Detection and clearance in Alzheimer’s disease: leading with illusive chemical, structural and morphological features of the targets

Highly specific interactions between biomolecules,such as antigen-antibody,protein-ligand,or nucleic acid base pair complementary are on the basis of the organization of complex organisms.The same principles may be tentatively used in molecular medicine for diagnosis and therapeutics.A molecule can be designed to selectively bind a protease and thereby inhibit the production of a peptide that forms toxic aggregates in the brain or an antibody may be produced to bind specifically to that peptide for detection or clearance purposes.Unfortunately,interference in biological systems is not that simple.For a start there is the inhibition of the physiological role of the protease;moreover,several cleavage fragments may be produced,which may continue to diverge due to putative post-translational modification and self-assembly processes,hiding the toxic target in a“soup”of peptide species varying in size,structure and chemical composition.A perspective of the current status and challenges in targeting peptide species for diagnosis and treatment in the context of Alzheimer’s disease is given.

Oxidative stress in N88S seipinopathy:novel insights into the mechanisms of neurodegeneration and therapeutic avenues

Lipid droplets (LDs) are ubiquitous cellular orga nelles that perform functions mostly dedicated to energy homeostasis and lipid metabolism.As neutral lipid depots (triacylglycerol,sterol esters),they can be rapidly mobilized through lipase-mediated hydrolysis (lipolysis) or via lipophagy,a specific form of autophagy devoted to consumption of LDs inside the lysosome.

-765G > C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia

AIM： To investigate the relationship between the -765G 〉 C COX-2 polymorphism and the development of different gastric lesions： atrophy or intestinal metaplasia and gastric adenocarcinoma. METHODS： A cross-sectional study was performed involving 320 Portuguese individuals （210 without evidence of neoplastic disease, 73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal metaplasia） using a PCR-RFLP method.RESULTS： -765C allele was overrepresented in the patients with gastric adenocarcinoma （51%） when compared either with the control group （38%） or patients with atrophy or intestinal metaplasia （27%）. Callele was found to be very common in our population （0.22）, and a multivariate logistic regression analysis revealed nearly 3-fold increased risk for the progression to gastric adenocarcinoma in patients with atrophy or intestinal metaplasia carrying the -765C allele （OR = 2.67, 95% CI = 1.03-6.93; P = 0.04）.CONCLUSION： -765C carrier status should be considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.

IL-6/IL-6R as a potential key signaling pathway in prostate cancer development

Interleukin-6(IL-6)is a pleiotropic cytokine involved in prostate regulation and in prostate cancer(PC)development/progression.IL-6 acts as a paracrine and autocrine growth stimulator in benign and tumor prostate cells.The levels of IL-6 and respective receptors are increased during prostate carcinogenesis and tumor progression.Several studies reported that increased serum and plasma IL-6 and soluble interleukin-6 receptor levels are associated with aggressiveness of the disease and are associated with a poor prognosis in PC patients.In PC treatment,patients diagnosed with advanced stages are frequently submitted to hormonal castration,although most patients will eventually fail this therapy and die from recurrent castration-resistant prostate cancer(CRPC).Therefore,it is important to understand the mechanisms involved in CRPC.Several pathways have been proposed to be involved in CRPC development,and their understanding will improve the way to more effective therapies.In fact,the prostate is known to be dependent,not exclusively,on androgens,but also on growth factors and cytokines.The signaling pathway mediated by IL-6 may be an alternative pathway in the CRPC phenotype acquisition and cancer progression,under androgen deprivation conditions.The principal goal of this review is to evaluate the role of IL-6 pathway signaling in human PC development and progression and discuss the interaction of this pathway with the androgen recepto pathway.Furthermore,we intend to evaluate the inclusion of IL-6 and its receptor levels as a putative new class of tumor biomarkers.The IL-6/IL-6R signaling pathway may be included as a putative molecular marker for aggressiveness in PC and it may be able to maintain tumor growth through the AR pathway under androgen-deprivation conditions.The importance of the IL-6/IL-6R pathway in regulation of PC cells makes it a good candidate for targeted therapy.

