Reduced Disease Severity Research Articles

Environmental enrichment affects immunity and reduces disease severity in pigs after co-infection, with stronger effects when applied from birth than from weaning

We investigated whether environmental enrichment applied at different life stages of pigs affects the susceptibility to and severity of disease by studying immune cell functions around weaning and during nursery, the effects of infection in ex vivo models and in vivo using a co-infection model of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) followed by an Actinobacillus pleuropneumoniae infection. Pigs were either conventionally housed (CCH) or enriched housed throughout life, with enrichment consisting of extra space, rooting materials and co-mingling with another litter before weaning (EEH), or they were switched from conventional to enriched housing at weaning (CEH). Sixty days after birth, ten pigs per treatment were infected with PRRSV followed by an A. pleuropneumoniae infection eight days later. Six other pigs per treatment were euthanized before their pen mates were exposed to the co-infection. From these piglets, bronchial-alveolar fluid was collected, and precision cut lung slices were taken to test the effect of the treatments in an in vitro infection model. At six days after weaning EEH pigs had higher whole blood cell counts and higher concentrations of IL1ß and TNFα than CCH and CEH pigs. In the ex vivo precision cut lung slice model no differences in cytokine response in lung tissue after infection with swine influenza or A. pleuropneumoniae were observed between treatments. After experimental co-infection the proportion of EEH pigs with lung lesions (3/10) tended to be lower than in CCH (8/10), with CEH (6/10) being in between. In conclusion, enriched housing from birth reduced disease severity to co-infection with PRRSV and A. pleuropneumoniae. Enrichment applied after weaning also seemed to decrease the pathological lung deviations to the co-infection as compared to barren housed pigs, but to a much lower extent.

Probiotic Supplements Benefit Psoriasis Therapy Rather Than Affecting Disease Risk: Evidence from NHANES Machine-Learning and Meta-Analysis Study.

This research aimed to evaluate the impact of probiotic supplementation on the severity of psoriasis symptoms and its association with the risk of developing the disease. We analyzed the association between probiotic usage and psoriasis among 21,942 participants from the 2009-2014 NHANES, employing advanced machine learning techniques for data analysis. A separate meta-analysis was conducted to assess the effects of probiotics on the severity, life quality, and some related inflammation factors. Dichotomous data were analyzed using odds ratios (ORs) corresponding to the 95% confidence interval (CI). Analysis of NHANES data did not reveal a statistically significant association between probiotic intake and the risk of psoriasis. However, the meta-analysis indicated that probiotic supplementation significantly lowers Psoriasis Area and Severity Index (PASI) scores both for change in PASI score and post-data change, and enhances PASI 75 (OR = 4.80, 95% CI = 2.92-7.89) and clearance responses (OR = 3.14, 95% CI = 1.99-4.96), as well as reduced levels of inflammatory markers. While the improvement of life quality was only observed in the post-treatment data. While probiotic supplements do not appear to reduce the risk of psoriasis, they have a significant positive effect on reducing disease severity. Registered on PROSPERO: Registration number CRD42023484417.

Magnesium Supplementation Modifies Arthritis Synovial and Splenic Transcriptomic Signatures Including Ferroptosis and Cell Senescence Biological Pathways

Background: Rheumatoid arthritis (RA) is a common systemic autoimmune inflammatory disease that can cause joint damage. We have recently reported that oral magnesium supplementation significantly reduces disease severity and joint damage in models of RA. Methods: In the present study, we analyzed the transcriptome of spleens and synovial tissues obtained from mice with KRN serum-induced arthritis (KSIA) consuming either a high Mg supplemented diet (Mg2800; n = 7) or a normal diet (Mg500; n = 7). Tissues were collected at the end of a 15-day KSIA experiment. RNA was extracted and used for sequencing and analyses. Results: There was an enrichment of differentially expressed genes (DEGs) belonging to Reactome and Gene Ontology (GO) pathways implicated in RA pathogenesis such as RHO GTPases, the RUNX1 pathway, oxidative stress-induced senescence, and the senescence-associated secretory phenotype. Actc1 and Nr4a3 were among the genes with the highest expression, while Krt79 and Ffar2 were among the genes with the lowest expression in synovial tissues of the Mg2800 group compared with the Mg500 group. Spleens had an enrichment for the metabolism of folate and pterines and the HSP90 chaperone cycle for the steroid hormone receptor. Conclusions: We describe the tissue transcriptomic consequences of arthritis-protecting Mg supplementation in KSIA mice. These results show that oral Mg supplementation may interfere with the response to oxidative stress and senescence and other processes known to participate in RA pathogenesis. We provide new evidence supporting the disease-suppressing effect of increased Mg intake in arthritis and its potential to become a new addition to the therapeutic options for RA and other autoimmune and inflammatory diseases.

