Disease Process Research Articles

Role of AKR1B10 in inflammatory diseases.

Inflammation is an important pathophysiological process in many diseases; it has beneficial and harmful effects. When exposed to various stimuli, the body triggers an inflammatory response to eliminate invaded pathogens and damaged tissues to maintain homeostasis. However, uncontrollable persistent or excessive inflammatory responses may damage tissues and induce various diseases, such as metabolic diseases (e.g. diabetes), autoimmune diseases, nervous system-related diseases, digestive system-related diseases, and even tumours. Aldo-keto reductase 1B10 (AKR1B10) is an important player in the development and progression of multiple diseases, such as tumours and inflammatory diseases. AKR1B10 is upregulated in solid tumours, such as hepatocellular carcinoma (HCC), non-small cell lung carcinoma, and breast cancer, and is a reliable serum marker. However, information on the role of AKR1B10 in inflammation is limited. In this study, we summarized the role of AKR1B10 in inflammatory diseases, including its expression, functional contribution to inflammatory responses, and regulation of signalling pathways related to inflammation. We also discussed the role of AKR1B10 in glucose and lipid metabolism and oxidative stress. This study provides novel information and increases the understanding of clinical inflammatory diseases.

Risk factors for exfoliation glaucoma - Current evidence and perspectives.

Exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) represent a complex matrix of ocular age-related neurodegenerative changes. Numerous decades of research on this disease entity have highlighted the unique clinical features of ocular protein-complex aggregates, which lead to tissue dysfunction of the ocular outflow channels, leading to irreversible optic nerve damage and glaucoma. While genetic studies have reported several genes associated with XFS and XFG, numerous studies have shown their association with common systemic diseases such as ischemic heart disease, cerebrovascular accidents, and hypertension. Environmental factors are also reported to play a role in the disease pathogenesis by epigenetic control of gene expression and partly explain the difference in the prevalence rates of the disease process. Despite the identification of possible triggers for the disease onset or for the development of glaucoma, the exact mechanisms or the role of several reported risk factors in disease pathogenesis remain a mystery. This review comprehensively evaluated the several risk factors in XFS and XFG while discussing the interactive interplay between the risk factors that determine the disease onset or phenotype in XFS and XFG.

Spatial Multi-Omics in Alzheimer’s Disease: A Multi-Dimensional Approach to Understanding Pathology and Progression

Alzheimer’s Disease (AD) presents a complex neuropathological landscape characterized by hallmark amyloid plaques and neurofibrillary tangles, leading to progressive cognitive decline. Despite extensive research, the molecular intricacies contributing to AD pathogenesis are inadequately understood. While single-cell omics technology holds great promise for application in AD, particularly in deciphering the understanding of different cell types and analyzing rare cell types and transcriptomic expression changes, it is unable to provide spatial distribution information, which is crucial for understanding the pathological processes of AD. In contrast, spatial multi-omics research emerges as a promising and comprehensive approach to analyzing tissue cells, potentially better suited for addressing these issues in AD. This article focuses on the latest advancements in spatial multi-omics technology and compares various techniques. Additionally, we provide an overview of current spatial omics-based research results in AD. These technologies play a crucial role in facilitating new discoveries and advancing translational AD research in the future. Despite challenges such as balancing resolution, increasing throughput, and data analysis, the application of spatial multi-omics holds immense potential in revolutionizing our understanding of human disease processes and identifying new biomarkers and therapeutic targets, thereby potentially contributing to the advancement of AD research.

Experimental Infection Models and Their Usefulness for White Spot Syndrome Virus (WSSV) Research in Shrimp

White spot syndrome virus (WSSV) is marked as one of the most economically devastating pathogens in shrimp aquaculture worldwide. Infection of cultured shrimp can lead to mass mortality (up to 100%). Although progress has been made, our understanding of WSSV’s infection process and the virus–host–environment interaction is far from complete. This in turn hinders the development of effective mitigation strategies against WSSV. Infection models occupy a crucial first step in the research flow that tries to elucidate the infectious disease process to develop new antiviral treatments. Moreover, since the establishment of continuous shrimp cell lines is a work in progress, the development and use of standardized in vivo infection models that reflect the host–pathogen interaction in shrimp is a necessity. This review critically examines key aspects of in vivo WSSV infection model development that are often overlooked, such as standardization, (post)larval quality, inoculum type and choice of inoculation procedure, housing conditions, and shrimp welfare considerations. Furthermore, the usefulness of experimental infection models for different lines of WSSV research will be discussed with the aim to aid researchers when choosing a suitable model for their research needs.

