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Poultry Science May 2024This experiment aimed to study the effect of 1% Artemisia annua added to the diet on growth performance, antioxidant capacity, immunity and intestinal morphology, and...
This experiment aimed to study the effect of 1% Artemisia annua added to the diet on growth performance, antioxidant capacity, immunity and intestinal morphology, and gut microbiota of geese. Seventy-two 35-day-old male geese (Zi goose) with similar body weight were selected and randomly divided into 2 groups. Each treatment group of 36 geese was divided into 6 subgroups, each having 6 male geese. The experiment lasted for 21 d. Control group (CON) was fed a basal diet and the experimental group (AAL) was fed a basal diet + 1% Artemisia annua. BW, ADG, and ADFI of the AAL group increased (p < 0.05) and the FCR decreased (p < 0.05) compared with the CON group. The addition of Artemisia annua to the diet increased catalase (CAT), glutathione peroxidase (GSH-px), and superoxide dismutase (SOD) enzyme activities, increased total antioxidant capacity (T-AOC), and decreased malondialdehyde (MDA) content in serum and jejunum of geese (p < 0.05). Meanwhile, serum IgA, IgG, IgM, and lysozyme (LZM), increased at different time points in the AAL group compared to the CON group (p < 0.05), and decrease in the content of interferon-γ (IFN-γ) , IL-6 (p < 0.05), but no effect on complement C3 and C4. Morphological observation of the small intestine showed that the jejunal crypt depth was decreased in the AAL group (p < 0.05) while elevating the jejunal villus height/crypt depth (p < 0.05). 16S rRNA sequencing results showed the Artemisia annua increased the diversity of cecum microbiota, increasing the relative abundance of Bacteroides, Fecalibacterium, and Paraprevotella. In conclusion, the addition of 1% Artemisia annua to the diet could improve the growth performance, antioxidant and immune ability of geese, as well as improve the development of the jejunum intestinal tract of geese, and change the structure of the cecum microbiota, which had a positive effect on the growth and development of geese. Artemisia annua can be further developed as a feed additive.
Topics: Animals; Gastrointestinal Microbiome; Artemisia annua; Geese; Animal Feed; Male; Diet; Antioxidants; Dietary Supplements; Random Allocation; Animal Nutritional Physiological Phenomena
PubMed: 38479097
DOI: 10.1016/j.psj.2024.103594 -
International Journal of Molecular... Mar 2024Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic...
Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Our objectives are to confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and to study their correlation with various disease parameters. Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients' data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Associations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. AGEs levels in SLE patients were significantly higher than in HC ( < 0.001). We found statistically significant positive associations with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL-6 and oral ulcers. We also found a negative statistically significant association with current positivity of anti-nuclear and anti-Ro60 antibodies. AGEs seem to have a contribution in LES pathophysiology, being associated with activity and damage and having a role as a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher or lower AGEs levels.
Topics: Humans; Cross-Sectional Studies; Lupus Erythematosus, Systemic; Biomarkers; Complement C4; Severity of Illness Index; Glycation End Products, Advanced
PubMed: 38474267
DOI: 10.3390/ijms25053022 -
Frontiers in Immunology 2023Deficiencies of the early complement components of the classical pathway (CP) are well-documented in association with systemic lupus erythematosus (SLE) or SLE-like...
Deficiencies of the early complement components of the classical pathway (CP) are well-documented in association with systemic lupus erythematosus (SLE) or SLE-like syndromes and severe pyogenic infections. Among these, complete C1s deficiency has been reported in nine cases so far. Here, we describe a 34-year-old male patient who presented with severe, recurrent infections since childhood, including meningitides with pneumococci and meningococci, erysipelas, subcutaneous abscess, and recurrent infections of the upper airways. The patient also exhibited adult-onset SLE, meeting 7/11 of the ACR criteria and 34 of the 2019 EULAR/ACR classification criteria, along with class IV-G (A) proliferative lupus nephritis (LN). A screening of the complement cascade showed immeasurably low CH50, while the alternative pathway (AP) function was normal. Subsequent determination of complement components revealed undetectable C1s with low levels of C1r and C1q, normal C3, and slightly elevated C4 and C2 concentrations. The patient had no anti-C1q antibodies. Renal biopsy showed class IV-G (A) LN with complement C1q positivity along the glomerular basement membranes (GBMs) and weak deposition of IgG, IgM, and complement C3 and C4 in the mesangium and GBM. In an ELISA-based functional assay determining C4d deposition, the patient's absent complement activity was fully restored by adding C1s. The genome of the patient was analyzed by whole genome sequencing showing two truncating variants in the gene. One mutation was located at nucleotide 514 in exon 5, caused by a nucleotide substitution from G to T, resulting in a nonsense mutation from Gly172 (p.Gly172*). The other mutation was located at nucleotide 750 in exon 7, where C was replaced by a G, resulting in a nonsense mutation from Tyr250 (p.Tyr250*). Both mutations create a premature stop codon and have not previously been reported in the literature. These genetic findings, combined with the absence of C1s in the circulation, strongly suggest a compound heterozygote C1s deficiency in our patient, without additional defect within the complement cascade. As in a previous C1s deficiency case, the patient responded well to rituximab. The present case highlights unanswered questions regarding the CP's role in SLE etiopathogenesis.
