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Colorectal cancer (CRC) remains a significant global health challenge, with barriers to effective prevention and treatment including tumor recurrence, chemoresistance, and limited overall survival rates. Anthocyanins, known for their strong anti-cancer properties, have shown promise in preventing and suppressing various cancers, including CRC. However, natural sources of anthocyanins often fail to provide sufficient quantities needed for therapeutic effects. Bioengineered crops, particularly anthocyanin-enriched tomatoes, offer a viable solution to enhance anthocyanin content. Given its large-scale production and consumption, tomatoes present an ideal target for bioengineering efforts aimed at increasing dietary anthocyanin intake. This review provides an overview of anthocyanins and their health benefits, elucidating the mechanisms by which anthocyanins modulate the transcription factors involved in CRC development. It also examines case studies demonstrating the successful bioengineering of tomatoes to boost anthocyanin levels. Furthermore, the review discusses the effects of anthocyanin extracts from bioengineered tomatoes on CRC prevention, highlighting their role in altering metabolic pathways and reducing tumor-related inflammation. Finally, this review addresses the challenges associated with bioengineering tomatoes and proposes future research directions to optimize anthocyanin enrichment in tomatoes.

Abstract The oral cavity is an entrance for respiratory viruses, such as influenza. Recently, saliva has been shown to exert both antimicrobial and antiviral activities. Thus, saliva may be a biological factor that contributes to the prevention of influenza infection. However, the actual salivary anti-influenza A virus (IAV) activity in individuals and its determinant factors are unknown. By assessing individual variations in salivary anti-IAV activity in 92 people using an established new high-throughput system in this study, we found that the anti-IAV activity varied widely between individuals and showed a significant positive correlation with protein-bound sialic acid (BSA) level (ρ = 0.473; p

Mild cognitive impairment (MCI) is a high-risk condition for conversion to Alzheimer's disease (AD) dementia. However, individuals with MCI show heterogeneous patterns of pathology and conversion to AD dementia. Thus, detailed subtyping of MCI subjects and accurate prediction of the patients in whom MCI will convert to AD dementia is critical for identifying at-risk populations and the underlying biological features. To this end, we developed a model that simultaneously subtypes MCI subjects and predicts conversion to AD and performed an analysis of the underlying biological characteristics of each subtype. In particular, a heterogeneous mixture learning (HML) method was used to build a decision tree-based model based on multimodal data, including cerebrospinal fluid (CSF) biomarker data, structural magnetic resonance imaging (MRI) data, APOE genotype data, and age at examination. The HML model showed an average F1 score of 0.721, which was comparable to the random forest method and had significantly more predictive accuracy than the CART method. The HML-generated decision tree was also used to classify-five subtypes of MCI. Each MCI subtype was characterized in terms of the degree of abnormality in CSF biomarkers, brain atrophy, and cognitive decline. The five subtypes of MCI were further categorized into three groups: one subtype with low conversion rates (similar to cognitively normal subjects); three subtypes with moderate conversion rates; and one subtype with high conversion rates (similar to AD dementia patients). The subtypes with moderate conversion rates were subsequently separated into a group with CSF biomarker abnormalities and a group with brain atrophy. The subtypes identified in this study exhibited varying MCI-to-AD conversion rates and differing biological profiles.

The LAMA5 gene encodes laminin α5, an indispensable component of glomerular basement membrane and other types of basement membrane. A homozygous pathological variant in LAMA5 is known to cause a systemic developmental syndrome including glomerulopathy. However, the roles of heterozygous LAMA5 gene variants in human renal and systemic diseases have remained unclear. We performed whole-exome sequencing analyses of a family with slowly progressive nephropathy associated with hereditary focal segmental glomerulosclerosis, and we identified what we believe to be a novel probable pathogenic variant of LAMA5, NP_005551.3:p.Val3687Met. In vitro analyses revealed cell type–dependent changes in secretion of variant laminin α5 laminin globular 4-5 (LG4-5) domain. Heterozygous and homozygous knockin mice with a corresponding variant of human LAMA5, p.Val3687Met, developed focal segmental glomerulosclerosis–like pathology with reduced laminin α5 and increased glomerular vinculin levels, which suggested that impaired cell adhesion may underlie this glomerulopathy. We also identified pulmonary defects such as bronchial deformity and alveolar dilation. Reexaminations of the family revealed phenotypes compatible with reduced laminin α5 and increased vinculin levels in affected tissues. Thus, the heterozygous p.Val3687Met variant may cause a new syndromic nephropathy with focal segmental glomerulosclerosis through possibly defective secretion of laminin α5. Enhanced vinculin may be a useful disease marker.

