Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

Enhancing predictive accuracy in hypertriglyceridemia-induced acute pancreatitis:Role of red cell distribution width and prospective studies

This letter addresses the study titled“Red cell distribution width:A predictor of the severity of hypertriglyceridemia-induced acute pancreatitis”by Lv et al published in the World Journal of Experimental Medicine.The study offers a valuable analysis of red cell distribution width(RDW)as a predictive marker for persistent organ failure in patients with hypertriglyceridemia-induced acute pancreatitis.The study results suggest that RDW,combined with the Bedside Index for Severity in Acute Pancreatitis score,could enhance the predictive accuracy for severe outcomes.Further investigation into the role of RDW in different severities of acute pancreatitis is recommended.Additionally,the need for large-scale and multicenter prospective studies to validate these findings is emphasized.

Red cell distribution width/platelet ratio estimates the 3-year risk of decompensation in Metabolic Dysfunction-Associated Steatotic Liver Disease-induced cirrhosis

BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),respectively.Clinically Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these patients.However,due to its invasiveness and costs,CSPH is almost never evaluated in clinical practice.Therefore,recognizing noninvasively predicting tools still have more appeal across healthcare systems.The red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been explored.AIM In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients.METHODS Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 years.At baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were collected.During FUP,DEs(timing and modaities)were recorded.CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines.RESULTS Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P<0.0001,except for FIB-4(P:0.007)and ALBI(P:0.011)].Receiving operator curve analysis revealed RPR>0.472 and>0.894 as the best cut-offs in the prediction respectively of 3-year first DE,as well as its superiority compared to the other non-invasive tools examined.RPR(P:0.02)and the presence of baseline-CSPH(P:0.04)were significantly and independently associated with the DE.Patients presenting baseline-CSPH and RPR>0.472 showed higher risk of decompensation(P:0.0023).CONCLUSION Altogether these findings suggest the RPR as a valid and potentially applicable non-invasive tool in the prediction of timing and modalities of decompensation in MASLD-related cACLD patients.

Red cell distribution width-to-albumin ratio is a simple promising prognostic marker in acute cholangitis requiring biliary drainage

Background: It is crucial to assess the severity of acute cholangitis(AC). There are currently several prognostic markers. However, the accuracies of these markers are not satisfied. The present study aimed to investigate the predictive value of the red cell distribution width(RDW)-to-albumin ratio(RAR) for the prognosis of AC. Methods: We retrospectively evaluated consecutive patients diagnosed with AC between May 2019 and March 2022. RAR was calculated, and its predictive ability for in-hospital mortality, intensive care unit(ICU) admission, bacteremia, and the length of hospitalization were analyzed. Results: Out of 438 patients, 34(7.8%) died. Multivariate analysis showed that malignant etiology [odds ratio(OR) = 4.816, 95% confidence interval(CI): 1.936-11.980], creatinine(OR = 1.649, 95% CI: 1.095-2.484), and RAR(OR = 2.064, 95% CI: 1.494-2.851) were independent risk factors for mortality. When adjusted for relevant covariates, including age, sex, malignant etiology, Tokyo severity grading(TSG), Charlson comorbidity index, and creatinine, RAR significantly predicted mortality(adjusted OR = 1.833, 95% CI: 1.280-2.624). When the cut-off of RAR was set to 3.8, its sensitivity and specificity for mortality were 94.1% and 56.7%, respectively. Patients with an RAR of > 3.8 had a 20.9-fold(OR = 20.9, 95% CI: 4.9-88.6) greater risk of mortality than the remaining patients. The area under the curve value of RAR for mortality was 0.835(95% CI: 0.770-0.901), which was significantly higher than that of TSG and the other prognostic markers, such as C-reactive protein-to-albumin ratio, and procalcitonin-to-albumin ratio. Lastly, RAR was not inferior to TSG in predicting ICU admission, bacteremia, and the length of hospitalization. Conclusions: RAR successfully predicted the in-hospital mortality, ICU admission, bacteremia, and the length of hospitalization of patients with AC, especially in-hospital mortality. RAR is a promising marker that is more convenient than TSG and other prognostic markers for predicting the prognosis of patients with AC.

