Healthy and Osteoarthritis-Affected Joints Facing the Cellular Crosstalk.

Osteoarthritis (OA) is a chronic, progressive, severely debilitating, and multifactorial joint disease that is recognized as the most common type of arthritis. During the last decade, it shows an incremental global rise in prevalence and incidence. The interaction between etiologic factors that mediate joint degradation has been explored in numerous studies. However, the underlying processes that induce OA remain obscure, largely due to the variety and complexity of these mechanisms. During synovial joint dysfunction, the osteochondral unit undergoes cellular phenotypic and functional alterations. At the cellular level, the synovial membrane is influenced by cartilage and subchondral bone cleavage fragments and extracellular matrix (ECM) degradation products from apoptotic and necrotic cells. These "foreign bodies" serve as danger-associated molecular patterns (DAMPs) that trigger innate immunity, eliciting and sustaining low-grade inflammation in the synovium. In this review, we explore the cellular and molecular communication networks established between the major joint compartments-the synovial membrane, cartilage, and subchondral bone of normal and OA-affected joints.

From Low-Grade Inflammation in Osteoarthritis to Neuropsychiatric Sequelae: A Narrative Review.

Nowadays, osteoarthritis (OA), a common, multifactorial musculoskeletal disease, is considered to have a low-grade inflammatory pathogenetic component. Lately, neuropsychiatric sequelae of the disease have gained recognition. However, a link between the peripheral inflammatory process of OA and the development of neuropsychiatric pathology is not completely understood. In this review, we provide a narrative that explores the development of neuropsychiatric disease in the presence of chronic peripheral low-grade inflammation with a focus on its signaling to the brain. We describe the development of a pro-inflammatory environment in the OA-affected joint. We discuss inflammation-signaling pathways that link the affected joint to the central nervous system, mainly using primary sensory afferents and blood circulation via circumventricular organs and cerebral endothelium. The review describes molecular and cellular changes in the brain, recognized in the presence of chronic peripheral inflammation. In addition, changes in the volume of gray matter and alterations of connectivity important for the assessment of the efficacy of treatment in OA are discussed in the given review. Finally, the narrative considers the importance of the use of neuropsychiatric diagnostic tools for a disease with an inflammatory component in the clinical setting.

Inflammatory Cytokine-Producing Cells and Inflammation Markers in the Synovium of Osteoarthritis Patients Evidenced in Human Herpesvirus 7 Infection.

A direct association between joint inflammation and the progression of osteoarthritis (OA) has been proposed, and synovitis is considered a powerful driver of the disease. Among infections implicated in the development of joint disease, human herpesvirus 7 (HHV-7) infection remains poorly characterized. Therefore, we assessed synovitis in OA patients; determined the occurrence and distribution of the HHV-7 antigen within the synovial membrane of OA-affected subjects; and correlated plasma levels of the pro-inflammatory cytokines tumor necrosis factor (TNF), interleukin-6 (IL-6), and TNF expressed locally within lesioned synovial tissues with HHV-7 observations, suggesting differences in persistent latent and active infection. Synovial HHV-7, CD4, CD68, and TNF antigens were detected immunohistochemically. The plasma levels of TNF and IL-6 were measured by an enzyme-linked immunosorbent assay. Our findings confirm the presence of persistent HHV-7 infection in 81.5% and reactivation in 20.5% of patients. In 35.2% of patients, virus-specific DNA was extracted from synovial membrane tissue samples. We evidenced the absence of histopathologically detectable synovitis and low-grade changes in the majority of OA patients enrolled in the study, in both HHV-7 PCR+ and HHV-7 PCR‒ groups. The number of synovial CD4-positive cells in the HHV-7 polymerase chain reaction (PCR)+ group was significantly higher than that in the HHV-7 PCR‒ group. CD4- and CD68-positive cells were differently distributed in both HHV-7 PCR+ and HHV-7 PCR‒ groups, as well as in latent and active HHV-7 infection. The number of TNF+ and HHV-7+ lymphocytes, as well as HHV-7+ vascular endothelial cells, was strongly correlated. Vascular endothelial cells, especially in the case of infection reactivation, appeared vulnerable. The balance between virus latency and reactivation is a long-term relationship between the host and infectious agent, and the immune system appears to be involved in displaying overreaction when a shift in the established equilibrium develops.

