Nutritional and biofunctional characterizations of four novel edible aquatic plants of Bangladesh.

Aquatic plants are a cheap and renewable biomass rich in bioactive and biofunctional compounds, holding valorization prospects for use in food and pharmaceuticals. Four commonly found edible aquatic plants in Bangladesh, namely red water lily (Nymphaea nouchali), white water lily (Nympheae alba), malancha (Alternanthera philoxeroides), and red seaweed (Gracilaria tenuistipitata), were compared in terms of proximate composition, bioactive compounds, antioxidant activity, mineral and heavy metal contents, and amino acid composition. The crude protein content was the highest in A. philoxeroids (26.96 %), followed by G. tenuistipitata (25.21 %), N. nouchali (25.14 %), and N. alba (23.54 %). The sequence of crude lipid content of four aquatic plants was A. philoxeroids (4.8 %) > N. nouchali (4.0 %) > G. tenuistipitata (3.4 %) > N. alba (2.4 %). The aquatic plants were rich in carbohydrates, with G. tenuistipitata having 37.02 %, significantly (P < 0.05) lower than N. alba (46.12 %), N. nouchali (45.73 %), and A. philoxeroids (42.88 %). The ash content in the studied plants varied between 14.63 % and 24.97 %. Substantial numbers of bioactive compounds were identified in these plants: 42 in N. alba, 41 in N. nouchali, 40 in A. philoxeroides, and 36 in G. tenuistipitata, as determined by GC-MS analysis. G. tenuistipitata showed the highest amount of total phenolic (121.05 ± 2.43 mg gallic acid equivalent/g) and flavonoid (128.03 ± 0.79 mg quercetin equivalent/g) content. The DPPH, hydrogen peroxide, and ferric reducing power assays showed the free radical scavenging ability increased in a dose dependent manner. These aquatic plants contained substantial amounts of minerals, namely Ca ranging from 42.05 ± 2.34 to 441.65 ± 4.67 mg/kg, K ranging from 80.15 ± 1.82 to 97.81 ± 1.74 mg/kg, and Na ranging from 41.16 ± 1.32 to 53.37 ± 1.64 mg/kg. The heavy metal contents of Cu, Ni, and Pb were 0.93 ± 0.06 to 1.25 ± 0.09 mg/kg, 0.44 ± 0.02 to 3.86 ± 0.56 mg/kg, and 0.22 ± 0.02 to 0.67 ± 0.05 mg/kg, respectively. Thirteen different amino acids were identified, with leucine, glycine, alanine, lysine, and phenylalanine dominating, and their contents varying by species. Therefore, regular consumption of these aquatic plants might be a healthy approach to addressing malnutrition and enhancing biofunctional activities.

Small molecules targeting HDAC6 for cancer treatment: Current progress and novel strategies.

Histone deacetylase 6 (HDAC6) plays a crucial role in the initiation and progression of various cancers, as its overexpression is linked to tumor growth, invasion, migration, survival, apoptosis, and angiogenesis. Therefore, HDAC6 has emerged as an attractive target for anticancer drug discovery in the past decade. However, the development of conventional HDAC6 inhibitors has been hampered by their limited clinical efficacy, acquired resistance, and inability to inhibit non-enzymatic functions of HDAC6. To overcome these challenges, new strategies, such as dual-acting inhibitors, targeted protein degradation (TPD) technologies (including PROTACs, HyT), are essential to enhance the anticancer activity of HDAC6 inhibitors. In this review, we focus on the recent advances in the design and development of HDAC6 modulators, including isoform-selective HDAC6 inhibitors, HDAC6-based dual-target inhibitors, and targeted protein degraders (PROTACs, HyT), from the perspectives of rational design, pharmacodynamics, pharmacokinetics, and clinical status. Finally, we discuss the challenges and future directions for HDAC6-based drug discovery for cancer therapy.

Biosynthesis and metabolic engineering of isoflavonoids in model plants and crops: a review.