The Prognostic Value of Red Cell Distribution Width in Critically Ill Cerebral Infarction Patients:A Retrospective Cohort Study

Objective:Red blood cell distribution width(RDW)has been utilized as a prognostic indicator for mortality risk assessment in cardiovascular and cerebrovascular patients.Nevertheless,the prognostic significance of RDW in critically ill patients with cerebral infarction is yet to be investigated.The objective of this study is to examine the association between RDW and the risk of all-cause mortality in cerebral infarction patients admitted to the intensive care unit(ICU).Method:A retrospective cohort study was conducted using the Medical Information Mart for Intensive Care IV 2.2(MIMIC-IV)intensive care dataset for data analysis.The main results were the all-cause mortality rates at 3 and 12 months of follow-up.Cumulative curves were plotted using the Kaplan-Meier method,and Cox proportional hazards analysis was used to examine the relationship between RDW and mortality rates in critically ill cerebral infarction patients.Results:The findings indicate that RDW serves as a significant prognostic factor for mortality risk in critically ill stroke patients,specifically at the 3 and 12-month follow-up periods.The observed correlation between increasing RDW levels and higher mortality rates among cerebral infarction patients further supports the potential utility of RDW as a predictive indicator.Conclusion:RDW emerges as an independent predictor of mortality risk during the 3 and 12-month follow-up periods for critically ill patients with cerebral infarction.

Red cell distribution width: A predictor of the severity of hypertriglyceridemia-induced acute pancreatitis

BACKGROUND Compared with patients with other causes of acute pancreatitis,those with hypertriglyceridemia-induced acute pancreatitis(HTG-AP)are more likely to develop persistent organ failure(POF).Therefore,recognizing the individuals at risk of developing POF early in the HTG-AP process is a vital for improving outcomes.Bedside index for severity in acute pancreatitis(BISAP),a simple parameter that is obtained 24 h after admission,is an ideal index to predict HTG-AP severity;however,the suboptimal sensitivity limits its clinical application.Hence,current clinical scoring systems and biochemical parameters are not sufficient for predicting HTG-AP severity.AIM To elucidate the early predictive value of red cell distribution width(RDW)for POF in HTG-AP.METHODS In total,102 patients with HTG-AP were retrospectively enrolled.Demographic and clinical data,including RDW,were collected from all patients on admission.RESULTS Based on the Revised Atlanta Classification,37(33%)of 102 patients with HTG-AP were diagnosed with POF.On admission,RDW was significantly higher in patients with HTG-AP and POF than in those without POF(14.4%vs 12.5%,P<0.001).The receiver operating characteristic curve demonstrated a good discrim-inative power of RDW for POF with a cutoff of 13.1%,where the area under the curve(AUC),sensitivity,and specificity were 0.85,82.4%,and 77.9%,respectively.When the RDW was≥13.1%and one point was added to the original BISAP to obtain a new BISAP score,we achieved a higher AUC,sensitivity,and specificity of 0.89,91.2%,and 67.6%,respectively.CONCLUSION RDW is a promising predictor of POF in patients with HTG-AP,and the addition of RDW can promote the sensitivity of BISAP.

The mucosal immune system in the oral cavity——an orchestra of T cell diversity

The mucosal immune system defends against a vast array of pathogens, yet it exhibits limited responses to commensal microorganisms under healthy conditions. The oral-pharyngeal cavity, the gateway for both the gastrointestinal and respiratory tracts, is composed of complex anatomical structures and is constantly challenged by antigens from air and food. The mucosal immune system of the oral-pharyngeal cavity must prevent pathogen entry while maintaining immune homeostasis, which is achieved via a range of mechanisms that are similar or different to those utilized by the gastrointestinal immune system. In this review, we summarize the features of the mucosal immune system,focusing on T cell subsets and their functions. We also discuss our current understanding of the oral-pharyngeal mucosal immune system.

