Combination of amino acids reduces pigmentation in B16F0 melanoma cells

Amino acids, the building blocks of proteins, play significant roles in numerous physiological events in mammals. As the effects of amino acids on melanogenesis have yet to be demonstrated, the present study was conducted to identify whether amino acids, in particular alanine, glycine, isoleucine and leucine, influence melanogenesis in B16F0 melanoma cells. Glycine and L-isoleucine, but not D-isoleucine, reduced melanogenesis in a concentration-dependent manner without any morphological changes in B16F0 melanoma cells. L-Alanine and L-leucine, but not D-alanine and D-leucine, also reduced melanogenesis without any morphological changes in B16F0 melanoma cells. However these amino acids did not show a concentration-dependency. Combination of L-alanine and the other amino acids, particularly 4 amino acids combination, had an additive effect on the inhibition of melanogenesis compared with single treatment of L-alanine. None of the amino acids affected the activity of tyrosinase, a key enzyme in melanogenesis. These results suggest that L-alanine, glycine, L-isoleucine and L-leucine, but not the D-form amino acids, have a hypopigmenting effect in B16F0 melanoma cells, and that these effects are not due to the inhibition of tyrosinase activity. Combination of these 4 amino acids had the additive effect on hypopigmentation that was as similar as that of kojic acid.     

A tumor metastasis‐associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity

Although neoantigens are one of the most favorable targets in cancer immunotherapy, it is less versatile and costly to apply neoantigen‐derived cancer vaccines to patients due to individual variation. It is, therefore, important to find highly immunogenic antigens between tumor‐specific or associated antigens that are shared among patients. Considering the cancer immunoediting theory, immunogenic tumor cells cannot survive in the early phase of tumor progression including two processes: elimination and equilibrium. We hypothesized that highly immunogenic molecules are allowed to be expressed in tumor cells after an immune suppressive tumor microenvironment was established, if these molecules contribute to tumor survival. In the current study, we focused on TWIST1 as a candidate for highly immunogenic antigens because it is upregulated in tumor cells under hypoxia and promotes tumor metastasis, which is observed in the late phase of tumor progression. We demonstrated that TWIST1 had an immunogenic peptide sequence TWIST1_140–162, which effectively activated TWIST1‐specific CD4⁺ T‐cells. In a short‐term culture system, we detected more TWIST1‐specific responses in breast cancer patients compared with in healthy donors. Vaccination with the TWIST1 peptide also showed efficient expansion of TWIST1‐reactive HTLs in humanized mice. These findings indicate that TWIST1 is a highly immunogenic shared antigen and a favorable target for cancer immunotherapy.     

Femur fracture during abdominal breech delivery

BACKGROUND: While vaginal breech delivery, although rare, can cause femur fracture, abdominal breech delivery is not expected to cause it. CASE: A 2,490-g female infant was delivered at term by elective cesarean section for breech presentation. She sustained a fracture of the femur shaft. A simple splinting led to a complete healing of the fracture without sequelae. CONCLUSION: Although abdominal breech delivery reduces the risk of birth trauma, we must be aware that femur fracture can occur regardless of the mode of delivery.     

The Simultaneous Onset of Pancreatitis and Colitis as Immune-related Adverse Events in a Patient Receiving Nivolumab Treatment for Renal Cell Carcinoma

Immune checkpoint inhibitors (ICIs), which have anti-tumor effects, are currently approved for treatment of several kinds of advanced malignancies. However, with their increasing use, a variety of immune-related adverse events (irAEs) in administered patients have been reported. We herein report a rare case of the simultaneous onset of acute pancreatitis and colitis as irAEs during nivolumab treatment given to a patient with renal cell carcinoma, who then shown marked improvement with corticosteroid therapy.     

Dietary intake of seaweed and minerals and prevalence of allergic rhinitis in Japanese pregnant females: baseline data from the Osaka Maternal and Child Health Study

PURPOSE: It may be worthwhile to assess the possible protective effect of the traditional Japanese diet on allergic disorders. This cross-sectional study investigated the relationship between dietary intake of seaweed, vegetables, fruit, antioxidants, fiber, and minerals and the prevalence of allergic rhinitis. METHODS: Study subjects were 1002 Japanese pregnant women. Allergic rhinitis (including cedar pollinosis) was defined as present if subjects had received drug treatment at some point during the previous 12 months. Information on dietary factors was collected by using a self-administered diet history questionnaire. RESULTS: Seaweed intake was associated independently with a decreased prevalence of allergic rhinitis. Significant inverse dose-response relationships were found between calcium and phosphorus intake and allergic rhinitis prevalence. There also was a tendency for an inverse association between magnesium consumption and allergic rhinitis. Additional adjustment for calcium or magnesium intake apparently did not influence the inverse association with seaweed consumption. Consumption of vegetables, fruit, vitamins C and E, fiber, and zinc showed no association with allergic rhinitis, whereas a significant positive relationship was observed between beta-carotene intake and allergic rhinitis. CONCLUSIONS: High dietary intake of seaweed, calcium, magnesium, and phosphorus may be associated with a decreased prevalence of allergic rhinitis.     