Upregulated tissue expression of T helper (Th) 17 pathogenic interleukin (IL)-23 and IL-1ß in Hashimoto's thyroiditis but not in Graves' disease.

T helper (Th) 17 cells and interleukin (IL)-17 play a significant role in the pathogenesis of autoimmune thyroid disease (AITD). However, it has recently become clear that Th17 cells are more heterogeneous and exhibit two different phenotypes, whereas IL-23 and IL-1ß are crucial for the generation of pathogenic Th17 lymphocytes. We aimed to investigate the association between IL-17 and Th17-promoting cytokines in AITD by studying the immunoexpression patterns of IL-17, IL-23, and IL-1ß in thyroid tissue. Following thyroidectomy, 29 patients with AITD (21 cases of Hashimoto's thyroiditis (HT) and 8 cases of Graves' disease (GD)) and 18 patients with colloid goiter, as controls, were enrolled in this study, and immunohistochemistry was performed. The expression level of IL-17 in thyrocytes was significantly higher in HT and GD patients than in colloid goiter patients. Immunopositivity for both IL-23 and IL-1ß was significantly increased in HT patients compared to GD and colloid goiter patients. However, no difference was found between IL-23 or IL-1ß expression in patients with GD and colloid goiter. A positive correlation between IL-17 and IL-23 as well as IL-17 and IL-1ß expression was observed in HT patients (r = 0.574, p = 0.007 and r = 0.461, p = 0.036, respectively). In the GD group, IL-17 was positively correlated with IL-1ß (r = 0.817, p = 0.013) but not with IL-23 expression. We found increased IL-23 and IL-1ß expression in the HT group but not in the GD group. Furthermore, both interleukins were correlated with IL-17 immunopositivity in thyroid tissue, suggesting that pathogenic Th17-promoting cytokines may play a role in HT pathogenesis.

Detection frequency of human herpesviruses-6A, -6B, and -7 genomic sequences in central nervous system DNA samples from post-mortem individuals with unspecified encephalopathy.

In this autopsy-based study, human herpesvirus-6 (HHV-6) and -7 (HHV-7) genomic sequence frequency, HHV-6 variants, HHV-6 load and the expression of HHV-6 antigens in brain samples from the individuals, with and without unspecified encephalopathy (controls), using nested and real-time polymerase chain reactions, restriction endonuclease, and immunohistochemical analysis were examined. GraphPad Prism 6.0 Mann-Whitney nonparametric and chi-square test and Fisher's exact test were used for statistical analysis. The encephalopathy diagnoses were shown by magnetic resonance imaging made during their lifetime and macro- and microscopically studied autopsy tissue materials. Widespread HHV-6 and/or HHV-7 positivity was detected in the brain tissue of various individuals with encephalopathy, as well as in controls (51/57, 89.4 % and 35/51, 68.6 %, respectively; p = 0.009). Significantly higher detection frequency of single HHV-6 and concurrent HHV-6 + HHV-7 DNA was found in pia mater meninges, frontal lobe, temporal lobe, and olfactory tract DNAs in individuals with encephalopathy compared to the control group. HHV-6 load and higher frequency of the viral load >10 copies/10(6) cells significantly differed in samples from individuals with and without encephalopathy. The expression of HHV-6 antigens was revealed in different neural cell types with strong predominance in the encephalopathy group. In all HHV-6-positive autopsy samples of individuals with and without encephalopathy, HHV-6B was revealed. Significantly higher detection frequency of beta-herpesvirus DNA, more often detected HHV-6 load >10 copies/10(6) cells, as well as the expression of HHV-6 antigens in different brain tissue samples from individuals with encephalopathy in comparison with control group indicate on potential involvement of these viruses in encephalopathy development.

