Call for Paper from Food Science and Human Wellness

Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,biochemistry,microbiology,immunology and toxicology.

Call for Paper from Food Science and Human Wellness

Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,bio-chemistry,microbiology,immunology and toxicology.

Commentary on:“Human neural stem cell-derived artificial organelles to improve oxidative phosphorylation”

Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata et al.,2023).Mitochondrial dysfunction,characterized by an imbalance in ATP levels and excessive production of mitochondrial reactive oxygen species,is a key factor that impedes neural regeneration in neurodegenerative diseases and after neuronal injury(Han et al.,2016,2020;Zheng et al.,2016;Zong et al.,2024).

Human endogenous retrovirus type-W and multiple sclerosis–related smoldering neuroinflammation

Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.

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

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

Spatial transcriptomics combined with single-nucleus RNA sequencing reveals glial cell heterogeneity in the human spinal cord

Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous system.Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord.Here,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal cord.To explore the conservation and divergence across species,we compared these findings with those from mice.In the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic subclusters.In the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice.Additionally,we detected sex differences in gene expression in human spinal cord glial cells.Specifically,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in females.In all microglial subtypes,all differentially expressed genes were located on the sex chromosomes.In addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in males.Collectively,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cordrelated illnesses,including chronic pain,amyotrophic lateral sclerosis,and multiple sclerosis.

Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.

Exploring the role of N-acetyltransferases in diseases:a focus on N-acetyltransferase 9 in neurodegeneration

Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivotal to basic cellular processes.Close to 80%-90%of proteins are acetylated during translation,which is an irreversible process that affects protein structure,function,life,and localization.In this review,we have discussed the various N-acetyltransferases present in humans,their function,and how they might play a role in diseases.Furthermore,we have focused on N-acetyltransferase 9 and its role in microtubule stability.We have shed light on how N-acetyltransferase 9 and acetylation of proteins can potentially play a role in neurodegenerative diseases.We have specifically discussed the N-acetyltransferase 9-acetylation independent function and regulation of c-Jun N-terminal kinase signaling and microtubule stability during development and neurodegeneration.

Differences in diversity and composition of mucosa-associated colonic microbiota in colorectal cancer and non-colorectal cancer in Indonesia

BACKGROUND Colorectal cancer is the third most common malignancy and the fourth leading cause of cancer-related deaths worldwide.Several studies have shown an association between gut microbiota and colorectal cancer.Gut microbiota is unique and can be influenced by geographic factors and habits.This study aimed to determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer.AIM To determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer in Indonesia.METHODS This case-control study included 59 subjects(35 colorectal cancer patients and 24 non-colorectal cancer patients indicated for colonoscopy at Dr.Cipto Mangunkusumo Gastrointestinal Endoscopy Center and Fatmawati Hospital.Microbiota examination was performed using 16S rRNA sequencing.Bioinformatics analysis was performed using the wf-metagenomics pipeline from EPI2Me-Labs(Oxford Nanopore Technologies platform).RESULTS Patients with colorectal cancer had a higher median index value on the Shannon index(3.28 vs 2.82,P>0.05)and a lower value on the Simpson index(0.050 vs 0.060,P>0.05).Significant differences in beta diversity were observed at the genus(P=0.002)and species levels(P=0.001).Firmicutes,Proteobacteria,Bacteroidetes,and Fusobacteria were the dominant phyla.The genera Bacteroides,Campylobacter,Peptostreptococcus,and Parvimonas were found more frequently in colorectal cancer,while Faecalibacterium,Haemophilus,and Phocaeicola were more frequently found in non-colorectal cancer.The relative abundance of Fusobacterium nucleatum,Bacteroides fragilis,Enterococcus faecalis,Campylobacter hominis,and Enterococcus faecalis species was significantly elevated in patients with colorectal cancer.Meanwhile,Faecalibacterium prausnitzii,Faecalibacterium duncaniae,and Prevotella copri were more commonly found in non-colorectal cancer.CONCLUSION Patients with colorectal cancer exhibit distinct differences in the composition and diversity of their colonic mucosal microbiota compared to those with non-colorectal cancer.This study was reviewed and approved by the Ethics Committee of Faculty of Medicine,Universitas Indonesia(No.KET-1517/UN2.F1/ETIK/PPM.00.02/2023).

