Recent Publications
Mulate Zerihun, Nir Qvit: Selective inhibitors targeting Fis1/Mid51 protein-protein interactions protect against hypoxia-induced damage in cardiomyocytes (Front Pharmacol . )
Cardiovascular diseases (CVDs) are the most common non-communicable diseases globally. An estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths. Mitochondria play critical roles in cellular metabolic homeostasis, cell survival, and cell death, as well as producing most of the cell's energy. Protein-protein interactions (PPIs) have a significant role in physiological and pathological processes, and aberrant PPIs are associated with various diseases, therefore they are potential drug targets for a broad range of therapeutic areas. Due to their ability to mimic natural interaction motifs and cover relatively larger interaction region, peptides are very promising as PPI inhibitors. To expedite drug discovery, computational approaches are widely used for screening potential lead compounds. Here, we developed peptides that inhibit mitochondrial fission 1 (Fis1)/mitochondrial dynamics 51 kDa (Mid51) PPI to reduce the cellular damage that can lead to various human pathologies, such as CVDs.
Aysar Nashef: Towards system genetics analysis of head and neck squamous cell carcinoma using the mouse model, cellular platform, and clinical human data (Animal Model Exp Med .)
Head and neck squamous cell cancer (HNSCC) is a leading global malignancy. Every year, More than 830 000 people are diagnosed with HNSCC globally, with more than 430 000 fatalities. HNSCC is a deadly diverse malignancy with many tumor locations and biological characteristics....In this report, we explore and discuss potential research prospects utilizing the Collaborative Cross mouse model and crossing it to mice carrying single or double knockout genes (e.g. Smad4 and P53 genes) to identify genetic factors affecting the development of this complex disease using genome-wide association studies, epigenetics, microRNA, long noncoding RNA, lncRNA, histone modifications, methylation, phosphorylation, and proteomics.
Orna Schwartz, Hanan Rohana, Maya Azrad, Avi Peretz: Characterization of community-acquired Clostridioides difficile strains in Israel, 2020-2022 (Front Microbiol . )
The prevalence of community-acquired Clostridioides difficile infection (CA-CDI) has been rising, due to changes in antibiotics prescribing practices, emergence of hypervirulent strains and improved diagnostics. This study explored CA-CDI epidemiology by examining strain diversity and virulence factors of CA-CDI isolates collected across several geographical regions in Israel.
Shmuel Silnitsky, Mulate Zerihun, Nir Qvit: An Update on Protein Kinases as Therapeutic Targets-Part I: Protein Kinase C Activation and Its Role in Cancer and Cardiovascular Diseases (Int J Mol Sci .)
Protein kinases are one of the most significant drug targets in the human proteome, historically harnessed for the treatment of cancer, cardiovascular disease, and a growing number of other conditions, including autoimmune and inflammatory processes. Since the approval of the first kinase inhibitors in the late 1990s and early 2000s, the field has grown exponentially, comprising 98 approved therapeutics to date, 37 of which were approved between 2016 and 2021. While many of these small-molecule protein kinase inhibitors that interact orthosterically with the protein kinase ATP binding pocket have been massively successful for oncological indications, their poor selectively for protein kinase isozymes have limited them due to toxicities in their application to other disease spaces. Thus, recent attention has turned to the use of alternative allosteric binding mechanisms and improved drug platforms such as modified peptides to design protein kinase modulators with enhanced selectivity and other pharmacological properties. Herein we review the role of different protein kinase C (PKC) isoforms in cancer and cardiovascular disease, with particular attention to PKC-family inhibitors.
Bacteroides is increased in an autism cohort and induces autism-relevant behavioral changes in mice in a sex-dependent manner (NPJ Biofilms Microbiomes . )
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition which is defined by decreased social communication and the presence of repetitive or stereotypic behaviors. Recent evidence has suggested that the gut-brain axis may be important in neurodevelopment in general and may play a role in ASD in particular. Here, we present a study of the gut microbiome in 96 individuals diagnosed with ASD in Israel, compared to 42 neurotypical individuals.
(Julie Carmel, Nasreen Ghanayem, Rasha Mayouf, Natalia Saleev, Ipsita Chaterjee, Dmitriy Getselter, Evgeny Tikhonov, Sondra Turjeman, Monia Shaalan, Saleh Khateeb, Tanya Kronos, Tali Bretler-Zager, Omry Koren, Evan Elliott)
Inbar Ben Shachar, Ilan Atlas: Assessment of oncological safety and utility of hysteroscopy in high grade endometrial cancers: Results from an Israel gynecologic oncology group study (Eur J Obstet Gynecol Reprod Biol . )
Compares survival measures of women with Stage I high-grade endometrial cancer who underwent either hysteroscopy or a non-hysteroscopic procedure as a diagnostic procedure.
