Immune Diseases Research Articles

Restricting datasets to classifiable samples augments discovery of immune disease biomarkers

Immunological diseases are typically heterogeneous in clinical presentation, severity and response to therapy. Biomarkers of immune diseases often reflect this variability, especially compared to their regulated behaviour in health. This leads to a common difficulty that frustrates biomarker discovery and interpretation – namely, unequal dispersion of immune disease biomarker expression between patient classes necessarily limits a biomarker’s informative range. To solve this problem, we introduce dataset restriction, a procedure that splits datasets into classifiable and unclassifiable samples. Applied to synthetic flow cytometry data, restriction identifies biomarkers that are otherwise disregarded. In advanced melanoma, restriction finds biomarkers of immune-related adverse event risk after immunotherapy and enables us to build multivariate models that accurately predict immunotherapy-related hepatitis. Hence, dataset restriction augments discovery of immune disease biomarkers, increases predictive certainty for classifiable samples and improves multivariate models incorporating biomarkers with a limited informative range. This principle can be directly extended to any classification task.

Responsive Multi-Arm PEG-Modified COF Nanocomposites: Dynamic Photothermal, pH/ROS Dual-Responsive, Targeted Carriers for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is a chronic immune disease characterized by the infiltration of immune cells and the proliferation of fibroblast-like synoviocytes (FLS) at the joint site, leading to inflammation and joint destruction. However, the available treatment options targeting both inflammatory and proliferative FLS are limited. Herein, we present three covalent organic frameworks (COFs) photothermal composite systems modified with multi-armed PEG for the treatment of RA. These systems exhibited a dual response under low pH and high reactive oxygen species (ROS) conditions at the site of inflammation, with a specific focus on delivering the protein drug ribonuclease A (RNase A). This protein, in combination with photothermal therapy, effectively targeted and eliminated FLS while reducing ROS production by immune cells. Notably, molecular docking studies revealed the interaction between RNase A and NF-κB p65 protein, and Western blotting confirmed its inhibitory effect on NF-κB activity. In vitro and in vivo experiments verified the significant reduction in joint swelling and deformities in adjuvant-induced arthritis (AIA) rats after treatment with RNase A delivered by multi-armed PEG-modified COF ligands, restoring joint morphology to normal. In vivo plasma indices demonstrated the ability of this treatment to scavenge and reduce pro-inflammatory cytokines while maintaining a favorable biosafety profile. These findings underscore the promising therapeutic potential of COFs for the treatment of RA, highlighting their unique capabilities in addressing both inflammatory and proliferative aspects of the disease and expanding the scope of biomedical applications for COFs. This article is protected by copyright. All rights reserved.

Characterization of cord blood immune and stem cells from Vietnamese infants

Cord blood has emerged as a valuable and versatile resource, holding within its grasp a myriad of immune and stem cell types with immense therapeutic potential. Moreover, immune profiling in cord blood, a burgeoning field of research, offers profound insight into the early immune development of newborns, paving the way for understanding immune health, disease susceptibility, and therapeutic interventions. Therefore, in this research, we aimed to characterize the diverse immune and stem cell types present in the cord blood of Vietnamese infants. In this study, a total of 59 cord blood samples were examined for immune cell populations. Cell populations were identified using flow cytometry based on the expression of specific markers on the cell surface. The results showed that the CD3+/CD4+ population accounted for the greatest proportion of lymphocytes (46.71 ± 8.99%), followed by the CD3+/CD8+ population (22.58 ± 6.73%). The mature B-cell population (CD3-/CD19+) accounted for 9.52 ± 3.28%, while CD3+/CD19+ cells accounted for an average of 8.59 ± 5.77%. Moreover, the NK population (CD3-/CD56+ cells) accounted for 6.44 ± 4.9%, T lymphocytes carrying both CD4 and CD8 markers (CD3+/CD4+/CD8+) accounted for 0.63 ± 0.41%, and NKT cells (CD3+/CD56+) accounted for only 0.30 ± 0.53%. Moreover, the number of hematopoietic stem cells (HSCs) tends to increase in umbilical cord blood units with a high volume and number of TNCs and MNCs. In contrast, the number of HSCs was negatively correlated with the ratio of B lymphocytes. The TCD4 ratio was positively correlated with the number of HSCs but negatively correlated with the NK ratio (p = 0.01). The study initially characterized the diversity of some stem and immune cell types present in the umbilical cord blood of Vietnamese infants. These findings laid the groundwork for developing novel immune profiles and expanding the potential applications of umbilical cord blood in cellular therapy.

