Alleviating sepsis: Revealing the protective role of costunolide in a cecal ligation and puncture rat model.

Objectives: Sepsis poses a significant threat to human life, rendering it a burdensome medical disease. Despite significant advancements, the current state of medical science still lacks a viable and efficacious cure. Costunolide (COST) is a multifaceted sesquiterpene lactone that exhibits a range of actions, including anti-inflammatory and antioxidant properties. We investigated the potential impacts of COST on a rat sepsis model caused by cecal ligation and puncture (CLP). Materials and Methods: We created an experimental rat model with the following groups: SHAM, CLP, CLP+low dose COST, and CLP+high dose COST. Blood, kidney, and lung samples were collected. Inflammatory mediators such as interleukin-1beta (IL-1ß), IL-6, tumor necrosis factor-alpha (TNF- α), and nuclear factor kappa-B (NF-κB) were investigated. In addition, we assessed oxidative stress by measuring 8-Hydroxydeoxyguanosine (8-OHdG) immunopositivity, MDA levels, glutathione (GSH), and superoxide dismutase (SOD) activity. Histopathological and immunohistochemical examinations backed up our findings. Results: Compared to the CLP group, the COST group showed a reduction in inflammatory and oxidative stress indicators. The expression of inflammatory mediators was suppressed by COST, and histological examinations revealed improvements in kidney and lung tissues in the treatment groups. Conclusion: Our study highlights the preventive effects of COST against CLP-induced sepsis-related injury. Considering its beneficial effects against many diseases, COST is worthy as to be evaluated against sepsis.

Therapeutic Peptides, Proteins and their Nanostructures for Drug Delivery and Precision Medicine.

Peptide and protein nanostructures with tunable structural features, multifunctionality, biocompatibility and biomolecular recognition capacity enable development of efficient targeted drug delivery tools for precision medicine applications. In this review article, we present various techniques employed for the synthesis and self-assembly of peptides and proteins into nanostructures. We discuss design strategies utilized to enhance their stability, drug-loading capacity, and controlled release properties, in addition to the mechanisms by which peptide nanostructures interact with target cells, including receptor-mediated endocytosis and cell-penetrating capabilities. We also explore the potential of peptide and protein nanostructures for precision medicine, focusing on applications in personalized therapies and disease-specific targeting for diagnostics and therapeutics in diseases such as cancer.

Therapeutic synthetic and natural materials for immunoengineering.

Immunoengineering is a rapidly evolving field that has been driving innovations in manipulating immune system for new treatment tools and methods. The need for materials for immunoengineering applications has gained significant attention in recent years due to the growing demand for effective therapies that can target and regulate the immune system. Biologics and biomaterials are emerging as promising tools for controlling immune responses, and a wide variety of materials, including proteins, polymers, nanoparticles, and hydrogels, are being developed for this purpose. In this review article, we explore the different types of materials used in immunoengineering applications, their properties and design principles, and highlight the latest therapeutic materials advancements. Recent works in adjuvants, vaccines, immune tolerance, immunotherapy, and tissue models for immunoengineering studies are discussed.

Fast mass spectrometry search and clustering of untargeted metabolomics data.

The throughput of mass spectrometers and the amount of publicly available metabolomics data are growing rapidly, but analysis tools such as molecular networking and Mass Spectrometry Search Tool do not scale to searching and clustering billions of mass spectral data in metabolomics repositories. To address this limitation, we designed MASST+ and Networking+, which can process datasets that are up to three orders of magnitude larger than those processed by state-of-the-art tools.

Boron Compound-Based Treatments Against Multidrug-Resistant Bacterial Infections in Lung Cancer In Vitro Model.

Multidrug-resistant bacteria is one of the most important public health problems. Increasing rates of antibacterial resistance also affect the outcomes of medical approaches. Cancer treatment because of immune system deficiency (chemotherapy or steroids usage) commonly can cause infection. Lung cancer is the dominant cause of cancer-related deaths, and infection is the most common cause of death among those patients. In this study, it was aimed to determine the antimicrobial, antibiofilm, and anticancer activity of boron compounds. A549 lung cancer cell line was infected with Acinetobacter baumannii (ATCC 19606), Klebsiella pneumoniae (ATCC 700603), and Pseudomonas aeruginosa (ATCC 27853). In order to determine the fractional inhibitory concentration (FIC) index, antibiotics and boron compound concentrations prepared according to the minimum inhibitory concentration (MIC) values were determined by the checkerboard method. In our study results, the antibiofilm activity was an average of 46% in A. baumannii+boron compounds, 45% in P. aeruginosa+boron compounds, and 43% in K. pneumoniae. Cell culture analysis results show a decrease in viability and antioxidant capacity and an increase in total oxidant status after adding boron compounds to the culture. Immunofluorescence results show a correlation with MTT, and boron compounds increased 8-OHdG expression in comparison to antibiotic administration. In conclusion, boron compounds have promising effects on bacteria, especially in resistant bacteria spp.