Topics: Adult; Humans; Male; Codon, Nonsense; Complement C1q; Complement C1s; Hereditary Complement Deficiency Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Nucleotides; Reinfection
PubMed: 38469558
DOI: 10.3389/fimmu.2023.1257525 -
Genome Biology and Evolution Apr 2024Evolutionary convergences are observed at all levels, from phenotype to DNA and protein sequences, and changes at these different levels tend to be correlated. Notably,...
Evolutionary convergences are observed at all levels, from phenotype to DNA and protein sequences, and changes at these different levels tend to be correlated. Notably, convergent mutations can lead to convergent changes in phenotype, such as changes in metabolism, drug resistance, and other adaptations to changing environments. We propose a two-component approach to detect mutations subject to convergent evolution in protein alignments. The "Emergence" component selects mutations that emerge more often than expected, while the "Correlation" component selects mutations that correlate with the convergent phenotype under study. With regard to Emergence, a phylogeny deduced from the alignment is provided by the user and is used to simulate the evolution of each alignment position. These simulations allow us to estimate the expected number of mutations in a neutral model, which is compared to the observed number of mutations in the data studied. In Correlation, a comparative phylogenetic approach, is used to measure whether the presence of each of the observed mutations is correlated with the convergent phenotype. Each component can be used on its own, for example Emergence when no phenotype is available. Our method is implemented in a standalone workflow and a webserver, called ConDor. We evaluate the properties of ConDor using simulated data, and we apply it to three real datasets: sedge PEPC proteins, HIV reverse transcriptase, and fish rhodopsin. The results show that the two components of ConDor complement each other, with an overall accuracy that compares favorably to other available tools, especially on large datasets.
Topics: Animals; Phylogeny; Evolution, Molecular; Fishes; Rhodopsin; Mutation
PubMed: 38451738
DOI: 10.1093/gbe/evae040 -
Frontiers in Immunology 2024Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). This study aimed to identify LN specific-genes and potential therapeutic targets.
INTRODUCTION
Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). This study aimed to identify LN specific-genes and potential therapeutic targets.
METHODS
We performed high-throughput transcriptome sequencing on peripheral blood mononuclear cells (PBMCs) from LN patients. Healthy individuals and SLE patients without LN were used as controls. To validate the sequencing results, qRT-PCR was performed for 5 upregulated and 5 downregulated genes. Furthermore, the effect of the TNFRSF17-targeting drug IBI379 on patient plasma cells and B cells was evaluated by flow cytometry.
RESULTS
Our analysis identified 1493 and 205 differential genes in the LN group compared to the control and SLE without LN groups respectively, with 70 genes common to both sets, marking them as LN-specific. These LN-specific genes were significantly enriched in the 'regulation of biological quality' GO term and the cell cycle pathway. Notably, several genes including TNFRSF17 were significantly overexpressed in the kidneys of both LN patients and NZB/W mice. TNFRSF17 levels correlated positively with urinary protein levels, and negatively with complement C3 and C4 levels in LN patients. The TNFRSF17-targeting drug IBI379 effectively induced apoptosis in patient plasma cells without significantly affecting B cells.
DISCUSSION
Our findings suggest that TNFRSF17 could serve as a potential therapeutic target for LN. Moreover, IBI379 is presented as a promising treatment option for LN.
