Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.

Levels of Empathy among Dental Students in Five Chilean Universities

Aim: To compare empathic levels among dental students of five Dental Faculties in Chile. Material and Methods: Empathic orientation of dental students was measured using the Jefferson Scale of Physician Empathy, the Spanish version for students (S version), validated in Chile and culturally adapted to dental students. The data were compared using analysis of variance trifactorial (model III) and by a discriminant analysis. Results: It was found that differences exist between universities empathic orientation, courses, and gender. Conclusions: The results showed a great variability of empathetic guidance values on the factors studied. Discriminant test confirm the similarity and differences found among faculties from the data matrix provided by the scale used. It is not possible in this investigation to explain the variability found.

Comparative effects of different types of exercise on health-related quality of life during and after active cancer treatment:A systematic review and network meta-analysis

Background The positive influence of most types of exercise has been reported repeatedly,but what the most effective exercise approaches are for improving health-related quality of life(HRQoL)in people with cancer remains unknown.The aim of this systematic review and network meta-analysis was to synthesize the evidence from intervention studies to assess the effects of different types of exercise on HRQoL during and after cancer treatment.Methods MEDLINE,SPORTDiscus,the Cochrane Library,Web of Science,and Scopus were searched for randomized controlled trials aimed at testing the effects of exercise interventions meant to improve HRQoL in people with cancer.Separate analyses were conducted for HRQoL as measured by general and cancer-specific questionnaires.We also evaluated whether the effects of exercise were different during and after cancer treatment in both the physical and mental HRQoL domains.Results In total,93 studies involving 7435 people with cancer were included.Network effect size estimates comparing exercise intervention vs.usual care were significant for combined exercise(0.35,95%confidence interval(95%CI):0.14–0.56)for HRQoL as measured by general questionnaires,and for combined(0.31,95%CI:0.13–0.48),mind–body exercise(0.54,95%CI:0.18–0.89),and walking(0.39,95%CI:0.04–0.74)for HRQoL as measured by cancer-specific questionnaires.Conclusion Exercise programs combining aerobic and resistance training can be recommended to improve HRQoL during and after cancer treatment.The scarcity and heterogeneity of these studies prevents us from making recommendations about other exercise modalities due to insufficient evidence.

Immediate effect of high-intensity exercise on brain-derived neurotrophic factor in healthy young adults:A systematic review and meta-analysis

Background Although brain-derived neurotrophic factor(BDNF)has been identified as a molecular biomarker of the neurophysiological effects induced by exercise,the acute effects of high-intensity exercise(HIE)on BDNF levels are inconclusive.This study aims to estimate the immediate effects of HIE on BDNF levels in healthy young adults.Methods A systematic search was conducted in the MEDLINE,Scopus,Cochrane CENTRAL,and SPORTDiscuss databases up to December 2020.Randomized controlled trials(RCTs)and non-RCTs reporting pre-post changes in serum or plasma BDNF after an acute intervention of HIE compared to a control condition were included.Pooled effect sizes(p-ESs)and 95%confidence intervals(95%CIs)were calculated for RCTs using a random effects model with Stata/SE(Version 15.0;StataCorp.,College Station,TX,USA).The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.PROPERO registration number:CRD42020221047.Results A total of 22 studies with 552 individuals(age range:20-31 years;59.1%male)were included.The meta-analysis included 10 RCTs that reported valid outcome data.Higher BDNF levels were observed when HIE interventions were compared with non-exercise(p-ES=0.55,95%CI:0.12-0.98;I^(2)=25.7%;n=4 studies)and light-intensity exercise(p-ES=0.78,95%CI:0.15-1.40;I^(2)=52.4%;n=3 studies)but not moderate-intensity exercise(p-ES=0.93,95%CI:-0.16 to 2.02;I^(2)=88.5%;n=4 studies)conditions.Conclusion In comparison to non-exercise or light-intensity exercises,an immediate increase in BDNF levels may occur when young adults perform HIE.Given the benefits obtained maximizing circulating BDNF when performing HIE and its potential effects on brain health,our findings suggest that HIE could be recommended by clinicians as a useful exercise strategy to healthy adults.

