Macrophage Extracellular Traps: Current Opinions and the State of Research regarding Various Diseases

Macrophages are an important component of the human immune system and play a key role in the immune response, which can protect the body against infection and regulate the development of tissue inflammation. Some studies found that macrophages can produce extracellular traps (ETs) under various conditions of stimulation. ETs are web-like structures that consist of proteins and DNA. ETs are thought to immobilize and kill microorganisms, as well as play an important role in tissue damage, inflammatory progression, and autoimmune diseases. In this review, the structure, identification, mechanism, and research progress of macrophage extracellular traps (METs) in related diseases are reviewed.

Phages in the Gut Ecosystem

Phages, short for bacteriophages, are viruses that specifically infect bacteria and are the most abundant biological entities on earth found in every explored environment, from the deep sea to the Sahara Desert. Phages are abundant within the human biome and are gaining increasing recognition as potential modulators of the gut ecosystem. For example, they have been connected to gastrointestinal diseases and the treatment efficacy of Fecal Microbiota Transplant. The ability of phages to modulate the human gut microbiome has been attributed to the predation of bacteria or the promotion of bacterial survival by the transfer of genes that enhance bacterial fitness upon infection. In addition, phages have been shown to interact with the human immune system with variable outcomes. Despite the increasing evidence supporting the importance of phages in the gut ecosystem, the extent of their influence on the shape of the gut ecosystem is yet to be fully understood. Here, we discuss evidence for phage modulation of the gut microbiome, postulating that phages are pivotal contributors to the gut ecosystem dynamics. We therefore propose novel research questions to further elucidate the role(s) that they have within the human ecosystem and its impact on our health and well-being.

Human gut-microbiome-derived propionate coordinates proteasomal degradation via HECTD2 upregulation to target EHMT2 in colorectal cancer

The human microbiome plays an essential role in the human immune system, food digestion, and protection from harmful bacteria by colonizing the human intestine. Recently, although the human microbiome affects colorectal cancer (CRC) treatment, the mode of action between the microbiome and CRC remains unclear. This study showed that propionate suppressed CRC growth by promoting the proteasomal degradation of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) through HECT domain E3 ubiquitin protein ligase 2 (HECTD2) upregulation. In addition, EHMT2 downregulation reduced the H3K9me2 level on the promoter region of tumor necrosis factor α-induced protein 1 (TNFAIP1) as a novel direct target of EHMT2. Subsequently, TNFAIP1 upregulation induced the apoptosis of CRC cells. Furthermore, using Bacteroides thetaiotaomicron culture medium, we confirmed EHMT2 downregulation via upregulation of HECTD2 and TNFAIP1 upregulation. Finally, we observed the synergistic effect of propionate and an EHMT2 inhibitor (BIX01294) in 3D spheroid culture models. Thus, we suggest the anticancer effects of propionate and EHMT2 as therapeutic targets for colon cancer treatment and may provide the possibility for the synergistic effects of an EHMT2 inhibitor and microbiome in CRC treatment.

PHYSIOLOGICAL PREDICTORS OF LONG-TERM EFFECTS OF COVID-19 IN PATIENTS WITH SARS-COV-2: FOCUS ON LYMPHOCYTE PROLIFERATION-IMPROVING MICRONUTRIENTS

Patients with long-term effects of coronavirus disease, the so-called “long-term COVID-19 syndrome” (long-COVID-19) after SARS-CoV-2 infection, have a postponed recovery lasting from 4 weeks and up to six months, spread worldwide. Physiological predictors based on human blood biomarkers and host-virus responses to SARS-CoV-2 are still unknown. There is growing evidence about the impact of micronutrients on improving lymphocyte proliferation and their essential roles for a functioning human immune system and regulating metabolic health. This paper aims to review information about micronutrients in patients with SARS-CoV-2 infection that determines long-COVID-19 outcomes and highlight the importance of diagnostics in predictors of long-COVID-19. We reviewed articles returned from searches on PubMed/SCOPUS/Web of Science/ EMBASE databases using a combination of terms “long COVID-19”, “long-term effects of COVID-19”, “post-COVID-19 symptoms”, “COVID-19 associated stress”, “micronutrients”. Evidence indicates the relationship between lymphocyte proliferation improving micronutrient level and long-COVID-19 induction. Zinc, selenium, iron, manganese have an immunomodulatory function in innate and adaptive immune responses to viral infection. Anti-inflammatory functions of Vits A and B groups include the regulation of lymphocyte proliferation and metabolic health. Further research using sampling and artificial intelligence-assisted algorithms could assist in the recognition of the correlation of micronutrients and long-COVID-19 clinical outcomes

The design of bioactive marine peptides as a HIV-1 protease inhibitor

Background: Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV or AIDS) is a disease related to the human immune system. Given its important role in viral replication, HIV1 protease (HIV1 PR) becomes the major therapeutic target in the treatment of AIDS. In this case, we need a dynamic aspect of molecular interactions that can demonstrate the important role of conformational variability in the design of HIV1 PR inhibitors. There are several inhibitor candidates from marine organisms, such as the LLEYSL and LLEYSI bioactive peptides produced by oysters (Crassostrea gigas). Objective: Proteinpeptide docking method was used in silico to identify, evaluate, and explore the molecular interactions between bioactive peptide molecules and HIV-1 protease macromolecules. Methods: The sequencing of bioactive peptide molecules was modeled into 3D conformation using the PEPFOLD software. The best conformation was chosen for the study of molecular interactions against HIV1 protease macromolecules using the PatchDock software. The molecular interactions formed were further observed using the BIOVIA Discovery Studio 2020 software. Results: The results of this study indicated that the LLEYSL bioactive peptide had the best affinity with an ACE score of minus 1284.70 kJ per mol. Conclusion: Bioactive peptide molecule is predicted to be a candidate for HIV1 protease inhibitor. Keywords: AIDS, HIV1 protease, bioactive peptides, protein-peptide docking, in silico

