EDITOR’S CHOICE – Novel Patents Targeting Interleukin-17A; Implications in Cancer and Inflammation

Journal: Recent Patents on Anti-Cancer Drug Discovery

Author(s): Juan F. Santibanez*, Suncica Bjelica


Background: IL-17A is a founding member of the IL-17 family that has been implicated in the pathogenesis of inflammatory-associated diseases such as cancer and autoimmune disease. In cancer, IL-17A participates in many key events for tumor development, in part by affecting innate and adaptive immune system and also by direct modulation of many pro-tumor events. Moreover, IL-17A dysregulation at the site of inflammation is associated with rheumatoid arthritis, multiple sclerosis, psoriasis, among others. IL-17A has emerged as a topic of interest and is under profound investigation for its involvement in several types of inflammatory-associated diseases.

Objective: This review aims to present an overview of the state of the art of IL-17A role in cancer and inflammation, as well as to describe recent patents targeting IL-17A with relevant clinical and biological properties for the prevention and treatment of cancer and inflammatory diseases.

Methods: Relevant information was obtained by searching in PubMed using IL-17A or IL-17, cancer and inflammation as keywords, while relevant patents were obtained mainly from Google Patents.

Results: Literature data indicated IL-17A as important biomolecule in the physiopathology of cancer and inflammatory diseases. Whereas, novel patents (2010 to 2017) targeting IL-17A are focused mainly on describing strategies to modulate IL-17A per se, co-modulation by bispecific antibodies to blocking IL-17A and important cytokines for IL-17A functions, upstream mechanisms and compounds to regulate IL-17A expression.

Conclusion: The promising effects of patented agents against IL-17A may open new opportunities to therapeutic intervention targeting at different levels of involvement in the pathogenesis of cancer and inflammatory diseases.

Read more here: http://www.eurekaselect.com/159948/article


PRESS RELEASE – Targeting inflammation to prevent preterm birth

A molecule named rytvela decreases uteroplacental inflammation, prevents preterm birth and improves perinatal outcomes through biased antagonism of the IL-1 receptor (functional selectivity)

Preterm birth (PTB) affects more than 10% of pregnancies worldwide and is the leading cause of neonatal mortality. Current treatments target myometrial contractility and are largely ineffective at improving perinatal outcomes. Myometrial contractions represent the final stage of a long process of uterine activation orchestrated by in utero inflammatory processes. If triggered prematurely (e.g. by infection), inflammation inevitably leads to preterm labor, with the timing of onset being inversely correlated with adverse neonatal outcomes and associated lifelong complications. Interleukin-1 (IL-1) is a major proinflammatory cytokine that has been firmly linked to human PTB and fetal organ injuries.

In a review article published in Current Pharmaceutical Design, Nadeau-Vallée et al. summarize the most recent evidence on the efficacy of molecules that target IL-1 to prevent PTB. Of all inhibitors of IL-1, the selective IL-1 receptor inhibitor rytvela (all-d heptapeptide) stands out preclinically as superiorly potent, effective, and safe in the prevention of PTB and its consequences. “Rytvela exerts benefits in decreasing uteroplacental inflammation, decreasing premature birth, prolonging gestation, increasing fetal survival, and improving fetal and neonatal outcome including that of the neurodevelopment” says Dr. Sylvain Chemtob, neonatologist, researcher, and principal author of the article. “Other than preventing preterm labor, rytvela also decreases inflammation inside the fetal compartment and in fetal organs, which is of significant importance because numerous neonatal conditions have been linked to inflammation independent of prematurity. Antenatal treatment with rytvela results in normalisation of lung, intestine and cerebral pathology scores during development and at adulthood”.

The effects of rytvela have been validated in vitro in murine and human uterine and immune cells, and in vivo in numerous murine models of PTB. Mechanistically, rytvela binds on a site remote from the binding site of IL-1 and act as a biased ligand by selectively inhibiting the p38/JNK/AP-1 pathway while preserving the activity of transcription factor NF-kB. This innovative mechanism of action may help decrease adverse effects (e.g. immunosuppression) which are particularly undesirable in the context of pregnancy.