Isoflavonoids, the major secondary metabolites within the flavonoid biosynthetic pathway, play important roles in plant defense and exhibit free radical scavenging properties in mammals. Recent advancements in understanding the synthesis, transport, and regulation of isoflavonoids have identified their biosynthetic pathways as promising targets for metabolic engineering, offering potential benefits such as enhanced plant resistance, improved biomass, and restoration of soil fertility. This review provides an overview of recent breakthroughs in isoflavonoid biosynthesis, encompassing key enzymes in the biosynthetic pathway, transporters influencing their subcellular localization, molecular mechanisms regulating the metabolic pathway (including transcriptional and post-transcriptional regulation, as well as epigenetic modifications). Metabolic engineering strategies aimed at boosting isoflavonoid content in both leguminous and non-leguminous plants. Additionally, we discuss emerging technologies and resources for precise isoflavonoid regulation. This comprehensive review primarily focuses on model plants and crops, offering insights for more effective and sustainable metabolic engineering approaches to enhance nutritional quality and stress tolerance.

Structural and biofunctional diversity of sulfated polysaccharides from the genus Codium (Bryopsidales, Chlorophyta): A review.

It is believed that polysaccharides will become a focal point for future production of food, pharmaceuticals, and materials due to their ubiquitous and renewable nature, as well as their exceptional properties that have been extensively validated in the fields of nutrition, healthcare, and materials. Sulfated polysaccharides derived from seaweed sources have attracted considerable attention owing to their distinctive structures and properties. The genus Codium, represented by the species C. fragile, holds significance as a vital economic green seaweed and serves as a traditional Chinese medicinal herb. To date, the cell walls of the genus Codium have been found to contain at least four types of sulfated polysaccharides, specifically pyruvylated ß-d-galactan sulfates, sulfated arabinogalactans, sulfated ß-l-arabinans, and sulfated ß-d-mannans. These sulfated polysaccharides exhibit diverse biofunctions, including anticoagulant, immune-enhancing, anticancer, antioxidant activities, and drug-carrying capacity. This review explores the structural and biofunctional diversity of sulfated polysaccharides derived from the genus Codium. Additionally, in addressing the impending challenges within the industrialization of these polysaccharides, encompassing concerns regarding scale-up production and quality control, we outline potential strategies to address these challenges from the perspectives of raw materials, extraction processes, purification technologies, and methods for quality control.

Small molecules targeting selected histone methyltransferases (HMTs) for cancer treatment: Current progress and novel strategies.

Histone methyltransferases (HMTs) play a critical role in gene post-translational regulation and diverse physiological processes, and are implicated in a plethora of human diseases, especially cancer. Increasing evidences demonstrate that HMTs may serve as a potential therapeutic target for cancer treatment. Thus, the development of HMTs inhibitor have been pursued with steadily increasing interest over the past decade. However, the disadvantages such as insufficient clinical efficacy, moderate selectivity, and propensity for acquired resistance have hindered the development of conventional HMT inhibitors. New technologies and methods are imperative to enhance the anticancer activity of HMT inhibitors. In this review, we first review the structure and biological functions of the several essential HMTs, such as EZH2, G9a, PRMT5, and DOT1L. The internal relationship between these HMTs and cancer is also expounded. Next, we mainly focus on the latest progress in the development of HMT modulators encompassing dual-target inhibitors, targeted protein degraders and covalent inhibitors from perspectives such as rational design, pharmacodynamics, pharmacokinetics, and clinical status. Lastly, we also discuss the challenges and future directions for HMT-based drug discovery for cancer therapy.

A cuproptosis-related lncRNA signature-based prognostic model featuring on metastasis and drug selection strategy for patients with lung adenocarcinoma.