Epidermal growth factor receptor and K-Ras in non-small cell lung cancer-molecular pathways involved and targeted therapies

Lung cancer is currently the leading cause of cancer death in Western nations.Non-small cell lung cancer(NSCLC)represents 80%of all lung cancers,and adenocarcinoma is the predominant histological type.Despite the intensive research carried out on this field and therapeutic advances,the overall prognosis of these patients remains unsatisfactory,with a 5-year overall survival rate of less than 15%.Nowadays,pharmacogenetics and pharmacogenomics represent the key to successful treatment.Recent studies suggest the existence of two distinct molecular pathways in the carcinogenesis of lung adenocarcinoma:one associated with smoking and activation of the K-Ras oncogene and the other not associated with smoking and activation of the epidermal growth factor receptor(EGFR).The K-ras mutation is mainly responsible for primary resistance to new molecules which inhibit tyrosine kinase EGFR(erlotinib and gefitinib)and most of the EGFR mutations are responsible for increased tumor sensitivity to these drugs.This article aims to conduct a systematic review of the literature regarding the molecular pathways involving the EGFR,K-Ras and EGFR targeted therapies in NSCLC tumor behavior.

Osteoblasts are inherently programmed to repel sensory innervation

Tissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of axons.Sensory innervation is part of the neuronal network of the bone tissue with a defined spatiotemporal occurrence during bone development.Yet,the current understanding of the mechanisms regulating the map of sensory innervation in the bone tissue is still limited.Here,we demonstrated that differentiation of human mesenchymal stem cells to osteoblasts leads to a marked impairment of their ability to promote axonal growth,evidenced under sensory neurons and osteoblastic-lineage cells crosstalk.The mechanisms by which osteoblast lineage cells provide this nonpermissive environment for axons include paracrine-induced repulsion and loss of neurotrophic factors expression.We identified a drastic reduction of NGF and BDNF production and stimulation of Sema3A,Wnt4;and Shh expression culminating at late stage of OB differentiation.We noted a correlation between Shh expression profile,OB differentiation stages,and OB-mediated axonal repulsion.Blockade of Shh activity and signaling reversed the repulsive action of osteoblasts on sensory axons.Finally,to strengthen our model,we localized the expression of Shh by osteoblasts in bone tissue.Overall,our findings provide evidence that the signaling profile associated with osteoblast phenotype differentiating program can regulate the patterning of sensory innervation,and highlight osteoblast-derived Shh as an essential player in this cue-induced regulation.

Iron overload and immunity

Progress in the characterization of genes involved in the control of iron homeostasis in humans and in mice has improved the definition of iron overload and of the cells affected by it. The cell involved in iron overload with the greatest effect on immunity is the macrophage. Intriguing evidence has emerged, however, in the last 12 years indicating that parenchymal iron overload is linked to genes classically associated with the immune system. This review offers an update of the genes and proteins relevant to iron metabolism expressed in cells of the innate immune system, and addresses the question of how this system is affected in clinical situations of iron overload. The relationship between iron and the major cells of adaptive immunity, the T lymphocytes, will also be reviewed. Most studies addressing this last question in humans were performed in the clinical model of Hereditary Hemochromatosis. Data will also be reviewed demonstrating howthe disruption of molecules essentially involved in adaptive immune responses result in the spontaneous development of iron overload and how they act as modifiers of iron overload.

