Photodynamic Therapy Synergizes CD47 Blockade Strategy for Enhanced Antitumor Therapy.

The antitumor strategies based on innate immunity activation have become favored by researchers in recent years. In particular, strategies targeting antiphagocytic signaling blockade to enhance phagocytosis have been widely reported. For example, the addition of prophagocytic signals such as calreticulin could make the strategy significantly more effective. In this study, an antitumor strategy that combines photodynamic therapy (PDT) with CD47 blockade has been reported. This approach promotes the maturation of dendritic cells and the presentation of tumor antigens by PDT-mediated tumor immunogenic cell death, as well as the enhancement of cytotoxic T lymphocyte infiltration in tumor areas and the phagocytic activity of phagocytes. Furthermore, the downregulation and blockage of CD47 protein could further promote phagocytic activity, strengthen the innate immune system, and ultimately elevate the antitumor efficacy and inhibit tumor metastasis.

Correlation analysis of peripheral platelet markers and disease phenotypes in Alzheimer's disease.

INTRODUCTION: Platelets serve as the primary peripheral reservoir of amyloid beta (Aß). However, there is limited research on platelet markers in routine blood examinations, particularly with regard to the large platelet ratio (P-LCR) in Alzheimer's disease (AD). METHODS: This study included 512 AD patients and 205 healthy controls (HCs). Platelet markers and apolipoprotein E (APOE) 4 status were assessed in all participants. RESULTS: The study revealed that P-LCR was significantly elevated in AD patients compared to HCs. In AD patients carrying APOE4, P-LCR significantly negatively correlated with Montreal Cognitive Assessment scores. There was an observed increasing trend in the rate of change in P-LCR with disease progression. Binary logistic regression analysis indicated that P-LCR may constitute a risk factor for AD, after adjusting for age, sex, APOE4, and body mass index. DISCUSSION: P-LCR is associated with disease severity in AD patients carrying APOE4. P-LCR may be a promising marker to reflect platelet activity in AD patients. HIGHLIGHTS: P-LCR significantly negatively correlated with MoCA scores in AD patients with APOE4. The rate of change in P-LCR showed an increasing trend with disease progression. P-LCR may be a risk factor for AD.

Meta-analysis and systematic review of peripheral platelet-associated biomarkers to explore the pathophysiology of alzheimer's disease.

INTRODUCTION: Platelets are the primary peripheral reserve of amyloid precursor protein (APP), providing more than 90% of blood amyloid-beta (Aß). Some oxidative stress markers and neurotransmitter markers were also differentially expressed in the peripheral platelets of AD. Therefore, the present study explored the differences in platelet-associated biomarkers between AD and healthy controls using meta-analysis and systematic review to reveal the value of platelet in the pathogenesis and development of AD. METHODS: We searched all the related studies that probed into the platelets in AD based on PubMed, Embase, and web of science databases from the establishment to November 04, 2021. RESULTS: Eighty-eight studies were included in the meta-analysis, and the platelets data of 702 AD and 710 controls were analyzed. The results of standardized mean difference (SMD) showed that platelets in AD had lower levels of APP ratio (SMD: -1.89; p < 0.05), ADAM10 (SMD: -1.16; p < 0.05), Na + -K + -ATPase (SMD: -7.23; p < 0.05), but higher levels of HMW/LMW tau (SMD: 0.92; p < 0.05), adenosine A2 receptor (SMD: 4.27; p < 0.05), MAO-B (SMD: 1.73; p < 0.05), NO (SMD: 4.25; p < 0.05) and ONOO- (SMD: 7.33; p < 0.05). In the systematic review, some other platelet markers seem to be meaningful in AD patients. CONCLUSION: The results of the present meta-analysis and systematic review demonstrated that the alterations of APP metabolic enzymes, oxidative stress markers, and neurotransmitter factors in platelets were similar to their changes in the central nervous system of AD, suggesting that platelet could be a good source of peripheral biomarkers and may play an important role in the pathophysiological development of AD.

