Reduced Disease Severity Research Articles

Investigations into Economic Returns Resulting from Foliar Fungicides and Application Timing on Management of Tar Spot in Indiana Hybrid Corn.

Tar spot, caused by Phyllachora maydis, is the most significant yield-limiting disease of corn (Zea mays L.) in Indiana. Currently, fungicides are an effective management tool for this disease, and partial returns from their use under different disease severity conditions has not previously been studied. Between 2019 and 2021, two separate field experiments were conducted in each year in Indiana to assess the efficacy of nine foliar fungicide products and nine fungicide application timings based on corn growth stages on tar spot symptoms and stromata, canopy greenness, yield, and influence on partial returns. All fungicides evaluated significantly suppressed tar spot development in the canopy and increased canopy greenness over the nontreated control. Additionally, applications of mefentrifluconazole + pyraclostrobin, metconazole + pyraclostrobin, cyproconazole + picoxystrobin at tassel, and propiconazole + benzovindiflupyr + azoxystrobin between the tassel and dough growth stages were the most effective at significantly reducing disease severity, increasing canopy greenness, protecting yield, and offered the greatest partial return. Fungicide products varied in their ability to protect yield under low and high disease severity conditions relative to the nontreated control. Consistently, positive yield increases were observed when disease severity was high, which translated to greater profitability relative to low severity conditions. On average, the yield increases across foliar fungicide products and timed application treatments were 544.6 and 1,020.7 kg/ha greater, and partial returns using a grain value of $0.17/kg were $92.6/ha and $173.5/ha greater, respectively, when high severity conditions occurred. This research demonstrates that foliar fungicides and appropriately timed fungicide applications can profitably be used to manage tar spot in Indiana under high disease severity conditions.

Boosting Solanum tuberosum resistance to Alternaria solani through green synthesized ferric oxide (Fe2O3) nanoparticles

Potato (Solanum tuberosum) is the third crucial global crop facing threats from Alternaria solani, a necrotrophic fungal pathogen causing early blight disease. Beyond crop impact, it leads to substantial production reduction and economic losses worldwide. This study introduces a green synthesis method for producing Ferric Oxide nanoparticles (FNPs) using dried Guava (Psidium guajava) leaves. Guava leaf extract acts as a reducing agent, with iron (III) chloride hexahydrate (FeCl3·6H2O) as the oxidizing agent. This study employed various characterization techniques for Ferric Oxide nanoparticles (FNPs). Fourier Transform Infrared Spectroscopy (FTIR) revealed peaks at 877 cm−1, 1180 cm−1, 1630 cm−1, 1833 cm−1, 2344 cm−1, and 3614 cm−1, associated with Maghemite vibrations, polyphenol compounds, and amino acids. UV–Vis spectroscopy exhibited a characteristic absorbance peak at 252 nm for FNPs. Scanning Electron Microscope (SEM) images illustrated particle sizes of 29-41 nm, and Energy Dispersive Spectroscopy (EDS) indicated elemental composition. X-ray diffraction (XRD) confirmed crystalline FNPs with peaks at 26.78, 30.64, 36.06, 38.21, 43.64, 53.52, 57.42, 63.14 and 78.32. Disease resistance assays demonstrated FNPs’ effectiveness against A. solani, reducing disease incidence and severity. In the leaf detach assay, concentrations of 15, 10 and 5 mg/L showed a dose-dependent reduction in disease severity and incidence. The Greenhouse Assay confirmed FNPs’ concentration-dependent effect on disease incidence and severity. The study also explored FNPs’ potential as biocontrol agents showing no adverse effects on overall plant development. Additionally, the study highlighted the agronomic potential of FNPs in enhancing plant growth and development emphasizing their role as micronutrients in biofortification. The findings suggest the promising application of FNPs in plant protection and biofortification strategies.

