Retrospective analysis of canine monocytic ehrlichiosis in Thailand with emphasis on hematological and ultrasonographic changes

Background and Aim: Canine monocytic ehrlichiosis (CME) is a tropical endemic tick-borne disease that causes fatality or chronic infection involving many organs in dogs. This study aimed to examine the prevalence, risk factors, and hematological and ultrasonographic changes in the liver, gallbladder, kidneys, and spleen following CME infection. Materials and Methods: This retrospective study used 30,269 samples collected from dogs at the hematology section of the pathology unit of a university veterinary hospital and 35 samples collected from dogs at the diagnostic imaging unit. CME was determined using the buffy coat smear method. Data were analyzed using descriptive statistics and odds ratios. Results: CCl4 The data revealed that the average yearly prevalence of CME was 1.32%. Risk factors contributing to CME infection were a tick on the body during physical examination, lack of ectoparasite control, and outdoor living. All 148 dogs with CME infection had low platelet counts. The percentages of CME-infected dogs with elevated serum alanine aminotransferase, alkaline phosphatase, and both enzymes above the normal range were 33.6%, 65.9%, and 29.8%, respectively. The rates for elevated serum levels of blood urea nitrogen, creatinine, and both compounds were 33.1%, 19.1%, and 17.3%, respectively. The most common ultrasonographic changes were liver abnormalities (hyperechogenicity or hypoechogenicity, hepatomegaly, and hypoechoic nodules), hyperechogenicity of the kidneys, and an enlarged spleen. These ultrasonographic changes were consistent with the hematology results, which showed a greater elevation of serum liver enzyme levels than renal enzymes. Conclusion: Ultrasonographic changes during CME infection and after treatment with doxycycline can help to monitor and identify persistent pathological changes in the target organs resulting from immune response to CME.

Potential target for mitigation of COVID-19 by food-derived bioactive peptides

Oral administration of food protein hydrolysate and naturally occurring peptides exert beneficial effects beyond conventional nutritional functions by supplying amino acids for protein synthesis. These peptides are referred to as food-derived bioactive peptides. The coronavirus disease 2019 (COVID-19) is caused by sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some host and viral proteins are involved in the entry of SARS-CoV-2 into cells and their replication. Peptides with specific sequences can interact with these proteins and have potential prophylactic and therapeutic activities against COVID-19. However, it is difficult to deliver food-derived peptides to target organs without degradation by exopeptidases in the body. Alternatively, food-derived peptides and amino acid metabolites have been suggested to decrease risk factors of COVID-19 by modulating the renin-angiotensin system, the innate immune system, and the antioxidant system. This mini-review is based on in vivo responses to food-derived peptides and aims to introduce potential targets for these peptides in decreasing the risk and severity of COVID-19.

The state of estrogen-dependent organs of women with surgical menopause and hormone replacement therapy

The research aims at studying the dynamics and character o f disorders in the target-organs and appraisingthe quality оf life in women with surgical menopause (SM ) on the background o f hormonal replacement therapy (HRT).Application o f Femoston as the preferable preparation was determined by functional state оf estrogen-dependent organs (cardiovascular system, bone tissue, and mamma) and accompanying extragenital diseases.Hormonal replacement therapy effectively reduces early climacterics disorders connected with menopause and promotes prophylaxis o f late complications o f menopause development (cardiovascular disease and osteoporosis). Femoston is the preparation o f choice fo r women with surgical menopause as it exerts minimum influence on the metabolism and doesnt have anabolic or glucocorticoid effects.

Comparative effectiveness of endometriosis-associated infertility therapy

Endometnosis is not a disease of individual organs and systems, but of the whole organism, the treatment of which requires complex action. The effect of all drugs used to treat endometriosis is to suppress growth factors and the development of pathological implants at different levels of the system - from the hypothalamus to target organs. The problem of restoring reproductive function in patients with endometriosis-associated infertility remains very urgent at the present time. This is due to the prevalence of this pathological process - in the structure of female infertility, endometriosis is about 50%.

Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients: a pilot study

Purpose To develop quantitative molecular imaging biomarkers of immune-related adverse event (irAE) development in malignant melanoma (MM) patients receiving immune-checkpoint inhibitors (ICI) imaged with 18F-FDG PET/CT. Methods 18F-FDG PET/CT images of 58 MM patients treated with anti-PD-1 or anti-CTLA-4 ICI were retrospectively analyzed for indication of irAE. Three target organs, most commonly affected by irAE, were considered: bowel, lung, and thyroid. Patient charts were reviewed to identify which patients experienced irAE, irAE grade, and time to irAE diagnosis. Target organs were segmented using a convolutional neural network (CNN), and novel quantitative imaging biomarkers — SUV percentiles (SUVX%) of 18F-FDG uptake within the target organs — were correlated with the clinical irAE status. Area under the receiver-operating characteristic curve (AUROC) was used to quantify irAE detection performance. Patients who did not experience irAE were used to establish normal ranges for target organ 18F-FDG uptake. Results A total of 31% (18/58) patients experienced irAE in the three target organs: bowel (n=6), lung (n=5), and thyroid (n=9). Optimal percentiles for identifying irAE were bowel (SUV95%, AUROC=0.79), lung (SUV95%, AUROC=0.98), and thyroid (SUV75%, AUROC=0.88). Optimal cut-offs for irAE detection were bowel (SUV95%>2.7 g/mL), lung (SUV95%>1.7 g/mL), and thyroid (SUV75%>2.1 g/mL). Normal ranges (95% confidence interval) for the SUV percentiles in patients without irAE were bowel [1.74, 2.86 g/mL], lung [0.73, 1.46 g/mL], and thyroid [0.86, 1.99 g/mL]. Conclusions Increased 18F-FDG uptake within irAE-affected organs provides predictive information about the development of irAE in MM patients receiving ICI and represents a potential quantitative imaging biomarker for irAE. Some irAE can be detected on 18F-FDG PET/CT well before clinical symptoms appear.

Comparison of Surface Equivalent Dose in CBCT, Digital Panoramic and Intra-Oral X-Ray Generators Using InstadoseTM Device: An In-Vitro Study

Background: Radiation protection in the dental examination is often overlooked because the doses delivered are negligible. However, the volume of dental radiological examinations will constitute almost 15% of all the radiological examinations carried out in the medical field. Aim: This study aims to evaluate and compare the surface equivalent dose on various target organs from various radiology devices on the RINN phantom, and the effect of numerous scanning protocols on said dose using dosimetry badge (Instadose). Objectives: The main objective is to study surface equivalent doses delivered in various critical organ regions in the facial region with the help of an Instadose device and to compare the doses delivered between 2D programs against 3D programs. Materials and Methods: RINN phantom was mounted on a dental chair for use against Planmeca ProMax 3D Classic and Planmeca intraoral ProX. Models. An Instadose badge was placed on various anatomical landmarks, and radiographic exposure protocols were applied to vary the parameters. The equivalent dose was calculated by connecting the dosimeter to a laptop and performing an instant reading output on the Instadose software. Results: The Thyroid showed a mean of 0.350, 0.0000, 0.0133, and 0.0000 in response to exposure by intraoral machine ProX, Panoramic, CBCT, and CBCT in ULD mode respectively. The dose absorbed by the left salivary glands was found to be significantly lower than the right salivary glands in panoramic exposures. Conclusion: It was revealed that a significant reduction in the dose when applying the Ultra-Low Dose protocol was noticed, and it reached up to 100% in the thyroid. It was also noted that there is no need for a thyroid collar in CBCT and Panoramic exposures. Maintaining the KVp at a constant and the exposure time as a variant caused a change in the dose equivalent received by the floor of the mouth and the right salivary gland.

Investigations on the Accumulation, Tissue Distribution and Toxicity of Silver Nanoparticles in Amammalian Model

The current work aimed to investigate the potential toxicity of Ag-NPs in male rabbits as a mammalian model, following acute and sub-acute dermal exposure terms. The rabbits were topically exposed to a single acute dose of 2.0% Ag-NPs and the assessments were conducted4 days latter, while a dose of 0.5% was administered every other day for the sub-acute exposure in two time periods (7 and 14 days). The accumulation and retention of Ag+ ions in the skin and their distribution in other vital tissues were measured. In addition, the concentrations of total proteins, lipidparameters and levels of different oxidative stress biomarkers in the skin were also evaluated. The results demonstrated the ability of Ag-NPs to penetrate the skin and accumulate rapidly in the dermal skin, then spread out to the blood and other vital organs. The spleen and liver seemed to be the main target organs. The high levels of Ag+ tissue accumulation affected the concentration of total proteins and acted as a stressor stimulus within the skin, thereby, initiating oxidative stress. The liberated ROS caused disruption of the activities of the antioxidant enzymes GST, GSH, GR, GPx, SOD and CAT as well as increased levels of H2O2 and MDA. The current work showed that the toxicity of Ag-NPs could be attributed to the release of Ag+ ions and the subsequent excessive generation of ROS.

