Molecular Characterization of Inflammatory Tumors Facilitates Initiation of Effective Therapy

Inflammatory myofibroblastic tumor (IMT) is a rare, mesenchymal tumor that has an increased incidence in childhood. Tumors are usually isolated to the chest, abdomen, and retroperitoneum, but metastatic presentations can be seen. Presenting symptoms are nonspecific and include fever, weight loss, pain, shortness of breath, and cough. Approximately 85% of IMTs harbor actionable kinase fusions. The diagnosis can be delayed because of overlapping features with inflammatory disorders, such as elevated inflammatory markers, increased immunoglobin G levels, fever, weight loss, and morphologic similarity with nonmalignant conditions. We present a girl aged 11 years with a TFG-ROS1 fusion–positive tumor of the lung that was initially diagnosed as an immunoglobin G4–related inflammatory pseudotumor. She underwent complete left-sided pneumonectomy and later recurred with widely metastatic disease. We then report the case of a boy aged 9 years with widely metastatic TFG-ROS1 fusion–positive IMT with rapid molecular diagnosis. In both children, there was an excellent response to oral targeted therapy. These cases reveal that rapid molecular testing of inflammatory tumors is not only important for diagnosis but also reveals therapeutic opportunities. Targeted inhibitors produce significant radiologic responses, enabling potentially curative treatment approaches for metastatic ROS1 fusion IMT with previously limited treatment options. Primary care pediatricians and pediatric subspecialists have a crucial role in the early consultation of a pediatric oncology center experienced in molecular diagnostics to facilitate a comprehensive evaluation for children with inflammatory tumors.

Immunity Improvement and Gut Microbiota Remodeling of Mice by Wheat Germ Globulin

The wheat germ protein (WG) and it’s proteolytic peptide have a variety of biological activities. Our previous work showed that WG could improve immunity of the immunosuppressive mice established by cyclophosphamide. However, in the healthy condition and normal diet, as a supplementary food, the effects of immunity improvement and gut microbiota remodeling by the wheat germ globulin has not been studied yet. Here, we reported that WG could improve the immunity and remodel the gut microbiota of the mice, as a safe functional supplementary food for the first time. The increase of interleukin-6 (IL-6) and the decrease of tumor necrosis factor α (TNF-α) and interleukin-10 (IL-10) indicated that WG could enhance the levels of activated T cells and monocytes and anti-inflammatory ability, meanwhile, the significant increase of immunoglobin G (lgG) and the notable decrease of the immunoglobin M (lgM) and immunoglobin A (lgA) illustrated that WG could improve immunity by promoting the differentiation and maturation process of B cells, compared with the NC group. 16S rRNA sequencing showed WG could remodel the gut microbiota. At the phylum level, the Bacteroidetes were reduced and Firmicutes were increased in WG group, compared with NC group. At the genus level, the SCFA producing genera of unclassified_f_Lachnospiraceae, Blautia and especially the Roseburia (increased more than threefold) increased notably. Further, the level changes of cytokines and immunoglobulins were associated with the gut microbiota. This work showed that WG could improve immunity and has potential application value as an immune-enhancing functional food.

Immunological Approaches and Different Strategies for Vaccine Development against SARS-COV-2

Globally, SARS-CoV-2 outbreak is considered as pandemic viral infection by the World Health Organization (WHO). In the immunological response aspect, a very limited understanding has been progressed, mainly innate and adaptive immunity responses toward the virus. SARS-COV-2 causes severe respiratory disease and sometimes ended with the death. The body of the patients has ability to develop the immunity to cure the patient and more importantly both humoral and cellular immunity have studied against SARS-COV-2. There are different immune responses against the viral infection as it has seen in other previous diseases such as SARS-COV and MESR. On the base on immune response detected in recovered patients, scientists have started to develop the vaccines. Moreover, there are different strategies that used by researchers and pharmacological companies to develop vaccines including attenuated or killed viruses, RNA of a spike protein, and vector expressing a particular protein of the virus. The common antibodies have detected to work against SARS-COV-2 in sera of infected or recovered patients are immunoglobin G ( IgG) and immunoglobin M (IgM). The sera of patients recovered from COVID-19, after tittering of immunoglobulins (IgG titer) can be used for either treatment of disease or prophylaxis of infection by SARS-COV-2. This study gives an update on the current immunological approaches and vaccination strategies for the emerging SARS-COV-2, and discusses the challenges and hurdles to overcome for developing efficacious vaccines against this dangerous pathogen.