The effect of integrated medical care on the daily life of patients with coronary heart disease.

This study aims to explore the impact of comprehensive medical care on the daily life of patients with coronary heart disease (CHD) and to evaluate its effectiveness in improving quality of life, alleviating symptoms, and reducing the risk of cardiac events. A new comprehensive medical care scheme combining Traditional Chinese Medicine nursing differentiation, collaborative nursing interventions, and specialized community care was proposed. Patients with CHD were recruited as study subjects. Data were collected via questionnaires and interviews to assess the real-world impact of comprehensive medical care on the daily lives of patients. Significant improvements were observed in the observation group across multiple metrics. Baseline characteristics between the 2 groups showed no significant differences initially. Post-intervention, the observation group demonstrated significant improvements in left ventricular ejection fraction and self-assessment of stress (SAS), with left ventricular ejection fraction values increasing to 53.8% compared to 47.2% in the control group, and SAS scores decreasing markedly (P < .05). Additionally, the Disease Severity Index (DSI) indicated a significant reduction in disease severity in the observation group compared to a nonsignificant change in the control group (P > .05). Quality of life, assessed via MacNew and activities of daily living scores, also improved significantly post-intervention in the observation group compared to the control group (P < .05). Furthermore, the observation group exhibited a lower incidence of myocardial ischemia, myocardial infarction, and thrombosis over a 3-year period, with patient satisfaction significantly higher in the observation group (90% reported perfect contentment) compared to the control group (70% reported perfect contentment; P < .001). These findings suggest that the comprehensive nursing care approach significantly enhances cardiac function, quality of life, and patient satisfaction in CHD patients.

Trends in the epidemiology of pertussis in Malaga, Spain (2017-2024)

Description of the epidemiological evolution of pertussis in the province of Malaga, Spain (2017 - 2024), disease severity, and vaccination coverage. A cross-sectional study was conducted using reported cases from the Andalusian Notifiable Diseases Network (RedAlerta). The incidence of pertussis was calculated per 100,000 inhabitants for each health district, quarter, and year. Additionally, the relationship between severe cases (hospitalizations) and vaccination status was analyzed. A total of 181 pertussis cases were identified. Of these, 56.4% were reported during the pre-pandemic period (2017-2019), while 9.95% occurred between 2020 and 2023. An increase in cases was observed in the first quarter of 2024 (n = 61; 33.7% of the total cases), compared to previous years (1 to 46 cases). The 0 to 20-year group accounted for 71.3% of cases, of which 57.4% had received at least partial vaccination prior to contracting pertussis. Severe disease requiring hospitalization occurred in 25.6% of cases, with a higher frequently among unvaccinated individuals (70% vs 18.3%; p < 0.001). Among hospitalized cases, 42.4% had not received any prior doses of the vaccine. Additionally, 47.1% of the 17 pertussis cases in children aged =1 year had not received any vaccination and had no history of maternal vaccination during pregnancy. An increase in reported pertussis cases is observed in early 2024 in Malaga, but hospitalization rates among confirmed cases remained stable. A significant association is found between prior vaccination against pertussis and reduced disease severity (hospitalization) in the 0 to 20-year-old age group.

STING deficiency ameliorates mouse models of lupus and atherosclerosis.

