Training associated alterations in equine respiratory immunity using a multiomics comparative approach

Neutrophilic airway inflammation is highly prevalent in racehorses in training, with the term mild to moderate equine asthma (MMEA) being applied to the majority of such cases. Our proposed study is largely derived from the strong association between MMEA in racehorses and their entry into a race training program. The objectives of this study are to characterise the effect of training on the local pulmonary immune system by defining the gene and protein expression of tracheal wash (TW) derived samples from Thoroughbred racehorses prior to and following commencement of race training. Multiomics analysis detected 2138 differentially expressed genes and 260 proteins during the training period. Gene and protein sets were enriched for biological processes related to acute phase response, oxidative stress, haemopoietic processes, as well as to immune response and inflammation. This study demonstrated TW samples to represent a rich source of airway cells, protein and RNA to study airway immunity in the horse and highlighted the benefits of a multiomics methodological approach to studying the dynamics of equine airway immunity. Findings likely reflect the known associations between race-training and both airway inflammation and bleeding, offering further insight into the potential mechanisms which underpin training associated airway inflammation.

Inhibition of RANKL and Sema4d Improves Residual Ridge Resorption in Mice.

Residual ridge resorption (RRR) is a chronic and progressive bone resorption following tooth loss. It causes deterioration of the oral environments and leads to the pathogenesis of various systemic diseases. However, the molecular mechanisms and risk factors for RRR progression are still unclear and controversial. In this study, we developed a tooth extraction model using mice for analyzing long-term morphological and gene expression changes in the alveolar bone. We further applied ovariectomy to this model to elucidate the effects of osteoporosis on RRR progression. As a result, the alveolar bone loss was biphasic and consisted of rapid loss in the early stages and subsequently slow and sustained bone loss over a long period. Gene expression analysis indicated that ovariectomy increased the expression of pro-inflammatory cytokines in the alveolar bone and prolonged the activation of osteoclasts same as histological analysis. Furthermore, the expressions of Tnfsf11 and Sema4d kept increasing for a long time in OVX mice. Administration of neutralization antibodies for receptor activator of NF-κB ligand (RANKL) effectively suppressed RRR. Similarly, inhibition of Semaphorin 4d (Sema4d) also improved alveolar bone loss. This study demonstrated that osteoporosis is a risk factor for RRR and that RANKL and Sema4d suppression are potential treatments.

Acute COVID-19 gene-expression profiles show multiple etiologies of long-term sequelae

Two years into the SARS-CoV-2 pandemic, the post-acute sequelae of infection are compounding the global health crisis. Often debilitating, these sequelae are clinically heterogeneous and of unknown molecular etiology. Here, a transcriptome-wide investigation of this new condition was performed in a large cohort of acutely infected patients followed clinically into the post-acute period. Gene expression signatures of post-acute sequelae were already present in whole blood during the acute phase of infection, with both innate and adaptive immune cells involved. Plasma cells stood out as driving at least two distinct clusters of sequelae, one largely dependent on circulating antibodies against the SARS-CoV-2 spike protein and the other antibody-independent. Altogether, multiple etiologies of post-acute sequelae were found concomitant with SARS-CoV-2 infection, directly linking the emergence of these sequelae with the host response to the virus.

Training Associated Alterations in Equine Respiratory Immunity Using a Multiomics Comparative Approach

Neutrophilic airway inflammation is highly prevalent in racehorses in training, with the term mild to moderate equine asthma (MMEA) being applied to the majority of such cases. Our proposed study is largely derived from the strong association between MMEA in racehorses and their entry into a race training program. The objectives of this study are to characterise the effect of training on the local pulmonary immune system by defining the gene and protein expression of tracheal wash (TW) derived samples from Thoroughbred racehorses prior to and following commencement of race training. Multiomics analysis detected 2,138 differentially expressed genes and 260 proteins during the training period. Gene and protein sets were enriched for biological processes related to acute phase response, oxidative stress, haemopoietic processes, as well as to immune response and inflammation. This study demonstrated TW samples to represent a rich source of airway cells, protein and RNA to study airway immunity in the horse and highlighted the benefits of a multiomics methodological approach to studying the dynamics of equine airway immunity. Findings likely reflect the known associations between race-training and both airway inflammation and bleeding, offering further insight into the potential mechanisms which underpin training associated airway inflammation.