Comprehensive exploratory autoantibody profiling in patients with early rheumatoid arthritis treated with methotrexate or tocilizumab

Background We sought to identify immunoglobin G autoantibodies predictive of early treatment response to methotrexate, the recommended first-line therapy for patients with newly diagnosed rheumatoid arthritis, and to the interleukin-6 receptor inhibitor biologic tocilizumab, initiated as the first disease-modifying anti-rheumatic drug. Materials and methods In baseline sera of a subset of patients with newly diagnosed rheumatoid arthritis in the U-Act-Early study, selected based on specific responder/non-responder criteria using the Disease Activity Score assessing 28 joints (DAS28) within the first 20 weeks, we measured immunoglobin G antibody reactivity against 463 protein antigens and performed supervised cluster analysis to identify predictive autoantibodies for treatment response. The analysis subset comprised 56 patients in the methotrexate arm (22 responders, 34 non-responders) and 50 patients in the tocilizumab arm (34 responders, 16 non-responders). For comparison, these analyses were also performed in 50 age- and gender-matched healthy controls. Results Increased reactivity in responders versus non-responders was found in the methotrexate arm against two antigens—DOT1-like histone lysine methyltransferase (p = 0.009) and tropomyosin (p = 0.003)—and in the tocilizumab arm against one antigen—neuro-oncological ventral antigen 2 (p = 0.039). Decreased reactivity was detected against two antigens in the methotrexate arm—G1 to S phase transition 2 (p = 0.023) and the zinc finger protein ZPR1 (p = 0.021). Reactivity against the identified antigens was not statistically significant in either treatment arm for patients with rheumatoid factor–positive versus–negative or anti-cyclic citrullinated test–positive versus test–negative rheumatoid arthritis (p ≥ 0.06). Conclusions Comprehensive profiling of baseline sera revealed several novel immunoglobin G autoantibodies associated with early treatment response to methotrexate and to tocilizumab in disease-modifying anti-rheumatic drug-naive patients with rheumatoid arthritis. These findings could eventually yield clinically relevant predictive markers, if corroborated in different patient cohorts, and may facilitate future benefit in personalised healthcare.

Supplementation of Holstein dairy calves fed two levels of crude protein with methionine and lysine

This study aimed to investigate various levels of crude protein (CP) in starter diets and their supplementation with amino acids (AAs) on efficiency, health, and serum metabolites of dairy calves. Ninety-six newborn Holstein calves were allocated to eight treatments, namely T1) 18% CP unsupplemented starter, T2) T1 supplemented with additional 20% methionine, T3) T1 with additional 20% lysine and 20% methionine, T4) T1 with additional 20% lysine, T5) 22% CP unsupplemented starter, T6) T5 supplemented with additional 20% methionine, T7) T5 supplemented with additional 20% lysine and 20% methionine, and T8) T5 supplemented with additional 20% lysine. Consumption of the starter was not influenced by the level of CP. Calves that received the unsupplemented 22% CP starter had higher average daily gain (ADG) and final weight. But no significant differences among diets were found in feed efficiency. Skeletal growth did not exhibit a clear trend. Calves that received T3 had fewer bouts of diarrhea and reduced body temperature. However, there were no significant dietary effects on immunoglobin G (IgG) or total protein concentration in blood. T1–T3 decreased serum urea concentration. Thus, use of T3 resulted in an improved amino acid balance, and was less expensive than the 22% CP starter.Keywords: amino acid, feed intake, immunity, pre-ruminant calf

Evaluation of Immunoglobulin G Absorption from Goat Colostrum by Newborn Piglets

The aim of this study was to evaluate whether piglets absorb immunoglobin G (IgG) from goat colostrum and the potential effects of its ingestion on suckling piglets. Thirty-eight piglets with body weights ranging from 1000 to 1700 g were assigned to one of the three experimental treatments: Control group (C), where piglets were allowed to suckle normally, and porcine and goat groups. The piglets from the last two groups were removed from the sows after birth and received an oral 20 mL dose every 3 h of porcine (PC) or goat colostrum (GC), respectively, during first 12 h of life. Then, they were returned to newly farrowing sows to continue suckling until 20 d. The apparent efficiency of absorption (AEA) of IgG at 12 h was calculated as total serum IgG divided by ingested IgG. No diarrhea or symptoms of intolerance were observed at any time. On day 20, body weight and the number of dead piglets were similar in all three treatments (p > 0.05). At 12 h, the concentration of goat IgG in the serum of piglets fed GC was 8.11 mg/mL. AEA was 20.9% for goat IgG and 26.3% for porcine IgG (p > 0.05). Therefore, goat colostrum seems a promising alternative to study new feed supplements or artificial rearing of newborn piglets.