Progressive white matter degeneration in patients with spinocerebellar ataxia type 2.

PURPOSE: Spinocerebellar ataxia type 2 (SCA2) is a progressive neurodegenerative disorder characterized by cerebellar atrophy. However, studies to elucidate the longitudinal progression of the neuropathology are limited. We sought to identify brain macrostructural and microstructural alterations in patients with SCA2 using fixel-based analysis (FBA) to better understand its distribution patterns and progression. METHODS: We enrolled 9 patients with SCA2 and 16 age- and gender-matched controls. Longitudinal clinical and imaging data were collected at baseline, and 3.5 years later. Fiber density (FD), fiber-bundle cross-section (FC), and a combination of FD and FC (FDC) were calculated. The paired t-test was used to examine longitudinal differences. The associations between fixel-based metrics and clinical variables were explored in SCA2 patients. RESULTS: At baseline, patients with SCA2 displayed multiple white matter tracts with significantly decreased FD, FC, and FDC in the corticospinal tract, cerebellar peduncles, brainstem, corpus callosum, thalamus, striatum, and prefrontal cortex, compared to controls. Over time, many of these macrostructural and microstructural alterations progressed, manifesting lower FD, FC, and FDC in corticospinal tract, middle cerebellar peduncle, brainstem, striatum, fornix, and cingulum. No significant brain white matter alterations were found in the healthy controls over time. There was no association between the FBA-derived metrics and clinical variables in SCA2. CONCLUSION: This study provides evidence of brain macrostructural and microstructural alterations and of progression over time in SCA2. The FBA-derived metrics may serve as potential biomarkers of SCA2 progression.

Cortical changes in the brain of patients with hemifacial spasm.

OBJECTIVE: Hemifacial spasm (HFS) is a movement disorder characterized by involuntary muscle contractions on one side of the face. It is associated with disturbances in the brain's functional architecture. Despite this, the structural alterations in the brain related to HFS remain poorly understood. In this study, we investigated the cortical morphology changes in patients with HFS compared to healthy controls (HCs). METHODS: We analyzed 3D T1-weighted MRI images from 33 patients with left-sided primary HFS and 33 age- and sex-matched HCs. Measurements of cortical thickness (CTh), sulcal depth, local gyrification index (lGI), and fractal dimension were taken using a computational anatomy toolbox. A general linear model, accounting for age, gender, and total brain volume, was applied for statistical analyses. Significant clusters were then assessed for correlations with clinical parameters. RESULTS: The HFS patients displayed several cortical abnormalities when compared to HCs, including reduced CTh in the contralateral precentral gyrus and left orbitofrontal cortex, decreased sulcal depth in the left orbitofrontal cortex, and increased lGI in the right insula and superior temporal cortex. However, fractal dimension did not differ significantly between the groups. Additionally, in HFS patients, a notable negative correlation was found between the sulcal depth in the left orbitofrontal cortex and the Beck Depression Inventory-II scores. CONCLUSIONS: Our findings reveal that HFS is associated with specific surface-based morphological changes in the brain. These alterations contribute to a deeper understanding of the neurophysiological mechanisms involved in HFS and may have implications for future research and treatment strategies.

Clinical characterization of EFHD2 (swiprosin-1) in Glioma-associated macrophages and its role in regulation of immunosuppression.

Glioblastoma has been extensively studied due to its high mortality and short survival. The evolution mechanism of tumor-associated macrophages (TAMs) to Glioma-associated microglia and macrophages (GAMs) in the tumor microenvironment (TME) remains to be elucidated. The tumor cell-to-cell interaction patterns have not been well defined yet. The EF-Hand Domain Family Member D2 (EFHD2) has been reported to be differentially expressed as an immunomodulatory molecule in a variety of cancers. But large-scale clinical data from multiple ethnic communities have not been used to investigate the role of EFHD2 in glioma. RNA-seq data from 313 or 657 glioma patients from the Chinese Glioma Genome Atlas (CGGA) database and 603 glioma patients from the Cancer Genome Atlas (TCGA) database were analyzed retrospectively. Cell localization was performed using single-cell sequencing data from the CGGA database and the GSE131928 dataset. Mouse glioma cell lines and primary macrophages isolated from Efhd2 knockout mice were co-cultured to validate the immunomodulatory effects of EFHD2 on macrophages and the remodeling of TME of glioblastoma. EFHD2 is enriched in high-grade gliomas, isocitrate dehydrogenase wild-type, and 1p/19q non-co-deficient gliomas. It is a potential biomarker of glioma-proneuronal subtypes and an independent prognostic factor for overall survival in patients with malignant glioblastoma. EFHD2 regulates the monocyte-macrophage system function and positively correlates with immunosuppressive checkpoints. Further experimental data demonstrates that Efhd2 influences the polarization state of GAMs and inhibits the secretion of TGF-ß1. In vitro experiments have revealed that macrophages lacking Efhd2 suppress the vitality of two glioma cell lines and decelerate the growth of glioma xenografts. In conclusion, EFHD2 promises to be a key target for TME-related immunotherapy.

