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Winter ulcer disease (WUD) is widely recognized as a serious threat to animal welfare and a major contributor to revenue loss within the aquaculture sector, particularly affecting the salmon-farming industry. This highlights the significant impact of WUD on both animal well-being and the economic sustainability of fish farming. WUD causes hemorrhagic signs and results in dermal lesions and ulcers. This disease can lead to higher mortality rates and a considerable decline in the fish's market value. Moritella viscosa, a Gram-negative bacterium, is predominantly, but not exclusively, correlated with the emergence of WUD, mostly during the colder seasons. Waterborne transmission is the primary way for spreading the bacterium within a population. However, there is remarkable variation in the prevalence and characteristics of WUD in different regions. In Europe, this disease often occurs in the winter, and the intensity and occurrence of outbreaks are influenced by water temperature and salinity. In contrast, outbreaks are typically observed in the summer and mid-autumn in Eastern Canada. Despite the administration of various polyvalent vaccines, outbreaks of skin ulcers have been documented in Canada, and studies have highlighted the possible roles of other bacterial pathogens in Atlantic salmon. This review discusses the etiology, pathogenesis, and potential mitigation or prevention strategies for WUD, mainly in Atlantic salmon. Moreover, it underscores the necessity of conducting further investigations to discover the potential unknown causative agents of ulcerative disease and design appropriate vaccines or preventive strategies for these pathogens. [ABSTRACT FROM AUTHOR]

AIM: To investigate the mechanism of hyperplasia of mammary gland (HMG) and the potential differential metabolites in rats based on the serum metabolomics assessment by liquid chromatography-mass spectrometry (LC-MS). METHODS: Twelve specific-pathogen-free (SPF)-grade female Wistar rats were randomly and equally assigned to the normal and model groups. The model group received intramuscular injections of estradiol benzoate (0. 5 mg⋅kg-1⋅d-1) for 21 d, followed by intramuscular injections of progesterone (4 mg⋅kg-1⋅d-1) for 7 d for preparing the HMG model. The body weight and nipple diameter of the rats were measured, and the histopathological changes in their mammary gland were monitored. After the successful establishment of the model, rat serum was collected for LC-MS metabolomics analysis, the differential metabolites in the serum of the normal and model group rats were analyzed by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), and the metabolic pathway analysis of differential markers through the Kyoto Encyclopedia of Genes and Genomes (KEGG) open database was performed. RESULTS: Compared with the normal rats in the control group, no significant change was observed in the body weight (P> 0. 05), the diameter of the nipple was significantly enlarged (P<0. 01), the hematoxylin-eosin (HE) staining section of the mammary gland displayed typical HMG morphology, which together indicated that the modeling was successful. The metabolic patterns of the serum samples from both groups were significantly different, and 30 potentially differential metabolites were identified based on the variable importance in projection (VIP)≥2. 0 and P<0. 05, mainly including 3-dehydro-cholic acid, alcoholic acid, glycocholate-3-sulfate, glycine-deoxycholan-3-sulfate, glycine-deoxycholan-3-sulfate, 3a, 7b, and 12a trihydroxycholan-3-sulfate, cholic acid, and glycolic acid. Further receiver operating characteristic (ROC) analysis revealed that the area under the curve (AUC) of the 13 metabolites was >0. 9, implying the possible high sensitivity for the diagnosis of HMG. According to the KEGG pathway enrichment analysis, most of the differential metabolites were mainly concentrated in aldosterone synthesis and secretion, sphingomyelin metabolism, arachidonic acid metabolism, apoptosis and cholesterol metabolism. CONCLUSION: The pathogenesis of estrogen- and progesterone-induced HMG in rats may be related to the altered bile acids, their derivatives metabolism, and the lipid metabolism pathways. The 13 differential metabolites identified by serum metabolomics with high sensitivity may thus provide a reference for the diagnosis of HMG. [ABSTRACT FROM AUTHOR]

Aim: This study aims to evaluate the changes that may occur in the morphology of the anal sphincter muscles in hemorrhoidal disease. The relationship between the somatotype features of individuals and the disease was also evaluated. Materials and Methods: The study was conducted with 76 stage IV hemorrhoidal disease patients and 75 controls. Internal (IAS) and external (EAS) anal sphincter muscle thicknesses were measured at the middle anal canal level, and in four quadrants (anterior, posterior, right, left), puborectalis muscle thicknesses were measured at the upper anal canal level and in two quadrants (right, left) by using 3D-endoanal ultrasonography (3DEAUSG). Anal triangle dimensions were measured with a digital caliper and the area was calculated with the relevant formula. The somatotype features were determined using the Heath-Carter formula. Results: It was observed that the external anal sphincter muscle thicknesses were higher in the right and posterior quadrants of the patients compared to the control group. The internal anal sphincter muscle thicknesses were thicker in the right and anterior quadrants in the patient group. Somatotype features of individuals in the patient and control groups were similar. Conclusion: The thickening in some quadrants of the anal sphincter muscles in the patient group can be considered a result of hemorrhoidal disease. However, the fact that there is no difference the mean value cannot confirm its relationship with the disease. Therefore, it can be concluded that individual somatotype differences do not affect pathogenesis of hemorrhoidal disease. [ABSTRACT FROM AUTHOR]

Genome sequencing has revealed frequent mutations in Ras homolog family member A (RHOA) among various cancers with unique aberrant profiles and pathogenic effects, especially in peripheral T-cell lymphoma (PTCL). The discrete positional distribution and types of RHOA amino acid substitutions vary according to the tumor type, thereby leading to different functional and biological properties, which provide new insight into the molecular pathogenesis and potential targeted therapies for various tumors. However, the similarities and discrepancies in characteristics of RHOA mutations among various histologic subtypes of PTCL have not been fully elucidated. Herein we highlight the inconsistencies and complexities of the type and location of RHOA mutations and demonstrate the contribution of RHOA variants to the pathogenesis of PTCL by combining epigenetic abnormalities and activating multiple downstream pathways. The promising potential of targeting RHOA as a therapeutic modality is also outlined. This review provides new insight in the field of personalized medicine to improve the clinical outcomes for patients. [ABSTRACT FROM AUTHOR]

Oropouche fever caused by Oropouche virus (OROV) is a significant zoonosis in Central and South America. Despite its public health significance, we lack high-throughput diagnostics, therapeutics, and a comprehensive knowledge of OROV biology. Reporter viruses are valuable tools to rapidly study virus dynamics and develop neutralization and antiviral screening assays. OROV is a tri-segmented bunyavirus, which makes generating a reporter virus challenging, as introducing foreign elements into the viral genome typically affects fitness. We previously demonstrated that the non-structural gene NSm on the OROV medium (M) segment is non-essential for replication in vitro. Taking advantage of this, we have now generated a recombinant OROV expressing fluorescent protein ZsGreen in place of NSm. This reporter OROV is both stable and pathogenic in IFNAR-/- mice and provides a powerful tool for OROV pathogenesis studies and assay development. IMPORTANCE Emerging and reemerging infectious agents such as zoonotic bunyaviruses are of global health concern. Oropouche virus (OROV) causes recurring outbreaks of acute febrile illness in the Central and South American human populations. Biting midges are the primary transmission vectors, whereas sloths and non-human primates are their reservoir hosts. As global temperatures increase, we will likely see an expansion in arthropod-borne pathogens such as OROV. Therefore, developing reagents to study pathogen biology to aid in identifying druggable targets is essential. Here, we demonstrate the feasibility and use of a fluorescent OROV reporter in mice to study viral dynamics and pathogenesis. We show that this reporter OROV maintains characteristics such as growth and pathogenicity similar to the wild-type virus. Using this reporter virus, we can now develop methods to assist OROV studies and establish various high-throughput assays. [ABSTRACT FROM AUTHOR]

