An Insight into the Diverse Roles of Surfactant Proteins, SP-A and SP-D in Innate and Adaptive Immunity

Surfactant proteins SP-A and SP-D are hydrophilic, collagen-containing calcium-dependent lectins, which appear to have a range of innate immune functions at pulmonary as well as extrapulmonary sites. These proteins bind to target ligands on pathogens, allergens, and apoptotic cells, via C-terminal homotrimeric carbohydrate recognition domains, while the collagen region brings about the effector functions via its interaction with cell surface receptors. SP-A and SP-D deal with various pathogens, using a range of innate immune mechanisms such as agglutination/aggregation, enhancement of phagocytosis, and killing mechanisms by phagocytic cells and direct growth inhibition. SP-A and SP-D have also been shown to be involved in the control of pulmonary inflammation including allergy and asthma. Emerging evidence suggest that SP-A and SP-D are capable of linking innate immunity with adaptive immunity that includes modulation of dendritic cell function and helper T cell polarization. This review enumerates immunological properties of SP-A and SP-D inside and outside lungs and discusses their importance in human health and disease

Innate Immunopathological Mechanisms in Multiple Sclerosis

Multiple sclerosis (MS) is a progressive disease that affects the central nervous system. The core features of MS are demyelination and inflammation. Demyelination refers to degeneration of myelin that covers the neurons and helps facilitate neuronal impulses. Loss of myelin results in inability to conduct impulses, which causes core symptoms of MS such as unsteadiness, weakness, numbness, and tingling. Inflammation is observed at the site of demyelination in the form of scars, and hence, the term sclerosis. Innate immunity is that part of the immune system that is present from birth. Over the years, adaptive immunity has been extensively studied with respect to MS in human and experimental disease models. However, recent evidence has increasingly pointed to significant involvement of innate immune mechanisms in the pathogenesis of MS. This chapter reviews the latest evidence regarding innate immune components such as blood–brain barrier, microglial cells, and complement system, and their role in MS pathogenesis

Impact of obesity with impaired glucose tolerance on retinal degeneration in a rat model of metabolic syndrome.

PurposeMetabolic syndrome (MetS) is associated with several degenerative diseases, including retinal degeneration. Previously, we reported on progressive retinal degeneration in a spontaneous obese rat (WNIN/Ob) model. In this study, we investigated the additional effect of impaired glucose tolerance (IGT), an essential component of MetS, on retinal degeneration using the WNIN/GR-Ob rat model.MethodsThe retinal morphology and ultrastructure of WNIN/GR-Ob and age-matched littermate lean rats were studied by microscopy and immunohistochemistry. The retinal transcriptome of WNIN/GR-Ob was compared with the respective lean controls and with the WNIN/Ob model using microarray analysis. Expression of selected retinal marker genes was studied via real-time PCR.ResultsProgressive loss of photoreceptor cells was observed in WNIN/GR-Ob rats with an onset as early as 3 months. Similarly, thinning of the inner nuclear layer was observed from 6 months in these rats. Immunohistochemical analysis showed decreased levels of rhodopsin and postsynaptic density protein-95 (PSD-95) proteins and increased levels of glial fibrillary acidic protein (GFAP), vascular endothelial growth factor (VEGF), and calretinin in WNIN/GR-Ob rats compared with the age-matched lean controls, further supporting cellular stress/damage and retinal degeneration. The retinal transcriptome analysis indicated altered expression profiles in both the WNIN/GR-Ob and WNIN/Ob rat models compared to their respective lean controls; these pathways are associated with activation of pathways like cellular oxidative stress response, inflammation, apoptosis, and phototransduction, although the changes were more prominent in WNIN/GR-Ob than in WNIN/Ob animals.ConclusionsWNIN/GR-Ob rats with added glucose intolerance developed retinal degeneration similar to the parent line WNIN/Ob. The severity of retinal degeneration was greater in WNIN/GR-Ob rats compared to WNIN/Ob, suggesting a possible role for IGT in this model. Hence, the WNIN/GR-Ob model could be a valuable tool for investigating the impact of MetS on retinal degeneration pathology

