Biological Sciences and Engineering

Indian Institute of Technology Palakkad&nbsp;(IIT Palakkad or IIT PKD) is a public autonomous&nbsp;engineering&nbsp;and&nbsp;research&nbsp;institute located in&nbsp;Palakkad,&nbsp;Kerala. It was&nbsp;one of the five new&nbsp;IITs&nbsp;proposed in the&nbsp;2014 Union budget of India. The campus was inaugurated on 3 August 2015. The institute has 94 faculty, 978 students, and 63 non-teaching staffs.

IT Palakkad currently offers four-year Bachelor of Technology (B.Tech) and two years MS programmes in 8 different engineering disciplines including&nbsp;Computer Science, Electrical, Mechanical, Civil among others.

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IIT Palakkad

Interleukin-3 (IL-3) is a cytokine belonging to the family of common β (βc) and is involved in various biological systems. Its activity is mediated by the interaction with its receptor (IL-3R), a heterodimer composed of two distinct subunits: IL-3Rα and βc. IL-3 and its receptor, especially IL-3Rα, play a crucial role in pathologies like inflammatory diseases and therefore are interesting therapeutic targets. Here, we have performed an analysis of these proteins and their interaction based on structural and evolutionary information. We highlighted that IL-3 and IL-3Rα structural architectures are conserved across evolution and shared with other proteins belonging to the same βc family interleukin-5 (IL-5) and granulocyte–macrophage colony-stimulating factor (GM-CSF). The IL-3Rα/IL-3 interaction is mediated by a large interface in which most residues are surprisingly not conserved during evolution and across family members. In spite of this high variability, we suggested small regions constituted by few residues conserved during the evolution in both proteins that could be important for the binding affinity. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.

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Amino Acids

Structural and evolutionary exploration of the IL-3 family and its alpha subunit receptors

Intravenous immunoglobulin (IVIG) is used to treat several autoimmune and inflammatory diseases, but some patients are refractory to IVIG and require alternative treatments. Identifying a biomarker that could segregate IVIG responders from non-responders has been a subject of intense research. Unfortunately, previous transcriptomic studies aimed at addressing IVIG resistance have failed to predict a biomarker that could identify IVIG-non-responders. Therefore, we used a novel data mining technique on the publicly available transcriptomic data of Kawasaki disease (KD) patients treated with IVIG to identify potential biomarkers of IVIG response. By studying the boolean patterns hidden in the expression profiles of KD patients undergoing IVIG therapy, we have identified new metabolic pathways implicated in IVIG resistance in KD. These pathways could be used as biomarkers to segregate IVIG non-responders from responders prior to IVIG infusion. Also, boolean analysis of the transcriptomic data could be further extended to identify a universal biomarker that might predict IVIG response in other autoimmune diseases. © 2021 Elsevier B.V.

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Autoimmunity Reviews

Boolean analysis of the transcriptomic data to identify novel biomarkers of IVIG response

Hyaluronan (HA) is a naturally occurring non-sulfated glycosaminoglycan (GAG), cell-surface-associated biopolymer and is the key component of tissue extracellular matrix (ECM). Along with remarkable physicochemical properties, HA also has multifaceted biological effects that include but not limited to ECM organization, immunomodulation, and various cellular processes. Environmental cues such as tissue injury, infection or cancer change downstream signaling functionalities of HA. Unlike native HA, the fragments of HA have diversified effects on inflammation, cancer, fibrosis, angiogenesis and autoimmune response. In this review, we aim to discuss HA as a therapeutic delivery system development process, source, biophysical-chemical properties, and associated biological pathways (especially via cell surface receptors) of native and fragmented HA. We also tried to address an overview of the potential role of HA (native HA vs fragments) in the modulation of inflammation, immune response and various cancer targeting delivery applications. This review will also highlight the HA based therapeutic systems, medical devices and future perspectives of various biomedical applications were discussed in detail. © 2021 The Author(s)

Journal of Controlled Release

Recent advances and prospects of hyaluronan as a multifunctional therapeutic system

