P-aminobenzoic acid promotes retinal regeneration through activation of Ascl1a in zebrafish

The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabolites and retinal regeneration of zebrafish.Here,we performed an unbiased metabolome sequencing in the N-methyl-D-aspartic acid-damaged retinas of zebrafish to demonstrate the metabolomic mechanism of retinal regeneration.Among the differentially-ex pressed metabolites,we found a significant decrease in p-aminobenzoic acid in the N-methyl-D-aspartic acid-damaged retinas of zebrafish.Then,we investigated the role of p-aminobenzoic acid in retinal regeneration in adult zebrafish.Impo rtantly,p-aminobenzoic acid activated Achaetescute complex-like 1a expression,thereby promoting Müller glia reprogramming and division,as well as Müller glia-derived progenitor cell proliferation.Finally,we eliminated folic acid and inflammation as downstream effectors of PABA and demonstrated that PABA had little effect on Müller glia distribution.Taken together,these findings show that PABA contributes to retinal regeneration through activation of Achaetescute complex-like 1a expression in the N-methyl-Daspartic acid-damaged retinas of zebrafish.

PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons

PANoptosis is a newly identified type of regulated cell death that consists of pyroptosis,apoptosis,and nec roptosis,which simultaneously occur during the pathophysiological process of infectious and inflammatory diseases.Although our previous lite rature mining study suggested that PANoptosis might occur in neuronal ischemia/repe rfusion injury,little experimental research has been reported on the existence of PANoptosis.In this study,we used in vivo and in vitro retinal neuronal models of ischemia/repe rfusion injury to investigate whether PAN optosis-like cell death(simultaneous occurrence of pyroptosis,apo ptosis,and necroptosis)exists in retinal neuronal ischemia/repe rfusion injury.Our results showed that ischemia/repe rfusion injury induced changes in morphological features and protein levels that indicate PANoptosis-like cell death in retinal neurons both in vitro and in vivo.Ischemia/repe rfusion inju ry also significantly upregulated caspase-1,caspase-8,and NLRP3 expression,which are important components of the PANoptosome.These results indicate the existence of PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons and provide preliminary experimental evidence for future study of this new type of regulated cell death.

Therapeutic role of growth factors in treating diabetic wound

Wounds in diabetic patients,especially diabetic foot ulcers,are more difficult to heal compared with normal wounds and can easily deteriorate,leading to amputation.Common treatments cannot heal diabetic wounds or control their many complications.Growth factors are found to play important roles in regulating complex diabetic wound healing.Different growth factors such as transforming growth factor beta 1,insulin-like growth factor,and vascular endothelial growth factor play different roles in diabetic wound healing.This implies that a therapeutic modality modulating different growth factors to suit wound healing can significantly improve the treatment of diabetic wounds.Further,some current treatments have been shown to promote the healing of diabetic wounds by modulating specific growth factors.The purpose of this study was to discuss the role played by each growth factor in therapeutic approaches so as to stimulate further therapeutic thinking.

The regulatory role of Pin1 in neuronal death

Regulated cell death predominantly involves apoptosis,autophagy,and regulated necrosis.It is vital that we understand how key regulatory signals can control the process of cell death.Pin1 is a cis-trans isomerase that catalyzes the isomerization of phosphorylated serine or threonine-proline motifs of a protein,thereby acting as a crucial molecular switch and regulating the protein functionality and the signaling pathways involved.However,we know very little about how Pin1-associated pathways might play a role in regulated cell death.In this paper,we review the role of Pin1 in regulated cell death and related research progress and summarize Pin1-related pathways in regulated cell death.Aside from the involvement of Pin1 in the apoptosis that accompanies neurodegenerative diseases,accumulating evidence suggests that Pin1 also plays a role in regulated necrosis and autophagy,thereby exhibiting distinct effects,including both neurotoxic and neuroprotective effects.Gaining an enhanced understanding of Pin1 in neuronal death may provide us with new options for the development of therapeutic target for neurodegenerative disorders.

