Dysregulated dendritic cells in sepsis: functional impairment and regulated cell death.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Studies have indicated that immune dysfunction plays a central role in the pathogenesis of sepsis. Dendritic cells (DCs) play a crucial role in the emergence of immune dysfunction in sepsis. The major manifestations of DCs in the septic state are abnormal functions and depletion in numbers, which are linked to higher mortality and vulnerability to secondary infections in sepsis. Apoptosis is the most widely studied pathway of number reduction in DCs. In the past few years, there has been a surge in studies focusing on regulated cell death (RCD). This emerging field encompasses various forms of cell death, such as necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death (ADCD). Regulation of DC's RCD can serve as a possible therapeutic focus for the treatment of sepsis. Throughout time, numerous tactics have been devised and effectively implemented to improve abnormal immune response during sepsis progression, including modifying the functions of DCs and inhibiting DC cell death. In this review, we provide an overview of the functional impairment and RCD of DCs in septic states. Also, we highlight recent advances in targeting DCs to regulate host immune response following septic challenge.

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.

Interleukin-33/serum stimulation-2 pathway: Regulatory mechanisms and emerging implications in immune and inflammatory diseases.

Interleukin (IL)- 33, a nuclear factor and pleiotropic cytokine of the IL-1 family, is gaining attention owing to its important role in chronic inflammatory and autoimmune diseases. This review extends our knowledge of the effects exerted by IL-33 on target cells by binding to its specific receptor serum stimulation-2 (ST2). Depending on the tissue context, IL-33 performs multiple functions encompassing host defence, immune response, initiation and amplification of inflammation, tissue repair, and homeostasis. The levels and activity of IL-33 in the body are controlled by complex IL-33-targeting regulatory pathways. The unique temporal and spatial expression patterns of IL-33 are associated with host homeostasis and the development of immune and inflammatory disorders. Therefore, understanding the origin, function, and processes of IL-33 under various conditions is crucial. This review summarises the regulatory mechanisms underlying the IL-33/ST2 signalling axis and its potential role and clinical significance in immune and inflammatory diseases, and discusses the current complex and conflicting findings related to IL-33 in host responses.

The role of IL-6, IL-10, TNF-α and PD-1 expression on CD4 T cells in atrial fibrillation.

Backgrounds: While not completely understood, the electrical, structural, and communication pathways that play a role in the onset and progression of atrial fibrillation (AF) seem to be connected to the intricate interplay between neurohormones and cellular mediators. Our study's objective was to examine how the expression profiles of the inflammatory cytokines interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor (TNF), and programmed death 1 (PD-1) changed in Cluster of Differentiation 4 (CD4) T cells depending on whether atrial fibrillation was paroxysmal or permanent. This analysis would provide new diagnostic markers for the detection and management of atrial fibrillation. Methods: In a cross-sectional study, 60 healthy controls, 49 patients with persistent atrial fibrillation, and 50 patients with paroxysmal atrial fibrillation were compared. Serum biomarker levels are found using the ELISA method, which uses enzyme-linked immunosorbent assay. Echocardiography was used to assess heart function. Results: Patients with atrial fibrillation had serum concentrations of IL-6, TNF-a, and IL-10 that were considerably higher than but PD-1 was lower those in the non-AF control group and those in patients with persistent atrial fibrillation. According to the diameter of LA and the serum level of NT-proB-type natriuretic peptide (NT-proBNP) is greater than that of patients with paroxysmal atrial fibrillation than control group. Patients with persistent atrial fibrillation had increased serum levels of low-density lipoprotein cholesterol (LDL-C) compared with those without atrial fibrillation. While PD-1 in patients with paroxysmal atrial fibrillation is closely related to C-reactive protein (CRP), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and very low density lipoprotein cholesterol. In addition, PD-1 in patients with persistent atrial fibrillation is closely related to IL-6, TNF-a, and IL-10. Conclusion: Higher blood concentrations of NT-proBNP, IL-6, IL-10, TNF-, and LDL-C but low level of PD-1 are associated with progression from paroxysmal or chronic AF.

Association between aldosterone synthase (CYP11B2) -344C/T polymorphism and atrial fibrillation among Han and Kazak residents of the Xinjiang region.