Read more here: http://www.eurekaselect.com/155176

EDITOR’S CHOICE – Macrophage Polarization as a Therapeutic Target in Myocardial Infarction – Current Drug Targets

Journal: Current Drug Targets

Author(s): Yuanyuan Cheng, Jianhui Rong*

Graphical Abstract:



Background: Myocardial infarction is characterized by the interruption of blood flow through the heart, directly causing mortality and disability worldwide. Cardiac macrophages exhibit distinct phenotypes (e.g., M1 or M2) and functions (e.g., proinflammatory or anti-inflammatory) in response to the alterations of myocardial microenvironment, and subsequently exacerbate or resolve inflammation in the infarcted hearts. Regulation of macrophage polarization was implicated in myocardial infarction for the quality and outcome of cardiac healing.

Objective: The purpose of this review was to summarise the current understanding on the regulation of macrophage polarization in myocardial infarction and highlight the therapeutic potential of pharmacological regulators in the treatment of myocardial injury via modulating macrophage polarization.

Results: Timely control of M2/M1 ratio by endogenous mediators and pharmacological regulators should help the resolution of inflammation, promote wound healing and prevent cardiac fibrosis after myocardial infarction.

Conclusion: Macrophage polarization deserves better investigations as the therapeutic target for the development of novel drugs against myocardial injury.

Read more here: http://www.eurekaselect.com/156685/article


OPEN ACCESS ARTICLE – An Inflammation-related Nutrient Pattern is Associated with Both Brain and Cognitive Measures in a Multiethnic Elderly Population – Current Alzheimer Research

Journal: Current Alzheimer Research

Author(s): Yian Gu*, Jennifer J. Manly, Richard P. Mayeux, Adam M. Brickman



Background: Accumulating evidence suggests that dietary factors are associated with Alzheimer’s disease, cognition, and brain health in older adults. It is however unclear whether inflammation explains this association.

Objective: To examine whether an inflammation-related nutrient pattern (INP) was associated with neuroimaging and cognitive measures of brain health.

Method: The current cross-sectional study included 330 non-demented elderly (mean age 79 years at MRI scan) participants in a multi-ethnic, community-based cohort study who had information on nutritional intake (estimated from food frequency questionnaire), circulating C-reactive protein and interleukin- 6 (measured by ELISA), MRI scans, and cognition. Diet and blood samples were collected approximately 5.3 years prior to the MRI and cognitive test visit. We used a reduced rank regression model to derive an INP based on 24 nutrients’ relationship with CRP and interleukin-6. We examined the association of the INP with brain and cognitive measures using regression models adjusted for age, sex, race/ethnicity, education, caloric intake, APOE genotype, body mass index, and vascular burden, as well as intracranial volume for the brain MRI measures.

Results: The INP was characterized by low intake (effect loading <-0.15) of calcium, vitamins (D, E, A, B1, B2, B3, B5, B6), folate, Ω-3 poly-unsaturated fatty acids, and high intake (>0.15) of cholesterol. As designed, this INP was positively correlated with CRP (Pearson’s r=0.25 p=0.005) and interleukin-6 (r=0.30, p<0.0001). Each unit increase in INP was associated with 36.8 cm3 (p=0.023) smaller total brain volume and 0.21 (p=0.038) lower visuospatial z-score. Mediation analysis showed that TGMV (b=0.002, p=0.003) was associated with visuospatial cognitive function, and there was a significant mediation effect by TGMV (indirect effect: -0.049, 95% CI: -0.1121 ~ -0.0131) for the association between INP and visuospatial cognitive score.

Conclusions: Among older adults, a diet with high inflammatory potential is associated with less favorable brain and cognitive health.

Read more here: http://www.eurekaselect.com/158749


EDITOR’S CHOICE – Relationship between Proinflammatory Cytokines/Chemokines and Adipokines in Serum of Young Adults with Obesity – Endocrine, Metabolic & Immune Disorders – Drug Targets

Journal: Endocrine, Metabolic & Immune Disorders – Drug Targets

Author(s): Maraisa D. Borges, Eduardo L. Franca, Mahmi Fujimori, Silvia M.C. Silva, Patricia G.F. de Marchi,Alessandra L. Deluque, Adenilda C. Honorio-Franca*, Luiz C. de Abreu


Background and Objective: The adipose tissue has been recognized as an important endocrine organ, which is metabolically active and expresses and secretes various inflammatory cytokines. Inflammation is involved in obesity-related complications. As such, the present study investigated the correlation between biochemical parameters, serum proinflammatory cytokines and adipokines in individuals with obesity.