Systemic lupus erythematosus (SLE) is a systemic autoimmune syndrome characterized by autoreactive responses to nucleic acids, dysregulation of the type I Interferon (IFN-I) pathway, and accelerated atherosclerosis. The stimulator of interferon genes (STING), a cytosolic DNA-sensor, has pathogenic implications in various inflammatory diseases. However, its specific role in SLE pathogenesis, particularly in tissue damage, remains unclear. This study aimed to elucidate the role of STING in murine models of TLR7-driven lupus and atherosclerosis. A TLR7-driven lupus model was induced using imiquimod (IMQ) in wild type (WT) and STING knockout (Sting1-/-) mice on a B6 background. Mice were assessed for organ involvement, serum autoantibodies, and innate and adaptive immune responses. Additionally, Sting1-/- mice were backcrossed to Apolipoprotein E knockout (Apoe-/-) mice, and both Apoe-/- and Apoe-/-Sting1-/- mice were fed a high-fat chow (HFC) diet to induce atherosclerosis. Phenotypic assessments were conducted. Compared to IMQ-treated WT mice, Sting1-/- mice exhibited reduced disease severity in the lupus-like phenotype, characterized by decreased splenomegaly, lower renal immune complex deposition and renal damage, diminished expansion of myeloid cells, and reduced activation of T and B lymphocytes. IMQ-induced DNA release associated with IFN-β production and subsequent IFN-induced responses were attenuated in Sting1-/- mice. DNase I treatment mitigated IMQ-induced pro-inflammatory responses in WT mice but had no effect in Sting1-/- mice. Furthermore, STING deficiency conferred protection against vascular damage and reduced atherosclerosis burden, accompanied by decreased IFN-I production. Human monocyte-derived macrophages treated with IFN-I significantly internalized more acetylated LDL when compared to untreated cells, while an association between oxidized nucleic acids and disease activity and vascular damage was found in human SLE. These findings highlight a pathogenic role of STING and downstream IFN responses in TLR7-driven autoimmunity, vascular damage and atherosclerosis, supporting a therapeutic potential for STING inhibition in SLE treatment. Further research is warranted to elucidate the mechanisms underlying STING's involvement in these processes and to explore the feasibility of targeting STING as a therapeutic strategy in SLE and related autoimmune disorders.

Do plant resistance inducers reduce Plasmopara viticola infection on grapevine berry clusters at different growth stages?

Plant resistance inducers (PRIs) are promising alternatives to chemical fungicides. Their effectiveness against grapevine downy mildew (DM) has been demonstrated for leaves, yet research on berry clusters is limited. We investigated the efficacy of six PRIs on clusters of cv. Barbera and Merlot from the end of flowering (growth stage GS 69) to fruit setting (GS 71) and inoculated with a sporangial suspension of Plasmopara viticola (Pv) at 1, 3, 6, 12, and 19 days after treatment (DAT). Cerevisane (CER) and Pythium oligandrum (PYT) did not reduce DM severity compared to the nontreated control (NT). Fosetyl-Al (FOS) reduced DM severity at 1-6 DAT, with >50% reduction compared to NT. Laminarin (LAM) was effective at 6, 12, and 19 DAT, with 42.7%-to 50.0% efficacy compared to NT, while cos-oga (COS) and K-phosphonate (PHO) were effective at 12 and 19 DAT (60% efficacy). PRIs were also applied to clusters at initial flowering (GS 60), GS 69-71, and pea-sized berries (GS 75), which were then inoculated with Pv at 7 DAT. At GS 60, treatments with LAM and PHO reduced disease severity compared to NT by 77.5% and 83.6%, respectively. At GS 69-71, LAM, PHO, and FOS caused 54.7%-75.7% disease reduction. At GS 75, all PRIs exhibited a disease reduction > 75%. The efficacy of PRIs increased as the cluster developmental stage advanced, indicating an interaction with the ontogenic resistance of berries. Our results are relevant for the practical use of PRIs in protecting grapevine clusters from DM.

Validation study for assessing COVID-19 pneumonia treatments

This study investigates the effectiveness of Azvudine and nirmatrelvir-ritonavir (Paxlovid) in treating COVID-19 pneumonia through an analysis of real-world clinical data. We retrospectively collected data from COVID-19 patients hospitalized at the Second Xiangya Hospital of Central South University between December 21, 2022, and January 18, 2023. Using kernel density estimation, box-and-whisker plots, and Schoenfeld residual plots, we evaluated the transition of patients to negative status and assessed factors such as age, disease severity, and treatment effects. The findings revealed that both Azvudine and Paxlovid significantly reduced recovery times, with Azvudine showing notable benefits for patients aged 50–80. Our analysis indicated that these drugs improved lung CT values and reduced disease severity in moderate cases. The Cox model demonstrated robustness in predicting outcomes, and a nomogram was developed for individualized recovery probability assessment. These results provide important insights into optimizing COVID-19 treatment and the potential of predictive models in clinical decision-making.