IKKβ deletion from CNS macrophages increases neuronal excitability and accelerates the onset of EAE, while from peripheral macrophages reduces disease severity

BackgroundMultiple sclerosis (MS) is a neuroinflammatory demyelinating disease characterized by motor deficits and cognitive decline. Many immune aspects of the disease are understood through studies in the experimental autoimmune encephalomyelitis (EAE) model, including the contribution of the NF-κB transcription factor to neuroinflammation. However, the cell-specific roles of NF-κB to EAE and its cognitive comorbidities still needs further investigation. We have previously shown that the myeloid cell NF-κB plays a role in the healthy brain by exerting homeostatic regulation of neuronal excitability and synaptic plasticity and here we investigated its role in EAE.MethodsWe used constitutive MφIKKβΚΟ mice, in which depletion of IKKβ, the main activating kinase of NF-κB, was global to CNS and peripheral macrophages, and ΜgΙΚΚβKO mice, in which depletion was inducible and specific to CNS macrophages by 28 days after tamoxifen administration. We subjected these mice to MOG35-55 induced EAE and cuprizone-induced demyelination. We measured pathology by immunohistochemistry, investigated molecular mechanisms by RNA sequencing analysis and studied neuronal functions by in vivo electrophysiology in awake animals.ResultsGlobal depletion of IKKβ from myeloid cells in MφIKKβΚΟ mice accelerated the onset and significantly supressed chronic EAE. Knocking out IKKβ only from CNS resident macrophages accelerated the onset and exacerbated chronic EAE, accompanied by earlier demyelination and immune cell infiltration but had no effect in cuprizone-induced demyelination. Peripheral T cell effector functions were not affected by myeloid cell deletion of IKKβ, but CNS resident mechanisms, such as microglial activation and neuronal hyperexcitability were altered from early in EAE. Lastly, depletion of myeloid cell IKKβ resulted in enhanced late long-term potentiation in EAE.ConclusionsIKKβ-mediated activation of NF-κΒ in myeloid cells has opposing roles in EAE depending on the cell type and the disease stage. In CNS macrophages it is protective while in peripheral macrophages it is disease-promoting and acts mainly during chronic disease. Although clinically protective, CNS myeloid cell IKKβ deletion dysregulates neuronal excitability and synaptic plasticity in EAE. These effects of IKKβ on brain cognitive abilities deserve special consideration when therapeutic interventions that inhibit NF-κB are used in MS.

Sargramostim for Prophylactic Management of Gastrointestinal Immune-Related Adverse Events of Immune Checkpoint Inhibitor Therapy for Cancer

Immune checkpoint inhibitor (ICI) therapy improves outcomes in several cancers. Unfortunately, many patients experience grade 3–4 treatment-related adverse events, including gastrointestinal (GI) toxicities which are common. These GI immune-related adverse events (irAEs) induced by ICIs present significant clinical challenges, require prompt intervention, and result in treatment delays or discontinuations. The treatment for these potentially severe and even fatal GI irAEs which include enterocolitis, severe diarrhea, and hepatitis may interfere with the anti-cancer approach. Sargramostim (glycosylated, yeast-derived, recombinant human GM-CSF) is an agent that has been used in clinical practice for more than 30 years with a well-recognized safety profile and has been studied in many therapeutic areas. The mechanism of action of sargramostim may treat moderate-to-severe GI irAEs without impairing the anti-cancer therapy. Some early data also suggest a potential survival benefit. Through the differentiation/maturation of monocytes, macrophages, and neutrophils and induction of anti-inflammatory T cell responses, GM-CSF aids in GI homeostasis, mucosal healing, and mucosal immunity. GM-CSF knockout mice are susceptible to severe colitis which was prevented with murine GM-CSF administration. For some patients with GI mucosa and immune cell function impairment, e.g., Crohn’s disease, sargramostim reduces disease severity. In a prospective, randomized study (ECOG 1608), advanced melanoma patients had a reduction in grade 3–5 GI irAEs and less frequent colonic perforation in the sargramostim plus ipilimumab arm compared to ipilimumab alone. Sargramostim continues to be studied with ICIs for the prophylactic management of irAEs while also potentially providing a survival benefit.

P114 Role of NLRX1 Agonist NX-13 in Reducing Visceral Hypersensitivity in Preclinical Gastrointestinal Inflammation

