Triggering Of Response Research Articles

Insights Into the Immune Response of the Black Soldier Fly Larvae to Bacteria.

In insects, a complex and effective immune system that can be rapidly activated by a plethora of stimuli has evolved. Although the main cellular and humoral mechanisms and their activation pathways are highly conserved across insects, the timing and the efficacy of triggered immune responses can differ among different species. In this scenario, an insect deserving particular attention is the black soldier fly (BSF), Hermetia illucens (Diptera: Stratiomyidae). Indeed, BSF larvae can be reared on a wide range of decaying organic substrates and, thanks to their high protein and lipid content, they represent a valuable source of macromolecules useful for different applications (e.g., production of feedstuff, bioplastics, and biodiesel), thus contributing to the development of circular economy supply chains for waste valorization. However, decaying substrates bring the larvae into contact with different potential pathogens that can challenge their health status and growth. Although these life strategies have presumably contributed to shape the evolution of a sophisticated and efficient immune system in this dipteran, knowledge about its functional features is still fragmentary. In the present study, we investigated the processes underpinning the immune response to bacteria in H. illucens larvae and characterized their reaction times. Our data demonstrate that the cellular and humoral responses in this insect show different kinetics: phagocytosis and encapsulation are rapidly triggered after the immune challenge, while the humoral components intervene later. Moreover, although both Gram-positive and Gram-negative bacteria are completely removed from the insect body within a few hours after injection, Gram-positive bacteria persist in the hemolymph longer than do Gram-negative bacteria. Finally, the activity of two key actors of the humoral response, i.e., lysozyme and phenoloxidase, show unusual dynamics as compared to other insects. This study represents the first detailed characterization of the immune response to bacteria of H. illucens larvae, expanding knowledge on the defense mechanisms of this insect among Diptera. This information is a prerequisite to manipulating the larval immune response by nutritional and environmental factors to increase resistance to pathogens and optimize health status during mass rearing.

Defence responses triggered by Blumeria graminis f.sp. hordei in non‐host wheat genotypes results in a decrease in Puccinia triticina infection

AbstractNon‐host resistance is the resistance of plants against all so‐called non‐adapted pathogens, and is considered the most durable and efficient immune system of plants. We investigated barley powdery mildew (Blumeria graminis f.sp. hordei, Bgh)‐triggered defence responses in seven wheat genotypes, and the induction of resistance by this non‐host pathogen to challenge infection with leaf rust, Puccinia triticina Eriks (formerly known as Puccinia recondita f.sp. tritici). Bright‐field and ultraviolet microscopy revealed that although the germination of conidia on non‐host wheat leaves was generally lower than on host barley leaves, the 100% germination on Mv Mambó and only 50% germination on Mv 1 wheat genotypes are the two extremes. If we consider only the germinated conidia, papilla formation was the most frequently observed interaction on Mv 2 (90%) and Mv 4 (88%) genotypes. Epidermal cell death was pronounced on Mv Mambó (31%), but rare on Mv 2 (10%) and Mv 4 (11%), and a mesophyll hypersensitive response could even be detected. At sites of penetration attempts accumulation of H2O2 was shown by 3,3′‐diaminobenzidine staining. Ascorbate peroxidase, glutathione S‐transferase and catalase enzyme activities were augmented by 24.5%, 40.4%, and 21.5%, respectively, in wheat leaves 2 days after Bgh infection. Primary inoculation with Bgh, although with high variability, reduced the number of pustules in all wheat genotypes at first and third leaf stages upon inoculation with leaf rust races 12 and 61 by 10%–70% depending on the genotype, leaf stage and rust race.

Microscopic Kinetics in Poly(Methyl Methacrylate) Exposed to a Single Ultra-Short XUV/X-ray Laser Pulse.