Decreased DTI-ALPS and choroid plexus enlargement in fibromyalgia: a preliminary multimodal MRI study.

PURPOSE: The glymphatic system is a fluid exchange pathway that clears waste products that is crucial for the maintenance of brain homeostasis. However, the exact role it plays in the emergence of fibromyalgia (FM) is still not fully understood. Here, we explored the changes in non-invasive MRI proxy probably related to the glymphatic function in FM patients, and explored brain-behavior relationships. METHODS: A total of 40 participants, consisting of 20 individuals with FM and 20 healthy controls (HCs), were included in the study. The participants underwent structural T1-weighted MRI, diffusion tensor imaging (DTI), and clinical assessment. The data was obtained from an open access dataset. The study compared non-invasive MRI indices, including choroid plexus (CP) volume and DTI analysis along the perivascular space (ALPS), between the FM and HC groups. Furthermore, correlation analysis was conducted to determine the correlation between clinical parameters and both CP volume and DTI-ALPS index. RESULTS: Patients with FM had significantly higher CP volume and a lower DTI-ALPS index than HCs adjusting for age and intracranial volume. Higher CP volume was associated with lower DTI-ALPS index, and longer disease duration. CONCLUSION: Our findings demonstrate aberrant glymphatic function in FM, and that dysfunction in the brain glymphatic system may play a role in the neural mechanisms underlying FM.

Topological alterations in white matter structural networks in fibromyalgia.

PURPOSE: Neuroimaging studies employing analyses dependent on regional assumptions and specific neuronal circuits could miss characteristics of whole-brain structural connectivity critical to the pathophysiology of fibromyalgia (FM). This study applied the whole-brain graph-theoretical approach to identify whole-brain structural connectivity disturbances in FM. METHODS: This cross-sectional study used probabilistic diffusion tractography and graph theory analysis to evaluate the topological organization of brain white matter networks in 20 patients with FM and 20 healthy controls (HCs). The relationship between brain network metrics and clinical variables was evaluated. RESULTS: Compared with HCs, FM patients had lower clustering coefficient, local efficiency, hierarchy, synchronization, and higher normalized characteristic path length. Regionally, patients demonstrated a significant reduction in nodal efficiency and centrality; these regions were mainly located in the prefrontal, temporal cortex, and basal ganglia. The network-based statistical analysis (NBS) identified decreased structural connectivity in a subnetwork of prefrontal cortex, basal ganglia, and thalamus in FM. There was no correlation between network metrics and clinical variables (false discovery rate corrected). CONCLUSIONS: The current research demonstrated disrupted topological architecture of white matter networks in FM. Our results suggested compromised neural integration and segregation and reduced structural connectivity in FM.

Cortical Abnormalities in Patients with Fibromyalgia: A Pilot Study of Surface-Based Morphometry Analysis.

BACKGROUND: Although neuroanatomical studies correlated to fibromyalgia (FM) are gaining increasing interest, the cortical morphology of patients are largely unknown, and data on cortical gyrification are scarce. The objective of the present study is to assess the cortical morphology in female patients with FM compared with healthy controls (HC) using surface-based morphometry (SBM) analysis of magnetic resonance imaging (MRI). METHODS: T1-MRIs and clinical data of 20 FM patients and 20 HC subjects were obtained from a public data set via OpenNeuro. For each subject, surface parameters including cortical thickness, local gyrification index (LGI), sulcal depth, and fractal dimensionality were estimated using SBM analysis. These data were compared between two groups controlled by age. The correlations between regional SBM parameters showing group differences and clinical profiles were analyzed. RESULTS: Compared with HC subjects, FM patients showed reduced cortical thickness in right primary motor cortex, lower LGI in right rostral anterior cingulate and higher sulcal depth in right precuneus (P < 0.05 cluster level family- wise error corrected). In FM patients, correlation analysis showed that the cortical thickness in right primary motor cortex were inversely correlated with scores of pain catastrophizing scale (r = -0.498, P = 0.030) and pain self-perception scale (r = -0.527, P = 0.020), and disease duration (r = -0.488, P = 0.034), respectively. CONCLUSIONS: Our findings provide evidence of neuroanatomical aberrations in FM patients, which may provide insight into the neuropathology of FM.

