Pre-clinical validation of an RNA-based precision oncology platform for patient-therapy alignment in a diverse set of human malignancies resistant to standard treatments

Predicting tumor sensitivity to antineoplastics remains an elusive challenge, with no methods demonstrating predictive power. Joint analysis of tumors-from patients with distinct malignancies who had progressed on multiple lines of therapy-and drug perturbation transcriptional profiles predicted sensitivity to 28 of 350 drugs, 26 of which (93%) were confirmed in low-passage, patient-derived xenograft (PDX) models. Drugs were prioritized based on their ability to either invert the activity of individual Master Regulator proteins, with available high-affinity inhibitors, or of the modules they comprise (Tumor-Checkpoints), based on de novo mechanism of action analysis. Of 138 PDX mice enrolled in 16 single and 18 multi-protein treatment arms, a disease control rate (DCR) of 68% and 91%, and an objective response rate (ORR) of 12% and 17%, were achieved respectively, compared to 6% and 0% in the negative controls arm, with multi-protein drugs achieving significantly more durable responses. Thus, these approaches may effectively complement and expand current precision oncology approaches, as also illustrated by a case study.

Leptin Reduces Plin5 m6A Methylation through FTO to Regulate Lipolysis in Piglets

Perilipin5 (Plin5) is a scaffold protein that plays an important role in lipid droplets (LD) formation, but the regulatory effect of leptin on it is unclear. Our study aimed to explore the underlying mechanisms by which leptin reduces the N6-methyladenosine (m6A) methylation of Plin5 through fat mass and obesity associated genes (FTO) and regulates the lipolysis. To this end, 24 Landrace male piglets (7.73 ± 0.38 kg) were randomly sorted into two groups, either a control group (Control, n = 12) or a 1 mg/kg leptin recombinant protein treatment group (Leptin, n = 12). After 4 weeks of treatment, the results showed that leptin treatment group had lower body weight, body fat percentage and blood lipid levels, but the levels of Plin5 mRNA and protein increased significantly in adipose tissue (p < 0.05). Leptin promotes the up-regulation of FTO expression level in vitro, which in turn leads to the decrease of Plin5 M6A methylation (p < 0.05). In in vitro porcine adipocytes, overexpression of FTO aggravated the decrease of M6A methylation and increased the expression of Plin5 protein, while the interference fragment of FTO reversed the decrease of m6A methylation (p < 0.05). Finally, the overexpression in vitro of Plin5 significantly reduces the size of LD, promotes the metabolism of triglycerides and the operation of the mitochondrial respiratory chain, and increases thermogenesis. This study clarified that leptin can regulate Plin5 M6A methylation by promoting FTO to affect the lipid metabolism and energy consumption, providing a theoretical basis for treating diseases related to obesity.

Cesium based phasing of macromolecules: a general easy to use approach for solving the phase problem

Over the last decades the phase problem in macromolecular x-ray crystallography has become more controllable as methods and approaches have diversified and improved. However, solving the phase problem is still one of the biggest obstacles on the way of successfully determining a crystal structure. To overcome this caveat, we have utilized the anomalous scattering properties of the heavy alkali metal cesium. We investigated the introduction of cesium in form of cesium chloride during the three major steps of protein treatment in crystallography: purification, crystallization, and cryo-protection. We derived a step-wise procedure encompassing a “quick-soak”-only approach and a combined approach of CsCl supplement during purification and cryo-protection. This procedure was successfully applied on two different proteins: (i) Lysozyme and (ii) as a proof of principle, a construct consisting of the PH domain of the TFIIH subunit p62 from Chaetomium thermophilum for de novo structure determination. Usage of CsCl thus provides a versatile, general, easy to use, and low cost phasing strategy.

Prof. Zlatogorov, etc.-Assoc. Lavrinovich. Vaccine therapy and protein therapy. Ed. 2nd. Kharkov. 1923.

Already the first edition of this book, published under the title "Vaccine Therapy in Medicine" more than 8 years ago as an appendix to "Doctor. Gazeta , aroused interest not only among practitioners, but also among theoretical bacteriologists. The burning question of vaccine therapy in Zap. Europe and America have received a lot of attention before, but recently, due to the fact that protein treatment began to spread widely abroad, many issues of vaccine therapy have received completely different coverage.

KAJIAN PEMBERIAN PAKAN BERBAHAN BAKU LOKAL DENGAN KANDUNGAN PROTEIN YANG BERBEDA TERHADAP PERTUMBUHAN IKAN GURAME (Osphronemus goramy Lac.)

