Complications of Ziv-Aflibercept in Choroidal and Retinal Vascular Diseases

Introduction: The modern ophthalmology trends are changing rapidly every day with the introduction of much newer studies and research. Numerous anti-vascular endothelial growth factors (VEGF) are utilized as the mainstay in the treatment of intraocular vascular pathologies. The rationale of this study is to add to the literature regarding the safety and efficacy profile of the ziv-aflibercept as there is insubstantial data in patients with intraocular vascular pathologies being treated with this injection with prime focus on the complications of the injection. Materials and Methods: A prospective observational study was conducted at Opthalmology Department, Lahore General Hospital, Lahore between 14 August 2018 and 23 December 2019. Patients with choroidal and retinal vascular diseases like diabetic macular edema (DME), age-related macular degeneration (AMD) and retinal vein occlusion (RVO) who had no active infection of eye and had no history of myocardial infarction or cerebrovascular accident were added in this study. Results: Best-corrected visual acuity was significantly improved at 4, 8, and 12 weeks as compared to the baseline (p Conclusion: The use of ziv-aflibercept injection via intravitreal route under aseptic conditions for choroidal and retinal vascular diseases is effective as well as safe with mild and treatable ocular side effects.

Retinal capillary plexus in Parkinson’s disease using optical coherence tomography angiography

AIM:To evaluate the alterations of the retinal microvasculature and foveal avascular zone in patients with Parkinson’s disease(PD)using optical coherence tomography angiography(OCT-A).METHODS:A retrospective study of PD patients examined in the Ophthalmology Department of the General Hospital of Athens,“Georgios Gennimatas”from March 2021 to March 2022 was conducted.Totally 44 patients with PD were included and 18 healthy controls were examined,hence a total of 124 eyes were enrolled in the study.The foveal and parafoveal superficial and deep capillary plexus vascular density(fSCP-VD,fDCP-VD,pSCP-VD,pDCP-CD)and foveal avascular zone(FAZ)were quantified with OCTA.Optical coherence tomography(OCT)was used to measure macular thickness.Our statistical analysis was conducted by using a mixed effect linear regression model.RESULTS:After adjustment for age and gender,the mean parafoveal superficial capillary plexus vascular density(pSCP-VD)and mean parafoveal deep capillary plexus vascular density(pDCP-VD)were significantly decreased in individuals with PD(P<0.001 in both)by-2.35(95%CI-3.3,-1.45)and-7.5(95%CI-10.4,-4.6)respectively.fSCP-VD and fDCP-VD didn’t approach statistical significance.The FAZ area and perimeter were significantly decreased(P<0.001 in both)by-0.1 mm^(2)(95%CI-0.13,-0.07)and-0.49 mm^(2)(95%CI-0.66,-0.32)respectively.Circularity didn’t approach statistical significance.Central retinal thickness(CRT)was significantly decreased in individuals with PD(P<0.001)by-23.1μm(95%CI-30.2,-16)and temporal retinal thickness(TRT)was decreased(P=0.025)by-11μm(95%CI-22,-1.5)while nasal retinal thickness(NRT)only approached statistical significance(P=0.066).CONCLUSION:The mean pSCP-VD,pDCP-VD,CRT and TRT are significantly decreased and FAZ is altered in individuals with PD.These findings can be potentially used as biomarkers for the diagnosis and evaluation of early PD.