Mulate Zerihun, Shmuel Silnitsky, Nir Qvit: An Update on Protein Kinases as Therapeutic Targets-Part II: Peptides as Allosteric Protein Kinase C Modulators Targeting Protein-Protein Interactions (Int J Mol Sci .)
Human protein kinases are highly-sought-after drug targets, historically harnessed for treating cancer, cardiovascular disease, and an increasing number of autoimmune and inflammatory conditions. Most current treatments involve small molecule protein kinase inhibitors that interact orthosterically with the protein kinase ATP-binding pocket. As a result, these compounds are often poorly selective and highly toxic.
Wisam Sbeit, Maamoun Basheer, Amir Shahin, Sharbel Khoury, Botros Msheael, Nimer Assy, Tawfik Khoury: Clinical Predictors of Gastrointestinal Bleeding Source before Computed Tomography Angiography (J Clin Med .)
Acute gastrointestinal bleeding (GIB) is a commonly encountered medical emergency. In cases of negative endoscopic evaluations, computed tomography angiography (CTA) is usually the next diagnostic step. To date, data regarding positive CTA examinations are lacking. We aimed to assess the clinical and laboratory parameters that predict a positive CTA examination, as demonstrated by the extravasation of contrast material into the bowel lumen.
Omry Koren: The maternal gut microbiome in pregnancy: implications for the developing immune system (Nat Rev Gastroenterol Hepatol .)
The gut microbiome has important roles in host metabolism and immunity, and microbial dysbiosis affects human physiology and health. Maternal immunity and microbial metabolites during pregnancy, microbial transfer during birth, and transfer of immune factors, microorganisms and metabolites via breastfeeding provide critical sources of early-life microbial and immune training, with important consequences for human health. Only a few studies have directly examined the interactions between the gut microbiome and the immune system during pregnancy, and the subsequent effect on offspring development. In this Review, we aim to describe how the maternal microbiome shapes overall pregnancy-associated maternal, fetal and early neonatal immune systems, focusing on the existing evidence and highlighting current gaps to promote further research.
Moshe Bocher: Improving severity classification of Hebrew PET-CT pathology reports using test-time augmentation (J Biomed Inform .)
Classifying medical reports written in Hebrew is challenging due to the ambiguity and complexity of the language. This study proposes Text Test Time Augmentation (TTTA), a novel method to improve the classification accuracy of cancer severity levels from PET-CT diagnostic reports in Hebrew.
Afif Nakhleh: Common Bacterial Infections during the 3-Month Period after SARS-CoV-2 Infection: A Retrospective Cohort Study (Healthcare (Basel) .)
Correlations between SARS-CoV-2 and bacterial infections have mainly been studied in hospitals, and these studies have shown that such interactions may be lethal for many. In the context of community flora, less is known of the trends and consequences of viral infections relative to subsequent bacterial infections. This study aims to explore the prevalence and characteristics of bacterial infections in the three months following SARS-CoV-2 infections, in a community, real-world setting.
Jawad Sakas, Orit Radin, Noa Abrahami, Osnat Altshuler, Johnny S Younis: Testicular fine-needle aspiration in infertile men with absolute non-obstructive azoospermia: A single-centre cohort study (Aust N Z J Obstet Gynaecol .)
The methodology of surgically extracted sperm cells in fertility treatments remains debated, mainly due to the lack of data evaluating its predictive value on treatment outcomes. Aim: To gain insight into the effectiveness of testicular fine-needle aspiration (TEFNA) in a cohort of infertile men with absolute non-obstructive azoospermia and to examine whether the number of retrieved sperm cells affects the fertilisation rate.
Shemy Carasso: Artificial Intelligence-Powered Left Ventricular Ejection Fraction Analysis Using the LVivoEF Tool for COVID-19 Patients (J Clin Med . )
We sought to prospectively investigate the accuracy of an artificial intelligence (AI)-based tool for left ventricular ejection fraction (LVEF) assessment using a hand-held ultrasound device (HUD) in COVID-19 patients and to examine whether reduced LVEF predicts the composite endpoint of in-hospital death, advanced ventilatory support, shock, myocardial injury, and acute decompensated heart failure.
Michael Edelstein: Barriers to HPV vaccination in marginalized Roma communities in Slovakia (Front Public Health .)
Limited access to healthcare services leads to lower vaccination rates in marginalized Roma communities (MRCs). This study aimed to explore health system barriers to HPV vaccination faced by people from MRCs from multiple perspectives.
Maya Azrad, Layan Abu-Rahmoun, Zohar Hamo, Avi Peretz: Associations of motility and auto-aggregation with biofilm-formation capacity levels in Clostridioidesdifficile (Microb Pathog . )
Clostridioides difficile (C. difficile) is responsible for one of the most common nosocomial infections worldwide. This work assessed associations between biofilm-formation capacity levels of C. difficile and cell viability, motility, flagella, motility and auto-aggregation in 118 clinical isolates.