From Biomechanical Properties to Morphological Variations: Exploring the Interplay between Aortic Valve Cuspidity and Ascending Aortic Aneurysm.

Background: This research explores the biomechanical and structural characteristics of ascending thoracic aortic aneurysms (ATAAs), focusing on the differences between bicuspid aortic valve aneurysms (BAV-As) and tricuspid aortic valve aneurysms (TAV-As) with non-dilated aortas to identify specific traits of ATAAs. Methods: Clinical characteristics, laboratory indices, and imaging data from 26 adult patients operated on for aneurysms (BAV-A: n = 12; TAV-A: n = 14) and 13 controls were analyzed. Biomechanical parameters (maximal aortic diameter, strain, and stress) and structural analyses (collagen fiber organization, density, fragmentation, adipocyte deposits, and immune cell infiltration) were assessed. Results: Significant differences in biomechanical parameters were observed. Median maximal strain was 40.0% (control), 63.4% (BAV-A), and 45.3% (TAV-A); median maximal stress was 0.59 MPa (control), 0.78 MPa (BAV-A), and 0.48 MPa (TAV-A). BAV-A showed higher tangential modulus and smaller diameter, with substantial collagen fragmentation (p < 0.001 vs. TAV and controls). TAV-A exhibited increased collagen density (p = 0.025), thickening between media and adventitia layers, and disorganized fibers (p = 0.036). BAV-A patients had elevated adipocyte deposits and immune cell infiltration. Conclusions: This study highlights distinct pathological profiles associated with different valve anatomies. BAV-A is characterized by smaller diameters, higher biomechanical stress, and significant collagen deterioration, underscoring the necessity for tailored clinical strategies for effective management of thoracic aortic aneurysm.

Hydroxymethylglutaryl-CoA reductase activity is essential for mitochondrial ß-oxidation of fatty acids to prevent lethal accumulation of long-chain acylcarnitines in the mouse liver.

BACKGROUND AND PURPOSE: Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGCR), and exert adverse effects on mitochondrial function, although the mechanisms underlying these effects remain unclear. We used a tamoxifen-induced Hmgcr-knockout (KO) mouse model, a multi-omics approach and mitochondrial function assessments to investigate whether decreased HMGCR activity impacts key liver energy metabolism pathways. EXPERIMENTAL APPROACH: We established a new mouse strain using the Cre/loxP system, which enabled whole-body deletion of Hmgcr expression. These mice were crossed with Rosa26Cre mice and treated with tamoxifen to delete Hmgcr in all cells. We performed transcriptomic and metabolomic analyses and thus evaluated time-dependent changes in metabolic functions to identify the pathways leading to cell death in Hmgcr-KO mice. KEY RESULTS: Lack of Hmgcr expression resulted in lethality, due to acute liver damage caused by rapid disruption of mitochondrial fatty acid ß-oxidation and very high accumulation of long-chain (LC) acylcarnitines in both male and female mice. Gene expression and KO-related phenotype changes were not observed in other tissues. The progression to liver failure was driven by diminished peroxisome formation, which resulted in impaired mitochondrial and peroxisomal fatty acid metabolism, enhanced glucose utilization and whole-body hypoglycaemia. CONCLUSION AND IMPLICATIONS: Our findings suggest that HMGCR is crucial for maintaining energy metabolism balance, and its activity is necessary for functional mitochondrial ß-oxidation. Moreover, statin-induced adverse reactions might be rescued by the prevention of LC acylcarnitine accumulation.

Protective reactivity and alteration of the brain tissue in alcoholics evidenced by SOD1, MMP9 immunohistochemistry, and electron microscopy.