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP CLINICAL STUDY TO EVALUATE THE ANALGESIC EFFECT OF AQUEOUS EXTRACT OF TERMINALIA CHEBULA, A PROPRIETARY CHROMIUM COMPLEX, AND THEIR COMBINATION IN SUBJECTS WITH JOINT DISCOMFORT

Objective: To evaluate the analgesic effect of an aqueous extract of Terminalia chebula (TCE), a proprietary chromium complex (PCC), and theircombination in subjects with joint discomfort.Methods: A total of 100 patients with knee joint discomfort were randomized into five treatment groups - TCE 500 mg BID, TCE 500 mg BID+PCC400 µg OD, PCC 400 µg OD alone, placebo, and TCE 250 mg BID, for 12 weeks in a double-blinded manner. Assessment of symptoms of knee joint painand discomfort was done by modified Western Ontario and McMaster Universities Arthritis Index (mWOMAC) and knee swelling index (KSI); visualanalog scale (VAS) was used for subjective assessment of pain, stiffness, and disability. Statistical analysis was done with GraphPad Prism 6.Results: Absolute reduction in mWOMAC score in TCE 500 mg (19.82±8.35), TCE 500 mg+PCC 400 µg (13.10±5.69), PCC 400 µg (8.30±3.81), placebo(2.45±3.07), and TCE 250 mg (10.47±4.43), respectively, at the end of 12 weeks as compared to the baseline values. Absolute reduction in KSI inTCE 500 mg (28.95±16.82), TCE 500 mg+PCC 400 µg (19.14±9.50), PCC 400 µg (12.7±4.86), placebo (10.03±3.8), and TCE 250 mg (18.24±6.86),respectively, at the end of 12 weeks as compared to the baseline values (p<0.001). Similar results were seen with VAS assessments for pain, stiffness,and disability. All the treatments were well tolerated.Conclusion: TCE and PCC reduce joint discomfort.Keywords: Terminalia chebula extract, Proprietary chromium complex, Western Ontario and McMaster Universities Arthritis Index

Correlation between endothelial dysfunction, inflammatory status, oxidative stress and total (nitrite/ nitrate) in subjects with diabetes mellitus type 2

Background: Diabetes Mellitus is a systemic metabolic disorder associated with Endothelial dysfunction and increased systemic inflammatory state with oxidative stress leading to increased Cardiovascular risk. This study planned to correlate the level of Endothelial dysfunction with oxidative stress and inflammatory status.Methods: Study was conducted in 60 Diabetes Mellitus subjects of both genders with duration of more than two years. Endothelial dysfunction assessed as Augmentation Pressure and Augmentation Index generated from Radial artery waveforms by tonometer using Spygmocor PWA system. Plasma Total Nitrite/ Nitrate, High sensitive C - Reactive Protein, Malondialdehyde and Glutathione were measured.Results: Out of total 60 Diabetes Mellitus subjects 16 subjects were with Coronary Artery Disease. There was no significant difference in High sensitive C - Reactive Protein, Glutathione, Malondialdehyde and Total Nitrite/ Nitrate between Diabetes Mellitus with Coronary Artery Disease and without Coronary Artery Disease, however significant difference (p=0.02) was observed Augmentation Pressure between Diabetic alone (12.8±5.19 mm of Mercury) and diabetics with Coronary Artery Disease (16.13±33.47 mm of Mercury) and Augmentation Index (p=0.04) between Diabetic alone (29.8±5.68 mm of Mercury) and diabetics with Coronary Artery Disease (40.01±5.74). As endothelial function is age dependent the subjects were divided into three age groups (20-40 years, 40-60 years and more than 60 years). High sensitive C - Reactive Protein, Glutathione, Malondialdehyde, Total Nitrite/ Nitrate and Augmentation Index did not differ in the three age groups while Augmentation Pressure (p=0.0096) showed significant difference between age group 20-40 years (10.59±3.24) and age group more than 60 years (15.83±3.92).Conclusions: There is significant endothelial dysfunction observed in Diabetes Mellitus subjects and Diabetes Mellitus with coronary artery disease showed greater endothelial dyfunction. Thereby concluding that Diabetes Mellitus subjects were at higher risk for development of coronary artery disease and as endothelial dysfunction is an early event, it may have some prognostic value

