Insulin-Mimetic Activity of Herbal Extracts Identified with Large-Scale Total Internal Reflection Fluorescence Microscopy.

Diabetes mellitus is a spreading global pandemic. Type 2 diabetes mellitus (T2DM) is the predominant form of diabetes, in which a reduction in blood glucose uptake is caused by impaired glucose transporter 4 (GLUT4) translocation to the plasma membrane in adipose and muscle cells. Antihyperglycemic drugs play a pivotal role in ameliorating diabetes symptoms but often are associated with side effects. Hence, novel antidiabetic compounds and nutraceutical candidates are urgently needed. Phytogenic therapy can support the prevention and amelioration of impaired glucose homeostasis. Using total internal reflection fluorescence microscopy (TIRFM), 772 plant extracts of an open-access plant extract library were screened for their GLUT4 translocation activation potential, resulting in 9% positive hits. Based on commercial interest and TIRFM assay-based GLUT4 translocation activation, some of these extracts were selected, and their blood glucose-reducing effects in ovo were investigated using a modified hen's egg test (Gluc-HET). To identify the active plant part, some of the available candidate plants were prepared in-house from blossoms, leaves, stems, or roots and tested. Acacia catechu (catechu), Pulmonaria officinalis (lungwort), Mentha spicata (spearmint), and Saponaria officinalis (common soapwort) revealed their potentials as antidiabetic nutraceuticals, with common soapwort containing GLUT4 translocation-activating saponarin.

Incretin-Based Multi-Agonist Peptides Are Neuroprotective and Anti-Inflammatory in Cellular Models of Neurodegeneration.

Glucagon-like peptide-1 (GLP-1)-based drugs have been approved by the United States Food and Drug Administration (FDA) and are widely used to treat type 2 diabetes mellitus (T2DM) and obesity. More recent developments of unimolecular peptides targeting multiple incretin-related receptors ("multi-agonists"), including the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) and the glucagon (Gcg) receptor (GcgR), have emerged with the aim of enhancing drug benefits. In this study, we utilized human and mouse microglial cell lines, HMC3 and IMG, respectively, together with the human neuroblastoma SH-SY5Y cell line as cellular models of neurodegeneration. Using these cell lines, we studied the neuroprotective and anti-inflammatory capacity of several multi-agonists in comparison with a single GLP-1 receptor (GLP-1R) agonist, exendin-4. Our data demonstrate that the two selected GLP-1R/GIPR dual agonists and a GLP-1R/GIPR/GcgR triple agonist not only have neurotrophic and neuroprotective effects but also have anti-neuroinflammatory properties, as indicated by the decreased microglial cyclooxygenase 2 (COX2) expression, nitrite production, and pro-inflammatory cytokine release. In addition, our results indicate that these multi-agonists have the potential to outperform commercially available single GLP-1R agonists in neurodegenerative disease treatment.

BDNF-loaded chitosan-based mimetic mussel polymer conduits for repair of peripheral nerve injury.

Care for patients with peripheral nerve injury is multifaceted, as traditional methods are not devoid of limitations. Although the utilization of neural conduits shows promise as a therapeutic modality for peripheral nerve injury, its efficacy as a standalone intervention is limited. Hence, there is a pressing need to investigate a composite multifunctional neural conduit as an alternative treatment for peripheral nerve injury. In this study, a BDNF-loaded chitosan-based mimetic mussel polymer conduit was prepared. Its unique adhesion characteristics allow it to be suture-free, improve the microenvironment of the injury site, and have good antibacterial properties. Researchers utilized a rat sciatic nerve injury model to evaluate the progression of nerve regeneration at the 12-week postoperative stage. The findings of this study indicate that the chitosan-based mimetic mussel polymer conduit loaded with BDNF had a substantial positive effect on myelination and axon outgrowth. The observed impact demonstrated a favorable outcome in terms of sciatic nerve regeneration and subsequent functional restoration in rats with a 15-mm gap. Hence, this approach is promising for nerve tissue regeneration during peripheral nerve injury.

Modified Metal-Organic Framework (MOF-818) inspired by natural enzymes for intelligent detection of total antioxidants and bisphenol A in infant beverages.