While nearly one in nine people in the world deals with hunger, one in eight has obesity, and all face the threat of climate change. The production of rice, an important cereal crop and staple food for most of the world’s population, faces challenges due to climate change, the increasing global population, and the simultaneous prevalence of hunger and obesity worldwide. These issues could be addressed at least in part by genetically modified rice. Genetic engineering has greatly developed over the century. Genetically modified rice has been approved by the ISAAA’s GM approval database as safe for human consumption. The aim behind the development of this rice is to improve the crop yield, nutritional value, and food safety of rice grains. This review article provides a summary of the research data on genetically modified rice and its potential role in improving the double burden of malnutrition, primarily through increasing nutritional quality as well as grain size and yield. It also reviews the potential health benefits of certain bioactive components generated in genetically modified rice. Furthermore, this article discusses potential solutions to these challenges, including the use of genetically modified crops and the identification of quantitative trait loci involved in grain weight and nutritional quality. Specifically, a quantitative trait locus called grain weight on chromosome 6 has been identified, which was amplified by the Kasa allele, resulting in a substantial increase in grain weight and brown grain. An overexpressing a specific gene in rice, Oryza sativa plasma membrane H+-ATPase1, was observed to improve the absorption and assimilation of ammonium in the roots, as well as enhance stomatal opening and photosynthesis rate in the leaves under light exposure. Cloning research has also enabled the identification of several underlying quantitative trait loci involved in grain weight and nutritional quality. Finally, this article discusses the increasing threats of climate change such as methane–nitrous oxide emissions and global warming, and how they may be significantly improved by genetically modified rice through modifying a water-management technique. Taken together, this comprehensive review will be of particular importance to the field of bioactive components of cereal grains and food industries trying to produce high-quality functional cereal foods through genetic engineering.

Hepatitis B: Gene copy numbers associated with risk of infection The risk of contracting the hepatitis B virus may be linked to the number of copies of certain genes in an individual’s genome. A Japanese team led by Masataka Kikuchi, Osaka University, and Akihiro Nakaya, University of Tokyo, looked for repeated segments of the genome, known as copy number variants (CNVs), that differed between people with hepatitis B infections and those without. Studying around 3000 individuals of Japanese descent, the researchers identified several rare CNVs associated with immune function in hepatitis-affected individuals. They also found a common CNV in a gene called CNTN6 that the hepatitis B virus often uses to integrate itself into the genome of liver cells, a process that can lead to cancer. The findings underscore the importance of CNVs as inherited risk factors for hepatitis B and other viral infections.

Iron is an essential plant nutrient that is poorly bioavailable in alkaline soils, resulting in reduced agricultural productivity. Here, the authors report the synthesis of stable and cheap iron-chelator, proline-2’-deoxymugineic acid (PDMA), and demonstrate its utility as potential fertilizer.

Abstract Aims/Introduction The objective of the present study was to clarify the association of the type and number of first‐degree family history of diabetes (FHD) with the clinical characteristics, especially with residual β‐cell function, in type 2 diabetes patients. Materials and Methods A total of 1,131 type 2 diabetes patients were recruited and divided into four groups according to FHD information as follows: (i) patients without FHD (FHD−); (ii) those with at least one sibling who had diabetes without parental diabetes (FHD+); (iii) those with one parent (FHD++); or (iv) those with both parents (FHD+++) who had diabetes with or without a sibling with diabetes. Results The percentages of the FHD−, FHD+, FHD++ and FHD+++ groups were 49.4%, 13.4%, 34.0% and 3.2%, respectively. Patients in the FHD++ and FHD+++ groups were significantly younger at the time of diabetes diagnosis (P