Gourami fish (Osphronemus goramy Lac.) is a freshwater fish commodity that has high economic value because its very popular with all people. But the feed commonly used by gourami fish cultivators is factory-made feed, which is a commercial feed that usually costs quite a lot of money due to the material for making commercial feed, some of which still import from abroad. Therefore it is necessary to find a solution to reduce the cost of cultivation production by replacing commercial feed with homemade feed made from local raw materials. The purpose of this study was to examine the use of local raw materials formulated to make feed suitable for the growth of gourami fish (Osphronemus goramy Lac.) And to analyze the production costs of goramy feed made from local raw materials. This study consisted of 4 treatments and 3 replications using the completely randomized design (CRD) method. The treatments consisted of treatment A (30% protein), treatment B (33% protein), treatment C (36% protein), and treatment D (commercial). The results of this study indicate that the treatment of feed A, B, and C produced the same growth as commercial feed, and treatment of feed A resulted in the lowest feed production costs compared to other treatments. Key word: feed, growth, local raw materials, Oshphronemus goramy

Study of Feeding with Local Raw Materials with Different Protein for Growth Sultana Tilapia (Oreochromis niloticus)

Tilapia (Oreochromis niloticus) strain of Sultana (superior selection of salabintana) is a new variety developed by the Center for Freshwater Resources Development (BBPABT) Sukabumi, West Java. Sultana tilapia is the result of crossing 10 superior varieties such as gift tilapia, jica, white, and other superior tilapia. Many factors cause the high price of feed, one of which is dependent on imported raw materials for feed manufacture. This study aims to assess the effectiveness of the use of local raw materials with different protein content in feed for the growth of tilapia and reduce production costs by using local raw materials as feed ingredients. This research was conducted from March 21 to June 19, 2020 at the Integrated Field Laboratory of the Faculty of Agriculture, University of Lampung. The design used in this study was a completely randomized design (CRD) consisting of four treatments with three replications. The treatments given included 30% protein treatment (A), 33% protein treatment (B), 36% treatment (C), and commercial feed control (D) for 60 days of maintenance. The data obtained were analyzed by using the ANOVA test and followed by the Duncan test. The results obtained in this study are that treatment B has the best FCR value and is significantly different compared to other treatments so as to produce the best growth. Besides that, treatment A and C also had a significantly different FCR value compared to the control

First Insights on Early Host Plants and Dispersal Behavior of Halyomorpha halys (Hemiptera: Pentatomidae) from Overwintering to Crop Colonization

Following its first detection in North Italy in 2012, H. halys has become a serious threat in many crops, including hazelnut. The present study aimed at investigating dispersal capacity and behavior in relation to host plants of overwintered adults of H. halys before the colonization of hazelnut crop. Research was carried out in four polyculture areas (from 14 to 50 ha) in north-western Italy in 2018, by using (i) pheromone-baited traps, (ii) visual inspection and beating sheet sampling, and (iii) immunomarking-capture technique. The relative abundance of H. halys was similar between and within the study areas, and the early attractiveness of lures to adults after overwintering was confirmed; the host plants near a pheromone trap (less than 5 m) hosted higher numbers of H. halys than the same plant species far away. Hybrid plane, European spindletree, walnut, oak, and European elder were the first plants on which adult bugs were observed to feed. By immunomarking-capture technique, H. halys showed both short- and long-range dispersal from overwintering sites and/or early host plants to wild and crop plants. Marked adults were found in all zones of each area, irrespective of the distance from the protein treatment. Therefore, H. halys movement patterns depend on the ecosystem features, and plant host distribution and availability. This knowledge together with the interaction between pheromone and early host plants might contribute to the management of post-overwintering adults.

UJI KANDUNGAN KIMIA DAN CEMARAN LOGAM KERANG KIMA (Tridacna sp.) KERING YANG DIPERDAGANGKAN DI KABUPATEN KONAWE UTARA SULAWESI TENGGARA

