Improvement of beef cattle cow’s pregnancy rate using an effective dose of Galectin-1

Galectins are cited in the literature as multifunctional molecules that participate in several biological processes such as adhesion, proliferation and cell cycle, apoptosis, RNA processing, control of the inflammatory processes, and physiological mechanisms of reproduction. Galectin-1 has been cited as a mediator involved in preventing early embryonic death in mammals. Exogenous GAL-1 (eGAL-1) can be found, present in Tolerana®. The goal of this study was to evaluate whether eGAL-1 can improve the pregnancy rate after a complementary AI procedure. The pregnancy rate was analyzed by determining the pregnancy status by ultrasound, 25 to 35 days after Timed Artificial Insemination (TAI) of dams (n=3,469 beef cows). The effectiveness of GAL-1 was evaluated by comparing the pregnancy rate of two groups (Treatment and Control Groups) in 107 contemporaries’ groups (YG) established by the statistical model formed. Based on this, the single dose of eGAL-1 and correct administration can increase the probability of obtaining the pregnancy rate in beef cattle up to 8.68% (p < 0.0001). The recommendation to use a dose of eGAL1 during a TAI procedure was reasonable in beef cattle routine. In average, the whole procedure, using eGAL-1, spent 10 ± 5 seconds more time than the conventional procedure.

Small extrachromosomal circular DNA (eccDNA): major functions in evolution and cancer

Extrachromosomal circular DNA (eccDNA) refers to a type of circular DNA that originate from but are likely independent of chromosomes. Due to technological advancements, eccDNAs have recently emerged as multifunctional molecules with numerous characteristics. The unique topological structure and genetic characteristics of eccDNAs shed new light on the monitoring, early diagnosis, treatment, and prediction of cancer. EccDNAs are commonly observed in both normal and cancer cells and function via different mechanisms in the stress response to exogenous and endogenous stimuli, aging, and carcinogenesis and in drug resistance during cancer treatment. The structural diversity of eccDNAs contributes to the function and numerical diversity of eccDNAs and thereby endows eccDNAs with powerful roles in evolution and in cancer initiation and progression by driving genetic plasticity and heterogeneity from extrachromosomal sites, which has been an ignored function in evolution in recent decades. EccDNAs show great potential in cancer, and we summarize the features, biogenesis, evaluated functions, functional mechanisms, related methods, and clinical utility of eccDNAs with a focus on their role in evolution and cancer.

Identification of cathelicidin gene from Hoplobatrachus rugulosus and the antioxidant capacity of PC29 peptide

Cathelicidins, a group of vertebrate multifunctional molecules, play a role in innate immunity. In this study, a cathelicidin was identified from the lungs of frogs, Hoplobatrachus rugulosus. A 474 base pairs (bp) complementary DNA (cDNA) sequence encoded a 157 amino acid residue prepropeptide of H. rugulosus cathelicidin (cathelicidin-HR), which consisting of a 20-residue signal peptide sequence, a 108-residue cathelin region, and a 29-residue cathelicidin-HR peptide. Amino acid sequence alignment and cladogram analysis illustrated that cathelicidin-HR have a high degree of similarity to further amphibian cathelicidins. The cathelicidin-HR peptide displays very low antimicrobial activity but exhibits dose-dependent antioxidant activity. Moreover, this peptide expresses DNA damage inhibition against UV/H2O2-induction. The molecular docking indicated that DNA damage protection of cathelicidin-HR might occur via DNA-peptide complex formation. This is the first amphibian cathelicidin peptide that possesses DNA damage inhibitory activity which might play a crucial role in oxidative stress.

Stay on Target: Reengaging Cancer Vaccines in Combination Immunotherapy

Effective treatment of established tumors requires rational multicombination immunotherapy strategies designed to target all functions of the patient immune system and tumor immune microenvironment. While these combinations build on the foundation of successful immune checkpoint blockade antibodies, it is increasingly apparent that successful immunotherapy will also require a cancer vaccine backbone to engage the immune system, thereby ensuring that additional immuno-oncology agents will engage a tumor-specific immune response. This review summarizes ongoing clinical trials built upon the backbone of cancer vaccines and focusing on those clinical trials that utilize multicombination (3+) immuno-oncology agents. We examine combining cancer vaccines with multiple checkpoint blockade antibodies, novel multifunctional molecules, adoptive cell therapy and immune system agonists. These combinations and those yet to enter the clinic represent the future of cancer immunotherapy. With a cancer vaccine backbone, we are confident that current and coming generations of rationally designed multicombination immunotherapy can result in effective therapy of established tumors.

