Protein Deposition Research Articles

Inhibition of Bone Morphogenetic Protein Signaling Prevents Tau Pathology in iPSC Derived Neurons and PS19 Mice.

Many neurodegenerative disorders share a common pathologic feature involving the deposition of abnormal tau protein in the brain (tauopathies). This suggests that there may be some shared pathophysiologic mechanism(s). The largest risk factor for the majority of these disorders is aging, suggesting involvement of the aging process in the shared pathophysiology. We test the hypothesis that an increase in bone morphogenetic protein (BMP) signaling that occurs during aging contributes to the onset and progression of tauopathies. Human induced pluripotent stem cell (iPSC)-derived neurons from patients with Alzheimer's disease (AD) were used to investigate the effects of BMP signaling on tau phosphorylation and release and the mechanisms underlying these effects. Wildtype mice were used to examine effects of BMP signaling in vivo. P301S (PS19) mice were examined for the effects of BMP signaling in a model of tauopathy. Here, we show that BMP signaling, mediated by non-canonical p38 signaling, increases tau phosphorylation and release of p-tau in human iPSC-derived AD neurons. Further, there is an interaction between BMP signaling and apolipoprotein E4 (ApoE4) that significantly increases tau phosphorylation and release compared with ApoE3 neurons. Inhibiting BMP signaling reduces the changes in tau in the cultured human neurons, and it limits tau pathology and prevents cognitive decline in PS19 mice. Our study suggests that the age-related increase in BMP signaling may participate in the onset and progression of tau pathology. Thus, therapeutic interventions that reduce BMP signaling in the aging brain could potentially slow or prevent development of diseases involving tau hyperphosphorylation. ANN NEUROL 2024.

Traumatic Brain Injury and Alzheimer's Disease Biomarkers: A Systematic Review of Findings from Amyloid and Tau Positron Emission Tomography.

Traumatic brain injury (TBI) has been discussed as a risk factor for Alzheimer's disease (AD) due to its association with AD risk and earlier cognitive symptom onset. However, the mechanisms behind this relationship are unclear. Some studies have suggested TBI may increase pathological protein deposition in an AD-like pattern; others have failed to find such associations. This review covers literature that uses positron emission tomography (PET) of β-amyloid (Aβ) and/or tau to examine individuals with a history of TBI who are at increased risk for AD due to age. A comprehensive literature search was conducted on January 9, 2023, and 26 resulting citations met inclusion criteria. Common methodological concerns included small samples, limited clinical detail about participants' TBI, recall bias due to reliance on self-reported TBI, and an inability to establish causation. For both Aβ and tau, results were widespread but inconsistent. The regions that showed the most compelling evidence for increased Aβ deposition were the cingulate gyrus and cuneus/precuneus. Evidence for elevated tau was strongest in the medial temporal lobe, entorhinal cortex, precuneus, and frontal, temporal, parietal, and occipital lobes. However, conflicting findings across most regions in both Aβ- and tau-PET studies indicate the critical need for future work in expanded samples and with greater clinical detail to offer a clearer picture of the relationship between TBI and protein deposition in older individuals at risk for AD.

Elevation of Granulocyte Colony Stimulating Factor in Human AMD Donor RPE-Choroid.