Molecular Modeling Insights into Upadacitinib Selectivity upon Binding to JAK Protein Family

Rheumatoid arthritis (RA) is a chronic disease characterized by bone joint damage and incapacitation. The mechanism underlying RA pathogenesis is autoimmunity in the connective tissue. Cytokines play an important role in the human immune system for signal transduction and in the development of inflammatory responses. Janus kinases (JAK) participate in the JAK/STAT pathway, which mediates cytokine effects, in particular interleukin 6 and IFNγ. The discovery of small molecule inhibitors of the JAK protein family has led to a revolution in RA therapy. The novel JAK inhibitor upadacitinib (RinvoqTM) has a higher selectivity for JAK1 compared to JAK2 and JAK3 in vivo. Currently, details on the molecular recognition of JAK1 by upadacitinib are not available. We found that characteristics of hydrogen bond formation with the glycine loop and hinge in JAKs define the selectivity. Our molecular modeling study could provide insight into the drug action mechanism and pharmacophore model differences in JAK isoforms.

Gambaran Dukungan Keluarga Dan Kualitas Hidup Penderita HIV/AIDS : Literature Review

HIV (Human Immunodefisiensi Virus) is a virus that attacks the human immune system and weaknes the body’s ability to fight various types of diseases. The problem that arise due to HIV/AIDS are very complex. Including physical, psychological, socisl, and spiritual problems that affect the quality of life of people living with HIV/AIDS (PLWHA) so that they require family support. This study aimed to describe the description of family support and wuality of life of HIV/AIDS suffers. This study used the PubMed and Google Scholar database to search for articles in Indonesia. The searching used a combination of the keyword “Family Support” and “Quality Of Life” “HIV/AIDS”. The results of this study indicated that there was a corellation between family support and the quality of life of people living with HIV/AIDS(PLWH). The results of this study are expected to provide family social care for the quality of life in HIV patients, so that family support can be incluted in improving the quality of life of people living with HIV. Further research with a better methodology and theoretical framework is needed to find more sprcife therapies.Keywords : family support; Quality of life; HIV/AIDS AbstrakHIV (Human Immunodefisiensi Virus) adalah virus yang menyerang sistem kekebalan tubuh manusia dan melemahkan kemampuan tubuh untuk melawan berbagai jenis penyakit. Permasalahan yang timbul akibat HIV/AIDS sangat kompleks, dimana diantaranya terdapat masalah fisik, psikologis, sosial dan spiritual yang mempengaruhi kualitas hidup orang dengan HIV/AIDS (ODHA) sehingga memerlukan dukugan keluarga. Penelitian ini bertujuan untuk mengetahui gambaran dukungan keluarga dan Kualitas Hidup Penderita HIV/AIDS. Penelitian ini Menggunakan database PubMed dan GoogleScholar umtuk artikel berbahasa Indonesia. Pencarian digunakan dengan mengkombinasikan kata kunci “ Family Support” and “Quality of Life” “HIV/AIDS”. Hasil Penelitian ini Menunjukkan bahwa dukungan keluarga berhubungan dan berpengaruh terhadap kualitas hidup orang dengan HIV/AIDS (ODHA). Studi ini diharapkan Hasil penelitian ini diharapkan dapat memberikan sosial keluarga tehadap kualitas hidup pada pasien HIV, sehingga dukungan keluarga dapat dimasukkan dalam meningkatkan kualitas hidup orang dengan HIV. Penelitian lanjutan dengan metodologi dan kerangka teori yang lebih baik diperlukan untuk mencari terapi yang lebih spesifik,Kata kunci: Dukungan keluarga; Kualitas Hidup; HIV/AIDS

Mechanistic diversity in MHC class I antigen recognition

Throughout its evolution, the human immune system has developed a plethora of strategies to diversify the antigenic peptide sequences that can be targeted by the CD8+ T cell response against pathogens and aberrations of self. Here we provide a general overview of the mechanisms that lead to the diversity of antigens presented by MHC class I complexes and their recognition by CD8+ T cells, together with a more detailed analysis of recent progress in two important areas that are highly controversial: the prevalence and immunological relevance of unconventional antigen peptides; and cross-recognition of antigenic peptides by the T cell receptors of CD8+ T cells.

SARS-COV-2 acts as a test of Air Pollution, Lifestyle Disorders and Immune Tolerance dysregulation in human body

SARS-COV-2 is reported to be associated with severe immune dysregulation, delayed humoral responses and accelerated innate immune response mediated damages. As the pandemic is turning the world upside down, In order to address this disease we should first get an insight into the mechanism of action through which SARS-COV-2 is achieving the above said dysregulating or modulating effects on human immune system. T his article presents the basic or skeletal mechanism through which SARS-COV-2 dysregulates immune system by targeting innate immune system, adaptive immune system and different immune tolerance check points by dysregulating different miRNA’s and the preexisting conditions or comorbidities of the patients. This article comprises of the comparative and comprehensive literature review targeting all topics with the data available/reported till date in the scientific community.