Abstract Background NLRX1 activation reduces inflammation by decreasing oxidative stress and altering cellular metabolism within multiple cell types implicated in ulcerative colitis (UC). Colitis animal models demonstrated reduced disease severity and a phase 1b clinical trial showed signs of rapid symptom and endoscopic improvement in patients with active UC.1, 2 Abdominal pain driven by visceral hypersensitivity may persist in patients even after inflammation has resolved, negatively affecting their quality of life.3, 4 Therapeutic agents which address inflammation, epithelial healing, and visceral hypersensitivity concurrently may provide greater symptomatic relief and improved quality of life as many patients, even in remission, still complain of abdominal pain. We here describe the effects of oral NX-13 in a rat model of visceral hypersensitivity. Methods Rats (n=8) were dosed daily for a period of 3 days with NX-13 or vehicle. Under anesthesia, electrodes were positioned to monitor oblique abdominal muscle contraction and a colonic balloon catheter was inserted intra-anally. Visceral pain was assessed at baseline and 3 h post lipopolysaccharide injection (1 mg/kg subcutaneous) through measuring of visceromotor response (VMR) via electromyogram (EMG) recording and visual assessment of abdominal withdrawal reflex (AWR). Data are represented as median (IQR) and statistical significance determined by non-parametric Mann-Whitney U test. Results Compared to the vehicle control, oral NX-13 delayed the onset of muscle contraction in response to colonic distension in LPS-treated rats. Further, NX-13 treated rats experienced reduced contraction intensity and reduced sustained abdominal muscle contraction period compared to the vehicle control. Specifically, NX-13 decreased the number of AWR during colonic expansion compared to the control group (p=0.01, Fig1A). Moreover, NX-13 desensitized the VMR response by numerically increasing the minimum volume of the colonic distension balloon required to induce significant VMR. The mean minimum volume of water injected required to induce significant VMR increased 23%, from 650 μL in the vehicle group to 800 μL in the NX-13 treated rats (p=0.16, Fig1B). Lastly, NX-13 visually reduced the maximum abdominal EMG amplitude during colonic distention (p=0.19, Fig1C). Conclusion Adequate management of persistent pain in IBD patients with or without active bowel inflammation remains an unmet need in the treatment of IBD. The potential for NX-13 to specifically reduce visceral hypersensitivity and abdominal pain will be evaluated further in the ongoing phase 2 human NEXUS trial in patients with UC. 1Leber et al. J Immunol 203(12) 2Peyrin-Biroulet et al. JCC (17)Supp 3Abreu et al. JCC (14)Supp 4Wils et al. J Clin Med 11(15)

Trichoderma afroharzianum TRI07 metabolites inhibit Alternaria alternata growth and induce tomato defense-related enzymes

Identifying a viable substitute for the limited array of current antifungal agents stands as a crucial objective in modern agriculture. Consequently, extensive worldwide research has been undertaken to unveil eco-friendly and effective agents capable of controlling pathogens resistant to the presently employed fungicides. This study explores the efficacy of Trichoderma isolates in combating tomato leaf spot disease, primarily caused by Alternaria alternata. The identified pathogen, A. alternata Alt3, was isolated and confirmed through the ITS region (OQ888806). Six Trichoderma isolates were assessed for their ability to inhibit Alt3 hyphal growth using dual culture, ethyl acetate extract, and volatile organic compounds (VOCs) techniques. The most promising biocontrol isolate was identified as T. afroharzianum isolate TRI07 based on three markers: ITS region (OQ820171), translation elongation factor alpha 1 gene (OR125580), and RNA polymerase II subunit gene (OR125581). The ethyl acetate extract of TRI07 isolate was subjected to GC–MS analysis, revealing spathulenol, triacetin, and aspartame as the main compounds, with percentages of 28.90, 14.03, and 12.97%, respectively. Analysis of TRI07-VOCs by solid-phase microextraction technique indicated that the most abundant compounds included ethanol, hydroperoxide, 1-methylhexyl, and 1-octen-3-one. When TRI07 interacted with Alt3, 34 compounds were identified, with major components including 1-octen-3-one, ethanol, and hexanedioic acid, bis(2-ethylhexyl) ester. In greenhouse experiment, the treatment of TRI07 48 h before inoculation with A. alternata (A3 treatment) resulted in a reduction in disease severity (16.66%) and incidence (44.44%). Furthermore, A3 treatment led to improved tomato growth performance parameters and increased chlorophyll content. After 21 days post-inoculation, A3 treatment was associated with increased production of antioxidant enzymes (CAT, POD, SOD, and PPO), while infected tomato plants exhibited elevated levels of oxidative stress markers MDA and H2O2. HPLC analysis of tomato leaf extracts from A3 treatment revealed higher levels of phenolic acids such as gallic, chlorogenic, caffeic, syringic, and coumaric acids, as well as flavonoid compounds including catechin, rutin, and vanillin. The novelty lies in bridging the gap between strain-specific attributes and practical application, enhancing the understanding of TRI07’s potential for integrated pest management. This study concludes that TRI07 isolate presents potential natural compounds with biological activity, effectively controlling tomato leaf spot disease and promoting tomato plant growth. The findings have practical implications for agriculture, suggesting a sustainable biocontrol strategy that can enhance crop resilience and contribute to integrated pest management practices.