Alzheimer's disease early screening and staged detection with plasma proteome using machine learning and convolutional neural network.

Alzheimer's disease (AD) stands as the prevalent progressive neurodegenerative disease, precipitating cognitive impairment and even memory loss. Amyloid biomarkers have been extensively used in the diagnosis of AD. However, amyloid proteins offer limited information about the disease process and accurate diagnosis depends on the presence of a substantial accumulation of amyloid deposition which significantly impedes the early screening of AD. In this study, we have combined plasma proteomics with an ensemble learning model (CatBoost) to develop a cost-effective and non-invasive diagnostic method for AD. A longitudinal panel has been identified that can serve as reliable biomarkers across the entire progression of AD. Simultaneously, we have developed a neural network algorithm that utilizes plasma proteins to detect stages of Alzheimer's disease. Based on the developed longitudinal panel, the CatBoost model achieved an area under the operating curve of at least 0.90 in distinguishing mild cognitive impairment from cognitively normal. The neural network model was utilized for the detection of three stages of AD, and the results demonstrated that the neural network model exhibited an accuracy as high as 0.83, surpassing that of the traditional machine learning model.

Efficacy of stromal vascular fraction for knee osteoarthritis: A prospective, single-centre, non-randomized study with 2 years follow-up

BACKGROUND Current osteoarthritis (OA) treatments focus on symptom relief without addressing the underlying disease process. In regenerative medicine, current treatments have limitations. In regenerative medicine, more research is needed for intra-articular stromal vascular fraction (SVF) injections in OA, including dosage optimization, long-term efficacy, safety, comparisons with other treatments, and mechanism exploration. AIM To compare the efficacy of intra-articular SVF with corticosteroid (ICS) injections in patients with primary knee OA. METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA. Patients were randomly assigned (1:1) to receive either a single intra-articular SVF injection (group A) or a single intra-articular ICS (triamcinolone) (group B) injection. Patients were followed up at 1, 3, 6, 12, and 24 months. Visual analog score (VAS) and International Knee Documentation Committee (IKDC) scores were administered before the procedure and at all follow-ups. The safety of SVF in terms of adverse and severe adverse events was recorded. Statistical analysis was performed with SPSS Version 26.0, IBM Corp, Chicago, IL, United States. RESULTS Both groups had similar demographics and baseline clinical characteristics. Follow-up showed minor patient loss, resulting in 23 and 24 in groups A and B respectively. Group A experienced a notable reduction in pain, with VAS scores decreasing from 7.7 to 2.4 over 24 months, compared to a minor reduction from 7.8 to 6.2 in Group B. This difference in pain reduction in group A was statistically significant from the third month onwards. Additionally, Group A showed significant improvements in knee functionality, with IKDC scores rising from 33.4 to 83.10, whereas Group B saw a modest increase from 36.7 to 45.16. The improvement in Group A was statistically significant from 6 months and maintained through 24 months. CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA. More adequately powered, multi-center, double-blinded, randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.