The process of stone formation in the human body remains incompletely understood, which requires clinical and laboratory studies and the formulation of a new endogenous, nanotechnological concept of the mechanism of origin and formation of crystallization centers. Previously, the mechanism of sialolithiasis was considered a congenital disease associated with the pathology of the ducts in the structure of the glands themselves. To date, such morphological changes of congenital nature can be considered from the position of the intrauterine formation of endogenous bacterial infections complicated by the migration of antigenic structures initiating the formation of crystallization centers. The present work is devoted to the study of the morphology and composition of stones obtained as a result of surgical interventions for sialolithiasis. Presumably, nanoparticles of metals and other chemical compounds can be structural components of crystallization centers or incorporated into the conditions of chronic endogenous inflammation and the composition of antigenic structures, in complexes with protein and bacterial components. X-ray microtomography, X-ray fluorescence analysis, scanning transmission electron microscopy and microanalysis, mass spectrometry, and Raman spectroscopy were used to study the pathogenesis of stone formation. Immunoglobulins (Igs) of classes A and G, as well as nanoparticles of metals Pb, Fe, Cr, and Mo, were found in the internal structure of the stones. The complex of antigenic structures was an ovoid calcified layered matrix of polyvid microbial biofilms, with the inclusion of metal nanoparticles and chemical elements, as well as immunoglobulins. The obtained results of clinical and laboratory studies allow us to broaden the view on the pathogenesis of stone formation and suggest that the occurrence of the calcification of antigenic structures may be associated with the formation of IgG4-associated disease. [ABSTRACT FROM AUTHOR]

Background: A minority of patients with MSS tumors present a high tumor mutation burden (TMB) without underlying MMR defects. Methods: Publicly available genomic series were assessed for identification of patients with MSS gastric gastroesophageal junction, and esophageal adenocarcinomas and a high TMB, defined as more than 10 mutations per Mb. These were compared with MSS cancers and a low TMB for genetic alterations and for survival outcomes. Results: Patients with MSS cancers with high TMB in the MSK series were older but did not differ in other clinicopathologic parameters compared with MSS patients with low TMB. Mutations in tumor suppressors TP53 and APC and oncogenes KRAS and ERBB4 as well as amplifications of ERBB2 were more prevalent in the high TMB group of MSS cancers. Mutations in DDR associated genes, in epigenetic modifiers and in genes associated with immune response were more prevalent in the hIgh TMB group patients. However, high TMB was not associated with an improved survival in MSS gastric/gastroesophageal junction/esophageal adenocarcinomas (Log Rank p = 0.5). Conclusion: MSS Gastric/gastroesophageal junction/esophageal adenocarcinomas with TMB above 10 mutations per Mb possess a genomic landscape with increased alteration frequencies in common gastroesophageal cancer genes and pathways. [ABSTRACT FROM AUTHOR]

Background/Objectives: Posterior staphyloma (PS) is a hallmark of pathological myopia, corresponding to a circumscribed outpouching of the eyeball with choroidal thinning and inward scleral deformation at its edges. Its pathogenesis is still unclear, thus constituting a research priority as the prevalence of myopia is increasing worldwide. Recently, it has been suggested that the optic nerve sheaths or oblique muscles are potential promoters of PS through the traction or compression effect that they apply to the eye wall. The inferior oblique muscle (IOM) inserts 1–2 mm from the macula. The projection of its insertion is accessible using Optical Coherence Tomography (OCT). Before launching prospective studies, we sought to detect any choroidal thinning (ChT) in the temporal vicinity of the macula and to measure the distance between it and the fovea (FT-distance). Methods: This retrospective cross-sectional pilot study included 120 eyes. Using Spectralis®-OCT, the area centered by the Bruch's membrane opening–fovea axis was analyzed for ChT and FT-distance. Results: Of the 112 defined eyes, 70% (78 eyes) had ChT. Pachymetry was significantly thinner (p = 0.018) in eyes with than without ChT. The mean FT-distance was 3601.9 ± 93.6 µm. Conclusions: The location of ChT coincided with the insertion distance of the IOM, suggesting a link between them. The association between the presence of ChT and a thinner pachymetry suggests a reduced scleral resistance, as a thinner pachymetry is related to a thinner sclera. Our results suggest a link between ocular deformation and the IOM, which may be relevant for the pathogenesis of PS, warranting further investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: Muscle contracture refers to the pathologic process that results in fibrosis and permanent damage to a muscle. Theoretically, any muscle can be affected. This study retrospectively reviewed eight cases of the fibrotic contracture of the canine infraspinatus muscle. The treatment was the tendon's tenotomy at its insertion and the release of all adhesions. In three cases, a teres minor simultaneous contracture was detected intraoperatively, which was treated via the tenotomy of the affected muscle. This is the first study to report the contracture of the teres minor muscle and its simultaneous coexistence with the fibrotic contracture of the infraspinatus muscle. Postoperatively, strict limitation of physical activity for two weeks followed by a gradual return to the full limb's activity and analgesic and anti-inflammatory drugs were prescribed. The outcome was excellent, as the lameness resolved within two weeks in all cases. This retrospective study aims to compare its results with the literature to enrich the data on muscle contracture. Contracture of the infraspinatus and teres minor muscle should routinely be considered as a cause of thoracic limb lameness. (1) Background: Fibrotic contracture of the canine infraspinatus muscle (FCIM) is considered an uncommon musculotendinous condition mainly affecting hunting dogs. After an acute onset of a painful non-weight-bearing lameness over a period of one to four weeks, a characteristic circumducted gait is developed in the affected thoracic limb. (2) Methods: Eight client-owned dogs of varying breeds, both sexes, aged 4–9 years old, and weighing 14–26 kg participated in the study. The duration of lameness prior to their first consultation ranged from 10 to 450 days. All participants were thoroughly examined clinically, orthopedically, and radiographically. (3) Results: The dogs underwent infraspinatus tenotomy, resulting in improved limb function. In three cases, a teres minor muscle contracture was revealed intraoperatively and resolved via a tenotomy at its insertion. The findings showed that 15 days post-operation, all dogs returned to full activity. The results obtained confirm and reinforce the literature data around FCIM and describe the first recorded condition of the simultaneous contracture of the infraspinatus and teres minor muscles. (4) Conclusions: In every case of shoulder lameness, contractures of all shoulder muscles should be included in the differential diagnosis and patients should be assessed for concurrent contractures even if infraspinatus contracture is identified. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome with diarrhea (IBS-D) is a common intestinal condition that significantly impacts work efficiency and quality of life. The use of animal models is crucial for delving into the pathophysiology of IBS-D and exploring therapeutic options. However, a wide variety of animal models for IBS-D has been used in previous studies, posing a considerable challenge for researchers in selecting a suitable model. In this review, using the Web of Science database, we searched IBS-D-related research spanning from 2014 to 2023; described the differences in animal strains and modeling methods among various IBS-D features recapitulating models; summarized the frequency of model usage, pathogenesis, and pathological characteristics of these models; and discussed their current applications, limitations, and future perspectives. The objective is to offer theoretical guidance for future researchers, aiding them in choosing suitable animal models based on their experimental designs. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) is a highly contagious disease caused by the African swine fever virus (ASFV) that affects domestic pigs and various wild boars, such as African and European wild boars. It is classified as a reportable animal disease by the World Organization for Animal Health (OIE) and is a priority for disease prevention in China. Currently, there is no approved vaccine or treatment for ASF. However, establishing a scientific biosafety system in pig farms can significantly contribute to disease prevention and control. This article provides a comprehensive review of ASFV, covering its etiology, cell invasion mechanism, evasion of natural immune response, and progress in vaccine research. The aim is to offer a theoretical foundation for enhancing prevention and control strategies against ASF. [ABSTRACT FROM AUTHOR]