BACKGROUND: Accurate and quick judgement of the food quality can protect the legitimate rights of consumers. Currently, nanozymes are widely employed in the rapid detection of food due to their stability and economy. The contents of bisphenol A and antioxidant can be used to measure the quality of beverages. However, due to the complexity of the actual samples, it is still challenging to achieve the sensitive detection of both at the same time. The development of nanozyme with high enzyme activity is essential for sensitive detection of targets in complex foods. RESULTS: In this work, a novel nanomaterial (ZrTGA) was synthesized based on thioglycolic acid-modified Metal-Organic Framework (MOF-818). The interaction between Cu-S bonds and increase in the proportion of Cu1+ resulted in ZrTGA exhibiting higher peroxidase-like and polyphenol oxidase-like activities. These enzyme activities were 317 % and 200 % of the original values, respectively. With high enzyme activity can sensitively detect two important indicators of bisphenol A and antioxidants in beverages. The increased enzyme activity of ZrTGA enabled the content of both substances to be detected by smartphone extraction of RGB. Finally, through the output of the ''0″ and ''1″ signals of the logic gates, it is possible to quickly determine the level of the two substances and thus directly assess the quality of the beverages. SIGNIFICANCE: The modification of nanozyme enables the detection of substances at low concentrations based on enhancing dual-enzyme activity. The combination of mobile phone photography and logic gate technology enables the continuous detection of two important indicators in beverages, overcoming the limitations of traditional large-scale instruments. It also provides an alternative strategy for food quality detection.

Drugs targeting APOE4 that regulate beta-amyloid aggregation in the brain: Therapeutic potential for Alzheimer's disease.

Alzheimer's disease is characterized by progressive cognitive decline, and behavioural and psychological symptoms of dementia are common. The APOE ε4 allele, a genetic risk factor, significantly increases susceptibility to the disease. Despite efforts to effectively treat the disease, only seven drugs are approved for its treatment, and only two of these prevent its progression. This highlights the need to identify new pharmacological options. This review focuses on mimetic peptides, small molecule correctors and HAE-4 antibodies that target ApoE. These drugs reduce ß-amyloid-induced neurodegeneration in preclinical models. In addition, loop diuretics such as bumetanide and furosemide show the potential to reduce the prevalence of Alzheimer's disease in humans, and antidepressants such as imipramine improve cognitive function in individuals diagnosed with Alzheimer's disease. Consistent with this, both classes of drugs have been shown to exert neuroprotective effects by inhibiting ApoE4-catalysed Aß aggregation in preclinical models. Moreover, peroxisome proliferator-activated receptor ligands, particularly pioglitazone and rosiglitazone, reduce ApoE4-induced neurodegeneration in animal models. However, they do not prevent the cognitive decline in APOE ε4 allele carriers. Finally, ApoE4 impairs the integrity of the blood-brain barrier and haemostasis. On this basis, ApoE4 modulation is a promising avenue for the treatment of late-onset Alzheimer's disease.

PEGylated SOCS3 Mimetics Encapsulated into PLGA-NPs as Selective Inhibitors of JAK/STAT Pathway in TNBC Cells.

Introduction: SOCS3 (suppressor of cytokine signaling 3) protein is a crucial regulator of cytokine-induced inflammation, and its administration has been shown to have therapeutic effects. Recently, we designed a chimeric proteomimetic of SOCS3, mimicking the interfacing regions of a ternary complex composed of SOCS3, JAK2 (Janus kinase 2) and gp130 (glycoprotein 130) proteins. The derived chimeric peptide, KIRCONG chim, demonstrated limited mimetic function owing to its poor water solubility. Methods: We report investigations concerning a PEGylated variant of KIRCONG mimetic, named KIRCONG chim, bearing a PEG (Polyethylene glycol) moiety as a linker of noncontiguous SOCS3 regions. Its ability to bind to the catalytic domain of JAK2 was evaluated through MST (MicroScale Thermophoresis), as well as its stability in biological serum assays. The structural features of the cyclic compounds were investigated by CD (circular dichroism), nuclear magnetic resonance (NMR), and molecular dynamic (MD) studies. To evaluate the cellular effects, we employed a PLGA-nanoparticle as a delivery system after characterization using DLS and SEM techniques. Results: KIRCONG chim PEG-revealed selective penetration into triple-negative breast cancer (TNBC) MDA-MB-231 cells with respect to the human breast epithelial cell line (MCF10A), acting as a potent inhibitor of STAT3 phosphorylation. Discussion: Overall, the data indicated that miniaturization of the SOCS3 protein is a promising therapeutic approach for aberrant dysregulation of JAK/STAT during cancer progression.

