Pretreatment red blood cell distribution width as a predictive marker for postoperative complications after laparoscopic pancreatoduodenectomy

BACKGROUND Red blood cell distribution width(RDW)is associated with the development and progression of various diseases.AIM To explore the association between pretreatment RDW and short-term outcomes after laparoscopic pancreatoduodenectomy(LPD).METHODS A total of 804 consecutive patients who underwent LPD at our hospital between March 2017 and November 2021 were retrospectively analyzed.Correlations between pretreatment RDW and clinicopathological characteristics and short-term outcomes were investigated.RESULTS Patients with higher pretreatment RDW were older,had higher Eastern Cooperative Oncology Group scores and were associated with poorer short-term outcomes than those with normal RDW.High pretreatment RDW was an independent risk factor for postoperative complications(POCs)(hazard ratio=2.973,95%confidence interval:2.032-4.350,P<0.001)and severe POCs of grade IIIa or higher(hazard ratio=3.138,95%confidence interval:2.042-4.824,P<0.001)based on the Clavien-Dino classification system.Subgroup analysis showed that high pretreatment RDW was an independent risk factor for Clavien-Dino classi-fication grade IIIb or higher POCs,a comprehensive complication index score≥26.2,severe postoperative pancreatic fistula,severe bile leakage and severe hemorrhage.High pretreatment RDW was positively associated with the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and was negatively associated with albumin and the prognostic nutritional index.CONCLUSION Pretreatment RDW was a special parameter for patients who underwent LPD.It was associated with malnutrition,severe inflammatory status and poorer short-term outcomes.RDW could be a surrogate marker for nutritional and inflammatory status in identifying patients who were at high risk of developing POCs after LPD.

Efficient and Stable Perovskite Solar Cells and Modules Enabled by Tailoring Additive Distribution According to the Film Growth Dynamics

Gas quenching and vacuum quenching process are widely applied to accelerate solvent volatilization to induce nucleation of perovskites in blade-coating method.In this work,we found these two pre-crystallization processes lead to different order of crystallization dynamics within the perovskite thin film,resulting in the differences of additive distribution.We then tailor-designed an additive molecule named 1,3-bis(4-methoxyphenyl)thiourea to obtain films with fewer defects and holes at the buried interface,and prepared perovskite solar cells with a certified efficiency of 23.75%.Furthermore,this work also demonstrates an efficiency of 20.18%for the large-area perovskite solar module(PSM)with an aperture area of 60.84 cm^(2).The PSM possesses remarkable continuous operation stability for maximum power point tracking of T_(90)>1000 h in ambient air.

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.

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.

Predictive value of red blood cell distribution width and hematocrit for short-term outcomes and prognosis in colorectal cancer patients undergoing radical surgery

BACKGROUND Previous studies have reported that low hematocrit levels indicate poor survival in patients with ovarian cancer and cervical cancer,the prognostic value of hematocrit for colorectal cancer(CRC)patients has not been determined.The prognostic value of red blood cell distribution width(RDW)for CRC patients was controversial.AIM To investigate the impact of RDW and hematocrit on the short-term outcomes and long-term prognosis of CRC patients who underwent radical surgery.METHODS Patients who were diagnosed with CRC and underwent radical CRC resection between January 2011 and January 2020 at a single clinical center were included.The short-term outcomes,overall survival(OS)and disease-free survival(DFS)were compared among the different groups.Cox analysis was also conducted to identify independent risk factors for OS and DFS.RESULTS There were 4258 CRC patients who underwent radical surgery included in our study.A total of 1573 patients were in the lower RDW group and 2685 patients were in the higher RDW group.There were 2166 and 2092 patients in the higher hematocrit group and lower hematocrit group,respectively.Patients in the higher RDW group had more intraoperative blood loss(P<0.01)and more overall complications(P<0.01)than did those in the lower RDW group.Similarly,patients in the lower hematocrit group had more intraoperative blood loss(P=0.012),longer hospital stay(P=0.016)and overall complications(P<0.01)than did those in the higher hematocrit group.The higher RDW group had a worse OS and DFS than did the lower RDW group for tumor node metastasis(TNM)stage I(OS,P<0.05;DFS,P=0.001)and stage II(OS,P=0.004;DFS,P=0.01)than the lower RDW group;the lower hematocrit group had worse OS and DFS for TNM stage II(OS,P<0.05;DFS,P=0.001)and stage III(OS,P=0.001;DFS,P=0.001)than did the higher hematocrit group.Preoperative hematocrit was an independent risk factor for OS[P=0.017,hazard ratio(HR)=1.256,95%confidence interval(CI):1.041-1.515]and DFS(P=0.035,HR=1.194,95%CI:1.013-1.408).CONCLUSION A higher preoperative RDW and lower hematocrit were associated with more postoperative complications.However,only hematocrit was an independent risk factor for OS and DFS in CRC patients who underwent radical surgery,while RDW was not.

