Enhancing Stem Cell Therapy for Cartilage Repair in Osteoarthritis—A Hydrogel Focused Approach

Sem cells hold tremendous promise for the treatment of cartilage repair in osteoarthritis. In addition to their multipotency, stem cells possess immunomodulatory effects that can alleviate inflammation and enhance cartilage repair. However, the widely clinical application of stem cell therapy to cartilage repair and osteoarthritis has proven difficult due to challenges in large-scale production, viability maintenance in pathological tissue site and limited therapeutic biological activity. This review aims to provide a perspective from hydrogel-focused approach to address few key challenges in stem cell-based therapy for cartilage repair and highlight recent progress in advanced hydrogels, particularly microgels and dynamic hydrogels systems for improving stem cell survival, retention and regulation of stem cell fate. Finally, progress in hydrogel-assisted gene delivery and genome editing approaches for the development of next generation of stem cell therapy for cartilage repair in osteoarthritis are highlighted.

The influence of some physico-therapeutic stimuli on the nature of the inflammatory reaction

Inflammation belongs to those chapters of pathology that, being well studied, are, however, subject to frequent fundamental re-examination and arouse deep interest and attention among pathologists of all ages. If for every doctor of any specialty it is necessary to have a clear idea of the essence of the phenomenon that makes up the inflammatory reaction, then this is all the more necessary for a physiotherapist, since the result of the influence of most physiotherapeutic stimuli is a reaction approaching the type of inflammatory in its clinical manifestation, and when the stimulus increases, it directly passes into it (burn). The exact differentiation of these reactions and the clinical significance of such a facet can be clarified only by knowing the dynamic characteristics of an organism or a separate tissue site both in cases of inflammation and when exposed to physiotherapeutic stimuli. The latter provision formed the basis of this work,

Porphyrias in the Age of Targeted Therapies

The porphyrias are a group of eight rare genetic disorders, each caused by the deficiency of one of the enzymes in the heme biosynthetic pathway, resulting in the excess accumulation of heme precursors and porphyrins. Depending on the tissue site as well as the chemical characteristics of the accumulating substances, the clinical features of different porphyrias vary substantially. Heme precursors are neurotoxic, and their accumulation results in acute hepatic porphyria, while porphyrins are photoactive, and excess amounts cause cutaneous porphyrias, which present with photosensitivity. These disorders are clinically heterogeneous but can result in severe clinical manifestations, long-term complications and a significantly diminished quality of life. Medical management consists mostly of the avoidance of triggering factors and symptomatic treatment. With an improved understanding of the underlying pathophysiology and disease mechanisms, new treatment approaches have become available, which address the underlying defects at a molecular or cellular level, and promise significant improvement, symptom prevention and more effective treatment of acute and chronic disease manifestations.

Histopathological Review and Distribution of Granulomatous Inflammatory Disorders in Makurdi, North Central Nigeria

Granulomatous inflammation is a pattern of chronic inflammation characterized by the presence of granulomas consisting of microscopic aggregates of macrophages transformed into epithelioid cells surrounding by a collar of lymphocytes and occasioned plasma cells. The study aimed to determine the distribution by tissue site, histological patterns of granulomatous inflammatory disorders in Benue State University Teaching Hospital (BSUTH), Makurdi over a 5-year period. This was a 5 year (March 2013 – February 2018) retrospective study of all cases diagnosed as granulomatous inflammatory disorders on Haematoxylin and Eosin-stained sections at the Anatomical pathology Department. Ziehl-Neelsen special stain was also done on all specimens. A total of two hundred and thirty-six (236) cases of granulomatous inflammatory disorders were diagnosed, analysed and categorized based on the tissue site, on Haematoxylin and Eosin-stained sections; Ziehl-Neelsen special stain was done on all cases. The most common sites were cervical lymph nodes, appendix, skin, testicular tissues etc with the Eyelid been the least common site.