Predicting short-term major postoperative complications in intestinal resection for Crohn’s disease:A machine learning-based study

BACKGROUND Due to the complexity and numerous comorbidities associated with Crohn’s disease(CD),the incidence of postoperative complications is high,significantly impacting the recovery and prognosis of patients.Consequently,additional stu-dies are required to precisely predict short-term major complications following intestinal resection(IR),aiding surgical decision-making and optimizing patient care.AIM To construct novel models based on machine learning(ML)to predict short-term major postoperative complications in patients with CD following IR.METHODS A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022.The study participants were randomly allocated to either a training cohort or a validation cohort.The logistic regression and random forest(RF)were applied to construct models in the training cohort,with model discrimination evaluated using the area under the curves(AUC).The validation cohort assessed the performance of the constructed models.RESULTS Out of the 259 patients encompassed in the study,5.0%encountered major postoperative complications(Clavien-Dindo≥III)within 30 d following IR for CD.The AUC for the logistic model was 0.916,significantly lower than the AUC of 0.965 for the RF model.The logistic model incorporated a preoperative CD activity index(CDAI)of≥220,a diminished preoperative serum albumin level,conversion to laparotomy surgery,and an extended operation time.A nomogram for the logistic model was plotted.Except for the surgical approach,the other three variables ranked among the top four important variables in the novel ML model.CONCLUSION Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complic-ations in patients with CD,with the RF model showing more superiority.A preoperative CDAI of≥220,a di-minished preoperative serum albumin level,and an extended operation time might be the most crucial variables.The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.

Histopathological Patterns and Early Postoperative Complications among Patients with Surgically Treated Thyroid Diseases at Bugando Medical Centre, Mwanza, Tanzania

Background: Thyroid diseases are among the leading endocrine disorders affecting a large proportion of people worldwide and show geographical variation in incidence and histopathological pattern related to age, sex, dietary and environmental factors. Histopathological patterns of surgically treated thyroid diseases play an important role in early diagnosis and management of these diseases. There is, however, limited published data regarding histopathological reports on thyroid disease in our local setting. This study aimed to determine the histopathological patterns and highlight early postoperative complications among patients with surgically treated thyroid diseases at Bugando Medical Centre (BMC). Methods: This was a longitudinal study involving all patients with surgically treated thyroid diseases seen at BMC over a period of 6 months from October 2019 to March 2020. Results: A total of 84 patients were studied. Females outnumbered males by a female to male ratio of 11:1. The median age of patients was 44 [IQR, 35 - 54] years old, the youngest was 14 years old and the oldest was 76 years old. Colloid goiter was the most common non-neoplastic lesion accounting for 34 (44.7%) patients. Among the neoplastic lesions, follicular adenoma was the most commonly encountered benign pathologies (n = 16;21.1%), while papillary carcinoma was the most commonly encountered malignancy (n = 4;50%). Following thyroidectomy, 12 (14.3%) patients developed early complications, of which hemorrhage sometimes requiring blood transfusion was the leading intra/postoperative complications accounting for 4 (33.3%) patients. Other complications include temporary recurrent laryngeal nerve palsy 2 (16.7%), surgical site infection 2 (16.7%) and tracheomalacia, bronchospasm, thyroid abscess and respiratory obstruction in 1 (8.3%) patient each, respectively. In this study, malignant thyroid lesion (p Conclusion: This study demonstrated that colloid goiter was the most common non-neoplastic lesion, and on the neoplastic category, follicular adenoma was the most common benign lesion, while papillary carcinoma was the most frequent malignant lesion.

Sickle cell retinopathy and systemic disease

Sickle cell disease(SCD)is a widespread hemoglobinopathy that results in significant patient morbidity and mortality.Vascular occlusion can cause acute pain,acute chest syndrome,and avascular necrosis,while hemolysis and endothelial disruption can cause ischemic stroke,leg ulcers,pulmonary hypertension,and priapism.All ocular and orbital structures can be affected by SCD ischemic events,including orbital bone infarction,ischemic optic neuropathy,retinal artery occlusion,hyphema,secondary glaucoma,sickle cell maculopathy,and sickle cell retinopathy.Proliferative sickle cell retinopathy(PSR)is the most common cause of vision loss.Untreated PSR can lead to macular ischemia,vitreous hemorrhage,and tractional retinal detachment.Ophthalmic screening exams and multimodal imaging can lead to earlier detection of sickle cell retinopathy and improved patient outcomes.SCD patients undergoing vitreoretinal surgery may require coordination of care with hematologists to avoid ischemic complications.While hydroxyurea was the only United States Food and Drug Administration approved treatment for several decades,patients with SCD now have several more treatment options.Despite the United States screening all infants for SCD,there can be delays in diagnosis and treatment.This review article aims to provide an overview of sickle disease for the ophthalmologist,and to discuss emerging treatment options and current management of SCD ocular complications.

