Objectives Aging causes stiffness and decreased function of the renal artery (RA). Histological study with light microscopy can reveal microscopic structural remodeling but no functional changes. The present study aimed to clarify the association between structural and functional aging of the RA through the use of scanning acoustic microscopy. Methods Formalin-fixed, paraffin-embedded cross-sections

The emergence of SARS-CoV-2 has caused the current COVID-19 pandemic with catastrophic societal impact. Because many individuals shed virus for days before symptom onset, and many show mild or no symptoms, an emergent and unprecedented need exists for development and deployment of sensitive and high throughput molecular diagnostic tests. RNA-mediated oligonucleotide Annealing Selection and Ligation

Ferrochelatase (FECH) is the terminal enzyme in heme biosynthesis. We previously showed that FECH is required for endothelial cell growth in vitro and choroidal neovascularization in vivo. But FECH has not been explored in retinal neovascularization, which underlies diseases like proliferative diabetic retinopathy and retinopathy of prematurity. Here, we investigated the inhibition of FECH using genetic

Background: This study proposed a computational method to detect the cancer areas and calculate the tumor proportion score (TPS) of PD-L1 immunohistochemistry (IHC) expression for lung adenocarcinoma based on deep learning and transfer learning. Patients and methods: PD-L1 22C3 and SP142 IHC slides of lung adenocarcinoma samples on digitized whole-slide images (WSI) database were employed. We build

Blood levels of heat shock protein (HSP27) and natural IgG auto-antibodies to HSP27 (AAbs) are higher in healthy controls compared to cardiovascular disease patients. Vaccination of mice with recombinant HSP25 (rHSP25, murine ortholog of human rHSP27) increased AAb levels, attenuated atherogenesis and reduced plaque inflammation and cholesterol content. We sought to determine if the HSP27 immune complex

The histological basis of the human uterine endometrium has been established by 2D observation. However, the fundamental morphology of endometrial glands is not sufficiently understood because these glands have complicated winding and branching patterns. To construct a big picture of endometrial gland structure, we performed tissue-clearing-based 3D imaging of human uterine endometrial tissue. Our

Serology testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is increasingly being used during the current pandemic of Coronavirus Disease 2019 (COVID-19). The clinical and epidemiologic utilities of antibody-based SARS-CoV-2 testing are under debate. Characterizing these assays helps to understand the disease and provide scientific basis to decide how to best use these assays.

Ulcerative colitis is a condition characterised by the infiltration of leukocytes into the gastrointestinal wall. Leukocyte-MPO catalyses hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN) formation from chloride (Cl-) and thiocyanous (SCN-) anions, respectively. While HOCl indiscriminately oxidises biomolecules, HOSCN primarily targets low-molecular weight protein thiols. Oxidative damage mediated

Chronic salivary hypofunction and xerostomia are common side effects of radiation therapy which is an essential component in the curative management in patients with head & neck cancers. Over the years, improvements in delivery techniques such as image-guided intensity modulated radiation therapy have led to improvement in cancer management but chronic hyposalivation continues to be a challenge that

Canagliflozin (Cana) is an inhibitor of the sodium glucose transporter 2 (SGLT2), and is thought to act by blocking renal reuptake and intestinal absorption of glucose. Cana is FDA-approved for treatment of diabetes, and affords protection from cardiovascular and kidney diseases. In the context of the mouse Interventions Testing Program, genetically heterogeneous mice were given chow containing 180

Elevated Heat Shock Protein 27 levels predict relative freedom from cardiovascular events. In ApoE-/- mice HSP27 over-expression or twice daily subcutaneous injections reduce blood and plaque cholesterol levels, inflammation and atherogenesis. While natural antibodies to HSP27 are present in human blood their role is unknown. Here, we show that blood levels of both HSP27 and anti-HSP27 IgG antibodies