Bluetongue (BT) is an economically important contagious viral disease transmitted by insect vectors of Culicoides species affecting both domestic and wild ruminants caused by Genus Orbivirus of Reoviridae family. Present in vivo study for the first time conducted to understand the role of oxidative stress and acute phase proteins in the pathogenesis of endothelial injury in target blood vessels of BTV-4 infected sheep. Twelve sheep of either sex were divided into two groups of six animals each and infected intradermally at multiple sites in the neck region with 6×105.9 TCID50/ml of BTV-4 and animals of control group were inoculated with uninfected tissue culture fluid. Animals were sacrificed at 3, 7, 15, 28, 60, and 90 days post infection (dpi) and postmortem examination was conducted. Oxidative stress parameters like LPO, SOD, GPO and catalase in the blood vessels, hemolysate and serum were estimated. Oxidative stress parameter like LPO was upregulated and anti-oxidant parameters like SOD and GPO were downregulated in blood vessels homogenates, hemolysate and serum of BTV-4 infected animals than uninfected control. This shows the role of oxidative stress in causing endothelial cell damage during BTV infection. Acute phase proteins like CRP and fibrinogen in serum and plasma were estimated and found upregulated in BTV-4 infected animals, which shows that inflammatory changes during the disease causes vascular damage. Prothrombin time was estimated in plasma of BTV-4 infected animals and was prolonged in BTV infected animals indicating coagulation disorder. Increased oxidative stress and fibrinogen, and prolonged prothrombin time indicated the coagulation disorders induced by BTV infection by causing endothelial cell damage and severe vascular disease results in congestion, haemorrhages and edema in the blood vessels and other target organs in sheep. [ABSTRACT FROM AUTHOR]

We continue our review of on punctal stenosis by providing a detailed discussion of management modalities, their complications, and outcomes. There is a significant change in the understanding of punctal and peripunctal anatomy, puncto-canalicular junction, and the lacrimal pump mechanisms. While the snip punctoplasty procedures are still practiced, there is an increasing trend toward nonincisional procedures. The nonincisional procedures in select cases appear to be equally effective as the incisional ones. Although simple to use, punctal plugs never became the mainstay of treatment because of design issues and the inability to address the coexisting canalicular stenosis. Placing stents only in the lower punctum in cases of upper and lower punctal stenosis should be discouraged, and management needs to address punctal stenosis and not which punctum is involved. Several types of stents are used in the management of punctal stenosis, mostly based on surgeon's preference. The benefits of adjuvant mitomycin C are uncertain. In view of literature on how stent biofilms can themselves cause chronic inflammation, placing them for prolonged periods should be reviewed and debated. Enhanced understanding of the molecular pathogenesis of punctal stenosis and addressing the current controversies in management would help standardize the therapeutic interventions available in the lacrimal armamentarium. [ABSTRACT FROM AUTHOR]

Neurotrophic keratopathy is an uncommon degenerative corneal disorder characterized by compromised corneal sensory innervation resulting in the formation of epithelial defects and nonhealing corneal ulcers. Various treatment modalities are available to stabilize disease progression, improve patient well-being, and prevent vision loss. For eligible patients, medical and surgical reinnervation have emerged as pioneering therapies, holding promise for better management. We present a comprehensive review of the disorder, providing an update relevant to ophthalmologists on pathogenesis, diagnosis, treatment options, and novel therapies targeting pathophysiological pathways. [ABSTRACT FROM AUTHOR]

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma (CTCL) with its etiology not yet fully understood. Interleukin (IL)-35 is an inhibitory cytokine that belongs to the IL-12 family. Elevated IL-35 in the plasma and the tumor microenvironment increases tumorigenesis and indicates poor prognosis in different types of malignancies. The objective of this study is to estimate the expression levels of IL-35 in tissue and serum of MF patients versus healthy controls. This case-control study included 35 patients with patch, plaque, and tumor MF as well as 30 healthy controls. Patients were fully assessed, and serum samples and lesional skin biopsies were taken prior to starting treatment. The IL-35 levels were measured in both serum and tissue biopsies by ELISA technique. Both tissue and serum IL-35 levels were significantly higher in MF patients than in controls (P < 0.001) and tissue IL-35 was significantly higher than serum IL-35 in MF patients (P < 0.001). Tissue IL-35 was significantly higher in female patients and patients with recurrent MF compared to male patients and those without recurrent disease (P < 0.001). Since both tissue and serum IL-35 levels are increased in MF, IL-35 is suggested to have a possible role in MF pathogenesis. IL-35 can be a useful diagnostic marker for MF. Tissue IL-35 can also be an indicator of disease recurrence. [ABSTRACT FROM AUTHOR]

Translational research is key in advancing the diagnosis and therapy of systemic amyloidoses. This paper summarises our presentations at the ISA Workshop on Translation in Systemic Amyloidoses held in Athens on September 25-26, 2023. The critical advances made by the pioneers in the field are reviewed, with particular attention to the discoveries and developments of utmost importance to our understanding of what amyloid is and how the substance affects functions. Examples of translational research regarding the mechanisms of cardiac damage in light chain amyloidosis, the role of biomarkers in improving our understanding of the biology of the disease and patients' management, and the molecular mechanisms involved in the cytotoxicity are described. Advances in basic research continue to open new therapeutic avenues. [ABSTRACT FROM AUTHOR]

The incidence of intracerebral hemorrhage (ICH) is increasing every year, with very high rates of mortality and disability. The prognosis of elderly ICH patients is extremely unfavorable. Interleukin, as an important participant in building the inflammatory microenvironment of the central nervous system after ICH, has long been the focus of neuroimmunology research. However, there are no studies on the role IL31 play in the pathologic process of ICH. We collected para‐lesion tissue for immunofluorescence and flow cytometry from the elderly and young ICH patients who underwent surgery. Here, we found that IL31 expression in the lesion of elderly ICH patients was significantly higher than that of young patients. The activation of astrocytes after ICH releases a large amount of IL31, which binds to microglia through IL31R, causing a large number of microglia to converge to the hematoma area, leading to the spread of neuroinflammation, apoptosis of neurons, and ultimately resulting in poorer recovery of nerve function. Interfering with IL31 expression suppresses neuroinflammation and promotes the recovery of neurological function. Our study demonstrated that elderly patients release more IL31 after ICH than young patients. IL31 promotes the progression of neuroinflammation, leading to neuronal apoptosis as well as neurological decline. Suppression of high IL31 concentrations in the brain after ICH may be a promising therapeutic strategy for ICH. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) is a frequent important complication of systemic sclerosis (SSc). Factors relevant to aetiopathogenesis of SSc are also central to SSc-ILD. Severity of SSc-ILD is variable but it has a major impact on morbidity and mortality. Factors determining SSc-ILD susceptibility reflect the genetic architecture of SSc and are increasingly being defined. There are aspects linked to immunogenomics and non-immunological genetic factors that may be less conserved and underlie some of the geographical and racial diversity of SSc. These associations may also underlie important links between autoantibody subgroups and patient level risk of SSc-ILD. Examination of blood and tissue samples and observational clinical research together with integrated analysis of in vitro and in vivo preclinical models have elucidated pathogenic mechanisms of SSc-ILD. These have confirmed the potential importance of immune mechanisms in the innate and adaptive immune systemic as well as a significant role for profibrotic pathways especially transforming growth factor beta (TGFbeta) and its regulators and downstream mediators. Recent analysis of clinical trial cohorts as well as integrated and multilevel high dimensional analysis of bio-samples has shed further light on SSc-ILD. This is likely to underpin future advances in stratified and precision medicine for treatment of SSc. [ABSTRACT FROM AUTHOR]