[Development and Influencing Factors of Oral Microbiota in Early Life].

Oral cavity, an important component of and the gateway to the digestive system, is also the colonization site and the microecological environment of trillions of microorganisms. The establishment and succession of oral microbiota are of great importance for the development of human immune system, and function as a major determinant of oral and systemic health. Within a few hours after birth, early colonizers such as Streptococcus and Lactobacillus can be detected in an infant's mouth. The oral microbiota communities mature gradually along with the growth of the host, expanding in their species abundance and diversity. In addition to genetic factors, a number of cross-sectional studies have revealed that the development of oral microecosystems in early life is influenced and tuned by multiple external factors, including maternal health status, mode of delivery, feeding habits, antibiotics use, etc. The dysbiosis of oral microecology in early life is closely related to the pathogenesis and progression of oral and systemic diseases. Therefore, good oral hygiene habits are of vital importance to the early management of oral microbial diseases and their effective prevention and control. Herein, we summarized the colonization and succession of oral microbiota in early life and further discussed the key external factors that affect early life oral microecosystem, as well as the impact of early life oral microbiota on the host's health at a later stage, intending to help providing new insights into and new strategies for the management of the whole lifecycle oral and systemic health.

Admission fasting plasma glucose is an independent risk factor for 28-day mortality in patients with COVID-19.

Hyperglycemia commonly occurs in severe cases with COVID-19. In this study, we explored the associations between admission fasting plasma glucose (FPG) and 28-day mortality in COVID-19 patients. In this single centre retrospective study, 263 adult patients with COVID-19 were included. Demographic and clinical information were collected and compared between patients with and without diabetes. Cox regression analyses were used to investigate the risk factors of 28-day mortality in hospitals. Of 263 patients, 161 (61.2%) were male, 62 (25.6%) had a known history of diabetes, and 135 (51.3%) experienced elevated FPG (>7.0 mmol/L) at hospital admission. The median FPG in patients with diabetes was much higher than in patients without diabetes (12.79 vs. 6.47 mmol/L). Patients with diabetes had higher neutrophil count and D-dimer, less lymphocyte count, lower albumin level, and more fatal complications. Multivariable Cox regression analyses showed that age (per 10-year increase) (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.13-1.74), admission FPG between 7.0 and 11.0 and ≥11.1 mmol/L (HR, 1.90; 95% CI, 1.11-3.25 and HR, 2.09; 95% CI, 1.21-3.64, respectively), chronic obstructive pulmonary disease (HR, 2.89; 95% CI, 1.31-6.39), and cardiac injury (HR, 2.14; 95% CI, 1.33-3.47) were independent predictors of 28-day mortality in COVID-19 patients. Hyperglycemia on admission predicted worse outcome in hospitalized patients with COVID-19. Intensive monitoring and optimal glycemic control may improve the prognosis of COVID-19 patients.

Risk factors for mortality of critically ill patients with COVID-19 receiving invasive ventilation.

Rationale: Early invasive ventilation may improve outcomes for critically ill patients with COVID-19. The objective of this study is to explore risk factors for 28-day mortality of COVID-19 patients receiving invasive ventilation. Methods: 74 consecutive adult invasively ventilated COVID-19 patients were included in this retrospective study. The demographic and clinical data were compared between survivors and non-survivors, and Cox regression analysis was used to explore risk factors for 28-day mortality. The primary outcome was 28-day mortality after initiation of invasive ventilation. Secondary outcome was the time from admission to intubation. Results: Of 74 patients with COVID-19, the median age was 68.0 years, 53 (71.6%) were male, 47 (63.5%) had comorbidities with hypertension, and diabetes commonly presented. The most frequent symptoms were fever and dyspnea. The median time from hospital admission to intubation was similar in survivors and non-survivors (6.5 days vs. 5.0 days). The 28-day mortality was 81.1%. High Sequential Organ Failure Assessment (SOFA) score (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.23-1.92; p < 0.001) and longer time from hospital admission to intubation (HR, 2.41; 95% CI, 1.15-5.07; p = 0.020) were associated with 28-day mortality in invasively ventilated COVID-19 patients. Conclusions: The mortality of invasively ventilated COVID-19 patients was particularly striking. Patients with high SOFA score and receiving delayed invasive ventilation were at high risk of mortality.