A Narrative Review of the OX40-OX40L Pathway as a Potential Therapeutic Target in Atopic Dermatitis: Focus on Rocatinlimab and Amlitelimab.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease involving complex immune dysregulation, including the OX40-OX40L pathway. Rocatinlimab and amlitelimab, monoclonal antibodies targeting OX40 and OX40L, respectively, have shown promise in treating moderate-to-severe AD. Both therapies have demonstrated significant efficacy in reducing disease severity, with favorable safety profiles and no serious treatment-related adverse events. Both treatments outperformed placebo across key clinical endpoints, including skin clearance and symptom reduction, highlighting their potential as effective AD therapies. Although initial results are promising, further research is needed to evaluate the long-term effects, durability of response, and safety of these treatments. These findings support the therapeutic potential of targeting the OX40-OX40L pathway in AD, providing new options for patients with moderate-to-severe disease, with ongoing trials necessary to confirm their sustained benefits.

Boosting neuraminidase immunity in the presence of hemagglutinin with the next generation of influenza vaccines.

Neuraminidase (NA), the second most abundant surface glycoprotein on the influenza virus, plays a key role in viral replication and propagation. Despite growing evidence showing that NA-specific antibodies correlate with resistance to disease in humans, current licensed vaccines focus almost entirely on the hemagglutinin (HA) antigen. Here, we demonstrate that recombinant NA (rNA) protein is highly immunogenic in both naïve mice and ferrets, as well as in pre-immune ferrets, irrespective of the level of match with preexisting immunity. Ferrets vaccinated with rNA developed mild influenza disease symptoms upon challenge with human H3N2 influenza virus, and anti-NA antibody responses appeared correlated with reduction in disease severity. The addition of rNA to a quadrivalent HA-based vaccine induced robust NA-specific humoral immunity in ferrets, while retaining the ability to induce HA-specific immunity. These results demonstrate that the addition of rNA is a viable option to increase immunogenicity and potentially efficacy versus currently licensed influenza vaccines by means of boosting NA immunity.

Alleviating Continuous Cropping Obstacles in Celery Using Engineered Biochar: Insights into Chemical and Microbiological Aspects

In the pursuit of environmental sustainability and food security, biochar has emerged as a promising soil conditioner to mitigate continuous cropping obstacles (CCOs). This study explored the use of engineered biochar (WP400) with high adsorption capacity for phenolic acids in celery cultivation. Using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) for both target and suspect analyses, along with Biolog EcoPlate™ to track the functional diversity of soil bacteria, the study examined chemical and microbiological interactions at varying WP400 application rates. WP400 enhanced celery growth, reduced disease severity, and adsorbed p-coumaric acid (COU), a potential autotoxin. Additionally, other potential allelochemicals, predominantly fatty acid-related, were identified, suggesting a broader role for fatty acids in allelopathy. WP400 also influenced soil bacterial carbon utilization and altered microbial communities. However, higher WP400 doses (0.8% w/w) may not be beneficial for celery growth and reduced bacterial metabolic potential, indicating limitations to its effectiveness. Proper application of WP400 provides a sustainable solution for alleviating continuous cropping issues, promoting both environmental sustainability and agricultural development.

Antibody dynamics for heterologous boosters with aerosolized Ad5-nCoV following inactivated COVID-19 vaccines

ABSTRACT The COVID-19 pandemic has underscored vaccination as a crucial strategy for reducing disease severity and preventing hospitalizations. Heterologous boosters using aerosolized Ad5-nCoV following two doses of inactivated vaccine have demonstrated superior antibody responses. However, the comprehensive dynamics of this antibody boost and the optimal timing for heterologous boosters are still not fully understood. In this study, we investigated the dynamics of neutralizing antibody (nAb) responses in recipients of heterologous booster vaccinations with aerosolized Ad5-nCoV following either two (I-I-A) or three (I-I-I-A) doses of COVID-19 inactivated vaccines. The findings indicate that a booster dose of aerosolized Ad5-nCoV vaccine induced robust and durable nAb responses comparable to those elicited in BA.5 breakthrough infections with similar doses of inactivated vaccine. Notably, group I-I-A showed higher peak nAb titers against the WT strain, BA.5, and XBB.1 variants compared to group I-I-I-A, inversely correlating with the prior nAb levels. This suggesting the possible efficacy of the heterologous aerosolized Ad5-nCoV booster and indicates that pre-boost antibody levels may be related to the outcomes of booster vaccination.