Topics: Animals; Mice; Humans; Lupus Nephritis; Leukocytes, Mononuclear; Immunotherapy; Lupus Erythematosus, Systemic; High-Throughput Nucleotide Sequencing
PubMed: 38440734
DOI: 10.3389/fimmu.2024.1303611 -
Case Reports in Oncology 2024Acquired angioedema due to C1 esterase inhibitor deficiency (C1INH-AAE) is most associated with lymphoproliferative disorders (LPDs), particularly low-grade B-cell...
INTRODUCTION
Acquired angioedema due to C1 esterase inhibitor deficiency (C1INH-AAE) is most associated with lymphoproliferative disorders (LPDs), particularly low-grade B-cell subtypes. The condition remains under-recognized with long diagnostic delays due to various challenges including a lack of awareness of the condition.
CASE PRESENTATION
We discuss 4 cases of C1INH-AAE associated with low-grade B-cell LPDs, including various diagnostic and management challenges. As our cases illustrate, constitutional symptoms or overt manifestations of LPD at diagnosis are often absent. Hence, a comprehensive multimodal approach to screening for an underlying B-LPD is important when a diagnosis of acquired angioedema is made. Levels of complement C4, C1q, and C1INH are useful for diagnosing C1INH-AAE and for monitoring disease activity. Changes in these parameters may also indicate relapse of the underlying hematological malignancy. Treating the underlying disorder is important as this commonly leads to clinical improvement with decreased episodes of angioedema and normalization of complement studies.
CONCLUSION
Awareness of C1INH-AAE can lead to an early diagnosis of hematological malignancies. The absence of constitutional symptoms emphasizes the need for a comprehensive multimodal approach to screening for LPD in C1INH-AAE. C4, C1INH level, and function are useful for monitoring disease activity.
PubMed: 38404406
DOI: 10.1159/000536458 -
Journal of Ayub Medical College,... 2023We present the case of a 30-year-old woman who presented with 8-month history of intermittent fever, joint pains with morning stiffness, recurrent oral ulcers,...
We present the case of a 30-year-old woman who presented with 8-month history of intermittent fever, joint pains with morning stiffness, recurrent oral ulcers, photosensitivity, weight loss and hair fall. For the last 2 months, she had developed a dry cough with progressive shortening of breath. On examination, a cachexic lady with malar hyperpigmentation, alopecia, pallor, nail dystrophy and erythema over her hands and feet were noted. There were multiple punched-out skin ulcers of variable size over legs, arms and abdomen usually round in shape with well-defined even wound margins and scant serous discharge. Musculoskeletal examination revealed synovitis of both elbows and a few metacarpophalangeal and proximal interphalangeal joints. Chest X-ray and HRCT showed bilateral ground-glass opacification. Anti-Nuclear Antibody (ANA) was positive, 1:320, homogenous nuclear pattern. Anti-Ro antibody was highly positive and serum complement (C3, C4) levels were reduced. She was diagnosed with Lupus Vasculitis and started on steroids, mycophenolate mofetil and hydroxychloroquine.
Topics: Humans; Female; Adult; Cellulitis; Impetigo; Pakistan; Eye Diseases; Mycophenolic Acid
PubMed: 38404102
DOI: 10.55519/JAMC-03-11426 -
Journal of Ayub Medical College,... 2023We present the case of a 30-year-old woman who presented with 8-month history of intermittent fever, joint pains with morning stiffness, recurrent oral ulcers,...
We present the case of a 30-year-old woman who presented with 8-month history of intermittent fever, joint pains with morning stiffness, recurrent oral ulcers, photosensitivity, weight loss and hair fall. For the last 2 months, she had developed a dry cough with progressive shortening of breath. On examination, a cachexic lady with malar hyperpigmentation, alopecia, pallor, nail dystrophy and erythema over her hands and feet were noted. There were multiple punched-out skin ulcers of variable size over legs, arms and abdomen usually round in shape with well-defined even wound margins and scant serous discharge. Musculoskeletal examination revealed synovitis of both elbows and a few metacarpophalangeal and proximal interphalangeal joints. Chest X-ray and HRCT showed bilateral ground-glass opacification. Anti-Nuclear Antibody (ANA) was positive, 1:320, homogenous nuclear pattern. Anti-Ro antibody was highly positive and serum complement (C3, C4) levels were reduced. She was diagnosed with Lupus Vasculitis and started on steroids, mycophenolate mofetil and hydroxychloroquine.