Gastric cancer in a Caucasian population: Role of pepsinogen C genetic variants

AIM： To study the role of an insertion/deletion polymorphism in the pepsinogen C （PGC） gene, an effective marker for terminal differentiation of the stomach mucosa, in the susceptibility to the development of gastric lesions. METHODS： The study was performed with 99 samples of known gastric lesions and 127 samples without evidence of neoplastic disease. PCR was employed and the 6 polymorphic alleles were amplified： Allele 1 （510 bp）, Allele 2 （480 bp）, Allele 3/4 （450/460 bp）, Allele 5 （400 bp） and Allele 6 （310 bp）. RESULTS： Our results revealed that Allele 6 carriers seemed to have protection against the development of any gastric lesion （OR = 0.34; P 〈 0.001）, non-dysplastic lesions associated with gastric adenocarcinoma such as atrophy or intestinal metaplasia （OR = 0.28; P 〈 0.001） or invasive GC （OR = 0.39; P = 0.004）. CONCLUSION： Our study reveals that the Allele 6 carrier status has a protective role in the development of gastric lesions, probably due to its association with higher expression of PGC. Moreover, the frequency of Allele 6 carriers in the control group is far higher than that obtained in Asian populations, which might represent a genetic gap between Caucasian and Asian populations.

3D Photo-Fabrication for Tissue Engineering and Drug Delivery

The most promising strategies in tissue engineering involve the integration of a triad of biomaterials, living cells, and biologically active molecules to engineer synthetic environments that closely mimic the healing milieu present in human tissues, and that stimulate tissue repair and regeneration. To be clinically effective, these environments must replicate, as closely as possible, the main characteristics of the native extracellular matrix(ECM) on a cellular and subcellular scale. Photo-fabrication techniques have already been used to generate 3D environments with precise architectures and heterogeneous composition, through a multi-layer procedure involving the selective photocrosslinking reaction of a light-sensitive prepolymer. Cells and therapeutic molecules can be included in the initial hydrogel precursor solution, and processed into 3D constructs. Recently, photofabrication has also been explored to dynamically modulate hydrogel features in real time, providing enhanced control of cell fate and delivery of bioactive compounds. This paper focuses on the use of 3D photo-fabrication techniques to produce advanced constructs for tissue regeneration and drug delivery applications. State-of-the-art photo-fabrication techniques are described, with emphasis on the operating principles and biofabrication strategies to create spatially controlled patterns of cells and bioactive factors. Considering its fast processing, spatiotemporal control, high resolution, and accuracy, photo-fabrication is assuming a critical role in the design of sophisticated 3D constructs. This technology is capable of providing appropriate environments for tissue regeneration, and regulating the spatiotemporal delivery of therapeutics.

Animal plant warfare and secondary metabolite evolution

The enduring discussion,why plants produce secondary metabolites with pharmacologically and toxicologically active towards mammals traces back to the eminent role of medicinal plants in the millennia-old history of manhood.In recent years,the concept of an animal plant warfare emerged,which focused on the co-evolution between plants and herbivores.As a reaction to herbivory,plants developed mechanical defenses such as thorns and hard shells,which paved the way for adapted animal physiques.Plants evolved further defense systems by producing chemicals that exert toxic effects on the animals that ingest them.As a result of this selective pressure,animals developed special enzymes,e.g.cytochrome P450 monooxigenases(CYP450)that metabolize xenobiotic phytochemicals.As a next step in the evolutionary competition between plants and animals,plants evolved to produce non-toxic pro-drugs,which become toxic only after ingestion by animals through metabolization by enzymes such as CYP450.Because these sequestered evolutionary developments call to mind an arms race,the term animal plant warfare has been coined.The evolutionary competition between plants and animals may help to better understand the modes of action of medicinal plants and to foster the efficient and safe use of phytotherapy nowadays.