Choroidal inflammation, complement deposition, and accumulation of C-reactive protein (CRP) are involved in age-related macular degeneration (AMD) pathology. The pro-inflammatory signals that regulate immune cell recruitment in the choroid of patients with AMD remain to be determined. We performed cytokine profiling of human AMD and age-matched control donor tissue to identify inflammatory molecules upregulated in AMD tissue. Protein was isolated from 25 AMD and 21 control donor RPE/choroid macular punches. Total protein was quantified, and 50 µg assayed for expression of 40 cytokines using an inflammation array. We validated the elevated expression of granulocyte colony stimulating factor (G-CSF) protein by ELISA in a second cohort of 22 control and 26 AMD donors. To identify an AMD associated stressor responsible for upregulating G-CSF we assayed for changes in G-CSF protein secretion in RPE/choroid organ cultures treated with the monomeric (m)CRP, an inflammatory protein elevated in AMD. Using a multiplex array, we identified elevated G-CSF protein in the choroid of AMD donors compared to age-matched non-AMD controls. Differential expression of G-CSF was confirmed via ELISA in an independent cohort of samples (P = 0.01). The mCRP, which is deposited in AMD choroids, increased G-CSF protein secretion in RPE/choroid organ cultures. Single nuclei RNA sequencing identified choroidal endothelial cells and fibroblasts as the primary cell types responsible for increased G-CSF secretion in response to mCRP. The G-CSF receptor is expressed primarily by choroidal macrophages and dendritic cells and anti-G-CSFR colocalizes with anti-CD45 and anti-CD68 in human donor choroid tissue. Elevated G-CSF expression in AMD donor tissue as a result of increased levels of mCRP may be involved in immune cell recruitment in AMD contributing to inflammatory stress in the choroid.

On Multicell-Interaction Chip: In Situ Observing the Interactions between the Astrocytes with Lysosomal Dysfunction and BBB Cells.

Lysosomes in astrocytes play vital roles in toxic protein degradation in the brain. Lysosomal dysfunction can lead to abnormal protein deposits, which further induce damage to neurons and the blood-brain barrier (BBB), and thereby affect the interaction between the nervous and vascular systems. Therefore, investigating the interactions between astrocytes with lysosomal dysfunction and BBB cells is of significant importance. However, the lack of effective in vitro models hinders the study of this complex system. Herein, an 8-well arrayed microfence multicell interculture chip (AMMIC) with a hydrophilically optimized surface is introduced for investigating the interactions between astrocytes and BBB cells. Then, a novel lysosome-targeted photosensitizer, IVQ-2Br, is synthesized for inducing controllable oxidative stress damage in the lysosomes of astrocytes. By the combination of the 8-well AMMIC and IVQ-2Br, a model for studying the interactions between astrocytes with lysosomal dysfunction and BBB cells has been constructed. Particularly, severe secondary injuries to BBB cells brought about by oxidative stress, including alterations in cell morphology and activity as well as notable DNA damage, are in situ observed on the 8-well AMMIC. The mediators involved in this oxidative stress injury-mediated intercellular communication are validated to be reactive oxygen species (ROS) and exosomes. This work not only presents an in vitro modeling method for studying cell-cell interactions but also demonstrates the potential of in vitro models constructed through the integration of complex microfluidic chip techniques and photosensitizers for advancing biomedical research.

Loss of PTPN21 disrupted mitochondrial metabolic homeostasis and aggravated experimental pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a high-mortality lung disease with unclear pathogenesis. Convincing evidence suggests that an imbalance in mitochondrial homeostasis resulting from repeated injury to alveolar epithelial type 2 cells (AEC2) underlies IPF. Non-receptor protein tyrosine phosphatase 21 (PTPN21) performs various functions in cancer; however, its role in IPF has not been studied. This study aimed to investigate the role of PTPN21 in lung fibrosis. The experimental results showed that loss of PTPN21 exacerbated lung fibrosis by increasing cell numbers in bronchoalveolar lavage fluid, lung hydroxyproline content, and extracellular matrix protein expression of fibronectin and α-smooth muscle actin (α-SMA) in bleomycin-challenged mouse lungs. In A549 cells (AEC2), knockdown of PTPN21 suppressed focal adhesion and migration, reduced mitochondrial fission and increased fusion, increased the level of mitochondrial superoxide, decreased mitochondrial membrane potential and ATP levels. Simultaneously, knockdown of PTPN21 impaired autophagy, and increased intracellular reactive oxygen species levels. Treatment of fibroblasts (MRC-5) and primary human lung fibroblasts (PHLF)) with the supernatant from PTPN21-knockdown A549 cells increased the expression of fibronectin, collagen 1 and α-SMA. Conversely, overexpression of PTPN21 in A549 cells produced opposite effects. However, treatment of MRC-5 and PHLF with the supernatant from PTPN21-overexpressing A549 cells only slightly reduced the expression of fibronectin, collagen 1 in MRC-5 cells, but did not change the expression of α-SMA. In summary, this study revealed that the loss of PTPN21 in epithelial cells disrupted mitochondrial metabolic homeostasis, leading to epithelial cell inactivation and increased the deposition of extracellular matrix proteins in fibroblasts, thereby exacerbating experimental pulmonary fibrosis.