Cystathionine γ-lyase-derived H2S negatively regulates thymic egress via allosteric inhibition of sphingosine-1-phosphate lyase.

Thymic egress is a crucial process for thymocyte maturation, strictly regulated by sphingosine-1-phosphate lyase (S1PL). Recently, cystathionine γ-lyase (CSE), one of the enzymes producing hydrogen sulfide (H2S), has emerged as a vital immune process regulator. However, the molecular connection between CSE, H2S and thymic egress remains largely unexplored. In this study, we investigated the regulatory function of CSE in the thymic egress of immune cells. We showed that genetic knockout of CSE or pharmacological inhibition by CSE enzyme inhibitor NSC4056 or D,L-propargylglycine (PAG) significantly enhanced the migration of mature lymphocytes and monocytes from the thymus to the peripheral blood, and this redistribution effect could be reversed by treatment with NaHS, an exogenous donor of H2S. In addition, the CSE-generated H2S significantly increased the levels of S1P in the peripheral blood, thymus and spleen of mice, suppressed the production of proinflammatory cytokines and rescued pathogen-induced sepsis in cells and in vivo. Notably, H2S or polysulfide inhibited S1PL activity in cells and an in vitro purified enzyme assay. We found that this inhibition relied on a newly identified C203XC205 redox motif adjacent to the enzyme's active site, shedding light on the biochemical mechanism of S1PL regulation. In conclusion, this study uncovers a new function and mechanism for CSE-derived H2S in thymic egress and provides a potential drug target for treating S1P-related immune diseases.

OTULIN-related conditions: Report of a new case and review of the literature using GenIA

OTULIN encodes an eponymous linear deubiquitinase (DUB) essential for controlling inflammation as a negative regulator of the canonical NF-κB signaling pathway via the regulation of M1-Ub dynamics. Biallelic loss-of-function (LOF) mutations in OTULIN cause an autosomal recessive condition named Otulin-Related Autoinflammatory Syndrome (ORAS), also known as Otulipenia or AutoInflammation, Panniculitis, and Dermatosis Syndrome (AIPDS). Monoallelic OTULIN LOF, also known as OTULIN Haploinsufficiency (OHI) or Immunodeficiency 107 (IMD107), has been linked to an incompletely penetrant, dominantly inherited susceptibility to invasive Staphylococcal infections. At the same time, a recent novel ORAS-like inflammatory syndrome was described in association with a heterozygous missense mutation that appears to exert dominant negative (DN) effects. In this manuscript, we report the identification of a novel homozygous missense mutation, c.595 T > A; p.(Trp199Arg), in a Moroccan infant with an ORAS phenotype and provide experimental evidence for its pathogenicity. We go on to systematically review the literature for OTULIN-associated conditions by using the GenIA database (www.geniadb.net) to collect, extract and harmonize all clinical, laboratory and functional data for published patients and variants. Our comprehensive synthesis of genotypic, phenotypic, and mechanistic data enables a more in-depth view of the diverse mechanisms and pathways by which the OTULIN pathogenic variants may lead to human immune disease. This review may help variant classification activities and inform future variant evaluation, as well as the development of diagnostic and management guidelines. It also identifies current knowledge gaps and raises additional questions warranting future investigation.

CircADAMTS6 via stabilizing CAMK2A is involved in smoking-induced emphysema through driving M2 macrophage polarization

