A Macroscopic Two-Phase Blood Flow through a Bell Shaped Stenosis in an Artery with Permeable Wall

The present work concerns the effects of the hematocrit and the permeability of the wall on blood flow characteristics due to the presence of a bell shaped stenosis in an artery. In this analysis, the flowing blood is represented by a macroscopic two-phase model, as a suspension of erythrocytes in plasma. The analytical expressions for the flow characteristics, namely, the flow resistance (impedance), the wall shear stress distribution in the stenotic region and the shearing stress at the stenosis throat have been derived. Results for the effects of permeability as well as of hematocrit on these flow characteristics are shown graphically and discussed briefly

Immunomodulatory Potential of <em>Lactobacillus acidophilus</em>: Implications in Bone Health

Lactobacillus acidophilus is homofermentative anaerobic rod-shaped gram-positive bacteria. L. acidophilous is one of the most common probiotics and is used for the treatment of various gastrointestinal, metabolic and inflammatory disorders. L. acidophilous produces antimicrobial compounds, maintains gut permeability and prevents dysbiosis. L. acidophilus also shows various other properties such as: it is anticarcinogenic, lowers serum cholesterol level and improves lactase metabolism of host. One of the most significant property of L. acidophilous is that it modulates the immune system and can prevent various inflammatory disorders. L. acidophilous influences several immune cells such as Th17 cells and Tregs. Various studies reported that inflammation induces bone loss and leads to several bone pathologies such as osteoporosis, rheumatoid arthritis and periodontitis. Recent studies have shown the potential of probiotics in preventing inflammation mediated bone loss. L. acidophilous is one of these probiotics and is found capable in inhibition of various bone disorders. L. acidophilous restores the dysregulated immune homeostasis and prevents inflammatory bone loss. Thus, L. acidophilous can be a potential therapeutic for the management of various bone pathologies. In this book chapter we reviewed various immunomodulatory properties of L. acidophilous along with its efficacy in preventing dysbiosis and maintaining gut permeability. We also discussed the potential role of L. acidophilous as a therapeutic for the management of inflammation induced bone disorders

COVID-19 induced ARDS: immunopathology and therapeutics

The coronavirus disease-2019 (COVID-19) pandemic is a significant threat in the modern era. Clinical studies show that the most common symptom of severe COVID-19 is viral pneumonia-induced acute respiratory distress syndrome (ARDS). The underlying mechanisms by which severe respiratory disease syndrome-coronavirus-2 (SARS-CoV-2) results in ARDS and how certain host factors confer an increased risk of developing severe disease remain unknown. Therefore, identifying the distinctive features of this severe and fatal disease and the therapeutic approaches to COVID-19-induced ARDS remains an immediate need to serve as a basis for best practice models of standardized ARDS treatment. This review article aims to comprehensively discuss the immunopathology of ARDS and provides an overview of the precise role of both the innate and adaptive immune system, with emphasis on the current treatment strategies being tested in the COVID-19-induced ARDS patients. This knowledge will supposedly help in revealing further mechanistic insights into understanding COVID-19-induced ARDS

Quantum Dot Based Nano-Biosensors for Detection of Circulating Cell Free miRNAs in Lung Carcinogenesis: From Biology to Clinical Translation

Lung cancer is the most frequently occurring malignancy and the leading cause of cancer-related death for men in our country. The only recommended screening method is clinic based low-dose computed tomography (also called a low-dose CT scan, or LDCT). However, the effect of LDCT on overall mortality observed in lung cancer patients is not statistically significant. Over-diagnosis, excessive cost, risks associated with radiation exposure, false positive results and delay in the commencement of the treatment procedure questions the use of LDCT as a reliable technique for population-based screening. Therefore, identification of minimal-invasive biomarkers able to detect malignancies at an early stage might be useful to reduce the disease burden. Circulating nucleic acids are emerging as important source of information for several chronic pathologies including lung cancer. Of these, circulating cell free miRNAs are reported to be closely associated with the clinical outcome of lung cancer patients. Smaller size, sequence homology between species, low concentration and stability are some of the major challenges involved in characterization and specific detection of miRNAs. To circumvent these problems, synthesis of a quantum dot based nano-biosensor might assist in sensitive, specific and cost-effective detection of differentially regulated miRNAs. The wide excitation and narrow emission spectra of these nanoparticles result in excellent fluorescent quantum yields with a broader color spectrum which make them ideal bio-entities for fluorescence resonance energy transfer (FRET) based detection for sequential or simultaneous study of multiple targets. In addition, photo-resistance and higher stability of these nanoparticles allows extensive exposure and offer state-of-the art sensitivity for miRNA targeting. A major obstacle for integrating QDs into clinical application is the QD-associated toxicity. However, the use of non-toxic shells along with surface modification not only overcomes the toxicity issues, but also increases the ability of QDs to quickly detect circulating cell free miRNAs in a non-invasive mode. The present review illustrates the importance of circulating miRNAs in lung cancer diagnosis and highlights the translational prospects of developing QD-based nano-biosensor for rapid early disease detection

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Immunoporosis: Immunology of Osteoporosis—Role of T Cells

The role of immune system in various bone pathologies, such as osteoporosis, osteoarthritis, and rheumatoid arthritis is now well established. This had led to the emergence of a modern field of systems biology called as osteoimmunology, an integrated research between fields of immunology and bone biology under one umbrella. Osteoporosis is one of the most common inflammatory bone loss condition with more than 200 million individuals affected worldwide. T helper (Th) cells along with various other immune cells are major players involved in bone homeostasis. In the present review, we specifically discuss the role of various defined T lymphocyte subsets (Th cells comprising Th1, Th2, Th9, Th17, Th22, regulatory T cells, follicular helper T cells, natural killer T cells, γδ T cells, and CD8+ T cells) in the pathophysiology of osteoporosis. The study of the specific role of immune system in osteoporosis has now been proposed by our group as “immunoporosis: the immunology of osteoporosis” with special emphasis on the role of various subsets of T lymphocytes. The establishment of this new field had been need of the hour due to the emergence of novel roles of various T cell lymphocytes in accelerated bone loss observed during osteoporosis. Activated T cells either directly or indirectly through the secretion of various cytokines and factors modulate bone health and thereby regulate bone remodeling. Several studies have summarized the role of inflammation in pathogenesis of osteoporosis but very few reports had delineated the precise role of various T cell subsets in the pathobiology of osteoporosis. The present review thus for the first time clearly highlights and summarizes the role of various T lymphocytes in the development and pathophysiology of osteoporosis, giving birth to a new field of biology termed as “immunoporosis”. This novel field will thus provide an overview of the nexus between the cellular components of both bone and immune systems, responsible for the observed bone loss in osteoporosis. A molecular insight into the upcoming and novel field of immunoporosis would thus leads to development of innovative approaches for the prevention and treatment of osteoporosis

A Macroscopic Two-Phase Blood Flow through a Bell Shaped Stenosis in an Artery with Permeable Wall MSC 2010): 76Z05 38

Abstract The present work concerns the effects of the hematocrit and the permeability of the wall on blood flow characteristics due to the presence of a bell shaped stenosis in an artery. In this analysis, the flowing blood is represented by a macroscopic two-phase model, as a suspension of erythrocytes in plasma. The analytical expressions for the flow characteristics, namely, the flow resistance (impedance), the wall shear stress distribution in the stenotic region and the shearing stress at the stenosis throat have been derived. Results for the effects of permeability as well as of hematocrit on these flow characteristics are shown graphically and discussed briefly