Costunolide prevents renal ischemia-reperfusion injury in rats by reducing autophagy, apoptosis, inflammation, and DNA damage.

Objectives: Renal ischemia-reperfusion (I/R) is a vital health condition leading to acute kidney injury. Costunolide (COST) is an actively used molecule clinically for its anti-inflammatory, antioxidant, and immunomodulatory properties. In the present study, we searched for the possible protective effects of COST against renal ischemia/reperfusion (I/R) injury in rats. Materials and Methods: We established a renal I/R rat model. We divided forty rats into four groups: group I (sham), group II (I/R), group III (I/R+COST 5 mg/kg), and group IV (I/R+COST 10 mg/kg). We collected blood, kidney, and lung samples for analysis. Results: COST administration performed anti-oxidant and anti-inflammatory activity by reducing oxidant parameters and proinflammatory cytokine levels. COST alleviated DNA damage through declining 8-hydroxydeoxyguanosine (8-OHdG) levels. In addition, COST diminished tubular damage and inflammation by reducing kidney injury molecule-1 (KIM-1) production. COST administration also ameliorated apoptosis and autophagy by decreasing caspase-3 and microtubule-associated protein light chain 3B (MAPLC3, LC3B) expression. Conclusion: COST demonstrated protective effects against renal I/R-induced injury.

Peptide Hydrogels and Nanostructures Controlling Biological Machinery.

Peptides are versatile building blocks for the fabrication of various nanostructures that result in the formation of hydrogels and nanoparticles. Precise chemical functionalization promotes discrete structure formation, causing controlled bioactivity and physical properties for functional materials development. The conjugation of small molecules on amino acid side chains determines their intermolecular interactions in addition to their intrinsic peptide characteristics. Molecular information affects the peptide structure, formation, and activity. In this Perspective, peptide building blocks, nanostructure formation mechanisms, and the properties of these peptide materials are discussed with the results of recent publications. Bioinstructive and stimuli-responsive peptide materials have immense impacts on the nanomedicine field including drug delivery, cellular engineering, regenerative medicine, and biomedicine.

Metal-Chelating Self-Assembling Peptide Nanofiber Scaffolds for Modulation of Neuronal Cell Behavior.

Synthetic peptides are promising structural and functional components of bioactive and tissue-engineering scaffolds. Here, we demonstrate the design of self-assembling nanofiber scaffolds based on peptide amphiphile (PA) molecules containing multi-functional histidine residues with trace metal (TM) coordination ability. The self-assembly of PAs and characteristics of PA nanofiber scaffolds along with their interaction with Zn, Cu, and Mn essential microelements were studied. The effects of TM-activated PA scaffolds on mammalian cell behavior, reactive oxygen species (ROS), and glutathione levels were shown. The study reveals the ability of these scaffolds to modulate adhesion, proliferation, and morphological differentiation of neuronal PC-12 cells, suggesting a particular role of Mn(II) in cell-matrix interaction and neuritogenesis. The results provide a proof-of-concept for the development of histidine-functionalized peptide nanofiber scaffolds activated with ROS- and cell-modulating TMs to induce regenerative responses.

HypoRiPPAtlas as an Atlas of hypothetical natural products for mass spectrometry database search.

Recent analyses of public microbial genomes have found over a million biosynthetic gene clusters, the natural products of the majority of which remain unknown. Additionally, GNPS harbors billions of mass spectra of natural products without known structures and biosynthetic genes. We bridge the gap between large-scale genome mining and mass spectral datasets for natural product discovery by developing HypoRiPPAtlas, an Atlas of hypothetical natural product structures, which is ready-to-use for in silico database search of tandem mass spectra. HypoRiPPAtlas is constructed by mining genomes using seq2ripp, a machine-learning tool for the prediction of ribosomally synthesized and post-translationally modified peptides (RiPPs). In HypoRiPPAtlas, we identify RiPPs in microbes and plants. HypoRiPPAtlas could be extended to other natural product classes in the future by implementing corresponding biosynthetic logic. This study paves the way for large-scale explorations of biosynthetic pathways and chemical structures of microbial and plant RiPP classes.