Introduction: Lung adenocarcinoma is a common cause of mortality in patients with cancer. Recent studies have indicated that copper-related cell death may not occur in the same way as previously described. Long non-coding RNAs (lncRNAs) play a key role in the occurrence and development of tumors; however, the relationship between cuproptosis and lncRNAs in tumorigenesis and lung adenocarcinoma (LUAD) treatment has not been well established. Our study aimed to construct a model to analyze the prognosis of lung adenocarcinoma in patients using a carcinogenesis-related lncRNA (CR) signature. Methods: The transcriptional profiles of 507 samples from The Cancer Genome Atlas were assessed. Cox regression and co-expression analyses, and the least absolute shrinkage and selection operator (LASSO) were used to filter the CR and develop the model. The expression status of the six prognostic CRs was used to classify all samples into high- and low-risk groups. The overall disease-free survival rate was compared between the two groups. The Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were used to identify the pathways and mechanisms involved in this model. Subsequently, immunotherapy response, sensitivity, and correlation analyses for several anti-tumor medications were performed. In vitro experiments, including qPCR, were conducted in nine lung adenocarcinoma cell lines and 16 pairs of lung adenocarcinoma and para-carcinoma tissues. Results: After confirmation using the ROC curve, patients in the low-risk category benefited from both overall and disease-free survival. Gene Ontology analysis highlighted cell movement in the model. In the in vitro experiments, qPCR results showed the expression levels of six CRs in 16 pairs of carcinoma and para-carcinoma tissues, which were in accordance with the results of the model. AL138778.1 is a protective factor that can weaken the invasion and migration of A549 cells, and AL360270.1 is a hazardous factor that promotes the invasion and migration of A549 cells. According to this model, targeted treatments such as axitinib, gefitinib, linsitinib, pazopanib, and sorafenib may be more appropriate for low-risk patients. Conclusion: Six CR profiles (AL360270.1, AL138778.1, CDKN2A-DT, AP003778.1, LINC02718, and AC034102.8) with predictive values may be used to evaluate the prognosis of patients with lung adenocarcinoma undergoing therapy.

Finding the Common Single-Nucleotide Polymorphisms in Three Autoimmune Diseases and Exploring Their Bio-Function by Using a Reporter Assay.

In clinical practice, it is found that autoimmune thyroid disease often additionally occurs with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In addition, several studies showed that eye-specific autoimmune diseases may have a strong relationship with systemic autoimmune diseases. We focused on Graves' disease (GD) with ocular conditions, also known as Graves' ophthalmopathy (GO), trying to find out the potential genetic background related to GO, RA, and SLE. There were 40 GO cases and 40 healthy controls enrolled in this study. The association between single-nucleotide polymorphisms (SNPs) of the co-stimulatory molecule genes and GO was analyzed using a chi-square test. It showed that rs11571315, rs733618, rs4553808, rs11571316, rs16840252, and rs11571319 of CTLA4, rs3181098 of CD28, rs36084323 and rs10204525 of PDCD1, and rs11889352 and rs4675379 of ICOS were significantly associated with GO based on genotype analysis and/or allele analysis (p < 0.05). After summarizing the GO data and the previously published SLE and RA data, it was found that rs11571315, rs733618, rs4553808, rs16840252, rs11571319, and rs36084323 were shared in these three diseases. Furthermore, the bio-function was confirmed by dual-luciferase reporter assay. It was shown that rs733618 T > C and rs4553808 A > G significantly decreased the transcriptional activity (both p < 0.001). This study is the first to confirm that these three diseases share genetically predisposing factors, and our results support the proposal that rs733618 T > C and rs4553808 A > G have bio-functional effects on the transcriptional activity of the CTLA4 gene.

LncRNA FOXD3-AS1/miR-128-3p axis-mediated IGF2BP3 in glioma stimulates cancer angiogenesis and progression.

INTRODUCTION: The aim of the study was to research the mechanism by which IGF2BP3 regulates glioma progression as well as its upstream regulatory axis. MATERIAL AND METHODS: The researched mRNA was determined using differential expression analysis based on bioinformatics data, and its upstream miRNAs and lncRNAs were predicted. Interaction between genes we researched was identified by dual-luciferase method. The viability, migration, invasion and angiogenesis of glioma were measured with MTT, colony formation, Transwell and Matrigel tube formation experiments, respectively. The mRNA expression of each gene was tested with qRT-PCR. IGF2BP3 level was determined via western blot and immunohistochemistry. Subcellular fractionation of FOXD3-AS1 was tested with fluorescence in situ hybridization. In vivo tumorigenesis assay was conducted on nude mice. RESULTS: IGF2BP3 high level in glioma cells correlated with patient's prognosis. Downregulation of IGF2BP3 restrained proliferation, migration, invasion and angiogenesis in glioma cells both in vitro and in vivo. There was a binding relationship between IGF2BP3 and miR-128-3p. Besides, FOXD3-AS1 as a sponge of miR-128-3p was located mainly in cytoplasm. Additionally, FOXD3-AS1 facilitated IGF2BP3 level via sponging miR-128-3p to stimulate glioma angiogenesis. CONCLUSIONS: FOXD3-AS1 was a sponge of miR-128-3p through upregulating IGF2BP3 in glioma. Our findings shed light on diagnosis and treatment of glioma.