Background: Although lower household economic status is known to be a risk factor for obesity among school-age children, such an association among toddlers remains unclear. The present study investigated the association between household economic status and obesity in toddlers. Design: We conducted a cross-sectional study of children aged 4 years attending daycare centers in Japan. Information on subjective household economic status [“affluent”, “neither”, “less affluent”, or “non-affluent”] was collected via questionnaire from the children’s guardians in 2015. Based on measured values of height and weight, obesity was defined using the International Obesity Task Force cut-offs of overweight (BMI ≥17.47 for boys and ≥17.19 for girls). We used the logistic regression model to investigate the association between household economic status and obesity. Results: Among 1,848 respondents, the prevalence of obesity was 6.8%. Non-affluent household economic status was associated with a significantly higher probability of obesity in toddlers; the multivariate adjusted odds ratio for “non-affluent” households was 2.31 (95% confidence interval, 1.23–4.33) compared with “affluent” households. Conclusion: Perception of non-affluent economic status by the guardian was associated with a higher probability of toddler obesity. This result suggests that non-affluent household economic status is associated with obesity in toddlers.

Abstract Background Epidural anesthesia is widely used for postoperative analgesia and rarely causes permanent neurological complications. We report a case of paraplegia following abdominal surgery under combined epidural/general anesthesia. Case presentation A 75-year-old woman underwent a scheduled abdominal total hysterectomy and bilateral salpingo-oophorectomy for suspected endometrial cancer. In the operating room, an epidural catheter was inserted at T11/12 while the patient was conscious. The needle entered smoothly, with no observed bleeding, paresthesia, or pain, and general anesthesia was induced. During surgery, 4 mL of 0.25% levobupivacaine and 0.1 mg of fentanyl were administered via the epidural catheter, and a solution of 2.5 μg/mL fentanyl and 0.2% levobupivacaine was continuously infused at 4 mL/h for postoperative analgesia. The patient promptly regained consciousness and could move her bilateral lower extremities without difficulty upon leaving the operating room. During the first postoperative night, she complained of an absence of sensation and weakness in the lower extremities. By the morning of the second postoperative day, she had developed paralysis and sensory losses associated with touch, temperature, pinprick, and vibration below T5. The epidural infusion was stopped. Magnetic resonance imaging (MRI) revealed a hyperintense area of the thoracic cord from T8 to T11, and spinal cord infarction was suspected. Ossification of the yellow spinal ligaments between T11 and T12, resulting in thoracic canal stenosis and thoracic spinal cord compression, were observed. Notably, the epidural catheter was inserted at the same site where the thoracic canal stenosis was present. Conclusions Permanent neurological complications of epidural anesthesia are rare. Studies of neurological complications after epidural/spinal anesthesia have noted the possibility of spinal anomalies, such as lumbar stenosis, in relation to neurological complications after epidural/spinal anesthesia. In this case, the onset of spinal cord infarction may have occurred coincidentally with catheter insertion into the site of existing spinal stenosis. Therefore, it is important to evaluate lower extremity symptoms and consider spinal disease before administering epidural anesthesia. Spinal cord infarction may be prevented by preoperatively identifying spinal lesions using computed tomography or MRI in cases of suspected spinal disease.

Replicative DNA polymerases are frequently stalled at damaged template strands. Stalled replication forks are restored by the DNA damage tolerance (DDT) pathways, error-prone translesion DNA synthesis (TLS) to cope with excessive DNA damage, and error-free template switching (TS) by homologous DNA recombination. PDIP38 (Pol-delta interacting protein of 38 kDa), also called Pol δ-interacting protein 2 (PolDIP2), physically associates with TLS DNA polymerases, polymerase η (Polη), Polλ, and PrimPol, and activates them in vitro. It remains unclear whether PDIP38 promotes TLS in vivo, since no method allows for measuring individual TLS events in mammalian cells. We disrupted the PDIP38 gene, generating PDIP38-/- cells from the chicken DT40 and human TK6 B cell lines. These PDIP38-/- cells did not show a significant sensitivity to either UV or H2O2, a phenotype not seen in any TLS-polymerase-deficient DT40 or TK6 mutants. DT40 provides a unique opportunity of examining individual TLS and TS events by the nucleotide sequence analysis of the immunoglobulin variable (Ig V) gene as the cells continuously diversify Ig V by TLS (non-templated Ig V hypermutation) and TS (Ig gene conversion) during in vitro culture. PDIP38-/- cells showed a shift in Ig V diversification from TLS to TS. We measured the relative usage of TLS and TS in TK6 cells at a chemically synthesized UV damage (CPD) integrated into genomic DNA. The loss of PDIP38 also caused an increase in the relative usage of TS. The number of UV-induced sister chromatid exchanges, TS events associated with crossover, was increased a few times in PDIP38-/- human and chicken cells. Collectively, the loss of PDIP38 consistently causes a shift in DDT from TLS to TS without enhancing cellular sensitivity to DNA damage. We propose that PDIP38 controls the relative usage of TLS and TS increasing usage of TLS without changing the overall capability of DDT.