Inhibitor of apoptosis proteins (IAP) inhibitor APG-1387 monotherapy or in combination with programmed cell death 1 (PD-1) inhibitor toripalimab in patients with advanced solid tumors: results from two phase I trials.

BACKGROUND: APG-1387 is a novel second mitochondrial-derived activator of caspases mimetic, small-molecule inhibitor targeting inhibitor of apoptosis proteins. We report results from two phase I trials evaluating the tolerability, safety, and antitumor activity of APG-1387 monotherapy and APG-1387 plus toripalimab [a programmed cell death 1 (PD-1) inhibitor] for advanced solid tumors. PATIENTS AND METHODS: Participants aged ≥18 years who had histologically confirmed advanced solid tumors with no appropriate standard of care (or refractory to standard care) were eligible. Patients received escalating intravenous doses of APG-1387 alone or combined with fixed-dose toripalimab (240 mg every 3 weeks) in a '3 + 3' design. Primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) in the monotherapy trial, and recommended phase II dose (RP2D) in the combination therapy trial. Secondary endpoints included the pharmacokinetic and pharmacodynamic profiles and preliminary efficacy in both trials. RESULTS: In the monotherapy trial, 28 subjects were enrolled and received ≥1 treatment cycle. No DLT was reported among the 28 subjects, and the MTD was not reached. One participant (3.6%) had a grade ≥3 treatment-related adverse event (TRAE) of alanine aminotransferase elevation. In efficacy analysis of 23 participants, none achieved an objective response, and the disease control rate was 21.7%. In the combination trial, 22 subjects were enrolled and included in all analyses. There was one DLT of grade 3 lipase elevation. The MTD was not reached. Four grade ≥3 TRAEs occurred in three participants (13.6%), with the most common being lipase elevation (n = 2). The RP2D was 45 mg weekly. The objective response rate was 13.6%, with complete response achieved in one subject, and the disease control rate was 54.5%. CONCLUSIONS: APG-1387 45 mg weekly plus toripalimab was well tolerated and is recommended for further study, with preliminary clinical activity observed in study participants with advanced solid tumors.

3D Porous Polymer Scaffold-Conjugated KGF-Mimetic Peptide Promotes Functional Skin Regeneration in Chronic Diabetic Wounds.

The re-epithelialization process gets severely dysregulated in chronic nonhealing diabetic foot ulcers/wounds. Keratinocyte growth factor (KGF or FGF-7) is the major modulator of the re-epithelialization process, which regulates the physiological phenotypes of cutaneous keratinocytes. The existing therapeutic strategies of growth factor administration have several limitations. To overcome these, we have designed a KGF-mimetic peptide (KGFp, 13mer) based on the receptor interaction sites in murine KGF. KGFp enhanced migration and transdifferentiation of mouse bone marrow-derived MSCs toward keratinocyte-like cells (KLCs). A significant increase in the expression of skin-specific markers Bnc1 (28.5-fold), Ck5 (14.6-fold), Ck14 (26.1-fold), Ck10 (187.7-fold), and epithelial markers EpCam (23.3-fold) and Cdh1 (64.2-fold) was associated with the activation of ERK1/2 and STAT3 molecular signaling in the KLCs. Further, to enhance the stability of KGFp in the wound microenvironment, it was conjugated to biocompatible 3D porous polymer scaffolds without compromising its active binding sites followed by chemical characterization using Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, dynamic mechanical analysis, and thermogravimetry. In vitro evaluation of the KGFp-conjugated 3D polymer scaffolds revealed its potential for transdifferentiation of MSCs into KLCs. Transplantation of allogeneic MSCGFP using KGFp-conjugated 3D polymer scaffolds in chronic nonhealing type 2 diabetic wounds (db/db transgenic, 50-52 weeks old male mice) significantly enhanced re-epithelialization-mediated wound closure rate (79.3%) as compared to the control groups (Untransplanted -22.4%, MSCGFP-3D polymer scaffold -38.5%). Thus, KGFp-conjugated 3D porous polymer scaffolds drive the fate of the MSCs toward keratinocytes that may serve as potential stem cell delivery platform technology for tissue engineering and transplantation.

Smell cancer by machine learning-assisted peptide/MXene bioelectronic array.