Exploring the Bio-Functional Effect of Single Nucleotide Polymorphisms in the Promoter Region of the TNFSF4, CD28, and PDCD1 Genes.

In a prior study, we discovered that hematopoietic stem cell transplantation (HSCT) and/or autoimmune diseases, such as systemic lupus erythematosus, were associated with the rs1234314 C/G and rs45454293 C/T polymorphisms of TNFSF4, the rs5839828 C > del and rs36084323 C > T polymorphisms of PDCD1, and the rs28541784C/T, rs200353921A/T, rs3181096C/T, and rs3181098 G/A polymorphisms of CD28. However, the association does not imply causation. These single nucleotide polymorphisms (SNPs) are all located in the promoter region of these genes, so we used the dual-luminescence reporter assay to explore the effect of single nucleotide polymorphisms (SNPs) on transcriptional activity. For each promoter-reporter with a single SNP mutation, more than 10 independent experiments were carried out, and the difference in transcription activity was compared using one-way ANOVA and Tukey's honestly significant difference test. The results showed that the G-allele of rs1234314 had 0.32 ± 0.09 times the average amount of relative light units (RLU) compared to the C-allele (p = 0.003), the T-allele of rs45454293 had 4.63 ± 0.92 times the average amount of RLU compared to the C-allele (p < 0.001), the del-allele of rs5839828 had 1.37 ± 0.24 times the average amount of RLU compared to the G-allele (p < 0.001), and the T-allele of rs36084323 had 0.68 ± 0.07 times the average amount of RLU compared to the C-allele (p < 0.001). The CD28 SNPs studied here did not affect transcriptional activity. In conclusion, the findings of this study could only confirm that the SNP had a bio-functional effect on gene expression levels. According to the findings, several SNPs in the same gene have bio-functions that affect transcriptional activity. However, some increase transcriptional activity while others decrease it. Consequently, we inferred that the final protein level should be the integration result of the co-regulation of all the SNPs with the effect on transcriptional activity.

The biological functions of protein S-sulfhydration in eukaryotes and the ever-increasing understanding of its effects on bacteria.

As a critical endogenous signaling molecule, hydrogen sulfide may induce reversible post-translational modifications on cysteine residues of proteins, generating a persulfide bond known as S-sulfhydration. A systemic overview of the biofunctions of S-sulfhydration will equip us better to characterize its regulatory roles in antioxidant defense, inflammatory response, and cell fate, as well as its pathological mechanisms related to cardiovascular, neurological, and multiple organ diseases, etc. Nevertheless, the understanding of S-sulfhydration is mostly built on mammalian cells and animal models. We subsequently summarized the mediation effects of this specific post-transcriptional modification on physiological processes and virulence in bacteria. The high-sensitivity and high-throughput detection technologies are required for studying the signal transduction mechanism of H2S and protein S-sulfhydration modification. Herein, we reviewed the establishment and development of different approaches to assess S-sulfhydration, including the biotin-switch method, modified biotin-switch method, alkylation-based cysteine-labelled assay, and Tag-switch method. Finally, we discussed the limitations of the impacts of S-sulfhydration in pathogens-host interactions and envisaged the challenges to design drugs and antibiotics targeting the S-sulfhydrated proteins in the host or pathogens.

Binding stability of peptides to Co-Cr-Mo alloy affects proliferation and differentiation of osteoblast.

Cobalt-chromium-molybdenum (CCM) alloys possess high corrosion-resistant properties as well as good mechanical properties. Hence, the alloys are employed in medical implants such as artificial knee and hip joints, coronary stents, and removable partial dentures. To improve the biocompatibility of CCM alloys, we reported that CCM-binding peptide (CBP) linked to cell-adhesive motif Arg-Gly-Asp (RGD) improved the attachment of endothelial cells on CCM alloys. However, the stability of CBP adsorption on the alloy and its effect on osteoblast compatibility are still unclear. In this study, we evaluated the stabilization of the adsorption layer of CBP-RGD on CCM alloy surface and investigated the effect of CBP-RGD peptide on the proliferation and differentiation of the osteoblasts. CBP-RGD layer exhibited higher stabilization than the RGD adsorption layer for 7 days. In addition, the proliferation of osteoblast on CBP-RGD adsorbed alloy higher than that on RGD adsorbed alloy. Moreover, the calcification of cells cultured on the CBP-RGD adsorbed alloy was significantly higher than that of the cells on RGD adsorbed alloy. These findings indicate that the CBP binding was stable during the culture of osteoblasts on the CCM alloy.