A novel C19ORF12 mutation in two MPAN sisters treated with deferiprone.

BACKGROUND: Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a rare and devastating disease caused by pathogenic mutations in C19orf12 gene. MPAN is characterized by pathological iron accumulation in the brain and fewer than 100 cases of MPAN have been described. Although the diagnosis of MPAN has achieved a great breakthrough with the application of the whole exome gene sequencing technology, the therapeutic effect of iron chelation therapy in MPAN remains controversial. CASE PRESENTATION: We reported that two sisters from the same family diagnosed with MPAN had dramatically different responses to deferiprone (DFP) treatment. The diagnosis of MPAN were established based on typical clinical manifestations, physical examination, brain magnetic resonance imaging (MRI), cerebrospinal fluid analysis (CSF) and gene sequencing results. The clinical presentations of the two sisters with MPAN due to novel gene locus mutations were similar to those previously reported. There is no other difference in basic information except that the proband had a later onset age and fertility history. Both the proband and his second sister were treated with deferiprone (DFP), but they had dramatically different responses to the treatment. The proband's condition deteriorated sharply after treatment with DFP including psychiatric symptoms and movement disorders. However, the second sister of the proband became relatively stable after receiving the DFP treatment. After four years of follow-up, the patient still denies any new symptoms of neurological deficits. CONCLUSION: The findings of this study enriched the MPAN gene database and indicated that DFP might ameliorate symptom progression in patients without severe autonomic neuropsychiatric impairment at the early stage of the disease.

Serum biomarkers of colonic polyps in patients with acromegaly: a meta-analysis and systematic review.

PURPOSE: In the past few decades, acromegaly and colonic polyps have been associated with an increased risk of colorectal cancer. Previous studies highlighted the importance of serum biomarkers of colonic polyps in patients with acromegaly. METHODS: We reviewed studies on serum biomarkers of colonic polyps in patients with acromegaly, published on PubMed, Embase, Cochrane Library, Medline, and Chinese databases from January 1, 1966, to May 8, 2022. Meta-analysis and systematic review were conducted using Stata MP 14.0. RESULTS: Eight articles were included in this study. The mean (standard deviation) concentrations of serum biomarkers for acromegaly with and without colorectal polyps were extracted from these studies. Meta-analysis results showed that, compared to patients without colonic polyps, the levels of insulin-like growth factor-1 × upper limit of normal range (IGF-1 × ULN) and fasting insulin were significantly increased; while the levels of growth hormone (GH) were significantly decreased in patients with acromegaly and colonic polyps (IGF-1 × ULN: SMD 0.23; 95% CI 0.03-0.42, p < 0.05) (fasting insulin: SMD 0.95; 9 5% CI 0.11-1.8, p < 0.05) (GH: SMD - 0.25; 95% CI - 0.41 to - 0.08, p < 0.05). IGF-1 and FPG levels did not differ significantly (IGF-1: SMD -0.03; 95% CI - 0.22 to 0.17, p > 0.05) (FPG: SMD 0.14; 95% CI - 0.23 to 0.52, p > 0.05). The systematic review results suggest no significant differences in hemoglobin A1C, TSH, free thyroxine, FT4, T3, PRL, total cholesterol, HDL, LDL, fibrinogen, clathrate antigen, serum antigen 19-9, and α-fetoprotein levels, but serum Klotho levels. CONCLUSION: We present the first meta-analysis and systematic review of serum biomarkers in patients with acromegaly or colonic polyps. The prevalence of colonic lesion polyps, is associated with higher IGF-1 × ULN levels, higher insulin levels in acromegaly. Further research is required to confirm GH and serum soluble Klotho levels as biomarkers of colonic polyps. When IGF-1 × ULN, fasting insulin levels change in patients with acromegaly, the occurrence of colonic polyps should be monitored. Early detection may reduce the possibility of developing malignant colon neoplasms.

The role of Th17 cells/IL-17A in AD, PD, ALS and the strategic therapy targeting on IL-17A.