Harnessing Bacillus subtilis Spore Surface Display (BSSD) Technology for Mucosal Vaccines and Drug Delivery: Innovations in Respiratory Virus Immunization

Respiratory viruses present significant global health challenges due to their rapid evolution, efficient transmission, and zoonotic potential. These viruses primarily spread through aerosols and droplets, infecting respiratory epithelial cells and causing diseases of varying severity. While traditional intramuscular vaccines are effective in reducing severe illness and mortality, they often fail to induce sufficient mucosal immunity, thereby limiting their capacity to prevent viral transmission. Mucosal vaccines, which specifically target the respiratory tract’s mucosal surfaces, enhance the production of secretory IgA (sIgA) antibodies, neutralize pathogens, and promote the activation of tissue-resident memory B cells (BrMs) and local T cell responses, leading to more effective pathogen clearance and reduced disease severity. Bacillus subtilis spore surface display (BSSD) technology is emerging as a promising platform for the development of mucosal vaccines. By harnessing the stability and robustness of Bacillus subtilis spores to present antigens on their surface, BSSD technology offers several advantages, including enhanced stability, cost-effectiveness, and the ability to induce strong local immune responses. Furthermore, the application of BSSD technology in drug delivery systems opens new avenues for improving patient compliance and therapeutic efficacy in treating respiratory infections by directly targeting mucosal sites. This review examines the potential of BSSD technology in advancing mucosal vaccine development and explores its applications as a versatile drug delivery platform for combating respiratory viral infections.

Probiotics' supplementation alleviates disease severity and improves postural balance by repairing intestinal leak in patients suffering from osteoarthritis: a double-blinded clinical trial.

Increased intestinal leakiness and associated systemic inflammation are potential contributors to osteoarthritis (OA) and postural imbalance in the geriatric population. To date, no successful treatment to correct postural imbalance in OA is known. We aimed to explore the effects of a multistrain probiotic upon postural imbalance in OA-affected patients. In this randomised, double-blind trial with a placebo group, 147 patients suffering from knee OA (age span = 64-75 years) were divided into placebo (n 75) and probiotics (n 72) study groups. Vivomix 112 billion, multistrain probiotic was given once a day for 12 weeks. The outcomes of study variables were determined first at baseline and later after 12 weeks of intervention. These were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), knee flexion range of motion (ROM), pain intensity by visual analogue scale, handgrip strength (HGS), gait speed and balance control assessed in standing, semi-tandem and tandem stances. We determined plasma zonulin to determine intestinal leak along with c-reactive protein and 8-isoprostanes levels. A total of 136 OA patients taking placebo (n 71) and probiotics (n 65) were analysed. The probiotics group exhibited a reduction in pain intensity, disease severity and WOMAC scores along with improvement in balance scores, HGS and walking speed (P < 0·05 for all), no change in ROM, resting pain and 8-isoprostanes levels. The correlation analysis revealed a robust association of balance scores with plasma markers of intestinal leakiness and inflammation in probiotics but not in the placebo group. Probiotics reduce postural imbalance in OA patients partly due to a reduction in intestinal leakiness.

The Influence of a Plant-Based Diet on Skin Health: Inflammatory Skin Diseases, Skin Healing, and Plant-Based Sources of Micro- and Macro-Nutrients.

Dietary patterns have been shown to worsen or alleviate several dermatological diseases. A well-balanced, plant-based diet is known to have anti-inflammatory, probiotic, and antioxidant properties, along with weight loss-promoting effects. Moreover, a plant-based diet has a low glycemic load, improving metabolic disease. Due to these qualities, plant-based diets may have beneficial effects on inflammatory skin conditions. In this review, we aim to discuss the possible mechanisms by which a plant-based diet reduces disease severity in psoriasis, acne, hidradenitis suppurativa, and atopic dermatitis. We also aim to clarify how a plant-based diet may influence skin healing and identify sources of vitamins, nutrients, fatty acids, and protein in a well-balanced, plant-based diet. We performed a literature search on PubMed/MEDLINE databases with the following keywords: "plant-based" OR "vegan" OR "vegetarian" OR "meat" OR "diet" AND "psoriasis" OR "hidradenitis suppurativa" OR "acne" OR "atopic dermatitis" OR "skin healing" OR "dermatology". Our findings demonstrate that plant-based foods may improve inflammatory skin diseases by supporting the gut microbiome, exerting anti-inflammatory effects, providing barrier support, and improving glycemic control. With the proper education, there is an abundance of plant-based food sources or supplements that contain riboflavin, vitamin B12, vitamin A, omega-3 fatty acids, and protein, thereby ameliorating the risk of nutritional deficiencies. Thus, a plant-based diet may have therapeutic potential in dermatology. In spite of the evidence available, there is a paucity of clinical studies focusing specifically on plant-based diets and dermatologic conditions and further investigation is warranted.