High-Throughput Single-Cell Analysis of Local Nascent Protein Deposition in 3D Microenvironments via Extracellular Protein Identification Cytometry (EPIC).

Extracellular matrix (ECM) guides cell behavior and tissue fate. Cell populations are notoriously heterogeneous leading to large variations in cell behavior at the single-cell level. Although insights into population heterogeneity are valuable for fundamental biology, regenerative medicine, and drug testing, current ECM analysis techniques only provide either averaged population-level data or single-cell data from a limited number of cells. Here, extracellular protein identification cytometry (EPIC) is presented as a novel platform technology that enables high-throughput measurements of local nascent protein deposition at single-cell level. Specifically, human primary chondrocytes are microfluidically encapsulated in enzymatically crosslinked microgels of 16 picoliter at kHz rates, forming large libraries of discrete 3D single-cell microniches in which ECM can be deposited. ECM proteins are labeled using fluorescence immunostaining to allow for nondestructive analysis via flow cytometry. This approach reveals population heterogeneity in matrix deposition at unprecedented throughput, allowing for the identification and fluorescent activated cell sorting-mediated isolation of cellular subpopulations. Additionally, it is demonstrated that inclusion of a second cell into microgels allows for studying the effect of cell-cell contact on matrix deposition. In summary, EPIC enables high-throughput single-cell analysis of nascent proteins in 3D microenvironments, which is anticipated to advance fundamental knowledge and tissue engineering applications.

Dietary supplementation with functional amino acids improves the capacity of growing pigs to cope with a health challenge

This study aimed to assess the effects of additional dietary supplementation with a blend of functional amino acids (FAA) with Thr, Trp, and Met as a preventive (prior to health challenge), curative strategy (during health challenge) or both targeting the performance, body composition, metabolic biomarkers of growing group-housed pigs raised under a health challenge. Additionally, the influence of these feeding strategies on pig response was investigated after the challenge (during the finishing phase). Sixty weaned piglets [6.3 ± 0.9kg body weight (BW)] were distributed based on BW in a nursery barn to one of two dietary treatments (n=30): control (CN) or supplemented with FAA blend (FAA+; 120% of the Thr:Lys, Trp:Lys, and Met+Cys:Lys requirements) for 7 weeks. After 7 weeks, the pigs (27.9 ± 4.2kg of BW) were distributed in a randomized complete block design to one of four treatments for the period of the health challenge period in the growing phase: pigs fed a CN diet during the nursery period were either maintained on a CN diet (control; n=14) or switched to an FAA+ diet (curative strategy; n=14), whereas the pigs fed an FAA+ diet during the nursery period were either fed a CN diet (preventive strategy; n=14) or continued receiving an FAA+ diet (continuous strategy; n=14). The health challenge consisted of subjecting growing pigs to batch mixing, poor housing conditions, and oral inoculation with Salmonella Typhimurium (ST). Poor housing conditions were maintained for 4 weeks (weeks 8 to 11). After this period, the pigs received the same standard diets for 9 weeks (weeks 12 to 20), and the facilities were cleaned daily. The health challenge increased the rectal temperature (P < 0.01) and serum concentrations of haptoglobin (P < 0.05), IgA (P < 0.05), IgG (P < 0.01), triglycerides (P < 0.01), creatinine (P < 0.01), and urea (P < 0.01), while reducing serum concentrations of lactate dehydrogenase (P < 0.01), albumin (P < 0.01), and glucose (P < 0.05). Pigs fed a continuous FAA+ diet trend towards lower fecal ST shedding (P < 0.10) than did the curative strategy pigs and had better fecal consistency scores (P < 0.01) than did the control pigs. During the challenge period, pigs fed FAA+ curatively or continuously demonstrated higher average daily gain and feed efficiency compared to control pigs (P < 0.01). Greater (P < 0.05) protein deposition (+30%) and improved (P < 0.05) nitrogen retention efficiency (+20% to curative and +30% to continuous strategies) were observed in the pigs fed the FAA+ diet during the health challenge compared with the control pigs. Curative-fed FAA+ pigs had greater BW at the end of the finishing phase than did the control and preventive group (P < 0.05). In conclusion, the use of FAA supplementation as a curative or continuous strategy is highly effective at improving the performance and body composition of growing pigs under a health challenge.