Genetic Regulation of Streptococci by Small RNAs.

Streptococcal species constitute a large group of commensal and pathogenic Gram-positive bacteria that exist in a wide variety of habitats. The family of small RNAs is typically ranged in size from 50 to 300 nucleotides, and acts as regulators in bacteria. The last decade has witnessed the increasing findings of small RNAs (sRNAs), which play important regulatory roles in the variety of biological processes in streptococci. In this review, we summarized the recent achievements in the identification of streptococcal sRNAs, mainly in Streptococcus pyogenes and Streptococcus pneumoniae. In addition, we particularly focused on the functions that sRNAs exert in the regulatory networks of both phenotypical traits and pathogenicity. The fact that sRNAs act as a critical fine-tuning regulator of streptococci may not only reveal in-depth mechanisms of bacterial post-transcriptional regulations in response to environmental perturbance, but also provide promising approaches to the better management of streptococcal infections.

LY333531, a PKCß inhibitor, attenuates glomerular endothelial cell apoptosis in the early stage of mouse diabetic nephropathy via down-regulating swiprosin-1.

Glomerular endothelial cell (GEC) injury plays an important role in the early stage of diabetic nephropathy (DN). Previous studies show that a PKCß inhibitor is effective for treating DN. In the current study we further explored the effects and molecular mechanisms of PKCß inhibitors on GEC apoptosis in DN in streptozotocin-induced diabetic mice in vivo and high glucose- or PMA-treated human renal glomerular endothelial cells (HRGECs) in vitro. In the diabetic mice, hyperglycemia caused aggravated nephropathy and GEC apoptosis accompanied by significantly increased expression of swiprosin-1, a potentally pro-apoptotic protein. Administration of LY333531 (1 mg·kg-1·d-1 for 8 weeks) significantly attenuated both GEC apoptosis and swiprosin-1 upregulation in the diabetic mice. Similar results were observed in high glucose- or PMA-treated HRGECs in vitro. The pro-apoptotic role of swiprosin-1 was further examined using HRGECs treated with lentivirus mediating RNA interference or over-expression and swiprosin-1-knockout mice. Over-expression of swiprosin-1 in HRGECs resulted in increases in apoptosis and in caspase-9, caspase-3 and Bax expression. In contrast, knockdown of swiprosin-1 attenuated high glucose- or PMA-induced HRGECs apoptosis. Furthermore, over-expression of swiprosin-1 promoted interaction between swiprosin-1 and caspase-9 and increased the formation of apoptosomes. In diabetic swiprosin-1-/- mice, the kidney/body weight, urinary albumin, glomerular hypertrophy, mitochondrial apoptotic-associated proteins and GEC apoptosis were significantly attenuated as compared with those in diabetic swiprosin-1+/+ mice. These results demonstrate that swiprosin-1 is up-regulated by PKCß in the early stage of DN, and that PKCß facilitates GEC apoptosis through the mitochondrial-dependent pathway.

Unraveling the Intricate Web: Complement Activation Shapes the Pathogenesis of Sepsis-Induced Coagulopathy.

BACKGROUND: Sepsis-associated coagulopathy specifically refers to widespread systemic coagulation activation accompanied by a high risk of hemorrhage and organ damage, which in severe cases manifests as disseminated intravascular coagulation (DIC), or even develops into multiple organ dysfunction syndrome (MODS). The complement system and the coagulation system as the main columns of innate immunity and hemostasis, respectively, undergo substantial activation after sepsis. SUMMARY: Dysfunction of the complement, coagulation/fibrinolytic cascades caused by sepsis leads to "thromboinflammation," which ultimately amplifies the systemic inflammatory response and accelerates the development of MODS. Recent studies have revealed that massive activation of the complement system exacerbates sepsis-induced coagulation and even results in DIC, which suggests that inhibition of complement activation may have therapeutic potential in the treatment of septic coagulopathy. KEY MESSAGES: Sepsis-associated thrombosis involves the upregulation or activation of procoagulant factors, down-regulation or inactivation of anticoagulant factors, and impairment of the fibrinolytic mechanism. This review aims to summarize the latest literature and analyze the underlying molecular mechanisms of the activation of the complement system on the abnormal coagulation cascades in sepsis.

Glymphatic System Dysfunction Underlying Schizophrenia Is Associated With Cognitive Impairment.