The mechanisms of action of intravenous immunoglobulins (IVIg) in autoimmune diseases are not fully understood. The fixed duration of efficacy and noncumulative effects of IVIg in immune thrombocytopenia (ITP) and acquired von Willebrand disease (AVWD) suggest other mechanisms besides immunological ones. Additionally to the peripheral destruction of platelets in ITP, their medullary hypoproduction emerged as a new paradigm with rescue of thrombopoietin receptor agonists (TPO-RA). In an ITP mouse model, interleukin (IL)-11 blood levels increase following IVIg. IL-11 stimulates the production of platelets and other haemostasis factors; recombinant IL-11 (rIL-11) is thus used as a growth factor in post-chemotherapy thrombocytopenia. We therefore hypothesized that IVIg induces IL-11 over-production, which increases platelets, VWF and factor VIII (FVIII) levels in humans and mice. First, in an ITP mouse model, we show that IVIg or rIL-11 induces a rapid increase (72 h) in platelets, FVIII and VWF levels, whereas anti-IL-11 antibody greatly decreased this effect. Secondly, we quantify for the first time in patients with ITP, AVWD, inflammatory myopathies or Guillain–Barré syndrome the dramatic IL-11 increase following IVIg, regardless of the disease. As observed in mice, platelets, VWF and FVIII levels increased following IVIg. The late evolution (4 weeks) of post-IVIg IL-11 levels overlapped with those of VWF and platelets. These data may explain thrombotic events following IVIg and open perspectives to monitor post-IVIg IL-11/thrombopoietin ratios, and to assess rIL-11 use with or without TPO-RA as megakaryopoiesis co-stimulating factors to overcome the relative hypoproduction of platelets or VWF in corresponding autoimmune diseases, besides immunosuppressant. © 2021 British Society for Immunology

Clinical and Experimental Immunology

IVIg increases interleukin-11 levels, which in turn contribute to increased platelets, VWF and FVIII in mice and humans

Children and adolescents infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are predominantly asymptomatic or have mild symptoms compared with the more severe coronavirus disease 2019 (COVID-19) described in adults. However, SARS-CoV-2 is also associated with a widely reported but poorly understood paediatric systemic vasculitis. This multisystem inflammatory syndrome in children (MIS-C) has features that overlap with myocarditis, toxic-shock syndrome and Kawasaki disease. Current evidence indicates that MIS-C is the result of an exaggerated innate and adaptive immune response, characterized by a cytokine storm, and that it is triggered by prior SARS-CoV-2 exposure. Epidemiological, clinical and immunological differences classify MIS-C as being distinct from Kawasaki disease. Differences include the age range, and the geographical and ethnic distribution of patients. MIS-C is associated with prominent gastrointestinal and cardiovascular system involvement, admission to intensive care unit, neutrophilia, lymphopenia, high levels of IFNγ and low counts of naive CD4+ T cells, with a high proportion of activated memory T cells. Further investigation of MIS-C will continue to enhance our understanding of similar conditions associated with a cytokine storm. © 2021, Springer Nature Limited.

Nature Reviews Rheumatology

Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison

Foot-and-mouth disease virus (FMDV) causes a severe infection in ruminant animals. Here we present an in-depth transcriptional analysis of soft-palate tissue from cattle experimentally infected with FMDV. The differentially expressed genes from two Indian cattle (Bos indicus) breeds (Malnad Gidda and Hallikar) and Holstein Friesian (HF) crossbred calves, highlighted the activation of metabolic processes, mitochondrial functions and significant enrichment of innate antiviral immune response pathways in the indigenous calves. The results of RT-qPCR based validation of 12 genes was in alignment with the transcriptome data. The indigenous calves showing lesser virus load, elicited early neutralizing antibodies and IFN-γ immune responses. This study revealed that induction of potent innate antiviral response and cell mediated immunity in indigenous cattle, especially Malnad Gidda, significantly restricted FMDV replication during acute infection. These data highlighting the molecular processes associated with host-pathogen interactions, could aid in the conception of novel strategies to prevent and control FMDV infection in cattle. © 2021 The Authors