Gene-targeting to create null mutants or designed-point mutants is a powerful tool for the molecular dissection of complex phenotypes involving DNA repair, signal transduction, and metabolism. Because gene-targeting is critically impaired in mutants exhibiting attenuated homologous recombination (HR), it is believed that gene-targeting is mediated via homologous recombination, though the precise mechanism remains unknown. We explored gene-targeting in yeast and avian DT40 cells. In animal cells, gene-targeting is activated by DNA double strand breaks introduced into the genomic region where gene-targeting occurs. This is evidenced by the fact that introducing double strand breaks at targeted genome sequences via artificial endonucleases such as TALEN and CRISPR facilitates gene-targeting. We found that in fission yeast, Schizosaccharomyces pombe, gene-targeting was initiated from double strand breaks on both edges of the homologous arms in the targeting construct. Strikingly, we also found efficient gene-targeting initiated on the edges of homologous arms in avian DT40 cells, a unique animal cell line in which efficient gene-targeting has been demonstrated. It may be that yeast and DT40 cells share some mechanism in which unknown factors detect and recombine broken DNA ends at homologous arms accompanied by crossover. We found efficient targeted integration of gapped plasmids accompanied by crossover in the DT40 cells. To take advantage of this finding, we developed a targeted flip-in system for avian DT40 cells. This flip-in system enables the rapid generation of cells expressing tag-fused proteins and the stable expression of transgenes from OVA loci.

Objectives. We investigated the relationship between the stage of diabetic retinopathy and pulse wave velocity (PWV). Methods. This was a cross-sectional study of 689 patients (406 men and 283 women) with type 2 diabetes who were admitted to our hospital from 2004 to 2007. Brachial-ankle pulse wave velocity (baPWV) was measured by an arterial pressure measurement device as PWV/ABI. Diagnosis of diabetic retinopathy was made by ophthalmologists based on the Davis classification: no diabetic retinopathy (NDR), simple retinopathy (SDR), pre-proliferative retinopathy (pre-PDR), and proliferative retinopathy (PDR). Results. There was a significant difference in PWV between patients without diabetic retinopathy (1657.0±417.9 m/s (mean ± SD)) and with diabetic retinopathy (1847.1±423.9 m/s) (P

Comprehensive imaging of a biological individual can be achieved by utilizing the variation in spatial resolution, the scale of cathodoluminescence (CL), and near-infrared (NIR), as favored by imaging probe Gd2O3 co-doped lanthanide nanophosphors (NPPs). A series of Gd2O3:Ln3+/Yb3+ (Ln3+: Tm3+, Ho3+, Er3+) NPPs with multispectral emission are prepared by the sol-gel method. The NPPs show a wide range of emissions spanning from the visible to the NIR region under 980 nm excitation. The dependence of the upconverting (UC)/downconverting (DC) emission intensity on the dopant ratio is investigated. The optimum ratios of dopants obtained for emissions in the NIR regions at 810 nm, 1200 nm, and 1530 nm are applied to produce nanoparticles by the homogeneous precipitation (HP) method. The nanoparticles produced from the HP method are used to investigate the dual NIR and CL imaging modalities. The results indicate the possibility of using Gd2O3 co-doped Ln3+/Yb3+ (Ln3+: Tm3+, Ho3+, Er3+) in correlation with NIR and CL imaging. The use of Gd2O3 promises an extension of the object dimension to the whole-body level by employing magnetic resonance imaging (MRI).