Non-invasive detection of tumors is of utmost importance to save lives. Nonetheless, identifying tumors through gas analysis is a challenging task. In this work, biosensors with remarkable gas-sensing characteristics were developed using a self-assembly method consisting of peptides and MXene. Based on these biosensors, a mimetic biosensor array (MBA) was fabricated and integrated into a real-time testing platform (RTP). In addition, machine learning (ML) algorithms were introduced to improve the RTP's detection and identification capabilities of exhaled gas signals. The synthesized biosensor, with the ability to specifically bind to targeted gas molecules, demonstrated higher performance than the pristine MXene, with a response up to 150% greater. Besides, the MBA successfully detected 15 odor molecules affiliated with five categories of alcohols, ketones, aldehydes, esters, and acids by pattern recognition algorithms. Furthermore, with the ML assistance, the RTP detected the breath odor samples from volunteers of four categories, including healthy populations, patients of lung cancer, upper digestive tract cancer, and lower digestive tract cancer, with accuracies of 100%, 94.1%, 90%, and 95.2%, respectively. In summary, we have developed a cost-effective and precise model for non-invasive tumor diagnosis. Furthermore, this prototype also offers a versatile solution for diagnosing other diseases like nephropathy, diabetes, etc.

Engineering Magnetic Extracellular Vesicles Mimetics for Enhanced Targeting Chemodynamic Therapy to Overcome Ovary Cancer.

Chemodynamic therapy (CDT), employing metal ions to transform endogenous H2O2 into lethal hydroxyl radicals (•OH), has emerged as an effective approach for tumor treatment. Yet, its efficacy is diminished by glutathione (GSH), commonly overexpressed in tumors. Herein, a breakthrough strategy involving extracellular vesicle (EV) mimetic nanovesicles (NVs) encapsulating iron oxide nanoparticles (IONPs) and ß-Lapachone (Lapa) was developed to amplify intracellular oxidative stress. The combination, NV-IONP-Lapa, created through a serial extrusion from ovarian epithelial cells showed excellent biocompatibility and leveraged magnetic guidance to enhance endocytosis in ovarian cancer cells, resulting in selective H2O2 generation through Lapa catalysis by NADPH quinone oxidoreductase 1 (NQO1). Meanwhile, the iron released from IONPs ionization under acidic conditions triggered the conversion of H2O2 into •OH by the Fenton reaction. Additionally, the catalysis process of Lapa eliminated GSH in tumor, further amplifying oxidative stress. The designed NV-IONP-Lapa demonstrated exceptional tumor targeting, facilitating MR imaging, and enhanced tumor suppression without significant side effects. This study presents a promising NV-based drug delivery system for exploiting CDT against NQO1-overexpressing tumors by augmenting intratumoral oxidative stress.

Dual-recognition colorimetric platform based on porous Au@Pt nanozymes for highly sensitive washing-free detection of Staphylococcus aureus.

A dual-recognition strategy is reported to construct a one-step washing and highly efficient signal-transduction tag system for high-sensitivity colorimetric detection of Staphylococcus aureus (S. aureus). The porous (gold core)@(platinum shell) nanozymes (Au@PtNEs) as the signal labels show highly efficient peroxidase mimetic activity and are robust. For the sake of simplicity the detection involved the use of a vancomycin-immobilized magnetic bead (MB) and aptamer-functionalized Au@PtNEs for dual-recognition detection in the presence of S. aureus. In addition, we designed a magnetic plate to fit the 96-well microplate to ensure consistent magnetic properties of each well, which can quickly remove unreacted Au@PtNEs and sample matrix while avoiding tedious washing steps. Subsequently, Au@PtNEs catalyze hydrogen peroxide (H2O2) to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) generating a color signal. Finally, the developed Au@PtNEs-based dual-recognition washing-free colorimetric assay displayed a response in the range of S. aureus of 5 × 101-5 × 105 CFU/mL, and the detection limit was 40 CFU/mL within 1.5 h. In addition, S. aureus-fortified samples were analyzed to further evaluate the performance of the proposed method, which yielded average recoveries ranging from 93.66 to 112.44% and coefficients of variation (CVs) within the range 2.72-9.01%. These results furnish a novel horizon for the exploitation of a different mode of recognition and inexpensive enzyme-free assay platforms as an alternative to traditional enzyme-based immunoassays for the detection of other Gram-positive pathogenic bacteria.

Monolithic DNApatite: An Elastic Apatite with Sub-Nanometer Scale Organo-Inorganic Structures.

