Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

Advancing healthcare through laboratory on a chip technology:Transforming microorganism identification and diagnostics

In a recent case report in the World Journal of Clinical Cases,emphasized the crucial role of rapidly and accurately identifying pathogens to optimize patient treatment outcomes.Laboratory-on-a-chip(LOC)technology has emerged as a transformative tool in health care,offering rapid,sensitive,and specific identification of microorganisms.This editorial provides a comprehensive overview of LOC technology,highlighting its principles,advantages,applications,challenges,and future directions.Success studies from the field have demonstrated the practical benefits of LOC devices in clinical diagnostics,epidemiology,and food safety.Comparative studies have underscored the superiority of LOC technology over traditional methods,showcasing improvements in speed,accuracy,and portability.The future integration of LOC with biosensors,artificial intelligence,and data analytics promises further innovation and expansion.This call to action emphasizes the importance of continued research,investment,and adoption to realize the full potential of LOC technology in improving healthcare outcomes worldwide.

Multi-Step Clustering of Smart Meters Time Series:Application to Demand Flexibility Characterization of SME Customers

Customer segmentation according to load-shape profiles using smart meter data is an increasingly important application to vital the planning and operation of energy systems and to enable citizens’participation in the energy transition.This study proposes an innovative multi-step clustering procedure to segment customers based on load-shape patterns at the daily and intra-daily time horizons.Smart meter data is split between daily and hourly normalized time series to assess monthly,weekly,daily,and hourly seasonality patterns separately.The dimensionality reduction implicit in the splitting allows a direct approach to clustering raw daily energy time series data.The intraday clustering procedure sequentially identifies representative hourly day-unit profiles for each customer and the entire population.For the first time,a step function approach is applied to reduce time series dimensionality.Customer attributes embedded in surveys are employed to build external clustering validation metrics using Cramer’s V correlation factors and to identify statistically significant determinants of load-shape in energy usage.In addition,a time series features engineering approach is used to extract 16 relevant demand flexibility indicators that characterize customers and corresponding clusters along four different axes:available Energy(E),Temporal patterns(T),Consistency(C),and Variability(V).The methodology is implemented on a real-world electricity consumption dataset of 325 Small and Medium-sized Enterprise(SME)customers,identifying 4 daily and 6 hourly easy-to-interpret,well-defined clusters.The application of the methodology includes selecting key parameters via grid search and a thorough comparison of clustering distances and methods to ensure the robustness of the results.Further research can test the scalability of the methodology to larger datasets from various customer segments(households and large commercial)and locations with different weather and socioeconomic conditions.

Foot reflexology in autoimmune diseases:Effectiveness and mechanisms

Foot reflexology(FR)is a Chinese-originated and non-invasive complementary therapy increasingly used by functional,alternative and para-medical professionals.Enhance attempts are made to study FR in non-functional organic conditions.The present invited Editorial discusses the application of FR in autoimmune diseases(AD),highlighting a few successful studies demonstrating symptomatic relief and objective improvements.Despite promising results,the FR domain remains under-investigated and an urgent need to confirm and understand the effect of FR in chronic diseases,including AD,is highly recommended.

Evidence supporting the relationship between maternal asthma and risk for autism spectrum disorders

During pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing fetus.MIA has been associated with an increased risk of neurodevelopmental disorders,such as autism spectrum disorder(ASD)in the offspring.ASD is characterized by increased repetitive and stereotyped behaviors and decreased sociability.As of 2020,1 in 36 children are diagnosed with ASD by the age of 8 years,with ASD rates continuing to increase in prevalence in USA(Tamayo et al.,2023).Post-mortem brain studies,biomarker and transcriptomic studies,and epidemiology studies have provided compelling evidence of immune dysregulation in the circulation and brain of individuals diagnosed with ASD.Currently,the etiology of ASD is largely unknown,however,genetic components and environmental factors can contribute to increased susceptibility.Maternal allergic asthma(MAA),a form of MIA,has been identified as a potential risk factor for developing neurodevelopmental disorders(Patel et al.,2020).Asthma is a chronic inflammatory condition driven by a T-helper type(TH)2 immune response.

Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is well-documented.Nevertheless,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely understudied.The release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the penumbra.Our findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma concentrations.These amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate receptors.Blocking N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during hypoxia.It is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor activation.Thus,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain injury.Understanding these pathways co uld highlight new therapeutic targets to mitigate brain injury.

Link between caries,periodontitis,and pregnancy:The role of personalized oral hygiene

Optimal health during pregnancy is crucial for ensuring the well-being of the mother and the developing fetus.This article is focused on the impact of oral health and the role of personalized oral hygiene management in addressing prevalent dental issues among pregnant women,with particular emphasis on periodontal disease and dental caries.Despite the high prevalence of these dental problems and their association with obstetric complications such as pre-term birth and low birth weight,many pregnant women do not receive adequate dental care.This gap in care is often due to misconceptions about the safety of dental treat-ments during pregnancy and lack of awareness on the part of healthcare profes-sionals.Appreciations of the impacts of oral health and personalization of oral hygiene strategies such as tailored education and support,have proven effective in improving oral health in this population.Significant reductions in the incidence of caries and periodontal disease may be achieved by adapting care to the specific needs of each patient,thereby enhancing maternal and fetal health outcomes.Integration of personalized oral hygiene management into maternal health pro-grams and enhancement of ongoing education for pregnant women and healthcare professionals are essential steps in the reduction of pregnancy-related risks and improvement of maternal and neonatal well-being.Core Tip:In this article,we reviewed a recent study on the effects of personalized oral hygiene management on the oral health of pregnant women,as discussed in the article by Men et al.The study demonstrated that personalized oral hygiene interventions significantly improved oral health outcomes during pregnancy by reducing the prevalence of dental caries and periodontal disease.We emphasized the importance of individualized oral care programs that integrate education and tailored support,and we highlighted their significance in enhancing maternal and fetal health.This approach underscores the need for incorporating personalized oral hygiene management into routine prenatal care in order to optimize health outcomes.CONCLUSION This article emphasizes the critical role of personalized oral hygiene management in improving oral health during pregnancy.By tailoring oral care strategies to individual needs,significant improvements in dental health may be achieved,as evidenced by the reduced CAT scores observed in the experimental group in the study by Men et al[25].This personalized approach not only addresses common oral issues such as dental caries and periodontal disease but also underscores the broader implications for maternal and fetal health.Despite the positive results,there remains a gap in consistency in the application of oral health practices during pregnancy,partly due to misconceptions and lack of awareness among patients and healthcare providers.Future research should aim at validating these findings across diverse populations,investigating the impact of oral hygiene interventions at various stages of pregnancy,and evaluating their long-term effects on maternal and fetal health.Integrating personalized oral hygiene management into maternal health programs and promoting continuous education for pregnant women and healthcare professionals are essential steps toward enhancing overall health outcomes.By proactively managing oral health,the risks associated with pregnancy may be reduced while improving maternal and neonatal well-being.

Syndecans in Alzheimer's disease:pathogenetic mechanisms and potential therapeutic targets

With increasing age,humans become more susceptible to the onset of neurodegenerative diseases(NDs),and among these,Alzheimer's disease(AD)is the most frequent(Nicoletti et al.,2023).NDs are primarily characterized by neuronal loss and atrophy,but also by lesions involving the cerebral and/or cardiovascular system(Balistreri,2021).Lesions such as macroinfa rcts,microinfarcts,hemorrhages,white matter lesions,atherosclerosis,and arteriolosclerosis have also been significantly described in the preclinical stages of cognitive impairment characterizing NDs(Mariani et al.,2007).