量化中医学中“寒”与“热”的初步临床研究(英文)

目的:本研究探讨通过测量微循环相关指标客观衡量针刺效果的可能性,中医寒证针刺治疗前毛细血管灌注状态的意义,以及微循环相关指标在未来中医诊断中的意义。方法:本研究为前瞻性、非对照、不设盲临床研究。研究共纳入32例股骨骨折手术后的老年患者。这些患者均接受施于胃经梁丘穴的"豹斑点刺"针刺治疗。针刺治疗前后使用白光光谱学及激光多普勒测量微循环相关指标如血流速率、血流量、血红蛋白含量、氧饱和度等。结果:股骨骨折后,根据血流量的不同,患者被分为两组,即高灌注组和低灌注组。低灌注组的毛细血管血流量及血流速率在针刺治疗后明显增加,而高灌注组则无明显改变。如果不考虑患者在针刺治疗前的灌注状态,则统计分析表明所有患者针刺治疗前后的灌注状态均无明显改变,因此针刺的作用可能被患者的异质性所掩盖。结论:微循环相关指标对于客观衡量针刺的治疗效果及描述针刺治疗前的营养性功能以均衡比较组之间的差异有重要意义。在本试验中,局部寒证(腿部的毛细血管低灌注)可以通过针刺补气血的胃经梁丘穴得到显著改善,而在热证组(毛细血管高灌注)未见明显改变。未来的研究可以通过将中医营养参数测量的营养状态与中医诊断中的主要证候相联系而得到更多结论。

Ovarian cancer and DNA repair: DNA ligase IV as a potential key

Ovarian cancer(OC)is the sixth most common cancer and the seventh cause of death from cancer in women.The etiology and the ovarian carcinogenesis still need clarification although ovulation may be determinant due to its carcinogenic role in ovarian surface epithelium.The link between ovarian carcinogenesis and DNA repair is well established and it became clear that alterations in DNA damage response may affect the risk to develop OC.Polymorphisms are variations in the DNA sequence that exist in normal individuals of a population and are capable to change,among other mechanisms,the balance between DNA damage and cellular response.Consequently,genetic variability of the host has a great role in the development,progression and consequent prognosis of the oncologic patient as well as in treatment response.Standard treatment for OC patients is based on cytoreductive surgery,followed by chemotherapy with a platinum agent and a taxane.Although 80%of the patients respond to the first-line therapy,the development of resistance is common although the mechanisms underlying therapy failure remain mostly unknown.Because of their role in oncology,enzymes involved in the DNA repair pathways,like DNA Ligase IV(LIG4),became attractive study targets.It has been reported that variations in LIG4 activity can lead to a hyper-sensitivity to DNA damage,deregulation of repair and apoptosis mechanisms,affecting the susceptibility to cancer development and therapy response.To overcome resistance mechanisms,several investigations have been made and the strategy to target crucial molecular pathways,such as DNA repair,became one of the important areas in clinical oncology.This review aims to elucidate the link between DNA repair and OC,namely which concerns the role of LIG4 enzyme,and how genetic polymorphisms in LIG4 gene can modulate the activity of the enzyme and affect the ovarian carcinogenesis and treatment response.Moreover,we try to understand how LIG4 inhibition can be a potential contributor for the development of new cancer treatment strategies.

Usefulness of serum C-reactive protein and calprotectin for the early detection of colorectal anastomotic leakage:A prospective observational study