Hydroxyapatite (HA) exhibits outstanding biocompatibility, bioactivity, osteoconductivity, and natural anti-inflammatory properties. Pure HA, ion-doped HA, and HA-polymer composites are investigated, but critical limitations such as brittleness remain; numerous efforts are being made to address them. Herein, the novel self-crystallization of a polymeric single-stranded deoxyribonucleic acid (ssDNA) without additional phosphate ions for synthesizing deoxyribonucleic apatite (DNApatite) is presented. The synthesized DNApatite, DNA1Ca2.2(PO4)1.3OH2.1, has a repetitive dual phase of inorganic HA crystals and amorphous organic ssDNA at the sub-nm scale, forming nanorods. Its mechanical properties, including toughness and elasticity, are significantly enhanced compared with those of HA nanorod, with a Young's modulus similar to that of natural bone.

From masks to muscles: Mapping facial structure of Nycticebus.

Facial musculature in mammals underlies mastication and nonverbal communicative facial displays. Our understanding of primate facial expression comes primarily from haplorrhines (monkeys and apes), while our understanding of strepsirrhine (lemurs and lorises) facial expression remains incomplete. We examined the facial muscles of six specimens from three Nycticebus species (Nycticebus coucang, Nycticebus javanicus, and Nycticebus menagensis) using traditional dissection methodology and novel three-dimensional facial scanning to produce a detailed facial muscle map, and compared these results to another nocturnal strepsirrhine genus, the greater bushbaby (Otolemur spp.). We observed 19 muscles with no differences among Nycticebus specimens. A total of 17 muscles were observed in both Nycticebus and Otolemur, with little difference in attachment and function but some difference in directionality of movement. In the oral region, we note the presence of the depressor anguli oris, which has been reported in other primate species but is absent in Otolemur. The remaining muscle is a previously undescribed constrictor nasalis muscle located on the lateral nasal alar region, likely responsible for constriction of the nares. We propose this newly described muscle may relate to vomeronasal organ functioning and the importance of the use of nasal musculature in olfactory communication. We discuss how this combined methodology enabled imaging of small complex muscles. We further discuss how the facial anatomy of Nycticebus spp. relates to their unique physiology and behavioral ecology.

Nonswellable Hydrogel Patch with Tissue-Mimetic Mechanical Characteristics Remodeling In Vivo Microenvironment for Effective Adhesion Prevention.

Postoperative adhesion is a common complication after abdominal surgery, but current clinical products have unsatisfactory therapeutic effects. Here, we present a hydrogel patch formed in a single step through dialysis. The exchange of DMSO into water facilitates hydrophobic aggregate in situ formation and the formation of hydrogen bonds within the hydrogel. Thanks to the optimized component ratio and precise structural design. The hydrogel patch has soft-tissue-like mechanical characteristics, including high strength, high toughness, low modulus similar to the abdominal wall, good fatigue resistance, and fast self-recovery properties. The nonswellable hydrogel patch retains over 80% of its original mechanical properties after 7 days of immersion in physiological saline, with a maximum swelling ratio of 5.6%. Moreover, the hydrophobic biomultifunctionality of benzyl isothiocyanate can self-assemble onto the hydrogel patch during the sol-gel transition process, enabling it to remodel the inflammatory microenvironment through synergistic antibacterial, antioxidant, and anti-inflammatory effects. The hydrogel patch prevents postsurgical adhesion in a rat sidewall defect-cecum abrasion model and outperforms the leading commercial Interceed. It holds promising potential for clinical translation, considering that FDA-approved raw materials (PVA and gelatin) form the backbone of this effective hydrogel patch.

Treatment with αvß3-integrin-specific 29P attenuates pressure-overload induced cardiac remodelling after transverse aortic constriction in mice.