The effects of tarantula cubensis extract on renal ischemia reperfusion injury in rats.

BACKGROUND: Renal ischemia-reperfusion (IR) related acute kidney injury (AKI) is an important health problem and has not yet been fully treated. Tarantula cubensis extract (TCE) is a homeopathic drug that has antiinflammatory and antioxidant effects. This study aimed to investigate the effects of TCE on renal ischemia-reperfusion injury in rats. METHODS: This study was carried out on 48 Spraque-Dawley male rats, which were divided into six groups. The first, second, and third groups were control, sham, and IR groups, respectively. Group four received IR and 0.2 mL of 96% ethanol. Group five and six received ischemia and reperfusion and TCE 0.01 and 0.1 mg per rat (which correspond to approximately 0.04 mg/kg, and 0.4 mg/kg), respectively. Tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1ß), total antioxidant status (TAS), and total oxidant status (TOS) levels in renal tissue were measured by enzyme-linked immunosorbent assay (ELISA). Oxidative stress index (OSI) was obtained by proportioning TAS and TOS. Superoxide dismutase (SOD), myeloperoxidase (MPO) activities, and malondialdehyde (MDA) levels were determined by manual spectrophotometric methods. The histopathological changes were evaluated via hematoxylineosin and immunohistochemical staining. RESULTS: In IR group, renal tissue TNF-α and IL-1ß levels were significantly higher than control group (p < 0.0001 for both), and low(p < 0.0001 for both) and high dose (p < 0.0001 for both) TCE administration decreased these markers. Low and high doses of TCE decreased OSI values compared with IR group (p = 0.04 and p = 0.001 respectively). Although TCE decreased MDA levels, it was not statistically significant. MPO levels significantly decreased. In addition, TCE has been found to prevent hemorrhage, cast formation, and dilatation caused by IR in renal tissues stained with hematoxylin-eosin. And also, the most intense nuclear factor kappa B (NFκB) and caspase-3 immunopositivity found in IR group was decreased in both of the TCE groups. DISCUSSION: Although TCE showed a protective effect by inhibiting inflammation against IR damage in renal tissues, there was no clear effect on oxidative stress. Larger and more detailed studies are needed to clarify the issue.

Supramolecular presentation of bioinstructive peptides on soft multilayered nanobiomaterials stimulates neurite outgrowth.

Peptide amphiphiles (PAs) have emerged as effective molecular building blocks for creating self-assembling nanobiomaterials for multiple biomedical applications. Herein, we report a straightforward approach to assemble soft bioinstructive platforms to recreate the native neural extracellular matrix (ECM) aiming for neuronal regeneration based on the electrostatic-driven supramolecular presentation of laminin-derived IKVAV-containing self-assembling PA (IKVAV-PA) on biocompatible multilayered nanoassemblies. Spectroscopic and microscopic techniques show that the co-assembly of positively charged low-molecular-weight IKVAV-PA with oppositely charged high-molecular-weight hyaluronic acid (HA) triggers the formation of ordered ß-sheet structures denoting a one-dimensional nanofibrous network. The successful functionalization of poly(L-lysine)/HA layer-by-layer nanofilms with an outer positively charged layer of self-assembling IKVAV-PA is demonstrated by the quartz crystal microbalance with dissipation monitoring and the nanofibrous morphological properties revealed by atomic force microscopy. The bioactive ECM-mimetic supramolecular nanofilms promote the enhancement of primary neuronal cells' adhesion, viability, and morphology when compared to the PA without the IKVAV sequence and PA-free biopolymeric multilayered nanofilms, and stimulate neurite outgrowth. The nanofilms hold great promise as bioinstructive platforms for enabling the assembly of customized and robust multicomponent supramolecular biomaterials for neural tissue regeneration.

Seed priming with essential oils for sustainable wheat agriculture in semi-arid region.