News Roundup

Spring Festival Inscribed as UNESCO Intangible Cultural Heritage of Humanity The United Nations Educational,Scientific and Cultural Organisation(UNESCO)on 4 December 2024 inscribed the Spring Festival,social practices of the Chinese people in celebration of the traditional new year,on the Representative List of the Intangible Cultural Heritage of Humanity.

Incorporation of human β-defensin-1 into immunoliposomes to facilitate targeted autophagy therapy of colon carcinoma

Based on the discovery that humanβ-defensin-1(hBD-1)triggers autophagy in colon cancer cells and inhibits proliferation,we proposed the consideration of its druggability.As a protein,its stability,targetability and bioavailability must be improved.Compared with the traditional medicinal chemistry technology,nano-technology is more economical for increasing the druggability of hBD-1 and can be readily scaled up.Here,we propose an immunoliposome system containing hBD-1 to improve its stability and bioavailability.To enhance its targetability,anti-epidermal growth factor receptor(EGFR)antibodies were conjugated to the liposomal bilayer to produce immunoliposomes that can target EGFR,which is highly expressed in colon cancer cells.Although more studies are needed to su-pport clinical trials and large-scale manufacturing,these immunoliposomes have great potential as therapeutics.Thus,immunoliposomes are suitable nanovesicles to improve the druggability of hBD-1;however,additional basic and translational research of these systems is warranted.

A smart finger patch with coupled magnetoelastic and resistive bending sensors

In the era of Metaverse and virtual reality(VR)/augmented reality(AR),capturing finger motion and force interactions is crucial for immersive human-machine interfaces.This study introduces a flexible electronic skin for the index finger,addressing coupled perception of both state and process in dynamic tactile sensing.The device integrates resistive and giant magnetoelastic sensors,enabling detection of surface pressure and finger joint bending.This e-skin identifies three phases of finger action:bending state,dynamic normal force and tangential force(sweeping).The system comprises resistive carbon nanotubes(CNT)/polydimethylsiloxane(PDMS)films for bending sensing and magnetoelastic sensors(NdFeB particles,EcoFlex,and flexible coils)for pressure detection.The inward bending resistive sensor,based on self-assembled microstructures,exhibits directional specificity with a response time under 120 ms and bending sensitivity from 0°to 120°.The magnetoelastic sensors demonstrate specific responses to frequency and deformation magnitude,as well as sensitivity to surface roughness during sliding and material hardness.The system’s capability is demonstrated through tactile-based bread type and condition recognition,achieving 92%accuracy.This intelligent patch shows broad potential in enhancing interactions across various fields,from VR/AR interfaces and medical diagnostics to smart manufacturing and industrial automation.

Efficacy of disitamab vedotin-containing therapy in metastatic colorectal cancer: A case report

BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide.In cases of metastatic CRC(mCRC)that are resistant to conventional chemo-therapy-based treatments,the efficacy of available therapeutic options is typically low.CRC exhibiting overexpression or amplification of the human epidermal growth factor receptor 2(HER2)gene has shown responsiveness to HER2-targeted therapies.CASE SUMMARY We present the case of a 69-year-old woman diagnosed with mCRC with an NRAS p.G12V mutation and microsatellite stability,identified through tumor sequencing,along with HER2 overexpression detected by immunohistochemistry.She exhibited an excellent response to disitamab vedotin-containing therapy.To our knowledge,this is the first reported case of mCRC with HER2 overexpression and an NRAS p.G12V mutation achieving a remarkable clinical response to anti-HER2 therapy.CONCLUSION Disitamab vedotin demonstrates promising anti-tumor effects in HER2-overex-pressing mCRC,offering patients an additional treatment option.