Heart failure remains one of the largest clinical burdens globally, with little to no improvement in the development of disease-eradicating therapeutics. Integrin targeting has been used in the treatment of ocular disease and cancer, but little is known about its utility in the treatment of heart failure. Here we sought to determine whether the second generation orally available, αvß3-specific RGD-mimetic, 29P , was cardioprotective. Male mice were subjected to transverse aortic constriction (TAC) and treated with 50 µg/kg 29P or volume-matched saline as Vehicle control. At 3 weeks post-TAC, echocardiography showed that 29P treatment significantly restored cardiac function and structure indicating the protective effect of 29P treatment in this model of heart failure. Importantly, 29P treatment improved cardiac function giving improved fractional shortening, ejection fraction, heart weight and lung weight to tibia length fractions, together with partial restoration of Ace and Mme levels, as markers of the TAC insult. At a tissue level, 29P reduced cardiomyocyte hypertrophy and interstitial fibrosis, both of which are major clinical features of heart failure. RNA sequencing identified that, mechanistically, this occurred with concomitant alterations to genes involved molecular pathways associated with these processes such as metabolism, hypertrophy and basement membrane formation. Overall, targeting αvß3 with 29P provides a novel strategy to attenuate pressure-overload induced cardiac hypertrophy and fibrosis, providing a possible new approach to heart failure treatment.

A fast visual onsite method for detection and quantitation of food additives using an engineered metal nanohybrid-based catalyst.

Unsafe food additives pose a significant threat to global health, especially in developing countries. Many existing methods rely on clean laboratories, complicated optics equipment, trained personnel and lengthy detection time, which are not suitable for onsite food safety inspections in emergency situations, peculiarly in impoverished areas. In this paper, a fast and visual onsite method is designed for the detection and quantification of additives in food safety by engineering a nanohybrid (MoS2/SDBS/Cu-CuFe2O4)-based catalysis. Interestingly, the nanohybrid presents peroxidase-like mimetic activity toward the substrate containing 3,3',5,5'-tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2), which are then integrated simply into a detection kit. The blue oxidated TMB in this kit can be converted completely to colorless by some bio-molecule additives in commercial food, such as glutathione (GSH), cysteine (Cys), and ascorbic acid (AA). Remarkably, this process takes just less than 2 min and the detection limits are 2.8 nM, 5.5 nM and 47 nM, respectively. These results show excellent repeatability with a statistical analysis with (*P < 0.05) over 30 tests. Next, the images of the color changes can be captured clearly using a smartphone by red-green-blue (RGB) channels, which provides an opportunity for the development of field-operation device. Additionally, our approach is applied to some targets-indicative foods, showing a recovery range between 95.8 % and 104.2 %, offering an attractive and promising pathway for future practical food safety inspection applications. More importantly, this method can easily be extended to the detection of reducing substances in other analytical fields.

Design of a New Vaccine Prototype against Porcine Circovirus Type 2 (PCV2), M. hyopneumoniae and M. hyorhinis Based on Multiple Antigens Microencapsulation with Sulfated Chitosan.

This work evaluated in vivo an experimental-multivalent-vaccine (EMV) based on three Porcine Respiratory Complex (PRC)-associated antigens: Porcine Circovirus Type 2 (PCV2), M. hyopneumoniae (Mhyop) and M. hyorhinis (Mhyor), microencapsulated with sulfated chitosan (M- ChS + PRC-antigens), postulating chitosan sulphate (ChS) as a mimetic of the heparan sulfate receptor used by these pathogens for cell invasion. The EMV was evaluated physicochemically by SEM (Scanning-Electron-Microscopy), EDS (Energy-Dispersive-Spectroscopy), Pdi (Polydispersity-Index) and zeta potential. Twenty weaned pigs, distributed in four groups, were evaluated for 12 weeks. The groups 1 through 4 were as follows: 1-EMV intramuscular-route (IM), 2-EMV oral-nasal-route (O/N), 3-Placebo O/N (M-ChS without antigens), 4-Commercial-vaccine PCV2-Mhyop. qPCR was used to evaluate viral/bacterial load from serum, nasal and bronchial swab and from inguinal lymphoid samples. Specific humoral immunity was evaluated by ELISA. M-ChS + PRC-antigens measured between 1.3-10 µm and presented low Pdi and negative zeta potential, probably due to S (4.26%). Importantly, the 1-EMV protected 90% of challenged animals against PCV2 and Mhyop and 100% against Mhyor. A significant increase in antibody was observed for Mhyor (1-EMV and 2-EMV) and Mhyop (2-EMV), compared with 4-Commercial-vaccine. No difference in antibody levels between 1-EMV and 4-Commercial-vaccine for PCV2-Mhyop was observed. Conclusion: The results demonstrated the effectiveness of the first EMV with M-ChS + PRC-antigens in pigs, which were challenged with Mhyor, PCV2 and Mhyop, evidencing high protection for Mhyor, which has no commercial vaccine available.