We study the behavior of poly(methyl methacrylate) (PMMA) exposed to femtosecond pulses of extreme ultraviolet and X-ray laser radiation in the single-shot damage regime. The employed microscopic simulation traces induced electron cascades, the thermal energy exchange of electrons with atoms, nonthermal modification of the interatomic potential, and a triggered atomic response. We identify that the nonthermal hydrogen decoupling triggers ultrafast fragmentation of PMMA strains at the absorbed threshold dose of ~0.07 eV/atom. At higher doses, more hydrogen atoms detach from their parental molecules, which, at the dose of ~0.5 eV/atom, leads to a complete separation of hydrogens from carbon and oxygen atoms and fragmentation of MMA molecules. At the dose of ~0.7 eV/atom, the band gap completely collapses indicating that a metallic liquid is formed with complete atomic disorder. An estimated single-shot ablation threshold and a crater depth as functions of fluence agree well with the experimental data collected.

The COVID-19 policy response in Spain and Portugal: a study of measures to slow down infection rate

BackgroundThe COVID-19 global pandemic triggered massive policy responses worldwide. Measures taken during the pandemic differed across countries and time. Governance systems may influence the capacity of countries to respond promptly and mobilize the necessary resources in time. Identifying measures and when they appeared are critical questions to assess emergency response strategies. The objective of this study was to analyze the policy response to slow down the infection rate of COVID-19 cases in Portugal and Spain according to timing (related to death rates) and stringency.MethodsA descriptive comparative study of non-pharmaceutical interventions was conducted through a content analysis of policies and records review of official government sources. Portugal and Spain were selected considering the similarities between national health systems, but different government organization and epidemic impact. The Autonomous Community of Madrid was also included as example of subnational systems. Death rates were retrieved from daily statistics of open secondary sources.ResultsResults show that countries responded with a complex mix of measures across policy sectors, following dynamic patterns established by the epidemic evolution and governance systems. Policies aimed to reduce the spread of the virus, enable individuals and businesses to comply with restrictions, and reinforce National Health System's capacity. The declaration of state of emergency was a critical tool to organize actions under clear leadership, especially in devolved contexts.ConclusionsOur findings suggest that, in early epidemic phases, a centralized command can be more effective at timely enacting nationwide stringent measures. Evidence from this study contributes to the argument that a fast, robust, and early response might have been more effective at containing spread at the initial stages of the pandemic.Key messages The policy response included measured to reduce spread of infection, enhance adherence and strengthen health systems capacity to deal with the pandemic.The declaration of state of emergency was essential to ensure an organized, coherent, timely, and robust response, especially in devolved contexts.

ResponZIF Structures: Zeolitic Imidazolate Frameworks as Stimuli-Responsive Materials.

Zeolitic imidazolate frameworks (ZIFs) have long been recognized as a prominent subset of the metal-organic framework (MOF) family, in part because of their ease of synthesis and good thermal and chemical stability, alongside attractive properties for diverse potential applications. Prototypical ZIFs like ZIF-8 have become embodiments of the significant promise held by porous coordination polymers as next-generation designer materials. At the same time, their intriguing property of experiencing significant structural changes upon the application of external stimuli such as temperature, mechanical pressure, guest adsorption, or electromagnetic fields, among others, has placed this family of MOFs squarely under the umbrella of stimuli-responsive materials. In this review, we provide an overview of the current understanding of the triggered structural and electronic responses observed in ZIFs (linker and bond dynamics, crystalline and amorphous phase changes, luminescence, etc.). We then describe the state-of-the-art experimental and computational methodology capable of shedding light on these complex phenomena, followed by a comprehensive summary of the stimuli-responsive nature of four prototypical ZIFs: ZIF-8, ZIF-7, ZIF-4, and ZIF-zni. We further expose the relevant challenges for the characterization and fundamental understanding of responsive ZIFs, including how to take advantage of their flexible properties for new application avenues.

Neurophysiological and psychophysical effects of dry versus sham needling of the infraspinatus muscle in patients with chronic shoulder pain: a randomized feasibility study