Copyright of Kirkuk Journal of Science is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim - to analyze the current literature on the role of single nucleotide polymorphism (SNP) of human genes in shaping the clinical course of the new coronavirus disease (COVID-19). Results. Based on the results of the analysis and synthesis of the current literature on the role of SNP in shaping the clinical course and outcome of COVID-19, the clinical and prognostic significance of SNP of genes encoding receptors responsible for the penetration of SARS-CoV-2 into target cells has been demonstrated. The presence of the D-allele of the ACE gene (DD and ID genotypes) is associated with the highest risk of severe COVID-19, which makes it possible to offer it as an informative prognostic marker of COVID-19 severity. SNP of the TMPRSS2 co-receptor gene, known as the androgen responsive gene, at certain loci is prognostically important, as it leads to an increase in TMPRSS2 expression in men, which promotes virus fusion with the target cell membrane and has an unfavorable effect on the course of COVID-19 in men. The data accumulated in the current literature on the clinical and prognostic value of SNP host genes encoding the immune response has also been analyzed. The role of HLA SNP genes, genes encoding innate immunity factors (TLR), as well as genes encoding pro-inflammatory cytokines (IL-6, TNF-α, etc.) and acute-phase inflammatory components (CRP) in the development of severe COVID-19 and the risk of death has been demonstrated. Attention has been paid to the determined role of SNP in the ACE gene in the development of pulmonary embolism in patients with severe COVID-19. The article has analyzed publications on the SNP role of host genes in the development of clinical events that are currently interpreted as long COVID. The prognostic role of the IL-10 gene SNP and its receptor gene in the formation of long-term consequences of the new coronavirus infection has been demonstrated. Conclusions. SNP of host genes encoding receptors responsible for the entry of SARS-CoV-2 into target cells and SNP of genes encoding immune response have some prognostic value in assessing the risk of severe course and adverse effects of COVID-19. The accumulation of data on genetic risk factors for adverse outcomes of the new coronavirus disease will allow us to enhance the understanding of this infection pathogenesis, improve patient stratification and individualize therapeutic interventions. [ABSTRACT FROM AUTHOR]

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To explore the interaction between mast cells (MC) and gut-brain-skin axis in the pathogenesis of psoriasis. Methods Patients with moderate-to-severe plaque psoriasis were selected as test group and healthy volunteers of the same period as control group. Peripheral venous blood, skin lesions and feces were collected from each group and the levels of interleukin-23 (IL-23), interleukin-17 (IL-17), mast cell tryptase (MCT), corticotropin-releasing hormone (CRH), lipopolysaccharide (LPS) in serum and the expression of MC in skin lesions were measured, and the differences in intestinal flora were analyzed. The interaction between MC and intestinal-brain-skin axis in the pathogenesis of psoriasis, as well as the correlation between MC and Psoriasis Area and Severity Index (PASI) score of psoriasis were investigated. Results The serum levels of IL-17, IL-23, MCT, CRH, LPS and MC expression in the test group were significantly higher than those in the control group (P< 0.001), and were positively correlated with PASI score (rs =0.80, 0.52, 0.84, 0.75, 0.86, P < 0.001). MC expression in skin lesions was positively correlated with serum levels of IL-17, IL-23, MCT, CRH, LPS and PASI scores (rs=0.75, 0.76, 0.76, 0.81, 0.72, 0.76, P < 0.001). Shannon index and Simpson index of intestinal flora in the test group showed decreased a diversity (W = 34, 111, P <0.05); β diversity index was significantly different between the two groups (W = 2 818, 2 762, P <0.05); however, there was no significant difference in flora clustering between the two groups after dimensionality reduction by principal coordinate analysis (PCoA) and partial least squares discriminant analysis (PLS-DA) (F = 0.16, P > 0.05). Firmicutes/Bacteroidetes (F/B) ratio was positively correlated with PASI score, serum IL-17, IL-23, CRH, LPS, MCT levels and MC expression in skin lesions in the test group (rs = 0.89, 0.76, 0.49, 0.72, 0.76, 0.71, 0.53, P < 0.001 ), which, however, were higher than the increase in F/B ratio in the control group, showing not significant difference (Z = -1.21, P > 0.05). Significant differential bacteria from short chain fatty acids (SCFAs) sources including Lachnospirales, Lachnospiraceae, Anaerostipes, and Anaerostipes hadrus were reduced in the test group (W = 31, 31, 34, 30, P < 0.05), and negatively correlated with low to moderate serum and histological parameters (P < 0.001). Conclusion The expression and activation of MC are related to the severity of psoriatic lesions and the degree of inflammation and may be involved in the pathogenesis of psoriasis. Imbalance of intestinal flora in psoriasis patients is related to MC activation and the degree of psoriatic inflammation, and gut-brain-skin axis interaction may affect MC activation and play a role in the pathogenesis of psoriasis. [ABSTRACT FROM AUTHOR]

Gastric cancers (GCs) are among the most common and fatal malignancies in the world. Despite our increasing understanding of the molecular mechanisms underlying GC, further biomarkers are still needed for more in-depth examination, focused prognosis, and treatment. GC is one among the long non-coding RNAs, or lncRNAs, that have emerged as key regulators of the pathophysiology of cancer. This comprehensive review focuses on the diverse functions of long noncoding RNAs (lncRNAs) in the development of GC and their interactions with important intracellular signaling pathways. LncRNAs affect GC-related carcinogenic signaling cascades including pathways for EGFR, PI3K/AKT/mTOR, p53, Wnt/β-catenin, JAK/STAT, Hedgehog, NF-κB, and hypoxia-inducible factor. Dysregulated long non-coding RNA (lncRNA) expression has been associated with multiple characteristics of cancer, such as extended growth, apoptosis resistance, enhanced invasion and metastasis, angiogenesis, and therapy resistance. For instance, lncRNAs such as HOTAIR, MALAT1, and H19 promote the development of GC via altering these pathways. Beyond their main roles, GC lncRNAs exhibit potential as diagnostic and prognostic biomarkers. The overview discusses CRISPR/Cas9 genome-modifying methods, antisense oligonucleotides, small molecules, and RNA interference as potential therapeutic approaches to regulate the expression of long noncoding RNAs (lncRNAs). An in-depth discussion of the intricate functions that lncRNAs play in the development of the majority of stomach malignancies is provided in this review. It provides the groundwork for future translational research in lncRNA-based whole processes toward GC by highlighting their carcinogenic effects, regulatory roles in significant signaling cascades, and practical scientific uses as biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

The active form of vitamin D (VD) exerts hormonal effects by regulating the expression of genes involved in T‐cell activity, cell differentiation, and proliferation. Human T‐cell leukemia virus type 1 (HTLV‐1) is a causative agent of life‐threatening diseases, adult T‐cell leukemia (ATL) and HTLV‐1‐associated myelopathy (HAM). Among ATL patients, hypercalcemia is one of the most serious complications due to bone resorption. In this study, wild‐type mice administered UV‐irradiated HTLV‐1‐infected cells showed up to 47% decrease of plasma VD level compared with untreated mice. To clarify the effect of HTLV‐1 on plasma VD level, 315 samples registered in nationwide cohort study on ATL onset were measured. The VD level in HAM (14.98 ± 8.5 ng/mL) was significantly lower than those in asymptomatic carriers and ATL (p < 0.05). Upon comparing the VD levels in ATL stratified by disease subtypes, acute ATL showed a lower level (15.81 ± 12.0 ng/mL) than chronic and smoldering types (p < 0.05). In the longitudinal observation, VD levels were significantly higher in untreated spontaneous remission cases than in ATL progression cases, in which the VD levels decreased approximately 40% after onset. In cases of relapse after transplantation, the plasma VD level dropped to 38.7% of the pre‐relapse level, while in cases of complete remission, the VD level increased with improvement of the performance status. Taken together, these results suggest that plasma VD level is a potential indicator for the onset and relapse of HTLV‐1‐associated diseases. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) is a highly aggressive type of tumor characterized by delayed diagnosis, recurrence, metastasis, relapse, and drug resistance. The occurrence of HNC were associated with smoking, alcohol abuse (or both), human papillomavirus infection, and complex genetic and epigenetic predisposition. Currently, surgery and radiotherapy are the standard treatments for most patients with early‐stage HNC. For recurrent or metastatic (R/M) HNC, the first‐line treatment is platinum‐based chemotherapy combined with the antiepidermal growth factor receptor drug cetuximab, when resurgery and radiation therapy are not an option. However, curing HNC remains challenging, especially in cases with metastasis. In this review, we summarize the pathogenesis of HNC, including genetic and epigenetic changes, abnormal signaling pathways, and immune regulation mechanisms, along with all potential therapeutic strategies such as molecular targeted therapy, immunotherapy, gene therapy, epigenetic modifications, and combination therapies. Recent preclinical and clinical studies that may offer therapeutic strategies for future research on HNC are also discussed. Additionally, new targets and treatment methods, including antibody–drug conjugates, photodynamic therapy, radionuclide therapy, and mRNA vaccines, have shown promising results in clinical trials, offering new prospects for the treatment of HNC. [ABSTRACT FROM AUTHOR]