Combatting Sugar Beet Root Rot: Streptomyces Strains' Efficacy against Fusarium oxysporum.

Sugar beet root rot disease triggered by Fusarium oxysporum f. sp. radicis-betae is a destructive disease and dramatically affects the production and quality of the sugar beet industry. Employing beneficial microorganisms as a biocontrol strategy represents an eco-friendly and sustainable approach to combat various plant diseases. The distinct aspect of this study was to assess the antifungal and plant growth-promoting capabilities of recently isolated Streptomyces to treat sugar beet plants against infection with the phytopathogen F. oxysporum. Thirty-seven actinobacterial isolates were recovered from the rhizosphere of healthy sugar beet plants and screened for their potential to antagonize F. oxysporum in vitro. Two isolates SB3-15 and SB2-23 that displayed higher antagonistic effects were morphologically and molecularly identified as Streptomyces spp. Seed treatment with the fermentation broth of the selected Streptomyces strains SB3-15 and SB2-23 significantly reduced disease severity compared to the infected control in a greenhouse experiment. Streptomyces SB2-23 exhibited the highest protective activity with high efficacy ranging from 91.06 to 94.77% compared to chemical fungicide (86.44 to 92.36%). Furthermore, strain SB2-23 significantly increased plant weight, root weight, root length, and diameter. Likewise, it improves sucrose percentage and juice purity. As a consequence, the strain SB2-23's intriguing biocontrol capability and sugar beet root growth stimulation present promising prospects for its utilization in both plant protection and enhancement strategies.

The Protective Effect of Serum Levels of Vitamins C, D, and E and IgG and IgM Antibodies in Individuals Vaccinated Against COVID-19 and Experienced Disease Relapse

Background: Despite global control measures aimed at ending the COVID-19 pandemic, the disease continues to pose a threat to public health. In this study, we examined the serum levels of vitamins C, D, and E, as well as IgG and IgM antibodies in individuals who had previously been vaccinated against COVID-19 and subsequently experienced a relapse of the disease. Objectives: The objective of this study was to investigate the correlation between sufficient levels of vitamins E, D, and C, the severity of the disease, and the immunological response in vaccinated patients who have experienced a recurrence of COVID-19. Methods: Given the potential role of vitamins C, D, and E in the management of COVID-19, we conducted a study to examine the serum levels of these vitamins in individuals who had previously been vaccinated against COVID-19 and experienced a disease relapse, characterized by symptoms, such as body pain, shortness of breath, cough, and fever. We compared two groups of hospitalized individuals with varying disease severity to healthy individuals. Additionally, we investigated IgG and IgM antibodies in these patients due to the significance of antibody levels in determining disease severity. Results: Our results revealed significant differences in the levels of vitamins C, D, and E between hospitalized individuals and healthy individuals. Furthermore, a notable disparity in serum IgM and IgG levels was observed based on the severity of the disease. However, no significant difference was detected in the average levels of anti-SARS-CoV-2 immunoglobulins among the different groups, whether they had received the AstraZeneca or Sinopharm vaccines. Conclusions: Vitamins C, D, and E play supportive roles in the immune system, aiding the host's immune response. These findings suggest that maintaining adequate levels of these vitamins may be beneficial in preventing SARS-CoV-2 reinfection and reducing disease severity, particularly in cases where vaccine efficacy is uncertain.

Characterization of antifungal properties of avocado leaves and majagua flowers extracts and their potential application to control Alternaria alternata

Plant extracts are used as an alternative to a wide range of foods against different types of fungal pathogens. In the present study, the extracts of avocado leaves (Persea americana) and majagua flowers (Talipariti elatum) were tested according to their antifungal activity against different fungi. The most promising extracts were those of majagua flowers that were applied lyophilized and in aqueous extract, being very effective against Alternaria alternata and reaching a 50 % in vitro reduction. Antifungal properties were also evaluated during infection of apples by A. alternata. A decrease in infection progression was confirmed with up to a 30 % reduction in disease incidence and a 20 % reduction in disease severity. Majagua extracts were also tested combined with edible pectin coatings, greatly increasing their effectiveness up 60 % reduction. Thus, extracts of majagua could provide a feasible alternative to control fungal pathogens during postharvest.