BACKGROUND AND HYPOTHESIS: Despite the well-documented structural and functional brain changes in schizophrenia, the potential role of glymphatic dysfunction remains largely unexplored. This study investigates the glymphatic system's function in schizophrenia, utilizing diffusion tensor imaging (DTI) to analyze water diffusion along the perivascular space (ALPS), and examines its correlation with clinical symptoms. STUDY DESIGN: A cohort consisting of 43 people with schizophrenia and 108 healthy controls was examined. We quantified water diffusion metrics along the x-, y-, and z-axis in both projection and association fibers to derive the DTI-ALPS index, a proxy for glymphatic activity. The differences in the ALPS index between groups were analyzed using a 2-way ANCOVA controlling for age and sex, while partial correlations assessed the association between the ALPS index and clinical variables. STUDY RESULTS: People with schizophrenia showed a significantly reduced DTI-ALPS index across the whole brain and within both hemispheres (F = 9.001, P = .011; F = 10.024, P = .011; F = 5.927, P = .044; false discovery rate corrected), indicating potential glymphatic dysfunction in schizophrenia. The group by cognitive performance interaction effects on the ALPS index were not observed. Moreover, a lower ALPS index was associated with poorer cognitive performance on specific neuropsychological tests in people with schizophrenia. CONCLUSION: Our study highlights a lower ALPS index in schizophrenia, correlated with more pronounced cognitive impairments. This suggests that glymphatic dysfunction may contribute to the pathophysiology of schizophrenia, offering new insights into its underlying mechanisms.

EFHD2 regulates T cell receptor signaling and modulates T helper cell activation in early sepsis.

EFHD2 (EF-hand domain family, member D2) has been identified as a calcium-binding protein with immunomodulatory effects. In this study, we characterized the phenotype of Efhd2-deficient mice in sepsis and examined the biological functions of EFHD2 in peripheral T cell activation and T helper (Th) cell differentiation. Increased levels of EFHD2 expression accompanied peripheral CD4+ T cell activation in the early stages of sepsis. Transcriptomic analysis indicated that immune response activation was impaired in Efhd2-deficient CD4+ T cells. Further, Efhd2-deficient CD4+ T cells isolated from the spleen of septic mice showed impaired T cell receptor (TCR)-induced Th differentiation, especially Th1 and Th17 differentiation. In vitro data also showed that Efhd2-deficient CD4+ T cells exhibit impaired Th1 and Th17 differentiation. In the CD4+ T cells and macrophages co-culture model for antigen presentation, the deficiency of Efhd2 in CD4+ T cells resulted in impaired formation of immunological synapses. In addition, Efhd2-deficient CD4+ T cells exhibited reduced levels of phospho-LCK and phospho-ZAP70, and downstream transcription factors including Nfat, Nfκb and Nur77 following TCR engagement. In summary, EFHD2 may promote TCR-mediated T cell activation subsequent Th1 and Th17 differentiation in the early stages of sepsis by regulating the intensity of TCR complex formation.

Microascaceae from the Marine Environment, with Descriptions of Six New Species.

Most reported members of Microascaceae that have been reported originate from the terrestrial environment, where they act as saprobes or plant pathogens. However, our understanding of their species diversity and distribution in the marine environment remains vastly limited, with only 22 species in nine genera having been reported so far. A survey of the fungal diversity in intertidal areas of China's mainland has revealed the discovery of several Microascaceae strains from 14 marine algae and 15 sediment samples. Based on morphological characteristics and LSU-ITS-tef1-tub2 multilocus phylogeny using Bayesian inference and maximum likelihood methods, 48 strains were identified as 18 species belonging to six genera. Among these, six new species were discovered: Gamsia sedimenticola, Microascus algicola, M. gennadii, Scedosporium ellipsosporium, S. shenzhenensis, and S. sphaerospermum. Additionally, the worldwide distribution of the species within this family across various marine habitats was briefly reviewed and discussed. Our study expands the knowledge of species diversity and distribution of Microascaceae in the marine environment.

The associations of gut microbiota, endocrine system and bone metabolism.

Gut microbiota is of great importance in human health, and its roles in the maintenance of skeletal homeostasis have long been recognized as the "gut-bone axis." Recent evidence has indicated intercorrelations between gut microbiota, endocrine system and bone metabolism. This review article discussed the complex interactions between gut microbiota and bone metabolism-related hormones, including sex steroids, insulin-like growth factors, 5-hydroxytryptamine, parathyroid hormone, glucagon-like peptides, peptide YY, etc. Although the underlying mechanisms still need further investigation, the regulatory effect of gut microbiota on bone health via interplaying with endocrine system may provide a new paradigm for the better management of musculoskeletal disorders.