Nebulized Tranexamic Acid in Secondary Post-Tonsillectomy Hemorrhage: Case Series and Review of the Literature

Introduction: Post-tonsillectomy hemorrhage is a serious postoperative complication, and its acute management can present a challenge for the emergency provider. Although various strategies have been proposed, guidance on the best approach for management of this condition in the emergency department (ED) setting remains limited. Anecdotal reports of the use of nebulized tranexamic acid (TXA) for management of tonsillar bleeding have emerged over the past two years. Two recently published case reports describe the successful use of nebulized TXA for stabilization of post-tonsillectomy hemorrhage in an adult and a pediatric patient. Case Series: Eight patients who presented to our ED with secondary post-tonsillectomy hemorrhage received nebulized TXA for hemostatic management. The most common TXA dose used was 500 milligrams, and all but one patient received a single dose of the medication in the ED. Hemostatic benefit was observed in six patients, with complete bleeding cessation observed in five cases. Interventions prior to nebulized TXA administration were attempted in three of the six patients and included ice water gargle, direct pressure with TXA-soaked gauze, and nebulized racemic epinephrine. All but one of the patients were taken to the operating room for definitive management after initial stabilization in the ED. Conclusion: Nebulized TXA may offer a hemostatic benefit and aid in stabilization of tonsillectomy hemorrhage in the acute care setting, prior to definitive surgical intervention. Consideration of general principles of nebulization and aerosol particle size may be an important factor for drug delivery to the target tissue site.

Lymph-Derived Neutrophils Primarily Locate to the Subcapsular and Medullary Sinuses in Resting and Inflamed Lymph Nodes

Neutrophils are the first immune cells to be recruited from the blood to the tissue site of an infection or inflammation. It has been suggested that neutrophils are capable of migrating from the infected tissue via lymphatic vessels to the draining lymph nodes. However, it remains elusive as to which areas within the lymph nodes can be reached by such reversely migrating cells. To address this question, we applied a model for adoptive neutrophil transfer into the afferent lymphatic vessel that drains towards the popliteal lymph node in mice. We showed that resting and in vitro-activated neutrophils did not enter the lymph node parenchyma but localized primarily in the subcapsular and medullary sinuses. Within the medulla, neutrophils show random migration and are able to sense laser-induced sterile tissue injury by massively swarming to the damaged tissue site. Co-injected dendritic cells supported the entry of resting neutrophils into the lymph node parenchyma via the subcapsular sinus. In contrast, in vivo-activated adoptively transferred neutrophils were capable of migrating into the interfollicular areas of the lymph node. Collectively, the data presented here give further insights into the functional behavior of neutrophils within the lymph nodes.

Incomplete recruitment of protective T cells facilitates Trypanosoma cruzi persistence in the mouse colon

Trypanosoma cruzi is the etiological agent of Chagas disease. Following T cell mediated suppression of the acute phase infection, this intracellular eukaryotic pathogen persists in a limited sub-set of tissues at extremely low-levels. The reasons for this tissue-specific chronicity are not understood. Using a dual bioluminescent:fluorescent reporter strain, which allows experimental infections to be imaged at single-cell resolution, we have characterised the ‘hyper-local’ immunological microenvironment of rare parasitized cells in the mouse colon, a key site of persistence. We demonstrate that incomplete recruitment of T cells to infection foci permits the occurrence of repeated cycles of intracellular parasite replication and differentiation to motile trypomastigotes at a frequency sufficient to perpetuate chronic infections. The life-long persistence of parasites in this tissue site continues despite the presence, at a systemic level, of a highly effective T cell response. Overcoming this low-level dynamic host:parasite equilibrium represents a major challenge for vaccine development.

miR-338-3p inhibits cell growth, invasion, and EMT process in neuroblastoma through targeting MMP-2