Background: Despite improvements in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) remain prevalent in subjects undergoing therapy. HAND significantly affects individuals quality of life, as well as adherence to therapy, and, despite the increasing understanding of neuropathogenesis, no definitive diagnostic or prognostic marker has been

Purpose: To develop a digital algorithm and validate a semi-quantitative scoring method for surface methylene blue (MB) staining in whole lymph nodes (LN). Methods: Lymph nodes from canine models undergoing sentinel lymph node (SLN) mapping were prospectively assessed ex vivo and photographed. Two blinded observers evaluated all images and assigned a semi-quantitative score based on surface staining

Histopathological examination of temporal artery biopsy (TAB) remains the gold standard for the diagnosis of giant cell arteritis (GCA) but is associated with essential limitations that emphasize the need for an upgraded pathological process. This study pioneered the use of full-field optical coherence tomography (FF-OCT) for rapid and automated on-site pathological diagnosis of GCA. Sixteen TABs (12

Sepsis-induced acute kidney injury (S-AKI) is the most common complication in hospitalized and critically ill patients, highlighted by a rapid decline of kidney function occurring a few hours or days after sepsis onset. Systemic inflammation elicited by microbial infections is believed to lead to kidney damage under immunocompromised conditions. However, while AKI has been recognized as a disease with

Background: Allograft vasculopathy (AV) remains a major obstacle to long-term allograft survival. While the mouse aortic transplantation model has been proven as a useful tool for study of the pathogenesis of AV, simultaneous transplantation of the aorta alongside the transplantation of another organ may reveal more clinically relevant mechanisms that contribute to the pathogenesis of chronic allograft

Background: Anosmia is a frequent symptom in coronavirus disease 2019 (COVID-19) patients that generally resolves within weeks. In contrast, the anosmia caused by other upper respiratory infections affects a small proportion of patients and may take months to resolve or never resolve. The mechanisms behind COVID-19-induced olfactory dysfunction remain unknown. Here, we address the unique pathophysiology

Von Hippel-Lindau disease (VHL) is an autosomal dominant rare disease that causes the formation of angiogenic tumors. When functional, pVHL acts as an E3 ubiquitin ligase that negatively regulates hypoxia inducible factor (HIF). Genetic mutations that perturb the structure of pVHL result in dysregulation of HIF, causing a wide array of tumor pathologies including retinal angioma, pheochromocytoma,

Background: The transmembrane-TNF transgenic mouse, TgA86, has been shown to develop spontaneously peripheral arthritis with signs of axial involvement. To assess similarity to human spondyloarthritis we performed detailed characterization of the axial, peripheral and comorbid pathologies of this model. Methods: TgA86 bone pathologies were assessed at different ages using CT imaging of the spine, tail

Endothelial cell (EC) sensing of fluid shear stress regulates atherosclerosis, a disease of arteries that causes heart attack and stroke. Atherosclerosis preferentially develops at regions of arteries exposed to low oscillatory shear stress (LOSS), whereas high shear regions are protected. We show using inducible EC-specific genetic deletion in hyperlipidaemic mice that the Notch ligands JAG1 and DLL4

Objective: Patients with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibit not only respiratory symptoms but also symptoms of chemo-sensitive disorders and kidney failure. Cellular entry of SARS-CoV-2 depends on the binding of its spike protein to a cellular receptor named angiotensin-converting enzyme 2 (ACE2), and the subsequent spike

Hexaploid spring wheat (Triticum aestivum) may exhibit significant crown rot disease responses to infection by Fusarium pseudograminearum, with a range of susceptibility levels available in commercial cultivars. Dry conditions during grain-fill may lead to the expression of prematurely senescing culms, which typically fail to set grain. Assessment of hexaploid spring wheat plants exhibiting both non-senescent

Keloid is a benign dermal fibrotic disorder with some features similar to malignant tumors such as hyper-proliferation, apoptosis resistance and invasion. keloid remains a therapeutic challenge in terms of high recurrence rate and lack of satisfactory medical therapies, which is partially due to the incomplete understanding of keloid pathogenesis. A thorough understanding of the cellular and molecular

