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A Japanese case of Kindler syndrome.

A 25-year-old Japanese woman presented with contracture of the fingers and toes, and difficulty in opening her mouth. Her grandparents are first cousins, but none of the other members of the family are affected. Bulla formation started at birth on areas of the skin that received pressure, and in infancy and early childhood the lesions were limited only to the acral areas. She also had bilateral, incomplete syndactylies involving all web spaces (Fig. 1a). The formation of blisters ceased after the age of 15 years, but a generalized progressive poikiloderma then appeared with accompanying cutane

S100A8/S100A9 Links Diabetic Stress to Cardiac Progenitor Cell Dysfunction and Fibrotic Heart Failure: An Integrated Transcriptomic, Single-Cell, and Functional Study.

BACKGROUND: Diabetes markedly increases the risk of heart failure, yet the molecular signals connecting metabolic stress, myocardial fibrosis, and impaired cardiac repair remain incompletely understood. METHODS: We integrated bulk transcriptomic data from postischemic hearts (GSE26887), fibrosis-related genes from the CTD database, protein-protein interaction (PPI) analysis, and pathway enrichment (GO, KEGG, GSEA, and GSVA) to identify candidate mediators in diabetic versus nondiabetic heart failure. Single-cell RNA-sequencing datasets were analyzed with Seurat to map the cellular distributio

Proteomic insights into vaginal mesh complications and treatment targets.

OBJECTIVE: To characterize differences in vaginal proteomic profiles among women with mesh exposure, mesh-related pain, and controls. METHODS: 10 well-integrated mesh samples (removed incidentally or normally incorporated distant from complication), 10 mesh exposure samples, 10 mesh-pain samples and 10 control vaginal biopsies of participants without mesh from a Mesh and Pelvic Floor Tissue Biorepository were analyzed. Differentially expressed protein analysis, gene ontology enrichment, clinical covariate modeling and a hypothesis-driven assessment of 100 a priori specified proteins were perf

Ultrastructure of transport pathways in stressed synovium of the knee in anaesthetized rabbits.

1. The hydraulic conductance of the synovial lining of a rabbit knee increases greatly when intra-articular pressure (IAP) is raised above approximately 9 cmH2O (yield point). To investigate the cause, synovium was fixed in situ by perfusion at controlled IAP and prepared for transmission electron microscopy. Micrographs of synovium fixed below yield pressure (atmospheric pressure and 5 cmH2O IAP, ten joints) and above it (25 cmH2O IAP, five joints) were analysed by morphometry. 2. The discontinuous cellular lining consisted of fibroblast-like cells (67%) and macrophage-like cells (33%) separa

Immunoelectron microscopic localization of neural cell adhesion molecules (L1, N-CAM, and MAG) and their shared carbohydrate epitope and myelin basic protein in developing sciatic nerve.

The cellular and subcellular localization of the neural cell adhesion molecules L1, N-CAM, and myelin-associated glycoprotein (MAG), their shared carbohydrate epitope L2/HNK-1, and the myelin basic protein (MBP) were studied by pre- and post-embedding immunoelectron microscopic labeling procedures in developing mouse sciatic nerve. L1 and N-CAM showed a similar staining pattern. Both were localized on small, non-myelinated, fasciculating axons and axons ensheathed by non-myelinating Schwann cells. Schwann cells were also positive for L1 and N-CAM in their non-myelinating state and at the onset

[Right ventricular dysplasia: clinical characteristics of five patients].

The purpose of this study was to elucidate the clinical features of right ventricular (RV) dysplasia, a recently described clinical entity characterized by RV myopathic changes and ventricular tachycardia of left bundle branch block morphology. Five cases were reported, in which the diagnosis was established according to the criteria of Marcus. Case 1, a 33-year-old man, was referred to us for evaluation of his paroxysmal ventricular tachycardia of five years duration. Case 2, a 38-year-old man, was admitted because of shock caused by ventricular tachycardia. In both cases, the QRS configurati

Light-dependent corneal toxicity in streptozocin-treated rats.