Natural products are chemical compounds produced by living organisms. They are isolated and purified to determine their function and can potentially be used as therapeutic agents. The ability of some bioactive natural products to modify the course of cancer is fascinating and promising. In the past 50 years, there have been advancements in cancer therapy that have increased survival rates for localized tumors. However, there has been little progress in treating advanced renal cell carcinoma (RCC), which is resistant to radiation and chemotherapy. Oncogenes and tumor suppressors are two roles played by microRNAs (miRNAs). They are involved in important pathogenetic mechanisms like hypoxia and epithelial-mesenchymal transition (EMT); they control apoptosis, cell growth, migration, invasion, angiogenesis, and proliferation through target proteins involved in various signaling pathways. Depending on their expression pattern, miRNAs may identify certain subtypes of RCC or distinguish tumor tissue from healthy renal tissue. As diagnostic biomarkers of RCC, circulating miRNAs show promise. There is a correlation between the expression patterns of several miRNAs and the prognosis and diagnosis of patients with RCC. Potentially high-risk primary tumors may be identified by comparing original tumor tissue with metastases. Variations in miRNA expression between treatment-sensitive and therapy-resistant patients' tissues and serum allow for the estimation of responsiveness to target therapy. Our knowledge of miRNAs' function in RCC etiology has a tremendous uptick. Finding and validating their gene targets could have an immediate effect on creating anticancer treatments based on miRNAs. Several miRNAs have the potential to be used as biomarkers for diagnosis and prognosis. This review provides an in-depth analysis of the current knowledge regarding natural compounds and their modes of action in combating cancer. Also, this study aims to give information about the diagnostic and prognostic value of miRNAs as cancer biomarkers and their involvement in the pathogenesis of RCC. [ABSTRACT FROM AUTHOR]

Fungal diseases not only reduce the yield of edible mushrooms but also pose potential threats to the preservation and quality of harvested mushrooms. Cobweb disease, caused primarily by fungal pathogens from the Hypocreaceae family, is one of the most significant diseases affecting edible mushrooms. Deciphering the genomes of these pathogens will help unravel the molecular basis of their evolution and identify genes responsible for pathogenicity. Here, we present high-quality genome sequences of three cobweb disease fungi: Hypomyces aurantius Cb-Fv, Cladobotryum mycophilum CB-Ab, and Cladobotryum protrusum CB-Mi, isolated from Flammulina velutipes, Agaricus bisporus, and Morchella importuna, respectively. The assembled genomes of H. aurantius, C. mycophilum, and C. protrusum are 33.19 Mb, 39.83 Mb, and 38.10 Mb, respectively. This is the first report of the genome of H. aurantius. Phylogenetic analysis revealed that cobweb disease pathogens are closely related and diverged approximately 17.51 million years ago. CAZymes (mainly chitinases, glucan endo-1,3-beta-glucosidases, and secondary metabolite synthases), proteases, KP3 killer proteins, lipases, and hydrophobins were found to be conserved and strongly associated with pathogenicity, virulence, and adaptation in the three cobweb pathogens. This study provides insights into the genome structure, genome organization, and pathogenicity of these three cobweb disease fungi, which will be a valuable resource for comparative genomics studies of cobweb pathogens and will help control this disease, thereby enhancing mushroom quality. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease worldwide; therefore, since its initial description, significant progress has been made, yet a mystery remains regarding its pathogenesis and elusive root cause. The widespread distribution of pathological α-synuclein (αSyn) aggregates throughout the body raises inquiries regarding the etiology, which has prompted several hypotheses, with the most prominent one being αSyn-associated proteinopathy. The identification of αSyn protein within Lewy bodies, coupled with genetic evidence linking αSyn locus duplication, triplication, as well as point mutations to familial Parkinson's disease, has underscored the significance of αSyn in initiating and propagating Lewy body pathology throughout the brain. In monogenic and sporadic PD, the presence of early inflammation and synaptic dysfunction leads to αSyn aggregation and neuronal death through mitochondrial, lysosomal, and endosomal functional impairment. However, much remains to be understood about αSyn pathogenesis, which is heavily grounded in biomarkers and treatment strategies. In this review, we provide emerging new evidence on the current knowledge about αSyn's pathophysiological impact on PD, and its presumable role as a specific disease biomarker or main target of disease-modifying therapies, highlighting that this understanding today offers the best potential of disease-modifying therapy in the near future. [ABSTRACT FROM AUTHOR]

SUMMARY: 'Unavoidable pollutants', 'natural poisons', 'invisible thieves', and 'silent killers' are the popular names of a group of fundal metabolites, mycotoxins, and the disease caused by these toxins is referred to as mycotoxicosis. In poultry, this disease usually occurs when mycotoxins-producing fungi grow on grain and feed. Although more than 500 different mycotoxins have been identified, scientists have focussed only on mycotoxins of medical and agricultural concern, which are found to be toxic. The pathogenesis and therapeutics of mycotoxicosis in poultry production remain essential challenges. Oxidative stress is a driving force in the pathogenesis of mycotoxicosis. Oxidative stress induces cellular and nuclear damage and mitochondrial dysfunction through the overproduction of reactive oxygen species and reactive nitrogen species. Furthermore, mycotoxins induce ribosomal stress that activates multiple cellular pathways, such as nuclear transcription factor κβ and mitogen-activated protein kinase. Activation of these aberrant cellular signalling pathways and oxidative stress triggers a cascade of pro-inflammatory cytokines, which contributes to apoptosis and tissue/organ dysfunction, such as immunosuppression, hepatotoxicity, nephrotoxicity, neurotoxicity, and gastrointestinal tract toxicity. The consequences of this toxicity lead to poor feed conversion, feed refusal, poor growth rate, reduced fertility, and reduced hatchability of poultry. Therefore, optimally, a better understanding of the disease pathogenesis and oxidative stress is needed to identify specific and targeted therapeutic approaches to combat mycotoxicosis in poultry. This review describes the pathogenesis of mycotoxicosis with particular emphasis on oxidative stress in poultry. This also paves the way for preventive and therapeutic approaches aimed at limiting oxidative stress that can enhance growth, fertility, and production in poultry. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a prominent contributor to global morbidity and mortality rates. The intricate and diverse mechanisms underlying ischemia–reperfusion injury remain poorly comprehended. RNA methylation, an emerging epigenetic modification, plays a crucial role in regulating numerous biological processes, including immunity, DNA damage response, tumorigenesis, metastasis, stem cell renewal, adipocyte differentiation, circadian rhythms, cellular development and differentiation, and cell division. Among the various RNA modifications, N6-methyladenosine (m6A) modification stands as the most prevalent in mammalian mRNA. Recent studies have demonstrated the crucial involvement of m6A modification in the pathophysiological progression of ischemic stroke. This review aims to elucidate the advancements in ischemic stroke-specific investigations pertaining to m6A modification, consolidate the underlying mechanisms implicated in the participation of m6A modification during the onset of ischemic stroke, and deliberate on the potential of m6A modification as a viable therapeutic target for ischemic stroke. [ABSTRACT FROM AUTHOR]