Virus cause multiple outbreaks, for which comprehensive tailored therapeutic strategies are still missing. Virus and host cell dynamics are strictly connected, and convey in virion assembly to ensure virus spread in the body. Study of the systemic behavior of virus-host interaction at the single-cell level is a scientific challenge, considering the difficulties of using experimental approaches and

Background Awareness of residual disabilities amongst people living in countries recovering from prolonged armed conflicts and their socio-economic consequences is increasing. Robust data on the prevalence of such disabilities are important for planning cost effective health services. This study outlines the first community-based prevalence study of Major Limb Loss (MLL) in the Acholi sub region of

Objective: The gut microbiota (GM) can have complicated and often undetermined interactions with the function of many organs in the body. GM is altered in a variety of liver diseases, but the significance of such changes on the liver disease is still unclear. Hepatic autophagy deficiency causes liver injury accompanied with cholestasis. Here, we investigated the impact of such hepatic changes on GM

The COVID-19 pandemic has brought the world to a halt, with cases observed around the globe causing significant mortality. There is an urgent need for serological tests to detect antibodies against SARS-CoV-2, which could be used to assess the prevalence of infection, as well as ascertain individuals who may be protected from future infection. Current serological tests developed for SARS-CoV-2 rely

The outbreak of COVID-19 across the world has posed unprecedented and global challenges on multiple fronts. Most of the vaccine and drug development has focused on the spike proteins and viral RNA-polymerases. Using the bioinformatics and structural modeling approach, we modeled the structure of the envelope (E)-protein of novel SARS-CoV-2. The E-protein of this virus shares sequence similarity with

The Rice Yellow Mottle sobemovirus (RYMV) belongs to the most damaging pathogens devastating rice fields in Africa. P1, a key protein for RYMV, was reported as a potent RNAi suppressor counteracting RNA silencing in plant reporter systems. Here we describe the complete 3D structure and dynamics of P1. Its N-terminal region contains ZnF1, a structural CCCC-type zinc finger strongly affine to zinc and

The deposition of monomeric C-reactive protein (mCRP) in the myocardium aggravates ischemia-reperfusion injury (IRI) and myocardial infarction. Ischemic preconditioning (IPC) is known to protect the myocardium against IRI. We evaluated the effects of IPC on mCRP-deposited myocardium due to IRI in a rat model. Myocardial IRI was produced by ligation of the coronary artery. Direct IPC was applied before

Plasmacytoid dendritic cells (pDC) are the principal natural type I interferon producing dendritic cells. Neoplastic expansion of pDCs and pDC precursors leads to blastic plasmacytoid dendritic cell neoplasm (BPDCN) and clonal expansion of mature pDCs has been described in chronic myelomonocytic leukemia (CMML). The role of pDC expansion in acute myeloid leukemia (AML) is poorly studied. Here we characterize

A customized context-dependent validation of antibodies for the prospective use, rather than a general stamp of validity, is required for reproducibility and data validity, besides the need of standardized reagents. In-situ antibody staining is a technique broadly used in experimental settings and human diagnostic practice. The first typically, but not exclusively uses lightly fixed material (cell

Accumulating clinical observations suggest pathogenesis beyond viral pneumonia and its secondary consequences in COVID-19 patients. In particular, many patients develop profound hyperinflammation and hypercoagulopathy with disseminated thrombogenesis and thromboembolism, which we observe also in a Swedish COVID-19 intensive care patient cohort. To understand these vascular manifestations, it is important

Alzheimer’s disease (AD) has a multifactorial etiology, which requires a single multi-target approach for an efficient treatment. We have focused on E2F4, a transcription factor that regulates cell quiescence and tissue homeostasis, controls gene networks affected in AD, and is upregulated in the brain of Alzheimer’s patients and of APP/PS1 and 5xFAD transgenic mice. E2F4 contains an evolutionarily-conserved

Purpose Conjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection.