CERVICAL DEGENERATIVE MYELOPATHY, PANORAMIC REVIEW

Introduction: cervical degenerative myelopathy (DCM) is a general term that entails multiple etiologies. DCM is a group of pathological entities that originate compression of the cervical spinal cord, where spasticity, hyperreflexia, pathological reflexes, loss of manual dexterity, among others, are found. Objective: to detail the current information related to cervical degenerative myelopathy, epidemiology, clinical presentation, role of complementary examinations, pathophysiology, pathogenesis and treatment. Methodology: a total of 32 articles were analyzed in this review, including review and original articles, as well as clinical cases, of which 21 bibliographies were used because the other articles were not relevant to this study. The sources of information were PubMed, Google Scholar and Cochrane; the terms used to search for information in Spanish, Portuguese and English were: cervical degenerative myelopathy, cervical spondylotic myelopathy, cervical pain, ossification of the yellow ligament and degenerative disc disease. Results: cervical myelopathy occurs in almost all individuals with canal stenosis greater than 60%. Spinal cord injury (SCI) is a devastating disorder that influences remarkable neurological morbidity and significant wear and tear on quality of life. The incidence and prevalence of SCI in North America is between 4.1 and 60.5 per 100,000, robust epidemiological data is difficult to obtain because of the multifactorial etiology of the disease process. Conclusions: cervical degenerative myelopathy involves multiple etiologies, all these entities together represent the most common reason for degenerative and non-traumatic alteration of the spinal cord in adult individuals. Degenerative disorders are more common at C5 and C6 or C6 and C7, because of the increased mobility in these sections. It is difficult to obtain solid epidemiological data because of the multifactorial etiology of the disease process. The symptoms and signs presented by the pathology are varied, so an adequate physical examination and a good clinical history should be taken. The pathology can significantly alter neurological function and lead to disability, so early recognition and treatment can prevent further deterioration of affected individuals. Surgical decompression is almost universally indicated with the intention of preventing progression and achieving maximum recovery potential. KEY WORDS: myelopathy, cervical, degenerative, pain, spinal, neuralgia.

Investigation of the Shared Biomarkers in Heterotopic Ossification Between Ossification of the Ligamentum Flavum and Ankylosing Spondylitis.

Bioinformatics analysis of Gene Expression Omnibus (GEO). Ossification of the ligamentum flavum (OLF) and ankylosing spondylitis (AS) represent intricate conditions marked by the gradual progression of endochondral ossification. This investigation endeavors to unveil common biomarkers associated with heterotopic ossification and explore the potential molecular regulatory mechanisms. Microarray and RNA-sequencing datasets retrieved from the Gene Expression Omnibus (GEO) repository were harnessed to discern differentially expressed genes (DEGs) within the OLF and AS datasets. Subsequently, Weighted Gene Co-expression Network Analysis (WGCNA) was implemented to pinpoint co-expression modules linked to OLF and AS. Common genes were further subjected to an examination of functional pathway enrichment. Moreover, hub intersection genes were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) regression, followed by an evaluation of diagnostic performance in external OLF and AS cohorts. Lastly, an analysis of immune cell infiltration was conducted to scrutinize the correlation of immune cell presence with shared biomarkers in OLF and AS. A total of 1353 and 91 Differentially Expressed Genes (DEGs) were identified in OLF and AS, respectively. Using the Weighted Gene Co-expression Network Analysis (WGCNA), 2 modules were found to be notably significant for OLF and AS. The integrative bioinformatic analysis revealed 3 hub genes (MAB21L2, MEGF10, ISLR) as shared risk biomarkers, with MAB21L2 being the central focus. Receiver Operating Characteristic (ROC) analysis exhibited a strong diagnostic potential for these hub genes. Gene Ontology (GO) analysis indicated their involvement in the positive regulation of myoblast proliferation. Notably, MAB21L2 was singled out as the optimal common biomarker for OLF and AS. Furthermore, an analysis of immune infiltration demonstrated a correlation between MAB21L2 expression and changes in immune cells. Activated CD8 T cells were identified as shared differential immune infiltrating cells significantly linked to MAB21L2 in both OLF and AS. This study represents the first instance of identifying MAB21L2 as a prospective diagnostic marker for patients contending with OLF associated with AS. The research results indicate that the ECM-receptor interaction and the cell-cell adhesion may play a role in both disease processes. This newfound knowledge not only enhances our understanding of the pathogenesis behind spinal ligament ossification but also uncovers potential targets for therapeutic interventions.

Bronchopulmonary dysplasia: analysis and validation of ferroptosis-related diagnostic biomarkers and immune cell infiltration features.

