A Concise Overview of Biosensing Technologies for the Detection of Alzheimer's Disease Biomarkers

: Alzheimer's disease (AD) is a brain-linked pathophysiological condition with neuronal degeneration, cognition dysfunctions, and other debilitations. Due to the growing prevalence of AD, there is a highly commended tendency to accelerate and develop analytical technologies for easy, cost-effective, and sensitive detection of AD biomarkers. In the last decade, remarkable advancements have been achieved on the gate to the progression of biosensors, predominantly optical and electrochemical, to detect AD biomarkers. Biosensors are commanding analytical devices that can conduct biological responses on transducers into measurable signals. These analytical devices can assist the case finding and management of AD. This review focuses on up-to-date developments, contests, and tendencies regarding AD biosensing principally, emphasizing the exclusive possessions of nanomaterials.

Withanolide D of Ashwagandha improves Apoptosis in the Bone Marrow of Leukemic Murine Model

Background: Leukemia is one of the most occurring haematological pathologies in the world which develops due to the impairment in the hematopoietic machinery. Cellular death via apoptosis is severely impaired in this pathophysiological condition and leads to the progression of the disease. Objective: We have tried to unearth the efficacy of Withanolide D, a steroidal lactone derived from Withania somnifera or Ashwagandha on some of the apoptotic machinery components, i.e. TERT, BCL2 and PUMA in the experimental leukemic mice. Materials and Methods: LD50 and EC50 values of Withanolide D were estimated. Three groups of animals were taken for experimental purpose i.e. Group I = Leukemic, (L); Group II = Control, (C); Group III = Leukemic treated with Withanolide D, (L + WD). Group III received Withanolide D via oral route and other two groups received equal volume of distilled water. Various cytological, immunofluorescence and flow cytometric studies were taken into consideration post administration. Result: Leukemic group showed increased cellular proliferation and decreased cellular death as compared to control. Post Withanolide D administration TERT, BCL2 and PUMA expression started to shift towards normal status. This shift in the expressional values of increased apoptosis rate and decreased cellular proliferation revealed by cytological, immunofluorescence studies and flow cytometric investigations. Conclusion: As Withanolide D decreased the suppression of apoptosis and impaired the progression of the disease, so, we can conclude that Withanolide D of Ashwagandha may hold a promise towards a new therapeutic strategy in leukemia.

Aquaporins Are Differentially Regulated in Canine Cryptorchid Efferent Ductules and Epididymis

The efferent ductules and the epididymis are parts of the male reproductive system where spermatozoa mature. Specialized epithelial cells in these ducts contribute to the transport of fluids produced by spermatozoa’s metabolic activity. Aquaporins (AQPs) have been demonstrated to be expressed in the spermatozoan membrane and testis epithelial cells, where they contribute to regulating spermatozoan volume and transit through environments of differing osmolality. Due to the lack of detailed literature regarding AQP expression in the canine male genital tract, the aim of this study was to investigate both the distribution and expression of AQP7, AQP8, and AQP9 in the efferent ductules and epididymal regions (caput, corpus, and cauda) from normal and cryptorchid dogs by using immunohistochemistry, Western blotting, and real-time reverse transcription polymerase chain reaction (RT-PCR). Our results show different patterns for the distribution and expression of the examined AQPs, with particular evidence of their upregulation in the caput and downregulation in the cauda region of the canine cryptorchid epididymis. These findings are associated with a modulation of Hsp70 and caspase-3 expression, suggesting the participation of AQPs in the luminal microenvironment modifications that are peculiar characteristics of this pathophysiological condition.

Measuring Insulin Resistance in Humans

<b><i>Background:</i></b> Insulin resistance is a pathophysiological condition associated with diabetes and cardiometabolic diseases that is characterized by a diminished tissue response to insulin action. Our understanding of this complex phenomenon and its role in the pathogenesis of cardiometabolic diseases is rooted in the discovery of insulin, its isolation and purification, and the challenges encountered with its therapeutic use. <b><i>Summary:</i></b> In this historical perspective, we explore the evolution of the term “insulin resistance” and demonstrate how advances in insulin and glucose analytics contributed to the recognition and validation of this metabolic entity. We identify primary discoveries which were pivotal in expanding our knowledge of insulin resistance, the challenges in measurement and interpretation, contemporary techniques, and areas of future exploration. <b><i>Key Message:</i></b> Measurements of insulin resistance are important tools for defining and treating cardiometabolic diseases. Accurate quantification of this pathophysiological entity requires careful consideration of the assumptions and pitfalls of the methodological techniques and the historical and clinical context when interpreting and applying the results.

SHR/NCrl rats as a model of ADHD can be discriminated from controls based on their brain, blood, or urine metabolomes

Attention-Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorder characterized by inattention, impulsivity, and hyperactivity. The neurobiological mechanisms underlying ADHD are still poorly understood, and its diagnosis remains difficult due to its heterogeneity. Metabolomics is a recent strategy for the holistic exploration of metabolism and is well suited for investigating the pathophysiology of diseases and finding molecular biomarkers. A few clinical metabolomic studies have been performed on peripheral samples from ADHD patients but are limited by their access to the brain. Here, we investigated the brain, blood, and urine metabolomes of SHR/NCrl vs WKY/NHsd rats to better understand the neurobiology and to find potential peripheral biomarkers underlying the ADHD-like phenotype of this animal model. We showed that SHR/NCrl rats can be differentiated from controls based on their brain, blood, and urine metabolomes. In the brain, SHR/NCrl rats displayed modifications in metabolic pathways related to energy metabolism and oxidative stress further supporting their importance in the pathophysiology of ADHD bringing news arguments in favor of the Neuroenergetic theory of ADHD. Besides, the peripheral metabolome of SHR/NCrl rats also shared more than half of these differences further supporting the importance of looking at multiple matrices to characterize a pathophysiological condition of an individual. This also stresses out the importance of investigating the peripheral energy and oxidative stress metabolic pathways in the search of biomarkers of ADHD.