Effect of esketamine on reducing postpartum pain and depression

In this editorial,we comment on a recent article by Chen et al,that addressed the effect of intraoperative injection of esketamine on postoperative analgesia and postoperative rehabilitation after cesarean section.Poor management of postcesarean pain is associated with decreased maternal care for the baby,longer hospitalization,and higher risk of developing postpartum depression.Esketamine is a more potent S-enantiomer of ketamine which has shown promising analgesic and antidepressant properties for managing post-cesarean pain and depression in clinical studies.However,due to its potential adverse effects on the neurological and hemodynamic status of patients,it is recommended that its usage in low doses should be limited to cesarean candidates experiencing unbearable pain.Before any recommendation for routine perioperative use of esketamine,more standardized clinical trials are needed to strengthen our existing knowledge of its effectiveness in reducing postpartum pain and depression.

Macular microvascular and structural changes on optical coherence tomography angiography in atypical optic neuritis

BACKGROUND Atypical optic neuritis,consisting of neuromyelitis optica spectrum disorders(NMOSD)or myelin oligodendrocyte glycoprotein antibody disease(MOGAD),has a very similar presentation but different prognostic implications and longterm management strategies.Vascular and metabolic factors are being thought to play a role in such autoimmune neuro-inflammatory disorders,apart from the obvious immune mediated damage.With the advent of optical coherence tomography angiography(OCTA),it is easy to pick up on these subclinical macular microvascular and structural changes.AIM To study the macular microvascular and structural changes on OCTA in atypical optic neuritis.METHODS This observational cross-sectional study involved 8 NMOSD and 17 MOGAD patients,diagnosed serologically,as well as 10 healthy controls.Macular vascular density(MVD)and ganglion cell+inner plexiform layer thickness(GCIPL)were studied using OCTA.RESULTS There was a significant reduction in MVD in NMOSD and MOGAD affected as well as unaffected eyes when compared with healthy controls.NMOSD and MOGAD affected eyes had significant GCIPL thinning compared with healthy controls.NMOSD unaffected eyes did not show significant GCIPL thinning compared to healthy controls in contrast to MOGAD unaffected eyes.On comparing NMOSD with MOGAD,there was no significant difference in terms of MVD or GCIPL in the affected or unaffected eyes.CONCLUSION Although significant microvascular and structural changes are present on OCTA between atypical optic neuritis and normal patients,they could not help in differentiating between NMOSD and MOGAD cases.

Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons.Neuroinflammation has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be determined.Human leukocyte antigen.

Cardiovascular involvement in multisystem inflammatory syndrome in children and midterm follow-up from a pediatric tertiary center in India