Tracheobronchial amyloidosis following COVID-19 infection.

Deposition of amyloid proteins in extracellular space can occur due to uncontrolled inflammatory processes. Tracheobronchial amyloidosis (TBA) is a rare form of such disease. A 68-year-old woman was evaluated for chronic cough following a COVID-19 infection. Although post-viral sequelae were suspected, further investigation revealed TBA. This condition involves amyloid deposits within the airways. The temporal association with COVID-19 raises a potential etiological link, suggesting viral-induced inflammatory or immune-mediated processes may play a role. This case underlines the need to consider rare etiologies like TBA in patients with unresolved respiratory symptoms post-COVID-19.

3,4,5-trimethoxycinnamic acid methyl ester isolated from Polygala tenuifolia enhances hippocampal LTP through PKA and calcium-permeable AMPA receptor

Alzheimer’s disease (AD) is a degenerative brain disorder characterized by progressive cognitive decline and neuronal death due to extracellular deposition of amyloid β (Aβ) and intracellular deposition of tau proteins. Recently approved antibody drugs targeting Aβ have been shown to slow the progression of the disease, but they have minimal effects on cognitive improvement. Therefore, there is a need to develop drugs with cognitive-enhancing effects that can be used in conjunction with these antibody treatments. In this study, we investigated whether Polygala tenuifolia (PT), traditionally known for its cognitive-enhancing effects, can improve synaptic plasticity and identified its active components and mechanisms. PT demonstrated a dose-dependent effect in enhancing long-term potentiation (LTP), and among its components, 3,4,5-trimethoxycinnamic acid methyl ester (TMCA) showed a similar LTP-enhancing effect. TMCA increased the phosphorylation of the GluA1 subunit of the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and increased the amount of GluA1 on the synapse without affecting the amount of GluA2. Additionally, the increase in GluA1 induced by TMCA was inhibited by a PKA inhibitor. Consistent with these results, the enhancement of LTP by TMCA was inhibited by a GluA1 antagonist and a PKA inhibitor. In silico molecular docking experiments confirmed that TMCA binds to PKA. Finally, we confirmed the LTP-enhancing effect of TMCA in hippocampal slices from 5XFAD mice. These results suggest that PT and its active component, TMCA, can interact with PKA to enhance LTP, indicating the potential for improving cognitive function in AD patients

Arginine–NO pathway modulated energy metabolism in the hepatopancreas and muscle of female Litopenaeus vannamei