Impact of dietary nutrition regimens based on body composition analysis on bone metabolism in Alzheimer’s disease patients

BACKGROUND Body composition analysis(BCA)is primarily used in the management of conditions such as obesity and endocrine disorders.However,its potential in providing nutritional guidance for patients with Alzheimer’s disease(AD)remains relatively unexplored.AIM To explore the clinical efficacy of BCA-based dietary nutrition scheme on bone metabolism in AD patients.METHODS This retrospective study included 96 patients with AD complicated by osteoporosis who were admitted to The Third Hospital of Quzhou between January 2023 and December 2024.Based on data from previous similar studies,the patients were randomly assigned to either a routine diet(RD)group(n=48)or a personalized nutrition(PN)group(n=48).The RD group received conventional dietary guidance,while the PN group received individualized diet intervention measures based on human BCA.The intervention period lasted for 12 weeks.Bone mineral density(BMD),body mass index(BMI),muscle mass,mineral content,osteocalcin,25-hydroxyvitamin D,procollagen type I N-terminal propeptide(PINP),beta C-terminal telopeptide of type I collagen(β-CTX),and serum calcium were measured and compared between the two groups before and 12 weeks after the intervention.RESULTS No significant differences were observed between groups in terms of age,sex,height,BMI,or other baseline data(P>0.05).In both groups,BMI did not show significant changes after the intervention(P>0.05),whereas muscle mass and mineral content were significantly increased(P<0.05).After the intervention,BMI in the PN group did not differ significantly from that of the RD group,but muscle mass and mineral content were significantly higher in the PN group(P<0.05).After the intervention,a higher proportion of patients in the PN group had a T score>-1 compared to the RD group(P<0.05).The mini-mental state examination(MMSE)score was similar in both groups before the intervention.However,12 weeks after the intervention,the MMSE score in the PN group was significantly higher than that in the RD group(P<0.05).In both groups,the MMSE score significantly increased 12 weeks post-intervention compared to pre-intervention levels(P<0.05).Before the intervention,the levels of osteocalcin,serum calcium,PINP,β-CTX,and 25-hydroxyvitamin D were not significantly different between the two groups(P>0.05).After 12 weeks of intervention,the PN group exhibited higher levels of osteocalcin,serum calcium,and 25-hydroxyvitamin D,as well as lower levels of PINP andβ-CTX,compared to the RD group(P<0.05).In both groups,osteocalcin,serum calcium,and 25-hydroxyvitamin D levels were significantly higher,while PINP andβ-CTX levels were significantly lower after 12 weeks of intervention compared to baseline(P<0.05).CONCLUSION The human BCA-based dietary nutrition regimen plays a crucial role in improving BMD and bone metabolism,with effects that surpass those of conventional nutrition strategies.The findings of this study provide strong evidence for the nutritional management of AD patients.

N6-methyladenosine methyltransferase Wilms tumor 1-associated protein impedes diabetic wound healing through epigenetically activating DNA methyltransferase 1