Alcohol and its associated oxidative stress is one of the widespread contributors to the brain damage. Matrix metalloproteinases, which are extensively analyzed in brain pathology studies, are not sufficiently investigated in chronic alcohol consumption. This study evaluated regional brain damage caused by oxidative stress. Contribution of metalloproteinase-9 to this affection was evidenced in alcoholic subjects and correlated with ultrastructural changes. The authors found correlation between neuronal expression patterns of superoxide dismutase-1 and metalloproteinase-9 in nigral (r = 0.532, p < 0.001), striatal (r = 0.327, p < 0.001), and cortical (r = 0.306, p < 0.001) regions, and a significant decrease of nigral superoxide dismutase-1 median values accompanied by severe myelin damage.

Evaluation of Clinical Manifestations of Hemorrhoidal Disease, Carried Out Surgeries and Prolapsed Anorectal Tissues: Associations with ABO Blood Groups of Patients.

Hemorrhoidal disease (HD) is a chronic multifactorial disease. Increased abdominal pressure, along with hyperperfusion, neovascularization, overexpression of inflammatory mediators, and dysbiosis, contributes to the development of HD. The deterioration of the anchoring connective tissue with reduced collagen content and altered collagen ratios, dilatation of blood vessels and thrombosis, muscle injury, and inflammation gradually lead to clinically manifesting prolapse and bleeding from hemorrhoids. The associations of the ABO blood types with a disease have been investigated for the upper gastrointestinal tract only. This study aimed to evaluate HD clinical manifestations, surgeries carried out, and the status of prolapsed anorectal tissues by exploring the associations with the patients' ABO blood groups. Clinical and various morphological methods, combined with extensive bioinformatics, were used. The blood type 0, grade III and IV HD individuals constituted the largest group in a moderately-sized cohort of equally represented males and females studied and submitted to surgical treatment of hemorrhoids. There were significantly more complaints reported by HD females compared to males (p = 0.0094). The Longo technique appeared mostly used, and there were proportionally more surgeries performed below the dentate line for HD individuals with blood type 0 compared to other blood type patients (24% vs. 11%). HD males were found to present with significantly more often inflamed rectal mucosa (p < 0.05). Loosening and weakening of collagenous components of the rectal wall combined with vascular dilation and hemorrhage was found to differ in 0 blood type HD individuals compared to other types. HD males were demonstrated to develop the ruptures of vascular beds significantly more often when compared to HD females (p = 0.0165). Furthermore, 0 blood type HD males were significantly more often affected by a disease manifested with tissue hemorrhage compared to the 0 blood type HD females (p = 0.0081). Collectively, the local status of chronically injured anorectal tissue should be considered when applying surgical techniques. Future studies could include patients with HD grades I and II to gain a comprehensive understanding of the disease progression, allowing for a comparison of tissue changes at different disease stages.

The Role of the p16 and p53 Tumor Suppressor Proteins and Viral HPV16 E6 and E7 Oncoproteins in the Assessment of Survival in Patients with Head and Neck Cancers Associated with Human Papillomavirus Infections.

The role of HPV in the survival prognosis of patients with head and neck squamous cell carcinoma, especially patients with laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC), is still somewhat ambiguous. The present study aimed to explore the significance of tumor suppressor proteins and HPV16 E6 and E7 oncoproteins in the assessment of survival in patients with oropharyngeal squamous cell carcinoma (OPSCC), LSCC, and HPSCC associated with high-risk (HR-) and low-risk (LR-) HPV infections. By utilizing molecular and immunohistochemical investigations of HNSCC samples and patient data, univariate and multivariate survival analyses were conducted. The presence of HPV DNA (LR- and HR-HPV) was associated with a better 5-year OS and DSS for OPSCC and LSCC. The IHC overexpression of HPV16 E6 protein and p16 protein was associated with better survival in the univariate (for OPSCC) and multivariate (OPSCC and HPSCC) survival analyses. The overexpression of p53 was associated with better survival in OPSCC. HPV infection plays a significant role in the tumorigenesis of HNSCC, and the immunohistochemical assessment of HPV16 E6 protein expression should be interpreted as a useful prognostic marker for OPSCC and HPSCC.

Understanding Bartonella-Associated Infective Endocarditis: Examining Heart Valve and Vegetation Appearance and the Role of Neutrophilic Leukocytes.