Background Modern antiretroviral therapies (ART) have decreased the prevalence of HIV-associated nephropathy (HIVAN). Nonetheless, we continue to see children and adolescents with HIVAN all over the world. Furthermore, once HIVAN is established in children, it is difficult to revert its long-term progression, and we need better animal models of childhood HIVAN to test new treatments.

Background Sudden unexpected death in infancy (SUDI) comprises both natural and unnatural causes of death. However, a few epidemiological surveys have investigated SUDI in Japan.

Slide-free digital pathology techniques, including nondestructive 3D microscopy, are gaining interest as alternatives to traditional slide-based histology. In order to facilitate clinical adoption of these fluorescence-based techniques, software methods have been developed to convert grayscale fluorescence images into color images that mimic the appearance of standard absorptive chromogens such as

BACKGROUND and AIMS Extra-hepatic biliary atresia (BA) is a pediatric liver disease with no approved medical therapy. Recent studies using human samples and experimental modeling suggest that glutathione redox metabolism and heterogeneity play a role in disease pathogenesis. We sought to dissect the mechanistic basis of liver redox variation and explore how other stress responses affect cholangiocyte

Background & aims Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder leading to paralysis and death in children. SMA patients are more susceptible to dyslipidemia as well as liver steatosis, features reproduced in SMA mouse models. As current pre-clinical models of NAFLD are invariably imperfect and generally take a long time to develop, the rapid development of liver steatosis in

The prevalence of chronic widespread pain (CWP) in people with HIV (PWH) is high, yet the underlying mechanisms are elusive. Leukocytes synthesize the endogenous opioid, β-endorphin (β-END), within their endoplasmic reticulum (ER). When released into plasma, β-END dampens nociceptive transmission by binding to opioid receptors on sensory neurons. In the present study, we hypothesized that heme-induced

Gastric cancer is among the most malignant tumours with the highest incidence and mortality rates. The early detection and accurate histopathological diagnosis of gastric cancer are essential factors that can help increase the chances of successful treatment. While the worldwide shortage of pathologists has imposed burdens on current histopathology services, it also offers a unique opportunity for

Background This study evaluated the effects of the chronic consumption of different concentrations of alcohol on the experimental periodontitis (EP).

Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of liver disease worldwide.1 Animal models are widely used to investigate the mechanisms of fatty liver disease, but they do not faithfully represent NAFLD in humans.2 Thus, there is strong interest in studying NAFLD pathogenesis directly in humans whenever possible. One strategy that is gaining momentum is to utilize iPSC-derived

Background Leading to a sustained epidemic spread with >2,000,000 confirmed human infections, including >100,000 deaths, COVID-19 was caused by SARS-CoV-2 and resulted in acute respiratory distress syndrome (ARDS) and sepsis, which brought more challenges to the patient’s treatment. The S-glycoprotein, which recognized as the key factor for the entry of SARS-CoV-2 into the cell, contains two functional

Verticillium wilt, caused by the soil-borne fungus Verticillium dahliae, is one of the most harmful diseases in Mediterranean olive-growing areas. Although, the effects of both soil temperature and moisture on V. dahliae are well known, there is scant knowledge about what climatic drivers affect the occurrence of the pathogen on a landscape scale. Here, we investigate what climatic drivers determine

Background Platelet adhesion is the critical process mediating stable thrombus formation. Previous reports of cadherin-6 on human platelets have demonstrated its role in platelet aggregation and thrombus formation.