OBJECTIVES: Atrial fibrillation (AF) is one the most common and complex types of clinical arrhythmia syndromes. In recent years, an association between CYP11B2 gene polymorphisms and atrial myocardial fibrosis has received a significant amount of attention. This study explores the relationship between CYP11B2 gene-344C/T polymorphism and AF among Kazak and Han residents in the Xinjiang region and further clarifies the molecular mechanisms of atrial fibrillation. METHODS: The study is a case-control study using traditional methods. We selected 156 Kazak and 203 Han patient cases in the Xinjiang region who had non-valvular atrial fibrillation as well as 307 Kazak and 418 Han cases of non-AF patients as a control group. Blood samples were collected, and DNA was extracted from the peripheral blood samples. The presence of the CYP11B2 gene-344C/T polymorphism was determined using polymerase chain reaction-restriction enzyme fragment length polymorphism (PCR-RFLP). Differences in the genotypes and allele distributions among the 2 groups were compared using Statistical Package for Social Science (SPSS) 17.0 statistical software. Student's t test, the chi-squared test and logistic regression methods were used for the data analysis. RESULTS: The genotypes of both ethnic groups followed a Hardy-Weinberg genetic equilibrium distribution. The 2 patient groups, compared with their respective control groups, showed significant dominant models in CYP11B2 gene-344C/T polymorphism genotype frequency and B1 allele frequency (P<0.05). The frequencies of the CYP11B2 gene-344C/T polymorphism in the Kazak patient group were higher compared with the control groups (P<0.05). The frequencies of the CYP11B2 gene-344C/T polymorphisms in the Han patient group was also higher compared with the control group (P<0.05). Logistic regression analysis showed that the frequencies of the CYP11B2 gene-344C/T genotypes were significantly different between the Kazak and Han patient groups and the control groups. CONCLUSION: CYP11B2 gene -344C/T polymorphism is associated with AF.

Analysis of the risk factors and characteristics of coronary artery disease of Han, Uygur and Kazak patients with acute myocardial infarction in Xinjiang district.

To discuss the risk factors and characteristics of coronary artery disease of Han, Uygur and Kazak patients with acute myocardial infarction in Xinjiang district. A retrospective analysis of clinical data of 262 cases of Han patients, 166 cases of Uygur patients and 86 cases of Kazak patients was conducted, whose age, body mass index, cholesterol, uric acid, hypertension, type 2 diabetes, smoking, drinking, family history of coronary heart disease, relationship between PCI history and pathogenesis of acute myocardial infarction, and coronary artery disease characteristics were observed and compared in different groups. Between the Han and minority young patients, there were statistically significant differences in the distribution of BMI, lipoprotein a, positive family history of coronary heart disease, uric acid level, the combined aspects of smoking history (P<0.017); there were also statistically significant differences in BMI, TG, HDL-C, apolipoprotein B, positive family history of coronary heart disease distribution between minority young patients and older patients (P<0.017). There were statistically significant differences in the distribution of BMI, TC, HDL-C, LDL-C, apolipoprotein AI, positive family history of coronary heart disease between Han and Uygur patients (P<0.017). Han and Kazak patients had statistically significant differences in the distribution of BMI, TC, LDL-C, apolipoprotein B, lipoprotein a, type 2 diabetes and hypertension (P<0.017). Comparison of patients in Uygur and Kazak showed that there were statistically significant differences in the distribution of BMI, TC, LDL-C, apolipoprotein AI, apolipoprotein B and type 2 diabetes between the two groups (P<0.017). The proportion of zero lesions and single-vessel lesions in minority youth patients was higher than that of elderly patients (P<0.001), and the proportion of two and three lesions was less than that of elderly patients (P<0.001). Gensini score of Han patients was greater than that of Uygur patients (P<0.001) and the Kazak patients (P=0.005); The proportion of Han patients with single-vessel disease was less than that of Kazak patients (P=0.003), and the proportion of patients with double-vessel disease was greater than that of Kazak patients (P=0.007). There were ethnic differences in risk factors and the characteristics of coronary artery disease of AMI patients in Xinjiang district; there were differences between minority youth patients and elderly patients, young patients of Han.

Association of GGCX gene polymorphism with warfarin dose in atrial fibrillation population in Xinjiang.

OBJECTIVE: To study the effects of γ-glutamyl carboxylase (GGCX) rs2592551 polymorphism on warfarin dose in atrial fibrillation patients in Xinjiang region. METHODS: Polymerase chain reaction - restriction fragment length polymorphism and direct sequencing methods were used to detect the rs2592551 genotype in 269 atrial fibrillation patients with warfarin administration. The effects of different genotypes on warfarin dose were statistically analyzed. RESULTS: The rs2592551 polymorphism detection results were 136 cases of wild-type homozygous CC genotype (50.56%), 115 cases of heterozygous CT genotype (42.75%), 18 cases of homozygous TT genotype (6.69%). The allele frequency C was 71.93%, T was 28.07%. The stable warfarin dose average was 2.86 ± 0.61 mg/d in patients with CC genotype, 3.59 ± 0.93 mg/d in patients with CT genotype and 4.06 ± 0.88 mg/d in patients with TT genotype. The warfarin dose in different genotypes were compared, there was statistically significant difference between CC and TT, CC and CT (P <0. 05), but the TT and CT showed no significant difference (P > 0.05). CONCLUSION: In atrial fibrillation population in Xinjiang, patients with CT and TT genotypes in GGCX gene rs259251 loci required for significantly higher warfarin dose than those with CC genotype. Therefore, rs2592551 polymorphism may one of the factors affecting the warfarin dose in patients with atrial fibrillation.

TGF-ß1 signal pathway in the regulation of inflammation in patients with atrial fibrillation.