BACKGROUND: The endocardium and cardiac valves undergo severe impact during infective endocarditis (IE), and the formation of vegetation places IE patients at a heightened risk of embolic complications and mortality. The relevant literature indicates that 50% of IE cases exhibit structurally normal cardiac valves, with no preceding history of heart valve disease. Gram-positive cocci emerge as the predominant causative microorganisms in IE, while Gram-negative Bartonella spp., persisting in the endothelium, follow pathogenic pathways distinct from those of typical IE-causing agents. Employing clinical as well as advanced microbiological and molecular assays facilitated the identification of causative pathogens, and various morphological methods were applied to evaluate heart valve damage, shedding light on the role of neutrophilic leukocytes in host defense. In this research, the immunohistochemical analysis of neutrophilic leukocyte activation markers such as myeloperoxidase, neutrophil elastase, calprotectin, and histone H3, was performed. A distinct difference in the expression patterns of these markers was observed when comparing Bartonella spp.-caused and non-Bartonella spp.-caused IE. The markers exhibited significantly higher expression in non-Bartonella spp.-caused IE compared to Bartonella spp.-caused IE, and they were more prevalent in vegetation than in the valvular leaflets. Notably, the expression of these markers in all IE cases significantly differed from that in control samples. Furthermore, we advocated the use of 16S rRNA Next-Generation Sequencing on excised heart valves as an effective diagnostic tool for IE, particularly in cases where blood cultures yielded negative results. The compelling results achieved in this study regarding the enigmatic nature of Bartonella spp. IE's pathophysiology contribute significantly to our understanding of the peculiarities of inflammation and immune responses.

Alcoholism and cellular vulnerability in different brain regions.

Alcohol-induced damage causes dysfunction of selected brain regions. Multidisciplinary studies have provided an extensive description of changes observed in neurons and glia following alcohol consumption. In this study the authors have elucidated preferential cellular vulnerability in three different brain regions. Autopsy material of the prefrontal cortex, striatum, and substantia nigra obtained from the brain tissue of alcoholic subjects was used in this study. We found that dendritic tree and astroglial damage is irreversible, while neuronal somata and most axons do not display irreversible changes.

Serum Vitamin D Levels Explored in the Latvian Cohort of Patients with Basal Cell Carcinoma Linked to the Sonic Hedgehog and Vitamin D Binding Protein Cutaneous Tissue Indices.

Ultraviolet radiation is known as one of the major contributors to skin malignancies, including basal cell carcinoma (BCC), which is the most common type of skin cancer. It is a heterogeneous tumor, which presents with various types that are stratified into low- and high-risk tumors. Sunlight is important for overall health and vitamin D synthesis in the skin, whereas deviations from the optimal level of vitamin D are shown to be associated with the risk of the development of BCC. The accumulating evidence suggests the ability of vitamin D to antagonize the Sonic Hedgehog (SHH) signaling, the key tumor pathway, and play a protective role in the development of BCC. Additionally, a vitamin D binding protein (DBP) is shown to be implicated in the complex regulation of vitamin D. Here, we aimed to explore serum vitamin D in patients with different primary and recurrent BCC of the head and neck and investigate cutaneous DBP and SHH indices, confirmed immunohistochemically in these subjects. According to the results, 94.9% of the Latvian cohort of BCC patients were found to be deficient in vitamin D. No significant differences in serum vitamin D levels were found between genders, primary and recurrent tumors, and different types of BCC. Serum vitamin D was inversely associated with tumor size. Susceptible male individuals with low blood vitamin D levels were recognized at risk of developing aggressive and recurrent BCC confirmed by the use of hierarchical clustering analysis. In smaller tumors with a favorable course, such as superficial and nodular BCC, the association between high DBP and low SHH tissue expression was found, providing supportive evidence of the existence of a link between vitamin D, proteins involved in its metabolism, as exemplified by the DBP and SHH signaling pathway. The assumption of a deficiency in the protective effect of vitamin D in patients with high-risk BCCs was proposed in low DBP and high SHH tissue indices. New extensions to existing knowledge and characterization of the BCC signaling pathways and their cross-talk with vitamin D are warranted when searching for a preferential effect of vitamin D on skin cancer.

