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Plants (Basel, Switzerland) May 2024Enhancing the aerobic stability of whole-plant corn silage is essential for producing high-quality silage. Our research assessed the effect of inoculation with or and...
Enhancing the aerobic stability of whole-plant corn silage is essential for producing high-quality silage. Our research assessed the effect of inoculation with or and its modulation of the bacterial and fungal microbial community structure in an aerobic stage of whole-plant corn silage. Following treatment with a distilled sterile water control, , and (2 × 10 cfu/g), whole-plant corn was ensiled for 60 days. Samples were taken on days 0, 3, and 7 of aerobic exposure, and the results showed that inoculation with or improved the aerobic stability of silage when compared to the effect of the control ( < 0.05). Inoculation with attenuated the increase in pH value and the decrease in lactic acid in the aerobic stage ( < 0.05), reducing the filamentous fungal counts. On the other hand, inoculation with or increased the diversity of the fungal communities ( < 0.05), complicating the correlation between bacteria or fungi, reducing the relative abundance of and in bacterial communities, and inhibiting the tendency of to replace in fungal communities, thus delaying the aerobic spoilage process. Due to the prevention of the development of aerobic spoilage microorganisms, the silage injected with or exhibited improved aerobic stability.
PubMed: 38891280
DOI: 10.3390/plants13111471 -
Cells Jun 2024UVA exposure disturbs the metabolism of skin cells, often inducing oxidative stress and inflammation. Therefore, there is a need for bioactive compounds that limit such...
UVA exposure disturbs the metabolism of skin cells, often inducing oxidative stress and inflammation. Therefore, there is a need for bioactive compounds that limit such consequences without causing undesirable side effects. The aim of this study was to analyse in vitro the effects of the phytocannabinoids cannabigerol (CBG) and cannabidiol (CBD), which differ in terms of biological effects. Furthermore, the combined use of both compounds (CBG+CBD) has been analysed in order to increase their effectiveness in human skin fibroblasts and keratinocytes protection against UVA-induced alternation. The results obtained indicate that the effects of CBG and CBD on the redox balance might indeed be enhanced when both phytocannabinoids are applied concurrently. Those effects include a reduction in NOX activity, ROS levels, and a modification of thioredoxin-dependent antioxidant systems. The reduction in the UVA-induced lipid peroxidation and protein modification has been confirmed through lower levels of 4-HNE-protein adducts and protein carbonyl groups as well as through the recovery of collagen expression. Modification of antioxidant signalling (Nrf2/HO-1) through the administration of CBG+CBD has been proven to be associated with reduced proinflammatory signalling (NFκB/TNFα). Differential metabolic responses of keratinocytes and fibroblasts to the effects of the UVA and phytocannabinoids have indicated possible beneficial protective and regenerative effects of the phytocannabinoids, suggesting their possible application for the purpose of limiting the harmful impact of the UVA on skin cells.
Topics: Humans; Oxidation-Reduction; Skin; Ultraviolet Rays; Cannabinoids; Signal Transduction; Cannabidiol; Fibroblasts; Keratinocytes; Inflammation; Oxidative Stress; Antioxidants; Reactive Oxygen Species; NF-E2-Related Factor 2; Lipid Peroxidation
PubMed: 38891097
DOI: 10.3390/cells13110965 -
Cells May 2024Eukaryotic cells tether the nucleoskeleton to the cytoskeleton via a conserved molecular bridge, called the LINC complex. The core of the LINC complex comprises...
Eukaryotic cells tether the nucleoskeleton to the cytoskeleton via a conserved molecular bridge, called the LINC complex. The core of the LINC complex comprises SUN-domain and KASH-domain proteins that directly associate within the nuclear envelope lumen. Intra- and inter-chain disulphide bonds, along with KASH-domain protein interactions, both contribute to the tertiary and quaternary structure of vertebrate SUN-domain proteins. The significance of these bonds and the role of PDIs (protein disulphide isomerases) in LINC complex biology remains unclear. Reducing and non-reducing SDS-PAGE analyses revealed a prevalence of SUN2 homodimers in non-tumorigenic breast epithelia MCF10A cells, but not in the invasive triple-negative breast cancer MDA-MB-231 cell line. Furthermore, super-resolution microscopy revealed SUN2 staining alterations in MCF10A, but not in MDA-MB-231 nuclei, upon reducing agent exposure. While PDIA1 levels were similar in both cell lines, pharmacological inhibition of PDI activity in MDA-MB-231 cells led to SUN-domain protein down-regulation, as well as Nesprin-2 displacement from the nucleus. This inhibition also caused changes in perinuclear cytoskeletal architecture and lamin downregulation, and increased the invasiveness of PDI-inhibited MDA-MB-231 cells in space-restrictive in vitro environments, compared to untreated cells. These results emphasise the key roles of PDIs in regulating LINC complex biology, cellular architecture, biomechanics, and invasion.
