Pluripotent stem cells (PSCs), which include embryonic stem cells and induced pluripotent stem cells, have the potential for unlimited self-renewal and proliferation and the ability to differentiate into all three embryonic germ layers. Human PSCs (hPSCs) are used in drug discovery screening, disease models, and regenerative medicine. These cells maintain a transcriptional regulatory network based on a set of unique transcription factors to maintain their stem cell properties. Downstream of such transcriptional regulatory networks, various stem cell-specific metabolic programs are used to produce energy and metabolites as necessary. hPSCs and differentiated cells utilize different metabolic programs for self-renewal ability and maintenance of quiescence. Understanding the different metabolic features of hPSCs and differentiated cells can contribute to the development of technologies that are useful for regenerative medicine, such as the purification of differentiated cells. This review describes the unique metabolic programs active in hPSCs and their differences from somatic cells, with a focus on cardiomyocytes.

The early diagnosis of central nervous system infections is of great importance to minimize morbidity and mortality. Neurogranin is a postsynaptic neural protein, and when the blood–brain barrier is damaged, neurogranin levels increase in both the cerebrospinal fluid and serum. The aim of this study was to evaluate the level of serum neurogranin and to investigate its utility in the diagnosis of central nervous system infections. This study was conducted as a prospective case–control study of patients diagnosed with meningitis. The study initially included 55 patients, and 15 patients with proven central nervous system infection were ultimately included in the patient group. The results in the patient group were compared with those of the control group of 15 healthy subjects. The 15 patients comprised 4 women and 11 men with a mean cerebrospinal fluid neurogranin level of 432.4 ± 123.5 ng/ml. Correlation analysis revealed a moderate positive correlation between cerebrospinal fluid neurogranin levels and serum neurogranin levels. The mean serum neurogranin level was 198.6 ± 51.7 ng/ml in the control group but was significantly higher at 429.2 ± 104.3 ng/ml in the patient group. In conclusion, it may be useful to measure blood neurogranin levels in patients suspected of having central nervous system infections, especially in those for whom computed tomography, magnetic resonance imaging, or lumbar puncture cannot be performed.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food allergy characterized by repetitive vomiting within 1–4 h and/or diarrhea within 24 h after ingesting the causative food. We herein report a rare Japanese case of rice-induced FPIES. A six-month-old, female, Japanese patient presented to the emergency room (ER) with the complaint of vomiting after feeding. Postprandial vomiting had occurred occasionally since she started ingesting solid food at the age of 5 months. Rice-induced FPIES was suspected only after the fourth ER visit based on the characteristic history of recurrent vomiting occurring 1–2 h after ingesting food containing rice. Allergen-specific IgE testing and a skin prick test with an allergen scratch extract were both negative for rice. During an oral food challenge test (OFC), vomiting was observed after the patient ingested 2 g of rice porridge. Based on the OFC results and the entire clinical course, FPIES due to rice was diagnosed. A lymphocyte stimulation test with rice revealed a significantly elevated stimulation index. Rice-induced FPIES is rarely reported among Japanese infants despite rice being a staple in the Japanese diet. The prevalence of rice-induced FPIES differs greatly among populations, suggesting a multifactorial cause associated with its development. Delays in diagnosis are common in FPIES, and our case demonstrates the importance of obtaining a dietary history of food ingested prior to symptom onset in cases of infantile repetitive vomiting.

Surgical treatments offer the chance for cure in primary or metastatic liver cancers. However, many patients experience disease progression after surgical interventions, or cannot undergo surgery as they present with unresectable disease at diagnosis. In such cases, available treatment options (local and systemic) have been limited in efficacy, which led to dismal survival rates in advanced hepatocellular carcinoma (HCC), intrahepatic colangiocarcinoma (ICC) or metastatic pancreatic ductal adenocarcinoma (PDAC). More recent developments in oncology have offered renewed hope for advanced liver cancer patients. Hypofractionated radiation has shown feasibility and promise in unresectable setting, and is now being tested in a randomized phase III trial in HCC (clinicaltrials.gov identifier NCT03186898). Antiangiogenic agents have strongly impacted the management of advanced HCC, with multiple drug options in first line setting (sorafenib, lenvatinib) and second line setting (regorafenib, cabozantinib, ramucirumab). Chemotherapy based regimens are standard of care in ICC and PDAC. Immunotherapy with anti-PD-1/PD-L1 or anti-CTLA4 antibodies has shown real potential to transform advanced HCC therapy, both in first line and second line settings. Finally, combinations of these new strategies are very attractive approaches, as they promise durable and profound responses in advanced HCC. But in order to achieve this promise more broadly, these concepts require greater understanding based on mechanistic preclinical studies and validation in correlative studies in clinical trials as a basis to establish optimal combinatorial strategies. The insights gained from this “bench to the bedside and back” approach raise the hope for a more efficient development of targeted agents in combination, and in earlier stages of the disease, with the goal of increasing survival in patients afflicted with this aggressive and deadly diseases.

(Presented at the 2001st Meeting, July 4, 2022)