Identification of Potential Disease Biomarkers in the Ovaries of Dolang Sheep from Xinjiang using Transcriptomics and Bioinformatics Approaches

Background: The Dolang sheep is a well-known indigenous breed from the Xinjiang region of China. The most important characteristics of these sheep are a year-round estrus and a strong resistance to a variety of diseases. Although the molecular regulatory mechanisms governing the year-round estrus and adaptability in health and disease are well studied in various animals, the related information is limited for sheep, particularly, the Dolang variety. Methods: To identify differentially expressed genes (DEGs) that might be responsible for the year-round estrus and that are expressed under different physiological conditions in Dolang sheep, samples from ovaries collected at different reproductive periods were analyzed using high-throughput sequencing and subsequent transcriptomics and bioinformatics analyses. Result: We identified 28,717 expressed genes by RNA-Seq analysis and from a list of 987 candidate genes, we identified 308 that were differentially expressed in the ovaries of non-pregnant Dolang sheep in estrus and anestrus phases and those in the gestation phase. The genes DQA, DQB and LOC101106374 were upregulated during the gestation period. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that these three genes may improve immunity and prevent the occurrence of abortion, brucellosis, toxoplasmosis and globidiosis and can be used to monitor sheep health during pregnancy. Thus, DQA, DQB and LOC101106374 may serve as potential biomarkers for monitoring disease progression as well as abortion risk during pregnancy in sheep.

High Secretion of Interleukin-6 and Increased MINCLE Receptor Expression Upon Exposure to Mycobacterial Cord Factor Analog Trehalose-6, 6-Dibehenate (TDB) in Patients with Takayasu Arteritis

Introduction: Suspicion on the association between Takayasu Arteritis (TA) and Tubcerculosis (TB) has been in vogue for years. Prevalence of TB in TA is reported to be higher. We aimed to study innate immune responses in patients with TA on exposure to Trehalose-6,6-dibehenate (TDB), a synthetic analogue of Trehalose-6,6-Dimycolate (TDM, also known as mycobacterial cord factor) in comparison with healthy controls. Materials and Methods: Patients with type V TA, satisfying 1990 ACR criteria, and age and sex matched healthy controls were recruited. PBMCs were cultured with 5µg/ml, 50µg/ml or without any TDB for 48 hours in RPMI medium inside a 5% Co2 incubator. IL-6, TNF-α and IL-17 were measured in cell culture supernatant, which was separated from the cells at the end of the incubation period. Gene expressions of IL-6, IL-8, TNFα, IFN-γ, MINCLE and BCL-10 were quantified in real time PCR using specific primers and SYBR green chemistry. Results: Twenty two TA patients and 21 healthy controls were recruited. Both patients and controls showed response by secreting IL-6 and TNF-α upon stimulation by TDB. Relative induction (TDB stimulated TA sample / unstimulated control) of IL-6 was significantly higher in TA [31.88(0.74-168)] patients as compared to healthy controls [1.931(0.644-8.21); p<0.002], when co-cultured with 50µg/ml TDB. The expression of MINCLE, the TDB receptor was higher in TA samples than healthy controls upon TDB stimulation. Conclusion: Stimulation with mycobacterial synthetic analogue led to higher secretion of IL-6 and higher expression of MINCLE in PBMCs of patients with TA as compared to healthy controls.

Molecular mechanisms controlling the biological clock

This year’s awardees of the Nobel Prize in Physiology or Medicine – Michael Rosbash, Michael W. Young and Jeffrey C. Hall discovered genes responsible for controlling the biological clock. Their studies allowed to form the basic mechanism of the Transcription– Transla- tion Feedback Loop, known as TTFL. The transcription of the PERIOD gene and its partner <I>TIM</I> is inhibited by proteins encoded by them which are generated oscillatorily and autonomously. The biological clock controls many physiological processes by generating circadian oscillations in harmony with day and night patterns. The daily rhythm regulates sleep, eating meals, hormone release, blood pressure and body temperature.