BACKGROUND Colorectal anastomotic leakage(CAL)is one of the most dreaded complications after colorectal surgery,with an incidence that can be as high as 27%.This event is associated with increased morbidity and mortality;therefore,its early diagnosis is crucial to reduce clinical consequences and costs.Some biomarkers have been suggested as laboratory tools for the diagnosis of CAL.AIM To assess the usefulness of plasma C-reactive protein(CRP)and calprotectin(CLP)as early predictors of CAL.METHODS A prospective monocentric observational study was conducted including patients who underwent colorectal resection with anastomosis,from March 2017 to August 2019.Patients were divided into three groups:G1–no complications;G2–complications not related to CAL;and G3–CAL.Five biomarkers were measured and analyzed in the first 5 postoperative days(PODs),namely white blood cell(WBC)count,eosinophil cell count(ECC),CRP,CLP,and procalcitonin(PCT).Clinical criteria,such as abdominal pain and clinical condition,were also assessed.The correlation between biomarkers and CAL was evaluated.Receiver operating characteristic(ROC)curve analysis was used to compare the accuracy of these biomarkers as predictors of CAL,and the area under the ROC curve(AUROC),specificity,sensitivity,positive predictive value,and negative predictive value(NPV)during this period were estimated.RESULTS In total,25 of 396 patients developed CAL(6.3%),and the mean time for this diagnosis was 9.0±6.8 d.Some operative characteristics,such as surgical approach,blood loss,intraoperative complications,and duration of the procedure,were notably related to the development of CAL.The length of hospital stay was markedly higher in the group that developed CAL compared with the group with complications other than CAL and the group with no complications(median of 21 d vs 13 d and 7 d respectively;P<0.001).For abdominal pain,the best predictive performance was on POD4 and POD5,with the largest AUROC of 0.84 on POD4.Worsening of the clinical condition was associated with the diagnosis of CAL,presenting a higher predictive effect on POD5,with an AUROC of 0.9.WBC and ECC showed better predictive effects on POD5(AUROC=0.62 and 0.7,respectively).Those markers also presented a high NPV(94%-98%).PCT had the best predictive effect on POD5(AUROC=0.61),although it presented low accuracy.However,this biomarker revealed a high NPV on POD3,POD4,and POD5(96%,95%,and 96%,respectively).The mean CRP value on POD5 was significantly higher in the group that developed CAL compared with the group without complications(195.5±139.9 mg/L vs 59.5±43.4 mg/L;P<0.00001).On POD5,CRP had a NPV of 98%.The mean CLP value on POD3 was significantly higher in G3 compared with G1(5.26±3.58μg/mL vs 11.52±6.81μg/mL;P<0.00005).On POD3,the combination of CLP and CRP values showed a high diagnostic accuracy(AUROC=0.82),providing a 5.2 d reduction in the time to CAL diagnosis.CONCLUSION CRP and CLP are moderate predictors of CAL.However,the combination of these biomarkers presents an increased diagnostic accuracy,potentially decreasing the time to CAL diagnosis.

Insights into Late Embryogenesis Abundant (LEA) Proteins in Plants: From Structure to the Functions

Late Embryogenesis Abundant (LEA) proteins, a group of hydrophilic proteins, have been linked to survival in plants and animals in periods of stress, putatively through safeguarding enzymatic function and prevention of aggregation in times of dehydration/heat. Yet despite decades of effort, the molecular-level mechanisms defining this protective function remain unknown. In this paper, we summarize and review research discoveries of the classification of the LEA protein groups based on their amino acid sequence similarity and on the presence of distinctive conserved motifs. Moreover, we focus on high correlation between their accumulation and water deficit, reinforcing their functional relevance under abiotic stresses. We also discuss the biochemical properties of LEA proteins arising from their hydrophilic nature and by amino acid composition. Although significant similarities have not been found between the members of the different groups, a unifying and outstanding feature of most of them is their high hydrophilicity and high content of glycine. Therefore, we have highlighted the biotechnological applications of LEA genes, and the effects of over-expressing LEA genes from all LEA groups from different species of origin into different plant hosts. Apart from agronomical purposes, LEA proteins could be useful for other biotechnological applications in relation to their capacity to prevent aggregation of proteins.

Evaluation of biodegradable electric conductive tube-guides and mesenchymal stem cells