Currently, the regulational effect of arginine on the energy metabolism is unknown in broodstock shrimp nutrition. Accordingly, an eight-week feeding trial was conducted to confirm it in female Litopenaeus vannamei. Six diets were formulated to contain graded levels of arginine (2.90 %, 3.58 %, 4.08 %, 4.53 %, 5.04 % and 5.55 %). A total of 540 shrimp (with an initial weight of approximately 14 g) were allocated at random to six treatments, each of which consisted of three tanks with 30 shrimp each. The results showed that with the rise in the level of dietary arginine supplementation, growth performance showed an increasing trend, reaching the highest value in the 5.55 % arginine group. The gene expression of cellular energy sensor AMP-activated protein kinase was up-regulated in muscle and hepatopancreas. Dietary arginine supplementation decreased hemolymph glucose content and hepatopancreas crude lipid content, increased muscle crude lipid content, glycogen content in muscle and hepatopancreas. Dietary arginine increased muscle crude protein content, decreased hepatopancreas crude protein content and activated the target of rapamycin 1 pathway. Above results were further confirmed by gene expression. In addition, shrimp were injected with dsGFP and dsNOS for 48 h and successfully constructed the RNA interference model. The findings showed that the levels of nos, cgmp, ampk (a, b, c), genes involved in glucose metabolism, lipid metabolism and amino acid metabolism were inhibited. In the conclusion, arginine supplementation could promote growth performance through modulating energy metabolism. Arginine–NO pathway modulated energy metabolism in hepatopancreas and muscle to promote tissue glycogen synthesis, muscle protein and lipid deposition in female L. vannamei.

The role of fibromodulin in myocardial fibrosis in a diabetic cardiomyopathy rat model.

Diabetic cardiomyopathy (DCM) is pathologically characterized by excessive deposition of extracellular matrix proteins, leading to myocardial fibrosis. Fibromodulin (Fmod) plays a crucial role in the pathogenesis of fibrotic diseases. However, the role and mechanism of Fmod in DCM-related myocardial fibrosis remain unclear. In the present study, we established a DCM rat model and an in vitro model of rat primary cardiac fibroblasts (RPCFs) exposed to high glucose. We assessed mRNA and protein expression levels of Col1a1, Col3a1, α-SMA and Fmod in both models. Fmod-overexpressing (ov-Fmod) and Fmod-knockdown (si-Fmod) rat cardiac fibroblasts (RCFs) were generated. Subsequently, whole RNA sequencing was conducted on ov-Fmod RCFs. The gene Col15a1 was evaluated in the DCM rat and all cell models. The correlation between plasma levels of Fmod and Col15a1 in DCM rat models was assessed. Transcription and protein levels of Fmod, Col1a1, Col3a1 and α-SMA were significantly elevated in DCM rat hearts and RPCFs. In ov-Fmod RCFs, fibrosis markers were similarly increased, except for Col3a1, which decreased. The Col1a1/Col3a1 ratio was elevated. Conversely, knocking down Fmod yielded opposite results. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that Fmod participates in multiple fibrosis-related pathways, affecting Col15a1. Expression of Col15a1 was significantly decreased in all models, compared to controls, except in si-Fmod RCFs. Importantly, Col15a1 and Fmod in plasma exhibited an inverse relationship in DCM. In summary, Fmod is implicated in DCM, with Fmod overexpression downregulating Col15a1 and increasing the Col1a1/Col3a1 ratio. This mechanism may influence diastolic heart failure in DCM by modulating myocardial stiffness and elasticity.

Histidine is effective in promoting muscle growth and protein deposition: In vivo and in vitro experimental models of grass carp (Ctenopharyngodon idella)

For aquatic animals, histidine is an essential amino acid. This study examined its impact on muscle growth and protein deposition in grass carp, both in vivo and in vitro, and explored the underlying mechanisms. A total of 450 grass carp (594.63 ± 0.68 g) were assigned randomly to six groups of three replicates for each group that was fed with six diets containing 1.08 (basal diet), 2.91, 5.87, 8.83, 11.78, and 14.79 g/kg histidine for 63 d. Results indicated that based on PWG and muscle protein content, the histidine demands of adult grass carp were 8.94 (34.12 g/kg protein) and 8.54 g/kg diet (32.60 g/kg protein), respectively. Optimal histidine promoted myofiber hypertrophy, which could be correlated with cell proliferation-associated proteins [PCNA, E2F4 and Cyclin (B, D and E)] and myogenic regulators (MyoD, MyoG, MyHC and Myf6). Optimum histidine enhanced protein deposition, which could be correlated with the facilitation of protein synthesis (IGF-1/PI3K/AKT/TOR) as well as the suppression of ubiquitin-proteasome system and autophagy-lysosome system to inhibit protein degradation. Furthermore, optimal histidine raised muscle bound amino acid content and amino acid chemistry scores, thereby increasing muscle nutritional value.