Etiology, Risk Factors and Clinical Outcomes in Infective Endocarditis Patients Requiring Cardiac Surgery.

BACKGROUND: Infective endocarditis, which may be caused by various microbial agents, severely affects the innermost layer of the heart and often leads to poor clinical outcomes. The purpose of this study was to investigate the etiology, risk factors and short and long-term outcomes of infective endocarditis caused by various bacterial agents in patients requiring cardiac surgery. METHODS: One hundred and forty-four patients aged 18 years or above with indications for cardiac surgery due to S. aureus, Streptococcus spp., E. faecalis or coagulase-negative staphylococci caused infective endocarditis were included in this study. RESULTS: S. aureus, Streptococcus spp., E. faecalis and coagulase-negative staphylococci were the causative agents of infective endocarditis in 44 (30.6%), 35 (24.3%), 33 (22.9%) and 32 (22.2%) patients, respectively. The presence of bicuspid aortic valve was the most common predisposing factor confirmed in 19 (23.5%), whereas intravenous drug usage was the most common in 17 (11.8%) patients. No significant differences in intrahospital mortality due to infective endocarditis caused by various bacterial agents were found, however, the worsening of long-term prognosis of endocarditis caused by S. aureus when compared to E. faecalis was confirmed (p = 0.03). The presence of S. aureus was associated with significantly higher rates of embolic complications (p = 0.003). The presence of coagulase-negative staphylococci was associated with prosthetic valve endocarditis (p = 0.015) and perivalvular complications (p = 0.024). CONCLUSIONS: In contrast to E. faecalis, the presence of S. aureus determines the worsening of the long-term mortality from infective endocarditis. Perivalvular complications are associated with the presence of coagulase-negative staphylococci.

Risk factors associated with mortality in the infective endocarditis patients requiring cardiac surgery: a study based on Latvian population.

BACKGROUND: Increased life expectancy, developments in medicine and intracardiac devices, accessibility of cardiac surgery, decrease in the prevalence of rheumatic heart disease are changing infective endocarditis patient profile and thus risk factors for the adverse events. This single-center-based study covering the whole Latvian population aimed to assess the intrahospital and 3-year mortality of infective endocarditis patients who underwent cardiac surgery, as well as risk factors and laboratory indices predictive of adverse outcomes of the disease. METHODS: Clinical profiles, data of laboratory and instrumental analyses, operation and intensive care unit records of cardiac surgery patients treated in Pauls Stradins Clinical University Hospital, Riga, Latvia, between 2015 and 2019 were analyzed. RESULTS: We analyzed data from 242 episodes of surgically treated infective endocarditis in 233 patients. The median age of patients was 57.00 (45.00-68.00) years. The rate of intrahospital mortality was 11.16%. Risk factors associated with mortality in the univariate analyses were S. aureus infection (HR=2.27, 95% CI: 1.36-3.80; P=0.002) and systemic embolization of vegetations (HR=1.63, 95% CI: 1.00-2.64; P=0.048). Perivalvular complications (HR=1.98, 95% CI: 1.19-3.29; P=0.009) were found to be independently associated with mortality in multivariate analysis (HR=1.99, 95% CI: 1.05-3.78; P=0.035). One-year survival was 78.3%, whereas three-year -71.3%. CONCLUSIONS: Intrahospital mortality of surgically treated IE patients was 11.2%; however, one- and three-year mortality was 21.7 and 28.7%, respectively. Perivalvular complications were independently associated with mortality. Laboratory indices were not predictive of adverse outcomes.

Prevalence, Cell Tropism, and Clinical Impact of Human Parvovirus Persistence in Adenomatous, Cancerous, Inflamed, and Healthy Intestinal Mucosa.