BackgroundDry needling (DN) is increasingly used for treating myofascial trigger points (MTrPs) and has shown significant effects on pain and function. This study aimed to assess feasibility of conducting a randomized sham-controlled trial and to collect preliminary data on the effects of infraspinatus DN on corticospinal excitability and mechanical pain sensitivity.MethodThis randomized feasibility study included adults with chronic non-traumatic shoulder pain and a infraspinatus MTrP. Participants were randomized to receive real DN or sham DN in the infraspinatus MTrP. Feasibility outcomes included data pertaining to recruitment, retention of participants, completeness and safety of assessment procedures. Neurophysiological and psychophysical outcomes included corticospinal excitability and mechanical pain sensitivity measured by active motor threshold (aMT) and pressure pain threshold (PPT), respectively. They were assessed at baseline, immediately after and 24 h post-intervention.ResultsTwenty-one participants were recruited over a 6-month period. Nineteen participants completed the treatment and follow-up assessment. Motor evoked potential responses were discernible in all but 1 participant. Only 1 minor adverse event related to transcranial magnetic stimulation (mild headache) affected the measurements. No DN adverse effects were recorded in both groups. An overall completeness rate of 81% was reached, with 70% completeness in the DN group and 91% in the sham group. Data analysis revealed that real DN increased corticospinal excitability (reduced aMT) 24 h post-intervention (Mdn = − 5.96% MSO, IQR = 5.17, p = 0.04) and that sham DN triggered similar responses immediately after the intervention (Mdn = − 1.93% MSO, IQR = 1.11, p = 0.03). Increased mechanical pain sensitivity (reduced PPT) was significant only in the sham group, both immediately (Mdn = − 0.44 kg/cm2, IQR = 0.49, p = 0.01) and 24 h post-intervention (Mdn = − 0.52 kg/cm2, IQR = 1.02, p = 0.02). Changes in corticospinal excitability was positively correlated with changes in mechanical pain sensitivity in the DN group, both immediately (r = 0.77, p = 0.02) and 24 h post-intervention (r = 0.75, p = 0.05).ConclusionThe present study demonstrates the feasibility of quantifying the neurophysiological and psychophysical effects of DN, and provides recommendations and guidelines for future studies. Moreover, it provides preliminary evidence that DN may increase corticospinal excitability of the infraspinatus muscle in patients with chronic shoulder pain and that the relationship of neurophysiological and psychophysical effects is promising to better understand its mechanisms of action.Trial registrationNCT04316793; retrospectively registered November 3, 2020.

A Vimentin-Targeting Oral Compound with Host-Directed Antiviral and Anti-Inflammatory Actions Addresses Multiple Features of COVID-19 and Related Diseases.

ABSTRACTDamage in COVID-19 results from both the SARS-CoV-2 virus and its triggered overactive host immune responses. Therapeutic agents that focus solely on reducing viral load or hyperinflammation fail to provide satisfying outcomes in all cases. Although viral and cellular factors have been extensively profiled to identify potential anti-COVID-19 targets, new drugs with significant efficacy remain to be developed. Here, we report the potent preclinical efficacy of ALD-R491, a vimentin-targeting small molecule compound, in treating COVID-19 through its host-directed antiviral and anti-inflammatory actions. We found that by altering the physical properties of vimentin filaments, ALD-491 affected general cellular processes as well as specific cellular functions relevant to SARS-CoV-2 infection. Specifically, ALD-R491 reduced endocytosis, endosomal trafficking, and exosomal release, thus impeding the entry and egress of the virus; increased the microcidal capacity of macrophages, thus facilitating the pathogen clearance; and enhanced the activity of regulatory T cells, therefore suppressing the overactive immune responses. In cultured cells, ALD-R491 potently inhibited the SARS-CoV-2 spike protein and human ACE2-mediated pseudoviral infection. In aged mice with ongoing, productive SARS-CoV-2 infection, ALD-R491 reduced disease symptoms as well as lung damage. In rats, ALD-R491 also reduced bleomycin-induced lung injury and fibrosis. Our results indicate a unique mechanism and significant therapeutic potential for ALD-R491 against COVID-19. We anticipate that ALD-R491, an oral, fast-acting, and non-cytotoxic agent targeting the cellular protein with multipart actions, will be convenient, safe, and broadly effective, regardless of viral mutations, for patients with early- or late-stage disease, post-COVID-19 complications, and other related diseases.