Neurodegenerative diseases are a group of disorders characterized by progressive loss of certain populations of neurons, which eventually lead to dysfunction. These diseases include Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Immune pathway dysregulation is one of the common features of neurodegeneration. Recently, there is growing interest in the specific role of T helper Th 17 cells and Interleukin-17A (IL-17A), the most important cytokine of Th 17 cells, in the pathogenesis of the central nervous system (CNS) of neurodegenerative diseases. In the present study, we summarized current knowledge about the function of Th17/IL-17A, the physiology of Th17/IL-17A in diseases, and the contribution of Th17/IL-17A in AD, PD, and ALS. We also update the findings on IL-17A-targeting drugs as potentially immunomodulatory therapeutic agents for neurodegenerative diseases. Although the specific mechanism of Th17/IL-17A in this group of diseases is still controversial, uncovering the molecular pathways of Th17/IL-17A in neurodegeneration allows the identification of suitable targets to modulate these cellular processes. Therapeutics targeting IL-17A might represent potentially novel anti-neurodegeneration drugs.

Meta-analysis of the Connection Between Alzheimer Disease and Telomeres.

BACKGROUND: Alzheimer disease (AD) is the most common neurodegenerative disease of the central nervous system. The stability of the telomere-telomerase system is closely related to AD. A previous meta-analysis indicated that AD patients had shorter telomere length (TL) than control subjects. However, there are no consistent telomerase activity findings in AD patients, and the published telomerase studies were not meta-analyzed yet. METHODS: We searched all the related studies that probed into TL and/or telomerase activity in AD patients based on PubMed and Embase database from the establishment to September 2020. The Chinese National Knowledge Infrastructure, Wanfang and China Science and Technology Journal Database were also utilized. The quality of the included studies was evaluated by using Newcastle-Ottawa Scale. All the statistical analyses of this meta-analysis were performed using Stata version 15.0. RESULTS: Analyzing 30 TL data from 2248 AD patients and 4865 controls, AD patients had a significantly shorter TL than the controls, with a standardized mean difference of -0.70 (confidence interval: -0.95 to -0.46; P<0.05). The meta-analysis included 3 primary studies and did not find a significant difference in the telomerase activity between 233 AD patients and 132 controls, but AD patients had a trend of increased telomerase activity compared with controls (standardized mean difference: 0.47; confidence interval: -0.29 to 1.23; P>0.05). CONCLUSION: Our results showed that compared with the control group, the AD group had a shorter TL and may have higher telomerase activity.

Highly efficient and durable antibacterial cotton fabrics finished with zwitterionic polysulfobetaine by one-step eco-friendly strategy.

In this work, a novel formulation of polysulfobetaine, poly (sulfobetaine-acrylamide-allyl glycidyl ether) (PSPB-AM-AGE), was synthesized and grafted onto cotton. The synthesis of PSPB-AM-AGE and its grafting on the cotton fabrics were confirmed by FTIR, XPS and SEM. The PSPB-AM-AGE treated cotton fabrics exhibited a high level of antibacterial rate against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), which are 95.18% and 98.74%, separately, as well as a good laundry durability. The mechanical tests showed that the essential cotton properties can be largely preserved in the treatment process. Moreover, the hydrophilicity, air and water permeability of the cotton were improved after treated with PSPB-AM-AGE, indicating a better wearing comfort performance. The whiteness of the cotton fabrics did not decrease significantly. The safety evaluation demonstrated that PSPB-AM-AGE had no cytotoxicity. The developed antibacterial finishing introduced a new method to apply polysulfobetaine interfaced on cellulose, providing great potential for biomedical fabric application.

Practical insights on enzyme stabilization.

Enzymes are efficient catalysts designed by nature to work in physiological environments of living systems. The best operational conditions to access and convert substrates at the industrial level are different from nature and normally extreme. Strategies to isolate enzymes from extremophiles can redefine new operational conditions, however not always solving all industrial requirements. The stability of enzymes is therefore a key issue on the implementation of the catalysts in industrial processes which require the use of extreme environments that can undergo enzyme instability. Strategies for enzyme stabilization have been exhaustively reviewed, however they lack a practical approach. This review intends to compile and describe the most used approaches for enzyme stabilization highlighting case studies in a practical point of view.