Copper Metabolism and Cuproptosis:Molecular Mechanisms and Therapeutic Perspectives in Neurodegenerative Diseases

Copper is an essential trace element,and plays a vital role in numerous physiological processes within the human body.During normal metabolism,the human body maintains copper homeostasis.Copper deficiency or excess can adversely affect cellular function.Therefore,copper homeostasis is stringently regulated.Recent studies suggest that copper can trigger a specific form of cell death,namely,cuproptosis,which is triggered by excessive levels of intracellular copper.Cuproptosis induces the aggregation of mitochondrial lipoylated proteins,and the loss of iron-sulfur cluster proteins.In neurodegenerative diseases,the pathogenesis and progression of neurological disorders are linked to copper homeostasis.This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases.This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.

p38 MAPK inhibitor SB202190 suppresses ferroptosis in the glutamate-induced retinal excitotoxicity glaucoma model

Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogenactivated protein kinase(MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.

Research trends, hot spots and prospects for necroptosis in the field of neuroscience

There are two types of cell death-apoptosis and necrosis. Apoptosis is cell death regulated by cell signaling pathways, while necrosis has until recently been considered a passive mechanism of cell death caused by environmental pressures. However, recent studies show that necrosis can also be regulated by specific cell signaling pathways. This mode of death, termed necroptosis, has been found to be related to the occurrence and development of many diseases. We used bibliometrics to analyze the global output of literature on necroptosis in the field of neuroscience published in the period 2007–2019 to identify research hotspots and prospects. We included 145 necroptosisrelated publications and 2239 references published in the Web of Science during 2007–2019. Visualization analysis revealed that the number of publications related to necroptosis has increased year by year, reaching a peak in 2019. China is the country with the largest number of publications. Key word and literature analyses demonstrated that mitochondrial function change, stroke, ischemia/reperfusion and neuroinflammation are likely the research hotspots and future directions of necroptosis research in the nervous system. The relationship between immune response-related factors, damage-associated molecular patterns, pathogen-associated molecular patterns and necroptosis may become a potential research hotspot in the future. Taken together, our findings suggest that although the inherent limitations of bibliometrics may affect the accuracy of the literature-based prediction of research hotspots, the results obtained from the included publications can provide a reference for the study of necroptosis in the field of neuroscience.

Clinical efficacy of the partial rectus muscle transportation procedure for paralytic strabismus

AIM:To analyze the clinical efficacy of the partial rectus muscle transportation(PRT)procedure for paralytic strabismus due to single rectus muscle palsy.METHODS:In total,28 patients(31 eyes)who underwent the PRT procedure for paralytic strabismus due to single rectus muscle palsy were retrospectively examined.The following data were collected pre-and postoperatively:angle of deviation in the primary position,presence of diplopia in the primary position,presence of compensatory head posture,and motility of the affected eye.The follow-up period was 6 mo.RESULTS:Based on the preoperative and intraoperative findings,different operations were performed:2 eyes were treated with PRT,26 eyes were treated with PRT combined with the recession of the antagonist muscle(Am)of the paralytic rectus muscle,and 3 eyes were treated with PRT along with the recession of the Am and the yoke muscle(Ym).On the first day after the operation,24 patients were found to be orthophoric in the primary position,without diplopia or abnormal head posture.Moreover,2 patients with monocular lateral rectus muscle palsy had mild overcorrection to 5 prism diopters(PD)and 8 PD,respectively,whereas 2 patients with binocular lateral rectus muscle palsy had mild undercorrection to 8 PD and 10 PD,respectively.During the 6-month follow-up period,the mean deviation was rectified from 96.79±41.21 PD to 0.64±2.38 PD(t=12.48,P<0.001),whereas the deviations in the 2 patients with mild overcorrection were corrected to orthotropia.The mean preoperative limitation of motility improved from-4.55±0.51 to-2.65±0.61(t=-15.13,P<0.001)after 6 mo postoperatively.CONCLUSION:PRT is an effective treatment for complete paralytic strabismus due to single rectus muscle palsy,and can achieve stable clinical efficacy.