Epigenetic targeting of the ACE2 and NRP1 viral receptors limits SARS-CoV-2 infectivity

BackgroundSARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP1) receptors for entry into cells, and the serine protease TMPRSS2 for S protein priming. Inhibition of protease activity or the engagement with ACE2 and NRP1 receptors has been shown to be an effective strategy for blocking infectivity and viral spreading. Valproic acid (VPA; 2-propylpentanoic acid) is an epigenetic drug approved for clinical use. It produces potent antiviral and anti-inflammatory effects through its function as a histone deacetylase (HDAC) inhibitor. Here, we propose VPA as a potential candidate to tackle COVID-19, in which rapid viral spread and replication, and hyperinflammation are crucial elements.ResultsWe used diverse cell lines (HK-2, Huh-7, HUVEC, Caco-2, and BEAS-2B) to analyze the effect of VPA and other HDAC inhibitors on the expression of the ACE-2 and NRP-1 receptors and their ability to inhibit infectivity, viral production, and the inflammatory response. Treatment with VPA significantly reduced expression of the ACE2 and NRP1 host proteins in all cell lines through a mechanism mediated by its HDAC inhibitory activity. The effect is maintained after SARS-CoV-2 infection. Consequently, the treatment of cells with VPA before infection impairs production of SARS-CoV-2 infectious viruses, but not that of other ACE2- and NRP1-independent viruses (VSV and HCoV-229E). Moreover, the addition of VPA 1 h post-infection with SARS-CoV-2 reduces the production of infectious viruses in a dose-dependent manner without significantly modifying the genomic and subgenomic messenger RNAs (gRNA and sg mRNAs) or protein levels of N protein. The production of inflammatory cytokines (TNF-α and IL-6) induced by TNF-α and SARS-CoV-2 infection is diminished in the presence of VPA.ConclusionsOur data showed that VPA blocks three essential processes determining the severity of COVID-19. It downregulates the expression of ACE2 and NRP1, reducing the infectivity of SARS-CoV-2; it decreases viral yields, probably because it affects virus budding or virions stability; and it dampens the triggered inflammatory response. Thus, administering VPA could be considered a safe treatment for COVID-19 patients until vaccines have been rolled out across the world.

The Plant-Stress Metabolites, Hexanoic Aacid and Melatonin, Are Potential "Vaccines" for Plant Health Promotion.

A plethora of compounds stimulate protective mechanisms in plants against microbial pathogens and abiotic stresses. Some defense activators are synthetic compounds and trigger responses only in certain protective pathways, such as activation of defenses under regulation by the plant regulator, salicylic acid (SA). This review discusses the potential of naturally occurring plant metabolites as primers for defense responses in the plant. The production of the metabolites, hexanoic acid and melatonin, in plants means they are consumed when plants are eaten as foods. Both metabolites prime stronger and more rapid activation of plant defense upon subsequent stress. Because these metabolites trigger protective measures in the plant they can be considered as “vaccines” to promote plant vigor. Hexanoic acid and melatonin instigate systemic changes in plant metabolism associated with both of the major defense pathways, those regulated by SA- and jasmonic acid (JA). These two pathways are well studied because of their induction by different microbial triggers: necrosis-causing microbial pathogens induce the SA pathway whereas colonization by beneficial microbes stimulates the JA pathway. The plant’s responses to the two metabolites, however, are not identical with a major difference being a characterized growth response with melatonin but not hexanoic acid. As primers for plant defense, hexanoic acid and melatonin have the potential to be successfully integrated into vaccination-like strategies to protect plants against diseases and abiotic stresses that do not involve man-made chemicals.

The Rise of Vectored Vaccines: A Legacy of the COVID-19 Global Crisis.

The COVID-19 pandemic represents a milestone in vaccine research and development in a global context. A worldwide effort, as never seen before, involved scientists from all over the world in favor of the fast, accurate and precise construction and testing of immunogens against the new coronavirus, SARS-CoV-2. Among all the vaccine strategies put into play for study and validation, those based on recombinant viral vectors gained special attention due to their effectiveness, ease of production and the amplitude of the triggered immune responses. Some of these new vaccines have already been approved for emergency/full use, while others are still in pre- and clinical trials. In this article we will highlight what is behind adeno-associated vectors, such as those presented by the immunogens ChaAdOx1, Sputnik, Convidecia (CanSino, Tianjin, China), and Janssen (Johnson & Johnson, New Jersey, EUA), in addition to other promising platforms such as Vaccinia virus MVA, influenza virus, and measles virus, among others.