Glial-derived transforming growth factor β1(TGF-β1):a key factor in multiple sclerosis neuroinflammation

Glial cell activation and neuroinflammation in multiple sclerosis(MS):MS is an irreversible and progressive central nervous system(CNS)disease which originates in the autoimmune attack of lymphocytes against CNS myelin.This specialized membrane,synthesized by oligodendrocytes(OL)in the CNS,provides metabolic support to axons and allows for saltatory conduction in neurons.The lack of myelin(i.e.,demyelination)leads to axonal degeneration,neuronal death,and the consequent neurological disabilities(Franklin and Ffrench-Constant,2017).

Empathy Levels of Dental Students of Central America and the Caribbean

Objective: The aim of this study is to check whether there are differences in the distribution of empathy levels in dental students from nine faculties of dentistry Colombia, Panama, Costa Rica and Dominican Republic. Methods: The levels of empathy and matrices of empathy construct matrices are estimated dental students by using the Jefferson Scale of Physician Empathy, the Spanish version for students (S version) culturally validated in Colombia, Panama, Costa Rica and Dominican Republic measured by arbitrator criteria. Cronbach α is estimated. Data of empathic orientation of the studied factors between faculties are analyzed and compared by ANOVA and Duncan test and matrices of empathy construct using discriminant analysis. Results: We find that there are differences in levels of empathy between universities, courses, gender and interaction between the Dental Faculty (University) and Course. The comparison between matrices shows unexplained variances and differences observed between the levels of empathy in student populations. Conclusions: Variability in empathy is observed in the studied factors and among student populations. The variability is an empirical finding, but is not possible in this work, to explain why.

Empathy Gender in Dental Students in Latin America: An Exploratory and Cross-Sectional Study

Background: It is well-founded that empathy is an attribute that increases the likelihood of good communication between health professionals and patients, and it is usual that there is the conviction that empathy levels are higher in women than in men. Aims: A study comparing levels of empathy gender of students in 18 schools of dentistry from six Latin American countries was conducted. Method: An exploratory cross-sectional study of which empathy levels were measured by the Jefferson Scale of Empathy for dental students (S version) and these levels were compared between genders by t-student test, after verification of normal distribution and homoscedasticity. Results: Variability was found in the results of the comparisons. In some cases, empathy levels were higher in women, others in men and in most of them there were no differences between genders. Conclusions: The observed results do not support the belief that women are more empathetic than men. However, more studies must be performed in more powers and countries to verify that the results described constitute a scientific fact and not just a feature of dental students specifically in the countries studied.

Empathy Levels of Dentistry Students in Peru and Argentina

Objectives: To compare the empathy of students in two faculties of Dentistry in Peru and Argentina, three factors were considered: universities, academic year and gender. Material and Methods: Empathy matrices in Dentistry students were measured using the Jefferson Scale of Empathy, culturally validated in Peru and Argentina. Empathy data were compared among and within the faculties tested using a three-factor analysis of variance (model III), a Duncan test, and a discriminant analysis. The level of significance used was less than 0.05. Results: We found that differences existed between the students tested. The comparison between the levels of empathy in the studied factors and the presence of unexplained variance showed that empathy was able to differentiate populations. Conclusions: The results indicate variability in the empathy values associated with the factors studied. The discriminant test confirms the differences between faculties revealed by the data matrix resulting from the JSE. These differences are possibly due to the effect of educational and social factors.

Morphometric evaluation of wound healing in burns treated with Ulmo (Eucryphia cordifolia) honey alone and supplemented with ascorbic acid in guinea pig (Cavia porcellus)

Background:In the context of the search for cost-efficient treatments,Ulmo(Eurcyphia cordifolia)honey is an excellent alternative for treating burn wounds and could have a profound medical,social,and economic impact.Ascorbic acid is an enzymatic co-factor necessary for the synthesis of collagen and the proliferation of fibroblasts and has been proposed as a coadjuvant to strengthen the healing effects of honey.The aim of this work was to evaluate by morphometric studies the healing wounds caused by burns treated with Ulmo honey alone and supplemented with ascorbic acid in guinea pig(Cavia porcellus).Methods:Fifteen guinea pigs were used and divided randomly into three groups:positive control(C+),experimental with unsupplemented honey(H),and experimental with supplemented honey(SH).A uniform deep burn covering 1 cm2of the back skin was performed.The following indices were calculated for the morphometric study:superficial contraction index of the wound,deep contraction index of the wound,wound severity index,global healing index,global contraction index,and dermal proliferation area.Results:The superficial contraction index of the wound,global healing index,global contraction,and dermal proliferation area values of the experimental with supplemented honey group were higher than the other groups(P<0.05).Conclusions:According to these results,the combination of honey with an antioxidant(ascorbic acid)promotes an appropriate action to support the healing effect.This study showed that by supplementing the Ulmo honey with ascorbic acid,the healing and contraction effects can be strengthened in burn wounds compared to unsupplemented honey.These results were proof of the synergy between honey and ascorbic acid in healing burn wounds.