Correlation Analysis Between Changes of D-Dimer Level and Rheumatoid Arthritis Complicated with Interstitial Lung Disease

Objective:To explore the correlation between the change of D-dimer level and rheumatoid arthritis complicated with interstitial lung disease.Methods:From January 2022 to February 2024,20 rheumatoid arthritis patients complicated with interstitial lung disease(interstitial lung disease group),20 rheumatoid arthritis patients without interstitial lung disease(without interstitial lung disease group),and 20 healthy people(control group)in Xijing Hospital were selected for this study.The fasting venous blood of the three groups of subjects was collected and their D-dimer,C-reactive protein(CRP),rheumatoid factor(RF),and erythrocyte sedimentation rate(ESR)were detected.Subsequently,the correlation between each index and rheumatoid arthritis complicated with interstitial lung disease was analyzed.Results:The D-dimer level of the interstitial lung disease group was significantly higher than the other two groups(P<0.05).The D-dimer level of the group without interstitial lung disease was significantly higher than the control group(P<0.05).CRP levels in the interstitial lung disease group and the group without interstitial lung disease were significantly higher than those of the control group(P<0.05).The ESR and RF levels of the interstitial lung disease group were significantly higher than the other two groups(P<0.05).The levels of ESR and RF levels of the group without interstitial lung disease were significantly higher than the control group(P<0.05).Conclusion:D-dimer levels of rheumatoid arthritis patients are higher than those of healthy individuals,and those complicated with interstitial lung disease present even higher levels.This finding shows that there is a correlation between D-dimer levels and rheumatoid arthritis with interstitial lung disease,which may facilitate the evaluation and diagnosis of this disease.

Stem cell therapy in retinal diseases

Alteration of the outer retina leads to various diseases such as age-related macular degeneration or retinitis pigmentosa characterized by decreased visual acuity and ultimately blindness.Despite intensive research in the field of retinal disorders,there is currently no curative treatment.Several therapeutic approaches such as cell-based replacement and gene therapies are currently in development.In the context of cell-based therapies,different cell sources such as embryonic stem cells,induced pluripotent stem cells,or multipotent stem cells can be used for transplantation.In the vast majority of human clinical trials,retinal pigment epithelial cells and photoreceptors are the cell types considered for replacement cell therapies.In this review,we summarize the progress made in stem cell therapies ranging from the pre-clinical studies to clinical trials for retinal disease.

Automated Classification of Inherited Retinal Diseases in Optical Coherence Tomography Images Using Few-shot Learning

Objective To develop a few-shot learning(FSL) approach for classifying optical coherence tomography(OCT) images in patients with inherited retinal disorders(IRDs).Methods In this study, an FSL model based on a student–teacher learning framework was designed to classify images. 2,317 images from 189 participants were included. Of these, 1,126 images revealed IRDs, 533 were normal samples, and 658 were control samples.Results The FSL model achieved a total accuracy of 0.974–0.983, total sensitivity of 0.934–0.957, total specificity of 0.984–0.990, and total F1 score of 0.935–0.957, which were superior to the total accuracy of the baseline model of 0.943–0.954, total sensitivity of 0.866–0.886, total specificity of 0.962–0.971,and total F1 score of 0.859–0.885. The performance of most subclassifications also exhibited advantages. Moreover, the FSL model had a higher area under curves(AUC) of the receiver operating characteristic(ROC) curves in most subclassifications.Conclusion This study demonstrates the effective use of the FSL model for the classification of OCT images from patients with IRDs, normal, and control participants with a smaller volume of data. The general principle and similar network architectures can also be applied to other retinal diseases with a low prevalence.