The Dopaminergic System in the Ventral Tegmental Area Contributes to Morphine Analgesia and Tolerance.

Morphine has a strong analgesic effect and is suitable for various types of pain, so it is widely used. But long-term usage of morphine can lead to drug tolerance, which limits its clinical application. The complex mechanisms underlying the development of morphine analgesia into tolerance involve multiple nuclei in the brain. Recent studies reveal the signaling at the cellular and molecular levels as well as neural circuits contributing to morphine analgesia and tolerance in the ventral tegmental area (VTA), which is traditionally considered a critical center of opioid reward and addiction. Existing studies show that dopamine receptors and µ-opioid receptors participate in morphine tolerance through the altered activities of dopaminergic and/or non-dopaminergic neurons in the VTA. Several neural circuits related to the VTA are also involved in the regulation of morphine analgesia and the development of drug tolerance. Reviewing specific cellular and molecular targets and related neural circuits may provide novel precautionary strategies for morphine tolerance.

Efficacy and safety of selenium or vitamin E administration alone or in combination in ICU patients: A systematic review and meta-analysis.

BACKGROUND: Micronutrient administration that contributes to antioxidant defense has been extensively studied in critically ill patients, but consensus remains elusive. Selenium and vitamin E are two important micronutrients that have synergistic antioxidant effects. This meta-analysis aimed to assess the effect of selenium or vitamin E administration alone and the combination of both on clinical outcomes in patients hospitalized in the ICU. METHODS: After electronic searches on PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), SinoMed, VIP database and Wanfang data, initially 1767 papers were found, and 30 interventional studies were included in this analysis. We assessed the risk-difference between treatment and control (standard treatment) groups by pooling available data on length of stay (ICU length of stay and hospital length of stay), mortality (ICU mortality, hospital mortality, 28-day mortality, 6-month mortality and all-cause mortality), duration of mechanical ventilation, adverse events and new infections. RESULTS: By analyzing the included studies, we found no significant effect of selenium administration alone on mortality, mechanical ventilation duration, or adverse events in ICU patients. However, after excluding studies with high heterogeneity, the meta-analysis showed that selenium alone reduced the length of hospital stay (MD: -1.38; 95% CI: -2.52, -0.23; I-square: 0%). Vitamin E administration alone had no significant effect on mortality, duration of mechanical ventilation, or adverse events in ICU patients. However, after excluding studies with high heterogeneity, the meta-analysis showed that vitamin E alone could reduce the length of ICU stay (MD: -1.27; 95% CI: -1.86, -0.67; I-square: 16%). Combined administration of selenium and vitamin E had no significant effect on primary outcomes in ICU patients. CONCLUSIONS: Selenium administration alone may shorten the length of hospital stay, while vitamin E alone may reduce the length of ICU stay. The putative synergistic beneficial effect of combined administration of selenium and vitamin E in ICU patients has not been observed, but more clinical studies are pending to confirm it further.

Programmed death of intestinal epithelial cells in neonatal necrotizing enterocolitis: a mini-review.

Necrotizing enterocolitis (NEC) is one of the most fatal diseases in premature infants. Damage to the intestinal epithelial barrier (IEB) is an important event in the development of intestinal inflammation and the evolution of NEC. The intestinal epithelial monolayer formed by the tight arrangement of intestinal epithelial cells (IECs) constitutes the functional IEB between the organism and the extra-intestinal environment. Programmed death and regenerative repair of IECs are important physiological processes to maintain the integrity of IEB function in response to microbial invasion. However, excessive programmed death of IECs leads to increased intestinal permeability and IEB dysfunction. Therefore, one of the most fundamental questions in the field of NEC research is to reveal the pathological death process of IECs, which is essential to clarify the pathogenesis of NEC. This review focuses on the currently known death modes of IECs in NEC mainly including apoptosis, necroptosis, pyroptosis, ferroptosis, and abnormal autophagy. Furthermore, we elaborate on the prospect of targeting IECs death as a treatment for NEC based on exciting animal and clinical studies.

Corrigendum: Curcumin alleviates experimental colitis in mice by suppressing necroptosis of intestinal epithelial cells.

[This corrects the article DOI: 10.3389/fphar.2023.1170637.].