Methods: Based on the body mass index (BMI), 30 subjects were divided into 3 groups: eutrophic (GC, n = 10), overweight (GOW, n = 10) and obese (GOB, n = 10). Serum glucose, cholesterol (total-C, HDLC and LDL-C), triglycerides, total proteins, uric acid and insulin were determined, as well as cytokines IL-8, TNF-α, IL-1β, and IL-6, leptin and adiponectin.

Results: GOB showed the highest glucose, total and LDL-C, triglycerides, uric acid, insulin, leptin, IL- 8, IL-1β, IL-6, TNF-α and lowest adiponectin levels. In general, adiponectin exhibited an inverse correlation with BMI, abdominal circumference, LDL-C, IL-6, TNF-α, leptin and leptin-adiponectin ratio (LAR) and a positive correlation with HDL-C. Leptin was positively correlated with BMI, abdominal circumference, insulin, IL-6, TNF-α and LAR and negatively correlated with HDL-C and adiponectin. The LAR was positively correlated with BMI, waist circumference, insulin, TNF-α and negatively associated with HDL-C.

Conclusion: The results confirm that obesity changes the lipid and glycemic profiles of individuals, increases the proinflammatory adipokine levels and reduces those of anti-inflammatory adipokines, promoting a state of chronic inflammation.

Read more here: http://www.eurekaselect.com/159512/article


EDITOR’S CHOICE – Vigna unguiculata Trypsin Inhibitor – Current Enzyme Inhibition

Journal: Current Enzyme Inhibition

Author(s): Romana Parveen, Tooba Naz Shamsi, Sumbul Afreen, Mudsser Azam, Tasneem Fatma, Qazi Mohd. Rizwanul Haque, Sadaf Fatima*

Graphical Abstract:



Background: Trypsin Inhibitors are one of the most promising and investigated subject for their role in pharmacognostical and pharmacological studies.

Aim: The paper describes purification and characterization of trypsin inhibitor obtained from blackeyed cowpea (Vigna unguiculata).

Methods: The purification procedure of Vigna unguiculata trypsin inhibitor (VUTI) includes homogenization followed by ammonium sulphate precipitation. The protein thus precipitated was further dialysed and purified by ion exchange chromatography and gel permeation chromatography. The molecular weight was determined by SDS-PAGE. The protein thus purified was characterized biochemically to demonstrate curative potential as strong antioxidant, anti-inflammatory and antimicrobial agent.

Results: The 15 kDa VUTI obtained showed IC50 values 490 µg/ml compared to standard which was 254µg/ml in 1, 1-diphenyl-2-picrylhydrazyl (DPPH) assay. Also, the highest ferric reducing antioxidant power (FRAP) results confirmed the highest FRAP value of 0.405 mM at 1000 µg/ml and the lowest value of 0.113 mM at 100 μg/ml which were quite comparable to ascorbic acid (standard). Anti-inflammatory activity of VUTI was depicted by the method of inhibition of albumin denaturation where, VUTI showed high IC50 value of 696.46 µg/ml. Also, VUTI showed good antibacterial potential by inhibiting all tested bacterial strains with maximum inhibition against Bacillus subtilis (99.62%) and minimum against Staphylococcus aureus (34.62%). The results were quite comparable with standard drug ampicillin (5 mg/ml). Unfortunately, VUTI failed to show any activity against fungi.

Conclusion: Thus, the results obtained depict that VUTI additionally be a wonderful candidate for development of novel antibacterial drugs, and it can also be used to reduce the deletorious effects of free radicals.

Read more here: http://www.eurekaselect.com/153396/article

PODCAST: Preterm Birth and Neonatal Injuries

Author(s): Mathieu Nadeau-Vallee, Dima Obari, Alexandra Beaudry-Richard, Estefania Marin Sierra,Alexandre Beaulac, Noemie Maurice, David M. Olson*, Sylvain Chemtob*.

For article details, visit: http://www.eurekaselect.com/155176

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Podcast: Autoinflammation and Immunomodulation in Inflammatory Fibromyalgia Syndrome- A Review

Author(s): Samy Metyas*, Tamer Rezk, Daniel Arkfeld, Thomas Leptich.

For article details, visit: http://www.eurekaselect.com/145618

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