Accuracy improvement for classifying retinal OCT images by diseases using deep learning-based selective denoising approach

In ophthalmology,retinal optical coherence tomography(OCT)images with noticeable structural features help identify human eyes as healthy or diseased.The recently hot arti ficial intelligence(AI)realized this recognition process automatically.However,speckle noise in the original retinal OCT image reduces the accuracy of disease classi fication.This study presents a timesaving approach based on deep learning to improve classi fication accuracy by removing the noise from the original dataset.Firstly,four pre-trained convolutional neural networks(CNNs)from the ImageNet Large Scale Visual Recognition Challenge(ILSVRC)were trained to classify the original images into two categories:The noise reduction required(NRR)and the noise-free(NF)images.Among the CNNs,VGG19 BN performed best with 98%accuracy and 99%recall.Then,we used the block-matching and 3D filtering(BM3D)algorithm to denoise the NRR images.Those noise-removed NRR and the NF images form the processed dataset.The quality of images in the dataset is prominently ameliorated after denoising,which is valid to improve the models'performance.The original and processed datasets were tested on the four pre-trained CNNs to evaluate the effectiveness of our proposed approach.We have compared the CNNs,and the results show the performance of the CNNs trained with the processed dataset is improved by an average of 2.04%,5.19%,and 5.10%under overall accuracy(OA),Macro F1-score,and Micro F1-score,respectively.Especially for DenseNet161,the OA is improved to 98.14%.Our proposed method demonstrates its effectiveness in improving classi fication accuracy and opens a new solution to reduce denoising time-consuming for large datasets.

Game Theory-Based Dynamic Weighted Ensemble for Retinal Disease Classification

An automated retinal disease detection system has long been in exis-tence and it provides a safe,no-contact and cost-effective solution for detecting this disease.This paper presents a game theory-based dynamic weighted ensem-ble of a feature extraction-based machine learning model and a deep transfer learning model for automatic retinal disease detection.The feature extraction-based machine learning model uses Gaussian kernel-based fuzzy rough sets for reduction of features,and XGBoost classifier for the classification.The transfer learning model uses VGG16 or ResNet50 or Inception-ResNet-v2.A novel ensemble classifier based on the game theory approach is proposed for the fusion of the outputs of the transfer learning model and the XGBoost classifier model.The ensemble approach significantly improves the accuracy of retinal disease pre-diction and results in an excellent performance when compared to the individual deep learning and feature-based models.

Convolutional Neural Network-Based Classificationof Multiple Retinal Diseases Using Fundus Images

Use of deep learning algorithms for the investigation and analysis of medical images has emerged as a powerful technique.The increase in retinal dis-eases is alarming as it may lead to permanent blindness if left untreated.Automa-tion of the diagnosis process of retinal diseases not only assists ophthalmologists in correct decision-making but saves time also.Several researchers have worked on automated retinal disease classification but restricted either to hand-crafted fea-ture selection or binary classification.This paper presents a deep learning-based approach for the automated classification of multiple retinal diseases using fundus images.For this research,the data has been collected and combined from three distinct sources.The images are preprocessed for enhancing the details.Six layers of the convolutional neural network(CNN)are used for the automated feature extraction and classification of 20 retinal diseases.It is observed that the results are reliant on the number of classes.For binary classification(healthy vs.unhealthy),up to 100%accuracy has been achieved.When 16 classes are used(treating stages of a disease as a single class),93.3%accuracy,92%sensitivity and 93%specificity have been obtained respectively.For 20 classes(treating stages of the disease as separate classes),the accuracy,sensitivity and specificity have dropped to 92.4%,92%and 92%respectively.