Targeting Protein Misfolding and Aggregation as a Therapeutic Perspective in Neurodegenerative Disorders.

The abnormal deposition and intercellular propagation of disease-specific protein play a central role in the pathogenesis of many neurodegenerative disorders. Recent studies share the common observation that the formation of protein oligomers and subsequent pathological filaments is an essential step for the disease. Synucleinopathies such as Parkinson's disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA) are neurodegenerative diseases characterized by the aggregation of the α-synucleinprotein in neurons and/or in oligodendrocytes (glial cytoplasmic inclusions), neuronal loss, and astrogliosis. A similar mechanism of protein Tau-dependent neurodegeneration is a major feature of tauopathies, represented by Alzheimer's disease (AD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Pick's disease (PD). The specific inhibition of the protein misfolding and their interneuronal spreading represents a promising therapeutic strategy against both disease pathology and progression. The most recent research focuses on finding potential applications targeting the pathological forms of proteins responsible for neurodegeneration. This review highlights the mechanisms relevant to protein-dependent neurodegeneration based on the most common disorders and describes current therapeutic approaches targeting protein misfolding and aggregation.

Development of a novel radioiodinated compound for amyloid and tau deposition imaging in Alzheimer's disease and tauopathy mouse models

Non-invasive determination of amyloid-β peptide (Aβ) and tau deposition are important for early diagnosis and therapeutic intervention for Alzheimer's disease (AD) and non-AD tauopathies. In the present study, we investigated the capacity of a novel radioiodinated compound AD-DRK (123/125I-AD-DRK) with 50% inhibitory concentrations of 11 nM and 2 nM for Aβ and tau aggregates, respectively, as a single photon emission computed tomography (SPECT) ligand in living brains. In vitro and ex vivo autoradiography with 125I-AD-DRK was performed in postmortem human and two transgenic (Tg) mice lines with either fibrillar Aβ or tau accumulation, APP23 and rTg4510 mice. SPECT imaging of 123I-AD-DRK was performed in APP23 mice to investigate the ability of AD-DRK to visualize fibrillar protein deposition in the living brain. In-vitro autoradiogram of 125I-AD-DRK showed high specific radioactivity accumulation in the temporal cortex and hippocampus of AD patients and the motor cortex of progressive supranuclear palsy (PSP) patients enriched by Aβ and/or tau aggregates. Ex-vivo autoradiographic images also demonstrated a significant increase in 125I-AD-DRK binding in the forebrain of both APP23 and rTg450 mice compared to their corresponding non-Tg littermates. SPECT imaging successfully captured Aβ deposition in the living brain of aged APP23 mice. The present study developed a novel high-contrast SPECT agent for assisting the diagnosis of AD and non-AD tauopathies, likely benefiting from its affinity for both fibrillar Aβ and tau.

Research progress on treatments for Alzheimer's disease

Abstract. Alzheimers disease (AD) is an irreversible neurological degenerative disease characterized by progressive cognitive impairment, and its pathogenesis remains unclear. Its main pathological features include neurofibrillary tangles formed by hyperphosphorylated tau protein and amyloid beta (A) plaque deposition. As the disease progresses, the patients self-care ability will become worse and worse. In the later stages, the patient will have to rely on others for daily life, which places a great burden on the patient, family, and society. Currently, there are a limited number of AD treatment drugs and their efficacy is limited, and they cannot effectively improve the condition of AD. This article reviews different methods for treating AD and provides a reference for the treatment of AD. At present, the treatment of senile dementia is mainly divided into two categories. The current treatment methods include Lencamab, bee therapy related drugs, NSCs transplantation therapy, Panax notoginseng saponins, and hyperbaric oxygen therapy. It is necessary to explore new treatment methods and drugs to improve treatment effectiveness and widely apply dementia in the elderly.