Pneumoconiosis is the most common occupational disease among coal miners, which is a lung disease caused by long-term inhalation of coal dust and retention in the lungs. The early stage of this disease is highly insidious, and pulmonary fibrosis may occur in the middle and late stages, leading to an increase in patient pain index and mortality rate. Currently, there is a lack of effective treatment methods. The pathogenesis of pneumoconiosis is complex and has many influencing factors. Although the characteristics of coal dust have been considered the main cause of different mechanisms of pneumoconiosis, the effects of coal dust composition, particle size and shape, and coal dust concentration on the pathogenesis of pneumoconiosis have not been systematically elucidated. Meanwhile, considering the irreversibility of pneumoconiosis progression, early prediction for pneumoconiosis patients is particularly important. However, there is no early prediction standard for pneumoconiosis among coal miners. This review summarizes the relevant research on the pathogenesis and prediction of pneumoconiosis in coal miners in recent years. Firstly, the pathogenesis of coal worker pneumoconiosis and silicosis was discussed, and the impact of coal dust characteristics on pneumoconiosis was analyzed. Then, the early diagnostic methods for pneumoconiosis have been systematically introduced, with a focus on image collaborative computer-aided diagnosis analysis and biomarker detection. Finally, the challenge of early screening technology for miners with pneumoconiosis was proposed. [ABSTRACT FROM AUTHOR]

The respiratory tract acts as a crucial barrier influenced by environmental factors, particularly affecting the homeostasis of its mucous membranes. Environmental conditions, including climate and atmospheric composition, play a significant role in the development and progression of respiratory diseases such as bronchial asthma and allergic rhinitis. Various risk factors, including genetic predisposition, viral infections, allergen exposure, and pollutants, along with changes in the microbiome, are key determinants in the manifestation and progression of these diseases. Certain pollutants like ozone (O3), nitrogen dioxide (NO2), and particulate matter (PM2.5) contribute to airway inflammation and hyperresponsiveness, potentially leading to increased oxidative stress and respiratory distress. This study aims to comparatively analyze the clinical characteristics and processes of free radical oxidation in the tissues of the respiratory tract of children with respiratory diseases living at different altitudes in Kyrgyzstan. A total of 209 children, including 104 with chronic respiratory diseases and 105 healthy controls, were examined. The study included clinical examinations, endoscopic evaluations, and biopsies when necessary. Biological samples such as exhaled air condensate and nasal lavages were collected to measure various biochemical indicators including total lipids, hydroperoxides, diene conjugates, and oxidative index. Preliminary results indicate that children residing at higher altitudes exhibit more pronounced changes in respiratory tissues, likely due to climatic and environmental factors specific to high-altitude regions. These children showed significantly higher levels of free radical oxidation products and altered surface tension in biological samples compared to those living at lower altitudes. Complaints such as shortness of breath, difficulty breathing, cough, and nasal congestion were also more frequent among children at higher altitudes. The study highlights the need for further research to better understand the impact of altitude on respiratory health and to develop effective strategies for the treatment and prevention of respiratory diseases in children. Future research should focus on the longitudinal tracking of respiratory health, detailed environmental assessments, and the development of targeted public health strategies to address the unique challenges faced by high-altitude populations. Ultimately, this research aims to improve respiratory health outcomes for children living in diverse geographic settings. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Education & Science is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Androgens regulate broad physiologic and pathologic processes, including external genitalia development, prostate cancer progression, and anti-inflammatory effects in both cancer and asthma. In prostate cancer, several lines of evidence have implicated dietary and endogenous fatty acids in cell invasion, angiogenesis, and treatment resistance. However, the role of fatty acids in steroidogenesis and the mechanisms by which alterations in this pathway occur are not well understood. Here, we show that, of a panel of fatty acids tested, arachidonic acid and its specific metabolite 5-hydroxyeicosatetraenoic acid (5-HETE) regulate androgen metabolism. Arachidonic acid is metabolized to 5-HETE and reduces androgens by inducing aldo-keto reductase (AKR) family members AKR1C2 and AKR1C3 expression in human prostate, breast, and lung epithelial cells. Finally, we provide evidence that these effects require the expression of the antioxidant response sensor, nuclear factor erythroid 2-related factor 2 (Nrf2). Our findings identify an interconnection between conventional fatty acid metabolism and steroid metabolism that has broad relevance to androgen physiology and inflammatory regulation. [ABSTRACT FROM AUTHOR]

Melasma is an acquired chronic pigmentary disorder affecting millions of individuals worldwide. However, the pathogenesis of melasma remains unclear. This article provides a comprehensive review of the pathophysiological changes occurring in the skin microenvironment of melasma lesions, which can be summarized as follows: (1) skin barrier dysfunction and abnormal synthesis, transport, and intracellular distribution of melanin in the epidermis; (2) basement membrane damage; (3) solar elastosis, vascular changes, senescent fibroblasts, mast cell infiltration, and sebocyte participation in the dermis; and (4) systemic factors such as sex hormones and oxidative stress. Furthermore, potential therapeutic strategies are introduced to provide novel perspectives for fundamental and clinical research related to melasma. [ABSTRACT FROM AUTHOR]

There is an urgent need for new antifungal drugs to treat invasive fungal diseases. Unfortunately, the echinocandin drugs that are fungicidal against other important fungal pathogens are ineffective against Cryptococcus neoformans, the causative agent of life-threatening meningoencephalitis in immunocompromised people. Contributing mechanisms for echinocandin tolerance are emerging with connections to calcineurin signaling, the cell wall, and membrane composition. In this context, we discovered that a defect in phosphate uptake impairs the tolerance of C. neoformans to the echinocandin caspofungin. Our previous analysis of mutants lacking three high affinity phosphate transporters revealed reduced elaboration of the polysaccharide capsule and attenuated virulence in mice. We investigated the underlying mechanisms and found that loss of the transporters and altered phosphate availability influences the cell wall and membrane composition. These changes contribute to the shedding of capsule polysaccharide thus explaining the reduced size of capsules onmutants lacking the phosphate transporters. We also found an influence of the calcineurin pathway including calcium sensitivity and an involvement of the endoplasmic reticulum in the response to phosphate limitation. Furthermore, we identified membrane and lipid composition changes consistent with the role of phosphate in phospholipid biosynthesis and with previous studies implicating membrane integrity in caspofungin tolerance. Finally, we discovered a contribution of phosphate to titan cell formation, a cell type that displays modified cell wall and capsule composition. Overall, our analysis reinforces the importance of phosphate as a regulator of cell wall and membrane composition with implications for capsule attachment and antifungal drug susceptibility. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) is a prevalent malignancy affecting the hematopoietic system, encompassing both B-cell ALL (B-ALL) and T-cell ALL (T-ALL). T-ALL, characterized by the proliferation of T-cell progenitors in the bone marrow, presents significant treatment challenges, with patients often experiencing high relapse rates and poor long-term survival despite advances in chemotherapy and hematopoietic stem cell transplantation (HSCT). This review explores the pathogenesis and traditional treatment strategies of T-ALL, emphasizing the promising potential of chimeric antigen receptor (CAR) technology in overcoming current therapeutic limitations. CAR therapy, leveraging genetically modified immune cells to target leukemia-specific antigens, offers a novel and precise approach to T-ALL treatment. The review critically analyzes recent developments in CAR-T and CAR-NK cell therapies, their common targets, optimization strategies, clinical outcomes, and the associated challenges, providing a comprehensive overview of their clinical prospects in T-ALL treatment. [ABSTRACT FROM AUTHOR]

Introduction: As the SARS-CoV-2 virus continues to evolve and new variants emerge, it becomes crucial to understand the comparative pathological and immunological responses elicited by different strains. This study focuses on the original Wuhan strain and the Omicron variant, which have demonstrated significant differences in clinical outcomes and immune responses. Methods: We employed ferrets as an experimental model to assess the D614G variant (a derivative of the Wuhan strain) and the Omicron BA.5 variant. Each variant was inoculated into separate groups of ferrets to compare disease severity, viral dissemination, and immune responses. Results: The D614G variant induced more severe disease and greater viral spread than the Omicron variant. Notably, ferrets infected with the D614G variant exhibited a robust neutralizing antibody response, whereas those infected with the Omicron variant failed to produce a detectable neutralizing antibody response. Despite the clearance of the virus from nearly all tissues by 7 days post-infection, an increase in pathological lesions was observed from 14 to 21 days, particularly in those infected with the D614G variant, suggesting a sustained immune response even after viral clearance. Discussion: These findings underscore the adaptability of SARS-CoV-2 and illuminate how susceptibility and clinical manifestations vary across different strains and species. The results emphasize the necessity of considering both the direct effects of viral infection and the indirect, often prolonged, impacts of the immune response in evaluating the outcomes of SARS-CoV-2 infections. [ABSTRACT FROM AUTHOR]