Activation of T-bet, FOXP3, and EOMES in Target Organs From Piglets Infected With the Virulent PRRSV-1 Lena Strain

Transcription factors (TFs) modulate genes involved in cell-type-specific proliferative and migratory properties, metabolic features, and effector functions. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogen agents in the porcine industry; however, TFs have been poorly studied during the course of this disease. Therefore, we aimed to evaluate the expressions of the TFs T-bet, GATA3, FOXP3, and Eomesodermin (EOMES) in target organs (the lung, tracheobronchial lymph node, and thymus) and those of different effector cytokines (IFNG, TNFA, and IL10) and the Fas ligand (FASL) during the early phase of infection with PRRSV-1 strains of different virulence. Target organs from mock-, virulent Lena-, and low virulent 3249-infected animals humanely euthanized at 1, 3, 6, 8, and 13 days post-infection (dpi) were collected to analyze the PRRSV viral load, histopathological lesions, and relative quantification through reverse transcription quantitative PCR (RT-qPCR) of the TFs and cytokines. Animals belonging to both infected groups, but mainly those infected with the virulent Lena strain, showed upregulation of the TFs T-bet, EOMES, and FOXP3, together with an increase of the cytokine IFN-γ in target organs at the end of the study (approximately 2 weeks post-infection). These results are suggestive of a stronger polarization to Th1 cells and regulatory T cells (Tregs), but also CD4+ cytotoxic T lymphocytes (CTLs), effector CD8+ T cells, and γδT cells in virulent PRRSV-1-infected animals; however, their biological functionality should be the object of further studies.

Donor T-Cell Repertoire Profiling in Recipient Lymphoid and Parenchyma Organs Reveals GVHD Pathogenesis at Clonal Levels After Bone Marrow Transplantation in Mice

The diversity and composition of T-cell receptor (TCR) repertoire, which is the result of V, (D), and J gene recombination in TCR gene locus, has been found to be implicated in T-cell responses in autoimmunity, cancer, and organ transplantation. The correlation of T-cell repertoire with the pathogenesis of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation remains largely undefined. Here, by utilizing high-throughput sequencing of the genes encoding TCRβ-chain, we comprehensively analyzed the profile of T-cell repertoire in recipient lymphoid and GVHD target organs after bone marrow transplantation (BMT) in mice. In lymphoid organs, TCR diversity was narrowed, accompanied with reduced numbers of unique clones while increased accumulation of dominant clones in allogeneic T cells compared to syngeneic T cells. In an individual allogeneic recipient, donor-derived TCR clones were highly overlapped among tissue sites, and the degree of overlapping was increasing from day 7 to 14 after allogeneic BMT. The top clones in peripheral blood, gut, liver, and lungs were highly mutually shared in an allogenic recipient, indicating that blood has the potential to predict dominant clones in these GVHD target organs. T cells in GVHD target organs from allogeneic recipients had fewer overlapped clones with pre-transplant donor T cells compared to those from syngeneic recipients. Importantly, the top 10 clones in allogeneic recipients were not detectable in pre-transplant donor T cells, indicating clonal expansion of rare rearrangements. Interestingly, even starting from the same pool of donor repertoires, T cells had very few overlapped clones between each allogeneic recipient who developed completely different dominant clones. We were only able to trace a single clone shared by three replicate allogeneic recipients within the top 500 clones. Although dominant clones were different among allogeneic recipients, V26 genes were consistently used more frequently by TCR clones in allogeneic than syngeneic recipients. This is the first study to extensively examine the feature of T-cell repertoire in multiple lymphoid and parenchyma organs, which establishes the association between T-cell activation and GVHD pathogenesis at the level of TCR clones. Immune repertoire sequencing-based methods may represent a novel personalized strategy to guide diagnosis and therapy in GVHD.

Challenges for the Development of Extracellular Vesicle-Based Nucleic Acid Medicines

Nucleic acid drugs, such as siRNAs, antisense oligonucleotides, and miRNAs, exert their therapeutic effects by causing genetic changes in cells. However, there are various limitations in their delivery to target organs and cells, making their application to cancer treatment difficult. Extracellular vesicles (EVs) are lipid bilayer particles that are released from most cells, are stable in the blood, and have low immunogenicity. Methods using EVs to deliver nucleic acid drugs to target organs are rapidly being developed that take advantage of these properties. There are two main methods for loading nucleic acid drugs into EVs. One is to genetically engineer the parent cell and load the target gene into the EV, and the other is to isolate EVs and then load them with the nucleic acid drug. Target organ delivery methods include passive targeting using the enhanced permeation and retention effect of EVs and active targeting in which EVs are modified with antibodies, peptides, or aptamers to enhance their accumulation in tumors. In this review, we summarize the advantages of EVs as a drug delivery system for nucleic acid drugs, the methods of loading nucleic acid drugs into EVs, and the targeting of EVs to target organs.