BACKGROUND In multisystem inflammatory syndrome in children(MIS-C)with coronavirus disease 2019,there was paucity of data from low-income and middle-income countries on cardiovascular involvement and its longitudinal outcomes.We planned to estimate the pattern of cardiovascular involvement among children with MIS-C and its mid-term outcomes.AIM To determine association between cardiovascular abnormalities and clinical and laboratory parameters.To study the time-line for resolution of various abnormalities.METHODS In this prospective study done in a tertiary care hospital,270 were recruited from June 2020 to January 2022.Baseline demographic data and clinical presentation were recorded.Laboratory parameters and echocardiography were done at admission.Follow-up was done at 2 weeks,3 months,6 months and 1 year after diagnosis.Descriptive statistics were used for parametric and non-parametric data.Risk factors were identified by multivariate regression analysis.RESULTS The 211(78.2%)had cardiac involvement and 102 needed intensive care unit(ICU)admission.Cardiovascular abnormalities observed were shock 123(45.6%),coronary dilatation 28(10.4%),coronary aneurysm 77(28.5%),left ventricular(LV)dysfunction 78(29.3%),mitral regurgitation(MR)77(28.5%)and pericardial effusion 98(36.3%).Coronary artery aneurysm/dilatation during follow-up at 2 weeks and 1 year were 25.7%and 0.9%respectively.Multivariate regression analysis revealed breathlessness[odds ratio(OR)=3.91,95%CI:1.25-12.21,P=0.019]and hi-flow nasal cannula(HFNC)support(OR=8.5,95%CI:1.06-68.38,P=0.044)as predictors of cardiovascular involvement.Higher mean age(OR=1.16,95%CI:1.02-1.32,P=0.026),breathlessness(OR=4.99,95%CI:2.05-12.20,P<0.001),gallop(OR=4.45,95%CI:0.41-2.52,P=0.016),MR(OR=3.61,95%CI:1.53-8.53,P=0.004)and invasive ventilation(OR=4.01,95%CI:1.28-12.58,P=0.017)were predictive of LV dysfunction.Altered sensorium(OR=4.96,95%CI:2.23-11.02,P<0.001),headache(OR=6.61,95%CI:1.46-29.92,P=0.014),HFNC(OR=7.03,95%CI:2.04-24.29,P=0.002),non-rebreathing mask usage(OR=21.13,95%CI:9.00-49.61,P<0.001)and invasive ventilation(OR=5.64,95%CI:1.42-22.45,P=0.014)were risk factors for shock.Anemia was a risk factor for coronary involvement(OR=3.09,95%CI:1.79-5.34,P<0.001).CONCLUSION Significant number of children with MIS-C had cardiovascular involvement contributing to higher ICU management.Although shock resolved quickly,resolution of ventricular function and coronary abnormalities were slower,and hence warrants a structured long-term follow-up protocol.

Efficacy of antimicrobials in preventing resistance in solid organ transplant recipients:A systematic review of clinical trials

BACKGROUND In the absence of effective antimicrobials,transplant surgery is not viable,and antirejection immunosuppressants cannot be administered,as resistant infections compromise the life-saving goal of organ transplantation.AIM To evaluate the efficacy of antimicrobials in preventing resistance in solid organ transplant recipients.METHODS A systematic review was conducted using a search methodology consistent with the preferred reporting items for systematic reviews and meta-analyses.This review included randomized clinical trials that evaluated the efficacy of antimicrobial agents(prophylactic or therapeutic)aimed at preventing antimicrobial resistance.The search strategy involved analyzing multiple databases,including PubMed/MEDLINE,Web of Science,Embase,Scopus,and SciELO,as well as examining gray literature sources on Google Scholar.A comprehensive electronic database search was conducted from the databases’inception until May 2024,with no language restrictions.RESULTS After the final phase of the eligibility assessment,this systematic review ultimate-ly included 7 articles.A total of 2318 patients were studied.The most studied microorganisms were cytomegalovirus,although vancomycinresistant enterococci,Clostridioides difficile,and multidrug-resistant Enterobacterales were also analyzed.The antimicrobials used in the interventions were mainly maribavir,valganciclovir,gancic-lovir,and colistin-neomycin.Of concern,all clinical trials showed significant proportions of resistant microorga-nisms after the interventions,with no statistically significant differences between the groups(mean resistance 13.47%vs 14.39%),except for two studies that demonstrated greater efficacy of maribavir and valganciclovir(mean resistance 22.2%vs 41.1%in the control group;P<0.05).The total reported deaths in three clinical trials were 75,and there were 24 graft rejections in two studies.CONCLUSION All clinical trials reported significant proportions of antimicrobial-resistant microorganisms following interventions.More high-quality randomized clinical trials are needed to corroborate these results.

The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic pain.Sprouting can lead to the formation of new connections triggering abnormal sensory transmission.The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity.Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen.In this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury.We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting.Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical allodynia.Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent effect.The expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes.Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents.Analyses of peptidergic(calcitonin gene-related peptide-α)and non-peptidergic(isolectin B4)fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/isolectin B4 ratio in comparison with sham,suggesting increased receptive fields in the dorsal horn.Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats,this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury.Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord.The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain,an area with a critical need for treatment.