Reni-Cel, an Investigational AsCas12a Gene-Edited Cell Medicine, Led to Successful Engraftment, Increased Hemoglobin, and Reduced Transfusion Dependence in Patients with Transfusion-Dependent Beta-Thalassemia Treated in the Edithal Trial

Introduction: Transfusion-dependent β-thalassemia (TDT) is a genetic blood disorder caused by reduced or absent production of β-globin, which results in profound morbidity and reduced lifespan. Clinical evidence has shown that increased fetal hemoglobin (HbF, α2γ2) can lead to transfusion-independence, reduced disease severity, and improved quality of life (QoL). Renizgamglogene autogedtemcel (reni-cel) is an investigational gene-edited autologous hematopoietic stem cell medicine comprised of CD34+ cells edited at the distal CCAAT box (-118 to -113) of the promoter regions of the γ-globin genes (HBG1 and HBG2) with a highly specific and efficient, proprietary gene-editing nuclease, AsCas12a. These edits mimic naturally occurring variants of hereditary persistence of HbF in the HBG1 and HBG2 promoters and reactivate γ-globin expression, resulting in sustained and clinically meaningful production of HbF. In preclinical studies, editing CD34+ cells from patients with TDT at this genomic region led to improved erythropoiesis in vitro and erythroid progeny with increased total hemoglobin (Hb) production. The ongoing EdiThal trial (NCT05444894) is a Phase I/II, multicenter, open-label, single-arm study evaluating safety, tolerability, and efficacy of reni-cel in patients with TDT. Interim clinical data are reported and updated data will be presented. Methods: Eligible patients must be 18-35 years and have a diagnosis of TDT, defined as at least 100 mL/kg/year or 10 U/year of packed red blood cell (RBC) transfusions in the 2 years prior to informed consent. After plerixafor and filgrastim mobilization, autologous CD34+ hematopoietic stem and progenitor cells are collected by apheresis and edited at the HBG1 and HBG2 promoters. Patients then undergo myeloablative conditioning with pharmacokinetically adjusted busulfan and receive a single infusion of reni-cel (≥3 × 106 CD34+ cells/kg). Patients are monitored for engraftment, allelic editing levels, total Hb, HbF production, percentage of F-cells, transfusion requirement, and adverse events (AEs) for 24 months. Results: As of June 28, 2024, 7 patients with TDT had been dosed with reni-cel. The median (range) age of these patients was 19 (18-24) years, 57.1% were female, 42.9% had the β0/β0 or β0/β0-like genotype, and the majority (85.7%) were Asian. Patients were a median (range) of 10.5 (6.3-15.1) months post-reni-cel infusion, with 2 patients having &amp;gt;1 year follow-up. Neutrophil and platelet engraftment were achieved after a median (range) of 23.0 (16-30) and 38.0 (24-49) days (n=7), respectively. After reni-cel infusion, mean (standard deviation [SD]) total Hb levels remained above the transfusion-independence threshold of 9.0 g/dL, and increased to 12.5 (1.5) g/dL by Month 6 (n= 7). The mean (SD) HbF concentration increased early and was 11.3 (1.7) g/dL by Month 6 (n=7). The percentage of F-cells was 99.2% (0.8%) by Month 6 (n=5), indicating pancellular distribution of HbF. After receiving the last RBC transfusion at 0.7-2.2 months post-reni-cel infusion, all 7 patients have been transfusion independent for a range of 5.8-14.5 months. Patients showed sustained high levels of editing, with mean (SD) editing levels at Month 6 being 75.4% (5.3%) and 79.9% (9.1%) in peripheral blood nucleated cells (n=6) and bone marrow-derived CD34+ cells (n=4), respectively. The safety profile of reni-cel was consistent with myeloablative conditioning with busulfan. No serious AEs related to reni-cel were reported. Conclusions: Reni-cel treatment showed promising results for gene editing of the HBG1 and HBG2 promoters, with a rapid and sustained increase in total Hb well above the transfusion threshold and an increase in HbF levels with pancellular distribution. The data also demonstrate sustained high levels of editing and a favorable safety profile with successful engraftment. Additionally, patients have been transfusion-independent for up to 14.5 months. These findings, which include additional outcomes, build on clinical evidence to support the continued investigation of reni-cel in the EdiThal clinical trial.