The Metabolic Role of GRK2 in Insulin Resistance and Associated Conditions

Insulin resistance (IRES) is a pathophysiological condition characterized by the reduced response to insulin of several tissues, including myocardial and skeletal muscle. IRES is associated with obesity, glucose intolerance, dyslipidemia, and hypertension, evolves toward type 2 diabetes, and increases the risk of developing cardiovascular diseases. Several studies designed to explore the mechanisms involved in IRES allowed the identification of a multitude of potential molecular targets. Among the most promising, G Protein Coupled Receptor Kinase type 2 (GRK2) appears to be a suitable one given its functional implications in many cellular processes. In this review, we will discuss the metabolic role of GRK2 in those conditions that are characterized by insulin resistance (diabetes, hypertension, heart failure), and the potentiality of its inhibition as a therapeutic strategy to revert both insulin resistance and its associated phenotypes.

Molecular Imaging of Immunity and Inflammation and Its Impact on Precision Medicine

Biomedical research has, over the past decades, found components of the immune system at the functional center of almost every pathophysiological condition and disease [...]

Sinus Bradycardia after Extensive Neck Dissection and Total Thyroidectomy in a Pediatric Patient: A Case Report

Postoperative complications after total thyroidectomy with extensive neck dissection in thyroid malignancies are well documented in the current literature. However, sinus bradycardia as a postthyroidectomy complication is a rare phenomenon and, to the best of our knowledge, few studies have identified it as a perioperative condition. In our study, we report a case of 9-year-old boy with papillary thyroid carcinoma, who underwent total thyroidectomy and bilateral neck dissection. Postoperatively, the surgery was complicated by initial vocal cord paresis and chyle leak. The patient also suffered from asymptomatic sinus bradycardia which self-resolved. Although causative factors cannot be determined by a single case, hypothyroidism, carotid sinus hypersensitivity, and bilateral damage to the middle cervical sympathetic ganglion could play a significant role in this uncommon pathophysiological condition.

Defective development and microcirculation of intestine in Npr2 mutant mice

Intractable gastrointestinal (GI) diseases often develop during infancy. Our group previously reported that natriuretic peptide receptor B (NPR-B)-deficient Npr2slw/slw mice exhibit severe intestinal dysfunction, such as stenosis and distention, which resembles the dysfunction observed in Hirschsprung’s disease-allied disorders. However, the root cause of intestinal dysfunction and the detailed of pathophysiological condition in the intestine are not yet clear. Here, we report that the intestine of preweaning Npr2slw/slw mice showed bloodless blood vessels, and nodes were found in the lymphatic vessel. Additionally, the lacteals, smooth muscle, blood vessel, and nerves were barely observed in the villi of preweaning Npr2slw/slw mice. Moreover, intramuscular interstitial cells of Cajal (ICC-IM) were clearly reduced. In contrast, villi and ICC-IM were developed normally in surviving adult Npr2slw/slw mice. However, adult Npr2slw/slw mice exhibited partially hypoplastic blood vessels and an atrophied enteric nervous. Furthermore, adult Npr2slw/slw mice showed markedly reduced white adipose tissue. These findings suggest that the cause of GI dysfunction in preweaning Npr2slw/slw mice is attributed to defective intestinal development with microcirculation disorder. Thus, it is suggested that NPR-B signaling is involved in intestinal development and control of microcirculation and fat metabolism. This report provides new insights into intractable GI diseases, obesity, and NPR-B signaling.

Pathology and Pathogenesis of Adenomyosis

Adenomyosis represents a unique pathophysiological condition in which normal-appearing endometrial mucosa resides within myometrium and is thus protected from menstrual shedding. The resulting ectopic presence of endometrial tissue composed of glands and stroma is thought to affect normal contractile function and peristalsis of uterine smooth muscle, causing menometrorrhagia, infertility, and adverse obstetric outcomes. Since the first description of adenomyosis more than 150 years ago, pathologists have studied this lesion by examining tissue specimens, and have proposed multiple explanations to account for its pathogenesis. However, as compared with endometriosis, progress of adenomyosis research has been, at best, incremental mainly due to the lack of standardized protocols in sampling tissue and a lack of consensus diagnostic criteria in pathology practice. Despite these limitations, recent advances in revealing the detailed anatomy and biology of eutopic endometrium offer an unprecedented opportunity to study this common but relatively understudied disorder. Here, we briefly summarize the pathological aspects of adenomyosis from an historical background, and discuss conventional morphology and recent tissue-based molecular studies with a special emphasis on elucidating its tissue of origin from a pathologist's perspective. We also discuss unmet needs in pathology studies that would be important for advancing adenomyosis research.