Laccase: a green catalyst for the biosynthesis of poly-phenols.

Laccases (benzene diol: oxidoreductases, EC 1.10.3.2) are able to catalyze the oxidation of various compounds containing phenolic and aniline structures using dissolved oxygen in water. Laccase structural features and catalytic mechanisms focused on the polymerization of aromatic compounds are reported. A description about the most recent research on the biosynthesis of chemicals and polymers is made. Selected applications of this technology are considered as well as the advantages, shortcomings and future needs related with the use of laccases.

Synthesis and crystal structure of a highly selective colorimetric and fluorometric sensor for hydrogen sulfide.

A novel Cu(II) complex chemosensor for hydrogen sulfide with azo as the colorimetric group has been synthesized. The complex and ligand crystals were obtained and the molecular structures were characterized by X-ray diffraction and Electrospray ionization High resolution mass spectrometer (ESI-HRMS). The photophysical and recognition properties were examined. The complex can recognize S2- , with an obvious color change from yellow to red based on a copper ion complex displacement mechanism. By contrast, no obvious changes were observed in the presence of other anions (AcO- , H2 PO4- , F- , Cl- , Br- and I- ). We present a simple, easily prepared, yet efficient, inorganic reaction-based sensor for the detection of S2- . The complex should have many chemical and analytical applications in the sensing of hydrogen sulfide.

Enzymatic processing of protein-based fibers.

Wool and silk are major protein fiber materials used by the textile industry. Fiber protein structure-function relationships are briefly described here, and the major enzymatic processing routes for textiles and other novel applications are deeply reviewed. Fiber biomodification is described here with various classes of enzymes such as protease, transglutaminase, tyrosinase, and laccase. It is expected that the reader will get a perspective on the research done as a basis for new applications in other areas such as cosmetics and pharma.

The Synthesis and Anion Recognition Property of Symmetrical Chemosensors Involving Thiourea Groups: Theory and Experiments.

The synthesis of four symmetrical compounds containing urea/thiourea and anthracene/nitrobenzene groups was optimized. N,N'-Di((anthracen-9-yl)-methylene) thio-carbonohydrazide showed sensitive and selective binding ability for acetate ion among the studied anions. The presence of other competitive anions including F(-), H2PO4(-), Cl(-), Br(-) and I(-) did not interfere with the strong binding ability. The mechanism of the host-guest interaction was through multiple hydrogen bonds due to the conformational complementarity and higher basicity. A theoretical investigation explained that intra-molecular hydrogen bonds existed in the compound which could strengthen the anion binding ability. In addition, molecular frontier orbitals in molecular interplay were introduced in order to explain the red-shift phenomenon in the host-guest interaction process. Compounds based on thiourea and anthracene derivatives can thus be used as a chemosensor for detecting acetate ion in environmental and pharmaceutical samples.

Bioinspired, surfactant-free, dual-layer asymmetric structures based on polysaccharides, gelatin, and tannic acid for potential applications in biomedicine.

The formation of dual-layer asymmetric porous structures in surfactant-based systems is significantly influenced by emulsions. Surfactants self-assemble to alter the conformational arrangement of polysaccharides, while gravity disrupts the initial uniformity of the established equilibrium droplet concentration gradient in the emulsion, thus achieving delamination. Specifically, high-speed rotation and non-instantaneous freezing allow the gelatin solution to form two different states of foam layers. The integrated dual-layer asymmetric porous structure, composed of polysaccharides and tannic acid, is constructed with gelatin as a skeleton and surfactant. This innovative approach eliminates the need to consider the toxicity of chemically synthesized surfactants and expands the concept of gelatin utilization. This intriguing structure exhibits a variety of desirable characteristics within 30 days (e.g., tailorable performance, ultrarapid antioxidant activity, efficient antibacterial activity, low differential blood clotting index, and good hemocompatibility and cytocompatibility), suggesting its potential as a valuable reference for applying hierarchical porous structures, thereby offering more formulation flexibility for biomaterials with adjustable properties.