Social media advertising as strategy on consumer buying behaviour: conceptual paper

Social media advertising has rapid speed of change in the every industry generated the need to create, adapt and integrate conversations that will allow bridging the gaps between the brand and consumers. The objective of this study is to investigate theoretical evidences of the concept of Social media advertising and its impact on consumer buying behaviour in order to develop customer relationships. This is done by communicating, engaging, entertaining and triggering response through social media content to ultimately stage and develop a customer experience which will make sure the development a long-term relationship and immersing the brand within the consumer’s lifestyle. Moreover the study has various properties of social media marketing in regards to media platforms.

Dynamic earthquake triggering response tracks evolving unrest at Sierra Negra volcano, Galápagos Islands.

The propensity for dynamic earthquake triggering is thought to depend on the local stress state and amplitude of the stress perturbation. However, the nature of this dependency has not been confirmed within a single crustal volume. Here, we show that at Sierra Negra volcano, Galápagos Islands, the intensity of dynamically triggered earthquakes increased as inflation of a magma reservoir elevated the stress state. The perturbation of short-term seismicity within teleseismic surface waves also increased with peak dynamic strain. Following rapid coeruptive subsidence and reduction in stress and background seismicity rates, equivalent dynamic strains no longer triggered detectable seismicity. These findings offer direct constraints on the primary controls on dynamic triggering and suggest that the response to dynamic stresses may help constrain the evolution of volcanic unrest.

Multifunctional efficacy of the nodule endophyte Pseudomonas fragi in stimulating tomato immune response against Meloidogyne incognita

Root-knot nematodes severely affect the growth and productivity of agricultural plants in the world. Conversely, endophytic bacteria can be used to prevent plant diseases and increase crop yield. The nodule endophytic bacterium Pseudomonas fragi (Eichholz) Gruber has been reported to promote crop growth, but its role in nematode control is unclear. In this study, the biocontrol effect of P. fragi Sneb1990 against Meloidogyne incognita (Kofoid & White) Chitwood was assessed in tomato (Solanum lycopersicum L.). In vitro, the fermentation broth of P. fragi Sneb1990 provoked 76.8% juvenile mortality after 48 h and 71.9% egg mortality after 7 d. P. fragi Sneb1990 promoted plant growth and alleviated M. incognita disease symptoms in pot and field experiments. The split-root assay revealed that P. fragi Sneb1990 stimulated local and systemic immunity to suppress the penetration and development of M. incognita and that it enhanced the expression of PR1, PR2, PR3, PR5, and PDF1.2, which participate in the jasmonic acid and salicylic acid pathways. Furthermore, the flagellin polypeptide flg22 of P. fragi Sneb1990 triggered tomato immunity against M. incognita, stimulated reactive oxygen species production, and upregulated the expression of salicylic acid resistance-related genes. This is the first report of the suppression of M. incognita infection by the nodule endophyte P. fragi. In addition, the flagellin functional domain of P. fragi Sneb1990 triggered immune responses against M. incognita in tomato. Overall, our study highlights the potential of P. fragi Sneb1990 as a biocontrol agent against M. incognita.

Breeding season shift by the Oahu Elepaio (Chasiempis ibidis) in response to changing rainfall patterns

Anthropogenic climate change is affecting many bird species in a variety of ways, causing changes in their distribution, abundance, and food supply, and triggering responses such as shifting migration and nesting seasons. Most studies have focused on migratory birds that breed in temperate areas and little is known about effects of climate change on tropical birds. We used a 24 year dataset that included 1,632 nesting events of the Oahu Elepaio (Chasiempis ibidis), an endangered forest bird endemic to Hawaii, to investigate whether breeding phenology and performance were related to rainfall and whether a recent shift in the breeding season is related to changes in rainfall. Fecundity of the Oahu Elepaio was closely related to rainfall, with more offspring produced during years with higher rainfall. During the first 19 years of this study, from 1996 to 2014, all nests were initiated from November to June. From 2015 to 2019, up to 33% of annual reproduction occurred from August to October. Higher rainfall caused parallel increases in reproduction during the normal nesting season and the atypical season, with some birds nesting in both seasons. The change in breeding phenology of the Oahu Elepaio is unusual because it was not a gradual transition, but a sudden change of 6 months. The shift in breeding phenology coincided with unusually high summer and fall rainfall from tropical storms associated with a novel climate pattern in the northern Pacific Ocean from late 2014–2016 termed the warm blob. This pattern of warmer water and more frequent storms is expected to become more prevalent in the Central Pacific, so summer–fall breeding in the Oahu Elepaio is likely to continue and perhaps become more common. The Oahu Elepaio is flexible, adaptable, and may not be seriously affected by changing climatic conditions.