Cigarette smoke (CS), an indoor environmental pollutant, is a prominent risk factor for emphysema, which is a pathological feature of chronic obstructive pulmonary disease (COPD). Emerging function of circRNAs in immune responses and disease progression shed new light to explore the pathogenesis of emphysema. In this research, we demonstrated, by single-cell RNA sequencing (scRNAseq), that the ratio of M2 macrophages were increased in lung tissues of humans and mice with smoking-related emphysema. Further, our data showed that circADAMTS6 was associated with cigarette smoke extract (CSE)-induced M2 macrophage polarization. Mechanistically, in macrophages, circADAMTS6 stabilized CAMK2A mRNA via forming a circADAMTS6/IGF2BP2/CAMK2A RNA-protein ternary complex to activate CREB, which drives M2 macrophage polarization and leads to emphysema. In addition, in macrophages of mouse lung tissues, downregulation of circADAMTS6 reversed M2 macrophage polarization, the proteinase/anti-proteinase imbalance, and the elastin degradation, which protecting against CS-induced emphysema. Moreover, for macrophages and in a model with co-cultured lung organoids, the target of circADAMTS6 restored the growth of lung organoids compared to CSE-treated macrophages. Our results also demonstrated that, for smokers and COPD smokers, elevation of circADAMTS6 negatively correlated with lung function. Overall, this study reveals a novel mechanism for circADAMTS6-driven M2 macrophage polarization in smoking-related emphysema and postulates that circADAMTS6 could serve as a diagnostic and therapeutic marker for smoking-related emphysema.

Upregulated miR-146b-3p predicted rheumatoid arthritis development and regulated TNF-α-induced excessive proliferation, motility, and inflammation in MH7A cells

BackgroundRheumatoid arthritis (RA) is a chronic immune system disease with a high disability rate threatening the living quality of patients. Identifying potential biomarkers for RA is of necessity to improve the prevention and management of RA.ObjectivesThis study focused on miR-146b-3p evaluating its clinical significance and revealing the underlying regulatory mechanisms.Materials and methodsA total of 107 RA patients were enrolled, and both serum and synovial tissues were collected. Another 78 osteoarthritis patients (OA, providing synovial tissues), and 72 healthy individuals (providing serum samples) were enrolled as the control group. The expression of miR-146b-3p was analyzed by PCR and analyzed with ROC and Pearson correlation analyses evaluating its significance in diagnosis and development prediction of RA patients. In vitro, MH7A cells were treated with TNF-α. The regulation of cell proliferation, motility, and inflammation by miR-146b-3p was assessed by CCK8, Transwell, and ELISA assays.ResultsSignificant upregulation of miR-146b-3p was observed in serum and synovial tissues of RA patients, which distinguished RA patients and were positively correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP), and rheumatoid factor (RF) of RA patients. TNF-α promoted the proliferation and motility of MH7A cells and induced significant inflammation in cells. Silencing miR-146b-3p alleviated the effect of TNF-α and negatively regulated the expression of HMGCR. The knockdown of HMGCR reversed the protective effect of miR-146b-3p silencing on TNF-α-stimulated MH7A cells.ConclusionsIncreased miR-146b-3p served as a biomarker for the diagnosis and severity of RA. Silencing miR-146b-3p could suppress TNF-α-induced excessive proliferation, motility, and inflammation via regulating HMGCR in MH7A cells.

MANAGEMENT OF SIDHMA KUSTA: A CASE STUDY.

Psoriasis is an immune mediated disease with an unclear cause that is characterised by inflammation caused by Dysfunction of the immune system. Psoriatic plaque shows epidermic hyperplasia. Erythrodermic psoriasis is an acute condition in which almost all body surface is inflamed. This study is to show better management through ayurvedic treatment. In this case, a 35-year-old male patient diagnosed with erythrodermic psoriasis all over body predominantly on hands which is accompanied by erythema, dry, thin scaly lesions and itching. The condi-tion managed by Snehana(oleation), Pitta rechana(purgation), internal medicines, external application with Taila which is given according to avasthanusara(stage wise). Observation and results: The outcome is positive, significant in terms of reduction of erythema, itching, scales, dryness and healing of lesions produced noticeable improvement. Ayurvedic principles provide great im-provement in signs and symptoms and increase the quality of life in the treatment of psoriasis.

Detailed role of SR-A1 and SR-E3 in tumor biology, progression, and therapy.