The Effects of Some Different Cultural Techniques on the Transmission and Infectious Development of Pepper Yellow Leaf Curl Indonesia Virus on Red Chili

<p>An experiment is conducted to investigate the effects of cultural techniques on pepper yellow leaf curl disease caused by <em>Pepper yellow leaf curl Indonesia virus</em> (PepYLCIV). The investigation is conducted in the area where the disease has been endemic and <em>Bemisia tabaci</em> is abundant. Four cultural techniques are applied in separate lands and cannot interfere with each other. The methods applied are seed treatment, intercropping, trap cropping, and physical barrier. Seeds harvested from infected plants are used for seed treatment experiments, and local farmers use commercial sources for other experiments. The results confirmed that PepYLCIV was a seed-borne virus affected by hot water treatment at 65<sup>o</sup>C for 30 minutes. Turmeric crude extract could reduce the incidence and severity of the disease. The tomato is a better intercrop than eggplant, mung bean, and soybean in reducing disease incidence, but their effects on disease severity and yield reduction were not significantly different. Basil and marigolds were better barrier crops compared to cosmos and zinnia. A 125 cm high physical barrier using 50 mesh cheesecloth could reduce the disease incidence, but not the lower ones. Under different cultural techniques, PepYLCIV causes a 40.00–52.32% chili yield reduction.</p>

Manipulation of the seagrass-associated microbiome reduces disease severity.

Host-associated microbes influence host health and function and can be a first line of defence against infections. While research increasingly shows that terrestrial plant microbiomes contribute to bacterial, fungal, and oomycete disease resistance, no comparable experimental work has investigated marine plant microbiomes or more diverse disease agents. We test the hypothesis that the eelgrass (Zostera marina) leaf microbiome increases resistance to seagrass wasting disease. From field eelgrass with paired diseased and asymptomatic tissue, 16S rRNA gene amplicon sequencing revealed that bacterial composition and richness varied markedly between diseased and asymptomatic tissue in one of the two years. This suggests that the influence of disease on eelgrass microbial communities may vary with environmental conditions. We next experimentally reduced the eelgrass microbiome with antibiotics and bleach, then inoculated plants with Labyrinthula zosterae, the causative agent of wasting disease. We detected significantly higher disease severity in eelgrass with a native microbiome than an experimentally reduced microbiome. Our results over multiple experiments do not support a protective role of the eelgrass microbiome against L. zosterae. Further studies of these marine host-microbe-pathogen relationships may continue to show new relationships between plant microbiomes and diseases.

Deletion of Aurora kinase A prevents the development of polycystic kidney disease in mice

Aurora Kinase A (AURKA) promotes cell proliferation and is overexpressed in different types of polycystic kidney disease (PKD). To understand AURKA’s role in regulating renal cyst development we conditionally deleted the gene in mouse models of Autosomal Dominant PKD (ADPKD) and Joubert Syndrome, caused by Polycystin 1 (Pkd1) and Inositol polyphosphate-5-phosphatase E (Inpp5e) mutations respectively. We show that while Aurka is dispensable for collecting duct development and homeostasis, its deletion prevents cyst formation in both disease models. Cross-comparison of transcriptional changes implicated AKT signaling in cyst prevention and we show that (i) AURKA and AKT physically interact, (ii) AURKA regulates AKT activity in a kinase-independent manner and (iii) inhibition of AKT can reduce disease severity. AKT activation also regulates Aurka expression, creating a feed-forward loop driving renal cystogenesis. We find that the AURKA kinase inhibitor Alisertib stabilises the AURKA protein, agonizing its cystogenic functions. These studies identify AURKA as a master regulator of renal cyst development in different types of PKD, functioning in-part via AKT.