Parvoviruses are single-stranded DNA viruses, infecting many animals from insects to humans. Human parvovirus B19 (B19V) causes erythema infectiosum, arthropathy, anemia, and fetal death, and human bocavirus (HBoV) 1 causes respiratory tract infections, while HBoV2-4 are enteric. Parvoviral genomes can persist in diverse non-permissive tissues after acute infection, but the host-cell tropism and the impact of their tissue persistence are poorly studied. We searched for parvoviral DNA in a total of 427 intestinal biopsy specimens, as paired disease-affected and healthy mucosa, obtained from 130 patients with malignancy, ulcerative colitis (UC), or adenomas, and in similar intestinal segments from 55 healthy subjects. Only three (1.6%) individuals exhibited intestinal HBoV DNA (one each of HBoV1, 2, and 3). Conversely, B19V DNA persisted frequently in the intestine, with 50, 47, 31, and 27% detection rates in the patients with malignancy, UC, or adenomas, and in the healthy subjects, respectively. Intra-individually, B19V DNA persisted significantly more often in the healthy intestinal segments than in the inflamed colons of UC patients. The highest loads of B19V DNA were seen in the ileum and colon specimens of two healthy individuals. With dual-RNAscope in situ hybridization and immunohistochemistry assays, we located the B19V persistence sites of these intestines in mucosal B cells of lymphoid follicles and vascular endothelial cells. Viral messenger RNA transcription remained, however, undetected. RNA sequencing (RNA-seq) identified 272 differentially expressed cellular genes between B19V DNA-positive and -negative healthy ileum biopsy specimens. Pathway enrichment analysis revealed that B19V persistence activated the intestinal cell viability and inhibited apoptosis. Lifelong B19V DNA persistence thus modulates host gene expression, which may lead to clinical outcomes.

Plexus brachialis strain and compression deformation in the costo-axillary-brachial region: a cadaveric study.

OBJECTIVE: The aim of this study was to clarify the role of different mechanisms in nerve injury during arm abduction positions. The tasks were to determine the strain deformation of the plexus brachialis during arm abduction, to measure the pressures in the neurovascular bundle in the cervico-costoclavicular-axillary area, and evaluate the histological changes of nerve after the stretch test. MATERIAL AND METHODS: During the cadaveric study on 7 specimens 7-20 h after death, strain deformation of plexus brachialis as well as compression deformation caused by the surrounding structures of the neurovascular bundle were investigated in the arm abduction position of 0°, 90°, 12°, 150°, and 180°. One nerve sample was studied histologically after 15% stretch on the bench. RESULTS: The relative strain deformation of 3%-23% was documented during 0° to 180° abduction tests. The strain deformation from 0° to 90° was significant (P<0.001). The mean pressure change in the bundle was 13.6 mm Hg at 90°, 53.7 mm Hg at 120°, 73.4 mm Hg at 150°, and 89.0 mm Hg at 180° arm abduction. An increase in pressure was significant in the intervals: 0°-90° (P<0.001), 91°-120° (P<0.001), 121°-150° (P<0.001) and 151°-180° (P<0.05). CONCLUSIONS: Nerve traction and tissue compression arising during the arm abduction above 90° were found to be sufficient to induce lesions in neural bundles of the plexus brachialis.

Identification of High-Risk Human Papillomavirus DNA, p16, and E6/E7 Oncoproteins in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas.

Human papillomavirus (HPV) was proven to play a significant role in cancer development in the oropharynx. However, its role in the development of laryngeal (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC) remains to be clarified. High-risk HPV (HR-HPV) viral proteins E6 and E7 are considered to be pertinent to HPV-related carcinogenesis. Hence, our aim was to estimate LSCC and HPSCC for HR-HPV DNA, p16, and E6/E7 oncoprotein status by using molecular virology and immunohistochemistry methods. The prevalence of HPV16 infection was 22/41 (53.7%) and 20/31 (64.5%) for LSCC and HPSCC, accordingly. The majority of HPV16+ tumor samples were stage III or IV. In most samples, the presence of either HPV16 E6 or HPV16 E7 viral protein in dysplastic or tumor cells was confirmed using immunohistochemistry. Our results suggest a high prevalence of HPV16 as a primary HR-HPV type in LSCC and HPSCC. The lack of HPV E6/E7 oncoproteins in some tumor samples may suggest either the absence of viral integration or the presence of other mechanisms of tumorigenesis. The utilization of p16 IHC as a surrogate marker of HR-HPV infection is impractical in LSCC and HPSCC.