Antifungal Activity of Citrus Essential Oil in Controlling Sour Rot in Tahiti Acid Lime Fruits.

Sour rot, caused by Geotrichum citri-aurantii, is a significant post-harvest disease in citrus, resulting in economic losses due to the lack of effective fungicides. This study investigates the antifungal activity of citrus essential oils in controlling sour rot in Tahiti acid lime fruits. Essential oils were extracted via hydrodistillation with chemical composition analyzed by CG-MS and tested in vitro and in vivo. In vitro assays evaluated mycelial growth inhibition at 2 to 32 µL mL-1 concentrations. In vivo trials involved preventive and curative treatments on artificially inoculated fruits stored at 25 °C ± 2, and the results showed that Pera IAC sweet orange oil, at 32 µL mL-1, reduced disease severity by 96% in curative treatments. In contrast, Late IAC 585 willowleaf mandarin oil demonstrated moderate inhibition (44%) at the highest concentration in vitro. The oils did not affect key fruit quality parameters such as juice yield and total soluble solids. These findings suggest that citrus essential oils could be natural alternatives to synthetic fungicides for post-harvest sour rot management, combining effectiveness with maintaining fruit quality.

Genome sequencing and functional analysis of potential Trichoderma species for controlling Pythium schmitthenneri-Induced root rot in olive trees

Root rot disease caused by Pythium schmitthenneri is a significant challenge in olive (Olea europaea L.) cultivation. Due to the limitations of chemical control, this study explores the potential of Trichoderma species as a sustainable alternative with an overview in the genetic properties involved in it. Eight Trichoderma isolates were obtained from olive roots and identified using rDNA internal transcribed spacer (ITS) sequences, revealing four species: T. harzianum, T. longibrachiatum, T. virens, and T. viride. Among these, T. harzianum T-BM6 and T. virens T-KH4, showed 81.4 and 78.77 % inhibition rates of pathogen growth, respectively, in vitro. Greenhouse trials demonstrated that these isolates reduced disease severity to 18.75 % for T-BM6 and 31.25 % for T-KH4. All isolates produced cellulase, with T-BM6 exhibiting high cellulolytic activity. Genomic analysis highlighted key genes related to the MAPK signaling pathway, sulfur metabolism, and inositol phosphate metabolism in T-BM6, and phenylalanine, tyrosine, and tryptophan metabolism in T-KH4. These results suggest that T. harzianum T-BM6 and T. virens T-KH4 are promising candidates for biological control, offering a sustainable alternative to chemical treatments for managing olive root rot.

Inflammatory biomarker analysis confirms reduced disease severity in heterozygous patients with familial Mediterranean fever

IntroductionFamilial Mediterranean fever (FMF) is a genetic disease leading to recurrent episodes of inflammation. Two pathogenic variants are required for classical disease, but the disease can occur in heterozygous patients....

Effect of Integrin Blockade on Experimental Spondyloarthritis.

Spondyloarthritis (SpA) describes a group of diseases characterized by chronic inflammation in the spine and peripheral joints. While pathogenesis is still unclear, proinflammatory gut-derived immune cells have been identified in the joints of SpA patients. We previously identified an enriched population of integrin-expressing cells in the joints of SpA patients. Entry of gut-derived cells into joints may be mediated by these integrins. In the current study, we used the SKG murine model of SpA to study the impact of integrin blockade. Mice were injected with antibodies against the integrin α4β7 or the β7 monomer twice a week. Treatment with antibodies against α4β7 reduced disease severity in curdlan-injected SKG mice, with disease scores being comparable between treatment initiation times. Targeting the β7 monomer led to reduced arthritis severity compared to targeting the α4β7 dimer. Treatment with antibodies against α4β7 or β7 decreased expression of these integrins in CD4+ T cells, with the frequency of αE+β7+ T cells in the spleen and lymph nodes correlating with disease severity. In summary, we showed that integrin blockade showed potential for ameliorating disease in a murine model of SpA, lending support for further studies testing integrin blockade in SpA.