Breeding season shift by the Oahu Elepaio (Chasiempis ibidis) in response to changing rainfall patterns

Anthropogenic climate change is affecting many bird species in a variety of ways, causing changes in their distribution, abundance, and food supply, and triggering responses such as shifting migration and nesting seasons. Most studies have focused on migratory birds that breed in temperate areas and little is known about effects of climate change on tropical birds. We used a 24 year dataset that included 1,632 nesting events of the Oahu Elepaio (Chasiempis ibidis), an endangered forest bird endemic to Hawaii, to investigate whether breeding phenology and performance were related to rainfall and whether a recent shift in the breeding season is related to changes in rainfall. Fecundity of the Oahu Elepaio was closely related to rainfall, with more offspring produced during years with higher rainfall. During the first 19 years of this study, from 1996 to 2014, all nests were initiated from November to June. From 2015 to 2019, up to 33% of annual reproduction occurred from August to October. Higher rainfall caused parallel increases in reproduction during the normal nesting season and the atypical season, with some birds nesting in both seasons. The change in breeding phenology of the Oahu Elepaio is unusual because it was not a gradual transition, but a sudden change of 6 months. The shift in breeding phenology coincided with unusually high summer and fall rainfall from tropical storms associated with a novel climate pattern in the northern Pacific Ocean from late 2014–2016 termed the warm blob. This pattern of warmer water and more frequent storms is expected to become more prevalent in the Central Pacific, so summer–fall breeding in the Oahu Elepaio is likely to continue and perhaps become more common. The Oahu Elepaio is flexible, adaptable, and may not be seriously affected by changing climatic conditions.

Recent Advances in 2D Material-Mediated Immuno-Combined Cancer Therapy.

In the last years, cancer immunotherapy has started to attract a lot of attention, becoming one of the alternatives in the clinical treatment of cancer. Indeed, one of the advantages of immunotherapy is that both primary and distant tumors can be efficiently eradicated through a triggered immune response. Due to their large specific surface area and unique physicochemical properties, 2D materials have become popular in cancer immunotherapy, especially as efficient drug carriers. They have been also exploited as photothermal platforms, chemodynamic agents, and photosensitizers to further enhance the efficacy of the therapy. In this review, the focus is on the recent development of 2D materials as new tools to combine immunotherapy with chemotherapy, photothermal therapy, photodynamic therapy, chemodynamic therapy, radiotherapy, and radiodynamic therapy. These innovative synergistic approaches intend to go beyond the classical strategies based on a simple delivery function of immune modulators by nanomaterials. Furthermore, the effects of the 2D materials themselves and their surface properties (e.g., chemical modification and protein corona formation) on the induction of an immune response will be also discussed.

Iridium(Ⅲ) complex-based phosphorescent and electrochemiluminescent dual sensor for selective detection of glutathione

• Iridium complex-based phosphorescent and electrochemiluminescent dual sensors enabled selective detection of GSH. • Reduction of pdo to phen(OH) 2 upon reaction with GSH triggered PL turn-on and ECL turn-off response. • Sensing mechanisms were elucidated by DFT calculations and cyclic voltammetry. • Sensor 1 was applied to determination of GSH concentrations in human serum. Glutathione (GSH) is the most abundant biological thiol and involved in antioxidant defense systems in human cells. Lack of GSH increases the risk of oxidative stress, resulting in the progression of cancer. Therefore, a selective detection method for GSH is highly required. Herein, we report phosphorescent and electrochemiluminescent dual sensors ( 1-3 ) based on iridium complexes for the selective detection of GSH. These sensors have a 1,10-phenanthroline-5,6-dione (pdo) ancillary ligand as a common reaction site for GSH. Reduction of the pdo moiety to 1,10-phenanthroline-5,6-diol (phen(OH) 2 ) upon reaction of sensors with GSH triggered fluorescence turn-on response and electrochemiluminescence turn-off response with high selectivity for GSH. Sensing mechanisms were elucidated by DFT calculations and cyclic voltammetry. Sensor 1 was successfully applied to determination of GSH concentrations in human serum samples by ECL methods.