Genomics

Induction of antiviral and cell mediated immune responses significantly reduce viral load in an acute foot-and-mouth disease virus infection in cattle

Persistent ill health after acute COVID-19-referred to as long COVID, the post-acute COVID-19 syndrome, or the post-COVID-19 condition-has emerged as a major concern. We undertook an international consensus exercise to identify research priorities with the aim of understanding the long-term effects of acute COVID-19, with a focus on people with pre-existing airways disease and the occurrence of new-onset airways disease and associated symptoms. 202 international experts were invited to submit a minimum of three research ideas. After a two-phase internal review process, a final list of 98 research topics was scored by 48 experts. Patients with pre-existing or post-COVID-19 airways disease contributed to the exercise by weighting selected criteria. The highest-ranked research idea focused on investigation of the relationship between prognostic scores at hospital admission and morbidity at 3 months and 12 months after hospital discharge in patients with and without pre-existing airways disease. High priority was also assigned to comparisons of the prevalence and severity of post-COVID-19 fatigue, sarcopenia, anxiety, depression and risk of future cardiovascular complications in patients with and without pre-existing airways disease. Our approach has enabled development of a set of priorities that could inform future research studies and funding decisions. This prioritisation process could also be adapted to other, non-respiratory aspects of long COVID.

The Lancet Respiratory Medicine

The long-term sequelae of COVID-19: an international consensus on research priorities for patients with pre-existing and new-onset airways disease

COVID-19, coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic. At the time of writing this (October 14, 2020), more than 38.4 million people have become affected, and 1.0 million people have died across the world. The death rate is undoubtedly correlated with the cytokine storm and other pathological pulmonary characteristics, as a result of which the lungs cannot provide sufficient oxygen to the body's vital organs. While diversified drugs have been tested as a first line therapy, the complexity of fatal cases has not been reduced so far, and the world is looking for a treatment to combat the virus. However, to date, and despite such promise, we have received very limited information about the potential of nanomedicine to fight against COVID-19 or as an adjunct therapy in the treatment regimen. Over the past two decades, various therapeutic strategies, including direct-acting antiviral drugs, immunomodulators, a few non-specific drugs (simple to complex), have been explored to treat Acute Respiratory Distress Syndrome (ARDS), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), influenza, and sometimes the common flu, thus, correlating and developing specific drugs centric to COVID-19 is possible. This review article focuses on the pulmonary pathology caused by SARS-CoV-2 and other viral pathogens, highlighting possible nanomedicine therapeutic strategies that should be further tested immediately. © 2020 Elsevier Ltd

Nano Today

Potential immuno-nanomedicine strategies to fight COVID-19 like pulmonary infections

In The Journal of Clinical Investigation, Zhu et al.1 report that intravenous immunoglobulin (IVIG) targets IL-1$\beta$+ neutrophils to exert anti-inflammatory effects in multisystem inflammatory syndrome in children (MIS-C), a post-infectious inflammatory condition associated with COVID-19.

Cell Reports Medicine

Unraveling the mechanisms of IVIG immunotherapy in MIS-C

In this study, we reveal the microbiologically influenced corrosion (MIC) behavior of the new electroless NiP-TiNi nanocomposite coating in simulated seawater using the electrochemical impedance spectroscopy (EIS) technique after different periods of incubation time (7, 10, 14, 21, 28 days) in a sulfate-reducing bacteria (SRB) medium. The biofilm formation and the corrosion products were characterized using the scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). The EIS results revealed the carbon steel (CS)/NiP-TiNi and NiP-TiNi/SRB biofilm interfaces' characteristics after different incubation times in the SRB media. EIS measurements revealed that the NiP-TiNi nanocomposite coating's MIC resistances are superior relative to API X80 carbon steel and a TiNi-free NiP coating, with ∼93% of corrosion inhibition efficiency after 28 days of incubation. © 2021 The Author(s)