PURPOSE: To find the role of nitric oxide (NO) in streptozocin-induced corneal toxicity in rats. METHODS: Sprague-Dawley rats were injected intraperitoneally with streptozotocin (65 mg/kg). For exposure to light, each rat cage was placed in a box surrounded with aluminum foil and illuminated for 6 hours per day with two 20-W fluorescent lamps at a distance of 50 cm. When not exposed to light, each cage was placed in a dark room. Some animals with and without light exposure also were treated with and without streptozotocin treatment. Control animals did not receive streptozotocin and were hous

Fast Myosin Binding Protein-C Is a Vital Regulator in Young and Aged Fast Skeletal Muscle Homeostasis.

BACKGROUND: Skeletal muscle plays a vital role in voluntary movement and locomotion. Fast-twitch muscle fibres are characterized by their rapid contraction kinetics, high-force generation and a distinct gene expression profile compared to slow-twitch fibres. These fibres have a predominant expression of fast skeletal myosin binding protein-C (fMyBP-C). The role of fMyBP-C in skeletal muscle disease and aging remains poorly understood. To address this, our study employs mouse models with fMyBP-C ablation to investigate its significance in skeletal muscle physiology. METHODS: Skeletal muscle sa

Suppression of experimental atrial fibrillation in a canine model of rapid atrial pacing by the phosphodiesterase 3 inhibitor cilostazol.

OBJECTIVE: Atrial fibrillation (AF) represents the most common arrhythmia encountered in cardiology department. The purpose of this study was designed to investigate whether cilostazol, an oral phosphodiesterase 3 inhibitor (PDE3) could have protective effects on atrial remodeling in a canine model of AF and explore the potential molecular mechanisms. METHODS: Dogs were randomly assigned to Sham, Paced, Paced + cilostazol group, 7 dogs in each group. In Sham group, pacemaker was instrumented but without pacing. Rapid atrial pacing (RAP) at 600 or 500 bpm/min was maintained in Paced group and

Protective effects of Allium sativum against defects of hypercholesterolemia on pregnant rats and their offspring.

Sixty fertile female and male albino rats of Wistar strain (I male/ 3 females) were used in the present study. The females were divided into four groups of ten rats each. Group 1 received water and standard feeds for thirty-four days. Group 2 was fed with a cholesterol-containing diet (1%) for two weeks prior to onset of gestation and maintained administration till parturition, produce atherosclerosis (34 days). Group 3 received intragastric administration of 100mg homogenate of garlic (Allium sativum)/kg body weight for three weeks prior to onset of gestation as well as throughout the gestati

Bioinformatics analysis of TCGA data identifies a taurine metabolism-related subtype classification for predicting prognosis in colon adenocarcinoma.

BACKGROUND: The increasing incidence and mortality of colon adenocarcinoma (COAD) underscore the urgent clinical need for improved prognostic biomarkers. Current prognostic models often lack precision, highlighting the necessity for research focused on molecular signatures derived from The Cancer Genome Atlas (TCGA). This study aims to address this gap by utilizing TCGA data to identify a robust prognosis prediction model. METHODS: RNA-sequencing datasets and information on the clinical features of COAD patients were sourced from the TCGA database. Non-negative matrix factorization (NMF) was

Long non-coding RNA LINC00657 aggravates atrial fibrosis in atrial fibrillation via the miR-144-3p/ROCK1 competing endogenous RNA axis.

The clinical significance and fibrogenic mechanisms of long non-coding RNA LINC00657 in atrial fibrillation (AF) remain unclear. This study aimed to elucidate whether LINC00657 served as a mechanistic driver of atrial fibrogenesis in AF via modulation of the microRNA-144-3p (miR-144-3p)/Rho-associated coiled-coil containing protein kinase 1 (ROCK1) axis. LINC00657 expression was quantified in peripheral blood from 150 AF patients and 150 matched controls. Angiotensin II (Ang II)-stimulated primary rat cardiac fibroblasts and continuously infused C57BL/6 mice served as in vitro and in vivo fibr

Postmenopausal women with osteoarthritis and osteoporosis show different ultrastructural characteristics of trabecular bone of the femoral head.