Linking oral microbial proteolysis to aMMP-8 PoC diagnostics along with the stage and grade of periodontitis: A cross-sectional study.

Linking oral microbial proteolysis to aMMP-8 PoC diagnostics along with the stage and grade of periodontitis: A cross-sectional study.

Empagliflozin nanoparticles attenuates type2 diabetes induced cognitive impairment via oxidative stress and inflammatory pathway in high fructose diet induced hyperglycemic mice

There is snowballing evidence that type 2 diabetes (T2D) predisposes to neuropathophysiological alterations including oxidative stress and triggered inflammatory responses in brain that eventually culminates into cognitive impairment.Accumulating evidences suggest that SGLT2 inhibitor can be a promising intervention for cognitive decline in T2DM. In the present paper, the potential effects of Empagliflozin (EMPA), a SGLT2 inhibitor, against T2D induced cognitive dysfunction have been explored. The effect of EMPA on array of inflammatory mediators including Interleukin-6(IL-6), Interleukin -1β (IL-1β), and Tumour necrosis factor-α(TNF-α)), neuronal proteins including glycogen synthase kinase-3β (GSK- 3β), Phosphorylated tau (p-tau), amyloid beta (Aβ) (1–40, 1–42) and altered oxidative parameters including SOD, catalase, TBARS was determined in the high fructose diet induced hyperglycaemic mice. The obtained results were compared with EMPA nanoparticles (Nps) formulated in our laboratory and found that EMPA Nps significantly showed reduced levels of inflammatory mediators and oxidative stress. Further, decrease in levels of p-tau, Aβ (1–40) and Aβ (1–42) were also observed with EMPA nanoparticles.Thus, the study has demonstrated that EMPA Nps could be a promising therapy to alleviate the progression of cognitive decline in T2D.

Early Endothelial Activation in a Mouse Model of Graft vs Host Disease Following Chemotherapy.

Allogenic hematopoietic stem cell transplant (allo-HSCT) can lead to sinusoidal obstruction syndrome (SOS) and graft-versus-host disease (GvHD) in some individuals. GvHD is characterised by an immune triggered response that arises due to donor T cells recognizing the recipient tissue as “foreign”. SOS results in impaired liver function due to microvascular thrombosis and consequent obstruction of liver sinusoids. Endothelial damage occurs following chemotherapy and allo-HSCT and is strongly associated with GvHD onset as well as hepatic SOS. Animal models of GvHD are rarely clinically relevant, and endothelial dysfunction remains uncharacterised. Here we established and characterised a clinically relevant model of GvHD wherein Balb/C mice were subjected to myeloablative chemotherapy followed by transplantation of bone marrow (BM) cells± splenic T-cells from C57Bl6 mice, resulting in a mismatch of major histocompatibility complexes (MHC). Onset of disease indicated by weight loss and apoptosis in the liver and intestine was discovered at day 6 post-transplant in mice receiving BM+T-cells, with established GvHD detectable by histology of the liver within 3 weeks. Together with significant increases in pro-inflammatory cytokine gene expression in the liver and intestine, histopathological signs of GvHD and a significant increase in CD4+ and CD8+ effector and memory T-cells were seen. Endothelial activation including upregulation of vascular cell adhesion molecule (VCAM)- 1 and downregulation of endothelial nitric oxide synthase (eNOS) as well as thrombosis in the liver indicated concomitant hepatic SOS. Our findings confirm that endothelial activation is an early sign of acute GvHD and SOS in a clinically relevant mouse model of GvHD based on myeloablative chemotherapy. Preventing endothelial activation may be a viable therapeutic strategy to prevent GvHD.