Early and precise diagnosis of bronchopulmonary dysplasia (BPD) is essential to improve the prognosis of preterm infants with BPD. Studying ferroptosis-related genes for diagnostic markers of BPD was the objective of this study. Using the GEO database and the FerrDb database, we obtained the GSE32472 dataset and screened the ferroptosis-related differentially expressed mRNAs (FRDE-mRNAs). By using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), possible biological functions and pathways were identified for FRDE-mRNAs. Three machine learning algorithms (LASSO, SVM-RFE, Random Forest) were used to recognize hub genes, as well as CIBERSORT for exploring the immune landscape of BPD and controls. Functional predictions for hub genes were made using single-gene gene set enrichment analysis (GSEA). Twenty three FRDE-mRNAs were obtained and were mainly involved in autophagy, fatty acid metabolism and ferroptosis. The four hub genes (LPIN1, ACADSB, WIPI1 and SLC7A11) screened were utilized to construct a diagnostic nomogram. The receiver operating characteristic (ROC) curves and calibration curves demonstrateld that the nomogram exhibited good predictive performance. Eight types of immune cell markers differed significantly between BPD and controls. We developed a diagnostic model for BPD, which could facilitate the early diagnosis and timely intervention of BPD. The role of ferroptosis in bronchopulmonary dysplasia is rarely reported. The ferroptosis-related genes (LPIN1, ACADSB, WIPI1 and SLC7A11) we identified could serve as early diagnostic biomarkers for BPD. Immune cell infiltration features in BPD and signaling pathways associated with marker genes give new insight into the disease process and provide a basis for further research.

Molecular Chaperonin HSP60: Current Understanding and Future Prospects.

Molecular chaperones are highly conserved across evolution and play a crucial role in preserving protein homeostasis. The 60 kDa heat shock protein (HSP60), also referred to as chaperonin 60 (Cpn60), resides within mitochondria and is involved in maintaining the organelle's proteome integrity and homeostasis. The HSP60 family, encompassing Cpn60, plays diverse roles in cellular processes, including protein folding, cell signaling, and managing high-temperature stress. In prokaryotes, HSP60 is well understood as a GroEL/GroES complex, which forms a double-ring cavity and aids in protein folding. In eukaryotes, HSP60 is implicated in numerous biological functions, like facilitating the folding of native proteins and influencing disease and development processes. Notably, research highlights its critical involvement in sustaining oxidative stress and preserving mitochondrial integrity. HSP60 perturbation results in the loss of the mitochondria integrity and activates apoptosis. Currently, numerous clinical investigations are in progress to explore targeting HSP60 both in vivo and in vitro across various disease models. These studies aim to enhance our comprehension of disease mechanisms and potentially harness HSP60 as a therapeutic target for various conditions, including cancer, inflammatory disorders, and neurodegenerative diseases. This review delves into the diverse functions of HSP60 in regulating proteo-homeostasis, oxidative stress, ROS, apoptosis, and its implications in diseases like cancer and neurodegeneration.

Serum Biochemical Parameters of Broilers Affected by Wooden Breast Myopathy.

Wooden breast (WB) myopathy is a pathology of the pectoralis major muscle. Wooden breast is caused by multiple factors. The exact etiopathogenesis of this myodegenerative pathology is still unclear. Fast-growing commercial lines of broilers that are selected for high breast muscle yields are more susceptible to this myopathy. The biochemical analysis of blood is used to diagnose pathologies and understand disease processes. Therefore, the objective of this research was to determine and compare the changes in the blood serum biochemical parameters of Ross 308 chicken broilers without myopathy and those affected by WB myopathy. Blood samples were collected from male and female Ross 308 broilers that were 43 days old, with an average live weight of 2.98-3.09 kg. Representative blood samples were selected from broilers with WB (n = 33) and without WB (n = 33). In the laboratory, the blood was centrifugated, and biochemical tests were performed with an automated computerized biochemistry analyzer. The research results showed that broilers with WB had elevated blood serum levels of creatine kinase (CK) (p = 0.018), potassium (p = 0.010), and alanine aminotransferase (ALT) (p = 0.012). In conclusion, elevated serum levels of CK and potassium indicated that skeletal muscle cells were damaged. Moreover, increased ALT levels suggested a possible association between WB myopathy and liver damage. Additionally, these research findings underscore the diagnostic significance of CK and hint at its potential as a WB biomarker.

Bronchoalveolar Lavage and Oleic Acid Two-hit Model for Inducing Acute Respiratory Distress Syndrome in Swine Models.