Thioridazine: a potential adjuvant in pharmacotherapy of drug resistant tuberculosis Ki

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. Despite advances in control strategies, inadequate treatment and failure to comply with drug regimens have resulted in TB to emerge as one of the most common and deadly infectious diseases worldwide. The emergence of drug-resistant TBhas evolved as a formidable obstacle for comprehensive TB control. Drug-resistant TB can be classified as multi-drug-resistant TB, extensively drug-resistant TB and totally drug resistant TB (TDR-TB). There is a paucity in the development of new drugs against drug-resistant mycobacteria. The focus has shifted to the exploration of anti-mycobacterial properties of drugs approved for other indications. Thioridazine, a drug approved for use in schizophrenia is one such potential agent, which has shown anti-mycobacterial activity. There is evidence of anti-mycobacterial action of Thioridazine in in-vitro and mouse models. There is a compelling need for new anti-mycobacterial drugs that are more effective and have less toxicity. Further clinical trials are advocated favoring the use of thioridazine as an adjuvant in the treatment of TB, especially TDR-TB

Protective role of complement factor H against the development of preeclampsia

Pregnancy is an immunologically regulated, complex process. A tightly controlled complement system plays a crucial role in the successful establishment of pregnancy and parturition. Complement inhibitors at the feto-maternal interface are likely to prevent inappropriate complement activation to protect the fetus. In the present study, we aimed to understand the role of Factor H (FH), a negative regulator of complement activation, in normal pregnancy and in a model of pathological pregnancy, i.e. preeclampsia (PE). The distribution and expression of FH was investigated in placental tissues, various placental cells, and in the sera of healthy (CTRL) or PE pregnant women via immunohistochemistry, RT-qPCR, ELISA, and Western blot. Our results showed a differential expression of FH among the placental cell types, decidual stromal cells (DSCs), decidual endothelial cells (DECs), and extravillous trophoblasts (EVTs). Interestingly, FH was found to be considerably less expressed in the placental tissues of PE patients compared to normal placental tissue both at mRNA and protein levels. Similar results were obtained by measuring circulating FH levels in the sera of third trimester CTRL and PE mothers. Syncytiotrophoblast microvesicles, isolated from the placental tissues of PE and CTRL women, downregulated FH expression by DECs. The present study appears to suggest that FH is ubiquitously present in the normal placenta and plays a homeostatic role during pregnancy

COVID-19, Pre-Eclampsia, and Complement System

Copyright © 2021 Agostinis, Mangogna, Balduit, Aghamajidi, Ricci, Kishore and Bulla. COVID-19 is characterized by virus-induced injury leading to multi-organ failure, together with inflammatory reaction, endothelial cell (EC) injury, and prothrombotic coagulopathy with thrombotic events. Complement system (C) via its cross-talk with the contact and coagulation systems contributes significantly to the severity and pathological consequences due to SARS-CoV-2 infection. These immunopathological mechanisms overlap in COVID-19 and pre-eclampsia (PE). Thus, mothers contracting SARS-CoV-2 infection during pregnancy are more vulnerable to developing PE. SARS-CoV-2 infection of ECs, via its receptor ACE2 and co-receptor TMPRSS2, can provoke endothelial dysfunction and disruption of vascular integrity, causing hyperinflammation and hypercoagulability. This is aggravated by bradykinin increase due to inhibition of ACE2 activity by the virus. C is important for the progression of normal pregnancy, and its dysregulation can impact in the form of PE-like syndrome as a consequence of SARS-CoV-2 infection. Thus, there is also an overlap between treatment regimens of COVID-19 and PE. C inhibitors, especially those targeting C3 or MASP-2, are exciting options for treating COVID-19 and consequent PE. In this review, we examine the role of C, contact and coagulation systems as well as endothelial hyperactivation with respect to SARS-CoV-2 infection during pregnancy and likely development of PE.Ferring COVID-19 Investigational Grant (GRAVISAR to RB); Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy (RC24/19 to GR and 09/21 to CA)