Guillain-Barré syndrome (GBS) is an autoimmune-mediated acute polyradiculoneuropathy. Its key feature is focal segmental demyelination along with inflammatory cell infiltration and axonal damage. In clinical practice, anti-ganglioside antibodies in the body fluid of GBS patients show heterogeneity, and conventional immunotherapy is ineffective in some GBS subtypes. Drawing on treatment options for other neuroimmune diseases, targeted regulation of antibody-complement system has now become an important direction in GBS treatment research. This paper examines the immune response mechanisms involving complement, antibodies and related inflammatory factors, explores new strategy in GBS immunotherapy, so as to provide theoretical basis and research entry points for GBS individualized treatment.

The circadian clock is a highly conserved timekeeping system in organisms, which maintains physiological homeostasis by precisely regulating periodic fluctuations in gene expression. Substantial clinical and experimental evidence has established a close association between circadian rhythm disruption and the development of various malignancies. Research has revealed characteristic alterations in the circadian gene expression profiles in tumor tissues, primarily manifested as a dysfunction of core clock components (particularly circadian locomotor output cycles kaput (CLOCK) and brain and muscle ARNT-like 1 (BMAL1)) and the widespread dysregulation of their downstream target genes. Notably, CLOCK demonstrates non-canonical oncogenic functions, including epigenetic regulation via histone acetyltransferase activity and the circadian-independent modulation of cancer pathways. This review systematically elaborates on the oncogenic mechanisms mediated by CLOCK/BMAL1, encompassing multidimensional effects such as cell cycle control, DNA damage response, metabolic reprogramming, and tumor microenvironment (TME) remodeling. Regarding the therapeutic strategies, we focus on cutting-edge approaches such as chrononutritional interventions, chronopharmacological modulation, and treatment regimen optimization, along with a discussion of future perspectives. The research breakthroughs highlighted in this work not only deepen our understanding of the crucial role of circadian regulation in cancer biology but also provide novel insights for the development of chronotherapeutic oncology, particularly through targeting the non-canonical functions of circadian proteins to develop innovative anti-cancer strategies.
Humans ; ARNTL Transcription Factors/physiology* ; Neoplasms/therapy* ; CLOCK Proteins/physiology* ; Circadian Clocks/genetics* ; Animals ; Circadian Rhythm/genetics* ; Tumor Microenvironment ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic

Guillain-Barré syndrome (GBS) is an autoimmune-mediated acute polyradiculoneuropathy. Its key feature is focal segmental demyelination along with inflammatory cell infiltration and axonal damage. In clinical practice, anti-ganglioside antibodies in the body fluid of GBS patients show heterogeneity, and conventional immunotherapy is ineffective in some GBS subtypes. Drawing on treatment options for other neuroimmune diseases, targeted regulation of antibody-complement system has now become an important direction in GBS treatment research. This paper examines the immune response mechanisms involving complement, antibodies and related inflammatory factors, explores new strategy in GBS immunotherapy, so as to provide theoretical basis and research entry points for GBS individualized treatment.

Objective:To investigate the clinicopathological and molecular genetic characteristics of Crohn′s disease (CD).Methods:A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes.Results:Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium.Conclusions:CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.

Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.
Animals ; Mice ; Dark Adaptation ; Light ; Retina ; Retinal Cone Photoreceptor Cells/metabolism* ; Adaptation, Ocular ; Neuroglia/physiology* ; Cell Communication ; Thyroid Hormones

OBJECTIVETo analyze clinical characteristics, genetic mutation and therapeutic effect of seven patients diagnosed with congenital hyperinsulinism(CHI).

METHODSClinical data for the patients was retrospectively analyzed.

RESULTSAll patients presented with hyperinsulinism(serum insulin:2.0-58.4 mU/L),even after hypoglycemia (blood glucose: 0.7-2.39 mmol/L) has developed. Mutations were identified in 4 patients (57.1%), which included a heterozygous c.262C to T(p.R88C) mutation in exon 4 of the UCP2 gene, a heterozygous c.1495C to A(p.G499C) mutation in exon 12 of the GLUD1 gene, a heterozygous c.1493C to T(p.S498L) mutation in exon 1 of the GLUD1 gene, and a heterozygous c.4432G to A(p.G1478R) mutation in exon 37 of the ABCC8 gene. The patient carrying a maternally inherited ABCC8 mutation was treated with cornstarch and had his blood glucose kept normal. All other patients responded well to diazoxide.

CONCLUSIONA genetic diagnosis was attained for 51.7% of patients in this study. Mild CHI patients can have their blood glucose controlled by giving cornstarch. Diazoxide is safe and effective for most CHI patients.

AIM To evaluate the prevention and treatment of N-(2-mercaptopropionyl)-glycine sodium (MPG-Na) and tiopronin (MPG) on acute liver injury. METHODS The experimental mouse model of hepatotoxicity induced by D-galactosamine (Gal) was applied to investigate preventive and remedial effects. In the preventive experiment, the mice were ip administered with MPG-Na or MPG 37.5，75 and 150 mg·kg~(-1), respectively, for 7 d. Gal 800 mg·kg~(-1) was ip given into the mice 30 min after the last administration. In the remedial experiment, the mice were ip given Gal 800 mg·kg~(-1) and 30 min later followed by MPG-Na or MPG 37.5, 75 and 150 mg·kg~(-1) , respectively, for 2 d. The mice were euthanized and serum was prepared 24 h (pre-treatment) or 48 h (post-treatment) after Gal injection. The activities of serum glutamyl pyruvic transaminase (GPT) and glutamyl oxaloacetic transaminase (GOT), the contents of total protein (TP) and albumin (Alb), and the Alb/globulin (A/G) ratio were determined. The liver tissues were collected for histopathological assessment (HE staining) under light microscope. RESULTS Compared with normal control group, the activities of serum GPT and GOT in model group were significantly increased. The injuries such as fatty degeneration and liver cell necrosis were observed. Compared with model group, the activities of GPT and GOT in pre-treatment groups were obviously decreased in MPG-Na 150 mg·kg~(-1) group. In post-treatment groups, the activity of GPT decreased in 3 MPG-Na groups. The contents of TP, Alb and A/G ratio had little change. In addition, MPG-Na alleviated the injuries such as fatty degeneration and liver cell necrosis obviously. Compared with MPG, MPG-Na showed similar effect. CONCLUSION MPG-Na has an obvious protective effect against Gal-induced acute liver injury in mice and the efficiency is equivalent as MPG.