Prognostic impact of the red cell distribution width in esophageal cancer patients: A systematic review and meta-analysis

AIM To clarify the previous discrepant conclusions, we performed a meta-analysis to evaluate the prognostic value of red cell distribution width(RDW) in esophageal cancer(EC). METHODS We searched the PubM ed, EMBASE, Web of Science and Cochrane Library databases to identify clinical studies, followed by using STATA version 12.0 for statistical analysis. Studies that met the following criteria were considered eligible:(1) Studies including EC patients who underwent radical esophagectomy;(2) studies including patients with localized disease without distant metastasis;(3) studies including patients without preoperative neoadjuvant therapy;(4) studies including patients without previous antiinflammatory therapies and with available preoperative laboratory outcomes;(5) studies reporting association between the preoperative RDW and overall survival(OS)/disease-free survival(DFS)/cancer-specific survival(CSS); and(6) studies published in English.RESULTS A total of six articles, published between 2015 and 2017, fulfilled the selection criteria in the end. Statistical analysis showed that RDW was not associated with the prognosis of EC patients, irrespective of OS/CSS [hazard ratio(HR) = 1.27, 95% confidence interval(CI): 0.97-1.57, P = 0.000] or DFS(HR = 1.42, 95%CI: 0.96-1.88, P = 0.000). Subgroup analysis indicated that elevated RDW was significantly associated with worse OS/CSS of EC patients when RDW > 13%(HR = 1.45, 95%CI: 1.13-1.76, P = 0.000), when the patient number ≤ 400(HR = 1.45, 95%CI: 1.13-1.76, P = 0.000) and when the study type was retrospective(HR = 1.42, 95%CI : 1.16-1.69, P = 0.000).CONCLUSION Contrary to our general understanding, this meta-analysis revealed that RDW cannot serve as an indicator of poor prognosis in patients with EC. However, it may still be a useful predictor of unfavorable prognosis using an appropriate cut-off value.

Red cell distribution width to platelet ratio: New and promising prognostic marker in acute pancreatitis

AIM: To evaluate the accuracy of red cell distribution width (RDW) to platelet ratio (RPR) to predict in-hospital mortality in acute pancreatitis (AP).

Effect of Deformation of Red Cell on Nutritional Transport in Capillary-Tissue Exchange System

A mathematical analysis of a model for nutritional exchange in a capillary-tissue exchange system is presented in this paper. This model consist of a single file flow of red blood cell in capillary when diameter of red blood cell is greater than tube diameter, In this case, the cell must be deformed. Due to concentration gradients, the dissolved nutrient in substrate diffuses into surrounding tissue. Introducing approximations of the lubrication theory, squeezing flow of plasma in between the gap between cell and capillary wall have been solved with the help of approximate mathematical techniques. The computational results for concentration of dissolved nutrients, diffusive flux and normal component of velocity have been presented and discussed through graphs. We have also shown the effect of deformation parameter and permeability on these results.

Is it possible to block the cancer cells in circulating blood by extracorporeal circulation? Implications of the immune system and other factors (review)

The presence of cancer cells in circulating blood and the possibility of colonization in the tissues of the body worsen in a determinant way the prognosis of the disease. Nevertheless, there are factors in the body that can lead to a prognostic improvement, even in such conditions. In addition to the immune system, other favorable factors can act at the level of the microenvironment of the tumor so much that cases of spontaneous total regression, not only of primary tumors but also metastases, have been reported in the literature. Since it was recently reported that patients with renal tumors and in permanent hemodialysis present at post mortem examination, a metastatic spread much less extensive than observed in patients deceased for renal tumors but not on hemodialysis. The authors maintain it likely that the dialytic membrane concurs to block at least in part the cancer cells circulating in the blood. The possibility to block cancer cells can be extended in addition to the dialytic membrane also to other types of filters inserted in the extracorporeal circulation. The block of the cancer cells thus is obtained and that occurs in regional lymph nodes and in the microenvironment of the tumor causing a relative increase in the elements of the immune system compared to the number of cancer cells, which could determine clearly positive therapeutic results also in cases with advanced metastatic spread.

The effects of low-dose splenic irradiation and radiotherapy on immune system of patients with locally advanced non-small cell lung cancer