The first host defense systems are the innate immune response and the inflammatory response. Among innate immune cells, macrophages, are crucial because they preserve tissue homeostasis and eradicate infections by phagocytosis, or the ingestion of particles. Macrophages exhibit phenotypic variability contingent on their stimulation state and tissue environment and may be detected in several tissues. Meanwhile, critical inflammatory functions are played by macrophage scavenger receptors, in particular, SR-A1 (CD204) and SR-E3 (CD206), in a variety of pathophysiologic events. Such receptors, which are mainly found on the surface of multiple types of macrophages, have different effects on processes, including atherosclerosis, innate and adaptive immunity, liver and lung diseases, and, more recently, cancer. Although macrophage scavenger receptors have been demonstrated to be active across the disease spectrum, conflicting experimental findings and insufficient signaling pathways have hindered our comprehension of the molecular processes underlying its array of roles. Herein, as SR-A1 and SR-E3 functions are often binary, either protecting the host or impairing the pathophysiology of cancers has been reviewed. We will look into their function in malignancies, with an emphasis on their recently discovered function in macrophages and the possible therapeutic benefits of SR-A1 and SR-E3 targeting.

ROLE OF CYTOKINES CHANGES IN THE DEVELOPMENT OF PULMONARY TUBERCULOSIS

Introduction: Mycobacterium tuberculosis (MTB) remains a global health threat, demanding attention due to its wide geographic distribution. Immunity to MTB relies on Th1-cell activity, particularly cytokines such as Interferon-γ (IFN-γ), Tumor Necrosis Factor-α (TNF-α) and Transforming Growth Factor-beta (TGF-β) play crucial roles in protective immunity against MTB. This study delves into the impact of cytokine changes on immune responses and disease progression in the development of pulmonary tuberculosis (pTB). Methodology: This three-year study involved 300 participants, stratified into 100 healthy controls and 200 with pTB. Blood samples were collected, and serum cytokine levels (TNF-α, IFN-γ, TGF-β) were analyzed using ELISA kits. Results: In the pTB group, significant increases (P<0.001) in TNF-α, IFN-γ, and TGF-β indicated infection and inflammation. Males with pTB exhibited higher cytokine levels than controls, a pattern mirrored in females (P<0.001). Among males aged 20-40 with pTB, all parameters increased significantly. Similarly, females aged 20-40 with pTB showed significant elevations. In the 41-60 age group, both genders with pTB had significantly increased levels (P<0.001). Correlation analysis revealed a significant correlation among immunological parameters, emphasizing the impact of age and gender on cytokine changes in pTB. Conclusion: These cytokines are valuable markers for assessing disease activity and inflammation in pulmonary tuberculosis (pTB).

The safety and tolerability of Annona muricata leaf product in people living with cancer: Study protocol

ObjectivesThe objective of this study was to design a clinical study protocol to investigate the safety and tolerability of Annona muricata, in people living with advanced malignancy. Anecdotal clinical evidence suggests this herb has potential anti-cancer activity. There are numerous pre-clinical studies detailing Annona muricata’s main bioactive constituents. To date, clinical studies evaluating the efficacy, safety and tolerability are limited. DesignThis phase 1 open label study will involve people living with stage III and IV cancers of any type, who are not undergoing chemotherapeutic treatment. MethodsThe primary outcome is safety and tolerability of an Annona muricata leaf product as measured by participants’ self-reporting of adverse effects experienced and the proportion of participants completing the study. Secondary outcomes include biomarkers of inflammation and immune function, disease status and self-reported quality of life scores. Participants (n = 24) will be allocated to one of two groups for 12 weeks. Participants will commence at different timepoints and be assigned to either 530 mg or 1060 mg of Annona muricata daily. The study has been approved by the Human Research Ethics Committee Bellberry and will be reported in compliance with the SPIRIT statement. This study has been registered with the Australian New Zealand Clinical Trials Register. Results and conclusionsThe results of this study will provide safety and tolerability data for clinicians involved in the care of people living with cancer who choose to use Annona muricata products as an integrative approach to their healthcare. The results of this study will inform further research about the potential role of Annona muricata in cancer.

Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies

Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease. Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes. With the development of immunological technology, many studies have shown that diabetic nephropathy is an immune complex disease, and that most patients have immune dysfunction. However, the immune response associated with diabetic nephropathy and autoimmune kidney disease, or caused by ischemia or infection with acute renal injury, is different, and has a com-plicated pathological mechanism. In this review, we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism, to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

Prediction of Prognosis in Patients with Sepsis Based on Platelet-Related Genes.