This study aimed to explore the regulatory mechanisms of miR-338-3p and matrix metalloproteinase-2 (MMP-2) in neuroblastoma. Putative target interaction regions of miR-338-3p on MMP-2 were predicted by miRcode and miRbase bioinformatics tools. Relative expression of miRNA-338-3p and MMP-2 in neuroblastoma tissues and GI-LI-N and SK-N-SH cells was determined by reverse transcription polymerase chain reaction experiment. Furthermore, the cell proliferation was determined by Cell Counting Kit-8 assay, the cell apoptosis rate was analyzed by flow cytometry assay, and the cell invasion was evaluated by transwell assay. miR-338-3p expression was downregulated, whereas MMP-2 expression was upregulated in metastasis tissue site compared to that in primary tissue site in total. Furthermore, miR-338-3p overexpression suppressed proliferation, invasion, and epithelial–mesenchymal transition (EMT) of neuroblastoma cells but promoted apoptosis, and the knockdown of MMP-2 triggered similar effects. Furthermore, MMP-2 was directly targeted by miR-338-3p, and overexpression of MMP-2 rescued the inhibitory effects of miR-338-3p on human neuroblastoma cell progression. Collectively, these data demonstrated that miR-338-3p could suppress cell growth, invasion, and EMT pathway and induce apoptosis in neuroblastoma cells by targeting MMP-2. MiR-338-3p sponged MMP-2 to regulate the PI3K/AKT pathway in human neuroblastoma cells.

Impact of anatomic site on antigen-presenting cells in cancer

Checkpoint blockade immunotherapy (CBT) can induce long-term clinical benefits in patients with advanced cancer; however, response rates to CBT vary by cancer type. Cancers of the skin, lung, and kidney are largely responsive to CBT, while cancers of the pancreas, ovary, breast, and metastatic lesions to the liver respond poorly. The impact of tissue-resident immune cells on antitumor immunity is an emerging area of investigation. Recent evidence indicates that antitumor immune responses and efficacy of CBT depend on the tissue site of the tumor lesion. As myeloid cells are predominantly tissue-resident and can shape tumor-reactive T cell responses, it is conceivable that tissue-specific differences in their function underlie the tissue-site-dependent variability in CBT responses. Understanding the roles of tissue-specific myeloid cells in antitumor immunity can open new avenues for treatment design. In this review, we discuss the roles of tissue-specific antigen-presenting cells (APCs) in governing antitumor immune responses, with a particular focus on the contributions of tissue-specific dendritic cells. Using the framework of the Cancer-Immunity Cycle, we examine the contributions of tissue-specific APC in CBT-sensitive and CBT-resistant carcinomas, highlight how these cells can be therapeutically modulated, and identify gaps in knowledge that remain to be addressed.

The subepidermal moisture scanner: the technology explained

The objective of this article is to explain the biophysical principles underlying the design of the subepidermal moisture (SEM) scanner, commercially known as the ‘SEM scanner’. We also describe the mode of operation of the SEM scanner in monitoring tissue health and detecting subtle abnormal changes in tissue physiology in patients and anatomical sites at a risk of a pressure ulcer (PU: also known as a pressure injury). The technology of the SEM scanner was approved last year for sales in the US by the Food and Drug Administration (FDA). The SEM scanner detects changes in fluid contents of human skin and subdermal tissues, to a tissue depth of several millimetres, by measuring ‘capacitance’, an electrical property of the locally examined tissue site to store electric charge. The capacitance of tissues, called ‘biocapacitance’, is strongly affected by the amount of fluid (water) in the tissue. When the first cells die in a forming PU, inflammatory signalling causes the permeability of blood vessel walls to increase and oedema to develop. Simply, the scanner detects the early appearance of oedema, which is called ‘micro-oedema.’ Calculation of a ‘SEM-delta’ value, which compares biocapacitance measurements, acquired across several tissue sites, some of which are healthy and others where the PU may evolve, eliminates potential effects of systemic changes in tissue fluid contents and provides a consistent quantitative measure of the tissue health conditions at the monitored anatomical site. Here, we describe SEM scanner technology, how it operates and has been laboratory tested (in computer simulations, in silico) before commercial launch. We explain why targeting the physical biomarker of oedema leads to the documented success of the SEM scanner in the multiple published clinical trials, proving its ability to early detect PUs that form under intact skin.