Intestinal complications in patients with Crohn's disease in the Brazilian public healthcare system between 2011 and 2020

BACKGROUND This is a secondary database study using the Brazilian public healthcare system database.AIM To describe intestinal complications(ICs)of patients in the Brazilian public healthcare system with Crohn’s disease(CD)who initiated and either only received conventional therapy(CVT)or also initiated anti-tumor necrosis factor(anti-TNF)therapy between 2011 and 2020.METHODS This study included patients with CD[international classification of diseases–10th revision(ICD-10):K50.0,K50.1,or K50.8](age:≥18 years)with at least one claim of CVT(sulfasalazine,azathioprine,mesalazine,or methotrexate).IC was defined as a CD-related hospitalization,pre-defined procedure codes(from rectum or intestinal surgery groups),and/or associated disease(pre-defined ICD-10 codes),and overall(one or more type of ICs).RESULTS In the 16809 patients with CD that met the inclusion criteria,the mean follow-up duration was 4.44(2.37)years.In total,14697 claims of ICs were found from 4633 patients.Over the 1-and 5-year of follow-up,8.3%and 8.2%of the patients with CD,respectively,presented at least one IC,of which fistula(31%)and fistulotomy(48%)were the most commonly reported.The overall incidence rate(95%CI)of ICs was 6.8(6.5–7.04)per 100 patient years for patients using only-CVT,and 9.2(8.8–9.6)for patients with evidence of anti-TNF therapy.CONCLUSION The outcomes highlighted an important and constant rate of ICs over time in all the CD populations assessed,especially in patients exposed to anti-TNF therapy.This outcome revealed insights into the real-world treatment and complications relevant to patients with CD and highlights that this disease remains a concern that may require additional treatment strategies in the Brazilian public healthcare system.

Retinal thickness and vascular parameters using optical coherence tomography in Alzheimer's disease:a meta-analysis

Examining the retinal tissue has the potential to provide a unique method and technique to quantify Alzheimer’s disease-related changes in participants at various stages of the disease.In this metaanalysis,we aimed to investigate the association of various optical coherence tomography parameters with Alzheimer’s disease and whether retinal measurements can be used to diffe rentiate between Alzheimer’s disease and control subjects.Scientific databases including Google Schola r,Web of Science,and PubMed were systematically searched for published articles that evaluated retinal nerve fiber layer thickness and retinal microvascular network in Alzheimer’s disease and control subjects.Seventy-three studies(5850 participants,including 2249 Alzheimer’s disease patients and 3601controls) were included in this meta-analysis.Relative to controls,Alzheimer’s disease patients had a significantly lower global retinal nerve fiber layer thickness(standardized mean difference [SMD]=-0.79,95% confidence intervals [CI]:-1.03 to-0.54,P <0.00001) as well as each quadrant being thinner in Alzheimer’s disease versus controls.Regarding macular paramete rs,values measured by optical coherence tomography were significantly lower in Alzheimer’s disease than controls for macular thickness(pooled SMD:-0.44,95% CI:-0.67 to-0.20,P=0.0003),foveal thickness(pooled SMD=-0.39,95% CI:-0.58 to-0.19,P <0.0001),ganglion cell inner plexiform layer(SMD=-1.26,95% CI:-2.24 to-0.27,P=0.01) and macular volume(pooled SMD=-0.41,95% CI-0.76 to-0.07,P=0.02).Analysis using optical coherence tomography angiography parameters revealed mixed results between Alzheimer’s disease and controls.Superficial vessel density(pooled SMD=-0.42,95% CI:-0.68 to-0.17,P=0.0001) and deep vessel density(pooled SMD=-0.46,95% CI:-0.75 to-0.18,P=0.001) were found to be thinner in Alzheimer’s disease patients whereas the foveal avascular zone(SMD=0.84,95% CI:0.17-1.51,P=0.01) was larger in controls.Vascular density and thickness of various retinal laye rs were decreased in Alzheimer’s disease patients compared to controls.Our results provide evidence for optical coherence tomography technology having the potential to detect retinal and microvascular changes in patients diagnosed with Alzheimer’s disease and aid in monito ring and early diagnosis methods.