BACKGROUND Diabetic wound injury is a significant and common complication in individuals with diabetes.N6-methyladenosine(m6A)-related epigenetic regulation is widely involved in the pathogenesis of diabetes complications.However,the function of m6A methyltransferase Wilms tumor 1-associated protein(WTAP)in diabetic wound healing remains elusive.AIM To investigate the potential epigenetic regulatory mechanism of WTAP during diabetic wound healing.METHODS Human umbilical vein endothelial cells(HUVECs)were induced with high glucose(HG)to establish in vitro cell model.Male BALB/c mice were intraperitoneally injected with streptozotocin to mimic diabetes,and full-thickness excision was made to mimic diabetic wound healing.HG-induced HUVECs and mouse models were treated with WTAP siRNAs and DNA methyltransferase 1(DNMT1)overexpression vectors.Cell viability and migration ability were detected by cell counting kit-8 and Transwell assays.In vitro angiogenesis was measured using a tube formation experiment.The images of wounds were captured,and re-epithelialization and collagen deposition of skin tissues were analyzed using hematoxylin and eosin staining and Masson’s trichrome staining.RESULTS The expression of several m6A methyltransferases,including METTL3,METTL14,METTL16,KIAA1429,WTAP,and RBM15,were measured.WTAP exhibited the most significant elevation in HG-induced HUVECs compared with the normal control.WTAP depletion notably restored cell viability and enhanced tube formation ability and migration of HUVECs suppressed by HG.The unclosed wound area of mice was smaller in WTAP knockdowntreated mice than in control mice at nine days post-wounding,along with enhanced re-epithelialization rate and collagen deposition.The m6A levels on DNMT1 mRNA in HUVECs were repressed by WTAP knockdown in HUVECs.The mRNA levels and expression of DNMT1 were inhibited by WTAP depletion in HUVECs.Overexpression of DNMT1 in HUVECs notably reversed the effects of WTAP depletion on HG-induced HUVECs.CONCLUSION WTAP expression is elevated in HG-induced HUVECs and epigenetically regulates the m6A modification of DNMT1 to impair diabetic wound healing.

Colony-stimulating factor 3 and its receptor promote leukocyte immunoglobulin-like receptor B2 expression and ligands in gastric

BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2(LILRB2)in GC.We hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands,angiopoietin-like protein 2(ANGPTL2)and human leukocyte antigen-G(HLA-G),contributing to immunosuppression.AIM To investigate the relationship between CSF3/CSF3R and LILRB2,as well as its ligands ANGPTL2 and HLA-G,in GC.METHODS Transcriptome sequencing data from The Cancer Genome Atlas were analyzed,stratifying patients by CSF3R expression.Differentially expressed genes and immune checkpoints were evaluated.Immunohistochemistry(IHC)was performed on GC tissues.Correlation analyses of CSF3R,LILRB2,ANGPTL2,and HLA-G were conducted using The Cancer Genome Atlas data and IHC results.GC cells were treated with CSF3,and expression levels of LILRB2,ANGPTL2,and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western blotting.RESULTS Among 122 upregulated genes in high CSF3R expression groups,LILRB2 showed the most significant increase.IHC results indicated high expression of LILRB2(63.0%),ANGPTL2(56.5%),and HLA-G(73.9%)in GC tissues.Strong positive correlations existed between CSF3R and LILRB2,ANGPTL2,and HLA-G mRNA levels(P<0.001).IHC confirmed positive correlations between CSF3R and LILRB2(P<0.001),and HLA-G(P=0.010),but not ANGPTL2(P>0.05).CSF3 increased LILRB2,ANGPTL2,and HLA-G expression in GC cells.Heterogeneous nuclear ribonucleoprotein H1 modulation significantly altered their expression,impacting CSF3’s regulatory effects.CONCLUSION The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands,with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.

基于GRU-DRSN的双通道人体活动识别

人体活动识别(human activity recognizition, HAR)在医疗、军工、智能家居等领域有很大的应用空间。传统机器学习方法特征提取难度较大且精度不高。针对上述问题并结合传感器时序特性,提出了一种融合CBAM(convolutional block attention module)注意力机制的GRU-DRSN双通道并行模型,有效避免了传统串行模型因网络深度加深引起梯度爆炸和消失问题。同时并行结构使得两条支路具有相同的优先级,使用深度残差收缩网络(deep residual shrinkage network, DRSN)提取数据的深层空间特征,同时使用门控循环结构(gated recurrent unit, GRU)学习活动样本在时间序列上的特征,同时进行提取样本不同维度的特征,并通过CBAM模块进行特征的权重分配,最后通过Softmax层进行识别,实现了端对端的人体活动识别。使用公开数据集(wireless sensor data mining, WISDM)进行验证,模型平均精度达到了97.6%,与传统机器学习模型和前人所提神经网络模型相比,有更好的识别效果。