Heme-Mimetic Photosensitizer with Iron-Targeting and Internalizing Properties for Enhancing PDT Activity and Promoting Infected Diabetic Wound Healing.

The management of multibacterial infections remains clinically challenging in the care and treatment of chronic diabetic wounds. Photodynamic therapy (PDT) offers a promising approach to addressing bacterial infections. However, the limited target specificity and internalization properties of traditional photosensitizers (PSs) toward Gram-negative bacteria pose significant challenges to their antibacterial efficacy. In this study, we designed an iron heme-mimetic PS (MnO2@Fe-TCPP(Zn)) based on the iron dependence of bacteria that can be assimilated by bacteria and retained in different bacteria strains (Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus) and which shows high PDT antibacterial efficacy. For accelerated wound healing after antibacterial treatment, MnO2@Fe-TCPP(Zn) was loaded into a zwitterionic hydrogel with biocompatibility and antifouling properties to form a nanocomposite antibacterial hydrogel (PSB-MnO2@Fe-TCPP(Zn)). In the multibacterial infectious diabetic mouse wound model, the PSB-MnO2@Fe-TCPP(Zn) hydrogel dressing rapidly promoted skin regeneration by effectively inhibiting bacterial infections, eliminating inflammation, and promoting angiogenesis. This study provides an avenue for developing broad-spectrum antibacterial nanomaterials for combating the antibiotic resistance crisis and promoting the healing of complex bacterially infected wounds.

The emerging role of heart-on-a-chip systems in delineating mechanisms of SARS-CoV-2-induced cardiac dysfunction.

Coronavirus disease 2019 (COVID-19) has been a major global health concern since its emergence in 2019, with over 680 million confirmed cases as of April 2023. While COVID-19 has been strongly associated with the development of cardiovascular complications, the specific mechanisms by which viral infection induces myocardial dysfunction remain largely controversial as studies have shown that the severe acute respiratory syndrome coronavirus-2 can lead to heart failure both directly, by causing damage to the heart cells, and indirectly, by triggering an inflammatory response throughout the body. In this review, we summarize the current understanding of potential mechanisms that drive heart failure based on in vitro studies. We also discuss the significance of three-dimensional heart-on-a-chip technology in the context of the current and future pandemics.

Exploring Bimetallic Nanoparticles in Alzheimer's Therapy: A Novel Bio-Assisted Synthesis with Multitarget Potential.

Unlocking the potential of metal nanoparticles (NPs) in biomedical applications represents a leading endeavor in contemporary research. Among these, gold NPs (AuNPs) and silver NPs (AgNPs) have shown promising strides in combatting complex neurodegenerative ailments like Alzheimer's disease. Yet, the unexplored realm of bimetallic Au/Ag-NP harbors immense potential, concealing undiscovered opportunities for enhanced therapeutic effectiveness through the synergistic interaction of metal ions. Nonetheless, the limitations of traditional synthesis methods have restricted the preparation, biocompatibility, and versatility of these NPs, prompting an urgent requirement for innovative approaches. Biobased synthetic methodologies have emerged as a noteworthy solution to address these challenges. Our study ventures into uncharted terrain, harnessing collagen-mimicking peptide nanofibers as a bioactive template for the synthesis of bimetallic NPs. These green NPs exhibit remarkable activity in inhibiting amyloid ß (Aß) protein aggregation with almost 74% inhibition, surpassing the individual impacts of Au and Ag NPs, which show inhibition percentages of 66 and 43, respectively. The bimetallic Au/Ag-NPs not only demonstrate powerful inhibition of Aß, but they also demonstrate inhibitory activity against esterase (∼50%) and against reactive oxygen species (ROS) (∼75%), metamorphosing into multifaceted therapeutic agents for Alzheimer's disease. Au/Ag-NPs have proven highly beneficial in surpassing cellular barriers, as evidenced by studies on tissue penetration, 3D uptake, and endosomal escape, and these attributes also hold promise for the future treatment modalities. The findings indicate that the intrinsic traits of Au/Ag-NPs provide numerous mechanistic benefits, such as inhibiting Aß and acetylcholinesterase (AChE), and reducing stress related to ROS, in addition to their advantageous internalization properties. This research represents a notable advancement in the development of multitargeted treatments for neurodegenerative disorders using bimetallic NPs, diverging from the prevalent emphasis on AuNPs in the current literature.