Acute respiratory distress syndrome (ARDS) is a widespread and often fatal clinical syndrome marked by the acute onset of pulmonary edema and inflammatory-mediated disruptions in alveolar-capillary permeability resulting in impaired gas exchange and tissue oxygenation with subsequent acute respiratory failure that accounts for 10.4% of all intensive care unit admissions worldwide and boasts a mortality rate of 38.5%. The current treatment for ARDS remains largely supportive. This is largely because of the many challenges of achieving a stable and sustainable animal model that recreates the pathophysiology of ARDS experimentally in a controlled setting to allow research to elucidate potential treatments of ARDS moving forward. The bronchoalveolar lavage and oleic acid models are currently the 2 most frequently used experimental models in inducing ARDS in animal models. This study demonstrated that combining them into a "two-hit model" can produce sustained ARDS in swine models per the Horowitz index (PaO2/FiO2 ratio of ≤300 mmHg). Additionally, expected changes in pH, pCO2, lung compliance, cytokines, and tissue histopathology were observed and add to our confidence and reliability that the "two-hit model" produces symptomatic ARDS in a manner very similar to that observed in humans. In conclusion, we demonstrated a viable animal model of human ARDS that is maintained for a prolonged period, suitable for continuous monitoring of the progression, and evaluation of potential future treatments and procedures to reduce patient morbidity and mortality. To carry out this two-hit model, lung injury was induced through a combination of bronchoalveolar lavage and oleic acid administration and the disease process of ARDS is subsequently tracked through clinically relevant parameters such as respiratory mechanics, cytokine response, aretrial blood gas (ABG) changes, and observation of postmortem histopathologic changes. This promising new model has the capacity to successfully replicate human ARDS which is a well-known and notoriously multifactorial pathogenic process to reproduce experimentally for an extended period of time. The "two-hit model" is a viable and appropriate model for the research of novel treatments for ARDS.

АНТАГОНИСТ РЕЦЕПТОРОВ СИГМА-1, СОЕДИНЕНИЕ BD-1063, ПОДАВЛЯЕТ Са2+-ОТВЕТЫ, ВЫЗЫВАЕМЫЕ МОЛИКСАНОМ В МАКРОФАГАХ

Sigma-1 receptors are ubiquitous multifunctional ligand-operated molecular chaperones in the endoplasmic reticulum membrane with a unique history, structure, and pharmacological profile. Acting as chaperones, sigma-1 receptors modulate a wide range of cellular processes in health and disease, including Ca2+ signaling processes. The pharmacological analogue of oxidized glutathione, drug molixan®, is used as an immunomodulator and cytoprotector in the complex therapy of bacterial, viral and oncological diseases; effective in the prevention and treatment of coronavirus infection COVID-19. To elucidate the involvement of sigma-1 receptors in the effect of molixan on the intracellular Ca2+ concentration in macrophages and in the regulation of Ca2+ signaling processes in macrophages in general, the effect of the sigma-1 receptor selective antagonist, compound BD-1063, on Ca2+ responses induced by molixan in rat peritoneal macrophages was investigated. Using Fura-2AM microfluorimetry we have shown for the first time that compound BD-1063 significantly suppresses both Ca2+ mobilization from intracellular Ca2+ stores and subsequent store-dependent Ca2+ entry, induced by molixan in peritoneal macrophages. The data obtained indicate the involvement of sigma-1 receptors in the complex signaling cascade triggered by molixan and leading to intracellular Ca2+ concentration increase in macrophages. The results also suggest the involvement of sigma-1 receptors in the regulation of store-dependent Ca2+ entry in macrophages.

Gypenoside XVII Reduces Synaptic Glutamate Release and Protects against Excitotoxic Injury in Rats.

