Brief Review on Apoptosis in Microbial Infection

2021 ◽  
pp. 121-127
Author(s):  
Abdulaziz Alanazi ◽  
Mishal E. Alanazi ◽  
Arwa F. Alanazi ◽  
Amani F. Alanazi ◽  
Badi Alanazi ◽  
...  
Keyword(s):  
Microbial Infection

SKY59, A Novel Recycling Antibody for Complement-mediated Diseases

2020 ◽  
Vol 27 (25) ◽  
pp. 4157-4164 ◽  
Author(s):  
Taku Fukuzawa ◽  
Junichi Nezu
Keyword(s):  
Inhibitory Effect ◽  
Biologic Agent ◽  
Microbial Infection ◽  
Duration Of Action ◽  
Complement Activity ◽  
Body Of Knowledge ◽  
Therapeutic Benefits ◽  
Long Duration ◽  
Recycling Technology ◽  
Current Therapies

Background: The complement system usually helps protect against microbial infection, but it could also be involved in the onset of various diseases. Inhibition of complement component 5 (C5) with eculizumab has resulted in a significant reduction of hemolysis, reduction of thromboembolic events, and increased survival in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH). However, eculizumab requires frequent intravenous infusions due to the abundance of C5 in plasma and some patients may still experience breakthrough hemolysis. This review introduces the recent body of knowledge on recycling technology and discusses the likely therapeutic benefits of SKY59, a novel recycling antibody, for PNH and complement-mediated disorders. Methods: By using recycling technology, we created a novel anti-C5 antibody, SKY59, capable of binding to C5 pH-dependently. Results: In cynomolgus monkeys, SKY59 robustly inhibited C5 and complement activity for significantly longer than a conventional antibody. SKY59 also showed an inhibitory effect on C5 variant p.Arg885His, whereas eculizumab does not suppress complement activity in patients with this type of mutation. Conclusion: SKY59 is a promising anti-C5 biologic agent that has significant advantages over current therapies such as long duration of action and efficacy against C5 variants.

Novel Thiazole-Based Thiazolidinones as Potent Anti-infective Agents: In silico PASS and Toxicity Prediction, Synthesis, Biological Evaluation and Molecular Modelling

2020 ◽  
Vol 23 (2) ◽  
pp. 126-140 ◽  
Author(s):  
Christophe Tratrat
Keyword(s):  
In Silico ◽  
Antimicrobial Agents ◽  
Target Identification ◽  
Biological Evaluation ◽  
Microbial Infection ◽  
Toxicity Prediction ◽  
Discovery Studio ◽  
Bacteria And Fungi ◽  
Multiple Drugs ◽  
Antibacterial And Antifungal

Aims and Objective: The infectious disease treatment remains a challenging concern owing to the increasing number of pathogenic microorganisms associated with resistance to multiple drugs. A promising approach for combating microbial infection is to combine two or more known bioactive heterocyclic pharmacophores in one molecular platform. Herein, the synthesis and biological evaluation of novel thiazole-thiazolidinone hybrids as potential antimicrobial agents were dissimilated. Materials and Methods: The preparation of the substituted 5-benzylidene-2-thiazolyimino-4- thiazolidinones was achieved in three steps from 2-amino-5-methylthiazoline. All the compounds have been screened in PASS antibacterial activity prediction and in a panel of bacteria and fungi strains. Minimum inhibitory concentration and minimum bacterial concentration were both determined by microdilution assays. Molecular modeling was conducted using Accelrys Discovery Studio 4.0 client. ToxPredict (OPEN TOX) and ProTox were used to estimate the toxicity of the title compounds. Results: PASS prediction revealed the potentiality antibacterial property of the designed thiazolethiazolidinone hybrids. All tested compounds were found to kill and to inhibit the growth of a vast variety of bacteria and fungi, and were more potent than the commercial drugs, streptomycin, ampicillin, bifomazole and ketoconazole. Further, in silico study was carried out for prospective molecular target identification and revealed favorable interaction with the target enzymes E. coli MurB and CYP51B of Aspergillus fumigatus. Toxicity prediction revealed that none of the active compounds was found toxic. Conclusion: Substituted 5-benzylidene-2-thiazolyimino-4-thiazolidinones, endowing remarkable antibacterial and antifungal properties, were identified as a novel class of antimicrobial agents and may find a potential therapeutic use to eradicate infectious diseases.

Phytochemistry, Traditional Uses and Pharmacological properties of Enhydra fluctuans Lour: A Comprehensive Review.