Strategy For Controlling Bacterial Leaf Blight (Xanthomonas sp.) on Eucalyptus Pellita Plants by Administering P. aeruginosa RE081

The demand for Eucalyptus Pellita seeds as a high-throughput inoculum (HTI) crop commodity in the field is extremely high. However, Xanthomonas sp., a bacteria that causes bacterial leaf blight, poses a significant challenge in ensuring a steady supply of healthy seedlings in nurseries. Researchers have explored using the rhizobacteria P. aeruginosa RE081 as an environmentally friendly biocontrol agent to address this issue. This study aims to determine the optimal concentration of P. aeruginosa RE081 that can effectively reduce the incidence and severity of bacterial leaf blight caused by Xanthomonas sp. The research was conducted using a completely randomized design, with different concentrations of P. aeruginosa RE081 (105, 106, 107, 108 CFU/mL) being tested. The findings indicate that the biological agent's concentration significantly impacts plant disease occurrence and severity. In vivo testing revealed that P. aeruginosa RE081 reduced disease severity by only 2.13% at a 108 CFU/mL concentration. Interestingly, concentrations lower than 108 CFU/mL increased disease severity compared to the control group.

Efficacy of convalescent plasma in hospitalized COVID-19 patients: findings from a controlled trial.

The COVID-19 pandemic has driven the search for alternative therapies, including convalescent plasma, historically used in infectious diseases. Despite results in other diseases, its effectiveness against COVID-19 remains uncertain with conflicting results in clinical trials. A pragmatic, single-center, prospective, and open randomized controlled trial was carried out in a hospital in Brazil, with the aim of evaluating the impact of convalescent plasma on the clinical improvement of patients hospitalized with COVID-19. The World Health Organization (WHO) ordinal scale was used to measure clinical improvement, focusing on the reduction in disease severity by up to 2 points, while antibody and C-reactive protein levels were monitored over time. After hospital admission, participants were randomized 1:1 to receive convalescent plasma and standard treatment or to be part of the control group with standard treatment. Follow-up was carried out on days 1, 3, 7, 14 and/or at discharge. From January 14 to April 4, 2022, 38 patients were included, but 3 were excluded due to protocol deviations, resulting in a total of 35 patients: 19 in the control group and 16 in the plasma group. There was no significant difference in clinical improvement between the convalescent plasma group and the control group, nor in secondary outcomes. The study had limitations due to the small number of patients and limited representation of COVID-19 cases. Broader investigations are needed to integrate therapies into medical protocols, both for COVID-19 and other diseases. Conducting randomized studies is challenging due to the complexity of medical conditions and the variety of treatments available.

Evaluation of the Immune Checkpoints, TIM-3 and PD-1, as well as Anti-Inflammatory Cytokines IL-10, and TGF-β along with Diseases Activity in Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) is a skin disease caused by mast cells that produce inflammatory mediators. Immune checkpoint receptors such as program death-1 (PD-1) and T-cell immunoglobulin and mucin domain 3 (TIM-3) are essential for the pathophysiology of many autoimmune and allergic diseases. The aim of this study was to investigate the expression of PD-1 and TIM-3 in CSU patients and their relationship to the anti-inflammatory cytokines (TGF-β and IL-10). In the current study, peripheral blood mononuclear cells (PBMCs) from CSU patients and healthy individuals were used and the Urticaria Activity Score 7 (UAS7) was used to assess disease severity. TaqMan-based RT-PCR was used to assess the expression of TIM-3 and PD-1 as well as the anti-inflammatory cytokines transforming growth factor-β (TGF-β) and IL-10. The protein concentrations of TGF-β and IL-10 were also measured by ELISA. The relationship between the expression of TIM-3 and PD-1 as well as TGF- β and IL-10 and the severity of the disease was investigated. The results showed that PD-1 mRNA expression was significantly increased in CSU patients (P<0.0001), while TGF- β and IL-10 levels were higher in CSU patients, but this difference was not significant (p=0.638, p= 0.798). The increase in protein level of IL-10 was significant (P<0.0001). There was also a positive correlation between the expression of PD-1 and TGF- β molecules and disease activity (P=0.0043, P=0.0018). In conclusion, the study found that the immune system expresses inhibitory molecules and anti-inflammatory cytokines to control disease severity. The higher expression of PD-1 molecules and IL-10 is associated with disease severity, suggesting that the immune system is trying to control inflammation and reduce disease severity.

Using oral molecular hydrogen supplements to combat microinflammation in humans: a pilot observational study.