Quantification, identification and comparison of oligopeptides on five tea categories with different fermentation degree by Kjeldahl method and ultra-high performance liquid chromatography coupled with quadrupole-orbitrap ultra-high resolution mass spectrometry.

Peptides with different lengths or amino sequences could have specific tastes or bio-activities. So far, either the quantity or pattern differences of peptide among various of teas were unknown. Here, firstly, we developed a method for tea oligopeptide quantification and made comparison of their contents. Secondly, we applied ultra-high performance liquid chromatography coupled with quadrupole-orbitrap ultra-high resolution mass spectrometry (UHPLC-Quadrupole-Orbitrap-UHRMS) to sequence oligopeptides. As a result, the total amount of oligopeptides in white tea and dark tea were higher, followed by black tea and green tea, finally with oolong tea. It suggested that withering which undergoes with endogenous protease and post-fermented that undergoes with a participation of exotic micro-organisms were key in oligopeptide enrichment. Thirdly, a total of 902 abundant identified peptides, most of which were tripeptide, tetrapeptide, pentapeptide, and hexapeptide were screened against several existing peptide databases. There were a series of taste peptides and bio-active peptides existing.

Research Progress on Polydopamine Nanoparticles for Tissue Engineering.

Tissue engineering is an interdisciplinary field that aims to develop biological substitutes for the replacement, repair, or enhancement of tissue function. The physical and chemical characteristics of biomaterials exert a profound influence on the biological responses and the following biofunction. Nanostructured coatings have been widely applied as an effective surface modification strategy to improve the bioactivity of biomaterials. Especially, polydopamine and polydopamine-derived nanoparticles are found with excessive adhesiveness, redox activity, photothermal conversion capacity, paramagnetism and conductivity other than excellent biocompatibility, and hydrophilicity. In this article, advances about polydopamine nanoparticles in tissue engineering applications are reviewed, including the repair of bone, cartilage, skin, heart, and nerve, to provide strategies for future biomaterial design.

Biofunctional magnesium coating of implant materials by physical vapour deposition.

The lack of bioactivity of conventional medical materials leads to low osseointegration ability that may result in the occurrence of aseptic loosening in the clinic. To achieve high osseointegration, surface modifications with multiple biofunctions including degradability, osteogenesis, angiogenesis and antibacterial properties are required. However, the functions of conventional bioactive coatings are limited. Thus novel biofunctional magnesium (Mg) coatings are believed to be promising candidates for surface modification of implant materials for use in bone tissue repair. By physical vapour deposition, many previous researchers have deposited Mg coatings with high purity and granular microstructure on titanium alloys, polyetheretherketone, steels, Mg alloys and silicon. It was found that the Mg coatings with high-purity could considerably control the degradation rate in the initial stage of Mg alloy implantation, which is the most important problem for the application of Mg alloy implants. In addition, Mg coating on titanium (Ti) implant materials has been extensively studied both in vitro and in vivo, and the results indicated that their corrosion behaviour and biocompatibility are promising. Mg coatings continuously release Mg ions during the degradation process, and the alkaline environment caused by Mg degradation has obvious antibacterial effects. Meanwhile, the Mg coating has beneficial effects on osteogenesis and osseointegration, and increases the new bone-regenerating ability. Mg coatings also exhibit favourable osteogenic and angiogenic properties in vitro and increased long-term bone formation and early vascularization in vivo. Inhibitory effects of Mg coatings on osteoclasts have also been proven, which play a great role in osteoporotic patients. In addition, in order to obtain more biofunctions, other alloying elements such as copper have been added to the Mg coatings. Thus, Mg-coated Ti acquired biofunctions including degradability, osteogenesis, angiogenesis and antibacterial properties. These novel multi-functional Mg coatings are expected to significantly enhance the long-term safety of bone implants for the benefit of patients. This paper gives a brief review of studies of the microstructure, degradation behaviours and biofunctions of Mg coatings, and directions for future research are also proposed.