Identification of cathelicidin gene from Hoplobatrachus rugulosus and the antioxidant capacity of PC29 peptide

Cathelicidins, a group of vertebrate multifunctional molecules, play a role in innate immunity. Cathelicidins are antimicrobial peptides (AMPs) that are involved in protection against microbial invasion. Presently, cathelicidin peptides have been identified from only 14 amphibian species. In the study, a novel cathelicidin was identified from the lungs of frogs, Hoplobatrachus rugulosus. A 474 base pairs (bp) complementary DNA (cDNA) sequence encoded a 157 amino acid residue prepropeptide of H. rugulosus cathelicidin (cathelicidin-HR), which consisting of a 20-residue signal peptide sequence, a 108-residue cathelin region, and a 29-residue cathelicidin peptide (PC29). Amino acid sequence alignment and cladogram analysis illustrated that cathelicidin-HR have a high degree of similarity to further amphibian cathelicidins. The PC29 peptide displays antimicrobial activity only against Bacillus subtilis and Enterococcus faecalis. However, the PC29 peptide performed dose-dependent antioxidant activity. This is the first cathelicidin antioxidant peptide identified from the lung which provided a template for the development of potent bi-functional peptide therapeutic agents.

Oriented arrangement of simple monomers enabled by confinement: towards living supramolecular polymerization

The living supramolecular polymerization technique provides an exciting research avenue. However, in comparison with the thermodynamic spontaneous nucleation, using simple monomers to realize living supramolecular polymerization is hardly possible from an energy principle. This is because the activation barrier of kinetically trapped simple monomer (nucleation step) is insufficiently high to control the kinetics of subsequent elongation. Here, with the benefit of the confinement from the layered double hydroxide (LDH) nanomaterial, various simple monomers, (such as benzene, naphthalene and pyrene derivatives) successfully form living supramolecular polymer (LSP) with length control and narrow dispersity. The degree of polymerization can reach ~6000. Kinetics studies reveal LDH overcomes a huge energy barrier to inhibit undesired spontaneous nucleation of monomers and disassembly of metastable states. The universality of this strategy will usher exploration into other multifunctional molecules and promote the development of functional LSP.

Decreased levels of circulating cytokines VEGF, TNF-β and IL-15 indicate PD-L1 overexpression in tumours of primary breast cancer patients

Programmed death ligand 1 (PD-L1) overexpression has been associated with poor clinical outcomes in several human cancers whose increased malignant behaviour might be related to PD-L1 mediated systemic immunological tolerance. This study aims to verify if circulating cytokines may serve as a proxy for non-invasive identification of sensitive prognostic biomarkers reflecting tumour and its microenvironment. Immunohistochemistry was used to measure PD-L1 expression in tumour tissue sections of 148 chemonaïve breast cancer (BC) patients. The panel of 51 cytokines was analysed using multiplex bead arrays. High PD-L1 expression in tumours was associated with shorter progression-free survival (HR 3.25; 95% CI 1.39–7.61; P = 0.006) and low circulating levels of three multifunctional molecules; VEGF, TNF-β and IL-15 (P = 0.001). In multivariate analysis, patients with low VEGF had 4.6-fold increased risk of PD-L1 overexpression (P = 0.008), present in 76.5% of patients with all these three cytokines below the median (vs. 35.6% among the others; P = 0.002). The area under the curve value of 0.722 (95% CI 0.59–0.85; P = 0.004) shows that this combination of cytokines has a moderate ability to discriminate between PD-L1 high vs. PD-L1 low patients. Plasma cytokines, therefore, could serve as potential non-invasive biomarkers for the identification of high-risk BC cases.

Novel multifunctional nano-hybrid polyhedral oligomeric silsesquioxane-based molecules with high cell permeability: molecular design and application for diagnosis and treatment of tumors

Octathiol POSS was used to connect PEG-400, hexene, folic acid, fluorescein, and thioguanine using a simple and efficient photo-initiated one-pot method to prepare multifunctional molecules, which have targeted imaging and therapeutic functions.