Topics: Humans; Female; Adult; Mycophenolic Acid; Fever; Arthralgia; Vasculitis
PubMed: 38404096
DOI: 10.55519/JAMC-03-10849 -
Biomedicine & Pharmacotherapy =... Apr 2024Riboflavin (RF) as a photosensitizer has been used in corneal surgery and the inactivation of blood products. However, the effect of RF on immune cells after ultraviolet...
Riboflavin (RF) as a photosensitizer has been used in corneal surgery and the inactivation of blood products. However, the effect of RF on immune cells after ultraviolet (UV) light stimulation has not been investigated. This study pioneered a novel application method of RF. Firstly, UV-stimulated RF was co-cultured with human peripheral blood mononuclear cells in vitro, and the apoptosis rate of lymphocyte subsets, cell proliferation inhibition rate and concentrations of IL-1β, IL-6, IL-10, TNF-α were assessed. UV-stimulated RF was then administered intravenously to mice via the tail vein for a consecutive period of 5 days. The levels of immunoglobulin (IgG, IgM, IgA), complement (C3, C4) and cytokines (IFN-γ, IL-4, IL17, TGF-β) were detected by ELISA. Flow cytometry was employed to analyze the populations of CD3+T, CD4+T, CD8+T and CD4+T/CD8+T cells in spleen lymphocytes of mice. The data showed that UV-stimulated RF can effectively induce apoptosis in lymphocytes, and different lymphocyte subtypes exhibited varying degrees of treatment tolerance. Additionally, the proliferative capacity of lymphocytes was suppressed, while their cytokine secretion capability was augmented. The animal experiments demonstrated that UV-stimulated RF led to a significant reduction observed in serum immunoglobulin and complement levels, accompanied by an elevation in IFN-γ, IL-17 and TGF-β levels, as well as a decline in IL-4 level. In summary, the results of both in vitro and in vivo experiments have demonstrated that UV-stimulated RF, exhibits the ability to partially inhibit immune function. This novel approach utilizing RF may offer innovative perspectives for diseases requiring immunosuppressive treatment.
Topics: Humans; Mice; Animals; Leukocytes, Mononuclear; Interleukin-4; Mice, Inbred BALB C; Cytokines; Riboflavin; Transforming Growth Factor beta; Immunoglobulins; CD4-Positive T-Lymphocytes
PubMed: 38401513
DOI: 10.1016/j.biopha.2024.116278 -
International Journal of Molecular... Feb 2024Complement component 4 binding protein α () is an immune gene which is responsible for the complement regulation function of by binding and inactivating the Complement...
Complement component 4 binding protein α () is an immune gene which is responsible for the complement regulation function of by binding and inactivating the Complement component C4b () component of the classical Complement 3 () invertase pathway. Our previous findings revealed that was differentially expressed by comparing the transcriptome in high-fat and low-fat bovine mammary epithelial cell lines (BMECs) from Chinese Holstein dairy cows. In this study, a gene knockout BMECs line model was constructed via using a CRISPR/Cas9 system to investigate the function of in lipid metabolism. The results showed that levels of triglyceride (TG) were increased, while levels of cholesterol (CHOL) and free fatty acid (FFA) were decreased ( < 0.05) after knocking out in BMECs. Additionally, most kinds of fatty acids were found to be mainly enriched in the pathway of the biosynthesis of unsaturated fatty acids, linoleic acid metabolism, fatty acid biosynthesis, and regulation of lipolysis in adipocyte. Meanwhile, the RNA-seq showed that most of the differentially expressed genes (DEGs) are related to PI3K-Akt signaling pathway. The expressions of 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 (HMGCS1), Carnitine Palmitoyltransferase 1A (CPT1A), Fatty Acid Desaturase 1 (FADS1), and Stearoyl-Coenzyme A desaturase 1 (SCD1) significantly changed when the gene was knocked out. Collectively, gene, which is an immune gene, played an important role in lipid metabolism in BMECs. These findings provide a new avenue for animal breeders: this gene, with multiple functions, should be reasonably utilized.
Topics: Animals; Cattle; Female; Complement C4; Epithelial Cells; Fatty Acids; Lipid Metabolism; Mammary Glands, Animal; Milk; Phosphatidylinositol 3-Kinases; Transcriptome
PubMed: 38397050
DOI: 10.3390/ijms25042375