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.

Application of neutrophil-lymphocyte ratio and red blood cell distribution width in diabetes mellitus complicated with heart failure

BACKGROUND Accumulating clinical evidence has shown that diabetes mellitus(DM)is a serious risk factor for cardiovascular disorders and an important factor for adverse cardiovascular events.AIM To explore the value of the combined determination of the neutrophil-lymphocyte ratio(NLR)and red blood cell distribution width(RDW)in the early diagnosis and prognosis evaluation of DM complicated with heart failure(HF).METHODS We retrospectively analyzed clinical data on 65 patients with type 2 DM(T2DM)complicated with HF(research group,Res)and 60 concurrent patients with uncomplicated T2DM(control group,Con)diagnosed at Zhejiang Provincial People’s Hospital between January 2019 and December 2021.The NLR and RDW values were determined and comparatively analyzed,and their levels in T2DM+HF patients with different cardiac function grades were recorded.The receiver operating characteristic(ROC)curves were plotted to determine the NLR and RDW values(alone and in combination)for the early diagnosis of HF.The correlation between NLR and RDW with the presence or absence of cardiac events was also investigated.RESULTS Higher NLR and RDW levels were identified in the Res vs the Con groups(P<0.05).The NLR and RDW increased gradually and synchronously with the deterioration of cardiac function in the Res group,with marked differences in their levels among patients with grade II,III,and IV HF(P<0.05).ROC curve analysis revealed that NLR combined with RDW detection had an area under the curve of 0.915,a sensitivity of 76.9%,and a specificity of 100%for the early diagnosis of HF.Furthermore,HF patients with cardiac events showed higher NLR and RDW values compared with HF patients without cardiac events.CONCLUSION NLR and RDW were useful laboratory indicators for the early diagnosis of DM complicated with HF,and their joint detection was beneficial for improving diagnostic efficiency.Additionally,NLR and RDW values were directly proportional to patient outcomes.

Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.

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.

Neural stem cell-derived exosomes promote mitochondrial biogenesis and restore abnormal protein distribution in a mouse model of Alzheimer's disease

Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.

Bioaccumulation,subcellular distribution and chemical forms of cadmium in Aster subulatus Michx.

【Objective】Through analyzing the bioaccumulation capacity,subcellular distribution and chemical forms of cadmium(Cd)in Aster subulatus Michx.,this study was to provide reference for revealing the Cd tolerance mechanism of A.subulatus Michx.【Method】After cultured for 24 d under the action of Hoagland nutrient solution and gradient Cd concentrations(0,30,60 and 90 mg/L),A.subulatus Michx.were harvested,and its leaf,stem and root were treated by differential centrifugation,chemical reagent extraction,and digested with graphite digester,respectively,then the Cd content in the root,stem and leaf were determined by atomic absorption spectroscopy.【Result】The experimental results indicated that the bioaccumulation capacity of Cd in A.subulatus Michx.was root>stem>leaf,and the maximum Cd concentration in the root,stem and leaf of A.subulatus Michx.were 130.74,78.69 and 56.62 mg/kg(fresh matter),respectively.Most of Cd stored in the cell wall and the soluble fractions of the root and leaf of A.subulatus Michx.,with only a smaller portion Cd in organelle fraction.Analysis result of subcellular Cd content showed that 52.27%-58.61%of Cd for root was mainly stored in the soluble fraction,but 42.10%-63.28%of Cd for leaf was mainly stored in the cell wall fraction.The concentration of pectates and protein integrated-Cd was higher in the root and leaf compared to other chemical forms Cd.Pectates and protein integrated-Cd was the main chemical forms Cd in the root and leaf of A.subulatus Michx.,and their percentages were 68.91%-74.80%and 57.38%-83.80%,respectively.Cd treatment could significantly increase the proportion of water-soluble organic acid Cd from 13.64%to 22.72%in root and undissolved phosphate Cd from 10.02%to 32.78%in leaf with increasing Cd concentration in the culture medium.【Conclusion】The root,stem and leaf of A.subulatus Michx.has strong bioaccumulation capacity to Cd,Cd is primarily stored in the soluble fractions of the root and cell wall fractions of the leaf,and less toxic pectates and protein integrated-Cd is the main chemical forms Cd in the root and leaf of A.subulatus Michx.,this might be the main mechanism of Cd tolerance in A.subulatus Michx.