The study aimed to develop a risk prognostic model using platelet-related genes (PRGs) to predict sepsis patient outcomes. Sepsis patient data from the Gene Expression Omnibus (GEO) database and PRGs from the Molecular Signatures Database (MSigDB) were analyzed. Differential analysis identified 1139 differentially expressed genes (DEGs) between sepsis and control groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed enrichment in functions related to immune cell regulation and pathways associated with immune response and infectious diseases. A risk prognostic model was established using LASSO and Cox regression analyses, incorporating 10 PRGs selected based on their association with sepsis prognosis. The model demonstrated good stratification and prognostic effects, confirmed by survival and receiver operating characteristic (ROC) curve analyses. It served as an independent prognostic factor in sepsis patients. Further analysis using the CIBERSORT algorithm showed higher infiltration of activated natural killer (NK) cells and lower infiltration of CD8 T cells and CD4 T cells naïve in the high-risk group compared to the low-risk group. Additionally, expression levels of human leukocyte antigen (HLA) genes were significantly lower in the high-risk group. In conclusion, the 10-gene risk model based on PRGs accurately predicted sepsis patient prognosis and immune infiltration levels. This study provides valuable insights into the role of platelets in sepsis prognosis and diagnosis, offering potential implications for personalized treatment strategies.

Comprehensive Summary of Safety Data on Nirsevimab in Infants and Children from All Pivotal Randomized Clinical Trials.

Nirsevimab is approved in the US for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season and in children aged ≤24 months who remain vulnerable to severe RSV disease through their second RSV season. We summarize a pre-specified analysis of nirsevimab safety data from three randomized controlled trials: Phase 2b (NCT02878330; healthy infants born ≥29 to <35 weeks' gestational age [wGA]); Phase 3 MELODY (NCT03979313; healthy infants born ≥35 wGA); and Phase 2/3 MEDLEY (NCT03959488; infants with congenital heart disease [CHD] and/or chronic lung disease of prematurity [CLD] or born ≤35 wGA). Participants (randomized 2:1) received a single intramuscular dose of nirsevimab or comparator (placebo, Phase 2b/MELODY; 5× once-monthly palivizumab, MEDLEY) before their first RSV season (recipients < 5 kg, nirsevimab 50 mg; ≥5 kg, nirsevimab 100 mg). In MEDLEY, children with CHD/CLD continued to a second RSV season: first-season nirsevimab recipients received nirsevimab 200 mg; first-season palivizumab recipients were re-randomized 1:1 to receive nirsevimab 200 mg or 5× once-monthly palivizumab. The incidence, severity, and nature of AEs were similar across treatments (nirsevimab, n = 3184; placebo, n = 1284; palivizumab, n = 304). Most AEs were mild to moderate in severity, with ≥98% unrelated to treatment. AEs of special interest occurred infrequently (<1%): no anaphylaxis or thrombocytopenia were treatment-related, and no immune complex disease was reported. Deaths (incidence < 1.0%) were all unrelated to treatment. A single dose per season of nirsevimab for the prevention of RSV disease had a favorable safety profile, irrespective of wGA or comorbidities.

Colon Cancer Genetic and Epigenetic Changes, Etiopathogenesis, Risk Factors, Treatment: Literature Review

Background. Colorectal cancer (CRC) ranks as the third leading cause of cancerrelated mortality worldwide. Recent years have witnessed an increase in the incidence of CRC. The main reasons are ageing population, increased consumption of processed food, obesity, genetic predispositions. Aim. To review the latest scientific developments and novel factors on the epidemiology, etiology, pathoge­nesis of colon cancer, focusing on the influence of genetics and epigenetics, risk factors, and the advancement of prevention and treatment methods. Material and methods. The research method is a literature review. Publications were searched in the PubMed database using the following keywords and their combinations in English: colon cancer, colorectal cancer, management, prevalence, causes, risk factors, genetic and epigenetic changes. Selection criteria for publications: scientific articles in English relevant to the research topic and 90% of articles published in the last 10 years (2014–2024). Results. Using theoretical analysis methods, 72 publications were selected that met the inclusion criteria. Our findings emphasize the central role of genetic mutations (particularly in APC, TP53, KRAS and MMR) and epigenetic alterations, such as DNA methylation and histone modification, in the pathogenesis of colorectal cancer. These genetic and epigenetic factors drive the progression from benign polyps to malignant carcinomas, with environmental, lifestyle, and chronic disease factors also playing a critical role. In particular, diet, physical inactivity, smoking and alcohol significantly increase risk, especially in men and those over 50. Innovations such as CRISPR/Cas9 offer new avenues for targeted treatments, while advances in vaccines and liquid biopsy techniques are improving immune response activation and disease monitoring. In addition, diets rich in fiber, antioxidants and healthy fats, as well as the use of probiotics and NSAIDs, are key to reducing cancer risk through their anti-inflammatory effects and promoting gut health. Conclussions. This review highlights the significant impact of genetic and epigenetic factors on colorectal cancer (CRC) development, in addition to the role of lifestyle and environmental exposures. It highlights the potential of CRISPR/Cas9, immunotherapies, and liquid biopsies in pioneering personalized CRC treatments and early detection. Advances in prevention and technology promise a new era of personalized, effective CRC management strategies.