Construction of asymmetric dual-layer polysaccharide-based porous structure on multiple sources for potential application in biomedicine.

Biomedical materials can produce high efficiency and special behavior with an integrated internal structure. It is possible that changing the structure of biomedical materials could extend and promote the application of eco-friendly and multifunctional biomaterials. However, the instantaneous formation of complex structures between tannic acid (TA) and polysaccharides is disrupted, and the reconstruction of the new porous structure becomes a key issue. Here, we present an innovative one-step forming method for an asymmetric dual-layer porous structure of carboxymethyl chitosan (CC)/sodium alginate (SA)/TA, which can be utilized in various biomedical applications. Even after 6 months of storage, it still demonstrates a range of desirable properties including tailorable performance, efficient antibacterial activity, ultrarapid antioxidant activity, low differential blood clotting index and cytotoxicity. This suggests its potential for regulating and controlling wound bleeding, providing flexible possibilities for potential applications in biomedicine.

Analysis of the Association Between Pathogen Exposure and the Risk of Dementia.

Background: Previous research has suggested that pathogen infections may serve as potential contributors to dementia. Objective: Consequently, the study aimed to evaluate whether pathogen exposure heightens the risk of dementia. Methods: Between 2006 and 2010, a total of 8,144 individuals from the UK Biobank had data on pathogen antibodies and were included in the baseline assessment. Cox proportional hazard models were employed for the analysis. Results: Out of the 8,144 participants, 107 eventually developed dementia, while 55 participants were diagnosed with Alzheimer's disease (AD). Multivariate Cox regression analysis revealed that the levels of pathogen antibody titers of EBV and C. trachomatis were associated with an increased risk of dementia/AD. The highest quartile of EBV EBNA-1 and EBV VCA p18, and the second quartile of H. pylori VacA significantly increased the risk of dementia compared lower quartile (EBV EBNA-1: HR = 1.938, p = 0.018; EBV VCA p18: HR = 1.824, p = 0.040; H. pylori VacA: HR = 1.890, p = 0.033). Besides, the highest quartile of EBV VCA p18 had a higher risk of AD compared lower quartile (HR = 2.755, p = 0.029). Conclusions: The study demonstrated that exposure to EBV, H. pylori, and C. trachomatis substantially elevated the risk of dementia/AD. Despite the relatively widespread occurrence of EBV infection in the population, elevated pathogen antibody titers were still found to increase the risk of dementia/AD. Besides, since C. trachomatis and C. pneumoniae are quite homologous, this study found that trachomatis (C. trachomatis/C. pneumoniae) may be significantly associated with the risk of AD/dementia.

Associations of cerebrospinal fluid profiles with severity and mortality risk of amyotrophic lateral sclerosis.

Background: The relationship between routine cerebrospinal fluid (CSF) testing and the disease phenotype of amyotrophic lateral sclerosis (ALS) is unclear, and there are some contradictions in current studies. Methods: This study aimed to analyze the relationship between CSF profiles and disease phenotype in ALS patients. We collected 870 ALS patients and 96 control subjects admitted to West China Hospital of Sichuan University. CSF microprotein, albumin, IgG, index of IgG (IgGindex), albumin quotient (QALB), and serum IgG were examined. Results: In ALS patients, CSF IgG, and QALB were significantly increased, while CSF IgGindex was decreased, compared with control subjects. Approximately one-third of ALS patients had higher CSF IgG levels. The multiple linear regression analysis identified that CSF IgGindex was weakly negatively associated with ALS functional rating scale revised (ALSFRS-R) scores (ß = -0.062, p = 0.041). This significance was found in male ALS but not in female ALS. The Cox survival analyses found that upregulated CSF IgG was significantly associated with the increased mortality risk in ALS [HR = 1.219 (1.010-1.470), p = 0.039]. Conclusion: In the current study, the higher CFS IgG was associated with increased mortality risk of ALS. CSF IgGindex may be associated with the severity of ALS. These findings may be sex-specific.