Ligand Binding Mechanism and Its Relationship with Conformational Changes in Adenine Riboswitch.

Riboswitches are naturally occurring RNA aptamers that control the expression of essential bacterial genes by binding to specific small molecules. The binding with both high affinity and specificity induces conformational changes. Thus, riboswitches were proposed as a possible molecular target for developing antibiotics and chemical tools. The adenine riboswitch can bind not only to purine analogues but also to pyrimidine analogues. Here, long molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) computational methodologies were carried out to show the differences in the binding model and the conformational changes upon five ligands binding. The binding free energies of the guanine riboswitch aptamer with C74U mutation complexes were compared to the binding free energies of the adenine riboswitch (AR) aptamer complexes. The calculated results are in agreement with the experimental data. The differences for the same ligand binding to two different aptamers are related to the electrostatic contribution. Binding dynamical analysis suggests a flexible binding pocket for the pyrimidine ligand in comparison with the purine ligand. The 18 µs of MD simulations in total indicate that both ligand-unbound and ligand-bound aptamers transfer their conformation between open and closed states. The ligand binding obviously affects the conformational change. The conformational states of the aptamer are associated with the distance between the mass center of two key nucleotides (U51 and A52) and the mass center of the other two key nucleotides (C74 and C75). The results suggest that the dynamical character of the binding pocket would affect its biofunction. To design new ligands of the adenine riboswitch, it is recommended to consider the binding affinities of the ligand and the conformational change of the ligand binding pocket.

LncRNA TUG1 contributes to ESCC progression via regulating miR-148a-3p/MCL-1/Wnt/ß-catenin axis in vitro.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies. Latest studies report that long noncoding RNAs (LncRNAs) play an essential role in diversified pathological processes of ESCC, although the mechanism by which they do so remains unknown. This study aimed to explore the parts of lncRNA taurine upregulated gene 1 (TUG1) in ESCC tissues and cells, its biofunctional effect and its underlying regulatory mechanism in ESCC. METHODS: The levels of TUG1 and miR-148a-3p were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in ESCC cells and tissues. The biofunctional effects were examined by MTT, flow cytometry, and transwell assay. The protein expression levels of epithelial-mesenchymal transition (EMT)-related proteins and MCL-1 were determined by western blot analysis. The binding sites between miR-148a-3p and TUG1 or MCL-1 were predicted by online software starBase and confirmed by dual luciferase reporter assay. RESULTS: The mRNA expression of TUG1 was significantly upregulated in ESCC tissues or cells, and was negatively correlated to miR-148a-3p expression in tissues. Knockdown of TUG1 inhibited the proliferation, migration, and invasion, promoted apoptosis, and relieved the EMT progression in EC9706 and OE19 cells. Besides, knockdown of miR-148a-3p inverted positive effects from TUG1 deletion on ESCC cells. Besides, MCL-1 reversed the inhibitive effects from TUG1 deletion on expression of EMT-associated proteins (Wnt1, C-myc, CyclinD1, and ß-catenin) above subsequently. CONCLUSION: TUG1 regulated the biofunction and EMT progression of ESCC by mediating miR-148a-3p/MCL-1/Wnt/ß-catenin axis in vitro.

Titanium-Tissue Interface Reaction and Its Control With Surface Treatment.

Titanium (Ti) and its alloys are widely used for medical and dental implant devices-artificial joints, bone fixators, spinal fixators, dental implant, etc. -because they show excellent corrosion resistance and good hard-tissue compatibility (bone formation and bone bonding ability). Osseointegration is the first requirement of the interface structure between titanium and bone tissue. This concept of osseointegration was immediately spread to dental-materials researchers worldwide to show the advantages of titanium as an implant material compared with other metals. Since the concept of osseointegration was developed, the cause of osseointegration has been actively investigated. The surface chemical state, adsorption characteristics of protein, and bone tissue formation process have also been evaluated. To accelerate osseointegration, roughened and porous surfaces are effective. HA and TiO2 coatings prepared by plasma spray and an electrochemical technique, as well as alkalinization of the surface, are also effective to improve hard-tissue compatibility. Various immobilization techniques for biofunctional molecules have been developed for bone formation and prevention of platelet and bacteria adhesion. These techniques make it possible to apply Ti to a scaffold of tissue engineering. The elucidation of the mechanism of the excellent biocompatibility of Ti can provide a shorter way to develop optimal surfaces. This review should enhance the understanding of the properties and biocompatibility of Ti and highlight the significance of surface treatment.