Background: Persistent inflammation over time can cause gradual harm to the body. Molecular hydrogen has the potential to specifically counteract reactive oxygen species (ROS), reduce disease severity, and enhance overall health. Investigations of the anti-inflammatory and antioxidant properties of oral solid hydrogen capsules (OSHCs) are currently limited, prompting our examination of the beneficial effects of OSHCs. Subsequently, we conducted a clinical study to assess the impact of OSHCs supplementation on individuals with chronic inflammation. Materials and methods: Initially, we evaluated the oxidative reduction potential (ORP) properties of the OSHCs solution by comparing it to hydrogen-rich water (HRW) and calcium hydride (CaH2) treated water. In our outpatient department, stable patients with chronic illnesses who were treated with varying doses of OSHCs were randomized into low-, medium-, and high-dose groups for 4 weeks. Primary outcomes included changes in the serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) concentrations after four weeks of OSHCs consumption. Secondary outcomes included changes in the Brief Fatigue Inventory-Taiwan (BFI-T) fatigue scale, Control Status Scale for Diabetes (CSSD70) scores, and Disease Activity Score 28 (DAS28). Results: Compared to HRW and CaH2, OSHCs demonstrated a prolonged reduction in ORP for 60 minutes in vitro and enabled a regulated release of hydrogen over 24 hours. A total of 30 participants, with 10 in each dosage (low/medium/high) group, completed the study. The average ESR120 significantly decreased from the first week to the fourth week, with a noticeable dose effect (low-dose group, p = 0.494; high-dose group, p = 0.016). Overall, the average CRP concentration showed a distinct decreasing trend after four weeks of OSHCs administration (w0 vs. w4, p = 0.077). The average DAS28 score demonstrated a significant decrease following OSHCs treatment. Furthermore, there were improvements in the BFI-T and CSSD70 scores. Conclusion: OSHCs supplementation may exert anti-inflammatory and antioxidant effects on individuals with chronic inflammation. However, further clinical studies could be investigated to explore the potential therapeutic effects of OSHCs.

Blocking the CTLA-4 and PD-1 pathways during pulmonary paracoccidioidomycosis improves immunity, reduces disease severity, and increases the survival of infected mice.

Immune checkpoint pathways, i.e., coinhibitory pathways expressed as feedback following immune activation, are crucial for controlling an excessive immune response. Cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1) are the central classical checkpoint inhibitory (CPI) molecules used for the control of neoplasms and some infectious diseases, including some fungal infections. As the immunosuppression of severe paracoccidioidomycosis (PCM), a chronic granulomatous fungal disease, was shown to be associated with the expression of coinhibitory molecules, we hypothesized that the inhibition of CTLA-4 and PD-1 could have a beneficial effect on pulmonary PCM. To this end, C57BL/6 mice were infected with Paracoccidioides brasiliensis yeasts and treated with monoclonal antibodies (mAbs) α-CTLA-4, α-PD-1, control IgG, or PBS. We verified that blockade of CTLA-4 and PD-1 reduced the fungal load in the lungs and fungal dissemination to the liver and spleen and decreased the size of pulmonary lesions, resulting in increased survival of mice. Compared with PBS-treated infected mice, significantly increased levels of many pro- and anti-inflammatory cytokines were observed in the lungs of α-CTLA-4-treated mice, but a drastic reduction in the liver was observed following PD-1 blockade. In the lungs of α-CPI and IgG-treated mice, there were no changes in the frequency of inflammatory leukocytes, but a significant reduction in the total number of these cells was observed. Compared with PBS-treated controls, α-CPI- and IgG-treated mice exhibited reduced pulmonary infiltration of several myeloid cell subpopulations and decreased expression of costimulatory molecules. In addition, a decreased number of CD4+ and CD8+ T cells but sustained numbers of Th1, Th2, and Th17 T cells were detected. An expressive reduction in several Treg subpopulations and their maturation and suppressive molecules, in addition to reduced numbers of Treg, TCD4+, and TCD8+ cells expressing costimulatory and coinhibitory molecules of immunity, were also detected. The novel cellular and humoral profiles established in the lungs of α-CTLA-4 and α-PD-1-treated mice but not in control IgG-treated mice were more efficient at controlling fungal growth and dissemination without causing increased tissue pathology due to excessive inflammation. This is the first study demonstrating the efficacy of CPI blockade in the treatment of pulmonary PCM, and further studies combining the use of immunotherapy with antifungal drugs are encouraged.