Non-ionic surfactant PEG: Enhanced cutinase-catalyzed hydrolysis of polyethylene terephthalate.

To enhance the enzymatic digestibility of polyethylene terephthalate (PET), which is highly oriented and crystallized, a polyethylene glycol (PEG) surfactant of varying molecular weights was utilized to improve the stability of mutant cutinase from Humicola insolens (HiC) and to increase the accessibility of the enzyme to the substrate. Leveraging the optimal conditions for HiC hydrolysis of PET, the introduction of 1 % w/v PEG significantly increased the yield of PET hydrolysis products. PEG600 was particularly effective, increasing the yield by 64.58 % compared to using HiC alone. Moreover, the mechanisms by which PEG600 and PEG6000 enhance enzyme digestion were extensively examined using circular dichroism and fluorescence spectroscopy. The results from CD and fluorescence analyses indicated that PEG alters the protein conformation, thereby affecting the catalytic effect of the enzyme. Moreover, PEG improved the affinity between HiC and PET by lowering the surface tension of the solution, substantially enhancing PET hydrolysis. This study suggests that PEG holds considerable promise as an enzyme protector, significantly aiding in the hydrophilic modification and degradation of PET in an environmentally friendly and sustainable manner.

The characteristic and prognostic role of blood inflammatory markers in patients with Huntington's disease from China.

Objectives: This study aims to elucidate the role of peripheral inflammation in Huntington's disease (HD) by examining the correlation of peripheral inflammatory markers with clinical manifestations and disease prognosis. Methods: This investigation involved 92 HD patients and 92 matched healthy controls (HCs). We quantified various peripheral inflammatory markers and calculated their derived metrics including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). Clinical assessments spanning cognitive, motor, and disease severity were administered. Comparative analysis of inflammatory markers and clinical correlations between HD and controls was performed. Kaplan-Meier survival analysis and Cox regression model were used to assess the effect of inflammatory markers on survival. Results: The study revealed that HD patients had significantly reduced lymphocyte counts, and LMR. Conversely, NLR, PLR, and SII were elevated compared to HCs. Lymphocyte levels inversely correlated with the age of onset and monocyte levels inversely correlated with the UHDRS-total functional capacity (TFC) scores. After adjusting for age, sex, and CAG repeat length, lymphocyte count, NLR, PLR, and SII were significantly correlated with the progression rate of TFC scores. Elevated levels of white blood cells and monocytes were associated with an increased risk of disability and mortality in the HD cohort. Conclusion: Our findings indicate that HD patients display a distinct peripheral inflammatory profile with increased NLR, PLR, and SII levels compared to HCs. The peripheral inflammation appears to be linked with accelerated disease progression and decreased survival in HD.

Construction of porous structure-based carboxymethyl chitosan/ sodium alginate/ tea polyphenols for wound dressing.

Polysaccharide-based materials with porous structure were selected as the basic skeleton to prepare a flexible and biodegradable wound dressing. The carboxymethyl chitosan/sodium alginate/tea polyphenols (CC/SA/TP) with a two-layer porous structure exhibits a variety of performances. The specific combined structure with ordered and lamellar porous structure was constructed by high-speed homogenized foaming, Ca2+ crosslinking and two-step freeze-drying methods. Moreover, the CC/SA/TP porous structure owns better shape retention and recovery because of the 3D network with an "egg-box" structure formed by impregnation. Tea polyphenols are efficiently encapsulated into a porous structure and released in a sustained pattern. After storing for 60 days, the CC/SA/TP porous structure still exhibits great suitable water vapor transmittance, efficient antibacterial activity and ultrarapid antioxidant activity. Meanwhile, the relatively low differential blood clotting index (BCI) and cytotoxicity of the CC/SA/TP porous structure indicate that it possesses the possibility of adjusting and controlling wound bleeding. The test results reveal that the CC/SA/TP porous structure might be expected to play a great potential role in biomedical applications of wound dressing.