Herpes simplex virus (HSV), an epidemic human pathogen threatening global public health, gains notoriety for its complex pathogenesis that encompasses lytic infection of mucosal cells, latent infection within neurons, and periodic reactivation. This intricate interplay, coupled with HSV's sophisticated immune evasion strategies, gives rise to various diseases, including genital lesions, neonatal encephalitis, and cancer. Despite more than 70 years of relentless research, an effective preventive or therapeutic vaccine against HSV has yet to emerge, primarily due to the limited understanding of virus-host interactions, which in turn impedes the identification of effective vaccine targets. However, HSV's unique pathological features, including its substantial genetic load capacity, high replicability, transmissibility, and neurotropism, render it a promising candidate for various applications, spanning oncolytic virotherapy, gene and immune therapies, and even as an imaging tracer in neuroscience. In this review, we comprehensively update recent breakthroughs in HSV pathogenesis and immune evasion, critically summarize the progress made in vaccine candidate development, and discuss the multifaceted applications of HSV as a biological tool. Importantly, we highlight both success and challenges, emphasizing the critical need for intensified research into HSV, with the aim of providing deeper insights that can not only advance HSV treatment strategies but also broaden its application horizons. [ABSTRACT FROM AUTHOR]

Burkholderia pseudomallei (Bp) causes the tropical disease melioidosis that afflicts an estimated 165,000 people each year. Bp is a facultative intracellular pathogen that transits through distinct intracellular stages including attachment to host cells, invasion through the endocytic pathway, escape from the endosome, replication in the cytoplasm, generation of protrusions towards neighboring cells, and host cell fusion allowing Bp infection to spread without exiting the intracellular environment. We have identified a TetR-like transcriptional regulator, BP1026B_II1561, that is up-regulated during the late stages of infection as Bp protrudes toward neighboring cells. We have characterized BP1026B_ II1561 and determined that it has a role in pathogenesis. A deletional mutant of BP1026B_II1561 is attenuated in RAW264.7 macrophage and BALB/c mouse models of infection. Using RNA-seq, we found that BP1026B_II1561 controls secondary metabolite biosynthesis, fatty acid degradation, and propanoate metabolism. In addition, we identified that BP1026B_II1561 directly controls expression of an outer membrane porin and genes in the shikimate biosynthetic pathway using ChIP-seq. Transposon mutants of genes within the BP1026B_ II1561 regulon show defects during intracellular replication in RAW264.7 cells confirming the role of this transcriptional regulator and the pathways it controls in pathogenesis. BP1026B_II1561 also up-regulates the majority of the enzymes in shikimate and tryptophan biosynthetic pathways, suggesting their importance for Bp physiology. To investigate this, we tested fluorinated analogs of anthranilate and tryptophan, intermediates and products of the shikimate and tryptophan biosynthetic pathways, respectively, and showed inhibition of Bp growth at nanomolar concentrations. The expression of these pathways by BP1026b_II1561 and during intracellular infection combined with the inhibition of Bp growth by fluorotryptophan/anthranilate highlights these pathways as potential targets for therapeutic intervention against melioidosis. In the present study, we have identified BP1026B_II1561 as a critical transcriptional regulator for Bp pathogenesis and partially characterized its role during host cell infection. [ABSTRACT FROM AUTHOR]

Recurrent vulvovaginal candidiasis is a prevalent condition among women of reproductive age， significantly impacting their physical and mental well-being due to its recurrent nature and challenging treatment. The etiology remains elusive， while treatment options exhibit considerable variability. This paper provides a comprehensive review on the pathogenesis and therapeutic approaches targeting virulence factors associated with recurrent vulvovaginal candidiasis， aiming to offer valuable insights for understanding the underlying mechanisms and optimizing treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Oral microbiota comprises polymicrobial communities shaped by mutualistic coevolution with the host, contributing to homeostasis and regulating immune function. Nevertheless, dysbiosis of oral bacterial communities is associated with a number of clinical symptoms that ranges from infections to oral cancer. Peri-implant diseases are biofilm-associated inflammatory conditions affecting the soft and hard tissues around dental implants. Characterization and identification of the biofilm community are essential for the understanding of the pathophysiology of such diseases. For that sampling methods should be representative of the biofilm communities Therefore, there is a need to know the effect of different sampling strategies on the biofilm characterization by next generation sequencing. Methods: With the aim of selecting an appropriate microbiome sampling procedure for periimplant biofilms, next generation sequencing was used for characterizing the bacterial communities obtained by three different sampling strategies two months after transepithelial abutment placement: adjacent periodontal crevicular fluid (ToCF), crevicular fluid from transepithelial abutment (TACF) and transepithelial abutment (TA). Results: Significant differences in multiple alpha diversity indices were detected at both the OTU and the genus level between different sampling procedures. Differentially abundant taxa were detected between sample collection strategies, including peri-implant health and disease related taxa. At the community level significant differences were also detected between TACF and TA and also between TA and ToCF. Moreover, differential network properties and association patterns were identified. Conclusions: The selection of sample collection strategy can significantly affect the community composition and structure. Trial registration: This research is part of a randomized clinical trial that was designed to assess the effect of transepithelial abutment surface on the biofilm formation. The trial was registered at Trial Registration ClinicalTrials.gov under the number NCT03554876. [ABSTRACT FROM AUTHOR]

The hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide. HEV is classified into eight genotypes, labeled HEV-1 through HEV-8. Genotypes 1 and 2 exclusively infect humans, while genotypes 3, 4, and 7 can infect both humans and animals. In contrast, genotypes 5, 6, and 8 are restricted to infecting animals. While most individuals with a strong immune system experience a self-limiting infection, those who are immunosuppressed may develop chronic hepatitis. Pregnant women are particularly vulnerable to severe illness and mortality due to HEV infection. In addition to liver-related complications, HEV can also cause extrahepatic manifestations, including neurological disorders. The immune response is vital in determining the outcome of HEV infection. Deficiencies in T cells, NK cells, and antibody responses are linked to poor prognosis. Interestingly, HEV itself contains microRNAs that regulate its replication and modify the host's antiviral response. Diagnosis of HEV infection involves the detection of HEV RNA and anti-HEV IgM/IgG antibodies. Supportive care is the mainstay of treatment for acute infection, while chronic HEV infection may be cleared with the use of ribavirin and pegylated interferon. Prevention remains the best approach against HEV, focusing on sanitation infrastructure improvements and vaccination, with one vaccine already licensed in China. This comprehensive review provides insights into the spread, genotypes, prevalence, and clinical effects of HEV. Furthermore, it emphasizes the need for further research and attention to HEV, particularly in cases of acute hepatitis, especially among solid-organ transplant recipients. [ABSTRACT FROM AUTHOR]