Pregnancy and retinal and retinal vascular complications

Pregnancy requires several changes in the body of the mother to successfully carry and deliver a child.Multiple alterations occur,including changes in cardiovascular system to meet the increased demands of the mother and placenta,the tilting of the hypercoagulable status to a more pro-coagulable state to prevent excessive blood loss post-delivery,and immunologic manipulations to protect the mother and fetus and decreasing the risk of a fatal immunologic response to the allogeneic fetus.These alterations are physiologically normal and expected,but can become pathologic when thresholds are crossed.Pregnancy may cause or exacerbate underlying retinal vascular diseases,a class of disorders compromised predominantly of retinal vein occlusion(RVO),retinal artery occlusion(RAO),central serous retinopathy(CSR),diabetic retinopathy,and hypertensive-related retinopathy,which includes pre-eclampsia,eclampsia,and hemolysis,elevated liver enzymes,and low platelets(HELLP)syndrome.The majority of the literature on retinal changes associated with pregnancy has focused on diabetic retinopathy,while the knowledge regarding the pathogenesis and treatment options of other pregnancy-related vascular diseases remains scarce.Understanding the implications pregnancy has on these rare,but severe,retinal vascular complications can help guide clinical management and potential treatment modalities.This paper aims to serve as a review of the retinal manifestations of diseases outside of diabetic retinopathy.

Mixed Connective Tissue Disease Complicated by Retinal Microvasculopathy and Its Relationship with Fragile-X Syndrome

Purpose: To report an unusual case of retinal microvasculopathy secondary to mixed connective tissue disease (MCTD) on a background history of fragile-X syndrome (FXS). Methods: Case report and literature review. Results: A cotton wool spot was discovered in a 29-year-old female who presented with an ischaemic digit secondary to Raynaud’s phenomenon. She also has a background history of MCTD and FXS. Fundus examination and automated perimetry findings were normal. Magnet resonance imaging and computed tomography aortogram did not demonstrate any evidence of vasculitis in the head and neck. She was tested positively for U1-ribonuclear peptide. Interestingly, the re-distribution of Fragile-X related gene 1 has been suggested to trigger autoimmune responses in experiments. This finding makes the case peculiar as it suggests an alternate explanation for this patient’s clinical findings. Conclusion: Retinal vasculopathy is a rare complication of MCTD. The background history of FXS potentially highlights an alternate autoimmune pathogenetic mechanism.

Ultrasonic evaluation of central retinal artery hemodynamics in patients with hypertensive disorder complicating pregnancy and the correlation with disease

Objective:To study the correlation between central retinal artery hemodynamic characteristics in patients with hypertensive disorder complicating pregnancy and endothelial injury molecules as well as trophoblast cell apoptosis molecules.Methods: 45 healthy pregnant women, 37 patients with gestational hypertension and 24 patients with preeclampsia who gave birth in Obstetrics Department of our hospital between May 2013 and December 2015 were selected and included in the control group, GH group and PE group respectively. Central retinal artery ultrasonography was done to determine peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI), serum was collected to determine interleukin-6 (IL-6), IL-17, IL-24, chemokine ligand 10 (CXCL10) and cartilage glycoprotein 40 (YKL40) content, and placenta tissue was collected to determine Fas, FasL, Bax, Caspase-3, Caspase-9, XIAP, Survivin and Livin expression.Results: Central retinal artery PSV and EDV as well as XIAP, Survivin and Livin expression in placenta of GH group and PE group were significantly lower than those of control group (P<0.05) while central retinal artery RI, serum IL-6, IL-17, IL-24, CXCL10 and YKL40 content as well as Fas, FasL, Bax, Caspase-3 and Caspase-9 expression in placenta were significantly higher than those of control group (P<0.05). Central retinal artery PSV and EDV as well as XIAP, Survivin and Livin expression in placenta of PE group were significantly lower than those of GH group (P<0.05) while central retinal artery RI, serum IL-6, IL-17, IL-24, CXCL10 and YKL40 content as well as Fas, FasL, Bax, Caspase-3 and Caspase-9 expression in placenta were significantly higher than those of GH group (P<0.05). Serum IL-6, IL-17, IL-24, CXCL10 and YKL40 content as well as Fas, FasL, Bax, Caspase-3 and Caspase-9 expression in placenta were negatively correlated with PSV and EDV, and positively correlated with RI;XIAP, Survivin and Livin expression in placenta were positively correlated with PSV and EDV, and negatively correlated with RI. Conclusions:Central retinal artery blood flow characteristics in patients with hypertensive disorder complicating pregnancy are the significantly increased blood flow resistance and the significantly decreased blood flow volume, and the above blood flow characteristics are associated with maternal endothelial injury and trophoblast cell apoptosis.

Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues.Pyrroloquinoline quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary administration.Pyrroloquinoline quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many studies.In this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian life.Through the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and death.Pyrroloquinoline quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully elucidated.Here,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological contexts.In addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

Indirubin alleviates retinal neurodegeneration through the regulation of PI3K/AKT signaling

Retinal neurodegenerative disease is a leading cause of blindness among the elderly in developed countries,including glaucoma,diabetic retinopathy,traumatic optic neuropathy and optic neuritis,etc.The current clinical treatment is not very effective.We investigated indirubin,one of the main bioactive components of the traditional Chinese medicine Danggui Longhui Pill,in the present study for its role in retinal neurodegeneration.Indirubin exhibited no detectable tissue toxicity in vivo or cytotoxicity in vitro.Moreover,indirubin improved visual function and ameliorated retinal neurodegeneration in mice after optic nerve crush injury in vivo.Furthermore,indirubin reduced the apoptosis of retinal ganglion cells induced by oxidative stress in vitro.In addition,indirubin significantly suppressed the increased production of intracellular reactive oxygen species and the decreased activity of superoxide dismutase induced by oxidative stress.Mechanically,indirubin played a neuroprotective role by regulating the PI3K/AKT/BAD/BCL-2 signaling.In conclusion,indirubin protected retinal ganglion cells from oxidative damage and alleviated retinal neurodegeneration induced by optic nerve crush injury.The present study provides a potential therapeutic medicine for retinal neurodegenerative diseases.

N-acetylserotonin alleviates retinal ischemia-reperfusion injury via HMGB1/RAGE/NF-κB pathway in rats

AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling pathway.METHODS:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye.Eighty male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)counting.The expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot analysis.The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats.With NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression.Additionally,NAS exhibited an anti-inflammatory effect by reducing IL-1βexpression.The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR rats.CONCLUSION:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.

How inflammation influences psychiatric disease

Recent studies highlight the strong correlation between infectious diseases and the development of neuropsychiatric disorders.In this editorial,we comment on the article“Anti-infective therapy durations predict psychological stress and laparoscopic surgery quality in pelvic abscess patients”by Zhang et al,published in the recent issue of the World Journal of Psychiatry 2023;13(11):903-911.Our discussion highlighted the potential consequences of anxiety,depression,and psychosis,which are all linked to bacterial,fungal,and viral infections,which are relevant to the impact of inflammation on the sequelae in mental health as those we are observing after the coronavirus disease 2019 pandemic.We focus specifically on the immune mechanisms triggered by inflammation,the primary contributor to psychiatric complications.Importantly,pathophysiological mechanisms such as organ damage,post-injury inflammation,and infectioninduced endocrine alterations,including hypocortisolism or autoantibody formation,significantly contribute to the development of chronic low-grade inflammation,promoting the emergence or development of psychiatric alterations in susceptible individuals.As inflammation can have long-term effects on patients,a multidisciplinary treatment plan can avoid complications and debilitating health issues,and it is crucial to recognize and address the mental health implications.