The molecular interaction of ADAMTS-1 and fibulin-1 and its potential contribution to breast cancer biology

Aim: Fibulins and ADAMTSs are two families of extracellular matrix proteins implicated in key functional and pathological processes. The fact that the fibulin-1 and ADAMTS-1 proteins interact raises new questions about the roles of these extracellular matrix proteins in modulating tumor progression. Herein, we described the functional implications of the interaction between fibulin-1 and ADAMTS-1 on the behavior of breast cancer cell lines. Methods: Fibulin-1 and ADAMTS-1 were exogenously expressed in MCF-7 and MDA-MB-231 cell lines to assay the effect of their interaction in cellular properties. Results: ADAMTS-1 expression exacerbates tumor effects in terms of proliferation, invasion and mammosphere formation. In contrast, the simultaneous expression of ADAMTS-1 and fibulin-1 impairs these effects. The analysis of the expression of both proteins in human breast cancer tissue arrays provides new insights into the complex roles of fibulin-1 and ADAMTS-1 in this type of tumor. ;Conclusion: Our results suggests that the interaction between ADAMTS-1 and fibulin-1 induces a pronounced anti-tumoral effect.

The use of fibroblasts as a valuable strategy for studying mitochondrial impairment in neurological disorders

Neurological disorders(NDs)are characterized by progressive neuronal dysfunction leading to synaptic failure,cognitive impairment,and motor injury.Among these diseases,Alzheimer’s disease(AD),Parkinson’s disease(PD),Huntington’s disease(HD),and amyotrophic lateral sclerosis(ALS)have raised a significant research interest.These disorders present common neuropathological signs,including neuronal dysfunction,protein accumulation,oxidative damage,and mitochondrial abnormalities.In this context,mitochondrial impairment is characterized by a deficiency in ATP production,excessive production of reactive oxygen species,calcium dysregulation,mitochondrial transport failure,and mitochondrial dynamics deficiencies.These defects in mitochondrial health could compromise the synaptic process,leading to early cognitive dysfunction observed in these NDs.Interestingly,skin fibroblasts from AD,PD,HD,and ALS patients have been suggested as a useful strategy to investigate and detect early mitochondrial abnormalities in these NDs.In this context,fibroblasts are considered a viable model for studying neurodegenerative changes due to their metabolic and biochemical relationships with neurons.Also,studies of our group and others have shown impairment of mitochondrial bioenergetics in fibroblasts from patients diagnosed with sporadic and genetic forms of AD,PD,HD,and ALS.Interestingly,these mitochondrial abnormalities have been observed in the brain tissues of patients suffering from the same pathologies.Therefore,fibroblasts represent a novel strategy to study the genesis and progression of mitochondrial dysfunction in AD,PD,HD,and ALS.This review discusses recent evidence that proposes fibroblasts as a potential target to study mitochondrial bioenergetics impairment in neurological disorders and consequently to search for new biomarkers of neurodegeneration.

Recovering information in probabilistic quantum teleportation

In this paper we redesign the probabilistic teleportation scheme considered in Phys.Rev.A 61,034301(2000)by Wan-Li Li et al.,where the optimal state extraction protocol complements the basic teleportation process with a partially entangled pure state channel,in order to transfer the unknown state with fidelity 1.Unlike that scheme,where the information of the unknown state is lost if the state extraction fails,our proposal teleports exactly and optimally an unknown state,and allows to recover faithfully that state when the process has not succeeded.In order to study the resilience of the scheme,we apply it to the teleportation problem through a quantum channel in a mixed state with pure dephasing.We find that a successful process transfers an unfaithful state,namely,the outcome state acquires the decoherence of the channel,but the unknown state is recovered by the sender with fidelity 1 if the teleportation fails.In addition,in this case,the fidelity of the teleported state has quantum features only if the channel has an amount of entanglement different from zero.