States has been ranked first place with the highest citations (30,775) and H-index (88), despite a low publication number (29.95%), which was subsequent to China. The journal Shock accounted for the largest number of publications in this area. R. S. Hotchkiss, affiliated with Washington University, was considered to have published the most papers in the relevant fields (57) and achieved the highest citation frequencies (9,523). The primary keywords on the topic of programmed cell death in sepsis remarkably focused on "inflammation" "immunosuppression", and "oxidative stress", which were recognized as the core mechanisms of sepsis, eventually attributing to programmed cell death. The involved research on programmed cell death induced by immune dysregulation of sepsis was undoubtedly the hotspot in the pertinent areas. Conclusions: The United States has been academically outstanding in sepsis-related research. There appears to be an incompatible performance between publications and quantity with China. Frontier advances may be consulted in the journal Shock. The leading-edge research on the scope of programmed cell death in sepsis should preferably focus on immune dissonance-related studies in the future.

Geminal cross-coupling synthesis, ion-induced emission and lysosome imaging of cationic tetraarylethene oligoelectrolytes.

Neutral conjugated tetraarylethenes OFn (n = 1-3) and the corresponding cationic conjugated oligoelectrolytes OFn+ (n = 1-3) with aggregation-induced emission activity have been designed and synthesized using geminal cross-coupling. OFn+ (n = 1-3) feature ion-induced emission in aqueous solution. They are used for lysosomal fluorescence imaging and tracing of lysosome events.