Topics: Humans; Cell Line, Tumor; Neoplasm Invasiveness; Protein Disulfide-Isomerases; Female; Down-Regulation; Breast Neoplasms; Membrane Proteins; Nuclear Proteins; Nuclear Envelope; Triple Negative Breast Neoplasms; Intracellular Signaling Peptides and Proteins
PubMed: 38891038
DOI: 10.3390/cells13110906 -
Foods (Basel, Switzerland) May 2024Prickly ash peel oleoresin (PPO) is a highly concentrated oil of Prickly ash essential oil and has a stronger aroma. However, its low water solubility, high volatility,...
Prickly ash peel oleoresin (PPO) is a highly concentrated oil of Prickly ash essential oil and has a stronger aroma. However, its low water solubility, high volatility, difficulty in transport and storage, and decomposition by light, heat, and oxygen limit its wider application. To solve this problem, this study used freeze-drying or spray-drying, with soybean protein isolate (SPI) or gum Arabic (GA), combined with aqueous maltodextrin (MD) as the encapsulating agents to prepare four types of PPO microcapsules (POMs). Spray-dried microcapsules with GA as the encapsulating agent achieved a high encapsulation efficiency (EE) of 92.31 ± 0.31%, improved the thermal stability of the PPO, and had spherical morphology. (Headspace solid-phase microextraction/gas chromatography-mass spectrometry) HS-SPME/GC-MS detected 41 volatile compounds in PPO; of these, linalool, β-myrcene, sabinene, and D-limonene were identified as key flavor components. Principal component analysis (PCA) effectively distinguished the significant differences in flavor between PPO, spray-dried SPI/MD microcapsules (SS), and spray-dried GA/MD microcapsules (SG). During 15 days of air-exposure, the loss of flavor from SG (54.62 ± 0.54%) was significantly lower than PPO (79.45 ± 1.45%) and SS (57.55 ± 0.36%). During the air-exposure period, SG consistently had the highest antioxidant capacity, making it desirable for PPO packaging, and expanding its potential applications within the food industry.
PubMed: 38890954
DOI: 10.3390/foods13111726 -
BMC Plant Biology Jun 2024Tropospheric ozone is an air pollutant that causes negative effects on vegetation, leading to significant losses in crop productivity. It is generated by chemical...
BACKGROUND
Tropospheric ozone is an air pollutant that causes negative effects on vegetation, leading to significant losses in crop productivity. It is generated by chemical reactions in the presence of sunlight between primary pollutants resulting from human activity, such as nitrogen oxides and volatile organic compounds. Due to the constantly increasing emission of ozone precursors, together with the influence of a warming climate on ozone levels, crop losses may be aggravated in the future. Therefore, the search for solutions to mitigate these losses becomes a priority. Ozone-induced abiotic stress is mainly due to reactive oxygen species generated by the spontaneous decomposition of ozone once it reaches the apoplast. In this regard, compounds with antioxidant activity offer a viable option to alleviate ozone-induced damage. Using enzymatic technology, we have developed a process that enables the production of an extract with biostimulant properties from okara, an industrial soybean byproduct. The biostimulant, named as OEE (Okara Enzymatic Extract), is water-soluble and is enriched in bioactive compounds present in okara, such as isoflavones. Additionally, it contains a significant fraction of protein hydrolysates contributing to its functional effect. Given its antioxidant capacity, we aimed to investigate whether OEE could alleviate ozone-induced damage in plants. For that, pepper plants (Capsicum annuum) exposed to ozone were treated with a foliar application of OEE.
RESULTS
OEE mitigated ozone-induced damage, as evidenced by the net photosynthetic rate, electron transport rate, effective quantum yield of PSII, and delayed fluorescence. This protection was confirmed by the level of expression of genes associated with photosystem II. The beneficial effect was primarily due to its antioxidant activity, as evidenced by the lipid peroxidation rate measured through malondialdehyde content. Additionally, OEE triggered a mild oxidative response, indicated by increased activities of antioxidant enzymes in leaves (catalase, superoxide dismutase, and guaiacol peroxidase) and the oxidative stress index, providing further protection against ozone-induced stress.