AIM: To study the therapeutic effect of three tubeguides with electrical conductivity associated to mesenchymal stem cells(MSCs) on neuro-muscular regeneration after neurotmesis.METHODS: Rats with 10-mm gap nerve injury were tested using polyvinyl alcohol(PVA), PVA-carbon nanotubes(CNTs) and MSCs, and PVA-polypyrrole(PPy). The regenerated nerves and tibialis anterior muscles were processed for stereological studies after 20 wk. The functional recovery was assessed serially for gait biomechanical analysis, by extensor postural thrust, sciatic functional index and static sciatic functionalindex(SSI), and by withdrawal reflex latency(WRL). In vitro studies included cytocompatibility, flow cytometry, reverse transcriptase polymerase chain reaction and karyotype analysis of the MSCs. Histopathology of lung, liver, kidneys, and regional lymph nodes ensured the biomaterials biocompatibility. RESULTS: SSI remained negative throughout and independently from treatment. Differences between treted groups in the severity of changes in WRL existed, showing a faster regeneration for PVA-CNTs-MSCs(P < 0.05). At toe-off, less acute ankle joint angles were seen for PVA-CNTs-MSCs group(P = 0.051) suggesting improved ankle muscles function during the push off phase of the gait cycle. In PVA-PPy and PVA-CNTs groups, there was a 25% and 42% increase of average fiber area and a 13% and 21% increase of the "minimal Feret's diameter" respectively. Stereological analysis disclosed a significantly(P < 0.05) increased myelin thickness(M), ratio myelin thickness/axon diameter(M/d) and ratio axon diameter/fiber diameter(d/D; g-ratio) in PVA-CNT-MSCs group(P < 0.05). CONCLUSION: Results revealed that treatment with MSCs and PVA-CNTs tube-guides induced better nerve fiber regeneration. Functional and kinematics analysis revealed positive synergistic effects brought by MSCs and PVA-CNTs. The PVA-CNTs and PVA-PPy are promising scaffolds with electric conductive properties, bio- and cytocompatible that might prevent the secondary neurogenic muscular atrophy by improving the reestablishment of the neuro-muscular junction.

Syngamy,pronucleus,pronuclear breakdown and zygote

The terms syngamy,pronucleus,pronuclear breakdown and zygote are common for experts dealing with reproductive cell morphology.However,these terms are often not correctly used in scientific and didactic literature.At fertilization,the sperm postacrosomal plasma membrane fuses with the oocyte plasma membrane(oolema).Together with the release of a sperm soluble factor into the oocyte cytoplasm.

使用温度记录法衡量气功的治疗效应(英文)

A contemporary understanding of traditional Chinese medicine(Heidelberg Model of TCM)considers TCM to be a traditional model

Exosomal glypican-1 is elevated in pancreatic cancer precursors and can signal genetic predisposition in the absence of endoscopic ultrasound abnormalities

BACKGROUND Individuals within specific risk groups for pancreatic ductal adenocarcinoma(PDAC)[mucinous cystic lesions(MCLs),hereditary risk(HR),and new-late onset diabetes mellitus(NLOD)]represent an opportunity for early cancer detection.Endoscopic ultrasound(EUS)is a premium image modality for PDAC screening and precursor lesion characterization.While no specific biomarker is currently clinically available for this purpose,glypican-1(GPC1)is overexpressed in the circulating exosomes(crExos)of patients with PDAC compared with healthy subjects or those harboring benign pancreatic diseases.AIM To evaluate the capacity of GPC1+crExos to identify individuals at higher risk within these specific groups,all characterized by EUS.METHODS This cross-sectional study with a prospective unicentric cohort included 88 subjects:40 patients with MCL,20 individuals with HR,and 20 patients with NLOD.A control group(CG)was submitted to EUS for other reasons than pancreatic pathology,with normal pancreas and absence of hereditary risk factors(n=8).The inclusion period was between October 2016 and January 2019,and the study was approved by the Ethics Committee of Centro Hospitalar Universitário de São João,Porto,Portugal.All patients provided written informed consent.EUS and blood tests for quantification of GPC1+crExos by flow cytometry and carbohydrate antigen 19-9(CA 19-9)levels by ELISA were performed in all subjects.EUS-guided tissue acquisition was done whenever necessary.For statistical analysis,SPSS®27.0(IBM Corp.,Armonk,NY,United States)version was used.All graphs were created using GraphPad Prism 7.00(GraphPad Software,San Diego,CA,United States).RESULTS Half of MCLs harbored worrisome features(WF)or high-risk stigmata(HRS).Pancreatic abnormalities were detected by EUS in 10.0%and 35.0%in HR and NLOD individuals,respectively,all considered non-malignant and“harmless.”Median levels of GPC1+crExos were statistically different:MCL[99.4%,interquartile range(IQR):94.9%-99.8%],HR(82.0%,IQR:28.9%-98.2%),NLOD(12.6%,IQR:5.2%-63.4%),and CG(16.2%,IQR:6.6%-20.1%)(P<0.0001).Median levels of CA 19-9 were within the normal range in all groups(standard clinical cut-off of 37 U/mL).Within HR,individuals with a positive history of cancer had higher median levels of GPC1+crExos(97.9%;IQR:61.7%-99.5%),compared to those without(59.7%;IQR:26.3%-96.4%),despite no statistical significance(P=0.21).Pancreatic cysts with WF/HRS were statistically associated with higher median levels of GPC1+crExos(99.6%;IQR:97.6%-99.8%)compared to those without(96.5%;IQR:81.3%-99.5%)(P=0.011),presenting an area under the receiver operating characteristic curve value of 0.723(sensitivity 75.0%and specificity 67.7%,using a cutoff of 98.5%;P=0.012).CONCLUSION GPC1+crExos may act as biomarker to support the diagnosis and stratification of PDAC precursor lesions,and in signaling individuals with genetic predisposition in the absence of EUS abnormalities.