Plasma levels of Th17-associated cytokines and selenium status in autoimmune thyroid diseases.

INTRODUCTION: The contribution of Th17 cytokines to autoimmune thyroid disease (AITD) is generally accepted. However, the roles of Th17 cells in the initiation and progression of Hashimoto's thyroiditis (HT) and Graves' disease (GD) remain unclear. Selenium deficiency, along with genetic predisposition and environmental factors, may have a role in thyroid autoimmunity. AIM: We aimed to assess (1) the Th17 immune response by measuring plasma levels of Th17- and Treg-associated cytokines and (2) the selenium status in treatment-naïve Latvian patients with newly diagnosed GD or HT. METHODS: Eleven GD patients, 41 HT patients, and 26 healthy subjects were recruited for this study. Plasma levels of IL-17a, IL-22, IL-23, IL-6, and IL-10 were detected by xMAP technology, while selenium was detected fluorometrically. RESULTS AND CONCLUSIONS: No significant differences in IL-17a, IL-22, IL-23, IL-6, or IL-10 levels were found among the HT patients, GD patients, and controls. In the HT patients, IL-17a levels were positively correlated with IL-22, IL-23, IL-6, and IL-10, while IL-22 was correlated with IL-6, IL-23, and IL-10. In the GD patients, IL-17a levels were positively correlated with IL-22, IL-23, and IL-10; IL-22 was positively correlated with IL-23, IL-6, and IL-10; FT3 was positively correlated with IL-17a, IL-23, and IL-10; and FT4 was positively correlated with IL-17a and IL-10 levels. Plasma selenium levels were negatively correlated with antithyroid peroxidase antibody titers in the HT patients. Although no difference in selenium levels was observed between the AITD patients and controls, the selenium status of the Latvian patients with GD or HT was at a suboptimal level.

Low cardiac content of long-chain acylcarnitines in TMLHE knockout mice prevents ischaemia-reperfusion-induced mitochondrial and cardiac damage.

Increased tissue content of long-chain acylcarnitines may induce mitochondrial and cardiac damage by stimulating ROS production. N6-trimethyllysine dioxygenase (TMLD) is the first enzyme in the carnitine/acylcarnitine biosynthesis pathway. Inactivation of the TMLHE gene (TMLHE KO) in mice is expected to limit long-chain acylcarnitine synthesis and thus induce a cardio- and mitochondria-protective phenotype. TMLHE gene deletion in male mice lowered acylcarnitine concentrations in blood and cardiac tissues by up to 85% and decreased fatty acid oxidation by 30% but did not affect muscle and heart function in mice. Metabolome profile analysis revealed increased levels of polyunsaturated fatty acids (PUFAs) and a global shift in fatty acid content from saturated to unsaturated lipids. In the risk area of ischemic hearts in TMLHE KO mouse, the OXPHOS-dependent respiration rate and OXPHOS coupling efficiency were fully preserved. Additionally, the decreased long-chain acylcarnitine synthesis rate in TMLHE KO mice prevented ischaemia-reperfusion-induced ROS production in cardiac mitochondria. This was associated with a 39% smaller infarct size in the TMLHE KO mice. The arrest of the acylcarnitine biosynthesis pathway in TMLHE KO mice prevents ischaemia-reperfusion-induced damage in cardiac mitochondria and decreases infarct size. These results confirm that the decreased accumulation of ROS-increasing fatty acid metabolism intermediates prevents mitochondrial and cardiac damage during ischaemia-reperfusion.