Excitotoxicity is a common pathological process in neurological diseases caused by excess glutamate. The purpose of this study was to evaluate the effect of gypenoside XVII (GP-17), a gypenoside monomer, on the glutamatergic system. In vitro, in rat cortical nerve terminals (synaptosomes), GP-17 dose-dependently decreased glutamate release with an IC50 value of 16 μM. The removal of extracellular Ca2+ or blockade of N-and P/Q-type Ca2+ channels and protein kinase A (PKA) abolished the inhibitory effect of GP-17 on glutamate release from cortical synaptosomes. GP-17 also significantly reduced the phosphorylation of PKA, SNAP-25, and synapsin I in cortical synaptosomes. In an in vivo rat model of glutamate excitotoxicity induced by kainic acid (KA), GP-17 pretreatment significantly prevented seizures and rescued neuronal cell injury and glutamate elevation in the cortex. GP-17 pretreatment decreased the expression levels of sodium-coupled neutral amino acid transporter 1, glutamate synthesis enzyme glutaminase and vesicular glutamate transporter 1 but increased the expression level of glutamate metabolism enzyme glutamate dehydrogenase in the cortex of KA-treated rats. In addition, the KA-induced alterations in the N-methyl-D-aspartate receptor subunits GluN2A and GluN2B in the cortex were prevented by GP-17 pretreatment. GP-17 also prevented the KA-induced decrease in cerebral blood flow and arginase II expression. These results suggest that (i) GP-17, through the suppression of N- and P/Q-type Ca2+ channels and consequent PKA-mediated SNAP-25 and synapsin I phosphorylation, reduces glutamate exocytosis from cortical synaptosomes; and (ii) GP-17 has a neuroprotective effect on KA-induced glutamate excitotoxicity in rats through regulating synaptic glutamate release and cerebral blood flow.

Targeting Therapeutic Windows for Rheumatoid Arthritis Prevention.

Rheumatoid arthritis (RA) is a worldwide public health problem. Interventions to delay or prevent the onset of RA have attracted much attention in recent years, and researchers are now exploring various prevention strategies. At present, there is still no unified consensus for RA prevention, but targeting therapeutic windows and implementing interventions for at-risk individuals are extremely important. Due to the limited number of clinical trials on pharmacologic interventions, further studies are needed to explore and establish optimal intervention regimens and effective measures to prevent progression to RA. In this review, we introduce the RA disease process and risk factors, and present research on the use of both Western and Chinese medicine from clinical perspectives regarding RA prevention. Furthermore, we describe several complete and ongoing clinical studies on the use of Chinese herbal formulae for the prevention of RA.

Deciphering the Key Players of the Bacterial Microbiota Associated with Aerial Crown Gall Tumors on Rhododendron: Insights into the Gallobiome

Tumorigenic agrobacteria are widespread plant pathogens causing crown gall and cane gall diseases in various agricultural crops. These pathogens genetically transform the host plant and thus form an ecological niche (galls) in which specific metabolites (i.e., opines) are produced. Opines provide the pathogen with multiple competitive advantages, but they can also be utilized by other bacteria colonizing galls. To gain a thorough understanding of disease processes and ecology, it is necessary to consider the pathogen in the context of its microbial environment within the diseased plant (i.e., the pathobiome). Therefore, in this study, we investigated the bacterial pathobiome associated with aerial crown gall tumors (gallobiome) on rhododendron. For this purpose, a combination of cultivation-dependent and cultivation-independent approaches were applied, which also involved development of a novel amplicon sequencing approach targeting the recA housekeeping gene. The 16S rRNA and recA gene amplicon sequencing clearly indicated that Rhizobium rhododendri and the group of Agrobacterium spp. primarily belonging to the so-called “rubi” clade were the dominant members of bacterial microbiota in rhododendron galls. While the tumor-inducing (Ti) plasmid-harboring R. rhododendri strains are causative agents of crown gall disease, Agrobacterium spp. strains isolated in this study were nonpathogenic and carried genes for the catabolism of opines, enabling these bacteria to efficiently colonize tumor tissue. Taken together, our results clearly showed that the tumorigenic R. rhododendri and nonpathogenic opine-catabolizing Agrobacterium spp. were the key players within the bacterial microbiota associated with aerial crown gall tumors on rhododendron. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .

The Role of Bacteria in Acute Oak Decline in South-West Poland.

The process of multifactorial oak disease has been of interest to scientists from all over the world for many years. Recently, a new phenomenon has been added to the model related to oak decline, acute oak dieback, which causes oak decline and was first described in the UK. This study presents research on this phenomenon in the area of the largest oak stand complex in Poland, the so-called Krotoszyn Plateau. This work was carried out in two stages. In the first stage, 54 trees were tested for the presence of bacteria using molecular biology (real-time PCR). Subsequently, a tissue fragment was taken for inoculation from the trees in which the presence of B. goodwinii and G. quercinecans bacteria was confirmed. The isolates obtained were used to test Koch's postulates and for biochemical analyses for Polish strains. In addition, the results obtained were also compared with the presence of A. biguttatus, which is considered a bacterial vector, which, in turn, confirmed that the bacteria responsible for the AOD phenomenon can also be present in trees not inhabited by this insect. The results obtained confirmed the presence of bacteria and their potential to cause necrosis in oaks, which fits into the model of the spiral disease that has been causing mass mortality of oaks in this naturally and economically valuable area since the 1980s.