Anti-scarring effect of sodium hyaluronate at filtration pathway after filtering surgery in rabbits

AIM: To investigate the anti-scarring effect of sodium hyaluronate(HA) at filtration pathway after filtering surgery in a rabbit model.METHODS: Fifteen healthy adult New Zealand white rabbits were selected for trabeculectomy in both eyes. The right eyes were used as HA group with 0.1 m L HA injected into the anterior chamber at the end of the operation;the left eyes were used with 0.1 m L sodium lactate Ringer’s solution(RS) injected into the anterior chamber as RS group. Intraocular pressure(IOP), filtering blebs morphology, inflammatory reaction and complications were observed at the 7, 60, and 90 d after surgery.RESULTS: One day after surgery, the IOP of HA and RS groups were 12.75±1.92 and 10.50±1.59 mm Hg(P=0.005). At the 7;day postoperative, the filtering blebs of each group were functional type and TGF-β expression was significantly difference in both groups(0.10±0.01 vs 0.14±0.02, P=0.024). After 60 d of the operation, all filtering blebs were scarring and alpha-smooth muscle actin(α-SMA) expression was significantly difference in both groups(0.40±0.04 vs 0.35±0.02, P=0.032). α-SMA positive cells were mainly distributed in the junction of conjunctiva and sclera and around the blood vessels. The collagen volume fraction(CVF) of HA and RS group was(75.49±7.01)% and(79.93±5.35)%(P=0.044). On the 90;day after the operation, CVF was(82.57±5.19)% and(88.08±1.75)% in HA and RS groups(P=0.036). There was no α-SMA positive cell in HA group, while a few positive cells were observed in RS group(P=0.000).CONCLUSION: HA has effect of anti-scar and antiinflammation on filtration pathway after filtering surgery within 3 mo by inhibiting fibroblast proliferation and collagen deposition.

Do pyroptosis, apoptosis, and necroptosis (PANoptosis) exist in cerebral ischemia? Evidence from cell and rodent studies

Some scholars have recently developed the concept of PANoptosis in the study of infectious diseases where pyroptosis,apoptosis and necroptosis act in consort in a multimeric protein complex,PANoptosome.This allows all the components of PANoptosis to be regulated simultaneously.PANoptosis provides a new way to study the regulation of cell death,in that different types of cell death may be regulated at the same time.To test whether PANoptosis exists in diseases other than infectious diseases,we chose cerebral ischemia/reperfusion injury as the research model,collected articles researching cerebral ischemia/reperfusion from three major databases,obtained the original research data from these articles by bibliometrics,data mining and other methods,then integrated and analyzed these data.We selected papers that investigated at least two of the components of PANoptosis to check its occurrence in ischemia/reperfusion.In the cell model simulating ischemic brain injury,pyroptosis,apoptosis and necroptosis occur together and this phenomenon exists widely in different passage cell lines or primary neurons.Pyroptosis,apoptosis and necroptosis also occurred in rat and mouse models of ischemia/reperfusion injury.This confirms that PANoptosis is observed in ischemic brain injury and indicates that PANoptosis can be a target in the regulation of various central nervous system diseases.

Endoplasmic reticulum stress: molecular mechanism and therapeutic targets

The endoplasmic reticulum(ER)functions as a quality-control organelle for protein homeostasis,or"proteostasis".The protein quality control systems involve ER-associated degradation,protein chaperons,and autophagy.

The national multi-center artificial intelligent myopia prevention and control project

In recent years,the incidence of myopia has increased at an alarming rate among children and adolescents in China.The exploration of an effective prevention and control method for myopia is in urgent need.With the development of information technology in the past decade,artificial intelligence with the Internet of Things technology(AIoT)is characterized by strong computing power,advanced algorithm,continuous monitoring,and accurate prediction of long-term progression.Therefore,big data and artificial intelligence technology have the potential to be applied to data mining of myopia etiology and prediction of myopia occurrence and development.More recently,there has been a growing recognition that myopia study involving AIoT needs to undergo a rigorous evaluation to demonstrate robust results.