2020 ◽  
Vol 21 ◽  
Author(s):  
Antica Barua ◽  
Muhammad Shaiful Alam ◽  
Md. Junaid ◽  
Yeasmin Akter ◽  
Syeda Samira Afrose ◽  
...  
Keyword(s):  
Sesquiterpene Lactone ◽  
Chemical Constituents ◽  
Phytochemical Analysis ◽  
Microbial Infection ◽  
Scientific Databases ◽  
Traditional Uses ◽  
Cns Depressant ◽  
Isoflavone Glycoside ◽  
Online Library ◽  
Pharmacologically Active

Background: Enhydra fluctuans Lour, a tropical herb, commonly known as helencha or harkuch, belonging to family Asteraceae, and is an edible semi-aquatic herbaceous vegetable plant with serrate leaves, grows commonly in different parts of the world. Enhydra fluctuans possesses potential pharmacological role against inflammation, cancer, diarrhea, microbial infection, diabetes, and so on. Aim of the review: This review aims to provide the most current information on the botanical characterization, distribution, traditional uses, chemical constituents, as well as the pharmacological activities of Enhydra fluctuans Lour. Materials and methods: The recently updated information on Enhydra fluctuans was gathered from scientific journals, books, and worldwide accepted scientific databases via a library and electronic search (PubMed, Elsevier, Google Scholar, Springer, Scopus, Web of Science, Wiley online library. All of the full-text articles and abstracts related to Enhydra were screened. The most important and relevant articles were carefully chosen for study in this review. Results: Crude extracts and isolated compounds of Enhydra fluctuans Lour has been reported pharmacologically active against cytoprotective, analgesic and anti-inflammatory, antimicrobial, anticancer, anti-diarrhoeal, antihelmintic, CNS depressant, hepatoprotective, thrombolytic, antidiabetic, anti-oxidant, phagocytic and cytotoxic, and neuroprotective potential activities. Discussion: Phytochemical analysis from different studies has reported Germacranolide, Sesquiterpene lactone, Flavonoid, Essential oil, Steroid, Diterpenoid, Melampolide, Sesquiterpene lactone, Isoflavone glycoside as major compounds of Enhydra fluctuans Lour. Conclusions: However, more research is important to explore the mode of action of bioactive components of the plant and its therapeutic capabilities.

The Role of Formyl Peptide Receptors in Microbial Infection and Inflammation

2003 ◽  
Vol 2 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Yingying Le ◽  
Ronghua Sun ◽  
Guoguang Ying ◽  
Pablo Iribarren ◽  
Ji Wang
Keyword(s):  
Microbial Infection ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide ◽  
Infection And Inflammation

scholarly journals GSDMD contributes to host defence against Staphylococcus aureus skin infection by suppressing the Cxcl1–Cxcr2 axis

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Zhen-Zhen Liu ◽  
Yong-Jun Yang ◽  
Feng-Hua Zhou ◽  
Ke Ma ◽  
Xiao-Qi Lin ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Skin Infection ◽  
Bacterial Colonization ◽  
Critical Role ◽  
Host Defence ◽  
Skin Damage ◽  
Microbial Infection ◽  
Caspase 1 ◽  
Deficient Mice

AbstractGasdermin D (GSDMD), a member of the gasdermin protein family, is a caspase substrate, and its cleavage is required for pyroptosis and IL-1β secretion. To date, the role and regulatory mechanism of GSDMD during cutaneous microbial infection remain unclear. Here, we showed that GSDMD protected against Staphylococcus aureus skin infection by suppressing Cxcl1–Cxcr2 signalling. GSDMD deficiency resulted in larger abscesses, more bacterial colonization, exacerbated skin damage, and increased inflammatory cell infiltration. Although GSDMD deficiency resulted in defective IL-1β production, the critical role of IL-1β was counteracted by the fact that Caspase-1/11 deficiency also resulted in less IL-1β production but did not aggravate disease severity during S. aureus skin infection. Interestingly, GSDMD-deficient mice had increased Cxcl1 secretion accompanied by increased recruitment of neutrophils, whereas Caspase-1/11-deficient mice presented similar levels of Cxcl1 and neutrophils as wild-type mice. Moreover, the absence of GSDMD promoted Cxcl1 secretion in bone marrow-derived macrophages induced by live, dead, or different strains of S. aureus. Corresponding to higher transcription and secretion of Cxcl1, enhanced NF-κB activation was shown in vitro and in vivo in the absence of GSDMD. Importantly, inhibiting the Cxcl1–Cxcr2 axis with a Cxcr2 inhibitor or anti-Cxcl1 blocking antibody rescued host defence defects in the GSDMD-deficient mice. Hence, these results revealed an important role of GSDMD in suppressing the Cxcl1–Cxcr2 axis to facilitate pathogen control and prevent tissue damage during cutaneous S. aureus infection.

scholarly journals Antimicrobial α-defensins as Multi-target Inhibitors Against Amyloid Formation and Microbial Infection

2021 ◽  
Author(s):  
Yanxian Zhang ◽  
Yonglan Liu ◽  
Yijing Tang ◽  
Dong Zhang ◽  
Huacheng He ◽  
...  
Keyword(s):  
Risk Factors ◽  
Thyroid Carcinoma ◽  
Type Ii Diabetes ◽  
Amyloid Formation ◽  
Type Ii ◽  
Amyloid Aggregation ◽  
Microbial Infection ◽  
Medullary Thyroid ◽  
Parkinson’S Diseases ◽  
Amyloid Diseases

Amyloid aggregation and microbial infection are considered as pathological risk factors for developing amyloid diseases, including Alzheimer’s (AD), type II diabetes (T2D), Parkinson’s diseases (PD), and medullary thyroid carcinoma (MTC)....

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