Whole genome sequencing based analysis of inflammation biomarkers in the Trans-Omics for Precision Medicine (TOPMed) consortium.

Inflammation biomarkers can provide valuable insight into the role of inflammatory processes in many diseases and conditions. Sequencing based analyses of such biomarkers can also serve as an exemplar of the genetic architecture of quantitative traits. To evaluate the biological insight, which can be provided by a multi-ancestry, whole-genome based association study, we performed a comprehensive analysis of 21 inflammation biomarkers from up to 38 465 individuals with whole-genome sequencing from the Trans-Omics for Precision Medicine (TOPMed) program (with varying sample size by trait, where the minimum sample size was n = 737 for MMP-1). We identified 22 distinct single-variant associations across 6 traits-E-selectin, intercellular adhesion molecule 1, interleukin-6, lipoprotein-associated phospholipase A2 activity and mass, and P-selectin-that remained significant after conditioning on previously identified associations for these inflammatory biomarkers. We further expanded upon known biomarker associations by pairing the single-variant analysis with a rare variant set-based analysis that further identified 19 significant rare variant set-based associations with 5 traits. These signals were distinct from both significant single variant association signals within TOPMed and genetic signals observed in prior studies, demonstrating the complementary value of performing both single and rare variant analyses when analyzing quantitative traits. We also confirm several previously reported signals from semi-quantitative proteomics platforms. Many of these signals demonstrate the extensive allelic heterogeneity and ancestry-differentiated variant-trait associations common for inflammation biomarkers, a characteristic we hypothesize will be increasingly observed with well-powered, large-scale analyses of complex traits.

Quercetin-Loaded Bioglass Injectable Hydrogel Promotes m6A Alteration of Per1 to Alleviate Oxidative Stress for Periodontal Bone Defects.

Periodontal disease ranks third among noncommunicable illnesses, behind cancer and cardiovascular disease, and is closely related to the occurrence and progression of various systemic diseases. However, elucidating the processes of periodontal disease and promoting periodontal bone regeneration remains a challenge. Here, quercetin is demonstrated to reduce the oxidative stress state of orofacial mesenchymal stem cells (OMSCs) in vitro and to affect the osteogenic growth of OMSCs through molecular mechanisms that mediate the m6A change in Per1. Nevertheless, the limited therapeutic efficacy of systemic medication and the limitations of local medication resulting from the small, moist, and highly dynamic periodontal environment make it challenging to treat periodontal tissues with medication. Herein, a biosafe injectable hydrogel drug-controlled delivery system is constructed as a bone-enhancing factory and loaded with quercetin to treat oxidative stress injury in periodontal tissues. This drug-carrying system made up of nanoscale bioglass microspheres and a light-cured injectable hydrogel, allows effective drug particle loading and cementation in the dynamic and moist periodontal environment. Furthermore, the system demonstrates the ability to stimulate OMSCs osteogenic differentiation in a Per1-dependent manner, which ultimately promotes periodontal bone repair, suggesting that this system has potential for clinical periodontal therapy.

The potential for senotherapy as a novel approach to extend life quality in veterinary medicine

Cellular senescence, a condition where cells undergo arrest and can assume an inflammatory phenotype, has been associated with initiation and perpetuation of inflammation driving multiple disease processes in rodent models and humans. Senescent cells secrete inflammatory cytokines, proteins, and matrix metalloproteinases, termed the senescence associated secretory phenotype (SASP), which accelerates the aging processes. In preclinical models, drug interventions termed “senotherapeutics” selectively clear senescent cells and represent a promising strategy to prevent or treat multiple age-related conditions in humans and veterinary species. In this review, we summarize the current available literature describing in vitro evidence for senotheraputic activity, preclinical models of disease, ongoing human clinical trials, and potential clinical applications in veterinary medicine. These promising data to date provide further justification for future studies identifying the most active senotherapeutic combinations, dosages, and routes of administration for use in veterinary medicine.