The Test of Chemical Content and Metal Contamination of Dry Clam (Tridacna sp.) Traded in North Konawe Regency Southeast SulawesiABSTRACT The aim of this study was to determine the characteristics of chemical composition (water, ash, protein, fat, and carbohydrate) and Metal Contamination of Dry Clam. The analysis of the data used in this study is to use descriptive analysis. The results of the analysis of the chemical content of the highest treatment of water content are found in P2 with a value of 25.84%. The highest ash content was found in the P2 treatment with a value of 13.84%. The highest level of protein treatment was at P3 with a value of 14.28%. The highest treatment fat content was in P3 with a value of 2.43% and the highest treatment carbohydrate content was in P2 with a value of 1.88% and. The results of the analysis of heavy metals were the highest Cd levels were at P3 with a value of 0.074 mg / Kg and the lowest was at P1 0.057 mg / Kg and the highest Pb metal at P3 0.026 mg / Kg the lowest was at P1 0.016 mg / Kg.Keywords: Clam (Tridacna sp.), Chemical content, Heavy metals ABSTRAKTujuan penelitian ini adalah untuk mengetahui karakteristik komposisi kimiawi (air, abu, protein, lemak, dan karbohidrat) dan cemaran Logam berat pada Kerang kima Kering. Analisis data yang digunakan dalam penelitian ini adalah menggunakan analisis deskriptif. Hasil analisis kadar kimia perlakuan kadar air tertinggi terdapat pada P2 dengan nilai 25,84%. Kadar abu tertinggi terdapat pada perlakuan P2 dengan nilai 13,84%. Perlakuan protein tertinggi terdapat pada P3 dengan nilai 14,28%. Kadar lemak perlakuan tertinggi terdapat pada P3 dengan nilai 2,43% dan kadar karbohidrat perlakuan tertinggi terdapat pada P2 dengan nilai 1,88% dan. Hasil analisis logam berat kadar Cd tertinggi pada P3 dengan nilai 0,074 mg / Kg dan terendah pada P1 0,057 mg / Kg dan logam Pb tertinggi pada P3 0,026 mg / Kg, terendah pada P1. 0,016 mg / Kg.Kata kunci Kerang kima (Tridacna sp.) kering, Kandungan Kimia, Logam berat

Helicobacter pylori infection induces STAT3 phosphorylation on Ser727 and autophagy in human gastric epithelial cells and mouse stomach

Helicobacter pylori (H. pylori) infection is considered as one of the principal risk factors of gastric cancer. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) plays an important role in inflammation-associated gastric carcinogenesis. In the canonical STAT3 pathway, phosphorylation of STAT3 on Tyr705 is a major event of STAT3 activation. However, recent studies have demonstrated that STAT3 phosphorylated on Ser727 has an independent function in mitochondria. In the present study, we found that human gastric epithelial AGS cells infected with H. pylori resulted in localization of STAT3 phosphorylated on Ser727 (P-STAT3Ser727), predominantly in the mitochondria. Notably, H. pylori-infected AGS cells exhibited the loss of mitochondrial integrity and increased expression of the microtubule-associated protein light chain 3 (LC3), the autophagosomal membrane-associated protein. Treatment of AGS cells with a mitophagy inducer, carbonyl cyanide 3-chlorophenylhydrazone (CCCP), resulted in accumulation of P-STAT3Ser727 in mitochondria. In addition, the elevated expression and mitochondrial localization of LC3 induced by H. pylori infection were attenuated in AGS cells harboring STAT3 mutation defective in Ser727 phosphorylation (S727A). We also observed that both P-STAT3Ser727 expression and LC3 accumulation were increased in the mitochondria of H. pylori-inoculated mouse stomach.

The Caprine Casein-Alpha-S2 Protein Modulates the Molecular Mechanism 2 of Insulin Signal Transduction in Type2 Diabetes Rat

This study purpose was to investigate the association of casein-alpha-S2 protein of Caprine milk and molecular mechanismofinsulin signaltransduction in type2 diabetes mellitus (T2DM). The Caprine milk CSN1S2 protein treatment of 0, 375, 750, and 1500mg/kg BW were conducted to the control and T2DM rats. We observed several physiological parameters of all rats. The levels of insulin and TNF-α in the plasma were measured using ELISA.The expressions of proteins and mRNA levels of diabetes-related genes in the pancreas tissues were analyzed using Western Blotting and Real-Time PCR, respectively. Our study found that diabetic rats had lower body weight, food intake, and fecal weight compared with control rats. The Caprine milk CSN1S2 protein consumption affected the body weight of diabetic rats to increase, especially at the dose of 750mg/kg BW.Interestingly, the genes associated with insulin signaling were improved by the CSN1S2 protein treatment in diabetic rats, although their blood glucose and cholesterol level were not affected. The diabetic rats showed an elevated insulin level and GLUT4 protein expression after treatment. We also reported that the CSN1S2-treated diabetic rats had a gradually reduced expression of TNF-α and VCAM-1 in dose-dependent. Moreover, the 750mg/kg BW of CSN1S2 treatment enhanced the mRNA expressions of INS-receptor, GLUT4, IGF-1, CAMKK, and CAMKIV in diabetic rats. The ability of Caprine milk CSN1S2 protein to regulate the molecular mechanisms in the diabetes-signaling pathway indicated its potential therapeutic effects on diabetes management.