Tongluo Jiedu as an adjuvant therapy for oral cancer

Oral cancer is one of the malignant neoplasms that present major global health challenge.It is the sixth most prevalent type of cancer in the world,with a high incidence and mortality rate.This letter is a review of the study by Yin et al which was published in the World Journal of Clinical Cases(2024).The study evaluated the effect of Tongluo Jiedu as an adjuvant treatment for oral cancer.Over the years,there has been a continuous search for effective and less invasive treatments for oral cancer.This article emphasizes and discusses various therapeutic options currently available,and it highlights that early intervention and multidisciplinary management are crucial for improving outcomes.Traditional Chinese medicine,particularly Tongluo Jiedu,presents potential complementary approach to co-nventional oral cancer therapies.Future research on Tongluo Jiedu should be focused on validation of its efficacy and safety through large,well-designed clinical trials,as well as better understanding of the molecular mechanisms in-volved,and optimization of therapeutic combinations.Additionally,continuous education of health professionals is key to the effective and safe integration of this traditional medicine into clinical practice.Continuous research is essential for optimization of therapeutic strategies and for addressing the challenges presented by this neoplasm.

Getting physical with medical education:Exercise based virtual anatomy review classes for medical students

The benefits of regular physical activity are well known.Yet,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary setting.To investigate the incorporation of PA into medical curriculum,we developed a series of optional exercise-based review sessions designed to reinforce musculoskeletal(MSK)anatomy course material.These synchronous sessions were co-taught by a group fitness instructor and an anatomy instructor.The fitness instructor would lead students through both strength and yoga style exercises,while the anatomy instructor asked questions about relevant anatomical structures related to course material previously covered.After the sessions,participants were asked to evaluate the classes on their self-reported exam preparedness in improving MSK anatomy knowledge,PA levels,and mental wellbeing.Thirty participants completed surveys;a majority agreed that the classes increased understanding of MSK concepts(90.0%)and activity levels(97.7%).Many(70.0%)felt that the classes helped reduce stress.The majority of respondents(90.0%)agreed that the classes contributed to increased feelings of social connectedness.Overall,medical students saw benefit in PA based interventions to supplement MSK course concepts.Along with increasing activity levels and promoting health behaviours,integrating PA into medical curriculum may improve comprehension of learning material,alleviate stress and foster social connectivity among medical students.

Current and future perspectives in the management and treatment of colorectal cancer

In this editorial,we reviewed the article by Fadlallah et al that was recently published in the World Journal of Clinical Oncology.The article provided a comprehensive and in-depth view of the management and treatment of colorectal cancer(CRC),one of the leading causes of cancer-related morbidity and mortality worldwide.The article analyzed the therapeutic modalities and their sequencing,focusing on total neoadjuvant therapy for locally advanced rectal cancer.It highlighted the role of immunotherapy in tumors with high microsatellite instability or deficient mismatch repair,addressing recent advances that have improved prognosis and therapeutic response in localized and metastatic CRC.Innovations in surgical techniques,advanced radiotherapy,and systemic agents targeting specific mutational profiles are also discussed,reflecting on how they revolutionized clinical management.Circulating tumor DNA has emerged as a promising tool for detecting minimal residual disease,prognosis,and therapeutic monitoring,solidifying its role in precision oncology.This review emphasized the importance of technological and therapeutic advancements in improving clinical outcomes and personalizing CRC treatment.

A novel flexible nerve guidance conduit promotes nerve regeneration while providing excellent mechanical properties

Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduits may be used.The ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve regeneration.We designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align them.Subsequently,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber lumen.The presence of aligned fibers on the inner surface can promote the extension of nerve cells along the fibers.The helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide stability.Our novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.

Reassessing the AMPK-MTORC1 balance in autophagy in the central nervous system

Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and function.This cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino acids.This process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein markers.Some of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).

Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.