Exploring the Therapeutic Potential of Noncoding RNAs in Alzheimer's Disease.

Despite significant research efforts, Alzheimer's disease (AD), the primary cause of dementia in older adults worldwide, remains a neurological challenge for which there are currently no effective therapies. There are substantial financial, medical, and personal costs associated with this condition.Important pathological features of AD include hyperphosphorylated microtubule-associated protein Tau, the formation of amyloid β (Aβ) peptides from amyloid precursor protein (APP), and continuous inflammation that ultimately results in neuronal death. Important histological markers of AD, amyloid plaques, and neurofibrillary tangles are created when Aβ and hyperphosphorylated Tau build-up. Nevertheless, a thorough knowledge of the molecular players in AD pathophysiology is still elusive. Recent studies have shown how noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), regulate gene expression at the transcriptional and posttranscriptional levels in a variety of diseases, including AD. There is increasing evidence to support the involvement of these ncRNAs in the genesis and progression of AD, making them promising as biomarkers and therapeutic targets. As a result, therapeutic approaches that target regulatory ncRNAs are becoming more popular as potential means of preventing the progression of AD. This review explores the posttranscriptional relationships between ncRNAs and the main AD pathways, highlighting the potential of ncRNAs to advance AD treatment. In AD, ncRNAs, especially miRNAs, change expression and present potential targets for therapy. MiR-346 raises Aβ through APP messenger Ribonucleic Acid (mRNA), whereas miR-107 may decrease Aβ by targeting beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). They are promising early AD biomarkers due to their stability in cerebrospinal fluid (CSF) and blood. Furthermore, additional research is necessary to determine the role that RNA fragments present in AD-related protein deposits play in AD pathogenesis.

Dual Photonics Probing of Nano- to Submicron-Scale Structural Alterations in Human Brain Tissues/Cells and Chromatin/DNA with the Progression of Alzheimer's Disease.

Understanding alterations in structural disorders in tissue/cells/building blocks, such as DNA/chromatin in the human brain, at the nano to submicron level provides us with efficient biomarkers for Alzheimer's detection. Here, we report a dual photonics technique to detect nano- to submicron-scale alterations in brain tissues/cells and DNA/chromatin due to the early to late progression of Alzheimer's disease in humans. Using a recently developed mesoscopic light transport technique, fine-focused nano-sensitive partial wave spectroscopy (PWS), we measure the degree of structural disorder in tissues. Furthermore, the chemical-specific inverse participation ratio technique (IPR) was used to measure the DNA/chromatin structural alterations. The results of the PWS and IPR experiments showed a significant increase in the degree of structural disorder at the nano to submicron scale at different stages of AD relative to their controls for both the tissue/cell and DNA cellular levels. The increase in the structural disorder in cells/tissues and DNA/chromatin in the nuclei can be attributed to higher mass density fluctuations in the tissue and DNA/chromatin damage in the nuclei caused by the rearrangements of macromolecules due to the deposition of the amyloid beta protein and damage in DNA/chromatin with the progress of AD.

Poly(2-hydroxyethyl methacrylate-co-methacrylated hyaluronan-β-cyclodextrin) hydrogel: A potential contact lens material with high hydrophilicity, good mechanical properties and sustained drug delivery