Acellular Mineralized Exoskeleton Shrimp (MES): A Natural Source of Bioactive Factors for Tissue Regeneration—Preliminary Results

Current challenges in the development of scaffolds for bone regeneration include the engineering of biomaterials that can withstand a natural dynamic physiology on the bone that provides a matrix capable of supporting cell migration and tissue ingrowth. The objective of the present work was to develop and characterize a new biomembrane—Mineralized Exoskeleton Shrimp (MES) developed from the exoskeleton of paleomonetes. The integration of MES as a biomaterial for tissue regeneration relies on the growing evidence that the shrimp is characterized by a hierarchically arranged chitin fiber structure, mineralized predominately by calcium carbonate and/or calcium phosphate, bringing beneficial effects in bone regeneration. Additionally, the tridimensional MES structure, can act as a “tent” for Guided Bone Regeneration (GBR). Recently, our team has characterized the MES biomaterial by in vitro (human osteoblastic cellular cultures and immersion of the membrane in modified synthetic plasma) and in vivo (soft tissue in lab mice and hard tissue in rabbit model). The cellular growth in the MES membrane was very exuberant in cellular culture with osteoblastic colonization on its surface (histophilic and biocompatible). After the immersion in modified synthetic plasma for one week, a mass mineralization occurred throughout the membrane’s surface (bioactive). The analysis of histological samples from experimental surgery in lab mice showed that the MES membrane wasn’t toxic to soft tissues and that it caused a moderate inflammatory response (first reabsorption signs at 8 weeks). The MES could act as a cell-guiding template that contains the necessary cues and adequate three-dimensional set to facilitate cell adhesion and promote tissue regeneration upon implantation and subsequent biodegradation.

Anxiety and pre-symptomatic testing for neurodegenerative disorders

In this retrospective study we have investigated the anxiety as an impact of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Huntington disease (HD), Machado-Joseph disease (MJD)?and familial amyloidotic polyneuropathy (FAP)?V30MTTR. The study included 686 subjects: 586 (85.4%) were the offspring at risk for FAP, 92 (13.4%) for HD and 8 (1.2%) to MJD. Of these, 352 received the carrier result and 305 the non-carrier result. As indicator of anxiety distress was taken the Self-Rating Anxiety Scale of Zung (SAS), applied in the pre-test and the three post-test moments: three weeks, 6 months and one year after notification of test results. Values decreased significantly along the four evaluation moments, regardless the studied disease or test result. For female population, SAS means cores revealed results of clinical anxiety at pre-test, only decreasing to non clinical scores a year after PST disclosure.