Objectives Materials and Methods Results Conclusion Toll‐like receptor (TLR)‐9, may play a role in periodontal disease inflammation. This study measured TLR‐9 and its related molecules, absence in melanoma‐2 (AIM‐2) and Z‐DNA‐binding protein‐1 (ZBP‐1), in gingival crevicular fluid (GCF) from patients with varying stages of periodontal disease to assess the role of pathogen‐derived nucleic acids in inflammation.The study comprised 80 participants: 20 with Stage III Grade C periodontitis, 20 with Stage III Grade B periodontitis (P‐Stage III‐B), 19 with gingivitis, and 21 with periodontal health. Parameters including probing depth (PD), clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BOP) were recorded. ELISA was used to analyze TLR‐9, AIM‐2, and ZBP‐1 levels in GCF. Nonparametric tests were used for statistical comparisons.The total amount of TLR‐9 was higher in P‐Stage III‐B than in the healthy group (p < 0.05). Similarly, the gingivitis group exhibited elevated GCF TLR‐9 levels compared to the healthy group (p < 0.05). GCF AIM‐2 and ZBP‐1 levels remained consistent across groups (p > 0.05). Significant correlations were found between GCF TLR‐9 and CAL (p < 0.05), BOP (p < 0.05), PI (p < 0.01), and GCF volume (p < 0.001).These findings suggested that the TLR‐9‐mediated inflammatory process plays a role in periodontal disease, as evidenced by the increased levels of TLR‐9 in GCF. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Prevention & Treatment For Stomatological Diseases is the property of Journal of Prevention & Treatment For Stomatological Diseases Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Psoriasis is one of the most common autoimmune skin diseases. Increasing evidence shows that alterations in the diversity and function of microbiota can participate in the pathogenesis of psoriasis through various pathways and mechanisms. Objective: To review the connection between microbial changes and psoriasis, how microbial-targeted therapy can be used to treat psoriasis, as well as the potential of prebiotics, probiotics, synbiotics, fecalmicrobiota transplantation, diet, and Traditional Chinese Medicine as supplementary and adjunctive therapies. Methods: Literature related to the relationship between psoriasis and gut microbiota was searched in PubMed and CNKI. Results: Adjunct therapies such as dietary interventions, traditional Chinese medicine, and probiotics can enhance gut microbiota abundance and diversity in patients with psoriasis. These therapies stimulate immune mediators including IL-23, IL-17, IL-22, and modulate gamma interferon (IFN-g) along with the NF-kB pathway, thereby suppressing the release of pro-inflammatory cytokines and ameliorating systemic inflammatory conditions. Conclusion: This article discusses the direction of future research and clinical treatment of psoriasis from the perspective of intestinal microbiota and the mechanism of traditional Chinese medicine, so as to provide clinicians with more comprehensive diagnosis and treatment options and bring greater hope to patients with psoriasis. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased platelet destruction and impaired production, leading to an elevated bleeding tendency. Recent studies have demonstrated an important link between the gut microbiota and the onset and progression of several immune diseases in humans, emphasizing that gut microbiota-derived metabolites play a non-negligible role in autoimmune diseases. The gut microbiota and its metabolites, such as short-chain fatty acids, oxidized trimethylamine, tryptophan metabolites, secondary bile acids and lipopolysaccharides, can alter intestinal barrier permeability by modulating immune cell differentiation and cytokine secretion, which in turn affects the systemic immune function of the host. It is therefore reasonable to hypothesize that ecological dysregulation of the gut microbiota may be an entirely new factor in the triggering of ITP. This article reviews the potential immune-related mechanisms of the gut microbiota and representative metabolites in ITP, as well as the important influence of leaky gut on the development of ITP, with a view to enriching the theoretical system of ITP-related gut microecology and providing new ideas for the study of ITP. [ABSTRACT FROM AUTHOR]

While circulating metabolites and immune system have been increasingly linked to hypothyroidism risk, the causality underlying these associations remains largely uninterrogated. We used Mendelian randomization to identified putative causal traits for hypothyroidism via integrating omics data. Briefly, we utilized 1180 plasma metabolites and 731 immune cells traits as exposures to identify putatively causal traits for hypothyroidism in the discovery (40,926 cases) and replication cohorts (14,871 cases). By combining MR results from two large-scale cohorts, we ultimately identified 21 putatively causal traits, including five plasma metabolites and 16 immune cell traits. CD3 on CD28+ CD4+ T cell and 1-(1-enyl-palmitoyl)-2-oleoyl-GPE (p-16:0/18:1) demonstrated the most pronounced positive and negative associations with hypothyroidism risk, respectively. The odds ratio and 95% confidence interval were 1.09 (1.07, 1.12) and 0.81 (0.75, 0.87), respectively. No evidence of horizontal pleiotropy, heterogeneity among instrumental variables or reverse causation were found for these 21 significant associations. Our study elucidates key metabolites and immune cell traits associated with hypothyroidism. These findings provide new insights into the etiology and potential therapeutic targets for hypothyroidism. This study elucidates key metabolites and immune cell traits associated with hypothyroidism. These findings provide new insights into the etiology and potential therapeutic targets for hypothyroidism. [ABSTRACT FROM AUTHOR]

Mitochondria are crucial organelles responsible for energy generation in eukaryotic cells. Oxidative stress, calcium disorders, and mitochondrial DNA abnormalities can all cause mitochondrial dysfunction. It is now well documented that mitochondrial dysfunction significantly contributes to the pathogenesis of numerous illnesses. Hence, it is vital to investigate innovative treatment methods targeting mitochondrial dysfunction. Extracellular vesicles (EVs) are cell-derived nanovesicles that serve as intercellular messengers and are classified into small EVs (sEVs, < 200 nm) and large EVs (lEVs, > 200 nm) based on their sizes. It is worth noting that certain subtypes of EVs are rich in mitochondrial components (even structurally intact mitochondria) and possess the ability to transfer them or other contents including proteins and nucleic acids to recipient cells to modulate their mitochondrial function. Specifically, EVs can modulate target cell mitochondrial homeostasis as well as mitochondria-controlled apoptosis and ROS generation by delivering relevant substances. In addition, the artificial modification of EVs as delivery carriers for therapeutic goods targeting mitochondria is also a current research hotspot. In this article, we will focus on the ability of EVs to modulate the mitochondrial function of target cells, aiming to offer novel perspectives on therapeutic approaches for diverse conditions linked to mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Simple Summary: Microsatellite instability (MSI) is crucial in colorectal cancer (CRC) due to deficient mismatch repair (MMR), often caused by MLH1 and MSH2 loss of function. This defect affects microsatellite loci globally. Recently, MSI at tetranucleotide loci has been identified as a distinct entity, potentially arising from isolated MSH3 loss of function due to its translocation to the cytoplasm under interleukin-6 (IL-6) influence. This study examined the impact of MSH3 and IL-6 signaling pathway polymorphisms (MSH3 exon 1, MSH3+3133A/G, IL-6-174G/C, IL-6R+48892A/C, and gp130+148G/C) on MSI types in sporadic CRC. A significant difference in gp130+148G/C genotypes (p = 0.037) and alleles (p = 0.031) was found, with the C allele being less common in tumors with di- and tetranucleotide instability (related to isolated MSH3 loss of function) compared to tumors without microsatellite instability. A functional polymorphism in gp130 may influence the IL-6 pathway, leading to MSI linked to MSH3 loss of function. Microsatellite instability (MSI) has been recognized as an important factor in colorectal cancer (CRC). It arises due to deficient mismatch repair (MMR), mostly attributed to MLH1 and MSH2 loss of function leading to a global MMR defect affecting mononucleotide and longer microsatellite loci. Recently, microsatellite instability at tetranucleotide loci, independent of the global MMR defect context, has been suggested to represent a distinct entity with possibly different consequences for tumorigenesis. It arises as a result of an isolated MSH3 loss of function due to its translocation from the nucleus to the cytoplasm under the influence of interleukin-6 (IL-6). In this study the influence of MSH3 and IL-6 signaling pathway polymorphisms (MSH3 exon 1, MSH3+3133A/G, IL-6-174G/C, IL-6R+48892A/C, and gp130+148G/C) on the occurrence of different types of microsatellite instability in sporadic CRC was examined by PCR–RFLP and real-time PCR SNP analyses. A significant difference in distribution of gp130+148G/C genotypes (p = 0.037) and alleles (p = 0.031) was observed in CRC patients with the C allele being less common in tumors with di- and tetranucleotide instability (isolated MSH3 loss of function) compared to tumors without microsatellite instability. A functional polymorphism in gp130 might modulate the IL-6 signaling pathway, directing it toward the occurrence of microsatellite instability corresponding to the IL-6-mediated MSH3 loss of function. [ABSTRACT FROM AUTHOR]