Human umbilical cord mesenchymal stem cell-derived exosomes loaded into a composite conduit promote functional recovery after peripheral nerve injury in rats

Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue regeneration.In previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal regeneration.This three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)tube.However,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains unknown.In this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived exosomes.Repair effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in rats.The results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft transplantation.More CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve reconnection.Therefore,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.

Rebuilding insight into the pathophysiology of Alzheimer’s disease through new blood-brain barrier models

The blood-brain barrier is a unique function of the microvasculature in the brain parenchyma that maintains homeostasis in the central nervous system.Blood-brain barrier breakdown is a common pathology in various neurological diseases,such as Alzheimer’s disease,stroke,multiple sclerosis,and Parkinson’s disease.Traditionally,it has been considered a consequence of neuroinflammation or neurodegeneration,but recent advanced imaging techniques and detailed studies in animal models show that blood-brain barrier breakdown occurs early in the disease process and may precede neuronal loss.Thus,the blood-brain barrier is attractive as a potential therapeutic target for neurological diseases that lack effective therapeutics.To elucidate the molecular mechanism underlying blood-brain barrier breakdown and translate them into therapeutic strategies for neurological diseases,there is a growing demand for experimental models of human origin that allow for functional assessments.Recently,several human induced pluripotent stem cell-derived blood-brain barrier models have been established and various in vitro blood-brain barrier models using microdevices have been proposed.Especially in the Alzheimer’s disease field,the human evidence for blood-brain barrier dysfunction has been demonstrated and human induced pluripotent stem cell-derived blood-brain barrier models have suggested the putative molecular mechanisms of pathological blood-brain barrier.In this review,we summarize recent evidence of blood-brain barrier dysfunction in Alzheimer’s disease from pathological analyses,imaging studies,animal models,and stem cell sources.Additionally,we discuss the potential future directions for blood-brain barrier research.

Integrins and their potential roles in mammalian pregnancy

Integrins are a highly complex family of receptors that, when expressed on the surface of cells, can mediate reciprocal cell-to-cell and cell-to-extracellular matrix(ECM) interactions leading to assembly of integrin adhesion complexes(IACs) that initiate many signaling functions both at the membrane and deeper within the cytoplasm to coordinate processes including cell adhesion, migration, proliferation, survival, differentiation, and metabolism. All metazoan organisms possess integrins, and it is generally agreed that integrins were associated with the evolution of multicellularity, being essential for the association of cells with their neighbors and surroundings, during embryonic development and many aspects of cellular and molecular biology. Integrins have important roles in many aspects of embryonic development, normal physiology, and disease processes with a multitude of functions discovered and elucidated for integrins that directly influence many areas of biology and medicine, including mammalian pregnancy, in particular implantation of the blastocyst to the uterine wall, subsequent placentation and conceptus(embryo/fetus and associated placental membranes) development. This review provides a succinct overview of integrin structure, ligand binding, and signaling followed with a concise overview of embryonic development, implantation, and early placentation in pigs, sheep, humans, and mice as an example for rodents. A brief timeline of the initial localization of integrin subunits to the uterine luminal epithelium(LE) and conceptus trophoblast is then presented, followed by sequential summaries of integrin expression and function during gestation in pigs, sheep, humans, and rodents. As appropriate for this journal, summaries of integrin expression and function during gestation in pigs and sheep are in depth, whereas summaries for humans and rodents are brief. Because similar models to those illustrated in Fig. 1, 2, 3, 4, 5 and 6 are present throughout the scientific literature, the illustrations in this manuscript are drafted as Viking imagery for entertainment purposes.