Spatial search weighting information contained in cell velocity distribution

Cell migration plays a significant role in physiological and pathological processes.Understanding the characteristics of cell movement is crucial for comprehending biological processes such as cell functionality,cell migration,and cell–cell interactions.One of the fundamental characteristics of cell movement is the specific distribution of cell speed,containing valuable information that still requires comprehensive understanding.This article investigates the distribution of mean velocities along cell trajectories,with a focus on optimizing the efficiency of cell food search in the context of the entire colony.We confirm that the specific velocity distribution in the experiments corresponds to an optimal search efficiency when spatial weighting is considered.The simulation results indicate that the distribution of average velocity does not align with the optimal search efficiency when employing average spatial weighting.However,when considering the distribution of central spatial weighting,the specific velocity distribution in the experiment is shown to correspond to the optimal search efficiency.Our simulations reveal that for any given distribution of average velocity,a specific central spatial weighting can be identified among the possible central spatial weighting that aligns with the optimal search strategy.Additionally,our work presents a method for determining the spatial weights embedded in the velocity distribution of cell movement.Our results have provided new avenues for further investigation of significant topics,such as relationship between cell behavior and environmental conditions throughout their evolutionary history,and how cells achieve collective cooperation through cell-cell communication.

Particle residence time distribution and axial dispersion coefficient in a pressurized circulating fluidized bed by using multiphase particle-in-cell simulation

The particle residence time distribution(RTD)and axial dispersion coefficient are key parameters for the design and operation of a pressurized circulating fluidized bed(PCFB).In this study,the effects of pressure(0.1-0.6 MPa),fluidizing gas velocity(2-7 m·s^(-1)),and solid circulation rate(10-90 kg·m^(-2)·s^(-1))on particle RTD and axial dispersion coefficient in a PCFB are numerically investigated based on the multiphase particle-in-cell(MP-PIC)method.The details of the gas-solid flow behaviors of PCFB are revealed.Based on the gas-solid flow pattern,the particles tend to move more orderly under elevated pressures.With an increase in either fluidizing gas velocity or solid circulation rate,the mean residence time of particles decreases while the axial dispersion coefficient increases.With an increase in pressure,the core-annulus flow is strengthened,which leads to a wider shape of the particle RTD curve and a larger mean particle residence time.The back-mixing of particles increases with increasing pressure,resulting in an increase in the axial dispersion coefficient.

Visualizing the distribution of mitochondrial molecular mRNAs of cerebellar Purkinje cells by RNAscope

Objective To investigate the distribution of mitochondria-associated molecule mRNA in cerebellar Purkinje cells.Methods Transgenic technology was used to prepare Pcp2-tdTomato mouse labeled Purkinje cells.The mRNAs of mitochondria-associated molecules Mfn2,Mfn1,Ucp4,Drp1,Ucp2,Mcu and Nclx were detected in situ by RNAscope technique.Results The results of this study showed that Mfn2,Mfn1,Ucp4 and Drp1 were highly expressed in Purkinje cell body(Bin 3>10%).However,Ucp2,Mcu and Nclx were less expressed.In addition,Mfn2,Mfn1,Ucp4,Drp1,Ucp2,Mcu and Nclx were less expressed in dendrites.Conclusion Current research focuses on developing new and more specific molecules to regulate the activity of Purkinje cells and opening therapeutic windows for Purkinje cells related diseases.The molecule identification of potential drug targets,mechanisms of action,and structural basis of their activity will crucially promote preclinical development.