CD4+CD8αα+ is the dominant phenotype of intraepithelial lymphocytes and regulated by ThPOK and Runx3 in oral lichen planus.

Oral lichen planus (OLP) is a common T cell-mediated oral mucosal immune inflammatory disease. Intraepithelial lymphocytes (IELs) are a unique subset of T cells that play an important role in regulating immune response. This study aims to investigate the phenotype and the differentiation mechanism of IELs in OLP. The expression of CD4, CD8α, CD8β, T-helper-inducing POZ/Krueppel-like factor (ThPOK), and RUNX family transcription factor 3 (Runx3) in the epithelium and peripheral blood mononuclear cells (PBMCs) of OLP was determined by immunofluorescence and immunohistochemistry. Then, the correlations among them were analyzed. Naïve CD4+ T cells were sorted from blood of OLP patients and stimulated with retinoic acid (RA) and transforming growth factor-β1 (TGF-β1). Then the expression of CD4, CD8α, CD8β, ThPOK, and Runx3 was investigated by immunocytochemistry. CD8α expression and CD8αα+ cells were upregulated in the epithelium of OLP, whereas they were downregulated in PBMCs of OLP. CD8β was not expressed in the epithelium of OLP. CD4, CD8α, and Runx3 expression and CD4+CD8α+ cells were increased, whereas ThPOK expression was decreased in the epithelium of OLP. CD8α expression was positively correlated with Runx3 expression, whereas ThPOK expression was negatively correlated with Runx3 expression. After RA and TGF-β1 stimulation, CD8α and Runx3 expression was upregulated, and ThPOK expression was downregulated in naïve CD4+ T cells. CD4+CD8αα+ IELs may be the dominant phenotype of IELs in OLP, and the differentiation of CD4+CD8αα+ IELs in OLP is negatively regulated by ThPOK and positively regulated by Runx3.

Building Data Triangulation Capacity for Routine Immunization and Vaccine Preventable Disease Surveillance Programs to Identify Immunization Coverage Inequities.

The Expanded Programme on Immunization (EPI) and Vaccine Preventable Disease (VPD) Surveillance (VPDS) programs generate multiple data sources (e.g., routine administrative data, VPD case data, and coverage surveys). However, there are challenges with the use of these siloed data for programmatic decision-making, including poor data accessibility and lack of timely analysis, contributing to missed vaccinations, immunity gaps, and, consequently, VPD outbreaks in populations with limited access to immunization and basic healthcare services. Data triangulation, or the integration of multiple data sources, can be used to improve the availability of key indicators for identifying immunization coverage gaps, under-immunized (UI) and un-immunized (zero-dose (ZD)) children, and for assessing program performance at all levels of the healthcare system. Here, we describe the data triangulation processes, prioritization of indicators, and capacity building efforts in Bangladesh, Nigeria, and Rwanda. We also describe the analyses used to generate meaningful data, key indicators used to identify immunization coverage inequities and performance gaps, and key lessons learned. Triangulation processes and lessons learned may be leveraged by other countries, potentially leading to programmatic changes that promote improved access and utilization of vaccination services through the identification of UI and ZD children.

Delayed colonization of Bifidobacterium spp. and low prevalence of B. infantis among infants of Asian ancestry born in Singapore: insights from the GUSTO cohort study.