Background The identity and spatial distribution of prostatic cell types has been determined in humans but not in dogs, even though aging- and prostate-related voiding disorders are common in both species and mechanistic factors, such as prostatic collagen accumulation, appear to be shared between species. In this publication we characterize the regional distribution of prostatic cell types in the

High frequency ultrasonography is a routine approach to monitor the aorta of live mice. Ultrasound using a para-sternal view can visualize the proximal thoracic aorta, but not the descending thoracic region due to the confounders of lungs and ribs. To overcome this issue, we report a para-spinal dorsal approach for ultrasound imaging of the descending thoracic aorta in mice. This novel approach enables

The study of pulmonary samples from individuals who have died as a direct result of COVID-19 infection is vital to our understanding of the pathogenesis of this disease. Histopathologic studies of lung tissue from autopsy of patients with COVID-19 specific mortality are only just emerging. All existing reports have relied on traditional 2-dimensional slide-based histological methods for specimen preparation

Uterine leiomyomas (ULs) constitute a considerable health burden in the general female population. The fumarate hydratase (FH) deficient subtype is found in up to 1.6% and can occur in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome.

As cattle movement data in the United States are scarce due to the absence of mandatory traceability programs, previous epidemic models for U.S. cattle production systems heavily rely on contact rates estimated based on expert opinions and survey data. These models are often based on static networks and ignore the sequence of movement, possibly overestimating the epidemic sizes. In this research, we

The response of pathophysiological research to emerging epidemics often occurs after the epidemic and, as a consequence, has little to no impact on improving patient outcomes or on developing high-quality evidence to inform clinical management strategies during the epidemic. Rapid and informed guidance of epidemic (research) responses to severe infectious disease outbreaks requires quick compilation

Potato spindle tuber viroid and other pospiviroids can cause serious diseases in potato and tomato crops. Consequently, pospiviroids are regulated in several countries. Since seed transmission is considered as a pathway for the introduction and spread of pospiviroids, some countries demand for the testing of seed lots of solanaceous crops for the presence of pospiviroids. A real-time RT-PCR test, named

Pulmonary hypertension and cor pulmonale are complications of severe equine asthma, as a consequence of pulmonary hypoxic vasoconstriction. However, as pulmonary hypertension is only partially reversible by oxygen administration, other etiological factors are likely involved. In human chronic obstructive pulmonary disease, pulmonary artery remodeling contributes to the development of pulmonary hypertension

Background An endometrial sampling procedure is a gold standard for the diagnostic evaluation of women with abnormal uterine bleeding (AUB) with primary aim to identify the cause, especially to determine whether carcinoma or premalignant lesions are present. The objective of the study is therefore to review endometrial biopsy specimen histopathological findings and associated factors at a tertiary

BACKGROUND Cytoskeletal structural proteins maintain cell structural integrity by bridging extracellular matrix (ECM) with contractile filaments. During AAA development, (i) aortic medial degeneration is associated with loss of smooth muscle cell (SMC) integrity, and (ii) fibrogenic mesenchymal cells (FMSCs) mediates ECM remodeling. Calpains cleave cytoskeletal proteins that maintain cell structural

Introduction COVID-19, is caused by a new strain of coronavirus called SARS-coronavirus-2 (SARS-CoV-2), which is a positive sense single strand RNA virus. In humans, it binds to angiotensin converting enzyme 2 (ACE2) with the help a structure on its surface called the S-spike. COVID-19 poses intriguing issues with imperative relevance to clinicians. The pathogenesis of GI symptoms, diabetes-associated

Background: Tsetse flies transmit trypanosomes that cause the debilitating diseases human African trypanosomosis (HAT) or sleeping sickness in humans and animal African trypanosomosis (AAT) or nagana in livestock. The riverine tsetse species Glossina palpalis gambiensis Vanderplank (Diptera: Glossinidae) inhabits riparian forests along river systems in West Africa. The Government of Senegal has embarked

Sepsis is a life-threatening condition due to a dysregulated immunological response to infection. Apart from source control and broad-spectrum antibiotics, management is based on fluid resuscitation and vasoactive drugs. Fluid resuscitation implicates the risk of volume overload, which in turn is associated with longer stay in intensive care, prolonged use of mechanical ventilation and increased mortality