CONCLUSIONS
The present results support that OEE protects plants from ozone exposure. Taking into consideration that the promotion of plant resistance against abiotic damage is an important goal of biostimulants, we assume that its use as a new biostimulant could be considered.
Topics: Ozone; Glycine max; Stress, Physiological; Antioxidants; Capsicum; Photosynthesis; Plant Extracts
PubMed: 38890606
DOI: 10.1186/s12870-024-05290-3 -
BMC Genomics Jun 2024Ancient northern East Asians (ANEA) from the Yellow River region, who pioneered millet cultivation, play a crucial role in understanding the origins of...
BACKGROUND
Ancient northern East Asians (ANEA) from the Yellow River region, who pioneered millet cultivation, play a crucial role in understanding the origins of ethnolinguistically diverse populations in modern China and the entire landscape of deep genetic structure and variation discovery in modern East Asians. However, the direct links between ANEA and geographically proximate modern populations, as well as the biological adaptive processes involved, remain poorly understood.
RESULTS
Here, we generated genome-wide SNP data for 264 individuals from geographically different Han populations in Shandong. An integrated genomic resource encompassing both modern and ancient East Asians was compiled to examine fine-scale population admixture scenarios and adaptive traits. The reconstruction of demographic history and hierarchical clustering patterns revealed that individuals from the Shandong Peninsula share a close genetic affinity with ANEA, indicating long-term genetic continuity and mobility in the lower Yellow River basin since the early Neolithic period. Biological adaptive signatures, including those related to immune and metabolic pathways, were identified through analyses of haplotype homozygosity and allele frequency spectra. These signatures are linked to complex traits such as height and body mass index, which may be associated with adaptations to cold environments, dietary practices, and pathogen exposure. Additionally, allele frequency trajectories over time and a haplotype network of two highly differentiated genes, ABCC11 and SLC10A1, were delineated. These genes, which are associated with axillary odor and bilirubin metabolism, respectively, illustrate how local adaptations can influence the diversification of traits in East Asians.
CONCLUSIONS
Our findings provide a comprehensive genomic dataset that elucidates the fine-scale genetic history and evolutionary trajectory of natural selection signals and disease susceptibility in Han Chinese populations. This study serves as a paradigm for integrating spatiotemporally diverse ancient genomes in the era of population genomic medicine.
Topics: Humans; China; Genetics, Population; Haplotypes; Polymorphism, Single Nucleotide; Genomics; Evolution, Molecular; Gene Frequency; Asian People; Genome, Human
PubMed: 38890579
DOI: 10.1186/s12864-024-10514-9 -
American Journal of Clinical Dermatology Jul 2024Abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is efficacious in moderate-to-severe atopic dermatitis with a manageable long-term safety profile. (Clinical Trial)
Clinical Trial
BACKGROUND
Abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is efficacious in moderate-to-severe atopic dermatitis with a manageable long-term safety profile.
OBJECTIVE
We aimed to provide updated integrated long-term safety results for abrocitinib from available data accrued up to a maximum of almost 4 years in patients with moderate-to-severe atopic dermatitis from the JADE clinical development program.
METHODS
Analysis included 3802 patients (exposure: 5213.9 patient-years) from the phase II monotherapy study (NCT02780167) and the phase III studies JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE TEEN (NCT03796676), JADE COMPARE (NCT03720470), JADE DARE (NCT04345367; 200 mg only), JADE REGIMEN (NCT03627767), and JADE EXTEND (NCT03422822; data cutoff 25 September, 2021). Data from patients receiving one or more doses of abrocitinib 200 mg or 100 mg were pooled in a consistent-dose cohort (patients were allocated to receive the same abrocitinib dose throughout exposure in the qualifying parent study and/or long-term study) or a variable-dose cohort (patients received open-label abrocitinib 200 mg; responders were randomized to abrocitinib 200 mg, 100 mg, or placebo, and could then receive abrocitinib 200 mg plus topical corticosteroids as rescue therapy). Incidence rates of adverse events of special interest were assessed. Cox regression analysis of risk factors for herpes zoster and serious infections was performed.