The loss of ancestral microbes, or the "disappearing microbiota hypothesis" has been proposed to play a critical role in the rise of inflammatory and immune diseases in developed nations. The effect of this loss is most consequential during early-life, as initial colonizers of the newborn gut contribute significantly to the development of the immune system. In this longitudinal study (day 3, week 3, and month 3 post-birth) of infants of Asian ancestry born in Singapore, we studied how generational immigration status and common perinatal factors affect bifidobacteria and Bifidobacterium longum subsp. infantis (B. infantis) colonization. Cohort registry identifier: NCT01174875. Our findings show that first-generation migratory status, perinatal antibiotics usage, and cesarean section birth, significantly influenced the abundance and acquisition of bifidobacteria in the infant gut. Most importantly, 95.6% of the infants surveyed in this study had undetectable B. infantis, an early and beneficial colonizer of infant gut due to its ability to metabolize the wide variety of human milk oligosaccharides present in breastmilk and its ability to shape the development of a healthy immune system. A comparative analysis of B. infantis in 12 countries by their GDP per capita showed a remarkably low prevalence of this microbe in advanced economies, especially Singapore. This study provides new insights into infant gut microbiota colonization, showing the impact of generational immigration on early-life gut microbiota acquisition. It also warrants the need to closely monitor the declining prevalence of beneficial microbes such as B. infantis in developed nations and its potential link to increasing autoimmune and allergic diseases.

Evaluation of the effects of decellularized umbilical cord Wharton's Jelly ECM on polyhydroxy butyrate electrospun scaffolds: A new strategy for cartilage tissue engineering

The field of regenerative medicine has recently witnessed the emergence of the allogeneic decellularized extracellular matrix as a scaffold with natural biological signals in tissue engineering. In the present study, to prevent immune rejection and disease transmission, Wharton's Jelly extracellular matrix (WJM) derived from the human umbilical cord was first decellularized (DWJM). Eventually, the fibrous scaffolds based on poly 3-hydroxybutyrate (PHB) and five different concentrations (0, 1, 3, 5, and 10 wt%) of DWJM were fabricated through electrospinning. The results demonstrate reducing the diameter of the fibers, improved mechanical properties, hydrophilicity, and degradation rate in the scaffold containing 3 wt % DWJM. Excellent biocompatibility and increased chondrocyte cell adherence rate on the substrate of PHB-DWJM 3 % scaffolds compared with pure PHB scaffolds can be attributed to the high amounts of Collagen, sulfated glycosaminoglycans (GAGs), and hyaluronic acid (HA) in the DWJM. In conclusion, the physicochemical properties and biological activities of PHB-DWJM scaffolds indicate that blending DWJM with PHB electrospun scaffold can provide a suitable environment for articular cartilage tissue regeneration.

Aging and Autophagy: Roles in Musculoskeletal System Injury.

Aging is a multifactorial process that ultimately leads to a decline in physiological function and a consequent reduction in the health span, and quality of life in elderly population. In musculoskeletal diseases, aging is often associated with a gradual loss of skeletal muscle mass and strength, resulting in reduced functional capacity and an increased risk of chronic metabolic diseases, leading to impaired function and increased mortality. Autophagy is a highly conserved physiological process by which cells, under the regulation of autophagy-related genes, degrade their own organelles and large molecules by lysosomal degradation. This process is unique to eukaryotic cells and is a strict regulator of homeostasis, the maintenance of energy and substance balance. Autophagy plays an important role in a wide range of physiological and pathological processes such as cell homeostasis, aging, immunity, tumorigenesis and neurodegenerative diseases. On the one hand, under mild stress conditions, autophagy mediates the restoration of homeostasis and proliferation, reduction of the rate of aging and delay of the aging process. On the other hand, under more intense stress conditions, an inadequate suppression of autophagy can lead to cellular aging. Conversely, autophagy activity decreases during aging. Due to the interrelationship between aging and autophagy, limited literature exists on this topic. Therefore, the objective of this review is to summarize the current concepts on aging and autophagy in the musculoskeletal system. The aim is to better understand the mechanisms of age-related changes in bone, joint and muscle, as well as the interaction relationship between autophagy and aging. Its goal is to provide a comprehensive perspective for the improvement of diseases of the musculoskeletal system.