Reference Values for Cranial Morphology Based on Three-dimensional Scan Analysis in 1-month-old Healthy Infants in Japan

Currently, molded helmet therapy is used to treat infants with deformational plagiocephaly. However, the indices of normal cranial shape remain unclear, and thus, the prevalence of deformational plagiocephaly is unknown, particularly in Japan. We investigated the reference values for cranial morphological characteristics in 1-month-old Japanese infants using a three-dimensional scanner, to determine the prevalence of deformational plagiocephaly. One hundred fifty-three healthy infants who visited three hospitals (from April 2020 to March 2021) were enrolled. Cranial shape was measured using a three-dimensional scanner and was analyzed using image analysis software. Outcome measures were cranial volume, length, width, length-width ratio, circumference, asymmetry, and vault asymmetry index; cephalic index; and anterior, posterior, and overall symmetry ratios. The cranial vault asymmetry index >3.5% or ≥10% were diagnosed as deformational or severe deformational plagiocephaly, respectively. The mean age at measurement was 35.7 days. The mean cranial volume was 559 mL; cranial length, 129 mm; cranial width, 110 mm; length-width ratio, 118%; cephalic index, 85.2%; cranial circumference, 377 mm, cranial asymmetry, 6.4 mm; cranial vault asymmetry index, 5.0%; and anterior, posterior, and overall asymmetry ratios, 93.1%, 91.3%, and 96.4%, respectively. The prevalence of deformational and severe deformational plagiocephaly was 64.7% and 6.6%, respectively. Sex-based differences were observed for cranial volume and width. The results obtained in this study can be considered standard values that can facilitate the differentiation of abnormal infant cranial morphological characteristics for Japanese medical practitioners.     

Universal Screening for Familial Hypercholesterolemia in Children in Kagawa,Japan

Aim: Familial hypercholesterolemia (FH) is an underdiagnosed autosomal dominant genetic disorder characterized by high levels of plasma low-density lipoprotein cholesterol (LDL-C) from birth. This study aimed to assess the genetic identification of FH in children with high LDL-C levels who are identified in a universal pediatric FH screening in Kagawa, Japan. Method: In 2018 and 2019, 15,665 children aged 9 or 10 years underwent the universal lipid screening as part of the annual health checkups for the prevention of lifestyle-related diseases in the Kagawa prefecture. After excluding secondary hyper-LDL cholesterolemia at the local medical institutions, 67 children with LDL-C levels of ≥ 140 mg/dL underwent genetic testing to detect FH causative mutations at four designated hospitals. Results: The LDL-C levels of 140 and 180 mg/dL in 15,665 children corresponded to the 96.3 and 99.7 percentile values, respectively. Among 67 children who underwent genetic testing, 41 had FH causative mutations (36 in the LDL-receptor, 4 in proprotein convertase subtilisin/kexin type 9, and 1 in apolipoprotein B). The area under the curve of receiver operating characteristic curve predicting the presence of FH causative mutation by LDL-C level was 0.705, and FH causative mutations were found in all children with LDL-C levels of ≥ 250 mg/dL. Conclusion: FH causative mutations were confirmed in almost 60% of the referred children, who were identified through the combination of the lipid universal screening as a part of the health checkup system and the exclusion of secondary hyper-LDL cholesterolemia at the local medical institutions.     

Severe Post-COVID-19 Organizing Pneumonia during Cancer Immunochemotherapy

A 44-year-old man developed coronavirus disease 2019 (COVID-19) pneumonia during immunochemotherapy consisting of carboplatin, paclitaxel, and pembrolizumab for non-small cell lung cancer. Low-grade fever, followed by mild hypoxemia, and febrile neutropenia, were observed, and granulocyte colony-stimulating factor (G-CSF) was administered until the recovery of neutropenia, when he developed a high fever, severe hypoxemia, and hypotension accompanied by consolidation in the bilateral lungs. His conditions promptly improved after treatment including hydrocortisone and the primary and metastatic tumors remained regressed for 10 months without further treatment. Post-COVID-19 organizing pneumonia during cancer immunochemotherapy can be aggravated by immune-checkpoint inhibitors and G-CSF.