RESULTS
Overall, this safety analysis of long-term data up to a maximum of ~ 4 years of abrocitinib exposure does not indicate any changes from the previously reported risk profile. The most frequent serious infections (per Medical Dictionary for Regulatory Activities preferred term) with consistent-dose abrocitinib 200 mg and 100 mg were herpes zoster (0.5% and 0.2%), pneumonia (0.2% with either dose), and herpes simplex (0.1% with either dose). Risk factors for herpes zoster were a history of herpes zoster, abrocitinib 200-mg dose, age ≥ 65 years, absolute lymphocyte count < 1 × 10/mm before the event, and residing in Asia. For serious infections, > 100 kg body weight was a risk factor. Incidence rate/100 patient-years (95% confidence interval) with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in older (aged ≥ 65 years) patients versus younger (aged 18 to < 65 years) patients for serious adverse events (17.6 [11.7‒25.4] vs 6.7 [5.8‒7.8]), malignancy excluding non-melanoma skin cancer (2.4 [0.6‒6.0] vs 0.1 [0.0‒0.4]), non-melanoma skin cancer (2.4 [0.6‒6.1] vs 0.2 [0.1‒0.4]), lymphopenia (3.5 [1.3‒7.6] vs 0.1 [0.0‒0.3]), and venous thromboembolism (1.7 [0.4‒5.1] vs 0.1 [0.0‒0.3]). Incident rate/100 patient-years (95% confidence interval) of non-melanoma skin cancer with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in current/former smokers (0.9 [0.4‒1.6]) vs never-smokers (0.0 [0.0‒0.1]).
CONCLUSIONS
This safety update showed a consistent profile for abrocitinib with no new safety signals and continues to support that abrocitinib has a manageable long-term safety profile in patients with moderate-to-severe atopic dermatitis. Risk of specific adverse events was higher in certain patient populations, especially those aged ≥ 65 years. [Video abstract available.] CLINICAL TRIAL REGISTRATION: NCT02780167; study start date: April, 2016; primary completion date: March, 2017; study completion date: April, 2017. NCT03349060; study start date: 7 December, 2017; study completion date: 26 March, 2019. NCT03575871; study start date: 29 June, 2018; study completion date: 13 August, 2019. NCT03720470; study start date: 29 October, 2018; primary completion date: 27 December, 2019; study completion date: 6 March, 2020. NCT03796676; study start date: 18 February, 2019; study completion date: 8 April, 2020. NCT03627767; study start date: 11 June, 2018; primary completion date: 2 September, 2020; study completion date: 7 October, 2020. NCT04345367; study start date: 11 June, 2020; primary completion date: 16 December, 2020; study completion date: 13 July, 2021. NCT03422822; study start date: 8 March, 2018; study completion date: ongoing (estimated completion date: 31 January, 2026).
Topics: Adolescent; Adult; Aged; Female; Humans; Male; Middle Aged; Young Adult; Administration, Oral; Boron Compounds; Dermatitis, Atopic; Herpes Zoster; Janus Kinase Inhibitors; Pyrimidines; Severity of Illness Index; Sulfonamides; Treatment Outcome
PubMed: 38888681
DOI: 10.1007/s40257-024-00869-w -
Translational Vision Science &... Jun 2024Recombinant human nerve growth factor (rhNGF; cenegermin-bkbj, OXERVATE) is the first and only U.S. Food and Drug Administration-approved treatment for moderate to...
PURPOSE
Recombinant human nerve growth factor (rhNGF; cenegermin-bkbj, OXERVATE) is the first and only U.S. Food and Drug Administration-approved treatment for moderate to severe neurotrophic keratopathy. The aim of this study was to determine the feasibility of incorporating a version of rhNGF in a mucoadhesive hydrogel capable of sustained drug release to the ocular surface.
METHODS
Hydrogels loaded with rhNGF were synthesized by conjugating chitosan with azidobenzoic acid (Az-Ch), adding rhNGF, and exposing the solution to ultraviolet (UV) radiation to induce photocrosslinking. Az-Ch hydrogels were evaluated for physical properties and rhNGF release profiles. Cytocompatbility of Az-Ch was assessed using immortalized human corneal limbal epithelial (HCLE) cells. TF1 erythroleukemic cell proliferation and HCLE cell proliferation and migration were used to assess the bioactivity of rhNGF released from Az-Ch hydrogels.
RESULTS
Az-Ch formed hydrogels in <10 seconds of UV exposure and demonstrated high optical transparency (75-85 T%). Az-Ch hydrogels exhibited good cytocompatibility with no demonstratable effect on HCLE cell morphology or viability. rhNGF was released gradually over 24 hours from Az-Ch hydrogels and retained its ability to induce TF1 cell proliferation. No significant difference was observed between rhNGF released from Az-Ch and freshly prepared rhNGF solutions on HCLE cell proliferation or percent wound closure after 12 hours; however, both were significantly better than control (P < 0.01).