Immunological features and functional analysis of anti-CFH autoantibodies in patients with atypical hemolytic uremic syndrome.

OBJECTIVE: Atypical hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. Anti-complement factor H (CFH) antibodies were thought to participate in the pathogenesis of aHUS. The aim of this study was to address the functions and properties of CFH autoantibodies in a Chinese Han cohort of aHUS patients. METHODS: Thirty-six anti-CFH antibody-positive aHUS patients at the acute phase of the disease were involved in this study. Clinical data of the patients were collected. Anti-CFH immunoglobulin G (IgG) subclasses and antibody isotypes were detected by ELISA. Epitope mapping was performed using recombinant CFH fragments (SCRs 1-4, SCR 7, SCRs 11-14, and SCRs 19-20). Purified IgG from plasma from seven patients were used for functional analyses. RESULTS: All patients presented with the classic triad of HUS. The anti-CFH autoantibodies mostly bound to the SCRs 19-20 domains of CFH but not the SCRs 1-4 domains. CFI cofactor activity was not disturbed by the anti-CFH antibody in any of the seven patients. Purified IgG interfered with the binding of CFH to C3b and CFH-mediated sheep erythrocyte protection in all seven patients. IgG from 4/5 (80%) patients tested inhibited the binding of CFH to glomerular endothelial cells. CONCLUSIONS: Our study suggests that the properties of CFH antibodies from patients with aHUS, including the recognition of SCRs and IgG subclasses, can influence and impair the biological role of CFH and therefore contribute to aHUS susceptibility.

Functional Control of Peptide Amphiphile Assemblies via Modulation of Internal Cohesion and Surface Chemistry Switch.

Understanding the impacts of the internal cohesion and surface chemistry of supramolecular systems on the collective behaviors in the contacts between the systems and biomolecules can greatly expand the functional diversity and adaptivity of supramolecular nanostructures. Here we show how the tuned molecular interactions modulate the morphologies and internal cohesion of peptide amphiphile (PA) self-assemblies and their resultant functions. Circular dichroism spectroscopy, fluorescence probing, atomic force and electron microscopy, along with molecular dynamics simulations, revealed that the PA self-assembly formed compact long fibers when surface charge repulsion was screened, but formed loose short fibers or micelle-like assemblies when hydrogen bonding was disrupted or hydrophobic core was enhanced. More importantly, depending on the strength of the phospholipid affinity for the cationic segment of the PA, the same internal cohesion of PA nanostructures can lead to either cell death or cell survival, providing unique insights into the design of supramolecular materials.

Multifunctional protein microparticles for medical applications.

Micro- and nano-scale intelligent devices can revolutionize the medical field. Although proteins are promising materials for creating biocompatible miniature medical devices with biological functions, construction of complicated solid-state architectures, using inherently vulnerable proteins, remains challenging. Here, I present a sophisticated strategy for constructing a multifunctional microparticle for medical applications using multiple proteins; this strategy achieved the retention of function, increased stability, and orientation control of the proteins in the fabricated particle. As proof-of-concept, the particle, designed to cope with excess reactive oxygen species (ROS) involved in many diseases, was constructed by combining three proteins with different functions. The body of the particle was fabricated using albumin and superoxide dismutase (SOD), and the antibody was incorporated into the surface of the particle in an orientation-controlled manner. The constructed protein microparticle exhibited coordinated activities for coping with ROS, such as capture of the ROS-secreting cells by the incorporated antibody, followed by the elimination of 70% ROS, secreted from the captured cells, by the SOD in the particle. Additionally, diapocynin, loaded to the particle via the drug-binding ability of albumin, was released from the particle, preventing ROS production in the cells. This multifunctional microparticle, constructed from proteins, will profoundly impact the development of intelligent protein-based miniature devices used in medical fields.