Subcellular distribution of prohibitin 1 in rat liver during liver regeneration and its cellular implication

BACKGROUND The function of prohibitin 1(Phb1)during liver regeneration(LR)remains relatively unexplored.Our previous research identified downregulation of Phb1 in rat liver mitochondria 24 h after 70%partial hepatectomy(PHx),as determined by subcellular proteomic analysis.AIM To investigate the potential role of Phb1 during LR.METHODS We examined changes in Phb1 mRNA and protein levels,subcellular distribution,and abundance in rat liver during LR following 70%PHx.We also evaluated mitochondrial changes and apoptosis using electron microscopy and flow cytometry.RNA-interference-mediated knockdown of Phb1(PHBi)was performed in BRL-3A cells.RESULTS Compared with sham-operation control groups,Phb1 mRNA and protein levels in 70%PHx test groups were downregulated at 24 h,then upregulated at 72 and 168 h.Phb1 was mainly located in mitochondria,showed a reduced abundance at 24 h,significantly increased at 72 h,and almost recovered to normal at 168 h.Phb1 was also present in nuclei,with continuous increase in abundance observed 72 and 168 h after 70%PHx.The altered ultrastructure and reduced mass of mitochondria during LR had almost completely recovered to normal at 168 h.PHBi in BRL-3A cells resulted in increased S-phase entry,a higher number of apoptotic cells,and disruption of mitochondrial membrane potential.CONCLUSION Phb1 may contribute to maintaining mitochondrial stability and could play a role in regulating cell proliferation and apoptosis of rat liver cells during LR.

Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

Induced pluripotent stem cell-related approaches to generate dopaminergic neurons for Parkinson's disease

The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative disease.Although the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and therapy.The induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease therapies.The current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem cells.The benefits of induced pluripotent stem cell-based research are highlighted.Various dopaminergic neuron differentiation protocols from induced pluripotent stem cells are compared.The emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are evaluated.Finally,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.

Modulation of the Nogo signaling pathway to overcome amyloid-β-mediated neurite inhibition in human pluripotent stem cell-derived neurites

Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's disease.The accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is believed to induce neuritic abnormalities,including reduced growth,extension,and abnormal growth cone morphology,all of which contribute to decreased connectivity.However,the precise cellular and molecular mechanisms governing this response remain unknown.In this study,we used an innovative approach to demonstrate the effect of amyloid-βon neurite dynamics in both two-dimensional and three-dimensional cultu re systems,in order to provide more physiologically relevant culture geometry.We utilized various methodologies,including the addition of exogenous amyloid-βpeptides to the culture medium,growth substrate coating,and the utilization of human-induced pluripotent stem cell technology,to investigate the effect of endogenous amyloid-βsecretion on neurite outgrowth,thus paving the way for potential future applications in personalized medicine.Additionally,we also explore the involvement of the Nogo signaling cascade in amyloid-β-induced neurite inhibition.We demonstrate that inhibition of downstream ROCK and RhoA components of the Nogo signaling pathway,achieved through modulation with Y-27632(a ROCK inhibitor)and Ibuprofen(a Rho A inhibitor),respectively,can restore and even enhance neuronal connectivity in the presence of amyloid-β.In summary,this study not only presents a novel culture approach that offers insights into the biological process of neurite growth and inhibition,but also proposes a specific mechanism for reduced neural connectivity in the presence of amyloid-βpeptides,along with potential intervention points to restore neurite growth.Thereby,we aim to establish a culture system that has the potential to serve as an assay for measuring preclinical,predictive outcomes of drugs and their ability to promote neurite outgrowth,both generally and in a patient-specific manner.

Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.