Drought is one of the major constraints to global crop production. A number of sustainable systems have focused on the development of environmentally friendly innovative biotechnological interventions to prevent yield losses. The use of essential oils as a seed priming agent can make an important contribution as a natural stimulant in increasing drought stress tolerance. This study focuses on the effects of seeds coated with different doses (D0 (0%), D1 (0.01%), D2 (0.05%), D3 (0.10%) and D4 (0.25%)) of sage, rosemary and lavender essential oils on wheat germination, seedling establishment and yield parameters. Turkey's local wheat genotype Köse was used as plant material. The impact of the seed priming on germination rate, coleoptile length, shoot length, root length, shoot fresh and dry weight, root fresh and dry weight, relative water content (RWC), proline, and chlorophyll contents was assessed in laboratory experiments. In addition, the effect of essential oil types on yield parameters and agronomic components (plant height, spike height, number of grains per spike, grain yield per spike, grain yield per unit area, thousand-grain weight) was evaluated in a field experiment during the 2019-2020 crop seasons in a semi-arid climate. According to laboratory results, the highest germination rate among all treatment doses was determined in the D2 treatment (rosemary 93.30%, sage 94.00% and lavender 92.50%), while the lowest germination rates for all essential oil types were determined in the D4 treatment (rosemary 41.70%, sage 40.90% and lavender 40.90%). Increasing treatment doses showed a similar suppressive effect on the other parameters. In the field experiment, the highest grain yield (256.52 kg/da) and thousand-grain weight (43.30 g) were determined in the rosemary treatment. However, the priming treatment has an insignificant on the number of grains per spike and the spike length. The light of these results, the effects of essential oil types and doses on yield parameters were discussed. The findings highlight the importance of using essential oils in seed priming methods for sustainable agricultural practices.

Peptide Nanofiber System for Sustained Delivery of Anti-VEGF Proteins to the Eye Vitreous.

Ranibizumab is a recombinant VEGF-A antibody used to treat the wet form of age-related macular degeneration. It is intravitreally administered to ocular compartments, and the treatment requires frequent injections, which may cause complications and patient discomfort. To reduce the number of injections, alternative treatment strategies based on relatively non-invasive ranibizumab delivery are desired for more effective and sustained release in the eye vitreous than the current clinical practice. Here, we present self-assembled hydrogels composed of peptide amphiphile molecules for the sustained release of ranibizumab, enabling local high-dose treatment. Peptide amphiphile molecules self-assemble into biodegradable supramolecular filaments in the presence of electrolytes without the need for a curing agent and enable ease of use due to their injectable nature-a feature provided by shear thinning properties. In this study, the release profile of ranibizumab was evaluated by using different peptide-based hydrogels at varying concentrations for improved treatment of the wet form of age-related macular degeneration. We observed that the slow release of ranibizumab from the hydrogel system follows extended- and sustainable release patterns without any dose dumping. Moreover, the released drug was biologically functional and effective in blocking the angiogenesis of human endothelial cells in a dose-dependent manner. In addition, an in vivo study shows that the drug released from the hydrogel nanofiber system can stay in the rabbit eye's posterior chamber for longer than a control group that received only a drug injection. The tunable physiochemical characteristics, injectable nature, and biodegradable and biocompatible features of the peptide-based hydrogel nanofiber show that this delivery system has promising potential for intravitreal anti-VEGF drug delivery in clinics to treat the wet form age-related macular degeneration.

Sulfated GAG mimetic peptide nanofibers enhance chondrogenic differentiation of mesenchymal stem cells in 3D in vitro models.

Articular cartilage, which is exposed to continuous repetitive compressive stress, has limited self-healing capacity in the case of trauma. Thus, it is crucial to develop new treatment options for the effective regeneration of the cartilage tissue. Current cellular therapy treatment options are microfracture and autologous chondrocyte implantation; however, these treatments induce the formation of fibrous cartilage, which degenerates over time, rather than functional hyaline cartilage tissue. Tissue engineering studies using biodegradable scaffolds and autologous cells are vital for developing an effective long-term treatment option. 3D scaffolds composed of glycosaminoglycan-like peptide nanofibers are synthetic, bioactive, biocompatible, and biodegradable and trigger cell-cell interactions that enhance chondrogenic differentiation of cells without using any growth factors. We showed differentiation of mesenchymal stem cells into chondrocytes in both 2D and 3D culture, which produce a functional cartilage extracellular matrix, employing bioactive cues integrated into the peptide nanofiber scaffold without adding exogenous growth factors.

Retraction notice to "Electroactive peptide-based supramolecular polymers" [Materials Today Bio, Volume 10, March 2021, 100099].

[This retracts the article DOI: 10.1016/j.mtbio.2021.100099.].

An interpretable machine learning approach to identify mechanism of action of antibiotics.