CONCLUSIONS
rhNGF-loaded Az-Ch hydrogels exhibited favorable physical, optical, and drug-release properties, as well as retained drug bioactivity. This drug delivery system has the potential to be further developed for in vivo and translational clinical applications.
TRANSLATIONAL RELEVANCE
Az-Ch hydrogels may be used to enhance rhNGF therapy in patients with NK.
Topics: Nerve Growth Factor; Humans; Chitosan; Hydrogels; Cell Proliferation; Cell Movement; Ultraviolet Rays; Cross-Linking Reagents; Limbus Corneae; Recombinant Proteins; Drug Delivery Systems
PubMed: 38888287
DOI: 10.1167/tvst.13.6.12 -
Tobacco Induced Diseases 2024Cigarette package inserts that describe quitting benefits and tips may promote cessation; however, research is needed to understand better their effects, including...
INTRODUCTION
Cigarette package inserts that describe quitting benefits and tips may promote cessation; however, research is needed to understand better their effects, including potentially enhancing the effects of pictorial health warning labels (PHWLs).
METHODS
A randomized trial with a 2×2 factorial design was conducted with adult smokers (n=356) assigned to either small text-only health warning labels (HWLs; control); inserts with cessation messages, and the small text-only HWLs (inserts-only); large PHWLs (PHWLs-only); both inserts and PHWLs (inserts + PHWLs). Participants received a 14-day supply of their preferred cigarettes with packs labeled to reflect their group. Upon finishing the trial, participants reported their past 14-day frequency of noticing, reading, thinking about smoking harms and cessation benefits, talking about labels, and forgoing cigarettes because of the labels. Ordered logistic models regressed these outcomes on labeling groups, and mediation analyses assessed whether attention (i.e. noticing, reading) to labels mediated effects of labeling exposure on other outcomes (i.e. thinking about harms/benefits, talking, forgoing).
RESULTS
The inserts + PHWLs group reported higher frequencies than the control group for all outcomes. Compared to the control group, both the inserts-only and PHWLs-only groups reported higher frequency of noticing (AOR=3.53 and 2.46, respectively) and reading labels (AOR=2.89 and 1.71), thinking about smoking risks because of the labels (AOR=1.93 and 1.82), and talking about labels (AOR=2.30 and 2.70). Participants in the inserts-only group also reported more frequent thinking about quitting benefits (AOR=1.98). Attention mediated all labeling effects except for the contrast between PHWLs only and control.
CONCLUSIONS
Compared to text-only HWLS, cigarette labeling that involves inserts, PHWLs, or both appears more effective at drawing attention to warnings, which mediated the effects on cessation-related psychosocial and behavioral outcomes.
PubMed: 38887598
DOI: 10.18332/tid/189198 -
Frontiers in Immunology 2024The rate and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with solid cancer tumors actively treated with immune... (Meta-Analysis)
Meta-Analysis
UNLABELLED
The rate and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with solid cancer tumors actively treated with immune checkpoint inhibitors (ICIs) have not been fully determined. The goal of this meta-analysis was to explore this issue, which can be helpful to clinicians in their decision-making concerning patient treatment. We conducted a thorough search for relevant cohort studies in the databases PubMed, Embase, Cochrane Library, and Web of Science. Mortality and infection rate were the primary endpoints, and the incidence of severe or critical disease was the secondary result. A total of 6,267 cases (individual patients) were represented in 15 studies. Prior exposure to ICIs was not correlated with an elevated risk of SARS-CoV-2 infection (relative risk (RR) 1.04, 95% CI 0.57-1.88, z = 0.12, = 0.905) or mortality (RR 1.22, 95% CI 0.99-1.50, z = 1.90, = 0.057). However, the results of the meta-analysis revealed that taking ICIs before SARS-CoV-2 diagnosis increased the chance of developing severe or critical disease (RR 1.51, 95% CI 1.09-2.10, z = 2.46, = 0.014). No significant inter-study heterogeneity was observed. The infection and mortality rates of SARS-CoV-2 in patients with solid tumors who previously received ICIs or other antitumor therapies did not differ significantly. However, secondary outcomes showed that ICIs treatment before the diagnosis of SARS-CoV-2 infection was significantly associated with the probability of severe or critical illness.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/#recordDetails PROSPERO, identifier CRD42023393511.
Topics: Humans; COVID-19; Neoplasms; Immune Checkpoint Inhibitors; SARS-CoV-2; Prognosis
PubMed: 38887296
DOI: 10.3389/fimmu.2024.1259112