Objective： The aim of the research was to study the effects of low-dose splenic irradiation and radiotherapy on immune system of patients with locally advanced non-small cell lung cancer （NSCLC）. Methods： Twelve cases of stage III NSCLC in Tumor Radiotherapy Center of our hospital （the Affiliated Hospital of Medical College Qingdao University, China） were collected from July 2011 to July 2012; all patients were under 75 years old with clear pathology, measurable lesions and good personal statement. They were randomly divided into combined treatment group （D1 ＋ D2） and control group （D1）. The control group （D1） only received radiotherapy to the chest; combined treatment group （D1 ＋ D2） received low-dose splenic irradiation plus conventional dose irradiation. Flow cytometry was used to detect the peripheral blood T lymphocyte immune indexes of patients before, during and after the treatment, classification by five blood cell analyzer was used to determine white blood cells, neutrophils, hemoglobin and platelet count. The radiation induced toxicity including esophagitis, pneumonia and gastrointestinal reaction was observed, as well as the dose when it happened. Results： There was no significant difference in the ratio between two groups in cells CD4＋, CD8＋ and CD4＋/CD8＋ after radiotherapy （P 〉 0.05）. There was no change in these indicators in combined treatment group after treatment （P 〉 0.05）, but it decreased in control group （P 〈 0.05）. There was no significant difference in the incidences of radiation esophagitis, pneumonia, gastrointestinal reactions and bone marrow suppression between two groups （P 〉 0.05）, but the patients in combined treatment group seemed to tolerate high dose well （P 〈 0.05）. Conclusion： Low-dose splenic irradiation combined with radiotherapy to the chest can alleviate the injury degree of acute radiation induced the toxicity of locally advanced NSCLC patients, through affect the patient＇s immune function.

INFLUENCE OF ELECTROACUPUNCTURE ON HYPERTENSION VASCULAR DEMENTIA AND ITS RED CELL IMMUNE FUNCTION IN THE RAT

Objective: To probe into the effect of electroacupuncture (EA)on vascular dementia and red cell immune function in the rat. Methods: 30 SD rats were made into renal hypertension rats(RHR) by clamping the kidney arteries with silver clip. 42 days later, their bilateral common carotid arteries were blocked repeatedly to cause cerebral ischemia. The Hypertension vascular dementia model was then set up. Then they were randomly divided into VD model group, EA groupand medication group (Dihydroergotoxine, DHET), with 10 cases in each group. The therapeutic course was 28 days. The ability of learning and memory was using an obs erved by water maze, and the function of red blood cell immune was detected after treatment. Results: the latecy of the EA group and medication group was shorter than that of model group (P<0.05, P<0.005), and that of EA group was shorter than medication group (P<0.05, P<0.005). EA and medication could increase the RBCC 3b receptor flower circle rate and reduce the RBCIC flower circle rate significantly(P<0.05, P< 0.01). Conclusion: The results indicated that EA therapy could raise the ability of learning and memory and improve the function of red cell immune in VD rats, while the therapeutic effect of EAis better than DHET.

B cell development and antibody responses in human immune system mice:current status and future perspective

Humanized immune system(HIS)mice have been developed and used as a small surrogate model to study human immune function under normal or disease conditions.Although variations are found between models,most HIS mice show robust human T cell responses.However,there has been unsuccessful in constructing HIS mice that produce high-affinity human antibodies,primarily due to defects in terminal B cell differentiation,antibody affinity maturation,and development of primary follicles and germinal centers.In this review,we elaborate on the current knowledge about and previous attempts to improve human B cell development in HIS mice,and propose a potential strategy for constructing HIS mice with improved humoral immunity by transplantation of human follicular dendritic cells(FDCs)to facilitate the development of secondary follicles.

Pure red cell aplasia due to parvovirus B19 infection after liver transplantation:A case report and review of the literature

Pure red cell aplasia （PRCA） due to parvovirus B19 （PVB19） infectiori after solid organ transplantation has been rarely reported and most of the cases were renal transplant recipients, Few have been described after liver transplantation. Moreover, little information on the management of this easily recurring disease is available at present. We describe the first case of a Chinese liver transplant recipient with PVB19-induced PRCA during immunosuppressive therapy. The patient suffered from progressive anemia with the lowest hemoglobin level of 21 g/L. Bone marrow biopsy showed selectively inhibited erythropoiesis with giant pronormoblasts. Detection of PVB19-DNA in serum with quantitative polymerase chain reaction （PCR） revealed a high level of viral load. After 2 courses of intravenous immunoglobulin （IVIG） therapy, bone marrow erythropoiesis recovered with his hemoglobin level increased to 123 g/L. He had a lowlevel PVB19 load for a 5-too follow-up period without recurrence of PRCA, and finally the virus was cleared. Our case indicates that clearance of PVB19 by IVIG in transplant recipients might be delayed after recovery of anemia.