Environmental Enrichment Cage for Laboratory Mice: A Downloadable Alternative.

Environmentally enriched housing (EE) provides a stimulating and species-typical environment that enhances brain plasticity and cognition, while reducing disease severity in laboratory animals. However, standardizing EE protocols has been challenging due to issues such as variability, high pricing, or limited laboratory space. To address these challenges, we present a replicable and cost-efficient cage protocol that is accessible to researchers with limited resources and space constraints. The protocol is designed to provide a stimulating and species-typical environment for the animals. It incorporates elements such as social interaction, physical exercise, cognitive stimulation, manipulable objects, environmental variability, and sensory stimulation. As evidenced in our previous studies using our protocol, users can expect to observe similar neuroplastic and health-wise benefits that accompany EE experimental paradigms. These included straightforward step-by-step guide, which allows for construction of functional EE cages in under 8 hr. Basic knowledge of 3D printing and laser cutting is required, but no advanced skills are necessary. The protocol enables researchers to create stimulating and replicable environments that promote animal welfare, enhance brain plasticity, and yield valuable experimental results for low cost. © 2024 Wiley Periodicals LLC. Basic Protocol: An effective and cost-efficient environmental enrichment cage designed to encourage standardization amongst laboratory protocols.

A chlorogenic acid-conjugated nanomicelle attenuates disease severity in experimental arthritis.

Rheumatoid arthritis (RA) is a systemic immune disorder marked by synovitis, bone damage, and cartilage erosion, leading to increased socio-economic burdens and reduced quality of life. Despite its unknown cause, advancements in understanding its pathophysiology have facilitated novel therapeutic approaches. Current treatments, including disease-modifying anti-rheumatic drugs (DMARDs) and biologics, often result in low efficacy and unnecessary side effects. To address the limitations of these drugs, carrier-based drug delivery systems, such as nanomicelles, have emerged as a promising solution. In this study, nanomicelles were synthesised utilizing PLGA (poly(lactic-co-glycolic acid)) as a backbone; this backbone is conjugated with chlorogenic acid (CGA), which is known for suppressing inflammation, and incorporates methotrexate (MTX), a model drug that is established for RA treatment. The nanomicelles were extensively characterized in terms of size, charge, drug loading, and drug-release behaviour. The in vivo assessment of MTX-PLGA-b-CGA nanomicelles in a collagen-induced arthritis model demonstrated a remarkable reduction in joint swelling, cartilage erosion, and disease severity. Furthermore, histological findings confirmed cartilage integrity and reduced expression of key pro-inflammatory markers, including receptor activator of nuclear factor kappa beta ligand (RANKL) and tumor necrosis factor (TNF-α). The approach based on the MTX-PLGA-b-CGA nanomicelles presents a biocompatible and potentially effective therapeutic strategy for management of the severity and progression of RA, providing a hopeful alternative for RA treatment.

Turf-Type Tall Fescue Brown Patch Resistance as Influenced by Morphological Characteristics

Brown patch (caused by multiple species of Rhizoctonia and Rhizoctonia-like fungi) is one of the major turfgrass diseases impacting turf-type tall fescue [ Schedonorus arundinaceus (Schreb.) Dumort., nom. cons.] lawns during the summer season. Selection of tall fescue cultivars with brown patch resistance is an important cultural management practice to reduce disease severity and limit reliance on fungicides. A greenhouse experiment was conducted to quantify differences in brown patch resistance among 15 tall fescue cultivars and correlate disease resistance with plant morphological characteristics. Prior to R. solani inoculation, leaf blade width, sheath width and length, endophyte stem infection, and relative growth rate were measured. Disease resistance was determined as a percentage of the canopy blighted as measured using digital image techniques. Brown patch severity after 21 days in Experiments 1 and 2 ranged from 36.7 to 72.7% and 20.8 to 41.8%, respectively, among all cultivars. There were significant differences among morphological characteristics for the cultivars. Increased brown patch was associated with cultivars with a faster growth rate, wider sheath width, and decreased sheath length. This study demonstrates the importance of cultivar selection for reducing brown patch severity in tall fescue lawns. Additionally, tall fescue cultivars with higher shoot density and narrow leaves should not be avoided due to concerns of increased brown patch susceptibility.