OBJECTIVE: To observe the expression changes of inflammatory markers TGF-ß1, Smad3 and IL-6 in patients with atrial fibrillation (AF), and to explore the significance of TGF-ß1 signaling pathway in the structural remodeling of AF. METHODS: The expression of TGF-ß1, Smad3 and IL-6 in 50 cases with AF and 30 normal cases were detected by RT-PCR and ELISA. RESULTS: The TGF-ß1, Smad3 and IL-6 mRNA and protein expression levels in patients with AF were significantly higher than that in the control group (P<0.05), but there was no significantly different between the paroxysmal AF group and the persistent AF group (P>0.05). The TGF-ß1mRNA expression in the ⩾ 50 years subgroup was significantly higher than that in the <50 years subgroups, and it was higher in the NYHA III subgroup than in the I/II grade subgroup. It was also higher in the left ventricular ejection fraction (LVEF) <50% subgroup than in LVEF ⩾ 50% group, and it was significantly higher in the AF time ⩾ 36 months subgroup than that in <36 months subgroup (P<0.05). The Smad3 and IL-6 expressions in the in the LVEF <50% subgroup were both high that than that in LVEF ⩾ 50% group, and higher in the AF time ⩾ 36 months subgroup than that in <36 months subgroup (P<0.05). There were a positive correlation between TGF-ß1, Smad3 and IL-6 (r=0.687, r=0.547). There were also a positive correlation between Smad3 and IL-6 mRNA (r=0.823). CONCLUSIONS: AF is associated with inflammation, and the inflammation is also involved in the fibrillation and sustain of AF. The TGF-ß1 signal pathway may be involved in the process of atrial structural remodeling in patients with AF, and iss related with the occurrence and maintenance of AF.

[The prevalence and distributing feature of atrial fibrillation in Xinjiang Uygur Autonomous Region Kazaks adult population].

OBJECTIVE: To investigate the prevalence and distributing feature of atrial fibrillation (AF) in Xinjiang Kazaks adult population. METHODS: Four-stage selected random samples aged 30-89 years from Tacheng, Yili and Aletai were analyzed. An epidemical study of AF was performed including inquiring medical history, recording electrocardiogram and auscultation. RESULTS: A total of 22 514 adults were surveyed. The prevalence of AF in Xinjiang Kazaks adult population was 0.37%, which was increasing with aging. The prevalence was higher in men than in women (0.5% vs 0.2%, P < 0.01). In AF patients, 23 was valvular AF. Ischemic stroke was the most frequent type and the stroke rate in the patients with AF was significantly higher than that without AF (6.0% vs 1.2%, P < 0.01). CONCLUSIONS: The prevalence of AF in Xinjiang Kazaks adult population is lower than the reported national prevalence but patients with AF in this population would not like to take the necessary medicine. Therefore, the control of AF need to be reinforced.

[Viable myocardium detecting by CARTO voltage mapping in swine model of acute myocardial infarction].

OBJECTIVE: To evaluate the accuracy and practicability of detecting viable myocardium by CARTO voltage mapping in swine model of acute myocardial infarction (MI). METHODS: MI was induced in 13 anesthetized swines via occluding the distal of left anterior descending coronary arteries by angioplasty balloon for 60-90 minutes. The viable myocardium detection by CARTO voltage mapping was made after reconstruction of the left ventricle using CARTO and the results were compared with TTC staining. The standard of CARTO voltage to detect viable myocardium was 0.5 - 1.5 mV while viable myocardium showed pink color by TTC staining. RESULTS: Eleven out of 13 swines survived the operation and 2 swines died of ventricular fibrillation at 45 and 65 minutes post ischemia. Left ventricle was divided into 16 segments and 176 segments from 11 swines were analyzed. Viable myocardium detected by CARTO voltage mapping was identical as identified by TTC staining (Kappa = 0.816, P < 0.001). Taken the TTC result as standard, the sensitivity, specificity and accuracy rate of CARTO voltage mapping are 71.8%, 96.5% and 90.9% respectively. CONCLUSION: CARTO voltage mapping could be used as a reliable tool to detect viable myocardium in this model.

[Electrocardiogram Minnesota codings from 30 000 adult cases with Kazakh ethnicity in Xinjiang, China].

OBJECTIVE: To observe the abnormal Minnesota code (MC) distribution and interrelated characteristic on electrocardiograms (ECGs) of the adult Kazakh population. METHODS: Resting ECGs and blood press of randomly sampled 30 000 adult Kazakh people in three Northern regions of Xinjiang were continuously examined and analyzed, using Minnesota code recommended by WHO as the classification of ECG. RESULTS: The overall rate of abnormal ECG findings was 248.60 per thousand, and the main abnormality in males was 146.83 per thousand, compared to 157.71 per thousand in females. The prevalence rates of abnormal ST-T changes, the total arrhythmia and atrial fibrillation (AF) were 100.03 per thousand, 71.17 per thousand and 2.83 per thousand respectively. There were statistically significant differences among the main abnormities from the three regions. CONCLUSION: The ECGs abnormalities of adult Kazakh people were high. There was significant relation found between the main abnormalities and hypertension. The prevalence of AF was different from the domestically reported literature that calls for further study.