Is increased red cell distribution width an indicating marker of nonalcoholic steatohepatitis and fibrotic stage?

Red cell distribution width (RDW) may play an important role in predicting steatohepatitis and liver fibrosis. In the original study, it was aimed to determine whether RDW could be used for this purpose or not. There are studies indicating that higher RDW is correlated well with components of metabolic syndrome. Because nonalcoholic fatty liver disease is now recognized as the hepatic manifestation of metabolic syndrome, possible impact of the accompanying confounders on the study findings should have been detailed. There may be a patient selection bias due to use of improper cut-off values for alcohol consumption and inclusion of only subjects with normal aminotransferase levels and normal abdominal ultrasonography. Patients without hepatosteatosis on ultrasonography and with any restriction of aminotransferase levels should have been included in the control group, because isolated aminotransferase elevation is not decisive in the diagnosis of hepatosteatosis. Although iron, vitamin B12 and folic acid deficiencies were included in exclusion criteria, functional forms of these molecules like methylmalonic acid, homocysteine, ferritin levels and total iron binding capacity, which are more sensitive and specific parameters for vitamin B12 and folic acid deficiencies, were not mentioned. Consequently, RDW, an inexpensive, non-invasive, but powerful indicator overlooked on whole blood analysis, itself without other inflammatory markers may not accurately provide information about progression of nonalcoholic steatohepatitis and fibrosis.

Red cell distribution width and nonalcoholic steatohepatitis

Red cell distribution width is a measure of deviation of the volume of red blood cells.It is a marker of anisocytosis and often used to evaluate the possible causes of anemia.Elevated red cell distribution width levels are also associated with acute and chronic inflammatory responses.In nonalcoholic steatohepatitis,inflammation is accompanied with steatosis.For assuming red cell distribution width as a marker of nonalcoholic steatohepatitis,intervening factors such as levels of inflammatory markers should also be evaluated.

RETREATMENT WITH FLUDARABINE AND CYCLOSPORINE FOR ONE CASE OF REFRACTORY PURE RED CELL APLASIA

MANY cases of pure red cell aplasia （PRCA） were mediated by over-function of immune cells, and responded well to immunosuppressive therapy. Sometimes refractory cases also arose. Fludarabine is an analogue of adenosine resistant to deamination which is widely used for B-chronic lymphocytic leukemia （CLL） and other hematological malignancies.^2 As a strong immunosuppressive agent, fludarabine has generally been used in nonmyeloblative conditioning regimens for hematopoietic stem cells transplantation for hematological malignancies and severe aplastic anemia recently.^3 In this study,

Predictive value of red cell distribution width on left atrial thrombus or left atrial spontaneous echo contrast in patients with non-valvular atrial fibrillation

Objective To evaluate the predictive value of red cell distribution width （RDW） on left atrial thrombus （LAT） or left atrial spontane- ous echo contrast （LASEC） in patients with non-valvular atrial fibrillation （AF）. Methods We reviewed 692 patients who were diagnosed as non-valvular AF and underwent transesophageal echocardiography （TEE） in Guangdong Cardiovascular Institute from April 2014 to December 2015. The baseline clinical characteristics, laboratory test of blood routine, electrocardiograph measurements were analyzed. Results Eighty-four patients were examined with LAT/LASEC under TEE. The mean RDW level was significantly higher in LAT/LASEC patients compared with the non-LAT/LASEC patients （13.59% ± 1.07% ws. 14.34% ± 1.34%; P 〈 0.001）. Receiver-operating characteristic curve analysis was performed and indicated the best RDW cut point was 13.16%. Furthermore, multivariate logistic regression analysis indicated that RDW level 〉 13.16% could be an independent risk factor for LAT/LASEC in patients with AF. Conclusion Elevated RDW level is associated with the presence of LAT/LASEC and could be with moderate predictive value for LAT/LASEC in patients with non-valvular AF.

Hepatitis E virus-related acute liver failure associated with pure red cell aplasia

The Editor welcomes submissions for possible publication in the Letters to the Editor section. Letters commenting on an article published in the Journal or other interesting pieces will be considered if they are received within 6 weeks of the time the article was published. Authors of the article being commented on will be given an opportunity to offer a timely response to the letter. Authors of letters will be notified that the letter has been received. Unpublished letters cannot be returned.