As antibiotic resistance is becoming a major public health problem worldwide, one of the approaches for novel antibiotic discovery is re-purposing drugs available on the market for treating antibiotic resistant bacteria. The main economic advantage of this approach is that since these drugs have already passed all the safety tests, it vastly reduces the overall cost of clinical trials. Recently, several machine learning approaches have been developed for predicting promising antibiotics by training on bioactivity data collected on a set of small molecules. However, these methods report hundreds/thousands of bioactive molecules, and it remains unclear which of these molecules possess a novel mechanism of action. While the cost of high-throughput bioactivity testing has dropped dramatically in recent years, determining the mechanism of action of small molecules remains a costly and time-consuming step, and therefore computational methods for prioritizing molecules with novel mechanisms of action are needed. The existing approaches for predicting bioactivity of small molecules are based on uninterpretable machine learning, and therefore are not capable of determining known mechanism of action of small molecules and prioritizing novel mechanisms. We introduce InterPred, an interpretable technique for predicting bioactivity of small molecules and their mechanism of action. InterPred has the same accuracy as the state of the art in bioactivity prediction, and it enables assigning chemical moieties that are responsible for bioactivity. After analyzing bioactivity data of several thousand molecules against bacterial and fungal pathogens available from Community for Open Antimicrobial Drug Discovery and a US Food and Drug Association-approved drug library, InterPred identified five known links between moieties and mechanism of action.

Therapeutic effects of apocynin on ovarian ischemia-reperfusion induced lung injury.

Ovarian ischemia-reperfusion (I-R) injury may damage remote organs, including the lungs. We investigated whether apocynin, a NADPH oxidase inhibitor, might protect against ovarian I-R induced apoptosis in the lungs of rats. Bilateral ovarian I-R was induced for 3 h, then apocynin was applied at two concentrations. Lung tissue was evaluated using spectrophotometric and immunohistochemical methods. We found that I-R increased total oxidant status (TOS), oxidative stress index (OSI) and myeloperoxidase (MPO) levels, and immunostaining of nuclear factor kappa-B (NF-κB), light chain 3B (LC3B), interleukin 1-beta (IL-1ß), caspase-3 and tumor necrosis factor-alpha (TNF-α), but decreased superoxide dismutase (SOD) values. Apocynin application to I-R injured rats enhanced recovery of lung tissue oxidants and improved both histology and frequency of apoptosis.

An Overview of Ischemia-Reperfusion Injury: Review on Oxidative Stress and Inflammatory Response.

Ischemia-reperfusion is a common health problem leading to several health conditions. The pathophysiology of ischemia-reperfusion is quite complex. Oxidative stress and inflammatory response contribute to ischemia-reperfusion mechanisms. Various parameters like proinflammatory cytokines, reactive oxygen species, occur during ischemia-reperfusion . There are several ways to investigate these values through biochemical and histopathologic findings. Malondialdehyde, glutathione, myeloperoxidase, superoxide dismutase, interleukin 6, interleukin 1ß, tumor necrosis factor alpha, caspase-3, nuclear factor-kappa ß, and LC3B (microtubu le-associated protein light chain 3, LC3) can be evaluated among these indicators.

Urapidil alleviates ovarian torsion detorsion injury via regulating oxidative stress, apoptosis, autophagia, and inflammation.

OBJECTIVES: This study aimed to determine anti-inflammatory, antioxidant, and antiapoptotic properties of urapidil (Ura) against ovarian torsion detorsion (T/D) injury in rats. MATERIALS AND METHODS: 40 female Wistar albino rats were grouped as sham, T/D, T/D+dimethyl sulfoxide (DMSO), T/D+Urapidil (Ura) 0.5 mg/kg (low dose), and T/D+Urapidil (Ura) 5 mg/kg (high dose) groups. In treatment groups, Ura was administered intraperitoneally just before detorsion. Biochemical parameters (TAS, TOS, MDA, MPO, and SOD) and immunohistochemical (IL-1ß, TNF-α, NF-κB, LC3B, and Caspase-3) analyzes were performed. RESULTS: In the T/D group, OSI and MPO levels were elevated significantly while TAS values decreased compared with the sham group. A significant difference occurred in the low dose treatment group in TAS and OSI levels compared with the T/D group. In the high dose treatment group, significant elevation in TAS but reduction in OSI and MDA levels were observed compared with the T/D group. Immunohistochemical staining resulted in IL-1ß, TNF-α, NF-κB, LC3B, and caspase-3 immunopositivity in the T/D group, while Ura treatment decreased those parameters. Intensive congestion and hemorrhage were observed in the T/D group, but contrary to this, treatment groups had alleviated congestion and hemorrhage. CONCLUSION: These results suggest that Ura demonstrated protective effects against ovarian T/D injury via anti-oxidative, anti-inflammatory, and anti-apoptotic features.