A novel poly(2-hydroxyethyl methacrylate-co-methacrylated hyaluronan-β-cyclodextrin) [p(HEMA-co-mHA-β-CD)] hydrogel was developed as a potential contact lens for ophthalmic disease. The hydrogel was synthesized from the copolymerization of 2-hydroxyethyl methacrylate (HEMA) monomer and mHA-β-CD as a hydrophilic macromolecular crosslinker. By adjusting the methacrylate substitution degree in hyaluronan (20–29 %) and the mHA-β-CD content (5–11 %), transparent p(HEMA-co-mHA-β-CD) hydrogels were achieved. p(HEMA-co-m20HA-β-CD) hydrogels exhibited an enhanced tensile modulus (from 0.35 to 0.88 MPa) with a decreased elongation at break (from 255 % to 108 %), meanwhile they showed increased hydrophilicity with a decreased water contact angle (from 83.4° to 48.6°) and an increased equilibrium water content (from 38.2 % to 46.4 %). Increasing the mHA-β-CD content resulted in a higher encapsulation and cumulative release of hydrophilic levofloxacin hydrochloride or hydrophobic puerarin, due to the improved hydrophilicity and the formation of β-CD/drug inclusion complexes. Compared with pHEMA hydrogel, p(HEMA-co-m20HA-β-CD) hydrogels better inhibited the deposition of lysozyme and bovine serum albumin, and the bacterial adhesion against S. aureus and E. coli. The hydrogels were stable at physiological conditions and non-toxic to immortalized human keratinocytes. With good mechanical properties, tear protein deposition resistance, antibacterial activity, and sustained drug delivery capabilities, p(HEMA-co-m20HA-β-CD) hydrogels were identified as a promising contact lens material for eye diseases.

Polyamino Acid Based Zwitterionic Coating can Inhibit Coagulation and Inflammation Through Anti-Fouling and Restoring Microenvironment.

Protein adhesion and thrombosis formation caused by limited surface properties pose great challenges to biomedical implants. Although various hydrophilic coating or drug release coatings are reported, the single coating cannot cope with cases under the condition of complex physiological environment, which causes the coating effect is limited. In this study, a polyamino acid-derived zwitterionic coating is constructed to eliminate reactive oxygen species (ROS) in the microenvironment. It is demonstrated that the coating has excellent hydrophilicity, stability, and lubricity, and can obviously prevent protein adhesion. At the same time, the coating can eliminate hydrogen peroxide and maintain the stability of the microenvironment. The in vivo and in vitro experiments show that the coating has good biocompatibility, and inhibits thrombus. Amino acid zwitterion coating prevents protein deposition, alleviates the inflammatory process, inhibit of thrombosis, reduces the risk of implantable medical devices, and prolongs their service time. Hence, the work paves a new way to develop amino acid based zwitterionic polymer coating that can reduce the implant complications.

Utilising brewer’s spent grain as a cost-effective feed formula for sustainable house cricket (Acheta domesticus) rearing

Abstract This study investigates the potential of brewer’s spent grain (BSG) as a cost-effective alternative to soybean meal in the diets of house crickets (Acheta domesticus) to enhance sustainable cricket rearing. BSG, a by-product of the brewing industry, was chosen due to its local availability and high protein content (38%). Here, the impacts of varying levels of BSG substitution (0%, 10%, 20% and 30%) on the growth performance, nutrient utilisation, chemical composition, and volatile compound profiles of crickets over a 45-day period was assessed. Crickets were reared under controlled conditions and divided into five groups, each receiving one of the experimental diets. Growth performance parameters, including body weight, average daily gain, and feed conversion ratio, were measured. Chemical analysis of the crickets and their diets was conducted, focusing on protein efficiency ratio, apparent dry matter digestibility (ADMD), and nitrogen retention. Volatile compounds were identified using gas chromatography-mass spectrometry. Crickets fed BSG diets exhibited higher protein deposition and lower fat content compared to those on a commercial diet, suggesting BSG’s potential to improve protein quality while reducing fat accumulation. ADMD was also higher in BSG-fed crickets, likely due to the prebiotic effects of components such as β-glucans and arabinoxylans. Additionally, the inclusion of BSG up to 30% in cricket diets reduced production costs by up to 29% compared to a commercial diet. Volatile compound analysis revealed that crickets fed BSG diets produced different odour profiles, with 2-heptanone, a compound with a fruity aroma, detected only in BSG-fed crickets. These findings suggest that BSG is a viable and sustainable ingredient for cricket feed, offering both economic and nutritional benefits while also influencing the sensory characteristics of crickets. Further research is recommended to optimise BSG inclusion levels and explore its broader applications in insect and animal farming.