BackgroundOsteoporosis (OP) and osteoarthritis (OA) are public health diseases affecting the quality of life of the elderly, and bring about a heavy burden to the society and family of patients. It has been debated whether or not there is an inverse relationship between these two disorders.MethodsTo compare the exact difference in bone tissue structure between osteoporosis and osteoarthritis, we observed the ultrastructure of trabecular bone from the femoral heads using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). A total of 15 femoral head specimens from post

Understanding Mesangial Pathobiology in AL-Amyloidosis and Monoclonal Ig Light Chain Deposition Disease.

Patients with plasma cell dyscrasias produce free abnormal monoclonal Ig light chains that circulate in the blood stream. Some of them, termed glomerulopathic light chains, interact with the mesangial cells and trigger, in a manner dependent of their structural and physicochemical properties, a sequence of pathological events that results in either light chain-derived (AL) amyloidosis (AL-Am) or light chain deposition disease (LCDD). The mesangial cells play a key role in the pathogenesis of both diseases. The interaction with the pathogenic light chain elicits specific cellular processes, whi

The Bone Extracellular Matrix as an Ideal Milieu for Cancer Cell Metastases.

Bone is a preferential site for cancer metastases, including multiple myeloma, prostate, and breast cancers.The composition of bone, especially the extracellular matrix (ECM), make it an attractive site for cancer cell colonization and survival. The bone ECM is composed of living cells embedded within a matrix composed of both organic and inorganic components. Among the organic components, type I collagen provides the tensile strength of bone. Inorganic components, including hydroxyapatite crystals, are an integral component of bone and provide bone with its rigidity. Under normal circumstance

Extracellular matrix dysregulation in aging, calcification, and cancer diseases: insights into cellular senescence, inflammation, and novel therapeutic strategies.

This review underscores the dynamic role of the extracellular matrix (ECM) in regulating cellular behavior and maintaining tissue homeostasis, highlighting its pivotal involvement in aging, calcification, and cancer diseases. In healthy tissues, controlled ECM remodeling provides essential biochemical and mechanical cues, but dysregulation (driven by chronic inflammation, cellular senescence, and altered intercellular communication) leads to fibrosis, calcification, and the creation of a pro-tumorigenic microenvironment. Senescent cells contribute to these changes through senescence-associated

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… In addition, mature collagen fibrils are often associated with the fibril-associated collagens with interrupted triple helices (FACIT) family, which includes collagens such as types IX and XII 65 . …

Bleeding Propensity in Waldenström Macroglobulinemia: Potential Causes and Evaluation.

Waldenström macroglobulinemia (WM) is a rare, incurable, low-grade, B cell lymphoma. Symptomatic disease commonly results from marrow or organ infiltration and hyperviscosity secondary to immunoglobulin M paraprotein, manifesting as anemia, bleeding and neurological symptoms among others. The causes of the bleeding phenotype in WM are complex and involve several intersecting mechanisms. Evidence of defects in platelet function is lacking in the literature, but factors impacting platelet function and coagulation pathways such as acquired von Willebrand factor syndrome, hyperviscosity, abnormal

Potential Targeting Mechanisms for Bone-Directed Therapies.

Bone development is characterized by complex regulation mechanisms, including signal transduction and transcription factor-related pathways, glycobiological processes, cellular interactions, transportation mechanisms, and, importantly, chemical formation resulting from hydroxyapatite. Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. Howe

Премии победителей и резюме 32nd Ежегодный симпозиум Общества протеинов; Бостон, ОЭТ, июль 9-12, 2018.

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The Synthetic Collagen-Binding Peptide NIPEP-OSS Delays Mouse Myeloma Progression.

Multiple myeloma (MM) is the second most common hematological malignancy. It is a clonal B-cell disorder characterized by the proliferation of malignant plasma cells in the bone marrow, the presence of monoclonal serum immunoglobulin, and osteolytic lesions. An increasing amount of evidence shows that the interactions of MM cells and the bone microenvironment play a significant role, suggesting that these interactions may be good targets for therapy. The osteopontin-derived collagen-binding motif-bearing peptide NIPEP-OSS stimulates biomineralization and enhances bone remodeling dynamics. Due